ID WDR46_HUMAN Reviewed; 610 AA. AC O15213; A6NDP5; Q5HYZ0; Q5STK5; Q5STR3; DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot. DT 30-NOV-2010, sequence version 3. DT 27-MAR-2024, entry version 189. DE RecName: Full=WD repeat-containing protein 46; DE AltName: Full=WD repeat-containing protein BING4; GN Name=WDR46; Synonyms=BING4, C6orf11; ORFNames=FP221; 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 [LARGE SCALE MRNA], AND VARIANT ALA-94. RX PubMed=15498874; DOI=10.1073/pnas.0404089101; RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X., RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.; RT "Large-scale cDNA transfection screening for genes related to cancer RT development and progression."; RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ALA-341. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-94. RC TISSUE=Lung; 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 [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-372, AND VARIANT ALA-94. RX PubMed=9545376; DOI=10.1006/jmbi.1998.1637; RA Herberg J.A., Beck S., Trowsdale J.; RT "TAPASIN, DAXX, RGL2, HKE2 and four new genes (BING 1, 3 to 5) form a dense RT cluster at the centromeric end of the MHC."; RL J. Mol. Biol. 277:839-857(1998). RN [5] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-41, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient RT phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-41, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [7] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH DDX21; NCL; NOP2 AND RP EBNA1BP2. RX PubMed=23848194; DOI=10.1111/gtc.12077; RA Hirai Y., Louvet E., Oda T., Kumeta M., Watanabe Y., Horigome T., RA Takeyasu K.; RT "Nucleolar scaffold protein, WDR46, determines the granular compartmental RT localization of nucleolin and DDX21."; RL Genes Cells 18:780-797(2013). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-41, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-41, AND IDENTIFICATION BY RP 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 [10] {ECO:0007744|PDB:7MQ8, ECO:0007744|PDB:7MQ9, ECO:0007744|PDB:7MQA} RP STRUCTURE BY ELECTRON MICROSCOPY (2.70 ANGSTROMS), FUNCTION, SUBUNIT, AND RP SUBCELLULAR LOCATION. RX PubMed=34516797; DOI=10.1126/science.abj5338; RA Singh S., Vanden Broeck A., Miller L., Chaker-Margot M., Klinge S.; RT "Nucleolar maturation of the human small subunit processome."; RL Science 373:eabj5338-eabj5338(2021). CC -!- FUNCTION: Scaffold component of the nucleolar structure. Required for CC localization of DDX21 and NCL to the granular compartment of the CC nucleolus (PubMed:23848194). Part of the small subunit (SSU) CC processome, first precursor of the small eukaryotic ribosomal subunit. CC During the assembly of the SSU processome in the nucleolus, many CC ribosome biogenesis factors, an RNA chaperone and ribosomal proteins CC associate with the nascent pre-rRNA and work in concert to generate RNA CC folding, modifications, rearrangements and cleavage as well as targeted CC degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). CC {ECO:0000269|PubMed:23848194, ECO:0000269|PubMed:34516797}. CC -!- SUBUNIT: Part of the small subunit (SSU) processome, composed of more CC than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3 CC (PubMed:34516797). Interacts with DDX21, NCL, NOP2 and EBNA1BP2 CC (PubMed:23848194). {ECO:0000269|PubMed:23848194, CC ECO:0000269|PubMed:34516797}. CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:23848194, CC ECO:0000269|PubMed:34516797}. 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; AF447870; AAQ04645.1; -; mRNA. DR EMBL; AL662820; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL662827; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL844527; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BX000343; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; Z97184; CAB09994.2; -; Genomic_DNA. DR EMBL; AL031228; CAB09994.2; JOINED; Genomic_DNA. DR EMBL; BC000388; AAH00388.1; -; mRNA. DR CCDS; CCDS4772.1; -. DR RefSeq; NP_001157739.1; NM_001164267.1. DR RefSeq; NP_005443.3; NM_005452.5. DR PDB; 7MQ8; EM; 3.60 A; LW=1-610. DR PDB; 7MQ9; EM; 3.87 A; LW=1-610. DR PDB; 7MQA; EM; 2.70 A; LW=1-610. DR PDBsum; 7MQ8; -. DR PDBsum; 7MQ9; -. DR PDBsum; 7MQA; -. DR AlphaFoldDB; O15213; -. DR EMDB; EMD-23936; -. DR EMDB; EMD-23937; -. DR EMDB; EMD-23938; -. DR SMR; O15213; -. DR BioGRID; 114694; 172. DR ComplexPortal; CPX-2511; Small ribosomal subunit processome. DR IntAct; O15213; 17. DR MINT; O15213; -. DR STRING; 9606.ENSP00000363746; -. DR iPTMnet; O15213; -. DR PhosphoSitePlus; O15213; -. DR SwissPalm; O15213; -. DR BioMuta; WDR46; -. DR EPD; O15213; -. DR jPOST; O15213; -. DR MassIVE; O15213; -. DR MaxQB; O15213; -. DR PaxDb; 9606-ENSP00000363746; -. DR PeptideAtlas; O15213; -. DR ProteomicsDB; 48513; -. DR Pumba; O15213; -. DR Antibodypedia; 29045; 61 antibodies from 19 providers. DR DNASU; 9277; -. DR Ensembl; ENST00000374617.9; ENSP00000363746.4; ENSG00000227057.10. DR Ensembl; ENST00000383208.8; ENSP00000372695.4; ENSG00000206284.8. DR Ensembl; ENST00000432609.6; ENSP00000402869.2; ENSG00000236222.8. DR Ensembl; ENST00000432933.6; ENSP00000399454.2; ENSG00000204221.11. DR Ensembl; ENST00000457382.6; ENSP00000405614.2; ENSG00000226916.8. DR GeneID; 9277; -. DR KEGG; hsa:9277; -. DR MANE-Select; ENST00000374617.9; ENSP00000363746.4; NM_005452.6; NP_005443.3. DR UCSC; uc003ods.4; human. DR AGR; HGNC:13923; -. DR CTD; 9277; -. DR DisGeNET; 9277; -. DR GeneCards; WDR46; -. DR HGNC; HGNC:13923; WDR46. DR HPA; ENSG00000227057; Low tissue specificity. DR MIM; 611440; gene. DR neXtProt; NX_O15213; -. DR OpenTargets; ENSG00000227057; -. DR PharmGKB; PA25924; -. DR VEuPathDB; HostDB:ENSG00000227057; -. DR eggNOG; KOG1272; Eukaryota. DR GeneTree; ENSGT00390000007075; -. DR HOGENOM; CLU_022996_2_0_1; -. DR InParanoid; O15213; -. DR OMA; KYTFIYD; -. DR OrthoDB; 125824at2759; -. DR PhylomeDB; O15213; -. DR TreeFam; TF300861; -. DR PathwayCommons; O15213; -. DR Reactome; R-HSA-6790901; rRNA modification in the nucleus and cytosol. DR Reactome; R-HSA-6791226; Major pathway of rRNA processing in the nucleolus and cytosol. DR SignaLink; O15213; -. DR BioGRID-ORCS; 9277; 597 hits in 1155 CRISPR screens. DR ChiTaRS; WDR46; human. DR GeneWiki; WDR46; -. DR GenomeRNAi; 9277; -. DR Pharos; O15213; Tbio. DR PRO; PR:O15213; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; O15213; Protein. DR Bgee; ENSG00000227057; Expressed in granulocyte and 95 other cell types or tissues. DR ExpressionAtlas; O15213; baseline and differential. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0032040; C:small-subunit processome; IDA:UniProtKB. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0000462; P:maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA); IBA:GO_Central. DR GO; GO:0042274; P:ribosomal small subunit biogenesis; IDA:UniProtKB. DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 1. DR InterPro; IPR012952; BING4_C_dom. DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf. DR InterPro; IPR036322; WD40_repeat_dom_sf. DR InterPro; IPR001680; WD40_rpt. DR InterPro; IPR040315; WDR46/Utp7. DR PANTHER; PTHR14085:SF3; WD REPEAT-CONTAINING PROTEIN 46; 1. DR PANTHER; PTHR14085; WD-REPEAT PROTEIN BING4; 1. DR Pfam; PF08149; BING4CT; 1. DR Pfam; PF00400; WD40; 1. DR SMART; SM01033; BING4CT; 1. DR SMART; SM00320; WD40; 4. DR SUPFAM; SSF50978; WD40 repeat-like; 1. DR PROSITE; PS50082; WD_REPEATS_2; 1. DR PROSITE; PS50294; WD_REPEATS_REGION; 1. DR Genevisible; O15213; HS. PE 1: Evidence at protein level; KW 3D-structure; Nucleus; Phosphoprotein; Reference proteome; Repeat; KW WD repeat. FT CHAIN 1..610 FT /note="WD repeat-containing protein 46" FT /id="PRO_0000051395" FT REPEAT 193..234 FT /note="WD 1" FT REPEAT 235..272 FT /note="WD 2" FT REPEAT 274..312 FT /note="WD 3" FT REPEAT 315..354 FT /note="WD 4" FT REPEAT 357..396 FT /note="WD 5" FT REPEAT 399..436 FT /note="WD 6" FT REGION 1..103 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 538..610 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 7..31 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 567..597 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 41 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18220336, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT VARIANT 94 FT /note="T -> A (in dbSNP:rs3130257)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:15498874, ECO:0000269|PubMed:9545376" FT /id="VAR_053433" FT VARIANT 124 FT /note="S -> Y (in dbSNP:rs34704405)" FT /id="VAR_053434" FT VARIANT 341 FT /note="V -> A (in dbSNP:rs14398)" FT /evidence="ECO:0000269|PubMed:14574404" FT /id="VAR_022025" SQ SEQUENCE 610 AA; 68071 MW; 0C11DA8ED92CA39E CRC64; METAPKPGKD VPPKKDKLQT KRKKPRRYWE EETVPTTAGA SPGPPRNKKN RELRPQRPKN AYILKKSRIS KKPQVPKKPR EWKNPESQRG LSGTQDPFPG PAPVPVEVVQ KFCRIDKSRK LPHSKAKTRS RLEVAEAEEE ETSIKAARSE LLLAEEPGFL EGEDGEDTAK ICQADIVEAV DIASAAKHFD LNLRQFGPYR LNYSRTGRHL AFGGRRGHVA ALDWVTKKLM CEINVMEAVR DIRFLHSEAL LAVAQNRWLH IYDNQGIELH CIRRCDRVTR LEFLPFHFLL ATASETGFLT YLDVSVGKIV AALNARAGRL DVMSQNPYNA VIHLGHSNGT VSLWSPAMKE PLAKILCHRG GVRAVAVDST GTYMATSGLD HQLKIFDLRG TYQPLSTRTL PHGAGHLAFS QRGLLVAGMG DVVNIWAGQG KASPPSLEQP YLTHRLSGPV HGLQFCPFED VLGVGHTGGI TSMLVPGAGE PNFDGLESNP YRSRKQRQEW EVKALLEKVP AELICLDPRA LAEVDVISLE QGKKEQIERL GYDPQAKAPF QPKPKQKGRS STASLVKRKR KVMDEEHRDK VRQSLQQQHH KEAKAKPTGA RPSALDRFVR //