ID ITB2_BOVIN Reviewed; 769 AA.
AC P32592;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 1.
DT 24-JAN-2024, entry version 182.
DE RecName: Full=Integrin beta-2;
DE AltName: Full=Cell surface adhesion glycoproteins LFA-1/CR3/p150,95 subunit beta;
DE AltName: Full=Complement receptor C3 subunit beta;
DE AltName: CD_antigen=CD18;
DE Flags: Precursor;
GN Name=ITGB2; Synonyms=CD18;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1351021; DOI=10.1016/0378-1119(92)90586-e;
RA Shuster D.E., Bosworth B.T., Kehrli M.E. Jr.;
RT "Sequence of the bovine CD18-encoding cDNA: comparison with the human and
RT murine glycoproteins.";
RL Gene 114:267-271(1992).
RN [2]
RP VARIANT LAD GLY-128, AND DISEASE.
RX PubMed=1384046; DOI=10.1073/pnas.89.19.9225;
RA Shuster D.E., Kehrli M.E. Jr., Ackermann M.R., Gilbert R.O.;
RT "Identification and prevalence of a genetic defect that causes leukocyte
RT adhesion deficiency in Holstein cattle.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:9225-9229(1992).
CC -!- FUNCTION: Integrin ITGAL/ITGB2 is a receptor for ICAM1, ICAM2, ICAM3
CC and ICAM4. Integrin ITGAL/ITGB2 is also a receptor for the secreted
CC form of ubiquitin-like protein ISG15; the interaction is mediated by
CC ITGAL. Integrins ITGAM/ITGB2 and ITGAX/ITGB2 are receptors for the iC3b
CC fragment of the third complement component and for fibrinogen. Integrin
CC ITGAX/ITGB2 recognizes the sequence G-P-R in fibrinogen alpha-chain.
CC Integrin ITGAM/ITGB2 recognizes P1 and P2 peptides of fibrinogen gamma
CC chain. Integrin ITGAM/ITGB2 is also a receptor for factor X. Integrin
CC ITGAD/ITGB2 is a receptor for ICAM3 and VCAM1. Contributes to natural
CC killer cell cytotoxicity. Involved in leukocyte adhesion and
CC transmigration of leukocytes including T-cells and neutrophils.
CC Triggers neutrophil transmigration during lung injury through
CC PTK2B/PYK2-mediated activation. Integrin ITGAL/ITGB2 in association
CC with ICAM3, contributes to apoptotic neutrophil phagocytosis by
CC macrophages. {ECO:0000250|UniProtKB:P05107}.
CC -!- SUBUNIT: Heterodimer of an alpha and a beta subunit. The ITGB2 beta
CC subunit associates with the ITGAL, ITGAM, ITGAX or ITGAD alpha
CC subunits. Found in a complex with CD177 and ITGAM/CD11b. Interacts with
CC FGR. Interacts with COPS5 and RANBP9. Interacts with FLNA (via filamin
CC repeats 4, 9, 12, 17, 19, 21, and 23). Interacts with THBD.
CC {ECO:0000250|UniProtKB:P05107}.
CC -!- INTERACTION:
CC P32592; Q7BHI8: lktA; Xeno; NbExp=3; IntAct=EBI-11509482, EBI-11580242;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P05107};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:P05107}.
CC Membrane raft {ECO:0000250|UniProtKB:P05107}; Single-pass type I
CC membrane protein {ECO:0000250|UniProtKB:P05107}.
CC -!- DOMAIN: The VWFA domain (or beta I domain) contains three cation-
CC binding sites: the ligand-associated metal ion-binding site (LIMBS or
CC SyMBS), the metal ion-dependent adhesion site (MIDAS), and the adjacent
CC MIDAS site (ADMIDAS). This domain is also part of the ligand-binding
CC site. {ECO:0000250|UniProtKB:P05107}.
CC -!- PTM: Both Ser-745 and Ser-756 become phosphorylated when T-cells are
CC exposed to phorbol esters. Phosphorylation on Thr-758 (but not on Ser-
CC 756) allows interaction with 14-3-3 proteins.
CC {ECO:0000250|UniProtKB:P05107}.
CC -!- DISEASE: Note=Defects in ITGB2 are the cause of leukocyte adhesion
CC deficiency (LAD). The mutation causing LAD (Gly-128) is prevalent among
CC Holstein cattle throughout the world, placing this disorder among the
CC most common genetic diseases known in animal agriculture. All cattle
CC with the mutant allele are related to one bull, who through the use of
CC artificial insemination sired many calves in the 1950s and 1960s.
CC {ECO:0000269|PubMed:1384046}.
CC -!- SIMILARITY: Belongs to the integrin beta chain family. {ECO:0000305}.
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DR EMBL; M81233; AAA30438.1; -; mRNA.
DR PIR; JC1121; JC1121.
DR RefSeq; NP_786975.1; NM_175781.1.
DR RefSeq; XP_015329203.1; XM_015473717.1.
DR AlphaFoldDB; P32592; -.
DR SMR; P32592; -.
DR IntAct; P32592; 1.
DR STRING; 9913.ENSBTAP00000059292; -.
DR GlyCosmos; P32592; 5 sites, No reported glycans.
DR PaxDb; 9913-ENSBTAP00000022687; -.
DR PeptideAtlas; P32592; -.
DR Ensembl; ENSBTAT00000076413.1; ENSBTAP00000069668.1; ENSBTAG00000017060.6.
DR GeneID; 281877; -.
DR KEGG; bta:281877; -.
DR CTD; 3689; -.
DR VEuPathDB; HostDB:ENSBTAG00000017060; -.
DR VGNC; VGNC:30327; ITGB2.
DR eggNOG; KOG1226; Eukaryota.
DR GeneTree; ENSGT01090000259987; -.
DR HOGENOM; CLU_011772_2_1_1; -.
DR InParanoid; P32592; -.
DR OrthoDB; 5475862at2759; -.
DR TreeFam; TF105392; -.
DR Reactome; R-BTA-166016; Toll Like Receptor 4 (TLR4) Cascade.
DR Reactome; R-BTA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR Reactome; R-BTA-202733; Cell surface interactions at the vascular wall.
DR Reactome; R-BTA-216083; Integrin cell surface interactions.
DR Reactome; R-BTA-6798695; Neutrophil degranulation.
DR Proteomes; UP000009136; Chromosome 1.
DR Bgee; ENSBTAG00000017060; Expressed in monocyte and 103 other cell types or tissues.
DR ExpressionAtlas; P32592; baseline and differential.
DR GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR GO; GO:0005925; C:focal adhesion; IBA:GO_Central.
DR GO; GO:0008305; C:integrin complex; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
DR GO; GO:0001540; F:amyloid-beta binding; IBA:GO_Central.
DR GO; GO:0005178; F:integrin binding; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; ISS:UniProtKB.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0006909; P:phagocytosis; IEA:UniProtKB-KW.
DR GO; GO:1904996; P:positive regulation of leukocyte adhesion to vascular endothelial cell; ISS:UniProtKB.
DR GO; GO:0031623; P:receptor internalization; ISS:UniProtKB.
DR Gene3D; 6.20.50.10; -; 1.
DR Gene3D; 1.20.5.100; Cytochrome c1, transmembrane anchor, C-terminal; 1.
DR Gene3D; 2.10.25.10; Laminin; 4.
DR Gene3D; 3.30.1680.10; ligand-binding face of the semaphorins, domain 2; 1.
DR Gene3D; 2.60.40.1510; ntegrin, alpha v. Chain A, domain 3; 1.
DR Gene3D; 3.40.50.410; von Willebrand factor, type A domain; 1.
DR InterPro; IPR013111; EGF_extracell.
DR InterPro; IPR015439; Integrin_b-2_sf.
DR InterPro; IPR033760; Integrin_beta_N.
DR InterPro; IPR015812; Integrin_bsu.
DR InterPro; IPR014836; Integrin_bsu_cyt_dom.
DR InterPro; IPR012896; Integrin_bsu_tail.
DR InterPro; IPR036349; Integrin_bsu_tail_dom_sf.
DR InterPro; IPR002369; Integrin_bsu_VWA.
DR InterPro; IPR032695; Integrin_dom_sf.
DR InterPro; IPR016201; PSI.
DR InterPro; IPR036465; vWFA_dom_sf.
DR PANTHER; PTHR10082; INTEGRIN BETA SUBUNIT; 1.
DR PANTHER; PTHR10082:SF15; INTEGRIN BETA-2; 1.
DR Pfam; PF07974; EGF_2; 1.
DR Pfam; PF08725; Integrin_b_cyt; 1.
DR Pfam; PF07965; Integrin_B_tail; 1.
DR Pfam; PF00362; Integrin_beta; 1.
DR Pfam; PF17205; PSI_integrin; 1.
DR PIRSF; PIRSF002512; Integrin_B; 1.
DR PRINTS; PR01186; INTEGRINB.
DR SMART; SM00187; INB; 1.
DR SMART; SM01241; Integrin_b_cyt; 1.
DR SMART; SM01242; Integrin_B_tail; 1.
DR SMART; SM00423; PSI; 1.
DR SUPFAM; SSF57196; EGF/Laminin; 2.
DR SUPFAM; SSF69687; Integrin beta tail domain; 1.
DR SUPFAM; SSF69179; Integrin domains; 1.
DR SUPFAM; SSF103575; Plexin repeat; 1.
DR SUPFAM; SSF53300; vWA-like; 1.
DR PROSITE; PS00022; EGF_1; 2.
DR PROSITE; PS01186; EGF_2; 2.
DR PROSITE; PS00243; INTEGRIN_BETA; 3.
PE 1: Evidence at protein level;
KW Calcium; Cell adhesion; Cell membrane; Disease variant; Disulfide bond;
KW EGF-like domain; Glycoprotein; Integrin; Magnesium; Membrane;
KW Metal-binding; Phagocytosis; Phosphoprotein; Pyrrolidone carboxylic acid;
KW Receptor; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..22
FT /evidence="ECO:0000250"
FT CHAIN 23..769
FT /note="Integrin beta-2"
FT /id="PRO_0000016340"
FT TOPO_DOM 23..700
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 701..723
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 724..769
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 24..74
FT /note="PSI"
FT /evidence="ECO:0000255"
FT DOMAIN 124..363
FT /note="VWFA"
FT /evidence="ECO:0000250|UniProtKB:P05106"
FT DOMAIN 449..496
FT /note="EGF-like 1"
FT /evidence="ECO:0000250|UniProtKB:P05106"
FT DOMAIN 497..540
FT /note="EGF-like 2"
FT /evidence="ECO:0000250|UniProtKB:P05106"
FT DOMAIN 541..581
FT /note="EGF-like 3"
FT /evidence="ECO:0000250|UniProtKB:P05106"
FT DOMAIN 582..617
FT /note="EGF-like 4"
FT /evidence="ECO:0000250|UniProtKB:P05106"
FT MOTIF 397..399
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT BINDING 136
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /note="in MIDAS binding site"
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT BINDING 138
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /note="in ADMIDAS binding site"
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT BINDING 138
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /note="in MIDAS binding site"
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT BINDING 141
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /note="in ADMIDAS binding site"
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT BINDING 142
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /note="in ADMIDAS binding site"
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT BINDING 173
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /note="in LIMBS binding site"
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT BINDING 229
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /note="in LIMBS binding site"
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT BINDING 231
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /note="in LIMBS binding site"
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT BINDING 233
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /note="in LIMBS binding site"
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT BINDING 234
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /note="in LIMBS binding site"
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT BINDING 234
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /note="in MIDAS binding site"
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT BINDING 264
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /note="in ADMIDAS binding site and liganded-open
FT conformation"
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT BINDING 347
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /note="in ADMIDAS binding site and unliganded-closed
FT conformation"
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT MOD_RES 23
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT MOD_RES 745
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT MOD_RES 756
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT MOD_RES 758
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT MOD_RES 760
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT CARBOHYD 50
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 116
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 254
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 501
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 642
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 25..43
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT DISULFID 33..447
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT DISULFID 36..62
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT DISULFID 46..73
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT DISULFID 191..198
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT DISULFID 246..286
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT DISULFID 386..400
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT DISULFID 420..445
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT DISULFID 449..467
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT DISULFID 459..470
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT DISULFID 472..481
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT DISULFID 483..514
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT DISULFID 497..512
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT DISULFID 506..517
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT DISULFID 519..534
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT DISULFID 536..559
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT DISULFID 541..557
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT DISULFID 549..562
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT DISULFID 564..573
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT DISULFID 575..598
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT DISULFID 582..596
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT DISULFID 590..601
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT DISULFID 603..612
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT DISULFID 615..618
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT DISULFID 622..662
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT DISULFID 628..647
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT DISULFID 631..643
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT DISULFID 670..695
FT /evidence="ECO:0000250|UniProtKB:P05107"
FT VARIANT 128
FT /note="D -> G (in LAD)"
FT /evidence="ECO:0000269|PubMed:1384046"
SQ SEQUENCE 769 AA; 84400 MW; 5903ADF4E8998CEA CRC64;
MLRQRPQLLL LAGLLALQSV LSQECTNYKV STCRDCIESG PGCAWCQKLN FTGQGEPDSI
RCDTRAELLS KGCPADDIME PKSLAETRDS QAGSRKQLSP QEVTLYLRPG QAVAFNVTFR
RAKGYPIDLY YLMDLSYSMV DDLVNVKKLG GDLLRALNGI TESGRIGFGS FVDKTVLPFV
NTHPEKLRNP CPNKEKECQP PFAFRHVLKL TDNSKQFETE VGKQLISGNL DAPEGGLDAM
MQVAACPEEI GWRNVTRLLV FATDDGFHFA GDGKLGAILT PNDGRCHLED NLYKSSNEFD
YPSVGQLAHK LAESNIQPIF AVTKKMVKTY EKLTEIIPKS AVGELSEDSR NVVELIKNAY
NKLSSRVFLD HSTLPDTLKV TYDSFCSNGK SQVDQPRGDC DGVQINVPIT FQVKVTATEC
IQQQSFTIRA LGFTDTVTVR VLPQCECQCR DASRDGSICG GRGSMECGVC RCDAGYIGKN
CECQTQGRSS QELEGSCRKD NSSIICSGLG DCICGQCVCH TSDVPNKKIY GQFCECDNVN
CERYDGQVCG GEKRGLCFCG TCRCDEQYEG SACQCLKSTQ GCLNLDGVEC SGRGRCRCNV
CQCDPGYQPP LCSECPGCPV PCAGFAPCTE CLKFDKGPFA KNCSAACGQT KLLSSPVPGR
KCKERDSEGC WMTYTLVQRD GRDRYDVHVD DMLECVKGPN IAAIVGGTVG GVVLVGILLL
VIWKALTHLS DLREYHRFEK EKLKSQWNND NPLFKSATTT VMNPKFAES
//
