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: Annotation score: 5 out of 5-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. Dephosphorylates ROCK2 at Tyr-722 resulting in stimulatation of its RhoA binding activity. Dephosphorylates CDC73 (PubMed:26742426).4 Publications

Catalytic activityi

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.PROSITE-ProRule annotation2 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
  • insulin receptor binding Source: BHF-UCL
  • non-membrane spanning protein tyrosine phosphatase activity Source: UniProtKB
  • phosphatidylinositol-4,5-bisphosphate 3-kinase activity Source: Reactome
  • phosphoprotein phosphatase activity Source: UniProtKB
  • protein tyrosine phosphatase activity Source: UniProtKB
  • SH3/SH2 adaptor activity Source: BHF-UCL

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Enzyme and pathway databases

BioCyciZFISH:HS01636-MONOMER.
ZFISH:HS17253-MONOMER.
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 (SIRP) 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-5654699. SHC-mediated 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-5654719. SHC-mediated cascade:FGFR4.
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-8865999. MET activates PTPN11.
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.

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein phosphatase non-receptor type 11 (EC:3.1.3.481 Publication)
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

HGNCiHGNC:9644. PTPN11.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Nucleus 1 Publication

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • mitochondrion Source: Ensembl
  • nucleus Source: UniProtKB
  • protein complex Source: Ensembl
Complete GO annotation...

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_015614279Y → C in NS1 and LPRD1; does not affect subcellular location; decreases protein tyrosine phosphatase activity against CDC73. 7 PublicationsCorresponds to variant rs121918456dbSNPEnsembl.1
Natural variantiVAR_027188279Y → S in LPRD1. 2 PublicationsCorresponds to variant rs121918456dbSNPEnsembl.1
Natural variantiVAR_027190465A → T in LPRD1. 1 PublicationCorresponds to variant rs121918468dbSNPEnsembl.1
Natural variantiVAR_027191468G → A in LPRD1. 2 PublicationsCorresponds to variant rs121918469dbSNPEnsembl.1
Natural variantiVAR_015621472T → M in LPRD1; does not affect subcellular location; decreases protein tyrosine phosphatase activity against CDC73. 5 PublicationsCorresponds to variant rs121918457dbSNPEnsembl.1
Natural variantiVAR_027192502R → L in LPRD1. 1 PublicationCorresponds to variant rs397507542dbSNPEnsembl.1
Natural variantiVAR_027193502R → W in LPRD1; reduced phosphatase activity. 2 PublicationsCorresponds to variant rs397507541dbSNPEnsembl.1
Natural variantiVAR_027194510Q → P in LPRD1; does not affect subcellular location; decreases protein tyrosine phosphatase activity against CDC73. 4 PublicationsCorresponds to variant rs397509345dbSNPEnsembl.1
Natural variantiVAR_076499514Q → E in NS1 and LPRD1; does not affect subcellular location; decreases protein tyrosine phosphatase activity against CDC73. 3 PublicationsCorresponds to variant rs397507549dbSNPEnsembl.1
Natural variantiVAR_027196514Q → P in LPRD1. 1 PublicationCorresponds to variant rs121918470dbSNPEnsembl.1
Noonan syndrome 1 (NS1)14 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 rs267606990dbSNPEnsembl.1
Natural variantiVAR_01560142T → A in NS1. 2 PublicationsCorresponds to variant rs397507501dbSNPEnsembl.1
Natural variantiVAR_02718458N → K in NS1. 1 PublicationCorresponds to variant rs397507506dbSNPEnsembl.1
Natural variantiVAR_06606059T → A in NS1. 1 Publication1
Natural variantiVAR_01560260G → A in NS1. 1 PublicationCorresponds to variant rs397507509dbSNPEnsembl.1
Natural variantiVAR_01560361D → G in NS1. 4 PublicationsCorresponds to variant rs121918461dbSNPEnsembl.1
Natural variantiVAR_01560461D → N in NS1. 2 PublicationsCorresponds to variant rs397507510dbSNPEnsembl.1
Natural variantiVAR_01560562Y → D in NS1; also in Noonan patients manifesting juvenile myelomonocytic leukemia. 4 PublicationsCorresponds to variant rs121918460dbSNPEnsembl.1
Natural variantiVAR_01560663Y → C in NS1. 6 PublicationsCorresponds to variant rs121918459dbSNPEnsembl.1
Natural variantiVAR_02718569E → Q in NS1. 1 PublicationCorresponds to variant rs397507511dbSNPEnsembl.1
Natural variantiVAR_01560772A → G in NS1. 3 PublicationsCorresponds to variant rs121918454dbSNPEnsembl.1
Natural variantiVAR_01560872A → S in NS1. 3 PublicationsCorresponds to variant rs121918453dbSNPEnsembl.1
Natural variantiVAR_01560973T → I in NS1; also in Noonan patients manifesting juvenile myelomonocytic leukemia. 4 PublicationsCorresponds to variant rs28933387dbSNPEnsembl.1
Natural variantiVAR_01561076E → D in NS1. 3 PublicationsCorresponds to variant rs397507514dbSNPEnsembl.1
Natural variantiVAR_02718679Q → P in NS1. 1 Publication1
Natural variantiVAR_01561179Q → R in NS1. 4 PublicationsCorresponds to variant rs121918466dbSNPEnsembl.1
Natural variantiVAR_015612106D → A in NS1. 2 PublicationsCorresponds to variant rs397507517dbSNPEnsembl.1
Natural variantiVAR_015613139E → D in NS1. 2 PublicationsCorresponds to variant rs397507520dbSNPEnsembl.1
Natural variantiVAR_027187256Q → R in NS1. 1 PublicationCorresponds to variant rs397507523dbSNPEnsembl.1
Natural variantiVAR_015614279Y → C in NS1 and LPRD1; does not affect subcellular location; decreases protein tyrosine phosphatase activity against CDC73. 7 PublicationsCorresponds to variant rs121918456dbSNPEnsembl.1
Natural variantiVAR_015615282I → V in NS1. 3 PublicationsCorresponds to variant rs397507529dbSNPEnsembl.1
Natural variantiVAR_015617285F → L in NS1. 1 PublicationCorresponds to variant rs397507531dbSNPEnsembl.1
Natural variantiVAR_015616285F → S in NS1. 2 PublicationsCorresponds to variant rs121918463dbSNPEnsembl.1
Natural variantiVAR_015619308N → D in NS1; common mutation. 5 PublicationsCorresponds to variant rs28933386dbSNPEnsembl.1
Natural variantiVAR_015618308N → S in NS1; some patients also manifest giant cell lesions of bone and soft tissue. 2 PublicationsCorresponds to variant rs121918455dbSNPEnsembl.1
Natural variantiVAR_015620309I → V in NS1; unknown pathological significance. 1 PublicationCorresponds to variant rs201787206dbSNPEnsembl.1
Natural variantiVAR_027189415T → M in NS1. 1 PublicationCorresponds to variant rs121918467dbSNPEnsembl.1
Natural variantiVAR_071706495P → S in NS1; increased phosphatase activity. 1 PublicationCorresponds to variant rs397507539dbSNPEnsembl.1
Natural variantiVAR_015622505R → K in NS1. 1 PublicationCorresponds to variant rs397507543dbSNPEnsembl.1
Natural variantiVAR_015623506S → T in NS1. 2 PublicationsCorresponds to variant rs121918458dbSNPEnsembl.1
Natural variantiVAR_016003507G → R in NS1 and JMML; JMML patient also shows growth retardation and pulmonic stenosis. 2 PublicationsCorresponds to variant rs397507545dbSNPEnsembl.1
Natural variantiVAR_015624508M → V in NS1. 3 PublicationsCorresponds to variant rs397507547dbSNPEnsembl.1
Natural variantiVAR_027195510Q → R in NS1. 1 Publication1
Natural variantiVAR_076499514Q → E in NS1 and LPRD1; does not affect subcellular location; decreases protein tyrosine phosphatase activity against CDC73. 3 PublicationsCorresponds to variant rs397507549dbSNPEnsembl.1
Natural variantiVAR_027197564L → F in NS1. 1 PublicationCorresponds to variant rs397516797dbSNPEnsembl.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 rs121918461dbSNPEnsembl.1
Natural variantiVAR_01599261D → Y in JMML. 1 Publication1
Natural variantiVAR_01599369E → K in JMML; also in myelodysplastic syndrome. 1 Publication1
Natural variantiVAR_01599672A → T in JMML. 1 PublicationCorresponds to variant rs121918453dbSNPEnsembl.1
Natural variantiVAR_01599772A → V in JMML. 1 PublicationCorresponds to variant rs121918454dbSNPEnsembl.1
Natural variantiVAR_01599876E → A in JMML; also in myelodysplastic syndrome. 1 PublicationCorresponds to variant rs121918465dbSNPEnsembl.1
Natural variantiVAR_01599976E → G in JMML. 1 PublicationCorresponds to variant rs121918465dbSNPEnsembl.1
Natural variantiVAR_01600076E → K in JMML; increases protein tyrosine phosphatase activity against CDC73. 2 PublicationsCorresponds to variant rs28933388dbSNPEnsembl.1
Natural variantiVAR_01600176E → V in JMML. 1 PublicationCorresponds to variant rs121918465dbSNPEnsembl.1
Natural variantiVAR_016002507G → A in JMML. 1 PublicationCorresponds to variant rs397507546dbSNPEnsembl.1
Natural variantiVAR_016003507G → R in NS1 and JMML; JMML patient also shows growth retardation and pulmonic stenosis. 2 PublicationsCorresponds to variant rs397507545dbSNPEnsembl.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.
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.

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.
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 FCRL3, 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).By similarity25 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ARP1027512EBI-297779,EBI-608057
CCKBRP322395EBI-297779,EBI-1753137
CD244Q9BZW85EBI-297779,EBI-1580565
CD33P201385EBI-297779,EBI-3906571
DDR1Q083454EBI-297779,EBI-711879
EEF1A1P681052EBI-297779,EBI-7645934From a different organism.
EEF1A2Q71V392EBI-297779,EBI-7645815From a different organism.
ERBB2P046262EBI-297779,EBI-641062
FLT1P179482EBI-297779,EBI-1026718
GAB1Q1348039EBI-297779,EBI-517684
GAB2Q9UQC24EBI-297779,EBI-975200
GRB2P629936EBI-297779,EBI-401755
IGF1RP080693EBI-297779,EBI-475981
INSRP062132EBI-297779,EBI-475899
IRS1P355683EBI-297779,EBI-517592
Irs1P355703EBI-297779,EBI-520230From a different organism.
KIR2DL3P436284EBI-297779,EBI-8632435
KITP1072129EBI-297779,EBI-1379503
METP0858113EBI-297779,EBI-1039152
MPZL1O952974EBI-297779,EBI-963338
PDGFRBP096198EBI-297779,EBI-641237
PECAM1P162847EBI-297779,EBI-716404
PXNP490233EBI-297779,EBI-702209
RPIAP492474EBI-297779,EBI-744831
SirpaP977103EBI-297779,EBI-7945080From a different organism.
TRIM32Q130493EBI-297779,EBI-742790

GO - Molecular functioni

  • insulin receptor binding Source: BHF-UCL
  • SH3/SH2 adaptor activity Source: BHF-UCL

Protein-protein interaction databases

BioGridi111745. 122 interactors.
DIPiDIP-516N.
IntActiQ06124. 68 interactors.
MINTiMINT-199832.
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
Turni3 – 6Combined sources4
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
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

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2SHPX-ray2.00A/B1-529[»]
3B7OX-ray1.60A237-533[»]
3MOWX-ray2.30A262-532[»]
3O5XX-ray2.00A262-532[»]
3TKZX-ray1.80A1-106[»]
3TL0X-ray2.05A1-106[»]
3ZM0X-ray1.50A248-531[»]
3ZM1X-ray1.40A248-531[»]
3ZM2X-ray1.50A248-531[»]
3ZM3X-ray1.50A248-531[»]
4DGPX-ray2.30A1-532[»]
4DGXX-ray2.30A1-532[»]
4GWFX-ray2.10A/B1-543[»]
4H1OX-ray2.20A1-543[»]
4H34X-ray2.70A1-543[»]
4JE4X-ray2.31A1-103[»]
4JEGX-ray2.30A97-217[»]
4JMGX-ray1.40B579-591[»]
4NWFX-ray2.10A/B1-543[»]
4NWGX-ray2.45A/B1-543[»]
4OHDX-ray2.70A1-532[»]
4OHEX-ray2.51A1-467[»]
A469-532[»]
4OHHX-ray2.70A1-532[»]
4OHIX-ray2.20A1-532[»]
4OHLX-ray2.40A/B1-532[»]
4PVGX-ray2.40A240-532[»]
4QSYX-ray2.10A1-106[»]
4RDDX-ray1.60A262-532[»]
5DF6X-ray1.78A1-222[»]
5EHPX-ray1.85A/B1-529[»]
5EHRX-ray1.70A/B1-529[»]
5I6VX-ray1.87A/B1-529[»]
5IBMX-ray2.18A/B1-529[»]
5IBSX-ray2.32A/B1-529[»]
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

Contains 2 SH2 domains.PROSITE-ProRule annotation
Contains 1 tyrosine-protein phosphatase domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, SH2 domain

Phylogenomic databases

eggNOGiKOG0790. Eukaryota.
COG5599. LUCA.
GeneTreeiENSGT00770000120452.
HOGENOMiHOG000273907.
HOVERGENiHBG000223.
InParanoidiQ06124.
KOiK07293.
OMAiKEYGAMR.
OrthoDBiEOG091G0VZ3.
PhylomeDBiQ06124.
TreeFamiTF351632.

Family and domain databases

Gene3Di3.30.505.10. 2 hits.
3.90.190.10. 1 hit.
InterProiIPR029021. Prot-tyrosine_phosphatase-like.
IPR000242. PTPase_domain.
IPR000980. SH2.
IPR016130. Tyr_Pase_AS.
IPR003595. Tyr_Pase_cat.
IPR012152. Tyr_Pase_non-rcpt_typ-6/11.
IPR000387. TYR_PHOSPHATASE_dom.
[Graphical view]
PfamiPF00017. SH2. 2 hits.
PF00102. Y_phosphatase. 1 hit.
[Graphical view]
PIRSFiPIRSF000929. Tyr-Ptase_nr_6. 1 hit.
PRINTSiPR00700. PRTYPHPHTASE.
PR00401. SH2DOMAIN.
SMARTiSM00194. PTPc. 1 hit.
SM00404. PTPc_motif. 1 hit.
SM00252. SH2. 2 hits.
[Graphical view]
SUPFAMiSSF52799. SSF52799. 1 hit.
SSF55550. SSF55550. 2 hits.
PROSITEiPS50001. SH2. 2 hits.
PS00383. 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.

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 rs267606990dbSNPEnsembl.1
Natural variantiVAR_01560142T → A in NS1. 2 PublicationsCorresponds to variant rs397507501dbSNPEnsembl.1
Natural variantiVAR_02718458N → K in NS1. 1 PublicationCorresponds to variant rs397507506dbSNPEnsembl.1
Natural variantiVAR_06606059T → A in NS1. 1 Publication1
Natural variantiVAR_01560260G → A in NS1. 1 PublicationCorresponds to variant rs397507509dbSNPEnsembl.1
Natural variantiVAR_01599060G → V in myelodysplastic syndrome. 1 PublicationCorresponds to variant rs397507509dbSNPEnsembl.1
Natural variantiVAR_01560361D → G in NS1. 4 PublicationsCorresponds to variant rs121918461dbSNPEnsembl.1
Natural variantiVAR_01560461D → N in NS1. 2 PublicationsCorresponds to variant rs397507510dbSNPEnsembl.1
Natural variantiVAR_01599161D → V in JMML; also in myelodysplastic syndrome. 1 PublicationCorresponds to variant rs121918461dbSNPEnsembl.1
Natural variantiVAR_01599261D → Y in JMML. 1 Publication1
Natural variantiVAR_01560562Y → D in NS1; also in Noonan patients manifesting juvenile myelomonocytic leukemia. 4 PublicationsCorresponds to variant rs121918460dbSNPEnsembl.1
Natural variantiVAR_01560663Y → C in NS1. 6 PublicationsCorresponds to variant rs121918459dbSNPEnsembl.1
Natural variantiVAR_01599369E → K in JMML; also in myelodysplastic syndrome. 1 Publication1
Natural variantiVAR_02718569E → Q in NS1. 1 PublicationCorresponds to variant rs397507511dbSNPEnsembl.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 rs397507512dbSNPEnsembl.1
Natural variantiVAR_01560772A → G in NS1. 3 PublicationsCorresponds to variant rs121918454dbSNPEnsembl.1
Natural variantiVAR_01560872A → S in NS1. 3 PublicationsCorresponds to variant rs121918453dbSNPEnsembl.1
Natural variantiVAR_01599672A → T in JMML. 1 PublicationCorresponds to variant rs121918453dbSNPEnsembl.1
Natural variantiVAR_01599772A → V in JMML. 1 PublicationCorresponds to variant rs121918454dbSNPEnsembl.1
Natural variantiVAR_01560973T → I in NS1; also in Noonan patients manifesting juvenile myelomonocytic leukemia. 4 PublicationsCorresponds to variant rs28933387dbSNPEnsembl.1
Natural variantiVAR_01599876E → A in JMML; also in myelodysplastic syndrome. 1 PublicationCorresponds to variant rs121918465dbSNPEnsembl.1
Natural variantiVAR_01561076E → D in NS1. 3 PublicationsCorresponds to variant rs397507514dbSNPEnsembl.1
Natural variantiVAR_01599976E → G in JMML. 1 PublicationCorresponds to variant rs121918465dbSNPEnsembl.1
Natural variantiVAR_01600076E → K in JMML; increases protein tyrosine phosphatase activity against CDC73. 2 PublicationsCorresponds to variant rs28933388dbSNPEnsembl.1
Natural variantiVAR_01600176E → V in JMML. 1 PublicationCorresponds to variant rs121918465dbSNPEnsembl.1
Natural variantiVAR_02718679Q → P in NS1. 1 Publication1
Natural variantiVAR_01561179Q → R in NS1. 4 PublicationsCorresponds to variant rs121918466dbSNPEnsembl.1
Natural variantiVAR_015612106D → A in NS1. 2 PublicationsCorresponds to variant rs397507517dbSNPEnsembl.1
Natural variantiVAR_015613139E → D in NS1. 2 PublicationsCorresponds to variant rs397507520dbSNPEnsembl.1
Natural variantiVAR_027187256Q → R in NS1. 1 PublicationCorresponds to variant rs397507523dbSNPEnsembl.1
Natural variantiVAR_015614279Y → C in NS1 and LPRD1; does not affect subcellular location; decreases protein tyrosine phosphatase activity against CDC73. 7 PublicationsCorresponds to variant rs121918456dbSNPEnsembl.1
Natural variantiVAR_027188279Y → S in LPRD1. 2 PublicationsCorresponds to variant rs121918456dbSNPEnsembl.1
Natural variantiVAR_015615282I → V in NS1. 3 PublicationsCorresponds to variant rs397507529dbSNPEnsembl.1
Natural variantiVAR_015617285F → L in NS1. 1 PublicationCorresponds to variant rs397507531dbSNPEnsembl.1
Natural variantiVAR_015616285F → S in NS1. 2 PublicationsCorresponds to variant rs121918463dbSNPEnsembl.1
Natural variantiVAR_015619308N → D in NS1; common mutation. 5 PublicationsCorresponds to variant rs28933386dbSNPEnsembl.1
Natural variantiVAR_015618308N → S in NS1; some patients also manifest giant cell lesions of bone and soft tissue. 2 PublicationsCorresponds to variant rs121918455dbSNPEnsembl.1
Natural variantiVAR_015620309I → V in NS1; unknown pathological significance. 1 PublicationCorresponds to variant rs201787206dbSNPEnsembl.1
Natural variantiVAR_027189415T → M in NS1. 1 PublicationCorresponds to variant rs121918467dbSNPEnsembl.1
Natural variantiVAR_027190465A → T in LPRD1. 1 PublicationCorresponds to variant rs121918468dbSNPEnsembl.1
Natural variantiVAR_027191468G → A in LPRD1. 2 PublicationsCorresponds to variant rs121918469dbSNPEnsembl.1
Natural variantiVAR_015621472T → M in LPRD1; does not affect subcellular location; decreases protein tyrosine phosphatase activity against CDC73. 5 PublicationsCorresponds to variant rs121918457dbSNPEnsembl.1
Natural variantiVAR_071706495P → S in NS1; increased phosphatase activity. 1 PublicationCorresponds to variant rs397507539dbSNPEnsembl.1
Natural variantiVAR_027192502R → L in LPRD1. 1 PublicationCorresponds to variant rs397507542dbSNPEnsembl.1
Natural variantiVAR_027193502R → W in LPRD1; reduced phosphatase activity. 2 PublicationsCorresponds to variant rs397507541dbSNPEnsembl.1
Natural variantiVAR_015622505R → K in NS1. 1 Publication