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Protein

Integrin alpha-M

Gene

ITGAM

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Integrin ITGAM/ITGB2 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 ITGAM/ITGB2 is also a receptor for fibrinogen, factor X and ICAM1. It recognizes P1 and P2 peptides of fibrinogen gamma chain. Regulates neutrophil migration (PubMed:28807980). In association with beta subunit ITGB2/CD18, required for CD177-PRTN3-mediated activation of TNF primed neutrophils (PubMed:21193407). May regulate phagocytosis-induced apoptosis in extravasated neutrophils (By similarity). May play a role in mast cell development (By similarity).By similarityCurated2 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi465 – 473Sequence analysis9
Calcium bindingi529 – 537Sequence analysis9
Calcium bindingi592 – 600Sequence analysis9

GO - Molecular functioni

  • complement component C3b binding Source: ARUK-UCL
  • heat shock protein binding Source: CAFA
  • metal ion binding Source: UniProtKB-KW
  • protein heterodimerization activity Source: ARUK-UCL

GO - Biological processi

Keywordsi

Molecular functionIntegrin, Receptor
Biological processCell adhesion, Immunity, Innate immunity
LigandCalcium, Magnesium, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade
R-HSA-202733 Cell surface interactions at the vascular wall
R-HSA-216083 Integrin cell surface interactions
R-HSA-6785807 Interleukin-4 and 13 signaling
R-HSA-6798695 Neutrophil degranulation
SignaLinkiP11215
SIGNORiP11215

Names & Taxonomyi

Protein namesi
Recommended name:
Integrin alpha-M
Alternative name(s):
CD11 antigen-like family member B
CR-3 alpha chain
Cell surface glycoprotein MAC-1 subunit alpha
Leukocyte adhesion receptor MO1
Neutrophil adherence receptor
CD_antigen: CD11b
Gene namesi
Name:ITGAM
Synonyms:CD11B, CR3A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000169896.16
HGNCiHGNC:6149 ITGAM
MIMi120980 gene
neXtProtiNX_P11215

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini17 – 1104ExtracellularSequence analysisAdd BLAST1088
Transmembranei1105 – 1128HelicalSequence analysisAdd BLAST24
Topological domaini1129 – 1152CytoplasmicSequence analysisAdd BLAST24

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Systemic lupus erythematosus 6 (SLEB6)2 Publications
Disease susceptibility may be associated with variations affecting the gene represented in this entry.
Disease descriptionA chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.
See also OMIM:609939

Keywords - Diseasei

Systemic lupus erythematosus

Organism-specific databases

DisGeNETi3684
MalaCardsiITGAM
MIMi609939 phenotype
OpenTargetsiENSG00000169896
Orphaneti536 Systemic lupus erythematosus
PharmGKBiPA29949

Chemistry databases

ChEMBLiCHEMBL3826

Polymorphism and mutation databases

BioMutaiITGAM
DMDMi1708572

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 161 PublicationAdd BLAST16
ChainiPRO_000001628917 – 1152Integrin alpha-MAdd BLAST1136

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi66 ↔ 73By similarity
Glycosylationi86N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi105 ↔ 123By similarity
Glycosylationi240N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi391N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi469N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi654 ↔ 711By similarity
Glycosylationi692N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi696N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi734N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi770 ↔ 776By similarity
Glycosylationi801N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi847 ↔ 864By similarity
Glycosylationi880N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi900N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi911N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi940N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi946N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi978N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi993N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi998 ↔ 1022By similarity
Glycosylationi1021N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi1027 ↔ 1032By similarity
Glycosylationi1044N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1050N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1075N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiP11215
MaxQBiP11215
PaxDbiP11215
PeptideAtlasiP11215
PRIDEiP11215
ProteomicsDBi52719

PTM databases

iPTMnetiP11215
PhosphoSitePlusiP11215

Expressioni

Tissue specificityi

Predominantly expressed in monocytes and granulocytes (PubMed:1346576). Expressed in neutrophils (at protein level) (PubMed:21193407).2 Publications

Gene expression databases

BgeeiENSG00000169896
CleanExiHS_ITGAM
ExpressionAtlasiP11215 baseline and differential
GenevisibleiP11215 HS

Organism-specific databases

HPAiCAB025091
CAB072870
HPA002274

Interactioni

Subunit structurei

Heterodimer of an alpha and a beta subunit. ITGAM associates with ITGB2. Found in a complex with CD177 and ITGB2/CD18 (PubMed:21193407). Interacts with JAM3 (PubMed:15194813, PubMed:12208882). Interacts with THBD (PubMed:27055590).4 Publications

GO - Molecular functioni

  • complement component C3b binding Source: ARUK-UCL
  • heat shock protein binding Source: CAFA
  • protein heterodimerization activity Source: ARUK-UCL

Protein-protein interaction databases

BioGridi109890, 10 interactors
ComplexPortaliCPX-1826 Integrin alphaM-beta2 complex
CORUMiP11215
IntActiP11215, 3 interactors
MINTiP11215
STRINGi9606.ENSP00000441691

Chemistry databases

BindingDBiP11215

Structurei

Secondary structure

11152
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi149 – 156Combined sources8
Helixi163 – 180Combined sources18
Beta strandi185 – 200Combined sources16
Helixi202 – 207Combined sources6
Helixi211 – 215Combined sources5
Helixi227 – 236Combined sources10
Turni237 – 239Combined sources3
Helixi241 – 243Combined sources3
Beta strandi249 – 259Combined sources11
Helixi268 – 270Combined sources3
Helixi272 – 277Combined sources6
Beta strandi280 – 288Combined sources9
Helixi289 – 291Combined sources3
Helixi294 – 303Combined sources10
Helixi308 – 311Combined sources4
Beta strandi312 – 317Combined sources6
Helixi318 – 324Combined sources7
Helixi325 – 333Combined sources9
Helixi1130 – 1132Combined sources3
Helixi1133 – 1143Combined sources11
Beta strandi1147 – 1149Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1A8Xmodel-A17-1152[»]
1BHOX-ray2.701/2149-337[»]
1BHQX-ray2.701/2149-337[»]
1IDNX-ray2.701/2149-337[»]
1IDOX-ray1.70A143-331[»]
1JLMX-ray2.00A143-334[»]
1M1UX-ray2.30A139-331[»]
1MF7X-ray1.25A144-333[»]
1N9ZX-ray2.50A144-335[»]
1NA5X-ray1.50A144-335[»]
2LKENMR-A1129-1152[»]
2LKJNMR-A1129-1152[»]
3Q3GX-ray2.70E/G/I/L148-337[»]
3QA3X-ray3.00E/G/I/L148-337[»]
4M76X-ray2.80B143-337[»]
4XW2X-ray2.00A145-337[»]
ProteinModelPortaliP11215
SMRiP11215
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP11215

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati18 – 75FG-GAP 1PROSITE-ProRule annotationAdd BLAST58
Repeati76 – 135FG-GAP 2PROSITE-ProRule annotationAdd BLAST60
Domaini150 – 328VWFAPROSITE-ProRule annotationAdd BLAST179
Repeati339 – 390FG-GAP 3PROSITE-ProRule annotationAdd BLAST52
Repeati391 – 442FG-GAP 4PROSITE-ProRule annotationAdd BLAST52
Repeati443 – 503FG-GAP 5PROSITE-ProRule annotationAdd BLAST61
Repeati506 – 564FG-GAP 6PROSITE-ProRule annotationAdd BLAST59
Repeati569 – 629FG-GAP 7PROSITE-ProRule annotationAdd BLAST61

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1131 – 1135GFFKR motif5

Domaini

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

Sequence similaritiesi

Belongs to the integrin alpha chain family.Curated

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IPBA Eukaryota
ENOG410ZFBE LUCA
GeneTreeiENSGT00760000118782
HOGENOMiHOG000113114
HOVERGENiHBG100530
InParanoidiP11215
KOiK06461
OMAiVTSENNM
OrthoDBiEOG091G01BZ
PhylomeDBiP11215
TreeFamiTF105391

Family and domain databases

Gene3Di2.130.10.130, 2 hits
3.40.50.410, 1 hit
InterProiView protein in InterPro
IPR013517 FG-GAP
IPR013519 Int_alpha_beta-p
IPR000413 Integrin_alpha
IPR013649 Integrin_alpha-2
IPR018184 Integrin_alpha_C_CS
IPR028994 Integrin_alpha_N
IPR032695 Integrin_dom_sf
IPR002035 VWF_A
IPR036465 vWFA_dom_sf
PfamiView protein in Pfam
PF01839 FG-GAP, 1 hit
PF00357 Integrin_alpha, 1 hit
PF08441 Integrin_alpha2, 1 hit
PF00092 VWA, 1 hit
PRINTSiPR01185 INTEGRINA
SMARTiView protein in SMART
SM00191 Int_alpha, 5 hits
SM00327 VWA, 1 hit
SUPFAMiSSF53300 SSF53300, 1 hit
SSF69179 SSF69179, 3 hits
PROSITEiView protein in PROSITE
PS51470 FG_GAP, 7 hits
PS00242 INTEGRIN_ALPHA, 1 hit
PS50234 VWFA, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P11215-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MALRVLLLTA LTLCHGFNLD TENAMTFQEN ARGFGQSVVQ LQGSRVVVGA
60 70 80 90 100
PQEIVAANQR GSLYQCDYST GSCEPIRLQV PVEAVNMSLG LSLAATTSPP
110 120 130 140 150
QLLACGPTVH QTCSENTYVK GLCFLFGSNL RQQPQKFPEA LRGCPQEDSD
160 170 180 190 200
IAFLIDGSGS IIPHDFRRMK EFVSTVMEQL KKSKTLFSLM QYSEEFRIHF
210 220 230 240 250
TFKEFQNNPN PRSLVKPITQ LLGRTHTATG IRKVVRELFN ITNGARKNAF
260 270 280 290 300
KILVVITDGE KFGDPLGYED VIPEADREGV IRYVIGVGDA FRSEKSRQEL
310 320 330 340 350
NTIASKPPRD HVFQVNNFEA LKTIQNQLRE KIFAIEGTQT GSSSSFEHEM
360 370 380 390 400
SQEGFSAAIT SNGPLLSTVG SYDWAGGVFL YTSKEKSTFI NMTRVDSDMN
410 420 430 440 450
DAYLGYAAAI ILRNRVQSLV LGAPRYQHIG LVAMFRQNTG MWESNANVKG
460 470 480 490 500
TQIGAYFGAS LCSVDVDSNG STDLVLIGAP HYYEQTRGGQ VSVCPLPRGR
510 520 530 540 550
ARWQCDAVLY GEQGQPWGRF GAALTVLGDV NGDKLTDVAI GAPGEEDNRG
560 570 580 590 600
AVYLFHGTSG SGISPSHSQR IAGSKLSPRL QYFGQSLSGG QDLTMDGLVD
610 620 630 640 650
LTVGAQGHVL LLRSQPVLRV KAIMEFNPRE VARNVFECND QVVKGKEAGE
660 670 680 690 700
VRVCLHVQKS TRDRLREGQI QSVVTYDLAL DSGRPHSRAV FNETKNSTRR
710 720 730 740 750
QTQVLGLTQT CETLKLQLPN CIEDPVSPIV LRLNFSLVGT PLSAFGNLRP
760 770 780 790 800
VLAEDAQRLF TALFPFEKNC GNDNICQDDL SITFSFMSLD CLVVGGPREF
810 820 830 840 850
NVTVTVRNDG EDSYRTQVTF FFPLDLSYRK VSTLQNQRSQ RSWRLACESA
860 870 880 890 900
SSTEVSGALK STSCSINHPI FPENSEVTFN ITFDVDSKAS LGNKLLLKAN
910 920 930 940 950
VTSENNMPRT NKTEFQLELP VKYAVYMVVT SHGVSTKYLN FTASENTSRV
960 970 980 990 1000
MQHQYQVSNL GQRSLPISLV FLVPVRLNQT VIWDRPQVTF SENLSSTCHT
1010 1020 1030 1040 1050
KERLPSHSDF LAELRKAPVV NCSIAVCQRI QCDIPFFGIQ EEFNATLKGN
1060 1070 1080 1090 1100
LSFDWYIKTS HNHLLIVSTA EILFNDSVFT LLPGQGAFVR SQTETKVEPF
1110 1120 1130 1140 1150
EVPNPLPLIV GSSVGGLLLL ALITAALYKL GFFKRQYKDM MSEGGPPGAE

PQ
Length:1,152
Mass (Da):127,179
Last modified:October 1, 1996 - v2
Checksum:iDF77408ED5EE25F9
GO
Isoform 2 (identifier: P11215-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     499-499: G → GQ

Show »
Length:1,153
Mass (Da):127,307
Checksum:i4383332408BB4234
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti965L → P in AAA59491 (PubMed:2833753).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04387077R → H Influences susceptibility to SLE. 2 PublicationsCorresponds to variant dbSNP:rs1143679Ensembl.1
Natural variantiVAR_043871441M → T1 PublicationCorresponds to variant dbSNP:rs1143680Ensembl.1
Natural variantiVAR_043872858A → V1 PublicationCorresponds to variant dbSNP:rs1143683Ensembl.1
Natural variantiVAR_0438731146P → S1 PublicationCorresponds to variant dbSNP:rs1143678Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_047365499G → GQ in isoform 2. 2 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J03925 mRNA Translation: AAA59544.1
M18044 mRNA Translation: AAA59491.1
S52227
, S52152, S52153, S52154, S52155, S52157, S52159, S52161, S52164, S52165, S52167, S52169, S52170, S52173, S52174, S52180, S52181, S52184, S52189, S52191, S52192, S52203, S52212, S52213, S52216, S52219, S52220, S52221, S52222, S52226 Genomic DNA Translation: AAB24821.1
BC096346 mRNA Translation: AAH96346.1
BC096347 mRNA Translation: AAH96347.1
BC096348 mRNA Translation: AAH96348.1
BC099660 mRNA Translation: AAH99660.1
J04145 mRNA Translation: AAA59903.1
M76724 Genomic DNA Translation: AAA58410.1
M84477 Genomic DNA Translation: AAA51960.1
CCDSiCCDS45470.1 [P11215-1]
CCDS54004.1 [P11215-2]
PIRiA31108 RWHU1B
RefSeqiNP_000623.2, NM_000632.3 [P11215-1]
NP_001139280.1, NM_001145808.1 [P11215-2]
UniGeneiHs.172631

Genome annotation databases

EnsembliENST00000287497; ENSP00000287497; ENSG00000169896 [P11215-1]
ENST00000544665; ENSP00000441691; ENSG00000169896 [P11215-2]
GeneIDi3684
KEGGihsa:3684
UCSCiuc002ebq.4 human [P11215-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiITAM_HUMAN
AccessioniPrimary (citable) accession number: P11215
Secondary accession number(s): Q4VAK0, Q4VAK1, Q4VAK2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: October 1, 1996
Last modified: June 20, 2018
This is version 206 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

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