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Protein

Tyrosine-protein phosphatase non-receptor type 6

Gene

Ptpn6

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

Catalytic activityi

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.PROSITE-ProRule annotationBy similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei421 – 4211SubstrateBy similarity
Active sitei455 – 4551Phosphocysteine intermediatePROSITE-ProRule annotation
Binding sitei502 – 5021SubstrateBy similarity

GO - Molecular functioni

  1. natural killer cell lectin-like receptor binding Source: RGD
  2. protein tyrosine phosphatase activity Source: RGD
  3. transmembrane receptor protein tyrosine phosphatase activity Source: UniProtKB

GO - Biological processi

  1. cell differentiation Source: UniProtKB
  2. cell proliferation Source: UniProtKB
  3. peptidyl-tyrosine dephosphorylation Source: GOC
  4. protein dephosphorylation Source: UniProtKB
  5. regulation of ERK1 and ERK2 cascade Source: UniProtKB
  6. response to wounding Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein phosphatase non-receptor type 6 (EC:3.1.3.48)
Alternative name(s):
Protein-tyrosine phosphatase SHP-1
Gene namesi
Name:Ptpn6
Synonyms:Ptph6
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Unplaced

Organism-specific databases

RGDi620660. Ptpn6.

Subcellular locationi

Cytoplasm 1 Publication. Nucleus 1 Publication
Note: In neurons, translocates into the nucleus after treatment with angiotensin II. Shuttles between the cytoplasm and nucleus via its association with PDPK (By similarity).By similarity

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-SubCell
  2. nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 613613Tyrosine-protein phosphatase non-receptor type 6PRO_0000094760Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei66 – 661PhosphotyrosineBy similarity
Modified residuei379 – 3791PhosphotyrosineBy similarity
Modified residuei538 – 5381PhosphotyrosineBy similarity
Modified residuei566 – 5661Phosphotyrosine; by LYNBy similarity

Post-translational modificationi

Phosphorylated on tyrosine residues. Binding of KITLG/SCF to KIT increases tyrosine phosphorylation (By similarity). Phosphorylation at Tyr-566 enhances phosphatase activity (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP81718.
PRIDEiP81718.

PTM databases

PhosphoSiteiP81718.

Expressioni

Developmental stagei

Highly expressed in embryonic cerebral cortex between day 18 and up to birth. Expression levels decrease after birth (at protein level).1 Publication

Gene expression databases

GenevestigatoriP81718.

Interactioni

Subunit structurei

Monomer. Binds PTPNS1. Interacts with CDK2, FCRL2, FCRL3, FCRL4, CD300LF and CD84. Interacts with MILR1 (tyrosine-phosphorylated). Interacts with KIT. 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 (By similarity). Interacts with MTUS1. Interacts with the tyrosine phosphorylated form of PDPK1 (By similarity).By similarity

Protein-protein interaction databases

BioGridi250571. 2 interactions.

Structurei

3D structure databases

ProteinModelPortaliP81718.
SMRiP81718. Positions 6-528.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini6 – 10297SH2 1PROSITE-ProRule annotationCuratedAdd
BLAST
Domaini112 – 215104SH2 2PROSITE-ProRule annotationCuratedAdd
BLAST
Domaini246 – 517272Tyrosine-protein phosphatasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni455 – 4617Substrate bindingBy similarity

Domaini

The N-terminal SH2 domain functions as an auto-inhibitory domain, blocking the catalytic domain in the ligand-free close conformation.By similarity

Sequence similaritiesi

Contains 2 SH2 domains.PROSITE-ProRule annotationCurated
Contains 1 tyrosine-protein phosphatase domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, SH2 domain

Phylogenomic databases

eggNOGiCOG5599.
HOGENOMiHOG000273907.
HOVERGENiHBG000223.
InParanoidiP81718.
KOiK05697.
PhylomeDBiP81718.

Family and domain databases

Gene3Di3.30.505.10. 2 hits.
3.90.190.10. 1 hit.
InterProiIPR029021. Prot-tyrosine_phosphatase-like.
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]
PfamiPF00017. SH2. 2 hits.
PF00102. Y_phosphatase. 1 hit.
[Graphical view]
PIRSFiPIRSF000929. Tyr-Ptase_nr_6. 1 hit.
PRINTSiPR00700. PRTYPHPHTASE.
PR00401. SH2DOMAIN.
SMARTiSM00194. PTPc. 1 hit.
SM00252. SH2. 2 hits.
[Graphical view]
SUPFAMiSSF52799. SSF52799. 1 hit.
SSF55550. SSF55550. 2 hits.
PROSITEiPS50001. SH2. 2 hits.
PS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50055. TYR_PHOSPHATASE_PTP. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P81718-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLSRGWFHRD LSGPDAETLL KGRGVPGSFL ARPSRKNQGD FSLSVRVDDQ
60 70 80 90 100
VTHIRIQNSG DFYDLYGGEK FATSTELVEY YTQQQGILQD RDGTIIHLKY
110 120 130 140 150
PLNCSDPTSE RWYHGHMSGG QAESLLQAKG EPWTFLVRES LSQPGDFVLS
160 170 180 190 200
VLNDQPKAAP GSPLRVTHIK VMCEGGRYTV GGSETFDSLT DLVEHFKKTG
210 220 230 240 250
IEEASGAFVY LRQPYYATRV NAADIENRVL ELNKKQESED TAKAGFWEEF
260 270 280 290 300
ESLQKQEAKN LHQRLEGQRP ENKSKNRYKN ILPFDHSRVI LQGRDSNIPG
310 320 330 340 350
SDYINANYVK NQLLGPDENS KTYIASQGCL DATVNDFWQM AWQENTRVIV
360 370 380 390 400
MTTREVEKGR NKCVPYWPEV GTQRVYGLYS VTNCKEHDTA EYKLRTLQIS
410 420 430 440 450
PLDNGDLVRE IWHYQYLSWP DHGVPSEPGG VLSFLDQINQ RQESLPHAGP
460 470 480 490 500
IIVHCSAGIG RTGTIIVIDM LMESVSTKGL DCDIDIQKTI QMVRAQRSGM
510 520 530 540 550
VQTEAQYKFI YVAIAQFIET TKKKLEIIQS QRGQESEYGN ITYPPALRSA
560 570 580 590 600
HAKASRTSSK HKEEVYENVH SKNKKEEKVK KQRSADKEKN KGSLKRNISL
610
TPCRGLRWAD RDL
Length:613
Mass (Da):69,578
Last modified:May 1, 1999 - v1
Checksum:i29364B22E8F45C87
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U77038 mRNA. Translation: AAD00262.1.
RefSeqiNP_446360.1. NM_053908.1.
UniGeneiRn.18985.

Genome annotation databases

GeneIDi116689.
KEGGirno:116689.
UCSCiRGD:620660. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U77038 mRNA. Translation: AAD00262.1.
RefSeqiNP_446360.1. NM_053908.1.
UniGeneiRn.18985.

3D structure databases

ProteinModelPortaliP81718.
SMRiP81718. Positions 6-528.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi250571. 2 interactions.

PTM databases

PhosphoSiteiP81718.

Proteomic databases

PaxDbiP81718.
PRIDEiP81718.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi116689.
KEGGirno:116689.
UCSCiRGD:620660. rat.

Organism-specific databases

CTDi5777.
RGDi620660. Ptpn6.

Phylogenomic databases

eggNOGiCOG5599.
HOGENOMiHOG000273907.
HOVERGENiHBG000223.
InParanoidiP81718.
KOiK05697.
PhylomeDBiP81718.

Miscellaneous databases

NextBioi619552.
PROiP81718.

Gene expression databases

GenevestigatoriP81718.

Family and domain databases

Gene3Di3.30.505.10. 2 hits.
3.90.190.10. 1 hit.
InterProiIPR029021. Prot-tyrosine_phosphatase-like.
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]
PfamiPF00017. SH2. 2 hits.
PF00102. Y_phosphatase. 1 hit.
[Graphical view]
PIRSFiPIRSF000929. Tyr-Ptase_nr_6. 1 hit.
PRINTSiPR00700. PRTYPHPHTASE.
PR00401. SH2DOMAIN.
SMARTiSM00194. PTPc. 1 hit.
SM00252. SH2. 2 hits.
[Graphical view]
SUPFAMiSSF52799. SSF52799. 1 hit.
SSF55550. SSF55550. 2 hits.
PROSITEiPS50001. SH2. 2 hits.
PS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50055. TYR_PHOSPHATASE_PTP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "The rat SH2-containing protein-tyrosine phosphatase SHP-1 is a positive regulator of NGF-induced neuronal differentiation of PC12 cells."
    Aoki N., Yamaguchi-Aoki Y., Ullrich A.
    Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Angiotensin II-induced neural differentiation via angiotensin II type 2 (AT2) receptor-MMS2 cascade involving interaction between AT2 receptor-interacting protein and Src homology 2 domain-containing protein-tyrosine phosphatase 1."
    Li J.-M., Mogi M., Tsukuda K., Tomochika H., Iwanami J., Min L.-J., Nahmias C., Iwai M., Horiuchi M.
    Mol. Endocrinol. 21:499-511(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION, INTERACTION WITH MTUS1.

Entry informationi

Entry nameiPTN6_RAT
AccessioniPrimary (citable) accession number: P81718
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 19, 2003
Last sequence update: May 1, 1999
Last modified: March 4, 2015
This is version 111 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.