RBBP9_HUMAN
ID RBBP9_HUMAN Reviewed; 186 AA.
AC O75884; D3DW31; Q5JPH9; Q9H1D8;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 26-SEP-2001, sequence version 2.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Serine hydrolase RBBP9 {ECO:0000303|PubMed:20080647};
DE EC=3.-.-.- {ECO:0000269|PubMed:19329999, ECO:0000269|PubMed:20080647};
DE AltName: Full=B5T-overexpressed gene protein {ECO:0000250|UniProtKB:O88350};
DE Short=Protein BOG {ECO:0000250|UniProtKB:O88350};
DE AltName: Full=Retinoblastoma-binding protein 10;
DE Short=RBBP-10;
DE AltName: Full=Retinoblastoma-binding protein 9;
DE Short=RBBP-9;
GN Name=RBBP9; Synonyms=BOG, RBBP10;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=9697699; DOI=10.1038/1258;
RA Woitach J.T., Zhang M., Niu C.-H., Thorgeirsson S.S.;
RT "A retinoblastoma-binding protein that affects cell-cycle control and
RT confers transforming ability.";
RL Nat. Genet. 19:371-374(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Fetal brain;
RX PubMed=12296629; DOI=10.1023/a:1019886918029;
RA Chen J.-Z., Yang Q.-S., Wang S., Meng X.-F., Ying K., Xie Y., Mao Y.-M.;
RT "Cloning and expression of a novel retinoblastoma binding protein cDNA,
RT RBBP10.";
RL Biochem. Genet. 40:273-282(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lymph node;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORM 1).
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION, ACTIVITY REGULATION, ACTIVE SITE, AND MUTAGENESIS OF SER-75.
RX PubMed=19329999; DOI=10.1038/nbt.1531;
RA Bachovchin D.A., Brown S.J., Rosen H., Cravatt B.F.;
RT "Identification of selective inhibitors of uncharacterized enzymes by high-
RT throughput screening with fluorescent activity-based probes.";
RL Nat. Biotechnol. 27:387-394(2009).
RN [8]
RP FUNCTION, TISSUE SPECIFICITY, AND MUTAGENESIS OF SER-75.
RX PubMed=20080647; DOI=10.1073/pnas.0911646107;
RA Shields D.J., Niessen S., Murphy E.A., Mielgo A., Desgrosellier J.S.,
RA Lau S.K., Barnes L.A., Lesperance J., Bouvet M., Tarin D., Cravatt B.F.,
RA Cheresh D.A.;
RT "RBBP9: a tumor-associated serine hydrolase activity required for
RT pancreatic neoplasia.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:2189-2194(2010).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
RP INTERACTION WITH RB1.
RX PubMed=21689726; DOI=10.1016/j.exphem.2011.05.008;
RA O'Connor M.D., Wederell E., Robertson G., Delaney A., Morozova O.,
RA Poon S.S., Yap D., Fee J., Zhao Y., McDonald H., Zeng T., Hirst M.,
RA Marra M.A., Aparicio S.A., Eaves C.J.;
RT "Retinoblastoma-binding proteins 4 and 9 are important for human
RT pluripotent stem cell maintenance.";
RL Exp. Hematol. 39:866-879.E1(2011).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS), AND ACTIVE SITE.
RX PubMed=19004028; DOI=10.1002/prot.22278;
RA Vorobiev S.M., Su M., Seetharaman J., Huang Y.J., Chen C.X., Maglaqui M.,
RA Janjua H., Proudfoot M., Yakunin A., Xiao R., Acton T.B., Montelione G.T.,
RA Tong L.;
RT "Crystal structure of human retinoblastoma binding protein 9.";
RL Proteins 74:526-529(2009).
CC -!- FUNCTION: Serine hydrolase whose substrates have not been identified
CC yet (PubMed:19329999, PubMed:20080647). May negatively regulate basal
CC or autocrine TGF-beta signaling by suppressing SMAD2-SMAD3
CC phosphorylation (PubMed:20080647). May play a role in the
CC transformation process due to its capacity to confer resistance to the
CC growth-inhibitory effects of TGF-beta through interaction with RB1 and
CC the subsequent displacement of E2F1 (PubMed:9697699).
CC {ECO:0000269|PubMed:19329999, ECO:0000269|PubMed:20080647,
CC ECO:0000269|PubMed:9697699}.
CC -!- ACTIVITY REGULATION: Inhibited by the natural product emetine produced
CC by the ipecac root. {ECO:0000269|PubMed:19329999}.
CC -!- SUBUNIT: Interacts with RB1; the interaction disrupts RB1 binding to
CC E2F1 (PubMed:21689726). Interacts with RBL1 and RBL2 (By similarity).
CC {ECO:0000250|UniProtKB:O88350, ECO:0000269|PubMed:21689726}.
CC -!- INTERACTION:
CC O75884; O95199: RCBTB2; NbExp=3; IntAct=EBI-11310604, EBI-742404;
CC O75884; Q9NYB0: TERF2IP; NbExp=2; IntAct=EBI-11310604, EBI-750109;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O75884-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O75884-2; Sequence=VSP_004374;
CC -!- TISSUE SPECIFICITY: Expressed at higher levels in tumor tissues such as
CC carcinoma. {ECO:0000269|PubMed:20080647, ECO:0000269|PubMed:9697699}.
CC -!- MISCELLANEOUS: Plays a role in maintaining pluripotency in human stem
CC cells in vitro. {ECO:0000269|PubMed:21689726}.
CC -!- SIMILARITY: Belongs to the RBBP9 family. {ECO:0000305}.
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DR EMBL; AF039564; AAC63498.1; -; mRNA.
DR EMBL; AF237576; AAL83721.1; -; mRNA.
DR EMBL; AL832411; CAI46193.1; -; mRNA.
DR EMBL; AL121893; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471133; EAX10236.1; -; Genomic_DNA.
DR EMBL; CH471133; EAX10237.1; -; Genomic_DNA.
DR EMBL; CH471133; EAX10238.1; -; Genomic_DNA.
DR EMBL; BC015938; AAH15938.1; -; mRNA.
DR CCDS; CCDS13136.1; -. [O75884-1]
DR RefSeq; NP_006597.2; NM_006606.2. [O75884-1]
DR PDB; 2QS9; X-ray; 1.72 A; A/B=1-186.
DR PDB; 7OEX; X-ray; 1.51 A; A/B=1-186.
DR PDBsum; 2QS9; -.
DR PDBsum; 7OEX; -.
DR AlphaFoldDB; O75884; -.
DR SMR; O75884; -.
DR BioGRID; 115964; 10.
DR IntAct; O75884; 2.
DR STRING; 9606.ENSP00000336866; -.
DR BindingDB; O75884; -.
DR ChEMBL; CHEMBL1075121; -.
DR DrugCentral; O75884; -.
DR GuidetoPHARMACOLOGY; 2874; -.
DR ESTHER; human-RBBP9; Hydrolase_RBBP9_YdeN.
DR iPTMnet; O75884; -.
DR PhosphoSitePlus; O75884; -.
DR BioMuta; RBBP9; -.
DR EPD; O75884; -.
DR jPOST; O75884; -.
DR MassIVE; O75884; -.
DR MaxQB; O75884; -.
DR PaxDb; O75884; -.
DR PeptideAtlas; O75884; -.
DR PRIDE; O75884; -.
DR ProteomicsDB; 50241; -. [O75884-1]
DR ProteomicsDB; 50242; -. [O75884-2]
DR Antibodypedia; 9405; 327 antibodies from 28 providers.
DR DNASU; 10741; -.
DR Ensembl; ENST00000337227.9; ENSP00000336866.4; ENSG00000089050.16. [O75884-1]
DR GeneID; 10741; -.
DR KEGG; hsa:10741; -.
DR MANE-Select; ENST00000337227.9; ENSP00000336866.4; NM_006606.3; NP_006597.2.
DR UCSC; uc002wqy.5; human. [O75884-1]
DR CTD; 10741; -.
DR DisGeNET; 10741; -.
DR GeneCards; RBBP9; -.
DR HGNC; HGNC:9892; RBBP9.
DR HPA; ENSG00000089050; Low tissue specificity.
DR MIM; 602908; gene.
DR neXtProt; NX_O75884; -.
DR OpenTargets; ENSG00000089050; -.
DR PharmGKB; PA34256; -.
DR VEuPathDB; HostDB:ENSG00000089050; -.
DR eggNOG; ENOG502QVNM; Eukaryota.
DR GeneTree; ENSGT00390000014861; -.
DR HOGENOM; CLU_088863_1_0_1; -.
DR InParanoid; O75884; -.
DR OMA; NHWFPWL; -.
DR OrthoDB; 1320428at2759; -.
DR PhylomeDB; O75884; -.
DR TreeFam; TF106470; -.
DR PathwayCommons; O75884; -.
DR SignaLink; O75884; -.
DR BioGRID-ORCS; 10741; 6 hits in 1073 CRISPR screens.
DR ChiTaRS; RBBP9; human.
DR EvolutionaryTrace; O75884; -.
DR GeneWiki; RBBP9; -.
DR GenomeRNAi; 10741; -.
DR Pharos; O75884; Tchem.
DR PRO; PR:O75884; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; O75884; protein.
DR Bgee; ENSG00000089050; Expressed in pigmented layer of retina and 179 other tissues.
DR Genevisible; O75884; HS.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:0042127; P:regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0009624; P:response to nematode; IEA:Ensembl.
DR GO; GO:0060510; P:type II pneumocyte differentiation; IEA:Ensembl.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR010662; Hydrolase_RBBP9/YdeN.
DR Pfam; PF06821; Ser_hydrolase; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Hydrolase; Reference proteome.
FT CHAIN 1..186
FT /note="Serine hydrolase RBBP9"
FT /id="PRO_0000097180"
FT REGION 63..67
FT /note="Involved in binding to RB1"
FT /evidence="ECO:0000305|PubMed:9697699"
FT ACT_SITE 75
FT /note="Charge relay system"
FT /evidence="ECO:0000305|PubMed:19004028,
FT ECO:0000305|PubMed:19329999"
FT ACT_SITE 138
FT /note="Charge relay system"
FT /evidence="ECO:0000305|PubMed:19004028"
FT ACT_SITE 165
FT /note="Charge relay system"
FT /evidence="ECO:0000305|PubMed:19004028"
FT VAR_SEQ 152..186
FT /note="RLETKLHKFTDCGHFQNTEFHELITVVKSLLKVPA -> SWTPNCTNSLTVV
FT TFRTQSSMN (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9697699"
FT /id="VSP_004374"
FT MUTAGEN 75
FT /note="S->A: Loss of catalytic activity. Fails to block
FT TGF-beta-mediated anti-proliferative signal in tumor
FT cells."
FT /evidence="ECO:0000269|PubMed:19329999,
FT ECO:0000269|PubMed:20080647"
FT CONFLICT 2
FT /note="A -> V (in Ref. 1; AAC63498)"
FT /evidence="ECO:0000305"
FT CONFLICT 13..14
FT /note="NG -> KI (in Ref. 1; AAC63498)"
FT /evidence="ECO:0000305"
FT CONFLICT 18
FT /note="V -> E (in Ref. 1; AAC63498)"
FT /evidence="ECO:0000305"
FT CONFLICT 93..94
FT /note="IV -> LI (in Ref. 1; AAC63498)"
FT /evidence="ECO:0000305"
FT CONFLICT 102..103
FT /note="DL -> EF (in Ref. 1; AAC63498)"
FT /evidence="ECO:0000305"
FT CONFLICT 115
FT /note="T -> S (in Ref. 1; AAC63498)"
FT /evidence="ECO:0000305"
FT CONFLICT 129
FT /note="Y -> H (in Ref. 1; AAC63498)"
FT /evidence="ECO:0000305"
FT STRAND 6..10
FT /evidence="ECO:0007829|PDB:7OEX"
FT STRAND 13..15
FT /evidence="ECO:0007829|PDB:7OEX"
FT TURN 18..20
FT /evidence="ECO:0007829|PDB:7OEX"
FT HELIX 24..32
FT /evidence="ECO:0007829|PDB:7OEX"
FT STRAND 38..41
FT /evidence="ECO:0007829|PDB:7OEX"
FT TURN 47..49
FT /evidence="ECO:0007829|PDB:7OEX"
FT HELIX 52..61
FT /evidence="ECO:0007829|PDB:7OEX"
FT STRAND 69..74
FT /evidence="ECO:0007829|PDB:7OEX"
FT HELIX 76..87
FT /evidence="ECO:0007829|PDB:7OEX"
FT STRAND 91..97
FT /evidence="ECO:0007829|PDB:7OEX"
FT HELIX 106..110
FT /evidence="ECO:0007829|PDB:7OEX"
FT HELIX 120..126
FT /evidence="ECO:0007829|PDB:7OEX"
FT STRAND 128..135
FT /evidence="ECO:0007829|PDB:7OEX"
FT STRAND 139..141
FT /evidence="ECO:0007829|PDB:7OEX"
FT HELIX 143..153
FT /evidence="ECO:0007829|PDB:7OEX"
FT STRAND 156..162
FT /evidence="ECO:0007829|PDB:7OEX"
FT TURN 164..166
FT /evidence="ECO:0007829|PDB:7OEX"
FT HELIX 172..181
FT /evidence="ECO:0007829|PDB:7OEX"
SQ SEQUENCE 186 AA; 21000 MW; F645E159DCB759BF CRC64;
MASPSKAVIV PGNGGGDVTT HGWYGWVKKE LEKIPGFQCL AKNMPDPITA RESIWLPFME
TELHCDEKTI IIGHSSGAIA AMRYAETHRV YAIVLVSAYT SDLGDENERA SGYFTRPWQW
EKIKANCPYI VQFGSTDDPF LPWKEQQEVA DRLETKLHKF TDCGHFQNTE FHELITVVKS
LLKVPA
