A family of transmembrane proteins with homology to the MET-hepatocyte growth factor receptor

Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):674-8. doi: 10.1073/pnas.93.2.674.


In hunting for unknown genes on the human X chromosome, we identified a cDNA in Xq28 encoding a transmembrane protein (SEX) of 1871 amino acids. SEX shares significant homology with the extracellular domain of the receptors encoded by the oncogenes MET, RON, and SEA [hepatocyte growth factor (HGF) receptor family]. Further screenings of cDNA libraries identified three additional sequences closely related to SEX: these were named SEP, OCT, and NOV and were located on human chromosomes 3p, 1, and 3q, respectively. The proteins encoded by these genes contain large cytoplasmic domains characterized by a distinctive highly conserved sequence (SEX domain). Northern blot analysis revealed different expression of the SEX family of genes in fetal tissues, with SEX, OCT, and NOV predominantly expressed in brain, and SEP expressed at highest levels in kidney. In situ hybridization analysis revealed that SEX has a distinctive pattern of expression in the developing nervous system of the mouse, where it is found in postmitotic neurons from the first stages of neuronal differentiation (9.5 day postcoitus). The SEX protein (220 kDa) is glycosylated and exposed at the cell surface. Unlike the receptors of the HGF family, p220SEX, a MET-SEX chimera or a constitutively dimerized TPR-SEX does not show tyrosine kinase activity. These data define a gene family (SEX family) involved in the development of neural and epithelial tissues, which encodes putative receptors with unexpected enzymatic or binding properties.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Chromosomes, Human, Pair 3
  • DNA, Complementary / genetics
  • Epithelium / metabolism
  • Fetus / metabolism
  • Gene Expression Regulation, Developmental
  • Gene Library
  • Humans
  • Membrane Glycoproteins / genetics*
  • Mice
  • Molecular Sequence Data
  • Multigene Family*
  • Nerve Tissue / metabolism
  • Proto-Oncogene Proteins c-met
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptors, Cell Surface
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • Tissue Distribution
  • X Chromosome


  • DNA, Complementary
  • Membrane Glycoproteins
  • PLXNA3 protein, human
  • Receptors, Cell Surface
  • Proto-Oncogene Proteins c-met
  • Receptor Protein-Tyrosine Kinases

Associated data

  • GENBANK/X87197
  • GENBANK/X87831
  • GENBANK/X87832
  • GENBANK/X87904