PTPN6 (protein tyrosine phosphatase non-receptor type 6)

Gene

• Entrez ID: 5777
• Gene name: Protein tyrosine phosphatase non-receptor type 6
• Gene symbol: PTPN6
• Synonyms: HCP, HCPH, HPTP1C, PTP-1C, SH-PTP1, SHP-1, SHP-1L, SHP1
• Chromosome: 12
• Chromosome location: 12p13.31
• Summary: The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. N-terminal part of this PTP contains two tandem Src homolog (SH2) domains, which act as protein phospho-tyrosine binding domains, and mediate the interaction of this PTP with its substrates. This PTP is expressed primarily in hematopoietic cells, and functions as an important regulator of multiple signaling pathways in hematopoietic cells. This PTP has been shown to interact with, and dephosphorylate a wide spectrum of phospho-proteins involved in hematopoietic cell signaling. Multiple alternatively spliced variants of this gene, which encode distinct isoforms, have been reported. [provided by RefSeq, Jul 2008]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs200900053	G>A	Conflicting-interpretations-of-pathogenicity	Intron variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT054334	hsa-miR-1225-3p	Microarray, qRT-PCR	23593351
MIRT733323	hsa-miR-4649-3p	Luciferase reporter assay, qRT-PCR, Western blot, MTT	26081980
MIRT738279	hsa-miR-186-5p	PAR-CLIP	26701625
MIRT738941	hsa-miR-211-3p	PAR-CLIP	26701625
MIRT741296	hsa-miR-328-5p	PAR-CLIP	26701625
MIRT743590	hsa-miR-4270	PAR-CLIP	26701625
MIRT744557	hsa-miR-4441	PAR-CLIP	26701625
MIRT744659	hsa-miR-4447	PAR-CLIP	26701625
MIRT744985	hsa-miR-4472	PAR-CLIP	26701625
MIRT745923	hsa-miR-4525	PAR-CLIP	26701625
MIRT749505	hsa-miR-5010-5p	PAR-CLIP	26701625
MIRT750231	hsa-miR-520d-5p	PAR-CLIP	26701625
MIRT750286	hsa-miR-524-5p	PAR-CLIP	26701625
MIRT752464	hsa-miR-6134	PAR-CLIP	26701625
MIRT754029	hsa-miR-6731-5p	PAR-CLIP	26701625
MIRT754732	hsa-miR-6754-5p	PAR-CLIP	26701625
MIRT754938	hsa-miR-6760-5p	PAR-CLIP	26701625
MIRT756136	hsa-miR-6795-5p	PAR-CLIP	26701625
MIRT758544	hsa-miR-6885-5p	PAR-CLIP	26701625
MIRT758595	hsa-miR-6887-5p	PAR-CLIP	26701625
MIRT758954	hsa-miR-7109-5p	PAR-CLIP	26701625
MIRT759272	hsa-miR-7156-3p	PAR-CLIP	26701625
MIRT760233	hsa-miR-8085	PAR-CLIP	26701625
MIRT760584	hsa-miR-92a-2-5p	PAR-CLIP	26701625

Transcription factors

Transcription factor	Regulation	Reference
NFKB1	Unknown	18948549
NPM1	Activation	16825495
PKNOX1	Activation	20864515
RELA	Unknown	18948549
STAT3	Repression	14630083;16825495;21792937
STAT3	Unknown	15870198
USF1	Unknown	12071971
USF2	Unknown	12071971

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001784	Function	Phosphotyrosine residue binding	IMP	12051764
GO:0001784	Function	Phosphotyrosine residue binding	IPI	11986327, 12051764
GO:0002244	Process	Hematopoietic progenitor cell differentiation	IEA
GO:0002924	Process	Negative regulation of humoral immune response mediated by circulating immunoglobulin	IEA
GO:0004725	Function	Protein tyrosine phosphatase activity	IMP	10206955, 17562706
GO:0004725	Function	Protein tyrosine phosphatase activity	TAS
GO:0005001	Function	Transmembrane receptor protein tyrosine phosphatase activity	IDA	11266449
GO:0005515	Function	Protein binding	IPI	7228577, 7528537, 7528577, 8114715, 8574854, 8577729, 8627166, 8648092, 8691146, 8691154, 9148918, 9285411, 9603468, 9774457, 9842885, 10206955, 10540326, 10556798, 10660620, 10764762, 10887109, 11489943, 11907092, 16254138, 16339535, 16493035, 17416557, 17562706, 17947393, 18086677
GO:0005576	Component	Extracellular region	TAS
GO:0005634	Component	Nucleus	IDA	19838216
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005730	Component	Nucleolus	IDA
GO:0005737	Component	Cytoplasm	IDA	10940933, 19838216
GO:0005829	Component	Cytosol	TAS
GO:0005911	Component	Cell-cell junction	IEA
GO:0006470	Process	Protein dephosphorylation	IDA	11266449
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS	7781604
GO:0008284	Process	Positive regulation of cell population proliferation	IMP	19749791, 19838216
GO:0008285	Process	Negative regulation of cell population proliferation	NAS	10497187
GO:0014068	Process	Positive regulation of phosphatidylinositol 3-kinase signaling	IMP	19838216
GO:0016020	Component	Membrane	TAS	10506221
GO:0017124	Function	SH3 domain binding	IEA
GO:0018108	Process	Peptidyl-tyrosine phosphorylation	IDA	9285411, 18802077
GO:0019221	Process	Cytokine-mediated signaling pathway	TAS
GO:0019901	Function	Protein kinase binding	IPI	11266449
GO:0030154	Process	Cell differentiation	IDA	11266449
GO:0030168	Process	Platelet activation	TAS
GO:0030220	Process	Platelet formation	IEA
GO:0031295	Process	T cell costimulation	TAS
GO:0032715	Process	Negative regulation of interleukin-6 production	ISS
GO:0032720	Process	Negative regulation of tumor necrosis factor production	ISS
GO:0032991	Component	Protein-containing complex	IMP	17562706
GO:0033277	Process	Abortive mitotic cell cycle	IEA
GO:0033630	Process	Positive regulation of cell adhesion mediated by integrin	IEA
GO:0035335	Process	Peptidyl-tyrosine dephosphorylation	IMP	17562706
GO:0035556	Process	Intracellular signal transduction	IEA
GO:0035580	Component	Specific granule lumen	TAS
GO:0035855	Process	Megakaryocyte development	IEA
GO:0042105	Component	Alpha-beta T cell receptor complex	IEA
GO:0042130	Process	Negative regulation of T cell proliferation	IEA
GO:0042169	Function	SH2 domain binding	IEA
GO:0042267	Process	Natural killer cell mediated cytotoxicity	IEA
GO:0042981	Process	Regulation of apoptotic process	TAS	10506221
GO:0043312	Process	Neutrophil degranulation	TAS
GO:0043407	Process	Negative regulation of MAP kinase activity	IEA
GO:0045577	Process	Regulation of B cell differentiation	IEA
GO:0050732	Process	Negative regulation of peptidyl-tyrosine phosphorylation	IMP	19749791
GO:0050839	Function	Cell adhesion molecule binding	IEA
GO:0050853	Process	B cell receptor signaling pathway	IEA
GO:0050860	Process	Negative regulation of T cell receptor signaling pathway	IEA
GO:0050900	Process	Leukocyte migration	TAS
GO:0051279	Process	Regulation of release of sequestered calcium ion into cytosol	IEA
GO:0060338	Process	Regulation of type I interferon-mediated signaling pathway	TAS
GO:0070062	Component	Extracellular exosome	HDA	19056867, 20458337
GO:0070372	Process	Regulation of ERK1 and ERK2 cascade	IDA	11266449
GO:0070527	Process	Platelet aggregation	IEA
GO:0071345	Process	Cellular response to cytokine stimulus	TAS
GO:0140031	Function	Phosphorylation-dependent protein binding	IPI	11162587, 12163025
GO:1904724	Component	Tertiary granule lumen	TAS
GO:1905867	Process	Epididymis development	IEA
GO:2000045	Process	Regulation of G1/S transition of mitotic cell cycle	IMP	19838216

Other IDs

• MIM: 176883
• HGNC: 9658
• e!Ensembl: ENSG00000111679

Protein

• UniProt ID: P29350
• Protein name: Tyrosine-protein phosphatase non-receptor type 6 (EC 3.1.3.48) (Hematopoietic cell protein-tyrosine phosphatase) (Protein-tyrosine phosphatase 1C) (PTP-1C) (Protein-tyrosine phosphatase SHP-1) (SH-PTP1)
• Protein function: Modulates signaling by tyrosine phosphorylated cell surface receptors such as KIT and the EGF receptor/EGFR. The SH2 regions may interact with other cellular components to modulate its own phosphatase activity against interacting substrates. Together with MTUS1, induces UBE2V2 expression upon angiotensin II stimulation. Plays a key role in hematopoiesis.
• PDB: 1FPR, 1GWZ, 1X6C, 2B3O, 2RMX, 2YU7, 3PS5, 4GRY, 4GRZ, 4GS0, 4HJP, 4HJQ, 6SM5
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00017	SH2	4 → 79	SH2 domain	Domain
  PF00017	SH2	110 → 194	SH2 domain	Domain
  PF00102	Y_phosphatase	270 → 514	Protein-tyrosine phosphatase	Domain

• Sequence:

  MVRWFHRDLSGLDAETLLKGRGVHGSFLARPSRKNQGDFSLSVRVGDQVTHIRIQNSGDF
  YDLYGGEKFATLTELVEYYTQQQGVLQDRDGTIIHLKYPLNCSDPTSERWYHGHMSGGQA
  ETLLQAKGEPWTFLVRESLSQPGDFVLSVLSDQPKAGPGSPLRVTHIKVMCEGGRYTVGG
  LETFDSLTDLVEHFKKTGIEEASGAFVYLRQPYYATRVNAADIENRVLELNKKQESEDTA
  KAGFWEEFESLQKQEVKNLHQRLEGQRPENKGKNRYKNILPFDHSRVILQGRDSNIPGSD
  YINANYIKNQLLGPDENAKTYIASQGCLEATVNDFWQMAWQENSRVIVMTTREVEKGRNK
  CVPYWPEVGMQRAYGPYSVTNCGEHDTTEYKLRTLQVSPLDNGDLIREIWHYQYLSWPDH
  GVPSEPGGVLSFLDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMENISTKGLDC
  DIDIQKTIQMVRAQRSGMVQTEAQYKFIYVAIAQFIETTKKKLEVLQSQKGQESEYGNIT
  YPPAMKNAHAKASRTSSKHKEDVYENLHTKNKREEKVKKQRSADKEKSKGSLKRK

• Sequence length: 595