USP12

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 key	Position(s)	DescriptionActions	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
Inferred from mutant phenotypeⁱ
- 19075014
metal ion binding Source: UniProtKB-KW
thiol-dependent ubiquitin-specific protease activity
Source: UniProtKB
Inferred from direct assayⁱ
- 19075014
thiol-dependent ubiquitinyl hydrolase activity
Source: UniProtKB
Inferred from direct assayⁱ
- 19075014

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

protein deubiquitination
Source: UniProtKB
Inferred from direct assayⁱ
- 19075014
- 24145035
ubiquitin-dependent protein catabolic process Source: InterPro

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Hydrolase, Protease, Thiol protease
Biological process	Ubl conjugation pathway
Ligand	Metal-binding, Zinc

Enzyme and pathway databases

Reactomeⁱ	R-HSA-5689880 Ub-specific processing proteases

Reactomeⁱ

R-HSA-5689880 Ub-specific processing proteases

Protein family/group databases

MEROPS protease database More...MEROPSⁱ	C19.020

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	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 13

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000152484.13
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:20485 USP12
MIMⁱ	603091 gene
neXtProtⁱ	NX_O75317

Subcellular locationⁱ

GO - Cellular component

Pathology & Biotechⁱ

Mutagenesis

Feature key	Position(s)	DescriptionActions	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

DisGeNET More...DisGeNETⁱ	219333
Open Targets More...OpenTargetsⁱ	ENSG00000152484
PharmGKBⁱ	PA37236

Polymorphism and mutation databases

BioMutaⁱ	USP12

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
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	O75317
PaxDbⁱ	O75317
PeptideAtlas More...PeptideAtlasⁱ	O75317
PRIDEⁱ	O75317
ProteomicsDBⁱ	49890

PTM databases

iPTMnetⁱ	O75317
PhosphoSitePlusⁱ	O75317

Expressionⁱ

Gene expression databases

Bgeeⁱ	ENSG00000152484 Expressed in 232 organ(s), highest expression level in esophagogastric junction muscularis propria
CleanExⁱ	HS_USP12
ExpressionAtlasⁱ	O75317 baseline and differential
Genevisibleⁱ	O75317 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	HPA007288

HPAⁱ

HPA007288

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

With	Entry	#Exp.	IntAct	Notes
WDR20	Q8TBZ3	4	EBI-2511507,EBI-2511486

With

Entry

#Exp.

IntAct

Notes

WDR20

Q8TBZ3

4

EBI-2511507,EBI-2511486

Protein-protein interaction databases

BioGridⁱ	128522, 36 interactors
CORUMⁱ	O75317
IntActⁱ	O75317, 16 interactors
STRINGⁱ	9606.ENSP00000282344

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Helixⁱ	22 – 27	Combined sources	6
Turnⁱ	29 – 31	Combined sources	3
Beta strandⁱ	38 – 41	Combined sources	4
Beta strandⁱ	42 – 46	Combined sources	5
Helixⁱ	47 – 58	Combined sources	12
Helixⁱ	61 – 68	Combined sources	8
Helixⁱ	81 – 92	Combined sources	12
Beta strandⁱ	95 – 101	Combined sources	7
Helixⁱ	103 – 105	Combined sources	3
Helixⁱ	107 – 109	Combined sources	3
Helixⁱ	115 – 117	Combined sources	3
Beta strandⁱ	119 – 121	Combined sources	3
Helixⁱ	128 – 146	Combined sources	19
Helixⁱ	171 – 176	Combined sources	6
Beta strandⁱ	178 – 186	Combined sources	9
Turnⁱ	187 – 189	Combined sources	3
Beta strandⁱ	192 – 204	Combined sources	13
Beta strandⁱ	208 – 211	Combined sources	4
Helixⁱ	212 – 217	Combined sources	6
Beta strandⁱ	220 – 225	Combined sources	6
Helixⁱ	227 – 229	Combined sources	3
Beta strandⁱ	231 – 233	Combined sources	3
Turnⁱ	234 – 237	Combined sources	4
Beta strandⁱ	238 – 240	Combined sources	3
Beta strandⁱ	242 – 250	Combined sources	9
Beta strandⁱ	253 – 259	Combined sources	7
Beta strandⁱ	262 – 265	Combined sources	4
Turnⁱ	266 – 269	Combined sources	4
Beta strandⁱ	270 – 273	Combined sources	4
Beta strandⁱ	282 – 285	Combined sources	4
Beta strandⁱ	299 – 308	Combined sources	10
Helixⁱ	312 – 314	Combined sources	3
Beta strandⁱ	317 – 324	Combined sources	8
Beta strandⁱ	327 – 332	Combined sources	6
Beta strandⁱ	335 – 339	Combined sources	5
Turnⁱ	341 – 343	Combined sources	3
Helixⁱ	344 – 347	Combined sources	4
Beta strandⁱ	350 – 352	Combined sources	3
Beta strandⁱ	362 – 368	Combined sources	7

Show more details

3D structure databases

ProteinModelPortalⁱ	O75317
SMRⁱ	O75317
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	39 – 369	USPAdd BLAST		331

Sequence similaritiesⁱ

Belongs to the peptidase C19 family. USP12/USP46 subfamily.Curated

Phylogenomic databases

eggNOGⁱ	KOG1864 Eukaryota ENOG410XQ81 LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00890000139367
HOGENOMⁱ	HOG000231498
HOVERGENⁱ	HBG054038
InParanoidⁱ	O75317
KEGG Orthology (KO) More...KOⁱ	K11842
OMAⁱ	TANCKIN
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0FC5
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
Pfam protein domain database More...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

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]FASTA Add 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.BLAST Align Show all Add to basket

	Entry	Entry name		Protein names	Gene names	Length	Annotation
	A0A087WWP2	A0A087WWP2_HUMAN		Ubiquitin carboxyl-terminal hydrola... Ubiquitin carboxyl-terminal hydrolase 12	USP12	90	Annotation score:
	A0A087WUU2	A0A087WUU2_HUMAN		Ubiquitin carboxyl-terminal hydrola... Ubiquitin carboxyl-terminal hydrolase 12	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
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS31952.1
NCBI Reference Sequences More...RefSeqⁱ	NP_872294.2, NM_182488.3
UniGeneⁱ	Hs.42400

Genome annotation databases

Ensemblⁱ	ENST00000282344; ENSP00000282344; ENSG00000152484
GeneIDⁱ	219333
KEGGⁱ	hsa:219333
UCSC genome browser More...UCSCⁱ	uc001uqy.4 human

Protein	Similar proteins		Species	Score	Length	Source
O75317	Ubiquitin carboxyl-terminal hydrolase 12		CALJA		370	UniRef100_O75317
USP12 isoform 1		PANTR		370
Ubiquitin carboxyl-terminal hydrolase 12		MACMU		370
USP12 isoform 1		PONAB		370
Ubiquitin specific peptidase 12		Cebus capucinus imitator		370
+7

Protein	Similar proteins		Species	Score	Length	Source
O75317	Ubiquitin carboxyl-terminal hydrolase 12		SALSA		372	UniRef90_O75317
Ubiquitin carboxyl-terminal hydrolase 12		CALJA		370
USP12 isoform 1		PANTR		370
Ubiquitin carboxyl-terminal hydrolase 12		MACMU		370
USP12 isoform 1		PONAB		370
+94

Protein	Similar proteins		Species	Score	Length	Source
O75317	Ubiquitin carboxyl-terminal hydrolase 12		SALSA		372	UniRef50_O75317
Ubiquitin carboxyl-terminal hydrolase 46		DANRE		370
Ubiquitin carboxyl-terminal hydrolase 46		RAT		366
Ubiquitin carboxyl-terminal hydrolase 46	)	HUMAN		366
Ubiquitin carboxyl-terminal hydrolase 46		MOUSE		366
+696

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:	September 12, 2018
	This is version 157 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, Complete proteome, Reference proteome

UniProtKB

UniParc

Help

UniRef

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Annotation systems

Supporting data

UniProtKB - O75317 (UBP12_HUMAN)

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Ubiquitin carboxyl-terminal hydrolase 12

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Miscellaneous

Sites

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

Protein family/group databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Organism-specific databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

Family and domain databases

Computationally mapped potential isoform sequencesi

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

Experimental Info

Sequence databases

Genome annotation databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Expressionⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Computationally mapped potential isoform sequencesⁱ

Sequence cautionⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ