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Reviewed, UniProtKB/Swiss-Prot P11215 (ITAM_HUMAN)

Last modified July 22, 2008. Version 101. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (8) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Integrin alpha-M
Alternative name(s):
    Cell surface glycoprotein MAC-1 subunit alpha
    CR-3 alpha chain
    Leukocyte adhesion receptor MO1
    Neutrophil adherence receptor
    CD11 antigen-like family member B
    CD_antigen=CD11b
Gene names
Name: ITGAM
Synonyms: CD11B, CR3A
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length1152 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

Integrin alpha-M/beta-2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles. It is identical with CR-3, the receptor for the iC3b fragment of the third complement component. It probably recognizes the R-G-D peptide in C3b. Integrin alpha-M/beta-2 is also a receptor for fibrinogen, factor X and ICAM1. It recognizes P1 and P2 peptides of fibrinogen gamma chain.

Subunit structure

Heterodimer of an alpha and a beta subunit. Alpha-M associates with beta-2.

Subcellular location

Membrane; Single-pass type I membrane protein.

Tissue specificity

Predominantly expressed in monocytes and granulocytes.

Domain

The integrin I-domain (insert) is a VWFA domain. Integrins with I-domains do not undergo protease cleavage.

Involvement in disease

Genetic variations in ITGAM influence susceptibility to systemic lupus erythematosus (SLE) [MIM:152700]. SLE is a chronic, inflammatory and often febrile multisystemic disorder of connective tissue. It affects principally the skin, joints, kidneys and serosal membranes. It is thought to represent a failure of the regulatory mechanisms of the autoimmune system.

Sequence similarities

Belongs to the integrin alpha chain family.

Contains 7 FG-GAP repeats.

Contains 1 VWFA domain.

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Ontologies

Keywords

   Biological processCell adhesion
   Cellular componentMembrane
   Coding sequence diversityPolymorphism
   DiseaseSystemic lupus erythematosus
   DomainRepeat
Signal
Transmembrane
   LigandCalcium
Magnesium
   Molecular functionIntegrin
Receptor
   PTMGlycoprotein
   Technical term3D-structure
Direct protein sequencing

Gene Ontology (GO)

   Biological processcell adhesion Ref.6

Traceable author statement. Source: ProtInc

   Cellular componentintegrin complex Ref.6

Traceable author statement. Source: ProtInc

   Molecular functionglycoprotein binding

Inferred from physical interaction. Source: UniProtKB

Complete GO annotation...

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical view

Molecule processing

Signal peptide1 – 1616
Chain17 – 11521136Integrin alpha-M

Regions

Topological domain17 – 11041088Extracellular Potential
Transmembrane1105 – 112824 Potential
Topological domain1129 – 115224Cytoplasmic Potential
Repeat31 – 8454FG-GAP 1
Repeat85 – 16379FG-GAP 2
Domain164 – 350187VWFA
Repeat337 – 40064FG-GAP 3
Repeat401 – 45252FG-GAP 4
Repeat454 – 51562FG-GAP 5
Repeat517 – 57559FG-GAP 6
Repeat580 – 63253FG-GAP 7
Calcium binding465 – 4739 Potential
Calcium binding529 – 5379 Potential
Calcium binding592 – 6009 Potential
Motif1131 – 11355GFFKR motif

Amino acid modifications

Glycosylation861N-linked (GlcNAc...) Potential
Glycosylation2401N-linked (GlcNAc...) Potential
Glycosylation3911N-linked (GlcNAc...) Potential
Glycosylation4691N-linked (GlcNAc...) Potential
Glycosylation6921N-linked (GlcNAc...) Potential
Glycosylation6961N-linked (GlcNAc...) Potential
Glycosylation7341N-linked (GlcNAc...) Potential
Glycosylation8011N-linked (GlcNAc...) Potential
Glycosylation8801N-linked (GlcNAc...) Potential
Glycosylation9001N-linked (GlcNAc...) Potential
Glycosylation9111N-linked (GlcNAc...) Potential
Glycosylation9401N-linked (GlcNAc...) Potential
Glycosylation9461N-linked (GlcNAc...) Potential
Glycosylation9781N-linked (GlcNAc...) Potential
Glycosylation9931N-linked (GlcNAc...) Potential
Glycosylation10211N-linked (GlcNAc...) Potential
Glycosylation10441N-linked (GlcNAc...) Potential
Glycosylation10501N-linked (GlcNAc...) Potential
Glycosylation10751N-linked (GlcNAc...) Potential
Disulfide bond66 ↔ 73 By similarity
Disulfide bond105 ↔ 123 By similarity
Disulfide bond654 ↔ 711 By similarity
Disulfide bond770 ↔ 776 By similarity
Disulfide bond847 ↔ 864 By similarity
Disulfide bond998 ↔ 1022 By similarity
Disulfide bond1027 ↔ 1032 By similarity

Natural variations

Natural variant771R → H Influences susceptibility to SLE. dbSNP rs1143679.
Natural variant4411M → T: dbSNP rs11861251.
Natural variant8581A → V: dbSNP rs1143683.
Natural variant11461P → S: dbSNP rs1143678.

Experimental info

Sequence conflict4991G → GQ Ref.1 Ref.6
Sequence conflict9651L → P Ref.2 Ref.3

Secondary structure

1 ................................ 1152
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
P11215-1 [UniParc].

Last modified October 1, 1996. Version 2.
Checksum: DF77408ED5EE25F9

FASTA1,152127,179
        10         20         30         40         50         60 
MALRVLLLTA LTLCHGFNLD TENAMTFQEN ARGFGQSVVQ LQGSRVVVGA PQEIVAANQR 

        70         80         90        100        110        120 
GSLYQCDYST GSCEPIRLQV PVEAVNMSLG LSLAATTSPP QLLACGPTVH QTCSENTYVK 

       130        140        150        160        170        180 
GLCFLFGSNL RQQPQKFPEA LRGCPQEDSD IAFLIDGSGS IIPHDFRRMK EFVSTVMEQL 

       190        200        210        220        230        240 
KKSKTLFSLM QYSEEFRIHF TFKEFQNNPN PRSLVKPITQ LLGRTHTATG IRKVVRELFN 

       250        260        270        280        290        300 
ITNGARKNAF KILVVITDGE KFGDPLGYED VIPEADREGV IRYVIGVGDA FRSEKSRQEL 

       310        320        330        340        350        360 
NTIASKPPRD HVFQVNNFEA LKTIQNQLRE KIFAIEGTQT GSSSSFEHEM SQEGFSAAIT 

       370        380        390        400        410        420 
SNGPLLSTVG SYDWAGGVFL YTSKEKSTFI NMTRVDSDMN DAYLGYAAAI ILRNRVQSLV 

       430        440        450        460        470        480 
LGAPRYQHIG LVAMFRQNTG MWESNANVKG TQIGAYFGAS LCSVDVDSNG STDLVLIGAP 

       490        500        510        520        530        540 
HYYEQTRGGQ VSVCPLPRGR ARWQCDAVLY GEQGQPWGRF GAALTVLGDV NGDKLTDVAI 

       550        560        570        580        590        600 
GAPGEEDNRG AVYLFHGTSG SGISPSHSQR IAGSKLSPRL QYFGQSLSGG QDLTMDGLVD 

       610        620        630        640        650        660 
LTVGAQGHVL LLRSQPVLRV KAIMEFNPRE VARNVFECND QVVKGKEAGE VRVCLHVQKS 

       670        680        690        700        710        720 
TRDRLREGQI QSVVTYDLAL DSGRPHSRAV FNETKNSTRR QTQVLGLTQT CETLKLQLPN 

       730        740        750        760        770        780 
CIEDPVSPIV LRLNFSLVGT PLSAFGNLRP VLAEDAQRLF TALFPFEKNC GNDNICQDDL 

       790        800        810        820        830        840 
SITFSFMSLD CLVVGGPREF NVTVTVRNDG EDSYRTQVTF FFPLDLSYRK VSTLQNQRSQ 

       850        860        870        880        890        900 
RSWRLACESA SSTEVSGALK STSCSINHPI FPENSEVTFN ITFDVDSKAS LGNKLLLKAN 

       910        920        930        940        950        960 
VTSENNMPRT NKTEFQLELP VKYAVYMVVT SHGVSTKYLN FTASENTSRV MQHQYQVSNL 

       970        980        990       1000       1010       1020 
GQRSLPISLV FLVPVRLNQT VIWDRPQVTF SENLSSTCHT KERLPSHSDF LAELRKAPVV 

      1030       1040       1050       1060       1070       1080 
NCSIAVCQRI QCDIPFFGIQ EEFNATLKGN LSFDWYIKTS HNHLLIVSTA EILFNDSVFT 

      1090       1100       1110       1120       1130       1140 
LLPGQGAFVR SQTETKVEPF EVPNPLPLIV GSSVGGLLLL ALITAALYKL GFFKRQYKDM 

      1150 
MSEGGPPGAE PQ

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References

« Hide 'large scale' references
[1]"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."
Corbi A.L., Kishimoto T.K., Miller L.J., Springer T.A.
J. Biol. Chem. 263:12403-12411(1988) [PubMed: 2457584] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"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."
Arnaout M.A., Remold-O'Donnell E., Pierce M.W., Harris P., Tenen D.G.
Proc. Natl. Acad. Sci. U.S.A. 85:2776-2780(1988) [PubMed: 2833753] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Amino acid sequence of the alpha subunit of human leukocyte adhesion receptor Mo1 (complement receptor type 3)."
Arnaout M.A., Gupta S.K., Pierce M.W., Tenen D.G.
J. Cell Biol. 106:2153-2158(1988) [PubMed: 2454931] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"Structural analysis of the CD11b gene and phylogenetic analysis of the alpha-integrin gene family demonstrate remarkable conservation of genomic organization and suggest early diversification during evolution."
Fleming J.C., Pahl H.L., Gonzalez D.A., Smith T.F., Tenen D.G.
J. Immunol. 150:480-490(1993) [PubMed: 8419480] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]"cDNA sequence for the alpha M subunit of the human neutrophil adherence receptor indicates homology to integrin alpha subunits."
Hickstein D.D., Hickey M.J., Ozols J., Baker D.M., Back A.L., Roth G.J.
Proc. Natl. Acad. Sci. U.S.A. 86:257-261(1989) [PubMed: 2563162] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 9-1152.
[7]"The promoter of the CD11b gene directs myeloid-specific and developmentally regulated expression."
Shelley C.S., Arnaout M.A.
Proc. Natl. Acad. Sci. U.S.A. 88:10525-10529(1991) [PubMed: 1683702] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-9.
[8]"Characterization of the myeloid-specific CD11b promoter."
Pahl H.L., Rosmarin A.G., Tenen D.G.
Blood 79:865-870(1992) [PubMed: 1346576] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-9.
Tissue: Blood.
[9]"N-terminal sequence of human leukocyte glycoprotein Mo1: conservation across species and homology to platelet IIb/IIIa."
Pierce M.W., Remold-O'Donnell E., Todd R.F. III, Arnaout M.A.
Biochim. Biophys. Acta 874:368-371(1986) [PubMed: 3539202] [Abstract]
Cited for: PROTEIN SEQUENCE OF 17-31.
[10]"Crystal structure of the A domain from the alpha subunit of integrin CR3 (CD11b/CD18)."
Lee J.O., Rieu P., Arnaout M.A., Liddington R.
Cell 80:631-638(1995) [PubMed: 7867070] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 148-331.
[11]"Two conformations of the integrin A-domain (I-domain): a pathway for activation?"
Lee J.O., Bankston L.A., Arnaout M.A., Liddington R.C.
Structure 3:1333-1340(1995) [PubMed: 8747460] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 148-334.
[12]"Cation binding to the integrin CD11b I domain and activation model assessment."
Baldwin E.T., Sarver R.W., Bryant G.L. Jr., Curry K.A., Fairbanks M.B., Finzel B.C., Garlick R.L., Heinrikson R.L., Horton N.C., Kelley L.L., Mildner A.M., Moon J.B., Mott J.E., Mutchler V.T., Tomich C.S., Watenpaugh K.D., Wiley V.H.
Structure 6:923-935(1998) [PubMed: 9687375] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 148-337.
[13]"Experimental support for a beta-propeller domain in integrin alpha-subunits and a calcium binding site on its lower surface."
Oxvig C., Springer T.A.
Proc. Natl. Acad. Sci. U.S.A. 95:4870-4875(1998) [PubMed: 9560195] [Abstract]
Cited for: 3D-STRUCTURE MODELING OF 17-616.
[14]"A nonsynonymous functional variant in integrin-alpha(M) (encoded by ITGAM) is associated with systemic lupus erythematosus."
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.
Nat. Genet. 40:152-154(2008) [PubMed: 18204448] [Abstract]
Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO SLE, VARIANT HIS-77.
[15]"Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci."
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., Nath S.K., Gut