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Protein

Ubiquitin carboxyl-terminal hydrolase 12

Gene

USP12

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Enzyme 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

HGNCiHGNC:20485. USP12.

Subcellular locationi

GO - Cellular componenti

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.

PTM databases

iPTMnetiO75317.
PhosphoSitePlusiO75317.

Expressioni

Gene expression databases

BgeeiENSG00000152484.
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. 35 interactors.
IntActiO75317. 16 interactors.
STRINGi9606.ENSP00000282344.

Structurei

Secondary structure

1370
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi22 – 27Combined sources6
Turni29 – 31Combined sources3
Beta strandi38 – 41Combined sources4
Beta strandi42 – 46Combined sources5
Helixi47 – 58Combined sources12
Helixi61 – 68Combined sources8
Helixi81 – 92Combined sources12
Beta strandi95 – 101Combined sources7
Helixi103 – 105Combined sources3
Helixi107 – 109Combined sources3
Helixi115 – 117Combined sources3
Beta strandi119 – 121Combined sources3
Helixi128 – 146Combined sources19
Helixi171 – 176Combined sources6
Beta strandi178 – 186Combined sources9
Turni187 – 189Combined sources3
Beta strandi192 – 204Combined sources13
Beta strandi208 – 211Combined sources4
Helixi212 – 217Combined sources6
Beta strandi220 – 225Combined sources6
Helixi227 – 229Combined sources3
Beta strandi231 – 233Combined sources3
Turni234 – 237Combined sources4
Beta strandi238 – 240Combined sources3
Beta strandi242 – 250Combined sources9
Beta strandi253 – 259Combined sources7
Beta strandi262 – 265Combined sources4
Turni266 – 269Combined sources4
Beta strandi270 – 273Combined sources4
Beta strandi282 – 285Combined sources4
Beta strandi299 – 308Combined sources10
Helixi312 – 314Combined sources3
Beta strandi317 – 324Combined sources8
Beta strandi327 – 332Combined sources6
Beta strandi335 – 339Combined sources5
Turni341 – 343Combined sources3
Helixi344 – 347Combined sources4
Beta strandi350 – 352Combined sources3
Beta strandi362 – 368Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5K16X-ray2.60A/B16-370[»]
5K1AX-ray2.30A/C/E/G40-370[»]
5K1BX-ray3.30A4-370[»]
5K1CX-ray3.00A16-370[»]
5L8WX-ray2.79A1-370[»]
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.
GeneTreeiENSGT00880000137875.
HOGENOMiHOG000231498.
HOVERGENiHBG054038.
InParanoidiO75317.
KOiK11842.
OMAiEHNAARE.
OrthoDBiEOG091G0FC5.
PhylomeDBiO75317.
TreeFamiTF314144.

Family and domain databases

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

Sequencei

Sequence statusi: Complete.

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

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, AL355473 Genomic DNA. Translation: CAH70555.1.
AL355473, AL158062 Genomic DNA. Translation: CAI16331.1.
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

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.

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: June 7, 2017
This is version 151 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 13
    Human chromosome 13: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Peptidase families
    Classification of peptidase families and list of entries
  5. SIMILARITY comments
    Index of protein domains and families