TISIDB

Summary
Symbol	SIRPA
Name	signal-regulatory protein alpha
Aliases	SHPS1; SIRP; MYD-1; BIT; SHPS-1; SIRPalpha; CD172a; SIRPalpha2; MFR; SIRP-ALPHA-1; PTPNS1; protein tyrosine ......
Chromosomal Location	20p13
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 [ TOP ]
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 [ TOP ]
Biological Process	GO:0050900 leukocyte migration
Molecular Function	GO:0017124 SH3 domain binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
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
Symbol	SIRPA
Name	signal-regulatory protein alpha
Aliases	SHPS1; SIRP; MYD-1; BIT; SHPS-1; SIRPalpha; CD172a; SIRPalpha2; MFR; SIRP-ALPHA-1; PTPNS1; protein tyrosine ......
Chromosomal Location	20p13
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

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Literatures describing the relation between SIRPA and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
25697354	Lung Carcinoma	Inhibit immunity	Exogenous 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.
29473266	Burkitt Lymphoma	Inhibit immunity	With 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.
22945919	Acute Myeloid Leukemia	Inhibit immunity; Candidate for immunotherapy target	Disruption 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
Symbol	SIRPA
Name	signal-regulatory protein alpha
Aliases	SHPS1; SIRP; MYD-1; BIT; SHPS-1; SIRPalpha; CD172a; SIRPalpha2; MFR; SIRP-ALPHA-1; PTPNS1; protein tyrosine ......
Chromosomal Location	20p13
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

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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
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	SIRPA
Name	signal-regulatory protein alpha
Aliases	SHPS1; SIRP; MYD-1; BIT; SHPS-1; SIRPalpha; CD172a; SIRPalpha2; MFR; SIRP-ALPHA-1; PTPNS1; protein tyrosine ......
Chromosomal Location	20p13
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

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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
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.857	0.0109
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	1.442	0.576
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.429	0.822
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.341	0.41
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.554	0.815
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.069	0.982
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.027	0.948
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.018	0.993
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.086	0.971
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.53	0.792
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	1.004	0.736
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.342	0.0236

> Mutation difference between responders and non-responders

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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
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	7.1	0	7.1	0.452
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	0	10	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	0	0	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	0	0	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	6.2	-6.2	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	14.3	-14.3	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	SIRPA
Name	signal-regulatory protein alpha
Aliases	SHPS1; SIRP; MYD-1; BIT; SHPS-1; SIRPalpha; CD172a; SIRPalpha2; MFR; SIRP-ALPHA-1; PTPNS1; protein tyrosine ......
Chromosomal Location	20p13
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 [ TOP ]

Summary
Symbol	SIRPA
Name	signal-regulatory protein alpha
Aliases	SHPS1; SIRP; MYD-1; BIT; SHPS-1; SIRPalpha; CD172a; SIRPalpha2; MFR; SIRP-ALPHA-1; PTPNS1; protein tyrosine ......
Chromosomal Location	20p13
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 [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	SIRPA
Name	signal-regulatory protein alpha
Aliases	SHPS1; SIRP; MYD-1; BIT; SHPS-1; SIRPalpha; CD172a; SIRPalpha2; MFR; SIRP-ALPHA-1; PTPNS1; protein tyrosine ......
Chromosomal Location	20p13
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 [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	SIRPA
Name	signal-regulatory protein alpha
Aliases	SHPS1; SIRP; MYD-1; BIT; SHPS-1; SIRPalpha; CD172a; SIRPalpha2; MFR; SIRP-ALPHA-1; PTPNS1; protein tyrosine ......
Chromosomal Location	20p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of SIRPA expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	SIRPA
Name	signal-regulatory protein alpha
Aliases	SHPS1; SIRP; MYD-1; BIT; SHPS-1; SIRPalpha; CD172a; SIRPalpha2; MFR; SIRP-ALPHA-1; PTPNS1; protein tyrosine ......
Chromosomal Location	20p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between SIRPA and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	SIRPA
Name	signal-regulatory protein alpha
Aliases	SHPS1; SIRP; MYD-1; BIT; SHPS-1; SIRPalpha; CD172a; SIRPalpha2; MFR; SIRP-ALPHA-1; PTPNS1; protein tyrosine ......
Chromosomal Location	20p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting SIRPA collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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