Description: Homo sapiens integrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor) (ITGA4), mRNA. RefSeq Summary (NM_000885): The gene encodes a member of the integrin alpha chain family of proteins. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain that function in cell surface adhesion and signaling. The encoded preproprotein is proteolytically processed to generate light and heavy chains that comprise the alpha 4 subunit. This subunit associates with a beta 1 or beta 7 subunit to form an integrin that may play a role in cell motility and migration. This integrin is a therapeutic target for the treatment of multiple sclerosis, Crohn's disease and inflammatory bowel disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]. Transcript (Including UTRs) Position: hg19 chr2:182,321,619-182,402,468 Size: 80,850 Total Exon Count: 28 Strand: + Coding Region Position: hg19 chr2:182,322,382-182,400,254 Size: 77,873 Coding Exon Count: 28
ID:ITA4_HUMAN DESCRIPTION: RecName: Full=Integrin alpha-4; AltName: Full=CD49 antigen-like family member D; AltName: Full=Integrin alpha-IV; AltName: Full=VLA-4 subunit alpha; AltName: CD_antigen=CD49d; Flags: Precursor; FUNCTION: Integrins alpha-4/beta-1 (VLA-4) and alpha-4/beta-7 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. 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. INTERACTION: P05556:ITGB1; NbExp=3; IntAct=EBI-703044, EBI-703066; P49023:PXN; NbExp=3; IntAct=EBI-703044, EBI-702209; O43294:TGFB1I1; NbExp=2; IntAct=EBI-703044, EBI-1051449; SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. DOMAIN: The SG1 motif is involved in binding to chondroitin sulfate glycosaminoglycan and cell adhesion. PTM: Phosphorylation on Ser-1027 inhibits PXN binding. SIMILARITY: Belongs to the integrin alpha chain family. SIMILARITY: Contains 7 FG-GAP repeats. SEQUENCE CAUTION: Sequence=AAB59613.1; Type=Frameshift; Positions=13; Sequence=CAA34852.1; Type=Frameshift; Positions=13;
Neutrophils Yukinori Okada et al. PLoS genetics 2011, Identification of nine novel loci associated with white blood cell subtypes in a Japanese population., PLoS genetics.
[PubMed 21738478]
smoking cessation Uhl ,et al. Pharmacogenomics 2010, Genome-wide association for smoking cessation success: participants in the Patch in Practice trial of nicotine replacement , Pharmacogenomics 2010 11- 3 : 357-67.
[PubMed 20235792]
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P13612
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
FW340057 - Screening. JD484836 - Sequence 465860 from Patent EP1572962. JD195400 - Sequence 176424 from Patent EP1572962. JD158681 - Sequence 139705 from Patent EP1572962. JD417108 - Sequence 398132 from Patent EP1572962. BC055419 - Homo sapiens integrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor), mRNA (cDNA clone IMAGE:4805867), complete cds. AJ504733 - Homo sapiens partial mRNA for integrin alpha-4 subunit (IA4 gene), variant sequence. AJ508356 - Homo sapiens partial mRNA for integrin alpha-4 subunit (IA4 gene), wild type. L12002 - Human integrin alpha 4 subunit mRNA, complete cds. JD129537 - Sequence 110561 from Patent EP1572962. JD330971 - Sequence 311995 from Patent EP1572962. JD451447 - Sequence 432471 from Patent EP1572962. AK303478 - Homo sapiens cDNA FLJ60208 complete cds, highly similar to Integrin alpha-4 precursor. BC016671 - Homo sapiens integrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor), mRNA (cDNA clone IMAGE:4342576), partial cds. JD457999 - Sequence 439023 from Patent EP1572962. JD253570 - Sequence 234594 from Patent EP1572962. JD404925 - Sequence 385949 from Patent EP1572962. X16983 - Human mRNA for integrin alpha-4 subunit. AB527164 - Synthetic construct DNA, clone: pF1KB7332, Homo sapiens ITGA4 gene for integrin, alpha 4, without stop codon, in Flexi system. BC146277 - Synthetic construct Homo sapiens clone IMAGE:100015216, MGC:180251 integrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor) (ITGA4) mRNA, encodes complete protein. BC156712 - Synthetic construct Homo sapiens clone IMAGE:100062220, MGC:190207 integrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor) (ITGA4) mRNA, encodes complete protein. AK311738 - Homo sapiens cDNA, FLJ18780. AB208885 - Homo sapiens mRNA for integrin alpha 4 precursor variant protein. AK303220 - Homo sapiens cDNA FLJ59131 complete cds, highly similar to Integrin alpha-4 precursor. AK310610 - Homo sapiens cDNA, FLJ17652. AJ510246 - Homo sapiens partial mRNA for integrin alpha-4 subunit (IA4 gene), nucleotide A variant. AJ510247 - Homo sapiens partial mRNA for integrin alpha-4 subunit (IA4 gene), nucleotide G variant. BC080190 - Homo sapiens integrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor), mRNA (cDNA clone IMAGE:6069246), complete cds. CU687336 - Synthetic construct Homo sapiens gateway clone IMAGE:100022933 5' read ITGA4 mRNA. KJ901531 - Synthetic construct Homo sapiens clone ccsbBroadEn_10925 ITGA4 gene, encodes complete protein. AJ510248 - Homo sapiens partial mRNA for integrin alpha-4 subunit (IA4 gene), nucleotide T variant. AJ510249 - Homo sapiens partial mRNA for integrin alpha-4 subunit (IA4 gene), nucleotide C variant. JD266256 - Sequence 247280 from Patent EP1572962. JD048193 - Sequence 29217 from Patent EP1572962. JD357501 - Sequence 338525 from Patent EP1572962.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa04510 - Focal adhesion hsa04512 - ECM-receptor interaction hsa04514 - Cell adhesion molecules (CAMs) hsa04640 - Hematopoietic cell lineage hsa04670 - Leukocyte transendothelial migration hsa04672 - Intestinal immune network for IgA production hsa04810 - Regulation of actin cytoskeleton hsa05140 - Leishmaniasis hsa05410 - Hypertrophic cardiomyopathy (HCM) hsa05412 - Arrhythmogenic right ventricular cardiomyopathy (ARVC) hsa05414 - Dilated cardiomyopathy
BioCarta from NCI Cancer Genome Anatomy Project h_LairPathway - Cells and Molecules involved in local acute inflammatory response h_lympathway - Adhesion and Diapedesis of Lymphocytes h_lymphocytePathway - Adhesion Molecules on Lymphocyte h_monocytePathway - Monocyte and its Surface Molecules
Reactome (by CSHL, EBI, and GO)
Protein P13612 (Reactome details) participates in the following event(s):
R-HSA-198941 VCAM1 binds Integrin alpha4beta1 R-HSA-202706 Integrin alpha4beta1 binds JAM2:JAM3 R-HSA-2752118 SPP1 (osteopontin) binds Integrin alpha4beta1 R-NUL-2752136 Osteopontin binds Integrin alpha4beta1 R-HSA-199032 MADCAM1-1 binds Integrin alpha4beta7 R-HSA-265429 THBS1 (Thrombospondin-1) binds Integrin alpha3beta1, alpha4beta1 R-HSA-216050 Integrins alpha4beta1, alpha8beta1, alphaVbeta1, alphaVbeta3, alphaVbeta6 bind Fibronectin matrix R-HSA-198933 Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell R-HSA-216083 Integrin cell surface interactions R-HSA-202733 Cell surface interactions at the vascular wall R-HSA-8949275 RUNX3 Regulates Immune Response and Cell Migration R-HSA-1280218 Adaptive Immune System R-HSA-1474244 Extracellular matrix organization R-HSA-109582 Hemostasis R-HSA-8878159 Transcriptional regulation by RUNX3 R-HSA-168256 Immune System R-HSA-212436 Generic Transcription Pathway R-HSA-73857 RNA Polymerase II Transcription R-HSA-74160 Gene expression (Transcription)
US Server
