STRINGSTRING
VPS11 VPS11 CHMP2A CHMP2A RBM8A RBM8A ATG12 ATG12 RXRA RXRA NCF2 NCF2 BRCA1 BRCA1 GABARAPL1 GABARAPL1 TGFBRAP1 TGFBRAP1 ATG16L1 ATG16L1 SQSTM1 SQSTM1 RABGEF1 RABGEF1 VPS16 VPS16 ATG5 ATG5 CYBB CYBB NCF4 NCF4 GABARAPL2 GABARAPL2 YIPF1 YIPF1 VPS18 VPS18 ATG14 ATG14 CYBA CYBA PIK3C3 PIK3C3 WIPI1 WIPI1 VPS33A VPS33A RAB5A RAB5A NRBF2 NRBF2 APP APP NCF1 NCF1 RUBCN RUBCN MON1A MON1A CCZ1B CCZ1B ULK1 ULK1 CCZ1 CCZ1 LIN9 LIN9 VPS39 VPS39 UVRAG UVRAG PIK3R4 PIK3R4 MTOR MTOR BECN1 BECN1 RABIF RABIF VPS8 VPS8
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splice isoforms or post-translational modifications are collapsed, i.e. each node represents all the proteins produced by a single, protein-coding gene locus.
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query proteins and first shell of interactors
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second shell of interactors
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proteins of unknown 3D structure
filled nodes:
a 3D structure is known or predicted
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Known Interactions
from curated databases
experimentally determined
Predicted Interactions
gene neighborhood
gene fusions
gene co-occurrence
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textmining
co-expression
protein homology
Your Input:
VPS11Vacuolar 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)
CHMP2ACharged multivesicular body protein 2a; Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential functio [...] (222 aa)
RBM8ARNA-binding protein 8A; Required for pre-mRNA splicing as component of the spliceosome. Core component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junctions on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. The EJC marks the position of the exon-exon junction in the mature mRNA for the gene expression machinery and the core components remain bound to spliced [...] (174 aa)
ATG12Ubiquitin-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. (140 aa)
RXRARetinoic acid receptor RXR-alpha; Receptor for retinoic acid that acts as a transcription factor. Forms homo- or heterodimers with retinoic acid receptors (RARs) and binds to target response elements in response to their ligands, all-trans or 9-cis retinoic acid, to regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 to regulate transcription. The high affinity ligand for retinoid X receptors (RXRs) is 9-cis retinoic acid. In the absence of ligand, th [...] (462 aa)
NCF2Neutrophil cytosol factor 2; NCF2, NCF1, and a membrane bound cytochrome b558 are required for activation of the latent NADPH oxidase (necessary for superoxide production). (526 aa)
BRCA1Breast cancer type 1 susceptibility protein; E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The E3 ubiquitin-protein ligase activity is required for its tumor suppressor function. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic [...] (1884 aa)
GABARAPL1Gamma-aminobutyric acid receptor-associated protein-like 1; GABA type A receptor associated protein like 1. (146 aa)
TGFBRAP1Transforming growth factor-beta receptor-associated protein 1; Plays a role in the TGF-beta/activin signaling pathway. It associates with inactive heteromeric TGF-beta and activin receptor complexes, mainly through the type II receptor, and is released upon activation of signaling. May recruit SMAD4 to the vicinity of the receptor complex and facilitate its interaction with receptor-regulated Smads, such as SMAD2. (860 aa)
ATG16L1Autophagy-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. Negatively regulates NOD1- and NOD2-driven inflammatory cytokine response. Instead, promotes with NOD2 an autophagy-dependent antibacterial pathway. Plays a r [...] (624 aa)
SQSTM1Sequestosome-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. Along with WDFY3, involved in the formation and autophagic degradation of cytoplasmic ubiquitin-containing inclusions (p62 bodies, ALIS/aggresome-like induced structures). Along with WDFY3, required to recruit ubiquitinated proteins to PML bodies in the nucleus. May regulate the activation of NFKB1 by TNF-alpha, nerve gro [...] (440 aa)
RABGEF1Rab5 GDP/GTP exchange factor; Rab effector protein acting as linker between gamma-adaptin, RAB4A or RAB5A. Involved in endocytic membrane fusion and membrane trafficking of recycling endosomes. Stimulates nucleotide exchange on RAB5A. Can act as a ubiquitin ligase (By similarity). (505 aa)
VPS16Vacuolar 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)
ATG5Autophagy 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)
CYBBCytochrome b-245 heavy chain; Critical component of the membrane-bound oxidase of phagocytes that generates superoxide. It is the terminal component of a respiratory chain that transfers single electrons from cytoplasmic NADPH across the plasma membrane to molecular oxygen on the exterior. Also functions as a voltage-gated proton channel that mediates the H(+) currents of resting phagocytes. It participates in the regulation of cellular pH and is blocked by zinc. (570 aa)
NCF4Neutrophil cytosol factor 4; Component of the NADPH-oxidase, a multicomponent enzyme system responsible for the oxidative burst in which electrons are transported from NADPH to molecular oxygen, generating reactive oxidant intermediates. It may be important for the assembly and/or activation of the NADPH-oxidase complex. (348 aa)
GABARAPL2Gamma-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)
YIPF1Protein YIPF1; Yip1 domain family member 1; Belongs to the YIP1 family. (306 aa)
VPS18Vacuolar 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)
ATG14Beclin 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. Plays a role in autophagosome formation and MAP1LC3/LC3 conjugation to phosphatidylethanolamine. Promotes BECN1 translocation from the trans-Golgi network to autophagosomes. Enhances PIK3C3 activity in a BECN1-dependent manner. Essential for the autophagy-dependent phosphorylation of BECN1. Stimulates the phosphorylation of BECN1, but suppresses the phosphorylation PIK3C3 by AMPK. Binds to STX17-SNAP29 [...] (492 aa)
CYBACytochrome b-245 light chain; Critical component of the membrane-bound oxidase of phagocytes that generates superoxide. Associates with NOX3 to form a functional NADPH oxidase constitutively generating superoxide. Belongs to the p22phox family. (195 aa)
PIK3C3Phosphatidylinositol 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)
WIPI1WD 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. 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 maybe other phos [...] (446 aa)
VPS33AVacuolar 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 [...] (596 aa)
RAB5ARas-related protein Rab-5A; Small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate cellular responses such as of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Active GTP-bound form is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. RAB5A is required for the fusion of plasma membranes and early endosomes. Contributes to the regulati [...] (215 aa)
NRBF2Nuclear receptor-binding factor 2; May modulate transcriptional activation by target nuclear receptors. Can act as transcriptional activator (in vitro). (287 aa)
APPGamma-secretase C-terminal fragment 50; Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on neighboring cells promotes synaptogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis- inducing pathways such as those mediated by G(O) and JIP. Inhibits [...] (770 aa)
NCF1Neutrophil cytosol factor 1; NCF2, NCF1, and a membrane bound cytochrome b558 are required for activation of the latent NADPH oxidase (necessary for superoxide production). (390 aa)
RUBCNRun 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. (972 aa)
MON1AVacuolar fusion protein MON1 homolog A; Plays an important role in membrane trafficking through the secretory apparatus. Not involved in endocytic trafficking to lysosomes (By similarity). Acts in concert with CCZ1, as a guanine exchange factor (GEF) for RAB7, promotes the exchange of GDP to GTP, converting it from an inactive GDP-bound form into an active GTP-bound form. (652 aa)
CCZ1BCCZ1 homolog B, vacuolar protein trafficking and biogenesis associated. (482 aa)
ULK1Serine/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 [...] (1050 aa)
CCZ1CCZ1 homolog, vacuolar protein trafficking and biogenesis associated. (482 aa)
LIN9Protein lin-9 homolog; Acts as a tumor suppressor. Inhibits DNA synthesis. Its ability to inhibit oncogenic transformation is mediated through its association with RB1. Plays a role in the expression of genes required for the G1/S transition; Belongs to the lin-9 family. (558 aa)
VPS39Vam6/Vps39-like protein; 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. Does not affect TGF-beta-induced SMAD2 or SMAD3 phosphorylation, nor SMAD2/SMAD4 complex formation. (886 aa)
UVRAGUV radiation resistance-associated gene protein; Versatile protein that is involved in regulation of different cellular pathways implicated in membrane trafficking. Involved in regulation of the COPI-dependent retrograde transport from Golgi and the endoplasmic reticulum by associating with the NRZ complex; the function is dependent on its binding to phosphatidylinositol 3- phosphate (PtdIns(3)P). During autophagy acts as regulatory subunit of the alternative PI3K complex II (PI3KC3- C2) that mediates formation of phosphatidylinositol 3-phosphate and is believed to be involved in matur [...] (699 aa)
PIK3R4Phosphoinositide 3-kinase regulatory subunit 4; Regulatory 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 cytokinesis, probably in the context of PI3KC3-C2 ; Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. (1358 aa)
MTORSerine/threonine-protein kinase mTOR; Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals. MTOR directly or indirectly regulates the phosphorylation of at least 800 proteins. Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2). Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. This includes phosphorylation of EIF [...] (2549 aa)
BECN1Beclin-1-C 35 kDa; Plays a central role in autophagy. Acts as core 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. Essential for the formation of PI3KC3-C2 but not PI3KC3-C1 PI3K complex fo [...] (450 aa)
RABIFGuanine nucleotide exchange factor MSS4; Guanine-nucleotide-releasing protein that acts on members of the SEC4/YPT1/RAB subfamily. Stimulates GDP release from both YPT1 and RAB3A, but is less active on these proteins than on the SEC4 protein. Might play a general role in vesicular transport; Belongs to the DSS4/MSS4 family. (123 aa)
VPS8Vacuolar protein sorting-associated protein 8 homolog; Plays a role in vesicle-mediated protein trafficking of the endocytic membrane transport pathway. Believed to act as a component of the putative CORVET endosomal tethering complexes which 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 CORVET complex is proposed to function as a Rab5 effector to mediate early endosome fusion probably in specific endosome subpo [...] (1428 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, human, man
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