SHPS1_HUMAN
ID SHPS1_HUMAN Reviewed; 504 AA.
AC P78324; A2A2E1; A8K411; B2R6C3; O00683; O43799; Q8N517; Q8TAL8; Q9H0Z2;
AC Q9UDX2; Q9UIJ6; Q9Y4U9;
DT 28-MAR-2003, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 2.
DT 03-AUG-2022, entry version 216.
DE RecName: Full=Tyrosine-protein phosphatase non-receptor type substrate 1;
DE Short=SHP substrate 1;
DE Short=SHPS-1;
DE AltName: Full=Brain Ig-like molecule with tyrosine-based activation motifs;
DE Short=Bit;
DE AltName: Full=CD172 antigen-like family member A;
DE AltName: Full=Inhibitory receptor SHPS-1;
DE AltName: Full=Macrophage fusion receptor;
DE AltName: Full=MyD-1 antigen;
DE AltName: Full=Signal-regulatory protein alpha-1;
DE Short=Sirp-alpha-1;
DE AltName: Full=Signal-regulatory protein alpha-2;
DE Short=Sirp-alpha-2;
DE AltName: Full=Signal-regulatory protein alpha-3;
DE Short=Sirp-alpha-3;
DE AltName: Full=p84;
DE AltName: CD_antigen=CD172a;
DE Flags: Precursor;
GN Name=SIRPA; Synonyms=BIT, MFR, MYD1, PTPNS1, SHPS1, SIRP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS SER-44; SER-50;
RP ILE-52; HIS-54; VAL-57; ALA-75; GLU-95; SER-96; GLU-100; SER-107; SER-109
RP AND THR-132.
RC TISSUE=Brain;
RX PubMed=9070220; DOI=10.1006/bbrc.1996.6047;
RA Yamao T., Matozaki T., Amano K., Matsuda Y., Takahashi N., Ochi F.,
RA Fujioka Y., Kasuga M.;
RT "Mouse and human SHPS-1: molecular cloning of cDNAs and chromosomal
RT localization of genes.";
RL Biochem. Biophys. Res. Commun. 231:61-67(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), POLYMORPHISM, PHOSPHORYLATION,
RP GLYCOSYLATION, INTERACTION WITH PTPN11; PTPN6 AND GRB2, AND VARIANTS
RP SER-44; SER-50; ILE-52; HIS-54; VAL-57; ALA-75; GLU-95; SER-96; GLU-100;
RP SER-107; SER-109 AND THR-132.
RC TISSUE=Placenta;
RX PubMed=9062191; DOI=10.1038/386181a0;
RA Kharitonenkov A., Chen Z., Sures I., Wang H., Schilling J., Ullrich A.;
RT "A family of proteins that inhibit signalling through tyrosine kinase
RT receptors.";
RL Nature 386:181-186(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10585853; DOI=10.1042/bj3440667;
RA Sano S., Ohnishi H., Kubota M.;
RT "Gene structure of mouse BIT/SHPS-1.";
RL Biochem. J. 344:667-675(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS SER-44;
RP SER-50; ILE-52; HIS-54; VAL-57; ALA-75; GLU-95; SER-96; GLU-100; SER-107;
RP SER-109 AND THR-132.
RC TISSUE=Thalamus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANTS
RP SER-44; SER-50; ILE-52; HIS-54; VAL-57; ALA-75; GLU-95; SER-96; GLU-100;
RP SER-107; SER-109 AND THR-132.
RC TISSUE=Brain, Kidney, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 76-504.
RC TISSUE=Monocyte;
RX PubMed=9485180;
RX DOI=10.1002/(sici)1521-4141(199801)28:01<1::aid-immu1>3.0.co;2-v;
RA Brooke G.P., Parsons K.R., Howard C.J.;
RT "Cloning of two members of the SIRP alpha family of protein tyrosine
RT phosphatase binding proteins in cattle that are expressed on monocytes and
RT a subpopulation of dendritic cells and which mediate binding to CD4 T
RT cells.";
RL Eur. J. Immunol. 28:1-11(1998).
RN [8]
RP FUNCTION, AND INTERACTION WITH FYB1; SCAP2 AND PTK2B.
RX PubMed=10469599; DOI=10.1016/s0960-9822(99)80401-1;
RA Timms J.F., Swanson K.D., Marie-Cardine A., Raab M., Rudd C.E.,
RA Schraven B., Neel B.G.;
RT "SHPS-1 is a scaffold for assembling distinct adhesion-regulated multi-
RT protein complexes in macrophages.";
RL Curr. Biol. 9:927-930(1999).
RN [9]
RP PHOSPHORYLATION BY JAK2, AND INTERACTION WITH PTPN11 AND JAK2.
RX PubMed=10842184; DOI=10.1074/jbc.m004238200;
RA Stofega M.R., Argetsinger L.S., Wang H., Ullrich A., Carter-Su C.;
RT "Negative regulation of growth hormone receptor/JAK2 signaling by signal
RT regulatory protein alpha.";
RL J. Biol. Chem. 275:28222-28229(2000).
RN [10]
RP FUNCTION, AND INTERACTION WITH CD47.
RX PubMed=11509594; DOI=10.4049/jimmunol.167.5.2547;
RA Latour S., Tanaka H., Demeure C., Mateo V., Rubio M., Brown E.J.,
RA Maliszewski C., Lindberg F.P., Oldenborg A., Ullrich A., Delespesse G.,
RA Sarfati M.;
RT "Bidirectional negative regulation of human T and dendritic cells by CD47
RT and its cognate receptor signal-regulator protein-alpha: down-regulation of
RT IL-12 responsiveness and inhibition of dendritic cell activation.";
RL J. Immunol. 167:2547-2554(2001).
RN [11]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-245.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [12]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-270 AND ASN-292.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-496, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 31-149, AND DISULFIDE BOND.
RX PubMed=17369261; DOI=10.1074/jbc.m611511200;
RA Hatherley D., Harlos K., Dunlop D.C., Stuart D.I., Barclay A.N.;
RT "The structure of the macrophage signal regulatory protein alpha
RT (SIRPalpha) inhibitory receptor reveals a binding face reminiscent of that
RT used by T cell receptors.";
RL J. Biol. Chem. 282:14567-14575(2007).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 31-149 IN COMPLEX WITH CD47, AND
RP DISULFIDE BOND.
RX PubMed=18657508; DOI=10.1016/j.molcel.2008.05.026;
RA Hatherley D., Graham S.C., Turner J., Harlos K., Stuart D.I., Barclay A.N.;
RT "Paired receptor specificity explained by structures of signal regulatory
RT proteins alone and complexed with CD47.";
RL Mol. Cell 31:266-277(2008).
CC -!- FUNCTION: Immunoglobulin-like cell surface receptor for CD47. Acts as
CC docking protein and induces translocation of PTPN6, PTPN11 and other
CC binding partners from the cytosol to the plasma membrane. Supports
CC adhesion of cerebellar neurons, neurite outgrowth and glial cell
CC attachment. May play a key role in intracellular signaling during
CC synaptogenesis and in synaptic function (By similarity). Involved in
CC the negative regulation of receptor tyrosine kinase-coupled cellular
CC responses induced by cell adhesion, growth factors or insulin. Mediates
CC negative regulation of phagocytosis, mast cell activation and dendritic
CC cell activation. CD47 binding prevents maturation of immature dendritic
CC cells and inhibits cytokine production by mature dendritic cells.
CC {ECO:0000250, ECO:0000269|PubMed:10469599,
CC ECO:0000269|PubMed:11509594}.
CC -!- SUBUNIT: Binds PTPN11 when tyrosine-phosphorylated, except in
CC macrophages, where it primarily binds PTPN6. Binds GRB2 in vitro. Binds
CC FGR (By similarity). Binds JAK2 irrespective of its phosphorylation
CC status and forms a stable complex. Binds SCAP1 and/or SCAP2. The
CC resulting complex recruits FYB1. Binds PTK2B. {ECO:0000250,
CC ECO:0000269|PubMed:18657508}.
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P78324-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P78324-2; Sequence=VSP_007030;
CC Name=4;
CC IsoId=P78324-4; Sequence=VSP_040799;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Highly expressed in brain. Detected on
CC myeloid cells, but not T-cells. Detected at lower levels in heart,
CC placenta, lung, testis, ovary, colon, liver, small intestine, prostate,
CC spleen, kidney, skeletal muscle and pancreas.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:16335952,
CC ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:9062191}.
CC -!- PTM: Phosphorylated on tyrosine residues in response to stimulation
CC with EGF, growth hormone, insulin and PDGF. Dephosphorylated by PTPN11.
CC {ECO:0000269|PubMed:10842184, ECO:0000269|PubMed:9062191}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; D86043; BAA12974.1; -; mRNA.
DR EMBL; Y10375; CAA71403.1; -; mRNA.
DR EMBL; AB023430; BAA87929.1; -; mRNA.
DR EMBL; AK290776; BAF83465.1; -; mRNA.
DR EMBL; AK312521; BAG35420.1; -; mRNA.
DR EMBL; AL034562; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL117335; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC026692; AAH26692.1; -; mRNA.
DR EMBL; BC033092; AAH33092.1; -; mRNA.
DR EMBL; BC038510; AAH38510.1; -; mRNA.
DR EMBL; BC075849; AAH75849.1; -; mRNA.
DR EMBL; Y11047; CAA71944.1; -; mRNA.
DR CCDS; CCDS13022.1; -. [P78324-1]
DR CCDS; CCDS82593.1; -. [P78324-2]
DR PIR; JC5287; JC5287.
DR RefSeq; NP_001035111.1; NM_001040022.1. [P78324-1]
DR RefSeq; NP_001035112.1; NM_001040023.1. [P78324-1]
DR RefSeq; NP_001317657.1; NM_001330728.1. [P78324-2]
DR RefSeq; NP_542970.1; NM_080792.2. [P78324-1]
DR RefSeq; XP_005260727.1; XM_005260670.3. [P78324-2]
DR PDB; 2JJS; X-ray; 1.85 A; A/B=31-149.
DR PDB; 2JJT; X-ray; 2.30 A; A/B=31-149.
DR PDB; 2UV3; X-ray; 1.80 A; A/B=31-149.
DR PDB; 2WNG; X-ray; 2.49 A; A=31-350.
DR PDB; 4CMM; X-ray; 1.92 A; A=31-149.
DR PDB; 6BIT; X-ray; 2.19 A; G/H=31-147.
DR PDB; 6NMR; X-ray; 2.42 A; E/I/M/S=31-149.
DR PDB; 6NMS; X-ray; 2.11 A; C/S=31-149.
DR PDB; 6NMT; X-ray; 1.83 A; C=31-149.
DR PDB; 6NMU; X-ray; 2.55 A; C/S=31-149.
DR PDB; 6NMV; X-ray; 2.61 A; S=31-149.
DR PDB; 7KPG; X-ray; 2.27 A; S=33-147.
DR PDBsum; 2JJS; -.
DR PDBsum; 2JJT; -.
DR PDBsum; 2UV3; -.
DR PDBsum; 2WNG; -.
DR PDBsum; 4CMM; -.
DR PDBsum; 6BIT; -.
DR PDBsum; 6NMR; -.
DR PDBsum; 6NMS; -.
DR PDBsum; 6NMT; -.
DR PDBsum; 6NMU; -.
DR PDBsum; 6NMV; -.
DR PDBsum; 7KPG; -.
DR AlphaFoldDB; P78324; -.
DR SMR; P78324; -.
DR BioGRID; 126752; 85.
DR IntAct; P78324; 13.
DR MINT; P78324; -.
DR STRING; 9606.ENSP00000382941; -.
DR GlyConnect; 650; 13 N-Linked glycans (4 sites).
DR GlyGen; P78324; 10 sites, 14 N-linked glycans (4 sites), 1 O-linked glycan (3 sites).
DR iPTMnet; P78324; -.
DR PhosphoSitePlus; P78324; -.
DR BioMuta; SIRPA; -.
DR DMDM; 327478534; -.
DR EPD; P78324; -.
DR jPOST; P78324; -.
DR MassIVE; P78324; -.
DR MaxQB; P78324; -.
DR PaxDb; P78324; -.
DR PeptideAtlas; P78324; -.
DR PRIDE; P78324; -.
DR ProteomicsDB; 57564; -. [P78324-1]
DR ProteomicsDB; 57565; -. [P78324-2]
DR ProteomicsDB; 57566; -. [P78324-4]
DR ABCD; P78324; 101 sequenced antibodies.
DR Antibodypedia; 3458; 977 antibodies from 48 providers.
DR DNASU; 140885; -.
DR Ensembl; ENST00000356025.7; ENSP00000348307.3; ENSG00000198053.12. [P78324-1]
DR Ensembl; ENST00000358771.5; ENSP00000351621.4; ENSG00000198053.12. [P78324-1]
DR Ensembl; ENST00000400068.7; ENSP00000382941.4; ENSG00000198053.12. [P78324-1]
DR Ensembl; ENST00000622179.4; ENSP00000478763.1; ENSG00000198053.12. [P78324-2]
DR GeneID; 140885; -.
DR KEGG; hsa:140885; -.
DR MANE-Select; ENST00000358771.5; ENSP00000351621.4; NM_001040023.2; NP_001035112.1.
DR UCSC; uc002wfq.3; human. [P78324-1]
DR CTD; 140885; -.
DR DisGeNET; 140885; -.
DR GeneCards; SIRPA; -.
DR HGNC; HGNC:9662; SIRPA.
DR HPA; ENSG00000198053; Tissue enhanced (brain).
DR MIM; 602461; gene.
DR neXtProt; NX_P78324; -.
DR OpenTargets; ENSG00000198053; -.
DR PharmGKB; PA34006; -.
DR VEuPathDB; HostDB:ENSG00000198053; -.
DR eggNOG; ENOG502S1XD; Eukaryota.
DR GeneTree; ENSGT00960000186656; -.
DR HOGENOM; CLU_044430_2_0_1; -.
DR InParanoid; P78324; -.
DR OMA; EYACIQT; -.
DR OrthoDB; 904196at2759; -.
DR PhylomeDB; P78324; -.
DR TreeFam; TF341862; -.
DR PathwayCommons; P78324; -.
DR Reactome; R-HSA-202733; Cell surface interactions at the vascular wall.
DR Reactome; R-HSA-391160; Signal regulatory protein family interactions.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; P78324; -.
DR SIGNOR; P78324; -.
DR BioGRID-ORCS; 140885; 12 hits in 1076 CRISPR screens.
DR ChiTaRS; SIRPA; human.
DR EvolutionaryTrace; P78324; -.
DR GeneWiki; Signal-regulatory_protein_alpha; -.
DR GenomeRNAi; 140885; -.
DR Pharos; P78324; Tbio.
DR PRO; PR:P78324; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; P78324; protein.
DR Bgee; ENSG00000198053; Expressed in right frontal lobe and 183 other tissues.
DR Genevisible; P78324; HS.
DR GO; GO:0009986; C:cell surface; IDA:ARUK-UCL.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0101003; C:ficolin-1-rich granule membrane; TAS:Reactome.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0070821; C:tertiary granule membrane; TAS:Reactome.
DR GO; GO:0098632; F:cell-cell adhesion mediator activity; IPI:ARUK-UCL.
DR GO; GO:0030695; F:GTPase regulator activity; ISS:ARUK-UCL.
DR GO; GO:1990405; F:protein antigen binding; IPI:ARUK-UCL.
DR GO; GO:0086080; F:protein binding involved in heterotypic cell-cell adhesion; ISS:ARUK-UCL.
DR GO; GO:0019903; F:protein phosphatase binding; ISS:ARUK-UCL.
DR GO; GO:1990782; F:protein tyrosine kinase binding; ISS:ARUK-UCL.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0007155; P:cell adhesion; TAS:ProtInc.
DR GO; GO:0016477; P:cell migration; ISS:ARUK-UCL.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; ISS:ARUK-UCL.
DR GO; GO:0071346; P:cellular response to interferon-gamma; ISS:ARUK-UCL.
DR GO; GO:0071347; P:cellular response to interleukin-1; ISS:ARUK-UCL.
DR GO; GO:0071349; P:cellular response to interleukin-12; IMP:ARUK-UCL.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISS:ARUK-UCL.
DR GO; GO:0035696; P:monocyte extravasation; ISS:ARUK-UCL.
DR GO; GO:0071650; P:negative regulation of chemokine (C-C motif) ligand 5 production; ISS:ARUK-UCL.
DR GO; GO:1900016; P:negative regulation of cytokine production involved in inflammatory response; ISS:ARUK-UCL.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; ISS:ARUK-UCL.
DR GO; GO:1903720; P:negative regulation of I-kappaB phosphorylation; ISS:ARUK-UCL.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IMP:ARUK-UCL.
DR GO; GO:0032688; P:negative regulation of interferon-beta production; ISS:ARUK-UCL.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; ISS:ARUK-UCL.
DR GO; GO:0046329; P:negative regulation of JNK cascade; ISS:ARUK-UCL.
DR GO; GO:0071641; P:negative regulation of macrophage inflammatory protein 1 alpha production; ISS:ARUK-UCL.
DR GO; GO:0045019; P:negative regulation of nitric oxide biosynthetic process; ISS:ARUK-UCL.
DR GO; GO:0050765; P:negative regulation of phagocytosis; ISS:ARUK-UCL.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISS:ARUK-UCL.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; ISS:ARUK-UCL.
DR GO; GO:0050766; P:positive regulation of phagocytosis; IBA:GO_Central.
DR GO; GO:0050870; P:positive regulation of T cell activation; IBA:GO_Central.
DR GO; GO:0010468; P:regulation of gene expression; IMP:ARUK-UCL.
DR GO; GO:0032649; P:regulation of interferon-gamma production; IMP:ARUK-UCL.
DR GO; GO:0032651; P:regulation of interleukin-1 beta production; ISS:ARUK-UCL.
DR GO; GO:0032675; P:regulation of interleukin-6 production; ISS:ARUK-UCL.
DR GO; GO:0045428; P:regulation of nitric oxide biosynthetic process; ISS:ARUK-UCL.
DR GO; GO:0032680; P:regulation of tumor necrosis factor production; IGI:ARUK-UCL.
DR Gene3D; 2.60.40.10; -; 3.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003597; Ig_C1-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR013106; Ig_V-set.
DR Pfam; PF07654; C1-set; 2.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00409; IG; 2.
DR SMART; SM00407; IGc1; 2.
DR SMART; SM00406; IGv; 1.
DR SUPFAM; SSF48726; SSF48726; 3.
DR PROSITE; PS50835; IG_LIKE; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Disulfide bond; Glycoprotein;
KW Immunoglobulin domain; Membrane; Phosphoprotein; Reference proteome;
KW Repeat; SH3-binding; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..30
FT /evidence="ECO:0000255"
FT CHAIN 31..504
FT /note="Tyrosine-protein phosphatase non-receptor type
FT substrate 1"
FT /id="PRO_0000014941"
FT TOPO_DOM 31..373
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 374..394
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 395..504
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 32..137
FT /note="Ig-like V-type"
FT DOMAIN 148..247
FT /note="Ig-like C1-type 1"
FT DOMAIN 254..348
FT /note="Ig-like C1-type 2"
FT REGION 336..364
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 402..504
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 429..432
FT /note="SH2-binding"
FT /evidence="ECO:0000255"
FT MOTIF 439..444
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT MOTIF 453..456
FT /note="SH2-binding"
FT /evidence="ECO:0000255"
FT MOTIF 470..473
FT /note="SH2-binding"
FT /evidence="ECO:0000255"
FT MOTIF 496..499
FT /note="SH2-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 448..466
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 429
FT /note="Phosphotyrosine; by Tyr-kinases"
FT /evidence="ECO:0000255"
FT MOD_RES 453
FT /note="Phosphotyrosine; by Tyr-kinases"
FT /evidence="ECO:0000255"
FT MOD_RES 470
FT /note="Phosphotyrosine; by Tyr-kinases"
FT /evidence="ECO:0000250|UniProtKB:P97710"
FT MOD_RES 496
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT CARBOHYD 245
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952"
FT CARBOHYD 270
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 292
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 319
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 55..121
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:17369261, ECO:0000269|PubMed:18657508"
FT DISULFID 170..228
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 273..331
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 130
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_040799"
FT VAR_SEQ 422
FT /note="Q -> QVQSL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_007030"
FT VARIANT 6..7
FT /note="PA -> RS"
FT /id="VAR_015462"
FT VARIANT 20
FT /note="A -> P"
FT /id="VAR_015463"
FT VARIANT 40
FT /note="D -> E (in dbSNP:rs1349896458)"
FT /id="VAR_015464"
FT VARIANT 44
FT /note="L -> S (in dbSNP:rs143735290)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9062191,
FT ECO:0000269|PubMed:9070220"
FT /id="VAR_015465"
FT VARIANT 50
FT /note="T -> S (in dbSNP:rs17855609)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9062191,
FT ECO:0000269|PubMed:9070220"
FT /id="VAR_015466"
FT VARIANT 52
FT /note="T -> I (in dbSNP:rs17855610)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9062191,
FT ECO:0000269|PubMed:9070220"
FT /id="VAR_015468"
FT VARIANT 54
FT /note="R -> H (in dbSNP:rs17855611)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9062191,
FT ECO:0000269|PubMed:9070220"
FT /id="VAR_015470"
FT VARIANT 57
FT /note="A -> V (in dbSNP:rs17855612)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9062191,
FT ECO:0000269|PubMed:9070220"
FT /id="VAR_015471"
FT VARIANT 61
FT /note="I -> N (in dbSNP:rs1371837011)"
FT /id="VAR_015472"
FT VARIANT 68
FT /note="W -> R"
FT /id="VAR_015473"
FT VARIANT 75
FT /note="G -> A (in dbSNP:rs1057114)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9062191,
FT ECO:0000269|PubMed:9070220"
FT /id="VAR_015474"
FT VARIANT 77
FT /note="E -> K (in dbSNP:rs1182420620)"
FT /id="VAR_015475"
FT VARIANT 81
FT /note="N -> H"
FT /id="VAR_015477"
FT VARIANT 95
FT /note="D -> E (in dbSNP:rs138283486)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9062191,
FT ECO:0000269|PubMed:9070220"
FT /id="VAR_015478"
FT VARIANT 96
FT /note="L -> S"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9062191,
FT ECO:0000269|PubMed:9070220"
FT /id="VAR_015479"
FT VARIANT 100
FT /note="N -> E (requires 2 nucleotide substitutions;
FT dbSNP:rs386811662)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9062191,
FT ECO:0000269|PubMed:9070220"
FT /id="VAR_015480"
FT VARIANT 107
FT /note="R -> S (in dbSNP:rs17855615)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9062191,
FT ECO:0000269|PubMed:9070220"
FT /id="VAR_015483"
FT VARIANT 109
FT /note="G -> S (in dbSNP:rs17855616)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9062191,
FT ECO:0000269|PubMed:9070220"
FT /id="VAR_015484"
FT VARIANT 125
FT /note="R -> Q (in dbSNP:rs767136065)"
FT /id="VAR_015485"
FT VARIANT 132
FT /note="V -> T (requires 2 nucleotide substitutions;
FT dbSNP:rs386811663)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9062191,
FT ECO:0000269|PubMed:9070220"
FT /id="VAR_015486"
FT VARIANT 134
FT /note="F -> L"
FT /id="VAR_015487"
FT VARIANT 163
FT /note="Q -> D (requires 2 nucleotide substitutions)"
FT /id="VAR_015488"
FT VARIANT 181
FT /note="T -> S"
FT /id="VAR_015489"
FT VARIANT 190
FT /note="E -> Q"
FT /id="VAR_015490"
FT VARIANT 201..202
FT /note="VG -> AR"
FT /id="VAR_015491"
FT VARIANT 214
FT /note="K -> N"
FT /id="VAR_015492"
FT VARIANT 220
FT /note="E -> G"
FT /id="VAR_015493"
FT VARIANT 222
FT /note="V -> I (in dbSNP:rs143385810)"
FT /id="VAR_015494"
FT VARIANT 236
FT /note="Q -> R"
FT /id="VAR_015495"
FT VARIANT 239..240
FT /note="PL -> SF"
FT /id="VAR_015496"
FT VARIANT 251
FT /note="R -> Q (in dbSNP:rs377448893)"
FT /id="VAR_015497"
FT VARIANT 261
FT /note="Q -> L"
FT /id="VAR_015498"
FT VARIANT 263
FT /note="V -> M (in dbSNP:rs754806675)"
FT /id="VAR_015499"
FT VARIANT 271
FT /note="V -> I"
FT /id="VAR_015500"
FT VARIANT 276
FT /note="R -> T"
FT /id="VAR_015501"
FT VARIANT 302
FT /note="V -> L (in dbSNP:rs2422666)"
FT /id="VAR_015502"
FT VARIANT 339
FT /note="P -> S"
FT /id="VAR_015503"
FT VARIANT 353
FT /note="P -> L (in dbSNP:rs138876160)"
FT /id="VAR_015504"
FT VARIANT 357
FT /note="G -> S (in dbSNP:rs1200233096)"
FT /id="VAR_015505"
FT VARIANT 367
FT /note="S -> P"
FT /id="VAR_015506"
FT VARIANT 370
FT /note="R -> Q (in dbSNP:rs778218860)"
FT /id="VAR_015507"
FT VARIANT 389
FT /note="A -> E"
FT /id="VAR_015508"
FT VARIANT 443
FT /note="Q -> R"
FT /id="VAR_015509"
FT VARIANT 460
FT /note="P -> L (in dbSNP:rs1168490568)"
FT /id="VAR_015510"
FT VARIANT 486
FT /note="A -> L (requires 2 nucleotide substitutions)"
FT /id="VAR_015511"
FT VARIANT 491
FT /note="P -> L (in dbSNP:rs367629199)"
FT /id="VAR_015512"
FT CONFLICT 259
FT /note="T -> I (in Ref. 7; CAA71944)"
FT /evidence="ECO:0000305"
FT CONFLICT 503
FT /note="R -> K (in Ref. 7; CAA71944)"
FT /evidence="ECO:0000305"
FT STRAND 41..46
FT /evidence="ECO:0007829|PDB:2UV3"
FT STRAND 51..53
FT /evidence="ECO:0007829|PDB:2UV3"
FT STRAND 56..58
FT /evidence="ECO:0007829|PDB:2UV3"
FT STRAND 66..70
FT /evidence="ECO:0007829|PDB:2UV3"
FT STRAND 77..85
FT /evidence="ECO:0007829|PDB:2UV3"
FT STRAND 90..94
FT /evidence="ECO:0007829|PDB:2UV3"
FT STRAND 96..98
FT /evidence="ECO:0007829|PDB:6NMU"
FT STRAND 106..110
FT /evidence="ECO:0007829|PDB:2UV3"
FT HELIX 113..115
FT /evidence="ECO:0007829|PDB:2UV3"
FT STRAND 117..125
FT /evidence="ECO:0007829|PDB:2UV3"
FT STRAND 127..129
FT /evidence="ECO:0007829|PDB:2UV3"
FT STRAND 132..136
FT /evidence="ECO:0007829|PDB:2UV3"
FT STRAND 140..145
FT /evidence="ECO:0007829|PDB:2UV3"
FT STRAND 152..154
FT /evidence="ECO:0007829|PDB:2WNG"
FT STRAND 165..178
FT /evidence="ECO:0007829|PDB:2WNG"
FT STRAND 181..186
FT /evidence="ECO:0007829|PDB:2WNG"
FT STRAND 194..199
FT /evidence="ECO:0007829|PDB:2WNG"
FT STRAND 207..216
FT /evidence="ECO:0007829|PDB:2WNG"
FT HELIX 221..223
FT /evidence="ECO:0007829|PDB:2WNG"
FT STRAND 225..231
FT /evidence="ECO:0007829|PDB:2WNG"
FT STRAND 240..245
FT /evidence="ECO:0007829|PDB:2WNG"
FT HELIX 246..248
FT /evidence="ECO:0007829|PDB:2WNG"
FT STRAND 255..261
FT /evidence="ECO:0007829|PDB:2WNG"
FT STRAND 269..281
FT /evidence="ECO:0007829|PDB:2WNG"
FT STRAND 283..289
FT /evidence="ECO:0007829|PDB:2WNG"
FT STRAND 292..298
FT /evidence="ECO:0007829|PDB:2WNG"
FT STRAND 310..318
FT /evidence="ECO:0007829|PDB:2WNG"
FT STRAND 328..335
FT /evidence="ECO:0007829|PDB:2WNG"
FT STRAND 341..346
FT /evidence="ECO:0007829|PDB:2WNG"
SQ SEQUENCE 504 AA; 54967 MW; 18D2FD04F6182AD0 CRC64;
MEPAGPAPGR LGPLLCLLLA ASCAWSGVAG EEELQVIQPD KSVLVAAGET ATLRCTATSL
IPVGPIQWFR GAGPGRELIY NQKEGHFPRV TTVSDLTKRN NMDFSIRIGN ITPADAGTYY
CVKFRKGSPD DVEFKSGAGT ELSVRAKPSA PVVSGPAARA TPQHTVSFTC ESHGFSPRDI
TLKWFKNGNE LSDFQTNVDP VGESVSYSIH STAKVVLTRE DVHSQVICEV AHVTLQGDPL
RGTANLSETI RVPPTLEVTQ QPVRAENQVN VTCQVRKFYP QRLQLTWLEN GNVSRTETAS
TVTENKDGTY NWMSWLLVNV SAHRDDVKLT CQVEHDGQPA VSKSHDLKVS AHPKEQGSNT
AAENTGSNER NIYIVVGVVC TLLVALLMAA LYLVRIRQKK AQGSTSSTRL HEPEKNAREI
TQDTNDITYA DLNLPKGKKP APQAAEPNNH TEYASIQTSP QPASEDTLTY ADLDMVHLNR
TPKQPAPKPE PSFSEYASVQ VPRK
