CDB15:0000320 COL18A1 — ITGB1

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

Title

Journal:; Year Published:

Abstract

Human tumstatin and human endostatin exhibit distinct antiangiogenic activities mediated by alpha v beta 3 and alpha 5 beta 1 integrins.

Proceedings of the National Academy of Sciences of the United States of America, 2003; PubMed, Homo sapiens COL18A1 — Homo sapiens ITGB1
ABSTRACT: Tumstatin and endostatin are two inhibitors of angiogenesis derived from precursor human collagen molecules known as alpha 3 chain of type IV collagen and alpha1 chain of type XVIII collagen, respectively. Although both these inhibitors are noncollagenous (NC1) domain fragments of collagens, they only share a 14% amino acid homology. In the present study we evaluated the functional receptors, mechanism of action, and intracellular signaling induced by these two collagen-derived inhibitors. Human tumstatin prevents angiogenesis via inhibition of endothelial cell proliferation and promotion of apoptosis with no effect on migration, whereas human endostatin prevents endothelial cell migration with no effect on proliferation. We demonstrate that human tumstatin binds to alpha v beta 3 integrin in a vitronectin/fibronectin/RGD cyclic peptide independent manner, whereas human endostatin competes with fibronectin/RGD cyclic peptide to bind alpha 5 beta 1 integrin. The activity of human tumstatin is mediated by alpha v beta 3 integrin, whereas the activity of human endostatin is mediated by alpha 5 beta 1 integrin. Additionally, although human tumstatin binding to alpha v beta 3 integrin leads to the inhibition of Cap-dependent translation (protein synthesis) mediated by focal adhesion kinase/phosphatidylinositol 3-kinase/Akt/mTOR/4E-BP1 pathway, human endostatin binding to alpha 5 beta 1 integrin leads to the inhibition of focal adhesion kinase/c-Raf/MEK1/2/p38/ERK1 mitogen-activated protein kinase pathway, with no effect on phosphatidylinositol 3-kinase/Akt/mTOR/4E-BP1 and Cap-dependent translation. Collectively, such distinct properties of human tumstatin and human endostatin provide the first insight into their diverse antiangiogenic actions and argue for combining them for targeting tumor angiogenesis.
Basic Information on COL18A1
Ligand Name: collagen type XVIII alpha 1 chain
Other Symbols: KNO, KS, KNO1
Ligand Location: secreted based on hpa, perplexity, uniprot
HGNC Gene Symbol Report: COL18A1
GeneCards: COL18A1
HGNC Gene Group: MicroRNA host genes, Collagens
Interactions with other Receptors for COL18A1
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
Interactions with other Ligands for ITGB1
ADAM12 — ITGB1ADAM15 — ITGB1ADAM17 — ITGB1ADAM2 — ITGB1ADAM9 — ITGB1ANGPT1 — ITGB1CD14 — ITGB1CHAD — ITGB1COL11A1 — ITGB1COL1A1 — ITGB1COL1A2 — ITGB1COL2A1 — ITGB1COL3A1 — ITGB1COL4A1 — ITGB1COL4A3 — ITGB1COL4A4 — ITGB1COL4A5 — ITGB1COL4A6 — ITGB1COL5A1 — ITGB1CXCL12 — ITGB1F13A1 — ITGB1FBLN1 — ITGB1FBN1 — ITGB1FGA — ITGB1VEGFD — ITGB1FN1 — ITGB1HSPG2 — ITGB1ICAM4 — ITGB1LAMA1 — ITGB1LAMA2 — ITGB1LAMA4 — ITGB1LAMA5 — ITGB1LAMB1 — ITGB1LAMB3 — ITGB1LAMC1 — ITGB1LAMC2 — ITGB1LGALS3BP — ITGB1MATN1 — ITGB1MDK — ITGB1NID1 — ITGB1NPNT — ITGB1PLG — ITGB1RELN — ITGB1SEMA7A — ITGB1SPP1 — ITGB1TGM2 — ITGB1THBS1 — ITGB1THBS2 — ITGB1TIMP2 — ITGB1TNC — ITGB1VCAM1 — ITGB1VCAN — ITGB1VEGFA — ITGB1VEGFC — ITGB1VTN — ITGB1ANGPTL2 — ITGB1CCN4 — ITGB1CLEC11A — ITGB1LGALS1 — ITGB1PLA2G2A — ITGB1SPON2 — ITGB1ADAM28 — ITGB1AGGF1 — ITGB1AGRN — ITGB1ANGPT2 — ITGB1ANGPTL4 — ITGB1CCN2 — ITGB1CCN3 — ITGB1CD40LG — ITGB1CDH1 — ITGB1COL10A1 — ITGB1COL11A2 — ITGB1COL13A1 — ITGB1COL4A2 — ITGB1COL8A1 — ITGB1COL8A2 — ITGB1CSPG4 — ITGB1CX3CL1 — ITGB1ICAM5 — ITGB1IL1B — ITGB1JAM2 — ITGB1L1CAM — ITGB1LAMA3 — ITGB1LAMB2 — ITGB1LGALS3 — ITGB1LGALS8 — ITGB1MFGE8 — ITGB1MIA — ITGB1NTN4 — ITGB1PLAUR — ITGB1SVEP1 — ITGB1TGFB1 — ITGB1TGFB3 — ITGB1THBS4 — ITGB1THY1 — ITGB1TIMP1 — ITGB1VWF — ITGB1