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. 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. A functional genomic approach has identified a gene, designated PATE, that codes for a secreted protein with preferential prostate and testis expression (1Bera T.K. Maitra R. Iavarone C. Salvatore G. Kumar V. Vincent J.J. Sathyanarayana B.K. Duray P. Lee B.K. Pastan I. Proc. Natl. Acad. Sci. U. S. A. 2002; 99: 3058-3063Crossref PubMed Scopus (36) Google Scholar). PATE protein includes 10 cysteine residues, with the C-terminal cysteine residue positioned within a cysteine-asparagine (CN) dipeptide sequence. The distribution of cysteine residues conforms to a consensus cysteine pattern found in a large family of three-fingered proteins (TFPs), 3The abbreviations used are: TFP, three-fingered protein; uPAR, urokinase-type plasminogen activator receptor; ACh, acetylcholine; nAChR, nicotinic acetylcholine receptor; RT, reverse transcription; GPI, glycosylphosphatidylinositol; h, human; m, mouse; d, dog; TEV, tomato etch virus; PNGase F, peptide:N-glycosidase F; DHT, dihydroxytestosterone. 3The abbreviations used are: TFP, three-fingered protein; uPAR, urokinase-type plasminogen activator receptor; ACh, acetylcholine; nAChR, nicotinic acetylcholine receptor; RT, reverse transcription; GPI, glycosylphosphatidylinositol; h, human; m, mouse; d, dog; TEV, tomato etch virus; PNGase F, peptide:N-glycosidase F; DHT, dihydroxytestosterone. characterized by a distinct disulfide bonding pattern between 8 and 10 cysteine residues (2Fry B.G. Wuster W. Kini R.M. Brusic V. Khan A. Venkataraman D. Rooney A.P. J. Mol. Evol. 2003; 57: 110-129Crossref PubMed Scopus (273) Google Scholar, 3Ploug M. Ellis V. FEBS Lett. 1994; 349: 163-168Crossref PubMed Scopus (243) Google Scholar). This domain is additionally found in uPAR and murine Ly-6 GPI-anchored proteins, and is also called an Ly-6/uPAR domain (3Ploug M. Ellis V. FEBS Lett. 1994; 349: 163-168Crossref PubMed Scopus (243) Google Scholar). Interestingly, the TFP architecture is seen also in the transforming growth factor-β receptor family of proteins, including BMP2 and activin receptors (4Ploug M. Curr. Pharm. Des. 2003; 9: 1499-1528Crossref PubMed Scopus (151) Google Scholar). A large protein family encompassing an extensive group of GPI-anchored, transmembrane, and secreted proteins contains this domain. The prototype-secreted protein members of this family include short chain snake and frog toxins, which in many cases bind with high affinity to neuronal receptors and block their activity (5Tsetlin V.I. Hucho F. FEBS Lett. 2004; 557: 9-13Crossref PubMed Scopus (114) Google Scholar, 6Tremeau O. Lemaire C. Drevet P. Pinkasfeld S. Ducancel F. Boulain J.C. Menez A. J. Biol. Chem. 1995; 270: 9362-9369Abstract Full Text Full Text PDF PubMed Scopus (131) Google Scholar, 7Kolbe H.V. Huber A. Cordier P. Rasmussen U.B. Bouchon B. Jaquinod M. Vlasak R. Delot E.C. Kreil G. J. Biol. Chem. 1993; 268: 16458-16464Abstract Full Text PDF PubMed Google Scholar). Until recently, the only recognized secreted mammalian TFP/Ly-6/uPAR proteins were SLURP-1 (secreted mammalian Ly-6/uPAR-related protein) (8Adermann K. Wattler F. Wattler S. Heine G. Meyer M. Forssmann W.G. Nehls M. Protein Sci. 1999; 8: 810-819Crossref PubMed Scopus (112) Google Scholar) and SLURP-2 (9Tsuji H. Okamoto K. Matsuzaka Y. Iizuka H. Tamiya G. Inoko H. Genomics. 2003; 81: 26-33Crossref PubMed Scopus (76) Google Scholar), which are located on human chromosome 8q24.3 within a cluster of Ly-6-like human genes that otherwise code for GPI-linked proteins. Consistent with the putative ligand function of some secreted TFP/Ly-6/uPAR proteins, SLURP-1 was recently identified as a neuromodulator of the α7 nicotinic receptor (α7 nAChR), suggesting that it may regulate calcium homeostasis (10Chimienti F. Hogg R.C. Plantard L. Lehmann C. Brakch N. Fischer J. Huber M. Bertrand D. Hohl D. Hum. Mol. Genet. 2003; 12: 3017-3024Crossref PubMed Scopus (217) Google Scholar). It is clear that members of the secreted TFP/Ly-6/uPAR protein family, to which the PATE protein belongs, interact with partner proteins that, in many cases, are membrane-tethered receptors. The human PATE gene is telomerically juxtaposed to the gene encoding acrosomal vesicle protein 1 (ACRV1), also known as the SP10 gene (11Freemerman A.J. Flickinger C.J. Herr J.C. Mol. Reprod. Dev. 1995; 41: 100-108Crossref PubMed Scopus (18) Google Scholar). Interestingly, the ACRV1 protein also contains 10 cysteine residues that conform to the TFP/Ly-6/uPAR domain, suggesting that the two genes ACRV1 and PATE may be part of a single chromosomal locus comprising TFP/Ly-6/uPAR genes. In this study, report the and expression of additional human PATE-like genes (PATE-M, PATE-DJ, and PATE-B) that co-localize with the ACRV1 and PATE genomic These novel PATE-like genes code for secreted proteins the TFP/Ly-6/uPAR domain. show selective expression in prostate and/or testis. We have identified the murine and Pate-B genes that to the mouse the mouse Pate-like genomic locus includes an additional active Pate-like which secreted proteins, whereas in the human these mouse Pate-like genes are expression of the mouse Pate-like genes in as as of and testosterone on their expression in prostate indicate that these genes function in and and are likely of the sequence similarity between TFP/Ly-6/uPAR proteins that modulate activity of nicotinic acetylcholine receptors and the PATE (Pate)-like proteins, to see whether these proteins also possess activity. These showed that certain PATE (Pate)-like proteins modulate the activity of Taken together, our findings indicate that in addition to participation of the PATE (Pate)-like genes in functions related to fertility and reproduction, are likely to function as important modulators of neural activity. and otherwise and were The antibodies were were in and of the and PATE (Pate)-like and reverse were the the PATE (Pate)-like for of PATE (Pate)-like of the human PATE-like genes as as the mouse Pate-like genes was with human mouse as and reverse were that an and the at to the of a of PATE (Pate)-like human PATE-like were the were and the mouse Pate-like were and for of PATE (Pate)-like sequence the TFP family of proteins is except for the pattern of in the and an to PATE-like genes by protein as was a of protein and of identified PATE and PATE-like genes us to a to PATE-like genes in the genomic We two protein sequence and to and found in PATE-like proteins. The two are for and for a of in to The were and to We the genomic locus by and genes in the human and loci in the mouse in the and in the and were 10 located and were to single genes. In human and the were by for that the and the protein sequence. The was located in the region of each The putative gene was by expressed sequence by each gene with a in human by and PATE-like genes and were by a S. K. M. 2004; PubMed Scopus Google Scholar) on a sequence of and by C. J. J. Mol. Biol. PubMed Scopus Google Scholar). of and was with the expression This codes for the by coding for the coding for the human was to the A for the tomato etch was also between the of the Pate-like proteins and the encoding the Pate-like proteins were the to as of were with the expression of coding for the proteins. The secreted proteins in the were on protein and the Pate-like proteins were by the protein A with of were and of were in the in were used as a of to were by the in a of for were an in the the were with for at in 1 were and with each of the were were as C. Mol. 2004; PubMed Scopus Google Scholar). is an that and of to in were with and were a the and were with The were which of were at a of were at and at were 8 with two of ACh, and the PATE-like were for at the an of the were with at the The for and receptors were and to the PATE were to the on J. 2002; PubMed Scopus Google Scholar). was for the the to that the for the was to the of at were for each of PATE were on between the of each to PATE with the of the were on of were on a by with PATE The of were with for protein was as F. O. M. C. R. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar), and were with protein proteins were with 1 of PNGase of a PATE-like PATE gene codes for a protein expressed in human including and vesicle (1Bera T.K. Maitra R. Iavarone C. Salvatore G. Kumar V. Vincent J.J. Sathyanarayana B.K. Duray P. Lee B.K. Pastan I. Proc. Natl. Acad. Sci. U. S. A. 2002; 99: 3058-3063Crossref PubMed Scopus (36) Google Scholar, Maitra R. Kumar V. S. R. T.K. Pastan I. PubMed Scopus Google Scholar). additional PATE-like designated PATE-B, and PATE-DJ, which to the genomic locus as the PATE gene of these genes by in human demonstrated selective expression in prostatic and/or with expression in The PATE-B gene was expressed primarily in prostate with expression in whereas the and genes showed a reverse pattern of expression of known genes within a of comprising the human PATE-like genes demonstrated that the genes show preferential expression in Consistent with ACRV1 vesicle protein 1 gene also known as demonstrated expressed primarily in (11Freemerman A.J. Flickinger C.J. Herr J.C. Mol. Reprod. Dev. 1995; 41: 100-108Crossref PubMed Scopus (18) Google expression of human PATE-like genes and genes. of the human PATE-like genes and genes was with the human tissues. and reverse were that an and the at to the of a the PATE, PATE-DJ, and PATE-B the and reverse were located in the and for the and was for that induced gene is expressed in as a for showed that the human PATE-like genes code for proteins that include a putative and 10 cysteine residues of genomic and showed that in PATE-like proteins the is by the whereas protein domains and are by two and in PATE and additional designated and are between 1 and and code for a of The ACRV1 gene a to the PATE-like of the human PATE-like and mouse Pate-like proteins and of PATE (Pate)-like genes. The of the PATE (Pate)-like genes is are as The coding region is in pattern 1 to pattern to in the PATE-like genes a Interestingly, PATE-B and two and of the that include the putative the codes for proteins comprising 10 cysteine residues, the codes only for of at the of PATE-like of of human PATE-like genes of residues to the by the with high a and for each PATE-like protein this region is in a protein for has demonstrated for PATE Maitra R. Kumar V. S. R. T.K. Pastan I. PubMed Scopus Google Scholar) and ACRV1 J.C. R.M. J. Flickinger C.J. Biol. Reprod. PubMed Scopus Google Scholar), and it is likely that these the function in the PATE-B, PATE-DJ, and proteins. human with coding for the PATE-B protein and for the presence of PATE-B have that the PATE-B protein is secreted the of PATE-B and and the of PATE-B and were This demonstrated at of PATE-B and in prostate and the expressed these genes. PATE-like in the PATE-like for additional human PATE-like genes within the human gene cluster two PATE-like designated and a of and reverse on these genomic in to expression of these genes. of 14 Pate-like within the to the PATE-like human PATE-like gene locus the ACRV1 gene to the PATE-B gene, encompassing The human genes to the PATE-like gene locus are as PATE, PATE-DJ, PATE-B, and and this region for The syntenic mouse genomic was identified and demonstrated the vesicle protein J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar) also called J. Biol. Chem. Full Text PDF PubMed Google Scholar), identified here as the mouse Pate-B and to mouse the mouse Pate-C, and Pate-B genes additional two mouse Pate-like designated and were identified between and of the mouse genomic Pate-like gene locus of genomic between the mouse and genes. of this additional Pate-like genes 1 and The human to the mouse was mouse Pate-like genes code for putative Pate-like proteins comprising a located in and that the mouse and mouse genes to the human and were in addition to expression of the mouse gene and was the of an additional active mouse Pate-like designated Pate-E, Pate-Q, and 1 and and We the syntenic mouse locus many active Pate-like genes as with the human this a for the Pate-like proteins in Pate-like genes be to their expression Pate-E, and were expressed in prostate and whereas and expression was to prostatic tissue. and showed expression in testis. and showed expression in prostate testis in showed significant expression levels in and and mouse Pate-like were the active mouse Pate-like genes in of Pate-like murine Pate-like Pate-P and Pate-Q, were expressed in the mouse these genes are to each code for proteins and include an cysteine residue in addition to the consensus Pate-like 10 cysteine residues. placental expression here is a a Pate-Q sequence. Castration Pate-like in the by selective distribution of Pate-like gene expression in the and that the Pate-like proteins are likely in see whether in may gene of and on prostate expression of the Pate-like genes. gene expression has in the and prostate Pate-like gene expression in each The in mice expressed the two Pate-like Pate-B and expression of and In the Pate-B and genes were expressed in the Pate-B and were expressed in the to this expression The of expression of expression and to the of Pate-B expression that was of In to the and expression of Pate-B and Pate-E, the gene demonstrated high expression in and and this expression In the expression of the gene as a for of prostate as the gene The PATE-B Protein to the of and in and of clusters of human and mouse PATE (Pate)-like genes expressed in in functions related to their antibodies the human PATE-B these the whether the PATE-B protein to sperm and whether the PATE-B protein be in and/or malignant prostate tissue. with antibodies demonstrated of sperm primarily in the acrosomal region of was by of addition to the antibodies of a protein PATE-B protein and of and PATE-B protein expression in the of prostatic include as as clusters of malignant epithelial that prostate in the to the of epithelial only a of epithelial demonstrated the PATE-B protein PATE-B was and the epithelial clusters in the prostatic showed a PATE-B as with that seen in the epithelial A and in the of prostatic epithelial only a of malignant demonstrated PATE-B expression of was by of and addition of PATE-B in of these was as in and of Pate-like of the syntenic locus a to that of the mouse located between the and genes. This showed that the mouse Pate-like genes Pate-Q, Pate-C, Pate-E, and Pate-B have We to the mouse and genes. The locus includes Pate-like genes that code for proteins that including protein protein protein C. P. H. J. M. N. K. 2002; PubMed Scopus Google Scholar), and an additional Pate-like genes that be a mouse of the Pate-like gene locus and additional Pate-like genes located between and be to by of Pate-like see whether Pate-like proteins in mammalian and to whether these proteins expressed mouse Pate-C, and Pate-P proteins in a mammalian expression that whereas Pate-P protein with the and proteins each two 1 and with PNGase F, in of the and proteins and and and that these proteins are with The protein showed a single consensus whereas an an Y. Y. FEBS Lett. 2004; PubMed Scopus Google Scholar). PATE (Pate)-like of expression of the PATE (Pate)-like genes and their in identified the clusters of and and the of the PATE (Pate)-like proteins in mammalian to functions may The similarity in between snake that bind to and modulate the activity of the recently mammalian proteins J. J. PubMed Scopus Google Scholar), and to modulate activity and the PATE (Pate)-like proteins us to whether these proteins possess for expressed the expression and in that in to of the PATE (Pate)-like proteins. In this of the of This to by The is a J. 2002; PubMed Scopus Google Scholar) as it the of to This showed that of mouse to and α7 human PATE-B to the in on of to PATE to by the of in the presence of the In an in the was of to the α7 nAChR, a that was significant on of the in the and presence of and a the to human α7 a significant on that also a Interestingly, the protein to the human α7 a significant in to the on a also a In of the PATE (Pate)-like proteins and and showed activity of the of PATE (Pate)-like in certain PATE (Pate)-like proteins modulate the activity of nicotinic This with the similarity between the PATE-like protein family and the the mammalian TFP/Ly-6/uPAR and proteins. as that neuron-rich also PATE (Pate)-like genes. Consistent with of mouse Pate-like gene expression show that mouse in addition to extensive expression in prostate is expressed in the and expression in prostate and is extensively expressed in in this it was to the of human PATE-like gene expression in neuron-rich as This be to the expression levels in for and/or expression only in of the that PATE-like are in their these and to the with an of of This showed levels of expression in the A of of this PATE and were expressed in of the PATE-B was expressed in tissue. was the extensive expression of This was seen in the and and and expression levels were in the and with levels in the and was expressed in the and and expression in the was to the This in to the expression of the and in the testis testis and also expressed 8 and that expression in neuronal is A testis with showed levels of expression in This is significant it that the of expression in the is at to that seen in testis of is by the tissue. We report here syntenic human and mouse genomic loci that clusters of genes coding for secreted proteins each comprising a TFP/Ly-6/uPAR domain. expression in humans and mice for of the PATE (Pate)-like proteins in related only to fertility and also to neuronal activity. The mouse and human PATE (Pate)-like genes code for proteins that to that protein for This is with the demonstrated of ACRV1 J.C. R.M. J. Flickinger C.J. Biol. Reprod. PubMed Scopus Google Scholar), PATE Maitra R. Kumar V. S. R. T.K. Pastan I. PubMed Scopus Google Scholar), and Pate-B J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google to domains to for addition of are in the PATE (Pate)-like proteins. to the PATE-like gene locus, a cluster of human Ly-6 genes on chromosome and each of these genes codes for a protein that includes the pattern seen in the PATE (Pate)-like proteins. the of the secreted proteins SLURP-1 (8Adermann K. Wattler F. Wattler S. Heine G. Meyer M. Forssmann W.G. Nehls M. Protein Sci. 1999; 8: 810-819Crossref PubMed Scopus (112) Google Scholar) and SLURP-2 (9Tsuji H. Okamoto K. Matsuzaka Y. Iizuka H. Tamiya G. Inoko H. Genomics. 2003; 81: 26-33Crossref PubMed Scopus (76) Google Scholar), this locus codes only for membrane-tethered proteins. In active genes in the human and mouse PATE (Pate)-like loci code for secreted TFP/Ly-6/uPAR proteins. are to the secreted SLURP-1 and SLURP-2 proteins and to the extensive group of secreted snake and frog the TFP/Ly-6/uPAR domain. the PATE (Pate)-like proteins are likely to be that bind to their activity. SLURP-1 and secreted proteins in to the proteins, bind to and modulate the activity of nicotinic acetylcholine receptors (10Chimienti F. Hogg R.C. Plantard L. Lehmann C. Brakch N. Fischer J. Huber M. Bertrand D. Hohl D. Hum. Mol. Genet. 2003; 12: 3017-3024Crossref PubMed Scopus (217) Google Scholar, J. J. PubMed Scopus Google Scholar) on the of cells. as these proteins modulate that in the PATE (Pate)-like proteins possess and also modulate the activity of that human PATE-like genes are expressed in as prostate and testis. This that the PATE (Pate)-like genes function solely in the mouse Pate-Q and Pate-P genes show selective expression in an tissue. expression of a group of Pate-like genes in the of and/or mice also that the Pate-like proteins are likely to function in that are of expression is by the expression in the prostate of Pate-B and Pate-E, of which expression of certain Pate-like genes was only in mice and mice Taken as a these participation in the of Pate-like gene expression. with antibodies demonstrated human PATE-B protein at the sperm acrosomal The secreted TFP/Ly-6/uPAR proteins PATE, and ACRV1 bind to on the sperm Maitra R. Kumar V. S. R. T.K. Pastan I. PubMed Scopus Google Scholar, J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, Flickinger C.J. R.M. Herr J.C. Biol. Reprod. 1994; PubMed Scopus Google Scholar), suggesting receptors for these proteins on the sperm These also in with is known the mouse Pate-B which has to modulate calcium in sperm J. Biol. Chem. Full Text PDF PubMed Google Scholar). It is to that receptors for the PATE-B protein on human also showed that the human PATE-B protein to and malignant prostatic epithelial cells. their and the that only that these may in a of epithelial cells. are and are the prostate with only an and and and and prostatic cells. the PATE-B are of the is in of our findings on the function of the PATE-like proteins It was also that malignant prostatic epithelial showed PATE-B expression. seen with only certain This expression was that seen in the be to whether PATE-B expression in these malignant prostate to their the may of PATE-B protein in sperm and prostatic likely participation in PATE (Pate)-like proteins a to that of the snake and A. PubMed Scopus Google Scholar, V. J. 1999; PubMed Scopus Google Scholar). are extensively between the TFP/Ly-6/uPAR snake and the (5Tsetlin V.I. Hucho F. FEBS Lett. 2004; 557: 9-13Crossref PubMed Scopus (114) Google Scholar), a Interestingly, mammalian a GPI-anchored TFP/Ly-6/uPAR calcium by with neuronal nicotinic acetylcholine receptors I. N. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). to the secreted PATE (Pate)-like proteins, the secreted SLURP-1 protein the human α7 nicotinic (10Chimienti F. Hogg R.C. Plantard L. Lehmann C. Brakch N. Fischer J. Huber M. Bertrand D. Hohl D. Hum. Mol. Genet. 2003; 12: 3017-3024Crossref PubMed Scopus (217) Google Scholar). is only between snake and the mammalian TFP/Ly-6/uPAR proteins SLURP-1 and also a functional to whether PATE (Pate)-like proteins possess demonstrated that certain PATE (Pate)-like proteins in modulate the activity of nicotinic acetylcholine receptors. of the PATE (Pate)-like proteins and the activity of and the α7 and the of the of the PATE (Pate)-like proteins, to only have for their activity. We that additional PATE (Pate)-like proteins also possess and are in to for The of by the of nicotinic and and for each S. J. Sci. 2004; PubMed Scopus Google Scholar). that of their activity a of the that have for the PATE (Pate)-like proteins, each protein with and in a may this of for a is by our findings with human PATE-B, which on the up-regulates activity of a α7 is on an In a Pate-P the a α7 as by snake be by the and that proteins activity only the PATE (Pate)-like proteins in activity in with this Taken our are with a function for the PATE (Pate)-like proteins. This them in the family of the TFP/Ly-6/uPAR proteins SLURP-1 and are the functions of the PATE (Pate)-like proteins to be with their extensive expression in It is known that and sperm many receptors. the and have demonstrated to be in human and the α7 likely as a in the and of sperm C. Kumar P. S. Biol. Reprod. PubMed Scopus Google Scholar, P. S. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). the human acrosome by acetylcholine protein the α7 C. S. Biol. Reprod. 2002; PubMed Scopus Google Scholar, S. Biol. Reprod. 2003; PubMed Scopus Google Scholar), and it has that the sperm may be of important to the acrosome and sperm C. Kumar P. S. Biol. Reprod. PubMed Scopus Google Scholar, C. S. Mol. Hum. Reprod. PubMed Scopus Google Scholar). This in sperm and has to the of a sperm as with a S. Biol. 2004; PubMed Scopus (76) Google Scholar). this to the participation of was to be receptors and in the of to the This of in and neuronal the activity of the PATE (Pate)-like proteins and their expression in neuronal and tissues. In have identified a family of secreted TFP/Ly-6/uPAR proteins, designated the PATE (Pate)-like proteins, that likely important in and neuronal of their functions likely to for of the and the