CDB15:0000974 L1CAM — 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

Plasmin-sensitive dibasic sequences in the third fibronectin-like domain of L1-cell adhesion molecule (CAM) facilitate homomultimerization and concomitant integrin recruitment.

The Journal of cell biology, 2000; PubMed, Homo sapiens L1CAM — Homo sapiens ITGAV

ABSTRACT: L1 is a multidomain transmembrane neural recognition molecule essential for neurohistogenesis. While moieties in the immunoglobulin-like domains of L1 have been implicated in both heterophilic and homophilic binding, the function of the fibronectin (FN)-like repeats remains largely unresolved. Here, we demonstrate that the third FN-like repeat of L1 (FN3) spontaneously homomultimerizes to form trimeric and higher order complexes. Remarkably, these complexes support direct RGD-independent interactions with several integrins, including alpha(v)beta(3) and alpha(5)beta(1). A pep- tide derived from the putative C-C' loop of FN3 (GSQRKHSKRHIHKDHV(852)) also forms trimeric complexes and supports alpha(v)beta(3) and alpha(5)beta(1) binding. Substitution of the dibasic RK(841) and KR(845) sequences within this peptide or the FN3 domain limited multimerization and abrogated integrin binding. Evidence is presented that the multimerization of, and integrin binding to, the FN3 domain is regulated both by conformational constraints imposed by other domains and by plasmin- mediated cleavage within the sequence RK( downward arrow)HSK( downward arrow)RH(846). The integrin alpha(9)beta(1), which also recognizes the FN3 domain, colocalizes with L1 in a manner restricted to sites of cell-cell contact. We propose that distal receptor ligation events at the cell-cell interface may induce a conformational change within the L1 ectodomain that culminates in receptor multimerization and integrin recruitment via interaction with the FN3 domain.

A single immunoglobulin-like domain of the human neural cell adhesion molecule L1 supports adhesion by multiple vascular and platelet integrins.

The Journal of cell biology, 1997; PubMed, Homo sapiens L1CAM — Homo sapiens ITGAV

ABSTRACT: The neural cell adhesion molecule L1 has been shown to function as a homophilic ligand in a variety of dynamic neurological processes. Here we demonstrate that the sixth immunoglobulin-like domain of human L1 (L1-Ig6) can function as a heterophilic ligand for multiple members of the integrin superfamily including alphavbeta3, alphavbeta1, alpha5beta1, and alphaIIbbeta3. The interaction between L1-Ig6 and alphaIIbbeta3 was found to support the rapid attachment of activated human platelets, whereas a corresponding interaction with alphavbeta3 and alphavbeta1 supported the adhesion of umbilical vein endothelial cells. Mutation of the single Arg-Gly-Asp (RGD) motif in human L1-Ig6 effectively abrogated binding by the aforementioned integrins. A L1 peptide containing this RGD motif and corresponding flanking amino acids (PSITWRGDGRDLQEL) effectively blocked L1 integrin interactions and, as an immobilized ligand, supported adhesion via alphavbeta3, alphavbeta1, alpha5beta1, and alphaIIbbeta3. Whereas beta3 integrin binding to L1-Ig6 was evident in the presence of either Ca2+, Mg2+, or Mn2+, a corresponding interaction with the beta1 integrins was only observed in the presence of Mn2+. Furthermore, such Mn2+-dependent binding by alpha5beta1 and alphavbeta1 was significantly inhibited by exogenous Ca2+. Our findings suggest that physiological levels of calcium will impose a hierarchy of integrin binding to L1 such that alphavbeta3 or active alphaIIbbeta3 > alphavbeta1 > alpha5beta1. Given that L1 can interact with multiple vascular or platelet integrins it is significant that we also present evidence for de novo L1 expression on blood vessels associated with certain neoplastic or inflammatory diseases. Together these findings suggest an expanded and novel role for L1 in vascular and thrombogenic processes.

Basic Information on L1CAM

Ligand Name: L1 cell adhesion molecule

Other Symbols: HSAS1, SPG1, HSAS, MASA, MIC5, S10, CD171, NCAM-L1, CAML1

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

HGNC Gene Symbol Report: L1CAM

GeneCards: L1CAM

HGNC Gene Group: Ig-like cell adhesion molecule family, CD molecules, Fibronectin type III domain containing, Immunoglobulin superfamily domain containing

Functional Annotations for L1CAM

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 L1CAM

L1CAM — CNTN1 ・ L1CAM — EGFR ・ L1CAM — ERBB2 ・ L1CAM — ERBB3 ・ L1CAM — ITGA5 ・ L1CAM — ALCAM ・ L1CAM — FGFR1 ・ L1CAM — ITGA2B ・ L1CAM — ITGA9 ・ L1CAM — ITGB1 ・ L1CAM — ITGB3 ・ L1CAM — L1CAM ・ L1CAM — NRP1

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 ・ 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