Full text data of RPS24
RPS24
[Confidence: low (only semi-automatic identification from reviews)]
40S ribosomal protein S24
Note: presumably soluble (membrane word is not in UniProt keywords or features)
40S ribosomal protein S24
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P62847
ID RS24_HUMAN Reviewed; 133 AA.
AC P62847; E7EPK6; P16632; Q5T0P7; Q5T0P8; Q7Z3D1;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 16-AUG-2004, sequence version 1.
DT 22-JAN-2014, entry version 111.
DE RecName: Full=40S ribosomal protein S24;
GN Name=RPS24;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=2210388; DOI=10.1016/0378-1119(90)90103-X;
RA Brown S.J., Jewell A., Maki C.G., Roufa D.J.;
RT "A cDNA encoding human ribosomal protein S24.";
RL Gene 91:293-296(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING.
RX PubMed=8647458; DOI=10.1016/0378-1119(96)88652-5;
RA Xu W.-B., Roufa D.J.;
RT "The gene encoding human ribosomal protein S24 and tissue-specific
RT expression of differentially spliced mRNAs.";
RL Gene 169:257-262(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Placenta;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Thymus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Retina;
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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Kidney, and Muscle;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 1-8; 50-61; 69-83 AND 119-132, ACETYLATION AT
RP MET-1, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Quadroni M.;
RL Submitted (OCT-2004) to UniProtKB.
RN [10]
RP PROTEIN SEQUENCE OF 69-83.
RC TISSUE=Placenta;
RX PubMed=8706699; DOI=10.1111/j.1432-1033.1996.0144u.x;
RA Vladimirov S.N., Ivanov A.V., Karpova G.G., Musolyamov A.K.,
RA Egorov T.A., Thiede B., Wittmann-Liebold B., Otto A.;
RT "Characterization of the human small-ribosomal-subunit proteins by N-
RT terminal and internal sequencing, and mass spectrometry.";
RL Eur. J. Biochem. 239:144-149(1996).
RN [11]
RP INVOLVEMENT IN DBA3, AND TISSUE SPECIFICITY.
RX PubMed=17186470; DOI=10.1086/510020;
RA Gazda H.T., Grabowska A., Merida-Long L.B., Latawiec E.,
RA Schneider H.E., Lipton J.M., Vlachos A., Atsidaftos E., Ball S.E.,
RA Orfali K.A., Niewiadomska E., Da Costa L., Tchernia G., Niemeyer C.,
RA Meerpohl J.J., Stahl J., Schratt G., Glader B., Backer K., Wong C.,
RA Nathan D.G., Beggs A.H., Sieff C.A.;
RT "Ribosomal protein S24 gene is mutated in Diamond-Blackfan anemia.";
RL Am. J. Hum. Genet. 79:1110-1118(2006).
RN [12]
RP FUNCTION.
RX PubMed=18230666; DOI=10.1093/hmg/ddn015;
RA Choesmel V., Fribourg S., Aguissa-Toure A.H., Pinaud N., Legrand P.,
RA Gazda H.T., Gleizes P.E.;
RT "Mutation of ribosomal protein RPS24 in Diamond-Blackfan anemia
RT results in a ribosome biogenesis disorder.";
RL Hum. Mol. Genet. 17:1253-1263(2008).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-9, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
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.,
RA Buerckstuemmer T., 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 [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [17]
RP STRUCTURE BY ELECTRON MICROSCOPY (5.0 ANGSTROMS) OF 80S RIBOSOME.
RX PubMed=23636399; DOI=10.1038/nature12104;
RA Anger A.M., Armache J.P., Berninghausen O., Habeck M., Subklewe M.,
RA Wilson D.N., Beckmann R.;
RT "Structures of the human and Drosophila 80S ribosome.";
RL Nature 497:80-85(2013).
CC -!- FUNCTION: Required for processing of pre-rRNA and maturation of
CC 40S ribosomal subunits.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=P62847-1, P16632-1;
CC Sequence=Displayed;
CC Name=2;
CC IsoId=P62847-2, P16632-2;
CC Sequence=VSP_005724;
CC Name=3;
CC IsoId=P62847-3; Sequence=VSP_039113;
CC Name=4;
CC IsoId=P62847-4; Sequence=VSP_045672;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Mature tissues, such as adult brain, skeletal
CC muscle, heart, and kidney, express low levels, whereas tissues and
CC organs with significant populations of proliferating cells, such
CC as fetal brain, placenta, bone marrow, and various glandular
CC organs, contain significantly higher levels.
CC -!- DISEASE: Diamond-Blackfan anemia 3 (DBA3) [MIM:610629]: A form of
CC Diamond-Blackfan anemia, a congenital non-regenerative hypoplastic
CC anemia that usually presents early in infancy. Diamond-Blackfan
CC anemia is characterized by a moderate to severe macrocytic anemia,
CC erythroblastopenia, and an increased risk of developing leukemia.
CC 30 to 40% of Diamond-Blackfan anemia patients present with short
CC stature and congenital anomalies, the most frequent being
CC craniofacial (Pierre-Robin syndrome and cleft palate), thumb and
CC urogenital anomalies. Note=The disease is caused by mutations
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the ribosomal protein S24e family.
CC -!- WEB RESOURCE: Name=Diamond-Blackfan Anemia mutation database;
CC URL="http://www.dbagenes.unito.it/home.php?select_db=RPS24";
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DR EMBL; M31520; AAA36588.1; -; mRNA.
DR EMBL; U12202; AAB08007.1; -; Genomic_DNA.
DR EMBL; U12202; AAB08006.1; -; Genomic_DNA.
DR EMBL; BX336465; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK311776; BAG34719.1; -; mRNA.
DR EMBL; AK311910; BAG34851.1; -; mRNA.
DR EMBL; BX537975; CAD97939.1; -; mRNA.
DR EMBL; AL512628; CAI16467.1; -; Genomic_DNA.
DR EMBL; AL512628; CAI16468.1; -; Genomic_DNA.
DR EMBL; CH471083; EAW54623.1; -; Genomic_DNA.
DR EMBL; CH471083; EAW54625.1; -; Genomic_DNA.
DR EMBL; BC000523; AAH00523.1; -; mRNA.
DR EMBL; BC003149; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC071926; AAH71926.1; -; mRNA.
DR PIR; JC4671; JC4671.
DR PIR; JH0213; JH0213.
DR RefSeq; NP_001017.1; NM_001026.4.
DR RefSeq; NP_001135755.1; NM_001142283.1.
DR RefSeq; NP_001135757.1; NM_001142285.1.
DR RefSeq; NP_148982.1; NM_033022.3.
DR UniGene; Hs.280130; -.
DR PDB; 3J3A; EM; 5.00 A; Y=1-133.
DR PDBsum; 3J3A; -.
DR ProteinModelPortal; P62847; -.
DR SMR; P62847; 3-128.
DR IntAct; P62847; 22.
DR MINT; MINT-4719640; -.
DR STRING; 9606.ENSP00000414321; -.
DR PhosphoSite; P62847; -.
DR DMDM; 51338645; -.
DR PaxDb; P62847; -.
DR PRIDE; P62847; -.
DR DNASU; 6229; -.
DR Ensembl; ENST00000360830; ENSP00000354074; ENSG00000138326.
DR Ensembl; ENST00000372360; ENSP00000361435; ENSG00000138326.
DR Ensembl; ENST00000440692; ENSP00000414321; ENSG00000138326.
DR GeneID; 6229; -.
DR KEGG; hsa:6229; -.
DR UCSC; uc001jzs.3; human.
DR CTD; 6229; -.
DR GeneCards; GC10P079793; -.
DR HGNC; HGNC:10411; RPS24.
DR HPA; HPA003364; -.
DR MIM; 602412; gene.
DR MIM; 610629; phenotype.
DR neXtProt; NX_P62847; -.
DR Orphanet; 124; Blackfan-Diamond anemia.
DR PharmGKB; PA34815; -.
DR eggNOG; COG2004; -.
DR HOGENOM; HOG000186306; -.
DR HOVERGEN; HBG000969; -.
DR InParanoid; P62847; -.
DR KO; K02974; -.
DR OMA; TENREQC; -.
DR OrthoDB; EOG7PS1J8; -.
DR PhylomeDB; P62847; -.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_17015; Metabolism of proteins.
DR Reactome; REACT_1762; 3' -UTR-mediated translational regulation.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; RPS24; human.
DR GeneWiki; RPS24; -.
DR GenomeRNAi; 6229; -.
DR NextBio; 24179; -.
DR PRO; PR:P62847; -.
DR ArrayExpress; P62847; -.
DR Bgee; P62847; -.
DR CleanEx; HS_RPS24; -.
DR Genevestigator; P62847; -.
DR GO; GO:0022627; C:cytosolic small ribosomal subunit; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IBA:RefGenome.
DR GO; GO:0000166; F:nucleotide binding; IEA:InterPro.
DR GO; GO:0003735; F:structural constituent of ribosome; NAS:UniProtKB.
DR GO; GO:0031369; F:translation initiation factor binding; ISS:UniProtKB.
DR GO; GO:0034101; P:erythrocyte homeostasis; IMP:UniProtKB.
DR GO; GO:0000462; P:maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA); IBA:RefGenome.
DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; TAS:Reactome.
DR GO; GO:0006614; P:SRP-dependent cotranslational protein targeting to membrane; TAS:Reactome.
DR GO; GO:0006414; P:translational elongation; TAS:Reactome.
DR GO; GO:0006413; P:translational initiation; TAS:Reactome.
DR GO; GO:0006415; P:translational termination; TAS:Reactome.
DR GO; GO:0019083; P:viral transcription; TAS:Reactome.
DR Gene3D; 3.30.70.330; -; 1.
DR HAMAP; MF_00545; Ribosomal_S24e; 1; -.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait.
DR InterPro; IPR012678; Ribosomal_L23/L15e_core_dom.
DR InterPro; IPR001976; Ribosomal_S24e.
DR InterPro; IPR018098; Ribosomal_S24e_CS.
DR PANTHER; PTHR10496; PTHR10496; 1.
DR Pfam; PF01282; Ribosomal_S24e; 1.
DR ProDom; PD006052; Ribosomal_S24e; 1.
DR SUPFAM; SSF54189; SSF54189; 1.
DR PROSITE; PS00529; RIBOSOMAL_S24E; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Diamond-Blackfan anemia; Direct protein sequencing; Phosphoprotein;
KW Reference proteome; Ribonucleoprotein; Ribosomal protein.
FT CHAIN 1 133 40S ribosomal protein S24.
FT /FTId=PRO_0000137623.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 9 9 Phosphothreonine.
FT VAR_SEQ 131 133 Missing (in isoform 2).
FT /FTId=VSP_005724.
FT VAR_SEQ 131 133 PKE -> KK (in isoform 3).
FT /FTId=VSP_039113.
FT VAR_SEQ 131 133 PKE -> MRELGLGVQALGRISQEERCTDVKNSKARESRGV
FT VWQVEVPGPWSVWTCGRLRRGCGKYLQVAVTWRKTENREQC
FT CQACLLERALVRNGAFMSPASPAPAGSPHPVDGDLVLHLPE
FT ALSATLTLSPHIQAINKSFGPFFEIHQESSCFSPPSCLSGL
FT GH (in isoform 4).
FT /FTId=VSP_045672.
SQ SEQUENCE 133 AA; 15423 MW; CE9065C0764D60A6 CRC64;
MNDTVTIRTR KFMTNRLLQR KQMVIDVLHP GKATVPKTEI REKLAKMYKT TPDVIFVFGF
RTHFGGGKTT GFGMIYDSLD YAKKNEPKHR LARHGLYEKK KTSRKQRKER KNRMKKVRGT
AKANVGAGKK PKE
//
ID RS24_HUMAN Reviewed; 133 AA.
AC P62847; E7EPK6; P16632; Q5T0P7; Q5T0P8; Q7Z3D1;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 16-AUG-2004, sequence version 1.
DT 22-JAN-2014, entry version 111.
DE RecName: Full=40S ribosomal protein S24;
GN Name=RPS24;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=2210388; DOI=10.1016/0378-1119(90)90103-X;
RA Brown S.J., Jewell A., Maki C.G., Roufa D.J.;
RT "A cDNA encoding human ribosomal protein S24.";
RL Gene 91:293-296(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING.
RX PubMed=8647458; DOI=10.1016/0378-1119(96)88652-5;
RA Xu W.-B., Roufa D.J.;
RT "The gene encoding human ribosomal protein S24 and tissue-specific
RT expression of differentially spliced mRNAs.";
RL Gene 169:257-262(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Placenta;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Thymus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Retina;
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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Kidney, and Muscle;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 1-8; 50-61; 69-83 AND 119-132, ACETYLATION AT
RP MET-1, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Quadroni M.;
RL Submitted (OCT-2004) to UniProtKB.
RN [10]
RP PROTEIN SEQUENCE OF 69-83.
RC TISSUE=Placenta;
RX PubMed=8706699; DOI=10.1111/j.1432-1033.1996.0144u.x;
RA Vladimirov S.N., Ivanov A.V., Karpova G.G., Musolyamov A.K.,
RA Egorov T.A., Thiede B., Wittmann-Liebold B., Otto A.;
RT "Characterization of the human small-ribosomal-subunit proteins by N-
RT terminal and internal sequencing, and mass spectrometry.";
RL Eur. J. Biochem. 239:144-149(1996).
RN [11]
RP INVOLVEMENT IN DBA3, AND TISSUE SPECIFICITY.
RX PubMed=17186470; DOI=10.1086/510020;
RA Gazda H.T., Grabowska A., Merida-Long L.B., Latawiec E.,
RA Schneider H.E., Lipton J.M., Vlachos A., Atsidaftos E., Ball S.E.,
RA Orfali K.A., Niewiadomska E., Da Costa L., Tchernia G., Niemeyer C.,
RA Meerpohl J.J., Stahl J., Schratt G., Glader B., Backer K., Wong C.,
RA Nathan D.G., Beggs A.H., Sieff C.A.;
RT "Ribosomal protein S24 gene is mutated in Diamond-Blackfan anemia.";
RL Am. J. Hum. Genet. 79:1110-1118(2006).
RN [12]
RP FUNCTION.
RX PubMed=18230666; DOI=10.1093/hmg/ddn015;
RA Choesmel V., Fribourg S., Aguissa-Toure A.H., Pinaud N., Legrand P.,
RA Gazda H.T., Gleizes P.E.;
RT "Mutation of ribosomal protein RPS24 in Diamond-Blackfan anemia
RT results in a ribosome biogenesis disorder.";
RL Hum. Mol. Genet. 17:1253-1263(2008).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-9, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
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.,
RA Buerckstuemmer T., 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 [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [17]
RP STRUCTURE BY ELECTRON MICROSCOPY (5.0 ANGSTROMS) OF 80S RIBOSOME.
RX PubMed=23636399; DOI=10.1038/nature12104;
RA Anger A.M., Armache J.P., Berninghausen O., Habeck M., Subklewe M.,
RA Wilson D.N., Beckmann R.;
RT "Structures of the human and Drosophila 80S ribosome.";
RL Nature 497:80-85(2013).
CC -!- FUNCTION: Required for processing of pre-rRNA and maturation of
CC 40S ribosomal subunits.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=P62847-1, P16632-1;
CC Sequence=Displayed;
CC Name=2;
CC IsoId=P62847-2, P16632-2;
CC Sequence=VSP_005724;
CC Name=3;
CC IsoId=P62847-3; Sequence=VSP_039113;
CC Name=4;
CC IsoId=P62847-4; Sequence=VSP_045672;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Mature tissues, such as adult brain, skeletal
CC muscle, heart, and kidney, express low levels, whereas tissues and
CC organs with significant populations of proliferating cells, such
CC as fetal brain, placenta, bone marrow, and various glandular
CC organs, contain significantly higher levels.
CC -!- DISEASE: Diamond-Blackfan anemia 3 (DBA3) [MIM:610629]: A form of
CC Diamond-Blackfan anemia, a congenital non-regenerative hypoplastic
CC anemia that usually presents early in infancy. Diamond-Blackfan
CC anemia is characterized by a moderate to severe macrocytic anemia,
CC erythroblastopenia, and an increased risk of developing leukemia.
CC 30 to 40% of Diamond-Blackfan anemia patients present with short
CC stature and congenital anomalies, the most frequent being
CC craniofacial (Pierre-Robin syndrome and cleft palate), thumb and
CC urogenital anomalies. Note=The disease is caused by mutations
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the ribosomal protein S24e family.
CC -!- WEB RESOURCE: Name=Diamond-Blackfan Anemia mutation database;
CC URL="http://www.dbagenes.unito.it/home.php?select_db=RPS24";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; M31520; AAA36588.1; -; mRNA.
DR EMBL; U12202; AAB08007.1; -; Genomic_DNA.
DR EMBL; U12202; AAB08006.1; -; Genomic_DNA.
DR EMBL; BX336465; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK311776; BAG34719.1; -; mRNA.
DR EMBL; AK311910; BAG34851.1; -; mRNA.
DR EMBL; BX537975; CAD97939.1; -; mRNA.
DR EMBL; AL512628; CAI16467.1; -; Genomic_DNA.
DR EMBL; AL512628; CAI16468.1; -; Genomic_DNA.
DR EMBL; CH471083; EAW54623.1; -; Genomic_DNA.
DR EMBL; CH471083; EAW54625.1; -; Genomic_DNA.
DR EMBL; BC000523; AAH00523.1; -; mRNA.
DR EMBL; BC003149; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC071926; AAH71926.1; -; mRNA.
DR PIR; JC4671; JC4671.
DR PIR; JH0213; JH0213.
DR RefSeq; NP_001017.1; NM_001026.4.
DR RefSeq; NP_001135755.1; NM_001142283.1.
DR RefSeq; NP_001135757.1; NM_001142285.1.
DR RefSeq; NP_148982.1; NM_033022.3.
DR UniGene; Hs.280130; -.
DR PDB; 3J3A; EM; 5.00 A; Y=1-133.
DR PDBsum; 3J3A; -.
DR ProteinModelPortal; P62847; -.
DR SMR; P62847; 3-128.
DR IntAct; P62847; 22.
DR MINT; MINT-4719640; -.
DR STRING; 9606.ENSP00000414321; -.
DR PhosphoSite; P62847; -.
DR DMDM; 51338645; -.
DR PaxDb; P62847; -.
DR PRIDE; P62847; -.
DR DNASU; 6229; -.
DR Ensembl; ENST00000360830; ENSP00000354074; ENSG00000138326.
DR Ensembl; ENST00000372360; ENSP00000361435; ENSG00000138326.
DR Ensembl; ENST00000440692; ENSP00000414321; ENSG00000138326.
DR GeneID; 6229; -.
DR KEGG; hsa:6229; -.
DR UCSC; uc001jzs.3; human.
DR CTD; 6229; -.
DR GeneCards; GC10P079793; -.
DR HGNC; HGNC:10411; RPS24.
DR HPA; HPA003364; -.
DR MIM; 602412; gene.
DR MIM; 610629; phenotype.
DR neXtProt; NX_P62847; -.
DR Orphanet; 124; Blackfan-Diamond anemia.
DR PharmGKB; PA34815; -.
DR eggNOG; COG2004; -.
DR HOGENOM; HOG000186306; -.
DR HOVERGEN; HBG000969; -.
DR InParanoid; P62847; -.
DR KO; K02974; -.
DR OMA; TENREQC; -.
DR OrthoDB; EOG7PS1J8; -.
DR PhylomeDB; P62847; -.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_17015; Metabolism of proteins.
DR Reactome; REACT_1762; 3' -UTR-mediated translational regulation.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; RPS24; human.
DR GeneWiki; RPS24; -.
DR GenomeRNAi; 6229; -.
DR NextBio; 24179; -.
DR PRO; PR:P62847; -.
DR ArrayExpress; P62847; -.
DR Bgee; P62847; -.
DR CleanEx; HS_RPS24; -.
DR Genevestigator; P62847; -.
DR GO; GO:0022627; C:cytosolic small ribosomal subunit; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IBA:RefGenome.
DR GO; GO:0000166; F:nucleotide binding; IEA:InterPro.
DR GO; GO:0003735; F:structural constituent of ribosome; NAS:UniProtKB.
DR GO; GO:0031369; F:translation initiation factor binding; ISS:UniProtKB.
DR GO; GO:0034101; P:erythrocyte homeostasis; IMP:UniProtKB.
DR GO; GO:0000462; P:maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA); IBA:RefGenome.
DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; TAS:Reactome.
DR GO; GO:0006614; P:SRP-dependent cotranslational protein targeting to membrane; TAS:Reactome.
DR GO; GO:0006414; P:translational elongation; TAS:Reactome.
DR GO; GO:0006413; P:translational initiation; TAS:Reactome.
DR GO; GO:0006415; P:translational termination; TAS:Reactome.
DR GO; GO:0019083; P:viral transcription; TAS:Reactome.
DR Gene3D; 3.30.70.330; -; 1.
DR HAMAP; MF_00545; Ribosomal_S24e; 1; -.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait.
DR InterPro; IPR012678; Ribosomal_L23/L15e_core_dom.
DR InterPro; IPR001976; Ribosomal_S24e.
DR InterPro; IPR018098; Ribosomal_S24e_CS.
DR PANTHER; PTHR10496; PTHR10496; 1.
DR Pfam; PF01282; Ribosomal_S24e; 1.
DR ProDom; PD006052; Ribosomal_S24e; 1.
DR SUPFAM; SSF54189; SSF54189; 1.
DR PROSITE; PS00529; RIBOSOMAL_S24E; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Diamond-Blackfan anemia; Direct protein sequencing; Phosphoprotein;
KW Reference proteome; Ribonucleoprotein; Ribosomal protein.
FT CHAIN 1 133 40S ribosomal protein S24.
FT /FTId=PRO_0000137623.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 9 9 Phosphothreonine.
FT VAR_SEQ 131 133 Missing (in isoform 2).
FT /FTId=VSP_005724.
FT VAR_SEQ 131 133 PKE -> KK (in isoform 3).
FT /FTId=VSP_039113.
FT VAR_SEQ 131 133 PKE -> MRELGLGVQALGRISQEERCTDVKNSKARESRGV
FT VWQVEVPGPWSVWTCGRLRRGCGKYLQVAVTWRKTENREQC
FT CQACLLERALVRNGAFMSPASPAPAGSPHPVDGDLVLHLPE
FT ALSATLTLSPHIQAINKSFGPFFEIHQESSCFSPPSCLSGL
FT GH (in isoform 4).
FT /FTId=VSP_045672.
SQ SEQUENCE 133 AA; 15423 MW; CE9065C0764D60A6 CRC64;
MNDTVTIRTR KFMTNRLLQR KQMVIDVLHP GKATVPKTEI REKLAKMYKT TPDVIFVFGF
RTHFGGGKTT GFGMIYDSLD YAKKNEPKHR LARHGLYEKK KTSRKQRKER KNRMKKVRGT
AKANVGAGKK PKE
//
MIM
602412
*RECORD*
*FIELD* NO
602412
*FIELD* TI
*602412 RIBOSOMAL PROTEIN S24; RPS24
*FIELD* TX
DESCRIPTION
The RPS24 gene encodes a protein involved in ribosomal RNA biogenesis
read more(summary by Choesmel et al., 2008).
CLONING
Eukaryotic ribosomes are composed of 4 RNA species (see 180450) and at
least 80 proteins. Brown et al. (1990) isolated a human ribosomal
protein gene encoding a predicted 133-amino acid protein by probing a
fibrosarcoma cDNA library with a ribosomal protein gene from Chinese
hamster. By comparing the in vitro translation product with S24 from
purified ribosomes on 2-dimensional gels, Brown et al. (1990) showed
that the gene encodes the 40S ribosomal subunit protein S24 (RPS24).
GENE STRUCTURE
Xu and Roufa (1996) reported that RPS24 is organized into 6 exons and is
differentially spliced to yield 2 isoforms, S24a and S24c, that are
present in varying ratios in different tissues.
MAPPING
Jones et al. (1997) used PCR of radiation and somatic cell hybrid panels
to map the RPS24 gene to 10q22-q23. Kenmochi et al. (1998) confirmed the
RPS24 mapping assignment reported by Jones et al. (1997).
GENE FUNCTION
Choesmel et al. (2008) demonstrated that RPS24 is required for the
pre-rRNA processing at the 5-prime external transcribed spacer (ETS) of
the 45S rRNA precursor molecule.
BIOCHEMICAL FEATURES
- Crystal Structure
Choesmel et al. (2008) determined the crystal structure of the P. abyssi
RPS24e protein, which is homologous to human RPS24. The protein is built
around a 4-stranded anti-parallel beta-sheet surrounded by 3 short
alpha-helices. It shows homology to the prokaryotic ribosomal protein
L23, which is a component of the large ribosomal subunit.
MOLECULAR GENETICS
Diamond-Blackfan anemia (DBA) is a rare congenital red cell aplasia
characterized by anemia, bone marrow erythroblastopenia, and congenital
anomalies. In approximately 25% of probands, heterozygous mutations in
the ribosomal protein S19 gene (RPS19; 603474) have been found; see DBA1
(105650). Gazda et al. (2006) reported identification of de novo
nonsense and splice site mutations in another ribosomal protein, RPS24
(602412.0001-602412.0003), in approximately 2% of RPS19
mutation-negative probands with Diamond-Blackfan anemia (DBA3; 610629).
This finding strongly suggested that DBA is a disorder of ribosome
synthesis and that mutations in other ribosomal proteins or associated
genes that lead to disrupted ribosomal biogenesis and/or function may
also cause DBA.
Choesmel et al. (2008) found that lymphoblastoid cells derived from DBA3
patients with RPS24 mutations (602412.0001-612412.0003) had altered
pre-rRNA processing, with lower levels of 41S pre-rRNA and accumulation
of the 30S species, resulting in a lower 41S/30S ratio compared to
controls. There was also less 21S and 18S-E pre-rRNA compared to
controls, but the 21S/18S-E ratio was similar to controls. HeLa cells
with siRNA against RPS24 showed a loss of free 40S ribosomal subunits
and an accumulation of 60S subunits, indicating that RPS24 is essential
for the production of the small ribosomal subunit 40S. Pulse-chase
labeling and Northern blot studies of siRNA-knockdown cells showed lack
of formation of 41S, 21S, and 18S-E pre-rRNA, although 28S was normal
and 30S was increased. These findings suggested inhibition of cleavage
at the 5-prime external transcribed spacer (ETS), as well as blocking of
the subsequent processing of internal spacer-1 (ITS1) at the 3-prime end
of the 18S rRNA. The pattern of the 60S rRNA subunit was normal, as were
patterns of 28S and 5.8S rRNAs. RPS19 was also decreased, likely due to
impaired synthesis of the 40S subunit. The pattern resulting from RPS24
depletion was similar to that of RPS19 depletion, in that depletion of
RPS19 results in delayed maturation of the 40S subunit (Flygare et al.,
2007). However, RPS19 depletion resulted in increased 41S and 21S
pre-rRNAs levels, consistent with a defect in processing at ITS1.
Studies combining deletions of RPS24 and RPS19 indicated that the 2
exert interdependent functions in pre-rRNA processing. Choesmel et al.
(2008) concluded that mutations in the RPS24 gene result in
haploinsufficiency, and that the pathogenesis of DBA is related to
defective ribosome biogenesis, which may result in apoptosis of rapidly
proliferating cells such as erythroid precursors.
Landowski et al. (2013) performed array CGH for copy number variation in
87 probands with Diamond-Blackfan anemia who were negative for mutation
in 10 known DBA-associated ribosomal protein genes and identified a
large de novo deletion in the RPS24 gene (602412.0004) in a
steroid-dependent male patient.
*FIELD* AV
.0001
DIAMOND-BLACKFAN ANEMIA 3
RPS24, GLN106TER
In a family with Diamond-Blackfan anemia (DBA3; 610629) in an autosomal
dominant pedigree pattern, Gazda et al. (2006) found a heterozygous
transition in exon 4 of the RPS24 gene, 316C-T, in affected individuals
that gave rise to a substitution of a stop codon for gln106 (Q106X).
Three members of the family were affected. Older members presented with
severe anemia and were dependent on small doses of steroid. Another
patient had been in steroid-induced remission since childhood and
presented with webbed neck.
.0002
DIAMOND-BLACKFAN ANEMIA 3
RPS24, ARG16TER
In a sporadic case of Diamond-Blackfan anemia (DBA3; 610629), Gazda et
al. (2006) identified a nonsense mutation, arg16 to stop, in the RPS24
gene. The amino acid substitution arose from a C-to-T transition at
nucleotide 46 in exon 2.
.0003
DIAMOND-BLACKFAN ANEMIA 3
RPS24, DEL/INS
In a family with 2 members affected by Diamond-Blackfan anemia (DBA3;
610629), Gazda et al. (2006) identified a deletion/insertion at the
intron 1/exon 2 boundary of RPS24 that resulted in skipping of exon 2
with deletion of 22 amino acids.
.0004
DIAMOND-BLACKFAN ANEMIA 3
RPS24, 5,134-BP DEL
In a steroid-dependent male patient with Diamond-Blackfan anemia (DBA3;
610629), Landowski et al. (2013) identified heterozygosity for a de novo
5,134-bp deletion at Chr10:79,460,166-79,465,299 (NCBI36), containing
exons 1 and 2 as well as part of exon 3 of the RPS24 gene. Validation
using mPCR assay showed confirmed reduction of PCR product for exons 1
to 3; mPCR in his unaffected parents showed ratios similar to controls,
indicating that the deletion occurred de novo.
*FIELD* RF
1. Brown, S. J.; Jewell, A.; Maki, C. G.; Roufa, D. J.: A cDNA encoding
human ribosomal protein S24. Gene 91: 293-296, 1990.
2. Choesmel, V.; Fribourg, S.; Aguissa-Toure, A.-H.; Pinaud, N.; Legrand,
P.; Gazda, H. T.; Gleizes, P.-E.: Mutation of ribosomal protein RPS24
in Diamond-Blackfan anemia results in a ribosome biogenesis disorder. Hum.
Molec. Genet. 17: 1253-1263, 2008.
3. Flygare, J.; Aspesi, A.; Bailey, J. C.; Miyake, K.; Caffrey, J.
M.; Karlsson, S.; Ellis, S. R.: Human RPS19, the gene mutated in
Diamond-Blackfan anemia, encodes a ribosomal protein required for
the maturation of 40S ribosomal subunits. Blood 109: 980-986, 2007.
4. Gazda, H. T.; Grabowska, A.; Merida-Long, L. B.; Latawiec, E.;
Schneider, H. E.; Lipton, J. M.; Vlachos, A.; Atsidaftos, E.; Ball,
S. E.; Orfali, K. A.; Niewiadomska, E.; Da Costa, L.; and 11 others
: Ribosomal protein S24 gene is mutated in Diamond-Blackfan anemia. Am.
J. Hum. Genet. 79: 1110-1118, 2006.
5. Jones, A.-M.; Marzella, R.; Rocchi, M.; Hewitt, J. E.: Mapping
of the human ribosomal small subunit protein gene RPS24 to the chromosome
10q22-q23 boundary. Genomics 39: 121-122, 1997.
6. Kenmochi, N.; Kawaguchi, T.; Rozen, S.; Davis, E.; Goodman, N.;
Hudson, T. J.; Tanaka, T.; Page, D. C.: A map of 75 human ribosomal
protein genes. Genome Res. 8: 509-523, 1998.
7. Landowski, M.; O'Donohue, M.-F.; Buros, C.; Ghazvinian, R.; Montel-Lehry,
N.; Vlachos, A.; Sieff, C. A.; Newburger, P. E.; Niewiadomska, E.;
Matysiak, M.; Glader, B.; Atsidaftos, E.; Lipton, J. M.; Beggs, A.
H.; Gleizes, P.-E.; Gazda, H. T.: Novel deletion of RPL15 identified
by array-comparative genomic hybridization in Diamond-Blackfan anemia. Hum.
Genet. 132: 1265-1274, 2013.
8. Xu, W.-B.; Roufa, D. J.: The gene encoding human ribosomal protein
S24 and tissue-specific expression of differentially spliced mRNAs. Gene 169:
257-262, 1996.
*FIELD* CN
Marla J. F. O'Neill - updated: 11/27/2013
Cassandra L. Kniffin - updated: 2/20/2013
Victor A. McKusick - updated: 11/28/2006
Patti M. Sherman - updated: 4/6/1999
*FIELD* CD
Rebekah S. Rasooly: 3/3/1998
*FIELD* ED
carol: 12/02/2013
mcolton: 11/27/2013
carol: 2/20/2013
ckniffin: 2/20/2013
alopez: 12/5/2006
terry: 11/28/2006
carol: 4/16/1999
psherman: 4/6/1999
alopez: 3/3/1998
*RECORD*
*FIELD* NO
602412
*FIELD* TI
*602412 RIBOSOMAL PROTEIN S24; RPS24
*FIELD* TX
DESCRIPTION
The RPS24 gene encodes a protein involved in ribosomal RNA biogenesis
read more(summary by Choesmel et al., 2008).
CLONING
Eukaryotic ribosomes are composed of 4 RNA species (see 180450) and at
least 80 proteins. Brown et al. (1990) isolated a human ribosomal
protein gene encoding a predicted 133-amino acid protein by probing a
fibrosarcoma cDNA library with a ribosomal protein gene from Chinese
hamster. By comparing the in vitro translation product with S24 from
purified ribosomes on 2-dimensional gels, Brown et al. (1990) showed
that the gene encodes the 40S ribosomal subunit protein S24 (RPS24).
GENE STRUCTURE
Xu and Roufa (1996) reported that RPS24 is organized into 6 exons and is
differentially spliced to yield 2 isoforms, S24a and S24c, that are
present in varying ratios in different tissues.
MAPPING
Jones et al. (1997) used PCR of radiation and somatic cell hybrid panels
to map the RPS24 gene to 10q22-q23. Kenmochi et al. (1998) confirmed the
RPS24 mapping assignment reported by Jones et al. (1997).
GENE FUNCTION
Choesmel et al. (2008) demonstrated that RPS24 is required for the
pre-rRNA processing at the 5-prime external transcribed spacer (ETS) of
the 45S rRNA precursor molecule.
BIOCHEMICAL FEATURES
- Crystal Structure
Choesmel et al. (2008) determined the crystal structure of the P. abyssi
RPS24e protein, which is homologous to human RPS24. The protein is built
around a 4-stranded anti-parallel beta-sheet surrounded by 3 short
alpha-helices. It shows homology to the prokaryotic ribosomal protein
L23, which is a component of the large ribosomal subunit.
MOLECULAR GENETICS
Diamond-Blackfan anemia (DBA) is a rare congenital red cell aplasia
characterized by anemia, bone marrow erythroblastopenia, and congenital
anomalies. In approximately 25% of probands, heterozygous mutations in
the ribosomal protein S19 gene (RPS19; 603474) have been found; see DBA1
(105650). Gazda et al. (2006) reported identification of de novo
nonsense and splice site mutations in another ribosomal protein, RPS24
(602412.0001-602412.0003), in approximately 2% of RPS19
mutation-negative probands with Diamond-Blackfan anemia (DBA3; 610629).
This finding strongly suggested that DBA is a disorder of ribosome
synthesis and that mutations in other ribosomal proteins or associated
genes that lead to disrupted ribosomal biogenesis and/or function may
also cause DBA.
Choesmel et al. (2008) found that lymphoblastoid cells derived from DBA3
patients with RPS24 mutations (602412.0001-612412.0003) had altered
pre-rRNA processing, with lower levels of 41S pre-rRNA and accumulation
of the 30S species, resulting in a lower 41S/30S ratio compared to
controls. There was also less 21S and 18S-E pre-rRNA compared to
controls, but the 21S/18S-E ratio was similar to controls. HeLa cells
with siRNA against RPS24 showed a loss of free 40S ribosomal subunits
and an accumulation of 60S subunits, indicating that RPS24 is essential
for the production of the small ribosomal subunit 40S. Pulse-chase
labeling and Northern blot studies of siRNA-knockdown cells showed lack
of formation of 41S, 21S, and 18S-E pre-rRNA, although 28S was normal
and 30S was increased. These findings suggested inhibition of cleavage
at the 5-prime external transcribed spacer (ETS), as well as blocking of
the subsequent processing of internal spacer-1 (ITS1) at the 3-prime end
of the 18S rRNA. The pattern of the 60S rRNA subunit was normal, as were
patterns of 28S and 5.8S rRNAs. RPS19 was also decreased, likely due to
impaired synthesis of the 40S subunit. The pattern resulting from RPS24
depletion was similar to that of RPS19 depletion, in that depletion of
RPS19 results in delayed maturation of the 40S subunit (Flygare et al.,
2007). However, RPS19 depletion resulted in increased 41S and 21S
pre-rRNAs levels, consistent with a defect in processing at ITS1.
Studies combining deletions of RPS24 and RPS19 indicated that the 2
exert interdependent functions in pre-rRNA processing. Choesmel et al.
(2008) concluded that mutations in the RPS24 gene result in
haploinsufficiency, and that the pathogenesis of DBA is related to
defective ribosome biogenesis, which may result in apoptosis of rapidly
proliferating cells such as erythroid precursors.
Landowski et al. (2013) performed array CGH for copy number variation in
87 probands with Diamond-Blackfan anemia who were negative for mutation
in 10 known DBA-associated ribosomal protein genes and identified a
large de novo deletion in the RPS24 gene (602412.0004) in a
steroid-dependent male patient.
*FIELD* AV
.0001
DIAMOND-BLACKFAN ANEMIA 3
RPS24, GLN106TER
In a family with Diamond-Blackfan anemia (DBA3; 610629) in an autosomal
dominant pedigree pattern, Gazda et al. (2006) found a heterozygous
transition in exon 4 of the RPS24 gene, 316C-T, in affected individuals
that gave rise to a substitution of a stop codon for gln106 (Q106X).
Three members of the family were affected. Older members presented with
severe anemia and were dependent on small doses of steroid. Another
patient had been in steroid-induced remission since childhood and
presented with webbed neck.
.0002
DIAMOND-BLACKFAN ANEMIA 3
RPS24, ARG16TER
In a sporadic case of Diamond-Blackfan anemia (DBA3; 610629), Gazda et
al. (2006) identified a nonsense mutation, arg16 to stop, in the RPS24
gene. The amino acid substitution arose from a C-to-T transition at
nucleotide 46 in exon 2.
.0003
DIAMOND-BLACKFAN ANEMIA 3
RPS24, DEL/INS
In a family with 2 members affected by Diamond-Blackfan anemia (DBA3;
610629), Gazda et al. (2006) identified a deletion/insertion at the
intron 1/exon 2 boundary of RPS24 that resulted in skipping of exon 2
with deletion of 22 amino acids.
.0004
DIAMOND-BLACKFAN ANEMIA 3
RPS24, 5,134-BP DEL
In a steroid-dependent male patient with Diamond-Blackfan anemia (DBA3;
610629), Landowski et al. (2013) identified heterozygosity for a de novo
5,134-bp deletion at Chr10:79,460,166-79,465,299 (NCBI36), containing
exons 1 and 2 as well as part of exon 3 of the RPS24 gene. Validation
using mPCR assay showed confirmed reduction of PCR product for exons 1
to 3; mPCR in his unaffected parents showed ratios similar to controls,
indicating that the deletion occurred de novo.
*FIELD* RF
1. Brown, S. J.; Jewell, A.; Maki, C. G.; Roufa, D. J.: A cDNA encoding
human ribosomal protein S24. Gene 91: 293-296, 1990.
2. Choesmel, V.; Fribourg, S.; Aguissa-Toure, A.-H.; Pinaud, N.; Legrand,
P.; Gazda, H. T.; Gleizes, P.-E.: Mutation of ribosomal protein RPS24
in Diamond-Blackfan anemia results in a ribosome biogenesis disorder. Hum.
Molec. Genet. 17: 1253-1263, 2008.
3. Flygare, J.; Aspesi, A.; Bailey, J. C.; Miyake, K.; Caffrey, J.
M.; Karlsson, S.; Ellis, S. R.: Human RPS19, the gene mutated in
Diamond-Blackfan anemia, encodes a ribosomal protein required for
the maturation of 40S ribosomal subunits. Blood 109: 980-986, 2007.
4. Gazda, H. T.; Grabowska, A.; Merida-Long, L. B.; Latawiec, E.;
Schneider, H. E.; Lipton, J. M.; Vlachos, A.; Atsidaftos, E.; Ball,
S. E.; Orfali, K. A.; Niewiadomska, E.; Da Costa, L.; and 11 others
: Ribosomal protein S24 gene is mutated in Diamond-Blackfan anemia. Am.
J. Hum. Genet. 79: 1110-1118, 2006.
5. Jones, A.-M.; Marzella, R.; Rocchi, M.; Hewitt, J. E.: Mapping
of the human ribosomal small subunit protein gene RPS24 to the chromosome
10q22-q23 boundary. Genomics 39: 121-122, 1997.
6. Kenmochi, N.; Kawaguchi, T.; Rozen, S.; Davis, E.; Goodman, N.;
Hudson, T. J.; Tanaka, T.; Page, D. C.: A map of 75 human ribosomal
protein genes. Genome Res. 8: 509-523, 1998.
7. Landowski, M.; O'Donohue, M.-F.; Buros, C.; Ghazvinian, R.; Montel-Lehry,
N.; Vlachos, A.; Sieff, C. A.; Newburger, P. E.; Niewiadomska, E.;
Matysiak, M.; Glader, B.; Atsidaftos, E.; Lipton, J. M.; Beggs, A.
H.; Gleizes, P.-E.; Gazda, H. T.: Novel deletion of RPL15 identified
by array-comparative genomic hybridization in Diamond-Blackfan anemia. Hum.
Genet. 132: 1265-1274, 2013.
8. Xu, W.-B.; Roufa, D. J.: The gene encoding human ribosomal protein
S24 and tissue-specific expression of differentially spliced mRNAs. Gene 169:
257-262, 1996.
*FIELD* CN
Marla J. F. O'Neill - updated: 11/27/2013
Cassandra L. Kniffin - updated: 2/20/2013
Victor A. McKusick - updated: 11/28/2006
Patti M. Sherman - updated: 4/6/1999
*FIELD* CD
Rebekah S. Rasooly: 3/3/1998
*FIELD* ED
carol: 12/02/2013
mcolton: 11/27/2013
carol: 2/20/2013
ckniffin: 2/20/2013
alopez: 12/5/2006
terry: 11/28/2006
carol: 4/16/1999
psherman: 4/6/1999
alopez: 3/3/1998
MIM
610629
*RECORD*
*FIELD* NO
610629
*FIELD* TI
#610629 DIAMOND-BLACKFAN ANEMIA 3; DBA3
*FIELD* TX
A number sign (#) is used with this entry because Diamond-Blackfan
read moreanemia-3 (DBA3) is caused by heterozygous mutation in the ribosomal
protein S24 gene (RPS24; 602412) on chromosome 10q22-q23.
For a general phenotypic description and a discussion of genetic
heterogeneity of Diamond-Blackfan anemia (DBA), see 105650.
MAPPING
Gazda et al. (2006) performed a genomewide linkage screen on an
extensive family with Diamond-Blackfan anemia. The found evidence for
linkage to a 5.8-Mb region on chromosome 10 as well as to regions on
chromosomes 8q (17.5 Mb) and 6 (3.8 Mb).
MOLECULAR GENETICS
In affected members of a family segregating Diamond-Blackfan anemia,
Gazda et al. (2006) detected no mutations in the RPS20 (603682) or RPL7
(604166) genes in the critical region on 8q, but they identified a
heterozygous nonsense mutation in exon 4 of the RPS24 gene on chromosome
10q22-q23 (602412.0001). Gazda et al. (2006) subsequently sequenced
RPS24 in 185 unrelated probands with DBA, representing both familial and
sporadic cases. They found another nonsense mutation in exon 2 in a
transfusion-dependent patient (602412.0002), and a deletion/insertion
mutation at the intron 1/exon 2 boundary in a steroid-dependent patient
and his father (602412.0003). The father did not have any signs of
anemia at that time; however, during childhood he presented with
multiple heart anomalies, elevated erythrocyte adenosine deaminase
activity (eADA), and moderate anemia, which was resistant to iron
treatment and at that time was attributed to his cardiac abnormalities.
No RPS24 mutation was found among 210 control individuals. Gazda et al.
(2006) concluded that the RPS24 gene is mutated in approximately 2% of
RPS19 (603474) mutation-negative DBA probands.
Landowski et al. (2013) performed array CGH for copy number variation in
87 probands with Diamond-Blackfan anemia who were negative for mutation
in 10 known DBA-associated ribosomal protein genes and identified a
large de novo deletion in the RPS24 gene (602412.0004) in a
steroid-dependent male patient.
PATHOGENESIS
Choesmel et al. (2008) found that lymphoblastoid cells derived from DBA3
patients with RPS24 mutations (602412.0001-612412.0003) had altered
pre-rRNA processing, with lower levels of 41S pre-rRNA and accumulation
of the 30S species, resulting in a lower 41S/30S ratio compared to that
in controls. There was also less 21S and 18S-E pre-rRNA compared to
controls, but the 21S/18S-E ratio was similar to that in controls. HeLa
cells with siRNA against RPS24 showed a loss of free 40S ribosomal
subunits and an accumulation of 60S subunits, indicating that RPS24 is
essential for the production of the small ribosomal subunit 40S.
Pulse-chase labeling and Northern blot studies of siRNA-knockdown cells
showed lack of formation of 41S, 21S, and 18S-E pre-rRNA, although 28S
was normal and 30S was increased. These findings suggested inhibition of
cleavage at the 5-prime external transcribed spacer (ETS), as well as
blocking of the subsequent processing of internal spacer-1 (ITS1) at the
3-prime end of the 18S rRNA. The pattern of the 60S rRNA subunit was
normal, as were patterns of 28S and 5.8S rRNAs. RPS19 was also
decreased, likely due to impaired synthesis of the 40S subunit. The
pattern resulting from RPS24 depletion was similar to that of RPS19
depletion, in that depletion of RPS19 results in delayed maturation of
the 40S subunit (Flygare et al., 2007). However, RPS19 depletion
resulted in increased 41S and 21S pre-rRNAs levels, consistent with a
defect in processing at ITS1. Studies combining deletions of RPS24 and
RPS19 indicated that the 2 exert interdependent functions in pre-rRNA
processing. Choesmel et al. (2008) concluded that mutations in the RPS24
gene result in haploinsufficiency, and that the pathogenesis of DBA is
related to defective ribosome biogenesis, which may result in apoptosis
of rapidly proliferating cells such as erythroid precursors.
*FIELD* RF
1. Choesmel, V.; Fribourg, S.; Aguissa-Toure, A.-H.; Pinaud, N.; Legrand,
P.; Gazda, H. T.; Gleizes, P.-E.: Mutation of ribosomal protein RPS24
in Diamond-Blackfan anemia results in a ribosome biogenesis disorder. Hum.
Molec. Genet. 17: 1253-1263, 2008.
2. Flygare, J.; Aspesi, A.; Bailey, J. C.; Miyake, K.; Caffrey, J.
M.; Karlsson, S.; Ellis, S. R.: Human RPS19, the gene mutated in
Diamond-Blackfan anemia, encodes a ribosomal protein required for
the maturation of 40S ribosomal subunits. Blood 109: 980-986, 2007.
3. Gazda, H. T.; Grabowska, A.; Merida-Long, L. B.; Latawiec, E.;
Schneider, H. E.; Lipton, J. M.; Vlachos, A.; Atsidaftos, E.; Ball,
S. E.; Orfali, K. A.; Niewiadomska, E.; Da Costa, L.; and 11 others
: Ribosomal protein S24 gene is mutated in Diamond-Blackfan anemia. Am.
J. Hum. Genet. 79: 1110-1118, 2006.
4. Landowski, M.; O'Donohue, M.-F.; Buros, C.; Ghazvinian, R.; Montel-Lehry,
N.; Vlachos, A.; Sieff, C. A.; Newburger, P. E.; Niewiadomska, E.;
Matysiak, M.; Glader, B.; Atsidaftos, E.; Lipton, J. M.; Beggs, A.
H.; Gleizes, P.-E.; Gazda, H. T.: Novel deletion of RPL15 identified
by array-comparative genomic hybridization in Diamond-Blackfan anemia. Hum.
Genet. 132: 1265-1274, 2013.
*FIELD* CN
Marla J. F. O'Neill - updated: 11/27/2013
Cassandra L. Kniffin - updated: 2/20/2013
*FIELD* CD
Anne M. Stumpf: 12/5/2006
*FIELD* ED
carol: 12/02/2013
mcolton: 11/27/2013
carol: 2/20/2013
ckniffin: 2/20/2013
carol: 11/1/2012
carol: 4/13/2011
alopez: 12/5/2006
*RECORD*
*FIELD* NO
610629
*FIELD* TI
#610629 DIAMOND-BLACKFAN ANEMIA 3; DBA3
*FIELD* TX
A number sign (#) is used with this entry because Diamond-Blackfan
read moreanemia-3 (DBA3) is caused by heterozygous mutation in the ribosomal
protein S24 gene (RPS24; 602412) on chromosome 10q22-q23.
For a general phenotypic description and a discussion of genetic
heterogeneity of Diamond-Blackfan anemia (DBA), see 105650.
MAPPING
Gazda et al. (2006) performed a genomewide linkage screen on an
extensive family with Diamond-Blackfan anemia. The found evidence for
linkage to a 5.8-Mb region on chromosome 10 as well as to regions on
chromosomes 8q (17.5 Mb) and 6 (3.8 Mb).
MOLECULAR GENETICS
In affected members of a family segregating Diamond-Blackfan anemia,
Gazda et al. (2006) detected no mutations in the RPS20 (603682) or RPL7
(604166) genes in the critical region on 8q, but they identified a
heterozygous nonsense mutation in exon 4 of the RPS24 gene on chromosome
10q22-q23 (602412.0001). Gazda et al. (2006) subsequently sequenced
RPS24 in 185 unrelated probands with DBA, representing both familial and
sporadic cases. They found another nonsense mutation in exon 2 in a
transfusion-dependent patient (602412.0002), and a deletion/insertion
mutation at the intron 1/exon 2 boundary in a steroid-dependent patient
and his father (602412.0003). The father did not have any signs of
anemia at that time; however, during childhood he presented with
multiple heart anomalies, elevated erythrocyte adenosine deaminase
activity (eADA), and moderate anemia, which was resistant to iron
treatment and at that time was attributed to his cardiac abnormalities.
No RPS24 mutation was found among 210 control individuals. Gazda et al.
(2006) concluded that the RPS24 gene is mutated in approximately 2% of
RPS19 (603474) mutation-negative DBA probands.
Landowski et al. (2013) performed array CGH for copy number variation in
87 probands with Diamond-Blackfan anemia who were negative for mutation
in 10 known DBA-associated ribosomal protein genes and identified a
large de novo deletion in the RPS24 gene (602412.0004) in a
steroid-dependent male patient.
PATHOGENESIS
Choesmel et al. (2008) found that lymphoblastoid cells derived from DBA3
patients with RPS24 mutations (602412.0001-612412.0003) had altered
pre-rRNA processing, with lower levels of 41S pre-rRNA and accumulation
of the 30S species, resulting in a lower 41S/30S ratio compared to that
in controls. There was also less 21S and 18S-E pre-rRNA compared to
controls, but the 21S/18S-E ratio was similar to that in controls. HeLa
cells with siRNA against RPS24 showed a loss of free 40S ribosomal
subunits and an accumulation of 60S subunits, indicating that RPS24 is
essential for the production of the small ribosomal subunit 40S.
Pulse-chase labeling and Northern blot studies of siRNA-knockdown cells
showed lack of formation of 41S, 21S, and 18S-E pre-rRNA, although 28S
was normal and 30S was increased. These findings suggested inhibition of
cleavage at the 5-prime external transcribed spacer (ETS), as well as
blocking of the subsequent processing of internal spacer-1 (ITS1) at the
3-prime end of the 18S rRNA. The pattern of the 60S rRNA subunit was
normal, as were patterns of 28S and 5.8S rRNAs. RPS19 was also
decreased, likely due to impaired synthesis of the 40S subunit. The
pattern resulting from RPS24 depletion was similar to that of RPS19
depletion, in that depletion of RPS19 results in delayed maturation of
the 40S subunit (Flygare et al., 2007). However, RPS19 depletion
resulted in increased 41S and 21S pre-rRNAs levels, consistent with a
defect in processing at ITS1. Studies combining deletions of RPS24 and
RPS19 indicated that the 2 exert interdependent functions in pre-rRNA
processing. Choesmel et al. (2008) concluded that mutations in the RPS24
gene result in haploinsufficiency, and that the pathogenesis of DBA is
related to defective ribosome biogenesis, which may result in apoptosis
of rapidly proliferating cells such as erythroid precursors.
*FIELD* RF
1. Choesmel, V.; Fribourg, S.; Aguissa-Toure, A.-H.; Pinaud, N.; Legrand,
P.; Gazda, H. T.; Gleizes, P.-E.: Mutation of ribosomal protein RPS24
in Diamond-Blackfan anemia results in a ribosome biogenesis disorder. Hum.
Molec. Genet. 17: 1253-1263, 2008.
2. Flygare, J.; Aspesi, A.; Bailey, J. C.; Miyake, K.; Caffrey, J.
M.; Karlsson, S.; Ellis, S. R.: Human RPS19, the gene mutated in
Diamond-Blackfan anemia, encodes a ribosomal protein required for
the maturation of 40S ribosomal subunits. Blood 109: 980-986, 2007.
3. Gazda, H. T.; Grabowska, A.; Merida-Long, L. B.; Latawiec, E.;
Schneider, H. E.; Lipton, J. M.; Vlachos, A.; Atsidaftos, E.; Ball,
S. E.; Orfali, K. A.; Niewiadomska, E.; Da Costa, L.; and 11 others
: Ribosomal protein S24 gene is mutated in Diamond-Blackfan anemia. Am.
J. Hum. Genet. 79: 1110-1118, 2006.
4. Landowski, M.; O'Donohue, M.-F.; Buros, C.; Ghazvinian, R.; Montel-Lehry,
N.; Vlachos, A.; Sieff, C. A.; Newburger, P. E.; Niewiadomska, E.;
Matysiak, M.; Glader, B.; Atsidaftos, E.; Lipton, J. M.; Beggs, A.
H.; Gleizes, P.-E.; Gazda, H. T.: Novel deletion of RPL15 identified
by array-comparative genomic hybridization in Diamond-Blackfan anemia. Hum.
Genet. 132: 1265-1274, 2013.
*FIELD* CN
Marla J. F. O'Neill - updated: 11/27/2013
Cassandra L. Kniffin - updated: 2/20/2013
*FIELD* CD
Anne M. Stumpf: 12/5/2006
*FIELD* ED
carol: 12/02/2013
mcolton: 11/27/2013
carol: 2/20/2013
ckniffin: 2/20/2013
carol: 11/1/2012
carol: 4/13/2011
alopez: 12/5/2006