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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)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini32 – 373342ExtracellularSequence analysisAdd
BLAST
Transmembranei374 – 39421HelicalSequence analysisAdd
BLAST
Topological domaini395 – 511117CytoplasmicSequence analysisAdd
BLAST

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)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3131Add
BLAST
Chaini32 – 513482Tyrosine-protein phosphatase non-receptor type substrate 1PRO_0000014942Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi54 – 541N-linked (GlcNAc...)Sequence analysis
Disulfide bondi55 ↔ 121PROSITE-ProRule annotation
Glycosylationi92 – 921N-linked (GlcNAc...)Sequence analysis
Glycosylationi168 – 1681N-linked (GlcNAc...)Sequence analysis
Disulfide bondi171 ↔ 229PROSITE-ProRule annotation
Glycosylationi180 – 1801N-linked (GlcNAc...)Sequence analysis
Glycosylationi205 – 2051N-linked (GlcNAc...)Sequence analysis
Glycosylationi209 – 2091N-linked (GlcNAc...)Sequence analysis
Glycosylationi246 – 2461N-linked (GlcNAc...)1 Publication
Glycosylationi271 – 2711N-linked (GlcNAc...)Sequence analysis
Disulfide bondi274 ↔ 332PROSITE-ProRule annotation
Glycosylationi293 – 2931N-linked (GlcNAc...)Sequence analysis
Glycosylationi302 – 3021N-linked (GlcNAc...)Sequence analysis
Glycosylationi312 – 3121N-linked (GlcNAc...)Sequence analysis
Glycosylationi320 – 3201N-linked (GlcNAc...)Sequence analysis
Glycosylationi345 – 3451N-linked (GlcNAc...)Sequence analysis
Glycosylationi367 – 3671N-linked (GlcNAc...)Sequence analysis
Modified residuei440 – 4401Phosphotyrosine; by Tyr-kinasesSequence analysis
Modified residuei464 – 4641Phosphotyrosine; by Tyr-kinasesSequence analysis
Modified residuei481 – 4811Phosphotyrosine; by Tyr-kinasesBy similarity
Modified residuei505 – 5051Phosphotyrosine; by Tyr-kinasesBy similarity

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.
PhosphoSiteiP97797.

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 interactions.
IntActiP97797. 3 interactions.
MINTiMINT-1668886.
STRINGi10090.ENSMUSP00000099491.

Structurei

Secondary structure

1
513
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi40 – 456Combined sources
Beta strandi51 – 533Combined sources
Beta strandi56 – 583Combined sources
Beta strandi66 – 738Combined sources
Beta strandi77 – 826Combined sources
Turni87 – 893Combined sources
Beta strandi92 – 954Combined sources
Beta strandi98 – 1003Combined sources
Beta strandi106 – 1083Combined sources
Helixi113 – 1153Combined sources
Beta strandi117 – 1259Combined sources
Beta strandi128 – 1314Combined sources
Beta strandi133 – 1375Combined sources
Beta strandi141 – 1455Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2YZ1X-ray1.40A/B32-146[»]
ProteinModelPortaliP97797.
SMRiP97797. Positions 32-346.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP97797.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini32 – 137106Ig-like V-typeAdd
BLAST
Domaini149 – 248100Ig-like C1-type 1Add
BLAST
Domaini255 – 34389Ig-like C1-type 2Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi440 – 4434SH2-bindingSequence analysis
Motifi450 – 4556SH3-bindingSequence analysis
Motifi464 – 4674SH2-bindingSequence analysis
Motifi481 – 4844SH2-bindingSequence analysis
Motifi505 – 5084SH2-bindingSequence analysis

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti6 – 61Missing in CAA71375 (Ref. 7) Curated
Sequence conflicti10 – 101R → L in AAB92591 (PubMed:9348339).Curated
Sequence conflicti32 – 343KEL → TEV in BAA20376 (PubMed:9073522).Curated
Sequence conflicti52 – 521V → I in BAA20376 (PubMed:9073522).Curated
Sequence conflicti57 – 571L → V in BAA20376 (PubMed:9073522).Curated
Sequence conflicti74 – 774QSRL → KAGC in CAA71375 (Ref. 7) Curated
Sequence conflicti126 – 1261K → R in BAA20376 (PubMed:9073522).Curated
Sequence conflicti126 – 1261K → R in AAB92591 (PubMed:9348339).Curated
Sequence conflicti154 – 1563VSG → YPV in CAA71375 (Ref. 7) Curated
Sequence conflicti164 – 1641D → Y in CAA71375 (Ref. 7) Curated
Sequence conflicti263 – 2631S → P in BAA20376 (PubMed:9073522).Curated
Sequence conflicti276 – 2761A → D in CAA71375 (Ref. 7) Curated
Sequence conflicti448 – 4492EK → RR in CAA71375 (Ref. 7) Curated
Sequence conflicti454 – 4585RAPEP → GSLEFL in CAA71375 (Ref. 7) Curated
Sequence conflicti490 – 4901S → N in BAA20376 (PubMed:9073522).Curated
Sequence conflicti490 – 4901S → N in AAB92591 (PubMed:9348339).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti29 – 291V → A in strain: BALB/c, C57BL/6 and ILS. 5 Publications
Natural varianti67 – 671K → R in strain: BALB/c, C57BL/6 and ILS. 4 Publications
Natural varianti74 – 741Q → P in strain: C57BL/6 and ILS. 3 Publications
Natural varianti83 – 831T → A in strain: C57BL/6 and ILS. 3 Publications
Natural varianti86 – 872HF → YV in strain: C57BL/6 and ILS.
Natural varianti90 – 901V → I in strain: C57BL/6 and ILS. 3 Publications
Natural varianti91 – 911T → R in strain: BALB/c, C57BL/6 and ILS. 5 Publications
Natural varianti96 – 961A → T in strain: BALB/c, C57BL/6 and ILS. 5 Publications
Natural varianti114 – 1141E → A in strain: C57BL/6 and ILS. 3 Publications
Natural varianti118 – 1181T → I in strain: C57BL/6 and ILS. 3 Publications
Natural varianti128 – 1281P → S in strain: BALB/c, C57BL/6 and ILS. 5 Publications
Natural varianti194 – 1941H → P in strain: BALB/c, C57BL/6 and ILS. 5 Publications
Natural varianti224 – 2241H → N in strain: BALB/c, C57BL/6 and ILS. 4 Publications
Natural varianti351 – 3511L → F in strain: C57BL/6 and ILS. 3 Publications
Natural varianti365 – 3651G → D in strain: C57BL/6 and ILS. 3 Publications

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei147 – 364218Missing in isoform 3. 3 PublicationsVSP_007031Add
BLAST
Alternative sequencei425 – 4284Missing in isoform 2. 5 PublicationsVSP_007032

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.
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.
UniGeneiMm.1682.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2YZ1X-ray1.40A/B32-146[»]
ProteinModelPortaliP97797.
SMRiP97797. Positions 32-346.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

PTM databases

iPTMnetiP97797.
PhosphoSiteiP97797.

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: September 7, 2016
This is version 153 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.