Tyrosine-protein phosphatase non-receptor type 6

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P29351 (PTN6_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 142. History...

Clusters with 100%, 90%, 50% identity |

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Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Tyrosine-protein phosphatase non-receptor type 6
EC=3.1.3.48

Alternative name(s):
70Z-SHP
Hematopoietic cell protein-tyrosine phosphatase
PTPTY-42
Protein-tyrosine phosphatase 1C
Short name=PTP-1C
SH-PTP1
Short name=SHP-1

Gene names

Name:	Ptpn6
Synonyms:	Hcp, Hcph, Ptp1C

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	595 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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. Ref.10
Catalytic activity	Protein tyrosine phosphate + H₂O = protein tyrosine + phosphate.
Subunit structure	Monomer. Interacts with FCRL2, FCRL3, FCRL4, CD84 and MTUS1 By similarity. Binds PTPNS1. Interacts with CD300LF and CDK2. Interacts with MILR1 (tyrosine-phosphorylated). Interacts with KIR2DL1; the interaction is enhanced by ARRB2 By similarity. Interacts (via SH2 1 domain) with ROS1; the interaction is direct and promotes ROS1 dephosphorylation By similarity. Interacts with EGFR; inhibits EGFR-dependent activation of MAPK/ERK. Interacts with LYN By similarity. Interacts with KIT. Interacts with the tyrosine phosphorylated form of PDPK1 By similarity. Ref.5 Ref.9 Ref.10 Ref.11 Ref.12
Subcellular location	Cytoplasm. Nucleus By similarity. Note: In neurons, translocates into the nucleus after treatment with angiotensin II. Shuttles between the cytoplasm and nucleus via its association with PDPK1 By similarity.
Tissue specificity	Expressed predominantly in hematopoietic cells. Ref.8
Domain	The N-terminal SH2 domain functions as an auto-inhibitory domain, blocking the catalytic domain in the ligand-free close conformation By similarity.
Post-translational modification	Phosphorylated on tyrosine residues. Phosphorylation at Tyr-564 enhances phosphatase activity By similarity. Binding of KITLG/SCF to KIT increases tyrosine phosphorylation. Ref.7 Ref.10
Involvement in disease	Defects in Ptpn6 are the cause of the motheaten (me) or viable motheaten (mev) phenotypes. Mice homozygous for the recessive allelic mutations develop severe defects in hematopoiesis.
Sequence similarities	Belongs to the protein-tyrosine phosphatase family. Non-receptor class 2 subfamily. Contains 2 SH2 domains. Contains 1 tyrosine-protein phosphatase domain.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Domain	Repeat SH2 domain
Molecular function	Hydrolase Protein phosphatase
PTM	Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	B cell receptor signaling pathway Inferred from mutant phenotype PubMed 9254656. Source: MGI cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB cytokine-mediated signaling pathway Traceable author statement PubMed 8943354. Source: MGI intracellular signal transduction Inferred from direct assay PubMed 10229828. Source: MGI natural killer cell mediated cytotoxicity Inferred from mutant phenotype PubMed 6971254. Source: MGI negative regulation of MAP kinase activity Inferred from mutant phenotype PubMed 9064344 PubMed 9254656. Source: MGI negative regulation of T cell proliferation Inferred from mutant phenotype PubMed 9064344. Source: MGI negative regulation of T cell receptor signaling pathway Inferred from mutant phenotype PubMed 9064344. Source: MGI negative regulation of humoral immune response mediated by circulating immunoglobulin Inferred from mutant phenotype PubMed 9254656. Source: MGI negative regulation of peptidyl-tyrosine phosphorylation Inferred from mutant phenotype PubMed 9254656. Source: MGI regulation of B cell differentiation Inferred from mutant phenotype PubMed 9254656. Source: MGI regulation of ERK1 and ERK2 cascade Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	alpha-beta T cell receptor complex Inferred from direct assay PubMed 9064344. Source: MGI cytosol Traceable author statement. Source: Reactome nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	SH2 domain binding Inferred from direct assay PubMed 8632004. Source: MGI SH3 domain binding Inferred from direct assay PubMed 8632004. Source: MGI transmembrane receptor protein tyrosine phosphatase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P29351-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P29351-2) The sequence of this isoform differs from the canonical sequence as follows: 1-3: MVR → MLSRG

Isoform 3 (identifier: P29351-3) The sequence of this isoform differs from the canonical sequence as follows: 1-39: Missing. 40-44: SLSVR → MLSRG

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 595

595

Tyrosine-protein phosphatase non-receptor type 6

PRO_0000094759

Regions

Domain

4 – 100

SH2 1

Domain

110 – 213

104

SH2 2

Domain

244 – 515

272

Tyrosine-protein phosphatase

Region

453 – 459

Substrate binding By similarity

Sites

Active site

453

Phosphocysteine intermediate By similarity

Binding site

419

Substrate By similarity

Binding site

500

Substrate By similarity

Amino acid modifications

Modified residue

Phosphotyrosine By similarity

Modified residue

377

Phosphotyrosine Ref.13

Modified residue

536

Phosphotyrosine Ref.13

Modified residue

564

Phosphotyrosine; by LYN By similarity

Natural variations

Alternative sequence

1 – 39

Missing in isoform 3.

VSP_005132

Alternative sequence

1 – 3

MVR → MLSRG in isoform 2.

VSP_005131

Alternative sequence

40 – 44

SLSVR → MLSRG in isoform 3.

VSP_005133

Natural variant

77 – 99

EYYTQ…HLKYP → VPRPHIWRAGGVTAAGQGRA LD in motheaten (me).

Natural variant

100 – 595

496

Missing in motheaten (me).

Experimental info

Sequence conflict

240

A → R in AAA37796. Ref.1

Sequence conflict

572

K → Q in AAA37796. Ref.1

Sequence conflict

586

E → D in AAH12660. Ref.6

Sequences

Sequence		Length	Mass (Da)
Isoform 1 [UniParc]. Last modified July 11, 2002. Version 2. Checksum: CF17300D032638D2 Show »	FASTA	595	67,559
10 20 30 40 50 60 MVRWFHRDLS GPDAETLLKG RGVPGSFLAR PSRKNQGDFS LSVRVDDQVT HIRIQNSGDF 70 80 90 100 110 120 YDLYGGEKFA TLTELVEYYT QQQGILQDRD GTIIHLKYPL NCSDPTSERW YHGHISGGQA 130 140 150 160 170 180 ESLLQAKGEP WTFLVRESLS QPGDFVLSVL NDQPKAGPGS PLRVTHIKVM CEGGRYTVGG 190 200 210 220 230 240 SETFDSLTDL VEHFKKTGIE EASGAFVYLR QPYYATRVNA ADIENRVLEL NKKQESEDTA 250 260 270 280 290 300 KAGFWEEFES LQKQEVKNLH QRLEGQRPEN KSKNRYKNIL PFDHSRVILQ GRDSNIPGSD 310 320 330 340 350 360 YINANYVKNQ LLGPDENSKT YIASQGCLDA TVNDFWQMAW QENTRVIVMT TREVEKGRNK 370 380 390 400 410 420 CVPYWPEVGT QRVYGLYSVT NSREHDTAEY KLRTLQISPL DNGDLVREIW HYQYLSWPDH 430 440 450 460 470 480 GVPSEPGGVL SFLDQINQRQ ESLPHAGPII VHCSAGIGRT GTIIVIDMLM ESISTKGLDC 490 500 510 520 530 540 DIDIQKTIQM VRAQRSGMVQ TEAQYKFIYV AIAQFIETTK KKLEIIQSQK GQESEYGNIT 550 560 570 580 590 YPPAVRSAHA KASRTSSKHK EEVYENVHSK SKKEEKVKKQ RSADKEKNKG SLKRK « Hide
Isoform 2 [UniParc]. Checksum: E8491CE77E06E989 Show »	FASTA	597	67,717
10 20 30 40 50 60 MLSRGWFHRD LSGPDAETLL KGRGVPGSFL ARPSRKNQGD FSLSVRVDDQ VTHIRIQNSG 70 80 90 100 110 120 DFYDLYGGEK FATLTELVEY YTQQQGILQD RDGTIIHLKY PLNCSDPTSE RWYHGHISGG 130 140 150 160 170 180 QAESLLQAKG EPWTFLVRES LSQPGDFVLS VLNDQPKAGP GSPLRVTHIK VMCEGGRYTV 190 200 210 220 230 240 GGSETFDSLT DLVEHFKKTG IEEASGAFVY LRQPYYATRV NAADIENRVL ELNKKQESED 250 260 270 280 290 300 TAKAGFWEEF ESLQKQEVKN LHQRLEGQRP ENKSKNRYKN ILPFDHSRVI LQGRDSNIPG 310 320 330 340 350 360 SDYINANYVK NQLLGPDENS KTYIASQGCL DATVNDFWQM AWQENTRVIV MTTREVEKGR 370 380 390 400 410 420 NKCVPYWPEV GTQRVYGLYS VTNSREHDTA EYKLRTLQIS PLDNGDLVRE IWHYQYLSWP 430 440 450 460 470 480 DHGVPSEPGG VLSFLDQINQ RQESLPHAGP IIVHCSAGIG RTGTIIVIDM LMESISTKGL 490 500 510 520 530 540 DCDIDIQKTI QMVRAQRSGM VQTEAQYKFI YVAIAQFIET TKKKLEIIQS QKGQESEYGN 550 560 570 580 590 ITYPPAVRSA HAKASRTSSK HKEEVYENVH SKSKKEEKVK KQRSADKEKN KGSLKRK « Hide
Isoform 3 [UniParc]. Checksum: CACF025DF9D7BC2D Show »	FASTA	556	63,179
10 20 30 40 50 60 MLSRGVDDQV THIRIQNSGD FYDLYGGEKF ATLTELVEYY TQQQGILQDR DGTIIHLKYP 70 80 90 100 110 120 LNCSDPTSER WYHGHISGGQ AESLLQAKGE PWTFLVRESL SQPGDFVLSV LNDQPKAGPG 130 140 150 160 170 180 SPLRVTHIKV MCEGGRYTVG GSETFDSLTD LVEHFKKTGI EEASGAFVYL RQPYYATRVN 190 200 210 220 230 240 AADIENRVLE LNKKQESEDT AKAGFWEEFE SLQKQEVKNL HQRLEGQRPE NKSKNRYKNI 250 260 270 280 290 300 LPFDHSRVIL QGRDSNIPGS DYINANYVKN QLLGPDENSK TYIASQGCLD ATVNDFWQMA 310 320 330 340 350 360 WQENTRVIVM TTREVEKGRN KCVPYWPEVG TQRVYGLYSV TNSREHDTAE YKLRTLQISP 370 380 390 400 410 420 LDNGDLVREI WHYQYLSWPD HGVPSEPGGV LSFLDQINQR QESLPHAGPI IVHCSAGIGR 430 440 450 460 470 480 TGTIIVIDML MESISTKGLD CDIDIQKTIQ MVRAQRSGMV QTEAQYKFIY VAIAQFIETT 490 500 510 520 530 540 KKKLEIIQSQ KGQESEYGNI TYPPAVRSAH AKASRTSSKH KEEVYENVHS KSKKEEKVKK 550 QRSADKEKNK GSLKRK « Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Protein tyrosine phosphatase containing SH2 domains: characterization, preferential expression in hematopoietic cells, and localization to human chromosome 12p12-p13." Yi T., Cleveland J.L., Ihle J.N. Mol. Cell. Biol. 12:836-846(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: DBA/2.
[2]	"Characterization of hematopoietic intracellular protein tyrosine phosphatases: description of a phosphatase containing an SH2 domain and another enriched in proline-, glutamic acid-, serine-, and threonine-rich sequences." Matthews R.J., Bowne D.B., Flores E., Thomas M.L. Mol. Cell. Biol. 12:2396-2405(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Mutations at the murine motheaten locus are within the hematopoietic cell protein-tyrosine phosphatase (Hcph) gene." Schultz L.D., Schweitzer P.A., Rajan T.V., Yi T., Ihle J.N., Matthews R.J., Thomas M.L., Beier D.R. Cell 73:1445-1454(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS MOTHEATEN AND VIABLE MOTHEATEN. Strain: C57BL/6J. Tissue: Bone marrow.
[4]	"Comparative sequence analysis of a gene-rich cluster at human chromosome 12p13 and its syntenic region in mouse chromosome 6." Ansari-Lari M.A., Oeltjen J.C., Schwartz S., Zhang Z., Muzny D.M., Lu J., Gorrell J.H., Chinault A.C., Belmont J.W., Miller W., Gibbs R.A. Genome Res. 8:29-40(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 3).
[5]	"Murine SHP-1 splice variants with altered Src homology 2 (SH2) domains. Implications for the SH2-mediated intramolecular regulation of SHP-1." Martin A., Tsui H.W., Shulman M.J., Isenman D., Tsui F.W. J. Biol. Chem. 274:21725-21734(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2), SUBUNIT. Strain: C3H. Tissue: Adrenal gland.
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]	"Protein tyrosine phosphatase-1C is rapidly phosphorylated in tyrosine in macrophages in response to colony stimulating factor-1." Yeung Y.-G., Berg K.L., Pixley F.J., Angeletti R.H., Stanley E.R. J. Biol. Chem. 267:23447-23450(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 54-68; 128-135; 137-151; 242-252; 278-285; 293-308 AND 373-382, PHOSPHORYLATION.
[8]	"Identification of novel protein tyrosine phosphatases of hematopoietic cells by polymerase chain reaction amplification." Yi T., Cleveland J.L., Ihle J.N. Blood 78:2222-2228(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 342-451, TISSUE SPECIFICITY. Strain: BALB/c. Tissue: Myeloid leukemia cell.
[9]	"High expression of inhibitory receptor SHPS-1 and its association with protein tyrosine phosphatase SHP-1 in macrophages." Veillette A., Thibaudeau E., Latour S. J. Biol. Chem. 273:22719-22728(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PTPNS1.
[10]	"SHP-1 binds and negatively modulates the c-Kit receptor by interaction with tyrosine 569 in the c-Kit juxtamembrane domain." Kozlowski M., Larose L., Lee F., Le D.M., Rottapel R., Siminovitch K.A. Mol. Cell. Biol. 18:2089-2099(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH KIT, FUNCTION IN MODULATING KIT SIGNALING, PHOSPHORYLATION.
[11]	"CMRF-35-like molecule-1, a novel mouse myeloid receptor, can inhibit osteoclast formation." Chung D.-H., Humphrey M.B., Nakamura M.C., Ginzinger D.G., Seaman W.E., Daws M.R. J. Immunol. 171:6541-6548(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CD300LF. Strain: C57BL/6.
[12]	"An immunoglobulin-like receptor, Allergin-1, inhibits immunoglobulin E-mediated immediate hypersensitivity reactions." Hitomi K., Tahara-Hanaoka S., Someya S., Fujiki A., Tada H., Sugiyama T., Shibayama S., Shibuya K., Shibuya A. Nat. Immunol. 11:601-607(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MILR1.
[13]	"Quantitative time-resolved phosphoproteomic analysis of mast cell signaling." Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R. J. Immunol. 179:5864-5876(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-377 AND TYR-536, MASS SPECTROMETRY. Tissue: Mast cell.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M68902 mRNA. Translation: AAA37796.1. M90389 mRNA. Translation: AAA40007.1. S63763 mRNA. No translation available. S63764 mRNA. No translation available. S63803 mRNA. No translation available. AC002397 Genomic DNA. Translation: AAC36009.1. AC002397 Genomic DNA. Translation: AAC36008.1. U65955 , U65952, U65953, U65954 Genomic DNA. Translation: AAD00152.1. U65955 , U65951, U65952, U65953, U65954 Genomic DNA. Translation: AAD00151.1. BC012660 mRNA. Translation: AAH12660.1.
IPI	IPI00225419. IPI00225422. IPI00310909.
PIR	A44390.
RefSeq	NP_001071173.1. NM_001077705.1. NP_038573.2. NM_013545.2.
UniGene	Mm.271799.
3D structure databases
ProteinModelPortal	P29351.
SMR	P29351. Positions 1-529.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-41455N.
IntAct	P29351. 1 interaction.
PTM databases
PhosphoSite	P29351.
Proteomic databases
PaxDb	P29351.
PRIDE	P29351.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000004377; ENSMUSP00000004377; ENSMUSG00000004266. ENSMUST00000112484; ENSMUSP00000108103; ENSMUSG00000004266. ENSMUST00000171549; ENSMUSP00000129124; ENSMUSG00000004266. ENSMUST00000174265; ENSMUSP00000133991; ENSMUSG00000004266.
GeneID	15170.
KEGG	mmu:15170.
UCSC	uc009drk.1. mouse.
Organism-specific databases
CTD	5777.
MGI	MGI:96055. Ptpn6.
Phylogenomic databases
eggNOG	COG5599.
GeneTree	ENSGT00700000104166.
HOVERGEN	HBG000223.
KO	K05697.
OMA	QAKGEPW.
OrthoDB	EOG4255SK.
Enzyme and pathway databases
Reactome	REACT_107772. Immune System. REACT_137402. Cell-Cell communication.
Gene expression databases
ArrayExpress	P29351.
Bgee	P29351.
CleanEx	MM_PTPN6.
Genevestigator	P29351.
GermOnline	ENSMUSG00000004266. Mus musculus.
Family and domain databases
Gene3D	3.30.505.10. 2 hits.
InterPro	IPR000980. SH2. IPR000387. Tyr/Dual-sp_Pase. IPR016130. Tyr_Pase_AS. IPR012152. Tyr_Pase_non-rcpt_typ-6/11. IPR000242. Tyr_Pase_rcpt/non-rcpt. [Graphical view]
Pfam	PF00017. SH2. 2 hits. PF00102. Y_phosphatase. 1 hit. [Graphical view]
PIRSF	PIRSF000929. Tyr-Ptase_nr_6. 1 hit.
PRINTS	PR00700. PRTYPHPHTASE. PR00401. SH2DOMAIN.
SMART	SM00194. PTPc. 1 hit. SM00252. SH2. 2 hits. [Graphical view]
PROSITE	PS50001. SH2. 2 hits. PS00383. TYR_PHOSPHATASE_1. 1 hit. PS50056. TYR_PHOSPHATASE_2. 1 hit. PS50055. TYR_PHOSPHATASE_PTP. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	PTPN6. mouse.
NextBio	287680.
SOURCE	Search...

Entry information

Entry name

PTN6_MOUSE

Accession

Primary (citable) accession number: P29351
Secondary accession number(s): O35128

Q9R0V6

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	July 11, 2002
Last modified:	April 3, 2013
This is version 142 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Alternative products

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents