WDR74_HUMAN
ID WDR74_HUMAN Reviewed; 385 AA.
AC Q6RFH5; A8K8G5; Q9BRC9; Q9H6X8; Q9NVY2;
DT 23-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=WD repeat-containing protein 74;
DE AltName: Full=NOP seven-associated protein 1;
GN Name=WDR74; Synonyms=NSA1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Eilbracht J., Hofmann A., Schmidt-Zachmann M.S.;
RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-361, 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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-214 AND SER-361, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-214 AND SER-361, 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 [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-361, 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 [9]
RP METHYLATION [LARGE SCALE ANALYSIS] AT LYS-311, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH MTREX.
RX PubMed=26456651; DOI=10.1016/j.bbrc.2015.09.160;
RA Hiraishi N., Ishida Y., Nagahama M.;
RT "AAA-ATPase NVL2 acts on MTR4-exosome complex to dissociate the nucleolar
RT protein WDR74.";
RL Biochem. Biophys. Res. Commun. 467:534-540(2015).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH NVL, AND MUTAGENESIS OF
RP 171-LYS--ASP-176; TRP-185 AND PHE-191.
RX PubMed=28416111; DOI=10.1016/j.str.2017.03.008;
RA Lo Y.H., Romes E.M., Pillon M.C., Sobhany M., Stanley R.E.;
RT "Structural Analysis Reveals Features of Ribosome Assembly Factor
RT Nsa1/WDR74 Important for Localization and Interaction with Rix7/NVL2.";
RL Structure 25:762-772(2017).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH MTREX.
RX PubMed=29107693; DOI=10.1016/j.bbrc.2017.10.148;
RA Hiraishi N., Ishida Y.I., Sudo H., Nagahama M.;
RT "WDR74 participates in an early cleavage of the pre-rRNA processing pathway
RT in cooperation with the nucleolar AAA-ATPase NVL2.";
RL Biochem. Biophys. Res. Commun. 495:116-123(2018).
CC -!- FUNCTION: Regulatory protein of the MTREX-exosome complex involved in
CC the synthesis of the 60S ribosomal subunit (PubMed:26456651).
CC Participates in an early cleavage of the pre-rRNA processing pathway in
CC cooperation with NVL (PubMed:29107693). Required for blastocyst
CC formation, is necessary for RNA transcription, processing and/or
CC stability during preimplantation development (By similarity).
CC {ECO:0000250|UniProtKB:Q8VCG3, ECO:0000269|PubMed:26456651,
CC ECO:0000269|PubMed:29107693}.
CC -!- SUBUNIT: Isoform 1 interacts (through WDR repeats) with NVL; the
CC interaction is independent of RNA or pre-60S ribosome particles.
CC Isoform 2 does not interact with NVL (PubMed:28416111). Interacts with
CC MTREX; the interaction dissociation in a late stage of rRNA synthesis
CC is required for appropriate maturation of pre-60S particles and depends
CC on the ATPase activity of NVL (PubMed:26456651, PubMed:29107693).
CC {ECO:0000269|PubMed:26456651, ECO:0000269|PubMed:28416111,
CC ECO:0000269|PubMed:29107693}.
CC -!- INTERACTION:
CC Q6RFH5; Q96PM5: RCHY1; NbExp=3; IntAct=EBI-722366, EBI-947779;
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:12429849,
CC ECO:0000269|PubMed:26456651, ECO:0000269|PubMed:28416111,
CC ECO:0000269|PubMed:29107693}. Nucleus {ECO:0000269|PubMed:28416111}.
CC Note=Nucleolar location depends on active PolI transcription of pre-
CC rRNA. {ECO:0000269|PubMed:28416111}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6RFH5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6RFH5-2; Sequence=VSP_011957;
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DR EMBL; AY500828; AAS48499.1; -; mRNA.
DR EMBL; AK001301; BAA91610.1; -; mRNA.
DR EMBL; AK025383; BAB15122.1; -; mRNA.
DR EMBL; AK292330; BAF85019.1; -; mRNA.
DR EMBL; BC006351; AAH06351.1; -; mRNA.
DR CCDS; CCDS44630.1; -. [Q6RFH5-1]
DR CCDS; CCDS76421.1; -. [Q6RFH5-2]
DR RefSeq; NP_001294906.1; NM_001307977.1. [Q6RFH5-2]
DR RefSeq; NP_060563.2; NM_018093.3. [Q6RFH5-1]
DR RefSeq; XP_005274112.1; XM_005274055.2.
DR AlphaFoldDB; Q6RFH5; -.
DR SMR; Q6RFH5; -.
DR BioGRID; 120092; 133.
DR IntAct; Q6RFH5; 29.
DR MINT; Q6RFH5; -.
DR STRING; 9606.ENSP00000432119; -.
DR iPTMnet; Q6RFH5; -.
DR PhosphoSitePlus; Q6RFH5; -.
DR SwissPalm; Q6RFH5; -.
DR BioMuta; WDR74; -.
DR DMDM; 55976441; -.
DR SWISS-2DPAGE; Q6RFH5; -.
DR EPD; Q6RFH5; -.
DR jPOST; Q6RFH5; -.
DR MassIVE; Q6RFH5; -.
DR MaxQB; Q6RFH5; -.
DR PaxDb; Q6RFH5; -.
DR PeptideAtlas; Q6RFH5; -.
DR PRIDE; Q6RFH5; -.
DR ProteomicsDB; 67316; -. [Q6RFH5-1]
DR ProteomicsDB; 67317; -. [Q6RFH5-2]
DR Antibodypedia; 28811; 199 antibodies from 24 providers.
DR DNASU; 54663; -.
DR Ensembl; ENST00000278856.9; ENSP00000278856.4; ENSG00000133316.16. [Q6RFH5-1]
DR Ensembl; ENST00000311713.11; ENSP00000308931.7; ENSG00000133316.16. [Q6RFH5-2]
DR Ensembl; ENST00000525239.5; ENSP00000432119.1; ENSG00000133316.16. [Q6RFH5-1]
DR Ensembl; ENST00000529106.5; ENSP00000435726.1; ENSG00000133316.16. [Q6RFH5-1]
DR GeneID; 54663; -.
DR KEGG; hsa:54663; -.
DR MANE-Select; ENST00000278856.9; ENSP00000278856.4; NM_001369450.1; NP_001356379.1.
DR UCSC; uc001nvl.3; human. [Q6RFH5-1]
DR CTD; 54663; -.
DR DisGeNET; 54663; -.
DR GeneCards; WDR74; -.
DR HGNC; HGNC:25529; WDR74.
DR HPA; ENSG00000133316; Group enriched (brain, choroid plexus).
DR MIM; 617947; gene.
DR neXtProt; NX_Q6RFH5; -.
DR OpenTargets; ENSG00000133316; -.
DR PharmGKB; PA142670578; -.
DR VEuPathDB; HostDB:ENSG00000133316; -.
DR eggNOG; KOG3881; Eukaryota.
DR GeneTree; ENSGT00390000015119; -.
DR HOGENOM; CLU_033769_2_0_1; -.
DR InParanoid; Q6RFH5; -.
DR OMA; YTGTTMG; -.
DR OrthoDB; 1439033at2759; -.
DR PhylomeDB; Q6RFH5; -.
DR TreeFam; TF314666; -.
DR PathwayCommons; Q6RFH5; -.
DR SignaLink; Q6RFH5; -.
DR BioGRID-ORCS; 54663; 614 hits in 1082 CRISPR screens.
DR ChiTaRS; WDR74; human.
DR GenomeRNAi; 54663; -.
DR Pharos; Q6RFH5; Tbio.
DR PRO; PR:Q6RFH5; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q6RFH5; protein.
DR Bgee; ENSG00000133316; Expressed in calcaneal tendon and 182 other tissues.
DR ExpressionAtlas; Q6RFH5; baseline and differential.
DR Genevisible; Q6RFH5; HS.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0030687; C:preribosome, large subunit precursor; IBA:GO_Central.
DR GO; GO:0001825; P:blastocyst formation; ISS:UniProtKB.
DR GO; GO:0042273; P:ribosomal large subunit biogenesis; IMP:UniProtKB.
DR GO; GO:0016070; P:RNA metabolic process; ISS:UniProtKB.
DR GO; GO:0006364; P:rRNA processing; IMP:UniProtKB.
DR Gene3D; 2.130.10.10; -; 2.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR InterPro; IPR037379; WDR74/Nsa1.
DR PANTHER; PTHR16038; PTHR16038; 1.
DR Pfam; PF00400; WD40; 1.
DR SMART; SM00320; WD40; 3.
DR SUPFAM; SSF50978; SSF50978; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Methylation; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; WD repeat.
FT CHAIN 1..385
FT /note="WD repeat-containing protein 74"
FT /id="PRO_0000051428"
FT REPEAT 40..80
FT /note="WD 1"
FT REPEAT 83..122
FT /note="WD 2"
FT REPEAT 128..168
FT /note="WD 3"
FT REPEAT 179..220
FT /note="WD 4"
FT REPEAT 224..266
FT /note="WD 5"
FT REPEAT 267..306
FT /note="WD 6"
FT REGION 320..385
FT /note="Required for nucleolar and nuclear location"
FT /evidence="ECO:0000269|PubMed:28416111"
FT REGION 323..345
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 360..385
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 324..344
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 214
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 311
FT /note="N6-methyllysine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 361
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT VAR_SEQ 308..326
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_011957"
FT MUTAGEN 171..176
FT /note="KNVRND->GSGS: Reduces interaction with NVL."
FT /evidence="ECO:0000269|PubMed:28416111"
FT MUTAGEN 185
FT /note="W->A: Reduces interaction with NVL."
FT /evidence="ECO:0000269|PubMed:28416111"
FT MUTAGEN 191
FT /note="F->A: Reduces interaction with NVL."
FT /evidence="ECO:0000269|PubMed:28416111"
FT CONFLICT 33
FT /note="F -> L (in Ref. 2; BAA91610)"
FT /evidence="ECO:0000305"
FT CONFLICT 229
FT /note="P -> S (in Ref. 2; BAA91610)"
FT /evidence="ECO:0000305"
FT CONFLICT 297..298
FT /note="RI -> GT (in Ref. 2; BAA91610)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 385 AA; 42441 MW; 8B4FA9730D8D5EC0 CRC64;
MAAAAARWNH VWVGTETGIL KGVNLQRKQA ANFTAGGQPR REEAVSALCW GTGGETQMLV
GCADRTVKHF STEDGIFQGQ RHCPGGEGMF RGLAQADGTL ITCVDSGILR VWHDKDKDTS
SDPLLELRVG PGVCRMRQDP AHPHVVATGG KENALKIWDL QGSEEPVFRA KNVRNDWLDL
RVPIWDQDIQ FLPGSQKLVT CTGYHQVRVY DPASPQRRPV LETTYGEYPL TAMTLTPGGN
SVIVGNTHGQ LAEIDLRQGR LLGCLKGLAG SVRGLQCHPS KPLLASCGLD RVLRIHRIQN
PRGLEHKVYL KSQLNCLLLS GRDNWEDEPQ EPQEPNKVPL EDTETDELWA SLEAAAKRKL
SGLEQPQGAL QTRRRKKKRP GSTSP
