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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.
R-RNO-6798695. Neutrophil degranulation.

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)DescriptionActionsGraphical viewLength
Topological domaini32 – 373ExtracellularSequence analysisAdd BLAST342
Transmembranei374 – 394HelicalSequence analysisAdd BLAST21
Topological domaini395 – 509CytoplasmicSequence analysisAdd BLAST115

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi436Y → F: Abolishes tyrosine phosphorylation and PTPN11 binding; when associated with F-460; F-477 and F-501. 1 Publication1
Mutagenesisi460Y → F: Abolishes tyrosine phosphorylation and PTPN11 binding; when associated with F-436; F-477 and F-501. 1 Publication1
Mutagenesisi477Y → 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 Publication1
Mutagenesisi501Y → 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 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 311 PublicationAdd BLAST31
ChainiPRO_000001494332 – 509Tyrosine-protein phosphatase non-receptor type substrate 1Add BLAST478

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi54N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi55 ↔ 122PROSITE-ProRule annotation
Glycosylationi93N-linked (GlcNAc...)Sequence analysis1
Glycosylationi169N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi172 ↔ 229PROSITE-ProRule annotation
Glycosylationi181N-linked (GlcNAc...)Sequence analysis1
Glycosylationi205N-linked (GlcNAc...)Sequence analysis1
Glycosylationi209N-linked (GlcNAc...)Sequence analysis1
Glycosylationi242N-linked (GlcNAc...)Sequence analysis1
Glycosylationi246N-linked (GlcNAc...)Sequence analysis1
Glycosylationi271N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi274 ↔ 332PROSITE-ProRule annotation
Glycosylationi293N-linked (GlcNAc...)Sequence analysis1
Glycosylationi312N-linked (GlcNAc...)Sequence analysis1
Glycosylationi320N-linked (GlcNAc...)Sequence analysis1
Glycosylationi345N-linked (GlcNAc...)Sequence analysis1
Modified residuei436Phosphotyrosine; by Tyr-kinasesSequence analysis1
Modified residuei460Phosphotyrosine; by Tyr-kinasesSequence analysis1
Modified residuei477Phosphotyrosine; by Tyr-kinases1 Publication1
Modified residuei501Phosphotyrosine; by Tyr-kinases1 Publication1

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.
PeptideAtlasiP97710.
PRIDEiP97710.

PTM databases

iPTMnetiP97710.
PhosphoSitePlusiP97710.
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

BgeeiENSRNOG00000004763.
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 interactor.
IntActiP97710. 4 interactors.
MINTiMINT-8019899.
STRINGi10116.ENSRNOP00000006408.

Structurei

3D structure databases

ProteinModelPortaliP97710.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini32 – 138Ig-like V-typeAdd BLAST107
Domaini150 – 248Ig-like C1-type 1Add BLAST99
Domaini255 – 349Ig-like C1-type 2Add BLAST95

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi436 – 439SH2-bindingSequence analysis4
Motifi446 – 451SH3-bindingSequence analysis6
Motifi460 – 463SH2-bindingSequence analysis4
Motifi477 – 480SH2-bindingSequence analysis4
Motifi501 – 504SH2-bindingSequence analysis4

Sequence similaritiesi

Keywords - Domaini

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

Phylogenomic databases

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

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)DescriptionActionsGraphical viewLength
Sequence conflicti8P → L (PubMed:9712053).Curated1
Sequence conflicti10Missing (PubMed:9712053).Curated1
Sequence conflicti25F → I in AAC68478 (PubMed:9774638).Curated1
Sequence conflicti58S → C in AAC18089 (PubMed:9712053).Curated1
Sequence conflicti99 – 100KR → MP AA sequence (PubMed:9774638).Curated2
Sequence conflicti162G → A in BAA20368 (PubMed:9271230).Curated1
Sequence conflicti189D → N in AAC68478 (PubMed:9774638).Curated1
Sequence conflicti205N → L AA sequence (PubMed:9774638).Curated1
Sequence conflicti209N → G AA sequence (PubMed:9774638).Curated1
Sequence conflicti405G → F AA sequence (PubMed:9774638).Curated1
Sequence conflicti416E → P AA sequence (PubMed:9774638).Curated1
Sequence conflicti418 – 421NARE → EGQN AA sequence (PubMed:9774638).Curated4
Sequence conflicti450R → E AA sequence (PubMed:9774638).Curated1
Sequence conflicti499Missing AA sequence (PubMed:9774638).Curated1

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.
XP_017446986.1. XM_017591497.1.
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.
XP_017446986.1. XM_017591497.1.
UniGeneiRn.53971.

3D structure databases

ProteinModelPortaliP97710.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247560. 1 interactor.
IntActiP97710. 4 interactors.
MINTiMINT-8019899.
STRINGi10116.ENSRNOP00000006408.

PTM databases

iPTMnetiP97710.
PhosphoSitePlusiP97710.
UniCarbKBiP97710.

Proteomic databases

PaxDbiP97710.
PeptideAtlasiP97710.
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.

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.
R-RNO-6798695. Neutrophil degranulation.

Miscellaneous databases

PROiP97710.

Gene expression databases

BgeeiENSRNOG00000004763.
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...

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: November 30, 2016
This is version 134 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.