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Gene_locus Report for: human-RBBP9

Homo sapiens (Human) Retinoblastoma-binding protein 9 and 10 (rbbp-10) (b5t overexpressed gene protein) (bog protein)

Retinoblastoma binding protein 9 is an aminopeptidase with a preference for removing aromatic amino acids in human cells (Tang et al.) (from OMIM) Woitach et al. (1998) described a new gene, designated BOG (B5T overexpressed gene now RBBP9), which was shown to be overexpressed in several transformed rat liver epithelial cell lines resistant to the growth-inhibitory effect of TGF-beta-1 (TGFB1; 190180), as well as in primary human liver tumors. The Bog protein was found to share homology with other retinoblastoma-binding proteins and contained the RB1-binding motif LXCXE. Woitach et al. (1998) demonstrated that Bog binds to the RB1 gene product. In vivo, Bog/Rb complexes do not contain E2F1, and Bog can displace E2F1 from E2F1/Rb complexes in vitro. Overexpression of Bog in normal RLE cells conferred resistance to the growth-inhibitory effect of TGF-beta-1. Furthermore, normal RLE cells were rapidly transformed when Bog was continuously overexpressed and formed hepatoblastoma-like tumors when transplanted into nude mice. Bog may be important in the transformation process, in part due to its capacity to transfer resistance to the growth-inhibitory effects of TGF-beta-1 through interaction with RB1 and the subsequent displacement of E2F1. Chen et al. (2002) cloned RBBP9, which they called RBBP10. Structure of RBBP9 was determined by Vorobiev et al. 2009. Using an activity-based proteomic approach to identify serine hydrolases in pancreatic cancers, Shields et al. (2010) identified RBBP9. RBBP9 activity, but not expression, was elevated in pancreatic cancers compared with normal tissue. Knockdown of RBBP9 in FG human pancreatic carcinoma cells reduced cell proliferation and altered cell morphology in culture, reduced colony formation in soft agar, and reduced tumor formation in nude mice. Expression of RBBP9 reversed the antiproliferative effect of TGF-beta (TGFB1; 190180) in FG human pancreatic carcinoma cells and inhibited TGF-beta-dependent SMAD2 (601366)/SMAD3 (603109) phosphorylation. Mutation of ser75 within a predicted serine hydrolase motif abrogated all RBBP9 activity and functioned as a dominant-negative mutation, permitting unexpectedly elevated TGF-beta activity and SMAD2/SMAD3 phosphorylation. By yeast 2-hybrid screening of a human fetal brain library using RBBP9 (602908) as bait, Chen et al. (2003) cloned YRDC. The deduced 279-amino acid protein contains a SUA5-YCIO-YRDC domain, a GTP-binding elongation factor signature, and a leucine zipper motif.

Block| X
Position in NCBI Life Tree|Homo sapiens
(Below N is a link to NCBI taxonomic web page and E link to ESTHER at designed phylum.)
> cellular organisms: N E > Eukaryota: N E > Opisthokonta: N E > Metazoa: N E > Eumetazoa: N E > Bilateria: N E > Deuterostomia: N E > Chordata: N E > Craniata: N E > Vertebrata: N E > Gnathostomata: N E > Teleostomi: N E > Euteleostomi: N E > Sarcopterygii: N E > Dipnotetrapodomorpha: N E > Tetrapoda: N E > Amniota: N E > Mammalia: N E > Theria: N E > Eutheria: N E > Boreoeutheria: N E > Euarchontoglires: N E > Primates: N E > Haplorrhini: N E > Simiiformes: N E > Catarrhini: N E > Hominoidea: N E > Hominidae: N E > Homininae: N E > Homo: N E > Homo sapiens: N E

Molecular evidence
No mutation
2 structures: 2QS9, 7OEX
No kinetic

No Substrate
4 inhibitors (e.g. : Ala(1-naph)-Pro-CN, Emetine, ML114... more)
>3 Genbank links 3 more: AF039564, AF237576, AL121893
1 UniProt : O75884
2 Structure : 7OEX, 2QS9
1 UniProt : O75884
1 Interpro : O75884
1 Pfam : O75884
1 PIRSF : O75884
1 SUPERFAM : O75884
1 EntrezGene : 10741
1 SNP : 10741
1 HUGO HGNC : 9892
1 IUPHAR : 2874
1 OMIM : 602908
1 Ensembl : ENSG00000089050
Graphical view for this peptide sequence: human-RBBP9
Colored MSA for Hydrolase_RBBP9_YdeN (raw)
Legend This sequence has been compared to family alignement (MSA)
red => minority aminoacid
blue => majority aminoacid
color intensity => conservation rate
title => sequence position(MSA position)aminoacid rate
Catalytic site
Catalytic site in the MSA


15 more
    Title: Mechanism-based traps enable protease and hydrolase substrate discovery
    Tang S, Beattie AT, Kafkova L, Petris G, Huguenin-Dezot N, Fiedler M, Freeman M, Chin JW
    Ref: Nature, 602:701, 2022 : PubMed


    Title: Application of the RBBP9 Serine Hydrolase Inhibitor, ML114, Decouples Human Pluripotent Stem Cell Proliferation and Differentiation
    Lim S, Shparberg RA, Coorssen JR, O'Connor MD
    Ref: Int J Mol Sci, 21:, 2020 : PubMed


    Title: Chemoproteomic Identification of Serine Hydrolase RBBP9 as a Valacyclovir-Activating Enzyme
    Shenoy VM, Thompson BR, Shi J, Zhu HJ, Smith DE, Amidon GL
    Ref: Mol Pharm, 17:1706, 2020 : PubMed


Other Papers

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Mail to: Nicolas Lenfant, Thierry Hotelier, Yves Bourne, Pascale Marchot and Arnaud Chatonnet.
Please cite: Lenfant 2013 Nucleic.Acids.Res. or Marchot Chatonnet 2012 Prot.Pept Lett.
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