Browse SIRPA

Summary
SymbolSIRPA
Namesignal-regulatory protein alpha
Aliases SHPS1; SIRP; MYD-1; BIT; SHPS-1; SIRPalpha; CD172a; SIRPalpha2; MFR; SIRP-ALPHA-1; PTPNS1; protein tyrosine ......
Chromosomal Location20p13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Membrane; Single-pass type I membrane protein.
Domain PF07654 Immunoglobulin C1-set domain
PF07686 Immunoglobulin V-set domain
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.

> Gene Ontology
 
Biological Process GO:0050900 leukocyte migration
Molecular Function GO:0017124 SH3 domain binding
Cellular Component -
> KEGG and Reactome Pathway
 
KEGG hsa04380 Osteoclast differentiation
Reactome R-HSA-202733: Cell surface interactions at the vascular wall
R-HSA-1500931: Cell-Cell communication
R-HSA-109582: Hemostasis
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-6798695: Neutrophil degranulation
R-HSA-391160: Signal regulatory protein (SIRP) family interactions
Summary
SymbolSIRPA
Namesignal-regulatory protein alpha
Aliases SHPS1; SIRP; MYD-1; BIT; SHPS-1; SIRPalpha; CD172a; SIRPalpha2; MFR; SIRP-ALPHA-1; PTPNS1; protein tyrosine ......
Chromosomal Location20p13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between SIRPA and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between SIRPA and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
25697354Lung CarcinomaInhibit immunityExogenous treatment of TSP-1 may be able to suppress the CD47-mediated tumor immune escape by disrupting the CD47-SIRP-a interaction. With the increasing surface expression of CD47, this suppression effect may be even more obvious in immune-selected cells. These findings prove that the TSP-1/CD47/SIRP-α signal axis is important to the evolution of tumor cells in the microenvironment of immunotherapy and identify thrombospondin-1 as a key signal with therapeutic benefits in overcoming long term relapse, providing new evidence for the clinical promise of cancer vaccination.
29473266Burkitt LymphomaInhibit immunityWith the use of Rag2-/- γc-/- mice harboring a transgene for human SIRPα under the control of human regulatory elements (hSIRPα-DKO mice), we here show that a blocking Ab to human SIRPα significantly enhanced the ADCP activity of macrophages derived from these mice for human cancer cells. The anti-human SIRPα Ab also markedly enhanced the inhibitory effect of rituximab on the growth of tumors formed by Raji cells in hSIRPα-DKO mice.
22945919Acute Myeloid LeukemiaInhibit immunity; Candidate for immunotherapy targetDisruption of SIRPα signaling in macrophages eliminates human acute myeloid leukemia stem cells in xenografts. In this study, we report that leukemia stem cell function in xenotransplant models of acute myeloid leukemia (AML) depends on SIRPα-mediated inhibition of macrophages through engagement with its ligand CD47. These findings support the development of therapeutics that antagonize SIRPα signaling to enhance macrophage-mediated elimination of AML.
Summary
SymbolSIRPA
Namesignal-regulatory protein alpha
Aliases SHPS1; SIRP; MYD-1; BIT; SHPS-1; SIRPalpha; CD172a; SIRPalpha2; MFR; SIRP-ALPHA-1; PTPNS1; protein tyrosine ......
Chromosomal Location20p13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of SIRPA in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolSIRPA
Namesignal-regulatory protein alpha
Aliases SHPS1; SIRP; MYD-1; BIT; SHPS-1; SIRPalpha; CD172a; SIRPalpha2; MFR; SIRP-ALPHA-1; PTPNS1; protein tyrosine ......
Chromosomal Location20p13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of SIRPA in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.8570.0109
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)651.4420.576
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.4290.822
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.3410.41
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.5540.815
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.0690.982
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.0270.948
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.0180.993
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.0860.971
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.530.792
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.0040.736
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.3420.0236
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of SIRPA in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14177.107.10.452
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 103100101
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27730001
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27590001
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91606.2-6.21
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47014.3-14.31
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolSIRPA
Namesignal-regulatory protein alpha
Aliases SHPS1; SIRP; MYD-1; BIT; SHPS-1; SIRPalpha; CD172a; SIRPalpha2; MFR; SIRP-ALPHA-1; PTPNS1; protein tyrosine ......
Chromosomal Location20p13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of SIRPA. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolSIRPA
Namesignal-regulatory protein alpha
Aliases SHPS1; SIRP; MYD-1; BIT; SHPS-1; SIRPalpha; CD172a; SIRPalpha2; MFR; SIRP-ALPHA-1; PTPNS1; protein tyrosine ......
Chromosomal Location20p13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of SIRPA. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by SIRPA.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolSIRPA
Namesignal-regulatory protein alpha
Aliases SHPS1; SIRP; MYD-1; BIT; SHPS-1; SIRPalpha; CD172a; SIRPalpha2; MFR; SIRP-ALPHA-1; PTPNS1; protein tyrosine ......
Chromosomal Location20p13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of SIRPA. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolSIRPA
Namesignal-regulatory protein alpha
Aliases SHPS1; SIRP; MYD-1; BIT; SHPS-1; SIRPalpha; CD172a; SIRPalpha2; MFR; SIRP-ALPHA-1; PTPNS1; protein tyrosine ......
Chromosomal Location20p13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of SIRPA expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolSIRPA
Namesignal-regulatory protein alpha
Aliases SHPS1; SIRP; MYD-1; BIT; SHPS-1; SIRPalpha; CD172a; SIRPalpha2; MFR; SIRP-ALPHA-1; PTPNS1; protein tyrosine ......
Chromosomal Location20p13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between SIRPA and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolSIRPA
Namesignal-regulatory protein alpha
Aliases SHPS1; SIRP; MYD-1; BIT; SHPS-1; SIRPalpha; CD172a; SIRPalpha2; MFR; SIRP-ALPHA-1; PTPNS1; protein tyrosine ......
Chromosomal Location20p13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting SIRPA collected from DrugBank database.
> Drugs from DrugBank database
 

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