E3 ubiquitin-protein ligase parkin

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functionⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityⁱ

• [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-N(6)-ubiquitinyl-L-lysine.1 Publication

  <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More...</a></p> Manual assertion based on experiment inⁱ

  • Ref.7

    "Structure of parkin reveals mechanisms for ubiquitin ligase activation."
    Trempe J.F., Sauve V., Grenier K., Seirafi M., Tang M.Y., Menade M., Al-Abdul-Wahid S., Krett J., Wong K., Kozlov G., Nagar B., Fon E.A., Gehring K.
    Science 340:1451-1455(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: X-RAY CRYSTALLOGRAPHY (6.5 ANGSTROMS), X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 141-465, RING-TYPE ZINC-FINGERS, CATALYTIC ACTIVITY, ACTIVE SITE, AUTOUBIQUITINATION, ACTIVITY REGULATION, MUTAGENESIS OF TRP-403.

  EC:2.3.2.31

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationⁱ

Sites

Regions

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functionⁱ

• actin binding Source: RGD
• beta-catenin binding Source: RGD
• chaperone binding Source: RGD
• cullin family protein binding Source: ParkinsonsUK-UCL
• enzyme binding Source: RGD
• F-box domain binding Source: ParkinsonsUK-UCL
• G protein-coupled receptor binding Source: ParkinsonsUK-UCL
• heat shock protein binding Source: RGD
• histone deacetylase binding Source: RGD
• Hsp70 protein binding Source: RGD
• identical protein binding Source: ParkinsonsUK-UCL
• kinase binding Source: RGD
• metal ion binding Source: UniProtKB-KW
• PDZ domain binding Source: ParkinsonsUK-UCL
• phospholipase binding Source: RGD
• protein-containing complex binding Source: RGD <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ
  • "Parkin binds to alpha/beta tubulin and increases their ubiquitination and degradation."
    Ren Y., Zhao J., Feng J.
    J Neurosci 23:3316-3324(2003) [PubMed] [Europe PMC] [Abstract]
• protein kinase binding Source: RGD <p>Inferred from Physical Interaction</p> <p>Covers physical interactions between the gene product of interest and another molecule (or ion, or complex).</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ipi">GO evidence code guide</a></p> Inferred from physical interactionⁱ
  • "Hydrogen Sulphide modulating mitochondrial morphology to promote mitophagy in endothelial cells under high-glucose and high-palmitate."
    Liu N., Wu J., Zhang L., Gao Z., Sun Y., Yu M., Zhao Y., Dong S., Lu F., Zhang W.
    J Cell Mol Med 21:3190-3203(2017) [PubMed] [Europe PMC] [Abstract]
• transcription corepressor activity Source: RGD
• tubulin binding Source: RGD
• ubiquitin binding Source: UniProtKB
• ubiquitin conjugating enzyme binding Source: ParkinsonsUK-UCL
• ubiquitin protein ligase activity Source: UniProtKB
• ubiquitin protein ligase binding Source: RGD
• ubiquitin-protein transferase activity Source: UniProtKB
• ubiquitin-specific protease binding Source: RGD

GO - Biological processⁱ

• adult locomotory behavior Source: ParkinsonsUK-UCL
• aggresome assembly Source: ParkinsonsUK-UCL
• autophagy of mitochondrion Source: ParkinsonsUK-UCLInferred from direct assayⁱ
  • "Disease-causing mutations in parkin impair mitochondrial ubiquitination, aggregation, and HDAC6-dependent mitophagy."
    Lee J.Y., Nagano Y., Taylor J.P., Lim K.L., Yao T.P.
    J Cell Biol 189:671-679(2010) [PubMed] [Europe PMC] [Abstract]
• brain development Source: RGD <p>Inferred from Expression Pattern</p> <p>Covers cases where the annotation is inferred from the timing or location of expression of a gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#iep">GO evidence code guide</a></p> Inferred from expression patternⁱ
  • "Developmental changes in the expression of parkin and UbcR7, a parkin-interacting and ubiquitin-conjugating enzyme, in rat brain."
    Wang M., Suzuki T., Kitada T., Asakawa S., Minoshima S., Shimizu N., Tanaka K., Mizuno Y., Hattori N.
    J Neurochem 77:1561-1568(2001) [PubMed] [Europe PMC] [Abstract]
• cellular protein catabolic process Source: RGD
• cellular response to hydrogen sulfide Source: RGDInferred from direct assayⁱ
  • "Hydrogen Sulphide modulating mitochondrial morphology to promote mitophagy in endothelial cells under high-glucose and high-palmitate."
    Liu N., Wu J., Zhang L., Gao Z., Sun Y., Yu M., Zhao Y., Dong S., Lu F., Zhang W.
    J Cell Mol Med 21:3190-3203(2017) [PubMed] [Europe PMC] [Abstract]
• cellular response to L-glutamate Source: RGDInferred from direct assayⁱ
  • "Glutamate excitotoxicity in neurons triggers mitochondrial and endoplasmic reticulum accumulation of Parkin, and, in the presence of N-acetyl cysteine, mitophagy."
    Van Laar V.S., Roy N., Liu A., Rajprohat S., Arnold B., Dukes A.A., Holbein C.D., Berman S.B.
    Neurobiol Dis 74:180-193(2015) [PubMed] [Europe PMC] [Abstract]
• cellular response to L-glutamine Source: RGDInferred from expression patternⁱ
  • "Parkin overexpression protects retinal ganglion cells against glutamate excitotoxicity."
    Hu X., Dai Y., Sun X.
    Mol Vis 23:447-456(2017) [PubMed] [Europe PMC] [Abstract]
• cellular response to manganese ion Source: RGDInferred from expression patternⁱ
  • "Expression changes of dopaminergic system-related genes in PC12 cells induced by manganese, silver, or copper nanoparticles."
    Wang J., Rahman M.F., Duhart H.M., Newport G.D., Patterson T.A., Murdock R.C., Hussain S.M., Schlager J.J., Ali S.F.
    Neurotoxicology 30:926-933(2009) [PubMed] [Europe PMC] [Abstract]
• cellular response to toxic substance Source: ParkinsonsUK-UCL
• dopamine metabolic process Source: RGD
• dopamine uptake involved in synaptic transmission Source: RGD
• free ubiquitin chain polymerization Source: RGD
• learning Source: RGD
• locomotory behavior Source: RGD
• mitochondrial fission Source: ParkinsonsUK-UCL
• mitochondrial fragmentation involved in apoptotic process Source: RGD <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ
  • "Parkin overexpression protects retinal ganglion cells against glutamate excitotoxicity."
    Hu X., Dai Y., Sun X.
    Mol Vis 23:447-456(2017) [PubMed] [Europe PMC] [Abstract]
• mitochondrion localization Source: ParkinsonsUK-UCLInferred from direct assayⁱ
  • "Disease-causing mutations in parkin impair mitochondrial ubiquitination, aggregation, and HDAC6-dependent mitophagy."
    Lee J.Y., Nagano Y., Taylor J.P., Lim K.L., Yao T.P.
    J Cell Biol 189:671-679(2010) [PubMed] [Europe PMC] [Abstract]
• mitochondrion organization Source: ParkinsonsUK-UCL
• mitochondrion to lysosome transport Source: RGD
• mitophagy Source: RGD
• modulation of chemical synaptic transmission Source: RGD
• negative regulation by host of viral genome replication Source: RGD
• negative regulation of actin filament bundle assembly Source: RGD
• negative regulation of canonical Wnt signaling pathway Source: RGD
• negative regulation of cell death Source: RGD
• negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway Source: ParkinsonsUK-UCL
• negative regulation of endoplasmic reticulum stress-induced neuron intrinsic apoptotic signaling pathway Source: RGD
• negative regulation of excitatory postsynaptic potential Source: RGDInferred from mutant phenotypeⁱ
  • "Pruning and loss of excitatory synapses by the parkin ubiquitin ligase."
    Helton T.D., Otsuka T., Lee M.C., Mu Y., Ehlers M.D.
    Proc Natl Acad Sci U S A 105:19492-19497(2008) [PubMed] [Europe PMC] [Abstract]
• negative regulation of exosomal secretion Source: RGD
• negative regulation of gene expression Source: RGD
• negative regulation of glucokinase activity Source: ParkinsonsUK-UCL
• negative regulation of insulin secretion Source: ParkinsonsUK-UCL
• negative regulation of intralumenal vesicle formation Source: RGD
• negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator Source: RGD
• negative regulation of JNK cascade Source: ParkinsonsUK-UCL
• negative regulation of mitochondrial fission Source: RGDInferred from mutant phenotypeⁱ
  • "The PARK2 gene is involved in the maintenance of pancreatic beta-cell functions related to insulin production and secretion."
    Jin H.S., Kim J., Lee S.J., Kim K., Go M.J., Lee J.Y., Lee H.J., Song J., Jeon B.T., Roh G.S., Kim S.J., Kim B.Y., Hong K.W., Yoo Y.H., Oh B., Kang Y., Jeong S.Y.
    Mol Cell Endocrinol 382:178-189(2014) [PubMed] [Europe PMC] [Abstract]
• negative regulation of mitochondrial fusion Source: ParkinsonsUK-UCL
• negative regulation of neuron apoptotic process Source: RGDInferred from mutant phenotypeⁱ
  • "Parkin overexpression protects retinal ganglion cells against glutamate excitotoxicity."
    Hu X., Dai Y., Sun X.
    Mol Vis 23:447-456(2017) [PubMed] [Europe PMC] [Abstract]
• negative regulation of neuron death Source: MGI <p>Inferred from Genetic Interaction</p> <p>Used to describe "traditional" genetic interactions such as suppressors and synthetic lethals as well as other techniques such as functional complementation, rescue experiments, or inferences about a gene drawn from the phenotype of a mutation in a different gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#igi">GO evidence code guide</a></p> Inferred from genetic interactionⁱ
  • "Phosphorylation by the c-Abl protein tyrosine kinase inhibits parkin's ubiquitination and protective function."
    Ko H.S., Lee Y., Shin J.H., Karuppagounder S.S., Gadad B.S., Koleske A.J., Pletnikova O., Troncoso J.C., Dawson V.L., Dawson T.M.
    Proc Natl Acad Sci U S A 107:16691-16696(2010) [PubMed] [Europe PMC] [Abstract]
• negative regulation of oxidative stress-induced neuron death Source: ParkinsonsUK-UCLInferred from genetic interactionⁱ
  • "ATF4 protects against neuronal death in cellular Parkinson's disease models by maintaining levels of parkin."
    Sun X., Liu J., Crary J.F., Malagelada C., Sulzer D., Greene L.A., Levy O.A.
    J Neurosci 33:2398-2407(2013) [PubMed] [Europe PMC] [Abstract]
• negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway Source: ParkinsonsUK-UCL
• negative regulation of primary amine oxidase activity Source: RGD
• negative regulation of protein phosphorylation Source: ParkinsonsUK-UCL
• negative regulation of reactive oxygen species biosynthetic process Source: RGDInferred from mutant phenotypeⁱ
  • "The PARK2 gene is involved in the maintenance of pancreatic beta-cell functions related to insulin production and secretion."
    Jin H.S., Kim J., Lee S.J., Kim K., Go M.J., Lee J.Y., Lee H.J., Song J., Jeon B.T., Roh G.S., Kim S.J., Kim B.Y., Hong K.W., Yoo Y.H., Oh B., Kang Y., Jeong S.Y.
    Mol Cell Endocrinol 382:178-189(2014) [PubMed] [Europe PMC] [Abstract]
• negative regulation of reactive oxygen species metabolic process Source: ParkinsonsUK-UCL
• negative regulation of release of cytochrome c from mitochondria Source: ParkinsonsUK-UCL
• negative regulation of spontaneous neurotransmitter secretion Source: RGD
• negative regulation of synaptic transmission, glutamatergic Source: RGDInferred from mutant phenotypeⁱ
  • "Pruning and loss of excitatory synapses by the parkin ubiquitin ligase."
    Helton T.D., Otsuka T., Lee M.C., Mu Y., Ehlers M.D.
    Proc Natl Acad Sci U S A 105:19492-19497(2008) [PubMed] [Europe PMC] [Abstract]
• negative regulation of transcription by RNA polymerase II Source: RGD
• neuron cellular homeostasis Source: ParkinsonsUK-UCL
• norepinephrine metabolic process Source: RGD
• parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization Source: RGD
• positive regulation of apoptotic process Source: RGDInferred from mutant phenotypeⁱ
  • "Sorafenib targets the mitochondrial electron transport chain complexes and ATP synthase to activate the PINK1-Parkin pathway and modulate cellular drug response."
    Zhang C., Liu Z., Bunker E., Ramirez A., Lee S., Peng Y., Tan A.C., Eckhardt S.G., Chapnick D.A., Liu X.
    J Biol Chem 292:15105-15120(2017) [PubMed] [Europe PMC] [Abstract]
• positive regulation of ATP biosynthetic process Source: RGDInferred from mutant phenotypeⁱ
  • "The PARK2 gene is involved in the maintenance of pancreatic beta-cell functions related to insulin production and secretion."
    Jin H.S., Kim J., Lee S.J., Kim K., Go M.J., Lee J.Y., Lee H.J., Song J., Jeon B.T., Roh G.S., Kim S.J., Kim B.Y., Hong K.W., Yoo Y.H., Oh B., Kang Y., Jeong S.Y.
    Mol Cell Endocrinol 382:178-189(2014) [PubMed] [Europe PMC] [Abstract]
• positive regulation of autophagy of mitochondrion Source: RGD
• positive regulation of dendrite extension Source: RGD
• positive regulation of DNA binding Source: ParkinsonsUK-UCL
• positive regulation of gene expression Source: RGD
• positive regulation of I-kappaB kinase/NF-kappaB signaling Source: ParkinsonsUK-UCL
• positive regulation of insulin secretion involved in cellular response to glucose stimulus Source: RGDInferred from mutant phenotypeⁱ
  • "The PARK2 gene is involved in the maintenance of pancreatic beta-cell functions related to insulin production and secretion."
    Jin H.S., Kim J., Lee S.J., Kim K., Go M.J., Lee J.Y., Lee H.J., Song J., Jeon B.T., Roh G.S., Kim S.J., Kim B.Y., Hong K.W., Yoo Y.H., Oh B., Kang Y., Jeong S.Y.
    Mol Cell Endocrinol 382:178-189(2014) [PubMed] [Europe PMC] [Abstract]
• positive regulation of mitochondrial fission Source: ParkinsonsUK-UCL
• positive regulation of mitochondrial fusion Source: ParkinsonsUK-UCL
• positive regulation of mitochondrial membrane potential Source: RGDInferred from mutant phenotypeⁱ
  • "The PARK2 gene is involved in the maintenance of pancreatic beta-cell functions related to insulin production and secretion."
    Jin H.S., Kim J., Lee S.J., Kim K., Go M.J., Lee J.Y., Lee H.J., Song J., Jeon B.T., Roh G.S., Kim S.J., Kim B.Y., Hong K.W., Yoo Y.H., Oh B., Kang Y., Jeong S.Y.
    Mol Cell Endocrinol 382:178-189(2014) [PubMed] [Europe PMC] [Abstract]
• positive regulation of mitophagy Source: RGDInferred from mutant phenotypeⁱ
  • "Hydrogen Sulphide modulating mitochondrial morphology to promote mitophagy in endothelial cells under high-glucose and high-palmitate."
    Liu N., Wu J., Zhang L., Gao Z., Sun Y., Yu M., Zhao Y., Dong S., Lu F., Zhang W.
    J Cell Mol Med 21:3190-3203(2017) [PubMed] [Europe PMC] [Abstract]
• positive regulation of mitophagy in response to mitochondrial depolarization Source: RGD
• positive regulation of neurotransmitter uptake Source: RGD
• positive regulation of proteasomal protein catabolic process Source: RGD
• positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: RGD
• positive regulation of protein binding Source: RGD
• positive regulation of protein linear polyubiquitination Source: RGD
• positive regulation of protein localization to membrane Source: RGD
• positive regulation of transcription by RNA polymerase II Source: ParkinsonsUK-UCL
• positive regulation of tumor necrosis factor-mediated signaling pathway Source: ParkinsonsUK-UCL
• proteasomal protein catabolic process Source: RGD
• proteasome-mediated ubiquitin-dependent protein catabolic process Source: ParkinsonsUK-UCL
• protein autoubiquitination Source: ParkinsonsUK-UCL
• protein destabilization Source: UniProtKB
• protein K11-linked ubiquitination Source: UniProtKB
• protein K48-linked ubiquitination Source: UniProtKB
• protein K63-linked ubiquitination Source: ParkinsonsUK-UCL
• protein K6-linked ubiquitination Source: UniProtKB
• protein localization to mitochondrion Source: ParkinsonsUK-UCLInferred from direct assayⁱ
  • "Disease-causing mutations in parkin impair mitochondrial ubiquitination, aggregation, and HDAC6-dependent mitophagy."
    Lee J.Y., Nagano Y., Taylor J.P., Lim K.L., Yao T.P.
    J Cell Biol 189:671-679(2010) [PubMed] [Europe PMC] [Abstract]
• protein metabolic process Source: RGD
• protein monoubiquitination Source: UniProtKB
• protein polyubiquitination Source: ParkinsonsUK-UCL
• protein stabilization Source: RGD
• protein ubiquitination Source: ParkinsonsUK-UCLInferred from direct assayⁱ
  • "Disease-causing mutations in parkin impair mitochondrial ubiquitination, aggregation, and HDAC6-dependent mitophagy."
    Lee J.Y., Nagano Y., Taylor J.P., Lim K.L., Yao T.P.
    J Cell Biol 189:671-679(2010) [PubMed] [Europe PMC] [Abstract]
• regulation of apoptotic process Source: GO_Central <p>Inferred from Biological aspect of Ancestor</p> <p>A type of phylogenetic evidence whereby an aspect of a descendent is inferred through the characterization of an aspect of a ancestral gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#iba">GO evidence code guide</a></p> Inferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• regulation of autophagy Source: UniProtKB
• regulation of cellular response to oxidative stress Source: ParkinsonsUK-UCL
• regulation of dopamine metabolic process Source: RGD
• regulation of gene expression Source: RGDInferred from mutant phenotypeⁱ
  • "Parkin overexpression protects retinal ganglion cells against glutamate excitotoxicity."
    Hu X., Dai Y., Sun X.
    Mol Vis 23:447-456(2017) [PubMed] [Europe PMC] [Abstract]
• regulation of mitochondrial membrane potential Source: RGD
• regulation of mitochondrion organization Source: ParkinsonsUK-UCL
• regulation of neurotransmitter secretion Source: RGD
• regulation of protein stability Source: RGD
• regulation of protein ubiquitination Source: RGD
• regulation of reactive oxygen species metabolic process Source: RGD
• response to corticosterone Source: RGDInferred from expression patternⁱ
  • "Regulation of hippocampal parkin protein by corticosteroids."
    Horowitz J.M., Pastor D.M., Kar S., Arinsburg S.A., Hallas B.H., Torres G.
    Neuroreport 14:2327-2330(2003) [PubMed] [Europe PMC] [Abstract]
• response to curcumin Source: RGDInferred from expression patternⁱ
  • "Curcumin prevents cisplatin-induced renal alterations in mitochondrial bioenergetics and dynamic."
    Ortega-Dominguez B., Aparicio-Trejo O.E., Garcia-Arroyo F.E., Leon-Contreras J.C., Tapia E., Molina-Jijon E., Hernandez-Pando R., Sanchez-Lozada L.G., Barrera-Oviedo D., Pedraza-Chaverri J.
    Food Chem Toxicol 107:373-385(2017) [PubMed] [Europe PMC] [Abstract]
• response to drug Source: RGDInferred from expression patternⁱ
  • "Effect of the neurotoxic dose of methamphetamine on gene expression of parkin and Pael-receptors in rat striatum."
    Nakahara T., Kuroki T., Ohta E., Kajihata T., Yamada H., Yamanaka M., Hashimoto K., Tsutsumi T., Hirano M., Uchimura H.
    Parkinsonism Relat Disord 9:213-219(2003) [PubMed] [Europe PMC] [Abstract]
• response to endoplasmic reticulum stress Source: RGDInferred from expression patternⁱ
  • "Down-regulation of parkin protein in transient focal cerebral ischemia: A link between stroke and degenerative disease?"
    Mengesdorf T., Jensen P.H., Mies G., Aufenberg C., Paschen W.
    Proc Natl Acad Sci U S A 99:15042-15047(2002) [PubMed] [Europe PMC] [Abstract]
• response to muscle activity Source: RGDInferred from expression patternⁱ
  • "Physical exercise mitigates doxorubicin-induced brain cortex and cerebellum mitochondrial alterations and cellular quality control signaling."
    Marques-Aleixo I., Santos-Alves E., Balca M.M., Moreira P.I., Oliveira P.J., Magalhaes J., Ascensao A.
    Mitochondrion 26:43-57(2016) [PubMed] [Europe PMC] [Abstract]
• response to oxidative stress Source: ParkinsonsUK-UCL
• response to unfolded protein Source: RGDInferred from expression patternⁱ
  • "Astrocytic but not neuronal increased expression and redistribution of parkin during unfolded protein stress."
    Ledesma M.D., Galvan C., Hellias B., Dotti C., Jensen P.H.
    J Neurochem 83:1431-1440(2002) [PubMed] [Europe PMC] [Abstract]
• startle response Source: RGD
• synaptic transmission, dopaminergic Source: RGD
• synaptic transmission, glutamatergic Source: RGD
• ubiquitin-dependent protein catabolic process Source: ParkinsonsUK-UCL
• zinc ion homeostasis Source: ParkinsonsUK-UCL

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsⁱ

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyⁱ

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationⁱ

Keywords - Cellular componentⁱ

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechⁱ

Mutagenesis

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingⁱ

Molecule processing

Amino acid modifications

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationⁱ

Keywords - PTMⁱ

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressionⁱ

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityⁱ

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactionⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structureⁱ

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsⁱ

GO - Molecular functionⁱ

• actin binding Source: RGD
• beta-catenin binding Source: RGD
• chaperone binding Source: RGD
• cullin family protein binding Source: ParkinsonsUK-UCL
• enzyme binding Source: RGD
• F-box domain binding Source: ParkinsonsUK-UCL
• G protein-coupled receptor binding Source: ParkinsonsUK-UCL
• heat shock protein binding Source: RGD
• histone deacetylase binding Source: RGD
• Hsp70 protein binding Source: RGD
• identical protein binding Source: ParkinsonsUK-UCL
• kinase binding Source: RGD
• PDZ domain binding Source: ParkinsonsUK-UCL
• phospholipase binding Source: RGD
• protein kinase binding Source: RGDInferred from physical interactionⁱ
  • "Hydrogen Sulphide modulating mitochondrial morphology to promote mitophagy in endothelial cells under high-glucose and high-palmitate."
    Liu N., Wu J., Zhang L., Gao Z., Sun Y., Yu M., Zhao Y., Dong S., Lu F., Zhang W.
    J Cell Mol Med 21:3190-3203(2017) [PubMed] [Europe PMC] [Abstract]
• tubulin binding Source: RGD
• ubiquitin binding Source: UniProtKB
• ubiquitin conjugating enzyme binding Source: ParkinsonsUK-UCL
• ubiquitin protein ligase binding Source: RGD
• ubiquitin-specific protease binding Source: RGD

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structureⁱ

Secondary structure

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsⁱ

Domains and Repeats

Region

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domainⁱ

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesⁱ

Zinc finger

Keywords - Domainⁱ

Phylogenomic databases

Family and domain databases

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (6)ⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusⁱ: Complete.

        10         20         30         40         50
MIVFVRFNSS YGFPVEVDSD TSIFQLKEVV AKRQGVPADQ LRVIFAGKEL 
        60         70         80         90        100
QNHLTVQNCD LEQQSIVHIV QRPQRKSHET NASGGDKPQS TPEGSIWEPR 
       110        120        130        140        150
SLTRVDLSSH ILPADSVGLA VILDTDSKSD SEAARGPEAK PTYHSFFVYC 
       160        170        180        190        200
KGPCHKVQPG KLRVQCGTCR QATLTLAQGP SCWDDVLIPN RMSGECQSPD 
       210        220        230        240        250
CPGTRAEFFF KCGAHPTSDK DTSVALNLIT NNSRSIPCIA CTDVRNPVLV 
       260        270        280        290        300
FQCNHRHVIC LDCFHLYCVT RLNDRQFVHD AQLGYSLPCV AGCPNSLIKE 
       310        320        330        340        350
LHHFRILGEE QYNRYQQYGA EECVLQMGGV LCPRPGCGAG LLPEQGQKKV 
       360        370        380        390        400
TCEGGNGLGC GFVFCRDCKE AYHEGECDSM FEASGATSQA YRVDQRAAEQ 
       410        420        430        440        450
ARWEEASKET IKKTTKPCPR CNVPIEKNGG CMHMKCPQPQ CKLEWCWNCG 
       460 
CEWNRACMGD HWFDV                                       

        10         20         30         40         50
MIVFVRFNSS YGFPVEVDSD TSIFQLKEVV AKRQGVPADQ LRVIFAGKEL 
        60         70         80         90        100
QNHLTVQNCD LEQQSIVHIV QRPQRKSHET NASGGDKPQS TPEGSIWEPR 
       110        120        130        140        150
SLTRVDLSSH ILPADSVGLA VILDTDSKSD SEAARGPEAK PTYHSFFVYC 
       160        170        180        190        200
KGPCHKVQPG KLRVQCGTCR QATLTLAQGP SCWDDVLIPN RMSGECQSPD 
       210        220        230        240        250
CPGTRAEFFF KCGAHPTSDK DTSVALNLIT NNSRSIPCIA CTDVRNPVLV 
       260        270        280        290        300
FQCNHRHVIC LDCFHLYCVT RLNDRQFVHD AQLGYSLPCV AGCPNSLIKE 
       310        320        330        340        350
LHHFRILGEE QYNRYQQYGA EECVLQMGGV LCPRPGCGAG LLPEQGQKKV 
       360        370        380        390        400
TCEGGNGLGC GFVFCRDCKE AYHEGECDSM FEASGATSQA YRVDQRAAEQ 
       410        420        430        440 
ARWEEASKET IKKTTKPCPR CNVPIEKNER MHVQYTMCIP GAHGGY     

        10         20         30         40         50
MSGECQSPDC PGTRAEFFFK CGAHPTSDKD TSVALNLITN NSRSIPCIAC 
        60         70         80         90        100
TDVRNPVLVF QCNHRHVICL DCFHLYCVTR LNDRQFVHDA QLGYSLPCVA 
       110        120        130        140        150
GCPNSLIKEL HHFRILGEEQ YNRYQQYGAE ECVLQMGGVL CPRPGCGAGL 
       160        170        180        190        200
LPEQGQKKVT CEGGNGLGCG FVFCRDCKEA YHEGECDSMF EASGATSQAY 
       210        220        230        240        250
RVDQRAAEQA RWEEASKETI KKTTKPCPRC NVPIEKNGGC MHMKCPQPQC 
       260        270 
KLEWCWNCGC EWNRACMGDH WFDV                             

        10         20         30         40         50
MIVFVRFNSS YGFPVEVDSD TSIFQLKEVV AKRQGVPADQ LRVIFAGKEL 
        60         70         80         90        100
QNHLTVQHPQ DGFCHKSHLA VHNLSQQDVT QNCDLEQQSI VHIVQRPQRK 
       110        120        130        140        150
SHETNASGGD KPQSTPEGSI WEPRSLTRVD LSSHILPADS VGLAVILDTD 
       160        170        180        190        200
SKSDSEAARG PEAKPTYHSF FVYCKGPCHK VQPGKLRVQC GTCRQATLTL 
       210        220        230        240        250
AQGPSCWDDV LIPNRMSGEC QSPDCPGTRA EFFFKCGAHP TSDKDTSVAL 
       260        270        280        290        300
NLITNNSRSI PCIACTDVRN PVLVFQCNHR HVICLDCFHL YCVTRLNDRQ 
       310        320        330        340        350
FVHDAQLGYS LPCVAGCPNS LIKELHHFRI LGEEQYNRYQ QYGAEECVLQ 
       360        370        380        390        400
MGGVLCPRPG CGAGLLPEQG QKKVTCEGGN GLGCGFVFCR DCKEAYHEGE 
       410        420        430        440        450
CDSMFEASGA TSQAYRVDQR AAEQARWEEA SKETIKKTTK PCPRCNVPIE 
       460        470        480 
KNGGCMHMKC PQPQCKLEWC WNCGCEWNRA CMGDHWFDV             

        10         20         30         40         50
MIVFVRFNSS YGFPVEVDSD TSIFQLKEVV AKRQGVPADQ LRVIFAGKEL 
        60         70         80         90        100
QNHLTVQNCD LEQQSIVHIV QRPQRKSHET NASGGDKPQS TPEGSIWEPR 
       110        120        130        140        150
SLTRVDLSSH ILPADSVGLA VILDTDSKSD SEAARGPEAK PTYHSFFVYC 
       160        170        180        190        200
KGPCHKVQPG KLRVQCGTCR QATLTLAQEF FFKCGAHPTS DKDTSVALNL 
       210        220        230        240        250
ITNNSRSIPC IACTDVRNPV LVFQCNHRHV ICLDCFHLYC VTRLNDRQFV 
       260        270        280        290        300
HDAQLGYSLP CVAGCPNSLI KELHHFRILG EEQYNRYQQY GAEECVLQMG 
       310        320        330        340        350
GVLCPRPGCG AGLLPEQGQK KVTCEGGNGL GCGFVFCRDC KEAYHEGECD 
       360        370        380        390        400
SMFEASGATS QAYRVDQRAA EQARWEEASK ETIKKTTKPC PRCNVPIEKN 
       410        420        430 
GGCMHMKCPQ PQCKLEWCWN CGCEWNRACM GDHWFDV               

        10         20         30         40         50
MSGECQSPDC PGTRAEFFFK CGAHPTSDKD TSVALNLITN NSRSIPCIAC 
        60         70         80         90        100
TDVRNPVLVF QCNHRHVICL DCFHLYCVTR LNDRQFVHDA QLGYSLPCVA 
       110        120        130        140        150
GCPNSLIKEL HHFRILGEEQ YNRYQQYGAE ECVLQMGGVL CPRPGCGAGL 
       160        170        180        190        200
LPEQGQKKVT CEGGNGLGCG FVFCRDCKEA YHEGECDSMF EASGATSQED 

VCT                                                    

Experimental Info

Alternative sequence

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityⁱ

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsⁱ

• 100% Identity
• 90% Identity
• 50% Identity

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesⁱ

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationⁱ

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousⁱ

Keywords - Technical termⁱ

Documents

1. PATHWAY comments
   Index of metabolic and biosynthesis pathways
2. PDB cross-references
   Index of Protein Data Bank (PDB) cross-references
3. SIMILARITY comments
   Index of protein domains and families