SIRPA

Protein identityUniProt · HPA

UniProt accession

P78324

Gene

SIRPA

Ensembl

ENSG00000198053

Chromosome

20

Canonical length

504 aa

Protein class

CD markers, Plasma proteins, Predicted membrane proteins

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

504 residues, UniProt reviewed canonical sequence.

>P78324|SIRPA
     1  MEPAGPAPGR LGPLLCLLLA ASCAWSGVAG EEELQVIQPD KSVLVAAGET ATLRCTATSL
    61  IPVGPIQWFR GAGPGRELIY NQKEGHFPRV TTVSDLTKRN NMDFSIRIGN ITPADAGTYY
   121  CVKFRKGSPD DVEFKSGAGT ELSVRAKPSA PVVSGPAARA TPQHTVSFTC ESHGFSPRDI
   181  TLKWFKNGNE LSDFQTNVDP VGESVSYSIH STAKVVLTRE DVHSQVICEV AHVTLQGDPL
   241  RGTANLSETI RVPPTLEVTQ QPVRAENQVN VTCQVRKFYP QRLQLTWLEN GNVSRTETAS
   301  TVTENKDGTY NWMSWLLVNV SAHRDDVKLT CQVEHDGQPA VSKSHDLKVS AHPKEQGSNT
   361  AAENTGSNER NIYIVVGVVC TLLVALLMAA LYLVRIRQKK AQGSTSSTRL HEPEKNAREI
   421  TQDTNDITYA DLNLPKGKKP APQAAEPNNH TEYASIQTSP QPASEDTLTY ADLDMVHLNR
   481  TPKQPAPKPE PSFSEYASVQ VPRK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SIRPA can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.45

Highest tissue expression

160 nTPM

Expression across tissuesHPA

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.43

gnomAD pLI

0.67

gnomAD missense Z

1.06

DepMap mean gene effect

0.08

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell adhesion
• cell migration
• cellular response to hydrogen peroxide
• cellular response to interleukin-1
• cellular response to interleukin-12
• cellular response to type II interferon
• monocyte extravasation
• negative regulation of canonical NF-kappaB signal transduction
• negative regulation of chemokine (C-C motif) ligand 5 production
• negative regulation of cytokine production involved in inflammatory response
• negative regulation of ERK1 and ERK2 cascade
• negative regulation of inflammatory response
• negative regulation of interferon-beta production
• negative regulation of interleukin-6 production
• negative regulation of JNK cascade
• negative regulation of lipopolysaccharide-mediated signaling pathway
• negative regulation of macrophage inflammatory protein 1 alpha production
• negative regulation of nitric oxide biosynthetic process
• negative regulation of phagocytosis
• negative regulation of tumor necrosis factor production
• positive regulation of phagocytosis
• positive regulation of reactive oxygen species metabolic process
• positive regulation of T cell activation
• regulation of gene expression
• regulation of interleukin-1 beta production
• regulation of interleukin-6 production
• regulation of nitric oxide biosynthetic process
• regulation of tumor necrosis factor production
• regulation of type II interferon production

Molecular functions

• cell-cell adhesion mediator activity
• GTPase regulator activity
• protein antigen binding
• protein binding involved in heterotypic cell-cell adhesion
• protein phosphatase binding
• protein phosphatase inhibitor activity
• protein tyrosine kinase binding
• SH3 domain binding

Cellular components

• cell surface
• extracellular exosome
• ficolin-1-rich granule membrane
• membrane
• plasma membrane
• tertiary granule membrane

Protein domainsUniProt · Pfam · InterPro

• Immunoglobulin C1-set
• Immunoglobulin domain subtype
• Immunoglobulin-like domain
• Immunoglobulin V-set domain
• Immunoglobulin-like fold
• Immunoglobulin-like domain superfamily
• Immunoglobulin-like Cell Surface Receptor
• Immunoglobulin C1-set domain
• Immunoglobulin V-set domain

KeywordsUniProt

• Disulfide bond
• Glycoprotein
• Immunoglobulin domain
• Membrane
• Phosphoprotein
• Repeat
• SH3-binding
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of SIRPA in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• TRIM2
• PTK2B
• CD47
• THBS1
• JAK2
• FGR