UBQLN2 (original) (raw)

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Protein-coding gene in the species Homo sapiens

UBQLN2
Available structuresPDBOrtholog search: PDBe RCSB List of PDB id codes1J8C
Identifiers
Aliases UBQLN2, ALS15, CHAP1, DSK2, N4BP4, PLIC2, HRIHFB2157, ubiquilin 2
External IDs OMIM: 300264; MGI: 1860283; HomoloGene: 81830; GeneCards: UBQLN2; OMA:UBQLN2 - orthologs
Gene location (Human)X chromosome (human)Chr.X chromosome (human)[1]X chromosome (human)Genomic location for UBQLN2Genomic location for UBQLN2BandXp11.21Start56,563,627 bp[1]End56,567,868 bp[1]
Gene location (Mouse)X chromosome (mouse)Chr.X chromosome (mouse)[2]X chromosome (mouse)Genomic location for UBQLN2Genomic location for UBQLN2BandX|X F3Start152,281,223 bp[2]End152,284,566 bp[2]
RNA expression patternBgeeHuman Mouse (ortholog)Top expressed incerebellar vermisPonspostcentral gyrusendothelial cellBrodmann area 23retinal pigment epitheliumentorhinal cortexsuperior vestibular nucleusseminal vesiculamiddle temporal gyrusTop expressed inhabenulaventral tegmental areaarcuate nucleusmedian eminencesubiculumseminal vesiculaparaventricular nucleus of hypothalamusanterior amygdaloid areaventromedial nucleusdorsomedial hypothalamic nucleusMore reference expression dataBioGPSMore reference expression data
Gene ontologyMolecular function protein binding polyubiquitin modification-dependent protein binding Cellular component cytoplasm autophagosome plasma membrane cytoplasmic vesicle nucleus membrane cytosol Biological process autophagy regulation of autophagosome assembly negative regulation of G protein-coupled receptor internalization regulation of macroautophagy ubiquitin-dependent ERAD pathway negative regulation of clathrin-dependent endocytosis positive regulation of ER-associated ubiquitin-dependent protein catabolic process autophagosome assembly ubiquitin-dependent protein catabolic process Sources:Amigo / QuickGO
OrthologsSpeciesHuman MouseEntrez2997854609EnsemblENSG00000188021ENSMUSG00000050148UniProtQ9UHD9Q9QZM0RefSeq (mRNA)NM_013444NM_018798RefSeq (protein)NP_038472NP_061268Location (UCSC)Chr X: 56.56 – 56.57 MbChr X: 152.28 – 152.28 MbPubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Ubiquilin-2 is a protein that in humans is encoded by the UBQLN2 gene.[5][6]

This gene encodes a ubiquitin-like protein (ubiquilin) that shares high degree of similarity with related products in yeast, rat and frog. Ubiquilins contain a N-terminal ubiquitin-like domain and a C-terminal ubiquitin-associated domain. They physically associate with both proteasomes and ubiquitin ligases, and are thus thought to functionally link the ubiquitination machinery to the proteasome to effect in vivo protein degradation. This ubiquilin has also been shown to bind the ATPase domain of the Hsp70-like Hspa13 (Stch) protein.[6]

Similarity to other proteins

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Human UBQLN2 shares a high degree of similarity with related ubiquilins including UBQLN1 and UBQLN4.[7]

Clinical significance

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In a small proportion of familial amyotrophic lateral sclerosis (fALS), the UBQLN2 gene is mutated, causing formation of a non-functional Ubiquilin 2 enzyme. This non-functioning enzyme leads to the accumulation of ubiquinated proteins in the lower motor neurons and upper corticospinal motor neurons, due to the fact that ubiquilin 2 normally degrades these ubiquinated proteins, but cannot if the ALS mutation is present.[8] The same accumulations occur in patients without UBQLN2 mutations, but with mutations in other genes, including TDP-43 and C9ORF72.[_citation needed_]

UBQLN2 has been shown to interact with HERPUD1[9] and UBE3A.[10]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000188021 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000050148 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Kaye FJ, Modi S, Ivanovska I, Koonin EV, Thress K, Kubo A, Kornbluth S, Rose MD (Mar 2000). "A family of ubiquitin-like proteins binds the ATPase domain of Hsp70-like Stch". FEBS Lett. 467 (2–3): 348–55. doi:10.1016/S0014-5793(00)01135-2. PMID 10675567.
  6. ^ a b "Entrez Gene: UBQLN2 ubiquilin 2".
  7. ^ Marín I (March 2014). "The ubiquilin gene family: evolutionary patterns and functional insights". BMC Evol Biol. 14 (1): 63. Bibcode:2014BMCEE..14...63M. doi:10.1186/1471-2148-14-63. PMC 4230246. PMID 24674348.
  8. ^ Deng HX, Chen W, Hong ST, Boycott KM, Gorrie GH, Siddique N, Yang Y, Fecto F, Shi Y, Zhai H, Jiang H, Hirano M, Rampersaud E, Jansen GH, Donkervoort S, Bigio EH, Brooks BR, Ajroud K, Sufit RL, Haines JL, Mugnaini E, Pericak-Vance MA, Siddique T (August 2011). "Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia". Nature. 477 (7363): 211–215. Bibcode:2011Natur.477..211D. doi:10.1038/nature10353. PMC 3169705. PMID 21857683.
  9. ^ Kim TY, Kim E, Yoon SK, Yoon JB (May 2008). "Herp enhances ER-associated protein degradation by recruiting ubiquilins". Biochem. Biophys. Res. Commun. 369 (2): 741–6. doi:10.1016/j.bbrc.2008.02.086. PMID 18307982.
  10. ^ Kleijnen MF, Shih AH, Zhou P, Kumar S, Soccio RE, Kedersha NL, Gill G, Howley PM (August 2000). "The hPLIC proteins may provide a link between the ubiquitination machinery and the proteasome". Mol. Cell. 6 (2): 409–19. doi:10.1016/S1097-2765(00)00040-X. PMID 10983987.