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Protein

Tyrosine-protein phosphatase non-receptor type substrate 1

Gene

Sirpa

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

Functioni

Immunoglobulin-like cell surface receptor for CD47. Acts as docking protein and induces translocation of PTPN6, PTPN11 and other binding partners from the cytosol to the plasma membrane. Supports adhesion of cerebellar neurons, neurite outgrowth and glial cell attachment. May play a key role in intracellular signaling during synaptogenesis and in synaptic function. Involved in the negative regulation of receptor tyrosine kinase-coupled cellular responses induced by cell adhesion, growth factors or insulin. Mediates negative regulation of phagocytosis, mast cell activation and dendritic cell activation. CD47 binding prevents maturation of immature dendritic cells and inhibits cytokine production by mature dendritic cells. May play a role in the release of nitric oxide by macrophages (By similarity).By similarity1 Publication

GO - Biological processi

  • cell migration Source: RGD
Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-RNO-202733. Cell surface interactions at the vascular wall.
R-RNO-2172127. DAP12 interactions.
R-RNO-391160. Signal regulatory protein (SIRP) family interactions.

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein phosphatase non-receptor type substrate 1
Short name:
SHP substrate 1
Short name:
SHPS-1
Alternative name(s):
Brain Ig-like molecule with tyrosine-based activation motifs
Short name:
Bit
CD172 antigen-like family member A
Inhibitory receptor SHPS-1
Macrophage fusion receptor
Macrophage membrane protein MFP150
Signal-regulatory protein alpha-1
Short name:
Sirp-alpha-1
CD_antigen: CD172a
Gene namesi
Name:Sirpa
Synonyms:Bit, Mfr, Ptpns1, Shps1, Sirp
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 3

Organism-specific databases

RGDi3449. Sirpa.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini32 – 373342ExtracellularSequence analysisAdd
BLAST
Transmembranei374 – 39421HelicalSequence analysisAdd
BLAST
Topological domaini395 – 509115CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi436 – 4361Y → F: Abolishes tyrosine phosphorylation and PTPN11 binding; when associated with F-460; F-477 and F-501. 1 Publication
Mutagenesisi460 – 4601Y → F: Abolishes tyrosine phosphorylation and PTPN11 binding; when associated with F-436; F-477 and F-501. 1 Publication
Mutagenesisi477 – 4771Y → F: Strongly reduces insulin-induced tyrosine phosphorylation and PTPN11 binding. Abolishes tyrosine phosphorylation and PTPN11 binding; when associated with F-436; F-460 and F-501. 1 Publication
Mutagenesisi501 – 5011Y → F: Strongly reduces insulin-induced tyrosine phosphorylation and PTPN11 binding. Abolishes tyrosine phosphorylation and PTPN11 binding; when associated with F-436; F-460 and F-477. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 31311 PublicationAdd
BLAST
Chaini32 – 509478Tyrosine-protein phosphatase non-receptor type substrate 1PRO_0000014943Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi54 – 541N-linked (GlcNAc...)Sequence analysis
Disulfide bondi55 ↔ 122PROSITE-ProRule annotation
Glycosylationi93 – 931N-linked (GlcNAc...)Sequence analysis
Glycosylationi169 – 1691N-linked (GlcNAc...)Sequence analysis
Disulfide bondi172 ↔ 229PROSITE-ProRule annotation
Glycosylationi181 – 1811N-linked (GlcNAc...)Sequence analysis
Glycosylationi205 – 2051N-linked (GlcNAc...)Sequence analysis
Glycosylationi209 – 2091N-linked (GlcNAc...)Sequence analysis
Glycosylationi242 – 2421N-linked (GlcNAc...)Sequence analysis
Glycosylationi246 – 2461N-linked (GlcNAc...)Sequence analysis
Glycosylationi271 – 2711N-linked (GlcNAc...)Sequence analysis
Disulfide bondi274 ↔ 332PROSITE-ProRule annotation
Glycosylationi293 – 2931N-linked (GlcNAc...)Sequence analysis
Glycosylationi312 – 3121N-linked (GlcNAc...)Sequence analysis
Glycosylationi320 – 3201N-linked (GlcNAc...)Sequence analysis
Glycosylationi345 – 3451N-linked (GlcNAc...)Sequence analysis
Modified residuei436 – 4361Phosphotyrosine; by Tyr-kinasesSequence analysis
Modified residuei460 – 4601Phosphotyrosine; by Tyr-kinasesSequence analysis
Modified residuei477 – 4771Phosphotyrosine; by Tyr-kinases1 Publication
Modified residuei501 – 5011Phosphotyrosine; by Tyr-kinases1 Publication

Post-translational modificationi

N-glycosylated.2 Publications
Phosphorylated on tyrosine residues in response to insulin, cell adhesion or epidermal growth factors. Dephosphorylated by PTPN11.4 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP97710.
PRIDEiP97710.

PTM databases

iPTMnetiP97710.
PhosphoSiteiP97710.
UniCarbKBiP97710.

Expressioni

Tissue specificityi

Highly expressed in brain, spleen, lung, liver and kidney. Detected at lower levels in heart. Highly expressed in alveolar and peritoneal macrophages, and at lower levels in dendritic cells.2 Publications

Gene expression databases

ExpressionAtlasiP97710. baseline and differential.
GenevisibleiP97710. RN.

Interactioni

Subunit structurei

Binds PTPN11 when tyrosine-phosphorylated, except in macrophages, where it primarily binds PTPN6. Binds GRB2 in vitro. Binds FGR. Binds JAK2 irrespective of its phosphorylation status and forms a stable complex. Binds SCAP1 and/or SCAP2. The resulting complex recruits FYB. Binds PTK2B (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Nphs1Q9R0442EBI-7945080,EBI-7945021
PTPN11Q061243EBI-7945080,EBI-297779From a different organism.
Ptpn11P414993EBI-7945080,EBI-7180604

Protein-protein interaction databases

BioGridi247560. 1 interaction.
IntActiP97710. 4 interactions.
MINTiMINT-8019899.
STRINGi10116.ENSRNOP00000006408.

Structurei

3D structure databases

ProteinModelPortaliP97710.
SMRiP97710. Positions 33-147.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini32 – 138107Ig-like V-typeAdd
BLAST
Domaini150 – 24899Ig-like C1-type 1Add
BLAST
Domaini255 – 34995Ig-like C1-type 2Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi436 – 4394SH2-bindingSequence analysis
Motifi446 – 4516SH3-bindingSequence analysis
Motifi460 – 4634SH2-bindingSequence analysis
Motifi477 – 4804SH2-bindingSequence analysis
Motifi501 – 5044SH2-bindingSequence analysis

Sequence similaritiesi

Keywords - Domaini

Immunoglobulin domain, Repeat, SH3-binding, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IKYM. Eukaryota.
ENOG410YKK2. LUCA.
GeneTreeiENSGT00440000033339.
HOVERGENiHBG056632.
InParanoidiP97710.
KOiK06551.
OMAiHEPEKNT.
OrthoDBiEOG7CG6ZQ.

Family and domain databases

Gene3Di2.60.40.10. 3 hits.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003006. Ig/MHC_CS.
IPR003597. Ig_C1-set.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
[Graphical view]
PfamiPF07654. C1-set. 2 hits.
PF07686. V-set. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 2 hits.
SM00407. IGc1. 2 hits.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 3 hits.
PROSITEiPS50835. IG_LIKE. 3 hits.
PS00290. IG_MHC. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P97710-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEPAGPAPGR LGPLLFCLLL SASCFCAGAS GKELKVTQAD KSVSVAAGDS
60 70 80 90 100
ATLNCTVSSL TPVGPIKWFK GEGQNRSPIY SFIGGEHFPR ITNVSDATKR
110 120 130 140 150
NNMDFSICIS NVTPEDAGTY YCVKFQKGIV EPDTEIKSGG GTTLYVLAKP
160 170 180 190 200
SSPEVSGPDS RGSPGQTVNF TCKSYGFSPR NITLKWLKDG KELSHLETTI
210 220 230 240 250
SSKSNVSYNI SSTVSVKLSP EDIHSRVICE VAHVTLEGRP LNGTANFSNI
260 270 280 290 300
IRVSPTLKIT QQPLTPASQV NLTCQVQKFY PKALQLNWLE NGNLSRTDKP
310 320 330 340 350
EHFTDNRDGT YNYTSLFLVN SSAHREDVVF TCQVEHDSQP AITENHTVRA
360 370 380 390 400
FAHSSSGGSM ETIPDNNAYY NWNVFIGVGV ACALLVVLLM AALYLLRIKQ
410 420 430 440 450
KKAKGSTSST RLHEPEKNAR EITQIQDTND INDITYADLN LPKEKKPAPR
460 470 480 490 500
VPEPNNHTEY ASIETGKLPR PEDTLTYADL DMVHLNRAQP TPKPEPSFSE

YASVQVQRK
Length:509
Mass (Da):55,691
Last modified:May 1, 1997 - v1
Checksum:i5BE1FE0A4DD429F4
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti8 – 81P → L (PubMed:9712053).Curated
Sequence conflicti10 – 101Missing (PubMed:9712053).Curated
Sequence conflicti25 – 251F → I in AAC68478 (PubMed:9774638).Curated
Sequence conflicti58 – 581S → C in AAC18089 (PubMed:9712053).Curated
Sequence conflicti99 – 1002KR → MP AA sequence (PubMed:9774638).Curated
Sequence conflicti162 – 1621G → A in BAA20368 (PubMed:9271230).Curated
Sequence conflicti189 – 1891D → N in AAC68478 (PubMed:9774638).Curated
Sequence conflicti205 – 2051N → L AA sequence (PubMed:9774638).Curated
Sequence conflicti209 – 2091N → G AA sequence (PubMed:9774638).Curated
Sequence conflicti405 – 4051G → F AA sequence (PubMed:9774638).Curated
Sequence conflicti416 – 4161E → P AA sequence (PubMed:9774638).Curated
Sequence conflicti418 – 4214NARE → EGQN AA sequence (PubMed:9774638).Curated
Sequence conflicti450 – 4501R → E AA sequence (PubMed:9774638).Curated
Sequence conflicti499 – 4991Missing AA sequence (PubMed:9774638).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D85183 mRNA. Translation: BAA12734.1.
D38468 mRNA. Translation: BAA20368.1.
U62328 mRNA. Translation: AAC68478.1.
AF055065 mRNA. Translation: AAC18089.1.
RefSeqiNP_037148.2. NM_013016.2.
UniGeneiRn.53971.

Genome annotation databases

EnsembliENSRNOT00000006408; ENSRNOP00000006408; ENSRNOG00000004763.
GeneIDi25528.
KEGGirno:25528.
UCSCiRGD:3449. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D85183 mRNA. Translation: BAA12734.1.
D38468 mRNA. Translation: BAA20368.1.
U62328 mRNA. Translation: AAC68478.1.
AF055065 mRNA. Translation: AAC18089.1.
RefSeqiNP_037148.2. NM_013016.2.
UniGeneiRn.53971.

3D structure databases

ProteinModelPortaliP97710.
SMRiP97710. Positions 33-147.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247560. 1 interaction.
IntActiP97710. 4 interactions.
MINTiMINT-8019899.
STRINGi10116.ENSRNOP00000006408.

PTM databases

iPTMnetiP97710.
PhosphoSiteiP97710.
UniCarbKBiP97710.

Proteomic databases

PaxDbiP97710.
PRIDEiP97710.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000006408; ENSRNOP00000006408; ENSRNOG00000004763.
GeneIDi25528.
KEGGirno:25528.
UCSCiRGD:3449. rat.

Organism-specific databases

CTDi140885.
RGDi3449. Sirpa.

Phylogenomic databases

eggNOGiENOG410IKYM. Eukaryota.
ENOG410YKK2. LUCA.
GeneTreeiENSGT00440000033339.
HOVERGENiHBG056632.
InParanoidiP97710.
KOiK06551.
OMAiHEPEKNT.
OrthoDBiEOG7CG6ZQ.

Enzyme and pathway databases

ReactomeiR-RNO-202733. Cell surface interactions at the vascular wall.
R-RNO-2172127. DAP12 interactions.
R-RNO-391160. Signal regulatory protein (SIRP) family interactions.

Miscellaneous databases

PROiP97710.

Gene expression databases

ExpressionAtlasiP97710. baseline and differential.
GenevisibleiP97710. RN.

Family and domain databases

Gene3Di2.60.40.10. 3 hits.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003006. Ig/MHC_CS.
IPR003597. Ig_C1-set.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
[Graphical view]
PfamiPF07654. C1-set. 2 hits.
PF07686. V-set. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 2 hits.
SM00407. IGc1. 2 hits.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 3 hits.
PROSITEiPS50835. IG_LIKE. 3 hits.
PS00290. IG_MHC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "A novel membrane glycoprotein, SHPS-1, that binds the SH2-domain-containing protein tyrosine phosphatase SHP-2 in response to mitogens and cell adhesion."
    Fujioka Y., Matozaki T., Noguchi T., Iwamatsu A., Yamao T., Takahashi N., Tsuda M., Takada T., Kasuga M.
    Mol. Cell. Biol. 16:6887-6899(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 42-60; 68-91; 128-137; 150-158; 174-189; 192-202; 204-212; 218-237; 259-270; 279-282; 405-415 AND 446-453, GLYCOSYLATION, PHOSPHORYLATION AT TYROSINE RESIDUES, INTERACTION WITH PTPN6 AND PTPN11.
    Tissue: Fetal fibroblast.
  2. "BIT, an immune antigen receptor-like molecule in the brain."
    Sano S., Ohnishi H., Omori A., Hasegawa J., Kubota M.
    FEBS Lett. 411:327-334(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 32-48 AND 446-453, FUNCTION, PHOSPHORYLATION AT TYROSINE RESIDUES.
    Strain: Sprague-Dawley.
    Tissue: Brain.
  3. "MFR, a putative receptor mediating the fusion of macrophages."
    Saginario C., Sterling H., Beckers C., Kobayashi R., Solimena M., Ullu E., Vignery A.
    Mol. Cell. Biol. 18:6213-6223(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 99-107; 128-149; 192-217; 405-417; 419-429; 446-467 AND 496-506, GLYCOSYLATION, TISSUE SPECIFICITY.
    Strain: Fischer 344.
    Tissue: Macrophage.
  4. "Signal-regulatory protein is selectively expressed by myeloid and neuronal cells."
    Adams S., van der Laan L.J.W., Vernon-Wilson E., Renardel de Lavalette C., Doepp E.A., Dijkstra C.D., Simmons D.L., van den Berg T.K.
    J. Immunol. 161:1853-1859(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-419, TISSUE SPECIFICITY.
    Strain: WAG/Rij.
    Tissue: Alveolar macrophage.
  5. Lubec G., Kang S.U., Lubec S.
    Submitted (SEP-2007) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 192-203; 218-226 AND 297-307, IDENTIFICATION BY MASS SPECTROMETRY.
    Strain: Sprague-Dawley.
    Tissue: Brain.
  6. "Epidermal growth factor stimulates the tyrosine phosphorylation of SHPS-1 and association of SHPS-1 with SHP-2, a SH2 domain-containing protein tyrosine phosphatase."
    Ochi F., Matozaki T., Noguchi T., Fujioka Y., Yamao T., Takada T., Tsuda M., Takeda H., Fukunaga K., Okabayashi Y., Kasuga M.
    Biochem. Biophys. Res. Commun. 239:483-487(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION IN RESPONSE TO EGF, INTERACTION WITH PTPN11.
  7. "Roles of the complex formation of SHPS-1 with SHP-2 in insulin-stimulated mitogen-activated protein kinase activation."
    Takada T., Matozaki T., Takeda H., Fukunaga K., Noguchi T., Fujioka Y., Okazaki I., Tsuda M., Yamao T., Ochi F., Kasuga M.
    J. Biol. Chem. 273:9234-9242(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT TYR-477 AND TYR-501, MUTAGENESIS OF TYR-436; TYR-460; TYR-477 AND TYR-501.

Entry informationi

Entry nameiSHPS1_RAT
AccessioniPrimary (citable) accession number: P97710
Secondary accession number(s): O08951, O70426, Q9QWI5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 28, 2003
Last sequence update: May 1, 1997
Last modified: June 8, 2016
This is version 129 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, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

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 one 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.