UniProt functional annotation for P35235



	UniProt functional annotation for P35235

UniProt code: P35235.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

Function: Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus (PubMed:14967142). Positively regulates MAPK signal transduction pathway (By similarity). Dephosphorylates GAB1, ARHGAP35 and EGFR (By similarity). Dephosphorylates ROCK2 at 'Tyr-722' resulting in stimulation of its RhoA binding activity (By similarity). Dephosphorylates CDC73 (By similarity). Dephosphorylates SOX9 on tyrosine residues, leading to inactivate SOX9 and promote ossification (PubMed:29644115). {ECO:0000250|UniProtKB:Q06124, ECO:0000269|PubMed:14967142, ECO:0000269|PubMed:29644115}.

Catalytic activity: Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] + phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA- COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620; EC=3.1.3.48; Evidence={ECO:0000255|PROSITE- ProRule:PRU10044};

Subunit: Interacts with CD84 and with phosphorylated SIT1 and MZPL1. Interacts with FCRL4, FCRL6 and ANKHD1. Interacts with GAREM1 (tyrosine phosphorylated); the interaction increases MAPK/ERK activity and does not affect the GRB2/SOS complex formation (By similarity). Interacts with PTPNS1 and BCAR3. Interacts with phosphorylated LIME1. Interacts with SHB and INPP5D/SHIP1. Interacts with KIR2DL1; the interaction is enhanced by ARRB2 (By similarity). 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 (By similarity). Interacts with MILR1 (tyrosine phosphorylated). Interacts with FLT1 (tyrosine-phosphorylated), FLT3 (tyrosine-phosphorylated), FLT4 (tyrosine-phosphorylated), KIT and GRB2. Interacts with ROS1; mediates PTPN11 phosphorylation. Interacts with PDGFRA (tyrosine phosphorylated). Interacts with PDGFRB (tyrosine phosphorylated); this interaction increases the PTPN11 phosphatase activity. Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated). Interacts with CEACAM1 (via cytoplasmic domain); this interaction depends on the monomer/dimer equilibrium and is phosphorylation-dependent (PubMed:19948503, PubMed:9867848). Interacts with MPIG6B (via ITIM motif) (PubMed:23112346). Interacts with SIGLEC10 (PubMed:23374343). {ECO:0000250|UniProtKB:P41499, ECO:0000250|UniProtKB:Q06124, ECO:0000269|PubMed:10068651, ECO:0000269|PubMed:10080542, ECO:0000269|PubMed:10521483, ECO:0000269|PubMed:10896938, ECO:0000269|PubMed:12181353, ECO:0000269|PubMed:14610044, ECO:0000269|PubMed:16684964, ECO:0000269|PubMed:16885344, ECO:0000269|PubMed:19948503, ECO:0000269|PubMed:20526344, ECO:0000269|PubMed:23112346, ECO:0000269|PubMed:23374343, ECO:0000269|PubMed:7521735, ECO:0000269|PubMed:8943348, ECO:0000269|PubMed:9062191, ECO:0000269|PubMed:9110989, ECO:0000269|PubMed:9393882, ECO:0000269|PubMed:9528781, ECO:0000269|PubMed:9722576, ECO:0000269|PubMed:9867848}.

Subcellular location: Cytoplasm.

Tissue specificity: Highly expressed in brain, heart and kidney. {ECO:0000269|PubMed:7681217}.

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.

Ptm: Phosphorylated on Tyr-542 and Tyr-580 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 by activated PDGFRB (By similarity). Phosphorylated upon activation of the receptor-type kinase PDGFRA. {ECO:0000250, ECO:0000269|PubMed:10080542, ECO:0000269|PubMed:16885344, ECO:0000269|PubMed:8943348}.

Disruption phenotype: Conditional deletion in limb and head mesenchyme leads to increased cartilage mass and deficient ossification: osteochondroprogenitors become chondrocytes and not osteoblasts caused by inability of PTPN11/SHP2 to mediate tyrosine dephosphorylation of SOX9. {ECO:0000269|PubMed:29644115}.

Similarity: Belongs to the protein-tyrosine phosphatase family. Non- receptor class 2 subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



Function:		Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus (PubMed:14967142). Positively regulates MAPK signal transduction pathway (By similarity). Dephosphorylates GAB1, ARHGAP35 and EGFR (By similarity). Dephosphorylates ROCK2 at 'Tyr-722' resulting in stimulation of its RhoA binding activity (By similarity). Dephosphorylates CDC73 (By similarity). Dephosphorylates SOX9 on tyrosine residues, leading to inactivate SOX9 and promote ossification (PubMed:29644115). {ECO:0000250\|UniProtKB:Q06124, ECO:0000269\|PubMed:14967142, ECO:0000269\|PubMed:29644115}.


Catalytic activity:		Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] + phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA- COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620; EC=3.1.3.48; Evidence={ECO:0000255\|PROSITE- ProRule:PRU10044};
Subunit:		Interacts with CD84 and with phosphorylated SIT1 and MZPL1. Interacts with FCRL4, FCRL6 and ANKHD1. Interacts with GAREM1 (tyrosine phosphorylated); the interaction increases MAPK/ERK activity and does not affect the GRB2/SOS complex formation (By similarity). Interacts with PTPNS1 and BCAR3. Interacts with phosphorylated LIME1. Interacts with SHB and INPP5D/SHIP1. Interacts with KIR2DL1; the interaction is enhanced by ARRB2 (By similarity). 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 (By similarity). Interacts with MILR1 (tyrosine phosphorylated). Interacts with FLT1 (tyrosine-phosphorylated), FLT3 (tyrosine-phosphorylated), FLT4 (tyrosine-phosphorylated), KIT and GRB2. Interacts with ROS1; mediates PTPN11 phosphorylation. Interacts with PDGFRA (tyrosine phosphorylated). Interacts with PDGFRB (tyrosine phosphorylated); this interaction increases the PTPN11 phosphatase activity. Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated). Interacts with CEACAM1 (via cytoplasmic domain); this interaction depends on the monomer/dimer equilibrium and is phosphorylation-dependent (PubMed:19948503, PubMed:9867848). Interacts with MPIG6B (via ITIM motif) (PubMed:23112346). Interacts with SIGLEC10 (PubMed:23374343). {ECO:0000250\|UniProtKB:P41499, ECO:0000250\|UniProtKB:Q06124, ECO:0000269\|PubMed:10068651, ECO:0000269\|PubMed:10080542, ECO:0000269\|PubMed:10521483, ECO:0000269\|PubMed:10896938, ECO:0000269\|PubMed:12181353, ECO:0000269\|PubMed:14610044, ECO:0000269\|PubMed:16684964, ECO:0000269\|PubMed:16885344, ECO:0000269\|PubMed:19948503, ECO:0000269\|PubMed:20526344, ECO:0000269\|PubMed:23112346, ECO:0000269\|PubMed:23374343, ECO:0000269\|PubMed:7521735, ECO:0000269\|PubMed:8943348, ECO:0000269\|PubMed:9062191, ECO:0000269\|PubMed:9110989, ECO:0000269\|PubMed:9393882, ECO:0000269\|PubMed:9528781, ECO:0000269\|PubMed:9722576, ECO:0000269\|PubMed:9867848}.
Subcellular location:		Cytoplasm.
Tissue specificity:		Highly expressed in brain, heart and kidney. {ECO:0000269\|PubMed:7681217}.
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.
Ptm:		Phosphorylated on Tyr-542 and Tyr-580 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 by activated PDGFRB (By similarity). Phosphorylated upon activation of the receptor-type kinase PDGFRA. {ECO:0000250, ECO:0000269\|PubMed:10080542, ECO:0000269\|PubMed:16885344, ECO:0000269\|PubMed:8943348}.
Disruption phenotype:		Conditional deletion in limb and head mesenchyme leads to increased cartilage mass and deficient ossification: osteochondroprogenitors become chondrocytes and not osteoblasts caused by inability of PTPN11/SHP2 to mediate tyrosine dephosphorylation of SOX9. {ECO:0000269\|PubMed:29644115}.
Similarity:		Belongs to the protein-tyrosine phosphatase family. Non- receptor class 2 subfamily. {ECO:0000305}.