Signal regulatory protein family interactions (Homo sapiens)

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1-5138, 17, 18122, 127-116, 141215, 16cytosolGRB2pSIRP-A:PYK2pSIRP alpha:CD47pSIRP alpha:CD47:SCAP2Protein tyrosine kinase 2 beta (PYK2)SIRP gammaSrc kinase-associated phosphoprotein 2 (SCAP2)Src kinases Src/FADK1SIRP alpha:CD47SHP-2/SHP-1Pulmonory surfactant proteins A and DSIRP beta1:DAP12SHP2/SHP1:pSIRP alpha:CD47pSIRP alpha:CD47:SCAP2:FYBCD47pSIRP-A:Grb2SIRP betaSIRP gamma:CD47ATPADPSIRP alphaDAP12ADAPSIRP alpha:SP-A/SP-D6


Description

Signal regulatory protein (SIRP)alpha, also known as SHPS-1 or SIRPA or CD172a, is a transmembrane protein expressed mostly on myeloid cells. CD47, a widely expressed transmembrane protein, is a ligand for SIRP alpha, with the two proteins constituting a cell-cell communication system. The interaction of SIRP alpha with CD47 is important for the regulation of migration and phagocytosis. SIRP alpha functions as a docking protein to recruit and activate SHP-1 or SHP-2 at the cell membrane in response to extracellular stimuli. SIRP alpha also binds other intracellular proteins including the adaptor molecules Src kinase-associated protein (SKAP2 SKAP55hom/R), Fyn-binding protein/SLP-76-associated phosphoprotein (FYB/SLAP-130) and the tyrosine kinase PYK2. SIRP alpha also binds the extracellular proteins, surfactant-A (SP-A) and surfactant-D (SP-D).
In addition to SIRP alpha there are two closely related proteins in the SIRP family namely SIRP beta and SIRP gamma. These three family proteins show high sequence similarity and similar extracellular structural topology, including three Ig domains, but their ligand binding topology might differ. SIRP beta is expressed on myeloid cells, including monocytes, granulocytes and DCs. A natural ligand for SIRP beta remains unknown; SIRP gamma can bind to CD47 but the binding affinity is lower than that of SIRP alpha.

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Bibliography

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  1. Brooke G, Holbrook JD, Brown MH, Barclay AN.; ''Human lymphocytes interact directly with CD47 through a novel member of the signal regulatory protein (SIRP) family.''; PubMed Europe PMC Scholia
  2. Hatherley D, Graham SC, Harlos K, Stuart DI, Barclay AN.; ''Structure of signal-regulatory protein alpha: a link to antigen receptor evolution.''; PubMed Europe PMC Scholia
  3. Kharitonenkov A, Chen Z, Sures I, Wang H, Schilling J, Ullrich A.; ''A family of proteins that inhibit signalling through tyrosine kinase receptors.''; PubMed Europe PMC Scholia
  4. Matozaki T, Murata Y, Okazawa H, Ohnishi H.; ''Functions and molecular mechanisms of the CD47-SIRPalpha signalling pathway.''; PubMed Europe PMC Scholia
  5. Hatherley D, Graham SC, Turner J, Harlos K, Stuart DI, Barclay AN.; ''Paired receptor specificity explained by structures of signal regulatory proteins alone and complexed with CD47.''; PubMed Europe PMC Scholia
  6. Kishore U, Greenhough TJ, Waters P, Shrive AK, Ghai R, Kamran MF, Bernal AL, Reid KB, Madan T, Chakraborty T.; ''Surfactant proteins SP-A and SP-D: structure, function and receptors.''; PubMed Europe PMC Scholia
  7. Gardai SJ, Xiao YQ, Dickinson M, Nick JA, Voelker DR, Greene KE, Henson PM.; ''By binding SIRPalpha or calreticulin/CD91, lung collectins act as dual function surveillance molecules to suppress or enhance inflammation.''; PubMed Europe PMC Scholia
  8. Tomasello E, Cant C, Bühring HJ, Vély F, André P, Seiffert M, Ullrich A, Vivier E.; ''Association of signal-regulatory proteins beta with KARAP/DAP-12.''; PubMed Europe PMC Scholia
  9. Timms JF, Swanson KD, Marie-Cardine A, Raab M, Rudd CE, Schraven B, Neel BG.; ''SHPS-1 is a scaffold for assembling distinct adhesion-regulated multi-protein complexes in macrophages.''; PubMed Europe PMC Scholia
  10. Liu Y, Bühring HJ, Zen K, Burst SL, Schnell FJ, Williams IR, Parkos CA.; ''Signal regulatory protein (SIRPalpha), a cellular ligand for CD47, regulates neutrophil transmigration.''; PubMed Europe PMC Scholia
  11. Piccio L, Vermi W, Boles KS, Fuchs A, Strader CA, Facchetti F, Cella M, Colonna M.; ''Adhesion of human T cells to antigen-presenting cells through SIRPbeta2-CD47 interaction costimulates T-cell proliferation.''; PubMed Europe PMC Scholia
  12. Barclay AN, Brown MH.; ''The SIRP family of receptors and immune regulation.''; PubMed Europe PMC Scholia
  13. Seiffert M, Cant C, Chen Z, Rappold I, Brugger W, Kanz L, Brown EJ, Ullrich A, Bühring HJ.; ''Human signal-regulatory protein is expressed on normal, but not on subsets of leukemic myeloid cells and mediates cellular adhesion involving its counterreceptor CD47.''; PubMed Europe PMC Scholia
  14. Hatherley D, Harlos K, Dunlop DC, Stuart DI, Barclay AN.; ''The structure of the macrophage signal regulatory protein alpha (SIRPalpha) inhibitory receptor reveals a binding face reminiscent of that used by T cell receptors.''; PubMed Europe PMC Scholia
  15. van den Berg TK, van Beek EM, Bühring HJ, Colonna M, Hamaguchi M, Howard CJ, Kasuga M, Liu Y, Matozaki T, Neel BG, Parkos CA, Sano S, Vignery A, Vivier E, Wright M, Zawatzky R, Barclay AN.; ''A nomenclature for signal regulatory protein family members.''; PubMed Europe PMC Scholia
  16. Oshima K, Ruhul Amin AR, Suzuki A, Hamaguchi M, Matsuda S.; ''SHPS-1, a multifunctional transmembrane glycoprotein.''; PubMed Europe PMC Scholia
  17. Liu Y, Tong Q, Zhou Y, Lee HW, Yang JJ, Bühring HJ, Chen YT, Ha B, Chen CX, Yang Y, Zen K.; ''Functional elements on SIRPalpha IgV domain mediate cell surface binding to CD47.''; PubMed Europe PMC Scholia
  18. Dietrich J, Cella M, Seiffert M, Bühring HJ, Colonna M.; ''Cutting edge: signal-regulatory protein beta 1 is a DAP12-associated activating receptor expressed in myeloid cells.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
114854view16:35, 25 January 2021ReactomeTeamReactome version 75
113300view11:37, 2 November 2020ReactomeTeamReactome version 74
112512view15:47, 9 October 2020ReactomeTeamReactome version 73
101424view11:30, 1 November 2018ReactomeTeamreactome version 66
100962view21:07, 31 October 2018ReactomeTeamreactome version 65
100499view19:41, 31 October 2018ReactomeTeamreactome version 64
100045view16:25, 31 October 2018ReactomeTeamreactome version 63
99597view14:59, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99215view12:43, 31 October 2018ReactomeTeamreactome version 62
94492view08:56, 14 September 2017MkutmonReactome release 61
86677view09:24, 11 July 2016ReactomeTeamreactome version 56
83190view10:19, 18 November 2015ReactomeTeamVersion54
81563view13:06, 21 August 2015ReactomeTeamVersion53
77029view08:32, 17 July 2014ReactomeTeamFixed remaining interactions
76734view12:09, 16 July 2014ReactomeTeamFixed remaining interactions
76060view10:12, 11 June 2014ReactomeTeamRe-fixing comment source
75770view11:27, 10 June 2014ReactomeTeamReactome 48 Update
75120view14:07, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74767view08:51, 30 April 2014ReactomeTeamReactome46
45225view17:35, 7 October 2011KhanspersOntology Term : 'myeloid cell' added !
42125view21:58, 4 March 2011MaintBotAutomatic update
39935view05:57, 21 January 2011MaintBotNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
ADAP ProteinO15117 (UniProt)
ADP Metabolite16761 (ChEBI)
ATP Metabolite15422 (ChEBI)
CD47 ProteinQ08722 (UniProt)
DAP12 ProteinO43914 (UniProt)
GRB2 ProteinP62993-1 (UniProt)
Protein tyrosine

kinase 2 beta (PYK2)

ProteinQ14289 (UniProt)
Pulmonory surfactant

proteins A and D

UnknownREACT_24725 (Reactome)
SHP-2/SHP-1 ProteinREACT_20250 (Reactome)
SHP2/SHP1:pSIRP

alpha:CD47

ComplexREACT_24824 (Reactome)
SIRP alpha ProteinP78324-1 (UniProt)
SIRP alpha:CD47 ComplexREACT_24285 (Reactome)
SIRP alpha:SP-A/SP-

D

ComplexREACT_24481 (Reactome)
SIRP beta ProteinO00241 (UniProt)
SIRP beta1:DAP12 ComplexREACT_24726 (Reactome)
SIRP gamma ProteinQ9P1W8 (UniProt)
SIRP gamma:CD47 ComplexREACT_24053 (Reactome)
Src kinase-

associated phosphoprotein 2 (SCAP2)

ProteinO75563 (UniProt)
Src kinases

Src/FADK1

ProteinREACT_24388 (Reactome)
pSIRP alpha:CD47 ComplexREACT_24659 (Reactome)
pSIRP alpha:CD47:

SCAP2

ComplexREACT_24452 (Reactome)
pSIRP alpha:CD47:

SCAP2:FYB

ComplexREACT_24378 (Reactome)
pSIRP-A:Grb2 ComplexREACT_24616 (Reactome)
pSIRP-A:PYK2 ComplexREACT_24348 (Reactome)

Annotated Interactions

No annotated interactions

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