P29350 (PTN6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

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

Gene names

Name:	PTPN6
Synonyms:	HCP, PTP1C

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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.18
Catalytic activity	Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.
Subunit structure	Monomer. Interacts with MTUS1 By similarity. Interacts with MILR1 (tyrosine-phosphorylated). Interacts with KIT By similarity. Binds PTPNS1, LILRB1 and LILRB2. Interacts with FCRL2, FCRL3, FCRL4, CD300LF, CDK2 and CD84. 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 LYN. Interacts with the tyrosine phosphorylated form of PDPK1. Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.25 Ref.26 Ref.31
Subcellular location	Cytoplasm. Nucleus. Note: In neurons, translocates into the nucleus after treatment with angiotensin II By similarity. Shuttles between the cytoplasm and nucleus via its association with PDPK1. Ref.26 Ref.31
Tissue specificity	Isoform 1 is expressed in hematopoietic cells. Isoform 2 is expressed in non-hematopoietic cells.
Post-translational modification	Phosphorylated on tyrosine residues. Binding of KITLG/SCF to KIT increases tyrosine phosphorylation By similarity. Phosphorylation at Tyr-564 enhances phosphatase activity. Ref.11 Ref.15 Ref.18 Ref.23 Ref.24 Ref.27 Ref.28
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
Domain	Repeat SH2 domain
Molecular function	Hydrolase Protein phosphatase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	G-protein coupled receptor signaling pathway Traceable author statement. Source: ProtInc T cell costimulation Traceable author statement. Source: Reactome apoptotic process Traceable author statement. Source: ProtInc cell differentiation Inferred from direct assay Ref.18. Source: UniProtKB cell junction assembly Traceable author statement. Source: Reactome cell proliferation Inferred from direct assay Ref.18. Source: UniProtKB interferon-gamma-mediated signaling pathway Traceable author statement. Source: Reactome leukocyte migration Traceable author statement. Source: Reactome negative regulation of peptidyl-tyrosine phosphorylation Inferred from mutant phenotype. Source: BHF-UCL peptidyl-tyrosine phosphorylation Inferred from direct assay Ref.12. Source: UniProtKB platelet activation Traceable author statement. Source: Reactome positive regulation of cell proliferation Inferred from mutant phenotype. Source: BHF-UCL positive regulation of phosphatidylinositol 3-kinase cascade Inferred from mutant phenotype. Source: BHF-UCL regulation of ERK1 and ERK2 cascade Inferred from direct assay Ref.18. Source: UniProtKB regulation of G1/S transition of mitotic cell cycle Inferred from mutant phenotype. Source: BHF-UCL regulation of interferon-gamma-mediated signaling pathway Traceable author statement. Source: Reactome regulation of type I interferon-mediated signaling pathway Traceable author statement. Source: Reactome type I interferon-mediated signaling pathway Traceable author statement. Source: Reactome
Cellular component	cytosol Traceable author statement. Source: Reactome membrane Traceable author statement. Source: ProtInc nucleus Inferred from direct assay. Source: BHF-UCL
Molecular function	protein kinase binding Inferred from physical interaction Ref.18. Source: UniProtKB transmembrane receptor protein tyrosine phosphatase activity Inferred from direct assay Ref.18. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CD22	P20273	4	EBI-78260,EBI-78277
PILRA	Q9UKJ1	5	EBI-78260,EBI-965833

Alternative products

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

Isoform 1 (identifier: P29350-1)

Also known as: Long;

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: P29350-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-3: MVR → MLSRG

Isoform 3 (identifier: P29350-2)

Also known as: Short;

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_0000094758

Regions

Domain

4 – 100

97

SH2 1

Domain

110 – 213

104

SH2 2

Domain

244 – 515

272

Tyrosine-protein phosphatase

Region

453 – 459

7

Substrate binding By similarity

Sites

Active site

453

1

Phosphocysteine intermediate

Binding site

419

1

Substrate By similarity

Binding site

500

1

Substrate By similarity

Amino acid modifications

Modified residue

10

1

Phosphoserine Ref.28

Modified residue

64

1

Phosphotyrosine Ref.28

Modified residue

277

1

N6-acetyllysine Ref.29

Modified residue

377

1

Phosphotyrosine By similarity

Modified residue

509

1

Phosphotyrosine Ref.24

Modified residue

536

1

Phosphotyrosine Ref.23 Ref.27

Modified residue

564

1

Phosphotyrosine; by LYN Ref.15 Ref.23 Ref.28

Natural variations

Alternative sequence

1 – 39

39

Missing in isoform 3.

VSP_005129

Alternative sequence

1 – 3

3

MVR → MLSRG in isoform 2.

VSP_007775

Alternative sequence

40 – 44

5

SLSVR → MLSRG in isoform 3.

VSP_005130

Experimental info

Sequence conflict

6

1

H → L in AAA82880. Ref.5

Sequence conflict

86

1

L → V in AAA36610. Ref.4

Sequence conflict

146

1

V → E in AAA82880. Ref.5

Sequence conflict

146

1

V → E in AAA82879. Ref.5

Secondary structure

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595

Helix Strand Turn

Details...

Helix

11 – 21

11

Beta strand

26 – 31

6

Beta strand

33 – 45

13

Beta strand

48 – 55

8

Beta strand

57 – 59

3

Beta strand

61 – 63

3

Beta strand

68 – 70

3

Helix

72 – 80

9

Beta strand

89 – 91

3

Helix

105 – 107

3

Helix

117 – 127

11

Beta strand

132 – 137

6

Beta strand

139 – 141

3

Beta strand

145 – 154

10

Beta strand

162 – 170

9

Beta strand

175 – 181

7

Beta strand

184 – 186

3

Helix

187 – 197

11

Beta strand

202 – 204

3

Helix

221 – 223

3

Helix

244 – 251

8

Turn

257 – 259

3

Turn

263 – 266

4

Beta strand

283 – 288

6

Beta strand

296 – 305

10

Helix

314 – 316

3

Beta strand

320 – 322

3

Helix

329 – 331

3

Helix

332 – 341

10

Beta strand

346 – 349

4

Beta strand

356 – 358

3

Beta strand

370 – 374

5

Beta strand

377 – 384

8

Beta strand

388 – 390

3

Beta strand

393 – 401

9

Beta strand

403 – 405

3

Beta strand

407 – 411

5

Helix

427 – 440

14

Beta strand

449 – 457

9

Helix

458 – 476

19

Helix

484 – 492

9

Helix

503 – 523

21

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Long) [UniParc]. Last modified December 1, 1992. Version 1. Checksum: 4D7736C21D3542D2	FASTA	595	67,561
	10 20 30 40 50 60 MVRWFHRDLS GLDAETLLKG RGVHGSFLAR PSRKNQGDFS LSVRVGDQVT HIRIQNSGDF 70 80 90 100 110 120 YDLYGGEKFA TLTELVEYYT QQQGVLQDRD GTIIHLKYPL NCSDPTSERW YHGHMSGGQA 130 140 150 160 170 180 ETLLQAKGEP WTFLVRESLS QPGDFVLSVL SDQPKAGPGS PLRVTHIKVM CEGGRYTVGG 190 200 210 220 230 240 LETFDSLTDL VEHFKKTGIE EASGAFVYLR QPYYATRVNA ADIENRVLEL NKKQESEDTA 250 260 270 280 290 300 KAGFWEEFES LQKQEVKNLH QRLEGQRPEN KGKNRYKNIL PFDHSRVILQ GRDSNIPGSD 310 320 330 340 350 360 YINANYIKNQ LLGPDENAKT YIASQGCLEA TVNDFWQMAW QENSRVIVMT TREVEKGRNK 370 380 390 400 410 420 CVPYWPEVGM QRAYGPYSVT NCGEHDTTEY KLRTLQVSPL DNGDLIREIW HYQYLSWPDH 430 440 450 460 470 480 GVPSEPGGVL SFLDQINQRQ ESLPHAGPII VHCSAGIGRT GTIIVIDMLM ENISTKGLDC 490 500 510 520 530 540 DIDIQKTIQM VRAQRSGMVQ TEAQYKFIYV AIAQFIETTK KKLEVLQSQK GQESEYGNIT 550 560 570 580 590 YPPAMKNAHA KASRTSSKHK EDVYENLHTK NKREEKVKKQ RSADKEKSKG SLKRK
	Isoform 2 [UniParc]. Checksum: 6A291A2860159389	FASTA	597	67,719
	10 20 30 40 50 60 MLSRGWFHRD LSGLDAETLL KGRGVHGSFL ARPSRKNQGD FSLSVRVGDQ VTHIRIQNSG 70 80 90 100 110 120 DFYDLYGGEK FATLTELVEY YTQQQGVLQD RDGTIIHLKY PLNCSDPTSE RWYHGHMSGG 130 140 150 160 170 180 QAETLLQAKG EPWTFLVRES LSQPGDFVLS VLSDQPKAGP GSPLRVTHIK VMCEGGRYTV 190 200 210 220 230 240 GGLETFDSLT DLVEHFKKTG IEEASGAFVY LRQPYYATRV NAADIENRVL ELNKKQESED 250 260 270 280 290 300 TAKAGFWEEF ESLQKQEVKN LHQRLEGQRP ENKGKNRYKN ILPFDHSRVI LQGRDSNIPG 310 320 330 340 350 360 SDYINANYIK NQLLGPDENA KTYIASQGCL EATVNDFWQM AWQENSRVIV MTTREVEKGR 370 380 390 400 410 420 NKCVPYWPEV GMQRAYGPYS VTNCGEHDTT EYKLRTLQVS PLDNGDLIRE IWHYQYLSWP 430 440 450 460 470 480 DHGVPSEPGG VLSFLDQINQ RQESLPHAGP IIVHCSAGIG RTGTIIVIDM LMENISTKGL 490 500 510 520 530 540 DCDIDIQKTI QMVRAQRSGM VQTEAQYKFI YVAIAQFIET TKKKLEVLQS QKGQESEYGN 550 560 570 580 590 ITYPPAMKNA HAKASRTSSK HKEDVYENLH TKNKREEKVK KQRSADKEKS KGSLKRK
	Isoform 3 (Short) [UniParc]. Checksum: E903558D44643643	FASTA	556	63,125
	10 20 30 40 50 60 MLSRGVGDQV THIRIQNSGD FYDLYGGEKF ATLTELVEYY TQQQGVLQDR DGTIIHLKYP 70 80 90 100 110 120 LNCSDPTSER WYHGHMSGGQ AETLLQAKGE PWTFLVRESL SQPGDFVLSV LSDQPKAGPG 130 140 150 160 170 180 SPLRVTHIKV MCEGGRYTVG GLETFDSLTD LVEHFKKTGI EEASGAFVYL RQPYYATRVN 190 200 210 220 230 240 AADIENRVLE LNKKQESEDT AKAGFWEEFE SLQKQEVKNL HQRLEGQRPE NKGKNRYKNI 250 260 270 280 290 300 LPFDHSRVIL QGRDSNIPGS DYINANYIKN QLLGPDENAK TYIASQGCLE ATVNDFWQMA 310 320 330 340 350 360 WQENSRVIVM TTREVEKGRN KCVPYWPEVG MQRAYGPYSV TNCGEHDTTE YKLRTLQVSP 370 380 390 400 410 420 LDNGDLIREI WHYQYLSWPD HGVPSEPGGV LSFLDQINQR QESLPHAGPI IVHCSAGIGR 430 440 450 460 470 480 TGTIIVIDML MENISTKGLD CDIDIQKTIQ MVRAQRSGMV QTEAQYKFIY VAIAQFIETT 490 500 510 520 530 540 KKKLEVLQSQ KGQESEYGNI TYPPAMKNAH AKASRTSSKH KEDVYENLHT KNKREEKVKK 550 QRSADKEKSK GSLKRK

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] (ISOFORM 1).
[2]	"A protein-tyrosine phosphatase with sequence similarity to the SH2 domain of the protein-tyrosine kinases." Shen S.H., Bastien L., Posner B.I., Chretien P. Nature 352:736-739(1991) [PubMed: 1652101] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). Tissue: Mammary gland.
[3]	Erratum Shen S.H., Bastien L., Posner B.I., Chretien P. Nature 353:868-868(1991) Cited for: SEQUENCE REVISION.
[4]	"Isolation of a src homology 2-containing tyrosine phosphatase." Plutzky J., Neel B.G., Rosenberg R.D. Proc. Natl. Acad. Sci. U.S.A. 89:1123-1127(1992) [PubMed: 1736296] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[5]	"Human protein tyrosine phosphatase 1C (PTPN6) gene structure: alternate promoter usage and exon skipping generate multiple transcripts." Banville D., Stocco R., Shen S.H. Genomics 27:165-173(1995) [PubMed: 7665165] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1; 2 AND 3).
[6]	"Large-scale sequencing in human chromosome 12p13: experimental and computational gene structure determination." Ansari-Lari M.A., Shen Y., Muzny D.M., Lee W., Gibbs R.A. Genome Res. 7:268-280(1997) [PubMed: 9074930] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]	"Gene silencing of SHP-1 gene in leukemias/lymphomas by aberrant methylation." Oka T., Ouchida M. Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2).
[8]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Umbilical cord blood.
[9]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	"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] (ISOFORM 2). Tissue: Placenta.
[11]	"Tyrosine phosphorylation of an SH2-containing protein tyrosine phosphatase is coupled to platelet thrombin receptor via a pertussis toxin-sensitive heterotrimeric G-protein." Li R.Y., Gaits F., Ragab A., Ragab-Thomas J.M.F., Chap H. EMBO J. 14:2519-2526(1995) [PubMed: 7781604] [Abstract] Cited for: PHOSPHORYLATION.
[12]	"A novel immunoglobulin superfamily receptor for cellular and viral MHC class I molecules." Cosman D., Fanger N., Borges L., Kubin M., Chin W., Peterson L., Hsu M.-L. Immunity 7:273-282(1997) [PubMed: 9285411] [Abstract] Cited for: INTERACTION WITH LILRB1.
[13]	"The MHC class I binding proteins LIR-1 and LIR-2 inhibit Fc receptor-mediated signaling in monocytes." Fanger N.A., Cosman D., Peterson L., Braddy S.C., Maliszewski C.R., Borges L. Eur. J. Immunol. 28:3423-3434(1998) [PubMed: 9842885] [Abstract] Cited for: INTERACTION WITH LILRB2.
[14]	"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.
[15]	"Functional interaction between SHPTP1 and the Lyn tyrosine kinase in the apoptotic response to DNA damage." Yoshida K., Kharbanda S., Kufe D. J. Biol. Chem. 274:34663-34668(1999) [PubMed: 10574931] [Abstract] Cited for: INTERACTION WITH LYN, PHOSPHORYLATION AT TYR-564.
[16]	"Molecular cloning and characterization of SPAP1, an inhibitory receptor." Xu M.-J., Zhao R., Zhao Z.J. Biochem. Biophys. Res. Commun. 280:768-775(2001) [PubMed: 11162587] [Abstract] Cited for: INTERACTION WITH FCRL2 AND FCRL3.
[17]	"Distinct interactions of the X-linked lymphoproliferative syndrome gene product SAP with cytoplasmic domains of members of the CD2 receptor family." Lewis J., Eiben L.J., Nelson D.L., Cohen J.I., Nichols K.E., Ochs H.D., Notarangelo L.D., Duckett C.S. Clin. Immunol. 100:15-23(2001) [PubMed: 11414741] [Abstract] Cited for: INTERACTION WITH CD84.
[18]	"Negative regulation of Ros receptor tyrosine kinase signaling. An epithelial function of the SH2 domain protein tyrosine phosphatase SHP-1." Keilhack H., Mueller M., Boehmer S.A., Frank C., Weidner K.M., Birchmeier W., Ligensa T., Berndt A., Kosmehl H., Guenther B., Mueller T., Birchmeier C., Boehmer F.D. J. Cell Biol. 152:325-334(2001) [PubMed: 11266449] [Abstract] Cited for: FUNCTION IN ROS1 DEPHOSPHORYLATION, INTERACTION WITH ROS1.
[19]	"The inhibitory potential of Fc receptor homolog 4 on memory B cells." Ehrhardt G.R.A., Davis R.S., Hsu J.T., Leu C.-M., Ehrhardt A., Cooper M.D. Proc. Natl. Acad. Sci. U.S.A. 100:13489-13494(2003) [PubMed: 14597715] [Abstract] Cited for: INTERACTION WITH FCRL4.
[20]	"IgSF13, a novel human inhibitory receptor of the immunoglobulin superfamily, is preferentially expressed in dendritic cells and monocytes." Sui L., Li N., Liu Q., Zhang W., Wan T., Wang B., Luo K., Sun H., Cao X. Biochem. Biophys. Res. Commun. 319:920-928(2004) [PubMed: 15184070] [Abstract] Cited for: INTERACTION WITH CD300LF.
[21]	"Signal transduction via the stem cell factor receptor/c-Kit." Ronnstrand L. Cell. Mol. Life Sci. 61:2535-2548(2004) [PubMed: 15526160] [Abstract] Cited for: REVIEW ON ROLE IN KIT SIGNALING.
[22]	"Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor." Roskoski R. Jr. Biochem. Biophys. Res. Commun. 337:1-13(2005) [PubMed: 16129412] [Abstract] Cited for: REVIEW ON ROLE IN KIT SIGNALING.
[23]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-536 AND TYR-564, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[24]	"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column." Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y. Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-509, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[25]	"An essential function for beta-arrestin 2 in the inhibitory signaling of natural killer cells." Yu M.-C., Su L.-L., Zou L., Liu Y., Wu N., Kong L., Zhuang Z.-H., Sun L., Liu H.P., Hu J.-H., Li D., Strominger J.L., Zang J.-W., Pei G., Ge B.-X. Nat. Immunol. 9:898-907(2008) [PubMed: 18604210] [Abstract] Cited for: INTERACTION WITH KIR2DL1.
[26]	"The nuclear localization of 3'-phosphoinositide-dependent kinase-1 is dependent on its association with the protein tyrosine phosphatase SHP-1." Sephton C.F., Zhang D., Lehmann T.M., Pennington P.R., Scheid M.P., Mousseau D.D. Cell. Signal. 21:1634-1644(2009) [PubMed: 19591923] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH PDPK1.
[27]	"An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells." Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., Wiley H.S., Qian W.-J. J. Proteome Res. 8:3852-3861(2009) [PubMed: 19534553] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-536, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[28]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10; TYR-64 AND TYR-564, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[29]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-277, MASS SPECTROMETRY.
[30]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[31]	"Compartmentalized CDK2 is connected with SHP-1 and beta-catenin and regulates insulin internalization." Fiset A., Xu E., Bergeron S., Marette A., Pelletier G., Siminovitch K.A., Olivier M., Beauchemin N., Faure R.L. Cell. Signal. 23:911-919(2011) [PubMed: 21262353] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH CDK2.
[32]	"Crystal structure of the catalytic domain of protein-tyrosine phosphatase SHP-1." Yang J., Liang X., Niu T., Meng W., Zhao Z., Zhou G.W. J. Biol. Chem. 273:28199-28207(1998) [PubMed: 9774441] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 248-399.
[33]	"Solution structures of the SH2 domain of human protein-tyrosine phosphatase SHP-1." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 110-214.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M74903 mRNA. Translation: AAA35963.1.
X62055 mRNA. Translation: CAA43982.1.
M77273 mRNA. Translation: AAA36610.1.
U15528 , U15536, U15535, U15534, U15533, U15532, U15531, U15530, U15529 Genomic DNA. Translation: AAA82880.1.
U15528 , U15537, U15535, U15534, U15533, U15532, U15531, U15530, U15529 Genomic DNA. Translation: AAA82879.1.
U47924 Genomic DNA. Translation: AAB51322.1.
U47924 Genomic DNA. Translation: AAB51323.1.
AB079851 Genomic DNA. Translation: BAC81774.1.
AB079851 Genomic DNA. Translation: BAC81775.1.
AK290421 mRNA. Translation: BAF83110.1.
CH471116 Genomic DNA. Translation: EAW88703.1.
BC002523 mRNA. Translation: AAH02523.1.
BC007667 mRNA. Translation: AAH07667.1.

IPI

IPI00183046.
IPI00218604.
IPI00396552.

PIR

S20825. B42031.

RefSeq

NP_002822.2. NM_002831.5.
NP_536858.1. NM_080548.4.
NP_536859.1. NM_080549.3.

UniGene

Hs.63489.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1FPR	X-ray	2.50	A	243-526	[»]
1GWZ	X-ray	2.50	A	243-541	[»]
1X6C	NMR	-	A	110-214	[»]
2B3O	X-ray	2.80	A	1-532	[»]
2RMX	NMR	-	A	110-214	[»]
2YU7	NMR	-	A	110-214	[»]
3PS5	X-ray	3.10	A	1-595	[»]

ProteinModelPortal

P29350.

SMR

P29350. Positions 1-529.

ModBase

Search...

Protein-protein interaction databases

IntAct

P29350. 15 interactions.

MINT

MINT-134053.

STRING

P29350.

PTM databases

PhosphoSite

P29350.

Polymorphism databases

DMDM

131469.

2D gel databases

OGP

P29350.

Proteomic databases

PRIDE

P29350.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000318974; ENSP00000326010; ENSG00000111679.

GeneID

5777.

KEGG

hsa:5777.

UCSC

uc001qsb.2. human.

Organism-specific databases

CTD

5777.

GeneCards

GC12P007055.

HGNC

HGNC:9658. PTPN6.

HPA

CAB004572.
HPA001466.

MIM

176883. gene.

neXtProt

NX_P29350.

PharmGKB

PA34002.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG14060.

HOVERGEN

HBG000223.

InParanoid

P29350.

PhylomeDB

P29350.

Enzyme and pathway databases

Pathway_Interaction_DB

bcr_5pathway. BCR signaling pathway.
epopathway. EPO signaling pathway.
il4_2pathway. IL4-mediated signaling events.
kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit).
vegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2.
tcrpathway. TCR signaling in naive CD4+ T cells.
cd8tcrpathway. TCR signaling in naive CD8+ T cells.

Reactome

REACT_111102. Signal Transduction.
REACT_111155. Cell-Cell communication.
REACT_604. Hemostasis.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P29350.

Bgee

P29350.

CleanEx

HS_PTPN6.

Genevestigator

P29350.

GermOnline

ENSG00000111679. Homo sapiens.

Family and domain databases

InterPro

IPR000980. SH2.
IPR000387. Tyr/Dual-specificity_Pase.
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.

KO

K05697.

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

BindingDB

P29350.

NextBio

22466.

PMAP-CutDB

P29350.

SOURCE

Search...

Entry information

Entry name

PTN6_HUMAN

Accession

Primary (citable) accession number: P29350
Secondary accession number(s): A8K306, Q969V8

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	December 1, 1992
Last modified:	January 25, 2012
This is version 146 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.