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Reviewed, UniProtKB/Swiss-Prot Q06124 (PTN11_HUMAN)

Last modified November 25, 2008. Version 110. Feed History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Tyrosine-protein phosphatase non-receptor type 11
    EC=3.1.3.48
Alternative name(s):
    Protein-tyrosine phosphatase 2C
      Short name=PTP-2C
    PTP-1D
    SH-PTP3
    SH-PTP2
      Short name=SHP-2
      Short name=Shp2
Gene names
Name: PTPN11
Synonyms: PTP2C, SHPTP2
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length597 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus.

Catalytic activity

Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate.

Subunit structure

Interacts with phosphorylated LIME1 and BCAR3. Interacts with SHB and INPP5D/SHIP1 By similarity. Interacts with PTPNS1 and CD84. Interacts with phosphorylated SIT1 and MPZL1. Interacts with FCRL3, FCRL4, FCRL6 and ANKHD1.

Subcellular location

Cytoplasm.

Tissue specificity

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

Domain

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.

Post-translational modification

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.

Involvement in disease

Defects in PTPN11 are the cause of LEOPARD syndrome [MIM:151100]. It is an autosomal dominant disorder allelic with Noonan syndrome. The acronym LEOPARD stands for lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and deafness.

Defects in PTPN11 are the cause of Noonan syndrome 1 (NS1) [MIM:163950]. Noonan syndrome (NS) is a disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis. It is a genetically heterogeneous and relatively common syndrome, with an estimated incidence of 1 in 1000-2500 live births. Mutations in PTPN11 account for more than 50% of the cases. Rarely, NS is associated with juvenile myelomonocytic leukemia (JMML). NS1 inheritance is autosomal dominant.

Defects in PTPN11 are a cause of Noonan-like syndrome [MIM:163955]; also known as Noonan-like/multiple giant cell lesion syndrome. It is an autosomal dominant disorder characterized by Noonan features associates with giant cell lesions of bone and soft tissue.

Defects in PTPN11 are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:607785]. JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia. It is characterized by leukocytosis with tissue infiltration and in vitro hypersensitivity of myeloid progenitors to granulocyte-macrophage colony stimulating factor.

Sequence similarities

Belongs to the protein-tyrosine phosphatase family. Non-receptor class 2 subfamily.

Contains 2 SH2 domains.

Contains 1 tyrosine-protein phosphatase domain.

Ontologies

Keywords

   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
   DiseaseDeafness
Disease mutation
   DomainRepeat
SH2 domain
   Molecular functionHydrolase
Protein phosphatase
   PTMPhosphoprotein
   Technical term3D-structure

Gene Ontology (GO)

   Biological processprotein amino acid dephosphorylation

Inferred from electronic annotation. Source: InterPro

sensory perception of sound

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular componentcytosol

Inferred from Experiment. Source: Reactome

   Molecular functionnon-membrane spanning protein tyrosine phosphatase activity Ref.4

Traceable author statement. Source: ProtInc

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

GAB1Q134801EBI-297779,EBI-517684
MPZL1O952972EBI-297779,EBI-963338

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q06124-1)

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.
Isoform 2 (identifier: Q06124-2)

Also known as: PTP2C;

The sequence of this isoform differs from the canonical sequence as follows:
     408-411: Missing.
Isoform 3 (identifier: Q06124-3)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 597597Tyrosine-protein phosphatase non-receptor type 11
PRO_0000094767

Regions

Domain6 – 10297SH2 1
Domain112 – 216105SH2 2
Domain247 – 521275Tyrosine-protein phosphatase

Sites

Active site4631Phosphocysteine intermediate

Amino acid modifications

Modified residue621Phosphotyrosine
Modified residue631Phosphotyrosine
Modified residue661Phosphotyrosine By similarity
Modified residue5461Phosphotyrosine; by PDGFR
Modified residue5841Phosphotyrosine; by PDGFR
Modified residue5951Phosphoserine

Natural variations

Alternative sequence408 – 4114Missing in isoform 2 and isoform 3.
VSP_016672
Alternative sequence4641S → R in isoform 3.
VSP_016673
Alternative sequence465 – 597133Missing in isoform 3.
VSP_016674
Natural variant21T → I in NS1.
VAR_027183
Natural variant421T → A in NS1.
VAR_015601
Natural variant581N → K in NS1.
VAR_027184
Natural variant601G → A in NS1.
VAR_015602
Natural variant601G → V in myelodysplastic syndrome.
VAR_015990
Natural variant611D → G in NS1.
VAR_015603
Natural variant611D → N in NS1.
VAR_015604
Natural variant611D → V in JMML; also in myelodysplastic syndrome.
VAR_015991
Natural variant611D → Y in JMML.
VAR_015992
Natural variant621Y → D in NS1; also in Noonan patients manifesting juvenile myelomonocytic leukemia.
VAR_015605
Natural variant631Y → C in NS1.
VAR_015606
Natural variant691E → K in JMML; also in myelodysplastic syndrome.
VAR_015993
Natural variant691E → Q in NS1.
VAR_027185
Natural variant711F → K in acute myeloid leukemia; requires 2 nucleotide substitutions.
VAR_015994
Natural variant711F → L in myelodysplastic syndrome.
VAR_015995
Natural variant721A → G in NS1.
VAR_015607
Natural variant721A → S in NS1.
VAR_015608
Natural variant721A → T in JMML.
VAR_015996
Natural variant721A → V in JMML.
VAR_015997
Natural variant731T → I in NS1; also in Noonan patients manifesting juvenile myelomonocytic leukemia.
VAR_015609
Natural variant761E → A in JMML; also in myelodysplastic syndrome.
VAR_015998
Natural variant761E → D in NS1.
VAR_015610
Natural variant761E → G in JMML.
VAR_015999
Natural variant761E → K in JMML.
VAR_016000
Natural variant761E → V in JMML.
VAR_016001
Natural variant791Q → P in NS1.
VAR_027186
Natural variant791Q → R in NS1.
VAR_015611
Natural variant1061D → A in NS1.
VAR_015612
Natural variant1391E → D in NS1.
VAR_015613
Natural variant2561Q → R in NS1.
VAR_027187
Natural variant2791Y → C in NS1 and LEOPARD syndrome.
VAR_015614
Natural variant2791Y → S in LEOPARD syndrome.
VAR_027188
Natural variant2821I → V in NS1.
VAR_015615
Natural variant2851F → L in NS1.
VAR_015617
Natural variant2851F → S in NS1.
VAR_015616
Natural variant3081N → D in NS1; common mutation.
VAR_015619
Natural variant3081N → S in NS1 and Noonan-like syndrome.
VAR_015618
Natural variant3091I → V in NS1.
VAR_015620
Natural variant4151T → M in NS1.
VAR_027189
Natural variant4651A → T in LEOPARD syndrome.
VAR_027190
Natural variant4681G → A in LEOPARD syndrome.
VAR_027191
Natural variant4721T → M in LEOPARD syndrome.
VAR_015621
Natural variant5021R → L in LEOPARD syndrome.
VAR_027192
Natural variant5021R → W in LEOPARD syndrome.
VAR_027193
Natural variant5051R → K in NS1.
VAR_015622
Natural variant5061S → T in NS1.
VAR_015623
Natural variant5071G → A in JMML.
VAR_016002
Natural variant5071G → R in patients with growth retardation, pulmonic stenosis and juvenile myelomonocytic leukemia.
VAR_016003
Natural variant5081M → V in NS1.
VAR_015624
Natural variant5101Q → P in LEOPARD syndrome.
VAR_027194
Natural variant5101Q → R in NS1.
VAR_027195
Natural variant5141Q → P in LEOPARD syndrome.
VAR_027196
Natural variant5641L → F in NS1.
VAR_027197

Experimental info

Mutagenesis4631C → S: Abolishes phosphatase activity
Sequence conflict5391S → R in BAA02740. Ref.3
Sequence conflict5521S → P in BAA02740. Ref.3

Secondary structure

..................................................................................... 597
Helix Strand Turn

Details...