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Protein

Tyrosine-protein phosphatase non-receptor type 12

Gene

PTPN12

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Dephosphorylates a range of proteins, and thereby regulates cellular signaling cascades (PubMed:18559503). Dephosphorylates cellular tyrosine kinases, such as ERBB2 and PTK2B/PYK2, and thereby regulates signaling via ERBB2 and PTK2B/PYK2 (PubMed:17329398, PubMed:27134172). Selectively dephosphorylates ERBB2 phosphorylated at 'Tyr-1112', 'Tyr-1196', and/or 'Tyr-1248' (PubMed:27134172).3 Publications

Catalytic activityi

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.PROSITE-ProRule annotation2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei36Substrate1 Publication1
Binding sitei199Substrate1 Publication1
Active sitei231Phosphocysteine intermediatePROSITE-ProRule annotation1
Binding sitei278Substrate1 Publication1

GO - Molecular functioni

  • non-membrane spanning protein tyrosine phosphatase activity Source: ProtInc
  • phosphoprotein phosphatase activity Source: UniProtKB
  • SH3 domain binding Source: UniProtKB

GO - Biological processi

  • cellular response to epidermal growth factor stimulus Source: UniProtKB
  • peptidyl-tyrosine dephosphorylation Source: UniProtKB
  • protein dephosphorylation Source: UniProtKB
  • regulation of epidermal growth factor receptor signaling pathway Source: UniProtKB
  • tissue regeneration Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Enzyme and pathway databases

BioCyciZFISH:HS05139-MONOMER.
BRENDAi3.1.3.48. 2681.
ReactomeiR-HSA-1250196. SHC1 events in ERBB2 signaling.
R-HSA-182971. EGFR downregulation.
R-HSA-186797. Signaling by PDGF.
R-HSA-8863795. Downregulation of ERBB2 signaling.
SIGNORiQ05209.

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein phosphatase non-receptor type 12 (EC:3.1.3.482 Publications)
Alternative name(s):
PTP-PEST1 Publication
Protein-tyrosine phosphatase G1
Short name:
PTPG1
Gene namesi
Name:PTPN12
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:9645. PTPN12.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell projection, Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi19S → E: Loss of phosphorylation site. 1 Publication1
Mutagenesisi36R → A: Decreases enzyme activity. 1 Publication1
Mutagenesisi63R → A: Decreases enzyme activity. 1 Publication1
Mutagenesisi64Y → A: Abolishes enzyme activity. 1 Publication1
Mutagenesisi66D → A: Abolishes enzyme activity. 1 Publication1
Mutagenesisi67I → A: Nearly abolishes enzyme activity. 1 Publication1
Mutagenesisi199D → A: Abolishes enzyme activity. 1 Publication1
Mutagenesisi200H → A: Decreases enzyme activity. 1 Publication1
Mutagenesisi270R → A: Decreases enzyme activity. 1 Publication1
Mutagenesisi278Q → A: Nearly abolishes enzyme activity. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi5782.
MalaCardsiPTPN12.
OpenTargetsiENSG00000127947.
PharmGKBiPA33987.

Chemistry databases

ChEMBLiCHEMBL3236.

Polymorphism and mutation databases

BioMutaiPTPN12.
DMDMi317373522.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000947711 – 780Tyrosine-protein phosphatase non-receptor type 12Add BLAST780

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1 Publication1
Modified residuei19PhosphoserineCombined sources1 Publication1
Modified residuei332PhosphoserineCombined sources1
Modified residuei435PhosphoserineCombined sources1
Modified residuei449PhosphoserineCombined sources1
Modified residuei468PhosphoserineCombined sources1
Modified residuei509PhosphothreonineCombined sources1
Modified residuei519PhosphothreonineCombined sources1
Modified residuei567PhosphoserineCombined sources1
Modified residuei569PhosphothreonineCombined sources1
Modified residuei571PhosphoserineCombined sources1
Modified residuei596PhosphoserineBy similarity1
Modified residuei598PhosphothreonineBy similarity1
Modified residuei603PhosphoserineCombined sources1
Modified residuei606PhosphoserineCombined sources1
Modified residuei608PhosphoserineCombined sources1
Modified residuei613PhosphoserineCombined sources1
Modified residuei673PhosphoserineCombined sources1
Modified residuei689PhosphoserineCombined sources1
Modified residuei693PhosphothreonineCombined sources1

Post-translational modificationi

Phosphorylated by STK24/MST3 and this results in inhibition of its activity.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ05209.
MaxQBiQ05209.
PaxDbiQ05209.
PeptideAtlasiQ05209.
PRIDEiQ05209.

PTM databases

DEPODiQ05209.
iPTMnetiQ05209.
PhosphoSitePlusiQ05209.

Expressioni

Gene expression databases

BgeeiENSG00000127947.
CleanExiHS_PTPN12.
ExpressionAtlasiQ05209. baseline and differential.
GenevisibleiQ05209. HS.

Organism-specific databases

HPAiHPA007097.

Interactioni

Subunit structurei

Interacts with TGFB1I1 (By similarity). Interacts with PSTPIP1 (PubMed:9857189). Interacts with PTK2B/PYK2 (PubMed:17329398). Interacts with LPXN (By similarity). Interacts with SORBS2; this interaction greatly enhances WASF1 dephosphorylation and might mediate partial translocation to focal adhesion sites (PubMed:18559503).By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BCAR1P569454EBI-2266035,EBI-702093
EGFRP005333EBI-2266035,EBI-297353
ERBB2P046264EBI-2266035,EBI-641062
PDGFRBP096193EBI-2266035,EBI-641237
PSTPIP1O435864EBI-2266035,EBI-1050964
SHC1P293534EBI-2266035,EBI-78835
TEKQ027632EBI-2266035,EBI-2257090

GO - Molecular functioni

  • SH3 domain binding Source: UniProtKB

Protein-protein interaction databases

BioGridi111746. 48 interactors.
IntActiQ05209. 48 interactors.
MINTiMINT-243699.
STRINGi9606.ENSP00000248594.

Chemistry databases

BindingDBiQ05209.

Structurei

Secondary structure

1780
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi3 – 17Combined sources15
Helixi27 – 44Combined sources18
Turni51 – 54Combined sources4
Helixi56 – 61Combined sources6
Helixi71 – 73Combined sources3
Beta strandi74 – 76Combined sources3
Beta strandi88 – 96Combined sources9
Beta strandi99 – 106Combined sources8
Helixi111 – 113Combined sources3
Helixi114 – 123Combined sources10
Beta strandi128 – 131Combined sources4
Beta strandi135 – 137Combined sources3
Beta strandi155 – 157Combined sources3
Beta strandi160 – 170Combined sources11
Beta strandi173 – 182Combined sources10
Beta strandi185 – 194Combined sources10
Helixi207 – 219Combined sources13
Beta strandi227 – 230Combined sources4
Beta strandi232 – 236Combined sources5
Helixi237 – 252Combined sources16
Helixi262 – 270Combined sources9
Helixi280 – 297Combined sources18

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5J8RX-ray2.04A/B/C/D1-305[»]
ProteinModelPortaliQ05209.
SMRiQ05209.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini28 – 293Tyrosine-protein phosphatasePROSITE-ProRule annotationAdd BLAST266

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni63 – 67Substrate binding1 Publication5
Regioni231 – 237Substrate bindingBy similarity7
Regioni345 – 438Interaction with TGFB1I1By similarityAdd BLAST94

Sequence similaritiesi

Contains 1 tyrosine-protein phosphatase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0789. Eukaryota.
COG5599. LUCA.
GeneTreeiENSGT00770000120452.
HOGENOMiHOG000252955.
HOVERGENiHBG007666.
InParanoidiQ05209.
KOiK18024.
OMAiTWSFHGP.
OrthoDBiEOG091G0B5O.
PhylomeDBiQ05209.
TreeFamiTF351977.

Family and domain databases

Gene3Di3.90.190.10. 1 hit.
InterProiIPR029021. Prot-tyrosine_phosphatase-like.
IPR000242. PTPase_domain.
IPR012266. Ptpn_12.
IPR016130. Tyr_Pase_AS.
IPR003595. Tyr_Pase_cat.
IPR000387. TYR_PHOSPHATASE_dom.
[Graphical view]
PfamiPF00102. Y_phosphatase. 1 hit.
[Graphical view]
PIRSFiPIRSF000932. Tyr-Ptase_nr12. 1 hit.
PRINTSiPR00700. PRTYPHPHTASE.
SMARTiSM00194. PTPc. 1 hit.
SM00404. PTPc_motif. 1 hit.
[Graphical view]
SUPFAMiSSF52799. SSF52799. 1 hit.
PROSITEiPS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50055. TYR_PHOSPHATASE_PTP. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q05209-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MEQVEILRKF IQRVQAMKSP DHNGEDNFAR DFMRLRRLST KYRTEKIYPT
60 70 80 90 100
ATGEKEENVK KNRYKDILPF DHSRVKLTLK TPSQDSDYIN ANFIKGVYGP
110 120 130 140 150
KAYVATQGPL ANTVIDFWRM IWEYNVVIIV MACREFEMGR KKCERYWPLY
160 170 180 190 200
GEDPITFAPF KISCEDEQAR TDYFIRTLLL EFQNESRRLY QFHYVNWPDH
210 220 230 240 250
DVPSSFDSIL DMISLMRKYQ EHEDVPICIH CSAGCGRTGA ICAIDYTWNL
260 270 280 290 300
LKAGKIPEEF NVFNLIQEMR TQRHSAVQTK EQYELVHRAI AQLFEKQLQL
310 320 330 340 350
YEIHGAQKIA DGVNEINTEN MVSSIEPEKQ DSPPPKPPRT RSCLVEGDAK
360 370 380 390 400
EEILQPPEPH PVPPILTPSP PSAFPTVTTV WQDNDRYHPK PVLHMVSSEQ
410 420 430 440 450
HSADLNRNYS KSTELPGKNE STIEQIDKKL ERNLSFEIKK VPLQEGPKSF
460 470 480 490 500
DGNTLLNRGH AIKIKSASPC IADKISKPQE LSSDLNVGDT SQNSCVDCSV
510 520 530 540 550
TQSNKVSVTP PEESQNSDTP PRPDRLPLDE KGHVTWSFHG PENAIPIPDL
560 570 580 590 600
SEGNSSDINY QTRKTVSLTP SPTTQVETPD LVDHDNTSPL FRTPLSFTNP
610 620 630 640 650
LHSDDSDSDE RNSDGAVTQN KTNISTASAT VSAATSTESI STRKVLPMSI
660 670 680 690 700
ARHNIAGTTH SGAEKDVDVS EDSPPPLPER TPESFVLASE HNTPVRSEWS
710 720 730 740 750
ELQSQERSEQ KKSEGLITSE NEKCDHPAGG IHYEMCIECP PTFSDKREQI
760 770 780
SENPTEATDI GFGNRCGKPK GPRDPPSEWT
Length:780
Mass (Da):88,106
Last modified:January 11, 2011 - v3
Checksum:i663DB3E5176FD7FD
GO
Isoform 2 (identifier: Q05209-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-130: Missing.

Note: No experimental confirmation available.
Show »
Length:650
Mass (Da):72,778
Checksum:i217EF3041B7E5EDB
GO
Isoform 3 (identifier: Q05209-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-119: Missing.

Note: No experimental confirmation available. Gene prediction based on EST data.
Show »
Length:661
Mass (Da):74,138
Checksum:i74E2947477636633
GO

Sequence cautioni

The sequence BAD92761 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti121I → V in BAA02648 (PubMed:1472029).Curated1
Sequence conflicti121I → V in AAB30047 (PubMed:7509295).Curated1
Sequence conflicti612N → D in BAG59344 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00638561K → R in colon cancer. 1 PublicationCorresponds to variant rs121434623dbSNPEnsembl.1
Natural variantiVAR_019512322V → I.Combined sources3 PublicationsCorresponds to variant rs9640663dbSNPEnsembl.1
Natural variantiVAR_020297573T → A.1 PublicationCorresponds to variant rs3750050dbSNPEnsembl.1
Natural variantiVAR_057129706E → K.Corresponds to variant rs2230602dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0462741 – 130Missing in isoform 2. 1 PublicationAdd BLAST130
Alternative sequenceiVSP_0541681 – 119Missing in isoform 3. CuratedAdd BLAST119

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D13380 mRNA. Translation: BAA02648.1.
M93425 mRNA. Translation: AAA36529.1.
AK289573 mRNA. Translation: BAF82262.1.
AK296764 mRNA. Translation: BAG59344.1.
AB209524 mRNA. Translation: BAD92761.1. Different initiation.
AC006451 Genomic DNA. Translation: AAQ96881.1.
CH236949 Genomic DNA. Translation: EAL24198.1.
CH471091 Genomic DNA. Translation: EAW77036.1.
CH471091 Genomic DNA. Translation: EAW77037.1.
BC050008 mRNA. Translation: AAH50008.2.
S69184 mRNA. Translation: AAB30047.2.
CCDSiCCDS47619.1. [Q05209-3]
CCDS47620.1. [Q05209-2]
CCDS5592.1. [Q05209-1]
PIRiJC1368.
RefSeqiNP_001124480.1. NM_001131008.1. [Q05209-3]
NP_001124481.1. NM_001131009.1. [Q05209-2]
NP_002826.3. NM_002835.3. [Q05209-1]
UniGeneiHs.61812.

Genome annotation databases

EnsembliENST00000248594; ENSP00000248594; ENSG00000127947. [Q05209-1]
ENST00000415482; ENSP00000392429; ENSG00000127947. [Q05209-3]
ENST00000435495; ENSP00000397991; ENSG00000127947. [Q05209-2]
GeneIDi5782.
KEGGihsa:5782.
UCSCiuc003ugh.3. human. [Q05209-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D13380 mRNA. Translation: BAA02648.1.
M93425 mRNA. Translation: AAA36529.1.
AK289573 mRNA. Translation: BAF82262.1.
AK296764 mRNA. Translation: BAG59344.1.
AB209524 mRNA. Translation: BAD92761.1. Different initiation.
AC006451 Genomic DNA. Translation: AAQ96881.1.
CH236949 Genomic DNA. Translation: EAL24198.1.
CH471091 Genomic DNA. Translation: EAW77036.1.
CH471091 Genomic DNA. Translation: EAW77037.1.
BC050008 mRNA. Translation: AAH50008.2.
S69184 mRNA. Translation: AAB30047.2.
CCDSiCCDS47619.1. [Q05209-3]
CCDS47620.1. [Q05209-2]
CCDS5592.1. [Q05209-1]
PIRiJC1368.
RefSeqiNP_001124480.1. NM_001131008.1. [Q05209-3]
NP_001124481.1. NM_001131009.1. [Q05209-2]
NP_002826.3. NM_002835.3. [Q05209-1]
UniGeneiHs.61812.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5J8RX-ray2.04A/B/C/D1-305[»]
ProteinModelPortaliQ05209.
SMRiQ05209.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111746. 48 interactors.
IntActiQ05209. 48 interactors.
MINTiMINT-243699.
STRINGi9606.ENSP00000248594.

Chemistry databases

BindingDBiQ05209.
ChEMBLiCHEMBL3236.

PTM databases

DEPODiQ05209.
iPTMnetiQ05209.
PhosphoSitePlusiQ05209.

Polymorphism and mutation databases

BioMutaiPTPN12.
DMDMi317373522.

Proteomic databases

EPDiQ05209.
MaxQBiQ05209.
PaxDbiQ05209.
PeptideAtlasiQ05209.
PRIDEiQ05209.

Protocols and materials databases

DNASUi5782.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000248594; ENSP00000248594; ENSG00000127947. [Q05209-1]
ENST00000415482; ENSP00000392429; ENSG00000127947. [Q05209-3]
ENST00000435495; ENSP00000397991; ENSG00000127947. [Q05209-2]
GeneIDi5782.
KEGGihsa:5782.
UCSCiuc003ugh.3. human. [Q05209-1]

Organism-specific databases

CTDi5782.
DisGeNETi5782.
GeneCardsiPTPN12.
H-InvDBHIX0033626.
HGNCiHGNC:9645. PTPN12.
HPAiHPA007097.
MalaCardsiPTPN12.
MIMi600079. gene.
neXtProtiNX_Q05209.
OpenTargetsiENSG00000127947.
PharmGKBiPA33987.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0789. Eukaryota.
COG5599. LUCA.
GeneTreeiENSGT00770000120452.
HOGENOMiHOG000252955.
HOVERGENiHBG007666.
InParanoidiQ05209.
KOiK18024.
OMAiTWSFHGP.
OrthoDBiEOG091G0B5O.
PhylomeDBiQ05209.
TreeFamiTF351977.

Enzyme and pathway databases

BioCyciZFISH:HS05139-MONOMER.
BRENDAi3.1.3.48. 2681.
ReactomeiR-HSA-1250196. SHC1 events in ERBB2 signaling.
R-HSA-182971. EGFR downregulation.
R-HSA-186797. Signaling by PDGF.
R-HSA-8863795. Downregulation of ERBB2 signaling.
SIGNORiQ05209.

Miscellaneous databases

ChiTaRSiPTPN12. human.
GeneWikiiPTPN12.
GenomeRNAii5782.
PROiQ05209.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000127947.
CleanExiHS_PTPN12.
ExpressionAtlasiQ05209. baseline and differential.
GenevisibleiQ05209. HS.

Family and domain databases

Gene3Di3.90.190.10. 1 hit.
InterProiIPR029021. Prot-tyrosine_phosphatase-like.
IPR000242. PTPase_domain.
IPR012266. Ptpn_12.
IPR016130. Tyr_Pase_AS.
IPR003595. Tyr_Pase_cat.
IPR000387. TYR_PHOSPHATASE_dom.
[Graphical view]
PfamiPF00102. Y_phosphatase. 1 hit.
[Graphical view]
PIRSFiPIRSF000932. Tyr-Ptase_nr12. 1 hit.
PRINTSiPR00700. PRTYPHPHTASE.
SMARTiSM00194. PTPc. 1 hit.
SM00404. PTPc_motif. 1 hit.
[Graphical view]
SUPFAMiSSF52799. SSF52799. 1 hit.
PROSITEiPS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50055. TYR_PHOSPHATASE_PTP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPTN12_HUMAN
AccessioniPrimary (citable) accession number: Q05209
Secondary accession number(s): A4D1C5
, B4DKY2, E9PBR5, E9PEH9, Q16130, Q59FD6, Q75MN8, Q86XU4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: January 11, 2011
Last modified: November 30, 2016
This is version 167 of the entry and version 3 of the sequence. [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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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.