ID   VCIP1_HUMAN             Reviewed;        1222 AA.
AC   Q96JH7; Q504T4; Q86T93; Q86W01; Q8N3A9; Q9H5R8;
DT   16-FEB-2004, integrated into UniProtKB/Swiss-Prot.
DT   16-FEB-2004, sequence version 2.
DT   22-APR-2020, entry version 153.
DE   RecName: Full=Deubiquitinating protein VCIP135;
DE            EC=3.4.19.12;
DE   AltName: Full=Valosin-containing protein p97/p47 complex-interacting protein 1;
DE   AltName: Full=Valosin-containing protein p97/p47 complex-interacting protein p135;
DE            Short=VCP/p47 complex-interacting 135-kDa protein;
GN   Name=VCPIP1; Synonyms=KIAA1850, VCIP135;
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 [LARGE SCALE MRNA].
RC   TISSUE=Brain;
RX   PubMed=11347906; DOI=10.1093/dnares/8.2.85;
RA   Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. XX. The
RT   complete sequences of 100 new cDNA clones from brain which code for large
RT   proteins in vitro.";
RL   DNA Res. 8:85-95(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Melanoma;
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Testis, and Uterus;
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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 586-1184.
RC   TISSUE=Lung;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-747; THR-763; SER-994 AND
RP   SER-1198, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1198, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Leukemic T-cell;
RX   PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA   Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA   Rodionov V., Han D.K.;
RT   "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT   reveals system-wide modulation of protein-protein interactions.";
RL   Sci. Signal. 2:RA46-RA46(2009).
RN   [7]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-408, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19608861; DOI=10.1126/science.1175371;
RA   Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA   Olsen J.V., Mann M.;
RT   "Lysine acetylation targets protein complexes and co-regulates major
RT   cellular functions.";
RL   Science 325:834-840(2009).
RN   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1198, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA   Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA   Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT   "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT   site occupancy during mitosis.";
RL   Sci. Signal. 3:RA3-RA3(2010).
RN   [9]
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   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1198, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA   Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA   Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT   "System-wide temporal characterization of the proteome and phosphoproteome
RT   of human embryonic stem cell differentiation.";
RL   Sci. Signal. 4:RS3-RS3(2011).
RN   [11]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=23827681; DOI=10.1016/j.cell.2013.05.046;
RA   Mevissen T.E., Hospenthal M.K., Geurink P.P., Elliott P.R., Akutsu M.,
RA   Arnaudo N., Ekkebus R., Kulathu Y., Wauer T., El Oualid F., Freund S.M.,
RA   Ovaa H., Komander D.;
RT   "OTU deubiquitinases reveal mechanisms of linkage specificity and enable
RT   ubiquitin chain restriction analysis.";
RL   Cell 154:169-184(2013).
RN   [12]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-747; SER-757; SER-768;
RP   SER-994; SER-998; SER-1077 AND SER-1198, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma, and Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [13]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
CC   -!- FUNCTION: Acts as a deubiquitinating enzyme. Necessary for VCP-mediated
CC       reassembly of Golgi stacks after mitosis. May play a role in VCP-
CC       mediated formation of transitional endoplasmic reticulum (tER).
CC       Mediates dissociation of the ternary complex containing STX5A, NSFL1C
CC       and VCP (By similarity). Hydrolyzes 'Lys-11'- and 'Lys-48'-linked
CC       polyubiquitin chains. {ECO:0000250, ECO:0000269|PubMed:23827681}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide
CC         and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-
CC         residue protein attached to proteins as an intracellular targeting
CC         signal).; EC=3.4.19.12; Evidence={ECO:0000269|PubMed:23827681};
CC   -!- SUBUNIT: Binds VCP and the ternary complex containing STX5A, NSFL1C and
CC       VCP. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum {ECO:0000250}. Golgi
CC       apparatus, Golgi stack {ECO:0000250}. Note=Associated with Golgi stacks
CC       and endoplasmic reticulum. {ECO:0000250}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAB15552.1; Type=Frameshift; Evidence={ECO:0000305};
CC       Sequence=BAB47479.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; AB058753; BAB47479.1; ALT_INIT; mRNA.
DR   EMBL; AL834476; CAD39135.1; -; mRNA.
DR   EMBL; AL832606; CAD89944.1; -; mRNA.
DR   EMBL; BC049379; AAH49379.1; -; mRNA.
DR   EMBL; BC094799; AAH94799.1; -; mRNA.
DR   EMBL; AK026785; BAB15552.1; ALT_FRAME; mRNA.
DR   CCDS; CCDS6192.1; -.
DR   RefSeq; NP_079330.2; NM_025054.4.
DR   SMR; Q96JH7; -.
DR   BioGrid; 123125; 70.
DR   IntAct; Q96JH7; 42.
DR   MINT; Q96JH7; -.
DR   STRING; 9606.ENSP00000309031; -.
DR   MEROPS; C64.006; -.
DR   iPTMnet; Q96JH7; -.
DR   MetOSite; Q96JH7; -.
DR   PhosphoSitePlus; Q96JH7; -.
DR   BioMuta; VCPIP1; -.
DR   DMDM; 42560002; -.
DR   EPD; Q96JH7; -.
DR   jPOST; Q96JH7; -.
DR   MassIVE; Q96JH7; -.
DR   MaxQB; Q96JH7; -.
DR   PaxDb; Q96JH7; -.
DR   PeptideAtlas; Q96JH7; -.
DR   PRIDE; Q96JH7; -.
DR   ProteomicsDB; 76963; -.
DR   Antibodypedia; 24885; 91 antibodies.
DR   DNASU; 80124; -.
DR   Ensembl; ENST00000310421; ENSP00000309031; ENSG00000175073.
DR   GeneID; 80124; -.
DR   KEGG; hsa:80124; -.
DR   UCSC; uc003xwn.4; human.
DR   CTD; 80124; -.
DR   GeneCards; VCPIP1; -.
DR   HGNC; HGNC:30897; VCPIP1.
DR   HPA; ENSG00000175073; Low tissue specificity.
DR   MIM; 611745; gene.
DR   neXtProt; NX_Q96JH7; -.
DR   OpenTargets; ENSG00000175073; -.
DR   PharmGKB; PA142670629; -.
DR   eggNOG; ENOG410IQZJ; Eukaryota.
DR   eggNOG; ENOG410ZMR9; LUCA.
DR   GeneTree; ENSGT00390000002854; -.
DR   HOGENOM; CLU_009674_0_0_1; -.
DR   InParanoid; Q96JH7; -.
DR   KO; K11861; -.
DR   OMA; AHSAHAV; -.
DR   OrthoDB; 222681at2759; -.
DR   PhylomeDB; Q96JH7; -.
DR   TreeFam; TF329469; -.
DR   Reactome; R-HSA-5689896; Ovarian tumor domain proteases.
DR   ChiTaRS; VCPIP1; human.
DR   GeneWiki; VCPIP1; -.
DR   GenomeRNAi; 80124; -.
DR   Pharos; Q96JH7; Tbio.
DR   PRO; PR:Q96JH7; -.
DR   Proteomes; UP000005640; Chromosome 8.
DR   RNAct; Q96JH7; protein.
DR   Bgee; ENSG00000175073; Expressed in tendon of biceps brachii and 165 other tissues.
DR   Genevisible; Q96JH7; HS.
DR   GO; GO:0005737; C:cytoplasm; IDA:LIFEdb.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR   GO; GO:0005795; C:Golgi stack; IEA:UniProtKB-SubCell.
DR   GO; GO:0004843; F:thiol-dependent ubiquitin-specific protease activity; IDA:UniProtKB.
DR   GO; GO:0016320; P:endoplasmic reticulum membrane fusion; IBA:GO_Central.
DR   GO; GO:0090168; P:Golgi reassembly; IBA:GO_Central.
DR   GO; GO:0000278; P:mitotic cell cycle; IEA:Ensembl.
DR   GO; GO:0035871; P:protein K11-linked deubiquitination; IDA:UniProtKB.
DR   GO; GO:0071108; P:protein K48-linked deubiquitination; IDA:UniProtKB.
DR   GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR   InterPro; IPR003323; OTU_dom.
DR   InterPro; IPR029071; Ubiquitin-like_domsf.
DR   InterPro; IPR039087; VCIP135.
DR   PANTHER; PTHR14843; PTHR14843; 1.
DR   Pfam; PF02338; OTU; 1.
DR   SUPFAM; SSF54236; SSF54236; 1.
DR   PROSITE; PS50802; OTU; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Endoplasmic reticulum; Golgi apparatus; Hydrolase;
KW   Phosphoprotein; Protease; Reference proteome; Thiol protease;
KW   Ubl conjugation pathway.
FT   CHAIN           1..1222
FT                   /note="Deubiquitinating protein VCIP135"
FT                   /id="PRO_0000065769"
FT   DOMAIN          208..361
FT                   /note="OTU"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00139"
FT   COMPBIAS        4..24
FT                   /note="Pro-rich"
FT   ACT_SITE        216
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        219
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        354
FT                   /evidence="ECO:0000250"
FT   MOD_RES         408
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000244|PubMed:19608861"
FT   MOD_RES         747
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:18669648,
FT                   ECO:0000244|PubMed:23186163"
FT   MOD_RES         757
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:23186163"
FT   MOD_RES         763
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000244|PubMed:18669648"
FT   MOD_RES         768
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:23186163"
FT   MOD_RES         994
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:18669648,
FT                   ECO:0000244|PubMed:23186163"
FT   MOD_RES         998
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:23186163"
FT   MOD_RES         1077
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:23186163"
FT   MOD_RES         1198
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:18669648,
FT                   ECO:0000244|PubMed:19690332, ECO:0000244|PubMed:20068231,
FT                   ECO:0000244|PubMed:21406692, ECO:0000244|PubMed:23186163"
FT   CONFLICT        169
FT                   /note="L -> P (in Ref. 2; CAD89944)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        437
FT                   /note="Q -> R (in Ref. 2; CAD89944)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        811
FT                   /note="P -> F (in Ref. 3; AAH49379)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        927
FT                   /note="Missing (in Ref. 3)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        988
FT                   /note="A -> S (in Ref. 3; AAH49379)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1222 AA;  134321 MW;  5CE99D723386782D CRC64;
     MSQPPPPPPP LPPPPPPPEA PQTPSSLASA AASGGLLKRR DRRILSGSCP DPKCQARLFF
     PASGSVSIEC TECGQRHEQQ QLLGVEEVTD PDVVLHNLLR NALLGVTGAP KKNTELVKVM
     GLSNYHCKLL SPILARYGMD KQTGRAKLLR DMNQGELFDC ALLGDRAFLI EPEHVNTVGY
     GKDRSGSLLY LHDTLEDIKR ANKSQECLIP VHVDGDGHCL VHAVSRALVG RELFWHALRE
     NLKQHFQQHL ARYQALFHDF IDAAEWEDII NECDPLFVPP EGVPLGLRNI HIFGLANVLH
     RPIILLDSLS GMRSSGDYSA TFLPGLIPAE KCTGKDGHLN KPICIAWSSS GRNHYIPLVG
     IKGAALPKLP MNLLPKAWGV PQDLIKKYIK LEEDGGCVIG GDRSLQDKYL LRLVAAMEEV
     FMDKHGIHPS LVADVHQYFY RRTGVIGVQP EEVTAAAKKA VMDNRLHKCL LCGALSELHV
     PPEWLAPGGK LYNLAKSTHG QLRTDKNYSF PLNNLVCSYD SVKDVLVPDY GMSNLTACNW
     CHGTSVRKVR GDGSIVYLDG DRTNSRSTGG KCGCGFKHFW DGKEYDNLPE AFPITLEWGG
     RVVRETVYWF QYESDSSLNS NVYDVAMKLV TKHFPGEFGS EILVQKVVHT ILHQTAKKNP
     DDYTPVNIDG AHAQRVGDVQ GQESESQLPT KIILTGQKTK TLHKEELNMS KTERTIQQNI
     TEQASVMQKR KTEKLKQEQK GQPRTVSPST IRDGPSSAPA TPTKAPYSPT TSKEKKIRIT
     TNDGRQSMVT LKSSTTFFEL QESIAREFNI PPYLQCIRYG FPPKELMPPQ AGMEKEPVPL
     QHGDRITIEI LKSKAEGGQS AAAHSAHTVK QEDIAVTGKL SSKELQEQAE KEMYSLCLLA
     TLMGEDVWSY AKGLPHMFQQ GGVFYSIMKK TMGMADGKHC TFPHLPGKTF VYNASEDRLE
     LCVDAAGHFP IGPDVEDLVK EAVSQVRAEA TTRSRESSPS HGLLKLGSGG VVKKKSEQLH
     NVTAFQGKGH SLGTASGNPH LDPRARETSV VRKHNTGTDF SNSSTKTEPS VFTASSSNSE
     LIRIAPGVVT MRDGRQLDPD LVEAQRKKLQ EMVSSIQASM DRHLRDQSTE QSPSDLPQRK
     TEVVSSSAKS GSLQTGLPES FPLTGGTENL NTETTDGCVA DALGAAFATR SKAQRGNSVE
     ELEEMDSQDA EMTNTTEPMD HS
//