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| | Rab39 | Ras-related protein Rab-39A; Plays a role in the maturation and acidification of phagosomes that engulf pathogens, such as S.aureus and M.tuberculosis. Plays a role in vesicular trafficking. Plays a role in the fusion of phagosomes with lysosomes. Negatively regulates LPS-induced autophagosome formation in macrophages possibly by implicating PI3K (By similarity). May be involved in multiple neurite formation ; Belongs to the small GTPase superfamily. Rab family. (217 aa) |
| | Il4 | Interleukin-4; Participates in at least several B-cell activation processes as well as of other cell types. It is a costimulator of DNA-synthesis. It induces the expression of class II MHC molecules on resting B-cells. It enhances both secretion and cell surface expression of IgE and IgG1. It also regulates the expression of the low affinity Fc receptor for IgE (CD23) on both lymphocytes and monocytes. Positively regulates IL31RA expression in macrophages. Stimulates autophagy in dendritic cells by interfering with mTORC1 signaling and through the induction of RUFY4. Belongs to the IL- [...] (140 aa) |
| | Gramd1a | Protein Aster-A; Cholesterol transporter that mediates non-vesicular transport of cholesterol from the plasma membrane (PM) to the endoplasmic reticulum (ER). Contains unique domains for binding cholesterol and the PM, thereby serving as a molecular bridge for the transfer of cholesterol from the PM to the ER. Plays a crucial role in cholesterol homeostasis and has the unique ability to localize to the PM based on the level of membrane cholesterol. In lipid-poor conditions localizes to the ER membrane and in response to excess cholesterol in the PM is recruited to the endoplasmic retic [...] (722 aa) |
| | Tollip | Toll-interacting protein; Component of the signaling pathway of IL-1 and Toll-like receptors. Inhibits cell activation by microbial products. Recruits IRAK1 to the IL-1 receptor complex. Inhibits IRAK1 phosphorylation and kinase activity. Connects the ubiquitin pathway to autophagy by functioning as a ubiquitin-ATG8 family adapter and thus mediating autophagic clearance of ubiquitin conjugates. The TOLLIP-dependent selective autophagy pathway plays an important role in clearance of cytotoxic polyQ proteins aggregates (By similarity). (274 aa) |
| | Rab8a | Ras-related protein Rab-8A; The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. That Rab is involved in polarized vesicular trafficking and neurotransmitter release. Together with RAB11A, RAB3IP, the exocyst complex, PARD3, PRKCI, ANXA2, CDC42 and DNMBP promotes t [...] (207 aa) |
| | Stk11 | Serine/threonine-protein kinase STK11; Tumor suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage response. Acts by phosphorylating the T-loop of AMPK family proteins, thus promoting their activity: phosphorylates PRKAA1, PRKAA2, BRSK1, BRSK2, MARK1, MARK2, MARK3, MARK4, NUAK1, NUAK2, SIK1, SIK2, SIK3 and SNRK but not MELK. Also phosphorylates non-AMPK family proteins such as STRADA, PTEN and possibly p53/TP [...] (436 aa) |
| | Ulk2 | Serine/threonine-protein kinase ULK2; Serine/threonine-protein kinase involved in autophagy in response to starvation. Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes. Part of regulatory feedback loops in autophagy: acts both as a downstream effector and a negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR. Activated via phosphorylation by AMPK, also acts as a negative regulator of AMPK through phosphorylation of the AMPK subunits PRKAA1, PRKAB2 and PRKAG1 [...] (1037 aa) |
| | Ubqln4 | Ubiquilin-4; Regulator of protein degradation that mediates the proteasomal targeting of misfolded, mislocalized or accumulated proteins (By similarity). Acts by binding polyubiquitin chains of target proteins via its UBA domain and by interacting with subunits of the proteasome via its ubiquitin-like domain (By similarity). Key regulator of DNA repair that represses homologous recombination repair: in response to DNA damage, recruited to sites of DNA damage following phosphorylation by ATM and acts by binding and removing ubiquitinated MRE11 from damaged chromatin, leading to MRE11 de [...] (596 aa) |
| | Rnf166 | E3 ubiquitin-protein ligase RNF166; E3 ubiquitin-protein ligase that promotes the ubiquitination of different substrates. In turn, participates in different biological processes including interferon production or autophagy. Plays a role in the activation of RNA virus-induced interferon-beta production by promoting the ubiquitination of TRAF3 and TRAF6. Plays also a role in the early recruitment of autophagy adapters to bacteria. Mediates 'Lys- 29' and 'Lys-33'-linked ubiquitination of SQSTM1 leading to xenophagic targeting of bacteria and inhibition of their replication. (237 aa) |
| | Tmem208 | Transmembrane protein 208; May function as a negative regulator of endoplasmic reticulum-stress induced autophagy. (173 aa) |
| | Vmp1 | Vacuole membrane protein 1; Stress-induced protein that, when overexpressed, promotes formation of intracellular vacuoles followed by cell death (By similarity). May be involved in the cytoplasmic vacuolization of acinar cells during the early stage of acute pancreatitis. Involved in cell-cell adhesion. Plays an essential role in formation of cell junctions. Plays a role in the initial stages of the autophagic process through its interaction with BECN1. Required for autophagosome formation (By similarity); Belongs to the VMP1 family. (406 aa) |
| | Gabarap | Gamma-aminobutyric acid receptor-associated protein; Ubiquitin-like modifier that plays a role in intracellular transport of GABA(A) receptors and its interaction with the cytoskeleton. Involved in apoptosis. Involved in autophagy. Whereas LC3s are involved in elongation of the phagophore membrane, the GABARAP/GATE-16 subfamily is essential for a later stage in autophagosome maturation (By similarity); Belongs to the ATG8 family. (117 aa) |
| | Phf23 | PHD finger protein 23; Acts as a negative regulator of autophagy, through promoting ubiquitination and degradation of LRSAM1, an E3 ubiquitin ligase that promotes autophagy in response to starvation or infecting bacteria. (401 aa) |
| | Dram1 | DNA damage-regulated autophagy modulator protein 1; Lysosomal modulator of autophagy that plays a central role in p53/TP53-mediated apoptosis. Not involved in p73/TP73-mediated autophagy (By similarity). (238 aa) |
| | Gpr137b | Integral membrane protein GPR137B; Lysosomal integral membrane protein that regulates the localization and activity of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. Interacts with Rag GTPases and increases the lysosomial localization and activity of Rag GTPases and thereby regulates mTORC1 translocation and activity in lysosome. Involved in the regulation of lysosomal morphology and autophagy (By similarity). Acts also as a negative regulator of osteoclast activity. Involved in interleukin-4-induced M2 macrophage polari [...] (385 aa) |
| | Atg10 | Ubiquitin-like-conjugating enzyme ATG10; E2-like enzyme involved in autophagy. Acts as an E2-like enzyme that catalyzes the conjugation of ATG12 to ATG5. ATG12 conjugation to ATG5 is required for autophagy. Likely serves as an ATG5-recognition molecule. Not involved in ATG12 conjugation to ATG3. Plays a role in adenovirus-mediated cell lysis. (211 aa) |
| | Retreg1 | Reticulophagy regulator 1; Endoplasmic reticulum-anchored autophagy receptor that mediates ER delivery into lysosomes through sequestration into autophagosomes. Promotes membrane remodeling and ER scission via its membrane bending capacity and targets the fragments into autophagosomes via interaction with ATG8 family proteins. Required for long-term survival of nociceptive and autonomic ganglion neurons. (480 aa) |
| | Atg3 | Ubiquitin-like-conjugating enzyme ATG3; E2 conjugating enzyme required for the cytoplasm to vacuole transport (Cvt), autophagy, and mitochondrial homeostasis. Responsible for the E2-like covalent binding of phosphatidylethanolamine to the C- terminal Gly of ATG8-like proteins (GABARAP, GABARAPL1, GABARAPL2 or MAP1LC3A). The ATG12-ATG5 conjugate plays a role of an E3 and promotes the transfer of ATG8-like proteins from ATG3 to phosphatidylethanolamine (PE). This step is required for the membrane association of ATG8-like proteins. The formation of the ATG8- phosphatidylethanolamine conju [...] (314 aa) |
| | Snap29 | Synaptosomal-associated protein 29; SNAREs, soluble N-ethylmaleimide-sensitive factor-attachment protein receptors, are essential proteins for fusion of cellular membranes. SNAREs localized on opposing membranes assemble to form a trans-SNARE complex, an extended, parallel four alpha-helical bundle that drives membrane fusion. SNAP29 is a SNARE involved in autophagy through the direct control of autophagosome membrane fusion with the lysososome membrane. Plays also a role in ciliogenesis by regulating membrane fusions. (260 aa) |
| | Tmbim6 | Bax inhibitor 1; Suppressor of apoptosis (By similarity). Modulates unfolded protein response signaling (By similarity). Modulates ER calcium homeostasis by acting as a calcium-leak channel (By similarity). Negatively regulates autophagy and autophagosome formation, especially during periods of nutrient deprivation, and reduces cell survival during starvation. (237 aa) |
| | Tbc1d5 | TBC1 domain family member 5; May act as a GTPase-activating protein for Rab family protein(s). May act as a GAP for RAB7A. Can displace RAB7A and retromer CSC subcomplex from the endosomal membrane to the cytosol; at least retromer displacement seems to require its catalytic activity. Required for retrograde transport of cargo proteins from endosomes to the trans- Golgi network (TGN); the function seems to require its catalytic activity. Involved in regulation of autophagy. May act as a molecular switch between endosomal and autophagosomal transport and is involved in reprogramming ves [...] (815 aa) |
| | Tfeb | Transcription factor EB; Transcription factor that specifically recognizes and binds E-box sequences (5'-CANNTG-3'). Efficient DNA-binding requires dimerization with itself or with another MiT/TFE family member such as TFE3 or MITF. In association with TFE3, activates the expression of CD40L in T-cells, thereby playing a role in T-cell-dependent antibody responses in activated CD4(+) T-cells and thymus-dependent humoral immunity. Specifically recognizes and binds the CLEAR-box sequence (5'- GTCACGTGAC-3') present in the regulatory region of many lysosomal genes, leading to activate the [...] (534 aa) |
| | Rmc1 | Regulator of MON1-CCZ1 complex; Componement of the CCZ1-MON1 RAB7A guanine exchange factor (GEF). Acts as a positive regulator of CCZ1-MON1A/B function necessary for endosomal/autophagic flux and efficient RAB7A localization. Belongs to the RMC1 family. (657 aa) |
| | Rab1b | Ras-related protein Rab-1B; The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (By similarity). Plays a role in the initial events of the autophagic vacuole development which take place at specialized regions of the endoplasmic reticulum (By similarity). Regulates [...] (201 aa) |
| | Fundc1 | FUN14 domain-containing protein 1; Acts as an activator of hypoxia-induced mitophagy, an important mechanism for mitochondrial quality control; Belongs to the FUN14 family. (155 aa) |
| | Wdr45b | WD repeat domain phosphoinositide-interacting protein 3; Component of the autophagy machinery that controls the major intracellular degradation process by which cytoplasmic materials are packaged into autophagosomes and delivered to lysosomes for degradation. Binds phosphatidylinositol 3-phosphate (PtdIns3P) forming on membranes of the endoplasmic reticulum upon activation of the upstream ULK1 and PI3 kinases and is recruited at phagophore assembly sites where it regulates the elongation of nascent phagophores downstream of WIPI2. In the cellular response to starvation, may also functi [...] (344 aa) |
| | Wdr24 | GATOR complex protein WDR24; As a component of the GATOR subcomplex GATOR2, functions within the amino acid-sensing branch of the TORC1 signaling pathway. Indirectly activates mTORC1 and the TORC1 signaling pathway through the inhibition of the GATOR1 subcomplex. It is negatively regulated by the upstream amino acid sensors SESN2 and CASTOR1. In addition to its role in regulation of the TORC1 complex, promotes the acidification of lysosomes and facilitates autophagic flux. (790 aa) |
| | Rb1cc1 | RB1-inducible coiled-coil protein 1; Involved in autophagy. Regulates early events but also late events of autophagosome formation through direct interaction with Atg16L1. Required for the formation of the autophagosome-like double-membrane structure that surrounds the Salmonella-containing vacuole (SCV) during S.typhimurium infection and subsequent xenophagy. Involved in repair of DNA damage caused by ionizing radiation, which subsequently improves cell survival by decreasing apoptosis. Inhibits PTK2/FAK1 and PTK2B/PYK2 kinase activity, affecting their downstream signaling pathways (B [...] (1588 aa) |
| | Atg4b | Cysteine protease ATG4B; Cysteine protease required for the cytoplasm to vacuole transport (Cvt) and autophagy. Cleaves the C-terminal amino acid of ATG8 family proteins MAP1LC3, GABARAPL1, GABARAPL2 and GABARAP, to reveal a C-terminal glycine. Exposure of the glycine at the C-terminus is essential for ATG8 proteins conjugation to phosphatidylethanolamine (PE) and insertion to membranes, which is necessary for autophagy. Has also an activity of delipidating enzyme for the PE-conjugated forms (By similarity). (393 aa) |
| | Vps16 | Vacuolar protein sorting-associated protein 16 homolog; Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Believed to act as a core component of the putative HOPS and CORVET endosomal tethering complexes which are proposed to be involved in the Rab5-to-Rab7 endosome conversion probably implicating MON1A/B, and via binding SNAREs and SNARE complexes to mediate tethering and docking events during SNARE-mediated membrane fusion. The HOPS complex is proposed to be recruited to Rab7 on the late [...] (839 aa) |
| | Map1lc3a | Microtubule-associated proteins 1A/1B light chain 3A; Ubiquitin-like modifier involved in formation of autophagosomal vacuoles (autophagosomes). Whereas LC3s are involved in elongation of the phagophore membrane, the GABARAP/GATE-16 subfamily is essential for a later stage in autophagosome maturation. (121 aa) |
| | Ptpn22 | Tyrosine-protein phosphatase non-receptor type 22; Acts as negative regulator of T-cell receptor (TCR) signaling by direct dephosphorylation of the Src family kinases LCK and FYN, ITAMs of the TCRz/CD3 complex, as well as ZAP70, VAV, VCP and other key signaling molecules (By similarity). Associates with and probably dephosphorylates CBL (By similarity). Dephosphorylates LCK at its activating 'Tyr-394' residue (By similarity). Dephosphorylates ZAP70 at its activating 'Tyr-492' residue (By similarity). Dephosphorylates the immune system activator SKAP2 (By similarity). Positively regulat [...] (802 aa) |
| | Cisd2 | CDGSH iron-sulfur domain-containing protein 2; Regulator of autophagy that contributes to antagonize BECN1- mediated cellular autophagy at the endoplasmic reticulum. Participates in the interaction of BCL2 with BECN1 and is required for BCL2-mediated depression of endoplasmic reticulum Ca(2+) stores during autophagy. Contributes to BIK-initiated autophagy, while it is not involved in BIK-dependent activation of caspases. Involved in life span control, probably via its function as regulator of autophagy (By similarity). Belongs to the CISD protein family. CISD2 subfamily. (135 aa) |
| | Trp53inp1 | Tumor protein p53-inducible nuclear protein 1; Antiproliferative and proapoptotic protein involved in cell stress response which acts as a dual regulator of transcription and autophagy. Acts as a positive regulator of autophagy. In response to cellular stress or activation of autophagy, relocates to autophagosomes where it interacts with autophagosome-associated proteins GABARAP, GABARAPL1/L2, MAP1LC3A/B/C and regulates autophagy. Acts as an antioxidant and plays a major role in p53/TP53-driven oxidative stress response. Possesses both a p53/TP53-independent intracellular reactive oxyg [...] (239 aa) |
| | Vcp | Transitional endoplasmic reticulum ATPase; Necessary for the fragmentation of Golgi stacks during mitosis and for their reassembly after mitosis. Involved in the formation of the transitional endoplasmic reticulum (tER). The transfer of membranes from the endoplasmic reticulum to the Golgi apparatus occurs via 50-70 nm transition vesicles which derive from part-rough, part-smooth transitional elements of the endoplasmic reticulum (tER). Vesicle budding from the tER is an ATP-dependent process. The ternary complex containing UFD1, VCP and NPLOC4 binds ubiquitinated proteins and is neces [...] (806 aa) |
| | Prkaa2 | 5'-AMP-activated protein kinase catalytic subunit alpha-2; Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts a [...] (552 aa) |
| | Atg4c | Cysteine protease ATG4C; Cysteine protease required for the cytoplasm to vacuole transport (Cvt) and autophagy. Cleaves the C-terminal amino acid of ATG8 family proteins MAP1LC3 and GABARAPL2, to reveal a C-terminal glycine. Exposure of the glycine at the C-terminus is essential for ATG8 proteins conjugation to phosphatidylethanolamine (PE) and insertion to membranes, which is necessary for autophagy. Has also an activity of delipidating enzyme for the PE-conjugated forms (By similarity). Is not essential for autophagy development under normal conditions but is required for a proper au [...] (458 aa) |
| | Tmem59 | Transmembrane protein 59; Acts as a regulator of autophagy in response to S.aureus infection by promoting activation of LC3 (MAP1LC3A, MAP1LC3B or MAP1LC3C). Acts by interacting with ATG16L1, leading to promote a functional complex between LC3 and ATG16L1 and promoting LC3 lipidation and subsequent activation of autophagy. Modulates the O-glycosylation and complex N-glycosylation steps occurring during the Golgi maturation of several proteins such as APP, BACE1, SEAP or PRNP. Inhibits APP transport to the cell surface and further shedding. (323 aa) |
| | Pink1 | Serine/threonine-protein kinase PINK1, mitochondrial; Protects against mitochondrial dysfunction during cellular stress by phosphorylating mitochondrial proteins. Involved in the clearance of damaged mitochondria via selective autophagy (mitophagy) by mediating activation and translocation of PRKN. Targets PRKN to dysfunctional depolarized mitochondria through the phosphorylation of MFN2 (By similarity). Activates PRKN in 2 steps: (1) by mediating phosphorylation at 'Ser-65' of PRKN and (2) mediating phosphorylation of ubiquitin, converting PRKN to its fully-active form. Required for u [...] (580 aa) |
| | Mfn2 | Mitofusin-2; Mitochondrial outer membrane GTPase that mediates mitochondrial clustering and fusion. Mitochondria are highly dynamic organelles, and their morphology is determined by the equilibrium between mitochondrial fusion and fission events. Overexpression induces the formation of mitochondrial networks. Membrane clustering requires GTPase activity and may involve a major rearrangement of the coiled coil domains (By similarity). Plays a central role in mitochondrial metabolism and may be associated with obesity and/or apoptosis processes. Plays an important role in the regulation [...] (757 aa) |
| | Vps33a | Vacuolar protein sorting-associated protein 33A; Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Believed to act as a core component of the putative HOPS and CORVET endosomal tethering complexes which are proposed to be involved in the Rab5-to-Rab7 endosome conversion probably implicating MON1A/B, and via binding SNAREs and SNARE complexes to mediate tethering and docking events during SNARE-mediated membrane fusion. The HOPS complex is proposed to be recruited to Rab7 on the late endosom [...] (598 aa) |
| | Gabarapl1 | Gamma-aminobutyric acid receptor-associated protein-like 1; Ubiquitin-like modifier that increases cell-surface expression of kappa-type opioid receptor through facilitating anterograde intracellular trafficking of the receptor. Involved in formation of autophagosomal vacuoles. Whereas LC3s are involved in elongation of the phagophore membrane, the GABARAP/GATE-16 subfamily is essential for a later stage in autophagosome maturation (By similarity). (117 aa) |
| | Sbf2 | Myotubularin-related protein 13; Guanine nucleotide exchange factor (GEF) which activates RAB21 and possibly RAB28 (By similarity). Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form (By similarity). In response to starvation-induced autophagy, activates RAB21 which in turn binds to and regulates SNARE protein VAMP8 endolysosomal transport required for SNARE-mediated autophagosome-lysosome fusion (By similarity). Acts as an adapter for the phosphatase MTMR2. Increases MTMR2 catalytic activity towards phosphatidylinositol 3,5 [...] (1872 aa) |
| | Rab39b | Ras-related protein Rab-39B; Small GTPases Rab involved in autophagy. The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (By similarity). May be involved in vesicular trafficking. Plays a role in synapse formation. May regulate the homeostasis of SNCA/alpha-synucl [...] (213 aa) |
| | Map1lc3b | Microtubule-associated proteins 1A/1B light chain 3B; Ubiquitin-like modifier involved in formation of autophagosomal vacuoles (autophagosomes). Plays a role in mitophagy which contributes to regulate mitochondrial quantity and quality by eliminating the mitochondria to a basal level to fulfill cellular energy requirements and preventing excess ROS production. Whereas LC3s are involved in elongation of the phagophore membrane, the GABARAP/GATE-16 subfamily is essential for a later stage in autophagosome maturation. Promotes primary ciliogenesis by removing OFD1 from centriolar satellit [...] (125 aa) |
| | Gabarapl2 | Gamma-aminobutyric acid receptor-associated protein-like 2; Ubiquitin-like modifier involved in intra-Golgi traffic. Modulates intra-Golgi transport through coupling between NSF activity and SNAREs activation. It first stimulates the ATPase activity of NSF which in turn stimulates the association with GOSR1 (By similarity). Involved in autophagy. Plays a role in mitophagy which contributes to regulate mitochondrial quantity and quality by eliminating the mitochondria to a basal level to fulfill cellular energy requirements and preventing excess ROS production. Whereas LC3s are involved [...] (117 aa) |
| | Vps11 | Vacuolar protein sorting-associated protein 11 homolog; Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Believed to act as a core component of the putative HOPS and CORVET endosomal tethering complexes which are proposed to be involved in the Rab5-to-Rab7 endosome conversion probably implicating MON1A/B, and via binding SNAREs and SNARE complexes to mediate tethering and docking events during SNARE-mediated membrane fusion. The HOPS complex is proposed to be recruited to Rab7 on the late [...] (941 aa) |
| | Atg14 | Beclin 1-associated autophagy-related key regulator; Required for both basal and inducible autophagy. Determines the localization of the autophagy-specific PI3-kinase complex PI3KC3-C1 (By similarity). Plays a role in autophagosome formation and MAP1LC3/LC3 conjugation to phosphatidylethanolamine. Promotes BECN1 translocation from the trans-Golgi network to autophagosomes (By similarity). Enhances PIK3C3 activity in a BECN1-dependent manner. Essential for the autophagy-dependent phosphorylation of BECN1 (By similarity). Stimulates the phosphorylation of BECN1, but suppresses the phosph [...] (492 aa) |
| | Gm38100 | Beclin-2; Involved in 2 distinct lysosomal degradation pathways: acts as a regulator of autophagy and as a regulator of G-protein coupled receptors turnover. Regulates degradation in lysosomes of a variety of G-protein coupled receptors via its interaction with GPRASP1/GASP1. (447 aa) |
| | Ulk1 | Serine/threonine-protein kinase ULK1; Serine/threonine-protein kinase involved in autophagy in response to starvation. Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes. Part of regulatory feedback loops in autophagy: acts both as a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR. Activated via phosphorylation by AMPK and also acts as a regulator of AMPK by mediating phosphorylation of AMPK subunits PRKAA1, PRKAB2 and PRKAG1, leadi [...] (1057 aa) |
| | Atg4a-ps | Cysteine protease; Cysteine protease required for the cytoplasm to vacuole transport (Cvt) and autophagy; Belongs to the peptidase C54 family. (396 aa) |
| | Prkn | E3 ubiquitin-protein ligase parkin; Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPTIN5, TOMM20, USP30, ZNF746 and AIMP2. Mediates monoubiquitination as well as 'Lys-6', 'Lys-11', 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination of substrates depending on the context. Participates in the removal and/or detoxification of abnormally folded or damaged protein by mediating 'Lys-63'-linked polyubiquitination of mi [...] (464 aa) |
| | Atg9a | Autophagy-related protein 9A; Involved in autophagy and cytoplasm to vacuole transport (Cvt) vesicle formation. Plays a key role in the organization of the preautophagosomal structure/phagophore assembly site (PAS), the nucleating site for formation of the sequestering vesicle. Cycles between a juxta-nuclear trans-Golgi network compartment and late endosomes. Nutrient starvation induces accumulation on autophagosomes. Starvation-dependent trafficking requires ULK1, ATG13 and SUPT20H (By similarity). Required for carbonyl cyanide m-chlorophenylhydrazone (CCCP)-induced ATG8 family protei [...] (839 aa) |
| | Pik3cb | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform; Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Involved in the activation of AKT1 upon stimulation [...] (1064 aa) |
| | Vps18 | Vacuolar protein sorting-associated protein 18 homolog; Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Believed to act as a core component of the putative HOPS and CORVET endosomal tethering complexes which are proposed to be involved in the Rab5-to-Rab7 endosome conversion probably implicating MON1A/B, and via binding SNAREs and SNARE complexes to mediate tethering and docking events during SNARE-mediated membrane fusion. The HOPS complex is proposed to be recruited to Rab7 on the late [...] (973 aa) |
| | Eva1a | Protein eva-1 homolog A; Acts as a regulator of programmed cell death, mediating both autophagy and apoptosis; Belongs to the EVA1 family. (156 aa) |
| | Atg2b | Autophagy-related protein 2 homolog B; Required for both autophagosome formation and regulation of lipid droplet morphology and dispersion. (2075 aa) |
| | Trp53inp2 | Tumor protein p53-inducible nuclear protein 2; Dual regulator of transcription and autophagy. Positively regulates autophagy and is required for autophagosome formation and processing. May act as a scaffold protein that recruits MAP1LC3A, GABARAP and GABARAPL2 and brings them to the autophagosome membrane by interacting with VMP1 where, in cooperation with the BECN1-PI3-kinase class III complex, they trigger autophagosome development. Acts as a transcriptional activator of THRA. (221 aa) |
| | Atg12 | Ubiquitin-like protein ATG12; Ubiquitin-like protein involved in autophagy vesicles formation. Conjugation with ATG5 through a ubiquitin-like conjugating system involving also ATG7 as an E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme, is essential for its function. The ATG12-ATG5 conjugate acts as an E3-like enzyme which is required for lipidation of ATG8 family proteins and their association to the vesicle membranes. (141 aa) |
| | Epg5 | Ectopic P granules protein 5 homolog; Involved in autophagy. May play a role in a late step of autophagy, such as clearance of autophagosomal cargo. Plays a key role in innate and adaptive immune response triggered by unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides from pathogens, and mediated by the nucleotide-sensing receptor TLR9. It is necessary for the translocation of CpG dinucleotides from early endosomes to late endosomes and lysosomes, where TLR9 is located. (2572 aa) |
| | Irf8 | Interferon regulatory factor 8; Plays a role as a transcriptional activator or repressor (By similarity). Specifically binds to the upstream regulatory region of type I IFN and IFN-inducible MHC class I genes (the interferon consensus sequence (ICS)). Plays a negative regulatory role in cells of the immune system. Involved in CD8(+) dendritic cell differentiation by forming a complex with the BATF-JUNB heterodimer in immune cells, leading to recognition of AICE sequence (5'-TGAnTCA/GAAA-3'), an immune-specific regulatory element, followed by cooperative binding of BATF and IRF8 and act [...] (424 aa) |
| | Wdr45 | WD repeat domain phosphoinositide-interacting protein 4; Component of the autophagy machinery that controls the major intracellular degradation process by which cytoplasmic materials are packaged into autophagosomes and delivered to lysosomes for degradation. Activated by the STK11/AMPK signaling pathway upon starvation, WDR45 is involved in autophagosome assembly downstream of WIPI2, regulating the size of forming autophagosomes. Probably recruited to membranes through its PtdIns3P activity. Belongs to the WD repeat SVP1 family. (360 aa) |
| | Atg5 | Autophagy protein 5; Involved in autophagic vesicle formation. Conjugation with ATG12, through a ubiquitin-like conjugating system involving ATG7 as an E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme, is essential for its function. The ATG12-ATG5 conjugate acts as an E3- like enzyme which is required for lipidation of ATG8 family proteins and their association to the vesicle membranes. Involved in mitochondrial quality control after oxidative damage, and in subsequent cellular longevity. Plays a critical role in multiple aspects of lymphocyte development and is ess [...] (275 aa) |
| | Wipi2 | WD repeat domain phosphoinositide-interacting protein 2; Component of the autophagy machinery that controls the major intracellular degradation process by which cytoplasmic materials are packaged into autophagosomes and delivered to lysosomes for degradation. Involved in an early step of the formation of preautophagosomal structures. Binds and is activated by phosphatidylinositol 3-phosphate (PtdIns3P) forming on membranes of the endoplasmic reticulum upon activation of the upstream ULK1 and PI3 kinases. Once activated, WIPI2 recruits at phagophore assembly sites the ATG12-ATG5-ATG16L1 [...] (445 aa) |
| | Atg101 | Autophagy-related protein 101; Autophagy factor required for autophagosome formation. Stabilizes ATG13, protecting it from proteasomal degradation. (218 aa) |
| | Hap1 | Huntingtin-associated protein 1; Originally identified as neuronal protein that specifically associates with HTT/huntingtin and the binding is enhanced by an expanded polyglutamine repeat within HTT possibly affecting HAP1 interaction properties. Both HTT and HAP1 are involved in intracellular trafficking and HAP1 is proposed to link HTT to motor proteins and/or transport cargos. Seems to play a role in vesicular transport within neurons and axons such as from early endosomes to late endocytic compartments and to promote neurite outgrowth. The vesicular transport function via associati [...] (628 aa) |
| | Atg7 | Ubiquitin-like modifier-activating enzyme ATG7; E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 family proteins for their conjugation with phosphatidylethanolamine. Both systems are needed for the ATG8 association to Cvt vesicles and autophagosomes membranes. Required for autophagic death induced by caspase-8 inhibition. Required for mitophagy which contributes to regulate mitochondrial quantity and quality by eliminating the mitochondria [...] (741 aa) |
| | Rnf41 | E3 ubiquitin-protein ligase NRDP1; Acts as E3 ubiquitin-protein ligase and regulates the degradation of target proteins. Polyubiquitinates MYD88 (By similarity). Negatively regulates MYD88-dependent production of proinflammatory cytokines. Can promote TRIF-dependent production of type I interferon and inhibits infection with vesicular stomatitis virus. Promotes also activation of TBK1 and IRF3. Involved in the ubiquitination of erythropoietin (EPO) and interleukin- 3 (IL-3) receptors. Thus, through maintaining basal levels of cytokine receptors, RNF41 is involved in the control of hema [...] (317 aa) |
| | Gpr137 | Integral membrane protein GPR137; Lysosomal integral membrane protein that may regulate MTORC1 complex translocation to lysosomes. May play a role in autophagy. (396 aa) |
| | Rab12 | Ras-related protein Rab-12; The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (By similarity). That Rab may play a role in protein transport from recycling endosomes to lysosomes regulating, for instance, the degradation of the transferrin receptor. Involved in au [...] (243 aa) |
| | Rab1a | Ras-related protein Rab-1A; The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. RAB1A regulates vesicular protein transport from the endoplasmic reticulum (ER) to the Golgi compartment and on to the cell surface, and plays a role in IL-8 and growth hormone secreti [...] (205 aa) |
| | Fnbp1l | Formin-binding protein 1-like; Required to coordinate membrane tubulation with reorganization of the actin cytoskeleton during endocytosis. May bind to lipids such as phosphatidylinositol 4,5-bisphosphate and phosphatidylserine and promote membrane invagination and the formation of tubules. Also promotes CDC42-induced actin polymerization by activating the WASL-WASPIP complex, the predominant form of WASL/N-WASP in cells. Actin polymerization may promote the fission of membrane tubules to form endocytic vesicles. Essential for autophagy of intracellular bacterial pathogens (By similarity). (609 aa) |
| | Wdr41 | WD repeat-containing protein 41; Non-catalytic component of the C9orf72-SMCR8 complex, a complex that has guanine nucleotide exchange factor (GEF) activity and regulates autophagy. The C9orf72-SMCR8 complex promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB8A and RAB39B into their active GTP-bound form, thereby promoting autophagosome maturation. The C9orf72-SMCR8 complex also acts as a negative regulator of autophagy initiation by interacting with the ATG1/ULK1 kinase complex and inhibiting its protein kinase activity. (460 aa) |
| | Usp10 | Ubiquitin carboxyl-terminal hydrolase 10; Hydrolase that can remove conjugated ubiquitin from target proteins such as p53/TP53, BECN1, SNX3 and CFTR. Acts as an essential regulator of p53/TP53 stability: in unstressed cells, specifically deubiquitinates p53/TP53 in the cytoplasm, leading to counteract MDM2 action and stabilize p53/TP53. Following DNA damage, translocates to the nucleus and deubiquitinates p53/TP53, leading to regulate the p53/TP53-dependent DNA damage response. Component of a regulatory loop that controls autophagy and p53/TP53 levels: mediates deubiquitination of BECN [...] (793 aa) |
| | Cd84 | SLAM family member 5; Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and differentiation of a wide variety of immune cells and thus are involved in the regulation and interconnection of both innate and adaptive immune response. Activities are controlled by presence or absence of small cytoplasmic adapter proteins, SH2D1A/SAP and/or SH2D1B/EAT-2. Can mediate natural killer (NK) cell cytotoxicity dependent on SH2D1A and SH2D1B. Increases proliferativ [...] (329 aa) |
| | Arfip2 | Arfaptin-2; Plays a role in constitutive metalloproteinase (MMP) secretion from the trans Golgi network. May have important functions during vesicle biogenesis at certain cargo subdomains, which could be predominantly utilized by secreted MMPs, such as MMP7 and MMP2. Participates also in autophagy by regulating the starvation-depdendent trafficking of ATG9A vesicles which deliver the PI4-kinase to the autophagosome initiation site. In addition, plays a role in NF-kappa-B inhibition by interacting with IKBKB and IKBKG. (341 aa) |
| | Becn1 | Beclin-1-C 35 kDa; Plays a central role in autophagy. Acts as core subunit of different PI3K complex forms that mediate formation of phosphatidylinositol 3-phosphate and are believed to play a role in multiple membrane trafficking pathways: PI3KC3-C1 is involved in initiation of autophagosomes and PI3KC3-C2 in maturation of autophagosomes and endocytosis. Involved in regulation of degradative endocytic trafficking and required for the abcission step in cytokinesis, probably in the context of PI3KC3-C2 (By similarity). Essential for the formation of PI3KC3-C2 but not PI3KC3-C1 PI3K comp [...] (448 aa) |
| | Rufy4 | RUN and FYVE domain-containing protein 4; Positively regulates macroautophagy in primary dendritic cells. Increases autophagic flux, probably by stimulating both autophagosome formation and facilitating tethering with lysosomes. Binds to phosphatidylinositol 3-phosphate (PtdIns3P) through its FYVE- type zinc finger. (563 aa) |
| | Lgals8 | Galectin-8; Beta-galactoside-binding lectin that acts as a sensor of membrane damage caused by infection and restricts the proliferation of infecting pathogens by targeting them for autophagy. Detects membrane rupture by binding beta-galactoside ligands located on the lumenal side of the endosome membrane; these ligands becoming exposed to the cytoplasm following rupture. Restricts infection by initiating autophagy via interaction with CALCOCO2/NDP52. Required to restrict infection of bacterial invasion such as S.typhimurium. Also required to restrict infection of Picornaviridae viruse [...] (325 aa) |
| | Tm9sf1 | Transmembrane 9 superfamily member 1; Plays an essential role in autophagy; Belongs to the nonaspanin (TM9SF) (TC 9.A.2) family. (606 aa) |
| | S100a9 | Protein S100-A9; S100A9 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. It can induce neutrophil chemotaxis, adhesion, can increase the bactericidal activity of neutrophils by promoting phagocytosis via activation of SYK, PI3K/AKT, and ERK1/2 and can induce degranulation of neutrophils by a MAPK-dependent mechanism. Predominantly found as calprotectin (S100A8/A9) which has a wide plethora of intra- and extracellular functions. The intracellular functions include: facilitating leukocyte arachidonic acid [...] (113 aa) |
| | Atg16l2 | Autophagy-related protein 16-2; May play a role in autophagy. (623 aa) |
| | Zkscan3 | Zinc finger protein with KRAB and SCAN domains 3; Transcriptional factor that binds to the consensus sequence 5'-[GT][AG][AGT]GGGG-3' and acts as a repressor of autophagy. Specifically represses expression of genes involved in autophagy and lysosome biogenesis/function such as MAP1LC3B, ULK1 or WIPI2. Associates with chromatin at the ITGB4 and VEGF promoters (By similarity). (553 aa) |
| | Pik3c3 | Phosphatidylinositol 3-kinase catalytic subunit type 3; Catalytic subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate; different complex forms are believed to play a role in multiple membrane trafficking pathways: PI3KC3-C1 is involved in initiation of autophagosomes and PI3KC3-C2 in maturation of autophagosomes and endocytosis. Involved in regulation of degradative endocytic trafficking and required for the abcission step in cytokinesis, probably in the context of PI3KC3-C2. Involved in the transport of lysosomal enzyme precursors to lysosomes. Requ [...] (887 aa) |
| | Tmem173 | Stimulator of interferon genes protein; Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta). Innate immune response is triggered in response to non-CpG double- stranded DNA from viruses and bacteria delivered to the cytoplasm. Acts by binding cyclic dinucleotides: recognizes and binds cyclic di-GMP (c-di-GMP), a second messenger produced by bacteria, and cyclic GMP-AMP (cGAMP), a messenger produced by CGAS in response to DNA virus in the cytosol. Upon binding of [...] (378 aa) |
| | Ei24 | Etoposide-induced protein 2.4; Acts as a negative growth regulator via p53-mediated apoptosis pathway. Regulates formation of degradative autolysosomes during autophagy (By similarity). (358 aa) |
| | Optn | Optineurin; Plays an important role in the maintenance of the Golgi complex, in membrane trafficking, in exocytosis, through its interaction with myosin VI and Rab8. Links myosin VI to the Golgi complex and plays an important role in Golgi ribbon formation. Plays a role in the activation of innate immune response during viral infection. Mechanistically, recruits TBK1 at the Golgi apparatus, promoting its trans-phosphorylation after RLR or TLR3 stimulation. In turn, activated TBK1 phosphorylates its downstream partner IRF3 to produce IFN-beta. Plays a neuroprotective role in the eye and [...] (584 aa) |
| | Acbd5 | Acyl-CoA-binding domain-containing protein 5; Acyl-CoA binding protein which acts as the peroxisome receptor for pexophagy but is dispensable for aggrephagy and nonselective autophagy. Binds medium- and long-chain acyl-CoA esters (By similarity). (509 aa) |
| | Rab7 | Ras-related protein Rab-7a; Key regulator in endo-lysosomal trafficking. Governs early- to-late endosomal maturation, microtubule minus-end as well as plus-end directed endosomal migration and positioning, and endosome-lysosome transport through different protein-protein interaction cascades. Plays a central role, not only in endosomal traffic, but also in many other cellular and physiological events, such as growth-factor-mediated cell signaling, nutrient-transportor mediated nutrient uptake, neurotrophin transport in the axons of neurons and lipid metabolism. Also involved in regulat [...] (207 aa) |
| | Rubcnl | Protein associated with UVRAG as autophagy enhancer; Regulator of autophagy that promotes autophagosome maturation by facilitating the biogenesis of phosphatidylinositol 3-phosphate (PtdIns(3)P) in late steps of autophagy. Acts by antagonizing RUBCN, thereby stimulating phosphatidylinositol 3-kinase activity of the PI3K/PI3KC3 complex (By similarity). Following anchorage to the autophagosomal SNARE STX17, promotes the recruitment of PI3K/PI3KC3 and HOPS complexes to the autophagosome to regulate the fusion specificity of autophagosomes with late endosomes/lysosomes (By similarity). Bin [...] (675 aa) |
| | Rab24 | Ras-related protein Rab-24; May be involved in autophagy-related processes; Belongs to the small GTPase superfamily. Rab family. (203 aa) |
| | Atg2a | Autophagy-related protein 2 homolog A; Involved in autophagosome assembly, regulating the size of nascent autophagosomes. Also regulates lipid droplets morphology and distribution within the cell; Belongs to the ATG2 family. (1914 aa) |
| | Dap | Death-associated protein 1; Negative regulator of autophagy. Involved in mediating interferon-gamma-induced cell death (By similarity). (102 aa) |
| | Plekhm1 | Pleckstrin homology domain-containing family M member 1; Proposed to act as a multivalent adapter protein that regulates Rab7-dependent and HOPS complex-dependent fusion events in the endolysosomal system and couples autophagic and the endocytic trafficking pathways. Required for late stages of endolysosomal maturation, facilitating both endocytosis-mediated degradation of growth factor receptors and autophagosome clearance. Seems to be involved in the terminal maturation of autophagosomes and to mediate autophagosome-lysosome fusion. Positively regulates lysosome peripheral distributi [...] (1074 aa) |
| | Tbc1d25 | TBC1 domain family member 25; Acts as a GTPase-activating protein specific for RAB33B. Involved in the regulation of autophagosome maturation, the process in which autophagosomes fuse with endosomes and lysosomes. (742 aa) |
| | Tbc1d17 | TBC1 domain family member 17; Probable GTPase-activating protein for Rab8; its transient association with Rab8 is mediated by OPTN. Inhibits Rab8-mediated endocytic trafficking, such as of transferrin receptor (TfR) and reduces Rab8 recruitnment to tubules emanating from the endocytic recycling compartment (ERC). Involved in regulation of autophagy. Mediates inhibition of autophagy caused by the OPTN variant GLC1E LYS- 50; the function requires its catalytic activity, however, the involved Rab is not known (By similarity). (645 aa) |
| | Tigar | Fructose-2,6-bisphosphatase TIGAR; Fructose-bisphosphatase hydrolyzing fructose-2,6-bisphosphate as well as fructose-1,6-bisphosphate (By similarity). Acts as a negative regulator of glycolysis by lowering intracellular levels of fructose-2,6-bisphosphate in a p53/TP53-dependent manner, resulting in the pentose phosphate pathway (PPP) activation and NADPH production. Contributes to the generation of reduced glutathione to cause a decrease in intracellular reactive oxygen species (ROS) content, correlating with its ability to protect cells from oxidative or metabolic stress-induced cell [...] (269 aa) |
| | Ambra1 | Activating molecule in BECN1-regulated autophagy protein 1; Regulates autophagy and development of the nervous system. Involved in autophagy in controlling protein turnover during neuronal development, and in regulating normal cell survival and proliferation. (1300 aa) |
| | Ubqln1 | Ubiquilin-1; Plays an important role in the regulation of different protein degradation mechanisms and pathways including ubiquitin- proteasome system (UPS), autophagy and endoplasmic reticulum-associated protein degradation (ERAD) pathway. Mediates the proteasomal targeting of misfolded or accumulated proteins for degradation by binding (via UBA domain) to their polyubiquitin chains and by interacting (via ubiquitin-like domain) with the subunits of the proteasome. Plays a role in the ERAD pathway via its interaction with ER-localized proteins UBXN4, VCP and HERPUD1 and may form a lin [...] (582 aa) |
| | Irgm1 | Immunity-related GTPase family M protein 1; Putative GTPase which is required for IFNG-mediated clearance of acute protozoan and bacterial infections. Functions in innate immune response probably through regulation of autophagy. May regulate proinflammatory cytokine production and prevent endotoxemia upon infection. Required for macrophage motility and possibly also for adhesion. Belongs to the TRAFAC class dynamin-like GTPase superfamily. IRG family. (409 aa) |
| | Atg9b | Autophagy-related protein 9B; Involved in autophagy and cytoplasm to vacuole transport (Cvt) vesicle formation. Plays a key role in the organization of the preautophagosomal structure/phagophore assembly site (PAS), the nucleating site for formation of the sequestering vesicle. (922 aa) |
| | Lrrk2 | Leucine-rich repeat serine/threonine-protein kinase 2; Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, autophagy, and vesicle trafficking. Is a key regulator of RAB GTPases by regulating the GTP/GDP exchange and interaction partners of RABs through phosphorylation. Phosphorylates RAB3A, RAB3B, RAB3C, RAB3D, RAB8A, RAB8B, RAB10, RAB12, RAB35, and RAB43. Regulates the RAB3IP-catalyzed GDP/GTP exchange for RAB8A through the phosphorylation of 'Thr-72' on RAB8A (By similarity). Inhibits the interacti [...] (2527 aa) |
| | Wdfy3 | WD repeat and FYVE domain-containing protein 3; Required for selective macroautophagy (aggrephagy). Acts as an adapter protein by linking specific proteins destined for degradation to the core autophagic machinery members, such as the ATG5- ATG12-ATG16L E3-like ligase, SQSTM1 and LC3. Involved in the formation and autophagic degradation of cytoplasmic ubiquitin-containing inclusions (p62 bodies, ALIS/aggresome-like induced structures) (By similarity). Important for normal brain development. Essential for the formation of axonal tracts throughout the brain and spinal cord, including the [...] (3508 aa) |
| | Lrsam1 | E3 ubiquitin-protein ligase LRSAM1; E3 ubiquitin-protein ligase that mediates monoubiquitination of TSG101 at multiple sites, leading to inactivate the ability of TSG101 to sort endocytic (EGF receptors) and exocytic (viral proteins) cargos (By similarity). Bacterial recognition protein that defends the cytoplasm from invasive pathogens (By similarity). Localizes to several intracellular bacterial pathogens and generates the bacteria-associated ubiquitin signal leading to autophagy-mediated intracellular bacteria degradation (xenophagy) (By similarity). (727 aa) |
| | Atg16l1 | Autophagy-related protein 16-1; Plays an essential role in autophagy: interacts with ATG12- ATG5 to mediate the conjugation of phosphatidylethanolamine (PE) to LC3 (MAP1LC3A, MAP1LC3B or MAP1LC3C), to produce a membrane-bound activated form of LC3 named LC3-II. Thereby, controls the elongation of the nascent autophagosomal membrane. Regulates mitochondrial antiviral signaling (MAVS)-dependent type I interferon (IFN-I) production (By similarity). Negatively regulates NOD1- and NOD2-driven inflammatory cytokine response. Instead, promotes with NOD2 an autophagy-dependent antibacterial pa [...] (623 aa) |
| | Atg4a | Cysteine protease ATG4A; Cysteine protease required for the cytoplasm to vacuole transport (Cvt) and autophagy. Cleaves the C-terminal amino acid of ATG8 family proteins to reveal a C-terminal glycine. Exposure of the glycine at the C-terminus is essential for ATG8 proteins conjugation to phosphatidylethanolamine (PE) and insertion to membranes, which is necessary for autophagy. Preferred substrate is GABARAPL2 followed by MAP1LC3A and GABARAP. Has also an activity of delipidating enzyme for the PE-conjugated forms (By similarity). (396 aa) |
| | C9orf72 | Guanine nucleotide exchange C9orf72 homolog; Component of the C9orf72-SMCR8 complex, a complex that has guanine nucleotide exchange factor (GEF) activity and regulates autophagy. In the complex, C9orf72 and SMCR8 probably constitute the catalytic subunits that promote the exchange of GDP to GTP, converting inactive GDP-bound RAB8A and RAB39B into their active GTP-bound form, thereby promoting autophagosome maturation (By similarity). The C9orf72-SMCR8 complex also acts as a regulator of autophagy initiation by interacting with the ATG1/ULK1 kinase complex and modulating its protein kin [...] (481 aa) |
| | Stx17 | Syntaxin-17; SNAREs, soluble N-ethylmaleimide-sensitive factor-attachment protein receptors, are essential proteins for fusion of cellular membranes. SNAREs localized on opposing membranes assemble to form a trans-SNARE complex, an extended, parallel four alpha-helical bundle that drives membrane fusion. STX17 is a SNARE of the autophagosome involved in autophagy through the direct control of autophagosome membrane fusion with the lysosome membrane. May also play a role in the early secretory pathway where it may maintain the architecture of the endoplasmic reticulum-Golgi intermediate [...] (301 aa) |
| | 5330417C22Rik | UPF0577 protein KIAA1324; May protect cells from cell death by inducing cytosolic vacuolization and upregulating the autophagy pathway. (1013 aa) |
| | Park7 | Protein/nucleic acid deglycase DJ-1; Protein and nucleotide deglycase that catalyzes the deglycation of the Maillard adducts formed between amino groups of proteins or nucleotides and reactive carbonyl groups of glyoxals. Thus, functions as a protein deglycase that repairs methylglyoxal- and glyoxal-glycated proteins, and releases repaired proteins and lactate or glycolate, respectively. Deglycates cysteine, arginine and lysine residues in proteins, and thus reactivates these proteins by reversing glycation by glyoxals. Acts on early glycation intermediates (hemithioacetals and aminoca [...] (189 aa) |
| | Sqstm1 | Sequestosome-1; Autophagy receptor required for selective macroautophagy (aggrephagy). Functions as a bridge between polyubiquitinated cargo and autophagosomes. Interacts directly with both the cargo to become degraded and an autophagy modifier of the MAP1 LC3 family. Required both for the formation and autophagic degradation of polyubiquitin- containing bodies, called ALIS (aggresome-like induced structures) and links ALIS to the autophagic machinery. Involved in midbody ring degradation (By similarity). May regulate the activation of NFKB1 by TNF-alpha, nerve growth factor (NGF) and [...] (442 aa) |
| | Vps39 | Vam6/Vps39-like protein; May play a role in clustering and fusion of late endosomes and lysosomes (By similarity). Regulator of TGF-beta/activin signaling, inhibiting SMAD3- and activating SMAD2-dependent transcription. Acts by interfering with SMAD3/SMAD4 complex formation, this would lead to inhibition of SMAD3-dependent transcription and relieve SMAD3 inhibition of SMAD2-dependent promoters, thus increasing SMAD2- dependent transcription (By similarity). Belongs to the VAM6/VPS39 family. (886 aa) |
| | Cltc | Clathrin heavy chain 1; Clathrin is the major protein of the polyhedral coat of coated pits and vesicles. Two different adapter protein complexes link the clathrin lattice either to the plasma membrane or to the trans- Golgi network. Acts as component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge. The TACC3/ch- TOG/clathrin complex is required for the maintenance of kinetochore fiber tension. Plays a role in early autophagosome formation. (1675 aa) |
| | Wipi1 | WD repeat domain phosphoinositide-interacting protein 1; Component of the autophagy machinery that controls the major intracellular degradation process by which cytoplasmic materials are packaged into autophagosomes and delivered to lysosomes for degradation. Plays an important role in starvation- and calcium- mediated autophagy, as well as in mitophagy (By similarity). Functions downstream of the ULK1 and PI3-kinases that produce phosphatidylinositol 3-phosphate (PtdIns3P) on membranes of the endoplasmic reticulum once activated. Binds phosphatidylinositol 3-phosphate (PtdIns3P), and [...] (446 aa) |
| | Nrbf2 | Nuclear receptor-binding factor 2; May modulate transcriptional activation by target nuclear receptors. Can act as transcriptional activator (in vitro) (By similarity). Involved in the induction of starvation-induced autophagy. Modulates ATG14-linked lipid kinase activity of PIK3C3 and stabilzes PI3K complex I (PI3KC3-C1) assembly. May play a role in neural progenitor cell survival during differentiation. (287 aa) |
| | Tmem41b | Transmembrane protein 41B; Required for normal motor neuron development. Required for autophagosome formation; Belongs to the TMEM41 family. (291 aa) |
| | Calcoco2 | Calcium-binding and coiled-coil domain-containing protein 2; Xenophagy-specific receptor required for autophagy-mediated intracellular bacteria degradation (By similarity). Acts as an effector protein of galectin-sensed membrane damage that restricts the proliferation of infecting pathogens upon entry into the cytosol by targeting LGALS8-associated bacteria for autophagy (By similarity). Initially orchestrates bacteria targeting to autophagosomes and subsequently ensures pathogen degradation by regulating pathogen- containing autophagosome maturation (By similarity). Bacteria targeting [...] (331 aa) |
| | Rubcn | Run domain Beclin-1-interacting and cysteine-rich domain-containing protein; Inhibits PIK3C3 activity; under basal conditions negatively regulates PI3K complex II (PI3KC3-C2) function in autophagy. Negatively regulates endosome maturation and degradative endocytic trafficking and impairs autophagosome maturation process. Can sequester UVRAG from association with a class C Vps complex (possibly the HOPS complex) and negatively regulates Rab7 activation (By similarity). (956 aa) |
| | Tmem150b | Modulator of macroautophagy TMEM150B; Modulator of macroautophagy that causes accumulation of autophagosomes under basal conditions and enhances autophagic flux (By similarity). Represses cell death and promotes long-term clonogenic survival of cells grown in the absence of glucose in a macroautophagy- independent manner (By similarity). May have some role in extracellular matrix engulfment or growth factor receptor recycling, both of which can modulate cell survival (By similarity). (238 aa) |
| | Tecpr1 | Tectonin beta-propeller repeat-containing protein 1; Tethering factor involved in autophagy. Involved in autophagosome maturation by promoting the autophagosome fusion with lysosomes: acts by associating with both the ATG5-ATG12 conjugate and phosphatidylinositol-3-phosphate (PtdIns(3)P) present at the surface of autophagosomes. Also involved in selective autophagy against bacterial pathogens, by being required for phagophore/preautophagosomal structure biogenesis and maturation (By similarity). (1166 aa) |
| | Hmgb1 | High mobility group protein B1; Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone involved in replication, transcription, chromatin remodeling, V(D)J recombination, DNA repair and genome stability. Proposed to be an universal biosensor for nucleic acids. Promotes host inflammatory response to sterile and infectious signals and is involved in the coordination and integration of innate and adaptive immune responses. In the cytoplasm functio [...] (215 aa) |
| | Hdac10 | Polyamine deacetylase HDAC10; Polyamine deacetylase (PDAC), which acts preferentially on N(8)-acetylspermidine, and also on acetylcadaverine and acetylputrescine. Exhibits attenuated catalytic activity toward N(1),N(8)-diacetylspermidine and very low activity, if any, toward N(1)-acetylspermidine. Histone deacetylase activity has been observed in vitro. Has also been shown to be involved in MSH2 deacetylation. The physiological relevance of protein/histone deacetylase activity is unclear and could be very weak. May play a role in the promotion of late stages of autophagy, possibly auto [...] (666 aa) |
| | Atg13 | Autophagy-related protein 13; Autophagy factor required for autophagosome formation and mitophagy. Target of the TOR kinase signaling pathway that regulates autophagy through the control of the phosphorylation status of ATG13 and ULK1, and the regulation of the ATG13-ULK1-RB1CC1 complex. Through its regulation of ULK1 activity, plays a role in the regulation of the kinase activity of mTORC1 and cell proliferation. (479 aa) |
| | Abl1 | Tyrosine-protein kinase ABL1; Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 (involved in branch formation); ANXA1 (involved in membrane anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH (involved in signaling); or MAPT and PXN (microtubule-bindin [...] (1142 aa) |
| | Lamp2 | Lysosome-associated membrane glycoprotein 2; Plays an important role in chaperone-mediated autophagy, a process that mediates lysosomal degradation of proteins in response to various stresses and as part of the normal turnover of proteins with a long biological half-live. Functions by binding target proteins, such as GAPDH and MLLT11, and targeting them for lysosomal degradation (By similarity). Required for the fusion of autophagosomes with lysosomes during autophagy. Cells that lack LAMP2 express normal levels of VAMP8, but fail to accumulate STX17 on autophagosomes, which is the mos [...] (416 aa) |
| | Sirt2 | NAD-dependent protein deacetylase sirtuin-2; NAD-dependent protein deacetylase, which deacetylates internal lysines on histone and alpha-tubulin as well as many other proteins such as key transcription factors. Participates in the modulation of multiple and diverse biological processes such as cell cycle control, genomic integrity, microtubule dynamics, cell differentiation, metabolic networks, and autophagy. Plays a major role in the control of cell cycle progression and genomic stability. Functions in the antephase checkpoint preventing precocious mitotic entry in response to microtu [...] (389 aa) |
| | Vps41 | Vacuolar protein sorting-associated protein 41 homolog; Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Believed to act in part as a core component of the putative HOPS endosomal tethering complex is proposed to be involved in the Rab5-to-Rab7 endosome conversion probably implicating MON1A/B, and via binding SNAREs and SNARE complexes to mediate tethering and docking events during SNARE-mediated membrane fusion. The HOPS complex is proposed to be recruited to Rab7 on the late endosomal me [...] (853 aa) |
| | Stbd1 | Starch-binding domain-containing protein 1; Acts as a cargo receptor for glycogen. Delivers its cargo to an autophagic pathway called glycophagy, resulting in the transport of glycogen to lysosomes. (338 aa) |
| | Xbp1 | X-box-binding protein 1, cytoplasmic form; Functions as a transcription factor during endoplasmic reticulum stress by regulating the unfolded protein response (UPR). Required for cardiac myogenesis and hepatogenesis during embryonic development and the development of secretory tissues such as exocrine pancreas and salivary gland. Involved in differentiation of B lymphocytes to plasma cells and production of immunoglobulins. Modulates the cellular response to ER stress in a PIK3R-dependent manner. Binds to the cis-acting X box present in the promoter regions of major histocompatibility [...] (267 aa) |
| | Nhlrc1 | E3 ubiquitin-protein ligase NHLRC1; E3 ubiquitin-protein ligase. Together with the phosphatase EPM2A/laforin, appears to be involved in the clearance of toxic polyglucosan and protein aggregates via multiple pathways. In complex with EPM2A/laforin and HSP70, suppresses the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system (UPS). Ubiquitinates the glycogen-targeting protein phosphatase subunits PPP1R3C/PTG and PPP1R3D in a laforin- dependent manner and targets them for proteasome-dependent degradation, thus decreasing glycogen [...] (401 aa) |
| | Foxo1 | Forkhead box protein O1; Transcription factor that is the main target of insulin signaling and regulates metabolic homeostasis in response to oxidative stress. Binds to the insulin response element (IRE) with consensus sequence 5'-TT[G/A]TTTTG-3' and the related Daf-16 family binding element (DBE) with consensus sequence 5'-TT[G/A]TTTAC-3'. Activity suppressed by insulin. Main regulator of redox balance and osteoblast numbers and controls bone mass. Orchestrates the endocrine function of the skeleton in regulating glucose metabolism. Acts synergistically with ATF4 to suppress osteocalc [...] (652 aa) |
| | Smcr8 | Guanine nucleotide exchange protein SMCR8; Component of the C9orf72-SMCR8 complex, a complex that has guanine nucleotide exchange factor (GEF) activity and regulates autophagy. In the complex, C9orf72 and SMCR8 probably constitute the catalytic subunits that promote the exchange of GDP to GTP, converting inactive GDP-bound RAB8A and RAB39B into their active GTP-bound form, thereby promoting autophagosome maturation (By similarity). The C9orf72-SMCR8 complex also acts as a negative regulator of autophagy initiation by interacting with the ATG1/ULK1 kinase complex and inhibiting its prot [...] (935 aa) |
| | Ubqln2 | Ubiquilin-2; Plays an important role in the regulation of different protein degradation mechanisms and pathways including ubiquitin- proteasome system (UPS), autophagy and the endoplasmic reticulum- associated protein degradation (ERAD) pathway. Mediates the proteasomal targeting of misfolded or accumulated proteins for degradation by binding (via UBA domain) to their polyubiquitin chains and by interacting (via ubiquitin-like domain) with the subunits of the proteasome. Plays a role in the ERAD pathway via its interaction with ER-localized proteins FAF2/UBXD8 and HERPUD1 and may form [...] (638 aa) |
| | Wdfy4 | WD repeat- and FYVE domain-containing protein 4; Plays a critical role in the regulation of cDC1-mediated cross-presentation of viral and tumor antigens in dendritic cells. Mechanistically, acts near the plasma membrane and interacts with endosomal membranes to promote endosomal-to-cytosol antigen trafficking. Plays also a role in B-cell survival through regulation of autophagy. (3024 aa) |
| | Vamp8 | Vesicle-associated membrane protein 8; SNAREs, soluble N-ethylmaleimide-sensitive factor-attachment protein receptors, are essential proteins for fusion of cellular membranes. SNAREs localized on opposing membranes assemble to form a trans-SNARE complex, an extended, parallel four alpha-helical bundle that drives membrane fusion. VAMP8 is a SNARE involved in autophagy through the direct control of autophagosome membrane fusion with the lysososome membrane via its interaction with the STX17-SNAP29 binary t- SNARE complex (By similarity). Also required for dense-granule secretion in plat [...] (101 aa) |
| | Ulk3 | Serine/threonine-protein kinase ULK3; Serine/threonine protein kinase that acts as a regulator of Sonic hedgehog (SHH) signaling and autophagy. Acts as a negative regulator of SHH signaling in the absence of SHH ligand: interacts with SUFU, thereby inactivating the protein kinase activity and preventing phosphorylation of GLI proteins (GLI1, GLI2 and/or GLI3). Positively regulates SHH signaling in the presence of SHH: dissociates from SUFU, autophosphorylates and mediates phosphorylation of GLI2, activating it and promoting its nuclear translocation. Phosphorylates in vitro GLI2, as we [...] (472 aa) |
| | Rab33b | Ras-related protein Rab-33B; Protein transport. Acts, in coordination with RAB6A, to regulate intra-Golgi retrograde trafficking (By similarity). It is involved in autophagy, acting as a modulator of autophagosome formation; Belongs to the small GTPase superfamily. Rab family. (229 aa) |
| | Prkaa1 | 5'-AMP-activated protein kinase catalytic subunit alpha-1; Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts a [...] (559 aa) |
| | Dram2 | DNA damage-regulated autophagy modulator protein 2; Plays a role in the initiation of autophagy. In the retina, might be involved in the process of photoreceptor cells renewal and recycling to preserve visual function. Induces apoptotic cell death when coexpressed with DRAM1. (267 aa) |
| | Usp13 | Ubiquitin carboxyl-terminal hydrolase 13; Deubiquitinase that mediates deubiquitination of target proteins such as BECN1, MITF, SKP2 and USP10 and is involved in various processes such as autophagy and endoplasmic reticulum-associated degradation (ERAD). Component of a regulatory loop that controls autophagy and p53/TP53 levels: mediates deubiquitination of BECN1, a key regulator of autophagy, leading to stabilize the PIK3C3/VPS34- containing complexes. Also deubiquitinates USP10, an essential regulator of p53/TP53 stability. In turn, PIK3C3/VPS34-containing complexes regulate USP13 st [...] (858 aa) |
| | Tmem74 | Transmembrane protein 74; Plays an essential role in autophagy. TMEM74-induced autophagy may involve PI3K signal transduction (By similarity). Belongs to the TMEM74 family. (305 aa) |
| | Depp1 | Protein DEPP1; Acts as a critical modulator of FOXO3-induced autophagy via increased cellular ROS. (205 aa) |
| | Atg4d | Cysteine protease ATG4D, mitochondrial; [Cysteine protease ATG4D]: Cysteine protease required for the cytoplasm to vacuole transport (Cvt) and autophagy. Cleaves the C- terminal amino acid of ATG8 family proteins MAP1LC3 and GABARAPL2, to reveal a C-terminal glycine. Exposure of the glycine at the C-terminus is essential for ATG8 proteins conjugation to phosphatidylethanolamine (PE) and insertion to membranes, which is necessary for autophagy. Has also an activity of delipidating enzyme for the PE-conjugated forms. (474 aa) |
| | Rnf185 | E3 ubiquitin-protein ligase RNF185; E3 ubiquitin-protein ligase that regulates selective mitochondrial autophagy by mediating 'Lys-63'-linked polyubiquitination of BNIP1. Acts in the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, which targets misfolded proteins that accumulate in the endoplasmic reticulum (ER) for ubiquitination and subsequent proteasome-mediated degradation. Protects cells from ER stress-induced apoptosis. Responsible for the cotranslational ubiquitination and degradation of CFTR in the ERAD pathway. Preferentially associates with the E2 enzymes UB [...] (228 aa) |
| | Epm2a | Laforin; Plays an important role in preventing glycogen hyperphosphorylation and the formation of insoluble aggregates, via its activity as glycogen phosphatase, and by promoting the ubiquitination of proteins involved in glycogen metabolism via its interaction with the E3 ubiquitin ligase NHLRC1/malin. Dephosphorylates phosphotyrosine and synthetic substrates, such as para-nitrophenylphosphate (pNPP), and has low activity with phosphoserine and phosphothreonine substrates (in vitro). Has also been shown to dephosphorylate MAPT. Shows strong phosphatase activity towards complex carbohy [...] (330 aa) |
| | Clec16a | Protein CLEC16A; Regulator of mitophagy through the upstream regulation of the RNF41/NRDP1-PRKN pathway. Mitophagy is a selective form of autophagy necessary for mitochondrial quality control. The RNF41/NRDP1-PRKN pathway regulates autophagosome-lysosome fusion during late mitophagy. May protect RNF41/NRDP1 from proteosomal degradation, RNF41/NRDP1 which regulates proteosomal degradation of PRKN. Plays a key role in beta cells functions by regulating mitophagy/autophagy and mitochondrial health. (1036 aa) |
| | S100a8 | Protein S100-A8; S100A8 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. It can induce neutrophil chemotaxis and adhesion. Predominantly found as calprotectin (S100A8/A9) which has a wide plethora of intra- and extracellular functions. The intracellular functions include: facilitating leukocyte arachidonic acid trafficking and metabolism, modulation of the tubulin-dependent cytoskeleton during migration of phagocytes and activation of the neutrophilic NADPH- oxidase. Activates NADPH-oxidase by facilitat [...] (89 aa) |
