CDB25:0004394 TIMP1 — ITGB1

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

Title

Journal:; Year Published:

Abstract

Identification of CD63 as a tissue inhibitor of metalloproteinase-1 interacting cell surface protein.

The EMBO journal, 2006; PubMed, Homo sapiens TIMP1 — Homo sapiens ITGB1

ABSTRACT: This study identified CD63, a member of the tetraspanin family, as a TIMP-1 interacting protein by yeast two-hybrid screening. Immunoprecipitation and confocal microscopic analysis confirmed CD63 interactions with TIMP-1, integrin beta1, and their co-localizations on the cell surface of human breast epithelial MCF10A cells. TIMP-1 expression correlated with the level of active integrin beta1 on the cell surface independent of cell adhesion. While MCF10A cells within a three-dimensional (3D) matrigel matrix form polarized acinar-like structures, TIMP-1 overexpression disrupted breast epithelial cell polarization and inhibited caspase-mediated apoptosis in centrally located cells, necessary for the formation and maintenance of the hollow acinar-like structures. Small hairpin RNA (shRNA)-mediated CD63 downregulation effectively reduced TIMP-1 binding to the cell surface, TIMP-1 co-localization with integrin beta1, and consequently reversed TIMP-1-mediated integrin beta1 activation, cell survival signaling and apoptosis inhibition. CD63 downregulation also restored polarization and apoptosis of TIMP-1 overexpressing MCF10A cells within a 3D-matrigel matrix. Taken together, the present study identified CD63 as a cell surface binding partner for TIMP-1, regulating cell survival and polarization via TIMP-1 modulation of tetraspanin/integrin signaling complex.

Basic Information on TIMP1

Ligand Name: TIMP metallopeptidase inhibitor 1

Other Symbols: TIMP, CLGI, EPO

Ligand Location: secreted based on hpa, perplexity, uniprot

HGNC Gene Symbol Report: TIMP1

GeneCards: TIMP1

HGNC Gene Group: Tissue inhibitor of metallopeptidases

Functional Annotations for TIMP1

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 TIMP1

TIMP1 — CD63 ・ TIMP1 — CD74 ・ TIMP1 — LRP1

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

Functional Annotations for ITGB1

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 ITGB1

ADAM12 — ITGB1 ・ ADAM15 — ITGB1 ・ ADAM17 — ITGB1 ・ ADAM2 — ITGB1 ・ ADAM9 — ITGB1 ・ ANGPT1 — ITGB1 ・ CD14 — ITGB1 ・ CHAD — ITGB1 ・ COL11A1 — ITGB1 ・ COL18A1 — ITGB1 ・ COL1A1 — ITGB1 ・ COL1A2 — ITGB1 ・ COL2A1 — ITGB1 ・ COL3A1 — ITGB1 ・ COL4A1 — ITGB1 ・ COL4A3 — ITGB1 ・ COL4A4 — ITGB1 ・ COL4A5 — ITGB1 ・ COL4A6 — ITGB1 ・ COL5A1 — ITGB1 ・ CXCL12 — ITGB1 ・ F13A1 — ITGB1 ・ FBLN1 — ITGB1 ・ FBN1 — ITGB1 ・ FGA — ITGB1 ・ VEGFD — ITGB1 ・ FN1 — ITGB1 ・ HSPG2 — ITGB1 ・ ICAM4 — ITGB1 ・ LAMA1 — ITGB1 ・ LAMA2 — ITGB1 ・ LAMA4 — ITGB1 ・ LAMA5 — ITGB1 ・ LAMB1 — ITGB1 ・ LAMB3 — ITGB1 ・ LAMC1 — ITGB1 ・ LAMC2 — ITGB1 ・ LGALS3BP — ITGB1 ・ MATN1 — ITGB1 ・ MDK — ITGB1 ・ NID1 — ITGB1 ・ NPNT — ITGB1 ・ PLG — ITGB1 ・ RELN — ITGB1 ・ SEMA7A — ITGB1 ・ SPP1 — ITGB1 ・ TGM2 — ITGB1 ・ THBS1 — ITGB1 ・ THBS2 — ITGB1 ・ TIMP2 — ITGB1 ・ TNC — ITGB1 ・ VCAM1 — ITGB1 ・ VCAN — ITGB1 ・ VEGFA — ITGB1 ・ VEGFC — ITGB1 ・ VTN — ITGB1 ・ ANGPTL2 — ITGB1 ・ CCN4 — ITGB1 ・ CLEC11A — ITGB1 ・ LGALS1 — ITGB1 ・ PLA2G2A — ITGB1 ・ SPON2 — ITGB1 ・ ADAM28 — ITGB1 ・ AGGF1 — ITGB1 ・ AGRN — ITGB1 ・ ANGPT2 — ITGB1 ・ ANGPTL4 — ITGB1 ・ CCN2 — ITGB1 ・ CCN3 — ITGB1 ・ CD40LG — ITGB1 ・ CDH1 — ITGB1 ・ COL10A1 — ITGB1 ・ COL11A2 — ITGB1 ・ COL13A1 — ITGB1 ・ COL4A2 — ITGB1 ・ COL8A1 — ITGB1 ・ COL8A2 — ITGB1 ・ CSPG4 — ITGB1 ・ CX3CL1 — ITGB1 ・ ICAM5 — ITGB1 ・ IL1B — ITGB1 ・ JAM2 — ITGB1 ・ L1CAM — ITGB1 ・ LAMA3 — ITGB1 ・ LAMB2 — ITGB1 ・ LGALS3 — ITGB1 ・ LGALS8 — ITGB1 ・ MFGE8 — ITGB1 ・ MIA — ITGB1 ・ NTN4 — ITGB1 ・ PLAUR — ITGB1 ・ SVEP1 — ITGB1 ・ TGFB1 — ITGB1 ・ TGFB3 — ITGB1 ・ THBS4 — ITGB1 ・ THY1 — ITGB1 ・ VWF — ITGB1