| IED ID | IndEnz0002002697 |
| Enzyme Type ID | protease002697 |
| Protein Name |
Integrin beta-1 Fibronectin receptor subunit beta Glycoprotein IIa GPIIA VLA-4 subunit beta CD antigen CD29 |
| Gene Name | ITGB1 FNRB MDF2 MSK12 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MNLQPIFWIGLISSVCCVFAQTDENRCLKANAKSCGECIQAGPNCGWCTNSTFLQEGMPTSARCDDLEALKKKGCPPDDIENPRGSKDIKKNKNVTNRSKGTAEKLKPEDITQIQPQQLVLRLRSGEPQTFTLKFKRAEDYPIDLYYLMDLSYSMKDDLENVKSLGTDLMNEMRRITSDFRIGFGSFVEKTVMPYISTTPAKLRNPCTSEQNCTSPFSYKNVLSLTNKGEVFNELVGKQRISGNLDSPEGGFDAIMQVAVCGSLIGWRNVTRLLVFSTDAGFHFAGDGKLGGIVLPNDGQCHLENNMYTMSHYYDYPSIAHLVQKLSENNIQTIFAVTEEFQPVYKELKNLIPKSAVGTLSANSSNVIQLIIDAYNSLSSEVILENGKLSEGVTISYKSYCKNGVNGTGENGRKCSNISIGDEVQFEISITSNKCPKKDSDSFKIRPLGFTEEVEVILQYICECECQSEGIPESPKCHEGNGTFECGACRCNEGRVGRHCECSTDEVNSEDMDAYCRKENSSEICSNNGECVCGQCVCRKRDNTNEIYSGKFCECDNFNCDRSNGLICGGNGVCKCRVCECNPNYTGSACDCSLDTSTCEASNGQICNGRGICECGVCKCTDPKFQGQTCEMCQTCLGVCAEHKECVQCRAFNKGEKKDTCTQECSYFNITKVESRDKLPQPVQPDPVSHCKEKDVDDCWFYFTYSVNGNNEVMVHVVENPECPTGPDIIPIVAGVVAGIVLIGLALLLIWKLLMIIHDRREFAKFEKEKMNAKWDTGENPIYKSAVTTVVNPKYEGK |
| Enzyme Length | 798 |
| Uniprot Accession Number | P05556 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Integrins alpha-1/beta-1, alpha-2/beta-1, alpha-10/beta-1 and alpha-11/beta-1 are receptors for collagen. Integrins alpha-1/beta-1 and alpha-2/beta-2 recognize the proline-hydroxylated sequence G-F-P-G-E-R in collagen. Integrins alpha-2/beta-1, alpha-3/beta-1, alpha-4/beta-1, alpha-5/beta-1, alpha-8/beta-1, alpha-10/beta-1, alpha-11/beta-1 and alpha-V/beta-1 are receptors for fibronectin. Alpha-4/beta-1 recognizes one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. Integrin alpha-5/beta-1 is a receptor for fibrinogen. Integrin alpha-1/beta-1, alpha-2/beta-1, alpha-6/beta-1 and alpha-7/beta-1 are receptors for lamimin. Integrin alpha-6/beta-1 (ITGA6:ITGB1) is present in oocytes and is involved in sperm-egg fusion (By similarity). Integrin alpha-4/beta-1 is a receptor for VCAM1. It recognizes the sequence Q-I-D-S in VCAM1. Integrin alpha-9/beta-1 is a receptor for VCAM1, cytotactin and osteopontin. It recognizes the sequence A-E-I-D-G-I-E-L in cytotactin. Integrin alpha-3/beta-1 is a receptor for epiligrin, thrombospondin and CSPG4. Alpha-3/beta-1 may mediate with LGALS3 the stimulation by CSPG4 of endothelial cells migration. Integrin alpha-V/beta-1 is a receptor for vitronectin. Beta-1 integrins recognize the sequence R-G-D in a wide array of ligands. When associated with alpha-7 integrin, regulates cell adhesion and laminin matrix deposition. Involved in promoting endothelial cell motility and angiogenesis. Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process and the formation of mineralized bone nodules. May be involved in up-regulation of the activity of kinases such as PKC via binding to KRT1. Together with KRT1 and RACK1, serves as a platform for SRC activation or inactivation. Plays a mechanistic adhesive role during telophase, required for the successful completion of cytokinesis. Integrin alpha-3/beta-1 provides a docking site for FAP (seprase) at invadopodia plasma membranes in a collagen-dependent manner and hence may participate in the adhesion, formation of invadopodia and matrix degradation processes, promoting cell invasion. ITGA4:ITGB1 binds to fractalkine (CX3CL1) and may act as its coreceptor in CX3CR1-dependent fractalkine signaling (PubMed:23125415, PubMed:24789099). ITGA4:ITGB1 and ITGA5:ITGB1 bind 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 (PubMed:18635536, PubMed:25398877). ITGA5:ITGB1 acts as a receptor for fibrillin-1 (FBN1) and mediates R-G-D-dependent cell adhesion to FBN1 (PubMed:12807887, PubMed:17158881). ITGA5:ITGB1 is a receptor for IL1B and binding is essential for IL1B signaling (PubMed:29030430). ITGA5:ITGB3 is a receptor for soluble CD40LG and is required for CD40/CD40LG signaling (PubMed:31331973). Plays an important role in myoblast differentiation and fusion during skeletal myogenesis (By similarity). {ECO:0000250|UniProtKB:P07228, ECO:0000250|UniProtKB:P09055, ECO:0000269|PubMed:10455171, ECO:0000269|PubMed:12473654, ECO:0000269|PubMed:12807887, ECO:0000269|PubMed:16256741, ECO:0000269|PubMed:17158881, ECO:0000269|PubMed:18635536, ECO:0000269|PubMed:18804435, ECO:0000269|PubMed:19064666, ECO:0000269|PubMed:21768292, ECO:0000269|PubMed:23125415, ECO:0000269|PubMed:24789099, ECO:0000269|PubMed:25398877, ECO:0000269|PubMed:29030430, ECO:0000269|PubMed:31331973, ECO:0000269|PubMed:7523423}.; FUNCTION: [Isoform 2]: Interferes with isoform 1 resulting in a dominant negative effect on cell adhesion and migration (in vitro). {ECO:0000305|PubMed:2249781}.; FUNCTION: [Isoform 5]: Isoform 5 displaces isoform 1 in striated muscles. {ECO:0000250|UniProtKB:P09055}.; FUNCTION: (Microbial infection) Integrin ITGA2:ITGB1 acts as a receptor for Human echoviruses 1 and 8. {ECO:0000269|PubMed:8411387}.; FUNCTION: (Microbial infection) Acts as a receptor for Cytomegalovirus/HHV-5. {ECO:0000269|PubMed:20660204}.; FUNCTION: (Microbial infection) Acts as a receptor for Epstein-Barr virus/HHV-4. {ECO:0000269|PubMed:17945327}.; FUNCTION: (Microbial infection) Integrin ITGA5:ITGB1 acts as a receptor for Human parvovirus B19. {ECO:0000269|PubMed:12907437}.; FUNCTION: (Microbial infection) Integrin ITGA2:ITGB1 acts as a receptor for Human rotavirus. {ECO:0000269|PubMed:12941907}.; FUNCTION: (Microbial infection) Acts as a receptor for Mammalian reovirus. {ECO:0000269|PubMed:16501085}.; FUNCTION: (Microbial infection) In case of HIV-1 infection, integrin ITGA5:ITGB1 binding to extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions. {ECO:0000269|PubMed:10397733}.; FUNCTION: (Microbial infection) Interacts with CotH proteins expressed by fungi of the order mucorales, the causative agent of mucormycosis, which plays an important role in epithelial cell invasion by the fungi (PubMed:32487760). Integrin ITGA3:ITGB1 may act as a receptor for R.delemar CotH7 in alveolar epithelial cells, which may be an early step in pulmonary mucormycosis disease progression (PubMed:32487760). {ECO:0000269|PubMed:32487760}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (4); Beta strand (21); Chain (1); Cross-link (1); Disulfide bond (28); Domain (1); Erroneous initiation (1); Glycosylation (12); Helix (21); Metal binding (11); Modified residue (5); Mutagenesis (14); Region (7); Repeat (4); Sequence conflict (5); Signal peptide (1); Topological domain (2); Transmembrane (1); Turn (6) |
| Keywords | 3D-structure;Acetylation;Alternative splicing;Calcium;Cell adhesion;Cell junction;Cell membrane;Cell projection;Direct protein sequencing;Disulfide bond;Endosome;Glycoprotein;Host cell receptor for virus entry;Host-virus interaction;Integrin;Isopeptide bond;Magnesium;Membrane;Metal-binding;Myogenesis;Phosphoprotein;Receptor;Reference proteome;Repeat;Signal;Transmembrane;Transmembrane helix;Ubl conjugation |
| Interact With | P12821-3; Q9BYF1; P78536; Q9BY76; P05067; P46109; P32927; P78423; P17813; P21333; P17301; P13612; P08648; P07948; Q13387-4; P27986-2; P18031; Q9Y490; O60784-2; P03192; P35282; P26039; P49023; Q71LX4 |
| Induction | INDUCTION: Induced in alveolar epithelial cells during exposure to the fungus R.delemar, a causative agent of mucormycosis. {ECO:0000269|PubMed:32487760}. |
| Subcellular Location | SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:32487760, ECO:0000303|PubMed:10455171}; Single-pass type I membrane protein {ECO:0000255}. Cell projection, invadopodium membrane {ECO:0000269|PubMed:10455171}; Single-pass type I membrane protein {ECO:0000255}. Cell projection, ruffle membrane {ECO:0000303|PubMed:10455171}; Single-pass type I membrane protein {ECO:0000255}. Recycling endosome {ECO:0000269|PubMed:16256741}. Melanosome {ECO:0000269|PubMed:17081065}. Cleavage furrow {ECO:0000269|PubMed:17956333}. Cell projection, lamellipodium {ECO:0000269|PubMed:11919189}. Cell projection, ruffle {ECO:0000269|PubMed:11919189}. Cell junction, focal adhesion {ECO:0000269|PubMed:17158881}. Cell surface {ECO:0000269|PubMed:17158881}. Note=Isoform 2 does not localize to focal adhesions. Highly enriched in stage I melanosomes. Located on plasma membrane of neuroblastoma NMB7 cells. In a lung cancer cell line, in prometaphase and metaphase, localizes diffusely at the membrane and in a few intracellular vesicles. In early telophase, detected mainly on the matrix-facing side of the cells. By mid-telophase, concentrated to the ingressing cleavage furrow, mainly to the basal side of the furrow. In late telophase, concentrated to the extending protrusions formed at the opposite ends of the spreading daughter cells, in vesicles at the base of the lamellipodia formed by the separating daughter cells. Colocalizes with ITGB1BP1 and metastatic suppressor protein NME2 at the edge or peripheral ruffles and lamellipodia during the early stages of cell spreading on fibronectin or collagen. Translocates from peripheral focal adhesions sites to fibrillar adhesions in a ITGB1BP1-dependent manner. Enriched preferentially at invadopodia, cell membrane protrusions that correspond to sites of cell invasion, in a collagen-dependent manner. Localized at plasma and ruffle membranes in a collagen-independent manner. {ECO:0000269|PubMed:10455171, ECO:0000303|PubMed:10455171}.; SUBCELLULAR LOCATION: [Isoform 5]: Cell membrane, sarcolemma {ECO:0000250|UniProtKB:P09055}. Cell junction {ECO:0000250|UniProtKB:P09055}. Note=In cardiac muscle, isoform 5 is found in costameres and intercalated disks. {ECO:0000250|UniProtKB:P09055}. |
| Modified Residue | MOD_RES 777; /note=Phosphothreonine; /evidence=ECO:0007744|PubMed:19690332; MOD_RES 783; /note=Phosphotyrosine; /evidence=ECO:0007744|PubMed:23186163; MOD_RES 785; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:24275569; MOD_RES 789; /note=Phosphothreonine; /evidence=ECO:0007744|PubMed:24275569; MOD_RES 794; /note=N6-acetyllysine; alternate; /evidence=ECO:0007744|PubMed:19608861 |
| Post Translational Modification | PTM: The cysteine residues are involved in intrachain disulfide bonds. {ECO:0000250}. |
| Signal Peptide | SIGNAL 1..20 |
| Structure 3D | Electron microscopy (3); X-ray crystallography (10) |
| Cross Reference PDB | 3G9W; 3T9K; 3VI3; 3VI4; 4DX9; 4WJK; 4WK0; 4WK2; 4WK4; 7CEB; 7CEC; 7NWL; 7NXD; |
| Mapped Pubmed ID | 10025398; 10209034; 10366422; 10490598; 10508610; 10521801; 10593924; 10604475; 10618392; 10673366; 10699464; 10713152; 10714768; 10873802; 10896784; 10906324; 10958683; 10982388; 11054877; 11145705; 11158588; 11279249; 11313964; 11518510; 11572855; 11756552; 11773441; 11803464; 11804587; 11857637; 11964076; 11970960; 11980922; 12070135; 12358597; 12376551; 12415008; 12423238; 12456677; 12480817; 12496264; 12592401; 12606711; 12617725; 12682293; 12721290; 12724312; 12879062; 14502569; 14514689; 14681217; 14715956; 15169870; 15225631; 15240572; 15345499; 15383545; 1542691; 15479743; 15713743; 15721307; 15721583; 15814684; 15851719; 1588291; 15949469; 16002401; 16051604; 16099422; 16140760; 16151532; 16258728; 16339170; 16385451; 16413178; 16507994; 16581764; 1660188; 16636067; 16702231; 16731529; 16754661; 16762923; 16782899; 16917503; 16945929; 1697296; 17027967; 17167768; 17170699; 17244649; 17269730; 17314405; 17377534; 17525755; 17583407; 17615292; 17690686; 18006505; 18177638; 18203656; 18218625; 18347018; 18555990; 18985028; 19005162; 19115199; 19342448; 19350017; 19367725; 19463016; 19502598; 19534724; 19738201; 19798053; 19887187; 20033473; 20159608; 20217867; 20460433; 20679435; 20690820; 20705068; 20711500; 20802515; 20802519; 20926684; 21378159; 21397862; 21646718; 21652699; 21690215; 21730051; 21806020; 21844907; 21947080; 21985969; 21988832; 22106087; 22134916; 22157815; 22174689; 22304920; 22413019; 22608513; 22623428; 22734669; 22884367; 22936677; 22940691; 22970203; 23092334; 23289620; 23414517; 23707487; 2412224; 2420006; 24344204; 24659802; 24814316; 25475857; 25694433; 2649503; 26496610; 26638075; 29358323; 31389670; 31871319; 33962943; 34188035; 6643500; 7529288; 7531291; 7532190; 7541634; 7542669; 7559467; 7559638; 7685013; 7693733; 7907877; 8107774; 8118028; 8314844; 8344274; 8538749; 8543060; 8598224; 8617364; 8645157; 8662891; 8756646; 8798539; 8798654; 8805223; 8816443; 8910476; 9013646; 9360995; 9361014; 9367446; 9396761; 9547293; 9565552; 9614184; 9645947; 9705280; 9722563; 9723655; 9725916; 9792683; 9822598; 9843499; 9858236; 9949188; 9988689; |
| Motif | |
| Gene Encoded By | |
| Mass | 88,415 |
| Kinetics | |
| Metal Binding | METAL 152; /note=Magnesium; METAL 154; /note=Calcium 1; via carbonyl oxygen; METAL 156; /note=Calcium 1; METAL 157; /note=Calcium 1; METAL 189; /note=Calcium 2; METAL 244; /note=Calcium 2; METAL 246; /note=Calcium 2; METAL 248; /note=Calcium 2; via carbonyl oxygen; METAL 249; /note=Calcium 2; METAL 249; /note=Magnesium; METAL 362; /note=Calcium 1; via carbonyl oxygen |
| Rhea ID | |
| Cross Reference Brenda |