Molecule Information

General Information of the Molecule (ID: Mol04323)

• Name: Integrin beta-1 (ITGB1) ,Homo sapiens
• Synonyms: Fibronectin receptor subunit beta; Glycoprotein IIa; VLA-4 subunit beta; CD_antigen=CD29
• Molecule Type: Protein
• Gene Name: ITGB1
• Gene ID: 3688
• Sequence:
  MNLQPIFWIGLISSVCCVFAQTDENRCLKANAKSCGECIQAGPNCGWCTNSTFLQEGMPT
  SARCDDLEALKKKGCPPDDIENPRGSKDIKKNKNVTNRSKGTAEKLKPEDITQIQPQQL
  V LRLRSGEPQTFTLKFKRAEDYPIDLYYLMDLSYSMKDDLENVKSLGTDLMNEMRRITS
  DF RIGFGSFVEKTVMPYISTTPAKLRNPCTSEQNCTSPFSYKNVLSLTNKGEVFNELVG
  KQR ISGNLDSPEGGFDAIMQVAVCGSLIGWRNVTRLLVFSTDAGFHFAGDGKLGGIVLP
  NDGQ CHLENNMYTMSHYYDYPSIAHLVQKLSENNIQTIFAVTEEFQPVYKELKNLIPKS
  AVGTL SANSSNVIQLIIDAYNSLSSEVILENGKLSEGVTISYKSYCKNGVNGTGENGRK
  CSNISI GDEVQFEISITSNKCPKKDSDSFKIRPLGFTEEVEVILQYICECECQSEGIPE
  SPKCHEG NGTFECGACRCNEGRVGRHCECSTDEVNSEDMDAYCRKENSSEICSNNGECV
  CGQCVCRK RDNTNEIYSGKFCECDNFNCDRSNGLICGGNGVCKCRVCECNPNYTGSACD
  CSLDTSTCE ASNGQICNGRGICECGVCKCTDPKFQGQTCEMCQTCLGVCAEHKECVQCR
  AFNKGEKKDT CTQECSYFNITKVESRDKLPQPVQPDPVSHCKEKDVDDCWFYFTYSVNG
  NNEVMVHVVEN PECPTGPDIIPIVAGVVAGIVLIGLALLLIWKLLMIIHDRREFAKFEK
  EKMNAKWDTGEN PIYKSAVTTVVNPKYEGK
• Function: Integrins alpha-1/beta-1, alpha-2/beta-1, alpha-10/beta-1 andalpha-11/beta-1 are receptors for collagen. Integrins alpha-1/beta-1and 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 alternativelyspliced CS-1 and CS-5 regions of fibronectin. Integrin alpha-5/beta-1is 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. Integrinalpha-6/beta-1 is present in oocytes and is involved insperm-egg fusion . Integrin alpha-4/beta-1 is a receptorfor VCAM1. It recognizes the sequence Q-I-D-S in VCAM1. Integrin alpha-9/beta-1 is a receptor for VCAM1, cytotactin and osteopontin. Itrecognizes 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 ofendothelial cells migration. Integrin alpha-V/beta-1 is a receptor forvitronectin. Beta-1 integrins recognize the sequence R-G-D in a widearray of ligands. When associated with alpha-7 integrin, regulates celladhesion and laminin matrix deposition. Involved in promotingendothelial cell motility and angiogenesis. Involved in osteoblastcompaction through the fibronectin fibrillogenesis cell-mediated matrixassembly process and the formation of mineralized bone nodules. May beinvolved in up-regulation of the activity of kinases such as PKC viabinding to KRT1. Together with KRT1 and RACK1, serves as a platform forSRC activation or inactivation. Plays a mechanistic adhesive roleduring telophase, required for the successful completion ofcytokinesis. Integrin alpha-3/beta-1 provides a docking site for FAP at invadopodia plasma membranes in a collagen-dependentmanner and hence may participate in the adhesion, formation ofinvadopodia and matrix degradation processes, promoting cell invasion.ITGA4:ITGB1 binds to fractalkine and may act as its coreceptorin CX3CR1-dependent fractalkine signaling . ITGA4:ITGB1 and ITGA5:ITGB1 bind to PLA2G2A via asite which is distinct from the classical ligand-binding site and this induces integrin conformational changes and enhancedligand binding to site 1 .ITGA5:ITGB1 acts as a receptor for fibrillin-1 and mediates R-G-D-dependent cell adhesion to FBN1 .ITGA5:ITGB1 acts as a receptor for fibronectin FN1 and mediates R-G-D-dependent cell adhesion to FN1 . ITGA5:ITGB1 is areceptor for IL1B and binding is essential for IL1B signaling. ITGA5:ITGB3 is a receptor for soluble CD40LG and isrequired for CD40/CD40LG signaling . Plays animportant role in myoblast differentiation and fusion during skeletalmyogenesis . ITGA9:ITGB1 may play a crucial role inSVEP1/polydom-mediated myoblast cell adhesion .Integrins ITGA9:ITGB1 and ITGA4:ITGB1 repress PRKCA-mediated L-typevoltage-gated channel Ca influx and ROCK-mediated calciumsensitivity in vascular smooth muscle cells via their interaction withSVEP1, thereby inhibit vasocontraction .{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:33962943, ECO:0000269|PubMed:35802072,ECO:0000269|PubMed:7523423}.; [Isoform 2]: Interferes with isoform 1 resulting in adominant negative effect on cell adhesion and migration .{ECO:0000305|PubMed:2249781}.; [Isoform 5]: Isoform 5 displaces isoform 1 in striatedmuscles. {ECO:0000250|UniProtKB:P09055}.; Integrin ITGA2:ITGB1 acts as a receptorfor Human echoviruses 1 and 8. {ECO:0000269|PubMed:8411387}.; Acts as a receptor forCytomegalovirus/HHV-5. {ECO:0000269|PubMed:20660204}.; Acts as a receptor for Epstein-Barrvirus/HHV-4. {ECO:0000269|PubMed:17945327}.; Integrin ITGA5:ITGB1 acts as a receptorfor Human parvovirus B19. {ECO:0000269|PubMed:12907437}.; Integrin ITGA2:ITGB1 acts as a receptorfor Human rotavirus. {ECO:0000269|PubMed:12941907}.; Acts as a receptor for Mammalianreovirus. {ECO:0000269|PubMed:16501085}.; In case of HIV-1 infection, integrinITGA5:ITGB1 binding to extracellular viral Tat protein seems to enhanceangiogenesis in Kaposi's sarcoma lesions.{ECO:0000269|PubMed:10397733}.; Interacts with CotH proteins expressedby fungi of the order mucorales, the causative agent of mucormycosis,which plays an important role in epithelial cell invasion by the fungi. Integrin ITGA3:ITGB1 may act as a receptor forR.delemar CotH7 in alveolar epithelial cells, which may be an earlystep in pulmonary mucormycosis disease progression .{ECO:0000269|PubMed:32487760}.; May serve as a receptor for adhesin A of N.meningitidis. {ECO:0000305|PubMed:21471204}.; Facilitates rabies infection in afibronectin-dependent manner and participates in rabies virus trafficafter internalization. {ECO:0000269|PubMed:31666383}.
• Uniprot ID: ITB1_HUMAN
• Ensembl ID: ENSG0000015009320
• HGNC ID: HGNC:6153

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Alpelisib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Head and neck cancer [ICD-11: 2D42.0] [1]

• Resistant Disease: Head and neck cancer [ICD-11: 2D42.0]
• Resistant Drug: Alpelisib
• Molecule Alteration: Function; Activation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3Kalpha and beta1 integrin signaling pathway; Regulation; N.A.
• In Vitro Model: Cal-33 cells; Tongue; Homo sapiens (Human); CVCL_1108
• In Vitro Model: FaDu cells; Pharynx; Homo sapiens (Human); CVCL_1218
• In Vitro Model: HSC-4 cells; Cervical lymph node; Homo sapiens (Human); CVCL_1289
• In Vitro Model: SAS cells; Oral; Homo sapiens (Human); CVCL_1675
• In Vitro Model: UT-SCC-5 cells; Head and Neck; Homo sapiens (Human); CVCL_7858
• In Vitro Model: UT-SCC-8 cells; Head and Neck; Homo sapiens (Human); CVCL_7869
• In Vitro Model: UT-SCC-14 cells; Head and Neck; Homo sapiens (Human); CVCL_7810
• In Vitro Model: UT-SCC-15 cells; Head and Neck; Homo sapiens (Human); CVCL_7811
• Experiment for Molecule Alteration: Whole exome sequencing assay; Western blot assay; Akt activity assay; 3D foci assay; Phosphorylation pathway analysis; Gene enrichment assay; Network analysis; Functional enrichment analysis
• Experiment for Drug Resistance: 3D colony formation assay
• Mechanism Description: In terms of PI3K/Akt pathway activity, Alpelisib treatment reduced phosphorylation of Akt (Ser473), GSK3beta (Ser9) and 4E-BP1 (Ser65) to a similar extent in responder and non-responder cell models (Fig. 2A, B and S2). Likewise, Akt activity was not significantly modified upon Alpelisib exposure (Fig. 2C). Taken together, our data show that inhibition of PI3Kalpha kinase causes varying degrees of radiochemosensitization in different HNSCC models and without an obvious mutational biomarker to predict drug effect.

References

• Ref 1: beta1 integrin mediates unresponsiveness to PI3Kalpha inhibition for radiochemosensitization of 3D HNSCC models. Biomed Pharmacother. 2024 Feb;171:116217.