WDR4_MOUSE
ID WDR4_MOUSE Reviewed; 413 AA.
AC Q9EP82; Q80V01;
DT 11-FEB-2002, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 2.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=tRNA (guanine-N(7)-)-methyltransferase non-catalytic subunit WDR4 {ECO:0000255|HAMAP-Rule:MF_03056};
DE AltName: Full=Protein Wuho homolog {ECO:0000303|PubMed:26751069};
DE Short=mWH {ECO:0000303|PubMed:26751069};
DE AltName: Full=WD repeat-containing protein 4 {ECO:0000255|HAMAP-Rule:MF_03056};
GN Name=Wdr4 {ECO:0000312|MGI:MGI:1889002};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10950928; DOI=10.1006/geno.2000.6258;
RA Michaud J., Kudoh J., Berry A., Bonne-Tamir B., Lalioti M.D., Rossier C.,
RA Shibuya K., Kawasaki K., Asakawa S., Minoshima S., Shimizu N.,
RA Antonarakis S.E., Scott H.S.;
RT "Isolation and characterization of a human chromosome 21q22.3 gene (WDR4)
RT and its mouse homologue that code for a WD-repeat protein.";
RL Genomics 68:71-79(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Bone marrow, and Lung;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=26751069; DOI=10.1371/journal.pbio.1002349;
RA Cheng I.C., Chen B.C., Shuai H.H., Chien F.C., Chen P., Hsieh T.S.;
RT "Wuho is a new member in maintaining genome stability through its
RT interaction with flap endonuclease 1.";
RL PLoS Biol. 14:E1002349-E1002349(2016).
RN [6]
RP FUNCTION.
RX PubMed=29574139; DOI=10.1016/j.cellsig.2018.03.007;
RA Lee C.C., Hsieh T.S.;
RT "Wuho/WDR4 deficiency inhibits cell proliferation and induces apoptosis via
RT DNA damage in mouse embryonic fibroblasts.";
RL Cell. Signal. 47:16-26(2018).
RN [7]
RP FUNCTION, AND PATHWAY.
RX PubMed=29983320; DOI=10.1016/j.molcel.2018.06.001;
RA Lin S., Liu Q., Lelyveld V.S., Choe J., Szostak J.W., Gregory R.I.;
RT "Mettl1/Wdr4-mediated m7G tRNA methylome is required for normal mRNA
RT translation and embryonic stem cell self-renewal and differentiation.";
RL Mol. Cell 71:244-255(2018).
CC -!- FUNCTION: Non-catalytic component of a methyltransferase complex
CC required for the formation of N(7)-methylguanine in a subset of RNA
CC species, such as tRNAs, mRNAs and microRNAs (miRNAs) (PubMed:29983320).
CC In the methyltransferase complex, it is required to stabilize and
CC induce conformational changes of the catalytic subunit (By similarity).
CC Required for the formation of N(7)-methylguanine at position 46 (m7G46)
CC in tRNA (PubMed:29983320). Also required for the formation of N(7)-
CC methylguanine at internal sites in a subset of mRNAs (By similarity).
CC Also required for methylation of a specific subset of miRNAs, such as
CC let-7 (By similarity). Acts as a regulator of embryonic stem cell self-
CC renewal and differentiation (PubMed:29983320). Independently of METTL1,
CC also plays a role in genome stability: localizes at the DNA replication
CC site and regulates endonucleolytic activities of FEN1
CC (PubMed:29574139). {ECO:0000255|HAMAP-Rule:MF_03056,
CC ECO:0000269|PubMed:29574139, ECO:0000269|PubMed:29983320}.
CC -!- PATHWAY: tRNA modification; N(7)-methylguanine-tRNA biosynthesis.
CC {ECO:0000269|PubMed:29983320}.
CC -!- SUBUNIT: Forms a heterodimer with the catalytic subunit METTL1.
CC Interacts with FEN1; the interaction is direct. {ECO:0000255|HAMAP-
CC Rule:MF_03056}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|HAMAP-Rule:MF_03056}.
CC Chromosome {ECO:0000255|HAMAP-Rule:MF_03056}. Note=Localizes at the
CC site of nascent DNA synthesis. {ECO:0000255|HAMAP-Rule:MF_03056}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethality at E9.5-10.5, possibly caused
CC by DNA damage. {ECO:0000269|PubMed:26751069}.
CC -!- SIMILARITY: Belongs to the WD repeat TRM82 family. {ECO:0000255|HAMAP-
CC Rule:MF_03056}.
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DR EMBL; AJ271893; CAC05585.1; -; mRNA.
DR EMBL; AJ271892; CAC05584.1; -; mRNA.
DR EMBL; AK144821; BAE26082.1; -; mRNA.
DR EMBL; AK152271; BAE31087.1; -; mRNA.
DR EMBL; AK153161; BAE31771.1; -; mRNA.
DR EMBL; BC039272; AAH39272.1; -; mRNA.
DR RefSeq; NP_067297.2; NM_021322.2.
DR AlphaFoldDB; Q9EP82; -.
DR SMR; Q9EP82; -.
DR BioGRID; 208322; 17.
DR STRING; 10090.ENSMUSP00000126061; -.
DR iPTMnet; Q9EP82; -.
DR PhosphoSitePlus; Q9EP82; -.
DR EPD; Q9EP82; -.
DR jPOST; Q9EP82; -.
DR MaxQB; Q9EP82; -.
DR PaxDb; Q9EP82; -.
DR PRIDE; Q9EP82; -.
DR ProteomicsDB; 297892; -.
DR GeneID; 57773; -.
DR KEGG; mmu:57773; -.
DR UCSC; uc008bvd.2; mouse.
DR CTD; 10785; -.
DR MGI; MGI:1889002; Wdr4.
DR eggNOG; KOG3914; Eukaryota.
DR InParanoid; Q9EP82; -.
DR OrthoDB; 937275at2759; -.
DR PhylomeDB; Q9EP82; -.
DR UniPathway; UPA00989; -.
DR BioGRID-ORCS; 57773; 12 hits in 72 CRISPR screens.
DR PRO; PR:Q9EP82; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q9EP82; protein.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0043527; C:tRNA methyltransferase complex; ISO:MGI.
DR GO; GO:0008176; F:tRNA (guanine-N7-)-methyltransferase activity; ISO:MGI.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IEA:UniProtKB-KW.
DR GO; GO:0006400; P:tRNA modification; ISS:UniProtKB.
DR Gene3D; 2.130.10.10; -; 2.
DR HAMAP; MF_03056; TRM82; 1.
DR InterPro; IPR028884; Trm82.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR PANTHER; PTHR16288; PTHR16288; 1.
DR Pfam; PF00400; WD40; 1.
DR SMART; SM00320; WD40; 4.
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 Acetylation; Chromosome; DNA damage; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; tRNA processing; WD repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P57081"
FT CHAIN 2..413
FT /note="tRNA (guanine-N(7)-)-methyltransferase non-catalytic
FT subunit WDR4"
FT /id="PRO_0000051349"
FT REPEAT 61..100
FT /note="WD 1"
FT REPEAT 102..141
FT /note="WD 2"
FT REPEAT 145..185
FT /note="WD 3"
FT REPEAT 188..228
FT /note="WD 4"
FT REPEAT 289..329
FT /note="WD 5"
FT REGION 380..413
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 388..413
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P57081"
FT MOD_RES 392
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P57081"
FT MOD_RES 412
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P57081"
FT CONFLICT 28
FT /note="T -> A (in Ref. 1; CAC05584/CAC05585)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 413 AA; 45756 MW; 8EAFB152CFE2884E CRC64;
MASSAGLALC AQTLVVRGGS RFLAFSTTGS DDDCVFTYDC STAEKKATPE DKGEDGQPAD
TGSDSILAST FSKSGRYFAL TDDSKRLILF RTKPWQCLSV RMVVRRCTAL TFTASEDRVL
VADKSGDVYS FSVLEPDGCG RLELGHLSML LDVAVSPDDQ FVLTADRDEK IRVSWAAAPH
SIESFCLGHT EFVSRILVVP SHPELLLSSS GDGTLRLWEY RSGRQLQCCD LAGLQEPGEQ
PGHKGLAASR IAFWGQESYV VLLCECVPVV FVFQLDASRQ QLVFRQRLTF PHRVWDVVFE
EARGLWVLQD CRDAPLVLWR PVGGEWQAAP DGAVSPRLCS HLRESWAMLE GSVGTDDSFR
SLYKATFDNM TSYLKKKEER LQQQLKKKRQ RSPFPGSPEQ TKKACPGQSA LSC
