ID SBDS_HUMAN Reviewed; 250 AA. AC Q9Y3A5; A8K0P4; Q96FX0; Q9NV53; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 4. DT 25-JAN-2012, entry version 103. DE RecName: Full=Ribosome maturation protein SBDS; DE AltName: Full=Shwachman-Bodian-Diamond syndrome protein; GN Name=SBDS; ORFNames=CGI-97; 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], AND VARIANTS SDS LYS-8; GLY-44; GLU-67; RP SER-87; THR-126; CYS-169 AND THR-212. RX MEDLINE=22397848; PubMed=12496757; DOI=10.1038/ng1062; RA Boocock G.R.B., Morrison J.A., Popovic M., Richards N., Ellis L., RA Durie P.R., Rommens J.M.; RT "Mutations in SBDS are associated with Shwachman-Diamond syndrome."; RL Nat. Genet. 33:97-101(2003). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX MEDLINE=20272150; PubMed=10810093; DOI=10.1101/gr.10.5.703; RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.; RT "Identification of novel human genes evolutionarily conserved in RT Caenorhabditis elegans by comparative proteomics."; RL Genome Res. 10:703-713(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain cortex, and Ovarian carcinoma; 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 [4] 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=PNS; 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 [6] RP PROTEIN SEQUENCE OF 2-19, CLEAVAGE OF INITIATOR METHIONINE, RP ACETYLATION AT SER-2, AND MASS SPECTROMETRY. RC TISSUE=Platelet; RA Bienvenut W.V., Claeys D.; RL Submitted (NOV-2005) to UniProtKB. RN [7] RP SUBCELLULAR LOCATION. RX PubMed=15860664; DOI=10.1182/blood-2005-02-0807; RA Austin K.M., Leary R.J., Shimamura A.; RT "The Shwachman-Diamond SBDS protein localizes to the nucleolus."; RL Blood 106:1253-1258(2005). RN [8] RP INTERACTION WITH NPM1 AND THE 60S RIBOSOMAL SUBUNIT, AND SUBCELLULAR RP LOCATION. RX PubMed=17475909; DOI=10.1182/blood-2007-02-075184; RA Ganapathi K.A., Austin K.M., Lee C.S., Dias A., Malsch M.M., Reed R., RA Shimamura A.; RT "The human Shwachman-Diamond syndrome protein, SBDS, associates with RT ribosomal RNA."; RL Blood 110:1458-1465(2007). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-124 AND TYR-128, AND RP MASS SPECTROMETRY. RC TISSUE=Cervix carcinoma; RX PubMed=17924679; DOI=10.1021/pr070152u; RA Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.; RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa RT cells and high confident phosphopeptide identification by cross- RT validation of MS/MS and MS/MS/MS spectra."; RL J. Proteome Res. 6:4150-4162(2007). RN [10] RP FUNCTION, AND INTERACTION WITH NIP7. RX PubMed=17643419; DOI=10.1016/j.yexcr.2007.06.024; RA Hesling C., Oliveira C.C., Castilho B.A., Zanchin N.I.; RT "The Shwachman-Bodian-Diamond syndrome associated protein interacts RT with HsNip7 and its down-regulation affects gene expression at the RT transcriptional and translational levels."; RL Exp. Cell Res. 313:4180-4195(2007). RN [11] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH RPA1; PRKDC AND RP THE 60S RIBOSOME SUBUNIT. RX PubMed=19602484; DOI=10.1093/hmg/ddp316; RA Ball H.L., Zhang B., Riches J.J., Gandhi R., Li J., Rommens J.M., RA Myers J.S.; RT "Shwachman-Bodian Diamond syndrome is a multi-functional protein RT implicated in cellular stress responses."; RL Hum. Mol. Genet. 18:3684-3695(2009). RN [12] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=19759903; DOI=10.1371/journal.pone.0007084; RA Orelio C., Verkuijlen P., Geissler J., van den Berg T.K., RA Kuijpers T.W.; RT "SBDS expression and localization at the mitotic spindle in human RT myeloid progenitors."; RL PLoS ONE 4:E7084-E7084(2009). RN [13] 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 [14] RP STRUCTURE BY NMR, AND RNA-BINDING. RX PubMed=20053358; DOI=10.1016/j.jmb.2009.12.039; RA de Oliveira J.F., Sforca M.L., Blumenschein T.M., Goldfeder M.B., RA Guimaraes B.G., Oliveira C.C., Zanchin N.I., Zeri A.C.; RT "Structure, dynamics, and RNA interaction analysis of the human SBDS RT protein."; RL J. Mol. Biol. 396:1053-1069(2010). RN [15] RP STRUCTURE BY NMR, FUNCTION, CHARACTERIZATION OF VARIANT SDS THR-126, RP AND MUTAGENESIS OF LYS-151. RX PubMed=21536732; DOI=10.1101/gad.623011; RA Finch A.J., Hilcenko C., Basse N., Drynan L.F., Goyenechea B., RA Menne T.F., Gonzalez Fernandez A., Simpson P., D'Santos C.S., RA Arends M.J., Donadieu J., Bellanne-Chantelot C., Costanzo M., RA Boone C., McKenzie A.N., Freund S.M., Warren A.J.; RT "Uncoupling of GTP hydrolysis from eIF6 release on the ribosome causes RT Shwachman-Diamond syndrome."; RL Genes Dev. 25:917-929(2011). CC -!- FUNCTION: Required for the assembly of mature ribosomes and CC ribosome biogenesis. Together with EFTUD1, triggers the GTP- CC dependent release of EIF6 from 60S pre-ribosomes in the cytoplasm, CC thereby activating ribosomes for translation competence by CC allowing 80S ribosome assembly and facilitating EIF6 recycling to CC the nucleus, where it is required for 60S rRNA processing and CC nuclear export. Required for normal levels of protein synthesis. CC May play a role in cellular stress resistance. May play a role in CC cellular response to DNA damage. May play a role in cell CC proliferation. CC -!- SUBUNIT: Associates with the 60S ribosomal subunit. Interacts with CC NPM1, RPA1 and PRKDC. May interact with NIP7. CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus, nucleolus. Nucleus, CC nucleoplasm. Cytoplasm, cytoskeleton, spindle. Note=Primarily CC detected in the cytoplasm, and at low levels in nucleus and CC nucleolus (PubMed:19602484 and PubMed:17475909). Detected in the CC nucleolus during G1 and G2 phase of the cell cycle, and diffusely CC distributed in the nucleus during S phase. Detected at the mitotic CC spindle. Colocalizes with the microtubule organizing center during CC interphase (PubMed:19759903). CC -!- TISSUE SPECIFICITY: Widely expressed. CC -!- DISEASE: Defects in SBDS are the cause of Shwachman-Diamond CC syndrome (SDS) [MIM:260400]. SDS is an autosomal recessive CC disorder characterized by pancreatic exocrine insufficiency, CC hematologic dysfunction, and skeletal abnormalities. CC -!- SIMILARITY: Belongs to the SDO1/SBDS family. CC -!- WEB RESOURCE: Name=SBDSbase; Note=SBDS mutation db; CC URL="http://bioinf.uta.fi/SBDSbase/"; CC -!- WEB RESOURCE: Name=GeneReviews; CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/SBDS"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY169963; AAN77490.1; -; mRNA. DR EMBL; AF151855; AAD34092.1; -; mRNA. DR EMBL; AK001779; BAA91905.1; -; mRNA. DR EMBL; AK289609; BAF82298.1; -; mRNA. DR EMBL; CH471140; EAX07906.1; -; Genomic_DNA. DR EMBL; BC065700; AAH65700.1; -; mRNA. DR IPI; IPI00427330; -. DR RefSeq; NP_057122.2; NM_016038.2. DR UniGene; Hs.110445; -. DR PDB; 2KDO; NMR; -; A=1-250. DR PDB; 2L9N; NMR; -; A=1-250. DR PDBsum; 2KDO; -. DR PDBsum; 2L9N; -. DR ProteinModelPortal; Q9Y3A5; -. DR SMR; Q9Y3A5; 1-250. DR IntAct; Q9Y3A5; 1. DR STRING; Q9Y3A5; -. DR PhosphoSite; Q9Y3A5; -. DR DMDM; 28380824; -. DR PeptideAtlas; Q9Y3A5; -. DR PRIDE; Q9Y3A5; -. DR Ensembl; ENST00000246868; ENSP00000246868; ENSG00000126524. DR GeneID; 51119; -. DR KEGG; hsa:51119; -. DR UCSC; uc003tvm.1; human. DR CTD; 51119; -. DR GeneCards; GC07M066452; -. DR H-InvDB; HIX0006728; -. DR HGNC; HGNC:19440; SBDS. DR HPA; HPA028891; -. DR MIM; 260400; phenotype. DR MIM; 607444; gene. DR neXtProt; NX_Q9Y3A5; -. DR Orphanet; 88; Idiopathic aplastic anemia. DR Orphanet; 811; Shwachman-Diamond syndrome. DR PharmGKB; PA134978742; -. DR eggNOG; prNOG07966; -. DR GeneTree; ENSGT00390000008135; -. DR HOGENOM; HBG333702; -. DR HOVERGEN; HBG039762; -. DR InParanoid; Q9Y3A5; -. DR OMA; DPYLARD; -. DR OrthoDB; EOG40ZQZH; -. DR PhylomeDB; Q9Y3A5; -. DR NextBio; 53897; -. DR ArrayExpress; Q9Y3A5; -. DR Bgee; Q9Y3A5; -. DR CleanEx; HS_SBDS; -. DR Genevestigator; Q9Y3A5; -. DR GermOnline; ENSG00000126524; Homo sapiens. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0000922; C:spindle pole; IDA:UniProtKB. DR GO; GO:0008017; F:microtubule binding; IDA:UniProtKB. DR GO; GO:0043022; F:ribosome binding; IDA:UniProtKB. DR GO; GO:0019843; F:rRNA binding; IDA:UniProtKB. DR GO; GO:0048539; P:bone marrow development; IMP:UniProtKB. DR GO; GO:0030282; P:bone mineralization; IMP:UniProtKB. DR GO; GO:0030595; P:leukocyte chemotaxis; IDA:UniProtKB. DR GO; GO:0042256; P:mature ribosome assembly; IDA:UniProtKB. DR GO; GO:0043148; P:mitotic spindle stabilization; IDA:UniProtKB. DR GO; GO:0042273; P:ribosomal large subunit biogenesis; IBA:RefGenome. DR GO; GO:0006364; P:rRNA processing; IMP:UniProtKB. DR InterPro; IPR018978; Ribosome_mat_SBDS_C. DR InterPro; IPR018023; Ribosome_mat_SBDS_CS. DR InterPro; IPR019783; Ribosome_mat_SBDS_N. DR InterPro; IPR002140; Ribosome_maturation_pr_SBDS. DR KO; K14574; -. DR PANTHER; PTHR10927; SBDS; 1. DR Pfam; PF01172; SBDS; 1. DR Pfam; PF09377; SBDS_C; 1. DR SUPFAM; SSF89895; Ribosome_mat_SBDS_N; 1. DR TIGRFAMs; TIGR00291; RNA_SBDS; 1. DR PROSITE; PS01267; UPF0023; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Complete proteome; Cytoplasm; Cytoskeleton; KW Direct protein sequencing; Disease mutation; Nucleus; Phosphoprotein; KW Reference proteome; Ribosome biogenesis. FT INIT_MET 1 1 Removed. FT CHAIN 2 250 Ribosome maturation protein SBDS. FT /FTId=PRO_0000123762. FT MOD_RES 2 2 N-acetylserine. FT MOD_RES 124 124 Phosphothreonine. FT MOD_RES 128 128 Phosphotyrosine. FT VARIANT 8 8 N -> K (in SDS; dbSNP:rs28942099). FT /FTId=VAR_015390. FT VARIANT 44 44 E -> G (in SDS). FT /FTId=VAR_015391. FT VARIANT 67 67 K -> E (in SDS). FT /FTId=VAR_015392. FT VARIANT 87 87 I -> S (in SDS). FT /FTId=VAR_015393. FT VARIANT 126 126 R -> T (in SDS; strongly reduced release FT of EIF6 from pre-60S ribosome subunits). FT /FTId=VAR_015394. FT VARIANT 169 169 R -> C (in SDS). FT /FTId=VAR_015395. FT VARIANT 212 212 I -> T (in SDS). FT /FTId=VAR_015396. FT MUTAGEN 151 151 K->N: Strongly reduced release of EIF6 FT from pre-60S ribosome subunits. FT CONFLICT 41 43 SGV -> RAW (in Ref. 2; AAD34092). FT CONFLICT 89 89 T -> A (in Ref. 2; AAD34092). FT CONFLICT 105 105 E -> G (in Ref. 2; AAD34092). FT CONFLICT 114 114 I -> F (in Ref. 2; AAD34092). FT CONFLICT 126 126 R -> G (in Ref. 2; AAD34092). FT CONFLICT 143 143 S -> L (in Ref. 2; AAD34092). FT CONFLICT 146 146 T -> P (in Ref. 2; AAD34092). FT STRAND 14 21 FT STRAND 26 35 FT STRAND 56 58 FT HELIX 68 74 FT HELIX 80 89 FT STRAND 97 103 FT HELIX 107 116 FT HELIX 130 140 FT HELIX 150 164 FT STRAND 168 170 FT STRAND 174 176 FT TURN 187 189 FT HELIX 190 193 FT STRAND 196 200 FT STRAND 208 210 FT HELIX 217 227 FT STRAND 234 236 FT STRAND 240 242 SQ SEQUENCE 250 AA; 28764 MW; D35C43003C05F5A7 CRC64; MSIFTPTNQI RLTNVAVVRM KRAGKRFEIA CYKNKVVGWR SGVEKDLDEV LQTHSVFVNV SKGQVAKKED LISAFGTDDQ TEICKQILTK GEVQVSDKER HTQLEQMFRD IATIVADKCV NPETKRPYTV ILIERAMKDI HYSVKTNKST KQQALEVIKQ LKEKMKIERA HMRLRFILPV NEGKKLKEKL KPLIKVIESE DYGQQLEIVC LIDPGCFREI DELIKKETKG KGSLEVLNLK DVEEGDEKFE //