title: PATE gene clusters code for multiple, secreted TFP/Ly-6/uPAR proteins that are expressed in reproductive and neuron-rich tissues and possess neuromodulatory activity.
abstract: We report here syntenic loci in humans and mice incorporating gene clusters coding for secreted proteins each comprising 10 cysteine residues. These conform to three-fingered protein/Ly-6/urokinase-type plasminogen activator receptor (uPAR) domains that shape three-fingered proteins (TFPs). The founding gene is PATE, expressed primarily in prostate and less in testis. We have identified additional human PATE-like genes (PATE-M, PATE-DJ, and PATE-B) that co-localize with the PATE locus, code for novel secreted PATE-like proteins, and show selective expression in prostate and/or testis. Anti-PATE-B-specific antibodies demonstrated the presence of PATE-B in the region of the sperm acrosome and at high levels on malignant prostatic epithelial cells. The syntenic mouse Pate-like locus encompasses 14 active genes coding for secreted proteins, which are all, except for Pate-P and Pate-Q, expressed primarily in prostate and/or testis. Pate-P and Pate-Q are expressed solely in placental tissue. Castration up-regulates prostate expression of mouse Pate-B and Pate-E, whereas testosterone ablates this induced expression. The sequence similarity between TFP/Ly-6/uPAR proteins that modulate activity of nicotinic acetylcholine receptors and the PATE (Pate)-like proteins stimulated us to see whether these proteins possess analogous activity. Pharmacological studies showed significant modulation of the nicotinic acetylcholines by the PATE-B, Pate-C, and Pate-P proteins. In concert with these findings, certain PATE (Pate)-like genes were extensively expressed in neuron-rich tissues. Taken together, our findings indicate that in addition to participation of the PATE (Pate)-like genes in functions related to fertility and reproduction, some of them likely act as important modulators of neural transmission.
authors.affiliation: Department of Cell Research and Immunology, Tel Aviv University, Ramat Aviv, 69978 Israel.
authors.forename: Fiana
authors.initials: F
authors.lastname: Levitin
authors.forename: Mordechai
authors.initials: M
authors.lastname: Weiss
authors.forename: Yoonsoo
authors.initials: Y
authors.lastname: Hahn
authors.forename: Omer
authors.initials: O
authors.lastname: Stern
authors.forename: Roger L
authors.initials: RL
authors.lastname: Papke
authors.forename: Robert
authors.initials: R
authors.lastname: Matusik
authors.forename: Srinivas R
authors.initials: SR
authors.lastname: Nandana
authors.forename: Ravit
authors.initials: R
authors.lastname: Ziv
authors.forename: Edward
authors.initials: E
authors.lastname: Pichinuk
authors.forename: Sharbel
authors.initials: S
authors.lastname: Salame
authors.forename: Tapan
authors.initials: T
authors.lastname: Bera
authors.forename: James
authors.initials: J
authors.lastname: Vincent
authors.forename: Byungkook
authors.initials: B
authors.lastname: Lee
authors.forename: Ira
authors.initials: I
authors.lastname: Pastan
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Wreschner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000950:Antigens, Ly / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D009474:Neurons / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics*; D055293:Receptors, Urokinase Plasminogen Activator; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014566:Urogenital System / Q000378:metabolism*; D014982:Xenopus laevis / Q000378:metabolism
chemical_list: D000950:Antigens, Ly; D008565:Membrane Proteins; C452641:PATE1 protein, human; C524898:PLAUR protein, human; C524899:Plaur protein, mouse; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator