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Protein

Ubiquitin carboxyl-terminal hydrolase 37

Gene

USP37

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).1 Publication

Catalytic activityi

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).1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei350NucleophileCurated1
Active sitei906Proton acceptorPROSITE-ProRule annotation1

GO - Molecular functioni

  • cysteine-type endopeptidase activity Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • thiol-dependent ubiquitin-specific protease activity Source: UniProtKB

GO - Biological processi

  • cell division Source: UniProtKB-KW
  • G1/S transition of mitotic cell cycle Source: UniProtKB
  • mitotic nuclear division Source: UniProtKB-KW
  • protein deubiquitination Source: FlyBase
  • protein K11-linked deubiquitination Source: UniProtKB
  • protein K48-linked deubiquitination Source: UniProtKB
  • ubiquitin-dependent protein catabolic process Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Cell cycle, Cell division, Mitosis, Ubl conjugation pathway

Enzyme and pathway databases

BioCyciZFISH:HS06081-MONOMER.
ReactomeiR-HSA-5689880. Ub-specific processing proteases.

Protein family/group databases

MEROPSiC19.053.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:USP37
Synonyms:KIAA1594
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:20063. USP37.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi32 – 34KEN → AAA: No effect. 1 Publication3
Mutagenesisi71 – 74RLML → ALMA: No effect. 1 Publication4
Mutagenesisi96 – 99RLFL → ALFA: No effect. 1 Publication4
Mutagenesisi160 – 163RKVL → AKVA: No effect. 1 Publication4
Mutagenesisi221 – 223KEN → AAA: No effect. 1 Publication3
Mutagenesisi350C → S: Abolishes deubiquitinase activity. 1 Publication1
Mutagenesisi628S → A: Abolishes phosphorylation by CDK2, leading to lower deubiquitinase activity. 1 Publication1
Mutagenesisi782 – 784KEN → AAA: Impaired interaction with FZR1/CDH1 and subsequent ubiquitination. 1 Publication3

Organism-specific databases

DisGeNETi57695.
OpenTargetsiENSG00000135913.
PharmGKBiPA134928706.

Polymorphism and mutation databases

BioMutaiUSP37.
DMDMi300669620.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000806671 – 979Ubiquitin carboxyl-terminal hydrolase 37Add BLAST979

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei170PhosphoserineCombined sources1
Modified residuei210PhosphoserineCombined sources1
Modified residuei628Phosphoserine; by CDK21 Publication1
Modified residuei650PhosphoserineCombined sources1
Modified residuei652PhosphoserineCombined sources1
Modified residuei770PhosphoserineCombined sources1

Post-translational modificationi

Polyubiquitinated via 'Lys-11'-linked ubiquitin by the APC(CDH1) complex during late mitosis, leading to its degradation. Able to mediate auto-deubiquitination.1 Publication
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.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ86T82.
MaxQBiQ86T82.
PaxDbiQ86T82.
PeptideAtlasiQ86T82.
PRIDEiQ86T82.

PTM databases

iPTMnetiQ86T82.
PhosphoSitePlusiQ86T82.

Expressioni

Tissue specificityi

Expressed in brain and prostate.1 Publication

Developmental stagei

Induced in G1 phase, accumulates at G1/S transition, and degraded in late mitosis following ubiquitination and degradation by the APC(CDH1) complex.1 Publication

Inductioni

Induced by E2F transcription factors in G1.1 Publication

Gene expression databases

BgeeiENSG00000135913.
CleanExiHS_USP37.
ExpressionAtlasiQ86T82. baseline and differential.
GenevisibleiQ86T82. HS.

Organism-specific databases

HPAiHPA045160.

Interactioni

Subunit structurei

Interacts with FZR1/CDH1.1 Publication

GO - Molecular functioni

  • protein kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi121720. 97 interactors.
IntActiQ86T82. 3 interactors.
MINTiMINT-4720282.
STRINGi9606.ENSP00000258399.

Structurei

Secondary structure

1979
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi5 – 14Combined sources10
Turni15 – 17Combined sources3
Beta strandi23 – 32Combined sources10
Beta strandi35 – 42Combined sources8
Beta strandi49 – 52Combined sources4
Turni54 – 56Combined sources3
Beta strandi57 – 64Combined sources8
Beta strandi69 – 76Combined sources8
Beta strandi81 – 88Combined sources8
Helixi89 – 103Combined sources15

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3U12X-ray2.08A/B4-125[»]
ProteinModelPortaliQ86T82.
SMRiQ86T82.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini341 – 951USPAdd BLAST611
Domaini704 – 723UIM 1PROSITE-ProRule annotationAdd BLAST20
Domaini806 – 825UIM 2PROSITE-ProRule annotationAdd BLAST20
Domaini828 – 847UIM 3PROSITE-ProRule annotationAdd BLAST20

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi32 – 34KEN box 13
Motifi71 – 79D-box 19
Motifi96 – 105D-box 210
Motifi160 – 168D-box 39
Motifi221 – 223KEN box 23
Motifi782 – 784KEN box 33

Domaini

The KEN box 3 is required for interaction with FZR1/CDH1 and is essential for APC(CDH1)-mediated ubiquitination.1 Publication

Sequence similaritiesi

Belongs to the peptidase C19 family.Curated
Contains 3 UIM (ubiquitin-interacting motif) domains.PROSITE-ProRule annotation
Contains 1 USP domain.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG1868. Eukaryota.
ENOG410XP8T. LUCA.
GeneTreeiENSGT00440000033542.
HOVERGENiHBG055893.
InParanoidiQ86T82.
KOiK11850.
OMAiWLQQYDM.
OrthoDBiEOG091G01DZ.
PhylomeDBiQ86T82.
TreeFamiTF323032.

Family and domain databases

CDDicd13312. PH_USP37_like. 1 hit.
InterProiIPR001394. Peptidase_C19_UCH.
IPR003903. UIM_dom.
IPR032069. USP37-like_PH.
IPR018200. USP_CS.
IPR028889. USP_dom.
[Graphical view]
PfamiPF00443. UCH. 1 hit.
PF16674. UCH_N. 1 hit.
PF02809. UIM. 3 hits.
[Graphical view]
SMARTiSM00726. UIM. 4 hits.
[Graphical view]
PROSITEiPS50330. UIM. 3 hits.
PS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q86T82-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MSPLKIHGPI RIRSMQTGIT KWKEGSFEIV EKENKVSLVV HYNTGGIPRI
60 70 80 90 100
FQLSHNIKNV VLRPSGAKQS RLMLTLQDNS FLSIDKVPSK DAEEMRLFLD
110 120 130 140 150
AVHQNRLPAA MKPSQGSGSF GAILGSRTSQ KETSRQLSYS DNQASAKRGS
160 170 180 190 200
LETKDDIPFR KVLGNPGRGS IKTVAGSGIA RTIPSLTSTS TPLRSGLLEN
210 220 230 240 250
RTEKRKRMIS TGSELNEDYP KENDSSSNNK AMTDPSRKYL TSSREKQLSL
260 270 280 290 300
KQSEENRTSG LLPLQSSSFY GSRAGSKEHS SGGTNLDRTN VSSQTPSAKR
310 320 330 340 350
SLGFLPQPVP LSVKKLRCNQ DYTGWNKPRV PLSSHQQQQL QGFSNLGNTC
360 370 380 390 400
YMNAILQSLF SLQSFANDLL KQGIPWKKIP LNALIRRFAH LLVKKDICNS
410 420 430 440 450
ETKKDLLKKV KNAISATAER FSGYMQNDAH EFLSQCLDQL KEDMEKLNKT
460 470 480 490 500
WKTEPVSGEE NSPDISATRA YTCPVITNLE FEVQHSIICK ACGEIIPKRE
510 520 530 540 550
QFNDLSIDLP RRKKPLPPRS IQDSLDLFFR AEELEYSCEK CGGKCALVRH
560 570 580 590 600
KFNRLPRVLI LHLKRYSFNV ALSLNNKIGQ QVIIPRYLTL SSHCTENTKP
610 620 630 640 650
PFTLGWSAHM AISRPLKASQ MVNSCITSPS TPSKKFTFKS KSSLALCLDS
660 670 680 690 700
DSEDELKRSV ALSQRLCEML GNEQQQEDLE KDSKLCPIEP DKSELENSGF
710 720 730 740 750
DRMSEEELLA AVLEISKRDA SPSLSHEDDD KPTSSPDTGF AEDDIQEMPE
760 770 780 790 800
NPDTMETEKP KTITELDPAS FTEITKDCDE NKENKTPEGS QGEVDWLQQY
810 820 830 840 850
DMEREREEQE LQQALAQSLQ EQEAWEQKED DDLKRATELS LQEFNNSFVD
860 870 880 890 900
ALGSDEDSGN EDVFDMEYTE AEAEELKRNA ETGNLPHSYR LISVVSHIGS
910 920 930 940 950
TSSSGHYISD VYDIKKQAWF TYNDLEVSKI QEAAVQSDRD RSGYIFFYMH
960 970
KEIFDELLET EKNSQSLSTE VGKTTRQAL
Length:979
Mass (Da):110,170
Last modified:July 13, 2010 - v2
Checksum:i9F47F06A744EA449
GO
Isoform 2 (identifier: Q86T82-2) [UniParc]FASTAAdd to basket

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

Show »
Length:885
Mass (Da):99,752
Checksum:iD5D5E4077F1155B4
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti223 – 224ND → DG in CAD89955 (PubMed:17974005).Curated2
Sequence conflicti345N → K in CAD97970 (PubMed:17974005).Curated1
Sequence conflicti456V → I in CAD89955 (PubMed:17974005).Curated1
Sequence conflicti552F → I in AAI44250 (PubMed:15489334).Curated1
Sequence conflicti567S → I in AAI44253 (PubMed:15489334).Curated1
Sequence conflicti576N → Y in AAI44253 (PubMed:15489334).Curated1
Sequence conflicti731K → E in CAD97970 (PubMed:17974005).Curated1
Sequence conflicti905G → D in CAD97970 (PubMed:17974005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_059752979L → S.4 PublicationsCorresponds to variant rs6436058dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0417401 – 72Missing in isoform 2. 1 PublicationAdd BLAST72
Alternative sequenceiVSP_041741612 – 634ISRPL…STPSK → M in isoform 2. 1 PublicationAdd BLAST23

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
RefSeqiNP_065986.2. NM_020935.2.
XP_005246777.1. XM_005246720.2. [Q86T82-1]
XP_005246778.1. XM_005246721.3. [Q86T82-1]
XP_005246779.1. XM_005246722.3. [Q86T82-1]
XP_011509840.1. XM_011511538.2. [Q86T82-1]
UniGeneiHs.166068.

Genome annotation databases

EnsembliENST00000258399; ENSP00000258399; ENSG00000135913. [Q86T82-1]
ENST00000415516; ENSP00000400902; ENSG00000135913. [Q86T82-2]
ENST00000418019; ENSP00000396585; ENSG00000135913. [Q86T82-1]
ENST00000454775; ENSP00000393662; ENSG00000135913. [Q86T82-1]
GeneIDi57695.
KEGGihsa:57695.
UCSCiuc002vie.3. human. [Q86T82-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
RefSeqiNP_065986.2. NM_020935.2.
XP_005246777.1. XM_005246720.2. [Q86T82-1]
XP_005246778.1. XM_005246721.3. [Q86T82-1]
XP_005246779.1. XM_005246722.3. [Q86T82-1]
XP_011509840.1. XM_011511538.2. [Q86T82-1]
UniGeneiHs.166068.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3U12X-ray2.08A/B4-125[»]
ProteinModelPortaliQ86T82.
SMRiQ86T82.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121720. 97 interactors.
IntActiQ86T82. 3 interactors.
MINTiMINT-4720282.
STRINGi9606.ENSP00000258399.

Protein family/group databases

MEROPSiC19.053.

PTM databases

iPTMnetiQ86T82.
PhosphoSitePlusiQ86T82.

Polymorphism and mutation databases

BioMutaiUSP37.
DMDMi300669620.

Proteomic databases

EPDiQ86T82.
MaxQBiQ86T82.
PaxDbiQ86T82.
PeptideAtlasiQ86T82.
PRIDEiQ86T82.

Protocols and materials databases

DNASUi57695.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000258399; ENSP00000258399; ENSG00000135913. [Q86T82-1]
ENST00000415516; ENSP00000400902; ENSG00000135913. [Q86T82-2]
ENST00000418019; ENSP00000396585; ENSG00000135913. [Q86T82-1]
ENST00000454775; ENSP00000393662; ENSG00000135913. [Q86T82-1]
GeneIDi57695.
KEGGihsa:57695.
UCSCiuc002vie.3. human. [Q86T82-1]

Organism-specific databases

CTDi57695.
DisGeNETi57695.
GeneCardsiUSP37.
HGNCiHGNC:20063. USP37.
HPAiHPA045160.
neXtProtiNX_Q86T82.
OpenTargetsiENSG00000135913.
PharmGKBiPA134928706.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1868. Eukaryota.
ENOG410XP8T. LUCA.
GeneTreeiENSGT00440000033542.
HOVERGENiHBG055893.
InParanoidiQ86T82.
KOiK11850.
OMAiWLQQYDM.
OrthoDBiEOG091G01DZ.
PhylomeDBiQ86T82.
TreeFamiTF323032.

Enzyme and pathway databases

BioCyciZFISH:HS06081-MONOMER.
ReactomeiR-HSA-5689880. Ub-specific processing proteases.

Miscellaneous databases

ChiTaRSiUSP37. human.
GeneWikiiUSP37.
GenomeRNAii57695.
PROiQ86T82.

Gene expression databases

BgeeiENSG00000135913.
CleanExiHS_USP37.
ExpressionAtlasiQ86T82. baseline and differential.
GenevisibleiQ86T82. HS.

Family and domain databases

CDDicd13312. PH_USP37_like. 1 hit.
InterProiIPR001394. Peptidase_C19_UCH.
IPR003903. UIM_dom.
IPR032069. USP37-like_PH.
IPR018200. USP_CS.
IPR028889. USP_dom.
[Graphical view]
PfamiPF00443. UCH. 1 hit.
PF16674. UCH_N. 1 hit.
PF02809. UIM. 3 hits.
[Graphical view]
SMARTiSM00726. UIM. 4 hits.
[Graphical view]
PROSITEiPS50330. UIM. 3 hits.
PS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiUBP37_HUMAN
AccessioniPrimary (citable) accession number: Q86T82
Secondary accession number(s): A2RUQ8
, B7ZM38, B7ZM41, E9PHL3, Q2KHT2, Q53S10, Q7Z3A5, Q9HCH8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 10, 2003
Last sequence update: July 13, 2010
Last modified: November 2, 2016
This is version 124 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Peptidase families
    Classification of peptidase families and list of entries
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.