ITGAM
Integrin alpha-M
Also known as: CD11B, CR3A, ITAM_HUMAN, MAC-1
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P11215
- Gene
- ITGAM
- Ensembl
- ENSG00000169896
- Chromosome
- 16
- Canonical length
- 1152 aa
- Protein class
- Cancer-related genes, CD markers, Disease related genes, Predicted intracellular proteins, Predicted membrane proteins
OverviewNCBI Gene
This gene encodes the integrin alpha M chain. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This I-domain containing alpha integrin combines with the beta 2 chain (ITGB2) to form a leukocyte-specific integrin referred to as macrophage receptor 1 ('Mac-1'), or inactivated-C3b (iC3b) receptor 3 ('CR3'). The alpha M beta 2 integrin is important in the adherence of neutrophils and monocytes to stimulated endothelium, and also in the phagocytosis of complement coated particles. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]
Canonical amino-acid sequenceUniProt
1152 residues, UniProt reviewed canonical sequence.
>P11215|ITGAM
1 MALRVLLLTA LTLCHGFNLD TENAMTFQEN ARGFGQSVVQ LQGSRVVVGA PQEIVAANQR
61 GSLYQCDYST GSCEPIRLQV PVEAVNMSLG LSLAATTSPP QLLACGPTVH QTCSENTYVK
121 GLCFLFGSNL RQQPQKFPEA LRGCPQEDSD IAFLIDGSGS IIPHDFRRMK EFVSTVMEQL
181 KKSKTLFSLM QYSEEFRIHF TFKEFQNNPN PRSLVKPITQ LLGRTHTATG IRKVVRELFN
241 ITNGARKNAF KILVVITDGE KFGDPLGYED VIPEADREGV IRYVIGVGDA FRSEKSRQEL
301 NTIASKPPRD HVFQVNNFEA LKTIQNQLRE KIFAIEGTQT GSSSSFEHEM SQEGFSAAIT
361 SNGPLLSTVG SYDWAGGVFL YTSKEKSTFI NMTRVDSDMN DAYLGYAAAI ILRNRVQSLV
421 LGAPRYQHIG LVAMFRQNTG MWESNANVKG TQIGAYFGAS LCSVDVDSNG STDLVLIGAP
481 HYYEQTRGGQ VSVCPLPRGR ARWQCDAVLY GEQGQPWGRF GAALTVLGDV NGDKLTDVAI
541 GAPGEEDNRG AVYLFHGTSG SGISPSHSQR IAGSKLSPRL QYFGQSLSGG QDLTMDGLVD
601 LTVGAQGHVL LLRSQPVLRV KAIMEFNPRE VARNVFECND QVVKGKEAGE VRVCLHVQKS
661 TRDRLREGQI QSVVTYDLAL DSGRPHSRAV FNETKNSTRR QTQVLGLTQT CETLKLQLPN
721 CIEDPVSPIV LRLNFSLVGT PLSAFGNLRP VLAEDAQRLF TALFPFEKNC GNDNICQDDL
781 SITFSFMSLD CLVVGGPREF NVTVTVRNDG EDSYRTQVTF FFPLDLSYRK VSTLQNQRSQ
841 RSWRLACESA SSTEVSGALK STSCSINHPI FPENSEVTFN ITFDVDSKAS LGNKLLLKAN
901 VTSENNMPRT NKTEFQLELP VKYAVYMVVT SHGVSTKYLN FTASENTSRV MQHQYQVSNL
961 GQRSLPISLV FLVPVRLNQT VIWDRPQVTF SENLSSTCHT KERLPSHSDF LAELRKAPVV
1021 NCSIAVCQRI QCDIPFFGIQ EEFNATLKGN LSFDWYIKTS HNHLLIVSTA EILFNDSVFT
1081 LLPGQGAFVR SQTETKVEPF EVPNPLPLIV GSSVGGLLLL ALITAALYKL GFFKRQYKDM
1141 MSEGGPPGAE PQLocalizationUniProt · AlphaFold · HPA
Whether an antibody against ITGAM can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Cell surface
- Secreted
- No
- Transmembrane segments
- 1
- Mean surface accessibility (rSASA)
- 0.27
- Highest tissue expression
- 173 nTPM
Expression across tissuesHPA
Tissue
- bone marrow: 173 nTPM
- spleen: 30 nTPM
- appendix: 23 nTPM
- lung: 15 nTPM
- adipose tissue: 13 nTPM
- smooth muscle: 11 nTPM
Single-cell type
- neutrophils: 731 nCPM
- neutrophil progenitors: 686 nCPM
- monocytes: 230 nCPM
- microglia: 201 nCPM
- monocyte progenitors: 120 nCPM
- macrophages: 117 nCPM
Immune cell
- basophil: 94 nTPM
- eosinophil: 70 nTPM
- neutrophil: 59 nTPM
- classical monocyte: 56 nTPM
- NK-cell: 55 nTPM
- gdT-cell: 31 nTPM
Brain region
- white matter: 23 nTPM
- thalamus: 19 nTPM
- pons: 16 nTPM
- medulla oblongata: 15 nTPM
- spinal cord: 14 nTPM
- midbrain: 11 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about ITGAM.
Disease | AllUniProt
Conditions ITGAM is implicated in, by any mechanism.
- Systemic lupus erythematosus 6 (SLEB6) MIM:609939
ReferencesPubMed · IEDB
Publications for ITGAM from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
3 publications
- Complement receptor Mac-1 is an adaptor for NB1 (CD177)-mediated PR3-ANCA neutrophil activation.
2011 · J Biol Chem · RCR 2.1 · 85 citations - Neutrophil alloantibodies react with cytoplasmic antigens: a possible cause of false-positive indirect immunofluorescence assays for antibodies to neutrophil cytoplasmic antigens.
1993 · Am J Kidney Dis · RCR 0.5 · 13 citations - Anti-CD11b antibody treatment suppresses the osteoclast generation, inflammatory cell infiltration, and autoantibody production in arthritis-prone FcγRIIB-deficient mice.
2018 · Arthritis Res Ther · RCR 0.4 · 10 citations
Reference: T cellIEDB
1 publication
- High-throughput identification of potential minor histocompatibility antigens by MHC tetramer-based screening: feasibility and limitations.
2011 · PLoS One · RCR 0.6 · 29 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.64
- gnomAD pLI
- 0
- gnomAD missense Z
- 1.42
- DepMap mean gene effect
- 0.04
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- amyloid-beta clearance
- cell adhesion
- cell-cell adhesion
- cell-cell adhesion via plasma-membrane adhesion molecules
- cell-matrix adhesion
- complement receptor mediated signaling pathway
- complement-mediated synapse pruning
- ectodermal cell differentiation
- forebrain development
- heterotypic cell-cell adhesion
- innate immune response
- integrin-mediated signaling pathway
- microglial cell activation
- negative regulation of dopamine metabolic process
- phagocytosis, engulfment
- positive regulation of microglial cell mediated cytotoxicity
- positive regulation of neutrophil degranulation
- positive regulation of protein targeting to membrane
- positive regulation of superoxide anion generation
- receptor-mediated endocytosis
- response to amphetamine
- response to curcumin
- response to estradiol
- response to Gram-positive bacterium
- response to ischemia
- response to mechanical stimulus
- vertebrate eye-specific patterning
Molecular functions
- amyloid-beta binding
- cargo receptor activity
- complement component C3b binding
- heat shock protein binding
- integrin binding
- metal ion binding
- signaling receptor activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Integrin alpha chain
- von Willebrand factor, type A
- FG-GAP repeat
- Integrin alpha beta-propellor
- Integrin alpha, first immunoglubulin-like domain
- Integrin alpha chain, C-terminal cytoplasmic region, conserved site
- Integrin alpha, N-terminal
- Integrin domain superfamily
- von Willebrand factor A-like domain superfamily
- Integrin alpha, second immunoglobulin-like domain
- Integrin alpha-X-like, third Ig-like domain
- von Willebrand factor type A domain
- Integrin alpha cytoplasmic region
- FG-GAP repeat
- Integrin alpha Ig-like domain 1
- Integrin alpha Ig-like domain 2
- Integrin alpha-X-like, Ig-like domain 3
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of ITGAM in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads ITGAM as an antibody target. Whether an autoantibody or antibody against ITGAM could matter depends on whether native ITGAM is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
ITGAM is annotated at the cell surface, where native ITGAM is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label ITGAM as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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