CDB15:0000329 COL1A1 — ITGB1

Experimentally validated in Mixed species; Orthology-inferred in Human, Mouse, Rat, Frog, Zebrafish, Chicken, Macaque, Pig, Dog, Cow, Chimp, Horse, Marmoset, Sheep

Title

Journal:; Year Published:

Abstract

cDNA cloning and chromosomal localization of human alpha(11) integrin. A collagen-binding, I domain-containing, beta(1)-associated integrin alpha-chain present in muscle tissues.

The Journal of biological chemistry, 1999; PubMed, Bos taurus COL1A1 — Homo sapiens ITGB1

ABSTRACT: We previously identified a novel integrin alpha-chain in human fetal muscle cells (Gullberg, D., Velling, T., Sjöberg, G., and Sejersen, T. (1995) Dev. Dyn. 204, 57-65). We have now isolated the full-length cDNA for this integrin subunit, alpha(11). The open reading frame of the cDNA encodes a precursor of 1188 amino acids. The predicted mature protein of 1166 amino acids contains seven conserved FG-GAP repeats, an I domain with a metal ion-dependent adhesion site motif, a short transmembrane region, and a unique cytoplasmic domain of 24 amino acids containing the sequence GFFRS. alpha(11), like other I domain integrins, lacks a dibasic cleavage site for generation of a heavy chain and a light chain, and it contains three potential divalent cation binding sites in repeats 5-7. The presence of 22 inserted amino acids in the extracellular stalk portion (amino acids 804-826) distinguishes the alpha(11) integrin sequence from other integrin alpha-chains. Amino acid sequence comparisons reveal the highest identity of 42% with the alpha(10) integrin chain. Immunoprecipitation with antibodies to alpha(11) integrin captures a 145-kDa protein distinctly larger than the 140-kDa alpha(2) integrin chain when analyzed by SDS-polyacrylamide gel electrophoresis under nonreducing conditions. Fluorescence in situ hybridization maps the integrin alpha(11) gene to chromosome 15q23, in the vicinity of an identified locus for Bardet-Biedl syndrome. Based on Northern blotting, integrin alpha(11) mRNA levels are high in the adult human uterus and in the heart and intermediate in skeletal muscle and some other tissues tested. During in vitro myogenic differentiation, alpha(11) mRNA and protein are up-regulated. Studies of ligand binding properties show that alpha(11)beta(1) binds collagen type I-Sepharose, and cultured muscle cells localize alpha(11)beta(1) into focal contacts on collagen type I. Future studies will reveal the importance of alpha(11)beta(1) for muscle development and integrity in adult muscle and other tissues.

β1-Integrin binding to collagen type 1 transmits breast cancer cells into chemoresistance by activating ABC efflux transporters.

Biochimica et biophysica acta. Molecular cell research, 2020; PubMed, Rattus norvegicus Col1a1 — Homo sapiens ITGB1

ABSTRACT: Molecular interactions of tumor cells with the microenvironment are regarded as onset of chemotherapy resistance, referred to as cell adhesion mediated drug resistance (CAM-DR). Here we elucidate a mechanism of CAM-DR in breast cancer cells in vitro. We show that human MCF-7 and MDA-MB-231 breast cancer cells decrease their sensitivity towards cisplatin, doxorubicin, and mitoxantrone cytotoxicity upon binding to collagen type 1 (COL1) or fibronectin (FN). The intracellular concentrations of doxorubicin and mitoxantrone were decreased upon cell cultivation on COL1, while cellular cisplatin levels remained unaffected. Since doxorubicin and mitoxantrone are transporter substrates, this refers to ATP binding cassette (ABC) efflux transporter activities. The activation of the transporters BCRP, P-gp and MRP1 was shown by fluorescence assays to distinguish the individual input of these transporters to resistance in presence of COL1 and related to their expression levels by western blot. An ABC transporter inhibitor was able to re-sensitize COL1-treated cells for doxorubicin and mitoxantrone toxicity. Antibody-blocking of β1-integrin (ITGB1) induced sensitization towards the indicated cytostatic drugs by attenuating the increased ABC efflux activity. This refers to a key role of ITGB1 for matrix binding and subsequent transporter activation. A downregulation of α2β1 integrin following COL1 binding appears as clear indication for the relationship between ITGB1 and ABC transporters in regulating resistance formation, while knockdown of ITGB1 leads to a significant upregulation of all three transporters. Our data provide evidence for a role of CAM-DR in breast cancer via an ITGB1 - transporter axis and offer promising therapeutic targets for cancer sensitization.

Basic Information on COL1A1

Ligand Name: collagen type I alpha 1 chain

Other Symbols: OI4

Ligand Location: secreted based on hpa, perplexity, uniprot

HGNC Gene Symbol Report: COL1A1

GeneCards: COL1A1

HGNC Gene Group: Collagens

Functional Annotations for COL1A1

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Receptors for COL1A1

COL1A1 — CD44 ・ COL1A1 — DDR1 ・ COL1A1 — DDR2 ・ COL1A1 — ITGA1 ・ COL1A1 — ITGA11 ・ COL1A1 — ITGA2 ・ COL1A1 — ITGAV ・ COL1A1 — GP6 ・ COL1A1 — LAIR1 ・ COL1A1 — OSCAR

Basic Information on ITGB1

Receptor Name: integrin subunit beta 1

Other Symbols: FNRB, MSK12, MDF2, CD29, GPIIA

Receptor Location: cell membrane based on hpa, perplexity, uniprot

HGNC Gene Symbol Report: ITGB1

GeneCards: ITGB1

HGNC Gene Group: CD molecules, Integrins

Functional Annotations for ITGB1

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Ligands for ITGB1

ADAM12 — ITGB1 ・ ADAM15 — ITGB1 ・ ADAM17 — ITGB1 ・ ADAM2 — ITGB1 ・ ADAM9 — ITGB1 ・ ANGPT1 — ITGB1 ・ CD14 — ITGB1 ・ CHAD — ITGB1 ・ COL11A1 — ITGB1 ・ COL18A1 — ITGB1 ・ COL1A2 — ITGB1 ・ COL2A1 — ITGB1 ・ COL3A1 — ITGB1 ・ COL4A1 — ITGB1 ・ COL4A3 — ITGB1 ・ COL4A4 — ITGB1 ・ COL4A5 — ITGB1 ・ COL4A6 — ITGB1 ・ COL5A1 — ITGB1 ・ CXCL12 — ITGB1 ・ F13A1 — ITGB1 ・ FBLN1 — ITGB1 ・ FBN1 — ITGB1 ・ FGA — ITGB1 ・ VEGFD — ITGB1 ・ FN1 — ITGB1 ・ HSPG2 — ITGB1 ・ ICAM4 — ITGB1 ・ LAMA1 — ITGB1 ・ LAMA2 — ITGB1 ・ LAMA4 — ITGB1 ・ LAMA5 — ITGB1 ・ LAMB1 — ITGB1 ・ LAMB3 — ITGB1 ・ LAMC1 — ITGB1 ・ LAMC2 — ITGB1 ・ LGALS3BP — ITGB1 ・ MATN1 — ITGB1 ・ MDK — ITGB1 ・ NID1 — ITGB1 ・ NPNT — ITGB1 ・ PLG — ITGB1 ・ RELN — ITGB1 ・ SEMA7A — ITGB1 ・ SPP1 — ITGB1 ・ TGM2 — ITGB1 ・ THBS1 — ITGB1 ・ THBS2 — ITGB1 ・ TIMP2 — ITGB1 ・ TNC — ITGB1 ・ VCAM1 — ITGB1 ・ VCAN — ITGB1 ・ VEGFA — ITGB1 ・ VEGFC — ITGB1 ・ VTN — ITGB1 ・ ANGPTL2 — ITGB1 ・ CCN4 — ITGB1 ・ CLEC11A — ITGB1 ・ LGALS1 — ITGB1 ・ PLA2G2A — ITGB1 ・ SPON2 — ITGB1 ・ ADAM28 — ITGB1 ・ AGGF1 — ITGB1 ・ AGRN — ITGB1 ・ ANGPT2 — ITGB1 ・ ANGPTL4 — ITGB1 ・ CCN2 — ITGB1 ・ CCN3 — ITGB1 ・ CD40LG — ITGB1 ・ CDH1 — ITGB1 ・ COL10A1 — ITGB1 ・ COL11A2 — ITGB1 ・ COL13A1 — ITGB1 ・ COL4A2 — ITGB1 ・ COL8A1 — ITGB1 ・ COL8A2 — ITGB1 ・ CSPG4 — ITGB1 ・ CX3CL1 — ITGB1 ・ ICAM5 — ITGB1 ・ IL1B — ITGB1 ・ JAM2 — ITGB1 ・ L1CAM — ITGB1 ・ LAMA3 — ITGB1 ・ LAMB2 — ITGB1 ・ LGALS3 — ITGB1 ・ LGALS8 — ITGB1 ・ MFGE8 — ITGB1 ・ MIA — ITGB1 ・ NTN4 — ITGB1 ・ PLAUR — ITGB1 ・ SVEP1 — ITGB1 ・ TGFB1 — ITGB1 ・ TGFB3 — ITGB1 ・ THBS4 — ITGB1 ・ THY1 — ITGB1 ・ TIMP1 — ITGB1 ・ VWF — ITGB1