Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q86T82 (UBP37_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 101. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ubiquitin carboxyl-terminal hydrolase 37

EC=3.4.19.12
Alternative name(s):
Deubiquitinating enzyme 37
Ubiquitin thioesterase 37
Ubiquitin-specific-processing protease 37
Gene names
Name:USP37
Synonyms:KIAA1594
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length979 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Deubiquitinase that antagonizes the anaphase-promoting complex (APC/C) during G1/S transition by mediating deubiquitination of cyclin-A (CCNA1 and CCNA2), thereby promoting S phase entry. Specifically mediates deubiquitination of 'Lys-11'-linked polyubiquitin chains, a specific ubiquitin-linkage type mediated by the APC/C complex. Also mediates deubiquitination of 'Lys-48'-linked polyubiquitin chains in vitro. Phosphorylation at Ser-628 during G1/S phase maximizes the deubiquitinase activity, leading to prevent degradation of cyclin-A (CCNA1 and CCNA2). Ref.9

Catalytic activity

Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal). Ref.6

Subunit structure

Interacts with FZR1/CDH1. Ref.9

Tissue specificity

Expressed in brain and prostate. Ref.6

Developmental stage

Induced in G1 phase, accumulates at G1/S transition, and degraded in late mitosis following ubiquitination and degradation by the APC(CDH1) complex. Ref.9

Induction

Induced by E2F transcription factors in G1. Ref.9

Domain

The KEN box 3 is required for interaction with FZR1/CDH1 and is essential for APC(CDH1)-mediated ubiquitination. Ref.9

Post-translational modification

Polyubiquitinated via 'Lys-11'-linked ubiquitin by the APC(CDH1) complex during late mitosis, leading to its degradation. Able to mediate auto-deubiquitination.

Phosphorylated at Ser-628 by CDK2 during G1/S phase but not during mitosis; phosphorylation at Ser-628 is required for deubiquitinase activity. Also polyubiquitinated during early G1 phase, without leading to degradation. Ref.9

Sequence similarities

Belongs to the peptidase C19 family.

Contains 3 UIM (ubiquitin-interacting motif) repeats.

Contains 1 USP domain.

Sequence caution

The sequence AAY14887.1 differs from that shown. Reason: Erroneous gene model prediction.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q86T82-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q86T82-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-72: Missing.
     612-634: ISRPLKASQMVNSCITSPSTPSK → M

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 979979Ubiquitin carboxyl-terminal hydrolase 37
PRO_0000080667

Regions

Domain341 – 951611USP
Repeat704 – 72320UIM 1
Repeat806 – 82520UIM 2
Repeat828 – 84720UIM 3
Motif32 – 343KEN box 1
Motif71 – 799D-box 1
Motif96 – 10510D-box 2
Motif160 – 1689D-box 3
Motif221 – 2233KEN box 2
Motif782 – 7843KEN box 3

Sites

Active site3501Nucleophile Probable
Active site9061Proton acceptor By similarity

Amino acid modifications

Modified residue6281Phosphoserine; by CDK2 Ref.9
Modified residue6501Phosphoserine Ref.7
Modified residue6521Phosphoserine Ref.7

Natural variations

Alternative sequence1 – 7272Missing in isoform 2.
VSP_041740
Alternative sequence612 – 63423ISRPL…STPSK → M in isoform 2.
VSP_041741
Natural variant9791L → S. Ref.1 Ref.3 Ref.4 Ref.5
Corresponds to variant rs6436058 [ dbSNP | Ensembl ].
VAR_059752

Experimental info

Mutagenesis32 – 343KEN → AAA: No effect. Ref.9
Mutagenesis71 – 744RLML → ALMA: No effect.
Mutagenesis96 – 994RLFL → ALFA: No effect.
Mutagenesis160 – 1634RKVL → AKVA: No effect.
Mutagenesis221 – 2233KEN → AAA: No effect. Ref.9
Mutagenesis3501C → S: Abolishes deubiquitinase activity. Ref.9
Mutagenesis6281S → A: Abolishes phosphorylation by CDK2, leading to lower deubiquitinase activity. Ref.9
Mutagenesis782 – 7843KEN → AAA: Impaired interaction with FZR1/CDH1 and subsequent ubiquitination. Ref.9
Sequence conflict223 – 2242ND → DG in CAD89955. Ref.1
Sequence conflict3451N → K in CAD97970. Ref.1
Sequence conflict4561V → I in CAD89955. Ref.1
Sequence conflict5521F → I in AAI44250. Ref.4
Sequence conflict5671S → I in AAI44253. Ref.4
Sequence conflict5761N → Y in AAI44253. Ref.4
Sequence conflict7311K → E in CAD97970. Ref.1
Sequence conflict9051G → D in CAD97970. Ref.1

Secondary structure

.................. 979
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 13, 2010. Version 2.
Checksum: 9F47F06A744EA449

FASTA979110,170
        10         20         30         40         50         60 
MSPLKIHGPI RIRSMQTGIT KWKEGSFEIV EKENKVSLVV HYNTGGIPRI FQLSHNIKNV 

        70         80         90        100        110        120 
VLRPSGAKQS RLMLTLQDNS FLSIDKVPSK DAEEMRLFLD AVHQNRLPAA MKPSQGSGSF 

       130        140        150        160        170        180 
GAILGSRTSQ KETSRQLSYS DNQASAKRGS LETKDDIPFR KVLGNPGRGS IKTVAGSGIA 

       190        200        210        220        230        240 
RTIPSLTSTS TPLRSGLLEN RTEKRKRMIS TGSELNEDYP KENDSSSNNK AMTDPSRKYL 

       250        260        270        280        290        300 
TSSREKQLSL KQSEENRTSG LLPLQSSSFY GSRAGSKEHS SGGTNLDRTN VSSQTPSAKR 

       310        320        330        340        350        360 
SLGFLPQPVP LSVKKLRCNQ DYTGWNKPRV PLSSHQQQQL QGFSNLGNTC YMNAILQSLF 

       370        380        390        400        410        420 
SLQSFANDLL KQGIPWKKIP LNALIRRFAH LLVKKDICNS ETKKDLLKKV KNAISATAER 

       430        440        450        460        470        480 
FSGYMQNDAH EFLSQCLDQL KEDMEKLNKT WKTEPVSGEE NSPDISATRA YTCPVITNLE 

       490        500        510        520        530        540 
FEVQHSIICK ACGEIIPKRE QFNDLSIDLP RRKKPLPPRS IQDSLDLFFR AEELEYSCEK 

       550        560        570        580        590        600 
CGGKCALVRH KFNRLPRVLI LHLKRYSFNV ALSLNNKIGQ QVIIPRYLTL SSHCTENTKP 

       610        620        630        640        650        660 
PFTLGWSAHM AISRPLKASQ MVNSCITSPS TPSKKFTFKS KSSLALCLDS DSEDELKRSV 

       670        680        690        700        710        720 
ALSQRLCEML GNEQQQEDLE KDSKLCPIEP DKSELENSGF DRMSEEELLA AVLEISKRDA 

       730        740        750        760        770        780 
SPSLSHEDDD KPTSSPDTGF AEDDIQEMPE NPDTMETEKP KTITELDPAS FTEITKDCDE 

       790        800        810        820        830        840 
NKENKTPEGS QGEVDWLQQY DMEREREEQE LQQALAQSLQ EQEAWEQKED DDLKRATELS 

       850        860        870        880        890        900 
LQEFNNSFVD ALGSDEDSGN EDVFDMEYTE AEAEELKRNA ETGNLPHSYR LISVVSHIGS 

       910        920        930        940        950        960 
TSSSGHYISD VYDIKKQAWF TYNDLEVSKI QEAAVQSDRD RSGYIFFYMH KEIFDELLET 

       970 
EKNSQSLSTE VGKTTRQAL 

« Hide

Isoform 2 [UniParc].

Checksum: D5D5E4077F1155B4
Show »

FASTA88599,752

References

« Hide 'large scale' references
[1]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT SER-979.
Tissue: Spinal cord.
[2]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT SER-979.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT SER-979.
Tissue: Testis.
[5]"Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O.
DNA Res. 7:273-281(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 49-979 (ISOFORM 1), VARIANT SER-979.
Tissue: Brain.
[6]"Cloning and enzymatic analysis of 22 novel human ubiquitin-specific proteases."
Quesada V., Diaz-Perales A., Gutierrez-Fernandez A., Garabaya C., Cal S., Lopez-Otin C.
Biochem. Biophys. Res. Commun. 314:54-62(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, ENZYME ACTIVITY.
[7]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-650 AND SER-652, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[8]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"Deubiquitinase USP37 is activated by CDK2 to antagonize APC(CDH1) and promote S phase entry."
Huang X., Summers M.K., Pham V., Lill J.R., Liu J., Lee G., Kirkpatrick D.S., Jackson P.K., Fang G., Dixit V.M.
Mol. Cell 42:511-523(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, UBIQUITINATION, PHOSPHORYLATION AT SER-628 BY CDK2, DOMAIN KEN BOX 3, DEVELOPMENTAL STAGE, INDUCTION, INTERACTION WITH FZR1, MUTAGENESIS OF 32-LYS--ASN-34; 71-ARG-LEU-74; 96-ARG-LEU-99; 160-ARG-LEU-163; 221-LYS--ASN-223; CYS-350; 782-LYS--ASN-784 AND SER-628.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AL832645 mRNA. Translation: CAD89955.1.
BX538024 mRNA. Translation: CAD97970.1.
AC012510 Genomic DNA. No translation available.
AC073838 Genomic DNA. Translation: AAY14887.1. Sequence problems.
CH471063 Genomic DNA. Translation: EAW70621.1.
BC112901 mRNA. Translation: AAI12902.1.
BC133007 mRNA. Translation: AAI33008.1.
BC133009 mRNA. Translation: AAI33010.1.
BC144249 mRNA. Translation: AAI44250.1.
BC144252 mRNA. Translation: AAI44253.1.
AB046814 mRNA. Translation: BAB13420.1.
RefSeqNP_065986.2. NM_020935.2.
XP_005246777.1. XM_005246720.1. [Q86T82-1]
XP_005246778.1. XM_005246721.1. [Q86T82-1]
XP_005246779.1. XM_005246722.1. [Q86T82-1]
UniGeneHs.166068.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3U12X-ray2.08A/B4-125[»]
ProteinModelPortalQ86T82.
SMRQ86T82. Positions 4-106, 337-598.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121720. 18 interactions.
IntActQ86T82. 3 interactions.
MINTMINT-4720282.
STRING9606.ENSP00000258399.

Protein family/group databases

MEROPSC19.053.

PTM databases

PhosphoSiteQ86T82.

Polymorphism databases

DMDM300669620.

Proteomic databases

MaxQBQ86T82.
PaxDbQ86T82.
PRIDEQ86T82.

Protocols and materials databases

DNASU57695.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000258399; ENSP00000258399; ENSG00000135913. [Q86T82-1]
ENST00000415516; ENSP00000400902; ENSG00000135913. [Q86T82-2]
ENST00000418019; ENSP00000396585; ENSG00000135913. [Q86T82-1]
ENST00000454775; ENSP00000393662; ENSG00000135913. [Q86T82-1]
GeneID57695.
KEGGhsa:57695.
UCSCuc002vie.2. human. [Q86T82-1]
uc002vig.2. human. [Q86T82-2]

Organism-specific databases

CTD57695.
GeneCardsGC02M219281.
HGNCHGNC:20063. USP37.
HPAHPA045160.
neXtProtNX_Q86T82.
PharmGKBPA134928706.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5207.
HOVERGENHBG055893.
InParanoidQ86T82.
KOK11850.
OMALQEFNNS.
OrthoDBEOG7HMS09.
PhylomeDBQ86T82.
TreeFamTF323032.

Gene expression databases

ArrayExpressQ86T82.
BgeeQ86T82.
CleanExHS_USP37.
GenevestigatorQ86T82.

Family and domain databases

InterProIPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19_UCH.
IPR003903. Ubiquitin-int_motif.
IPR028889. UCH/PAN2.
[Graphical view]
PfamPF00443. UCH. 1 hit.
PF02809. UIM. 3 hits.
[Graphical view]
SMARTSM00726. UIM. 4 hits.
[Graphical view]
PROSITEPS50330. UIM. 3 hits.
PS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSUSP37. human.
GeneWikiUSP37.
GenomeRNAi57695.
NextBio64543.
PROQ86T82.

Entry information

Entry nameUBP37_HUMAN
AccessionPrimary (citable) accession number: Q86T82
Secondary accession number(s): A2RUQ8 expand/collapse secondary AC list , B7ZM38, B7ZM41, E9PHL3, Q2KHT2, Q53S10, Q7Z3A5, Q9HCH8
Entry history
Integrated into UniProtKB/Swiss-Prot: October 10, 2003
Last sequence update: July 13, 2010
Last modified: June 11, 2014
This is version 101 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM