Protein:ITGA4 |
Protein Summary |
 Gene summary |
| Gene name: ITGA4 | ASpdb.0 ID: 3676 | Gene | Gene symbol | ITGA4 | Gene ID | 3676 |
| Gene name | integrin subunit alpha 4 |
| Synonyms | CD49D|IA4 |
| Cytomap | 2q31.3 |
| Type of gene | protein-coding |
| Description | integrin alpha-4269C wild typeCD49 antigen-like family member DVLA-4 subunit alphaalpha 4 subunit of VLA-4 receptorantigen CD49D, alpha-4 subunit of VLA-4 receptorintegrin alpha-IVvery late activation protein 4 receptor, alpha 4 subunit |
| Modification date | 20240413 |
| UniProtAcc | P13612 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | ITGA4 | GO:0005886 | plasma membrane | 12869515 |
| Gene | ITGA4 | GO:0007159 | leukocyte cell-cell adhesion | 1715889 |
| Gene | ITGA4 | GO:0007160 | cell-matrix adhesion | 22232704 |
| Gene | ITGA4 | GO:0009986 | cell surface | 1715889|18308860|20563599|23986478 |
| Gene | ITGA4 | GO:0019960 | C-X3-C chemokine binding | 23125415 |
| Gene | ITGA4 | GO:0034669 | integrin alpha4-beta7 complex | 18308860|23986478 |
| Gene | ITGA4 | GO:0090074 | negative regulation of protein homodimerization activity | 12869515 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| P13612-1 | P13612-1_4hkc_B.pdb | 4HKC | X-ray | 2.2 | B | 1006 | 1013 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| P13612 | ITGA4 | P13612-1 | P13612-2 | 1032 | 195 | 186 | 195 | Substitution | DYVKKFGENF | GSISKYRART | 186 | 195 |
| P13612 | ITGA4 | P13612-1 | P13612-2 | 1032 | 195 | 196 | 1032 | Deletion | none | none | 195 | 195 |
| Multiple sequence alignment of our canonical and alternatively spliced ITGA4 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of ITGA4 |
| UniProt-id | ENSG | ENST | ENSP |
| P13612-1 | ENSG00000115232.14 | ENST00000397033.7 | ENSP00000380227.2 |
| P13612-2 | ENSG00000115232.14 | ENST00000339307.8 | ENSP00000340149.4 |
| UniProt-id | NM ID | NP ID |
| P13612-1 | NM_000885.5 | NP_000876.3 |
| P13612-2 | NM_001316312.1 | NP_001303241.1 |
| Amino acid sequences of our canonical and alternatively spliced ITGA4 |
| accession_id | Protein sequence |
| P13612-1 | MAWEARREPGPRRAAVRETVMLLLCLGVPTGRPYNVDTESALLYQGPHNTLFGYSVVLHSHGANRWLLVGAPTANWLANASVINPGAIYR CRIGKNPGQTCEQLQLGSPNGEPCGKTCLEERDNQWLGVTLSRQPGENGSIVTCGHRWKNIFYIKNENKLPTGGCYGVPPDLRTELSKRI APCYQDYVKKFGENFASCQAGISSFYTKDLIVMGAPGSSYWTGSLFVYNITTNKYKAFLDKQNQVKFGSYLGYSVGAGHFRSQHTTEVVG GAPQHEQIGKAYIFSIDEKELNILHEMKGKKLGSYFGASVCAVDLNADGFSDLLVGAPMQSTIREEGRVFVYINSGSGAVMNAMETNLVG SDKYAARFGESIVNLGDIDNDGFEDVAIGAPQEDDLQGAIYIYNGRADGISSTFSQRIEGLQISKSLSMFGQSISGQIDADNNGYVDVAV GAFRSDSAVLLRTRPVVIVDASLSHPESVNRTKFDCVENGWPSVCIDLTLCFSYKGKEVPGYIVLFYNMSLDVNRKAESPPRFYFSSNGT SDVITGSIQVSSREANCRTHQAFMRKDVRDILTPIQIEAAYHLGPHVISKRSTEEFPPLQPILQQKKEKDIMKKTINFARFCAHENCSAD LQVSAKIGFLKPHENKTYLAVGSMKTLMLNVSLFNAGDDAYETTLHVKLPVGLYFIKILELEEKQINCEVTDNSGVVQLDCSIGYIYVDH LSRIDISFLLDVSSLSRAEEDLSITVHATCENEEEMDNLKHSRVTVAIPLKYEVKLTVHGFVNPTSFVYGSNDENEPETCMVEKMNLTFH VINTGNSMAPNVSVEIMVPNSFSPQTDKLFNILDVQTTTGECHFENYQRVCALEQQKSAMQTLKGIVRFLSKTDKRLLYCIKADPHCLNF LCNFGKMESGKEASVHIQLEGRPSILEMDETSALKFEIRATGFPEPNPRVIELNKDENVAHVLLEGLHHQRPKRYFTIVIISSSLLLGLI |
| P13612-2 | MAWEARREPGPRRAAVRETVMLLLCLGVPTGRPYNVDTESALLYQGPHNTLFGYSVVLHSHGANRWLLVGAPTANWLANASVINPGAIYR CRIGKNPGQTCEQLQLGSPNGEPCGKTCLEERDNQWLGVTLSRQPGENGSIVTCGHRWKNIFYIKNENKLPTGGCYGVPPDLRTELSKRI |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| ITGA4 (go to UniProt):P13612 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| P13612 | Topological domain | 35 | 977 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Substitution;Start=186;End=195 |
| P13612 | Topological domain | 35 | 977 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=196;End=1032 |
| P13612 | Transmembrane | 978 | 1001 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=196;End=1032 |
| P13612 | Topological domain | 1002 | 1032 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=196;End=1032 |
| P13612 | Repeat | 185 | 237 | Note=FG-GAP 3;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00803 | Type=Substitution;Start=186;End=195 |
| P13612 | Repeat | 185 | 237 | Note=FG-GAP 3;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00803 | Type=Deletion;Start=196;End=1032 |
| P13612 | Repeat | 238 | 291 | Note=FG-GAP 4;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00803 | Type=Deletion;Start=196;End=1032 |
| P13612 | Repeat | 292 | 351 | Note=FG-GAP 5;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00803 | Type=Deletion;Start=196;End=1032 |
| P13612 | Repeat | 355 | 412 | Note=FG-GAP 6;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00803 | Type=Deletion;Start=196;End=1032 |
| P13612 | Repeat | 416 | 478 | Note=FG-GAP 7;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00803 | Type=Deletion;Start=196;End=1032 |
| P13612 | Motif | 606 | 616 | Note=SG1 | Type=Deletion;Start=196;End=1032 |
| P13612 | Motif | 1003 | 1007 | Note=GFFKR motif | Type=Deletion;Start=196;End=1032 |
Gene Isoform Structures and Expression Levels for ITGA4 |
| Gene structures of our canonical and alternative spliced genes of ITGA4 * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
 |
| Expression levels of gene isoforms across TCGA. |
 |
Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of P13612-1 |
| 3D view using mol* of P13612-2 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of P13612-1 |
 |
| pLDDT distribution across the protein length of P13612-2 |
 |
Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of P13612-1 |
 |
| Ramachandran plot of P13612-2 |
 |
Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| P13612-1 | 1.07 | 332 | 1.016 | 925.071 | 0.447 | 0.802 | 0.987 | 0.251 | 1.242 | 0.202 | 0.775 | 54,55,56,57,58,126,129,130,131,132,133,135,136,146 ,147,191,199,202,203,204,205,206,207,208,209,210,2 12,216,217,221,250,253,254,255,256,257,258,259,266 ,268,305,308,309,310,311,312,313,314,321,328,329,3 70,371,372,373,374,384,432,433,434,435,436,437 |
| P13612-2 | 0.799 | 49 | 0.685 | 197.225 | 0.675 | 0.726 | 0.96 | 0.195 | 1.253 | 0.156 | 0.739 | 76,107,111,112,114,120,122,125,148,166,177,178,179 ,180,181,182,184,187,190,191,194 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
 |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of P13612-1_P13612-1_4hkc_B.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P13612-1_4hkc_B_P13612-2.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P13612-1_P13612-2.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P13612-1_vs_P13612-2.png |
 < |
| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P13612-1_vs_P13612-2.png |
 < |
Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to ITGA4 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P13612 | ITGA4 | DB05122 | R1295 | investigational | |
| P13612 | ITGA4 | DB05468 | R411 | investigational | |
| P13612 | ITGA4 | DB09033 | Vedolizumab | approved | antibody |
| P13612 | ITGA4 | DB00108 | Natalizumab | approved, investigational | antibody |
| P13612 | ITGA4 | DB05092 | CDP323 | investigational | |
| P13612 | ITGA4 | DB15791 | MK-0668 | experimental | |
| P13612 | ITGA4 | DB04997 | ATL1102 | investigational | |
| P13612 | ITGA4 | DB06822 | Tinzaparin | approved | inhibitor |
Related Diseases to ITGA4 |
| Previous studies relating to the alternative splicing of ITGA4 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| ITGA4 | 7587632 | Mechanisms of VCAM-1 and fibronectin binding to integrin alpha 4 beta 1: implications for integrin function and rational drug design. | Integrin alpha 4 beta 1 can mediate both cell-cell and cell-extracellular matrix adhesion by binding to either fibronectin or vascular cell adhesion molecule 1 (VCAM-1). Both interactions are important for extravasation of leukocytes from the blood implying that rationally designed inhibitors of alpha 4 beta 1 function may be useful for treating a various inflammatory conditions. The mechanisms of ligand binding by alpha 4 beta 1 are complicated by the fact that alternative splicing can generate different isoforms of the receptor-binding domains in both fibronectin and VCAM-1. Therefore, in addition to developing alpha 4 beta 1 antagonists, we have also been interested in identifying isoform-specific functions. Recombinant ligand variants have been tested in adhesion and direct receptor-binding assays and each molecule was found to have a different inherent affinity for alpha 4 beta 1 that endows them with different adhesive activities. This suggests that alternative splicing may regulate alpha 4 beta 1-dependent motility in vivo. The initial strategy that we have adopted to develop alpha 4 beta 1 inhibitors has been to identify key amino acid residues and peptide sequences participating in the receptor-ligand binding event and to use this information to generate synthetic mimetics. Three active sites have been identified in fibronectin by testing truncated proteins, expressing recombinant fragments and screening synthetic peptides. Two of these sites employ versions of a novel integrin-binding motif, LDVP/IDAP. A key active site in VCAM-1 has been identified by similar approaches as the related sequence IDSP. Since IDSP-like sequences are probably used by other integrin-binding immunoglobulins, derivatives of these peptides may turn out to be the forerunners of a new generation of therapeutic agents with multiple applications. | D007249 | Inflammation |
Clinically important variants in ITGA4 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
Copyright 2024-PresentThe University of Texas Health Science Center at Houston (UTHealth Houston) Web File Viewing | Emergency Information |