ITA4_MOUSE
ID ITA4_MOUSE Reviewed; 1039 AA.
AC Q00651;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Integrin alpha-4;
DE AltName: Full=CD49 antigen-like family member D;
DE AltName: Full=Integrin alpha-IV;
DE AltName: Full=Lymphocyte Peyer patch adhesion molecules subunit alpha;
DE Short=LPAM subunit alpha;
DE AltName: Full=VLA-4 subunit alpha;
DE AltName: CD_antigen=CD49d;
DE Flags: Precursor;
GN Name=Itga4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1840602; DOI=10.1083/jcb.115.4.1149;
RA Neuhaus H., Hu M.C.-T., Hemler M.E., Takada Y., Holzmann B., Weissman I.L.;
RT "Cloning and expression of cDNAs for the alpha subunit of the murine
RT lymphocyte-Peyer's patch adhesion molecule.";
RL J. Cell Biol. 115:1149-1158(1991).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1028, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1028, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Integrins alpha-4/beta-1 (VLA-4 or LPAM-2) and alpha-4/beta-7
CC (LPAM-1) are receptors for fibronectin. They recognize one or more
CC domains within the alternatively spliced CS-1 and CS-5 regions of
CC fibronectin. They are also receptors for VCAM1. Integrin alpha-4/beta-1
CC recognizes the sequence Q-I-D-S in VCAM1. Integrin alpha-4/beta-7 is
CC also a receptor for MADCAM1. It recognizes the sequence L-D-T in
CC MADCAM1. On activated endothelial cells integrin VLA-4 triggers
CC homotypic aggregation for most VLA-4-positive leukocyte cell lines. It
CC may also participate in cytolytic T-cell interactions with target
CC cells. ITGA4:ITGB1 binds to fractalkine (CX3CL1) and may act as its
CC coreceptor in CX3CR1-dependent fractalkine signaling. ITGA4:ITGB1 binds
CC to PLA2G2A via a site (site 2) which is distinct from the classical
CC ligand-binding site (site 1) and this induces integrin conformational
CC changes and enhanced ligand binding to site 1.
CC {ECO:0000250|UniProtKB:P13612}.
CC -!- SUBUNIT: Heterodimer of an alpha and a beta subunit. The alpha subunit
CC can sometimes be cleaved into two non-covalently associated fragments.
CC Alpha-4 associates with either beta-1 or beta-7. Alpha-4 interacts with
CC PXN, LPXN, and TGFB1I1/HIC5. Interacts with CSPG4 through CSPG4
CC chondroitin sulfate glycosaminoglycan. Interacts with JAML; integrin
CC alpha-4/beta-1 may regulate leukocyte to endothelial cells adhesion by
CC controlling JAML homodimerization. ITGA4:ITGB1 is found in a ternary
CC complex with CX3CR1 and CX3CL1 (By similarity). Interacts with MDK.
CC ITGA4:ITGB1 interacts with MDK; this interaction mediates MDK-induced
CC osteoblast cells migration through PXN phosphorylation (By similarity).
CC {ECO:0000250|UniProtKB:P13612}.
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- TISSUE SPECIFICITY: Peyer patch homing cells.
CC -!- DOMAIN: The SG1 motif is involved in binding to chondroitin sulfate
CC glycosaminoglycan and cell adhesion. {ECO:0000250}.
CC -!- PTM: Phosphorylation on Ser-1028 inhibits PXN binding. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the integrin alpha chain family. {ECO:0000305}.
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DR EMBL; X53176; CAA37316.1; -; mRNA.
DR PIR; A41131; A41131.
DR RefSeq; NP_034706.3; NM_010576.3.
DR AlphaFoldDB; Q00651; -.
DR SMR; Q00651; -.
DR ComplexPortal; CPX-3077; integrin alpha4-beta7 complex.
DR ComplexPortal; CPX-3118; integrin alpha4-beta1 complex.
DR CORUM; Q00651; -.
DR STRING; 10090.ENSMUSP00000099718; -.
DR BindingDB; Q00651; -.
DR ChEMBL; CHEMBL2111481; -.
DR GlyConnect; 2397; 1 N-Linked glycan (1 site).
DR GlyGen; Q00651; 12 sites, 1 N-linked glycan (1 site).
DR iPTMnet; Q00651; -.
DR PhosphoSitePlus; Q00651; -.
DR SwissPalm; Q00651; -.
DR EPD; Q00651; -.
DR MaxQB; Q00651; -.
DR PaxDb; Q00651; -.
DR PeptideAtlas; Q00651; -.
DR PRIDE; Q00651; -.
DR ProteomicsDB; 269004; -.
DR DNASU; 16401; -.
DR GeneID; 16401; -.
DR KEGG; mmu:16401; -.
DR CTD; 3676; -.
DR MGI; MGI:96603; Itga4.
DR eggNOG; KOG3637; Eukaryota.
DR InParanoid; Q00651; -.
DR OrthoDB; 189377at2759; -.
DR PhylomeDB; Q00651; -.
DR Reactome; R-MMU-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR Reactome; R-MMU-202733; Cell surface interactions at the vascular wall.
DR Reactome; R-MMU-216083; Integrin cell surface interactions.
DR BioGRID-ORCS; 16401; 0 hits in 60 CRISPR screens.
DR ChiTaRS; Itga4; mouse.
DR PRO; PR:Q00651; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q00651; protein.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0005911; C:cell-cell junction; IDA:MGI.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0070062; C:extracellular exosome; ISO:MGI.
DR GO; GO:0030426; C:growth cone; ISO:MGI.
DR GO; GO:0034669; C:integrin alpha4-beta7 complex; ISO:MGI.
DR GO; GO:0008305; C:integrin complex; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0003823; F:antigen binding; ISO:MGI.
DR GO; GO:0019960; F:C-X3-C chemokine binding; ISO:MGI.
DR GO; GO:0050839; F:cell adhesion molecule binding; ISO:MGI.
DR GO; GO:0001968; F:fibronectin binding; IMP:MGI.
DR GO; GO:0005178; F:integrin binding; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:1990405; F:protein antigen binding; ISO:MGI.
DR GO; GO:0060385; P:axonogenesis involved in innervation; ISO:MGI.
DR GO; GO:0001974; P:blood vessel remodeling; IMP:MGI.
DR GO; GO:0007155; P:cell adhesion; IMP:MGI.
DR GO; GO:0033627; P:cell adhesion mediated by integrin; IBA:GO_Central.
DR GO; GO:0016477; P:cell migration; IMP:MGI.
DR GO; GO:0098609; P:cell-cell adhesion; IBA:GO_Central.
DR GO; GO:0140039; P:cell-cell adhesion in response to extracellular stimulus; ISO:MGI.
DR GO; GO:0033631; P:cell-cell adhesion mediated by integrin; ISO:MGI.
DR GO; GO:0007160; P:cell-matrix adhesion; ISO:MGI.
DR GO; GO:0003366; P:cell-matrix adhesion involved in ameboidal cell migration; ISO:MGI.
DR GO; GO:1904646; P:cellular response to amyloid-beta; ISO:MGI.
DR GO; GO:0060710; P:chorio-allantoic fusion; IMP:MGI.
DR GO; GO:1990771; P:clathrin-dependent extracellular exosome endocytosis; ISO:MGI.
DR GO; GO:0050904; P:diapedesis; ISO:MGI.
DR GO; GO:0060324; P:face development; IMP:MGI.
DR GO; GO:0007507; P:heart development; IMP:MGI.
DR GO; GO:0007157; P:heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules; IMP:MGI.
DR GO; GO:0034113; P:heterotypic cell-cell adhesion; ISO:MGI.
DR GO; GO:0098657; P:import into cell; ISO:MGI.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0007159; P:leukocyte cell-cell adhesion; IMP:MGI.
DR GO; GO:0050900; P:leukocyte migration; IBA:GO_Central.
DR GO; GO:0050901; P:leukocyte tethering or rolling; ISO:MGI.
DR GO; GO:0060485; P:mesenchyme development; TAS:DFLAT.
DR GO; GO:0090074; P:negative regulation of protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:1990138; P:neuron projection extension; ISO:MGI.
DR GO; GO:1905351; P:pericyte cell migration; IMP:MGI.
DR GO; GO:2000353; P:positive regulation of endothelial cell apoptotic process; ISO:MGI.
DR GO; GO:1903039; P:positive regulation of leukocyte cell-cell adhesion; ISO:MGI.
DR GO; GO:0002687; P:positive regulation of leukocyte migration; ISO:MGI.
DR GO; GO:1903238; P:positive regulation of leukocyte tethering or rolling; ISO:MGI.
DR GO; GO:2000406; P:positive regulation of T cell migration; ISO:MGI.
DR GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; ISO:MGI.
DR GO; GO:0043113; P:receptor clustering; ISO:MGI.
DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; ISO:MGI.
DR GO; GO:0072678; P:T cell migration; IMP:MGI.
DR GO; GO:1904738; P:vascular associated smooth muscle cell migration; IMP:MGI.
DR GO; GO:0061032; P:visceral serous pericardium development; TAS:DFLAT.
DR Gene3D; 2.130.10.130; -; 1.
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; IPR028994; Integrin_alpha_N.
DR InterPro; IPR032695; Integrin_dom_sf.
DR Pfam; PF01839; FG-GAP; 2.
DR Pfam; PF08441; Integrin_alpha2; 1.
DR PRINTS; PR01185; INTEGRINA.
DR SMART; SM00191; Int_alpha; 6.
DR SUPFAM; SSF69179; SSF69179; 3.
DR SUPFAM; SSF69318; SSF69318; 1.
DR PROSITE; PS51470; FG_GAP; 7.
DR PROSITE; PS00242; INTEGRIN_ALPHA; 1.
PE 1: Evidence at protein level;
KW Calcium; Cell adhesion; Disulfide bond; Glycoprotein; Integrin; Membrane;
KW Metal-binding; Phosphoprotein; Receptor; Reference proteome; Repeat;
KW Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..40
FT /evidence="ECO:0000255"
FT CHAIN 41..1039
FT /note="Integrin alpha-4"
FT /id="PRO_0000016245"
FT TOPO_DOM 41..983
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 984..1007
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1008..1039
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 42..107
FT /note="FG-GAP 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00803"
FT REPEAT 117..184
FT /note="FG-GAP 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00803"
FT REPEAT 193..244
FT /note="FG-GAP 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00803"
FT REPEAT 246..298
FT /note="FG-GAP 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00803"
FT REPEAT 299..358
FT /note="FG-GAP 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00803"
FT REPEAT 362..419
FT /note="FG-GAP 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00803"
FT REPEAT 423..485
FT /note="FG-GAP 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00803"
FT MOTIF 613..623
FT /note="SG1"
FT MOTIF 1010..1014
FT /note="GFFKR motif"
FT BINDING 321
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 323
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 325
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 329
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 384
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 386
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 388
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 392
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 446
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 448
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 450
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 452
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 454
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT SITE 598..599
FT /note="Cleavage"
FT MOD_RES 1028
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT CARBOHYD 86
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 105
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 145
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 236
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 487
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 525
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 545
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 633
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 652
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 667
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 813
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 828
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 98..108
FT /evidence="ECO:0000250"
FT DISULFID 151..172
FT /evidence="ECO:0000250"
FT DISULFID 190..205
FT /evidence="ECO:0000250"
FT DISULFID 493..502
FT /evidence="ECO:0000250"
FT DISULFID 508..564
FT /evidence="ECO:0000250"
FT DISULFID 629..634
FT /evidence="ECO:0000250"
FT DISULFID 705..718
FT /evidence="ECO:0000250"
FT DISULFID 859..897
FT /evidence="ECO:0000250"
FT DISULFID 904..909
FT /evidence="ECO:0000250"
SQ SEQUENCE 1039 AA; 115696 MW; C8C0BC611F7E9847 CRC64;
MFSTKSAWLR NGGADQGPRG IALREAVMLL LYFGVPTGPS YNLDPENALL YQGPSGTLFG
YSVVLHSHGS KRWLIVGAPT ASWLSNASVV NPGAIYRCGI RKNPNQTCEQ LQSGSPSGEP
CGKTCLEERD NQWLGVTLSR QPGENGSIVT CGHRWKNIFY MKSDNKLPTG ICYVMPSDLR
TELSKRMAPC YKDYTRKFGE NFASCQAGIS SFYTQDLIVM GAPGSSYWTG TVFVYNITTN
QYKAFVDRQN QVKFGSYLGY SVGAGHFRSP HTTEVVGGAP QHEQIGKAYI FSIDENELNI
VYEMKGKKLG SYFGASVCAV DLNADGFSDL LVGAPMQSTI REEGRVFVYI NSGMGAVMVE
MERVLVGSDK YAARFGESIA NLGDIDNDGF EDIAIGAPQE DDLRGAVYIY NGRVDGISST
YSQRIEGQQI SKSLRMFGQS ISGQIDADNN GYVDVAVGAF QSDSAVLLRT RPVVIVEASL
SHPESVNRTK FDCTENGLPS VCMHLTLCFS YKGKEVPGYI VLFYNVSLDV HRKAESPSRF
YFFSNGTSDV ITGSIRVSSS GEKCRTHQAF MRKDVRDILT PIHVEATYHL GHHVITKRNT
EEFPPLQPIL QQKKEKDVIR KMINFARFCA YENCSADLQV SAKVGFLKPY ENKTYLAVGS
MKTIMLNVSL FNAGDDAYET TLNVQLPTGL YFIKILDLEE KQINCEVTES SGIVKLACSL
GYIYVDRLSR IDISFLLDVS SLSRAHEDLS ISVHASCENE GELDQVRDNR VTLTIPLRYE
VMLTVHGLVN PTSFVYGSSE ENEPETCMAE KLNLTFHVIN TGISMAPNVS VKIMVPNSFL
PQDDKLFNVL DVQTTTGQCH FKHYGRECTF AQQKGIAGTL TDIVKFLSKT DKRLLYCMKA
DQHCLDFLCN FGKMESGKEA SVHIQLEGRP SILEMDETSS LKFEIKATAF PEPHPKVIEL
NKDENVAHVF LEGLHHQRPK RHFTIIIITI SLLLGLIVLL LISCVMWKAG FFKRQYKSIL
QEENRRDSWS YVNSKSNDD
