Molecule Information

General Information of the Molecule (ID: Mol04339)

• Name: Integrin alpha-2 (ITGA2) ,Homo sapiens
• Synonyms: CD49 antigen-like family member B; Collagen receptor; Platelet membrane glycoprotein Ia; VLA-2 subunit alpha; CD_antigen=CD49b
• Molecule Type: Protein
• Gene Name: ITGA2
• Gene ID: 3673
• Sequence:
  MGPERTGAAPLPLLLVLALSQGILNCCLAYNVGLPEAKIFSGPSSEQFGYAVQQFINPKG
  NWLLVGSPWSGFPENRMGDVYKCPVDLSTATCEKLNLQTSTSIPNVTEMKTNMSLGLIL
  T RNMGTGGFLTCGPLWAQQCGNQYYTTGVCSDISPDFQLSASFSPATQPCPSLIDVVVV
  CD ESNSIYPWDAVKNFLEKFVQGLDIGPTKTQVGLIQYANNPRVVFNLNTYKTKEEMIV
  ATS QTSQYGGDLTNTFGAIQYARKYAYSAASGGRRSATKVMVVVTDGESHDGSMLKAVI
  DQCN HDNILRFGIAVLGYLNRNALDTKNLIKEIKAIASIPTERYFFNVSDEAALLEKAG
  TLGEQ IFSIEGTVQGGDNFQMEMSQVGFSADYSSQNDILMLGAVGAFGWSGTIVQKTSH
  GHLIFP KQAFDQILQDRNHSSYLGYSVAAISTGESTHFVAGAPRANYTGQIVLYSVNEN
  GNITVIQ AHRGDQIGSYFGSVLCSVDVDKDTITDVLLVGAPMYMSDLKKEEGRVYLFTI
  KEGILGQH QFLEGPEGIENTRFGSAIAALSDINMDGFNDVIVGSPLENQNSGAVYIYNG
  HQGTIRTKY SQKILGSDGAFRSHLQYFGRSLDGYGDLNGDSITDVSIGAFGQVVQLWSQ
  SIADVAIEAS FTPEKITLVNKNAQIILKLCFSAKFRPTKQNNQVAIVYNITLDADGFSS
  RVTSRGLFKEN NERCLQKNMVVNQAQSCPEHIIYIQEPSDVVNSLDLRVDISLENPGTS
  PALEAYSETAKV FSIPFHKDCGEDGLCISDLVLDVRQIPAAQEQPFIVSNQNKRLTFSV
  TLKNKRESAYNTG IVVDFSENLFFASFSLPVDGTEVTCQVAASQKSVACDVGYPALKRE
  QQVTFTINFDFNLQ NLQNQASLSFQALSESQEENKADNLVNLKIPLLYDAEIHLTRSTN
  INFYEISSDGNVPSI VHSFEDVGPKFIFSLKVTTGSVPVSMATVIIHIPQYTKEKNPLM
  YLTGVQTDKAGDISCN ADINPLKIGQTSSSVSFKSENFRHTKELNCRTASCSNVTCWLK
  DVHMKGEYFVNVTTRIW NGTFASSTFQTVQLTAAAEINTYNPEIYVIEDNTVTIPLMIM
  KPDEKAEVPTGVIIGSII AGILLLLALVAILWKLGFFKRKYEKMTKNPDEIDETTELSS
• Function: Integrin alpha-2/beta-1 is a receptor for laminin, collagen,collagen C-propeptides, fibronectin and E-cadherin. It recognizes theproline-hydroxylated sequence G-F-P-G-E-R in collagen. It isresponsible for adhesion of platelets and other cells to collagens,modulation of collagen and collagenase gene expression, forcegeneration and organization of newly synthesized extracellular matrix.; Integrin ITGA2:ITGB1 acts as a receptorfor Human rotavirus A. {ECO:0000269|PubMed:12941907}.; Integrin ITGA2:ITGB1 acts as a receptorfor Human echoviruses 1 and 8. {ECO:0000269|PubMed:8411387}.
• Uniprot ID: ITA2_HUMAN
• Ensembl ID: ENSG0000016417111
• HGNC ID: HGNC:6137

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

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Drug

Clinical Trial Drug(s) 1 drug(s) in total

Selumetinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Colorectal cancer [ICD-11: 2B91.1] [1]

• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Sensitive Drug: Selumetinib
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCT8 cells; Colon; Homo sapiens (Human); CVCL_2478
• In Vitro Model: HEK 293T cells; Kidney; Homo sapiens (Human); CVCL_0063
• In Vivo Model: BALB/c nude mice model; Mus musculus
• Experiment for Molecule Alteration: Western blot assay; qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; Apoptosis assay; Clone formation assay; Immunohistochemistry
• Mechanism Description: ACOX1 and ITGA2 were identified as risk biomarkers associated with 5-FU-resistance. We developed a risk signature, consisting of ACOX1 and ITGA2, that was able to distinguish well between 5-FU-resistance and 5-FU-sensitive. The single-cell sequencing data showed that ITGA2 was mainly enriched in malignant cells. ITGA2 was negatively correlated with IC50 values of most small molecule inhibitors, of which selumetinib had the highest negative correlation. Finally, knocking down ITGA2 can make 5-FU-resistant CRC cells sensitive to 5-FU and combining with selumetinib can improve the therapeutic effect of 5-FU resistant cells.

References

• Ref 1: Selumetinib overcomes ITGA2-induced 5-fluorouracil resistance in colorectal cancer. Int Immunopharmacol. 2024 Aug 20;137:112487.