P81718 · PTN6_RAT
- ProteinTyrosine-protein phosphatase non-receptor type 6
- GenePtpn6
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids613 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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
- H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] + phosphate
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 421 | substrate | ||||
Sequence: D | ||||||
Active site | 455 | Phosphocysteine intermediate | ||||
Sequence: C | ||||||
Binding site | 455-461 | substrate | ||||
Sequence: CSAGIGR | ||||||
Binding site | 502 | substrate | ||||
Sequence: Q |
GO annotations
Keywords
- Molecular function
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTyrosine-protein phosphatase non-receptor type 6
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionP81718
Proteomes
Organism-specific databases
PTM/Processing
Features
Showing features for chain, modified residue, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000094760 | 1-613 | Tyrosine-protein phosphatase non-receptor type 6 | |||
Sequence: MLSRGWFHRDLSGPDAETLLKGRGVPGSFLARPSRKNQGDFSLSVRVDDQVTHIRIQNSGDFYDLYGGEKFATSTELVEYYTQQQGILQDRDGTIIHLKYPLNCSDPTSERWYHGHMSGGQAESLLQAKGEPWTFLVRESLSQPGDFVLSVLNDQPKAAPGSPLRVTHIKVMCEGGRYTVGGSETFDSLTDLVEHFKKTGIEEASGAFVYLRQPYYATRVNAADIENRVLELNKKQESEDTAKAGFWEEFESLQKQEAKNLHQRLEGQRPENKSKNRYKNILPFDHSRVILQGRDSNIPGSDYINANYVKNQLLGPDENSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEVGTQRVYGLYSVTNCKEHDTAEYKLRTLQISPLDNGDLVREIWHYQYLSWPDHGVPSEPGGVLSFLDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGLDCDIDIQKTIQMVRAQRSGMVQTEAQYKFIYVAIAQFIETTKKKLEIIQSQRGQESEYGNITYPPALRSAHAKASRTSSKHKEEVYENVHSKNKKEEKVKKQRSADKEKNKGSLKRNISLTPCRGLRWADRDL | ||||||
Modified residue | 12 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 59 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 66 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Cross-link | 310 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | ||||||
Modified residue | 379 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 396 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 538 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 566 | Phosphotyrosine; by LYN | ||||
Sequence: Y |
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).
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
- PTM
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).
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 6-102 | SH2 1 | ||||
Sequence: WFHRDLSGPDAETLLKGRGVPGSFLARPSRKNQGDFSLSVRVDDQVTHIRIQNSGDFYDLYGGEKFATSTELVEYYTQQQGILQDRDGTIIHLKYPL | ||||||
Domain | 112-215 | SH2 2 | ||||
Sequence: WYHGHMSGGQAESLLQAKGEPWTFLVRESLSQPGDFVLSVLNDQPKAAPGSPLRVTHIKVMCEGGRYTVGGSETFDSLTDLVEHFKKTGIEEASGAFVYLRQPY | ||||||
Domain | 246-517 | Tyrosine-protein phosphatase | ||||
Sequence: FWEEFESLQKQEAKNLHQRLEGQRPENKSKNRYKNILPFDHSRVILQGRDSNIPGSDYINANYVKNQLLGPDENSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEVGTQRVYGLYSVTNCKEHDTAEYKLRTLQISPLDNGDLVREIWHYQYLSWPDHGVPSEPGGVLSFLDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGLDCDIDIQKTIQMVRAQRSGMVQTEAQYKFIYVAIAQF | ||||||
Region | 549-598 | Disordered | ||||
Sequence: SAHAKASRTSSKHKEEVYENVHSKNKKEEKVKKQRSADKEKNKGSLKRNI | ||||||
Compositional bias | 556-594 | Basic and acidic residues | ||||
Sequence: RTSSKHKEEVYENVHSKNKKEEKVKKQRSADKEKNKGSL |
Domain
The N-terminal SH2 domain functions as an auto-inhibitory domain, blocking the catalytic domain in the ligand-free close conformation.
Sequence similarities
Belongs to the protein-tyrosine phosphatase family. Non-receptor class 2 subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length613
- Mass (Da)69,578
- Last updated1999-05-01 v1
- Checksum29364B22E8F45C87
Computationally mapped potential isoform sequences
There are 5 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A0G2K163 | A0A0G2K163_RAT | Ptpn6 | 623 | ||
A0A0G2K064 | A0A0G2K064_RAT | Ptpn6 | 612 | ||
G3V9T9 | G3V9T9_RAT | Ptpn6 | 613 | ||
A0A8I5ZTX8 | A0A8I5ZTX8_RAT | Ptpn6 | 556 | ||
A0A8I5ZT59 | A0A8I5ZT59_RAT | Ptpn6 | 595 |
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 556-594 | Basic and acidic residues | ||||
Sequence: RTSSKHKEEVYENVHSKNKKEEKVKKQRSADKEKNKGSL |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U77038 EMBL· GenBank· DDBJ | AAD00262.1 EMBL· GenBank· DDBJ | mRNA |