Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Tyrosine-protein phosphatase non-receptor type 11

Gene

PTPN11

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

Functioni

Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus. Positively regulates MAPK signal transduction pathway (PubMed:28074573). Dephosphorylates GAB1, ARHGAP35 and EGFR (PubMed:28074573). Dephosphorylates ROCK2 at 'Tyr-722' resulting in stimulatation of its RhoA binding activity. Dephosphorylates CDC73 (PubMed:26742426).5 Publications

Catalytic activityi

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.PROSITE-ProRule annotation3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei429SubstrateBy similarity1
Active sitei463Phosphocysteine intermediate1
Binding sitei510SubstrateBy similarity1

GO - Molecular functioni

  • 1-phosphatidylinositol-3-kinase activity Source: Reactome
  • cell adhesion molecule binding Source: Ensembl
  • D1 dopamine receptor binding Source: Ensembl
  • insulin receptor binding Source: BHF-UCL
  • insulin receptor substrate binding Source: Ensembl
  • non-membrane spanning protein tyrosine phosphatase activity Source: UniProtKB
  • peptide hormone receptor binding Source: Ensembl
  • phosphatidylinositol-4,5-bisphosphate 3-kinase activity Source: Reactome
  • phospholipase binding Source: Ensembl
  • phosphoprotein phosphatase activity Source: UniProtKB
  • phosphotyrosine residue binding Source: UniProtKB
  • protein domain specific binding Source: Ensembl
  • protein tyrosine phosphatase activity Source: UniProtKB
  • receptor tyrosine kinase binding Source: Ensembl
  • SH3/SH2 adaptor activity Source: BHF-UCL

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protein phosphatase

Enzyme and pathway databases

BRENDAi3.1.3.48 2681
ReactomeiR-HSA-1059683 Interleukin-6 signaling
R-HSA-109704 PI3K Cascade
R-HSA-110056 MAPK3 (ERK1) activation
R-HSA-112411 MAPK1 (ERK2) activation
R-HSA-114604 GPVI-mediated activation cascade
R-HSA-1170546 Prolactin receptor signaling
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-1295596 Spry regulation of FGF signaling
R-HSA-1433557 Signaling by SCF-KIT
R-HSA-180292 GAB1 signalosome
R-HSA-186763 Downstream signal transduction
R-HSA-210990 PECAM1 interactions
R-HSA-210993 Tie2 Signaling
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-2586552 Signaling by Leptin
R-HSA-388841 Costimulation by the CD28 family
R-HSA-389513 CTLA4 inhibitory signaling
R-HSA-389948 PD-1 signaling
R-HSA-391160 Signal regulatory protein family interactions
R-HSA-418886 Netrin mediated repulsion signals
R-HSA-432142 Platelet sensitization by LDL
R-HSA-512988 Interleukin-3, 5 and GM-CSF signaling
R-HSA-5654689 PI-3K cascade:FGFR1
R-HSA-5654693 FRS-mediated FGFR1 signaling
R-HSA-5654695 PI-3K cascade:FGFR2
R-HSA-5654700 FRS-mediated FGFR2 signaling
R-HSA-5654706 FRS-mediated FGFR3 signaling
R-HSA-5654710 PI-3K cascade:FGFR3
R-HSA-5654712 FRS-mediated FGFR4 signaling
R-HSA-5654720 PI-3K cascade:FGFR4
R-HSA-5654726 Negative regulation of FGFR1 signaling
R-HSA-5654727 Negative regulation of FGFR2 signaling
R-HSA-5654732 Negative regulation of FGFR3 signaling
R-HSA-5654733 Negative regulation of FGFR4 signaling
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-877312 Regulation of IFNG signaling
R-HSA-8853659 RET signaling
R-HSA-8854691 Interleukin-20 family signaling
R-HSA-8865999 MET activates PTPN11
R-HSA-8934593 Regulation of RUNX1 Expression and Activity
R-HSA-9008059 Interleukin-37 signaling
R-HSA-9028731 Activated NTRK2 signals through FRS2 and FRS3
R-HSA-909733 Interferon alpha/beta signaling
R-HSA-912694 Regulation of IFNA signaling
R-HSA-936964 Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon
SignaLinkiQ06124
SIGNORiQ06124

Protein family/group databases

MoonDBiQ06124 Predicted

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein phosphatase non-receptor type 11 (EC:3.1.3.482 Publications)
Alternative name(s):
Protein-tyrosine phosphatase 1D
Short name:
PTP-1D
Protein-tyrosine phosphatase 2C
Short name:
PTP-2C
SH-PTP2
Short name:
SHP-2
Short name:
Shp2
SH-PTP3
Gene namesi
Name:PTPN11
Synonyms:PTP2C, SHPTP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000179295.16
HGNCiHGNC:9644 PTPN11
MIMi176876 gene
neXtProtiNX_Q06124

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

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

LEOPARD syndrome 1 (LPRD1)10 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and sensorineural deafness.
See also OMIM:151100
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_027188279Y → S in LPRD1. 2 PublicationsCorresponds to variant dbSNP:rs121918456EnsemblClinVar.1
Natural variantiVAR_027190465A → T in LPRD1. 1 PublicationCorresponds to variant dbSNP:rs121918468Ensembl.1
Natural variantiVAR_027191468G → A in LPRD1. 2 PublicationsCorresponds to variant dbSNP:rs121918469Ensembl.1
Natural variantiVAR_015621472T → M in LPRD1; does not affect subcellular location; decreases protein tyrosine phosphatase activity against CDC73. 5 PublicationsCorresponds to variant dbSNP:rs121918457Ensembl.1
Natural variantiVAR_027192502R → L in LPRD1. 1 PublicationCorresponds to variant dbSNP:rs397507542Ensembl.1
Natural variantiVAR_027193502R → W in LPRD1; reduced phosphatase activity. 2 PublicationsCorresponds to variant dbSNP:rs397507541Ensembl.1
Natural variantiVAR_027194510Q → P in LPRD1; does not affect subcellular location; decreases protein tyrosine phosphatase activity against CDC73. 4 PublicationsCorresponds to variant dbSNP:rs397509345Ensembl.1
Natural variantiVAR_027196514Q → P in LPRD1. 1 PublicationCorresponds to variant dbSNP:rs121918470Ensembl.1
Noonan syndrome 1 (NS1)15 Publications
The disease is caused by mutations affecting the gene represented in this entry. Mutations in PTPN11 account for more than 50% of the cases.
Disease descriptionA form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells. Some patients with NS1 develop multiple giant cell lesions of the jaw or other bony or soft tissues, which are classified as pigmented villonodular synovitis (PVNS) when occurring in the jaw or joints.
See also OMIM:163950
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0271832T → I in NS1. 1 PublicationCorresponds to variant dbSNP:rs267606990EnsemblClinVar.1
Natural variantiVAR_01560142T → A in NS1. 2 PublicationsCorresponds to variant dbSNP:rs397507501EnsemblClinVar.1
Natural variantiVAR_02718458N → K in NS1. 1 PublicationCorresponds to variant dbSNP:rs397507506EnsemblClinVar.1
Natural variantiVAR_06606059T → A in NS1. 1 PublicationCorresponds to variant dbSNP:rs886043790EnsemblClinVar.1
Natural variantiVAR_01560260G → A in NS1. 1 PublicationCorresponds to variant dbSNP:rs397507509EnsemblClinVar.1
Natural variantiVAR_01560361D → G in NS1. 4 PublicationsCorresponds to variant dbSNP:rs121918461EnsemblClinVar.1
Natural variantiVAR_01560461D → N in NS1. 2 PublicationsCorresponds to variant dbSNP:rs397507510EnsemblClinVar.1
Natural variantiVAR_01560562Y → D in NS1; also in Noonan patients manifesting juvenile myelomonocytic leukemia. 4 PublicationsCorresponds to variant dbSNP:rs121918460EnsemblClinVar.1
Natural variantiVAR_01560663Y → C in NS1. 6 PublicationsCorresponds to variant dbSNP:rs121918459EnsemblClinVar.1
Natural variantiVAR_02718569E → Q in NS1. 1 PublicationCorresponds to variant dbSNP:rs397507511EnsemblClinVar.1
Natural variantiVAR_01560772A → G in NS1. 3 PublicationsCorresponds to variant dbSNP:rs121918454EnsemblClinVar.1
Natural variantiVAR_01560872A → S in NS1. 3 PublicationsCorresponds to variant dbSNP:rs121918453EnsemblClinVar.1
Natural variantiVAR_01560973T → I in NS1; also in Noonan patients manifesting juvenile myelomonocytic leukemia. 4 PublicationsCorresponds to variant dbSNP:rs121918462EnsemblClinVar.1
Natural variantiVAR_01561076E → D in NS1. 3 PublicationsCorresponds to variant dbSNP:rs397507514EnsemblClinVar.1
Natural variantiVAR_02718679Q → P in NS1. 1 Publication1
Natural variantiVAR_01561179Q → R in NS1. 4 PublicationsCorresponds to variant dbSNP:rs121918466EnsemblClinVar.1
Natural variantiVAR_015612106D → A in NS1. 2 PublicationsCorresponds to variant dbSNP:rs397507517EnsemblClinVar.1
Natural variantiVAR_015613139E → D in NS1. 2 PublicationsCorresponds to variant dbSNP:rs397507520EnsemblClinVar.1
Natural variantiVAR_027187256Q → R in NS1. 1 PublicationCorresponds to variant dbSNP:rs397507523EnsemblClinVar.1
Natural variantiVAR_078101261L → F in NS1; increases MAPK signaling; increases protein tyrosine phosphatase activity; changed substrate selectivity for GAB1. 1 PublicationCorresponds to variant dbSNP:rs397507525EnsemblClinVar.1
Natural variantiVAR_078102261L → H in NS1; increases MAPK signaling; increased protein tyrosine phosphatase activity. 1 PublicationCorresponds to variant dbSNP:rs765642157Ensembl.1
Natural variantiVAR_078103262L → F in NS1; increases MAPK signaling; increased protein tyrosine phosphatase activity. 1 Publication1
Natural variantiVAR_078104262L → R in NS1; increases MAPK signaling; increased protein tyrosine phosphatase activity. 1 PublicationCorresponds to variant dbSNP:rs397507526EnsemblClinVar.1
Natural variantiVAR_078105265R → Q in NS1; increases MAPK signaling; increased protein tyrosine phosphatase activity. 1 PublicationCorresponds to variant dbSNP:rs376607329EnsemblClinVar.1
Natural variantiVAR_015615282I → V in NS1. 3 PublicationsCorresponds to variant dbSNP:rs397507529EnsemblClinVar.1
Natural variantiVAR_015617285F → L in NS1. 1 PublicationCorresponds to variant dbSNP:rs397507531EnsemblClinVar.1
Natural variantiVAR_015616285F → S in NS1. 2 PublicationsCorresponds to variant dbSNP:rs121918463EnsemblClinVar.1
Natural variantiVAR_015619308N → D in NS1; common mutation. 5 PublicationsCorresponds to variant dbSNP:rs28933386EnsemblClinVar.1
Natural variantiVAR_015618308N → S in NS1; some patients also manifest giant cell lesions of bone and soft tissue. 2 PublicationsCorresponds to variant dbSNP:rs121918455EnsemblClinVar.1
Natural variantiVAR_015620309I → V in NS1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs201787206EnsemblClinVar.1
Natural variantiVAR_027189415T → M in NS1. 1 PublicationCorresponds to variant dbSNP:rs121918467Ensembl.1
Natural variantiVAR_071706495P → S in NS1; increased phosphatase activity. 1 PublicationCorresponds to variant dbSNP:rs397507539Ensembl.1
Natural variantiVAR_015622505R → K in NS1. 1 PublicationCorresponds to variant dbSNP:rs397507543Ensembl.1
Natural variantiVAR_015623506S → T in NS1. 2 PublicationsCorresponds to variant dbSNP:rs121918458Ensembl.1
Natural variantiVAR_015624508M → V in NS1. 3 PublicationsCorresponds to variant dbSNP:rs397507547Ensembl.1
Natural variantiVAR_027195510Q → R in NS1. 1 Publication1
Natural variantiVAR_027197564L → F in NS1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs397516797Ensembl.1
Leukemia, juvenile myelomonocytic (JMML)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn aggressive pediatric myelodysplastic syndrome/myeloproliferative disorder characterized by malignant transformation in the hematopoietic stem cell compartment with proliferation of differentiated progeny. Patients have splenomegaly, enlarged lymph nodes, rashes, and hemorrhages.
See also OMIM:607785
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01599161D → V in JMML; also in myelodysplastic syndrome. 1 PublicationCorresponds to variant dbSNP:rs121918461EnsemblClinVar.1
Natural variantiVAR_01599261D → Y in JMML. 1 PublicationCorresponds to variant dbSNP:rs397507510EnsemblClinVar.1
Natural variantiVAR_01599369E → K in JMML; also in myelodysplastic syndrome. 1 PublicationCorresponds to variant dbSNP:rs397507511EnsemblClinVar.1
Natural variantiVAR_01599672A → T in JMML. 1 PublicationCorresponds to variant dbSNP:rs121918453EnsemblClinVar.1
Natural variantiVAR_01599772A → V in JMML. 1 PublicationCorresponds to variant dbSNP:rs121918454EnsemblClinVar.1
Natural variantiVAR_01599876E → A in JMML; also in myelodysplastic syndrome. 1 PublicationCorresponds to variant dbSNP:rs121918465EnsemblClinVar.1
Natural variantiVAR_01599976E → G in JMML. 1 PublicationCorresponds to variant dbSNP:rs121918465EnsemblClinVar.1
Natural variantiVAR_01600076E → K in JMML; increases protein tyrosine phosphatase activity against CDC73. 2 PublicationsCorresponds to variant dbSNP:rs121918464EnsemblClinVar.1
Natural variantiVAR_01600176E → V in JMML. 1 PublicationCorresponds to variant dbSNP:rs121918465EnsemblClinVar.1
Natural variantiVAR_016002507G → A in JMML. 1 PublicationCorresponds to variant dbSNP:rs397507546Ensembl.1
Metachondromatosis (MC)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA skeletal disorder with radiologic features of both multiple exostoses and Ollier disease, characterized by the presence of exostoses, commonly of the bones of the hands and feet, and enchondromas of the metaphyses of long bones and iliac crest.
See also OMIM:156250

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi463C → S: Abolishes phosphatase activity. 1 Publication1

Keywords - Diseasei

Deafness, Disease mutation

Organism-specific databases

DisGeNETi5781
GeneReviewsiPTPN11
MalaCardsiPTPN11
MIMi151100 phenotype
156250 phenotype
163950 phenotype
607785 phenotype
OpenTargetsiENSG00000179295
Orphaneti86834 Juvenile myelomonocytic leukemia
500 LEOPARD syndrome
2499 Metachondromatosis
648 Noonan syndrome
PharmGKBiPA33986

Chemistry databases

ChEMBLiCHEMBL3864
DrugBankiDB02779 Dodecane-Trimethylamine

Polymorphism and mutation databases

BioMutaiPTPN11
DMDMi84028248

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000947672 – 597Tyrosine-protein phosphatase non-receptor type 11Add BLAST596

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylthreonineCombined sources1
Modified residuei62PhosphotyrosineCombined sources1
Modified residuei66PhosphotyrosineBy similarity1
Modified residuei546Phosphotyrosine; by PDGFRBy similarity1
Modified residuei584Phosphotyrosine; by PDGFRCombined sources1

Post-translational modificationi

Phosphorylated on Tyr-546 and Tyr-584 upon receptor protein tyrosine kinase activation; which creates a binding site for GRB2 and other SH2-containing proteins. Phosphorylated upon activation of the receptor-type kinase FLT3. Phosphorylated upon activation of the receptor-type kinase PDGFRA (By similarity). Phosphorylated by activated PDGFRB.By similarity4 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ06124
MaxQBiQ06124
PaxDbiQ06124
PeptideAtlasiQ06124
PRIDEiQ06124
ProteomicsDBi58414
58415 [Q06124-2]
58416 [Q06124-3]
TopDownProteomicsiQ06124-2 [Q06124-2]

PTM databases

DEPODiQ06124
iPTMnetiQ06124
PhosphoSitePlusiQ06124

Expressioni

Tissue specificityi

Widely expressed, with highest levels in heart, brain, and skeletal muscle.3 Publications

Gene expression databases

BgeeiENSG00000179295
CleanExiHS_PTPN11
ExpressionAtlasiQ06124 baseline and differential
GenevisibleiQ06124 HS

Organism-specific databases

HPAiCAB005377

Interactioni

Subunit structurei

Interacts with phosphorylated LIME1 and BCAR3. Interacts with SHB and INPP5D/SHIP1 (By similarity). Interacts with MILR1 (tyrosine-phosphorylated). Interacts with FLT1 (tyrosine-phosphorylated), FLT3 (tyrosine-phosphorylated), FLT4 (tyrosine-phosphorylated), KIT and GRB2. Interacts with PDGFRA (tyrosine phosphorylated). Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated) (By similarity). Interacts with PTPNS1 and CD84. Interacts with phosphorylated SIT1 and MPZL1. Interacts with FCRL4, FCRL6 and ANKHD1. Interacts with KIR2DL1; the interaction is enhanced by ARRB2. Interacts with GAB2. Interacts with TERT; the interaction retains TERT in the nucleus. Interacts with PECAM1 and FER. Interacts with EPHA2 (activated); participates in PTK2/FAK1 dephosphorylation in EPHA2 downstream signaling. Interacts with ROS1; mediates PTPN11 phosphorylation. Interacts with PDGFRB (tyrosine phosphorylated); this interaction increases the PTPN11 phosphatase activity. Interacts with GAREM1 isoform 1 (tyrosine phosphorylated); the interaction increases MAPK/ERK activity and does not affect the GRB2/SOS complex formation. Interacts with CDC73 (PubMed:26742426). Interacts with CEACAM1 (via cytoplasmic domain); this interaction depends on the monomer/dimer equilibrium and is phosphorylation-dependent (By similarity). Interacts with MPIG6B (via ITIM motif) (PubMed:23112346). Interacts with SIGLEC10 (By similarity). Interacts with FCRL3 (via phosphorylated ITIM motifs) (PubMed:11162587, PubMed:19843936).By similarity27 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • cell adhesion molecule binding Source: Ensembl
  • D1 dopamine receptor binding Source: Ensembl
  • insulin receptor binding Source: BHF-UCL
  • insulin receptor substrate binding Source: Ensembl
  • peptide hormone receptor binding Source: Ensembl
  • phospholipase binding Source: Ensembl
  • phosphotyrosine residue binding Source: UniProtKB
  • protein domain specific binding Source: Ensembl
  • receptor tyrosine kinase binding Source: Ensembl
  • SH3/SH2 adaptor activity Source: BHF-UCL

Protein-protein interaction databases

BioGridi111745, 172 interactors
CORUMiQ06124
DIPiDIP-516N
ELMiQ06124
IntActiQ06124, 75 interactors
MINTiQ06124
STRINGi9606.ENSP00000340944

Chemistry databases

BindingDBiQ06124

Structurei

Secondary structure

1597
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni4 – 6Combined sources3
Helixi13 – 23Combined sources11
Beta strandi28 – 33Combined sources6
Beta strandi35 – 37Combined sources3
Beta strandi41 – 47Combined sources7
Beta strandi50 – 57Combined sources8
Beta strandi59 – 61Combined sources3
Beta strandi63 – 65Combined sources3
Beta strandi70 – 73Combined sources4
Helixi74 – 82Combined sources9
Beta strandi83 – 85Combined sources3
Beta strandi87 – 90Combined sources4
Beta strandi91 – 93Combined sources3
Helixi107 – 109Combined sources3
Beta strandi113 – 116Combined sources4
Helixi119 – 129Combined sources11
Beta strandi134 – 139Combined sources6
Beta strandi141 – 143Combined sources3
Beta strandi147 – 153Combined sources7
Beta strandi154 – 156Combined sources3
Beta strandi166 – 175Combined sources10
Beta strandi178 – 184Combined sources7
Beta strandi187 – 189Combined sources3
Helixi190 – 199Combined sources10
Beta strandi202 – 204Combined sources3
Turni205 – 207Combined sources3
Beta strandi208 – 210Combined sources3
Beta strandi218 – 222Combined sources5
Helixi223 – 225Combined sources3
Helixi226 – 234Combined sources9
Helixi251 – 253Combined sources3
Helixi256 – 258Combined sources3
Helixi259 – 262Combined sources4
Helixi266 – 269Combined sources4
Helixi271 – 276Combined sources6
Beta strandi277 – 279Combined sources3
Helixi286 – 288Combined sources3
Beta strandi289 – 291Combined sources3
Beta strandi304 – 310Combined sources7
Beta strandi319 – 321Combined sources3
Helixi323 – 325Combined sources3
Beta strandi327 – 331Combined sources5
Helixi335 – 337Combined sources3
Helixi338 – 347Combined sources10
Beta strandi352 – 355Combined sources4
Beta strandi359 – 361Combined sources3
Beta strandi364 – 366Combined sources3
Beta strandi376 – 380Combined sources5
Beta strandi383 – 392Combined sources10
Beta strandi394 – 405Combined sources12
Helixi413 – 415Combined sources3
Beta strandi417 – 424Combined sources8
Beta strandi429 – 431Combined sources3
Beta strandi434 – 436Combined sources3
Helixi437 – 451Combined sources15
Beta strandi459 – 467Combined sources9
Helixi468 – 486Combined sources19
Beta strandi488 – 492Combined sources5
Helixi494 – 502Combined sources9
Helixi512 – 528Combined sources17
Beta strandi585 – 589Combined sources5

3D structure databases

ProteinModelPortaliQ06124
SMRiQ06124
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ06124

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini6 – 102SH2 1PROSITE-ProRule annotationAdd BLAST97
Domaini112 – 216SH2 2PROSITE-ProRule annotationAdd BLAST105
Domaini247 – 521Tyrosine-protein phosphatasePROSITE-ProRule annotationAdd BLAST275

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni463 – 469Substrate bindingBy similarity7

Domaini

The SH2 domains repress phosphatase activity. Binding of these domains to phosphotyrosine-containing proteins relieves this auto-inhibition, possibly by inducing a conformational change in the enzyme.

Sequence similaritiesi

Keywords - Domaini

Repeat, SH2 domain

Phylogenomic databases

eggNOGiKOG0790 Eukaryota
COG5599 LUCA
GeneTreeiENSGT00920000148980
HOGENOMiHOG000273907
HOVERGENiHBG000223
InParanoidiQ06124
KOiK07293
OMAiKEYGAMR
OrthoDBiEOG091G0VZ3
PhylomeDBiQ06124
TreeFamiTF351632

Family and domain databases

Gene3Di3.30.505.10, 2 hits
3.90.190.10, 1 hit
InterProiView protein in InterPro
IPR029021 Prot-tyrosine_phosphatase-like
IPR000242 PTPase_domain
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR016130 Tyr_Pase_AS
IPR003595 Tyr_Pase_cat
IPR012152 Tyr_Pase_non-rcpt_typ-6/11
IPR000387 TYR_PHOSPHATASE_dom
PfamiView protein in Pfam
PF00017 SH2, 2 hits
PF00102 Y_phosphatase, 1 hit
PIRSFiPIRSF000929 Tyr-Ptase_nr_6, 1 hit
PRINTSiPR00700 PRTYPHPHTASE
PR00401 SH2DOMAIN
SMARTiView protein in SMART
SM00194 PTPc, 1 hit
SM00404 PTPc_motif, 1 hit
SM00252 SH2, 2 hits
SUPFAMiSSF52799 SSF52799, 1 hit
SSF55550 SSF55550, 2 hits
PROSITEiView protein in PROSITE
PS50001 SH2, 2 hits
PS00383 TYR_PHOSPHATASE_1, 1 hit
PS50056 TYR_PHOSPHATASE_2, 1 hit
PS50055 TYR_PHOSPHATASE_PTP, 1 hit

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

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

Isoform 1 (identifier: Q06124-1) [UniParc]FASTAAdd to basket
Also known as: PTP2Ci

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
MTSRRWFHPN ITGVEAENLL LTRGVDGSFL ARPSKSNPGD FTLSVRRNGA
60 70 80 90 100
VTHIKIQNTG DYYDLYGGEK FATLAELVQY YMEHHGQLKE KNGDVIELKY
110 120 130 140 150
PLNCADPTSE RWFHGHLSGK EAEKLLTEKG KHGSFLVRES QSHPGDFVLS
160 170 180 190 200
VRTGDDKGES NDGKSKVTHV MIRCQELKYD VGGGERFDSL TDLVEHYKKN
210 220 230 240 250
PMVETLGTVL QLKQPLNTTR INAAEIESRV RELSKLAETT DKVKQGFWEE
260 270 280 290 300
FETLQQQECK LLYSRKEGQR QENKNKNRYK NILPFDHTRV VLHDGDPNEP
310 320 330 340 350
VSDYINANII MPEFETKCNN SKPKKSYIAT QGCLQNTVND FWRMVFQENS
360 370 380 390 400
RVIVMTTKEV ERGKSKCVKY WPDEYALKEY GVMRVRNVKE SAAHDYTLRE
410 420 430 440 450
LKLSKVGQAL LQGNTERTVW QYHFRTWPDH GVPSDPGGVL DFLEEVHHKQ
460 470 480 490 500
ESIMDAGPVV VHCSAGIGRT GTFIVIDILI DIIREKGVDC DIDVPKTIQM
510 520 530 540 550
VRSQRSGMVQ TEAQYRFIYM AVQHYIETLQ RRIEEEQKSK RKGHEYTNIK
560 570 580 590
YSLADQTSGD QSPLPPCTPT PPCAEMREDS ARVYENVGLM QQQKSFR
Length:597
Mass (Da):68,436
Last modified:December 20, 2005 - v2
Checksum:i37E8BFC7ECA2D03F
GO
Isoform 2 (identifier: Q06124-2) [UniParc]FASTAAdd to basket
Also known as: PTP2C

The sequence of this isoform differs from the canonical sequence as follows:
     408-411: Missing.

Show »
Length:593
Mass (Da):68,011
Checksum:i9CDBEFFA5E6CCB45
GO
Isoform 3 (identifier: Q06124-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     408-411: Missing.
     464-464: S → R
     465-597: Missing.

Show »
Length:460
Mass (Da):52,828
Checksum:iEB8E1553B37F1CC0
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti539S → R in BAA02740 (PubMed:8216283).Curated1
Sequence conflicti552S → P in BAA02740 (PubMed:8216283).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0271832T → I in NS1. 1 PublicationCorresponds to variant dbSNP:rs267606990EnsemblClinVar.1
Natural variantiVAR_01560142T → A in NS1. 2 PublicationsCorresponds to variant dbSNP:rs397507501EnsemblClinVar.1
Natural variantiVAR_02718458N → K in NS1. 1 PublicationCorresponds to variant dbSNP:rs397507506EnsemblClinVar.1
Natural variantiVAR_06606059T → A in NS1. 1 PublicationCorresponds to variant dbSNP:rs886043790EnsemblClinVar.1
Natural variantiVAR_01560260G → A in NS1. 1 PublicationCorresponds to variant dbSNP:rs397507509EnsemblClinVar.1
Natural variantiVAR_01599060G → V in myelodysplastic syndrome. 1 PublicationCorresponds to variant dbSNP:rs397507509EnsemblClinVar.1
Natural variantiVAR_01560361D → G in NS1. 4 PublicationsCorresponds to variant dbSNP:rs121918461EnsemblClinVar.1
Natural variantiVAR_01560461D → N in NS1. 2 PublicationsCorresponds to variant dbSNP:rs397507510EnsemblClinVar.1
Natural variantiVAR_01599161D → V in JMML; also in myelodysplastic syndrome. 1 PublicationCorresponds to variant dbSNP:rs121918461EnsemblClinVar.1
Natural variantiVAR_01599261D → Y in JMML. 1 PublicationCorresponds to variant dbSNP:rs397507510EnsemblClinVar.1
Natural variantiVAR_01560562Y → D in NS1; also in Noonan patients manifesting juvenile myelomonocytic leukemia. 4 PublicationsCorresponds to variant dbSNP:rs121918460EnsemblClinVar.1
Natural variantiVAR_01560663Y → C in NS1. 6 PublicationsCorresponds to variant dbSNP:rs121918459EnsemblClinVar.1
Natural variantiVAR_01599369E → K in JMML; also in myelodysplastic syndrome. 1 PublicationCorresponds to variant dbSNP:rs397507511EnsemblClinVar.1
Natural variantiVAR_02718569E → Q in NS1. 1 PublicationCorresponds to variant dbSNP:rs397507511EnsemblClinVar.1
Natural variantiVAR_01599471F → K in acute myeloid leukemia; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_01599571F → L in myelodysplastic syndrome. 2 PublicationsCorresponds to variant dbSNP:rs397507512EnsemblClinVar.1
Natural variantiVAR_01560772A → G in NS1. 3 PublicationsCorresponds to variant dbSNP:rs121918454EnsemblClinVar.1
Natural variantiVAR_01560872A → S in NS1. 3 PublicationsCorresponds to variant dbSNP:rs121918453EnsemblClinVar.1
Natural variantiVAR_01599672A → T in JMML. 1 PublicationCorresponds to variant dbSNP:rs121918453EnsemblClinVar.1
Natural variantiVAR_01599772A → V in JMML. 1 PublicationCorresponds to variant dbSNP:rs121918454EnsemblClinVar.1
Natural variantiVAR_01560973T → I in NS1; also in Noonan patients manifesting juvenile myelomonocytic leukemia. 4 PublicationsCorresponds to variant dbSNP:rs121918462EnsemblClinVar.1
Natural variantiVAR_01599876E → A in JMML; also in myelodysplastic syndrome. 1 PublicationCorresponds to variant dbSNP:rs121918465EnsemblClinVar.1
Natural variantiVAR_01561076E → D in NS1. 3 PublicationsCorresponds to variant dbSNP:rs397507514EnsemblClinVar.1
Natural variantiVAR_01599976E → G in JMML. 1 PublicationCorresponds to variant dbSNP:rs121918465EnsemblClinVar.1
Natural variantiVAR_01600076E → K in JMML; increases protein tyrosine phosphatase activity against CDC73. 2 PublicationsCorresponds to variant dbSNP:rs121918464EnsemblClinVar.1
Natural variantiVAR_01600176E → V in JMML. 1 PublicationCorresponds to variant dbSNP:rs121918465EnsemblClinVar.1
Natural variantiVAR_02718679Q → P in NS1. 1 Publication1
Natural variantiVAR_01561179Q → R in NS1. 4 PublicationsCorresponds to variant dbSNP:rs121918466EnsemblClinVar.1
Natural variantiVAR_015612106D → A in NS1. 2 PublicationsCorresponds to variant dbSNP:rs397507517EnsemblClinVar.1
Natural variantiVAR_015613139E → D in NS1. 2 PublicationsCorresponds to variant dbSNP:rs397507520EnsemblClinVar.1
Natural variantiVAR_027187256Q → R in NS1. 1 PublicationCorresponds to variant dbSNP:rs397507523EnsemblClinVar.1
Natural variantiVAR_078101261L → F in NS1; increases MAPK signaling; increases protein tyrosine phosphatase activity; changed substrate selectivity for GAB1. 1 PublicationCorresponds to variant dbSNP:rs397507525EnsemblClinVar.1
Natural variantiVAR_078102261L → H in NS1; increases MAPK signaling; increased protein tyrosine phosphatase activity. 1 PublicationCorresponds to variant dbSNP:rs765642157Ensembl.1
Natural variantiVAR_078103262L → F in NS1; increases MAPK signaling; increased protein tyrosine phosphatase activity. 1 Publication1
Natural variantiVAR_078104262L → R in NS1; increases MAPK signaling; increased protein tyrosine phosphatase activity. 1 PublicationCorresponds to variant dbSNP:rs397507526EnsemblClinVar.1
Natural variantiVAR_078105265R → Q in NS1; increases MAPK signaling; increased protein tyrosine phosphatase activity. 1 PublicationCorresponds to variant dbSNP:rs376607329EnsemblClinVar.1
Natural variantiVAR_015614279Y → C in NS1 and LPRD1; does not affect subcellular location; decreases protein tyrosine phosphatase activity against CDC73. 7 Publications