Full text data of ITGAM
ITGAM
(CD11B, CR3A)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Integrin alpha-M (CD11 antigen-like family member B; CR-3 alpha chain; Cell surface glycoprotein MAC-1 subunit alpha; Leukocyte adhesion receptor MO1; Neutrophil adherence receptor; CD11b; Flags: Precursor)
Integrin alpha-M (CD11 antigen-like family member B; CR-3 alpha chain; Cell surface glycoprotein MAC-1 subunit alpha; Leukocyte adhesion receptor MO1; Neutrophil adherence receptor; CD11b; Flags: Precursor)
UniProt
P11215
ID ITAM_HUMAN Reviewed; 1152 AA.
AC P11215; Q4VAK0; Q4VAK1; Q4VAK2;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-1996, sequence version 2.
DT 22-JAN-2014, entry version 159.
DE RecName: Full=Integrin alpha-M;
DE AltName: Full=CD11 antigen-like family member B;
DE AltName: Full=CR-3 alpha chain;
DE AltName: Full=Cell surface glycoprotein MAC-1 subunit alpha;
DE AltName: Full=Leukocyte adhesion receptor MO1;
DE AltName: Full=Neutrophil adherence receptor;
DE AltName: CD_antigen=CD11b;
DE Flags: Precursor;
GN Name=ITGAM; Synonyms=CD11B, CR3A;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=2457584;
RA Corbi A.L., Kishimoto T.K., Miller L.J., Springer T.A.;
RT "The human leukocyte adhesion glycoprotein Mac-1 (complement receptor
RT type 3, CD11b) alpha subunit. Cloning, primary structure, and relation
RT to the integrins, von Willebrand factor and factor B.";
RL J. Biol. Chem. 263:12403-12411(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=2833753; DOI=10.1073/pnas.85.8.2776;
RA Arnaout M.A., Remold-O'Donnell E., Pierce M.W., Harris P., Tenen D.G.;
RT "Molecular cloning of the alpha subunit of human and guinea pig
RT leukocyte adhesion glycoprotein Mo1: chromosomal localization and
RT homology to the alpha subunits of integrins.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:2776-2780(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=2454931; DOI=10.1083/jcb.106.6.2153;
RA Arnaout M.A., Gupta S.K., Pierce M.W., Tenen D.G.;
RT "Amino acid sequence of the alpha subunit of human leukocyte adhesion
RT receptor Mo1 (complement receptor type 3).";
RL J. Cell Biol. 106:2153-2158(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX PubMed=8419480;
RA Fleming J.C., Pahl H.L., Gonzalez D.A., Smith T.F., Tenen D.G.;
RT "Structural analysis of the CD11b gene and phylogenetic analysis of
RT the alpha-integrin gene family demonstrate remarkable conservation of
RT genomic organization and suggest early diversification during
RT evolution.";
RL J. Immunol. 150:480-490(1993).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS
RP HIS-77; THR-441; VAL-858 AND SER-1146.
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 9-1152 (ISOFORM 2).
RX PubMed=2563162; DOI=10.1073/pnas.86.1.257;
RA Hickstein D.D., Hickey M.J., Ozols J., Baker D.M., Back A.L.,
RA Roth G.J.;
RT "cDNA sequence for the alpha M subunit of the human neutrophil
RT adherence receptor indicates homology to integrin alpha subunits.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:257-261(1989).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-9.
RX PubMed=1683702; DOI=10.1073/pnas.88.23.10525;
RA Shelley C.S., Arnaout M.A.;
RT "The promoter of the CD11b gene directs myeloid-specific and
RT developmentally regulated expression.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:10525-10529(1991).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-9.
RC TISSUE=Blood;
RX PubMed=1346576;
RA Pahl H.L., Rosmarin A.G., Tenen D.G.;
RT "Characterization of the myeloid-specific CD11b promoter.";
RL Blood 79:865-870(1992).
RN [9]
RP PROTEIN SEQUENCE OF 17-31.
RX PubMed=3539202; DOI=10.1016/0167-4838(86)90037-3;
RA Pierce M.W., Remold-O'Donnell E., Todd R.F. III, Arnaout M.A.;
RT "N-terminal sequence of human leukocyte glycoprotein Mo1: conservation
RT across species and homology to platelet IIb/IIIa.";
RL Biochim. Biophys. Acta 874:368-371(1986).
RN [10]
RP INTERACTION WITH JAM3.
RX PubMed=12208882; DOI=10.1084/jem.20020267;
RA Santoso S., Sachs U.J.H., Kroll H., Linder M., Ruf A., Preissner K.T.,
RA Chavakis T.;
RT "The junctional adhesion molecule 3 (JAM-3) on human platelets is a
RT counterreceptor for the leukocyte integrin Mac-1.";
RL J. Exp. Med. 196:679-691(2002).
RN [11]
RP INTERACTION WITH JAM3.
RX PubMed=15194813; DOI=10.1091/mbc.E04-04-0317;
RA Zen K., Babbin B.A., Liu Y., Whelan J.B., Nusrat A., Parkos C.A.;
RT "JAM-C is a component of desmosomes and a ligand for CD11b/CD18-
RT mediated neutrophil transepithelial migration.";
RL Mol. Biol. Cell 15:3926-3937(2004).
RN [12]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-900; ASN-940 AND ASN-946,
RP AND MASS SPECTROMETRY.
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
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 148-331.
RX PubMed=7867070; DOI=10.1016/0092-8674(95)90517-0;
RA Lee J.O., Rieu P., Arnaout M.A., Liddington R.;
RT "Crystal structure of the A domain from the alpha subunit of integrin
RT CR3 (CD11b/CD18).";
RL Cell 80:631-638(1995).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 148-334.
RX PubMed=8747460; DOI=10.1016/S0969-2126(01)00271-4;
RA Lee J.O., Bankston L.A., Arnaout M.A., Liddington R.C.;
RT "Two conformations of the integrin A-domain (I-domain): a pathway for
RT activation?";
RL Structure 3:1333-1340(1995).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 148-337.
RX PubMed=9687375; DOI=10.1016/S0969-2126(98)00093-8;
RA Baldwin E.T., Sarver R.W., Bryant G.L. Jr., Curry K.A.,
RA Fairbanks M.B., Finzel B.C., Garlick R.L., Heinrikson R.L.,
RA Horton N.C., Kelley L.L., Mildner A.M., Moon J.B., Mott J.E.,
RA Mutchler V.T., Tomich C.S., Watenpaugh K.D., Wiley V.H.;
RT "Cation binding to the integrin CD11b I domain and activation model
RT assessment.";
RL Structure 6:923-935(1998).
RN [16]
RP 3D-STRUCTURE MODELING OF 17-616.
RX PubMed=9560195; DOI=10.1073/pnas.95.9.4870;
RA Oxvig C., Springer T.A.;
RT "Experimental support for a beta-propeller domain in integrin alpha-
RT subunits and a calcium binding site on its lower surface.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:4870-4875(1998).
RN [17]
RP INVOLVEMENT IN SUSCEPTIBILITY TO SLE, AND VARIANT HIS-77.
RX PubMed=18204448; DOI=10.1038/ng.71;
RA Nath S.K., Han S., Kim-Howard X., Kelly J.A., Viswanathan P.,
RA Gilkeson G.S., Chen W., Zhu C., McEver R.P., Kimberly R.P.,
RA Alarcon-Riquelme M.E., Vyse T.J., Li Q.-Z., Wakeland E.K.,
RA Merrill J.T., James J.A., Kaufman K.M., Guthridge J.M., Harley J.B.;
RT "A nonsynonymous functional variant in integrin-alpha(M) (encoded by
RT ITGAM) is associated with systemic lupus erythematosus.";
RL Nat. Genet. 40:152-154(2008).
RN [18]
RP INVOLVEMENT IN SUSCEPTIBILITY TO SLE.
RX PubMed=18204446; DOI=10.1038/ng.81;
RA Harley J.B., Alarcon-Riquelme M.E., Criswell L.A., Jacob C.O.,
RA Kimberly R.P., Moser K.L., Tsao B.P., Vyse T.J., Langefeld C.D.,
RA Nath S.K., Guthridge J.M., Cobb B.L., Mirel D.B., Marion M.C.,
RA Williams A.H., Divers J., Wang W., Frank S.G., Namjou B.,
RA Gabriel S.B., Lee A.T., Gregersen P.K., Behrens T.W., Taylor K.E.,
RA Fernando M., Zidovetzki R., Gaffney P.M., Edberg J.C., Rioux J.D.,
RA Ojwang J.O., James J.A., Merrill J.T., Gilkeson G.S., Seldin M.F.,
RA Yin H., Baechler E.C., Li Q.-Z., Wakeland E.K., Bruner G.R.,
RA Kaufman K.M., Kelly J.A.;
RT "Genome-wide association scan in women with systemic lupus
RT erythematosus identifies susceptibility variants in ITGAM, PXK,
RT KIAA1542 and other loci.";
RL Nat. Genet. 40:204-210(2008).
CC -!- FUNCTION: Integrin alpha-M/beta-2 is implicated in various
CC adhesive interactions of monocytes, macrophages and granulocytes
CC as well as in mediating the uptake of complement-coated particles.
CC It is identical with CR-3, the receptor for the iC3b fragment of
CC the third complement component. It probably recognizes the R-G-D
CC peptide in C3b. Integrin alpha-M/beta-2 is also a receptor for
CC fibrinogen, factor X and ICAM1. It recognizes P1 and P2 peptides
CC of fibrinogen gamma chain.
CC -!- SUBUNIT: Heterodimer of an alpha and a beta subunit. Alpha-M
CC associates with beta-2. Interacts with JAM3.
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane
CC protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P11215-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P11215-2; Sequence=VSP_047365;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in monocytes and
CC granulocytes.
CC -!- DOMAIN: The integrin I-domain (insert) is a VWFA domain. Integrins
CC with I-domains do not undergo protease cleavage.
CC -!- DISEASE: Systemic lupus erythematosus 6 (SLEB6) [MIM:609939]: A
CC chronic, relapsing, inflammatory, and often febrile multisystemic
CC disorder of connective tissue, characterized principally by
CC involvement of the skin, joints, kidneys and serosal membranes. It
CC is of unknown etiology, but is thought to represent a failure of
CC the regulatory mechanisms of the autoimmune system. The disease is
CC marked by a wide range of system dysfunctions, an elevated
CC erythrocyte sedimentation rate, and the formation of LE cells in
CC the blood or bone marrow. Note=Disease susceptibility may be
CC associated with variations affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the integrin alpha chain family.
CC -!- SIMILARITY: Contains 7 FG-GAP repeats.
CC -!- SIMILARITY: Contains 1 VWFA domain.
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DR EMBL; J03925; AAA59544.1; -; mRNA.
DR EMBL; M18044; AAA59491.1; -; mRNA.
DR EMBL; S52227; AAB24821.1; -; Genomic_DNA.
DR EMBL; S52152; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52153; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52154; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52155; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52157; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52159; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52161; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52164; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52165; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52167; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52169; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52170; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52173; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52174; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52180; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52181; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52184; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52189; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52191; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52192; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52203; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52212; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52213; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52216; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52219; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52220; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52221; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52222; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52226; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; BC096346; AAH96346.1; -; mRNA.
DR EMBL; BC096347; AAH96347.1; -; mRNA.
DR EMBL; BC096348; AAH96348.1; -; mRNA.
DR EMBL; BC099660; AAH99660.1; -; mRNA.
DR EMBL; J04145; AAA59903.1; -; mRNA.
DR EMBL; M76724; AAA58410.1; -; Genomic_DNA.
DR EMBL; M84477; AAA51960.1; -; Genomic_DNA.
DR PIR; A31108; RWHU1B.
DR RefSeq; NP_000623.2; NM_000632.3.
DR RefSeq; NP_001139280.1; NM_001145808.1.
DR UniGene; Hs.172631; -.
DR PDB; 1A8X; Model; -; A=17-1152.
DR PDB; 1BHO; X-ray; 2.70 A; 1/2=149-337.
DR PDB; 1BHQ; X-ray; 2.70 A; 1/2=149-337.
DR PDB; 1IDN; X-ray; 2.70 A; 1/2=149-337.
DR PDB; 1IDO; X-ray; 1.70 A; A=143-331.
DR PDB; 1JLM; X-ray; 2.00 A; A=143-334.
DR PDB; 1M1U; X-ray; 2.30 A; A=139-331.
DR PDB; 1MF7; X-ray; 1.25 A; A=144-333.
DR PDB; 1N9Z; X-ray; 2.50 A; A=145-335.
DR PDB; 1NA5; X-ray; 1.50 A; A=144-335.
DR PDB; 2LKE; NMR; -; A=1129-1152.
DR PDB; 2LKJ; NMR; -; A=1129-1152.
DR PDB; 3Q3G; X-ray; 2.70 A; E/G/I/L=148-337.
DR PDB; 3QA3; X-ray; 3.00 A; E/G/I/L=148-337.
DR PDB; 4M76; X-ray; 2.80 A; B=143-337.
DR PDBsum; 1A8X; -.
DR PDBsum; 1BHO; -.
DR PDBsum; 1BHQ; -.
DR PDBsum; 1IDN; -.
DR PDBsum; 1IDO; -.
DR PDBsum; 1JLM; -.
DR PDBsum; 1M1U; -.
DR PDBsum; 1MF7; -.
DR PDBsum; 1N9Z; -.
DR PDBsum; 1NA5; -.
DR PDBsum; 2LKE; -.
DR PDBsum; 2LKJ; -.
DR PDBsum; 3Q3G; -.
DR PDBsum; 3QA3; -.
DR PDBsum; 4M76; -.
DR ProteinModelPortal; P11215; -.
DR SMR; P11215; 17-335, 345-1101.
DR MINT; MINT-1489258; -.
DR STRING; 9606.ENSP00000287497; -.
DR BindingDB; P11215; -.
DR ChEMBL; CHEMBL2111362; -.
DR PhosphoSite; P11215; -.
DR DMDM; 1708572; -.
DR PaxDb; P11215; -.
DR PRIDE; P11215; -.
DR Ensembl; ENST00000287497; ENSP00000287497; ENSG00000169896.
DR Ensembl; ENST00000544665; ENSP00000441691; ENSG00000169896.
DR GeneID; 3684; -.
DR KEGG; hsa:3684; -.
DR UCSC; uc002ebq.3; human.
DR CTD; 3684; -.
DR GeneCards; GC16P031271; -.
DR HGNC; HGNC:6149; ITGAM.
DR HPA; CAB025091; -.
DR HPA; HPA002274; -.
DR MIM; 120980; gene.
DR MIM; 609939; phenotype.
DR neXtProt; NX_P11215; -.
DR Orphanet; 536; Systemic lupus erythematosus.
DR PharmGKB; PA29949; -.
DR eggNOG; NOG301393; -.
DR HOGENOM; HOG000113114; -.
DR HOVERGEN; HBG100530; -.
DR InParanoid; P11215; -.
DR KO; K06461; -.
DR OMA; MMSEAGP; -.
DR OrthoDB; EOG7353W1; -.
DR Reactome; REACT_118779; Extracellular matrix organization.
DR Reactome; REACT_604; Hemostasis.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; P11215; -.
DR EvolutionaryTrace; P11215; -.
DR GeneWiki; Integrin_alpha_M; -.
DR GenomeRNAi; 3684; -.
DR NextBio; 14419; -.
DR PRO; PR:P11215; -.
DR ArrayExpress; P11215; -.
DR Bgee; P11215; -.
DR CleanEx; HS_ITGAM; -.
DR Genevestigator; P11215; -.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0008305; C:integrin complex; TAS:ProtInc.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0008201; F:heparin binding; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0050798; P:activated T cell proliferation; IEA:Ensembl.
DR GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR GO; GO:0007155; P:cell adhesion; TAS:ProtInc.
DR GO; GO:0045123; P:cellular extravasation; IEA:Ensembl.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0007159; P:leukocyte cell-cell adhesion; IEA:Ensembl.
DR GO; GO:0050900; P:leukocyte migration; TAS:Reactome.
DR GO; GO:0014005; P:microglia development; IEA:Ensembl.
DR GO; GO:0030593; P:neutrophil chemotaxis; IEA:Ensembl.
DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
DR InterPro; IPR013517; FG-GAP.
DR InterPro; IPR013519; Int_alpha_beta-p.
DR InterPro; IPR000413; Integrin_alpha.
DR InterPro; IPR013649; Integrin_alpha-2.
DR InterPro; IPR018184; Integrin_alpha_C_CS.
DR InterPro; IPR002035; VWF_A.
DR Pfam; PF01839; FG-GAP; 1.
DR Pfam; PF00357; Integrin_alpha; 1.
DR Pfam; PF08441; Integrin_alpha2; 1.
DR Pfam; PF00092; VWA; 1.
DR PRINTS; PR01185; INTEGRINA.
DR SMART; SM00191; Int_alpha; 5.
DR SMART; SM00327; VWA; 1.
DR PROSITE; PS51470; FG_GAP; 7.
DR PROSITE; PS00242; INTEGRIN_ALPHA; 1.
DR PROSITE; PS50234; VWFA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Cell adhesion;
KW Complete proteome; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Integrin; Magnesium; Membrane; Metal-binding;
KW Polymorphism; Receptor; Reference proteome; Repeat; Signal;
KW Systemic lupus erythematosus; Transmembrane; Transmembrane helix.
FT SIGNAL 1 16
FT CHAIN 17 1152 Integrin alpha-M.
FT /FTId=PRO_0000016289.
FT TOPO_DOM 17 1104 Extracellular (Potential).
FT TRANSMEM 1105 1128 Helical; (Potential).
FT TOPO_DOM 1129 1152 Cytoplasmic (Potential).
FT REPEAT 18 75 FG-GAP 1.
FT REPEAT 76 135 FG-GAP 2.
FT DOMAIN 150 328 VWFA.
FT REPEAT 339 390 FG-GAP 3.
FT REPEAT 391 444 FG-GAP 4.
FT REPEAT 445 503 FG-GAP 5.
FT REPEAT 506 564 FG-GAP 6.
FT REPEAT 569 629 FG-GAP 7.
FT CA_BIND 465 473 Potential.
FT CA_BIND 529 537 Potential.
FT CA_BIND 592 600 Potential.
FT MOTIF 1131 1135 GFFKR motif.
FT CARBOHYD 86 86 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 240 240 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 391 391 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 469 469 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 692 692 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 696 696 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 734 734 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 801 801 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 880 880 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 900 900 N-linked (GlcNAc...).
FT CARBOHYD 911 911 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 940 940 N-linked (GlcNAc...).
FT CARBOHYD 946 946 N-linked (GlcNAc...).
FT CARBOHYD 978 978 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 993 993 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1021 1021 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1044 1044 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1050 1050 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1075 1075 N-linked (GlcNAc...) (Potential).
FT DISULFID 66 73 By similarity.
FT DISULFID 105 123 By similarity.
FT DISULFID 654 711 By similarity.
FT DISULFID 770 776 By similarity.
FT DISULFID 847 864 By similarity.
FT DISULFID 998 1022 By similarity.
FT DISULFID 1027 1032 By similarity.
FT VAR_SEQ 499 499 G -> GQ (in isoform 2).
FT /FTId=VSP_047365.
FT VARIANT 77 77 R -> H (influences susceptibility to SLE;
FT dbSNP:rs1143679).
FT /FTId=VAR_043870.
FT VARIANT 441 441 M -> T (in dbSNP:rs11861251).
FT /FTId=VAR_043871.
FT VARIANT 858 858 A -> V (in dbSNP:rs1143683).
FT /FTId=VAR_043872.
FT VARIANT 1146 1146 P -> S (in dbSNP:rs1143678).
FT /FTId=VAR_043873.
FT CONFLICT 965 965 L -> P (in Ref. 2; AAA59491).
FT STRAND 149 156
FT HELIX 163 180
FT STRAND 185 200
FT HELIX 202 207
FT HELIX 211 215
FT HELIX 227 236
FT TURN 237 239
FT HELIX 241 243
FT STRAND 249 259
FT HELIX 268 270
FT HELIX 272 277
FT STRAND 280 288
FT HELIX 289 291
FT HELIX 294 303
FT HELIX 308 311
FT STRAND 312 317
FT HELIX 318 324
FT HELIX 325 333
FT HELIX 1130 1132
FT HELIX 1133 1143
FT STRAND 1147 1149
SQ SEQUENCE 1152 AA; 127179 MW; DF77408ED5EE25F9 CRC64;
MALRVLLLTA LTLCHGFNLD TENAMTFQEN ARGFGQSVVQ LQGSRVVVGA PQEIVAANQR
GSLYQCDYST GSCEPIRLQV PVEAVNMSLG LSLAATTSPP QLLACGPTVH QTCSENTYVK
GLCFLFGSNL RQQPQKFPEA LRGCPQEDSD IAFLIDGSGS IIPHDFRRMK EFVSTVMEQL
KKSKTLFSLM QYSEEFRIHF TFKEFQNNPN PRSLVKPITQ LLGRTHTATG IRKVVRELFN
ITNGARKNAF KILVVITDGE KFGDPLGYED VIPEADREGV IRYVIGVGDA FRSEKSRQEL
NTIASKPPRD HVFQVNNFEA LKTIQNQLRE KIFAIEGTQT GSSSSFEHEM SQEGFSAAIT
SNGPLLSTVG SYDWAGGVFL YTSKEKSTFI NMTRVDSDMN DAYLGYAAAI ILRNRVQSLV
LGAPRYQHIG LVAMFRQNTG MWESNANVKG TQIGAYFGAS LCSVDVDSNG STDLVLIGAP
HYYEQTRGGQ VSVCPLPRGR ARWQCDAVLY GEQGQPWGRF GAALTVLGDV NGDKLTDVAI
GAPGEEDNRG AVYLFHGTSG SGISPSHSQR IAGSKLSPRL QYFGQSLSGG QDLTMDGLVD
LTVGAQGHVL LLRSQPVLRV KAIMEFNPRE VARNVFECND QVVKGKEAGE VRVCLHVQKS
TRDRLREGQI QSVVTYDLAL DSGRPHSRAV FNETKNSTRR QTQVLGLTQT CETLKLQLPN
CIEDPVSPIV LRLNFSLVGT PLSAFGNLRP VLAEDAQRLF TALFPFEKNC GNDNICQDDL
SITFSFMSLD CLVVGGPREF NVTVTVRNDG EDSYRTQVTF FFPLDLSYRK VSTLQNQRSQ
RSWRLACESA SSTEVSGALK STSCSINHPI FPENSEVTFN ITFDVDSKAS LGNKLLLKAN
VTSENNMPRT NKTEFQLELP VKYAVYMVVT SHGVSTKYLN FTASENTSRV MQHQYQVSNL
GQRSLPISLV FLVPVRLNQT VIWDRPQVTF SENLSSTCHT KERLPSHSDF LAELRKAPVV
NCSIAVCQRI QCDIPFFGIQ EEFNATLKGN LSFDWYIKTS HNHLLIVSTA EILFNDSVFT
LLPGQGAFVR SQTETKVEPF EVPNPLPLIV GSSVGGLLLL ALITAALYKL GFFKRQYKDM
MSEGGPPGAE PQ
//
ID ITAM_HUMAN Reviewed; 1152 AA.
AC P11215; Q4VAK0; Q4VAK1; Q4VAK2;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-1996, sequence version 2.
DT 22-JAN-2014, entry version 159.
DE RecName: Full=Integrin alpha-M;
DE AltName: Full=CD11 antigen-like family member B;
DE AltName: Full=CR-3 alpha chain;
DE AltName: Full=Cell surface glycoprotein MAC-1 subunit alpha;
DE AltName: Full=Leukocyte adhesion receptor MO1;
DE AltName: Full=Neutrophil adherence receptor;
DE AltName: CD_antigen=CD11b;
DE Flags: Precursor;
GN Name=ITGAM; Synonyms=CD11B, CR3A;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=2457584;
RA Corbi A.L., Kishimoto T.K., Miller L.J., Springer T.A.;
RT "The human leukocyte adhesion glycoprotein Mac-1 (complement receptor
RT type 3, CD11b) alpha subunit. Cloning, primary structure, and relation
RT to the integrins, von Willebrand factor and factor B.";
RL J. Biol. Chem. 263:12403-12411(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=2833753; DOI=10.1073/pnas.85.8.2776;
RA Arnaout M.A., Remold-O'Donnell E., Pierce M.W., Harris P., Tenen D.G.;
RT "Molecular cloning of the alpha subunit of human and guinea pig
RT leukocyte adhesion glycoprotein Mo1: chromosomal localization and
RT homology to the alpha subunits of integrins.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:2776-2780(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=2454931; DOI=10.1083/jcb.106.6.2153;
RA Arnaout M.A., Gupta S.K., Pierce M.W., Tenen D.G.;
RT "Amino acid sequence of the alpha subunit of human leukocyte adhesion
RT receptor Mo1 (complement receptor type 3).";
RL J. Cell Biol. 106:2153-2158(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX PubMed=8419480;
RA Fleming J.C., Pahl H.L., Gonzalez D.A., Smith T.F., Tenen D.G.;
RT "Structural analysis of the CD11b gene and phylogenetic analysis of
RT the alpha-integrin gene family demonstrate remarkable conservation of
RT genomic organization and suggest early diversification during
RT evolution.";
RL J. Immunol. 150:480-490(1993).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS
RP HIS-77; THR-441; VAL-858 AND SER-1146.
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 9-1152 (ISOFORM 2).
RX PubMed=2563162; DOI=10.1073/pnas.86.1.257;
RA Hickstein D.D., Hickey M.J., Ozols J., Baker D.M., Back A.L.,
RA Roth G.J.;
RT "cDNA sequence for the alpha M subunit of the human neutrophil
RT adherence receptor indicates homology to integrin alpha subunits.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:257-261(1989).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-9.
RX PubMed=1683702; DOI=10.1073/pnas.88.23.10525;
RA Shelley C.S., Arnaout M.A.;
RT "The promoter of the CD11b gene directs myeloid-specific and
RT developmentally regulated expression.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:10525-10529(1991).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-9.
RC TISSUE=Blood;
RX PubMed=1346576;
RA Pahl H.L., Rosmarin A.G., Tenen D.G.;
RT "Characterization of the myeloid-specific CD11b promoter.";
RL Blood 79:865-870(1992).
RN [9]
RP PROTEIN SEQUENCE OF 17-31.
RX PubMed=3539202; DOI=10.1016/0167-4838(86)90037-3;
RA Pierce M.W., Remold-O'Donnell E., Todd R.F. III, Arnaout M.A.;
RT "N-terminal sequence of human leukocyte glycoprotein Mo1: conservation
RT across species and homology to platelet IIb/IIIa.";
RL Biochim. Biophys. Acta 874:368-371(1986).
RN [10]
RP INTERACTION WITH JAM3.
RX PubMed=12208882; DOI=10.1084/jem.20020267;
RA Santoso S., Sachs U.J.H., Kroll H., Linder M., Ruf A., Preissner K.T.,
RA Chavakis T.;
RT "The junctional adhesion molecule 3 (JAM-3) on human platelets is a
RT counterreceptor for the leukocyte integrin Mac-1.";
RL J. Exp. Med. 196:679-691(2002).
RN [11]
RP INTERACTION WITH JAM3.
RX PubMed=15194813; DOI=10.1091/mbc.E04-04-0317;
RA Zen K., Babbin B.A., Liu Y., Whelan J.B., Nusrat A., Parkos C.A.;
RT "JAM-C is a component of desmosomes and a ligand for CD11b/CD18-
RT mediated neutrophil transepithelial migration.";
RL Mol. Biol. Cell 15:3926-3937(2004).
RN [12]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-900; ASN-940 AND ASN-946,
RP AND MASS SPECTROMETRY.
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
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 148-331.
RX PubMed=7867070; DOI=10.1016/0092-8674(95)90517-0;
RA Lee J.O., Rieu P., Arnaout M.A., Liddington R.;
RT "Crystal structure of the A domain from the alpha subunit of integrin
RT CR3 (CD11b/CD18).";
RL Cell 80:631-638(1995).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 148-334.
RX PubMed=8747460; DOI=10.1016/S0969-2126(01)00271-4;
RA Lee J.O., Bankston L.A., Arnaout M.A., Liddington R.C.;
RT "Two conformations of the integrin A-domain (I-domain): a pathway for
RT activation?";
RL Structure 3:1333-1340(1995).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 148-337.
RX PubMed=9687375; DOI=10.1016/S0969-2126(98)00093-8;
RA Baldwin E.T., Sarver R.W., Bryant G.L. Jr., Curry K.A.,
RA Fairbanks M.B., Finzel B.C., Garlick R.L., Heinrikson R.L.,
RA Horton N.C., Kelley L.L., Mildner A.M., Moon J.B., Mott J.E.,
RA Mutchler V.T., Tomich C.S., Watenpaugh K.D., Wiley V.H.;
RT "Cation binding to the integrin CD11b I domain and activation model
RT assessment.";
RL Structure 6:923-935(1998).
RN [16]
RP 3D-STRUCTURE MODELING OF 17-616.
RX PubMed=9560195; DOI=10.1073/pnas.95.9.4870;
RA Oxvig C., Springer T.A.;
RT "Experimental support for a beta-propeller domain in integrin alpha-
RT subunits and a calcium binding site on its lower surface.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:4870-4875(1998).
RN [17]
RP INVOLVEMENT IN SUSCEPTIBILITY TO SLE, AND VARIANT HIS-77.
RX PubMed=18204448; DOI=10.1038/ng.71;
RA Nath S.K., Han S., Kim-Howard X., Kelly J.A., Viswanathan P.,
RA Gilkeson G.S., Chen W., Zhu C., McEver R.P., Kimberly R.P.,
RA Alarcon-Riquelme M.E., Vyse T.J., Li Q.-Z., Wakeland E.K.,
RA Merrill J.T., James J.A., Kaufman K.M., Guthridge J.M., Harley J.B.;
RT "A nonsynonymous functional variant in integrin-alpha(M) (encoded by
RT ITGAM) is associated with systemic lupus erythematosus.";
RL Nat. Genet. 40:152-154(2008).
RN [18]
RP INVOLVEMENT IN SUSCEPTIBILITY TO SLE.
RX PubMed=18204446; DOI=10.1038/ng.81;
RA Harley J.B., Alarcon-Riquelme M.E., Criswell L.A., Jacob C.O.,
RA Kimberly R.P., Moser K.L., Tsao B.P., Vyse T.J., Langefeld C.D.,
RA Nath S.K., Guthridge J.M., Cobb B.L., Mirel D.B., Marion M.C.,
RA Williams A.H., Divers J., Wang W., Frank S.G., Namjou B.,
RA Gabriel S.B., Lee A.T., Gregersen P.K., Behrens T.W., Taylor K.E.,
RA Fernando M., Zidovetzki R., Gaffney P.M., Edberg J.C., Rioux J.D.,
RA Ojwang J.O., James J.A., Merrill J.T., Gilkeson G.S., Seldin M.F.,
RA Yin H., Baechler E.C., Li Q.-Z., Wakeland E.K., Bruner G.R.,
RA Kaufman K.M., Kelly J.A.;
RT "Genome-wide association scan in women with systemic lupus
RT erythematosus identifies susceptibility variants in ITGAM, PXK,
RT KIAA1542 and other loci.";
RL Nat. Genet. 40:204-210(2008).
CC -!- FUNCTION: Integrin alpha-M/beta-2 is implicated in various
CC adhesive interactions of monocytes, macrophages and granulocytes
CC as well as in mediating the uptake of complement-coated particles.
CC It is identical with CR-3, the receptor for the iC3b fragment of
CC the third complement component. It probably recognizes the R-G-D
CC peptide in C3b. Integrin alpha-M/beta-2 is also a receptor for
CC fibrinogen, factor X and ICAM1. It recognizes P1 and P2 peptides
CC of fibrinogen gamma chain.
CC -!- SUBUNIT: Heterodimer of an alpha and a beta subunit. Alpha-M
CC associates with beta-2. Interacts with JAM3.
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane
CC protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P11215-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P11215-2; Sequence=VSP_047365;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in monocytes and
CC granulocytes.
CC -!- DOMAIN: The integrin I-domain (insert) is a VWFA domain. Integrins
CC with I-domains do not undergo protease cleavage.
CC -!- DISEASE: Systemic lupus erythematosus 6 (SLEB6) [MIM:609939]: A
CC chronic, relapsing, inflammatory, and often febrile multisystemic
CC disorder of connective tissue, characterized principally by
CC involvement of the skin, joints, kidneys and serosal membranes. It
CC is of unknown etiology, but is thought to represent a failure of
CC the regulatory mechanisms of the autoimmune system. The disease is
CC marked by a wide range of system dysfunctions, an elevated
CC erythrocyte sedimentation rate, and the formation of LE cells in
CC the blood or bone marrow. Note=Disease susceptibility may be
CC associated with variations affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the integrin alpha chain family.
CC -!- SIMILARITY: Contains 7 FG-GAP repeats.
CC -!- SIMILARITY: Contains 1 VWFA domain.
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DR EMBL; J03925; AAA59544.1; -; mRNA.
DR EMBL; M18044; AAA59491.1; -; mRNA.
DR EMBL; S52227; AAB24821.1; -; Genomic_DNA.
DR EMBL; S52152; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52153; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52154; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52155; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52157; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52159; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52161; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52164; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52165; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52167; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52169; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52170; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52173; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52174; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52180; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52181; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52184; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52189; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52191; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52192; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52203; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52212; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52213; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52216; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52219; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52220; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52221; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52222; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; S52226; AAB24821.1; JOINED; Genomic_DNA.
DR EMBL; BC096346; AAH96346.1; -; mRNA.
DR EMBL; BC096347; AAH96347.1; -; mRNA.
DR EMBL; BC096348; AAH96348.1; -; mRNA.
DR EMBL; BC099660; AAH99660.1; -; mRNA.
DR EMBL; J04145; AAA59903.1; -; mRNA.
DR EMBL; M76724; AAA58410.1; -; Genomic_DNA.
DR EMBL; M84477; AAA51960.1; -; Genomic_DNA.
DR PIR; A31108; RWHU1B.
DR RefSeq; NP_000623.2; NM_000632.3.
DR RefSeq; NP_001139280.1; NM_001145808.1.
DR UniGene; Hs.172631; -.
DR PDB; 1A8X; Model; -; A=17-1152.
DR PDB; 1BHO; X-ray; 2.70 A; 1/2=149-337.
DR PDB; 1BHQ; X-ray; 2.70 A; 1/2=149-337.
DR PDB; 1IDN; X-ray; 2.70 A; 1/2=149-337.
DR PDB; 1IDO; X-ray; 1.70 A; A=143-331.
DR PDB; 1JLM; X-ray; 2.00 A; A=143-334.
DR PDB; 1M1U; X-ray; 2.30 A; A=139-331.
DR PDB; 1MF7; X-ray; 1.25 A; A=144-333.
DR PDB; 1N9Z; X-ray; 2.50 A; A=145-335.
DR PDB; 1NA5; X-ray; 1.50 A; A=144-335.
DR PDB; 2LKE; NMR; -; A=1129-1152.
DR PDB; 2LKJ; NMR; -; A=1129-1152.
DR PDB; 3Q3G; X-ray; 2.70 A; E/G/I/L=148-337.
DR PDB; 3QA3; X-ray; 3.00 A; E/G/I/L=148-337.
DR PDB; 4M76; X-ray; 2.80 A; B=143-337.
DR PDBsum; 1A8X; -.
DR PDBsum; 1BHO; -.
DR PDBsum; 1BHQ; -.
DR PDBsum; 1IDN; -.
DR PDBsum; 1IDO; -.
DR PDBsum; 1JLM; -.
DR PDBsum; 1M1U; -.
DR PDBsum; 1MF7; -.
DR PDBsum; 1N9Z; -.
DR PDBsum; 1NA5; -.
DR PDBsum; 2LKE; -.
DR PDBsum; 2LKJ; -.
DR PDBsum; 3Q3G; -.
DR PDBsum; 3QA3; -.
DR PDBsum; 4M76; -.
DR ProteinModelPortal; P11215; -.
DR SMR; P11215; 17-335, 345-1101.
DR MINT; MINT-1489258; -.
DR STRING; 9606.ENSP00000287497; -.
DR BindingDB; P11215; -.
DR ChEMBL; CHEMBL2111362; -.
DR PhosphoSite; P11215; -.
DR DMDM; 1708572; -.
DR PaxDb; P11215; -.
DR PRIDE; P11215; -.
DR Ensembl; ENST00000287497; ENSP00000287497; ENSG00000169896.
DR Ensembl; ENST00000544665; ENSP00000441691; ENSG00000169896.
DR GeneID; 3684; -.
DR KEGG; hsa:3684; -.
DR UCSC; uc002ebq.3; human.
DR CTD; 3684; -.
DR GeneCards; GC16P031271; -.
DR HGNC; HGNC:6149; ITGAM.
DR HPA; CAB025091; -.
DR HPA; HPA002274; -.
DR MIM; 120980; gene.
DR MIM; 609939; phenotype.
DR neXtProt; NX_P11215; -.
DR Orphanet; 536; Systemic lupus erythematosus.
DR PharmGKB; PA29949; -.
DR eggNOG; NOG301393; -.
DR HOGENOM; HOG000113114; -.
DR HOVERGEN; HBG100530; -.
DR InParanoid; P11215; -.
DR KO; K06461; -.
DR OMA; MMSEAGP; -.
DR OrthoDB; EOG7353W1; -.
DR Reactome; REACT_118779; Extracellular matrix organization.
DR Reactome; REACT_604; Hemostasis.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; P11215; -.
DR EvolutionaryTrace; P11215; -.
DR GeneWiki; Integrin_alpha_M; -.
DR GenomeRNAi; 3684; -.
DR NextBio; 14419; -.
DR PRO; PR:P11215; -.
DR ArrayExpress; P11215; -.
DR Bgee; P11215; -.
DR CleanEx; HS_ITGAM; -.
DR Genevestigator; P11215; -.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0008305; C:integrin complex; TAS:ProtInc.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0008201; F:heparin binding; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0050798; P:activated T cell proliferation; IEA:Ensembl.
DR GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR GO; GO:0007155; P:cell adhesion; TAS:ProtInc.
DR GO; GO:0045123; P:cellular extravasation; IEA:Ensembl.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0007159; P:leukocyte cell-cell adhesion; IEA:Ensembl.
DR GO; GO:0050900; P:leukocyte migration; TAS:Reactome.
DR GO; GO:0014005; P:microglia development; IEA:Ensembl.
DR GO; GO:0030593; P:neutrophil chemotaxis; IEA:Ensembl.
DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
DR InterPro; IPR013517; FG-GAP.
DR InterPro; IPR013519; Int_alpha_beta-p.
DR InterPro; IPR000413; Integrin_alpha.
DR InterPro; IPR013649; Integrin_alpha-2.
DR InterPro; IPR018184; Integrin_alpha_C_CS.
DR InterPro; IPR002035; VWF_A.
DR Pfam; PF01839; FG-GAP; 1.
DR Pfam; PF00357; Integrin_alpha; 1.
DR Pfam; PF08441; Integrin_alpha2; 1.
DR Pfam; PF00092; VWA; 1.
DR PRINTS; PR01185; INTEGRINA.
DR SMART; SM00191; Int_alpha; 5.
DR SMART; SM00327; VWA; 1.
DR PROSITE; PS51470; FG_GAP; 7.
DR PROSITE; PS00242; INTEGRIN_ALPHA; 1.
DR PROSITE; PS50234; VWFA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Cell adhesion;
KW Complete proteome; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Integrin; Magnesium; Membrane; Metal-binding;
KW Polymorphism; Receptor; Reference proteome; Repeat; Signal;
KW Systemic lupus erythematosus; Transmembrane; Transmembrane helix.
FT SIGNAL 1 16
FT CHAIN 17 1152 Integrin alpha-M.
FT /FTId=PRO_0000016289.
FT TOPO_DOM 17 1104 Extracellular (Potential).
FT TRANSMEM 1105 1128 Helical; (Potential).
FT TOPO_DOM 1129 1152 Cytoplasmic (Potential).
FT REPEAT 18 75 FG-GAP 1.
FT REPEAT 76 135 FG-GAP 2.
FT DOMAIN 150 328 VWFA.
FT REPEAT 339 390 FG-GAP 3.
FT REPEAT 391 444 FG-GAP 4.
FT REPEAT 445 503 FG-GAP 5.
FT REPEAT 506 564 FG-GAP 6.
FT REPEAT 569 629 FG-GAP 7.
FT CA_BIND 465 473 Potential.
FT CA_BIND 529 537 Potential.
FT CA_BIND 592 600 Potential.
FT MOTIF 1131 1135 GFFKR motif.
FT CARBOHYD 86 86 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 240 240 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 391 391 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 469 469 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 692 692 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 696 696 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 734 734 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 801 801 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 880 880 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 900 900 N-linked (GlcNAc...).
FT CARBOHYD 911 911 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 940 940 N-linked (GlcNAc...).
FT CARBOHYD 946 946 N-linked (GlcNAc...).
FT CARBOHYD 978 978 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 993 993 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1021 1021 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1044 1044 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1050 1050 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1075 1075 N-linked (GlcNAc...) (Potential).
FT DISULFID 66 73 By similarity.
FT DISULFID 105 123 By similarity.
FT DISULFID 654 711 By similarity.
FT DISULFID 770 776 By similarity.
FT DISULFID 847 864 By similarity.
FT DISULFID 998 1022 By similarity.
FT DISULFID 1027 1032 By similarity.
FT VAR_SEQ 499 499 G -> GQ (in isoform 2).
FT /FTId=VSP_047365.
FT VARIANT 77 77 R -> H (influences susceptibility to SLE;
FT dbSNP:rs1143679).
FT /FTId=VAR_043870.
FT VARIANT 441 441 M -> T (in dbSNP:rs11861251).
FT /FTId=VAR_043871.
FT VARIANT 858 858 A -> V (in dbSNP:rs1143683).
FT /FTId=VAR_043872.
FT VARIANT 1146 1146 P -> S (in dbSNP:rs1143678).
FT /FTId=VAR_043873.
FT CONFLICT 965 965 L -> P (in Ref. 2; AAA59491).
FT STRAND 149 156
FT HELIX 163 180
FT STRAND 185 200
FT HELIX 202 207
FT HELIX 211 215
FT HELIX 227 236
FT TURN 237 239
FT HELIX 241 243
FT STRAND 249 259
FT HELIX 268 270
FT HELIX 272 277
FT STRAND 280 288
FT HELIX 289 291
FT HELIX 294 303
FT HELIX 308 311
FT STRAND 312 317
FT HELIX 318 324
FT HELIX 325 333
FT HELIX 1130 1132
FT HELIX 1133 1143
FT STRAND 1147 1149
SQ SEQUENCE 1152 AA; 127179 MW; DF77408ED5EE25F9 CRC64;
MALRVLLLTA LTLCHGFNLD TENAMTFQEN ARGFGQSVVQ LQGSRVVVGA PQEIVAANQR
GSLYQCDYST GSCEPIRLQV PVEAVNMSLG LSLAATTSPP QLLACGPTVH QTCSENTYVK
GLCFLFGSNL RQQPQKFPEA LRGCPQEDSD IAFLIDGSGS IIPHDFRRMK EFVSTVMEQL
KKSKTLFSLM QYSEEFRIHF TFKEFQNNPN PRSLVKPITQ LLGRTHTATG IRKVVRELFN
ITNGARKNAF KILVVITDGE KFGDPLGYED VIPEADREGV IRYVIGVGDA FRSEKSRQEL
NTIASKPPRD HVFQVNNFEA LKTIQNQLRE KIFAIEGTQT GSSSSFEHEM SQEGFSAAIT
SNGPLLSTVG SYDWAGGVFL YTSKEKSTFI NMTRVDSDMN DAYLGYAAAI ILRNRVQSLV
LGAPRYQHIG LVAMFRQNTG MWESNANVKG TQIGAYFGAS LCSVDVDSNG STDLVLIGAP
HYYEQTRGGQ VSVCPLPRGR ARWQCDAVLY GEQGQPWGRF GAALTVLGDV NGDKLTDVAI
GAPGEEDNRG AVYLFHGTSG SGISPSHSQR IAGSKLSPRL QYFGQSLSGG QDLTMDGLVD
LTVGAQGHVL LLRSQPVLRV KAIMEFNPRE VARNVFECND QVVKGKEAGE VRVCLHVQKS
TRDRLREGQI QSVVTYDLAL DSGRPHSRAV FNETKNSTRR QTQVLGLTQT CETLKLQLPN
CIEDPVSPIV LRLNFSLVGT PLSAFGNLRP VLAEDAQRLF TALFPFEKNC GNDNICQDDL
SITFSFMSLD CLVVGGPREF NVTVTVRNDG EDSYRTQVTF FFPLDLSYRK VSTLQNQRSQ
RSWRLACESA SSTEVSGALK STSCSINHPI FPENSEVTFN ITFDVDSKAS LGNKLLLKAN
VTSENNMPRT NKTEFQLELP VKYAVYMVVT SHGVSTKYLN FTASENTSRV MQHQYQVSNL
GQRSLPISLV FLVPVRLNQT VIWDRPQVTF SENLSSTCHT KERLPSHSDF LAELRKAPVV
NCSIAVCQRI QCDIPFFGIQ EEFNATLKGN LSFDWYIKTS HNHLLIVSTA EILFNDSVFT
LLPGQGAFVR SQTETKVEPF EVPNPLPLIV GSSVGGLLLL ALITAALYKL GFFKRQYKDM
MSEGGPPGAE PQ
//
MIM
120980
*RECORD*
*FIELD* NO
120980
*FIELD* TI
*120980 INTEGRIN, ALPHA-M; ITGAM
;;COMPLEMENT RECEPTOR TYPE 3, ALPHA SUBUNIT; CR3A;;
read moreMac1, ALPHA SUBUNIT; MAC1A;;
Mo1, ALPHA SUBUNIT; MO1A;;
CD11B
*FIELD* TX
CLONING
A major surface antigen family on human leukocytes includes complement
receptor type 3 (CR3A; also called ITGAM, Mac1, or Mo1), lymphocyte
function-associated (LFA) antigen type 1 (ITGAL; 153370), and p150,95
(ITGAX; 151510). These antigens share a common beta chain (ITGB2;
600065) of 94 kD, linked noncovalently to 1 of 3 alpha chains
distinctive to each. They promote adhesion of granulocytes to each other
and to endothelial cell monolayers. The apparent molecular weight of the
Mo1 alpha chain is 155 to 165 kD, that of the LFA1 alpha subunit is 180
kD, and that of the Leu M5 subunit is 130 to 150 kD. Pierce et al.
(1986) purified human Mo1 to homogeneity from normal granulocytes by
affinity chromatography and high performance liquid chromatography
(HPLC) and determined the N-terminal amino acid sequence of its alpha
subunit. The obtained sequence was identical, except for 2 conservative
substitutions, to that of the alpha subunit of Mac1 antigen (Springer et
al., 1985). Furthermore, Pierce et al. (1986) found that the N-terminal
amino acid sequence of the alpha subunit of Mo1 was homologous to the
alpha subunit of IIb/IIIa (607759), a glycoprotein that serves similar
adhesive functions on platelets and is deficient or defective in
Glanzmann thrombasthenia (273800). Patients with a history of recurrent
bacterial infections and an inherited deficiency of all 3 leukocyte
membrane surface antigens are thought to have reduced or absent
synthesis of the common beta subunit of the antigen family; see 116920.
Arnaout et al. (1988) described the isolation and analysis of 2 partial
cDNA clones encoding the alpha subunit of Mo1 in humans and guinea pigs.
A comparison of the coding region of the MO1A gene revealed significant
homology with the carboxyl-terminal portions of the alpha subunits of
fibronectin, vitronectin, and platelet IIb/IIIa receptors.
Corbi et al. (1988) described full-length cDNA clones for the alpha
subunit of Mac1.
Arnaout et al. (1988) reported the complete amino acid sequence as
deduced from cDNA for the human alpha subunit. The protein consists of
1,136 amino acids with a long amino-terminal extracytoplasmic domain, a
26-amino acid hydrophobic transmembrane segment, and a
19-carboxyl-terminal cytoplasmic domain. The alpha subunit is highly
similar in sequence to the alpha subunit of leukocyte p150,95.
MAPPING
By Southern analysis of DNA from hamster-human hybrids, Arnaout et al.
(1988) localized the human MO1A gene to chromosome 16, which has been
shown to contain the ITGAL gene (153370). By in situ hybridization,
Corbi et al. (1988) demonstrated that the genes encoding the alpha
subunits of LFA1 (ITGAL), Mac1, and p150,95 (ITGAX), all of which are
involved in leukocyte adhesion, constitute a cluster on 16p13.1-p11.
Callen et al. (1991) narrowed the assignment to 16p11.2.
GENE FUNCTION
Inflammation plays an essential role in the initiation and progression
of atherosclerosis. Simon et al. (2000) presented evidence that it also
has a role in vascular repair after mechanical arterial injury (i.e.,
percutaneous transluminal coronary angioplasty, or PTCA). In animal
models of vascular injury, leukocytes are recruited as a precursor to
intimal thickening. Markers of leukocyte activation, in particular,
increased expression of Mac1, which is responsible for firm leukocyte
adhesion to platelets and fibrinogen on denuded vessels, predict
restenosis after PTCA. To determine whether Mac1-mediated leukocyte
recruitment is causally related to neointimal formation, Simon et al.
(2000) subjected Mac1 knockout mice to a mechanical carotid artery
dilation and complete endothelial denudation. They found that the
selective absence of Mac1 impaired transplatelet leukocyte migration
into the vessel wall, reducing leukocyte accumulation. Diminished medial
leukocyte accumulation was accompanied by markedly reduced neointimal
thickening after vascular injury. These data established a role for
inflammation in neointimal thickening and suggested that leukocyte
recruitment to mechanically injured arteries may prevent restenosis.
Ranganathan et al. (2011) noted that previous work (Cao et al., 2006)
had shown colocalization of low density lipoprotein receptor-related
protein-1 (LRP1; 107770) with integrin alpha-M/beta-2 at the trailing
edge of migrating macrophages and that macrophage migration depended
upon coordinated action of LRP1 and alpha-M/beta-2, as well as tissue
plasminogen activator (PLAT; 173370) and its inhibitor, PAI1 (SERPINE1;
173360). Ranganathan et al. (2011) found that LRP1 specifically bound
integrin alpha-M/beta-2, but not integrin alpha-L/beta-2. Activation of
alpha-M/beta-2 by lipopolysaccharide (LPS) enhanced interaction between
LRP1 and alpha-M/beta-2 in macrophages. Transfection experiments in
HEK293 cells revealed that both the heavy and light chains of LRP1
contributed to alpha-M/beta-2 binding. Within the LRP1 heavy chain,
binding was mediated primarily via ligand-binding motifs 2 and 4. Within
alpha-M, the sequence EQLKKSKTL within the I domain was the major LRP1
recognition site. Exposure of alpha-M/beta-2-expressing HEK293 cells to
soluble LRP1 inhibited cell attachment to fibrinogen (see 134820). Mouse
macrophages lacking Lrp1 were deficient in alpha-M/beta-2
internalization upon LPS stimulation. Ranganathan et al. (2011)
concluded that LRP1 has a role in macrophage migration and that it is
critical for internalization of integrin alpha-M/beta-2.
MOLECULAR GENETICS
For discussion of a possible association between variation in the ITGAM
gene and systemic lupus erythematosus, see SLEB6 (609939).
*FIELD* RF
1. Arnaout, M. A.; Gupta, S. K.; Pierce, M. W.; Tenen, D. G.: Amino
acid sequence of the alpha subunit of human leukocyte adhesion receptor
Mo1 (complement receptor type 3). J. Cell Biol. 106: 2153-2158,
1988.
2. Arnaout, M. A.; Remold-O'Donnell, E.; Pierce, M. W.; Harris, P.;
Tenen, D. G.: Molecular cloning of the alpha-subunit of human and
guinea pig leukocyte adhesion glycoprotein Mo1: chromosomal localization
and homology to the alpha-subunits of integrins. Proc. Nat. Acad.
Sci. 85: 2776-2780, 1988.
3. Callen, D. F.; Chen, L. Z.; Nancarrow, J.; Whitmore, S. A.; Apostolou,
S.; Thompson, A. D.; Lane, S. A.; Stallings, R. L.; Hildebrand, C.
E.; Harris, P. G.; Sutherland, G. R.: Current state of the physical
map of human chromosome 16. (Abstract) Cytogenet. Cell Genet. 58:
1998 only, 1991.
4. Cao, C.; Lawrence, D. A.; Li, Y.; Von Arnim, C. A. F.; Herz, J.;
Su, E. J.; Makarova, A.; Hyman, B. T.; Strickland, D. K.; Zhang, L.
: Endocytic receptor LRP together with tPA and PAI-1 coordinates Mac-1-dependent
macrophage migration. EMBO J. 25: 1860-1870, 2006.
5. Corbi, A. L.; Kishimoto, T. K.; Miller, L. J.; Springer, T. A.
: The human leukocyte adhesion glycoprotein Mac-1 (complement receptor
type 3, CD11b) alpha subunit: cloning, primary structure, and relation
to the integrins, von Willebrand factor and factor B. J. Biol. Chem. 263:
12403-12411, 1988.
6. Corbi, A. L.; Larson, R. S.; Kishimoto, T. K.; Springer, T. A.;
Morton, C. C.: Chromosomal location of the genes encoding the leukocyte
adhesion receptors LFA-1, Mac-1 and p150,95: identification of a gene
cluster involved in cell adhesion. J. Exp. Med. 167: 1597-1607,
1988.
7. Pierce, M. W.; Remold-O'Donnell, E.; Todd, R. F., III; Arnaout,
M. A.: N-terminal sequence of human leukocyte glycoprotein Mo1: conservation
across species and homology to platelet IIb/IIIa. Biochim. Biophys.
Acta 874: 368-371, 1986.
8. Ranganathan, S.; Cao, C.; Catania, J.; Migliorini, M.; Zhang, L.;
Strickland, D. K.: Molecular basis for the interaction of low density
lipoprotein receptor-related protein 1 (LRP1) with integrin alpha-M/beta-2:
identification of binding sites within alpha-M/beta-2 for LRP1. J.
Biol. Chem. 286: 30535-30541, 2011.
9. Simon, D. I.; Chen, Z.; Seifert, P.; Edelman, E. R.; Ballantyne,
C. M.; Rogers, C.: Decreased neointimal formation in Mac-1 -/- mice
reveals a role for inflammation in vascular repair after angioplasty. J.
Clin. Invest. 105: 293-300, 2000.
10. Springer, T. A.; Teplow, D. B.; Dreyer, W. J.: Sequence homology
of the LFA-1 and Mac-1 leukocyte adhesion glycoproteins and unexpected
relation to leukocyte interferon. Nature 314: 540-542, 1985.
*FIELD* CN
Patricia A. Hartz - updated: 6/12/2013
Marla J. F. O'Neill - updated: 11/13/2009
Ada Hamosh - updated: 8/13/2008
Victor A. McKusick - updated: 3/10/2008
Victor A. McKusick - updated: 2/18/2000
*FIELD* CD
Victor A. McKusick: 6/24/1986
*FIELD* ED
tpirozzi: 07/09/2013
mgross: 6/12/2013
wwang: 3/1/2010
terry: 2/24/2010
wwang: 11/25/2009
terry: 11/13/2009
alopez: 8/22/2008
terry: 8/13/2008
alopez: 3/11/2008
terry: 3/10/2008
carol: 5/16/2007
carol: 5/15/2007
ckniffin: 5/15/2003
mcapotos: 3/29/2000
mcapotos: 3/24/2000
mcapotos: 3/23/2000
terry: 2/18/2000
kayiaros: 7/13/1999
dkim: 7/23/1998
mark: 6/12/1997
carol: 7/2/1992
carol: 5/4/1992
carol: 3/26/1992
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/26/1989
*RECORD*
*FIELD* NO
120980
*FIELD* TI
*120980 INTEGRIN, ALPHA-M; ITGAM
;;COMPLEMENT RECEPTOR TYPE 3, ALPHA SUBUNIT; CR3A;;
read moreMac1, ALPHA SUBUNIT; MAC1A;;
Mo1, ALPHA SUBUNIT; MO1A;;
CD11B
*FIELD* TX
CLONING
A major surface antigen family on human leukocytes includes complement
receptor type 3 (CR3A; also called ITGAM, Mac1, or Mo1), lymphocyte
function-associated (LFA) antigen type 1 (ITGAL; 153370), and p150,95
(ITGAX; 151510). These antigens share a common beta chain (ITGB2;
600065) of 94 kD, linked noncovalently to 1 of 3 alpha chains
distinctive to each. They promote adhesion of granulocytes to each other
and to endothelial cell monolayers. The apparent molecular weight of the
Mo1 alpha chain is 155 to 165 kD, that of the LFA1 alpha subunit is 180
kD, and that of the Leu M5 subunit is 130 to 150 kD. Pierce et al.
(1986) purified human Mo1 to homogeneity from normal granulocytes by
affinity chromatography and high performance liquid chromatography
(HPLC) and determined the N-terminal amino acid sequence of its alpha
subunit. The obtained sequence was identical, except for 2 conservative
substitutions, to that of the alpha subunit of Mac1 antigen (Springer et
al., 1985). Furthermore, Pierce et al. (1986) found that the N-terminal
amino acid sequence of the alpha subunit of Mo1 was homologous to the
alpha subunit of IIb/IIIa (607759), a glycoprotein that serves similar
adhesive functions on platelets and is deficient or defective in
Glanzmann thrombasthenia (273800). Patients with a history of recurrent
bacterial infections and an inherited deficiency of all 3 leukocyte
membrane surface antigens are thought to have reduced or absent
synthesis of the common beta subunit of the antigen family; see 116920.
Arnaout et al. (1988) described the isolation and analysis of 2 partial
cDNA clones encoding the alpha subunit of Mo1 in humans and guinea pigs.
A comparison of the coding region of the MO1A gene revealed significant
homology with the carboxyl-terminal portions of the alpha subunits of
fibronectin, vitronectin, and platelet IIb/IIIa receptors.
Corbi et al. (1988) described full-length cDNA clones for the alpha
subunit of Mac1.
Arnaout et al. (1988) reported the complete amino acid sequence as
deduced from cDNA for the human alpha subunit. The protein consists of
1,136 amino acids with a long amino-terminal extracytoplasmic domain, a
26-amino acid hydrophobic transmembrane segment, and a
19-carboxyl-terminal cytoplasmic domain. The alpha subunit is highly
similar in sequence to the alpha subunit of leukocyte p150,95.
MAPPING
By Southern analysis of DNA from hamster-human hybrids, Arnaout et al.
(1988) localized the human MO1A gene to chromosome 16, which has been
shown to contain the ITGAL gene (153370). By in situ hybridization,
Corbi et al. (1988) demonstrated that the genes encoding the alpha
subunits of LFA1 (ITGAL), Mac1, and p150,95 (ITGAX), all of which are
involved in leukocyte adhesion, constitute a cluster on 16p13.1-p11.
Callen et al. (1991) narrowed the assignment to 16p11.2.
GENE FUNCTION
Inflammation plays an essential role in the initiation and progression
of atherosclerosis. Simon et al. (2000) presented evidence that it also
has a role in vascular repair after mechanical arterial injury (i.e.,
percutaneous transluminal coronary angioplasty, or PTCA). In animal
models of vascular injury, leukocytes are recruited as a precursor to
intimal thickening. Markers of leukocyte activation, in particular,
increased expression of Mac1, which is responsible for firm leukocyte
adhesion to platelets and fibrinogen on denuded vessels, predict
restenosis after PTCA. To determine whether Mac1-mediated leukocyte
recruitment is causally related to neointimal formation, Simon et al.
(2000) subjected Mac1 knockout mice to a mechanical carotid artery
dilation and complete endothelial denudation. They found that the
selective absence of Mac1 impaired transplatelet leukocyte migration
into the vessel wall, reducing leukocyte accumulation. Diminished medial
leukocyte accumulation was accompanied by markedly reduced neointimal
thickening after vascular injury. These data established a role for
inflammation in neointimal thickening and suggested that leukocyte
recruitment to mechanically injured arteries may prevent restenosis.
Ranganathan et al. (2011) noted that previous work (Cao et al., 2006)
had shown colocalization of low density lipoprotein receptor-related
protein-1 (LRP1; 107770) with integrin alpha-M/beta-2 at the trailing
edge of migrating macrophages and that macrophage migration depended
upon coordinated action of LRP1 and alpha-M/beta-2, as well as tissue
plasminogen activator (PLAT; 173370) and its inhibitor, PAI1 (SERPINE1;
173360). Ranganathan et al. (2011) found that LRP1 specifically bound
integrin alpha-M/beta-2, but not integrin alpha-L/beta-2. Activation of
alpha-M/beta-2 by lipopolysaccharide (LPS) enhanced interaction between
LRP1 and alpha-M/beta-2 in macrophages. Transfection experiments in
HEK293 cells revealed that both the heavy and light chains of LRP1
contributed to alpha-M/beta-2 binding. Within the LRP1 heavy chain,
binding was mediated primarily via ligand-binding motifs 2 and 4. Within
alpha-M, the sequence EQLKKSKTL within the I domain was the major LRP1
recognition site. Exposure of alpha-M/beta-2-expressing HEK293 cells to
soluble LRP1 inhibited cell attachment to fibrinogen (see 134820). Mouse
macrophages lacking Lrp1 were deficient in alpha-M/beta-2
internalization upon LPS stimulation. Ranganathan et al. (2011)
concluded that LRP1 has a role in macrophage migration and that it is
critical for internalization of integrin alpha-M/beta-2.
MOLECULAR GENETICS
For discussion of a possible association between variation in the ITGAM
gene and systemic lupus erythematosus, see SLEB6 (609939).
*FIELD* RF
1. Arnaout, M. A.; Gupta, S. K.; Pierce, M. W.; Tenen, D. G.: Amino
acid sequence of the alpha subunit of human leukocyte adhesion receptor
Mo1 (complement receptor type 3). J. Cell Biol. 106: 2153-2158,
1988.
2. Arnaout, M. A.; Remold-O'Donnell, E.; Pierce, M. W.; Harris, P.;
Tenen, D. G.: Molecular cloning of the alpha-subunit of human and
guinea pig leukocyte adhesion glycoprotein Mo1: chromosomal localization
and homology to the alpha-subunits of integrins. Proc. Nat. Acad.
Sci. 85: 2776-2780, 1988.
3. Callen, D. F.; Chen, L. Z.; Nancarrow, J.; Whitmore, S. A.; Apostolou,
S.; Thompson, A. D.; Lane, S. A.; Stallings, R. L.; Hildebrand, C.
E.; Harris, P. G.; Sutherland, G. R.: Current state of the physical
map of human chromosome 16. (Abstract) Cytogenet. Cell Genet. 58:
1998 only, 1991.
4. Cao, C.; Lawrence, D. A.; Li, Y.; Von Arnim, C. A. F.; Herz, J.;
Su, E. J.; Makarova, A.; Hyman, B. T.; Strickland, D. K.; Zhang, L.
: Endocytic receptor LRP together with tPA and PAI-1 coordinates Mac-1-dependent
macrophage migration. EMBO J. 25: 1860-1870, 2006.
5. Corbi, A. L.; Kishimoto, T. K.; Miller, L. J.; Springer, T. A.
: The human leukocyte adhesion glycoprotein Mac-1 (complement receptor
type 3, CD11b) alpha subunit: cloning, primary structure, and relation
to the integrins, von Willebrand factor and factor B. J. Biol. Chem. 263:
12403-12411, 1988.
6. Corbi, A. L.; Larson, R. S.; Kishimoto, T. K.; Springer, T. A.;
Morton, C. C.: Chromosomal location of the genes encoding the leukocyte
adhesion receptors LFA-1, Mac-1 and p150,95: identification of a gene
cluster involved in cell adhesion. J. Exp. Med. 167: 1597-1607,
1988.
7. Pierce, M. W.; Remold-O'Donnell, E.; Todd, R. F., III; Arnaout,
M. A.: N-terminal sequence of human leukocyte glycoprotein Mo1: conservation
across species and homology to platelet IIb/IIIa. Biochim. Biophys.
Acta 874: 368-371, 1986.
8. Ranganathan, S.; Cao, C.; Catania, J.; Migliorini, M.; Zhang, L.;
Strickland, D. K.: Molecular basis for the interaction of low density
lipoprotein receptor-related protein 1 (LRP1) with integrin alpha-M/beta-2:
identification of binding sites within alpha-M/beta-2 for LRP1. J.
Biol. Chem. 286: 30535-30541, 2011.
9. Simon, D. I.; Chen, Z.; Seifert, P.; Edelman, E. R.; Ballantyne,
C. M.; Rogers, C.: Decreased neointimal formation in Mac-1 -/- mice
reveals a role for inflammation in vascular repair after angioplasty. J.
Clin. Invest. 105: 293-300, 2000.
10. Springer, T. A.; Teplow, D. B.; Dreyer, W. J.: Sequence homology
of the LFA-1 and Mac-1 leukocyte adhesion glycoproteins and unexpected
relation to leukocyte interferon. Nature 314: 540-542, 1985.
*FIELD* CN
Patricia A. Hartz - updated: 6/12/2013
Marla J. F. O'Neill - updated: 11/13/2009
Ada Hamosh - updated: 8/13/2008
Victor A. McKusick - updated: 3/10/2008
Victor A. McKusick - updated: 2/18/2000
*FIELD* CD
Victor A. McKusick: 6/24/1986
*FIELD* ED
tpirozzi: 07/09/2013
mgross: 6/12/2013
wwang: 3/1/2010
terry: 2/24/2010
wwang: 11/25/2009
terry: 11/13/2009
alopez: 8/22/2008
terry: 8/13/2008
alopez: 3/11/2008
terry: 3/10/2008
carol: 5/16/2007
carol: 5/15/2007
ckniffin: 5/15/2003
mcapotos: 3/29/2000
mcapotos: 3/24/2000
mcapotos: 3/23/2000
terry: 2/18/2000
kayiaros: 7/13/1999
dkim: 7/23/1998
mark: 6/12/1997
carol: 7/2/1992
carol: 5/4/1992
carol: 3/26/1992
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/26/1989
MIM
609939
*RECORD*
*FIELD* NO
609939
*FIELD* TI
%609939 SYSTEMIC LUPUS ERYTHEMATOSUS, SUSCEPTIBILITY TO, 6; SLEB6
*FIELD* TX
For a phenotypic description and a discussion of genetic heterogeneity
read moreof systemic lupus erythematosus (SLE), see 152700.
MAPPING
In a genomewide microsatellite marker screen in 105 SLE sib-pair
families, Gaffney et al. (1998) found significant linkage at 16q13, with
a lod score of 3.64 at D16S415. Gaffney et al. (2000) combined an
additional 82 SLE sib-pair families with the 105 previously studied SLE
families and confirmed linkage by combined analysis at 16q13, with a lod
score of 3.85 at D16S415.
Shai et al. (1999) also provided evidence for an SLE susceptibility
locus at 16q13 (maximum lod score of 2.14 with D16S3136).
Nath et al. (2004) performed a genomewide scan in 37 multiplex Hispanic
families that revealed suggestive linkage at 16p13 and 16q12-q21. Nath
et al. (2004) then studied 2 independent replication samples of
multiplex SLE families, consisting of 172 and 120 families,
respectively, and found significant linkage with high heterogeneity at
16q12-q13 in the latter group (hlod, 4.85; alpha, 35%; p = 0.0000045).
Lee and Nath (2005) conducted a metaanalysis of 12 genome scans
generated from 9 independent studies involving 605 SLE families with
1,355 affected individuals. They identified 16p12.3-16q12.2 as a
location that met genomewide significance (p less than 0.000417).
Gaffney et al. (2006) presented evidence for the possibility of
epistatic relationships among the loci within the 20p12 (SLEB7; 610065)
and 20q13 (SLEB8; 610066) and 16q12 regions in SLE families.
Systemic lupus erythematosus is a common systemic autoimmune disease
with complex etiology but strong clustering in families. Nath et al.
(2008) identified and replicated an association between the ITGAM gene
(120980) on chromosome 16p11.2 and risk of SLE in 3,818 individuals of
European descent. The strongest association was at a nonsynonymous SNP,
dbSNP rs1143679 (odds ratio = 1.78), resulting in an arg77-to-his (R77H)
substitution in exon 3 of the ITGAM gene. Nath et al. (2008) further
replicated this association in 2 independent samples of individuals of
African descent. The International Consortium for Systemic Lupus
Erythematosus Genetics et al. (2008) likewise identified an association
between SNPs in ITGAM in 720 women of European ancestry with SLE and in
2 additional independent sample sets.
Hom et al. (2008) performed a genomewide association study involving
more than 500,000 SNPs in DNA samples from 1,311 case subjects with SLE
and 1,783 control subjects; all subjects were North Americans of
European descent. Replication of the top loci was performed in 793 case
subjects and 857 control subjects from Sweden. Hom et al. (2008)
identified SNPs near the ITGAM and ITGAX (151510) that were associated
with SLE in the combined sample. In the combined analysis, the dbSNP
rs11574637 in the ITGAX gene achieved an odds ratio of 1.33 with a 95%
confidence interval of 1.22 to 1.46 and a P value of 3 x 10(-11). The
region of association extended approximately 150 kb and contained
several genes, and Hom et al. (2008) thought that variants of ITGAM were
driving the association.
Yang et al. (2009) confirmed the association of the ITGAM gene with SLE
in Chinese and Thai populations. Subphenotype stratification analyses
showed significantly more involvement of ITGAM in patients with renal
nephritis and neurologic disorders. The results supported a pivotal role
for dbSNP rs1143679 and also suggested an additional contribution from
dbSNP rs1143683, another nonsynonymous polymorphism, resulting in an
ala858-to-val substitution in exon 21 of the ITGAM gene. Therefore,
despite the low-allele frequencies of the risk alleles of the gene in
the 2 Asian populations, ITGAM was confirmed to be a risk factor related
to disease susceptibility and probably severe manifestations of SLE.
To confirm additional risk loci for SLE susceptibility, Gateva et al.
(2009) selected SNPs from 2,466 regions that showed nominal evidence
association to SLE (P less than 0.05) in a genomewide study and
genotyped them in an independent sample of 1,963 cases and 4,329
controls. Gateva et al. (2009) showed an association with the ITGAM gene
dbSNP rs11860650 (combined P value = 1.9 x 10(-20), odds ratio = 1.43,
95% confidence interval = 1.32-1.54).
*FIELD* RF
1. Gaffney, P. M.; Kearns, G. M.; Shark, K. B.; Ortmann, W. A.; Selby,
S. A.; Malmgren, M. L.; Rohlf, K. E.; Ockenden, T. C.; Messner, R.
P.; King, R. A.; Rich, S. S.; Behrens, T. W.: A genome-wide search
for susceptibility genes in human systemic lupus erythematosus sib-pair
families. Proc. Nat. Acad. Sci. 95: 14875-14879, 1998.
2. Gaffney, P. M.; Langefeld, C. D.; Graham, R. R.; Ortmann, W. A.;
Williams, A. H.; Rodine, P. R.; Moser, K. L.; Behrens, T. W.: Fine-mapping
chromosome 20 in 230 systemic lupus erythematosus sib pair and multiplex
families: evidence for genetic epistasis with chromosome 16q12. Am.
J. Hum. Genet. 78: 747-758, 2006.
3. Gaffney, P. M.; Ortmann, W. A.; Selby, S. A.; Shark, K. B.; Ockenden,
T. C.; Rohlf, K. E.; Walgrave, N. L.; Boyum, W. P.; Malmgren, M. L.;
Miller, M. E.; Kearns, G. M.; Messner, R. P.; King, R. A.; Rich, S.
S.; Behrens, T. W.: Genome screening in human systemic lupus erythematosus:
results from a second Minnesota cohort and combined analyses of 187
sib-pair families. Am. J. Hum. Genet. 66: 547-556, 2000.
4. Gateva, V.; Sandling, J. K.; Hom, G.; Taylor, K. E.; Chung, S.
A.; Sun, X.; Ortmann, W.; Kosoy, R.; Ferreira, R. C.; Nordmark, G.;
Gunnarsson, I.; Svenungsson, E.; and 24 others: A large-scale replication
study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci
for systemic lupus erythematosus. Nature Genet. 41: 1228-1233, 2009.
5. Hom, G.; Graham, R. R.; Modrek, B.; Taylor, K. E.; Ortmann, W.;
Garnier, S.; Lee, A. T.; Chung, S. A.; Ferreira, R. C.; Pant, P. V.
K.; Ballinger, D. G.; Kosoy, R.; and 15 others: Association of
systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX. New
Eng. J. Med. 358: 900-909, 2008.
6. International Consortium for Systemic Lupus Erythematosus Genetics;
Harley, J. B.; Alarcon-Riquelme, M. E.; Criswell, L. A.; Jacob, C.
O.; Kimberly, R. P.; Moser, K. L.; Tsao, B. P.; Vyse, T. J.; Langefeld,
C. D.: Genome-wide association scan in women with systemic lupus
erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542
and other loci. Nature Genet. 40: 204-210, 2008.
7. Lee, Y. H.; Nath, S. K.: Systemic lupus erythematosus susceptibility
loci defined by genome scan meta-analysis. Hum. Genet. 118: 434-443,
2005.
8. Nath, S. K.; Han, S.; Kim-Howard, X.; Kelly, J. A.; Viswanathan,
P.; Gilkeson, G. S.; Chen, W.; Zhu, C.; McEver, R. P.; Kimberly, R.
P.; Alarcon-Riquelme, M. E.; Vyse, T. J.; Li, Q.-Z.; Wakeland, E.
K.; Merrill, J. T.; James, J. A.; Kaufman, K. M.; Guthridge, J. M.;
Harley, J. B.: A nonsynonymous functional variant in integrin-alpha-M
(encoded by ITGAM) is associated with systemic lupus erythematosus. Nature
Genet. 40: 152-154, 2008.
9. Nath, S. K.; Namjou, B.; Hutchings, D.; Garriott, C. P.; Pongratz,
C.; Guthridge, J.; James, J. A.: Systemic lupus erythematosus (SLE)
and chromosome 16: confirmation of linkage to 16q12-13 and evidence
for genetic heterogeneity. Europ. J. Hum. Genet. 12: 668-672, 2004.
Note: Erratum: Europ. J. Hum. Genet. 12: 688 only, 2004.
10. Nath, S. K.; Quintero-Del-Rio, A. I.; Kilpatrick, J.; Feo, L.;
Ballesteros, M.; Harley, J. B.: Linkage at 12q24 with systemic lupus
erythematosus (SLE) is established and confirmed in Hispanic and European
American families. Am. J. Hum. Genet. 74: 73-82, 2004.
11. Shai, R.; Quismorio, F. P., Jr.; Li, L.; Kwon, O.-J.; Morrison,
J.; Wallace, D. J.; Neuwelt, C. M.; Brautbar, C.; Gauderman, W. J.;
Jacob, C. O.: Genome-wide screen for systemic lupus erythematosus
susceptibility genes in multiplex families. Hum. Molec. Genet. 8:
639-644, 1999.
12. Yang, W.; Zhao, M.; Hirankarn, N.; Lau, C. S.; Mok, C. C.; Chan,
T. M.; Wong, R. W. S.; Lee, K. W.; Mok, M. Y.; Wong, S. N.; Avihingsanon,
Y.; Lin N. G., I. O.; Lee, T. L.; Ho, M. H. K.; Lee, P. P. W.; Wong,
W. H. S.; Sham, P. C.; Lau,Y. L.: ITGAM is associated with disease
susceptibility and renal nephritis of systemic lupus erythematosus
in Hong Kong Chinese and Thai. Hum. Molec. Genet. 18: 2063-2070,
2009.
*FIELD* CN
Ada Hamosh - updated: 03/01/2010
George E. Tiller - updated: 2/24/2010
Marla J. F. O'Neill - updated: 11/13/2009
Ada Hamosh - updated: 8/21/2008
Victor A. McKusick - updated: 4/14/2006
*FIELD* CD
Marla J. F. O'Neill: 2/27/2006
*FIELD* ED
alopez: 03/01/2010
wwang: 3/1/2010
terry: 2/24/2010
wwang: 11/25/2009
terry: 11/13/2009
alopez: 8/26/2008
alopez: 8/21/2008
carol: 6/2/2008
alopez: 4/19/2006
terry: 4/14/2006
wwang: 2/28/2006
*RECORD*
*FIELD* NO
609939
*FIELD* TI
%609939 SYSTEMIC LUPUS ERYTHEMATOSUS, SUSCEPTIBILITY TO, 6; SLEB6
*FIELD* TX
For a phenotypic description and a discussion of genetic heterogeneity
read moreof systemic lupus erythematosus (SLE), see 152700.
MAPPING
In a genomewide microsatellite marker screen in 105 SLE sib-pair
families, Gaffney et al. (1998) found significant linkage at 16q13, with
a lod score of 3.64 at D16S415. Gaffney et al. (2000) combined an
additional 82 SLE sib-pair families with the 105 previously studied SLE
families and confirmed linkage by combined analysis at 16q13, with a lod
score of 3.85 at D16S415.
Shai et al. (1999) also provided evidence for an SLE susceptibility
locus at 16q13 (maximum lod score of 2.14 with D16S3136).
Nath et al. (2004) performed a genomewide scan in 37 multiplex Hispanic
families that revealed suggestive linkage at 16p13 and 16q12-q21. Nath
et al. (2004) then studied 2 independent replication samples of
multiplex SLE families, consisting of 172 and 120 families,
respectively, and found significant linkage with high heterogeneity at
16q12-q13 in the latter group (hlod, 4.85; alpha, 35%; p = 0.0000045).
Lee and Nath (2005) conducted a metaanalysis of 12 genome scans
generated from 9 independent studies involving 605 SLE families with
1,355 affected individuals. They identified 16p12.3-16q12.2 as a
location that met genomewide significance (p less than 0.000417).
Gaffney et al. (2006) presented evidence for the possibility of
epistatic relationships among the loci within the 20p12 (SLEB7; 610065)
and 20q13 (SLEB8; 610066) and 16q12 regions in SLE families.
Systemic lupus erythematosus is a common systemic autoimmune disease
with complex etiology but strong clustering in families. Nath et al.
(2008) identified and replicated an association between the ITGAM gene
(120980) on chromosome 16p11.2 and risk of SLE in 3,818 individuals of
European descent. The strongest association was at a nonsynonymous SNP,
dbSNP rs1143679 (odds ratio = 1.78), resulting in an arg77-to-his (R77H)
substitution in exon 3 of the ITGAM gene. Nath et al. (2008) further
replicated this association in 2 independent samples of individuals of
African descent. The International Consortium for Systemic Lupus
Erythematosus Genetics et al. (2008) likewise identified an association
between SNPs in ITGAM in 720 women of European ancestry with SLE and in
2 additional independent sample sets.
Hom et al. (2008) performed a genomewide association study involving
more than 500,000 SNPs in DNA samples from 1,311 case subjects with SLE
and 1,783 control subjects; all subjects were North Americans of
European descent. Replication of the top loci was performed in 793 case
subjects and 857 control subjects from Sweden. Hom et al. (2008)
identified SNPs near the ITGAM and ITGAX (151510) that were associated
with SLE in the combined sample. In the combined analysis, the dbSNP
rs11574637 in the ITGAX gene achieved an odds ratio of 1.33 with a 95%
confidence interval of 1.22 to 1.46 and a P value of 3 x 10(-11). The
region of association extended approximately 150 kb and contained
several genes, and Hom et al. (2008) thought that variants of ITGAM were
driving the association.
Yang et al. (2009) confirmed the association of the ITGAM gene with SLE
in Chinese and Thai populations. Subphenotype stratification analyses
showed significantly more involvement of ITGAM in patients with renal
nephritis and neurologic disorders. The results supported a pivotal role
for dbSNP rs1143679 and also suggested an additional contribution from
dbSNP rs1143683, another nonsynonymous polymorphism, resulting in an
ala858-to-val substitution in exon 21 of the ITGAM gene. Therefore,
despite the low-allele frequencies of the risk alleles of the gene in
the 2 Asian populations, ITGAM was confirmed to be a risk factor related
to disease susceptibility and probably severe manifestations of SLE.
To confirm additional risk loci for SLE susceptibility, Gateva et al.
(2009) selected SNPs from 2,466 regions that showed nominal evidence
association to SLE (P less than 0.05) in a genomewide study and
genotyped them in an independent sample of 1,963 cases and 4,329
controls. Gateva et al. (2009) showed an association with the ITGAM gene
dbSNP rs11860650 (combined P value = 1.9 x 10(-20), odds ratio = 1.43,
95% confidence interval = 1.32-1.54).
*FIELD* RF
1. Gaffney, P. M.; Kearns, G. M.; Shark, K. B.; Ortmann, W. A.; Selby,
S. A.; Malmgren, M. L.; Rohlf, K. E.; Ockenden, T. C.; Messner, R.
P.; King, R. A.; Rich, S. S.; Behrens, T. W.: A genome-wide search
for susceptibility genes in human systemic lupus erythematosus sib-pair
families. Proc. Nat. Acad. Sci. 95: 14875-14879, 1998.
2. Gaffney, P. M.; Langefeld, C. D.; Graham, R. R.; Ortmann, W. A.;
Williams, A. H.; Rodine, P. R.; Moser, K. L.; Behrens, T. W.: Fine-mapping
chromosome 20 in 230 systemic lupus erythematosus sib pair and multiplex
families: evidence for genetic epistasis with chromosome 16q12. Am.
J. Hum. Genet. 78: 747-758, 2006.
3. Gaffney, P. M.; Ortmann, W. A.; Selby, S. A.; Shark, K. B.; Ockenden,
T. C.; Rohlf, K. E.; Walgrave, N. L.; Boyum, W. P.; Malmgren, M. L.;
Miller, M. E.; Kearns, G. M.; Messner, R. P.; King, R. A.; Rich, S.
S.; Behrens, T. W.: Genome screening in human systemic lupus erythematosus:
results from a second Minnesota cohort and combined analyses of 187
sib-pair families. Am. J. Hum. Genet. 66: 547-556, 2000.
4. Gateva, V.; Sandling, J. K.; Hom, G.; Taylor, K. E.; Chung, S.
A.; Sun, X.; Ortmann, W.; Kosoy, R.; Ferreira, R. C.; Nordmark, G.;
Gunnarsson, I.; Svenungsson, E.; and 24 others: A large-scale replication
study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci
for systemic lupus erythematosus. Nature Genet. 41: 1228-1233, 2009.
5. Hom, G.; Graham, R. R.; Modrek, B.; Taylor, K. E.; Ortmann, W.;
Garnier, S.; Lee, A. T.; Chung, S. A.; Ferreira, R. C.; Pant, P. V.
K.; Ballinger, D. G.; Kosoy, R.; and 15 others: Association of
systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX. New
Eng. J. Med. 358: 900-909, 2008.
6. International Consortium for Systemic Lupus Erythematosus Genetics;
Harley, J. B.; Alarcon-Riquelme, M. E.; Criswell, L. A.; Jacob, C.
O.; Kimberly, R. P.; Moser, K. L.; Tsao, B. P.; Vyse, T. J.; Langefeld,
C. D.: Genome-wide association scan in women with systemic lupus
erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542
and other loci. Nature Genet. 40: 204-210, 2008.
7. Lee, Y. H.; Nath, S. K.: Systemic lupus erythematosus susceptibility
loci defined by genome scan meta-analysis. Hum. Genet. 118: 434-443,
2005.
8. Nath, S. K.; Han, S.; Kim-Howard, X.; Kelly, J. A.; Viswanathan,
P.; Gilkeson, G. S.; Chen, W.; Zhu, C.; McEver, R. P.; Kimberly, R.
P.; Alarcon-Riquelme, M. E.; Vyse, T. J.; Li, Q.-Z.; Wakeland, E.
K.; Merrill, J. T.; James, J. A.; Kaufman, K. M.; Guthridge, J. M.;
Harley, J. B.: A nonsynonymous functional variant in integrin-alpha-M
(encoded by ITGAM) is associated with systemic lupus erythematosus. Nature
Genet. 40: 152-154, 2008.
9. Nath, S. K.; Namjou, B.; Hutchings, D.; Garriott, C. P.; Pongratz,
C.; Guthridge, J.; James, J. A.: Systemic lupus erythematosus (SLE)
and chromosome 16: confirmation of linkage to 16q12-13 and evidence
for genetic heterogeneity. Europ. J. Hum. Genet. 12: 668-672, 2004.
Note: Erratum: Europ. J. Hum. Genet. 12: 688 only, 2004.
10. Nath, S. K.; Quintero-Del-Rio, A. I.; Kilpatrick, J.; Feo, L.;
Ballesteros, M.; Harley, J. B.: Linkage at 12q24 with systemic lupus
erythematosus (SLE) is established and confirmed in Hispanic and European
American families. Am. J. Hum. Genet. 74: 73-82, 2004.
11. Shai, R.; Quismorio, F. P., Jr.; Li, L.; Kwon, O.-J.; Morrison,
J.; Wallace, D. J.; Neuwelt, C. M.; Brautbar, C.; Gauderman, W. J.;
Jacob, C. O.: Genome-wide screen for systemic lupus erythematosus
susceptibility genes in multiplex families. Hum. Molec. Genet. 8:
639-644, 1999.
12. Yang, W.; Zhao, M.; Hirankarn, N.; Lau, C. S.; Mok, C. C.; Chan,
T. M.; Wong, R. W. S.; Lee, K. W.; Mok, M. Y.; Wong, S. N.; Avihingsanon,
Y.; Lin N. G., I. O.; Lee, T. L.; Ho, M. H. K.; Lee, P. P. W.; Wong,
W. H. S.; Sham, P. C.; Lau,Y. L.: ITGAM is associated with disease
susceptibility and renal nephritis of systemic lupus erythematosus
in Hong Kong Chinese and Thai. Hum. Molec. Genet. 18: 2063-2070,
2009.
*FIELD* CN
Ada Hamosh - updated: 03/01/2010
George E. Tiller - updated: 2/24/2010
Marla J. F. O'Neill - updated: 11/13/2009
Ada Hamosh - updated: 8/21/2008
Victor A. McKusick - updated: 4/14/2006
*FIELD* CD
Marla J. F. O'Neill: 2/27/2006
*FIELD* ED
alopez: 03/01/2010
wwang: 3/1/2010
terry: 2/24/2010
wwang: 11/25/2009
terry: 11/13/2009
alopez: 8/26/2008
alopez: 8/21/2008
carol: 6/2/2008
alopez: 4/19/2006
terry: 4/14/2006
wwang: 2/28/2006