P41499 (PTN11_RAT) 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 SYP
SH-PTP2
Short name=SHP-2
Short name=Shp2

Gene names

Name:

Ptpn11

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

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 By similarity.
Catalytic activity	Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.
Enzyme regulation	Inhibited by orthovanadate, molybdate and spermidine. Ref.2
Subunit structure	Interacts with phosphorylated SIT1, LIME1, BCAR3 and MZPL1. Interacts with FCRL3, FCRL4, FCRL6, ANKHD1, SHB, INPP5D/SHIP1 and CD84 By similarity. Interacts with MILR1 (tyrosine-phosphorylated). Interacts with FLT1 (tyrosine-phosphorylated), FLT3 (tyrosine-phosphorylated), FLT4 (tyrosine-phosphorylated), KIT and GRB2 By similarity. Interacts with PTPNS1. Interacts with KIR2DL1; the interaction is enhanced by ARRB2. Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated) By similarity. Interacts with GAB2 By similarity. 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 PDGFRA (tyrosine phosphorylated). Interacts with PDGFRB (tyrosine phosphorylated); this interaction increases the PTPN11 phosphatase activity By similarity. Interacts with ROS1; this mediates PTPN11 phosphorylation. Ref.4 Ref.5 Ref.6
Subcellular location	Cytoplasm By similarity.
Tissue specificity	Expressed in brain, muscle and lung. Ref.2
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. Phosphorylated by activated PDGFRB By similarity.
Sequence similarities	Belongs to the protein-tyrosine phosphatase family. Non-receptor class 2 subfamily. Contains 2 SH2 domains. Contains 1 tyrosine-protein phosphatase domain.
Biophysicochemical properties	Kinetic parameters: KM=15 mM for pNPP Ref.2 KM=13 µM for nAChR KM=67 nM for MBP Vmax=16 µmol/min/mg enzyme toward pNPP Vmax=98 nmol/min/mg enzyme toward nAChR Vmax=15 µmol/min/mg enzyme toward MBP pH dependence: Optimum pH is 8.5.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Domain	Repeat SH2 domain
Molecular function	Hydrolase Protein phosphatase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	DNA damage checkpoint Inferred from electronic annotation. Source: Compara activation of MAPK activity Inferred from electronic annotation. Source: Compara axonogenesis Inferred from electronic annotation. Source: Compara ephrin receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB glucose homeostasis Inferred from electronic annotation. Source: Compara hormone metabolic process Inferred from electronic annotation. Source: Compara hormone-mediated signaling pathway Inferred from electronic annotation. Source: Compara multicellular organismal reproductive process Inferred from electronic annotation. Source: Compara negative regulation of cortisol secretion Inferred from electronic annotation. Source: Compara negative regulation of growth hormone secretion Inferred from electronic annotation. Source: Compara negative regulation of insulin secretion Inferred from electronic annotation. Source: Compara nerve growth factor receptor signaling pathway Inferred from electronic annotation. Source: Compara organ growth Inferred from electronic annotation. Source: Compara positive regulation of glucose import in response to insulin stimulus Inferred from electronic annotation. Source: Compara positive regulation of hormone secretion Inferred from electronic annotation. Source: Compara regulation of cell adhesion mediated by integrin Inferred from sequence or structural similarity. Source: UniProtKB regulation of multicellular organism growth Inferred from electronic annotation. Source: Compara regulation of protein export from nucleus Inferred from electronic annotation. Source: Compara triglyceride metabolic process Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Inferred from direct assay PubMed 7711057. Source: RGD mitochondrion Inferred from direct assay PubMed 15378208. Source: RGD protein complex Inferred from direct assay PubMed 10973965. Source: RGD
Molecular_function	insulin receptor binding Inferred from direct assay PubMed 7711057. Source: RGD non-membrane spanning protein tyrosine phosphatase activity Inferred from sequence or structural similarity. Source: UniProtKB phospholipase binding Inferred from direct assay PubMed 16814162. Source: RGD
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P41499-1)

Also known as: PTP1Di;

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: P41499-2)

Also known as: PTP1D;

The sequence of this isoform differs from the canonical sequence as follows:
     409-412: Missing.

Note: Much higher phosphatase activity than isoform 1, optimum pH is 7.

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_0000094769
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 By similarity
	Binding site	429	1	Substrate By similarity
	Binding site	510	1	Substrate By similarity
Amino acid modifications
	Modified residue	62	1	Phosphotyrosine By similarity
	Modified residue	63	1	Phosphotyrosine By similarity
	Modified residue	66	1	Phosphotyrosine By similarity
	Modified residue	280	1	N6-acetyllysine By similarity
	Modified residue	546	1	Phosphotyrosine; by PDGFR By similarity
	Modified residue	562	1	Phosphoserine By similarity
	Modified residue	584	1	Phosphotyrosine; by PDGFR By similarity
	Modified residue	595	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	409 – 412	4	Missing in isoform 2.		VSP_016676
Experimental info
	Sequence conflict	75	1	A → P in AAA20543. Ref.1
	Sequence conflict	551	1	Y → S in AAA19133. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (PTP1Di) [UniParc]. Last modified December 20, 2005. Version 4. Checksum: 7155D1E99161F5C2	FASTA	597	68,458
	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 NDSKSKVTHV 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 WPDECALKEY GVMRVRNVRE SAAHDYTLRE LKLSKVGQAL LQGNTERTVW 430 440 450 460 470 480 QYHFRTWPDH GVPSDPGGVL DFLEEVHHKQ ESIVDAGPVV VHCSAGIGRT GTFIVIDILI 490 500 510 520 530 540 DIIREKGVDC DIDVPKTIQM VRSQRSGMVQ TEAQYRFIYM AVQHYIETLQ RRIEEEQKSK 550 560 570 580 590 RKGHEYTNIK YSLVDQTSGD QSPLPPCTPT PPCAEMREDS ARVYENVGLM QQQRSFR
	Isoform 2 (PTP1D) [UniParc]. Checksum: 3329F10F0F60AF48	FASTA	593	68,033
	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 NDSKSKVTHV 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 WPDECALKEY GVMRVRNVRE SAAHDYTLRE LKLSKVGQGN TERTVWQYHF 430 440 450 460 470 480 RTWPDHGVPS DPGGVLDFLE EVHHKQESIV DAGPVVVHCS AGIGRTGTFI VIDILIDIIR 490 500 510 520 530 540 EKGVDCDIDV PKTIQMVRSQ RSGMVQTEAQ YRFIYMAVQH YIETLQRRIE EEQKSKRKGH 550 560 570 580 590 EYTNIKYSLV DQTSGDQSPL PPCTPTPPCA EMREDSARVY ENVGLMQQQR SFR

References

[1]	"Identification of protein-tyrosine phosphatases prevalent in adipocytes by molecular cloning." Ding W., Zhang W.R., Sullivan K., Hashimoto N., Goldstein B.J. Biochem. Biophys. Res. Commun. 202:902-907(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Strain: Sprague-Dawley.
[2]	"RNA splicing regulates the activity of a SH2 domain-containing protein tyrosine phosphatase." Mei L., Dorherty C.A., Huganir R.L. J. Biol. Chem. 269:12254-12262(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY. Strain: Sprague-Dawley. Tissue: Brain.
[3]	"Purification and characterization of a rat liver protein-tyrosine phosphatase with sequence similarity to src-homology region 2." Hiraga A., Munakata H., Hata K., Suzuki Y., Tsuiki S. Eur. J. Biochem. 209:195-206(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE.
[4]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PTPNS1.
[5]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PTPNS1.
[6]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ROS1.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U09307 mRNA. Translation: AAA20543.1. U05963 mRNA. Translation: AAA19133.1.
IPI	IPI00324561. IPI00563975.
PIR	A53593.
RefSeq	NP_001171064.1. NM_001177593.1. NP_037220.2. NM_013088.2.
UniGene	Rn.98209.
3D structure databases
ProteinModelPortal	P41499.
SMR	P41499. Positions 3-529.
ModBase	Search...
Protein-protein interaction databases
STRING	10116.ENSRNOP00000041842.
PTM databases
PhosphoSite	P41499.
Proteomic databases
PaxDb	P41499.
PRIDE	P41499.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000046323; ENSRNOP00000041842; ENSRNOG00000030124.
GeneID	25622.
KEGG	rno:25622.
UCSC	RGD:3447. rat.
Organism-specific databases
CTD	5781.
RGD	3447. Ptpn11.
Phylogenomic databases
eggNOG	COG5599.
GeneTree	ENSGT00700000104166.
HOGENOM	HOG000273907.
HOVERGEN	HBG000223.
InParanoid	P41499.
KO	K07293.
OrthoDB	EOG4N8R4B.
Enzyme and pathway databases
Reactome	REACT_109781. Immune System. REACT_111984. Signal Transduction. REACT_114732. Cell-Cell communication.
Gene expression databases
Genevestigator	P41499.
GermOnline	ENSRNOG00000030124. Rattus norvegicus.
Family and domain databases
Gene3D	3.30.505.10. 2 hits.
InterPro	IPR000980. SH2. IPR000387. Tyr/Dual-sp_Pase. IPR016130. Tyr_Pase_AS. IPR012152. Tyr_Pase_non-rcpt_typ-6/11. IPR000242. Tyr_Pase_rcpt/non-rcpt. [Graphical view]
Pfam	PF00017. SH2. 2 hits. PF00102. Y_phosphatase. 1 hit. [Graphical view]
PIRSF	PIRSF000929. Tyr-Ptase_nr_6. 1 hit.
PRINTS	PR00700. PRTYPHPHTASE. PR00401. SH2DOMAIN.
SMART	SM00194. PTPc. 1 hit. SM00252. SH2. 2 hits. [Graphical view]
PROSITE	PS50001. SH2. 2 hits. PS00383. TYR_PHOSPHATASE_1. 1 hit. PS50056. TYR_PHOSPHATASE_2. 1 hit. PS50055. TYR_PHOSPHATASE_PTP. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	607397.

Entry information

Entry name

PTN11_RAT

Accession

Primary (citable) accession number: P41499
Secondary accession number(s): Q62626

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	December 20, 2005
Last modified:	April 3, 2013
This is version 124 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program