CDB15:0000023 ADAM9 — 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

MDC-9 (ADAM-9/Meltrin gamma) functions as an adhesion molecule by binding the alpha(v)beta(5) integrin.

Biochemical and biophysical research communications, 2001; PubMed, Homo sapiens ADAM9 — Homo sapiens ITGAV

ABSTRACT: MDC-9 is a widely expressed member of the metalloproteinase/disintegrin/cysteine-rich protein family. The disintegrin domain of MDC-9 lacks an RGD motif but has recently been reported to bind the alpha(6)beta(1) integrin; however, it is unclear whether MDC-9 can bind other integrins. In the present study myeloma cells, but not lymphoblastoid cells, were shown to bind to immobilised, recombinantly expressed MDC-9 disintegrin domain (A9dis). Binding was divalent cation-dependent, being supported by Mn(2+) and Ca(2+). Adhesion of myeloma cells to A9dis was completely inhibited by an antibody to the alpha(v)beta(5) integrin but not by antibodies to other subunits. RGD-containing peptides had no effect on binding, suggesting that MDC-9 interacts with alpha(v)beta(5) in an RGD-independent manner. Flow cytometric analyses demonstrated that myeloma cells, but not lymphoblastoid cells, expressed alpha(v)beta(5) on the cell membrane. These data indicated that the disintegrin domain of MDC-9 can function as an adhesion molecule by interacting with an alpha(v)beta(5) integrin.

The disintegrin domain of ADAM9: a ligand for multiple beta1 renal integrins.

The Biochemical journal, 2005; PubMed, Homo sapiens ADAM9 — Homo sapiens ITGAV

ABSTRACT: Renal tubular epithelial cells in all nephron segments express a distinct member of the metalloprotease-disintegrin family, ADAM9 (a disintegrin and metalloprotease 9), in a punctate basolateral distribution co-localized to the beta1 integrin chain [Mahimkar, Baricos, Visaya, Pollock and Lovett (2000) J. Am. Soc. Nephrol. 11, 595-603]. Discrete segments of the nephron express several defined beta1 integrins, suggesting that ADAM9 interacts with multiple renal integrins and thereby regulates epithelial cell-matrix interactions. Intact ADAM9 and a series of deletion constructs sequentially lacking the metalloprotease domain and the disintegrin domain were assembled as chimaeras with a C-terminal GFP (green fluorescent protein) tag. Stable expression of the ADAM9/GFP protein on the surface of HEK-293 cells (human embryonic kidney 293 cells) significantly decreased adhesion to types I and IV collagen, vitronectin and laminin, but had little effect on adhesion to fibronectin. Expression of the disintegrin/cysteine-rich/GFP construct yielded a similar, but more marked pattern of decreased adhesion. Expression of the cysteine-rich/GFP construct had no effect on adhesion, indicating that the disintegrin domain was responsible for the competitive inhibition of cell-matrix binding. To define the specific renal tubular beta1 integrins interacting with the ADAM9 disintegrin domain, a recombinant GST (glutathione S-transferase)-disintegrin protein was used as a substrate in adhesion assays in the presence or absence of specific integrin-blocking antibodies. Inclusion of antibodies to alpha1, alpha3, alpha6, alphav and beta1 blocked adhesion of HEK-293 cells to GST-disintegrin protein. Immobilized GST-disintegrin domain perfused with renal cortical lysates specifically recovered the alpha3, alpha6, alphav and beta1 integrin chains by Western analysis. It is concluded that ADAM9 is a polyvalent ligand, through its disintegrin domain, for multiple renal integrins of the beta1 class.

Basic Information on ADAM9

Ligand Name: ADAM metallopeptidase domain 9

Other Symbols: CORD9, MDC9, KIAA0021, MCMP, Mltng

Ligand Location: secreted based on hpa, perplexity, uniprot, cell membrane based on perplexity, uniprot

HGNC Gene Symbol Report: ADAM9

GeneCards: ADAM9

HGNC Gene Group: Metallopeptidases

Functional Annotations for ADAM9

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 ADAM9

ADAM9 — ITGA3 ・ ADAM9 — ITGA6 ・ ADAM9 — ITGB1 ・ ADAM9 — ITGB5 ・ ADAM9 — ITGA1

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 ・ 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 ・ COL18A1 — 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