Tyrosine-protein phosphatase non-receptor type 6

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Reviewed, UniProtKB/Swiss-Prot P29351 (PTN6_MOUSE)

Last modified January 19, 2010. Version 115. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    Tyrosine-protein phosphatase non-receptor type 6
    EC=3.1.3.48
Alternative name(s):
    Protein-tyrosine phosphatase 1C
      Short name=PTP-1C
    Hematopoietic cell protein-tyrosine phosphatase
    70Z-SHP
    SH-PTP1
      Short name=SHP-1
    PTPTY-42

Gene names

Name:	Ptpn6
Synonyms:	Hcp, Hcph, Ptp1C

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

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

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Protein attributes

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

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General annotation (Comments)

Function	Plays a key role in hematopoiesis. This PTPase activity may directly link growth factor receptors and other signaling proteins through protein-tyrosine phosphorylation. 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.
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. Interacts with KIR2DL1; the interaction is enhanced by ARRB2 By similarity. Ref.5 Ref.9 Ref.10
Subcellular location	Cytoplasm. Nucleus By similarity. Note: In neurons, translocates into the nucleus after treatment with angiotensin II By similarity.
Tissue specificity	Expressed predominantly in hematopoietic cells. Ref.8
Post-translational modification	Phosphorylated on tyrosine residues. Ref.7 Ref.11
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.

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Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Domain	Repeat SH2 domain
Molecular function	Hydrolase Protein phosphatase
PTM	Acetylation Phosphoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	B cell receptor signaling pathway Inferred from mutant phenotype. Source: MGI cytokine-mediated signaling pathway Traceable author statement. Source: MGI intracellular signaling cascade Inferred from direct assay. Source: MGI natural killer cell mediated cytotoxicity Inferred from mutant phenotype. Source: MGI negative regulation of MAP kinase activity Inferred from mutant phenotype. Source: MGI negative regulation of MAPKKK cascade Inferred from mutant phenotype. Source: MGI negative regulation of T cell proliferation Inferred from mutant phenotype. Source: MGI negative regulation of T cell receptor signaling pathway Inferred from mutant phenotype. Source: MGI negative regulation of humoral immune response mediated by circulating immunoglobulin Inferred from mutant phenotype. Source: MGI negative regulation of peptidyl-tyrosine phosphorylation Inferred from mutant phenotype. Source: MGI protein amino acid dephosphorylation Inferred from direct assay. Source: MGI regulation of B cell differentiation Inferred from mutant phenotype. Source: MGI
Cellular component	alpha-beta T cell receptor complex Inferred from direct assay. Source: MGI cytoplasm Traceable author statement. Source: MGI nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	SH2 domain binding Inferred from direct assay. Source: MGI SH3 domain binding Inferred from direct assay. Source: MGI phosphotyrosine binding Inferred from physical interaction. Source: MGI protein tyrosine phosphatase activity Inferred from direct assay. Source: MGI
Complete GO annotation...

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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

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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

Sites

Active site

453

Phosphocysteine intermediate By similarity

Amino acid modifications

Modified residue

Phosphoserine By similarity

Modified residue

Phosphotyrosine By similarity

Modified residue

277

N6-acetyllysine By similarity

Modified residue

377

Phosphotyrosine Ref.11

Modified residue

509

Phosphotyrosine By similarity

Modified residue

536

Phosphotyrosine Ref.11

Modified residue

564

Phosphotyrosine 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 Ref.1

Sequence conflict

240

A → R Ref.3

Sequence conflict

572

K → Q Ref.1

Sequence conflict

572

K → Q Ref.3

Sequence conflict

586

E → D in AAH12660. Ref.6

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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. 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. 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

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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: 1732748] [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: 1373816] [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: 8324828] [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: 9445485] [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: 10419485] [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: 15489334] [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: 1385421] [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: 1932742] [Abstract] Cited for: NUCLEOTIDE SEQUENCE 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: 9712903] [Abstract] Cited for: INTERACTION WITH PTPNS1.
[10]	"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: 14662855] [Abstract] Cited for: INTERACTION WITH CD300LF. Strain: C57BL/6.
[11]	"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: 17947660] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-377 AND TYR-536, MASS SPECTROMETRY. Tissue: Mast cell.
+	Additional computationally mapped references.

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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. NP_038573.2.
UniGene	Mm.271799
3D structure databases
SMR	P29351. Positions 2-526.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-41455N.
STRING	P29351.
PTM databases
PhosphoSite	P29351.
Proteomic databases
PRIDE	P29351.
Genome annotation databases
Ensembl	ENSMUST00000004377; ENSMUSP00000004377; ENSMUSG00000004266; Mus musculus. [Genome view] ENSMUST00000112484; ENSMUSP00000108103; ENSMUSG00000004266; Mus musculus. [Genome view]
GeneID	15170.
KEGG	mmu:15170.
NMPDR	fig\|10090.3.peg.15234.
UCSC	uc009drk.1. mouse.
Organism-specific databases
CTD	15170.
MGI	MGI:96055. Ptpn6.
Phylogenomic databases
eggNOG	roNOG08193.
HOVERGEN	P29351.
OrthoDB	EOG9MGVTB.
PhylomeDB	P29351.
Enzyme and pathway databases
BRENDA	3.1.3.48. 244.
Gene expression databases
ArrayExpress	P29351.
Bgee	P29351.
CleanEx	MM_PTPN6.
Genevestigator	P29351.
GermOnline	ENSMUSG00000004266. Mus musculus.
Family and domain databases
InterPro	IPR000387. Dual-sp/Tyr_phosphatase. IPR000980. SH2. IPR016130. Tyr_Pase_AS. IPR012152. Tyr_Pase_non-rcpt_typ-6/11. IPR000242. Tyr_Pase_rcpt/non-rcpt. [Graphical view]
Gene3D	G3DSA:3.30.505.10. SH2. 2 hits.
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 Resources
NextBio	287680.
SOURCE	Search...

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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:	January 19, 2010
This is version 115 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

MGD cross-references

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

SIMILARITY comments

Index of protein domains and families

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

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents