CDB15:0000665 FN1 — ITGB3

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

Title

Journal:; Year Published:

Abstract

Alpha5beta1, alphaVbeta3 and the platelet-associated integrin alphaIIbbeta3 coordinately regulate adhesion and migration of differentiating mouse trophoblast cells.

Developmental biology, 2004; PubMed, Homo sapiens FN1 — Mus Musculus Itgb3

ABSTRACT: During blastocyst implantation, interaction between integrins on the apical surface of the trophoblast and extracellular matrix (ECM) in the endometrium anchors the embryo to the uterine wall. Strong adhesion of the blastocyst to fibronectin (FN) requires integrin signaling initiated by exogenous fibronectin. However, it is not known how integrin signaling enhances blastocyst adhesion. We present new evidence that the integrin, alphaIIbbeta3, plays a key role in trophoblast adhesion to fibronectin during mouse peri-implantation development. Trafficking of alphaIIb to the apical surface of the trophoblast increased dramatically after blastocysts were exposed to fibronectin, whereas other fibronectin-binding integrins, alpha5beta1 and alphaVbeta3, were resident at the apical surface before ligand exposure. Functional comparisons among the three integrins revealed that ligation of alpha5beta1 most efficiently strengthened blastocyst fibronectin-binding activity, while subsequent trophoblast cell migration was dependent primarily on the beta3-class integrins. In vivo, alphaIIb was highly expressed by invasive trophoblast cells in the ectoplacental cone and trophoblast giant cells of the parietal yolk sac. These data demonstrate that trafficking of alphaIIb regulates adhesion between trophoblast cells and fibronectin as invasion of the endometrium commences.

β-Subunit Binding Is Sufficient for Ligands to Open the Integrin αIIbβ3 Headpiece.

The Journal of biological chemistry, 2016; PubMed, Homo sapiens FN1 — Homo sapiens ITGB3

ABSTRACT: The platelet integrin αIIbβ3 binds to a KQAGDV motif at the fibrinogen γ-chain C terminus and to RGD motifs present in loops in many extracellular matrix proteins. These ligands bind in a groove between the integrin α and β-subunits; the basic Lys or Arg side chain hydrogen bonds to the αIIb-subunit, and the acidic Asp side chain coordinates to a metal ion held by the β3-subunit. Ligand binding induces headpiece opening, with conformational change in the β-subunit. During this opening, RGD slides in the ligand-binding pocket toward αIIb, with movement of the βI-domain β1-α1 loop toward αIIb, enabling formation of direct, charged hydrogen bonds between the Arg side chain and αIIb. Here we test whether ligand interactions with β3 suffice for stable ligand binding and headpiece opening. We find that the AGDV tetrapeptide from KQAGDV binds to the αIIbβ3 headpiece with affinity comparable with the RGDSP peptide from fibronectin. AGDV induced complete headpiece opening in solution as shown by increase in hydrodynamic radius. Soaking of AGDV into closed αIIbβ3 headpiece crystals induced intermediate states similarly to RGDSP. AGDV has very little contact with the α-subunit. Furthermore, as measured by epitope exposure, AGDV, like the fibrinogen γ C-terminal peptide and RGD, caused integrin extension on the cell surface. Thus, pushing by the β3-subunit on Asp is sufficient for headpiece opening and ligand sliding, and no pulling by the αIIb subunit on Arg is required.

The fibronectin synergy site re-enforces cell adhesion and mediates a crosstalk between integrin classes.

eLife, 2017; PubMed, Homo sapiens FN1 — Mus Musculus Itgb3

ABSTRACT: Fibronectin (FN), a major extracellular matrix component, enables integrin-mediated cell adhesion via binding of α5β1, αIIbβ3 and αv-class integrins to an RGD-motif. An additional linkage for α5 and αIIb is the synergy site located in close proximity to the RGD motif. We report that mice with a dysfunctional FN-synergy motif (Fn1syn/syn) suffer from surprisingly mild platelet adhesion and bleeding defects due to delayed thrombus formation after vessel injury. Additional loss of β3 integrins dramatically aggravates the bleedings and severely compromises smooth muscle cell coverage of the vasculature leading to embryonic lethality. Cell-based studies revealed that the synergy site is dispensable for the initial contact of α5β1 with the RGD, but essential to re-enforce the binding of α5β1/αIIbβ3 to FN. Our findings demonstrate a critical role for the FN synergy site when external forces exceed a certain threshold or when αvβ3 integrin levels decrease below a critical level.

Basic Information on FN1

Ligand Name: fibronectin 1

Other Symbols: MSF, CIG, LETS, GFND2, FINC, lnc-ABCA12-8

Ligand Location: secreted based on perplexity, uniprot

HGNC Gene Symbol Report: FN1

GeneCards: FN1

HGNC Gene Group: Receptor ligands, Fibronectin type III domain containing

Functional Annotations for FN1

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 FN1

FN1 — CD44 ・ FN1 — COL13A1 ・ FN1 — ITGA2 ・ FN1 — ITGA2B ・ FN1 — ITGA3 ・ FN1 — ITGA4 ・ FN1 — ITGA5 ・ FN1 — ITGA8 ・ FN1 — ITGA9 ・ FN1 — ITGAV ・ FN1 — ITGB1 ・ FN1 — ITGB6 ・ FN1 — ITGB7 ・ FN1 — ITGB8 ・ FN1 — MAG ・ FN1 — SDC2 ・ FN1 — TSHR ・ FN1 — CD248 ・ FN1 — DPP4 ・ FN1 — FLRT2 ・ FN1 — SDC4

Basic Information on ITGB3

Receptor Name: integrin subunit beta 3

Other Symbols: GP3A, CD61, GPIIIa

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

HGNC Gene Symbol Report: ITGB3

GeneCards: ITGB3

HGNC Gene Group: CD molecules, Integrins

Functional Annotations for ITGB3

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 ITGB3

ADAM15 — ITGB3 ・ ADAM23 — ITGB3 ・ ANGPTL3 — ITGB3 ・ CCN1 — ITGB3 ・ FBLN2 — ITGB3 ・ FBN1 — ITGB3 ・ FGA — ITGB3 ・ ICAM4 — ITGB3 ・ MFGE8 — ITGB3 ・ NID1 — ITGB3 ・ TGM2 — ITGB3 ・ THBS1 — ITGB3 ・ VTN — ITGB3 ・ COMP — ITGB3 ・ CX3CL1 — ITGB3 ・ CXCL12 — ITGB3 ・ EDIL3 — ITGB3 ・ IL32 — ITGB3 ・ PLA2G2A — ITGB3 ・ SPP1 — ITGB3 ・ TNC — ITGB3 ・ AZGP1 — ITGB3 ・ CCN3 — ITGB3 ・ CD40LG — ITGB3 ・ COL18A1 — ITGB3 ・ COL4A3 — ITGB3 ・ DMP1 — ITGB3 ・ EGFL7 — ITGB3 ・ FCER2 — ITGB3 ・ FGB — ITGB3 ・ FGF1 — ITGB3 ・ FGF2 — ITGB3 ・ FGG — ITGB3 ・ HMGB1 — ITGB3 ・ IBSP — ITGB3 ・ IGF1 — ITGB3 ・ IGF2 — ITGB3 ・ IL1B — ITGB3 ・ L1CAM — ITGB3 ・ LAMA4 — ITGB3 ・ LGALS3 — ITGB3 ・ NRG1 — ITGB3 ・ PECAM1 — ITGB3 ・ PLAUR — ITGB3 ・ POSTN — ITGB3 ・ PTN — ITGB3 ・ RELN — ITGB3 ・ THY1 — ITGB3 ・ VWF — ITGB3