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SNCA SNCA ATXN1 ATXN1 EMC3 EMC3 APOE APOE NDUFA10 NDUFA10 LRPPRC LRPPRC RAB11A RAB11A VPS26A VPS26A KIAA1109 KIAA1109 TP53 TP53 SOD1 SOD1 VPS26B VPS26B APP APP NCSTN NCSTN RHO RHO NDUFS4 NDUFS4 VPS35 VPS35 LGALS4 LGALS4 HSPB3 HSPB3 PRKACA PRKACA ULK1 ULK1 PSEN1 PSEN1 IDH2 IDH2 PLA2G6 PLA2G6 HSP90AA1 HSP90AA1 APOD APOD NRDC NRDC HTT HTT CACNA2D1 CACNA2D1 MTOR MTOR DENND4B DENND4B PSEN2 PSEN2 QRSL1 QRSL1 PRKACB PRKACB HSP90AB1 HSP90AB1 SURF1 SURF1 OPN4 OPN4 OGDHL OGDHL PINK1 PINK1 PRKACG PRKACG PDHA1 PDHA1 NDUFAF6 NDUFAF6 OGDH OGDH IDH1 IDH1 DENND4A DENND4A MFN2 MFN2 CACNA2D2 CACNA2D2 CACNA2D3 CACNA2D3 FXN FXN EMC1 EMC1 DNM1L DNM1L DENND4C DENND4C VPS29 VPS29 C9orf72 C9orf72 CACNA1A CACNA1A
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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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experimentally determined
Predicted Interactions
gene neighborhood
gene fusions
gene co-occurrence
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textmining
co-expression
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SNCAAlpha-synuclein; Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release. Participates as a monomer in synaptic vesicle exocytosis by enhancing vesicle priming, fusion and dilation of exocytotic fusion pores. Mechanistically, acts by increasing local Ca(2+) release from microdomains which is essential for the enhancement of ATP-induced exocytosis. Acts also as a molecular chaperone in its multimeric membrane-bound state, assisting in the folding of synaptic fusion components called SNAREs [...] (140 aa)
ATXN1Ataxin-1; Chromatin-binding factor that repress Notch signaling in the absence of Notch intracellular domain by acting as a CBF1 corepressor. Binds to the HEY promoter and might assist, along with NCOR2, RBPJ- mediated repression. Binds RNA in vitro. May be involved in RNA metabolism. In concert with CIC and ATXN1L, involved in brain development (By similarity). (815 aa)
EMC3ER membrane protein complex subunit 3. (261 aa)
APOEApolipoprotein E; APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids. APOE is a core component of plasma lipoproteins and is involved in their production, conversion and clearance. Apoliproteins are amphipathic molecules that interact both with lipids of the lipoprotein particle core and the aqueous environment of the plasma. As such, APOE associates with chylomicrons, chylomicron remnants, very low density lipoproteins (VLDL) and intermediate density [...] (317 aa)
NDUFA10NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10, mitochondrial; Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. (355 aa)
LRPPRCLeucine-rich PPR motif-containing protein, mitochondrial; May play a role in RNA metabolism in both nuclei and mitochondria. In the nucleus binds to HNRPA1-associated poly(A) mRNAs and is part of nmRNP complexes at late stages of mRNA maturation which are possibly associated with nuclear mRNA export. May bind mature mRNA in the nucleus outer membrane. In mitochondria binds to poly(A) mRNA. Plays a role in translation or stability of mitochondrially encoded cytochrome c oxidase (COX) subunits. May be involved in transcription regulation. Cooperates with PPARGC1A to regulate certain mito [...] (1394 aa)
RAB11ARas-related protein Rab-11A; 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. The small Rab GTPase RAB11A regulates endocytic recycling. Acts as a major regulator of membrane delivery during cytokinesis. Together with MYO5B and RAB8A participates in epithelial c [...] (216 aa)
VPS26AVacuolar protein sorting-associated protein 26A; Acts as component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. The recruitment of the CSC to the endosomal membrane involves RAB7A and SNX3. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans- Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for car [...] (327 aa)
KIAA1109Transmembrane protein KIAA1109; KIAA1109. (5005 aa)
TP53Cellular tumor antigen p53; Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. Its pro-apoptotic activity is activated via its intera [...] (393 aa)
SOD1Superoxide dismutase [Cu-Zn]; Destroys radicals which are normally produced within the cells and which are toxic to biological systems; Belongs to the Cu-Zn superoxide dismutase family. (154 aa)
VPS26BVacuolar protein sorting-associated protein 26B; Acts as component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. The recruitment of the CSC to the endosomal membrane involves RAB7A and SNX3. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans- Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for car [...] (336 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)
NCSTNNicastrin; Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid- beta precursor protein). The gamma-secretase complex plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels. (709 aa)
RHORhodopsin; Photoreceptor required for image-forming vision at low light intensity. Required for photoreceptor cell viability after birth. Light- induced isomerization of the chromophore 11-cis-retinal to all-trans- retinal triggers a conformational change that activates signaling via G-proteins. Subsequent receptor phosphorylation mediates displacement of the bound G-protein alpha subunit by the arrestin SAG and terminates signaling. (348 aa)
NDUFS4NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial; Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. (175 aa)
VPS35Vacuolar protein sorting-associated protein 35; Acts as component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. The recruitment of the CSC to the endosomal membrane involves RAB7A and SNX3. The CSC seems to associate with the cytoplasmic domain of cargo proteins predominantly via VPS35; however, these interactions seem to be of low affinity and retromer SNX proteins may [...] (796 aa)
LGALS4Galectin-4; Galectin that binds lactose and a related range of sugars. May be involved in the assembly of adherens junctions. (323 aa)
HSPB3Heat shock protein beta-3; Inhibitor of actin polymerization. (150 aa)
PRKACAcAMP-dependent protein kinase catalytic subunit alpha; Phosphorylates a large number of substrates in the cytoplasm and the nucleus. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis. Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA and VASP. RORA is activated by phosphorylation. Required for glucose- mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts. Involved in the [...] (351 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)
PSEN1Presenilin-1 CTF subunit; Catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid- beta precursor protein). Requires the presence of the other members of the gamma-secretase complex for protease activity. Plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels. Stimulates cell-cell adhesion via its interaction with CDH1; this stabili [...] (467 aa)
IDH2Isocitrate dehydrogenase [NADP], mitochondrial; Plays a role in intermediary metabolism and energy production. It may tightly associate or interact with the pyruvate dehydrogenase complex; Belongs to the isocitrate and isopropylmalate dehydrogenases family. (452 aa)
PLA2G685/88 kDa calcium-independent phospholipase A2; Catalyzes the release of fatty acids from phospholipids. It has been implicated in normal phospholipid remodeling, nitric oxide- induced or vasopressin-induced arachidonic acid release and in leukotriene and prostaglandin production. May participate in fas mediated apoptosis and in regulating transmembrane ion flux in glucose- stimulated B-cells. Has a role in cardiolipin (CL) deacylation. Required for both speed and directionality of monocyte MCP1/CCL2- induced chemotaxis through regulation of F-actin polymerization at the pseudopods. (806 aa)
HSP90AA1Heat shock protein HSP 90-alpha; Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity which is essential for its chaperone activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function. Engages with a ra [...] (854 aa)
APODApolipoprotein D; APOD occurs in the macromolecular complex with lecithin- cholesterol acyltransferase. It is probably involved in the transport and binding of bilin. Appears to be able to transport a variety of ligands in a number of different contexts. (189 aa)
NRDCNardilysin; Cleaves peptide substrates on the N-terminus of arginine residues in dibasic pairs; Belongs to the peptidase M16 family. (1219 aa)
HTTHuntingtin, myristoylated N-terminal fragment; [Huntingtin]: May play a role in microtubule-mediated transport or vesicle function. (3142 aa)
CACNA2D1Voltage-dependent calcium channel subunit alpha-2/delta-1; The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Plays an important role in excitation- contraction coupling (By similarity). (1091 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)
DENND4BDENN domain-containing protein 4B; Guanine nucleotide exchange factor (GEF) which may activate RAB10. Promotes the exchange of GDP to GTP, converting inactive GDP- bound Rab proteins into their active GTP-bound form. (1496 aa)
PSEN2Presenilin-2 CTF subunit; Probable catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid- beta precursor protein). Requires the other members of the gamma- secretase complex to have a protease activity. May play a role in intracellular signaling and gene expression or in linking chromatin to the nuclear membrane. May function in the cytoplasmic partitioning of proteins. The holoprotein functions as a calcium-leak channel that allows the passive movement o [...] (448 aa)
QRSL1Glutamyl-tRNA(Gln) amidotransferase subunit A, mitochondrial; Allows the formation of correctly charged Gln-tRNA(Gln) through the transamidation of misacylated Glu-tRNA(Gln) in the mitochondria. The reaction takes place in the presence of glutamine and ATP through an activated gamma-phospho-Glu-tRNA(Gln). (528 aa)
PRKACBcAMP-dependent protein kinase catalytic subunit beta; Mediates cAMP-dependent signaling triggered by receptor binding to GPCRs. PKA activation regulates diverse cellular processes such as cell proliferation, the cell cycle, differentiation and regulation of microtubule dynamics, chromatin condensation and decondensation, nuclear envelope disassembly and reassembly, as well as regulation of intracellular transport mechanisms and ion flux. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subu [...] (398 aa)
HSP90AB1Heat shock protein HSP 90-beta; Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co- chaperones that modulate its substrate recognition, ATPase cycle and chaperone function. Engages with a range of client protein classes via its interact [...] (724 aa)
SURF1Surfeit locus protein 1; Component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, that regulates cytochrome c oxidase assembly. (300 aa)
OPN4Melanopsin; Photoreceptor required for regulation of circadian rhythm. Contributes to pupillar reflex and other non-image forming responses to light. May be able to isomerize covalently bound all-trans retinal back to 11-cis retinal (By similarity); Belongs to the G-protein coupled receptor 1 family. Opsin subfamily. (489 aa)
OGDHL2-oxoglutarate dehydrogenase-like, mitochondrial; Oxoglutarate dehydrogenase L; Belongs to the alpha-ketoglutarate dehydrogenase family. (1010 aa)
PINK1Serine/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. 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 ubiquinone reduct [...] (581 aa)
PRKACGcAMP-dependent protein kinase catalytic subunit gamma; Phosphorylates a large number of substrates in the cytoplasm and the nucleus. (351 aa)
PDHA1Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial; The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle. (428 aa)
NDUFAF6NADH dehydrogenase (ubiquinone) complex I, assembly factor 6; Involved in the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I) at early stages. May play a role in the biogenesis of MT-ND1. (333 aa)
OGDH2-oxoglutarate dehydrogenase, mitochondrial; 2-oxoglutarate dehydrogenase (E1) component of the 2- oxoglutarate dehydrogenase complex, which mediates the decarboxylation of alpha-ketoglutarate. The 2-oxoglutarate dehydrogenase complex catalyzes the overall conversion of 2- oxoglutarate to succinyl-CoA and CO(2). The 2- oxoglutarate dehydrogenase complex is mainly active in the mitochondrion. A fraction of the 2-oxoglutarate dehydrogenase complex also localizes in the nucleus and is required for lysine succinylation of histones: associates with KAT2A on chromatin and provides succinyl-C [...] (1034 aa)
IDH1Isocitrate dehydrogenase 1. (414 aa)
DENND4AC-myc promoter-binding protein; Probable guanine nucleotide exchange factor (GEF) which may activate RAB10. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. According to it may bind to ISRE-like element (interferon-stimulated response element) of MYC P2 promoter. (1906 aa)
MFN2Mitofusin-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 (Probable). Plays a central role in mitochondrial metabolism and may be associated with obesity and/or apoptosis processes (By similarity). Plays an important role in the [...] (757 aa)
CACNA2D2Voltage-dependent calcium channel subunit alpha-2/delta-2; The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q- type calcium channel (CACNA1A), N-type (CACNA1B), L-type (CACNA1C OR CACNA1D) and possibly T-type (CACNA1G). Overexpression induces apoptosis. (1150 aa)
CACNA2D3Voltage-dependent calcium channel subunit alpha-2/delta-3; The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q- type calcium channel (CACNA1A), N-type (CACNA1B), L-type (CACNA1C OR CACNA1D) but not T-type (CACNA1G) (By similarity). (1091 aa)
FXNFrataxin intermediate form; Promotes the biosynthesis of heme and assembly and repair of iron-sulfur clusters by delivering Fe(2+) to proteins involved in these pathways. May play a role in the protection against iron-catalyzed oxidative stress through its ability to catalyze the oxidation of Fe(2+) to Fe(3+); the oligomeric form but not the monomeric form has in vitro ferroxidase activity. May be able to store large amounts of iron in the form of a ferrihydrite mineral by oligomerization; however, the physiological relevance is unsure as reports are conflicting and the function has on [...] (210 aa)
EMC1ER membrane protein complex subunit 1; Belongs to the EMC1 family. (993 aa)
DNM1LDynamin-1-like protein; Functions in mitochondrial and peroxisomal division. Mediates membrane fission through oligomerization into membrane-associated tubular structures that wrap around the scission site to constrict and sever the mitochondrial membrane through a GTP hydrolysis-dependent mechanism. The specific recruitment at scission sites is mediated by membrane receptors like MFF, MIEF1 and MIEF2 for mitochondrial membranes. While the recruitment by the membrane receptors is GTP-dependent, the following hydrolysis of GTP induces the dissociation from the receptors and allows DNM1L [...] (749 aa)
DENND4CDENN domain-containing protein 4C; Guanine nucleotide exchange factor (GEF) activating RAB10. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB10 into its active GTP-bound form. Thereby, stimulates SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery to the plasma membrane in response to insulin. (1958 aa)
VPS29Vacuolar protein sorting-associated protein 29; Acts as component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. The recruitment of the CSC to the endosomal membrane involves RAB7A and SNX3. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans- Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for carg [...] (214 aa)
C9orf72Guanine nucleotide exchange C9orf72; 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. The C9orf72-SMCR8 complex also acts as a regulator of autophagy initiation by interacting with the ATG1/ULK1 kinase complex and modulating its protein kinase activity. Positivel [...] (481 aa)
CACNA1AVoltage-dependent P/Q-type calcium channel subunit alpha-1A; Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1A gives rise to P and/or Q- type calcium currents. P/Q-type calcium channels belong to the 'high- voltage activated' (HVA) group and are specifically blocked by the spider omega-agatoxin-IVA (AC P54282) (By similarity). [...] (2512 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, human, man
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