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

Summary

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: mouse all
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Genomic context

Location:: 20p13

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	20	NC_000020.11 (1894167..1940592)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	20	NC_060944.1 (1924358..1970769)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	20	NC_000020.10 (1874813..1921238)

Chromosome 20 - NC_000020.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Podocyte SIRPalpha reduction aggravates lupus nephritis via promoting T cell inflammatory responses.
Title: Podocyte SIRPα reduction aggravates lupus nephritis via promoting T cell inflammatory responses.
Surfactant protein D prevents mucin overproduction in airway goblet cells via SIRPalpha.
Title: Surfactant protein D prevents mucin overproduction in airway goblet cells via SIRPα.
Anti-tumor effect of PTEN and its effect on inhibition of the bone tumor through the CD47-SIRPalpha signaling pathway.
Title: Anti-tumor effect of PTEN and its effect on inhibition of the bone tumor through the CD47-SIRPα signaling pathway.
A mAb to SIRPalpha downregulates the priming of naive CD4 + T cell in Primary immune thrombocytopenia.
Title: A mAb to SIRPα downregulates the priming of naive CD4 + T cell in Primary immune thrombocytopenia.
SIRP-alpha-IL-6 axis induces immunosuppressive macrophages in non-small-cell lung cancer.
Title: SIRP-alpha-IL-6 axis induces immunosuppressive macrophages in non-small-cell lung cancer.
Clinical Significance of Signal Regulatory Protein Alpha (SIRPalpha) Expression in Hepatocellular Carcinoma.
Title: Clinical Significance of Signal Regulatory Protein Alpha (SIRPα) Expression in Hepatocellular Carcinoma.
Clinical significance of signal regulatory protein alpha and T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain expression in undifferentiated pleomorphic sarcoma.
Title: Clinical significance of signal regulatory protein alpha and T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain expression in undifferentiated pleomorphic sarcoma.
Thrombospondin-1, CD47, and SIRPalpha display cell-specific molecular signatures in human islets and pancreata.
Title: Thrombospondin-1, CD47, and SIRPα display cell-specific molecular signatures in human islets and pancreata.
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.
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.

Submit: New GeneRIF Correction See all GeneRIFs (100)

Phenotypes

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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 EBI GWAS CatalogPubMed
Genome-wide association study of liver enzymes in korean children. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide joint SNP and CNV analysis of aortic root diameter in African Americans: the HyperGEN study. EBI GWAS Catalog EBI GWAS CatalogPubMed
New gene functions in megakaryopoiesis and platelet formation. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

WI-14028 (e-PCR)
- UniSTS:41005

BCD2069 (e-PCR)
- UniSTS:37169

STS-M78966 (e-PCR)
- UniSTS:50492

RH68309 (e-PCR)
- UniSTS:84562

PTPNS1_1575 (e-PCR)
- UniSTS:280942

D20S203E (e-PCR)
- UniSTS:473202

G18068 (e-PCR)
- UniSTS:36226

D20S793 (e-PCR)
- UniSTS:10637

STS-D29515 (e-PCR)
- UniSTS:69535

RH11752 (e-PCR)
- UniSTS:67001

SHGC-31938 (e-PCR)
- UniSTS:29906

D20S1066 (e-PCR)
- UniSTS:63457

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	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
involved_in positive regulation of phagocytosis	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of reactive oxygen species metabolic process	IDA Inferred from Direct Assay 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 more info	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
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

EC 3.1.3.48

NP_001035112.1

EC 3.1.3.48

NP_001317657.1

EC 3.1.3.48

NP_542970.1

EC 3.1.3.48

XP_005260727.1

EC 3.1.3.48

XP_011527475.1

EC 3.1.3.48

XP_024307604.1

EC 3.1.3.48

XP_047295871.1

EC 3.1.3.48

XP_047295872.1

EC 3.1.3.48

XP_047295873.1

EC 3.1.3.48

XP_047295874.1

EC 3.1.3.48

XP_047295875.1

EC 3.1.3.48

XP_047295876.1

EC 3.1.3.48

XP_054179022.1

EC 3.1.3.48

XP_054179023.1

EC 3.1.3.48

XP_054179024.1

EC 3.1.3.48

XP_054179025.1

EC 3.1.3.48

XP_054179026.1

EC 3.1.3.48

XP_054179027.1

EC 3.1.3.48

XP_054179028.1

EC 3.1.3.48

XP_054179029.1

EC 3.1.3.48

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)

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

A2A2E1, A8K411, B2R6C3, O00683, O43799, P78324, Q8N517, Q8TAL8, Q9H0Z2, Q9UDX2, Q9UIJ6, Q9Y4U9

UniProtKB/TrEMBL

B4DP97

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
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

A2A2E1, A8K411, B2R6C3, O00683, O43799, P78324, Q8N517, Q8TAL8, Q9H0Z2, Q9UDX2, Q9UIJ6, Q9Y4U9

UniProtKB/TrEMBL

B4DP97

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
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/TrEMBL

B4DP97

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)
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

A2A2E1, A8K411, B2R6C3, O00683, O43799, P78324, Q8N517, Q8TAL8, Q9H0Z2, Q9UDX2, Q9UIJ6, Q9Y4U9

UniProtKB/TrEMBL

B4DP97

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_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000020.11 Reference GRCh38.p14 Primary Assembly

Range

1894167..1940592

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047439917.1 → XP_047295873.1 tyrosine-protein phosphatase non-receptor type substrate 1 isoform X4
XM_047439919.1 → XP_047295875.1 tyrosine-protein phosphatase non-receptor type substrate 1 isoform X5
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/TrEMBL

B4DP97

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

UniProtKB/TrEMBL

B4DP97

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

UniProtKB/Swiss-Prot

A2A2E1, A8K411, B2R6C3, O00683, O43799, P78324, Q8N517, Q8TAL8, Q9H0Z2, Q9UDX2, Q9UIJ6, Q9Y4U9
XM_047439918.1 → XP_047295874.1 tyrosine-protein phosphatase non-receptor type substrate 1 isoform X4
XM_047439920.1 → XP_047295876.1 tyrosine-protein phosphatase non-receptor type substrate 1 isoform X5
XM_047439915.1 → XP_047295871.1 tyrosine-protein phosphatase non-receptor type substrate 1 isoform X2
XM_011529173.3 → XP_011527475.1 tyrosine-protein phosphatase non-receptor type substrate 1 isoform X2

UniProtKB/TrEMBL

B4DP97

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

NC_060944.1 Alternate T2T-CHM13v2.0

Range

1924358..1970769

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054323051.1 → XP_054179026.1 tyrosine-protein phosphatase non-receptor type substrate 1 isoform X4
XM_054323053.1 → XP_054179028.1 tyrosine-protein phosphatase non-receptor type substrate 1 isoform X5
XM_054323047.1 → XP_054179022.1 tyrosine-protein phosphatase non-receptor type substrate 1 isoform X1
XM_054323052.1 → XP_054179027.1 tyrosine-protein phosphatase non-receptor type substrate 1 isoform X4
XM_054323048.1 → XP_054179023.1 tyrosine-protein phosphatase non-receptor type substrate 1 isoform X1
XM_054323050.1 → XP_054179025.1 tyrosine-protein phosphatase non-receptor type substrate 1 isoform X3
XM_054323054.1 → XP_054179029.1 tyrosine-protein phosphatase non-receptor type substrate 1 isoform X5
XM_054323049.1 → XP_054179024.1 tyrosine-protein phosphatase non-receptor type substrate 1 isoform X2