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Protein

Ubiquitin carboxyl-terminal hydrolase 12

Gene

USP12

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

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

Activity regulationi

Activated by interaction with WDR20 and WDR48 through different allosteric mechanisms.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei48Nucleophile1 Publication1
Metal bindingi186ZincCombined sources1
Metal bindingi189ZincCombined sources1
Metal bindingi233ZincCombined sources1
Metal bindingi236ZincCombined sources1
Active sitei317Proton acceptorPROSITE-ProRule annotation1

GO - Molecular functioni

  • cysteine-type endopeptidase activity Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • thiol-dependent ubiquitin-specific protease activity Source: UniProtKB
  • thiol-dependent ubiquitinyl hydrolase activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processUbl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-5689880 Ub-specific processing proteases

Protein family/group databases

MEROPSiC19.020

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

EuPathDBiHostDB:ENSG00000152484.13
HGNCiHGNC:20485 USP12
MIMi603091 gene
neXtProtiNX_O75317

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
Mutagenesisi48C → A: Loss of activity. 1 Publication1
Mutagenesisi48C → S: Loss of activity. 1 Publication1
Mutagenesisi190E → K: Impaired binding to WDR48. 1 Publication1
Mutagenesisi208 – 210QNT → GGG: Loss of activity. 1 Publication3
Mutagenesisi219F → A: Loss of activity. 1 Publication1
Mutagenesisi240Q → A: Impaired binding to WDR48; when associated with Ala-241. 1 Publication1
Mutagenesisi241E → A: Impaired binding to WDR48; when associated with Ala-240. 1 Publication1
Mutagenesisi264Y → A: Strong reduction of activity. 1 Publication1
Mutagenesisi279V → D: Impaired binding to WDR20; when associated with Ala-287. 1 Publication1
Mutagenesisi287F → A: Impaired binding to WDR20; when associated with Asp-279. 1 Publication1

Organism-specific databases

DisGeNETi219333
OpenTargetsiENSG00000152484
PharmGKBiPA37236

Polymorphism and mutation databases

BioMutaiUSP12

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000806341 – 370Ubiquitin carboxyl-terminal hydrolase 12Add BLAST370

Proteomic databases

EPDiO75317
MaxQBiO75317
PaxDbiO75317
PeptideAtlasiO75317
PRIDEiO75317
ProteomicsDBi49890

PTM databases

iPTMnetiO75317
PhosphoSitePlusiO75317

Expressioni

Gene expression databases

BgeeiENSG00000152484 Expressed in 232 organ(s), highest expression level in esophagogastric junction muscularis propria
CleanExiHS_USP12
ExpressionAtlasiO75317 baseline and differential
GenevisibleiO75317 HS

Organism-specific databases

HPAiHPA007288

Interactioni

Subunit structurei

Interacts with WDR48 (PubMed:19075014, PubMed:27650958, PubMed:27373336). Interacts with WDR20 (PubMed:20147737, PubMed:27373336). Component of the USP12/WDR20/WDR48 deubiquitinating complex (PubMed:20147737, PubMed:27373336). Interacts with PHLPP1 (PubMed:24145035).5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
WDR20Q8TBZ34EBI-2511507,EBI-2511486

Protein-protein interaction databases

BioGridi128522, 36 interactors
CORUMiO75317
IntActiO75317, 16 interactors
STRINGi9606.ENSP00000282344

Structurei

Secondary structure

1370
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO75317
SMRiO75317
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini39 – 369USPAdd BLAST331

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1864 Eukaryota
ENOG410XQ81 LUCA
GeneTreeiENSGT00890000139367
HOGENOMiHOG000231498
HOVERGENiHBG054038
InParanoidiO75317
KOiK11842
OMAiTANCKIN
OrthoDBiEOG091G0FC5
PhylomeDBiO75317
TreeFamiTF314144

Family and domain databases

InterProiView protein in InterPro
IPR038765 Papain_like_cys_pep_sf
IPR001394 Peptidase_C19_UCH
IPR018200 USP_CS
IPR028889 USP_dom
PfamiView protein in Pfam
PF00443 UCH, 1 hit
SUPFAMiSSF54001 SSF54001, 1 hit
PROSITEiView protein in PROSITE
PS00972 USP_1, 1 hit
PS00973 USP_2, 1 hit
PS50235 USP_3, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.iShow all

O75317-1 [UniParc]FASTAAdd to basket
« Hide
        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
Length:370
Mass (Da):42,858
Last modified:November 28, 2006 - v2
Checksum:i267EE6A3674F6440
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A087WWP2A0A087WWP2_HUMAN
Ubiquitin carboxyl-terminal hydrola...
USP12
90Annotation score:
A0A087WUU2A0A087WUU2_HUMAN
Ubiquitin carboxyl-terminal hydrola...
USP12
18Annotation score:

Sequence cautioni

The sequence AAC23551 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti173H → D in AAH26072 (PubMed:15489334).Curated1

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
CCDSiCCDS31952.1
RefSeqiNP_872294.2, NM_182488.3
UniGeneiHs.42400

Genome annotation databases

EnsembliENST00000282344; ENSP00000282344; ENSG00000152484
GeneIDi219333
KEGGihsa:219333
UCSCiuc001uqy.4 human

Similar proteinsi

Entry informationi

Entry nameiUBP12_HUMAN
AccessioniPrimary (citable) accession number: O75317
Secondary accession number(s): A8K0X0, Q5VZV3, Q8TC49
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 28, 2006
Last modified: September 12, 2018
This is version 157 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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