title: Characterization of non-specific cytotoxic cell receptor protein 1: a new member of the lectin-type subfamily of F-box proteins.
abstract: Our previous microarray study showed that the non-specific cytotoxic cell receptor protein 1 (Nccrp1) transcript is significantly upregulated in the gastric mucosa of carbonic anhydrase IX (CA IX)-deficient (Car9(-/-)) mice. In this paper, we aimed to characterize human NCCRP1 and to elucidate its relationship to CA IX. Recombinant NCCRP1 protein was expressed in Escherichia coli, and a novel polyclonal antiserum was raised against the purified full-length protein. Immunocytochemistry showed that NCCRP1 is expressed intracellularly, even though it has previously been described as a transmembrane protein. Using bioinformatic analyses, we identified orthologs of NCCRP1 in 35 vertebrate genomes, and up to five paralogs per genome. These paralogs are FBXO genes whose protein products are components of the E3 ubiquitin ligase complexes. NCCRP1 proteins have no signal peptides or transmembrane domains. NCCRP1 has mainly been studied in fish and was thought to be responsible for the cytolytic function of nonspecific cytotoxic cells (NCCs). Our analyses showed that in humans, NCCRP1 mRNA is expressed in tissues containing squamous epithelium, whereas it shows a more ubiquitous tissue expression pattern in mice. Neither human nor mouse NCCRP1 expression is specific to immune tissues. Silencing CA9 using siRNAs did not affect NCCRP1 levels, indicating that its expression is not directly regulated by CA9. Interestingly, silencing NCCRP1 caused a statistically significant decrease in the growth of HeLa cells. These studies provide ample evidence that the current name, "non-specific cytotoxic cell receptor protein 1," is not appropriate. We therefore propose that the gene name be changed to FBXO50.
authors.affiliation: Institute of Biomedical Technology, University of Tampere, Tampere, Finland. heini.kallio@uta.fi
authors.forename: Heini
authors.initials: H
authors.lastname: Kallio
authors.forename: Martti
authors.initials: M
authors.lastname: Tolvanen
authors.forename: Janne
authors.initials: J
authors.lastname: Jänis
authors.forename: Pei-wen
authors.initials: PW
authors.lastname: Pan
authors.forename: Eeva
authors.initials: E
authors.lastname: Laurila
authors.forename: Anne
authors.initials: A
authors.lastname: Kallioniemi
authors.forename: Sami
authors.initials: S
authors.lastname: Kilpinen
authors.forename: Vilppu J
authors.initials: VJ
authors.lastname: Tuominen
authors.forename: Jorma
authors.initials: J
authors.lastname: Isola
authors.forename: Jarkko
authors.initials: J
authors.lastname: Valjakka
authors.forename: Silvia
authors.initials: S
authors.lastname: Pastorekova
authors.forename: Jaromir
authors.initials: J
authors.lastname: Pastorek
authors.forename: Seppo
authors.initials: S
authors.lastname: Parkkila
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000502:physiology*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000502:physiology*; D019295:Computational Biology; D044783:F-Box Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D037102:Lectins; D051379:Mice; D010802:Phylogeny; D012333:RNA, Messenger / Q000032:analysis; D011946:Receptors, Antigen / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution; D044767:Ubiquitin-Protein Ligases
chemical_list: D000951:Antigens, Neoplasm; D044783:F-Box Proteins; D037102:Lectins; D012333:RNA, Messenger; D011946:Receptors, Antigen; C110644:nonspecific cytotoxic cell receptor protein 1; D044767:Ubiquitin-Protein Ligases; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases
references.citation: J Exp Clin Cancer Res. 2009 Jun 10;28:78
references.pmid: 19515249
references.citation: Nat Protoc. 2007;2(4):953-71
references.pmid: 17446895
references.citation: Genome Biol. 2000;1(5):REVIEWS3002
references.pmid: 11178263
references.citation: BMC Genomics. 2010 Jun 23;11:397
references.pmid: 20573196
references.citation: J Biol Chem. 2008 Oct 10;283(41):27799-27809
references.pmid: 18703501
references.citation: BMC Bioinformatics. 2009 May 08;10:136
references.pmid: 19426475
references.citation: Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16233-8
references.pmid: 19805286
references.citation: Cell Immunol. 1998 Jul 10;187(1):19-26
references.pmid: 9681999
references.citation: Nucleic Acids Res. 1997 Sep 1;25(17):3389-402
references.pmid: 9254694
references.citation: Genome Biol. 2008;9(9):R139
references.pmid: 18803840
references.citation: Mol Immunol. 1997 Aug-Sep;34(12-13):955-65
references.pmid: 9464530
references.citation: Nucleic Acids Res. 1994 Nov 11;22(22):4673-80
references.pmid: 7984417
references.citation: BMC Biochem. 2008 Nov 27;9:32
references.pmid: 19036170
references.citation: BMC Bioinformatics. 2009 Jan 30;10 Suppl 1:S24
references.pmid: 19208124
references.citation: Comp Biochem Physiol C Toxicol Pharmacol. 2005 Mar-Apr;140(3-4):287-94
references.pmid: 15897012
references.citation: Nucleic Acids Res. 2011 Jan;39(Database issue):D32-7
references.pmid: 21071399
references.citation: Nucleic Acids Res. 2009 Jan;37(Database issue):D211-5
references.pmid: 18940856
references.citation: Nucleic Acids Res. 2009 Jan;37(Database issue):D32-6
references.pmid: 18927115
references.citation: J Mol Evol. 2002 Mar;54(3):386-95
references.pmid: 11847564
references.citation: J Biol Chem. 2008 May 9;283(19):12717-29
references.pmid: 18203720
references.citation: Gastroenterology. 2002 Dec;123(6):1889-903
references.pmid: 12454846
references.citation: Nat Rev Drug Discov. 2011 Sep 16;10(10):767-77
references.pmid: 21921921
references.citation: Biosci Biotechnol Biochem. 2007 Nov;71(11):2623-31
references.pmid: 17986767
references.citation: Nucleic Acids Res. 2010 Jan;38(Database issue):D557-62
references.pmid: 19906699
references.citation: Fish Shellfish Immunol. 2004 Feb;16(2):163-72
references.pmid: 15123320
references.citation: Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):5777-81
references.pmid: 17389369
references.citation: J Comp Physiol B. 2006 Sep;176(7):599-605
references.pmid: 16676190
references.citation: Dev Comp Immunol. 2001 Oct-Dec;25(8-9):701-11
references.pmid: 11602191
references.citation: Virology. 1992 Apr;187(2):620-6
references.pmid: 1312272
references.citation: Mol Biol Evol. 2007 Aug;24(8):1596-9
references.pmid: 17488738
references.citation: Dev Comp Immunol. 2005;29(7):637-50
references.pmid: 15784294
references.citation: Nucleic Acids Res. 2005 Jan 20;33(2):511-8
references.pmid: 15661851