P81718 · PTN6_RAT

  • Protein
    Tyrosine-protein phosphatase non-receptor type 6
  • Gene
    Ptpn6
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Tyrosine phosphatase enzyme that plays important roles in controlling immune signaling pathways and fundamental physiological processes such as hematopoiesis. Dephosphorylates and negatively regulate several receptor tyrosine kinases (RTKs) such as EGFR, PDGFR and FGFR, thereby modulating their signaling activities. When recruited to immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing receptors such as immunoglobulin-like transcript 2/LILRB1, programmed cell death protein 1/PDCD1, CD3D, CD22 and other receptors involved in immune regulation, initiates their dephosphorylation and subsequently inhibits downstream signaling events. Modulates the signaling of several cytokine receptors including IL-4 receptor. Additionally, targets multiple cytoplasmic signaling molecules including STING1, LCK or STAT1 among others involved in diverse cellular processes including modulation of T-cell activation or cGAS-STING signaling. Within the nucleus, negatively regulates the activity of some transcription factors such as NFAT5 via direct dephosphorylation. Acts also as a key transcriptional regulator of hepatic gluconeogenesis by controlling recruitment of RNA polymerase II to the PCK1 promoter together with STAT5A.

Catalytic activity

Features

Showing features for binding site, active site.

TypeIDPosition(s)Description
Binding site421substrate
Active site455Phosphocysteine intermediate
Binding site455-461substrate
Binding site502substrate

GO annotations

AspectTerm
Cellular Componentalpha-beta T cell receptor complex
Cellular Componentapical dendrite
Cellular Componentcell-cell junction
Cellular Componentcytoplasm
Cellular Componentnucleus
Cellular Componentplasma membrane
Cellular Componentprotein-containing complex
Molecular Functioncell adhesion molecule binding
Molecular Functioncytokine receptor binding
Molecular Functionnatural killer cell lectin-like receptor binding
Molecular Functionnon-membrane spanning protein tyrosine phosphatase activity
Molecular Functionphosphorylation-dependent protein binding
Molecular Functionphosphotyrosine residue binding
Molecular Functionprotein kinase binding
Molecular Functionprotein tyrosine phosphatase activity
Molecular FunctionSH2 domain binding
Molecular FunctionSH3 domain binding
Molecular Functiontransmembrane receptor protein tyrosine phosphatase activity
Biological ProcessB cell receptor signaling pathway
Biological Processcell differentiation
Biological Processcellular response to macrophage colony-stimulating factor stimulus
Biological Processepididymis development
Biological Processhematopoietic progenitor cell differentiation
Biological Processintracellular signal transduction
Biological ProcessMAPK cascade
Biological Processmegakaryocyte development
Biological Processmitotic cell cycle
Biological Processnatural killer cell mediated cytotoxicity
Biological Processnegative regulation of angiogenesis
Biological Processnegative regulation of humoral immune response mediated by circulating immunoglobulin
Biological Processnegative regulation of inflammatory response to wounding
Biological Processnegative regulation of interleukin-6 production
Biological Processnegative regulation of MAPK cascade
Biological Processnegative regulation of mast cell activation involved in immune response
Biological Processnegative regulation of peptidyl-tyrosine phosphorylation
Biological Processnegative regulation of T cell proliferation
Biological Processnegative regulation of T cell receptor signaling pathway
Biological Processnegative regulation of tumor necrosis factor production
Biological Processplatelet aggregation
Biological Processplatelet formation
Biological Processpositive regulation of cell adhesion mediated by integrin
Biological Processpositive regulation of cell population proliferation
Biological Processpositive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
Biological Processprotein dephosphorylation
Biological Processregulation of B cell differentiation
Biological Processregulation of ERK1 and ERK2 cascade
Biological Processregulation of G1/S transition of mitotic cell cycle
Biological Processregulation of release of sequestered calcium ion into cytosol
Biological Processresponse to axon injury
Biological ProcessT cell proliferation
Biological ProcessT cell receptor signaling pathway

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Tyrosine-protein phosphatase non-receptor type 6
  • EC number
  • Alternative names
    • Protein-tyrosine phosphatase SHP-1

Gene names

    • Name
      Ptpn6
    • Synonyms
      Ptph6

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus

Accessions

  • Primary accession
    P81718

Proteomes

Organism-specific databases

Subcellular Location

Cytoplasm
Nucleus
Note: In neurons, translocates into the nucleus after treatment with angiotensin II. Shuttles between the cytoplasm and nucleus via its association with PDPK (By similarity).

Keywords

PTM/Processing

Features

Showing features for chain, modified residue, cross-link.

TypeIDPosition(s)Description
ChainPRO_00000947601-613Tyrosine-protein phosphatase non-receptor type 6
Modified residue12Phosphoserine
Modified residue59Phosphoserine
Modified residue66Phosphotyrosine
Cross-link310Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Modified residue379Phosphotyrosine
Modified residue396Phosphothreonine
Modified residue538Phosphotyrosine
Modified residue566Phosphotyrosine; by LYN

Post-translational modification

Phosphorylated on tyrosine residues. Binding of KITLG/SCF to KIT increases tyrosine phosphorylation (By similarity).
Phosphorylation at Tyr-566 by LYN enhances phosphatase activity. Phosphorylation at Thr-396 by TAOK3 leads to polyubiquitination and subsequent proteasomal degradation (By similarity).
Ubiquitinated after phosphorylation by TAOK3. Ubiquitinated by a cooperation between ITCH and WWP2 via 'Lys-27'-mediated polyubiquitin chains resulting in the reduction of its association with LCK.

Keywords

Proteomic databases

PTM databases

Expression

Developmental stage

Highly expressed in embryonic cerebral cortex between day 18 and up to birth. Expression levels decrease after birth (at protein level).

Interaction

Subunit

Monomer. Interacts with MTUS1 (PubMed:17068200).
Interacts with MILR1 (tyrosine-phosphorylated) (By similarity).
Interacts with KIT (By similarity).
Interacts with SIRPA/PTPNS1. Interacts with LILRB1 and LILRB2. Interacts with LILRB4. Interacts with FCRL2 and FCRL4. Interacts with FCRL3 and FCRL6 (tyrosine phosphorylated form). Interacts with CD84. Interacts with CD300LF. Interacts with CDK2. Interacts with KIR2DL1; the interaction is enhanced by ARRB2. Interacts (via SH2 1 domain) with ROS1; the interaction is direct and promotes ROS1 dephosphorylation. Interacts with EGFR; inhibits EGFR-dependent activation of MAPK/ERK. Interacts with the tyrosine phosphorylated form of PDPK1 (By similarity).
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). Interacts with KLRI1 and KLRI2 (PubMed:18713988).
Interacts with moesin/MSN. Interacts with CLEC12B (via ITIM motif) (By similarity).
Interacts with polymerase II components POLR2C and POLR2J; these interactions recruit RNA polymerase II to the PCK1 promoter. Interacts with TNFRSF10A; this interaction enables the inhibition of T-cell receptor signaling via LCK (By similarity).

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for domain, region, compositional bias.

TypeIDPosition(s)Description
Domain6-102SH2 1
Domain112-215SH2 2
Domain246-517Tyrosine-protein phosphatase
Region549-598Disordered
Compositional bias556-594Basic and acidic residues

Domain

The N-terminal SH2 domain functions as an auto-inhibitory domain, blocking the catalytic domain in the ligand-free close conformation.

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    613
  • Mass (Da)
    69,578
  • Last updated
    1999-05-01 v1
  • Checksum
    29364B22E8F45C87
MLSRGWFHRDLSGPDAETLLKGRGVPGSFLARPSRKNQGDFSLSVRVDDQVTHIRIQNSGDFYDLYGGEKFATSTELVEYYTQQQGILQDRDGTIIHLKYPLNCSDPTSERWYHGHMSGGQAESLLQAKGEPWTFLVRESLSQPGDFVLSVLNDQPKAAPGSPLRVTHIKVMCEGGRYTVGGSETFDSLTDLVEHFKKTGIEEASGAFVYLRQPYYATRVNAADIENRVLELNKKQESEDTAKAGFWEEFESLQKQEAKNLHQRLEGQRPENKSKNRYKNILPFDHSRVILQGRDSNIPGSDYINANYVKNQLLGPDENSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEVGTQRVYGLYSVTNCKEHDTAEYKLRTLQISPLDNGDLVREIWHYQYLSWPDHGVPSEPGGVLSFLDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGLDCDIDIQKTIQMVRAQRSGMVQTEAQYKFIYVAIAQFIETTKKKLEIIQSQRGQESEYGNITYPPALRSAHAKASRTSSKHKEEVYENVHSKNKKEEKVKKQRSADKEKNKGSLKRNISLTPCRGLRWADRDL

Computationally mapped potential isoform sequences

There are 5 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A0A0G2K163A0A0G2K163_RATPtpn6623
A0A0G2K064A0A0G2K064_RATPtpn6612
G3V9T9G3V9T9_RATPtpn6613
A0A8I5ZTX8A0A8I5ZTX8_RATPtpn6556
A0A8I5ZT59A0A8I5ZT59_RATPtpn6595

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias556-594Basic and acidic residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
U77038
EMBL· GenBank· DDBJ
AAD00262.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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