Full text data of USP4
USP4
(UNP, UNPH)
[Confidence: low (only semi-automatic identification from reviews)]
Ubiquitin carboxyl-terminal hydrolase 4; 3.4.19.12 (Deubiquitinating enzyme 4; Ubiquitin thioesterase 4; Ubiquitin-specific-processing protease 4; Ubiquitous nuclear protein homolog)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Ubiquitin carboxyl-terminal hydrolase 4; 3.4.19.12 (Deubiquitinating enzyme 4; Ubiquitin thioesterase 4; Ubiquitin-specific-processing protease 4; Ubiquitous nuclear protein homolog)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q13107
ID UBP4_HUMAN Reviewed; 963 AA.
AC Q13107; A8K6Y0; C9IY91; O43452; O43453; Q08AK8;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 17-OCT-2006, sequence version 3.
DT 22-JAN-2014, entry version 132.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 4;
DE EC=3.4.19.12;
DE AltName: Full=Deubiquitinating enzyme 4;
DE AltName: Full=Ubiquitin thioesterase 4;
DE AltName: Full=Ubiquitin-specific-processing protease 4;
DE AltName: Full=Ubiquitous nuclear protein homolog;
GN Name=USP4; Synonyms=UNP, UNPH;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Brain cortex;
RX PubMed=7784062;
RA Gray D.A., Inazawa J., Gupta K., Wong A., Ueda R., Takahashi T.;
RT "Elevated expression of Unph, a proto-oncogene at 3p21.3, in human
RT lung tumors.";
RL Oncogene 10:2179-2183(1995).
RN [2]
RP SEQUENCE REVISION.
RA Gray D.A.;
RL Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND ALTERNATIVE
RP SPLICING.
RC TISSUE=B-cell, and T-cell;
RX PubMed=9464533; DOI=10.1038/sj.onc.1201537;
RA Frederick A., Rolfe M., Chiu M.I.;
RT "The human UNP locus at 3p21.31 encodes two tissue-selective,
RT cytoplasmic isoforms with deubiquitinating activity that have reduced
RT expression in small cell lung carcinoma cell lines.";
RL Oncogene 16:153-165(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Leukocyte;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP INTERACTION WITH RB1, AND MUTAGENESIS OF GLU-463 AND 459-LEU--GLU-463.
RX PubMed=11571652; DOI=10.1038/sj.onc.1204824;
RA DeSalle L.M., Latres E., Lin D., Graner E., Montagnoli A., Baker R.T.,
RA Pagano M., Loda M.;
RT "The de-ubiquitinating enzyme Unp interacts with the retinoblastoma
RT protein.";
RL Oncogene 20:5538-5542(2001).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-311.
RX PubMed=16316627; DOI=10.1016/j.bbrc.2005.11.076;
RA Wada K., Tanji K., Kamitani T.;
RT "Oncogenic protein UnpEL/Usp4 deubiquitinates Ro52 by its isopeptidase
RT activity.";
RL Biochem. Biophys. Res. Commun. 339:731-736(2006).
RN [9]
RP FUNCTION, AUTODEUBIQUITINATION, UBIQUITINATION BY TRIM21, AND
RP MUTAGENESIS OF CYS-311.
RX PubMed=16472766; DOI=10.1016/j.bbrc.2006.01.144;
RA Wada K., Kamitani T.;
RT "UnpEL/Usp4 is ubiquitinated by Ro52 and deubiquitinated by itself.";
RL Biochem. Biophys. Res. Commun. 342:253-258(2006).
RN [10]
RP FUNCTION, INTERACTION WITH ADORA2A, AND TISSUE SPECIFICITY.
RX PubMed=16339847; DOI=10.1124/mol.105.015818;
RA Milojevic T., Reiterer V., Stefan E., Korkhov V.M., Dorostkar M.M.,
RA Ducza E., Ogris E., Boehm S., Freissmuth M., Nanoff C.;
RT "The ubiquitin-specific protease Usp4 regulates the cell surface level
RT of the A2A receptor.";
RL Mol. Pharmacol. 69:1083-1094(2006).
RN [11]
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.,
RA Buerckstuemmer T., 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 [12]
RP DEUBIQUITINATION OF PDPK1.
RX PubMed=22347420; DOI=10.1371/journal.pone.0031003;
RA Uras I.Z., List T., Nijman S.M.;
RT "Ubiquitin-specific protease 4 inhibits mono-ubiquitination of the
RT master growth factor signaling kinase PDK1.";
RL PLoS ONE 7:E31003-E31003(2012).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 296-932, DOMAINS
RP UBIQUITIN-LIKE, AND ZINC-BINDING SITES.
RX PubMed=21415856; DOI=10.1038/embor.2011.33;
RA Luna-Vargas M.P., Faesen A.C., van Dijk W.J., Rape M., Fish A.,
RA Sixma T.K.;
RT "Ubiquitin-specific protease 4 is inhibited by its ubiquitin-like
RT domain.";
RL EMBO Rep. 12:365-372(2011).
CC -!- FUNCTION: Hydrolase that deubiquitinates target proteins such as
CC the receptor ADORA2A, PDPK1 and TRIM21. Deubiquitination of
CC ADORA2A increases the amount of functional receptor at the cell
CC surface. Plays a role in the regulation of quality control in the
CC ER.
CC -!- CATALYTIC ACTIVITY: Thiol-dependent hydrolysis of ester,
CC thioester, amide, peptide and isopeptide bonds formed by the C-
CC terminal Gly of ubiquitin (a 76-residue protein attached to
CC proteins as an intracellular targeting signal).
CC -!- SUBUNIT: Interacts with RB1 (both dephosphorylated and
CC hypophosphorylated forms). Interacts with ADORA2A (via cytoplasmic
CC C-terminus); the interaction is direct. Interacts with RB1, RBL1
CC and RBL2.
CC -!- INTERACTION:
CC Self; NbExp=3; IntAct=EBI-723290, EBI-723290;
CC P29274:ADORA2A; NbExp=4; IntAct=EBI-723290, EBI-2902702;
CC Q7Z6Z7:HUWE1; NbExp=4; IntAct=EBI-723290, EBI-625934;
CC Q13546:RIPK1; NbExp=4; IntAct=EBI-723290, EBI-358507;
CC P19474:TRIM21; NbExp=3; IntAct=EBI-723305, EBI-81290;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By
CC similarity). Note=Shuttles between the nucleus and cytoplasm.
CC Exported to the cytoplasm in a CRM1-dependent manner and recycled
CC back to the nucleus via the importin alpha/beta heterodimeric
CC import receptor. The relative amounts found in the nucleus and
CC cytoplasm vary according to the cell type (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=UnpEL;
CC IsoId=Q13107-1; Sequence=Displayed;
CC Name=2; Synonyms=UnpES;
CC IsoId=Q13107-2; Sequence=VSP_005258;
CC Name=3;
CC IsoId=Q13107-3; Sequence=VSP_044814, VSP_044815;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Overexpressed in small cell tumors and
CC adenocarcinomas of the lung compared to wild-type lung (at protein
CC level). Expressed in the hippocampal neurons.
CC -!- DOMAIN: The Ubiquitin-like domain 2 inserts into the catalytic
CC domain and competes with the ubiquitin substrate, partially
CC inhibiting DUB activity.
CC -!- PTM: Monoubiquitinated by TRIM21. Ubiquitination does not lead to
CC its proteasomal degradation. Autodeubiquitinated.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. USP4 subfamily.
CC -!- SIMILARITY: Contains 1 DUSP domain.
CC -!- SIMILARITY: Contains 2 ubiquitin-like domains.
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DR EMBL; U20657; AAB72237.1; -; mRNA.
DR EMBL; AF017305; AAC27355.1; -; mRNA.
DR EMBL; AF017306; AAC27356.1; -; mRNA.
DR EMBL; AK291795; BAF84484.1; -; mRNA.
DR EMBL; AC121247; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC068017; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC125130; AAI25131.1; -; mRNA.
DR PIR; T09478; T09478.
DR RefSeq; NP_001238806.1; NM_001251877.1.
DR RefSeq; NP_003354.2; NM_003363.3.
DR RefSeq; NP_955475.1; NM_199443.2.
DR UniGene; Hs.403828; -.
DR UniGene; Hs.77500; -.
DR PDB; 2Y6E; X-ray; 2.40 A; A/B/C/D/E/F=296-932.
DR PDBsum; 2Y6E; -.
DR ProteinModelPortal; Q13107; -.
DR SMR; Q13107; 8-226, 297-483, 740-930.
DR IntAct; Q13107; 32.
DR MINT; MINT-3027027; -.
DR STRING; 9606.ENSP00000265560; -.
DR MEROPS; C19.010; -.
DR PhosphoSite; Q13107; -.
DR DMDM; 116242839; -.
DR PaxDb; Q13107; -.
DR PRIDE; Q13107; -.
DR Ensembl; ENST00000265560; ENSP00000265560; ENSG00000114316.
DR Ensembl; ENST00000351842; ENSP00000341028; ENSG00000114316.
DR Ensembl; ENST00000416417; ENSP00000400623; ENSG00000114316.
DR GeneID; 7375; -.
DR KEGG; hsa:7375; -.
DR UCSC; uc021wxv.1; human.
DR CTD; 7375; -.
DR GeneCards; GC03M049315; -.
DR HGNC; HGNC:12627; USP4.
DR HPA; HPA018499; -.
DR MIM; 603486; gene.
DR neXtProt; NX_Q13107; -.
DR PharmGKB; PA37252; -.
DR eggNOG; COG5560; -.
DR HOGENOM; HOG000264375; -.
DR HOVERGEN; HBG000864; -.
DR InParanoid; Q13107; -.
DR KO; K11835; -.
DR OMA; CERISRY; -.
DR PhylomeDB; Q13107; -.
DR ChiTaRS; USP4; human.
DR EvolutionaryTrace; Q13107; -.
DR GeneWiki; USP4; -.
DR GenomeRNAi; 7375; -.
DR NextBio; 28880; -.
DR PRO; PR:Q13107; -.
DR ArrayExpress; Q13107; -.
DR Bgee; Q13107; -.
DR CleanEx; HS_USP4; -.
DR Genevestigator; Q13107; -.
DR GO; GO:0005764; C:lysosome; TAS:ProtInc.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0004843; F:deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004221; F:ubiquitin thiolesterase activity; IMP:UniProtKB.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; IMP:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; IDA:UniProtKB.
DR GO; GO:0034394; P:protein localization to cell surface; IDA:UniProtKB.
DR GO; GO:0031647; P:regulation of protein stability; IDA:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR InterPro; IPR006615; Pept_C19_DUSP.
DR InterPro; IPR018200; Pept_C19ubi-hydrolase_C_CS.
DR InterPro; IPR001394; Peptidase_C19/C67.
DR InterPro; IPR028135; Ub_USP-typ.
DR InterPro; IPR028134; USP.
DR PANTHER; PTHR24006:SF34; PTHR24006:SF34; 1.
DR Pfam; PF06337; DUSP; 1.
DR Pfam; PF14836; Ubiquitin_3; 1.
DR Pfam; PF00443; UCH; 1.
DR SMART; SM00695; DUSP; 1.
DR PROSITE; PS51283; DUSP; 1.
DR PROSITE; PS00299; UBIQUITIN_1; FALSE_NEG.
DR PROSITE; PS50053; UBIQUITIN_2; FALSE_NEG.
DR PROSITE; PS00972; UCH_2_1; 1.
DR PROSITE; PS00973; UCH_2_2; 1.
DR PROSITE; PS50235; UCH_2_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome; Cytoplasm;
KW Hydrolase; Metal-binding; Nucleus; Polymorphism; Protease;
KW Proto-oncogene; Reference proteome; Repeat; Thiol protease;
KW Ubl conjugation; Ubl conjugation pathway; Zinc.
FT CHAIN 1 963 Ubiquitin carboxyl-terminal hydrolase 4.
FT /FTId=PRO_0000080621.
FT DOMAIN 11 122 DUSP.
FT DOMAIN 142 226 Ubiquitin-like 1.
FT DOMAIN 483 571 Ubiquitin-like 2.
FT REGION 405 407 Necessary for interaction with RBL2 (By
FT similarity).
FT REGION 459 463 Necessary for interaction with RB1 and
FT RBL2 (By similarity).
FT MOTIF 133 141 Nuclear export signal (By similarity).
FT MOTIF 767 772 Nuclear localization signal (By
FT similarity).
FT ACT_SITE 311 311 Nucleophile.
FT ACT_SITE 881 881 Proton acceptor (By similarity).
FT METAL 461 461 Zinc.
FT METAL 464 464 Zinc.
FT METAL 799 799 Zinc.
FT METAL 802 802 Zinc.
FT VAR_SEQ 232 279 KSSTAPSRNFTTSPKSSASPYSSVSASLIANGDSTSTCGMH
FT SSGVSRG -> N (in isoform 2).
FT /FTId=VSP_005258.
FT VAR_SEQ 233 313 SSTAPSRNFTTSPKSSASPYSSVSASLIANGDSTSTCGMHS
FT SGVSRGGSGFSASYNCQEPPSSHIQPGLCGLGNLGNTCFM
FT -> VSFFLPRLECNGAILAHCNFCLPGSSNSPASASRVAPS
FT HLANFFFFEMESHSVTKLECGGAVSAYSRVQVMLLPQPPEW
FT LG (in isoform 3).
FT /FTId=VSP_044814.
FT VAR_SEQ 314 963 Missing (in isoform 3).
FT /FTId=VSP_044815.
FT VARIANT 620 620 Y -> C (in dbSNP:rs9311440).
FT /FTId=VAR_028180.
FT MUTAGEN 311 311 C->A: Loss of activity. Its
FT ubiquitination by TRIM21 is enhanced.
FT MUTAGEN 459 463 LVCPE->AVRPH: Reduces the interaction
FT with RB1.
FT MUTAGEN 463 463 E->Q: Reduces the interaction with RB1.
FT CONFLICT 373 373 R -> S (in Ref. 1; AAB72237).
FT CONFLICT 744 744 S -> R (in Ref. 1; AAB72237).
FT HELIX 311 321
FT HELIX 324 331
FT HELIX 335 338
FT HELIX 350 362
FT STRAND 364 366
FT STRAND 368 370
FT HELIX 373 382
FT HELIX 384 386
FT STRAND 388 390
FT HELIX 394 408
FT HELIX 428 442
FT HELIX 446 451
FT STRAND 453 460
FT TURN 462 464
FT STRAND 467 480
FT HELIX 778 785
FT STRAND 797 799
FT TURN 800 803
FT STRAND 804 806
FT STRAND 809 816
FT STRAND 819 826
FT STRAND 828 830
FT STRAND 835 837
FT HELIX 852 854
FT STRAND 858 860
FT STRAND 864 874
FT STRAND 876 879
FT STRAND 881 887
FT TURN 889 891
FT STRAND 894 898
FT STRAND 901 904
FT HELIX 907 909
FT STRAND 915 922
SQ SEQUENCE 963 AA; 108565 MW; 63055C9ADFE36713 CRC64;
MAEGGGCRER PDAETQKSEL GPLMRTTLQR GAQWYLIDSR WFKQWKKYVG FDSWDMYNVG
EHNLFPGPID NSGLFSDPES QTLKEHLIDE LDYVLVPTEA WNKLLNWYGC VEGQQPIVRK
VVEHGLFVKH CKVEVYLLEL KLCENSDPTN VLSCHFSKAD TIATIEKEMR KLFNIPAERE
TRLWNKYMSN TYEQLSKLDN TVQDAGLYQG QVLVIEPQNE DGTWPRQTLQ SKSSTAPSRN
FTTSPKSSAS PYSSVSASLI ANGDSTSTCG MHSSGVSRGG SGFSASYNCQ EPPSSHIQPG
LCGLGNLGNT CFMNSALQCL SNTAPLTDYF LKDEYEAEIN RDNPLGMKGE IAEAYAELIK
QMWSGRDAHV APRMFKTQVG RFAPQFSGYQ QQDSQELLAF LLDGLHEDLN RVKKKPYLEL
KDANGRPDAV VAKEAWENHR LRNDSVIVDT FHGLFKSTLV CPECAKVSVT FDPFCYLTLP
LPLKKDRVME VFLVPADPHC RPTQYRVTVP LMGAVSDLCE ALSRLSGIAA ENMVVADVYN
HRFHKIFQMD EGLNHIMPRD DIFVYEVCST SVDGSECVTL PVYFRERKSR PSSTSSASAL
YGQPLLLSVP KHKLTLESLY QAVCDRISRY VKQPLPDEFG SSPLEPGACN GSRNSCEGED
EEEMEHQEEG KEQLSETEGS GEDEPGNDPS ETTQKKIKGQ PCPKRLFTFS LVNSYGTADI
NSLAADGKLL KLNSRSTLAM DWDSETRRLY YDEQESEAYE KHVSMLQPQK KKKTTVALRD
CIELFTTMET LGEHDPWYCP NCKKHQQATK KFDLWSLPKI LVVHLKRFSY NRYWRDKLDT
VVEFPIRGLN MSEFVCNLSA RPYVYDLIAV SNHYGAMGVG HYTAYAKNKL NGKWYYFDDS
NVSLASEDQI VTKAAYVLFY QRRDDEFYKT PSLSSSGSSD GGTRPSSSQQ GFGDDEACSM
DTN
//
ID UBP4_HUMAN Reviewed; 963 AA.
AC Q13107; A8K6Y0; C9IY91; O43452; O43453; Q08AK8;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 17-OCT-2006, sequence version 3.
DT 22-JAN-2014, entry version 132.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 4;
DE EC=3.4.19.12;
DE AltName: Full=Deubiquitinating enzyme 4;
DE AltName: Full=Ubiquitin thioesterase 4;
DE AltName: Full=Ubiquitin-specific-processing protease 4;
DE AltName: Full=Ubiquitous nuclear protein homolog;
GN Name=USP4; Synonyms=UNP, UNPH;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Brain cortex;
RX PubMed=7784062;
RA Gray D.A., Inazawa J., Gupta K., Wong A., Ueda R., Takahashi T.;
RT "Elevated expression of Unph, a proto-oncogene at 3p21.3, in human
RT lung tumors.";
RL Oncogene 10:2179-2183(1995).
RN [2]
RP SEQUENCE REVISION.
RA Gray D.A.;
RL Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND ALTERNATIVE
RP SPLICING.
RC TISSUE=B-cell, and T-cell;
RX PubMed=9464533; DOI=10.1038/sj.onc.1201537;
RA Frederick A., Rolfe M., Chiu M.I.;
RT "The human UNP locus at 3p21.31 encodes two tissue-selective,
RT cytoplasmic isoforms with deubiquitinating activity that have reduced
RT expression in small cell lung carcinoma cell lines.";
RL Oncogene 16:153-165(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Leukocyte;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP INTERACTION WITH RB1, AND MUTAGENESIS OF GLU-463 AND 459-LEU--GLU-463.
RX PubMed=11571652; DOI=10.1038/sj.onc.1204824;
RA DeSalle L.M., Latres E., Lin D., Graner E., Montagnoli A., Baker R.T.,
RA Pagano M., Loda M.;
RT "The de-ubiquitinating enzyme Unp interacts with the retinoblastoma
RT protein.";
RL Oncogene 20:5538-5542(2001).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-311.
RX PubMed=16316627; DOI=10.1016/j.bbrc.2005.11.076;
RA Wada K., Tanji K., Kamitani T.;
RT "Oncogenic protein UnpEL/Usp4 deubiquitinates Ro52 by its isopeptidase
RT activity.";
RL Biochem. Biophys. Res. Commun. 339:731-736(2006).
RN [9]
RP FUNCTION, AUTODEUBIQUITINATION, UBIQUITINATION BY TRIM21, AND
RP MUTAGENESIS OF CYS-311.
RX PubMed=16472766; DOI=10.1016/j.bbrc.2006.01.144;
RA Wada K., Kamitani T.;
RT "UnpEL/Usp4 is ubiquitinated by Ro52 and deubiquitinated by itself.";
RL Biochem. Biophys. Res. Commun. 342:253-258(2006).
RN [10]
RP FUNCTION, INTERACTION WITH ADORA2A, AND TISSUE SPECIFICITY.
RX PubMed=16339847; DOI=10.1124/mol.105.015818;
RA Milojevic T., Reiterer V., Stefan E., Korkhov V.M., Dorostkar M.M.,
RA Ducza E., Ogris E., Boehm S., Freissmuth M., Nanoff C.;
RT "The ubiquitin-specific protease Usp4 regulates the cell surface level
RT of the A2A receptor.";
RL Mol. Pharmacol. 69:1083-1094(2006).
RN [11]
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.,
RA Buerckstuemmer T., 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 [12]
RP DEUBIQUITINATION OF PDPK1.
RX PubMed=22347420; DOI=10.1371/journal.pone.0031003;
RA Uras I.Z., List T., Nijman S.M.;
RT "Ubiquitin-specific protease 4 inhibits mono-ubiquitination of the
RT master growth factor signaling kinase PDK1.";
RL PLoS ONE 7:E31003-E31003(2012).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 296-932, DOMAINS
RP UBIQUITIN-LIKE, AND ZINC-BINDING SITES.
RX PubMed=21415856; DOI=10.1038/embor.2011.33;
RA Luna-Vargas M.P., Faesen A.C., van Dijk W.J., Rape M., Fish A.,
RA Sixma T.K.;
RT "Ubiquitin-specific protease 4 is inhibited by its ubiquitin-like
RT domain.";
RL EMBO Rep. 12:365-372(2011).
CC -!- FUNCTION: Hydrolase that deubiquitinates target proteins such as
CC the receptor ADORA2A, PDPK1 and TRIM21. Deubiquitination of
CC ADORA2A increases the amount of functional receptor at the cell
CC surface. Plays a role in the regulation of quality control in the
CC ER.
CC -!- CATALYTIC ACTIVITY: Thiol-dependent hydrolysis of ester,
CC thioester, amide, peptide and isopeptide bonds formed by the C-
CC terminal Gly of ubiquitin (a 76-residue protein attached to
CC proteins as an intracellular targeting signal).
CC -!- SUBUNIT: Interacts with RB1 (both dephosphorylated and
CC hypophosphorylated forms). Interacts with ADORA2A (via cytoplasmic
CC C-terminus); the interaction is direct. Interacts with RB1, RBL1
CC and RBL2.
CC -!- INTERACTION:
CC Self; NbExp=3; IntAct=EBI-723290, EBI-723290;
CC P29274:ADORA2A; NbExp=4; IntAct=EBI-723290, EBI-2902702;
CC Q7Z6Z7:HUWE1; NbExp=4; IntAct=EBI-723290, EBI-625934;
CC Q13546:RIPK1; NbExp=4; IntAct=EBI-723290, EBI-358507;
CC P19474:TRIM21; NbExp=3; IntAct=EBI-723305, EBI-81290;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By
CC similarity). Note=Shuttles between the nucleus and cytoplasm.
CC Exported to the cytoplasm in a CRM1-dependent manner and recycled
CC back to the nucleus via the importin alpha/beta heterodimeric
CC import receptor. The relative amounts found in the nucleus and
CC cytoplasm vary according to the cell type (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=UnpEL;
CC IsoId=Q13107-1; Sequence=Displayed;
CC Name=2; Synonyms=UnpES;
CC IsoId=Q13107-2; Sequence=VSP_005258;
CC Name=3;
CC IsoId=Q13107-3; Sequence=VSP_044814, VSP_044815;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Overexpressed in small cell tumors and
CC adenocarcinomas of the lung compared to wild-type lung (at protein
CC level). Expressed in the hippocampal neurons.
CC -!- DOMAIN: The Ubiquitin-like domain 2 inserts into the catalytic
CC domain and competes with the ubiquitin substrate, partially
CC inhibiting DUB activity.
CC -!- PTM: Monoubiquitinated by TRIM21. Ubiquitination does not lead to
CC its proteasomal degradation. Autodeubiquitinated.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. USP4 subfamily.
CC -!- SIMILARITY: Contains 1 DUSP domain.
CC -!- SIMILARITY: Contains 2 ubiquitin-like domains.
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DR EMBL; U20657; AAB72237.1; -; mRNA.
DR EMBL; AF017305; AAC27355.1; -; mRNA.
DR EMBL; AF017306; AAC27356.1; -; mRNA.
DR EMBL; AK291795; BAF84484.1; -; mRNA.
DR EMBL; AC121247; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC068017; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC125130; AAI25131.1; -; mRNA.
DR PIR; T09478; T09478.
DR RefSeq; NP_001238806.1; NM_001251877.1.
DR RefSeq; NP_003354.2; NM_003363.3.
DR RefSeq; NP_955475.1; NM_199443.2.
DR UniGene; Hs.403828; -.
DR UniGene; Hs.77500; -.
DR PDB; 2Y6E; X-ray; 2.40 A; A/B/C/D/E/F=296-932.
DR PDBsum; 2Y6E; -.
DR ProteinModelPortal; Q13107; -.
DR SMR; Q13107; 8-226, 297-483, 740-930.
DR IntAct; Q13107; 32.
DR MINT; MINT-3027027; -.
DR STRING; 9606.ENSP00000265560; -.
DR MEROPS; C19.010; -.
DR PhosphoSite; Q13107; -.
DR DMDM; 116242839; -.
DR PaxDb; Q13107; -.
DR PRIDE; Q13107; -.
DR Ensembl; ENST00000265560; ENSP00000265560; ENSG00000114316.
DR Ensembl; ENST00000351842; ENSP00000341028; ENSG00000114316.
DR Ensembl; ENST00000416417; ENSP00000400623; ENSG00000114316.
DR GeneID; 7375; -.
DR KEGG; hsa:7375; -.
DR UCSC; uc021wxv.1; human.
DR CTD; 7375; -.
DR GeneCards; GC03M049315; -.
DR HGNC; HGNC:12627; USP4.
DR HPA; HPA018499; -.
DR MIM; 603486; gene.
DR neXtProt; NX_Q13107; -.
DR PharmGKB; PA37252; -.
DR eggNOG; COG5560; -.
DR HOGENOM; HOG000264375; -.
DR HOVERGEN; HBG000864; -.
DR InParanoid; Q13107; -.
DR KO; K11835; -.
DR OMA; CERISRY; -.
DR PhylomeDB; Q13107; -.
DR ChiTaRS; USP4; human.
DR EvolutionaryTrace; Q13107; -.
DR GeneWiki; USP4; -.
DR GenomeRNAi; 7375; -.
DR NextBio; 28880; -.
DR PRO; PR:Q13107; -.
DR ArrayExpress; Q13107; -.
DR Bgee; Q13107; -.
DR CleanEx; HS_USP4; -.
DR Genevestigator; Q13107; -.
DR GO; GO:0005764; C:lysosome; TAS:ProtInc.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0004843; F:deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004221; F:ubiquitin thiolesterase activity; IMP:UniProtKB.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; IMP:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; IDA:UniProtKB.
DR GO; GO:0034394; P:protein localization to cell surface; IDA:UniProtKB.
DR GO; GO:0031647; P:regulation of protein stability; IDA:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR InterPro; IPR006615; Pept_C19_DUSP.
DR InterPro; IPR018200; Pept_C19ubi-hydrolase_C_CS.
DR InterPro; IPR001394; Peptidase_C19/C67.
DR InterPro; IPR028135; Ub_USP-typ.
DR InterPro; IPR028134; USP.
DR PANTHER; PTHR24006:SF34; PTHR24006:SF34; 1.
DR Pfam; PF06337; DUSP; 1.
DR Pfam; PF14836; Ubiquitin_3; 1.
DR Pfam; PF00443; UCH; 1.
DR SMART; SM00695; DUSP; 1.
DR PROSITE; PS51283; DUSP; 1.
DR PROSITE; PS00299; UBIQUITIN_1; FALSE_NEG.
DR PROSITE; PS50053; UBIQUITIN_2; FALSE_NEG.
DR PROSITE; PS00972; UCH_2_1; 1.
DR PROSITE; PS00973; UCH_2_2; 1.
DR PROSITE; PS50235; UCH_2_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome; Cytoplasm;
KW Hydrolase; Metal-binding; Nucleus; Polymorphism; Protease;
KW Proto-oncogene; Reference proteome; Repeat; Thiol protease;
KW Ubl conjugation; Ubl conjugation pathway; Zinc.
FT CHAIN 1 963 Ubiquitin carboxyl-terminal hydrolase 4.
FT /FTId=PRO_0000080621.
FT DOMAIN 11 122 DUSP.
FT DOMAIN 142 226 Ubiquitin-like 1.
FT DOMAIN 483 571 Ubiquitin-like 2.
FT REGION 405 407 Necessary for interaction with RBL2 (By
FT similarity).
FT REGION 459 463 Necessary for interaction with RB1 and
FT RBL2 (By similarity).
FT MOTIF 133 141 Nuclear export signal (By similarity).
FT MOTIF 767 772 Nuclear localization signal (By
FT similarity).
FT ACT_SITE 311 311 Nucleophile.
FT ACT_SITE 881 881 Proton acceptor (By similarity).
FT METAL 461 461 Zinc.
FT METAL 464 464 Zinc.
FT METAL 799 799 Zinc.
FT METAL 802 802 Zinc.
FT VAR_SEQ 232 279 KSSTAPSRNFTTSPKSSASPYSSVSASLIANGDSTSTCGMH
FT SSGVSRG -> N (in isoform 2).
FT /FTId=VSP_005258.
FT VAR_SEQ 233 313 SSTAPSRNFTTSPKSSASPYSSVSASLIANGDSTSTCGMHS
FT SGVSRGGSGFSASYNCQEPPSSHIQPGLCGLGNLGNTCFM
FT -> VSFFLPRLECNGAILAHCNFCLPGSSNSPASASRVAPS
FT HLANFFFFEMESHSVTKLECGGAVSAYSRVQVMLLPQPPEW
FT LG (in isoform 3).
FT /FTId=VSP_044814.
FT VAR_SEQ 314 963 Missing (in isoform 3).
FT /FTId=VSP_044815.
FT VARIANT 620 620 Y -> C (in dbSNP:rs9311440).
FT /FTId=VAR_028180.
FT MUTAGEN 311 311 C->A: Loss of activity. Its
FT ubiquitination by TRIM21 is enhanced.
FT MUTAGEN 459 463 LVCPE->AVRPH: Reduces the interaction
FT with RB1.
FT MUTAGEN 463 463 E->Q: Reduces the interaction with RB1.
FT CONFLICT 373 373 R -> S (in Ref. 1; AAB72237).
FT CONFLICT 744 744 S -> R (in Ref. 1; AAB72237).
FT HELIX 311 321
FT HELIX 324 331
FT HELIX 335 338
FT HELIX 350 362
FT STRAND 364 366
FT STRAND 368 370
FT HELIX 373 382
FT HELIX 384 386
FT STRAND 388 390
FT HELIX 394 408
FT HELIX 428 442
FT HELIX 446 451
FT STRAND 453 460
FT TURN 462 464
FT STRAND 467 480
FT HELIX 778 785
FT STRAND 797 799
FT TURN 800 803
FT STRAND 804 806
FT STRAND 809 816
FT STRAND 819 826
FT STRAND 828 830
FT STRAND 835 837
FT HELIX 852 854
FT STRAND 858 860
FT STRAND 864 874
FT STRAND 876 879
FT STRAND 881 887
FT TURN 889 891
FT STRAND 894 898
FT STRAND 901 904
FT HELIX 907 909
FT STRAND 915 922
SQ SEQUENCE 963 AA; 108565 MW; 63055C9ADFE36713 CRC64;
MAEGGGCRER PDAETQKSEL GPLMRTTLQR GAQWYLIDSR WFKQWKKYVG FDSWDMYNVG
EHNLFPGPID NSGLFSDPES QTLKEHLIDE LDYVLVPTEA WNKLLNWYGC VEGQQPIVRK
VVEHGLFVKH CKVEVYLLEL KLCENSDPTN VLSCHFSKAD TIATIEKEMR KLFNIPAERE
TRLWNKYMSN TYEQLSKLDN TVQDAGLYQG QVLVIEPQNE DGTWPRQTLQ SKSSTAPSRN
FTTSPKSSAS PYSSVSASLI ANGDSTSTCG MHSSGVSRGG SGFSASYNCQ EPPSSHIQPG
LCGLGNLGNT CFMNSALQCL SNTAPLTDYF LKDEYEAEIN RDNPLGMKGE IAEAYAELIK
QMWSGRDAHV APRMFKTQVG RFAPQFSGYQ QQDSQELLAF LLDGLHEDLN RVKKKPYLEL
KDANGRPDAV VAKEAWENHR LRNDSVIVDT FHGLFKSTLV CPECAKVSVT FDPFCYLTLP
LPLKKDRVME VFLVPADPHC RPTQYRVTVP LMGAVSDLCE ALSRLSGIAA ENMVVADVYN
HRFHKIFQMD EGLNHIMPRD DIFVYEVCST SVDGSECVTL PVYFRERKSR PSSTSSASAL
YGQPLLLSVP KHKLTLESLY QAVCDRISRY VKQPLPDEFG SSPLEPGACN GSRNSCEGED
EEEMEHQEEG KEQLSETEGS GEDEPGNDPS ETTQKKIKGQ PCPKRLFTFS LVNSYGTADI
NSLAADGKLL KLNSRSTLAM DWDSETRRLY YDEQESEAYE KHVSMLQPQK KKKTTVALRD
CIELFTTMET LGEHDPWYCP NCKKHQQATK KFDLWSLPKI LVVHLKRFSY NRYWRDKLDT
VVEFPIRGLN MSEFVCNLSA RPYVYDLIAV SNHYGAMGVG HYTAYAKNKL NGKWYYFDDS
NVSLASEDQI VTKAAYVLFY QRRDDEFYKT PSLSSSGSSD GGTRPSSSQQ GFGDDEACSM
DTN
//
MIM
603486
*RECORD*
*FIELD* NO
603486
*FIELD* TI
*603486 UBIQUITIN-SPECIFIC PROTEASE 4; USP4
;;UBIQUITIN-SPECIFIC PROTEASE; UNP
*FIELD* TX
read more
DESCRIPTION
The ubiquitin-specific proteases (UBPs) are a group of deubiquitinating
enzymes that possess 2 signature motifs, the Cys box and the His box
(summary by Frederick et al., 1998).
CLONING
Gupta et al. (1993) isolated mouse cDNAs encoding Unp, a protein similar
to the human TRE oncogene. Using Western blots, Gupta et al. (1994)
found that Unp has an apparent molecular mass of 180 kD. They reported
that overexpression of Unp led to oncogenic transformation of NIH 3T3
cells injected into athymic mice.
By screening a human frontal cortex library with a murine Unp cDNA, Gray
et al. (1995) isolated cDNAs encoding human UNP. Analysis of the clones
revealed a large open reading with the potential to encode a protein of
854 amino acids, with a molecular mass of 97 kD. The human and mouse
proteins share 90% sequence identity. Northern blot analysis of primary
lung tumor samples indicated that levels of UNP mRNA were elevated in
small cell carcinomas and adenocarcinomas relative to normal adult lung.
Frederick et al. (1998) sequenced additional UNP cDNAs and found several
differences from the sequence reported by Gray et al. (1995), including
2 single nucleotide insertions that increased the length of the
predicted protein, UNPEL (UNP extended, long isoform), to 963 amino
acids. They also recovered cDNAs encoding a shorter isoform designated
UNPES. Both isoforms exhibited deubiquitinating activity. Antibodies
against UNP detected 2 proteins of 105 to 110 kD on Western blots. Using
immunocytochemistry of mammalian cells expressing epitope-tagged UNP and
cell fractionation studies, Frederick et al. (1998) demonstrated that
both isoforms of the human protein are localized primarily in the
cytosol. (In an erratum, Frederick et al. (1998) cited a personal
communication from the Gray laboratory stating that the data in Gupta et
al. (1993) locating Unp in the nuclear fraction of mammalian cell
extracts was apparently in error.) Northern blot analysis revealed UNP
expression as a closely-migrating cluster of mRNAs in all tissues
tested. However, the authors found no evidence for overexpression of UNP
transcripts in cell lines derived from small cell lung carcinomas.
GENE STRUCTURE
Di Fruscio et al. (1998) reported that the mouse Unp gene contains 22
exons distributed over 47 kb. A processed ribosomal S2 pseudogene was
identified in the third intron.
MAPPING
By analysis of an interspecific backcross, Gupta et al. (1993) mapped
the Unp gene to mouse chromosome 9 in a region showing homology of
synteny with human chromosome 3p.
By fluorescence in situ hybridization, Gray et al. (1995) mapped the
human UNP gene to 3p21.3, a region implicated in neoplasms of the lung.
Using the same technique, Frederick et al. (1998) refined the map
position to 3p21.31.
*FIELD* RF
1. Di Fruscio, M.; Gilchrist, C. A.; Baker, R. T.; Gray, D. A.: Genomic
structure of Unp, a murine gene encoding a ubiquitin-specific protease. Biochim.
Biophys. Acta 1398: 9-17, 1998.
2. Frederick, A.; Rolfe, M.; Chiu, M. I.: The human UNP locus at
3p21.31 encodes two tissue-selective, cytoplasmic isoforms with deubiquitinating
activity that have reduced expression in small cell lung carcinoma
cell lines. Oncogene 16: 153-165, 1998. Note: Erratum: Oncogene
16: 2293 only, 1998.
3. Gray, D. A.; Inazawa, J.; Gupta, K.; Wong, A.; Ueda, R.; Takahashi,
T.: Elevated expression of Unph, a proto-oncogene at 3p21.3, in human
lung tumors. Oncogene 10: 2179-2183, 1995.
4. Gupta, K.; Chevrette, M.; Gray, D. A.: The Unp proto-oncogene
encodes a nuclear protein. Oncogene 9: 1729-1731, 1994.
5. Gupta, K.; Copeland, N. G.; Gilbert, D. J.; Jenkins, N. A.; Gray,
D. A.: Unp, a mouse gene related to the tre oncogene. Oncogene 8:
2307-2310, 1993.
*FIELD* CD
Rebekah S. Rasooly: 2/3/1999
*FIELD* ED
carol: 06/11/2013
carol: 1/3/2013
alopez: 2/3/1999
*RECORD*
*FIELD* NO
603486
*FIELD* TI
*603486 UBIQUITIN-SPECIFIC PROTEASE 4; USP4
;;UBIQUITIN-SPECIFIC PROTEASE; UNP
*FIELD* TX
read more
DESCRIPTION
The ubiquitin-specific proteases (UBPs) are a group of deubiquitinating
enzymes that possess 2 signature motifs, the Cys box and the His box
(summary by Frederick et al., 1998).
CLONING
Gupta et al. (1993) isolated mouse cDNAs encoding Unp, a protein similar
to the human TRE oncogene. Using Western blots, Gupta et al. (1994)
found that Unp has an apparent molecular mass of 180 kD. They reported
that overexpression of Unp led to oncogenic transformation of NIH 3T3
cells injected into athymic mice.
By screening a human frontal cortex library with a murine Unp cDNA, Gray
et al. (1995) isolated cDNAs encoding human UNP. Analysis of the clones
revealed a large open reading with the potential to encode a protein of
854 amino acids, with a molecular mass of 97 kD. The human and mouse
proteins share 90% sequence identity. Northern blot analysis of primary
lung tumor samples indicated that levels of UNP mRNA were elevated in
small cell carcinomas and adenocarcinomas relative to normal adult lung.
Frederick et al. (1998) sequenced additional UNP cDNAs and found several
differences from the sequence reported by Gray et al. (1995), including
2 single nucleotide insertions that increased the length of the
predicted protein, UNPEL (UNP extended, long isoform), to 963 amino
acids. They also recovered cDNAs encoding a shorter isoform designated
UNPES. Both isoforms exhibited deubiquitinating activity. Antibodies
against UNP detected 2 proteins of 105 to 110 kD on Western blots. Using
immunocytochemistry of mammalian cells expressing epitope-tagged UNP and
cell fractionation studies, Frederick et al. (1998) demonstrated that
both isoforms of the human protein are localized primarily in the
cytosol. (In an erratum, Frederick et al. (1998) cited a personal
communication from the Gray laboratory stating that the data in Gupta et
al. (1993) locating Unp in the nuclear fraction of mammalian cell
extracts was apparently in error.) Northern blot analysis revealed UNP
expression as a closely-migrating cluster of mRNAs in all tissues
tested. However, the authors found no evidence for overexpression of UNP
transcripts in cell lines derived from small cell lung carcinomas.
GENE STRUCTURE
Di Fruscio et al. (1998) reported that the mouse Unp gene contains 22
exons distributed over 47 kb. A processed ribosomal S2 pseudogene was
identified in the third intron.
MAPPING
By analysis of an interspecific backcross, Gupta et al. (1993) mapped
the Unp gene to mouse chromosome 9 in a region showing homology of
synteny with human chromosome 3p.
By fluorescence in situ hybridization, Gray et al. (1995) mapped the
human UNP gene to 3p21.3, a region implicated in neoplasms of the lung.
Using the same technique, Frederick et al. (1998) refined the map
position to 3p21.31.
*FIELD* RF
1. Di Fruscio, M.; Gilchrist, C. A.; Baker, R. T.; Gray, D. A.: Genomic
structure of Unp, a murine gene encoding a ubiquitin-specific protease. Biochim.
Biophys. Acta 1398: 9-17, 1998.
2. Frederick, A.; Rolfe, M.; Chiu, M. I.: The human UNP locus at
3p21.31 encodes two tissue-selective, cytoplasmic isoforms with deubiquitinating
activity that have reduced expression in small cell lung carcinoma
cell lines. Oncogene 16: 153-165, 1998. Note: Erratum: Oncogene
16: 2293 only, 1998.
3. Gray, D. A.; Inazawa, J.; Gupta, K.; Wong, A.; Ueda, R.; Takahashi,
T.: Elevated expression of Unph, a proto-oncogene at 3p21.3, in human
lung tumors. Oncogene 10: 2179-2183, 1995.
4. Gupta, K.; Chevrette, M.; Gray, D. A.: The Unp proto-oncogene
encodes a nuclear protein. Oncogene 9: 1729-1731, 1994.
5. Gupta, K.; Copeland, N. G.; Gilbert, D. J.; Jenkins, N. A.; Gray,
D. A.: Unp, a mouse gene related to the tre oncogene. Oncogene 8:
2307-2310, 1993.
*FIELD* CD
Rebekah S. Rasooly: 2/3/1999
*FIELD* ED
carol: 06/11/2013
carol: 1/3/2013
alopez: 2/3/1999