CDB25:0003375 COL18A1 — ITGAV

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

Interaction of endostatin with integrins implicated in angiogenesis.

Proceedings of the National Academy of Sciences of the United States of America, 2001; PubMed, Homo sapiens COL18A1 — Homo sapiens ITGAV

ABSTRACT: Endostatin, a fragment of collagen XVIII, is a potent antagonist of angiogenesis and inhibitor of tumor growth in mouse models. At present, the mechanism of action of endostatin is unknown. We show here that recombinantly produced human endostatin interacts with alpha(5)- and alpha(v)-integrins on the surface of human endothelial cells. We further demonstrate that the endostatin-integrin interaction is of functional significance in vitro, as we found that immobilized endostatin supports endothelial cell survival and migration in an integrin-dependent manner. Soluble endostatin in turn inhibits integrin-dependent endothelial cell functions, such as cell migration. Taken together, these results implicate integrins as potential targets for endostatin function and support the importance of integrins in endothelial cell biology and angiogenesis.

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 ITGAV

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

Functional Annotations for COL18A1

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 COL18A1

COL18A1 — GPC1 ・ COL18A1 — GPC4 ・ COL18A1 — ITGA5 ・ COL18A1 — ITGB1 ・ COL18A1 — KDR ・ COL18A1 — PTPRS ・ COL18A1 — ITGB3

Basic Information on ITGAV

Receptor Name: integrin subunit alpha V

Other Symbols: VNRA, MSK8, VTNR, CD51

Receptor Location: cell membrane based on perplexity, uniprot

HGNC Gene Symbol Report: ITGAV

GeneCards: ITGAV

HGNC Gene Group: CD molecules, Integrins

Functional Annotations for ITGAV

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 ITGAV

ADAM15 — ITGAV ・ ADAM9 — ITGAV ・ ANGPTL3 — ITGAV ・ AZGP1 — ITGAV ・ COL1A1 — ITGAV ・ COL4A3 — ITGAV ・ CCN1 — ITGAV ・ EDIL3 — ITGAV ・ FBN1 — ITGAV ・ FGA — ITGAV ・ FGB — ITGAV ・ FGG — ITGAV ・ FN1 — ITGAV ・ IBSP — ITGAV ・ ICAM4 — ITGAV ・ L1CAM — ITGAV ・ LAMA4 — ITGAV ・ MFGE8 — ITGAV ・ NID1 — ITGAV ・ SPP1 — ITGAV ・ TGFB1 — ITGAV ・ TNC — ITGAV ・ VTN — ITGAV ・ CX3CL1 — ITGAV ・ CXCL12 — ITGAV ・ FNDC5 — ITGAV ・ PLA2G2A — ITGAV ・ ADAM23 — ITGAV ・ AGRN — ITGAV ・ ANGPT2 — ITGAV ・ CCN3 — ITGAV ・ CD40LG — ITGAV ・ COMP — ITGAV ・ DMP1 — ITGAV ・ EGFL7 — ITGAV ・ FBLN2 — ITGAV ・ FCER2 — ITGAV ・ FGF1 — ITGAV ・ FGF2 — ITGAV ・ HMGB1 — ITGAV ・ IGF1 — ITGAV ・ IGF2 — ITGAV ・ IL1B — ITGAV ・ NRG1 — ITGAV ・ PECAM1 — ITGAV ・ PLAUR — ITGAV ・ POSTN — ITGAV ・ PTN — ITGAV ・ TGFB3 — ITGAV ・ THBS1 — ITGAV ・ THY1 — ITGAV ・ VWF — ITGAV