UniProtKB - O75317 (UBP12_HUMAN)
Protein
Ubiquitin carboxyl-terminal hydrolase 12
Gene
USP12
Organism
Homo sapiens (Human)
Status
Functioni
Deubiquitinating enzyme. Has almost no deubiquitinating activity by itself and requires the interaction with WDR20 and WDR48 to have a high activity (PubMed:19075014, PubMed:27373336). Not involved in deubiquitination of monoubiquitinated FANCD2 (PubMed:19075014). In complex with WDR48, acts as a potential tumor suppressor by positively regulating PHLPP1 stability (PubMed:24145035).3 Publications
Miscellaneous
Knockdown of USP12 increases Akt activation.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 EC:3.4.19.12
Activity regulationi
Activated by interaction with WDR20 and WDR48 through different allosteric mechanisms.2 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 48 | Nucleophile1 Publication | 1 | |
Metal bindingi | 186 | ZincCombined sources | 1 | |
Metal bindingi | 189 | ZincCombined sources | 1 | |
Metal bindingi | 233 | ZincCombined sources | 1 | |
Metal bindingi | 236 | ZincCombined sources | 1 | |
Active sitei | 317 | Proton acceptorPROSITE-ProRule annotation | 1 |
GO - Molecular functioni
- cysteine-type endopeptidase activity Source: UniProtKB
- metal ion binding Source: UniProtKB-KW
- thiol-dependent ubiquitin-specific protease activity Source: UniProtKB
GO - Biological processi
- protein deubiquitination Source: UniProtKB
- ubiquitin-dependent protein catabolic process Source: InterPro
Keywordsi
Molecular function | Hydrolase, Protease, Thiol protease |
Biological process | Ubl conjugation pathway |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | O75317 |
Reactomei | R-HSA-5689880, Ub-specific processing proteases |
Protein family/group databases
MEROPSi | C19.020 |
Names & Taxonomyi
Protein namesi | Recommended name: Ubiquitin carboxyl-terminal hydrolase 12 (EC:3.4.19.12)Alternative name(s): Deubiquitinating enzyme 12 Ubiquitin thioesterase 12 Ubiquitin-hydrolyzing enzyme 1 Ubiquitin-specific-processing protease 12 |
Gene namesi | Name:USP12 Synonyms:UBH1, USP12L1 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:20485, USP12 |
MIMi | 603091, gene |
neXtProti | NX_O75317 |
VEuPathDBi | HostDB:ENSG00000152484.13 |
Subcellular locationi
Cytosol
- cytosol Source: GO_Central
Nucleus
- nucleoplasm Source: Reactome
- nucleus Source: GO_Central
Pathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 48 | C → A: Loss of activity. 1 Publication | 1 | |
Mutagenesisi | 48 | C → S: Loss of activity. 1 Publication | 1 | |
Mutagenesisi | 190 | E → K: Impaired binding to WDR48. 1 Publication | 1 | |
Mutagenesisi | 208 – 210 | QNT → GGG: Loss of activity. 1 Publication | 3 | |
Mutagenesisi | 219 | F → A: Loss of activity. 1 Publication | 1 | |
Mutagenesisi | 240 | Q → A: Impaired binding to WDR48; when associated with Ala-241. 1 Publication | 1 | |
Mutagenesisi | 241 | E → A: Impaired binding to WDR48; when associated with Ala-240. 1 Publication | 1 | |
Mutagenesisi | 264 | Y → A: Strong reduction of activity. 1 Publication | 1 | |
Mutagenesisi | 279 | V → D: Impaired binding to WDR20; when associated with Ala-287. 1 Publication | 1 | |
Mutagenesisi | 287 | F → A: Impaired binding to WDR20; when associated with Asp-279. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 219333 |
OpenTargetsi | ENSG00000152484 |
PharmGKBi | PA37236 |
Miscellaneous databases
Pharosi | O75317, Tbio |
Genetic variation databases
BioMutai | USP12 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000080634 | 1 – 370 | Ubiquitin carboxyl-terminal hydrolase 12Add BLAST | 370 |
Proteomic databases
EPDi | O75317 |
jPOSTi | O75317 |
MassIVEi | O75317 |
MaxQBi | O75317 |
PaxDbi | O75317 |
PeptideAtlasi | O75317 |
PRIDEi | O75317 |
ProteomicsDBi | 49890 |
PTM databases
iPTMneti | O75317 |
PhosphoSitePlusi | O75317 |
Expressioni
Gene expression databases
Bgeei | ENSG00000152484, Expressed in esophagogastric junction muscularis propria and 243 other tissues |
ExpressionAtlasi | O75317, baseline and differential |
Genevisiblei | O75317, HS |
Organism-specific databases
HPAi | ENSG00000152484, Low tissue specificity |
Interactioni
Subunit structurei
Binary interactionsi
Hide detailsO75317
With | #Exp. | IntAct |
---|---|---|
CALR [P27797] | 3 | EBI-2511507,EBI-1049597 |
DLST [P36957] | 3 | EBI-2511507,EBI-351007 |
NEK7 [Q8TDX7] | 3 | EBI-2511507,EBI-1055945 |
WDR20 [Q8TBZ3] | 5 | EBI-2511507,EBI-2511486 |
Protein-protein interaction databases
BioGRIDi | 128522, 40 interactors |
CORUMi | O75317 |
IntActi | O75317, 30 interactors |
STRINGi | 9606.ENSP00000282344 |
Miscellaneous databases
RNActi | O75317, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | O75317 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 39 – 369 | USPAdd BLAST | 331 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG1864, Eukaryota |
GeneTreei | ENSGT00940000153284 |
HOGENOMi | CLU_008279_2_0_1 |
InParanoidi | O75317 |
OMAi | KYWVKYL |
OrthoDBi | 378361at2759 |
PhylomeDBi | O75317 |
TreeFami | TF314144 |
Family and domain databases
InterProi | View protein in InterPro IPR038765, Papain-like_cys_pep_sf IPR001394, Peptidase_C19_UCH IPR018200, USP_CS IPR028889, USP_dom |
Pfami | View protein in Pfam PF00443, UCH, 1 hit |
SUPFAMi | SSF54001, SSF54001, 1 hit |
PROSITEi | View protein in PROSITE PS00972, USP_1, 1 hit PS00973, USP_2, 1 hit PS50235, USP_3, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
O75317-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MEILMTVSKF ASICTMGANA SALEKEIGPE QFPVNEHYFG LVNFGNTCYC
60 70 80 90 100
NSVLQALYFC RPFREKVLAY KSQPRKKESL LTCLADLFHS IATQKKKVGV
110 120 130 140 150
IPPKKFITRL RKENELFDNY MQQDAHEFLN YLLNTIADIL QEERKQEKQN
160 170 180 190 200
GRLPNGNIDN ENNNSTPDPT WVHEIFQGTL TNETRCLTCE TISSKDEDFL
210 220 230 240 250
DLSVDVEQNT SITHCLRGFS NTETLCSEYK YYCEECRSKQ EAHKRMKVKK
260 270 280 290 300
LPMILALHLK RFKYMDQLHR YTKLSYRVVF PLELRLFNTS GDATNPDRMY
310 320 330 340 350
DLVAVVVHCG SGPNRGHYIA IVKSHDFWLL FDDDIVEKID AQAIEEFYGL
360 370
TSDISKNSES GYILFYQSRD
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A087WWP2 | A0A087WWP2_HUMAN | Ubiquitin carboxyl-terminal hydrola... | USP12 | 90 | Annotation score: | ||
A0A087WUU2 | A0A087WUU2_HUMAN | Ubiquitin carboxyl-terminal hydrola... | USP12 | 18 | Annotation score: |
Sequence cautioni
The sequence AAC23551 differs from that shown. Reason: Erroneous initiation.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 173 | H → D in AAH26072 (PubMed:15489334).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF022789 mRNA Translation: AAC23551.1 Different initiation. AK289685 mRNA Translation: BAF82374.1 AL158062 Genomic DNA No translation available. AL355473 Genomic DNA No translation available. CH471075 Genomic DNA Translation: EAX08392.1 BC026072 mRNA Translation: AAH26072.1 |
CCDSi | CCDS31952.1 |
RefSeqi | NP_872294.2, NM_182488.3 |
Genome annotation databases
Ensembli | ENST00000282344; ENSP00000282344; ENSG00000152484 |
GeneIDi | 219333 |
KEGGi | hsa:219333 |
UCSCi | uc001uqy.4, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF022789 mRNA Translation: AAC23551.1 Different initiation. AK289685 mRNA Translation: BAF82374.1 AL158062 Genomic DNA No translation available. AL355473 Genomic DNA No translation available. CH471075 Genomic DNA Translation: EAX08392.1 BC026072 mRNA Translation: AAH26072.1 |
CCDSi | CCDS31952.1 |
RefSeqi | NP_872294.2, NM_182488.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5K16 | X-ray | 2.60 | A/B | 16-370 | [»] | |
5K1A | X-ray | 2.30 | A/C/E/G | 40-370 | [»] | |
5K1B | X-ray | 3.30 | A | 4-370 | [»] | |
5K1C | X-ray | 3.00 | A | 16-370 | [»] | |
5L8W | X-ray | 2.79 | A | 1-370 | [»] | |
SMRi | O75317 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 128522, 40 interactors |
CORUMi | O75317 |
IntActi | O75317, 30 interactors |
STRINGi | 9606.ENSP00000282344 |
Protein family/group databases
MEROPSi | C19.020 |
PTM databases
iPTMneti | O75317 |
PhosphoSitePlusi | O75317 |
Genetic variation databases
BioMutai | USP12 |
Proteomic databases
EPDi | O75317 |
jPOSTi | O75317 |
MassIVEi | O75317 |
MaxQBi | O75317 |
PaxDbi | O75317 |
PeptideAtlasi | O75317 |
PRIDEi | O75317 |
ProteomicsDBi | 49890 |
Protocols and materials databases
Antibodypediai | 22631, 262 antibodies |
Genome annotation databases
Ensembli | ENST00000282344; ENSP00000282344; ENSG00000152484 |
GeneIDi | 219333 |
KEGGi | hsa:219333 |
UCSCi | uc001uqy.4, human |
Organism-specific databases
CTDi | 219333 |
DisGeNETi | 219333 |
GeneCardsi | USP12 |
HGNCi | HGNC:20485, USP12 |
HPAi | ENSG00000152484, Low tissue specificity |
MIMi | 603091, gene |
neXtProti | NX_O75317 |
OpenTargetsi | ENSG00000152484 |
PharmGKBi | PA37236 |
VEuPathDBi | HostDB:ENSG00000152484.13 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1864, Eukaryota |
GeneTreei | ENSGT00940000153284 |
HOGENOMi | CLU_008279_2_0_1 |
InParanoidi | O75317 |
OMAi | KYWVKYL |
OrthoDBi | 378361at2759 |
PhylomeDBi | O75317 |
TreeFami | TF314144 |
Enzyme and pathway databases
PathwayCommonsi | O75317 |
Reactomei | R-HSA-5689880, Ub-specific processing proteases |
Miscellaneous databases
BioGRID-ORCSi | 219333, 31 hits in 876 CRISPR screens |
ChiTaRSi | USP12, human |
GenomeRNAii | 219333 |
Pharosi | O75317, Tbio |
PROi | PR:O75317 |
RNActi | O75317, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000152484, Expressed in esophagogastric junction muscularis propria and 243 other tissues |
ExpressionAtlasi | O75317, baseline and differential |
Genevisiblei | O75317, HS |
Family and domain databases
InterProi | View protein in InterPro IPR038765, Papain-like_cys_pep_sf IPR001394, Peptidase_C19_UCH IPR018200, USP_CS IPR028889, USP_dom |
Pfami | View protein in Pfam PF00443, UCH, 1 hit |
SUPFAMi | SSF54001, SSF54001, 1 hit |
PROSITEi | View protein in PROSITE PS00972, USP_1, 1 hit PS00973, USP_2, 1 hit PS50235, USP_3, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | UBP12_HUMAN | |
Accessioni | O75317Primary (citable) accession number: O75317 Secondary accession number(s): A8K0X0, Q5VZV3, Q8TC49 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 30, 2000 |
Last sequence update: | November 28, 2006 | |
Last modified: | February 10, 2021 | |
This is version 171 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human chromosome 13
Human chromosome 13: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Peptidase families
Classification of peptidase families and list of entries