WDR43_HUMAN
ID WDR43_HUMAN Reviewed; 677 AA.
AC Q15061; Q15395; Q92577;
DT 27-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 24-JUL-2007, sequence version 3.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=WD repeat-containing protein 43;
DE AltName: Full=U3 small nucleolar RNA-associated protein 5 homolog;
GN Name=WDR43; Synonyms=KIAA0007, UTP5;
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].
RC TISSUE=Bone marrow;
RX PubMed=7584026; DOI=10.1093/dnares/1.1.27;
RA Nomura N., Miyajima N., Sazuka T., Tanaka A., Kawarabayasi Y., Sato S.,
RA Nagase T., Seki N., Ishikawa K., Tabata S.;
RT "Prediction of the coding sequences of unidentified human genes. I. The
RT coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of
RT randomly sampled cDNA clones from human immature myeloid cell line KG-1.";
RL DNA Res. 1:27-35(1994).
RN [2]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=12429849; DOI=10.1091/mbc.e02-05-0271;
RA Scherl A., Coute Y., Deon C., Calle A., Kindbeiter K., Sanchez J.-C.,
RA Greco A., Hochstrasser D.F., Diaz J.-J.;
RT "Functional proteomic analysis of human nucleolus.";
RL Mol. Biol. Cell 13:4100-4109(2002).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-77, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-431, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [5]
RP FUNCTION, AND SUBUNIT.
RX PubMed=17699751; DOI=10.1101/gad.436707;
RA Prieto J.L., McStay B.;
RT "Recruitment of factors linking transcription and processing of pre-rRNA to
RT NOR chromatin is UBF-dependent and occurs independent of transcription in
RT human cells.";
RL Genes Dev. 21:2041-2054(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-431, 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-77; THR-394; SER-399;
RP SER-431; THR-656 AND SER-658, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
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., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [8]
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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-77; SER-431; SER-437;
RP SER-590; THR-656 AND SER-658, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [10]
RP POSSIBLE ASSOCIATION IN THE SSU PROCESSOME T-UTP SUBCOMPLEX.
RX PubMed=22916032; DOI=10.1371/journal.pgen.1002892;
RA Freed E.F., Prieto J.L., McCann K.L., McStay B., Baserga S.J.;
RT "NOL11, implicated in the pathogenesis of North American Indian childhood
RT cirrhosis, is required for pre-rRNA transcription and processing.";
RL PLoS Genet. 8:E1002892-E1002892(2012).
RN [11]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH UTP4 AND UTP15.
RX PubMed=24219289; DOI=10.1139/bcb-2013-0062;
RA Sato M., Araki N., Kumeta M., Takeyasu K., Taguchi Y., Asai T.,
RA Furukawa K., Horigome T.;
RT "Interaction, mobility, and phosphorylation of human orthologues of WD
RT repeat-containing components of the yeast SSU processome t-UTP sub-
RT complex.";
RL Biochem. Cell Biol. 91:466-475(2013).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-321; THR-394 AND SER-431, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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 [13]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-309 AND LYS-384, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25114211; DOI=10.1073/pnas.1413825111;
RA Impens F., Radoshevich L., Cossart P., Ribet D.;
RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by
RT external stimuli.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014).
RN [14]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-309 AND LYS-384, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [15]
RP FUNCTION, RNA-BINDING, AND DEVELOPMENTAL STAGE.
RX PubMed=31128943; DOI=10.1016/j.molcel.2019.05.007;
RA Bi X., Xu Y., Li T., Li X., Li W., Shao W., Wang K., Zhan G., Wu Z.,
RA Liu W., Lu J.Y., Wang L., Zhao J., Wu J., Na J., Li G., Li P., Shen X.;
RT "RNA Targets Ribogenesis Factor WDR43 to Chromatin for Transcription and
RT Pluripotency Control.";
RL Mol. Cell 0:0-0(2019).
CC -!- FUNCTION: Ribosome biogenesis factor that coordinates hyperactive
CC transcription and ribogenesis (PubMed:17699751). Involved in nucleolar
CC processing of pre-18S ribosomal RNA. Required for optimal pre-ribosomal
CC RNA transcription by RNA polymerase I (PubMed:17699751). Essential for
CC stem cell pluripotency and embryonic development. In the nucleoplasm,
CC recruited by promoter-associated/nascent transcripts and transcription
CC to active promoters where it facilitates releases of elongation factor
CC P-TEFb and paused RNA polymerase II to allow transcription elongation
CC and maintain high-level expression of its targets genes (By
CC similarity). {ECO:0000250|UniProtKB:Q6ZQL4,
CC ECO:0000269|PubMed:17699751}.
CC -!- SUBUNIT: Interacts directly with UTP4 and UTP15 (PubMed:24219289). May
CC be a component of the proposed t-UTP subcomplex of the ribosomal small
CC subunit (SSU) processome containing at least UTP4, WDR43, HEATR1,
CC UTP15, WDR75 (PubMed:17699751, PubMed:22916032). Binds to RNA; binding
CC is required for its chromatin association. Interacts with CDK9, DDX21
CC and SUPT6H. Interacts with RNA polymerase II (By similarity).
CC {ECO:0000250|UniProtKB:Q6ZQL4, ECO:0000269|PubMed:24219289,
CC ECO:0000305|PubMed:17699751, ECO:0000305|PubMed:22916032}.
CC -!- INTERACTION:
CC Q15061; Q969X6: UTP4; NbExp=3; IntAct=EBI-2563523, EBI-2602591;
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:12429849,
CC ECO:0000269|PubMed:24219289}. Nucleus, nucleolus fibrillar center
CC {ECO:0000269|PubMed:24219289}. Nucleus, nucleoplasm
CC {ECO:0000250|UniProtKB:Q6ZQL4}.
CC -!- DEVELOPMENTAL STAGE: Expressed during embryonic development, expression
CC decreases at blastocyst stage. {ECO:0000269|PubMed:31128943}.
CC -!- DOMAIN: N-terminal domain is required for nucleoplasm location and C-
CC terminal domain for nucleolus location. {ECO:0000250|UniProtKB:Q6ZQL4}.
CC -!- SIMILARITY: Belongs to the UTP5 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA05499.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA05499.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; D26488; BAA05499.1; ALT_INIT; mRNA.
DR EMBL; D87716; BAA13441.1; ALT_FRAME; mRNA.
DR CCDS; CCDS46251.1; -.
DR RefSeq; NP_055946.1; NM_015131.2.
DR PDB; 7MQ8; EM; 3.60 A; LK/LL=1-677.
DR PDB; 7MQ9; EM; 3.87 A; LK/LL=1-677.
DR PDB; 7MQA; EM; 2.70 A; LK/LL=1-677.
DR PDBsum; 7MQ8; -.
DR PDBsum; 7MQ9; -.
DR PDBsum; 7MQA; -.
DR AlphaFoldDB; Q15061; -.
DR SMR; Q15061; -.
DR BioGRID; 116772; 111.
DR IntAct; Q15061; 21.
DR MINT; Q15061; -.
DR STRING; 9606.ENSP00000384302; -.
DR GlyGen; Q15061; 2 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (1 site).
DR iPTMnet; Q15061; -.
DR PhosphoSitePlus; Q15061; -.
DR SwissPalm; Q15061; -.
DR BioMuta; WDR43; -.
DR DMDM; 158518532; -.
DR SWISS-2DPAGE; Q15061; -.
DR EPD; Q15061; -.
DR jPOST; Q15061; -.
DR MassIVE; Q15061; -.
DR MaxQB; Q15061; -.
DR PaxDb; Q15061; -.
DR PeptideAtlas; Q15061; -.
DR PRIDE; Q15061; -.
DR ProteomicsDB; 60416; -.
DR Antibodypedia; 51059; 77 antibodies from 15 providers.
DR DNASU; 23160; -.
DR Ensembl; ENST00000407426.8; ENSP00000384302.3; ENSG00000163811.12.
DR GeneID; 23160; -.
DR KEGG; hsa:23160; -.
DR MANE-Select; ENST00000407426.8; ENSP00000384302.3; NM_015131.3; NP_055946.1.
DR UCSC; uc002rmo.3; human.
DR CTD; 23160; -.
DR DisGeNET; 23160; -.
DR GeneCards; WDR43; -.
DR HGNC; HGNC:28945; WDR43.
DR HPA; ENSG00000163811; Low tissue specificity.
DR MIM; 616195; gene.
DR neXtProt; NX_Q15061; -.
DR OpenTargets; ENSG00000163811; -.
DR PharmGKB; PA134914163; -.
DR VEuPathDB; HostDB:ENSG00000163811; -.
DR eggNOG; KOG4547; Eukaryota.
DR GeneTree; ENSGT00390000004254; -.
DR HOGENOM; CLU_020516_1_0_1; -.
DR InParanoid; Q15061; -.
DR OMA; KRNADNH; -.
DR OrthoDB; 1032141at2759; -.
DR PhylomeDB; Q15061; -.
DR TreeFam; TF313160; -.
DR PathwayCommons; Q15061; -.
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; Q15061; -.
DR BioGRID-ORCS; 23160; 815 hits in 1086 CRISPR screens.
DR ChiTaRS; WDR43; human.
DR GenomeRNAi; 23160; -.
DR Pharos; Q15061; Tbio.
DR PRO; PR:Q15061; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q15061; protein.
DR Bgee; ENSG00000163811; Expressed in buccal mucosa cell and 202 other tissues.
DR ExpressionAtlas; Q15061; baseline and differential.
DR Genevisible; Q15061; HS.
DR GO; GO:0000785; C:chromatin; ISS:UniProtKB.
DR GO; GO:0001650; C:fibrillar center; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0000993; F:RNA polymerase II complex binding; ISS:UniProtKB.
DR GO; GO:0003711; F:transcription elongation regulator activity; ISS: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:2000234; P:positive regulation of rRNA processing; IMP:UniProtKB.
DR GO; GO:0045943; P:positive regulation of transcription by RNA polymerase I; IMP:UniProtKB.
DR GO; GO:2000036; P:regulation of stem cell population maintenance; ISS:UniProtKB.
DR GO; GO:0034243; P:regulation of transcription elongation from RNA polymerase II promoter; ISS:UniProtKB.
DR Gene3D; 2.130.10.10; -; 2.
DR InterPro; IPR007148; SSU_processome_Utp12.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR Pfam; PF04003; Utp12; 1.
DR Pfam; PF00400; WD40; 2.
DR SMART; SM00320; WD40; 5.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS50082; WD_REPEATS_2; 1.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; Ribosome biogenesis; RNA-binding; rRNA processing; Transcription;
KW Transcription regulation; Ubl conjugation; WD repeat.
FT CHAIN 1..677
FT /note="WD repeat-containing protein 43"
FT /id="PRO_0000051392"
FT REPEAT 11..51
FT /note="WD 1"
FT REPEAT 57..119
FT /note="WD 2"
FT REPEAT 124..163
FT /note="WD 3"
FT REPEAT 166..205
FT /note="WD 4"
FT REPEAT 207..259
FT /note="WD 5"
FT REPEAT 267..309
FT /note="WD 6"
FT REGION 414..445
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 582..677
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 428..445
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 602..649
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 650..667
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 77
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"
FT MOD_RES 321
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 394
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 399
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 431
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 437
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 590
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 656
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 658
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
FT CROSSLNK 309
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0007744|PubMed:25114211"
FT CROSSLNK 309
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 384
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0007744|PubMed:25114211"
FT CROSSLNK 384
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:28112733"
SQ SEQUENCE 677 AA; 74891 MW; 4EEAD92C30118ACD CRC64;
MAAGGGGSCD PLAPAGVPCA FSPHSQAYFA LASTDGHLRV WETANNRLHQ EYVPSAHLSG
TCTCLAWAPA RLQAKESPQR KKRKSEAVGM SNQTDLLALG TAVGSILLYS TVKGELHSKL
ISGGHDNRVN CIQWHQDSGC LYSCSDDKHI VEWNVQTCKV KCKWKGDNSS VSSLCISPDG
KMLLSAGRTI KLWVLETKEV YRHFTGHATP VSSLMFTTIR PPNESQPFDG ITGLYFLSGA
VHDRLLNVWQ VRSENKEKSA VMSFTVTDEP VYIDLTLSEN KEEPVKLAVV CRDGQVHLFE
HILNGYCKKP LTSNCTIQIA TPGKGKKSTP KPIPILAAGF CSDKMSLLLV YGSWFQPTIE
RVALNSREPH MCLVRDISNC WAPKVETAIT KVRTPVMNSE AKVLVPGIPG HHAAIKPAPP
QTEQVESKRK SGGNEVSIEE RLGAMDIDTH KKGKEDLQTN SFPVLLTQGL ESNDFEMLNK
VLQTRNVNLI KKTVLRMPLH TIIPLLQELT KRLQGHPNSA VLMVQWLKCV LTVHASYLST
LPDLVPQLGT LYQLMESRVK TFQKLSHLHG KLILLITQVT ASEKTKGATS PGQKAKLVYE
EESSEEESDD EIADKDSEDN WDEDEEESES EKDEDVEEED EDAEGKDEEN GEDRDTASEK
ELNGDSDLDP ENESEEE
