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Integrin alpha-4 (CD49 antigen-like family member D) (Integrin alpha-IV) (Lymphocyte Peyer patch adhesion molecules subunit alpha) (LPAM subunit alpha) (VLA-4 subunit alpha) (CD antigen CD49d)

 ITA4_MOUSE              Reviewed;        1039 AA.
Q00651;
01-APR-1993, integrated into UniProtKB/Swiss-Prot.
01-APR-1993, sequence version 1.
07-APR-2021, entry version 166.
RecName: Full=Integrin alpha-4;
AltName: Full=CD49 antigen-like family member D;
AltName: Full=Integrin alpha-IV;
AltName: Full=Lymphocyte Peyer patch adhesion molecules subunit alpha;
Short=LPAM subunit alpha;
AltName: Full=VLA-4 subunit alpha;
AltName: CD_antigen=CD49d;
Flags: Precursor;
Name=Itga4;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=1840602; DOI=10.1083/jcb.115.4.1149;
Neuhaus H., Hu M.C.-T., Hemler M.E., Takada Y., Holzmann B., Weissman I.L.;
"Cloning and expression of cDNAs for the alpha subunit of the murine
lymphocyte-Peyer's patch adhesion molecule.";
J. Cell Biol. 115:1149-1158(1991).
[2]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1028, AND IDENTIFICATION BY
MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
Thibault P.;
"The phagosomal proteome in interferon-gamma-activated macrophages.";
Immunity 30:143-154(2009).
[3]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1028, AND IDENTIFICATION BY
MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Brain, Lung, and Spleen;
PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
"A tissue-specific atlas of mouse protein phosphorylation and expression.";
Cell 143:1174-1189(2010).
-!- FUNCTION: Integrins alpha-4/beta-1 (VLA-4 or LPAM-2) and alpha-4/beta-7
(LPAM-1) are receptors for fibronectin. They recognize one or more
domains within the alternatively spliced CS-1 and CS-5 regions of
fibronectin. They are also receptors for VCAM1. Integrin alpha-4/beta-1
recognizes the sequence Q-I-D-S in VCAM1. Integrin alpha-4/beta-7 is
also a receptor for MADCAM1. It recognizes the sequence L-D-T in
MADCAM1. On activated endothelial cells integrin VLA-4 triggers
homotypic aggregation for most VLA-4-positive leukocyte cell lines. It
may also participate in cytolytic T-cell interactions with target
cells. ITGA4:ITGB1 binds to fractalkine (CX3CL1) and may act as its
coreceptor in CX3CR1-dependent fractalkine signaling. ITGA4:ITGB1 binds
to PLA2G2A via a site (site 2) which is distinct from the classical
ligand-binding site (site 1) and this induces integrin conformational
changes and enhanced ligand binding to site 1.
{ECO:0000250|UniProtKB:P13612}.
-!- SUBUNIT: Heterodimer of an alpha and a beta subunit. The alpha subunit
can sometimes be cleaved into two non-covalently associated fragments.
Alpha-4 associates with either beta-1 or beta-7. Alpha-4 interacts with
PXN, LPXN, and TGFB1I1/HIC5. Interacts with CSPG4 through CSPG4
chondroitin sulfate glycosaminoglycan. Interacts with JAML; integrin
alpha-4/beta-1 may regulate leukocyte to endothelial cells adhesion by
controlling JAML homodimerization. ITGA4:ITGB1 is found in a ternary
complex with CX3CR1 and CX3CL1 (By similarity). Interacts with MDK.
ITGA4:ITGB1 interacts with MDK; this interaction mediates MDK-induced
osteoblast cells migration through PXN phosphorylation (By similarity).
{ECO:0000250|UniProtKB:P13612}.
-!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
-!- TISSUE SPECIFICITY: Peyer patch homing cells.
-!- DOMAIN: The SG1 motif is involved in binding to chondroitin sulfate
glycosaminoglycan and cell adhesion. {ECO:0000250}.
-!- PTM: Phosphorylation on Ser-1028 inhibits PXN binding. {ECO:0000250}.
-!- SIMILARITY: Belongs to the integrin alpha chain family. {ECO:0000305}.
---------------------------------------------------------------------------
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EMBL; X53176; CAA37316.1; -; mRNA.
PIR; A41131; A41131.
RefSeq; NP_034706.3; NM_010576.3.
SMR; Q00651; -.
ComplexPortal; CPX-3077; integrin alpha4-beta7 complex.
ComplexPortal; CPX-3118; integrin alpha4-beta1 complex.
CORUM; Q00651; -.
STRING; 10090.ENSMUSP00000099718; -.
BindingDB; Q00651; -.
ChEMBL; CHEMBL2111481; -.
GlyConnect; 2397; 1 N-Linked glycan (1 site).
GlyGen; Q00651; 12 sites.
iPTMnet; Q00651; -.
PhosphoSitePlus; Q00651; -.
SwissPalm; Q00651; -.
EPD; Q00651; -.
MaxQB; Q00651; -.
PaxDb; Q00651; -.
PeptideAtlas; Q00651; -.
PRIDE; Q00651; -.
ProteomicsDB; 269004; -.
GeneID; 16401; -.
KEGG; mmu:16401; -.
CTD; 3676; -.
MGI; MGI:96603; Itga4.
eggNOG; KOG3637; Eukaryota.
InParanoid; Q00651; -.
OrthoDB; 189377at2759; -.
PhylomeDB; Q00651; -.
Reactome; R-MMU-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
Reactome; R-MMU-202733; Cell surface interactions at the vascular wall.
Reactome; R-MMU-216083; Integrin cell surface interactions.
BioGRID-ORCS; 16401; 0 hits in 45 CRISPR screens.
ChiTaRS; Itga4; mouse.
PRO; PR:Q00651; -.
Proteomes; UP000000589; Unplaced.
RNAct; Q00651; protein.
GO; GO:0009986; C:cell surface; ISO:MGI.
GO; GO:0005911; C:cell-cell junction; IDA:MGI.
GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
GO; GO:0070062; C:extracellular exosome; ISO:MGI.
GO; GO:0030426; C:growth cone; ISO:MGI.
GO; GO:0034669; C:integrin alpha4-beta7 complex; ISO:MGI.
GO; GO:0043025; C:neuronal cell body; ISO:MGI.
GO; GO:0005886; C:plasma membrane; ISO:MGI.
GO; GO:0003823; F:antigen binding; ISO:MGI.
GO; GO:0050839; F:cell adhesion molecule binding; ISO:MGI.
GO; GO:0001968; F:fibronectin binding; IMP:MGI.
GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
GO; GO:1990405; F:protein antigen binding; ISO:MGI.
GO; GO:0060385; P:axonogenesis involved in innervation; ISO:MGI.
GO; GO:0001974; P:blood vessel remodeling; IMP:MGI.
GO; GO:0007155; P:cell adhesion; IMP:MGI.
GO; GO:0016477; P:cell migration; IMP:MGI.
GO; GO:0098609; P:cell-cell adhesion; TAS:DFLAT.
GO; GO:0140039; P:cell-cell adhesion in response to extracellular stimulus; ISO:MGI.
GO; GO:0033631; P:cell-cell adhesion mediated by integrin; ISO:MGI.
GO; GO:0007160; P:cell-matrix adhesion; ISO:MGI.
GO; GO:0003366; P:cell-matrix adhesion involved in ameboidal cell migration; ISO:MGI.
GO; GO:1904646; P:cellular response to amyloid-beta; ISO:MGI.
GO; GO:0060710; P:chorio-allantoic fusion; IMP:MGI.
GO; GO:1990771; P:clathrin-dependent extracellular exosome endocytosis; ISO:MGI.
GO; GO:0050904; P:diapedesis; ISO:MGI.
GO; GO:0060324; P:face development; IMP:MGI.
GO; GO:0007507; P:heart development; IMP:MGI.
GO; GO:0007157; P:heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules; IMP:MGI.
GO; GO:0034113; P:heterotypic cell-cell adhesion; ISO:MGI.
GO; GO:0098657; P:import into cell; ISO:MGI.
GO; GO:0007229; P:integrin-mediated signaling pathway; IEA:UniProtKB-KW.
GO; GO:0007159; P:leukocyte cell-cell adhesion; IMP:MGI.
GO; GO:0050901; P:leukocyte tethering or rolling; ISO:MGI.
GO; GO:0060485; P:mesenchyme development; TAS:DFLAT.
GO; GO:0090074; P:negative regulation of protein homodimerization activity; ISS:UniProtKB.
GO; GO:1990138; P:neuron projection extension; ISO:MGI.
GO; GO:2000353; P:positive regulation of endothelial cell apoptotic process; ISO:MGI.
GO; GO:1903039; P:positive regulation of leukocyte cell-cell adhesion; ISO:MGI.
GO; GO:0002687; P:positive regulation of leukocyte migration; ISO:MGI.
GO; GO:1903238; P:positive regulation of leukocyte tethering or rolling; ISO:MGI.
GO; GO:2000406; P:positive regulation of T cell migration; ISO:MGI.
GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; ISO:MGI.
GO; GO:0043113; P:receptor clustering; ISO:MGI.
GO; GO:0034446; P:substrate adhesion-dependent cell spreading; ISO:MGI.
GO; GO:0072678; P:T cell migration; IMP:MGI.
GO; GO:0061032; P:visceral serous pericardium development; TAS:DFLAT.
Gene3D; 2.130.10.130; -; 1.
InterPro; IPR013517; FG-GAP.
InterPro; IPR013519; Int_alpha_beta-p.
InterPro; IPR000413; Integrin_alpha.
InterPro; IPR013649; Integrin_alpha-2.
InterPro; IPR018184; Integrin_alpha_C_CS.
InterPro; IPR028994; Integrin_alpha_N.
InterPro; IPR032695; Integrin_dom_sf.
Pfam; PF01839; FG-GAP; 2.
Pfam; PF08441; Integrin_alpha2; 1.
PRINTS; PR01185; INTEGRINA.
SMART; SM00191; Int_alpha; 6.
SUPFAM; SSF69179; SSF69179; 3.
PROSITE; PS51470; FG_GAP; 7.
PROSITE; PS00242; INTEGRIN_ALPHA; 1.
1: Evidence at protein level;
Calcium; Cell adhesion; Disulfide bond; Glycoprotein; Integrin; Membrane;
Metal-binding; Phosphoprotein; Receptor; Reference proteome; Repeat;
Signal; Transmembrane; Transmembrane helix.
SIGNAL 1..40
/evidence="ECO:0000255"
CHAIN 41..1039
/note="Integrin alpha-4"
/id="PRO_0000016245"
TOPO_DOM 41..983
/note="Extracellular"
/evidence="ECO:0000255"
TRANSMEM 984..1007
/note="Helical"
/evidence="ECO:0000255"
TOPO_DOM 1008..1039
/note="Cytoplasmic"
/evidence="ECO:0000255"
REPEAT 42..107
/note="FG-GAP 1"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00803"
REPEAT 117..184
/note="FG-GAP 2"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00803"
REPEAT 193..244
/note="FG-GAP 3"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00803"
REPEAT 246..298
/note="FG-GAP 4"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00803"
REPEAT 299..358
/note="FG-GAP 5"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00803"
REPEAT 362..419
/note="FG-GAP 6"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00803"
REPEAT 423..485
/note="FG-GAP 7"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00803"
CA_BIND 321..329
/evidence="ECO:0000255"
CA_BIND 384..392
/evidence="ECO:0000255"
CA_BIND 446..454
/evidence="ECO:0000255"
MOTIF 613..623
/note="SG1"
MOTIF 1010..1014
/note="GFFKR motif"
SITE 598..599
/note="Cleavage"
MOD_RES 1028
/note="Phosphoserine"
/evidence="ECO:0007744|PubMed:19144319,
ECO:0007744|PubMed:21183079"
CARBOHYD 86
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 105
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 145
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 236
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 487
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 525
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 545
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 633
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 652
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 667
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 813
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 828
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
DISULFID 98..108
/evidence="ECO:0000250"
DISULFID 151..172
/evidence="ECO:0000250"
DISULFID 190..205
/evidence="ECO:0000250"
DISULFID 493..502
/evidence="ECO:0000250"
DISULFID 508..564
/evidence="ECO:0000250"
DISULFID 629..634
/evidence="ECO:0000250"
DISULFID 705..718
/evidence="ECO:0000250"
DISULFID 859..897
/evidence="ECO:0000250"
DISULFID 904..909
/evidence="ECO:0000250"
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


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Related Genes :
[Itga4] Integrin alpha-4 (CD49 antigen-like family member D) (Integrin alpha-IV) (Lymphocyte Peyer patch adhesion molecules subunit alpha) (LPAM subunit alpha) (VLA-4 subunit alpha) (CD antigen CD49d)
[ITGA4 CD49D] Integrin alpha-4 (CD49 antigen-like family member D) (Integrin alpha-IV) (VLA-4 subunit alpha) (CD antigen CD49d)
[ITGA2 CD49B] Integrin alpha-2 (CD49 antigen-like family member B) (Collagen receptor) (Platelet membrane glycoprotein Ia) (GPIa) (VLA-2 subunit alpha) (CD antigen CD49b)
[ITGA6] Integrin alpha-6 (CD49 antigen-like family member F) (VLA-6) (CD antigen CD49f) [Cleaved into: Integrin alpha-6 heavy chain; Integrin alpha-6 light chain; Processed integrin alpha-6 (Alpha6p)]
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[CD44 LHR MDU2 MDU3 MIC4] CD44 antigen (CDw44) (Epican) (Extracellular matrix receptor III) (ECMR-III) (GP90 lymphocyte homing/adhesion receptor) (HUTCH-I) (Heparan sulfate proteoglycan) (Hermes antigen) (Hyaluronate receptor) (Phagocytic glycoprotein 1) (PGP-1) (Phagocytic glycoprotein I) (PGP-I) (CD antigen CD44)
[Itgb1] Integrin beta-1 (Fibronectin receptor subunit beta) (VLA-4 subunit beta) (CD antigen CD29)
[MUC1 PUM] Mucin-1 (MUC-1) (Breast carcinoma-associated antigen DF3) (Cancer antigen 15-3) (CA 15-3) (Carcinoma-associated mucin) (Episialin) (H23AG) (Krebs von den Lungen-6) (KL-6) (PEMT) (Peanut-reactive urinary mucin) (PUM) (Polymorphic epithelial mucin) (PEM) (Tumor-associated epithelial membrane antigen) (EMA) (Tumor-associated mucin) (CD antigen CD227) [Cleaved into: Mucin-1 subunit alpha (MUC1-NT) (MUC1-alpha); Mucin-1 subunit beta (MUC1-beta) (MUC1-CT)]
[Sirpa Bit Myd1 Ptpns1 Shps1 Sirp] Tyrosine-protein phosphatase non-receptor type substrate 1 (SHP substrate 1) (SHPS-1) (Brain Ig-like molecule with tyrosine-based activation motifs) (Bit) (CD172 antigen-like family member A) (Inhibitory receptor SHPS-1) (MyD-1 antigen) (Signal-regulatory protein alpha-1) (Sirp-alpha-1) (mSIRP-alpha1) (p84) (CD antigen CD172a)
[SLC3A2 MDU1] 4F2 cell-surface antigen heavy chain (4F2hc) (4F2 heavy chain antigen) (Lymphocyte activation antigen 4F2 large subunit) (Solute carrier family 3 member 2) (CD antigen CD98)
[Itgb7] Integrin beta-7 (Integrin beta-P) (M290 IEL antigen)
[ITGA4] Integrin subunit alpha 4 (Integrin, alpha 4 (Antigen CD49D, alpha 4 subunit of VLA-4 receptor))
[ITGB1] Integrin beta-1 (Fibronectin receptor subunit beta) (Integrin subunit beta-1) (VLA-4 subunit beta) (CD antigen CD29)
[CLEC4M CD209L CD209L1 CD299] C-type lectin domain family 4 member M (CD209 antigen-like protein 1) (DC-SIGN-related protein) (DC-SIGNR) (Dendritic cell-specific ICAM-3-grabbing non-integrin 2) (DC-SIGN2) (Liver/lymph node-specific ICAM-3-grabbing non-integrin) (L-SIGN) (CD antigen CD299)
[Itgb1] Integrin beta-1 (Beta oligodendroglia) (Beta OL) (Fibronectin receptor subunit beta) (VLA-4 subunit beta) (CD antigen CD29)
[ITGA6] Integrin alpha-6 (VLA-6) [Cleaved into: Integrin alpha-6 heavy chain; Integrin alpha-6 light chain]
[ITGB1] Integrin beta-1 (Fibronectin receptor subunit beta) (VLA-4 subunit beta) (CD antigen CD29)
[ITGB1] Integrin beta-1 (Fibronectin receptor subunit beta) (VLA-4 subunit beta) (CD antigen CD29)
[ITGB1] Integrin beta-1 (Fibronectin receptor subunit beta) (VLA-4 subunit beta) (CD antigen CD29)
[ITGB1] Integrin beta-1 (Fibronectin receptor subunit beta) (VLA-4 subunit beta) (CD antigen CD29)
[CD8A MAL] T-cell surface glycoprotein CD8 alpha chain (T-lymphocyte differentiation antigen T8/Leu-2) (CD antigen CD8a)
[ITGB1] Integrin beta-1 (Fibronectin receptor subunit beta) (VLA-4 subunit beta) (CD antigen CD29)
[CD209 CLEC4L] CD209 antigen (C-type lectin domain family 4 member L) (Dendritic cell-specific ICAM-3-grabbing non-integrin 1) (DC-SIGN) (DC-SIGN1) (CD antigen CD209)

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