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Protein

Tyrosine-protein phosphatase non-receptor type 11

Gene

Ptpn11

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus. Positively regulates MAPK signal transduction pathway. Dephosphorylates GAB1, ARHGAP35 and EGFR. Dephosphorylates ROCK2 at 'Tyr-722' resulting in stimulatation of its RhoA binding activity. Dephosphorylates CDC73.By similarity1 Publication

Catalytic activityi

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.PROSITE-ProRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei429SubstrateBy similarity1
Active sitei463Phosphocysteine intermediatePROSITE-ProRule annotation1
Binding sitei510SubstrateBy similarity1

GO - Molecular functioni

  • cell adhesion molecule binding Source: UniProtKB
  • insulin receptor binding Source: MGI
  • non-membrane spanning protein tyrosine phosphatase activity Source: UniProtKB
  • peptide hormone receptor binding Source: MGI
  • phospholipase binding Source: Ensembl
  • phosphoprotein phosphatase activity Source: MGI
  • phosphotyrosine residue binding Source: Ensembl
  • protein tyrosine phosphatase activity Source: MGI
  • receptor tyrosine kinase binding Source: UniProtKB
  • SH3/SH2 adaptor activity Source: MGI

GO - Biological processi

  • abortive mitotic cell cycle Source: MGI
  • activation of MAPK activity Source: MGI
  • atrioventricular canal development Source: MGI
  • axonogenesis Source: MGI
  • Bergmann glial cell differentiation Source: MGI
  • brain development Source: MGI
  • cellular response to epidermal growth factor stimulus Source: UniProtKB
  • cerebellar cortex formation Source: MGI
  • DNA damage checkpoint Source: MGI
  • ephrin receptor signaling pathway Source: UniProtKB
  • epidermal growth factor receptor signaling pathway Source: MGI
  • ERBB signaling pathway Source: MGI
  • face morphogenesis Source: MGI
  • genitalia development Source: MGI
  • glucose homeostasis Source: MGI
  • heart development Source: MGI
  • homeostasis of number of cells within a tissue Source: MGI
  • hormone-mediated signaling pathway Source: MGI
  • hormone metabolic process Source: MGI
  • inner ear development Source: MGI
  • integrin-mediated signaling pathway Source: MGI
  • intestinal epithelial cell migration Source: MGI
  • lipid metabolic process Source: MGI
  • megakaryocyte development Source: MGI
  • microvillus organization Source: MGI
  • multicellular organismal reproductive process Source: MGI
  • multicellular organism growth Source: MGI
  • negative regulation of cell adhesion mediated by integrin Source: MGI
  • negative regulation of cortisol secretion Source: MGI
  • negative regulation of growth hormone secretion Source: MGI
  • negative regulation of hormone secretion Source: MGI
  • negative regulation of insulin secretion Source: MGI
  • neurotrophin TRK receptor signaling pathway Source: MGI
  • organ growth Source: MGI
  • peptidyl-tyrosine dephosphorylation Source: UniProtKB
  • platelet-derived growth factor receptor signaling pathway Source: MGI
  • platelet formation Source: MGI
  • positive regulation of ERK1 and ERK2 cascade Source: MGI
  • positive regulation of glucose import in response to insulin stimulus Source: MGI
  • positive regulation of hormone secretion Source: MGI
  • positive regulation of mitotic cell cycle Source: MGI
  • positive regulation of signal transduction Source: MGI
  • regulation of cell adhesion mediated by integrin Source: UniProtKB
  • regulation of multicellular organism growth Source: MGI
  • regulation of protein complex assembly Source: MGI
  • regulation of protein export from nucleus Source: MGI
  • triglyceride metabolic process Source: MGI

Keywordsi

Molecular functionHydrolase, Protein phosphatase

Enzyme and pathway databases

ReactomeiR-MMU-1059683 Interleukin-6 signaling
R-MMU-109704 PI3K Cascade
R-MMU-110056 MAPK3 (ERK1) activation
R-MMU-112411 MAPK1 (ERK2) activation
R-MMU-114604 GPVI-mediated activation cascade
R-MMU-1257604 PIP3 activates AKT signaling
R-MMU-1295596 Spry regulation of FGF signaling
R-MMU-1433557 Signaling by SCF-KIT
R-MMU-180292 GAB1 signalosome
R-MMU-186763 Downstream signal transduction
R-MMU-210993 Tie2 Signaling
R-MMU-388841 Costimulation by the CD28 family
R-MMU-389513 CTLA4 inhibitory signaling
R-MMU-389948 PD-1 signaling
R-MMU-512988 Interleukin-3, 5 and GM-CSF signaling
R-MMU-5654689 PI-3K cascade:FGFR1
R-MMU-5654693 FRS-mediated FGFR1 signaling
R-MMU-5654695 PI-3K cascade:FGFR2
R-MMU-5654700 FRS-mediated FGFR2 signaling
R-MMU-5654706 FRS-mediated FGFR3 signaling
R-MMU-5654710 PI-3K cascade:FGFR3
R-MMU-5654712 FRS-mediated FGFR4 signaling
R-MMU-5654720 PI-3K cascade:FGFR4
R-MMU-5654726 Negative regulation of FGFR1 signaling
R-MMU-5654727 Negative regulation of FGFR2 signaling
R-MMU-5654732 Negative regulation of FGFR3 signaling
R-MMU-5654733 Negative regulation of FGFR4 signaling
R-MMU-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-MMU-8853659 RET signaling
R-MMU-8854691 Interleukin-20 family signaling
R-MMU-8865999 MET activates PTPN11
R-MMU-8934593 Regulation of RUNX1 Expression and Activity
R-MMU-909733 Interferon alpha/beta signaling
R-MMU-912694 Regulation of IFNA signaling
R-MMU-936964 Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon
SABIO-RKiP35235

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein phosphatase non-receptor type 11 (EC:3.1.3.48By similarity)
Alternative name(s):
Protein-tyrosine phosphatase SYP
SH-PTP2
Short name:
SHP-2
Short name:
Shp2
Gene namesi
Name:Ptpn11
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:99511 Ptpn11

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2620

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000947682 – 597Tyrosine-protein phosphatase non-receptor type 11Add BLAST596

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylthreonineBy similarity1
Modified residuei62PhosphotyrosineCombined sources1
Modified residuei66PhosphotyrosineCombined sources1
Modified residuei546Phosphotyrosine; by PDGFR1 Publication1
Modified residuei584Phosphotyrosine; by PDGFR1 Publication1

Post-translational modificationi

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 by activated PDGFRB (By similarity). Phosphorylated upon activation of the receptor-type kinase PDGFRA.By similarity3 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP35235
MaxQBiP35235
PaxDbiP35235
PeptideAtlasiP35235
PRIDEiP35235

PTM databases

iPTMnetiP35235
PhosphoSitePlusiP35235

Expressioni

Tissue specificityi

Highly expressed in brain, heart and kidney.1 Publication

Gene expression databases

BgeeiENSMUSG00000043733
GenevisibleiP35235 MM

Interactioni

Subunit structurei

Interacts with CD84 and with phosphorylated SIT1 and MZPL1. Interacts with FCRL4, FCRL6 and ANKHD1. Interacts with GAREM1 (tyrosine phosphorylated); the interaction increases MAPK/ERK activity and does not affect the GRB2/SOS complex formation (By similarity). Interacts with PTPNS1 and BCAR3. Interacts with phosphorylated LIME1. Interacts with SHB and INPP5D/SHIP1. Interacts with KIR2DL1; the interaction is enhanced by ARRB2 (By similarity). 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 (By similarity). Interacts with MILR1 (tyrosine phosphorylated). Interacts with FLT1 (tyrosine-phosphorylated), FLT3 (tyrosine-phosphorylated), FLT4 (tyrosine-phosphorylated), KIT and GRB2. Interacts with ROS1; mediates PTPN11 phosphorylation. Interacts with PDGFRA (tyrosine phosphorylated). Interacts with PDGFRB (tyrosine phosphorylated); this interaction increases the PTPN11 phosphatase activity. Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated). Interacts with CEACAM1 (via cytoplasmic domain); this interaction depends on the monomer/dimer equilibrium and is phosphorylation-dependent (PubMed:19948503, PubMed:9867848). Interacts with MPIG6B (via ITIM motif) (PubMed:23112346). Interacts with SIGLEC10 (PubMed:23374343).By similarity20 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • cell adhesion molecule binding Source: UniProtKB
  • insulin receptor binding Source: MGI
  • peptide hormone receptor binding Source: MGI
  • phospholipase binding Source: Ensembl
  • phosphotyrosine residue binding Source: Ensembl
  • receptor tyrosine kinase binding Source: UniProtKB
  • SH3/SH2 adaptor activity Source: MGI

Protein-protein interaction databases

BioGridi202477, 26 interactors
CORUMiP35235
DIPiDIP-29669N
IntActiP35235, 33 interactors
MINTiP35235
STRINGi10090.ENSMUSP00000058757

Structurei

Secondary structure

1597
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi13 – 22Combined sources10
Beta strandi28 – 33Combined sources6
Beta strandi35 – 37Combined sources3
Beta strandi41 – 47Combined sources7
Beta strandi50 – 55Combined sources6
Beta strandi63 – 68Combined sources6
Beta strandi71 – 73Combined sources3
Helixi74 – 83Combined sources10
Helixi85 – 87Combined sources3
Turni91 – 93Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AYAX-ray2.05A/B4-103[»]
1AYBX-ray3.00A4-103[»]
1AYCX-ray2.30A4-103[»]
1AYDX-ray2.20A4-103[»]
ProteinModelPortaliP35235
SMRiP35235
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP35235

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini6 – 102SH2 1PROSITE-ProRule annotationAdd BLAST97
Domaini112 – 216SH2 2PROSITE-ProRule annotationAdd BLAST105
Domaini247 – 525Tyrosine-protein phosphatasePROSITE-ProRule annotationAdd BLAST279

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni463 – 469Substrate bindingBy similarity7

Domaini

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.

Sequence similaritiesi

Keywords - Domaini

Repeat, SH2 domain

Phylogenomic databases

eggNOGiKOG0790 Eukaryota
COG5599 LUCA
GeneTreeiENSGT00910000144001
HOGENOMiHOG000273907
HOVERGENiHBG000223
InParanoidiP35235
KOiK07293
OMAiKEYGAMR
OrthoDBiEOG091G0VZ3
PhylomeDBiP35235
TreeFamiTF351632

Family and domain databases

Gene3Di3.30.505.10, 2 hits
3.90.190.10, 1 hit
InterProiView protein in InterPro
IPR029021 Prot-tyrosine_phosphatase-like
IPR000242 PTPase_domain
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR016130 Tyr_Pase_AS
IPR003595 Tyr_Pase_cat
IPR012152 Tyr_Pase_non-rcpt_typ-6/11
IPR000387 TYR_PHOSPHATASE_dom
PfamiView protein in Pfam
PF00017 SH2, 2 hits
PF00102 Y_phosphatase, 1 hit
PIRSFiPIRSF000929 Tyr-Ptase_nr_6, 1 hit
PRINTSiPR00700 PRTYPHPHTASE
PR00401 SH2DOMAIN
SMARTiView protein in SMART
SM00194 PTPc, 1 hit
SM00404 PTPc_motif, 1 hit
SM00252 SH2, 2 hits
SUPFAMiSSF52799 SSF52799, 1 hit
SSF55550 SSF55550, 2 hits
PROSITEiView protein in PROSITE
PS50001 SH2, 2 hits
PS00383 TYR_PHOSPHATASE_1, 1 hit
PS50056 TYR_PHOSPHATASE_2, 1 hit
PS50055 TYR_PHOSPHATASE_PTP, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P35235-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MTSRRWFHPN ITGVEAENLL LTRGVDGSFL ARPSKSNPGD FTLSVRRNGA
60 70 80 90 100
VTHIKIQNTG DYYDLYGGEK FATLAELVQY YMEHHGQLKE KNGDVIELKY
110 120 130 140 150
PLNCADPTSE RWFHGHLSGK EAEKLLTEKG KHGSFLVRES QSHPGDFVLS
160 170 180 190 200
VRTGDDKGES NDGKSKVTHV MIRCQELKYD VGGGERFDSL TDLVEHYKKN
210 220 230 240 250
PMVETLGTVL QLKQPLNTTR INAAEIESRV RELSKLAETT DKVKQGFWEE
260 270 280 290 300
FETLQQQECK LLYSRKEGQR QENKNKNRYK NILPFDHTRV VLHDGDPNEP
310 320 330 340 350
VSDYINANII MPEFETKCNN SKPKKSYIAT QGCLQNTVND FWRMVFQENS
360 370 380 390 400
RVIVMTTKEV ERGKSKCVKY WPDEYALKEY GVMRVRNVKE SAAHDYTLRE
410 420 430 440 450
LKLSKVGQAL LQGNTERTVW QYHFRTWPDH GVPSDPGGVL DFLEEVHHKQ
460 470 480 490 500
ESIVDAGPVV VHCSAGIGRT GTFIVIDILI DIIREKGVDC DIDVPKTIQM
510 520 530 540 550
VRSQRSGMVQ TEAQYRFIYM AVQHYIETLQ RRIEEEQKSK RKGHEYTNIK
560 570 580 590
YSLVDQTSGD QSPLPPCTPT PPCAEMREDS ARVYENVGLM QQQRSFR
Length:597
Mass (Da):68,460
Last modified:December 20, 2005 - v2
Checksum:iC742BED37E39EA23
GO
Isoform 2 (identifier: P35235-2) [UniParc]FASTAAdd to basket

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

Show »
Length:593
Mass (Da):68,035
Checksum:i6C71EEEECCF7F159
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti390E → G in BAE37500 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_016675408 – 411Missing in isoform 2. 2 Publications4

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D84372 mRNA Translation: BAA12328.1
AK159501 mRNA Translation: BAE35134.1
AK159587 mRNA Translation: BAE35207.1
AK163809 mRNA Translation: BAE37500.1
BC057398 mRNA Translation: AAH57398.1
BC059278 mRNA Translation: AAH59278.1
L08663 mRNA No translation available.
CCDSiCCDS39247.1 [P35235-1]
CCDS51637.1 [P35235-2]
PIRiA46209
RefSeqiNP_001103462.1, NM_001109992.1 [P35235-2]
NP_035332.1, NM_011202.3 [P35235-1]
UniGeneiMm.8681

Genome annotation databases

EnsembliENSMUST00000054547; ENSMUSP00000058757; ENSMUSG00000043733 [P35235-1]
ENSMUST00000100770; ENSMUSP00000098333; ENSMUSG00000043733 [P35235-2]
GeneIDi19247
KEGGimmu:19247
UCSCiuc008zio.2 mouse [P35235-1]
uc008zip.2 mouse [P35235-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiPTN11_MOUSE
AccessioniPrimary (citable) accession number: P35235
Secondary accession number(s): Q3TQ84, Q64509, Q6PCL5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: December 20, 2005
Last modified: May 23, 2018
This is version 198 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

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