(data stored in ACNUC21429 zone)

SWISSPROT: UBQL2_HUMAN

ID   UBQL2_HUMAN             Reviewed;         624 AA.
AC   Q9UHD9; O94798; Q5D027; Q9H3W6; Q9HAZ4;
DT   29-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 2.
DT   11-DEC-2019, entry version 172.
DE   RecName: Full=Ubiquilin-2;
DE   AltName: Full=Chap1;
DE   AltName: Full=DSK2 homolog;
DE   AltName: Full=Protein linking IAP with cytoskeleton 2;
DE            Short=PLIC-2;
DE            Short=hPLIC-2;
DE   AltName: Full=Ubiquitin-like product Chap1/Dsk2;
GN   Name=UBQLN2; Synonyms=N4BP4, PLIC2; ORFNames=HRIHFB2157;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH STCH.
RC   TISSUE=Lung;
RX   PubMed=10675567; DOI=10.1016/s0014-5793(00)01135-2;
RA   Kaye F.J., Modi S., Ivanovska I., Koonin E.V., Thress K., Kubo A.,
RA   Kornbluth S., Rose M.D.;
RT   "A family of ubiquitin-like proteins binds the ATPase domain of Hsp70-like
RT   Stch.";
RL   FEBS Lett. 467:348-355(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION
RP   WITH THE PROTEASOME AND UBE3A.
RC   TISSUE=B-cell;
RX   PubMed=10983987; DOI=10.1016/s1097-2765(00)00040-x;
RA   Kleijnen M.F., Shih A.H., Zhou P., Kumar S., Soccio R.E., Kedersha N.L.,
RA   Gill G., Howley P.M.;
RT   "The hPLIC proteins may provide a link between the ubiquitination machinery
RT   and the proteasome.";
RL   Mol. Cell 6:409-419(2000).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15772651; DOI=10.1038/nature03440;
RA   Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA   Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA   Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA   Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA   Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA   Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA   Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA   Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA   Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA   Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA   Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA   Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA   Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA   Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA   Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA   Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA   Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA   Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA   Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA   Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA   Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA   Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA   Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA   Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA   Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA   Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA   Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA   Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA   Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA   Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA   McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA   Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA   Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA   Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA   Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA   Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA   Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA   Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA   Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA   Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA   d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA   Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA   Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA   Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA   Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA   Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA   Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA   Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA   Rogers J., Bentley D.R.;
RT   "The DNA sequence of the human X chromosome.";
RL   Nature 434:325-337(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Placenta;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 37-624.
RC   TISSUE=Amygdala;
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 217-624, AND SUBCELLULAR
RP   LOCATION.
RC   TISSUE=Fetal brain;
RX   PubMed=9853615; DOI=10.1038/4315;
RA   Ueki N., Oda T., Kondo M., Yano K., Noguchi T., Muramatsu M.-A.;
RT   "Selection system for genes encoding nuclear-targeted proteins.";
RL   Nat. Biotechnol. 16:1338-1342(1998).
RN   [8]
RP   SUBUNIT, AND HETERODIMERIZATION WITH UBQLN1.
RX   PubMed=16813565; DOI=10.1042/bj20060441;
RA   Ford D.L., Monteiro M.J.;
RT   "Dimerization of ubiquilin is dependent upon the central region of the
RT   protein: evidence that the monomer, but not the dimer, is involved in
RT   binding presenilins.";
RL   Biochem. J. 399:397-404(2006).
RN   [9]
RP   INTERACTION WITH RAD23A.
RX   PubMed=17098253; DOI=10.1016/j.jmb.2006.10.056;
RA   Kang Y., Zhang N., Koepp D.M., Walters K.J.;
RT   "Ubiquitin receptor proteins hHR23a and hPLIC2 interact.";
RL   J. Mol. Biol. 365:1093-1101(2007).
RN   [10]
RP   FUNCTION, AND INTERACTION WITH HERPUD1.
RX   PubMed=18307982; DOI=10.1016/j.bbrc.2008.02.086;
RA   Kim T.Y., Kim E., Yoon S.K., Yoon J.B.;
RT   "Herp enhances ER-associated protein degradation by recruiting
RT   ubiquilins.";
RL   Biochem. Biophys. Res. Commun. 369:741-746(2008).
RN   [11]
RP   FUNCTION, SUBCELLULAR LOCATION, DOMAIN UBIQUITIN-LIKE, AND INTERACTION WITH
RP   EPS15; EPN1 AND EPN2.
RX   PubMed=18199683; DOI=10.1091/mbc.e07-08-0775;
RA   N'Diaye E.N., Hanyaloglu A.C., Kajihara K.K., Puthenveedu M.A., Wu P.,
RA   von Zastrow M., Brown E.J.;
RT   "The ubiquitin-like protein PLIC-2 is a negative regulator of G protein-
RT   coupled receptor endocytosis.";
RL   Mol. Biol. Cell 19:1252-1260(2008).
RN   [12]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP   METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP   [LARGE SCALE ANALYSIS].
RX   PubMed=19413330; DOI=10.1021/ac9004309;
RA   Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT   "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT   refined SCX-based approach.";
RL   Anal. Chem. 81:4493-4501(2009).
RN   [13]
RP   FUNCTION, SUBCELLULAR LOCATION, AND DOMAIN UBA.
RX   PubMed=19148225; DOI=10.1038/embor.2008.238;
RA   N'Diaye E.N., Kajihara K.K., Hsieh I., Morisaki H., Debnath J., Brown E.J.;
RT   "PLIC proteins or ubiquilins regulate autophagy-dependent cell survival
RT   during nutrient starvation.";
RL   EMBO Rep. 10:173-179(2009).
RN   [14]
RP   REVIEW.
RX   PubMed=20729634; DOI=10.4161/auto.6.7.13118;
RA   Rothenberg C., Monteiro M.J.;
RT   "Ubiquilin at a crossroads in protein degradation pathways.";
RL   Autophagy 6:979-980(2010).
RN   [15]
RP   FUNCTION, IDENTIFICATION IN A COMPLEX WITH UBQLN1 AND MAP1LC3A/B/C, AND
RP   PROTEOLYTIC DEGRADATION.
RX   PubMed=20529957; DOI=10.1093/hmg/ddq231;
RA   Rothenberg C., Srinivasan D., Mah L., Kaushik S., Peterhoff C.M.,
RA   Ugolino J., Fang S., Cuervo A.M., Nixon R.A., Monteiro M.J.;
RT   "Ubiquilin functions in autophagy and is degraded by chaperone-mediated
RT   autophagy.";
RL   Hum. Mol. Genet. 19:3219-3232(2010).
RN   [16]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [17]
RP   REVIEW.
RX   PubMed=22628307; DOI=10.1515/hsz-2012-0120;
RA   Lee D.Y., Brown E.J.;
RT   "Ubiquilins in the crosstalk among proteolytic pathways.";
RL   Biol. Chem. 393:441-447(2012).
RN   [18]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP   METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP   [LARGE SCALE ANALYSIS].
RX   PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA   Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA   Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA   Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT   "N-terminal acetylome analyses and functional insights of the N-terminal
RT   acetyltransferase NatB.";
RL   Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN   [19]
RP   INTERACTION WITH TARDBP.
RX   PubMed=23541532; DOI=10.1016/j.bbapap.2013.03.020;
RA   Cassel J.A., Reitz A.B.;
RT   "Ubiquilin-2 (UBQLN2) binds with high affinity to the C-terminal region of
RT   TDP-43 and modulates TDP-43 levels in H4 cells: characterization of
RT   inhibition by nucleic acids and 4-aminoquinolines.";
RL   Biochim. Biophys. Acta 1834:964-971(2013).
RN   [20]
RP   INTERACTION WITH UBQLN4.
RX   PubMed=23459205; DOI=10.1038/embor.2013.22;
RA   Lee D.Y., Arnott D., Brown E.J.;
RT   "Ubiquilin4 is an adaptor protein that recruits Ubiquilin1 to the autophagy
RT   machinery.";
RL   EMBO Rep. 14:373-381(2013).
RN   [21]
RP   REVIEW.
RX   PubMed=24674348; DOI=10.1186/1471-2148-14-63;
RA   Marin I.;
RT   "The ubiquilin gene family: evolutionary patterns and functional
RT   insights.";
RL   BMC Evol. Biol. 14:63-63(2014).
RN   [22]
RP   INTERACTION WITH C9ORF72.
RX   PubMed=24549040; DOI=10.1093/hmg/ddu068;
RA   Farg M.A., Sundaramoorthy V., Sultana J.M., Yang S., Atkinson R.A.,
RA   Levina V., Halloran M.A., Gleeson P.A., Blair I.P., Soo K.Y., King A.E.,
RA   Atkin J.D.;
RT   "C9ORF72, implicated in amytrophic lateral sclerosis and frontotemporal
RT   dementia, regulates endosomal trafficking.";
RL   Hum. Mol. Genet. 23:3579-3595(2014).
RN   [23]
RP   REVIEW.
RX   PubMed=24589709; DOI=10.1016/j.biocel.2014.02.018;
RA   Zhang K.Y., Yang S., Warraich S.T., Blair I.P.;
RT   "Ubiquilin 2: a component of the ubiquitin-proteasome system with an
RT   emerging role in neurodegeneration.";
RL   Int. J. Biochem. Cell Biol. 50:123-126(2014).
RN   [24]
RP   FUNCTION, INTERACTION WITH FAF2, AND CHARACTERIZATION OF VARIANT ALS15
RP   HIS-497.
RX   PubMed=24215460; DOI=10.1111/jnc.12606;
RA   Xia Y., Yan L.H., Huang B., Liu M., Liu X., Huang C.;
RT   "Pathogenic mutation of UBQLN2 impairs its interaction with UBXD8 and
RT   disrupts endoplasmic reticulum-associated protein degradation.";
RL   J. Neurochem. 129:99-106(2014).
RN   [25]
RP   STRUCTURE BY NMR OF 1-103.
RX   PubMed=11827521; DOI=10.1021/bi011892y;
RA   Walters K.J., Kleijnen M.F., Goh A.M., Wagner G., Howley P.M.;
RT   "Structural studies of the interaction between ubiquitin family proteins
RT   and proteasome subunit S5a.";
RL   Biochemistry 41:1767-1777(2002).
RN   [26]
RP   VARIANTS ALS15 HIS-497; SER-497; THR-506; SER-509 AND SER-525, AND
RP   CHARACTERIZATION OF VARIANTS ALS15 HIS-497 AND THR-506.
RX   PubMed=21857683; DOI=10.1038/nature10353;
RA   Deng H.X., Chen W., Hong S.T., Boycott K.M., Gorrie G.H., Siddique N.,
RA   Yang Y., Fecto F., Shi Y., Zhai H., Jiang H., Hirano M., Rampersaud E.,
RA   Jansen G.H., Donkervoort S., Bigio E.H., Brooks B.R., Ajroud K.,
RA   Sufit R.L., Haines J.L., Mugnaini E., Pericak-Vance M.A., Siddique T.;
RT   "Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS
RT   and ALS/dementia.";
RL   Nature 477:211-215(2011).
RN   [27]
RP   VARIANTS ALS15 THR-283 AND ARG-425, AND VARIANT VAL-282.
RX   PubMed=22892309; DOI=10.1016/j.neurobiolaging.2012.07.002;
RA   Synofzik M., Maetzler W., Grehl T., Prudlo J., Vom Hagen J.M., Haack T.,
RA   Rebassoo P., Munz M., Schols L., Biskup S.;
RT   "Screening in ALS and FTD patients reveals 3 novel UBQLN2 mutations outside
RT   the PXX domain and a pure FTD phenotype.";
RL   Neurobiol. Aging 33:E13-E17(2012).
RN   [28]
RP   VARIANT ALS15 ILE-487.
RX   PubMed=22717235; DOI=10.1016/j.neurobiolaging.2012.05.008;
RA   Williams K.L., Warraich S.T., Yang S., Solski J.A., Fernando R.,
RA   Rouleau G.A., Nicholson G.A., Blair I.P.;
RT   "UBQLN2/ubiquilin 2 mutation and pathology in familial amyotrophic lateral
RT   sclerosis.";
RL   Neurobiol. Aging 33:E3-E10(2012).
RN   [29]
RP   VARIANTS ALS15 ASN-155 AND THR-189.
RX   PubMed=22560112; DOI=10.1016/j.neurobiolaging.2012.03.015;
RA   Daoud H., Suhail H., Szuto A., Camu W., Salachas F., Meininger V.,
RA   Bouchard J.P., Dupre N., Dion P.A., Rouleau G.A.;
RT   "UBQLN2 mutations are rare in French and French-Canadian amyotrophic
RT   lateral sclerosis.";
RL   Neurobiol. Aging 33:E1-E5(2012).
RN   [30]
RP   INTERACTION WITH HNRNPA1 AND HNRNPU, AND CHARACTERIZATION OF VARIANTS ALS15
RP   HIS-497; SER-497; THR-506; SER-509 AND SER-525.
RX   PubMed=25616961; DOI=10.1093/hmg/ddv020;
RA   Gilpin K.M., Chang L., Monteiro M.J.;
RT   "ALS-linked mutations in ubiquilin-2 or hnRNPA1 reduce interaction between
RT   ubiquilin-2 and hnRNPA1.";
RL   Hum. Mol. Genet. 24:2565-2577(2015).
CC   -!- FUNCTION: Plays an important role in the regulation of different
CC       protein degradation mechanisms and pathways including ubiquitin-
CC       proteasome system (UPS), autophagy and the endoplasmic reticulum-
CC       associated protein degradation (ERAD) pathway. Mediates the proteasomal
CC       targeting of misfolded or accumulated proteins for degradation by
CC       binding (via UBA domain) to their polyubiquitin chains and by
CC       interacting (via ubiquitin-like domain) with the subunits of the
CC       proteasome (PubMed:10983987). Plays a role in the ERAD pathway via its
CC       interaction with ER-localized proteins FAF2/UBXD8 and HERPUD1 and may
CC       form a link between the polyubiquitinated ERAD substrates and the
CC       proteasome (PubMed:24215460, PubMed:18307982). Involved in the
CC       regulation of macroautophagy and autophagosome formation; required for
CC       maturation of autophagy-related protein LC3 from the cytosolic form
CC       LC3-I to the membrane-bound form LC3-II and may assist in the
CC       maturation of autophagosomes to autolysosomes by mediating
CC       autophagosome-lysosome fusion (PubMed:19148225, PubMed:20529957).
CC       Negatively regulates the endocytosis of GPCR receptors: AVPR2 and
CC       ADRB2, by specifically reducing the rate at which receptor-arrestin
CC       complexes concentrate in clathrin-coated pits (CCPs) (PubMed:18199683).
CC       {ECO:0000269|PubMed:10983987, ECO:0000269|PubMed:18199683,
CC       ECO:0000269|PubMed:18307982, ECO:0000269|PubMed:19148225,
CC       ECO:0000269|PubMed:20529957, ECO:0000269|PubMed:24215460}.
CC   -!- SUBUNIT: Homodimer. Forms heterodimer with UBQLN1. Binds UBE3A and
CC       BTRC. Interacts with the 19S proteasome subunit. Interacts with
CC       C9orf72. Interacts with HNRNPA1 and HNRNPU. Found in a complex with
CC       UBQLN1 and MAP1LC3A/B/C. Interacts with EPS15, EPN1 and EPN2. Interacts
CC       with HERPUD1. Interacts with RAD23A. Interacts with TARDBP. Interacts
CC       (via C-terminus) with FAF2 (via N-terminus). Interacts with UBQLN4.
CC       Binds CD47 (By similarity). {ECO:0000250|UniProtKB:Q9QZM0,
CC       ECO:0000269|PubMed:10675567, ECO:0000269|PubMed:10983987,
CC       ECO:0000269|PubMed:16813565, ECO:0000269|PubMed:17098253,
CC       ECO:0000269|PubMed:18199683, ECO:0000269|PubMed:18307982,
CC       ECO:0000269|PubMed:20529957, ECO:0000269|PubMed:23459205,
CC       ECO:0000269|PubMed:23541532, ECO:0000269|PubMed:24215460,
CC       ECO:0000269|PubMed:24549040, ECO:0000269|PubMed:25616961}.
CC   -!- INTERACTION:
CC       A0A1U9X8X8:-; NbExp=4; IntAct=EBI-947187, EBI-17234977;
CC       Q16186:ADRM1; NbExp=5; IntAct=EBI-947187, EBI-954387;
CC       O95994:AGR2; NbExp=4; IntAct=EBI-947187, EBI-712648;
CC       Q8TD06:AGR3; NbExp=4; IntAct=EBI-947187, EBI-3925742;
CC       P02745:C1QA; NbExp=3; IntAct=EBI-947187, EBI-1220209;
CC       P40199:CEACAM6; NbExp=4; IntAct=EBI-947187, EBI-4314501;
CC       Q6UWE3:CLPSL2; NbExp=4; IntAct=EBI-947187, EBI-12183429;
CC       Q15038:DAZAP2; NbExp=4; IntAct=EBI-947187, EBI-724310;
CC       Q01524:DEFA6; NbExp=4; IntAct=EBI-947187, EBI-10222451;
CC       Q12805:EFEMP1; NbExp=4; IntAct=EBI-947187, EBI-536772;
CC       O14964:HGS; NbExp=4; IntAct=EBI-947187, EBI-740220;
CC       P09651:HNRNPA1; NbExp=2; IntAct=EBI-947187, EBI-352662;
CC       P09651-2:HNRNPA1; NbExp=4; IntAct=EBI-947187, EBI-352677;
CC       Q00839:HNRNPU; NbExp=3; IntAct=EBI-947187, EBI-351126;
CC       P48723:HSPA13; NbExp=4; IntAct=EBI-947187, EBI-750892;
CC       Q96NZ9:PRAP1; NbExp=4; IntAct=EBI-947187, EBI-2116102;
CC       Q16378:PRR4; NbExp=4; IntAct=EBI-947187, EBI-738624;
CC       P41222:PTGDS; NbExp=4; IntAct=EBI-947187, EBI-948821;
CC       P54725:RAD23A; NbExp=5; IntAct=EBI-947187, EBI-746453;
CC       O48726:RPN13 (xeno); NbExp=4; IntAct=EBI-947187, EBI-7710745;
CC       A6ZKI3:RTL8C; NbExp=4; IntAct=EBI-947187, EBI-10174072;
CC       Q13049:TRIM32; NbExp=4; IntAct=EBI-947187, EBI-742790;
CC       Q8WWY7:WFDC12; NbExp=4; IntAct=EBI-947187, EBI-11958577;
CC       Q96DA0:ZG16B; NbExp=4; IntAct=EBI-947187, EBI-953824;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18199683}. Nucleus
CC       {ECO:0000269|PubMed:9853615}. Membrane {ECO:0000250|UniProtKB:Q9QZM0}.
CC       Cytoplasmic vesicle, autophagosome {ECO:0000269|PubMed:19148225}.
CC       Note=Colocalizes with a subset of proteasomes, namely those that are
CC       cytoskeleton associated or free in the cytosol. Associated with fibers
CC       in mitotic cells. {ECO:0000269|PubMed:10983987}.
CC   -!- INDUCTION: Highly expressed in mitotic cells from metaphase to
CC       telophase. Expression in non-mitotic cells is very low.
CC   -!- DOMAIN: The ubiquitin-like domain is essential for its inhibitory
CC       effect on GPCR endocytosis. Mediates its association with the subunits
CC       of the proteasome. {ECO:0000269|PubMed:18199683,
CC       ECO:0000303|PubMed:24589709}.
CC   -!- DOMAIN: The UBA domain is essential for its association with
CC       microtubule-associated protein 1 light chain 3 (MAP1LC3). Mediates its
CC       association with ubiquitinated substrates.
CC       {ECO:0000269|PubMed:19148225, ECO:0000303|PubMed:24589709}.
CC   -!- DOMAIN: Dimerization is dependent upon the central region of the
CC       protein containing the STI1 domains and is independent of its
CC       ubiquitin-like and UBA domains. {ECO:0000269|PubMed:16813565}.
CC   -!- PTM: Degraded during macroautophagy. {ECO:0000269|PubMed:20529957}.
CC   -!- DISEASE: Amyotrophic lateral sclerosis 15, with or without
CC       frontotemporal dementia (ALS15) [MIM:300857]: A neurodegenerative
CC       disorder affecting upper motor neurons in the brain and lower motor
CC       neurons in the brain stem and spinal cord, resulting in fatal
CC       paralysis. Sensory abnormalities are absent. The pathologic hallmarks
CC       of the disease include pallor of the corticospinal tract due to loss of
CC       motor neurons, presence of ubiquitin-positive inclusions within
CC       surviving motor neurons, and deposition of pathologic aggregates. The
CC       etiology of amyotrophic lateral sclerosis is likely to be
CC       multifactorial, involving both genetic and environmental factors. The
CC       disease is inherited in 5-10% of the cases. Patients with ALS15 may
CC       develop frontotemporal dementia. {ECO:0000269|PubMed:21857683,
CC       ECO:0000269|PubMed:22560112, ECO:0000269|PubMed:22717235,
CC       ECO:0000269|PubMed:22892309, ECO:0000269|PubMed:24215460,
CC       ECO:0000269|PubMed:25616961}. Note=The disease is caused by mutations
CC       affecting the gene represented in this entry.
DR   EMBL; AF189009; AAF17237.1; -; mRNA.
DR   EMBL; AF293385; AAG02474.1; -; mRNA.
DR   EMBL; AL354793; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471154; EAW93233.1; -; Genomic_DNA.
DR   EMBL; BC069237; AAH69237.1; -; mRNA.
DR   EMBL; AL442081; CAC09446.1; -; mRNA.
DR   EMBL; AB015344; BAA34801.1; -; mRNA.
DR   CCDS; CCDS14374.1; -.
DR   RefSeq; NP_038472.2; NM_013444.3.
DR   PDB; 1J8C; NMR; -; A=1-103.
DR   PDB; 2NBV; NMR; -; B=26-103.
DR   PDB; 6MUN; NMR; -; B/C=26-103.
DR   PDBsum; 1J8C; -.
DR   PDBsum; 2NBV; -.
DR   PDBsum; 6MUN; -.
DR   SMR; Q9UHD9; -.
DR   BioGrid; 119006; 94.
DR   CORUM; Q9UHD9; -.
DR   DIP; DIP-42116N; -.
DR   IntAct; Q9UHD9; 256.
DR   MINT; Q9UHD9; -.
DR   STRING; 9606.ENSP00000345195; -.
DR   MoonDB; Q9UHD9; Predicted.
DR   iPTMnet; Q9UHD9; -.
DR   PhosphoSitePlus; Q9UHD9; -.
DR   BioMuta; UBQLN2; -.
DR   DMDM; 124056593; -.
DR   EPD; Q9UHD9; -.
DR   jPOST; Q9UHD9; -.
DR   MassIVE; Q9UHD9; -.
DR   MaxQB; Q9UHD9; -.
DR   PaxDb; Q9UHD9; -.
DR   PeptideAtlas; Q9UHD9; -.
DR   PRIDE; Q9UHD9; -.
DR   ProteomicsDB; 84333; -.
DR   Ensembl; ENST00000338222; ENSP00000345195; ENSG00000188021.
DR   GeneID; 29978; -.
DR   KEGG; hsa:29978; -.
DR   UCSC; uc004dus.4; human.
DR   CTD; 29978; -.
DR   DisGeNET; 29978; -.
DR   EuPathDB; HostDB:ENSG00000188021.8; -.
DR   GeneCards; UBQLN2; -.
DR   GeneReviews; UBQLN2; -.
DR   HGNC; HGNC:12509; UBQLN2.
DR   HPA; CAB013481; -.
DR   HPA; HPA006431; -.
DR   MalaCards; UBQLN2; -.
DR   MIM; 300264; gene.
DR   MIM; 300857; phenotype.
DR   neXtProt; NX_Q9UHD9; -.
DR   OpenTargets; ENSG00000188021; -.
DR   Orphanet; 803; Amyotrophic lateral sclerosis.
DR   PharmGKB; PA37156; -.
DR   eggNOG; KOG0010; Eukaryota.
DR   eggNOG; COG5272; LUCA.
DR   GeneTree; ENSGT00940000162603; -.
DR   HOGENOM; HOG000234878; -.
DR   InParanoid; Q9UHD9; -.
DR   KO; K04523; -.
DR   OMA; PQQGTEN; -.
DR   OrthoDB; 1553668at2759; -.
DR   PhylomeDB; Q9UHD9; -.
DR   TreeFam; TF314412; -.
DR   Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR   ChiTaRS; UBQLN2; human.
DR   EvolutionaryTrace; Q9UHD9; -.
DR   GeneWiki; UBQLN2; -.
DR   GenomeRNAi; 29978; -.
DR   Pharos; Q9UHD9; Tbio.
DR   PRO; PR:Q9UHD9; -.
DR   Proteomes; UP000005640; Chromosome X.
DR   RNAct; Q9UHD9; protein.
DR   Bgee; ENSG00000188021; Expressed in 245 organ(s), highest expression level in cerebellar vermis.
DR   Genevisible; Q9UHD9; HS.
DR   GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR   GO; GO:0031593; F:polyubiquitin modification-dependent protein binding; IBA:GO_Central.
DR   GO; GO:0000045; P:autophagosome assembly; IBA:GO_Central.
DR   GO; GO:1900186; P:negative regulation of clathrin-dependent endocytosis; IMP:UniProtKB.
DR   GO; GO:1904021; P:negative regulation of G protein-coupled receptor internalization; IMP:UniProtKB.
DR   GO; GO:1903071; P:positive regulation of ER-associated ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR   GO; GO:2000785; P:regulation of autophagosome assembly; IMP:UniProtKB.
DR   GO; GO:0016241; P:regulation of macroautophagy; IMP:UniProtKB.
DR   GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IMP:UniProtKB.
DR   GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR   DisProt; DP01110; -.
DR   InterPro; IPR016024; ARM-type_fold.
DR   InterPro; IPR041243; STI1.
DR   InterPro; IPR006636; STI1_HS-bd.
DR   InterPro; IPR015940; UBA.
DR   InterPro; IPR009060; UBA-like_sf.
DR   InterPro; IPR015496; Ubiquilin.
DR   InterPro; IPR028430; Ubiquilin-2.
DR   InterPro; IPR000626; Ubiquitin-like_dom.
DR   InterPro; IPR029071; Ubiquitin-like_domsf.
DR   PANTHER; PTHR10677; PTHR10677; 1.
DR   PANTHER; PTHR10677:SF5; PTHR10677:SF5; 1.
DR   Pfam; PF17830; STI1; 1.
DR   Pfam; PF00627; UBA; 1.
DR   Pfam; PF00240; ubiquitin; 1.
DR   SMART; SM00727; STI1; 4.
DR   SMART; SM00165; UBA; 1.
DR   SMART; SM00213; UBQ; 1.
DR   SUPFAM; SSF46934; SSF46934; 1.
DR   SUPFAM; SSF48371; SSF48371; 1.
DR   SUPFAM; SSF54236; SSF54236; 1.
DR   PROSITE; PS50030; UBA; 1.
DR   PROSITE; PS50053; UBIQUITIN_2; 1.
PE   1: Evidence at protein level;
DR   PRODOM; Q9UHD9.
DR   SWISS-2DPAGE; Q9UHD9.
KW   3D-structure; Acetylation; Amyotrophic lateral sclerosis; Autophagy;
KW   Cytoplasm; Cytoplasmic vesicle; Disease mutation; Membrane;
KW   Neurodegeneration; Nucleus; Polymorphism; Reference proteome; Repeat.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000244|PubMed:19413330,
FT                   ECO:0000244|PubMed:22814378"
FT   CHAIN           2..624
FT                   /note="Ubiquilin-2"
FT                   /id="PRO_0000211011"
FT   DOMAIN          33..107
FT                   /note="Ubiquitin-like"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT   DOMAIN          178..206
FT                   /note="STI1 1"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          208..247
FT                   /note="STI1 2"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          379..426
FT                   /note="STI1 3"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          430..462
FT                   /note="STI1 4"
FT                   /evidence="ECO:0000255"
FT   REPEAT          491..493
FT                   /note="1"
FT   REPEAT          494..496
FT                   /note="2"
FT   REPEAT          497..499
FT                   /note="3"
FT   REPEAT          500..502
FT                   /note="4"
FT   REPEAT          503..505
FT                   /note="5"
FT   REPEAT          506..508
FT                   /note="6"
FT   REPEAT          509..511
FT                   /note="7"
FT   REPEAT          512..514
FT                   /note="8"
FT   REPEAT          515..517
FT                   /note="9"
FT   REPEAT          518..520
FT                   /note="10"
FT   REPEAT          521..523
FT                   /note="11"
FT   REPEAT          524..526
FT                   /note="12"
FT   DOMAIN          581..621
FT                   /note="UBA"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT   REGION          491..526
FT                   /note="12 X 3 AA tandem repeats of P-X-X"
FT   MOD_RES         2
FT                   /note="N-acetylalanine"
FT                   /evidence="ECO:0000244|PubMed:19413330,
FT                   ECO:0000244|PubMed:22814378"
FT   VARIANT         155
FT                   /note="S -> N (in ALS15; uncertain pathological
FT                   significance; dbSNP:rs374522677)"
FT                   /evidence="ECO:0000269|PubMed:22560112"
FT                   /id="VAR_068892"
FT   VARIANT         189
FT                   /note="P -> T (in ALS15; uncertain pathological
FT                   significance; dbSNP:rs1490021329)"
FT                   /evidence="ECO:0000269|PubMed:22560112"
FT                   /id="VAR_068893"
FT   VARIANT         235
FT                   /note="L -> H (in dbSNP:rs17002693)"
FT                   /id="VAR_052680"
FT   VARIANT         282
FT                   /note="A -> V (probable disease-associated mutation found
FT                   in a patient with frontotemporal dementia;
FT                   dbSNP:rs1001930696)"
FT                   /evidence="ECO:0000269|PubMed:22892309"
FT                   /id="VAR_068894"
FT   VARIANT         283
FT                   /note="A -> T (in ALS15; dbSNP:rs749463696)"
FT                   /evidence="ECO:0000269|PubMed:22892309"
FT                   /id="VAR_068895"
FT   VARIANT         425
FT                   /note="Q -> R (in ALS15; dbSNP:rs1243726473)"
FT                   /evidence="ECO:0000269|PubMed:22892309"
FT                   /id="VAR_068896"
FT   VARIANT         487
FT                   /note="T -> I (in ALS15)"
FT                   /evidence="ECO:0000269|PubMed:22717235"
FT                   /id="VAR_068897"
FT   VARIANT         497
FT                   /note="P -> H (in ALS15; leads to defective ubiquitin-
FT                   mediated proteasomal degradation; reduces binding to
FT                   HNRNPA1 and FAF2; increases translocation of HNRNPA1 to the
FT                   cytoplasm; adversely affects ERAD; dbSNP:rs387906709)"
FT                   /evidence="ECO:0000269|PubMed:21857683,
FT                   ECO:0000269|PubMed:24215460, ECO:0000269|PubMed:25616961"
FT                   /id="VAR_066562"
FT   VARIANT         497
FT                   /note="P -> S (in ALS15; reduces binding to HNRNPA1;
FT                   increases translocation of HNRNPA1 to the cytoplasm;
FT                   dbSNP:rs387906710)"
FT                   /evidence="ECO:0000269|PubMed:21857683,
FT                   ECO:0000269|PubMed:25616961"
FT                   /id="VAR_066563"
FT   VARIANT         506
FT                   /note="P -> T (in ALS15; leads to defective ubiquitin-
FT                   mediated proteasomal degradation; reduces binding to
FT                   HNRNPA1; increases translocation of HNRNPA1 to the
FT                   cytoplasm; dbSNP:rs387906711)"
FT                   /evidence="ECO:0000269|PubMed:21857683,
FT                   ECO:0000269|PubMed:25616961"
FT                   /id="VAR_066564"
FT   VARIANT         509
FT                   /note="P -> S (in ALS15; reduces binding to HNRNPA1;
FT                   increases translocation of HNRNPA1 to the cytoplasm;
FT                   dbSNP:rs387906712)"
FT                   /evidence="ECO:0000269|PubMed:21857683,
FT                   ECO:0000269|PubMed:25616961"
FT                   /id="VAR_066565"
FT   VARIANT         525
FT                   /note="P -> S (in ALS15; reduces binding to HNRNPA1;
FT                   increases translocation of HNRNPA1 to the cytoplasm;
FT                   dbSNP:rs369947678)"
FT                   /evidence="ECO:0000269|PubMed:21857683,
FT                   ECO:0000269|PubMed:25616961"
FT                   /id="VAR_066566"
FT   CONFLICT        544
FT                   /note="S -> R (in Ref. 1; AAF17237 and 7; BAA34801)"
FT                   /evidence="ECO:0000305"
FT   STRAND          23..25
FT                   /evidence="ECO:0000244|PDB:1J8C"
FT   STRAND          33..38
FT                   /evidence="ECO:0000244|PDB:1J8C"
FT   STRAND          43..48
FT                   /evidence="ECO:0000244|PDB:1J8C"
FT   HELIX           54..65
FT                   /evidence="ECO:0000244|PDB:1J8C"
FT   STRAND          69..76
FT                   /evidence="ECO:0000244|PDB:1J8C"
FT   STRAND          79..82
FT                   /evidence="ECO:0000244|PDB:1J8C"
FT   HELIX           87..91
FT                   /evidence="ECO:0000244|PDB:1J8C"
FT   STRAND          93..102
FT                   /evidence="ECO:0000244|PDB:1J8C"
SQ   SEQUENCE   624 AA;  65696 MW;  DF7DF8C4D7B71AC3 CRC64;
     MAENGESSGP PRPSRGPAAA QGSAAAPAEP KIIKVTVKTP KEKEEFAVPE NSSVQQFKEA
     ISKRFKSQTD QLVLIFAGKI LKDQDTLIQH GIHDGLTVHL VIKSQNRPQG QSTQPSNAAG
     TNTTSASTPR SNSTPISTNS NPFGLGSLGG LAGLSSLGLS STNFSELQSQ MQQQLMASPE
     MMIQIMENPF VQSMLSNPDL MRQLIMANPQ MQQLIQRNPE ISHLLNNPDI MRQTLEIARN
     PAMMQEMMRN QDLALSNLES IPGGYNALRR MYTDIQEPML NAAQEQFGGN PFASVGSSSS
     SGEGTQPSRT ENRDPLPNPW APPPATQSSA TTSTTTSTGS GSGNSSSNAT GNTVAAANYV
     ASIFSTPGMQ SLLQQITENP QLIQNMLSAP YMRSMMQSLS QNPDLAAQMM LNSPLFTANP
     QLQEQMRPQL PAFLQQMQNP DTLSAMSNPR AMQALMQIQQ GLQTLATEAP GLIPSFTPGV
     GVGVLGTAIG PVGPVTPIGP IGPIVPFTPI GPIGPIGPTG PAAPPGSTGS GGPTGPTVSS
     AAPSETTSPT SESGPNQQFI QQMVQALAGA NAPQLPNPEV RFQQQLEQLN AMGFLNREAN
     LQALIATGGD INAAIERLLG SQPS
//

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