VCIP1_MOUSE
ID VCIP1_MOUSE Reviewed; 1220 AA.
AC Q8CDG3; Q7TMU9; Q8BP90;
DT 16-FEB-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Deubiquitinating protein VCPIP1 {ECO:0000305};
DE EC=3.4.19.12 {ECO:0000250|UniProtKB:Q96JH7};
DE AltName: Full=Valosin-containing protein p97/p47 complex-interacting protein 1 {ECO:0000305};
DE AltName: Full=Valosin-containing protein p97/p47 complex-interacting protein p135 {ECO:0000250|UniProtKB:Q8CF97};
DE Short=VCP/p47 complex-interacting 135-kDa protein {ECO:0000250|UniProtKB:Q8CF97};
GN Name=Vcpip1 {ECO:0000312|MGI:MGI:1917925};
GN Synonyms=Vcip135 {ECO:0000250|UniProtKB:Q8CF97};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Embryo, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Brain, and Hematopoietic;
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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1196, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=32649882; DOI=10.1016/j.molcel.2020.06.027;
RA Huang J., Zhou Q., Gao M., Nowsheen S., Zhao F., Kim W., Zhu Q., Kojima Y.,
RA Yin P., Zhang Y., Guo G., Tu X., Deng M., Luo K., Qin B., Machida Y.,
RA Lou Z.;
RT "Tandem deubiquitination and acetylation of SPRTN promotes DNA-protein
RT crosslink repair and protects against aging.";
RL Mol. Cell 0:0-0(2020).
CC -!- FUNCTION: Deubiquitinating enzyme involved in DNA repair and reassembly
CC of the Golgi apparatus and the endoplasmic reticulum following mitosis
CC (By similarity). Necessary for VCP-mediated reassembly of Golgi stacks
CC after mitosis. Plays a role in VCP-mediated formation of transitional
CC endoplasmic reticulum (tER). Mediates dissociation of the ternary
CC complex containing STX5A, NSFL1C and VCP (By similarity). Also involved
CC in DNA repair following phosphorylation by ATM or ATR: acts by
CC catalyzing deubiquitination of SPRTN, thereby promoting SPRTN
CC recruitment to chromatin and subsequent proteolytic cleavage of
CC covalent DNA-protein cross-links (DPCs). Hydrolyzes 'Lys-11'- and 'Lys-
CC 48'-linked polyubiquitin chains (By similarity).
CC {ECO:0000250|UniProtKB:Q8CF97, ECO:0000250|UniProtKB:Q96JH7}.
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:0000250|UniProtKB:Q96JH7};
CC -!- SUBUNIT: Binds VCP and the ternary complex containing STX5A, NSFL1C and
CC VCP. {ECO:0000250|UniProtKB:Q8CF97}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q96JH7}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q96JH7}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:Q8CF97}. Golgi apparatus, Golgi stack
CC {ECO:0000250|UniProtKB:Q8CF97}. Note=Associated with Golgi stacks and
CC endoplasmic reticulum (By similarity). Displays cytoplasmic to nuclear
CC translocation in response to DNA-protein cross-links (DPCs)-inducing
CC agents (By similarity). {ECO:0000250|UniProtKB:Q8CF97,
CC ECO:0000250|UniProtKB:Q96JH7}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8CDG3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8CDG3-2; Sequence=VSP_009376, VSP_009377;
CC -!- PTM: Phosphorylated at Ser-1205 by ATM or ATR following induction of
CC covalent DNA-protein cross-links (DPCs).
CC {ECO:0000250|UniProtKB:Q96JH7}.
CC -!- DISRUPTION PHENOTYPE: Mice were born at nearly Mendelian ratios,
CC although the birth rate was slightly decreased (PubMed:32649882). Mice
CC display genomic instability and premature aging (PubMed:32649882).
CC Cells show an accumulation of DNA-protein cross-links (DPCs)
CC (PubMed:32649882). {ECO:0000269|PubMed:32649882}.
CC -!- MISCELLANEOUS: [Isoform 2]: May be due to an intron retention.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH52908.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK030104; BAC26787.1; -; mRNA.
DR EMBL; AK077494; BAC36830.1; -; mRNA.
DR EMBL; BC052908; AAH52908.1; ALT_INIT; mRNA.
DR EMBL; BC059209; AAH59209.1; -; mRNA.
DR CCDS; CCDS14814.1; -. [Q8CDG3-1]
DR RefSeq; NP_775619.2; NM_173443.3.
DR AlphaFoldDB; Q8CDG3; -.
DR SMR; Q8CDG3; -.
DR BioGRID; 214195; 26.
DR IntAct; Q8CDG3; 12.
DR MINT; Q8CDG3; -.
DR STRING; 10090.ENSMUSP00000051248; -.
DR iPTMnet; Q8CDG3; -.
DR PhosphoSitePlus; Q8CDG3; -.
DR EPD; Q8CDG3; -.
DR jPOST; Q8CDG3; -.
DR MaxQB; Q8CDG3; -.
DR PaxDb; Q8CDG3; -.
DR PeptideAtlas; Q8CDG3; -.
DR PRIDE; Q8CDG3; -.
DR ProteomicsDB; 300116; -. [Q8CDG3-1]
DR ProteomicsDB; 300117; -. [Q8CDG3-2]
DR DNASU; 70675; -.
DR GeneID; 70675; -.
DR KEGG; mmu:70675; -.
DR UCSC; uc007ags.3; mouse. [Q8CDG3-1]
DR CTD; 80124; -.
DR MGI; MGI:1917925; Vcpip1.
DR eggNOG; KOG4345; Eukaryota.
DR InParanoid; Q8CDG3; -.
DR OrthoDB; 222681at2759; -.
DR PhylomeDB; Q8CDG3; -.
DR TreeFam; TF329469; -.
DR Reactome; R-MMU-5689896; Ovarian tumor domain proteases.
DR BioGRID-ORCS; 70675; 10 hits in 71 CRISPR screens.
DR ChiTaRS; Vcpip1; mouse.
DR PRO; PR:Q8CDG3; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q8CDG3; protein.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005795; C:Golgi stack; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0045202; C:synapse; IDA:SynGO.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0016320; P:endoplasmic reticulum membrane fusion; ISO:MGI.
DR GO; GO:0007030; P:Golgi organization; ISO:MGI.
DR GO; GO:0090168; P:Golgi reassembly; ISO:MGI.
DR GO; GO:0000278; P:mitotic cell cycle; ISO:MGI.
DR GO; GO:0016579; P:protein deubiquitination; ISS:UniProtKB.
DR GO; GO:0035871; P:protein K11-linked deubiquitination; ISS:UniProtKB.
DR GO; GO:0071108; P:protein K48-linked deubiquitination; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0106300; P:protein-DNA covalent cross-linking repair; ISS:UniProtKB.
DR GO; GO:1905634; P:regulation of protein localization to chromatin; ISS:UniProtKB.
DR InterPro; IPR003323; OTU_dom.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR InterPro; IPR039087; VCPIP1.
DR InterPro; IPR045827; VCPIP1_N.
DR PANTHER; PTHR14843; PTHR14843; 1.
DR Pfam; PF02338; OTU; 1.
DR Pfam; PF19437; VCIP135_N; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR PROSITE; PS50802; OTU; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cytoplasm; DNA damage; DNA repair;
KW Endoplasmic reticulum; Golgi apparatus; Hydrolase; Nucleus; Phosphoprotein;
KW Protease; Reference proteome; Thiol protease; Ubl conjugation pathway.
FT CHAIN 1..1220
FT /note="Deubiquitinating protein VCPIP1"
FT /id="PRO_0000065770"
FT DOMAIN 207..360
FT /note="OTU"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00139"
FT REGION 1..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 724..778
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 988..1008
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1113..1140
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1185..1220
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..21
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 740..774
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 215
FT /evidence="ECO:0000250|UniProtKB:Q96FW1"
FT ACT_SITE 218
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q8CF97"
FT ACT_SITE 353
FT /evidence="ECO:0000250|UniProtKB:Q96FW1"
FT MOD_RES 407
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q96JH7"
FT MOD_RES 746
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96JH7"
FT MOD_RES 756
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96JH7"
FT MOD_RES 762
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q96JH7"
FT MOD_RES 767
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96JH7"
FT MOD_RES 993
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96JH7"
FT MOD_RES 997
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96JH7"
FT MOD_RES 1076
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96JH7"
FT MOD_RES 1196
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1205
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96JH7"
FT VAR_SEQ 904..906
FT /note="EDV -> KSN (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_009376"
FT VAR_SEQ 907..1220
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_009377"
FT CONFLICT 471
FT /note="Y -> C (in Ref. 2; AAH59209)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1220 AA; 134503 MW; 8062E3C17DCD2E3B CRC64;
MSQPPPPPPL PPPPPPPEAP QTSSSLAAAA SPGGLSKRRD RRILSGSCPD PKCQARLFFP
ASGSVSIECT ECGQRHEQQQ LLGVEEVTDP DVVLHNLLRN ALLGVTGAPK KNTELVKVMG
LSNYHCKLLS PILARYGMDK QTGRAKLLRD MNQGELFDCA LLGDRAFLIE PEHVNTVGYG
KDRSGSLLYL HDTLEDIKRA NKSQECLIPV HVDGDGHCLV HAVSRALVGR ELFWHALREN
LKQHFQQHLA RYQALFHDFI DAAEWEDIIN ECDPLFVPPE GVPLGLRNIH IFGLANVLHR
PIILLDSLSG MRSSGDYSAT FLPGLIPAEK CTGRDGHLNK PICIAWSSSG RNHYIPLVGI
KGAALPKLPM NLLPKAWGVP QDLIKKYIKL EEDGGCVIGG DRSLQDKYLL RLVAAMEEVF
MDKHGIHPSL VADVHQYFYR RTGVIGVQPE EVTAAAKKAV MDNRLHKCLL YGALSELHVP
SEWLAPGGKL YNLAKSTHGQ LRPDKNYSFP LNNLVCSYDP VKDVLLPDYG LSNLTACNWC
HGSSVRRVRG DGSIVYLDGD RTNSRSTGGK CGCGFKHFWE GKEYDNLPEA FPITLEWGGR
VVRETVYWFQ YESDPSLNSN VYDVAMKLVT KHFPGEFGSE ILVQKVVHTI LHQTAKKNPD
DYTPVNIDGA HAQRVGDVQG QELESQLPTK IILTGQKTKT LHKEELNMSK TERTIQQNIT
EQASVMQKRK TEKLKQEQKG QPRTVSPSTI RDGPSSAPAT PTKAPYSPTT SKEKKIRITT
NDGRQSMVTL KPSTTFFELQ ESIAREFNIP PYLQCIRYGF PPKELMPPQA GMEKEPVPLQ
HGDRITIEIL KGRAEGGPST AAHSAHTVKQ EEIAVTGKLS SKELQEQADK EMYSLCLLAT
LMGEDVWSYA KGLPHMFQQG GVFYNIMKKT MGMADGKHCT FPHLPGKTFV YNASEDRLEL
CVDAAGHFPI GPDVEDLVKE AVSQVRAEAT TRSRESSPSH GLLKLGSGGV VKKKSEQLHN
VTAFQGKGHS LGTASSHPHI DPRARETLAV RKHNTGTDFS NSSIKTEPPV FTAASSNSEL
IRIAPGVVTM RDGRQIDPDV VEAQRKKLQE MVSSIQASMD KHLRDQSAEQ APSDLSQRKV
EVVSSVRPVN LQTGLPEPFS LTGGTENLNT ETTDSHVADV LGAAFATRSK AQKENSMEEP
EEMDSQDAET TNTTEPMDHS
