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Protein

Ubiquitin carboxyl-terminal hydrolase 37

Gene

USP37

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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) (PubMed:21596315). Plays an important role in the regulation of DNA replication by stabilizing the licensing factor CDT1 (PubMed:27296872).2 Publications

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).2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei350Nucleophile1 Publication1
Active sitei906Proton acceptorPROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processCell cycle, Cell division, Mitosis, Ubl conjugation pathway

Enzyme and pathway databases

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:3.4.19.121 Publication)
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

EuPathDBiHostDB:ENSG00000135913.10
HGNCiHGNC:20063 USP37
neXtProtiNX_Q86T82

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 CDK22 Publications1
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
ProteomicsDBi69667
69668 [Q86T82-2]

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 Expressed in 202 organ(s), highest expression level in amniotic fluid
CleanExiHS_USP37
ExpressionAtlasiQ86T82 baseline and differential
GenevisibleiQ86T82 HS

Organism-specific databases

HPAiHPA045160

Interactioni

Subunit structurei

Interacts with FZR1/CDH1 (PubMed:21596315). Interacts with CDT1 (PubMed:27296872).2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi121720, 98 interactors
IntActiQ86T82, 3 interactors
MINTiQ86T82
STRINGi9606.ENSP00000258399

Structurei

Secondary structure

1979
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

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
Gene3Di2.30.29.180, 1 hit
InterProiView protein in InterPro
IPR038765 Papain_like_cys_pep_sf
IPR001394 Peptidase_C19_UCH
IPR003903 UIM_dom
IPR032069 USP37-like_PH
IPR038093 USP37-like_PH_sf
IPR018200 USP_CS
IPR028889 USP_dom
PfamiView protein in Pfam
PF00443 UCH, 1 hit
PF16674 UCH_N, 1 hit
PF02809 UIM, 3 hits
SMARTiView protein in SMART
SM00726 UIM, 4 hits
SUPFAMiSSF54001 SSF54001, 3 hits
PROSITEiView protein in PROSITE
PS50330 UIM, 3 hits
PS00972 USP_1, 1 hit
PS00973 USP_2, 1 hit
PS50235 USP_3, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q86W68Q86W68_HUMAN
USP37 protein
USP37
302Annotation score:

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 → S4 PublicationsCorresponds to variant dbSNP:rs6436058Ensembl.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

Similar proteinsi

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, 98 interactors
IntActiQ86T82, 3 interactors
MINTiQ86T82
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
ProteomicsDBi69667
69668 [Q86T82-2]

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
EuPathDBiHostDB:ENSG00000135913.10
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

ReactomeiR-HSA-5689880 Ub-specific processing proteases

Miscellaneous databases

ChiTaRSiUSP37 human
GeneWikiiUSP37
GenomeRNAii57695
PROiPR:Q86T82

Gene expression databases

BgeeiENSG00000135913 Expressed in 202 organ(s), highest expression level in amniotic fluid
CleanExiHS_USP37
ExpressionAtlasiQ86T82 baseline and differential
GenevisibleiQ86T82 HS

Family and domain databases

CDDicd13312 PH_USP37_like, 1 hit
Gene3Di2.30.29.180, 1 hit
InterProiView protein in InterPro
IPR038765 Papain_like_cys_pep_sf
IPR001394 Peptidase_C19_UCH
IPR003903 UIM_dom
IPR032069 USP37-like_PH
IPR038093 USP37-like_PH_sf
IPR018200 USP_CS
IPR028889 USP_dom
PfamiView protein in Pfam
PF00443 UCH, 1 hit
PF16674 UCH_N, 1 hit
PF02809 UIM, 3 hits
SMARTiView protein in SMART
SM00726 UIM, 4 hits
SUPFAMiSSF54001 SSF54001, 3 hits
PROSITEiView protein in PROSITE
PS50330 UIM, 3 hits
PS00972 USP_1, 1 hit
PS00973 USP_2, 1 hit
PS50235 USP_3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiUBP37_HUMAN
AccessioniPrimary (citable) accession number: Q86T82
Secondary accession number(s): A2RUQ8
, B7ZM38, B7ZM41, E9PHL3, Q2KHT2, Q53S10, Q7Z3A5, Q9HCH8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 10, 2003
Last sequence update: July 13, 2010
Last modified: September 12, 2018
This is version 133 of the entry and version 2 of the sequence. See 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families
  4. Peptidase families
    Classification of peptidase families and list of entries
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
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