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SIRPA signal regulatory protein alpha [ Homo sapiens (human) ]

Gene ID: 140885, updated on 21-Mar-2023

Summary

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Official Symbol
SIRPAprovided by HGNC
Official Full Name
signal regulatory protein alphaprovided by HGNC
Primary source
HGNC:HGNC:9662
See related
Ensembl:ENSG00000198053 MIM:602461; AllianceGenome:HGNC:9662
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
BIT; MFR; P84; SIRP; MYD-1; SHPS1; CD172A; PTPNS1
Summary
The protein encoded by this gene is a member of the signal-regulatory-protein (SIRP) family, and also belongs to the immunoglobulin superfamily. SIRP family members are receptor-type transmembrane glycoproteins known to be involved in the negative regulation of receptor tyrosine kinase-coupled signaling processes. This protein can be phosphorylated by tyrosine kinases. The phospho-tyrosine residues of this PTP have been shown to recruit SH2 domain containing tyrosine phosphatases (PTP), and serve as substrates of PTPs. This protein was found to participate in signal transduction mediated by various growth factor receptors. CD47 has been demonstrated to be a ligand for this receptor protein. This gene and its product share very high similarity with several other members of the SIRP family. These related genes are located in close proximity to each other on chromosome 20p13. Multiple alternatively spliced transcript variants have been determined for this gene. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in brain (RPKM 71.2), appendix (RPKM 27.2) and 23 other tissues See more
Orthologs
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Genomic context

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See SIRPA in Genome Data Viewer
Location:
20p13
Exon count:
12
Annotation release Status Assembly Chr Location
RS_2023_03 current GRCh38.p14 (GCF_000001405.40) 20 NC_000020.11 (1894167..1940592)
RS_2023_03 current T2T-CHM13v2.0 (GCF_009914755.1) 20 NC_060944.1 (1924358..1970769)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 20 NC_000020.10 (1874813..1921238)

Chromosome 20 - NC_000020.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105372501 Neighboring gene uncharacterized LOC124904857 Neighboring gene uncharacterized LOC107984088 Neighboring gene PDYN antisense RNA 1 Neighboring gene prodynorphin Neighboring gene Sharpr-MPRA regulatory region 7514

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. High SIRPA Expression Predicts Poor Prognosis and Correlates with Immune Infiltrates in Patients with Esophageal Carcinoma. Tao K, et al. J Healthc Eng, 2022. PMID 35222883, Free PMC Article
  2. Impact of SIRPα polymorphism on transplant outcomes in HLA-identical living donor kidney transplantation. Garcia-Sanchez C, et al. Clin Transplant, 2021 Sep. PMID 34180101
  3. Clinical significance of signal regulatory protein alpha (SIRPα) expression in esophageal squamous cell carcinoma. Koga N, et al. Cancer Sci, 2021 Aug. PMID 34009732, Free PMC Article
  4. SIRPα expression delineates subsets of intratumoral monocyte/macrophages with different functional and prognostic impact in follicular lymphoma. Chen YP, et al. Blood Cancer J, 2019 Oct 14. PMID 31611550, Free PMC Article
  5. TTI-621 (SIRPαFc), a CD47-blocking cancer immunotherapeutic, triggers phagocytosis of lymphoma cells by multiple polarized macrophage subsets. Lin GHY, et al. PLoS One, 2017. PMID 29084248, Free PMC Article

See all (146) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Loss of myeloid cell-specific SIRPalpha, but not CD47, attenuates inflammation and suppresses atherosclerosis.
    Title: Loss of myeloid cell-specific SIRPα, but not CD47, attenuates inflammation and suppresses atherosclerosis.
  2. SIRPalpha maintains macrophage homeostasis by interacting with PTK2B kinase in Mycobacterium tuberculosis infection and through autophagy and necroptosis.
    Title: SIRPα maintains macrophage homeostasis by interacting with PTK2B kinase in Mycobacterium tuberculosis infection and through autophagy and necroptosis.
  3. CD47-SIRPalpha Controls ADCC Killing of Primary T Cells by PMN Through a Combination of Trogocytosis and NADPH Oxidase Activation.
    Title: CD47-SIRPα Controls ADCC Killing of Primary T Cells by PMN Through a Combination of Trogocytosis and NADPH Oxidase Activation.
  4. High SIRPA Expression Predicts Poor Prognosis and Correlates with Immune Infiltrates in Patients with Esophageal Carcinoma.
    Title: High SIRPA Expression Predicts Poor Prognosis and Correlates with Immune Infiltrates in Patients with Esophageal Carcinoma.
  5. XBP1 regulates the protumoral function of tumor-associated macrophages in human colorectal cancer.
    Title: XBP1 regulates the protumoral function of tumor-associated macrophages in human colorectal cancer.
  6. CD47/SIRPalpha pathway mediates cancer immune escape and immunotherapy.
    Title: CD47/SIRPα pathway mediates cancer immune escape and immunotherapy.
  7. Imaging of Glioblastoma Tumor-Associated Myeloid Cells Using Nanobodies Targeting Signal Regulatory Protein Alpha.
    Title: Imaging of Glioblastoma Tumor-Associated Myeloid Cells Using Nanobodies Targeting Signal Regulatory Protein Alpha.
  8. Impact of SIRPalpha polymorphism on transplant outcomes in HLA-identical living donor kidney transplantation.
    Title: Impact of SIRPα polymorphism on transplant outcomes in HLA-identical living donor kidney transplantation.
  9. Clinical significance of signal regulatory protein alpha (SIRPalpha) expression in esophageal squamous cell carcinoma.
    Title: Clinical significance of signal regulatory protein alpha (SIRPα) expression in esophageal squamous cell carcinoma.
  10. TSP1-CD47-SIRPalpha signaling facilitates the development of endometriosis by mediating the survival of ectopic endometrium.
    Title: TSP1-CD47-SIRPα signaling facilitates the development of endometriosis by mediating the survival of ectopic endometrium.
Submit: New GeneRIF Correction See all GeneRIFs (93)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium.
EBI GWAS Catalog
Genome-wide association study of liver enzymes in korean children.
EBI GWAS Catalog
Genome-wide joint SNP and CNV analysis of aortic root diameter in African Americans: the HyperGEN study.
EBI GWAS Catalog
New gene functions in megakaryopoiesis and platelet formation.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables GTPase regulator activity ISS
Inferred from Sequence or Structural Similarity
more info
  
enables SH3 domain binding IEA
Inferred from Electronic Annotation
more info
  
enables cell-cell adhesion mediator activity IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein antigen binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein binding involved in heterotypic cell-cell adhesion ISS
Inferred from Sequence or Structural Similarity
more info
  
enables protein phosphatase binding ISS
Inferred from Sequence or Structural Similarity
more info
  
enables protein tyrosine kinase binding ISS
Inferred from Sequence or Structural Similarity
more info
  
Process Evidence Code Pubs
involved_in cell adhesion TAS
Traceable Author Statement
more info
 PubMed 
involved_in cell migration ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in cellular response to hydrogen peroxide ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in cellular response to interleukin-1 ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in cellular response to interleukin-12 IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cellular response to lipopolysaccharide ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in cellular response to type II interferon ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in heterotypic cell-cell adhesion IEA
Inferred from Electronic Annotation
more info
  
involved_in monocyte extravasation ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative regulation of ERK1 and ERK2 cascade ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative regulation of I-kappaB phosphorylation ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative regulation of JNK cascade ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative regulation of chemokine (C-C motif) ligand 5 production ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative regulation of cytokine production involved in inflammatory response ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative regulation of inflammatory response IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of interferon-beta production ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative regulation of interleukin-6 production ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative regulation of macrophage inflammatory protein 1 alpha production ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative regulation of nitric oxide biosynthetic process ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative regulation of phagocytosis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative regulation of protein phosphorylation ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative regulation of tumor necrosis factor production ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of T cell activation IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in positive regulation of phagocytosis IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in regulation of gene expression IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of interleukin-1 beta production ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of interleukin-6 production ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of nitric oxide biosynthetic process ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of tumor necrosis factor production IGI
Inferred from Genetic Interaction
more info
 PubMed 
involved_in regulation of tumor necrosis factor production ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of type II interferon production IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
located_in cell surface IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cell surface ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in cell surface TAS
Traceable Author Statement
more info
 PubMed 
located_in extracellular exosome HDA PubMed 
located_in ficolin-1-rich granule membrane TAS
Traceable Author Statement
more info
  
located_in membrane TAS
Traceable Author Statement
more info
 PubMed 
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
  
located_in tertiary granule membrane TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
tyrosine-protein phosphatase non-receptor type substrate 1
Names
CD172 antigen-like family member A
brain-immunoglobulin-like molecule with tyrosine-based activation motifs
inhibitory receptor SHPS-1
macrophage fusion receptor
myd-1 antigen
tyrosine phosphatase SHP substrate 1
NP_001035111.1
NP_001035112.1
NP_001317657.1
NP_542970.1
XP_005260727.1
XP_011527475.1
XP_024307604.1
XP_047295871.1
XP_047295872.1
XP_047295873.1
XP_047295874.1
XP_047295875.1
XP_047295876.1
XP_054179022.1
XP_054179023.1
XP_054179024.1
XP_054179025.1
XP_054179026.1
XP_054179027.1
XP_054179028.1
XP_054179029.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001040022.1 → NP_001035111.1  tyrosine-protein phosphatase non-receptor type substrate 1 isoform 1 precursor

    See identical proteins and their annotated locations for NP_001035111.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) uses an alternate, in-frame, splice donor site in the 3' coding region compared to variant 4. This variant encodes a shorter protein (isoform 1) compared to isoform 2. Variants 1, 2, and 3 encode the same protein (isoform 1).
    Source sequence(s)
    AL034562, BC075849, DA471662, DN989886
    Consensus CDS
    CCDS13022.1
    UniProtKB/Swiss-Prot
    P78324, Q9Y4U9
    Related
    ENSP00000382941.4, ENST00000400068.7
    Conserved Domains (4) summary
    cd00098
    Location:266 → 339
    IgC; Immunoglobulin Constant domain
    smart00410
    Location:41 → 144
    IG_like; Immunoglobulin like
    pfam07686
    Location:38 → 145
    V-set; Immunoglobulin V-set domain
    cl11960
    Location:143 → 254
    Ig; Immunoglobulin domain

  2. NM_001040023.2 → NP_001035112.1  tyrosine-protein phosphatase non-receptor type substrate 1 isoform 1 precursor

    See identical proteins and their annotated locations for NP_001035112.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR and uses an alternate, in-frame, splice donor site in the 3' coding region compared to variant 4. This variant encodes a shorter protein (isoform 1) compared to isoform 2. Variants 1, 2, and 3 encode the same protein (isoform 1).
    Source sequence(s)
    AL034562, BC038510, DN989886
    Consensus CDS
    CCDS13022.1
    UniProtKB/Swiss-Prot
    P78324, Q9Y4U9
    Related
    ENSP00000351621.4, ENST00000358771.5
    Conserved Domains (4) summary
    cd00098
    Location:266 → 339
    IgC; Immunoglobulin Constant domain
    smart00410
    Location:41 → 144
    IG_like; Immunoglobulin like
    pfam07686
    Location:38 → 145
    V-set; Immunoglobulin V-set domain
    cl11960
    Location:143 → 254
    Ig; Immunoglobulin domain

  3. NM_001330728.1 → NP_001317657.1  tyrosine-protein phosphatase non-receptor type substrate 1 isoform 2 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) encodes the longer protein (isoform 2).
    Source sequence(s)
    AL034562, BC026692, BC033092, DA471662, DN989886
    Consensus CDS
    CCDS82593.1
    UniProtKB/Swiss-Prot
    P78324
    Related
    ENSP00000478763.1, ENST00000622179.4
    Conserved Domains (3) summary
    cd05772
    Location:147 → 250
    IgC_SIRP_domain_2; Signal-regulatory protein (SIRP) immunoglobulin-like domain 2
    cd16085
    Location:252 → 355
    IgC_SIRP_domain_3; Signal-regulatory protein (SIRP) immunoglobulin-like domain 3
    cd16097
    Location:35 → 145
    IgV_SIRP; Immunoglobulin (Ig)-like domain of Signal-Regulatory Protein (SIRP)

  4. NM_080792.3 → NP_542970.1  tyrosine-protein phosphatase non-receptor type substrate 1 isoform 1 precursor

    See identical proteins and their annotated locations for NP_542970.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR and uses an alternate, in-frame, splice donor site in the 3' coding region compared to variant 4. This variant encodes a shorter protein (isoform 1) compared to isoform 2. Variants 1, 2, and 3 encode the same protein (isoform 1).
    Source sequence(s)
    AB023430, AL034562, AL117335
    Consensus CDS
    CCDS13022.1
    UniProtKB/Swiss-Prot
    P78324, Q9Y4U9
    Related
    ENSP00000348307.3, ENST00000356025.7
    Conserved Domains (4) summary
    cd00098
    Location:266 → 339
    IgC; Immunoglobulin Constant domain
    smart00410
    Location:41 → 144
    IG_like; Immunoglobulin like
    pfam07686
    Location:38 → 145
    V-set; Immunoglobulin V-set domain
    cl11960
    Location:143 → 254
    Ig; Immunoglobulin domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_03

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000020.11 Reference GRCh38.p14 Primary Assembly

    Range
    1894167..1940592
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047439917.1 → XP_047295873.1  tyrosine-protein phosphatase non-receptor type substrate 1 isoform X4

  2. XM_047439919.1 → XP_047295875.1  tyrosine-protein phosphatase non-receptor type substrate 1 isoform X5

  3. XM_005260670.4 → XP_005260727.1  tyrosine-protein phosphatase non-receptor type substrate 1 isoform X1

    See identical proteins and their annotated locations for XP_005260727.1

    UniProtKB/Swiss-Prot
    P78324
    Conserved Domains (3) summary
    cd05772
    Location:147 → 250
    IgC_SIRP_domain_2; Signal-regulatory protein (SIRP) immunoglobulin-like domain 2
    cd16085
    Location:252 → 355
    IgC_SIRP_domain_3; Signal-regulatory protein (SIRP) immunoglobulin-like domain 3
    cd16097
    Location:35 → 145
    IgV_SIRP; Immunoglobulin (Ig)-like domain of Signal-Regulatory Protein (SIRP)

  4. XM_024451836.2 → XP_024307604.1  tyrosine-protein phosphatase non-receptor type substrate 1 isoform X1

    Conserved Domains (3) summary
    cd05772
    Location:147 → 250
    IgC_SIRP_domain_2; Signal-regulatory protein (SIRP) immunoglobulin-like domain 2
    cd16085
    Location:252 → 355
    IgC_SIRP_domain_3; Signal-regulatory protein (SIRP) immunoglobulin-like domain 3
    cd16097
    Location:35 → 145
    IgV_SIRP; Immunoglobulin (Ig)-like domain of Signal-Regulatory Protein (SIRP)

  5. XM_047439916.1 → XP_047295872.1  tyrosine-protein phosphatase non-receptor type substrate 1 isoform X3

    UniProtKB/Swiss-Prot
    Q9Y4U9

  6. XM_047439918.1 → XP_047295874.1  tyrosine-protein phosphatase non-receptor type substrate 1 isoform X4

  7. XM_047439920.1 → XP_047295876.1  tyrosine-protein phosphatase non-receptor type substrate 1 isoform X5

  8. XM_047439915.1 → XP_047295871.1  tyrosine-protein phosphatase non-receptor type substrate 1 isoform X2

  9. XM_011529173.3 → XP_011527475.1  tyrosine-protein phosphatase non-receptor type substrate 1 isoform X2

    Conserved Domains (4) summary
    cd00098
    Location:266 → 339
    IgC; Immunoglobulin Constant domain
    smart00410
    Location:41 → 122
    IG_like; Immunoglobulin like
    pfam07686
    Location:38 → 145
    V-set; Immunoglobulin V-set domain
    cl11960
    Location:143 → 254
    Ig; Immunoglobulin domain

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060944.1 Alternate T2T-CHM13v2.0

    Range
    1924358..1970769
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054323051.1 → XP_054179026.1  tyrosine-protein phosphatase non-receptor type substrate 1 isoform X4

  2. XM_054323053.1 → XP_054179028.1  tyrosine-protein phosphatase non-receptor type substrate 1 isoform X5

  3. XM_054323047.1 → XP_054179022.1  tyrosine-protein phosphatase non-receptor type substrate 1 isoform X1

  4. XM_054323052.1 → XP_054179027.1  tyrosine-protein phosphatase non-receptor type substrate 1 isoform X4

  5. XM_054323048.1 → XP_054179023.1  tyrosine-protein phosphatase non-receptor type substrate 1 isoform X1

  6. XM_054323050.1 → XP_054179025.1  tyrosine-protein phosphatase non-receptor type substrate 1 isoform X3

  7. XM_054323054.1 → XP_054179029.1  tyrosine-protein phosphatase non-receptor type substrate 1 isoform X5

  8. XM_054323049.1 → XP_054179024.1  tyrosine-protein phosphatase non-receptor type substrate 1 isoform X2

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P78324.2 GenPept UniProtKB/Swiss-Prot:P78324

Gene LinkOut

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