Q06124 (PTN11_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tyrosine-protein phosphatase non-receptor type 11
EC=3.1.3.48

Alternative name(s):
Protein-tyrosine phosphatase 1D
Short name=PTP-1D
Protein-tyrosine phosphatase 2C
Short name=PTP-2C
SH-PTP2
Short name=SHP-2
Short name=Shp2
SH-PTP3

Gene names

Name:	PTPN11
Synonyms:	PTP2C, SHPTP2

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	597 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus. Dephosphorylates ROCK2 at Tyr-722 resulting in stimulatation of its RhoA binding activity. Ref.17 Ref.36 Ref.37
Catalytic activity	Protein tyrosine phosphate + H2O = protein tyrosine + phosphate. Ref.49
Subunit structure	Interacts with phosphorylated LIME1 and BCAR3. Interacts with SHB and INPP5D/SHIP1 By similarity. Interacts with MILR1 (tyrosine-phosphorylated). Interacts with FLT1 (tyrosine-phosphorylated), FLT3 (tyrosine-phosphorylated), FLT4 (tyrosine-phosphorylated), KIT and GRB2. Interacts with PDGFRA (tyrosine phosphorylated). Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated) By similarity. Interacts with PTPNS1 and CD84. Interacts with phosphorylated SIT1 and MPZL1. Interacts with FCRL3, FCRL4, FCRL6 and ANKHD1. Interacts with KIR2DL1; the interaction is enhanced by ARRB2. Interacts with GAB2. Interacts with TERT; the interaction retains TERT in the nucleus. Interacts with PECAM1 and FER. Interacts with EPHA2 (activated); participates in PTK2/FAK1 dephosphorylation in EPHA2 downstream signaling. Interacts with ROS1; mediates PTPN11 phosphorylation. Interacts with PDGFRB (tyrosine phosphorylated); this interaction increases the PTPN11 phosphatase activity. Ref.10 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.26 Ref.30 Ref.31 Ref.32 Ref.36 Ref.38 Ref.40 Ref.44
Subcellular location	Cytoplasm.
Tissue specificity	Widely expressed, with highest levels in heart, brain, and skeletal muscle. Ref.2 Ref.3 Ref.4
Domain	The SH2 domains repress phosphatase activity. Binding of these domains to phosphotyrosine-containing proteins relieves this auto-inhibition, possibly by inducing a conformational change in the enzyme.
Post-translational modification	Phosphorylated on Tyr-546 and Tyr-584 upon receptor protein tyrosine kinase activation; which creates a binding site for GRB2 and other SH2-containing proteins. Phosphorylated upon activation of the receptor-type kinase FLT3. Phosphorylated upon activation of the receptor-type kinase PDGFRA By similarity. Phosphorylated by activated PDGFRB. Ref.5 Ref.10 Ref.11 Ref.18 Ref.27 Ref.28 Ref.29 Ref.33 Ref.34 Ref.35 Ref.39 Ref.41 Ref.42 Ref.44
Involvement in disease	Defects in PTPN11 are the cause of LEOPARD syndrome type 1 (LEOPARD1) [MIM:151100]. It is an autosomal dominant disorder allelic with Noonan syndrome. The acronym LEOPARD stands for lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and deafness. Ref.54 Ref.61 Ref.65 Ref.66 Ref.67 Ref.69 Ref.70 Defects in PTPN11 are the cause of Noonan syndrome type 1 (NS1) [MIM:163950]. Noonan syndrome (NS) is a disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis. Some patients with Noonan syndrome type 1 develop multiple giant cell lesions of the jaw or other bony or soft tissues, which are classified as pigmented villomoduolar synovitis (PVNS) when occurring in the jaw or joints. Note=Mutations in PTPN11 account for more than 50% of the cases. Rarely, NS is associated with juvenile myelomonocytic leukemia (JMML). NS1 inheritance is autosomal dominant. Ref.50 Ref.53 Ref.55 Ref.56 Ref.57 Ref.58 Ref.60 Ref.62 Ref.63 Ref.64 Ref.68 Ref.71 Defects in PTPN11 are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:607785]. JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia. It is characterized by leukocytosis with tissue infiltration and in vitro hypersensitivity of myeloid progenitors to granulocyte-macrophage colony stimulating factor. Ref.63 Defects in PTPN11 are a cause of metachondromatosis (MC) [MIM:156250]. It is a skeletal disorder with radiologic fetarures of both multiple exostoses and Ollier disease, characterized by the presence of multiple enchondromas and osteochondroma-like lesions. Ref.45
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
Coding sequence diversity	Alternative splicing
Disease	Deafness Disease mutation
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	T cell costimulation Traceable author statement. Source: Reactome axon guidance Traceable author statement. Source: Reactome cell junction assembly Traceable author statement. Source: Reactome ephrin receptor signaling pathway Inferred from direct assay Ref.17. Source: UniProtKB epidermal growth factor receptor signaling pathway Traceable author statement. Source: Reactome fibroblast growth factor receptor signaling pathway Traceable author statement. Source: Reactome insulin receptor signaling pathway Traceable author statement. Source: Reactome interferon-gamma-mediated signaling pathway Traceable author statement. Source: Reactome leukocyte migration Traceable author statement. Source: Reactome platelet activation Traceable author statement. Source: Reactome regulation of cell adhesion mediated by integrin Inferred from mutant phenotype Ref.17. Source: UniProtKB 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
Molecular function	non-membrane spanning protein tyrosine phosphatase activity Inferred from mutant phenotype Ref.17. Source: UniProtKB protein binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GAB1	Q13480	3	EBI-297779,EBI-517684
GRB2	P62993	6	EBI-297779,EBI-401755
MPZL1	O95297	2	EBI-297779,EBI-963338

Alternative products

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

Isoform 1 (identifier: Q06124-1)

Also known as: PTP2Ci;

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: Q06124-2)

Also known as: PTP2C;

The sequence of this isoform differs from the canonical sequence as follows:
     408-411: Missing.

Isoform 3 (identifier: Q06124-3)

The sequence of this isoform differs from the canonical sequence as follows:
     408-411: Missing.
     464-464: S → R
     465-597: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 597

597

Tyrosine-protein phosphatase non-receptor type 11

PRO_0000094767

Regions

Domain

6 – 102

97

SH2 1

Domain

112 – 216

105

SH2 2

Domain

247 – 521

275

Tyrosine-protein phosphatase

Region

463 – 469

7

Substrate binding By similarity

Sites

Active site

463

1

Phosphocysteine intermediate

Binding site

429

1

Substrate By similarity

Binding site

510

1

Substrate By similarity

Amino acid modifications

Modified residue

62

1

Phosphotyrosine Ref.27 Ref.28 Ref.33 Ref.35 Ref.41 Ref.42

Modified residue

63

1

Phosphotyrosine Ref.33 Ref.41

Modified residue

66

1

Phosphotyrosine By similarity

Modified residue

280

1

N6-acetyllysine Ref.43

Modified residue

546

1

Phosphotyrosine; by PDGFR

Modified residue

562

1

Phosphoserine Ref.39

Modified residue

584

1

Phosphotyrosine; by PDGFR Ref.29 Ref.33 Ref.34 Ref.41 Ref.42

Modified residue

595

1

Phosphoserine Ref.34

Natural variations

Alternative sequence

408 – 411

4

Missing in isoform 2 and isoform 3.

VSP_016672

Alternative sequence

464

1

S → R in isoform 3.

VSP_016673

Alternative sequence

465 – 597

133

Missing in isoform 3.

VSP_016674

Natural variant

2

1

T → I in NS1. Ref.62

VAR_027183

Natural variant

42

1

T → A in NS1. Ref.53 Ref.62

VAR_015601

Natural variant

58

1

N → K in NS1. Ref.58

VAR_027184

Natural variant

59

1

T → A in NS1. Ref.71

VAR_066060

Natural variant

60

1

G → A in NS1. Ref.53

VAR_015602

Natural variant

60

1

G → V in myelodysplastic syndrome. Ref.63

VAR_015990

Natural variant

61

1

D → G in NS1. Ref.50 Ref.53 Ref.56 Ref.58

VAR_015603

Natural variant

61

1

D → N in NS1. Ref.53 Ref.58

VAR_015604

Natural variant

61

1

D → V in JMML; also in myelodysplastic syndrome. Ref.63

VAR_015991

Natural variant

61

1

D → Y in JMML. Ref.63

VAR_015992

Natural variant

62

1

Y → D in NS1; also in Noonan patients manifesting juvenile myelomonocytic leukemia. Ref.53 Ref.55 Ref.62 Ref.63

VAR_015605

Natural variant

63

1

Y → C in NS1. Ref.50 Ref.53 Ref.55 Ref.56 Ref.58 Ref.62

VAR_015606

Natural variant

69

1

E → K in JMML; also in myelodysplastic syndrome. Ref.63

VAR_015993

Natural variant

69

1

E → Q in NS1. Ref.58

VAR_027185

Natural variant

71

1

F → K in acute myeloid leukemia; requires 2 nucleotide substitutions. Ref.63

VAR_015994

Natural variant

71

1

F → L in myelodysplastic syndrome. Ref.58 Ref.63

VAR_015995

Natural variant

72

1

A → G in NS1. Ref.50 Ref.53 Ref.62

VAR_015607

Natural variant

72

1

A → S in NS1. Ref.50 Ref.56 Ref.58

VAR_015608

Natural variant

72

1

A → T in JMML. Ref.63

VAR_015996

Natural variant

72

1

A → V in JMML. Ref.63

VAR_015997

Natural variant

73

1

T → I in NS1; also in Noonan patients manifesting juvenile myelomonocytic leukemia. Ref.53 Ref.56 Ref.58 Ref.63
Corresponds to variant rs28933387 [ dbSNP | Ensembl ].

VAR_015609

Natural variant

76

1

E → A in JMML; also in myelodysplastic syndrome. Ref.63

VAR_015998

Natural variant

76

1

E → D in NS1. Ref.50 Ref.53 Ref.58

VAR_015610

Natural variant

76

1

E → G in JMML. Ref.63

VAR_015999

Natural variant

76

1

E → K in JMML. Ref.63
Corresponds to variant rs28933388 [ dbSNP | Ensembl ].

VAR_016000

Natural variant

76

1

E → V in JMML. Ref.63

VAR_016001

Natural variant

79

1

Q → P in NS1. Ref.62

VAR_027186

Natural variant

79

1

Q → R in NS1. Ref.50 Ref.53 Ref.57 Ref.58

VAR_015611

Natural variant

106

1

D → A in NS1. Ref.53 Ref.62

VAR_015612

Natural variant

139

1

E → D in NS1. Ref.53 Ref.58

VAR_015613

Natural variant

256

1

Q → R in NS1. Ref.58

VAR_027187

Natural variant

279

1

Y → C in NS1 and LEOPARD1. Ref.53 Ref.54 Ref.62 Ref.66 Ref.67 Ref.70

VAR_015614

Natural variant

279

1

Y → S in LEOPARD1. Ref.66 Ref.67

VAR_027188

Natural variant

282

1

I → V in NS1. Ref.50 Ref.53 Ref.58

VAR_015615

Natural variant

285

1

F → L in NS1. Ref.53

VAR_015617

Natural variant

285

1

F → S in NS1. Ref.53 Ref.56

VAR_015616

Natural variant

308

1

N → D in NS1; common mutation. Ref.50 Ref.53 Ref.56 Ref.58 Ref.62

VAR_015619

Natural variant

308

1

N → S in NS1; some patients also manifest giant cell lesions of bone and soft tissue. Ref.53 Ref.62

VAR_015618

Natural variant

309

1

I → V in NS1. Ref.53

VAR_015620

Natural variant

415

1

T → M in NS1. Ref.64

VAR_027189

Natural variant

465

1

A → T in LEOPARD1. Ref.65

VAR_027190

Natural variant

468

1

G → A in LEOPARD1. Ref.65 Ref.67

VAR_027191

Natural variant

472

1

T → M in LEOPARD1. Ref.54 Ref.62 Ref.66 Ref.67

VAR_015621

Natural variant

502

1

R → L in LEOPARD1. Ref.67

VAR_027192

Natural variant

502

1

R → W in LEOPARD1. Ref.67

VAR_027193

Natural variant

505

1

R → K in NS1. Ref.53

VAR_015622

Natural variant

506

1

S → T in NS1. Ref.55 Ref.60

VAR_015623

Natural variant

507

1

G → A in JMML. Ref.63

VAR_016002

Natural variant

507

1

G → R in patients with growth retardation, pulmonic stenosis and juvenile myelomonocytic leukemia. Ref.62 Ref.63

VAR_016003

Natural variant

508

1

M → V in NS1. Ref.50 Ref.53 Ref.62

VAR_015624

Natural variant

510

1

Q → P in LEOPARD1. Ref.61 Ref.67 Ref.69

VAR_027194

Natural variant

510

1

Q → R in NS1. Ref.68

VAR_027195

Natural variant

514

1

Q → P in LEOPARD1. Ref.66

VAR_027196

Natural variant

564

1

L → F in NS1. Ref.62

VAR_027197

Experimental info

Mutagenesis

463

1

C → S: Abolishes phosphatase activity. Ref.3

Sequence conflict

539

1

S → R in BAA02740. Ref.3

Sequence conflict

552

1

S → P in BAA02740. Ref.3

Secondary structure

1

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597

Helix Strand Turn

Details...

Helix

13 – 23

11

Beta strand

28 – 33

6

Beta strand

35 – 37

3

Beta strand

41 – 47

7

Beta strand

50 – 57

8

Beta strand

59 – 61

3

Beta strand

63 – 65

3

Beta strand

70 – 73

4

Helix

74 – 82

9

Beta strand

88 – 93

6

Helix

119 – 128

10

Beta strand

134 – 139

6

Beta strand

141 – 143

3

Beta strand

147 – 153

7

Beta strand

166 – 175

10

Beta strand

178 – 184

7

Beta strand

187 – 189

3

Helix

190 – 199

10

Helix

223 – 225

3

Helix

226 – 234

9

Helix

247 – 255

9

Helix

256 – 261

6

Helix

266 – 269

4

Helix

271 – 276

6

Beta strand

277 – 279

3

Turn

286 – 288

3

Beta strand

289 – 291

3

Beta strand

304 – 310

7

Beta strand

327 – 330

4

Turn

335 – 337

3

Helix

338 – 348

11

Beta strand

352 – 355

4

Beta strand

359 – 361

3

Beta strand

364 – 366

3

Beta strand

377 – 380

4

Beta strand

383 – 392

10

Beta strand

394 – 405

12

Beta strand

412 – 424

13

Beta strand

429 – 431

3

Helix

436 – 452

17

Beta strand

459 – 462

4

Beta strand

464 – 467

4

Helix

468 – 486

19

Beta strand

490 – 492

3

Helix

494 – 502

9

Helix

512 – 527

16

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (PTP2Ci) [UniParc]. Last modified December 20, 2005. Version 2. Checksum: 37E8BFC7ECA2D03F	FASTA	597	68,436
	10 20 30 40 50 60 MTSRRWFHPN ITGVEAENLL LTRGVDGSFL ARPSKSNPGD FTLSVRRNGA VTHIKIQNTG 70 80 90 100 110 120 DYYDLYGGEK FATLAELVQY YMEHHGQLKE KNGDVIELKY PLNCADPTSE RWFHGHLSGK 130 140 150 160 170 180 EAEKLLTEKG KHGSFLVRES QSHPGDFVLS VRTGDDKGES NDGKSKVTHV MIRCQELKYD 190 200 210 220 230 240 VGGGERFDSL TDLVEHYKKN PMVETLGTVL QLKQPLNTTR INAAEIESRV RELSKLAETT 250 260 270 280 290 300 DKVKQGFWEE FETLQQQECK LLYSRKEGQR QENKNKNRYK NILPFDHTRV VLHDGDPNEP 310 320 330 340 350 360 VSDYINANII MPEFETKCNN SKPKKSYIAT QGCLQNTVND FWRMVFQENS RVIVMTTKEV 370 380 390 400 410 420 ERGKSKCVKY WPDEYALKEY GVMRVRNVKE SAAHDYTLRE LKLSKVGQAL LQGNTERTVW 430 440 450 460 470 480 QYHFRTWPDH GVPSDPGGVL DFLEEVHHKQ ESIMDAGPVV VHCSAGIGRT GTFIVIDILI 490 500 510 520 530 540 DIIREKGVDC DIDVPKTIQM VRSQRSGMVQ TEAQYRFIYM AVQHYIETLQ RRIEEEQKSK 550 560 570 580 590 RKGHEYTNIK YSLADQTSGD QSPLPPCTPT PPCAEMREDS ARVYENVGLM QQQKSFR
	Isoform 2 (PTP2C) [UniParc]. Checksum: 9CDBEFFA5E6CCB45	FASTA	593	68,011
	10 20 30 40 50 60 MTSRRWFHPN ITGVEAENLL LTRGVDGSFL ARPSKSNPGD FTLSVRRNGA VTHIKIQNTG 70 80 90 100 110 120 DYYDLYGGEK FATLAELVQY YMEHHGQLKE KNGDVIELKY PLNCADPTSE RWFHGHLSGK 130 140 150 160 170 180 EAEKLLTEKG KHGSFLVRES QSHPGDFVLS VRTGDDKGES NDGKSKVTHV MIRCQELKYD 190 200 210 220 230 240 VGGGERFDSL TDLVEHYKKN PMVETLGTVL QLKQPLNTTR INAAEIESRV RELSKLAETT 250 260 270 280 290 300 DKVKQGFWEE FETLQQQECK LLYSRKEGQR QENKNKNRYK NILPFDHTRV VLHDGDPNEP 310 320 330 340 350 360 VSDYINANII MPEFETKCNN SKPKKSYIAT QGCLQNTVND FWRMVFQENS RVIVMTTKEV 370 380 390 400 410 420 ERGKSKCVKY WPDEYALKEY GVMRVRNVKE SAAHDYTLRE LKLSKVGQGN TERTVWQYHF 430 440 450 460 470 480 RTWPDHGVPS DPGGVLDFLE EVHHKQESIM DAGPVVVHCS AGIGRTGTFI VIDILIDIIR 490 500 510 520 530 540 EKGVDCDIDV PKTIQMVRSQ RSGMVQTEAQ YRFIYMAVQH YIETLQRRIE EEQKSKRKGH 550 560 570 580 590 EYTNIKYSLA DQTSGDQSPL PPCTPTPPCA EMREDSARVY ENVGLMQQQK SFR
	Isoform 3 [UniParc]. Checksum: EB8E1553B37F1CC0	FASTA	460	52,828
	10 20 30 40 50 60 MTSRRWFHPN ITGVEAENLL LTRGVDGSFL ARPSKSNPGD FTLSVRRNGA VTHIKIQNTG 70 80 90 100 110 120 DYYDLYGGEK FATLAELVQY YMEHHGQLKE KNGDVIELKY PLNCADPTSE RWFHGHLSGK 130 140 150 160 170 180 EAEKLLTEKG KHGSFLVRES QSHPGDFVLS VRTGDDKGES NDGKSKVTHV MIRCQELKYD 190 200 210 220 230 240 VGGGERFDSL TDLVEHYKKN PMVETLGTVL QLKQPLNTTR INAAEIESRV RELSKLAETT 250 260 270 280 290 300 DKVKQGFWEE FETLQQQECK LLYSRKEGQR QENKNKNRYK NILPFDHTRV VLHDGDPNEP 310 320 330 340 350 360 VSDYINANII MPEFETKCNN SKPKKSYIAT QGCLQNTVND FWRMVFQENS RVIVMTTKEV 370 380 390 400 410 420 ERGKSKCVKY WPDEYALKEY GVMRVRNVKE SAAHDYTLRE LKLSKVGQGN TERTVWQYHF 430 440 450 460 RTWPDHGVPS DPGGVLDFLE EVHHKQESIM DAGPVVVHCR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of a novel protein-tyrosine phosphatase SH-PTP3 with sequence similarity to the src-homology region 2." Adachi M., Sekiya M., Miyachi T., Matsuno K., Hinoda Y., Imai K., Yachi A. FEBS Lett. 314:335-339(1992) [PubMed: 1281790] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: T-cell.
[2]	"Identification of a human src homology 2-containing protein-tyrosine-phosphatase: a putative homolog of Drosophila corkscrew." Freeman R.M. Jr., Plutzky J., Neel B.G. Proc. Natl. Acad. Sci. U.S.A. 89:11239-11243(1992) [PubMed: 1280823] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY.
[3]	"Cloning, expression and mutational analysis of SH-PTP2, human protein-tyrosine phosphatase." Bastien L., Ramachandran C., Liu S., Adam M. Biochem. Biophys. Res. Commun. 196:124-133(1993) [PubMed: 8216283] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), MUTAGENESIS OF CYS-463, TISSUE SPECIFICITY.
[4]	"A widely expressed human protein-tyrosine phosphatase containing src homology 2 domains." Ahmad S., Banville D.L., Zhao Z., Fischer E.H., Shen S.H. Proc. Natl. Acad. Sci. U.S.A. 90:2197-2201(1993) [PubMed: 7681589] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY. Tissue: Umbilical cord.
[5]	"Activation of a phosphotyrosine phosphatase by tyrosine phosphorylation." Vogel W., Lammers R., Huang J., Ullrich A. Science 259:1611-1614(1993) [PubMed: 7681217] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PHOSPHORYLATION.
[6]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[7]	"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 2). Tissue: Brain.
[8]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"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 3). Tissue: Eye.
[10]	"Activation of the SH2-containing phosphotyrosine phosphatase SH-PTP2 by its binding site, phosphotyrosine 1009, on the human platelet-derived growth factor receptor." Lechleider R.J., Sugimoto S., Bennett A.M., Kashishian A.S., Cooper J.A., Shoelson S.E., Walsh C.T., Neel B.G. J. Biol. Chem. 268:21478-21481(1993) [PubMed: 7691811] [Abstract] Cited for: PHOSPHORYLATION, INTERACTION WITH PDGFRB.
[11]	"Protein-tyrosine-phosphatase SHPTP2 couples platelet-derived growth factor receptor beta to Ras." Bennett A.M., Tang T.L., Sugimoto S., Walsh C.T., Neel B.G. Proc. Natl. Acad. Sci. U.S.A. 91:7335-7339(1994) [PubMed: 8041791] [Abstract] Cited for: PHOSPHORYLATION BY PDGFRB.
[12]	"Activation of protein-tyrosine phosphatase SH-PTP2 by a tyrosine-based activation motif of a novel brain molecule." Ohnishi H., Kubota M., Ohtake A., Sato K., Sano S. J. Biol. Chem. 271:25569-25574(1996) [PubMed: 8810330] [Abstract] Cited for: INTERACTION WITH PTPNS1.
[13]	"A family of proteins that inhibit signalling through tyrosine kinase receptors." Kharitonenkov A., Chen Z., Sures I., Wang H., Schilling J., Ullrich A. Nature 386:181-186(1997) [PubMed: 9062191] [Abstract] Cited for: INTERACTION WITH PTPNS1.
[14]	"Tyrosine 1213 of Flt-1 is a major binding site of Nck and SHP-2." Igarashi K., Isohara T., Kato T., Shigeta K., Yamano T., Uno I. Biochem. Biophys. Res. Commun. 246:95-99(1998) [PubMed: 9600074] [Abstract] Cited for: INTERACTION WITH FLT1.
[15]	"Gab-family adapter proteins act downstream of cytokine and growth factor receptors and T- and B-cell antigen receptors." Nishida K., Yoshida Y., Itoh M., Fukada T., Ohtani T., Shirogane T., Atsumi T., Takahashi-Tezuka M., Ishihara K., Hibi M., Hirano T. Blood 93:1809-1816(1999) [PubMed: 10068651] [Abstract] Cited for: INTERACTION WITH GAB2.
[16]	"SHP2-interacting transmembrane adaptor protein (SIT), a novel disulfide-linked dimer regulating human T-cell activation." Marie-Cardine A., Kirchgessner H., Bruyns E., Shevchenko A., Mann M., Autschbach F., Ratnofsky S., Meuer S., Schraven B. J. Exp. Med. 189:1181-1194(1999) [PubMed: 10209036] [Abstract] Cited for: INTERACTION WITH SIT1.
[17]	"Activation of EphA2 kinase suppresses integrin function and causes focal-adhesion-kinase dephosphorylation." Miao H., Burnett E., Kinch M., Simon E., Wang B. Nat. Cell Biol. 2:62-69(2000) [PubMed: 10655584] [Abstract] Cited for: FUNCTION, INTERACTION WITH EPHA2.
[18]	"Dissecting the interaction of SHP-2 with PZR, an immunoglobulin family protein containing immunoreceptor tyrosine-based inhibitory motifs." Zhao R., Zhao Z.J. J. Biol. Chem. 275:5453-5459(2000) [PubMed: 10681522] [Abstract] Cited for: INTERACTION WITH MZPL1, DEPHOSPHORYLATION OF MZPL1.
[19]	"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 FCRL3.
[20]	"Cell surface receptors Ly-9 and CD84 recruit the X-linked lymphoproliferative disease gene product SAP." Sayos J., Martin M., Chen A., Simarro M., Howie D., Morra M., Engel P., Terhorst C. Blood 97:3867-3874(2001) [PubMed: 11389028] [Abstract] Cited for: INTERACTION WITH CD84.
[21]	"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.
[22]	"Structural and functional dissection of the cytoplasmic domain of the transmembrane adaptor protein SIT (SHP2-interacting transmembrane adaptor protein)." Pfrepper K.-I., Marie-Cardine A., Simeoni L., Kuramitsu Y., Leo A., Spicka J., Hilgert I., Scherer J., Schraven B. Eur. J. Immunol. 31:1825-1836(2001) [PubMed: 11433379] [Abstract] Cited for: INTERACTION WITH SIT1.
[23]	"Identification of Fer tyrosine kinase localized on microtubules as a platelet endothelial cell adhesion molecule-1 phosphorylating kinase in vascular endothelial cells." Kogata N., Masuda M., Kamioka Y., Yamagishi A., Endo A., Okada M., Mochizuki N. Mol. Biol. Cell 14:3553-3564(2003) [PubMed: 12972546] [Abstract] Cited for: INTERACTION WITH FER AND PECAM1.
[24]	"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.
[25]	"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.
[26]	"Activation of vascular endothelial growth factor receptor-3 and its downstream signaling promote cell survival under oxidative stress." Wang J.F., Zhang X., Groopman J.E. J. Biol. Chem. 279:27088-27097(2004) [PubMed: 15102829] [Abstract] Cited for: INTERACTION WITH FLT4.
[27]	"Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules." Zhang Y., Wolf-Yadlin A., Ross P.L., Pappin D.J., Rush J., Lauffenburger D.A., White F.M. Mol. Cell. Proteomics 4:1240-1250(2005) [PubMed: 15951569] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-62, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[28]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-62, MASS SPECTROMETRY.
[29]	"Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry." Tao W.A., Wollscheid B., O'Brien R., Eng J.K., Li X.-J., Bodenmiller B., Watts J.D., Hood L., Aebersold R. Nat. Methods 2:591-598(2005) [PubMed: 16094384] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-584, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[30]	"ANKHD1, ankyrin repeat and KH domain containing 1, is overexpressed in acute leukemias and is associated with SHP2 in K562 cells." Traina F., Favaro P.M.B., Medina Sde S., Duarte Ada S., Winnischofer S.M., Costa F.F., Saad S.T.O. Biochim. Biophys. Acta 1762:828-834(2006) [PubMed: 16956752] [Abstract] Cited for: INTERACTION WITH ANKHD1.
[31]	"ROS fusion tyrosine kinase activates a SH2 domain-containing phosphatase-2/phosphatidylinositol 3-kinase/mammalian target of rapamycin signaling axis to form glioblastoma in mice." Charest A., Wilker E.W., McLaughlin M.E., Lane K., Gowda R., Coven S., McMahon K., Kovach S., Feng Y., Yaffe M.B., Jacks T., Housman D. Cancer Res. 66:7473-7481(2006) [PubMed: 16885344] [Abstract] Cited for: INTERACTION WITH ROS1.
[32]	"FcRL6, a new ITIM-bearing receptor on cytolytic cells, is broadly expressed by lymphocytes following HIV-1 infection." Wilson T.J., Presti R.M., Tassi I., Overton E.T., Cella M., Colonna M. Blood 109:3786-3793(2007) [PubMed: 17213291] [Abstract] Cited for: INTERACTION WITH FCRL6.
[33]	"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-62; TYR-63 AND TYR-584, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[34]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-584 AND SER-595, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[35]	"Multiple reaction monitoring for robust quantitative proteomic analysis of cellular signaling networks." Wolf-Yadlin A., Hautaniemi S., Lauffenburger D.A., White F.M. Proc. Natl. Acad. Sci. U.S.A. 104:5860-5865(2007) [PubMed: 17389395] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-62, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[36]	"Nuclear protein tyrosine phosphatase Shp-2 is one important negative regulator of nuclear export of telomerase reverse transcriptase." Jakob S., Schroeder P., Lukosz M., Buchner N., Spyridopoulos I., Altschmied J., Haendeler J. J. Biol. Chem. 283:33155-33161(2008) [PubMed: 18829466] [Abstract] Cited for: INTERACTION WITH TERT, FUNCTION.
[37]	"Regulation of RhoA-dependent ROCKII activation by Shp2." Lee H.H., Chang Z.F. J. Cell Biol. 181:999-1012(2008) [PubMed: 18559669] [Abstract] Cited for: FUNCTION.
[38]	"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.
[39]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-562, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[40]	"A novel and critical role for tyrosine 663 in platelet endothelial cell adhesion molecule-1 trafficking and transendothelial migration." Dasgupta B., Dufour E., Mamdouh Z., Muller W.A. J. Immunol. 182:5041-5051(2009) [PubMed: 19342684] [Abstract] Cited for: INTERACTION WITH PECAM1.
[41]	"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-62; TYR-63 AND TYR-584, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[42]	"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 TYR-62 AND TYR-584, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[43]	"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-280, MASS SPECTROMETRY.
[44]	"Mutation of tyrosine residue 857 in the PDGF beta-receptor affects cell proliferation but not migration." Wardega P., Heldin C.H., Lennartsson J. Cell. Signal. 22:1363-1368(2010) [PubMed: 20494825] [Abstract] Cited for: PHOSPHORYLATION, INTERACTION WITH PDGFRB.
[45]	"Whole-genome sequencing of a single proband together with linkage analysis identifies a Mendelian disease gene." Sobreira N.L., Cirulli E.T., Avramopoulos D., Wohler E., Oswald G.L., Stevens E.L., Ge D., Shianna K.V., Smith J.P., Maia J.M., Gumbs C.E., Pevsner J., Thomas G., Valle D., Hoover-Fong J.E., Goldstein D.B. PLoS Genet. 6:E1000991-E1000991(2010) [PubMed: 20577567] [Abstract] Cited for: INVOLVEMENT IN MC.
[46]	"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].
[47]	"Crystal structure of the tyrosine phosphatase SHP-2." Hof P., Pluskey S., Dhe-Paganon S., Eck M.J., Shoelson S.E. Cell 92:441-450(1998) [PubMed: 9491886] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 3-530 (ISOFORM 2).
[48]	"Large-scale structural analysis of the classical human protein tyrosine phosphatome." Barr A.J., Ugochukwu E., Lee W.H., King O.N.F., Filippakopoulos P., Alfano I., Savitsky P., Burgess-Brown N.A., Mueller S., Knapp S. Cell 136:352-363(2009) [PubMed: 19167335] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 237-533.
[49]	"Salicylic acid based small molecule inhibitor for the oncogenic Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2)." Zhang X., He Y., Liu S., Yu Z., Jiang Z.X., Yang Z., Dong Y., Nabinger S.C., Wu L., Gunawan A.M., Wang L., Chan R.J., Zhang Z.Y. J. Med. Chem. 53:2482-2493(2010) [PubMed: 20170098] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 262-532 IN COMPLEX WITH INHIBITOR, CATALYTIC ACTIVITY.
[50]	"Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome." Tartaglia M., Mehler E.L., Goldberg R., Zampino G., Brunner H.G., Kremer H., van der Burgt I., Crosby A.H., Ion A., Jeffery S., Kalidas K., Patton M.A., Kucherlapati R.S., Gelb B.D. Nat. Genet. 29:465-468(2001) [PubMed: 11704759] [Abstract] Cited for: VARIANTS NS1 GLY-61; CYS-63; GLY-72; SER-72; ASP-76; ARG-79; VAL-282; ASP-308 AND VAL-508.
[51]	Erratum Tartaglia M., Mehler E.L., Goldberg R., Zampino G., Brunner H.G., Kremer H., van der Burgt I., Crosby A.H., Ion A., Jeffery S., Kalidas K., Patton M.A., Kucherlapati R.S., Gelb B.D. Nat. Genet. 29:491-491(2001)
[52]	Erratum Tartaglia M., Mehler E.L., Goldberg R., Zampino G., Brunner H.G., Kremer H., van der Burgt I., Crosby A.H., Ion A., Jeffery S., Kalidas K., Patton M.A., Kucherlapati R.S., Gelb B.D. Nat. Genet. 30:123-123(2001)
[53]	"PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity." Tartaglia M., Kalidas K., Shaw A., Song X., Musat D.L., van der Burgt I., Brunner H.G., Bertola D.R., Crosby A.H., Ion A., Kucherlapati R.S., Jeffery S., Patton M.A., Gelb B.D. Am. J. Hum. Genet. 70:1555-1563(2002) [PubMed: 11992261] [Abstract] Cited for: VARIANTS NS1 ALA-42; ALA-60; ASN-61; GLY-61; ASP-62; CYS-63; GLY-72; ILE-73; ASP-76; ARG-79; ALA-106; ASP-139; CYS-279; VAL-282; LEU-285; SER-285; ASP-308; SER-308; VAL-309; LYS-505 AND VAL-508.
[54]	"Grouping of multiple-lentigines/LEOPARD and Noonan syndromes on the PTPN11 gene." Digilio M.C., Conti E., Sarkozy A., Mingarelli R., Dottorini T., Marino B., Pizzuti A., Dallapiccola B. Am. J. Hum. Genet. 71:389-394(2002) [PubMed: 12058348] [Abstract] Cited for: VARIANTS LEOPARD1 CYS-279 AND MET-472.
[55]	"PTPN11 mutations in Noonan syndrome type I: detection of recurrent mutations in exons 3 and 13." Maheshwari M., Belmont J., Fernbach S., Ho T., Molinari L., Yakub I., Yu F., Combes A., Towbin J.A., Craigen W.J., Gibbs R.A. Hum. Mutat. 20:298-304(2002) [PubMed: 12325025] [Abstract] Cited for: VARIANTS NS1 ASP-62; CYS-63 AND THR-506.
[56]	"PTPN11 (protein-tyrosine phosphatase, nonreceptor-type 11) mutations in seven Japanese patients with Noonan syndrome." Kosaki K., Suzuki T., Muroya K., Hasegawa T., Sato S., Matsuo N., Kosaki R., Nagai T., Hasegawa Y., Ogata T. J. Clin. Endocrinol. Metab. 87:3529-3533(2002) [PubMed: 12161469] [Abstract] Cited for: VARIANTS NS1 GLY-61; CYS-63; SER-72; ILE-73; SER-285 AND ASP-308.
[57]	"PTPN11 mutation in a large family with Noonan syndrome and dizygous twinning." Schollen E., Matthijs G., Gewillig M., Fryns J.-P., Legius E. Eur. J. Hum. Genet. 11:85-88(2003) [PubMed: 12529711] [Abstract] Cited for: VARIANT NS1 ARG-79.
[58]	"Spectrum of mutations in PTPN11 and genotype-phenotype correlation in 96 patients with Noonan syndrome and five patients with cardio-facio-cutaneous syndrome." Musante L., Kehl H.G., Majewski F., Meinecke P., Schweiger S., Gillessen-Kaesbach G., Wieczorek D., Hinkel G.K., Tinschert S., Hoeltzenbein M., Ropers H.-H., Kalscheuer V.M. Eur. J. Hum. Genet. 11:201-206(2003) [PubMed: 12634870] [Abstract] Cited for: VARIANTS NS1 LYS-58; ASN-61; GLY-61; CYS-63; GLN-69; LEU-71; SER-72; ILE-73; ASP-76; ARG-79; ASP-139; ARG-256; VAL-282 AND ASP-308.
[59]	Erratum Musante L., Kehl H.G., Majewski F., Meinecke P., Schweiger S., Gillessen-Kaesbach G., Wieczorek D., Hinkel G.K., Tinschert S., Hoeltzenbein M., Ropers H.-H., Kalscheuer V.M. Eur. J. Hum. Genet. 11:551-551(2003)
[60]	"Noonan syndrome with leukaemoid reaction and overproduction of catecholamines: a case report." Kondoh T., Ishii E., Aoki Y., Shimizu T., Zaitsu M., Matsubara Y., Moriuchi H. Eur. J. Pediatr. 162:548-549(2003) [PubMed: 12739139] [Abstract] Cited for: VARIANT NS1 THR-506.
[61]	"A novel PTPN11 mutation in LEOPARD syndrome." Conti E., Dottorini T., Sarkozy A., Tiller G.E., Esposito G., Pizzuti A., Dallapiccola B. Hum. Mutat. 21:654-654(2003) [PubMed: 14961557] [Abstract] Cited for: VARIANT LEOPARD1 PRO-510.
[62]	"Correlation between PTPN11 gene mutations and congenital heart defects in Noonan and LEOPARD syndromes." Sarkozy A., Conti E., Seripa D., Digilio M.C., Grifone N., Tandoi C., Fazio V.M., Di Ciommo V., Marino B., Pizzuti A., Dallapiccola B. J. Med. Genet. 40:704-708(2003) [PubMed: 12960218] [Abstract] Cited for: VARIANTS NS1 ILE-2; ALA-42; ASP-62; CYS-63; GLY-72; PRO-79; ALA-106; CYS-279; ASP-308; SER-308; MET-472; ARG-507; VAL-508 AND PHE-564.
[63]	"Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia." Tartaglia M., Niemeyer C.M., Fragale A., Song X., Buechner J., Jung A., Haehlen K., Hasle H., Licht J.D., Gelb B.D. Nat. Genet. 34:148-150(2003) [PubMed: 12717436] [Abstract] Cited for: VARIANTS JMML TYR-61; VAL-61; LYS-69; THR-72; VAL-72; ALA-76; GLY-76; LYS-76; VAL-76; ALA-507 AND ARG-507, VARIANTS MYELODYSPLASTIC SYNDROME VAL-60; VAL-61; LYS-69; LEU-71 AND ALA-76, VARIANTS NS1 ASP-62 AND ILE-73, VARIANT ACUTE MYELOID LEUKEMIA LYS-71.
[64]	"Clinical variability in a Noonan syndrome family with a new PTPN11 gene mutation." Bertola D.R., Pereira A.C., de Oliveira P.S.L., Kim C.A., Krieger J.E. Am. J. Med. Genet. A 130:378-383(2004) [PubMed: 15384080] [Abstract] Cited for: VARIANT NS1 MET-415.
[65]	"Two novel and one recurrent PTPN11 mutations in LEOPARD syndrome." Yoshida R., Nagai T., Hasegawa T., Kinoshita E., Tanaka T., Ogata T. Am. J. Med. Genet. A 130:432-434(2004) [PubMed: 15389709] [Abstract] Cited for: VARIANTS LEOPARD1 THR-465 AND ALA-468.
[66]	"PTPN11 mutations in patients with LEOPARD syndrome: a French multicentric experience." French collaborative Noonan study group Keren B., Hadchouel A., Saba S., Sznajer Y., Bonneau D., Leheup B., Boute O., Gaillard D., Lacombe D., Layet V., Marlin S., Mortier G., Toutain A., Beylot C., Baumann C., Verloes A., Cave H. J. Med. Genet. 41:E117-E117(2004) [PubMed: 15520399] [Abstract] Cited for: VARIANTS LEOPARD1 CYS-279; SER-279; MET-472 AND PRO-514.
[67]	"Clinical and molecular analysis of 30 patients with multiple lentigines LEOPARD syndrome." Sarkozy A., Conti E., Digilio M.C., Marino B., Morini E., Pacileo G., Wilson M., Calabro R., Pizzuti A., Dallapiccola B. J. Med. Genet. 41:E68-E68(2004) [PubMed: 15121796] [Abstract] Cited for: VARIANTS LEOPARD1 CYS-279; SER-279; ALA-468; MET-472; TRP-502; LEU-502 AND PRO-510.
[68]	"Neurofibromatosis-Noonan syndrome: molecular evidence of the concurrence of both disorders in a patient." Bertola D.R., Pereira A.C., Passetti F., de Oliveira P.S.L., Messiaen L., Gelb B.D., Kim C.A., Krieger J.E. Am. J. Med. Genet. A 136:242-245(2005) [PubMed: 15948193] [Abstract] Cited for: VARIANT NS1 ARG-510.
[69]	"Genetic heterogeneity in LEOPARD syndrome: two families with no mutations in PTPN11." Kalidas K., Shaw A.C., Crosby A.H., Newbury-Ecob R., Greenhalgh L., Temple I.K., Law C., Patel A., Patton M.A., Jeffery S. J. Hum. Genet. 50:21-25(2005) [PubMed: 15690106] [Abstract] Cited for: VARIANT LEOPARD1 PRO-510.
[70]	"Acute myelomonocytic leukemia in a boy with LEOPARD syndrome (PTPN11 gene mutation positive)." Ucar C., Calyskan U., Martini S., Heinritz W. J. Pediatr. Hematol. Oncol. 28:123-125(2006) [PubMed: 16679933] [Abstract] Cited for: VARIANT LEOPARD1 CYS-279.
[71]	"PTPN11, SOS1, KRAS, and RAF1 gene analysis, and genotype-phenotype correlation in Korean patients with Noonan syndrome." Ko J.M., Kim J.M., Kim G.H., Yoo H.W. J. Hum. Genet. 53:999-1006(2008) [PubMed: 19020799] [Abstract] Cited for: VARIANT NS1 ALA-59.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D13540 mRNA. Translation: BAA02740.2.
L03535 mRNA. Translation: AAA36611.1.
L07527 mRNA. Translation: AAA17022.1.
L08807 mRNA. No translation available.
X70766 mRNA. Translation: CAA50045.1.
BT007106 mRNA. Translation: AAP35770.1.
AK289854 mRNA. Translation: BAF82543.1.
CH471054 Genomic DNA. Translation: EAW98012.1.
BC008692 mRNA. Translation: AAH08692.1.

IPI

IPI00298347.
IPI00658002.
IPI00658023.

PIR

JN0805.

RefSeq

NP_002825.3. NM_002834.3.

UniGene

Hs.506852.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2SHP	X-ray	2.00	A/B	3-529	[»]
3B7O	X-ray	1.60	A	237-533	[»]
3MOW	X-ray	2.30	A	262-532	[»]
3O5X	X-ray	2.00	A	262-532	[»]
3TKZ	X-ray	1.80	A	1-106	[»]
3TL0	X-ray	2.05	A	1-106	[»]

ProteinModelPortal

Q06124.

SMR

Q06124. Positions 3-532.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-516N.

IntAct

Q06124. 7 interactions.

MINT

MINT-199832.

STRING

Q06124.

PTM databases

PhosphoSite

Q06124.

Polymorphism databases

DMDM

84028248.

Proteomic databases

PRIDE

Q06124.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000392596; ENSP00000376375; ENSG00000179295.

GeneID

5781.

KEGG

hsa:5781.

UCSC

uc001ttw.1. human.
uc001ttx.1. human.

Organism-specific databases

CTD

5781.

GeneCards

GC12P112856.

HGNC

HGNC:9644. PTPN11.

HPA

CAB005377.

MIM

151100. phenotype.
156250. phenotype.
163950. phenotype.
176876. gene.
607785. phenotype.

neXtProt

NX_Q06124.

Orphanet

500. LEOPARD syndrome.
2499. Metachondromatosis.
648. Noonan syndrome.

PharmGKB

PA33986.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG05679.

GeneTree

ENSGT00600000084137.

HOGENOM

HBG379880.

HOVERGEN

HBG000223.

InParanoid

Q06124.

PhylomeDB

Q06124.

Enzyme and pathway databases

Pathway_Interaction_DB

angiopoietinreceptor_pathway. Angiopoietin receptor Tie2-mediated signaling.
epopathway. EPO signaling pathway.
fcer1pathway. Fc-epsilon receptor I signaling in mast cells.
fgf_pathway. FGF signaling pathway.
ifngpathway. IFN-gamma pathway.
igf1_pathway. IGF1 pathway.
il2_pi3kpathway. IL2 signaling events mediated by PI3K.
il2_stat5pathway. IL2 signaling events mediated by STAT5.
il2_1pathway. IL2-mediated signaling events.
il6_7pathway. IL6-mediated signaling events.
insulin_pathway. Insulin Pathway.
avb3_integrin_pathway. Integrins in angiogenesis.
trkrpathway. Neurotrophic factor-mediated Trk receptor signaling.
pdgfrbpathway. PDGFR-beta signaling pathway.
met_pathway. Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met).
kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit).
vegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2.
ret_pathway. Signaling events regulated by Ret tyrosine kinase.
tcrpathway. TCR signaling in naive CD4+ T cells.
vegfr1_pathway. VEGFR1 specific signals.

Reactome

REACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_111155. Cell-Cell communication.
REACT_604. Hemostasis.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q06124.

Bgee

Q06124.

CleanEx

HS_PTPN11.

Genevestigator

Q06124.

GermOnline

ENSG00000179295. 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

K07293.

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

NextBio

22484.

SOURCE

Search...

Entry information

Entry name

PTN11_HUMAN

Accession

Primary (citable) accession number: Q06124
Secondary accession number(s): A8K1D9, Q96HD7

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	December 20, 2005
Last modified:	January 25, 2012
This is version 149 of the entry and version 2 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.