Tyrosine-protein phosphatase non-receptor type 11

Protein attributes

Sequence length	597 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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 component	Cytoplasm
Coding sequence diversity	Alternative splicing
Disease	Deafness Disease mutation
Domain	Repeat SH2 domain
Molecular function	Hydrolase Protein phosphatase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	protein amino acid dephosphorylation Inferred from electronic annotation. Source: InterPro sensory perception of sound Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Inferred from Experiment. Source: Reactome
Molecular function	non-membrane spanning protein tyrosine phosphatase activity Ref.4 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GAB1	Q13480	1	EBI-297779,EBI-517684
MPZL1	O95297	2	EBI-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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 597

597

Tyrosine-protein phosphatase non-receptor type 11

PRO_0000094767

Regions

Domain

6 – 102

97

SH2 1

Domain

112 – 216

105

SH2 2

Domain

247 – 521

275

Tyrosine-protein phosphatase

Sites

Active site

463

1

Phosphocysteine intermediate

Amino acid modifications

Modified residue

62

1

Phosphotyrosine

Modified residue

63

1

Phosphotyrosine

Modified residue

66

1

Phosphotyrosine By similarity

Modified residue

546

1

Phosphotyrosine; by PDGFR

Modified residue

584

1

Phosphotyrosine; by PDGFR

Modified residue

595

1

Phosphoserine

Natural variations

Alternative sequence

408 – 411

4

Missing in isoform 2 and isoform 3.

VSP_016672

Alternative sequence

464

1

S → R in isoform 3.

VSP_016673

Alternative sequence

465 – 597

133

Missing in isoform 3.

VSP_016674

Natural variant

2

1

T → I in NS1.

VAR_027183

Natural variant

42

1

T → A in NS1.

VAR_015601

Natural variant

58

1

N → K in NS1.

VAR_027184

Natural variant

60

1

G → A in NS1.

VAR_015602

Natural variant

60

1

G → V in myelodysplastic syndrome.

VAR_015990

Natural variant

1

D → G in NS1.

VAR_015603

Natural variant

1

D → N in NS1.

VAR_015604

Natural variant

1

D → V in JMML; also in myelodysplastic syndrome.

VAR_015991

Natural variant

1

D → Y in JMML.

VAR_015992

Natural variant

62

1

Y → D in NS1; also in Noonan patients manifesting juvenile myelomonocytic leukemia.

VAR_015605

Natural variant

63

1

Y → C in NS1.

VAR_015606

Natural variant

69

1

E → K in JMML; also in myelodysplastic syndrome.

VAR_015993

Natural variant

69

1

E → Q in NS1.

VAR_027185

Natural variant

71

1

F → K in acute myeloid leukemia; requires 2 nucleotide substitutions.

VAR_015994

Natural variant

71

1

F → L in myelodysplastic syndrome.

VAR_015995

Natural variant

1

A → G in NS1.

VAR_015607

Natural variant

1

A → S in NS1.

VAR_015608

Natural variant

1

A → T in JMML.

VAR_015996

Natural variant

1

A → V in JMML.

VAR_015997

Natural variant

73

1

T → I in NS1; also in Noonan patients manifesting juvenile myelomonocytic leukemia.

VAR_015609

Natural variant

1

E → A in JMML; also in myelodysplastic syndrome.

VAR_015998

Natural variant

1

E → D in NS1.

VAR_015610

Natural variant

1

E → G in JMML.

VAR_015999

Natural variant

1

E → K in JMML.

VAR_016000

Natural variant