RNASET2 (ribonuclease T2)

Identity

Other names	RNASE6PL
	RP11-514O12.3
	bA514O12.3
Hugo	RNASET2
Location	6q27
Local_order	Telomeric to RPS6KA2, centromeric to FGFR1OP.

Note

This gene is the first human member of the Rh/T2/S-glycoprotein family of extracellular ribonucleases. It is a putative class II tumor suppressor gene potentially involved in the pathogenesis of several solid and haematologic human neoplasias such as ovarian cancer, melanoma and non-Hodgkin lymphoma.

DNA/RNA

	I-IX: RNASET2 exons.
Description	This gene is split in 9 exons spanning approximatly 27 kb of genomic DNA. The translation initiation codon is located to exon 1 and the stop codon to exon 9. Exons III and VI encode the two CAS motifs (Catalytic Active Sites) responsible for the ribonuclease activity of the RNASET2 protein.
Transcription	The RNASET2 gene is transcribed in the telomere-to-centromere orientation to produce an ubiquitously expressed mRNA approximately 1,4 kb in length. EST clones representing splice variants of the same gene have been described.
Pseudogene	A processed pseudogene showing 85% identity with RNASET2 mRNA maps to chromosome 7p11.2. The expression pattern of this pseudogene is not known.

Protein

Description	The full-length RNASET2 protein contains 256 aminoacids and displays an apparent MW of 36 kDa in its secreted form. Two 31 and 27 kDa C-terminal proteolytic products have also been observed intracellularly in several human cancer cell lines and localize to the lysosome.
Expression	Expression of the RNASET2 protein has been detected in several human ovarian cancer cell lines and in some melanoma, prostate, pancreatic and breast carcinoma cell lines.
Localisation	The RNASET2 protein can be detected either intracellularly within lysosomes and secretory pathway, or extracellularly in a secreted form (in cell culture supernatants).
Function	Biochemical function : RNASET2 is an acid ribonuclease with optimal activity at pH 5 and preferential cleavage of poly-A and poly-U homo-polyribonucleotides. Biological function : RNASET2 behaves as a class II tumor suppressor gene for ovarian cancer, since experimental overexpression of this gene in human ovarian cancer cell lines is associated with a significant decrease of their tumorigenic and metastasizing potential in vivo. Strikingly, the ribonuclease catalytic activity is apparently dispensable for RNASET2 to play such antioncogenic role. Indeed, a double CAS mutant cDNA construct encoding an almost inactive RNASET2 protein is still able to suppress tumorigenicity and metastasis when overexpressed in the same ovarian cancer cell lines. Such results have been recently confirmed in a human melanoma cell line.
Homology	The primary sequenze of RNASET2 shows strong homology to the Rh/T2/S family of secreted ribonucleases.

Mutations

Germinal	A common exon-9 missense C708T germline mutation has been described but no evidence for an association of this allele with human cancer was found.
Somatic	A few common polymorphisms in exons 1, 8 and 9 have been described.

Implicated in

Entity	Human ovarian carcinoma.
Disease	Loss of expression of RNASET2 occurs in a significant fraction of human ovarian cancer cell lines and primary ovarian tumours. When overexpressed by gene transfer experiments in human ovarian cancer cell lines displaying a low level of endogenous mRNA, RNASET2 strongly suppresses the tumorigenic and metastatic potential of these cell lines in vivo.
Cytogenetics	The RNASET2 genes maps in a genomic region (6q27) which is frequently deleted or otherwise rearranged in a wide range of human neoplasias, including ovarian cancer.

External links

	Nomenclature
Hugo	RNASET2
GDB	RNASET2
Entrez_Gene	RNASET2  8635  ribonuclease T2
	Cards
Atlas	RNASET2ID518ch6q27
GeneCards	RNASET2
Ensembl	RNASET2 [Search_View]   ENSG00000026297 [Gene_View]
Genatlas	RNASET2
GeneLynx	RNASET2
eGenome	RNASET2
euGene	8635
	Genomic and cartography
GoldenPath	RNASET2  -  6q27   chr6:167262994-167290067 -  6q27   [Description]    (hg18-Mar_2006)
Ensembl	RNASET2 - 6q27 [CytoView]
NCBI	Mapview
HomoloGene	RNASET2
	Gene and transcription
Genbank	AJ419865 [ ENTREZ ]
Genbank	AJ419866 [ ENTREZ ]
Genbank	AJ419867 [ ENTREZ ]
Genbank	AK000385 [ ENTREZ ]
Genbank	AK001769 [ ENTREZ ]
RefSeq	NM_003730 [ SRS ]    NM_003730 [ ENTREZ ]
RefSeq	AC_000049 [ SRS ]    AC_000049 [ ENTREZ ]
RefSeq	NC_000006 [ SRS ]    NC_000006 [ ENTREZ ]
RefSeq	NT_007422 [ SRS ]    NT_007422 [ ENTREZ ]
RefSeq	NW_923184 [ SRS ]    NW_923184 [ ENTREZ ]
AceView	RNASET2 AceView - NCBI
Unigene	Hs.529989 [ SRS ]    Hs.529989 [ NCBI ]     HS529989 [ spliceNest ]
Fast-db	17037 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	O00584 [ SRS]    O00584 [ EXPASY ]     O00584 [ INTERPRO ]
Prosite	PS00530 RNASE_T2_1 [ SRS ]    PS00530 RNASE_T2_1 [ Expasy ]
Prosite	PS00531 RNASE_T2_2 [ SRS ]    PS00531 RNASE_T2_2 [ Expasy ]
Interpro	IPR001568 RNase_T2 [ SRS ]    IPR001568 RNase_T2 [ EBI ]
CluSTr	O00584
Pfam	PF00445 Ribonuclease_T2 [ SRS ]    PF00445 Ribonuclease_T2 [ Sanger ]    pfam00445 [ NCBI-CDD ]
Blocks	O00584
HPRD	10197
	Protein Interaction databases
DIP	O00584
IntAct	O00584
	Polymorphism : SNP, mutations, diseases
SNP	RNASET2 [dbSNP-NCBI]
SNP	NM_003730 [SNP-NCI]
SNP	RNASET2 [GeneSNPs - Utah]  RNASET2] [HGBASE - SRS]
HAPMAP	RNASET2 [HAPMAP]
HGMD	RNASET2
	General knowledge
Family Browser	RNASET2 [UCSC Family Browser]
SOURCE	NM_003730
SMD	Hs.529989
SAGE	Hs.529989
Enzyme	3.1.27.- [ Enzyme-SRS ]   3.1.27.- [ Brenda-SRS ]   3.1.27.- [ KEGG ]   3.1.27.- [ WIT ]
GO	RNA binding [Amigo]  RNA binding
GO	endoribonuclease activity [Amigo]  endoribonuclease activity
GO	extracellular region [Amigo]  extracellular region
GO	RNA catabolic process [Amigo]  RNA catabolic process
GO	hydrolase activity [Amigo]  hydrolase activity
PubGene	RNASET2
TreeFam	RNASET2
CTD	8635 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	RNASET2 Related clones (RZPD - Berlin)
	PubMed
PubMed	9 Pubmed reference(s) in LocusLink

Bibliography

Mammalian Rh/T2/S-glycoprotein ribonuclease family genes: cloning of a human member located in a region of chromosome 6 (6q27) frequently deleted in human malignancies.

Trubia M, Sessa L, Taramelli R

Genomics. 1997 ; 42 (2) : 342-344.

PMID 9192857

Cloning and characterization of a senescence inducing and class II tumor suppressor gene in ovarian carcinoma at chromosome region 6q27.

Acquati F, Morelli C, Cinquetti R, Bianchi MG, Porrini D, Varesco L, Gismondi V, Rocchetti R, Talevi S, Possati L, Magnanini C, Tibiletti MG, Bernasconi B, Daidone MG, Shridhar V, Smith DI, Negrini M, Barbanti-Brodano G, Taramelli R

Oncogene. 2001 ; 20 (8) : 980-988.

PMID 11314033

Molecular cloning, tissue distribution, and chromosomal localization of the human homolog of the R2/Th/Stylar ribonuclease gene family.

Acquati F, Nucci C, Bianchi MG, Gorletta T, Taramelli R

Methods in molecular biology (Clifton, N.J.). 2001 ; 160 : 87-101.

PMID 11265308

Tumor and metastasis suppression by the human RNASET2 gene.

Acquati F, Possati L, Ferrante L, Campomenosi P, Talevi S, Bardelli S, Margiotta C, Russo A, Bortoletto E, Rocchetti R, Calza R, Cinquetti R, Monti L, Salis S, Barbanti-Brodano G, Taramelli R

International journal of oncology. 2005 ; 26 (5) : 1159-1168.

PMID 15809705

Characterization of RNASET2, the first human member of the Rh/T2/S family of glycoproteins.

Campomenosi P, Salis S, Lindqvist C, Mariani D, Nordstrˆm T, Acquati F, Taramelli R

Archives of biochemistry and biophysics. 2006 ; 449 (1-2) : 17-26.

PMID 16620762

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

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Contributor(s)

Written	02-2007	Francesco Acquati, Paola Campomenosi

Citation

This paper should be referenced as such :

Acquati F, Campomenosi P . RNASET2 (ribonuclease T2). Atlas Genet Cytogenet Oncol Haematol. February 2007 . URL : http://AtlasGeneticsOncology.org/Genes/RNASET2ID518ch6q27.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Wed Jul 2 08:26:50 2008