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nformation cite this page get shortened url switch to legacy parser print export download as pdf printable version in other projects wikidata item appearance move to sidebar hide from wikipedia the free encyclopedia protein coding gene in the species homo sapiens sirpa identifiers aliases sirpa bit cd172a mfr myd 1 p84 ptpns1 shps1 sirp signal regulatory protein alpha signal regulatory protein alpha external ids omim 602461 mgi 108563 genecards sirpa available structures pdb ortholog search pdbe rcsb list of pdb id codes 2jjs 2jjt 2uv3 2wng 4cmm gene location human chr chromosome 20 human 1 band 20p13 start 1 894 167 bp 1 end 1 940 592 bp 1 gene location mouse chr chromosome 2 mouse 2 band 2 f1 2 63 19 cm start 129 434 755 bp 2 end 129 474 148 bp 2 rna expression pattern bgee human mouse ortholog top expressed in right frontal lobe brodmann area 9 right hemisphere of cerebellum postcentral gyrus lateral nuclear group of thalamus prefrontal cortex superior frontal gyrus amygdala middle temporal gyrus nucleus accumbens top expressed in stroma of bone marrow granulocyte prefrontal cortex superior frontal gyrus primary visual cortex dentate gyrus of hippocampal formation granule cell cerebellar cortex tibiofemoral joint perirhinal cortex entorhinal cortex more reference expression data biogps more reference expression data gene ontology molecular function sh3 domain binding protein phosphatase binding gtpase regulator activity protein binding involved in heterotypic cell cell adhesion cell cell adhesion mediator activity protein antigen binding protein tyrosine kinase binding cellular component integral component of membrane plasma membrane extracellular exosome membrane tertiary granule membrane ficolin 1 rich granule membrane integral component of plasma membrane cell surface biological process cell adhesion leukocyte migration neutrophil degranulation negative regulation of protein phosphorylation regulation of gene expression cell migration positive regulation of cell cell adhesion regulation of interferon gamma production regulation of interleukin 1 beta production regulation of interleukin 6 production regulation of tumor necrosis factor production negative regulation of interferon beta production negative regulation of interleukin 6 production negative regulation of tumor necrosis factor production heterotypic cell cell adhesion monocyte extravasation negative regulation of nitric oxide biosynthetic process regulation of nitric oxide biosynthetic process negative regulation of jnk cascade negative regulation of inflammatory response negative regulation of phagocytosis positive regulation of phagocytosis regulation of catalytic activity positive regulation of t cell activation cellular response to hydrogen peroxide negative regulation of erk1 and erk2 cascade cellular response to lipopolysaccharide cellular response to interferon gamma cellular response to interleukin 1 cellular response to interleukin 12 negative regulation of macrophage inflammatory protein 1 alpha production negative regulation of chemokine c c motif ligand 5 production cell cell adhesion negative regulation of cytokine production involved in inflammatory response negative regulation of i kappab phosphorylation sources amigo quickgo orthologs databases ncbi entry oma entry species human mouse entrez 140885 19261 ensembl ensg00000198053 ensmusg00000037902 uniprot p78324 p97797 refseq mrna nm_001040022 nm_001040023 nm_080792 nm_001330728 nm_001177646 nm_001177647 nm_001291019 nm_001291020 nm_001291021 nm_001291022 nm_007547 nm_001355158 nm_001355160 refseq protein np_001035111 np_001035112 np_001317657 np_542970 np_001171118 np_001277948 np_001277949 np_001277950 np_001277951 np_031573 np_001342087 np_001342089 location ucsc chr 20 1 89 1 94 mb chr 2 129 43 129 47 mb pubmed search 3 4 wikidata view edit human view edit mouse signal regulatory protein α sirpα is a regulatory membrane glycoprotein from sirp family expressed mainly by myeloid cells and also by stem cells citation needed or neurons sirpα acts as inhibitory receptor and interacts with a broadly expressed transmembrane protein cd47 also called the don t eat me signal this interaction negatively controls effector function of innate immune cells such as host cell phagocytosis sirpα diffuses laterally on the macrophage membrane and accumulates at a phagocytic synapse to bind cd47 and signal self which inhibits the cytoskeleton intensive process of phagocytosis by the macrophage 5 this is analogous to the self signals provided by mhc class i molecules to nk cells via ig like or ly49 receptors 6 7 nb protein shown to the right is cd47 not sirp α structure edit the cytoplasmic region of sirpα is highly conserved between rats mice and humans cytoplasmic region contains a number of tyrosine residues which likely act as itims upon cd47 ligation sirpα is phosphorylated and recruits phosphatases like shp1 and shp2 8 the extracellular region contains three immunoglobulin superfamily domains single v set and two c1 set igsf domains sirp β and γ have the similar extracellular structure but different cytoplasmic regions giving contrasting types of signals sirp α polymorphisms are found in ligand binding igsf v set domain but it does not affect ligand binding one idea is that the polymorphism is important to protect the receptor of pathogens binding 6 9 ligands edit sirpα recognizes cd47 an anti phagocytic signal that distinguishes live cells from dying cells cd47 has a single ig like extracellular domain and five membrane spanning regions the interaction between sirpα and cd47 can be modified by endocytosis or cleavage of the receptor or interaction with surfactant proteins surfactant protein a and d are soluble ligands highly expressed in the lungs that bind to the same region of sirpα as cd47 and can therefore competitively block binding 9 10 signalling edit the extracellular domain of sirp α binds to cd47 and transmits intracellular signals through its cytoplasmic domain cd47 binding is mediated through the nh2 terminal v like domain of sirp α the cytoplasmic region contains four itims that become phosphorylated after binding of ligand the phosphorylation mediates activation of tyrosine kinase shp2 sirp α has been shown to bind also phosphatase shp1 adaptor protein scap2 and fyn binding protein recruitment of shp phosphatases to the membrane leads to the inhibition of myosin accumulation at the cell surface and results in the inhibition of phagocytosis 9 10 cancer edit cancer cells highly expressed cd47 that activate sirp α and inhibit macrophage mediated destruction in one study they engineered high affinity variants of sirp α that antagonized cd47 on cancer cells and caused increase phagocytosis of cancer cells 11 another study in mice found anti sirpα antibodies helped macrophages to reduce cancer growth and metastasis alone and in synergy with other cancer treatments 12 13 references edit 1 2 3 grch38 ensembl release 89 ensg00000198053 ensembl may 2017 1 2 3 grcm38 ensembl release 89 ensmusg00000037902 ensembl may 2017 human pubmed reference national center for biotechnology information u s national library of medicine mouse pubmed reference national center for biotechnology information u s national library of medicine tsai rk discher de march 2008 inhibition of self engulfment through deactivation of myosin ii at the phagocytic synapse between human cells the journal of cell biology 180 5 989 1003 doi 10 1083 jcb 200708043 pmc 2265407 pmid 18332220 1 2 barclay an february 2009 signal regulatory protein alpha sirpalpha cd47 interaction and function current opinion in immunology 21 1 47 52 doi 10 1016 j coi 2009 01 008 pmc 3128989 pmid 19223164 stefanidakis m newton g lee wy parkos ca luscinskas fw august 2008 endothelial cd47 interaction with sirpgamma is required for human t cell transendothelial migration under shear flow conditions in vitro blood 112 4 1280 1289 doi 10 1182 blood 2008 01 134429 pmc 2515120 pmid 18524990 okazawa h motegi s ohyama n ohnishi h tomizawa t kaneko y et al february 2005 negative regulation of phagocytosis in macrophages by the cd47 shps 1 system journal of immunology 174 4 2004 2011 doi 10 4049 jimmunol 174 4 2004 pmid 15699129 1 2 3 barclay an brown mh june 2006 the sirp family of receptors and immune regulation nature reviews immunology 6 6 457 464 doi 10 1038 nri1859 pmid 16691243 s2cid 7915923 1 2 van beek em cochrane f barclay an van den berg tk december 2005 signal regulatory proteins in the immune system journal of immunology 175 12 7781 7787 doi 10 4049 jimmunol 175 12 7781 pmid 16339510 weiskopf k ring am ho cc volkmer jp levin am volkmer ak et al july 2013 engineered sirpα variants as immunotherapeutic adjuvants to anticancer antibodies science 341 6141 88 91 bibcode 2013sci 341 88w doi 10 1126 science 1238856 pmc 3810306 pmid 23722425 potential new cancer treatment activates cancer engulfing cells feb 2017 yanagita t murata y tanaka d motegi si arai e daniwijaya ew et al january 2017 anti sirp α antibodies as a potential new tool for cancer immunotherapy jci insight 2 1 e89140 doi 10 1172 jci insight 89140 pmc 5214103 pmid 28097229 further reading edit oldenborg pa 2013 cd47 a cell surface glycoprotein which regulates multiple functions of hematopoietic cells in health and disease isrn hematology 2013 614619 doi 10 1155 2013 614619 pmc 3564380 pmid 23401787 yamauchi t takenaka k urata s shima t kikushige y tokuyama t et al february 2013 polymorphic sirpa is the genetic determinant for nod based mouse lines to achieve efficient human cell engraftment blood 121 8 1316 1325 doi 10 1182 blood 2012 06 440354 pmid 23293079 oldenborg pa july 2004 role of cd47 in erythroid cells and in autoimmunity leukemia lymphoma 45 7 1319 1327 doi 10 1080 1042819042000201989 pmid 15359629 s2cid 12642148 margolis rl breschel ts li sh kidwai as antonarakis se mcinnis mg et al july 1995 characterization of cdna clones containing cca trinucleotide repeats derived from human brain somatic cell and molecular genetics 21 4 279 284 doi 10 1007 bf02255782 pmid 8525433 s2cid 22174220 ohnishi h kubota m ohtake a sato k sano s october 1996 activation of protein tyrosine phosphatase sh ptp2 by a tyrosine based activation motif of a novel brain molecule the journal of biological chemistry 271 41 25569 25574 doi 10 1074 jbc 271 41 25569 pmid 8810330 fujioka y matozaki t noguchi t iwamatsu a yamao t takahashi n et al december 1996 a novel membrane glycoprotein shps 1 that binds the sh2 domain containing protein tyrosine phosphatase shp 2 in response to mitogens and cell adhesion molecular and cellular biology 16 12 6887 6899 doi 10 1128 mcb 16 12 6887 pmc 231692 pmid 8943344 sano s ohnishi h omori a hasegawa j kubota m july 1997 bit an immune antigen receptor like molecule in the brain febs letters 411 2 3 327 334 doi 10 1016 s0014 5793 97 00724 2 pmid 9271230 s2cid 39554802 brooke gp parsons kr howard cj january 1998 cloning of two members of the sirp alpha family of protein tyrosine phosphatase binding proteins in cattle that are expressed on monocytes and a subpopulation of dendritic cells and which mediate binding to cd4 t cells european journal of immunology 28 1 1 11 doi 10 1002 sici 1521 4141 199801 28 01 1 aid immu1 3 0 co 2 v pmid 9485180 timms jf carlberg k gu h chen h kamatkar s nadler mj et al july 1998 identification of major binding proteins and substrates for the sh2 containing protein tyrosine phosphatase shp 1 in macrophages molecular and cellular biology 18 7 3838 3850 doi 10 1128 mcb 18 7 3838 pmc 108968 pmid 9632768 veillette a thibaudeau e latour s august 1998 high expression of inhibitory receptor shps 1 and its association with protein tyrosine phosphatase shp 1 in macrophages the journal of biological chemistry 273 35 22719 22728 doi 10 1074 jbc 273 35 22719 pmid 9712903 jiang p lagenaur cf narayanan v january 1999 integrin associated protein is a ligand for the p84 neural adhesion molecule the journal of biological chemistry 274 2 559 562 doi 10 1074 jbc 274 2 559 pmid 9872987 ohnishi h yamada m kubota m hatanaka h sano s april 1999 tyrosine phosphorylation and association of bit with shp 2 induced by neurotrophins journal of neurochemistry 72 4 1402 1408 doi 10 1046 j 1471 4159 1999 721402 x pmid 10098842 s2cid 83600875 timms jf swanson kd marie cardine a raab m rudd ce schraven b et al august 1999 shps 1 is a scaffold for assembling distinct adhesion regulated multi protein complexes in macrophages current biology 9 16 927 930 bibcode 1999cbio 9 927t doi 10 1016 s0960 9822 99 80401 1 pmid 10469599 s2cid 16056124 seiffert m cant c chen z rappold i brugger w kanz l et al december 1999 human signal regulatory protein is expressed on normal but not on subsets of leukemic myeloid cells and mediates cellular adhesion involving its counterreceptor cd47 blood 94 11 3633 3643 doi 10 1182 blood v94 11 3633 pmid 10572074 s2cid 11033417 sano s ohnishi h kubota m december 1999 gene structure of mouse bit shps 1 the biochemical journal 344 pt 3 667 675 doi 10 1042 0264 6021 3440667 pmc 1220688 pmid 10585853 yang j cheng z niu t liang x zhao zj zhou gw february 2000 structural basis for substrate specificity of protein tyrosine phosphatase shp 1 the journal of biological chemistry 275 6 4066 4071 doi 10 1074 jbc 275 6 4066 pmid 10660565 stofega mr argetsinger ls wang h ullrich a carter su c september 2000 negative regulation of growth hormone receptor jak2 signaling by signal regulatory protein alpha the journal of biological chemistry 275 36 28222 28229 doi 10 1074 jbc m004238200 pmid 10842184 wu cj chen z ullrich a greene mi o rourke dm august 2000 inhibition of egfr mediated phosphoinositide 3 oh kinase pi3 k signaling and glioblastoma phenotype by signal regulatory proteins sirps oncogene 19 35 3999 4010 doi 10 1038 sj onc 1203748 pmid 10962556 s2cid 9020984 latour s tanaka h demeure c mateo v rubio m brown ej et al september 2001 bidirectional negative regulation of human t and dendritic cells by cd47 and its cognate receptor signal regulator protein alpha down regulation of il 12 responsiveness and inhibition of dendritic cell activation journal of immunology 167 5 2547 2554 doi 10 4049 jimmunol 167 5 2547 pmid 11509594 this article incorporates text from the united states national library of medicine which is in the public domain v t e proteins clusters of differentiation see also list of human clusters of differentiation 1 50 1 a c 1a 1b 1d 1e 2 3 γ δ ε 4 5 6 7 8 a 9 10 11 a b c d 13 14 15 16 a b 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 a b 33 34 35 36 37 38 39 40 41 42 a b c d 43 44 45 46 47 48 49 a b c d e f 50 51 100 51 52 53 54 55 56 57 58 59 61 62 e l p 63 64 a b c 66 a b c d e f 68 69 70 71 72 73 74 78 79 a b 80 81 82 83 84 85 a d e h j k 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 150 101 102 103 104 105 106 107 a b 108 109 110 111 112 113 114 115 116 117 118 119 120 a b 121 a b 122 123 124 125 126 127 129 130 131 132 133 134 135 136 137 138 140b 1...