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 (NCBI Gene): 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 tran

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
MIRT1275735	hsa-miR-296-3p	CLIP-seq
MIRT1275736	hsa-miR-3150b-3p	CLIP-seq
MIRT1275737	hsa-miR-3154	CLIP-seq
MIRT1275738	hsa-miR-4434	CLIP-seq
MIRT1275739	hsa-miR-4516	CLIP-seq
MIRT1275740	hsa-miR-4699-3p	CLIP-seq
MIRT1275741	hsa-miR-4784	CLIP-seq
MIRT2604592	hsa-miR-1224-5p	CLIP-seq
MIRT2604593	hsa-miR-3065-3p	CLIP-seq
MIRT2604594	hsa-miR-3622a-3p	CLIP-seq
MIRT2604595	hsa-miR-3622b-3p	CLIP-seq
MIRT2604596	hsa-miR-3622b-5p	CLIP-seq
MIRT2604597	hsa-miR-4701-5p	CLIP-seq
MIRT2604598	hsa-miR-4751	CLIP-seq
MIRT2604599	hsa-miR-544b	CLIP-seq
MIRT2604600	hsa-miR-588	CLIP-seq
MIRT2604592	hsa-miR-1224-5p	CLIP-seq
MIRT2604593	hsa-miR-3065-3p	CLIP-seq
MIRT2604594	hsa-miR-3622a-3p	CLIP-seq
MIRT2604595	hsa-miR-3622b-3p	CLIP-seq
MIRT2604596	hsa-miR-3622b-5p	CLIP-seq
MIRT2604597	hsa-miR-4701-5p	CLIP-seq
MIRT2604598	hsa-miR-4751	CLIP-seq
MIRT2604599	hsa-miR-544b	CLIP-seq
MIRT2604600	hsa-miR-588	CLIP-seq

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:0000165	Process	MAPK cascade	IBA
GO:0000165	Process	MAPK cascade	IEA
GO:0000278	Process	Mitotic cell cycle	IBA
GO:0001784	Function	Phosphotyrosine residue binding	IBA
GO:0001784	Function	Phosphotyrosine residue binding	IEA
GO:0001784	Function	Phosphotyrosine residue binding	IPI	11986327
GO:0002221	Process	Pattern recognition receptor signaling pathway	IDA	23910378
GO:0002244	Process	Hematopoietic progenitor cell differentiation	IEA
GO:0002283	Process	Neutrophil activation involved in immune response	ISS
GO:0002753	Process	Cytoplasmic pattern recognition receptor signaling pathway	IDA	29441066
GO:0002924	Process	Negative regulation of humoral immune response mediated by circulating immunoglobulin	IEA
GO:0004721	Function	Phosphoprotein phosphatase activity	IEA
GO:0004725	Function	Protein tyrosine phosphatase activity	IDA	17562706, 29925997
GO:0004725	Function	Protein tyrosine phosphatase activity	IEA
GO:0004725	Function	Protein tyrosine phosphatase activity	IMP	10206955, 17562706, 19749791
GO:0004725	Function	Protein tyrosine phosphatase activity	TAS
GO:0004726	Function	Non-membrane spanning protein tyrosine phosphatase activity	IBA
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, 12051764, 16254138, 16339535, 16493035, 17416557, 17562706, 17947393
GO:0005576	Component	Extracellular region	TAS
GO:0005634	Component	Nucleus	IDA	19838216
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005730	Component	Nucleolus	IDA
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IDA	9065461
GO:0005737	Component	Cytoplasm	IDA	10940933, 19838216
GO:0005737	Component	Cytoplasm	IEA
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IDA	23896411
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:0016020	Component	Membrane	TAS	10506221
GO:0016525	Process	Negative regulation of angiogenesis	IDA	23896411
GO:0016787	Function	Hydrolase activity	IEA
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	IBA
GO:0030154	Process	Cell differentiation	IDA	11266449
GO:0030220	Process	Platelet formation	IEA
GO:0031295	Process	T cell costimulation	IEA
GO:0031295	Process	T cell costimulation	TAS
GO:0031665	Process	Negative regulation of lipopolysaccharide-mediated signaling pathway	IEA
GO:0031665	Process	Negative regulation of lipopolysaccharide-mediated signaling pathway	ISS
GO:0032715	Process	Negative regulation of interleukin-6 production	IEA
GO:0032715	Process	Negative regulation of interleukin-6 production	ISS
GO:0032720	Process	Negative regulation of tumor necrosis factor production	IEA
GO:0032720	Process	Negative regulation of tumor necrosis factor production	ISS
GO:0032991	Component	Protein-containing complex	IMP	17562706
GO:0033007	Process	Negative regulation of mast cell activation involved in immune response	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:0042098	Process	T cell proliferation	IEA
GO:0042105	Component	Alpha-beta T cell receptor complex	IEA
GO:0042110	Process	T cell activation	IDA	38354704
GO:0042110	Process	T cell activation	IDA	38354704
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:0043409	Process	Negative regulation of MAPK cascade	IEA
GO:0045577	Process	Regulation of B cell differentiation	IEA
GO:0045766	Process	Positive regulation of angiogenesis	IDA	23896411
GO:0045824	Process	Negative regulation of innate immune response	IDA	34811497
GO:0050839	Function	Cell adhesion molecule binding	IEA
GO:0050852	Process	T cell receptor signaling pathway	IEA
GO:0050853	Process	B cell receptor signaling pathway	IEA
GO:0050859	Process	Negative regulation of B cell receptor signaling pathway	IDA	35941532
GO:0050860	Process	Negative regulation of T cell receptor signaling pathway	IEA
GO:0051279	Process	Regulation of release of sequestered calcium ion into cytosol	IEA
GO:0051897	Process	Positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IEA
GO:0051897	Process	Positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IMP	19838216
GO:0060338	Process	Regulation of type I interferon-mediated signaling pathway	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:0090594	Process	Inflammatory response to wounding	IDA	27830702
GO:0106015	Process	Negative regulation of inflammatory response to wounding	IDA	27830702
GO:0106015	Process	Negative regulation of inflammatory response to wounding	IEA
GO:0140031	Function	Phosphorylation-dependent protein binding	IPI	11162587, 12163025
GO:0160162	Process	CD27 signaling pathway	IDA	38354704
GO:0160162	Process	CD27 signaling pathway	IDA	38354704
GO:1900017	Process	Positive regulation of cytokine production involved in inflammatory response	IDA	8654373
GO:1902564	Process	Negative regulation of neutrophil activation	IDA	34234773
GO:1902564	Process	Negative regulation of neutrophil activation	IEA
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: Tyrosine phosphatase enzyme that plays important roles in controlling immune signaling pathways and fundamental physiological processes such as hematopoiesis (PubMed:14739280, PubMed:29925997). Dephosphorylates and negatively regulate several re
• PDB: 1FPR, 1GWZ, 1X6C, 2B3O, 2RMX, 2YU7, 3PS5, 4GRY, 4GRZ, 4GS0, 4HJP, 4HJQ, 6SM5, 8YHI
• 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

• Tissue specificity: TISSUE SPECIFICITY: Isoform 1 is expressed in hematopoietic cells. Isoform 2 is expressed in non-hematopoietic cells. {ECO:0000269|PubMed:1732748}.
• Sequence:

  MVRWFHRDLSGLDAETLLKGRGVHGSFLARPSRKNQGDFSLSVRVGDQVTHIRIQNSGDF
  YDLYGGEKFATLTELVEYYTQQQGVLQDRDGTIIHLKYPLNCSDPTSERWYHGHMSGGQA
  ETLLQAKGEPWTFLVRESLSQPGDFVLSVLSDQPKAGPGSPLRVTHIKVMCEGGRYTVGG
  LETFDSLTDLVEHFKKTGIEEASGAFVYLRQPYYATRVNAADIENRVLELNKKQESEDTA
  KAGFWEEFESLQKQEVKNLHQRLEGQRPENKGKNRYKNILPFDHSRVILQGRDSNIPGSD
  YINANYIKNQLLGPDENAKTYIASQGCLEATVNDFWQMAWQENSRVIVMTTREVEKGRNK
  CVPYWPEVGMQRAYGPYSVTNCGEHDTTEYKLRTLQVSPLDNGDLIREIWHYQYLSWPDH
  GVPSEPGGVLSFLDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMENISTKGLDC
  DIDIQKTIQMVRAQRSGMVQTEAQYKFIYVAIAQFIETTKKKLEVLQSQKGQESEYGNIT
  YPPAMKNAHAKASRTSSKHKEDVYENLHTKNKREEKVKKQRSADKEKSKGSLKRK

• Sequence length: 595

Pathways

KEGG:

Efferocytosis
Adherens junction
JAK-STAT signaling pathway
Natural killer cell mediated cytotoxicity
T cell receptor signaling pathway
B cell receptor signaling pathway
Pathogenic Escherichia coli infection
Leishmaniasis
Proteoglycans in cancer
PD-L1 expression and PD-1 checkpoint pathway in cancer

Reactome:

GPVI-mediated activation cascade
Regulation of KIT signaling
PECAM1 interactions
Costimulation by the CD28 family
PD-1 signaling
Platelet sensitization by LDL
Interleukin-3, Interleukin-5 and GM-CSF signaling
CD22 mediated BCR regulation
Neutrophil degranulation
Interferon gamma signaling
Interleukin-37 signaling
Interferon alpha/beta signaling
Interleukin receptor SHC signaling
Regulation of IFNA signaling
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Autism spectrum disorder	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BULLOUS PYODERMA GANGRENOSUM	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CALCINOSIS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEART VALVE DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEART VALVE DISEASES	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEART VALVE PROLAPSE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Relationship Type	References	Evidence Score
Adenocarcinoma of Lung	Associate	33839701	★☆☆☆☆ Found in Text Mining only
Alzheimer Disease	Associate	39336795	★☆☆☆☆ Found in Text Mining only
Arthritis Rheumatoid	Associate	37426641	★☆☆☆☆ Found in Text Mining only
Asthma	Associate	22371396	★☆☆☆☆ Found in Text Mining only
Ataxia Telangiectasia	Associate	12591278	★☆☆☆☆ Found in Text Mining only
Autoimmune Diseases	Inhibit	22458980	★☆☆☆☆ Found in Text Mining only
Autoimmune Diseases	Associate	31616406	★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Associate	21719561, 23938089, 23948750, 35045088	★☆☆☆☆ Found in Text Mining only
Burkitt Lymphoma	Associate	32449435	★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Associate	20424160	★☆☆☆☆ Found in Text Mining only
Carcinoma	Stimulate	21719561	★☆☆☆☆ Found in Text Mining only
Carcinoma Non Small Cell Lung	Associate	23842094	★☆☆☆☆ Found in Text Mining only
Castleman Disease	Associate	29496669	★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Associate	29693170	★☆☆☆☆ Found in Text Mining only
Cystic Fibrosis	Associate	35782124	★☆☆☆☆ Found in Text Mining only
Demyelinating Autoimmune Diseases CNS	Associate	19398961, 19559654	★☆☆☆☆ Found in Text Mining only
Demyelinating Diseases	Associate	18209728, 19398961	★☆☆☆☆ Found in Text Mining only
Fibrosis	Inhibit	29097680	★☆☆☆☆ Found in Text Mining only
Fibrosis	Associate	32434445	★☆☆☆☆ Found in Text Mining only
GATA2 Deficiency	Inhibit	11583976	★☆☆☆☆ Found in Text Mining only
GATA2 Deficiency	Associate	25614448, 32732362	★☆☆☆☆ Found in Text Mining only
Glioma	Associate	24510345	★☆☆☆☆ Found in Text Mining only
Hashimoto Disease	Associate	34522174	★☆☆☆☆ Found in Text Mining only
Hematologic Neoplasms	Associate	17540846	★☆☆☆☆ Found in Text Mining only
Hematologic Neoplasms	Inhibit	18948549, 22960265	★☆☆☆☆ Found in Text Mining only
HTLV I Infections	Associate	9520455	★☆☆☆☆ Found in Text Mining only
Inflammation	Associate	18209728, 19398961, 19559654, 22458980, 32434445, 37045900	★☆☆☆☆ Found in Text Mining only
Kidney Failure Chronic	Associate	30212930	★☆☆☆☆ Found in Text Mining only
Leukemia	Inhibit	11583976	★☆☆☆☆ Found in Text Mining only
Leukemia Lymphocytic Chronic B Cell	Associate	26053404	★☆☆☆☆ Found in Text Mining only
Leukemia Lymphocytic Chronic B Cell	Inhibit	28480959	★☆☆☆☆ Found in Text Mining only
Leukemia Lymphoma Adult T Cell	Inhibit	17540846	★☆☆☆☆ Found in Text Mining only
Leukemia Lymphoma Adult T Cell	Associate	29794791	★☆☆☆☆ Found in Text Mining only
Leukemia Myelogenous Chronic BCR ABL Positive	Associate	21821701	★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid Acute	Associate	15574429, 26547689, 40255396	★☆☆☆☆ Found in Text Mining only
Leukemia Prolymphocytic T Cell	Associate	31974418	★☆☆☆☆ Found in Text Mining only
Leukemia Promyelocytic Acute	Associate	8197173	★☆☆☆☆ Found in Text Mining only
Leukemia T Cell	Inhibit	12591278	★☆☆☆☆ Found in Text Mining only
Lymphoma Large B Cell Diffuse	Associate	23979523, 26565811	★☆☆☆☆ Found in Text Mining only
Lymphoma Large Cell Anaplastic	Associate	16469875	★☆☆☆☆ Found in Text Mining only
Lymphoma T Cell Cutaneous	Associate	29794791	★☆☆☆☆ Found in Text Mining only
Lymphoma T Cell Peripheral	Associate	30420593	★☆☆☆☆ Found in Text Mining only
Lymphoproliferative Disorders	Associate	12429820	★☆☆☆☆ Found in Text Mining only
Monoclonal Gammopathy of Undetermined Significance	Associate	17213358	★☆☆☆☆ Found in Text Mining only
Multi centric Castleman's Disease	Associate	29496669	★☆☆☆☆ Found in Text Mining only
Multiple Myeloma	Associate	17213358, 19147543, 19937797, 26545722	★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Inhibit	18209728, 19398961, 22458980	★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Associate	19398961, 19559654	★☆☆☆☆ Found in Text Mining only
Myelodysplastic Syndromes	Associate	15541478, 15953006	★☆☆☆☆ Found in Text Mining only
Neoplasms	Associate	11583976, 12591278, 16469875, 20068065, 23979523, 24100145, 24838641, 26565811, 28480959, 29794791, 39367146	★☆☆☆☆ Found in Text Mining only
Neoplasms	Inhibit	17540846, 18948549, 20424160, 26547689	★☆☆☆☆ Found in Text Mining only
Neoplasms	Stimulate	32454905	★☆☆☆☆ Found in Text Mining only
Nervous System Diseases	Associate	18209728	★☆☆☆☆ Found in Text Mining only
Pdgfrb Associated Chronic Eosinophilic Leukemia	Associate	18318760	★☆☆☆☆ Found in Text Mining only
Plaque Atherosclerotic	Stimulate	26742467	★☆☆☆☆ Found in Text Mining only
Polyradiculoneuropathy Chronic Inflammatory Demyelinating	Associate	18209728	★☆☆☆☆ Found in Text Mining only
Precursor T Cell Lymphoblastic Leukemia Lymphoma	Associate	18318760	★☆☆☆☆ Found in Text Mining only
Prostatitis	Associate	11836342	★☆☆☆☆ Found in Text Mining only
Pseudolymphoma	Associate	11583976	★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Associate	24838641, 26508024	★☆☆☆☆ Found in Text Mining only
Testicular Germ Cell Tumor	Associate	39367146	★☆☆☆☆ Found in Text Mining only
Urethral Neoplasms	Associate	33200223	★☆☆☆☆ Found in Text Mining only
Urinary Bladder Neoplasms	Associate	32454905, 36211821	★☆☆☆☆ Found in Text Mining only
Vitiligo	Associate	28129744	★☆☆☆☆ Found in Text Mining only