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 03-AUG-2022, entry version 185.
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 Q9UHD9; Q9NYB9-2: ABI2; NbExp=3; IntAct=EBI-947187, EBI-11096309;
CC Q9UHD9; O00154-4: ACOT7; NbExp=3; IntAct=EBI-947187, EBI-12007918;
CC Q9UHD9; O15072: ADAMTS3; NbExp=3; IntAct=EBI-947187, EBI-12200127;
CC Q9UHD9; Q16186: ADRM1; NbExp=5; IntAct=EBI-947187, EBI-954387;
CC Q9UHD9; O95994: AGR2; NbExp=5; IntAct=EBI-947187, EBI-712648;
CC Q9UHD9; Q8TD06: AGR3; NbExp=6; IntAct=EBI-947187, EBI-3925742;
CC Q9UHD9; Q9NP70: AMBN; NbExp=3; IntAct=EBI-947187, EBI-11893530;
CC Q9UHD9; Q7Z3H0-1: ANKRD33; NbExp=3; IntAct=EBI-947187, EBI-16746154;
CC Q9UHD9; P55056: APOC4; NbExp=3; IntAct=EBI-947187, EBI-18302142;
CC Q9UHD9; Q96B67: ARRDC3; NbExp=3; IntAct=EBI-947187, EBI-2875665;
CC Q9UHD9; P50553: ASCL1; NbExp=3; IntAct=EBI-947187, EBI-957042;
CC Q9UHD9; P45381: ASPA; NbExp=3; IntAct=EBI-947187, EBI-750475;
CC Q9UHD9; Q9UBB4: ATXN10; NbExp=3; IntAct=EBI-947187, EBI-702390;
CC Q9UHD9; P25311: AZGP1; NbExp=3; IntAct=EBI-947187, EBI-2513837;
CC Q9UHD9; P46379-2: BAG6; NbExp=3; IntAct=EBI-947187, EBI-10988864;
CC Q9UHD9; O43521: BCL2L11; NbExp=3; IntAct=EBI-947187, EBI-526406;
CC Q9UHD9; Q9NP55: BPIFA1; NbExp=3; IntAct=EBI-947187, EBI-953896;
CC Q9UHD9; Q6P1W5: C1orf94; NbExp=3; IntAct=EBI-947187, EBI-946029;
CC Q9UHD9; P02745: C1QA; NbExp=6; IntAct=EBI-947187, EBI-1220209;
CC Q9UHD9; P02746: C1QB; NbExp=3; IntAct=EBI-947187, EBI-2813376;
CC Q9UHD9; P02747: C1QC; NbExp=5; IntAct=EBI-947187, EBI-1220222;
CC Q9UHD9; Q86Z23: C1QL4; NbExp=3; IntAct=EBI-947187, EBI-12062109;
CC Q9UHD9; Q9BXJ5: C1QTNF2; NbExp=3; IntAct=EBI-947187, EBI-2817707;
CC Q9UHD9; Q9BXJ3: C1QTNF4; NbExp=3; IntAct=EBI-947187, EBI-11955105;
CC Q9UHD9; Q6UXA7: C6orf15; NbExp=8; IntAct=EBI-947187, EBI-11990870;
CC Q9UHD9; P07360: C8G; NbExp=3; IntAct=EBI-947187, EBI-9021652;
CC Q9UHD9; O75808: CAPN15; NbExp=3; IntAct=EBI-947187, EBI-6149008;
CC Q9UHD9; P06307: CCK; NbExp=3; IntAct=EBI-947187, EBI-6624398;
CC Q9UHD9; O15467: CCL16; NbExp=3; IntAct=EBI-947187, EBI-12204739;
CC Q9UHD9; P10147: CCL3; NbExp=3; IntAct=EBI-947187, EBI-8459634;
CC Q9UHD9; P80098: CCL7; NbExp=3; IntAct=EBI-947187, EBI-718759;
CC Q9UHD9; O00622: CCN1; NbExp=3; IntAct=EBI-947187, EBI-1237454;
CC Q9UHD9; Q8TCZ2: CD99L2; NbExp=3; IntAct=EBI-947187, EBI-2824782;
CC Q9UHD9; P55291: CDH15; NbExp=3; IntAct=EBI-947187, EBI-10215061;
CC Q9UHD9; Q12864: CDH17; NbExp=3; IntAct=EBI-947187, EBI-12278850;
CC Q9UHD9; Q9H305: CDIP1; NbExp=3; IntAct=EBI-947187, EBI-2876678;
CC Q9UHD9; P40199: CEACAM6; NbExp=5; IntAct=EBI-947187, EBI-4314501;
CC Q9UHD9; Q9Y240: CLEC11A; NbExp=3; IntAct=EBI-947187, EBI-3957044;
CC Q9UHD9; Q6UWE3: CLPSL2; NbExp=6; IntAct=EBI-947187, EBI-12183429;
CC Q9UHD9; Q8NE01: CNNM3; NbExp=3; IntAct=EBI-947187, EBI-741032;
CC Q9UHD9; Q03692: COL10A1; NbExp=3; IntAct=EBI-947187, EBI-2528309;
CC Q9UHD9; Q9UMD9: COL17A1; NbExp=3; IntAct=EBI-947187, EBI-2528742;
CC Q9UHD9; P08123: COL1A2; NbExp=5; IntAct=EBI-947187, EBI-983038;
CC Q9UHD9; P27658: COL8A1; NbExp=3; IntAct=EBI-947187, EBI-747133;
CC Q9UHD9; Q14055: COL9A2; NbExp=3; IntAct=EBI-947187, EBI-714971;
CC Q9UHD9; Q8IYK4: COLGALT2; NbExp=3; IntAct=EBI-947187, EBI-10263496;
CC Q9UHD9; P47710: CSN1S1; NbExp=3; IntAct=EBI-947187, EBI-2433045;
CC Q9UHD9; P05814: CSN2; NbExp=6; IntAct=EBI-947187, EBI-1642112;
CC Q9UHD9; P07498: CSN3; NbExp=3; IntAct=EBI-947187, EBI-2602175;
CC Q9UHD9; P01037: CST1; NbExp=3; IntAct=EBI-947187, EBI-1056240;
CC Q9UHD9; P01036: CST4; NbExp=3; IntAct=EBI-947187, EBI-1049999;
CC Q9UHD9; P33240: CSTF2; NbExp=5; IntAct=EBI-947187, EBI-711360;
CC Q9UHD9; Q9H0L4: CSTF2T; NbExp=5; IntAct=EBI-947187, EBI-747012;
CC Q9UHD9; P78358: CTAG1B; NbExp=3; IntAct=EBI-947187, EBI-1188472;
CC Q9UHD9; O95476: CTDNEP1; NbExp=3; IntAct=EBI-947187, EBI-5323433;
CC Q9UHD9; Q15038: DAZAP2; NbExp=3; IntAct=EBI-947187, EBI-724310;
CC Q9UHD9; Q08345-2: DDR1; NbExp=5; IntAct=EBI-947187, EBI-711903;
CC Q9UHD9; P59665: DEFA1B; NbExp=3; IntAct=EBI-947187, EBI-726336;
CC Q9UHD9; Q01524: DEFA6; NbExp=6; IntAct=EBI-947187, EBI-10222451;
CC Q9UHD9; Q30KQ5: DEFB115; NbExp=3; IntAct=EBI-947187, EBI-12253292;
CC Q9UHD9; Q6ICB0: DESI1; NbExp=5; IntAct=EBI-947187, EBI-2806959;
CC Q9UHD9; Q6E0U4: DMKN; NbExp=3; IntAct=EBI-947187, EBI-7943171;
CC Q9UHD9; Q9H596: DUSP21; NbExp=5; IntAct=EBI-947187, EBI-7357329;
CC Q9UHD9; Q16610: ECM1; NbExp=3; IntAct=EBI-947187, EBI-947964;
CC Q9UHD9; Q9H1Z8: ECRG4; NbExp=3; IntAct=EBI-947187, EBI-12208839;
CC Q9UHD9; Q12805: EFEMP1; NbExp=3; IntAct=EBI-947187, EBI-536772;
CC Q9UHD9; Q8IUX8: EGFL6; NbExp=3; IntAct=EBI-947187, EBI-715208;
CC Q9UHD9; P42566: EPS15; NbExp=2; IntAct=EBI-947187, EBI-396684;
CC Q9UHD9; Q96DN0: ERP27; NbExp=3; IntAct=EBI-947187, EBI-953772;
CC Q9UHD9; P30040: ERP29; NbExp=3; IntAct=EBI-947187, EBI-946830;
CC Q9UHD9; Q9HBU6: ETNK1; NbExp=3; IntAct=EBI-947187, EBI-2834493;
CC Q9UHD9; P00742: F10; NbExp=3; IntAct=EBI-947187, EBI-719750;
CC Q9UHD9; Q92567-2: FAM168A; NbExp=3; IntAct=EBI-947187, EBI-11978259;
CC Q9UHD9; Q8WU58: FAM222B; NbExp=3; IntAct=EBI-947187, EBI-2807642;
CC Q9UHD9; Q8NFU4: FDCSP; NbExp=3; IntAct=EBI-947187, EBI-12210457;
CC Q9UHD9; O60258: FGF17; NbExp=3; IntAct=EBI-947187, EBI-12184083;
CC Q9UHD9; P26885: FKBP2; NbExp=3; IntAct=EBI-947187, EBI-719873;
CC Q9UHD9; Q9BVV2: FNDC11; NbExp=3; IntAct=EBI-947187, EBI-744935;
CC Q9UHD9; P04066: FUCA1; NbExp=5; IntAct=EBI-947187, EBI-2512153;
CC Q9UHD9; O75084: FZD7; NbExp=3; IntAct=EBI-947187, EBI-746917;
CC Q9UHD9; P22466: GAL; NbExp=3; IntAct=EBI-947187, EBI-6624768;
CC Q9UHD9; Q9UBC7: GALP; NbExp=6; IntAct=EBI-947187, EBI-12244186;
CC Q9UHD9; Q9UBU3: GHRL; NbExp=3; IntAct=EBI-947187, EBI-10319458;
CC Q9UHD9; Q16538: GPR162; NbExp=3; IntAct=EBI-947187, EBI-22387200;
CC Q9UHD9; Q96SL4: GPX7; NbExp=3; IntAct=EBI-947187, EBI-749411;
CC Q9UHD9; Q02747: GUCA2A; NbExp=3; IntAct=EBI-947187, EBI-12244272;
CC Q9UHD9; Q16661: GUCA2B; NbExp=3; IntAct=EBI-947187, EBI-12349759;
CC Q9UHD9; A0A024R8L2: hCG_1987119; NbExp=3; IntAct=EBI-947187, EBI-14103818;
CC Q9UHD9; Q9Y5R4: HEMK1; NbExp=3; IntAct=EBI-947187, EBI-10329202;
CC Q9UHD9; P07686: HEXB; NbExp=3; IntAct=EBI-947187, EBI-7133736;
CC Q9UHD9; O14964: HGS; NbExp=3; IntAct=EBI-947187, EBI-740220;
CC Q9UHD9; P09651: HNRNPA1; NbExp=2; IntAct=EBI-947187, EBI-352662;
CC Q9UHD9; P09651-2: HNRNPA1; NbExp=4; IntAct=EBI-947187, EBI-352677;
CC Q9UHD9; Q00839: HNRNPU; NbExp=3; IntAct=EBI-947187, EBI-351126;
CC Q9UHD9; Q53GQ0: HSD17B12; NbExp=3; IntAct=EBI-947187, EBI-2963255;
CC Q9UHD9; P48723: HSPA13; NbExp=5; IntAct=EBI-947187, EBI-750892;
CC Q9UHD9; P42858: HTT; NbExp=12; IntAct=EBI-947187, EBI-466029;
CC Q9UHD9; P05362: ICAM1; NbExp=5; IntAct=EBI-947187, EBI-1035358;
CC Q9UHD9; P01562: IFNA1; NbExp=3; IntAct=EBI-947187, EBI-11478589;
CC Q9UHD9; P24592: IGFBP6; NbExp=3; IntAct=EBI-947187, EBI-947015;
CC Q9UHD9; P15814: IGLL1; NbExp=3; IntAct=EBI-947187, EBI-1222221;
CC Q9UHD9; P20809: IL11; NbExp=3; IntAct=EBI-947187, EBI-751694;
CC Q9UHD9; P0C7M6: IQCF3; NbExp=3; IntAct=EBI-947187, EBI-11953784;
CC Q9UHD9; P53990-3: IST1; NbExp=3; IntAct=EBI-947187, EBI-12188567;
CC Q9UHD9; P27987: ITPKB; NbExp=5; IntAct=EBI-947187, EBI-751388;
CC Q9UHD9; Q6GPH6-2: ITPRIPL1; NbExp=3; IntAct=EBI-947187, EBI-12337095;
CC Q9UHD9; Q96JJ6: JPH4; NbExp=3; IntAct=EBI-947187, EBI-2847044;
CC Q9UHD9; Q15726: KISS1; NbExp=3; IntAct=EBI-947187, EBI-23759979;
CC Q9UHD9; Q9NVR0: KLHL11; NbExp=3; IntAct=EBI-947187, EBI-2691832;
CC Q9UHD9; Q9P2K6: KLHL42; NbExp=5; IntAct=EBI-947187, EBI-739890;
CC Q9UHD9; P02538: KRT6A; NbExp=3; IntAct=EBI-947187, EBI-702198;
CC Q9UHD9; P59990: KRTAP12-1; NbExp=3; IntAct=EBI-947187, EBI-10210845;
CC Q9UHD9; Q7Z4W3: KRTAP19-3; NbExp=3; IntAct=EBI-947187, EBI-12020132;
CC Q9UHD9; Q3LI72: KRTAP19-5; NbExp=3; IntAct=EBI-947187, EBI-1048945;
CC Q9UHD9; Q6ISS4: LAIR2; NbExp=3; IntAct=EBI-947187, EBI-10250491;
CC Q9UHD9; Q14847-2: LASP1; NbExp=3; IntAct=EBI-947187, EBI-9088686;
CC Q9UHD9; O95835-2: LATS1; NbExp=3; IntAct=EBI-947187, EBI-17978514;
CC Q9UHD9; P31025: LCN1; NbExp=3; IntAct=EBI-947187, EBI-1052433;
CC Q9UHD9; P80188: LCN2; NbExp=5; IntAct=EBI-947187, EBI-11911016;
CC Q9UHD9; Q99732: LITAF; NbExp=3; IntAct=EBI-947187, EBI-725647;
CC Q9UHD9; P61968: LMO4; NbExp=3; IntAct=EBI-947187, EBI-2798728;
CC Q9UHD9; O95868: LY6G6D; NbExp=3; IntAct=EBI-947187, EBI-12382527;
CC Q9UHD9; Q9Y5V3: MAGED1; NbExp=3; IntAct=EBI-947187, EBI-716006;
CC Q9UHD9; P11226: MBL2; NbExp=5; IntAct=EBI-947187, EBI-5325353;
CC Q9UHD9; P21741: MDK; NbExp=3; IntAct=EBI-947187, EBI-722444;
CC Q9UHD9; Q9NQG6: MIEF1; NbExp=3; IntAct=EBI-947187, EBI-740987;
CC Q9UHD9; Q96C03-3: MIEF2; NbExp=3; IntAct=EBI-947187, EBI-11988931;
CC Q9UHD9; Q9UNW1: MINPP1; NbExp=3; IntAct=EBI-947187, EBI-4290963;
CC Q9UHD9; Q96BY2: MOAP1; NbExp=3; IntAct=EBI-947187, EBI-739825;
CC Q9UHD9; O75431: MTX2; NbExp=3; IntAct=EBI-947187, EBI-7415268;
CC Q9UHD9; Q969H8: MYDGF; NbExp=3; IntAct=EBI-947187, EBI-718622;
CC Q9UHD9; Q8IW45: NAXD; NbExp=3; IntAct=EBI-947187, EBI-8650724;
CC Q9UHD9; P41271-2: NBL1; NbExp=3; IntAct=EBI-947187, EBI-12135485;
CC Q9UHD9; Q9UHB4: NDOR1; NbExp=3; IntAct=EBI-947187, EBI-10249760;
CC Q9UHD9; Q13232: NME3; NbExp=3; IntAct=EBI-947187, EBI-713684;
CC Q9UHD9; Q9BVI4: NOC4L; NbExp=3; IntAct=EBI-947187, EBI-395927;
CC Q9UHD9; O60936: NOL3; NbExp=3; IntAct=EBI-947187, EBI-740992;
CC Q9UHD9; P48145: NPBWR1; NbExp=3; IntAct=EBI-947187, EBI-13061492;
CC Q9UHD9; P01160: NPPA; NbExp=3; IntAct=EBI-947187, EBI-953859;
CC Q9UHD9; Q9HCQ7: NPVF; NbExp=3; IntAct=EBI-947187, EBI-1753111;
CC Q9UHD9; P01303: NPY; NbExp=3; IntAct=EBI-947187, EBI-3905877;
CC Q9UHD9; Q496H8: NRN1L; NbExp=3; IntAct=EBI-947187, EBI-13079132;
CC Q9UHD9; Q9H0P0: NT5C3A; NbExp=3; IntAct=EBI-947187, EBI-3918356;
CC Q9UHD9; Q9BVL2: NUP58; NbExp=3; IntAct=EBI-947187, EBI-2811583;
CC Q9UHD9; Q17RF5: ODAPH; NbExp=3; IntAct=EBI-947187, EBI-10239029;
CC Q9UHD9; Q9UHM6: OPN4; NbExp=3; IntAct=EBI-947187, EBI-18058356;
CC Q9UHD9; Q8NG98: OR7D4; NbExp=3; IntAct=EBI-947187, EBI-18164026;
CC Q9UHD9; Q99650: OSMR; NbExp=3; IntAct=EBI-947187, EBI-2804080;
CC Q9UHD9; Q6UWI2: PARM1; NbExp=3; IntAct=EBI-947187, EBI-12350959;
CC Q9UHD9; Q9Y5G4-2: PCDHGA9; NbExp=3; IntAct=EBI-947187, EBI-12202741;
CC Q9UHD9; Q8IYJ0: PIANP; NbExp=3; IntAct=EBI-947187, EBI-12204277;
CC Q9UHD9; Q96FE7: PIK3IP1; NbExp=3; IntAct=EBI-947187, EBI-10285708;
CC Q9UHD9; Q13526: PIN1; NbExp=5; IntAct=EBI-947187, EBI-714158;
CC Q9UHD9; Q9NWW9: PLAAT2; NbExp=3; IntAct=EBI-947187, EBI-12253270;
CC Q9UHD9; P53816: PLAAT3; NbExp=3; IntAct=EBI-947187, EBI-746318;
CC Q9UHD9; Q96CS7: PLEKHB2; NbExp=3; IntAct=EBI-947187, EBI-373552;
CC Q9UHD9; Q969W9-2: PMEPA1; NbExp=3; IntAct=EBI-947187, EBI-13318883;
CC Q9UHD9; Q9UL41: PNMA3; NbExp=3; IntAct=EBI-947187, EBI-11278955;
CC Q9UHD9; O00592-2: PODXL; NbExp=5; IntAct=EBI-947187, EBI-12407415;
CC Q9UHD9; P56282: POLE2; NbExp=3; IntAct=EBI-947187, EBI-713847;
CC Q9UHD9; Q96HA1-2: POM121; NbExp=3; IntAct=EBI-947187, EBI-11956563;
CC Q9UHD9; P23284: PPIB; NbExp=5; IntAct=EBI-947187, EBI-359252;
CC Q9UHD9; P45877: PPIC; NbExp=5; IntAct=EBI-947187, EBI-953909;
CC Q9UHD9; O43447: PPIH; NbExp=3; IntAct=EBI-947187, EBI-1055615;
CC Q9UHD9; Q96NZ9: PRAP1; NbExp=6; IntAct=EBI-947187, EBI-2116102;
CC Q9UHD9; Q16378: PRR4; NbExp=6; IntAct=EBI-947187, EBI-738624;
CC Q9UHD9; Q13200: PSMD2; NbExp=3; IntAct=EBI-947187, EBI-357648;
CC Q9UHD9; Q9UIG4: PSORS1C2; NbExp=3; IntAct=EBI-947187, EBI-11974061;
CC Q9UHD9; P41222: PTGDS; NbExp=6; IntAct=EBI-947187, EBI-948821;
CC Q9UHD9; Q16769: QPCT; NbExp=3; IntAct=EBI-947187, EBI-2856807;
CC Q9UHD9; P54725: RAD23A; NbExp=6; IntAct=EBI-947187, EBI-746453;
CC Q9UHD9; P54727: RAD23B; NbExp=3; IntAct=EBI-947187, EBI-954531;
CC Q9UHD9; O43251-10: RBFOX2; NbExp=3; IntAct=EBI-947187, EBI-11963050;
CC Q9UHD9; Q9BX46-2: RBM24; NbExp=3; IntAct=EBI-947187, EBI-12224445;
CC Q9UHD9; Q9Y3C5: RNF11; NbExp=4; IntAct=EBI-947187, EBI-396669;
CC Q9UHD9; Q8TEB7: RNF128; NbExp=3; IntAct=EBI-947187, EBI-2341619;
CC Q9UHD9; Q9H0X6: RNF208; NbExp=6; IntAct=EBI-947187, EBI-751555;
CC Q9UHD9; P78317: RNF4; NbExp=3; IntAct=EBI-947187, EBI-2340927;
CC Q9UHD9; P62979: RPS27A; NbExp=3; IntAct=EBI-947187, EBI-357375;
CC Q9UHD9; Q7L4I2: RSRC2; NbExp=3; IntAct=EBI-947187, EBI-953753;
CC Q9UHD9; Q9BWD3: RTL8A; NbExp=3; IntAct=EBI-947187, EBI-741643;
CC Q9UHD9; Q17RB0: RTL8B; NbExp=3; IntAct=EBI-947187, EBI-10238588;
CC Q9UHD9; A6ZKI3: RTL8C; NbExp=5; IntAct=EBI-947187, EBI-10174072;
CC Q9UHD9; P05408: SCG5; NbExp=3; IntAct=EBI-947187, EBI-722635;
CC Q9UHD9; Q4G0G5: SCGB2B2; NbExp=3; IntAct=EBI-947187, EBI-12019232;
CC Q9UHD9; P04279-2: SEMG1; NbExp=3; IntAct=EBI-947187, EBI-12272118;
CC Q9UHD9; P05121: SERPINE1; NbExp=3; IntAct=EBI-947187, EBI-953978;
CC Q9UHD9; O75830: SERPINI2; NbExp=3; IntAct=EBI-947187, EBI-750144;
CC Q9UHD9; Q53EL9: SEZ6; NbExp=3; IntAct=EBI-947187, EBI-723710;
CC Q9UHD9; Q9BYH1-5: SEZ6L; NbExp=3; IntAct=EBI-947187, EBI-12012146;
CC Q9UHD9; Q8IWL1: SFTPA2; NbExp=6; IntAct=EBI-947187, EBI-12350685;
CC Q9UHD9; O43765: SGTA; NbExp=3; IntAct=EBI-947187, EBI-347996;
CC Q9UHD9; O15427: SLC16A3; NbExp=3; IntAct=EBI-947187, EBI-7600166;
CC Q9UHD9; Q96PX8: SLITRK1; NbExp=3; IntAct=EBI-947187, EBI-7137880;
CC Q9UHD9; P03973: SLPI; NbExp=3; IntAct=EBI-947187, EBI-355293;
CC Q9UHD9; P58511: SMIM11; NbExp=3; IntAct=EBI-947187, EBI-1051936;
CC Q9UHD9; Q96E16: SMIM19; NbExp=3; IntAct=EBI-947187, EBI-17657124;
CC Q9UHD9; Q9BVW6: SMIM2; NbExp=3; IntAct=EBI-947187, EBI-10300146;
CC Q9UHD9; P02814: SMR3B; NbExp=3; IntAct=EBI-947187, EBI-738612;
CC Q9UHD9; P14678-2: SNRPB; NbExp=3; IntAct=EBI-947187, EBI-372475;
CC Q9UHD9; P08294: SOD3; NbExp=3; IntAct=EBI-947187, EBI-10195782;
CC Q9UHD9; Q08648-4: SPAG11B; NbExp=3; IntAct=EBI-947187, EBI-14835966;
CC Q9UHD9; O43278-2: SPINT1; NbExp=3; IntAct=EBI-947187, EBI-12078338;
CC Q9UHD9; P16150: SPN; NbExp=3; IntAct=EBI-947187, EBI-10049055;
CC Q9UHD9; P10124: SRGN; NbExp=3; IntAct=EBI-947187, EBI-744915;
CC Q9UHD9; Q9UHB9-2: SRP68; NbExp=3; IntAct=EBI-947187, EBI-12210563;
CC Q9UHD9; O75886: STAM2; NbExp=3; IntAct=EBI-947187, EBI-373258;
CC Q9UHD9; P51687: SUOX; NbExp=3; IntAct=EBI-947187, EBI-3921347;
CC Q9UHD9; Q5VX71-3: SUSD4; NbExp=3; IntAct=EBI-947187, EBI-12017810;
CC Q9UHD9; Q96A09: TENT5B; NbExp=3; IntAct=EBI-947187, EBI-752030;
CC Q9UHD9; Q07654: TFF3; NbExp=3; IntAct=EBI-947187, EBI-10224676;
CC Q9UHD9; Q9BVV7: TIMM21; NbExp=3; IntAct=EBI-947187, EBI-6570759;
CC Q9UHD9; P16035: TIMP2; NbExp=3; IntAct=EBI-947187, EBI-1033507;
CC Q9UHD9; Q8N131: TMEM123; NbExp=3; IntAct=EBI-947187, EBI-749248;
CC Q9UHD9; Q9Y5U5-2: TNFRSF18; NbExp=3; IntAct=EBI-947187, EBI-12197205;
CC Q9UHD9; Q6UXN7: TOMM20L; NbExp=3; IntAct=EBI-947187, EBI-11954062;
CC Q9UHD9; Q9BUZ4: TRAF4; NbExp=3; IntAct=EBI-947187, EBI-3650647;
CC Q9UHD9; Q13049: TRIM32; NbExp=3; IntAct=EBI-947187, EBI-742790;
CC Q9UHD9; O95881: TXNDC12; NbExp=3; IntAct=EBI-947187, EBI-2564581;
CC Q9UHD9; Q8NBS9: TXNDC5; NbExp=3; IntAct=EBI-947187, EBI-2510815;
CC Q9UHD9; Q9BZF9: UACA; NbExp=3; IntAct=EBI-947187, EBI-350510;
CC Q9UHD9; P62987: UBA52; NbExp=3; IntAct=EBI-947187, EBI-357304;
CC Q9UHD9; Q9BSL1: UBAC1; NbExp=3; IntAct=EBI-947187, EBI-749370;
CC Q9UHD9; P0CG47: UBB; NbExp=3; IntAct=EBI-947187, EBI-413034;
CC Q9UHD9; P0CG48: UBC; NbExp=3; IntAct=EBI-947187, EBI-3390054;
CC Q9UHD9; Q7KZS0: UBE2I; NbExp=3; IntAct=EBI-947187, EBI-10180829;
CC Q9UHD9; Q13404: UBE2V1; NbExp=3; IntAct=EBI-947187, EBI-1050671;
CC Q9UHD9; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-947187, EBI-741480;
CC Q9UHD9; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-947187, EBI-947187;
CC Q9UHD9; Q04323-2: UBXN1; NbExp=3; IntAct=EBI-947187, EBI-11530712;
CC Q9UHD9; O94888: UBXN7; NbExp=3; IntAct=EBI-947187, EBI-1993627;
CC Q9UHD9; Q6NVU6: UFSP1; NbExp=3; IntAct=EBI-947187, EBI-12068150;
CC Q9UHD9; O95231: VENTX; NbExp=3; IntAct=EBI-947187, EBI-10191303;
CC Q9UHD9; P01282-2: VIP; NbExp=3; IntAct=EBI-947187, EBI-12320391;
CC Q9UHD9; P04004: VTN; NbExp=3; IntAct=EBI-947187, EBI-1036653;
CC Q9UHD9; Q2TAL6: VWC2; NbExp=3; IntAct=EBI-947187, EBI-11957238;
CC Q9UHD9; Q8IUB3: WFDC10B; NbExp=3; IntAct=EBI-947187, EBI-10261124;
CC Q9UHD9; Q8WWY7: WFDC12; NbExp=6; IntAct=EBI-947187, EBI-11958577;
CC Q9UHD9; Q8N6M9: ZFAND2A; NbExp=3; IntAct=EBI-947187, EBI-3921109;
CC Q9UHD9; Q8WV99: ZFAND2B; NbExp=3; IntAct=EBI-947187, EBI-747823;
CC Q9UHD9; O60844: ZG16; NbExp=3; IntAct=EBI-947187, EBI-746479;
CC Q9UHD9; Q96DA0: ZG16B; NbExp=6; IntAct=EBI-947187, EBI-953824;
CC Q9UHD9; O95201: ZNF205; NbExp=3; IntAct=EBI-947187, EBI-747343;
CC Q9UHD9; A0A1U9X8X8; NbExp=6; IntAct=EBI-947187, EBI-17234977;
CC Q9UHD9; Q96FB2; NbExp=3; IntAct=EBI-947187, EBI-2857623;
CC Q9UHD9; P0DTC6: 6; Xeno; NbExp=4; IntAct=EBI-947187, EBI-25475897;
CC Q9UHD9; P0DTD3: 9c; Xeno; NbExp=4; IntAct=EBI-947187, EBI-25475917;
CC Q9UHD9; O48726: RPN13; Xeno; NbExp=4; IntAct=EBI-947187, EBI-7710745;
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 variants
CC affecting the gene represented in this entry.
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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 AlphaFoldDB; Q9UHD9; -.
DR SMR; Q9UHD9; -.
DR BioGRID; 119006; 781.
DR CORUM; Q9UHD9; -.
DR DIP; DIP-42116N; -.
DR IntAct; Q9UHD9; 270.
DR MINT; Q9UHD9; -.
DR STRING; 9606.ENSP00000345195; -.
DR MoonDB; Q9UHD9; Predicted.
DR GlyGen; Q9UHD9; 20 sites, 2 O-linked glycans (20 sites).
DR iPTMnet; Q9UHD9; -.
DR MetOSite; 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 ABCD; Q9UHD9; 1 sequenced antibody.
DR Antibodypedia; 570; 303 antibodies from 34 providers.
DR DNASU; 29978; -.
DR Ensembl; ENST00000338222.7; ENSP00000345195.5; ENSG00000188021.9.
DR GeneID; 29978; -.
DR KEGG; hsa:29978; -.
DR MANE-Select; ENST00000338222.7; ENSP00000345195.5; NM_013444.4; NP_038472.2.
DR UCSC; uc004dus.4; human.
DR CTD; 29978; -.
DR DisGeNET; 29978; -.
DR GeneCards; UBQLN2; -.
DR HGNC; HGNC:12509; UBQLN2.
DR HPA; ENSG00000188021; Low tissue specificity.
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 VEuPathDB; HostDB:ENSG00000188021; -.
DR eggNOG; KOG0010; Eukaryota.
DR GeneTree; ENSGT00940000162603; -.
DR HOGENOM; CLU_024293_4_0_1; -.
DR InParanoid; Q9UHD9; -.
DR OMA; QMMNNPD; -.
DR OrthoDB; 1553668at2759; -.
DR PhylomeDB; Q9UHD9; -.
DR TreeFam; TF314412; -.
DR PathwayCommons; Q9UHD9; -.
DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR SignaLink; Q9UHD9; -.
DR SIGNOR; Q9UHD9; -.
DR BioGRID-ORCS; 29978; 9 hits in 705 CRISPR screens.
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 cerebellar vermis and 217 other tissues.
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:0042802; F:identical protein binding; IPI:IntAct.
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 InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR006636; STI1_HS-bd.
DR InterPro; IPR015940; UBA.
DR InterPro; IPR009060; UBA-like_sf.
DR InterPro; IPR028430; Ubiquilin-1/2.
DR InterPro; IPR000626; Ubiquitin-like_dom.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR PANTHER; PTHR10677:SF5; PTHR10677:SF5; 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;
KW 3D-structure; Acetylation; Amyotrophic lateral sclerosis; Autophagy;
KW Cytoplasm; Cytoplasmic vesicle; Disease variant; Membrane;
KW Neurodegeneration; Nucleus; Reference proteome; Repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|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 1..32
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 106..141
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 287..349
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 491..526
FT /note="12 X 3 AA tandem repeats of P-X-X"
FT REGION 512..556
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 287..313
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 325..349
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 530..556
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|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 variant found in
FT 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; dbSNP:rs1569254459)"
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:0007829|PDB:1J8C"
FT STRAND 33..38
FT /evidence="ECO:0007829|PDB:1J8C"
FT STRAND 43..48
FT /evidence="ECO:0007829|PDB:1J8C"
FT HELIX 54..65
FT /evidence="ECO:0007829|PDB:1J8C"
FT STRAND 69..76
FT /evidence="ECO:0007829|PDB:1J8C"
FT STRAND 79..82
FT /evidence="ECO:0007829|PDB:1J8C"
FT HELIX 87..91
FT /evidence="ECO:0007829|PDB:1J8C"
FT STRAND 93..102
FT /evidence="ECO:0007829|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
