Q8C0R0 · UBP37_MOUSE
- ProteinUbiquitin carboxyl-terminal hydrolase 37
- GeneUsp37
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids979 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Deubiquitinase that plays a role in different processes including cell cycle regulation, DNA replication or DNA damage response. 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. Phosphorylation at Ser-628 during G1/S phase maximizes the deubiquitinase activity, leading to prevent degradation of cyclin-A (CCNA1 and CCNA2). Plays an important role in the regulation of DNA replication by stabilizing the licensing factor CDT1. Plays also an essential role beyond S-phase entry to promote the efficiency and fidelity of replication by deubiquitinating checkpoint kinase 1/CHK1, promoting its stability. Sustains the DNA damage response (DDR) by deubiquitinating and stabilizing the ATP-dependent DNA helicase BLM. Mechanistically, DNA double-strand breaks (DSB) promotes ATM-mediated phosphorylation of USP37 and enhances the binding between USP37 and BLM. Promotes cell migration by deubiquitinating and stabilizing the epithelial-mesenchymal transition (EMT)-inducing transcription factor SNAI. Plays a role in the regulation of mitotic spindle assembly and mitotic progression by associating with chromatin-associated WAPL and stabilizing it through deubiquitination.
Catalytic activity
Features
Showing features for active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 350 | Nucleophile | ||||
Sequence: C | ||||||
Active site | 906 | Proton acceptor | ||||
Sequence: H |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | chromosome | |
Cellular Component | cytosol | |
Cellular Component | nucleus | |
Molecular Function | cysteine-type deubiquitinase activity | |
Molecular Function | cysteine-type endopeptidase activity | |
Biological Process | cell division | |
Biological Process | G1/S transition of mitotic cell cycle | |
Biological Process | protein deubiquitination | |
Biological Process | protein K11-linked deubiquitination | |
Biological Process | protein K48-linked deubiquitination | |
Biological Process | proteolysis | |
Biological Process | regulation of DNA replication |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameUbiquitin carboxyl-terminal hydrolase 37
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ8C0R0
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000259610 | 1-979 | Ubiquitin carboxyl-terminal hydrolase 37 | |||
Sequence: MSPLKIYGPIRIRSMQTGITKWKEGSFEIVEKDNRVSLLVHYNTGGIPRVFQLSHNIKNVVLRPSGIKQSRLMLTLQDNSFLSIDKVPSKDAEEMRLFLDAVHQNRLHAAMKASQGSGSFGTILGSRTSQKETNRQLSYSDNQASSKRGSLETKDEIPFRKVLGSPGRGPIKTVTGGGMAVTRTIPSLTLTSTPLRSGLLENRTEKRKRMLSGSELTEDYPKENDSSSNNKAMTDPSRKYLTSCREKQLSLKQAEENRTSGLLPLQSSSFYGSRAGSKDYSSGVTNLDRCNVSSQTPSAKRSLGFLPQPTPLSVKKLRCNQDYAGWNRPRVPLSSHQQQLQGFSNLGNTCYMNAILQSLFSLQSFANDLLKQSIPWKKIPFNALIRRFANLLIKKDICNSETKKELLKKVKNAISATAERFSGYVQNDAHEFLSQCLDQLKEDMEKLNKTWKTEPVLGEENLPDTSATKVFTCPVITNLEFEVQHSIICKACGETIPKREQFNDLSIDLPRRKKPLPPRSIQDSLDLFFRAEELEYSCEKCGGKCALVRHKFNRLPRVLILHLKRYSFNVALSLNNKLGQQVIIPRFLTLASHCTESTKPPVTLGWSAPVAISRPLRACQMMNSCITSPSAPSKKFTFKSKSSVTSCLDSDSEDELKRSVVLSQRLCDLPGNEQYQEDVEKDLKLCRLEPGKAELENSGFDRMSEEEVLAAVLEISRREASPVLSPEDDDKPTSSPDTGFAEDDIPEMPENPDAMEIEKSKTITEPGPASFTEITKDCDENKENKTPEGSQGEVDWLQQYDVDREREEQELQQALAQSLQEQEAWEQKEDDDLKRATELSLQEFNNSFLDSLGSDEDSGNEDVFDMEYTEAEAEELKRNAETGALPHSYRLISVVSHIGSTSSSGHYISDVYDIKKQAWFTYNDLEVSKIQEAAVQSDRDRSGYIFFYMHKEIFDELLETEKTSQALSMEVGRAARQAS | ||||||
Modified residue | 114 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 212 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 628 | Phosphoserine; by CDK2 | ||||
Sequence: S | ||||||
Modified residue | 650 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 652 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 770 | Phosphoserine | ||||
Sequence: S |
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. Phosphorylated at Ser-114 by ATM following DNA damage, which in turn increases its deubiquitination activity towards BLM.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Structure
Family & Domains
Features
Showing features for motif, compositional bias, region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 32-34 | KEN box 1 | ||||
Sequence: KDN | ||||||
Motif | 71-79 | D-box 1 | ||||
Sequence: RLMLTLQDN | ||||||
Motif | 96-105 | D-box 2 | ||||
Sequence: RLFLDAVHQN | ||||||
Compositional bias | 116-147 | Polar residues | ||||
Sequence: GSGSFGTILGSRTSQKETNRQLSYSDNQASSK | ||||||
Region | 116-178 | Disordered | ||||
Sequence: GSGSFGTILGSRTSQKETNRQLSYSDNQASSKRGSLETKDEIPFRKVLGSPGRGPIKTVTGGG | ||||||
Motif | 160-168 | D-box 3 | ||||
Sequence: RKVLGSPGR | ||||||
Region | 192-240 | Disordered | ||||
Sequence: STPLRSGLLENRTEKRKRMLSGSELTEDYPKENDSSSNNKAMTDPSRKY | ||||||
Compositional bias | 200-225 | Basic and acidic residues | ||||
Sequence: LENRTEKRKRMLSGSELTEDYPKEND | ||||||
Motif | 222-224 | KEN box 2 | ||||
Sequence: KEN | ||||||
Compositional bias | 226-240 | Polar residues | ||||
Sequence: SSSNNKAMTDPSRKY | ||||||
Domain | 341-951 | USP | ||||
Sequence: QGFSNLGNTCYMNAILQSLFSLQSFANDLLKQSIPWKKIPFNALIRRFANLLIKKDICNSETKKELLKKVKNAISATAERFSGYVQNDAHEFLSQCLDQLKEDMEKLNKTWKTEPVLGEENLPDTSATKVFTCPVITNLEFEVQHSIICKACGETIPKREQFNDLSIDLPRRKKPLPPRSIQDSLDLFFRAEELEYSCEKCGGKCALVRHKFNRLPRVLILHLKRYSFNVALSLNNKLGQQVIIPRFLTLASHCTESTKPPVTLGWSAPVAISRPLRACQMMNSCITSPSAPSKKFTFKSKSSVTSCLDSDSEDELKRSVVLSQRLCDLPGNEQYQEDVEKDLKLCRLEPGKAELENSGFDRMSEEEVLAAVLEISRREASPVLSPEDDDKPTSSPDTGFAEDDIPEMPENPDAMEIEKSKTITEPGPASFTEITKDCDENKENKTPEGSQGEVDWLQQYDVDREREEQELQQALAQSLQEQEAWEQKEDDDLKRATELSLQEFNNSFLDSLGSDEDSGNEDVFDMEYTEAEAEELKRNAETGALPHSYRLISVVSHIGSTSSSGHYISDVYDIKKQAWFTYNDLEVSKIQEAAVQSDRDRSGYIFFYMHK | ||||||
Domain | 704-723 | UIM 1 | ||||
Sequence: SEEEVLAAVLEISRREASPV | ||||||
Region | 719-795 | Disordered | ||||
Sequence: EASPVLSPEDDDKPTSSPDTGFAEDDIPEMPENPDAMEIEKSKTITEPGPASFTEITKDCDENKENKTPEGSQGEVD | ||||||
Compositional bias | 721-737 | Basic and acidic residues | ||||
Sequence: SPVLSPEDDDKPTSSPD | ||||||
Compositional bias | 775-789 | Basic and acidic residues | ||||
Sequence: TKDCDENKENKTPEG | ||||||
Motif | 782-784 | KEN box 3 | ||||
Sequence: KEN | ||||||
Domain | 806-825 | UIM 2 | ||||
Sequence: REEQELQQALAQSLQEQEAW | ||||||
Domain | 828-847 | UIM 3 | ||||
Sequence: KEDDDLKRATELSLQEFNNS |
Domain
The KEN box 3 is required for interaction with FZR1/CDH1 and is essential for APC(CDH1)-mediated ubiquitination.
Sequence similarities
Belongs to the peptidase C19 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q8C0R0-1
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.
- Name1
- Length979
- Mass (Da)110,063
- Last updated2003-03-01 v1
- ChecksumFF11DB673C1CA902
Q8C0R0-2
- Name2
- Differences from canonical
- 612-634: ISRPLRACQMMNSCITSPSAPSK → M
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A0R4J2D0 | A0A0R4J2D0_MOUSE | Usp37 | 979 | ||
A0A087WQE4 | A0A087WQE4_MOUSE | Usp37 | 22 |
Features
Showing features for compositional bias, alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 116-147 | Polar residues | ||||
Sequence: GSGSFGTILGSRTSQKETNRQLSYSDNQASSK | ||||||
Compositional bias | 200-225 | Basic and acidic residues | ||||
Sequence: LENRTEKRKRMLSGSELTEDYPKEND | ||||||
Compositional bias | 226-240 | Polar residues | ||||
Sequence: SSSNNKAMTDPSRKY | ||||||
Alternative sequence | VSP_052196 | 612-634 | in isoform 2 | |||
Sequence: ISRPLRACQMMNSCITSPSAPSK → M | ||||||
Sequence conflict | 622 | in Ref. 2; AAI39092 | ||||
Sequence: M → V | ||||||
Compositional bias | 721-737 | Basic and acidic residues | ||||
Sequence: SPVLSPEDDDKPTSSPD | ||||||
Compositional bias | 775-789 | Basic and acidic residues | ||||
Sequence: TKDCDENKENKTPEG |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK030013 EMBL· GenBank· DDBJ | BAC26734.1 EMBL· GenBank· DDBJ | mRNA | ||
AK035640 EMBL· GenBank· DDBJ | BAC29135.1 EMBL· GenBank· DDBJ | mRNA | ||
AK173210 EMBL· GenBank· DDBJ | BAD32488.1 EMBL· GenBank· DDBJ | mRNA | ||
BC139091 EMBL· GenBank· DDBJ | AAI39092.1 EMBL· GenBank· DDBJ | mRNA |