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Protein

Tyrosine-protein phosphatase non-receptor type substrate 1

Gene

Sirpa

Organism
Mus musculus (Mouse)
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 (By similarity).By similarity1 Publication

GO - Biological processi

  • actin filament organization Source: MGI
  • cell-matrix adhesion Source: MGI
  • cytoskeleton organization Source: MGI
  • hematopoietic progenitor cell differentiation Source: MGI
  • phagocytosis, engulfment Source: MGI
  • phagocytosis, recognition Source: MGI
  • positive regulation of phagocytosis Source: MGI
Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-MMU-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
MyD-1 antigen
Signal-regulatory protein alpha-1
Short name:
Sirp-alpha-1
Short name:
mSIRP-alpha1
p84
CD_antigen: CD172a
Gene namesi
Name:Sirpa
Synonyms:Bit, Myd1, Ptpns1, Shps1, Sirp
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:108563. Sirpa.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini32 – 373ExtracellularSequence analysisAdd BLAST342
Transmembranei374 – 394HelicalSequence analysisAdd BLAST21
Topological domaini395 – 511CytoplasmicSequence analysisAdd BLAST117

GO - Cellular componenti

  • extracellular exosome Source: MGI
  • integral component of plasma membrane Source: MGI
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 31Add BLAST31
ChainiPRO_000001494232 – 513Tyrosine-protein phosphatase non-receptor type substrate 1Add BLAST482

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi54N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi55 ↔ 121PROSITE-ProRule annotation
Glycosylationi92N-linked (GlcNAc...)Sequence analysis1
Glycosylationi168N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi171 ↔ 229PROSITE-ProRule annotation
Glycosylationi180N-linked (GlcNAc...)Sequence analysis1
Glycosylationi205N-linked (GlcNAc...)Sequence analysis1
Glycosylationi209N-linked (GlcNAc...)Sequence analysis1
Glycosylationi246N-linked (GlcNAc...)1 Publication1
Glycosylationi271N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi274 ↔ 332PROSITE-ProRule annotation
Glycosylationi293N-linked (GlcNAc...)Sequence analysis1
Glycosylationi302N-linked (GlcNAc...)Sequence analysis1
Glycosylationi312N-linked (GlcNAc...)Sequence analysis1
Glycosylationi320N-linked (GlcNAc...)Sequence analysis1
Glycosylationi345N-linked (GlcNAc...)Sequence analysis1
Glycosylationi367N-linked (GlcNAc...)Sequence analysis1
Modified residuei440Phosphotyrosine; by Tyr-kinasesSequence analysis1
Modified residuei464Phosphotyrosine; by Tyr-kinasesSequence analysis1
Modified residuei481Phosphotyrosine; by Tyr-kinasesBy similarity1
Modified residuei505Phosphotyrosine; by Tyr-kinasesBy similarity1

Post-translational modificationi

N-glycosylated.5 Publications
Phosphorylated on tyrosine residues.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP97797.
PaxDbiP97797.
PeptideAtlasiP97797.
PRIDEiP97797.

PTM databases

iPTMnetiP97797.
PhosphoSitePlusiP97797.

Expressioni

Tissue specificityi

Highly expressed in cerebral cortex, brain, spinal cord, cerebellum and spleen, and at much lower levels in kidney, thymus, heart, lung and liver. Within the cerebellum, highly expressed throughout the molecular layer, and in synaptic glomeruli in the granule cell layer. Detected in neurons of the hippocampus and dentate gyrus, and in olfactory bulb. Not detected in Purkinje cells. Highly expressed in the plexiform layers, optic fiber layer and the outer segments of the photoreceptor layer in the retina. Highly expressed in macrophages. Isoform 3 is detected at very low levels in all tissues tested.4 Publications

Developmental stagei

Highly expressed in the CNS of embryos from day 7 to 17.1 Publication

Gene expression databases

BgeeiENSMUSG00000037902.
CleanExiMM_SIRPA.

Interactioni

Subunit structurei

Binds PTPN11 when tyrosine-phosphorylated, except in macrophages, where it primarily binds PTPN6. Binds GRB2 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

Protein-protein interaction databases

BioGridi202490. 2 interactors.
IntActiP97797. 3 interactors.
MINTiMINT-1668886.
STRINGi10090.ENSMUSP00000099491.

Structurei

Secondary structure

1513
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi40 – 45Combined sources6
Beta strandi51 – 53Combined sources3
Beta strandi56 – 58Combined sources3
Beta strandi66 – 73Combined sources8
Beta strandi77 – 82Combined sources6
Turni87 – 89Combined sources3
Beta strandi92 – 95Combined sources4
Beta strandi98 – 100Combined sources3
Beta strandi106 – 108Combined sources3
Helixi113 – 115Combined sources3
Beta strandi117 – 125Combined sources9
Beta strandi128 – 131Combined sources4
Beta strandi133 – 137Combined sources5
Beta strandi141 – 145Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2YZ1X-ray1.40A/B32-146[»]
ProteinModelPortaliP97797.
SMRiP97797.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP97797.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini32 – 137Ig-like V-typeAdd BLAST106
Domaini149 – 248Ig-like C1-type 1Add BLAST100
Domaini255 – 343Ig-like C1-type 2Add BLAST89

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi440 – 443SH2-bindingSequence analysis4
Motifi450 – 455SH3-bindingSequence analysis6
Motifi464 – 467SH2-bindingSequence analysis4
Motifi481 – 484SH2-bindingSequence analysis4
Motifi505 – 508SH2-bindingSequence analysis4

Sequence similaritiesi

Keywords - Domaini

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

Phylogenomic databases

eggNOGiENOG410IKYM. Eukaryota.
ENOG410YKK2. LUCA.
HOVERGENiHBG056632.
InParanoidiP97797.
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]

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: P97797-1) [UniParc]FASTAAdd to basket
Also known as: a

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
MEPAGPAPGR LGPLLLCLLL SASCFCTGVT GKELKVTQPE KSVSVAAGDS
60 70 80 90 100
TVLNCTLTSL LPVGPIKWYR GVGQSRLLIY SFTGEHFPRV TNVSDATKRN
110 120 130 140 150
NMDFSIRISN VTPEDAGTYY CVKFQKGPSE PDTEIQSGGG TEVYVLAKPS
160 170 180 190 200
PPEVSGPADR GIPDQKVNFT CKSHGFSPRN ITLKWFKDGQ ELHHLETTVN
210 220 230 240 250
PSGKNVSYNI SSTVRVVLNS MDVHSKVICE VAHITLDRSP LRGIANLSNF
260 270 280 290 300
IRVSPTVKVT QQSPTSMNQV NLTCRAERFY PEDLQLIWLE NGNVSRNDTP
310 320 330 340 350
KNLTKNTDGT YNYTSLFLVN SSAHREDVVF TCQVKHDQQP AITRNHTVLG
360 370 380 390 400
LAHSSDQGSM QTFPGNNATH NWNVFIGVGV ACALLVVLLM AALYLLRIKQ
410 420 430 440 450
KKAKGSTSST RLHEPEKNAR EITQVQSLIQ DTNDINDITY ADLNLPKEKK
460 470 480 490 500
PAPRAPEPNN HTEYASIETG KVPRPEDTLT YADLDMVHLS RAQPAPKPEP
510
SFSEYASVQV QRK
Length:513
Mass (Da):56,425
Last modified:May 1, 1997 - v1
Checksum:i2AFDDD5FA6C1EC7C
GO
Isoform 2 (identifier: P97797-2) [UniParc]FASTAAdd to basket
Also known as: a', Large

The sequence of this isoform differs from the canonical sequence as follows:
     425-428: Missing.

Show »
Length:509
Mass (Da):55,997
Checksum:i55023F2FC1A002B5
GO
Isoform 3 (identifier: P97797-3) [UniParc]FASTAAdd to basket
Also known as: b, Small

The sequence of this isoform differs from the canonical sequence as follows:
     147-364: Missing.

Show »
Length:295
Mass (Da):32,145
Checksum:iCEFC347F69950D71
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti6Missing in CAA71375 (Ref. 7) Curated1
Sequence conflicti10R → L in AAB92591 (PubMed:9348339).Curated1
Sequence conflicti32 – 34KEL → TEV in BAA20376 (PubMed:9073522).Curated3
Sequence conflicti52V → I in BAA20376 (PubMed:9073522).Curated1
Sequence conflicti57L → V in BAA20376 (PubMed:9073522).Curated1
Sequence conflicti74 – 77QSRL → KAGC in CAA71375 (Ref. 7) Curated4
Sequence conflicti126K → R in BAA20376 (PubMed:9073522).Curated1
Sequence conflicti126K → R in AAB92591 (PubMed:9348339).Curated1
Sequence conflicti154 – 156VSG → YPV in CAA71375 (Ref. 7) Curated3
Sequence conflicti164D → Y in CAA71375 (Ref. 7) Curated1
Sequence conflicti263S → P in BAA20376 (PubMed:9073522).Curated1
Sequence conflicti276A → D in CAA71375 (Ref. 7) Curated1
Sequence conflicti448 – 449EK → RR in CAA71375 (Ref. 7) Curated2
Sequence conflicti454 – 458RAPEP → GSLEFL in CAA71375 (Ref. 7) Curated5
Sequence conflicti490S → N in BAA20376 (PubMed:9073522).Curated1
Sequence conflicti490S → N in AAB92591 (PubMed:9348339).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti29V → A in strain: BALB/c, C57BL/6 and ILS. 5 Publications1
Natural varianti67K → R in strain: BALB/c, C57BL/6 and ILS. 4 Publications1
Natural varianti74Q → P in strain: C57BL/6 and ILS. 3 Publications1
Natural varianti83T → A in strain: C57BL/6 and ILS. 3 Publications1
Natural varianti86 – 87HF → YV in strain: C57BL/6 and ILS. 2
Natural varianti90V → I in strain: C57BL/6 and ILS. 3 Publications1
Natural varianti91T → R in strain: BALB/c, C57BL/6 and ILS. 5 Publications1
Natural varianti96A → T in strain: BALB/c, C57BL/6 and ILS. 5 Publications1
Natural varianti114E → A in strain: C57BL/6 and ILS. 3 Publications1
Natural varianti118T → I in strain: C57BL/6 and ILS. 3 Publications1
Natural varianti128P → S in strain: BALB/c, C57BL/6 and ILS. 5 Publications1
Natural varianti194H → P in strain: BALB/c, C57BL/6 and ILS. 5 Publications1
Natural varianti224H → N in strain: BALB/c, C57BL/6 and ILS. 4 Publications1
Natural varianti351L → F in strain: C57BL/6 and ILS. 3 Publications1
Natural varianti365G → D in strain: C57BL/6 and ILS. 3 Publications1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_007031147 – 364Missing in isoform 3. 3 PublicationsAdd BLAST218
Alternative sequenceiVSP_007032425 – 428Missing in isoform 2. 5 Publications4

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D87967 mRNA. Translation: BAA13520.1.
D87968 mRNA. Translation: BAA13521.1.
D85785 mRNA. Translation: BAA20376.1.
U89694 mRNA. Translation: AAB92591.1.
AF072543 mRNA. Translation: AAC24886.1.
AF072544 mRNA. Translation: AAC24887.1.
AB024507 Genomic DNA. Translation: BAA89290.1.
AB018194 mRNA. Translation: BAA76555.1.
AB024507 Genomic DNA. Translation: BAA89289.1.
AF332079 mRNA. Translation: AAK56107.1.
AF332080 mRNA. Translation: AAK56108.1.
Y10349 mRNA. Translation: CAA71375.1.
CCDSiCCDS16729.1. [P97797-2]
CCDS71142.1. [P97797-1]
CCDS71143.1. [P97797-3]
PIRiJC5288.
JC5289.
RefSeqiNP_001171118.1. NM_001177647.2.
NP_001277948.1. NM_001291019.1.
NP_001277949.1. NM_001291020.1.
NP_031573.2. NM_007547.4.
XP_017172050.1. XM_017316561.1.
XP_017172058.1. XM_017316569.1.
UniGeneiMm.1682.

Genome annotation databases

GeneIDi19261.
KEGGimmu:19261.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D87967 mRNA. Translation: BAA13520.1.
D87968 mRNA. Translation: BAA13521.1.
D85785 mRNA. Translation: BAA20376.1.
U89694 mRNA. Translation: AAB92591.1.
AF072543 mRNA. Translation: AAC24886.1.
AF072544 mRNA. Translation: AAC24887.1.
AB024507 Genomic DNA. Translation: BAA89290.1.
AB018194 mRNA. Translation: BAA76555.1.
AB024507 Genomic DNA. Translation: BAA89289.1.
AF332079 mRNA. Translation: AAK56107.1.
AF332080 mRNA. Translation: AAK56108.1.
Y10349 mRNA. Translation: CAA71375.1.
CCDSiCCDS16729.1. [P97797-2]
CCDS71142.1. [P97797-1]
CCDS71143.1. [P97797-3]
PIRiJC5288.
JC5289.
RefSeqiNP_001171118.1. NM_001177647.2.
NP_001277948.1. NM_001291019.1.
NP_001277949.1. NM_001291020.1.
NP_031573.2. NM_007547.4.
XP_017172050.1. XM_017316561.1.
XP_017172058.1. XM_017316569.1.
UniGeneiMm.1682.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2YZ1X-ray1.40A/B32-146[»]
ProteinModelPortaliP97797.
SMRiP97797.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202490. 2 interactors.
IntActiP97797. 3 interactors.
MINTiMINT-1668886.
STRINGi10090.ENSMUSP00000099491.

PTM databases

iPTMnetiP97797.
PhosphoSitePlusiP97797.

Proteomic databases

MaxQBiP97797.
PaxDbiP97797.
PeptideAtlasiP97797.
PRIDEiP97797.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi19261.
KEGGimmu:19261.

Organism-specific databases

CTDi140885.
MGIiMGI:108563. Sirpa.

Phylogenomic databases

eggNOGiENOG410IKYM. Eukaryota.
ENOG410YKK2. LUCA.
HOVERGENiHBG056632.
InParanoidiP97797.
KOiK06551.

Enzyme and pathway databases

ReactomeiR-MMU-391160. Signal regulatory protein (SIRP) family interactions.

Miscellaneous databases

EvolutionaryTraceiP97797.
PROiP97797.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000037902.
CleanExiMM_SIRPA.

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_MOUSE
AccessioniPrimary (citable) accession number: P97797
Secondary accession number(s): O08907
, O35924, O88555, O88556, P97796, Q8R559, Q9QX57, Q9WTN4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 28, 2003
Last sequence update: May 1, 1997
Last modified: November 2, 2016
This is version 155 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

3D-structure, Complete proteome, Direct protein sequencing, 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

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.