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Reviewed, UniProtKB/Swiss-Prot P78324 (SHPS1_HUMAN)

Last modified November 25, 2008. Version 95. Feed History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Tyrosine-protein phosphatase non-receptor type substrate 1
      Short name=SHP substrate 1
      Short name=SHPS-1
Alternative name(s):
    Inhibitory receptor SHPS-1
    Signal-regulatory protein alpha-1
      Short name=Sirp-alpha-1
    Sirp-alpha-2
    Sirp-alpha-3
    MyD-1 antigen
    Brain Ig-like molecule with tyrosine-based activation motifs
      Short name=Bit
    Macrophage fusion receptor
    p84
    CD172 antigen-like family member A
    CD_antigen=CD172a
Gene names
Name: SIRPA
Synonyms: BIT, MFR, MYD1, PTPNS1, SHPS1, SIRP
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length503 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

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 By similarity. 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.

Subunit structure

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

Subcellular location

Membrane; Single-pass type I membrane protein.

Tissue specificity

Ubiquitous. Highly expressed in brain. Detected on myeloid cells, but not T-cells. Detected at lower levels in heart, placenta, lung, testis, ovary, colon, liver, small intestine, prostate, spleen, kidney, skeletal muscle and pancreas.

Post-translational modification

N-glycosylated.

Phosphorylated on tyrosine residues in response to stimulation with EGF, growth hormone, insulin and PDGF. Dephosphorylated by PTPN11.

Sequence similarities

Contains 2 Ig-like C1-type (immunoglobulin-like) domains.

Contains 1 Ig-like V-type (immunoglobulin-like) domain.

Ontologies

Keywords

   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainImmunoglobulin domain
Repeat
SH3-binding
Signal
Transmembrane
   PTMGlycoprotein
Phosphoprotein
   Technical term3D-structure

Gene Ontology (GO)

   Biological processcell adhesion Ref.1

Traceable author statement. Source: ProtInc

   Cellular componentintegral to membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane Ref.1

Traceable author statement. Source: ProtInc

   Molecular functionSH3 domain binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P78324-1)

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.
Isoform 2 (identifier: P78324-2)

The sequence of this isoform differs from the canonical sequence as follows:
     421-421: Q → QVQSL
Notes: No experimental confirmation available.
Isoform 3 (identifier: P78324-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-101: Missing.
Notes: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3030 Potential
Chain31 – 503473Tyrosine-protein phosphatase non-receptor type substrate 1
PRO_0000014941

Regions

Topological domain27 – 372346Extracellular Potential
Transmembrane373 – 39321 Potential
Topological domain394 – 503110Cytoplasmic Potential
Domain32 – 137106Ig-like V-type
Domain147 – 246100Ig-like C1-type 1
Domain253 – 34795Ig-like C1-type 2
Motif428 – 4314SH2-binding Potential
Motif438 – 4436SH3-binding Potential
Motif452 – 4554SH2-binding Potential
Motif469 – 4724SH2-binding Potential
Motif495 – 4984SH2-binding Potential

Amino acid modifications

Modified residue4281Phosphotyrosine; by Tyr-kinases Potential
Modified residue4521Phosphotyrosine; by Tyr-kinases Potential
Modified residue4691Phosphotyrosine; by Tyr-kinases By similarity
Modified residue4951Phosphotyrosine; by Tyr-kinases By similarity
Glycosylation2441N-linked (GlcNAc...)
Glycosylation2691N-linked (GlcNAc...) Potential
Glycosylation2911N-linked (GlcNAc...) Potential
Glycosylation3181N-linked (GlcNAc...) Potential
Disulfide bond55 ↔ 121
Disulfide bond169 ↔ 227 Potential
Disulfide bond272 ↔ 330 Potential

Natural variations

Alternative sequence1 – 101101Missing in isoform 3.
VSP_007029
Alternative sequence4211Q → QVQSL in isoform 2.
VSP_007030
Natural variant6 – 72PA → RS
VAR_015462
Natural variant201A → P
VAR_015463
Natural variant401D → E
VAR_015464
Natural variant441S → L
VAR_015465
Natural variant501S → T
VAR_015466
Natural variant521I → A Requires 2 nucleotide substitutions.
VAR_015467
Natural variant521I → T
VAR_015468
Natural variant541H → E Requires 2 nucleotide substitutions.
VAR_015469
Natural variant541H → R
VAR_015470
Natural variant571V → A
VAR_015471
Natural variant611I → N
VAR_015472
Natural variant681W → R
VAR_015473
Natural variant751A → G: dbSNP rs1057114.
VAR_015474
Natural variant771E → K
VAR_015475
Natural variant811N → H
VAR_015477
Natural variant951E → D
VAR_015478
Natural variant961S → L
VAR_015479
Natural variant1001E → N Requires 2 nucleotide substitutions.
VAR_015480
Natural variant1001E → T Requires 2 nucleotide substitutions.
VAR_015481
Natural variant1071S → C
VAR_015482
Natural variant1071S → R
VAR_015483
Natural variant1091S → G
VAR_015484
Natural variant1251R → Q
VAR_015485
Natural variant1311T → V Requires 2 nucleotide substitutions.
VAR_015486
Natural variant1331F → L
VAR_015487
Natural variant1621Q → D Requires 2 nucleotide substitutions.
VAR_015488
Natural variant1801T → S
VAR_015489
Natural variant1891E → Q
VAR_015490
Natural variant200 – 2012VG → AR
VAR_015491
Natural variant2131K → N
VAR_015492
Natural variant2191E → G
VAR_015493
Natural variant2211V → I
VAR_015494
Natural variant2351Q → R
VAR_015495
Natural variant238 – 2392PL → SF
VAR_015496
Natural variant2501R → Q
VAR_015497
Natural variant2601Q → L
VAR_015498
Natural variant2621V → M
VAR_015499
Natural variant2701V → I
VAR_015500
Natural variant2751R → T
VAR_015501
Natural variant3011V → L: dbSNP rs2422666.
VAR_015502
Natural variant3381P → S
VAR_015503
Natural variant3521P → L
VAR_015504
Natural variant3561G → S
VAR_015505
Natural variant3661S → P
VAR_015506
Natural variant3691R → Q
VAR_015507
Natural variant3881A → E
VAR_015508
Natural variant4421Q → R
VAR_015509
Natural variant4591P → L
VAR_015510
Natural variant4851A → L Requires 2 nucleotide substitutions.
VAR_015511
Natural variant4901P → L
VAR_015512

Experimental info

Sequence conflict1301D → DD in CAC12723 and CAB38874. Ref.3 Ref.4 Ref.5
Sequence conflict1301D → DD in AAH33092. Ref.6
Sequence conflict2581T → I in CAA71944. Ref.3
Sequence conflict4181E → K in AAF19260. Ref.5
Sequence conflict4841P → L in AAF19260. Ref.5
Sequence conflict4981V → I in AAF19260. Ref.5
Sequence conflict5021R → K in CAA71944. Ref.3

Secondary structure

......................... 503
Helix Strand Turn

Details...