WDR54_HUMAN
ID WDR54_HUMAN Reviewed; 334 AA.
AC Q9H977; B9A049; D6W5I3; Q53H85; Q86V45;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=WD repeat-containing protein 54 {ECO:0000305};
GN Name=WDR54 {ECO:0000312|HGNC:HGNC:25770};
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=Teratocarcinoma;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [7]
RP CROSS-LINKING, DOMAIN, SUBUNIT, ALTERNATIVE SPLICING, MUTAGENESIS OF
RP TRP-107; TRP-196; TRP-221; TRP-279; LYS-280 AND GLN-304, UBIQUITINATION,
RP AND SUBCELLULAR LOCATION.
RX PubMed=30458214; DOI=10.1016/j.bbamcr.2018.11.009;
RA Maeda A., Nishino T., Matsunaga R., Yokoyama A., Suga H., Yagi T.,
RA Konishi H.;
RT "Transglutaminase-mediated cross-linking of WDR54 regulates EGF receptor-
RT signaling.";
RL Biochim. Biophys. Acta 1866:285-295(2019).
RN [8]
RP TISSUE SPECIFICITY, AND ALTERNATIVE SPLICING.
RX PubMed=29987896; DOI=10.1002/ijc.31736;
RA Yuan Y., Qi G., Shen H., Guo A., Cao F., Zhu Y., Xiao C., Chang W.,
RA Zheng S.;
RT "Clinical significance and biological function of WD repeat domain 54 as an
RT oncogene in colorectal cancer.";
RL Int. J. Cancer 144:1584-1595(2019).
CC -!- FUNCTION: When cross-linked to form dimers and trimers, it has a
CC regulatory effect on ERK signaling pathway activity in response to EGF
CC stimulation. Colocalizes with the EGF receptor in WDR54-specific
CC vesicle where it sustains the internalization and controls the
CC degradation of the EGF receptor after EGF stimulation.
CC {ECO:0000269|PubMed:30458214}.
CC -!- SUBUNIT: Homodimer and homotrimer; forms tight forms of dimers and
CC trimers. {ECO:0000269|PubMed:30458214}.
CC -!- INTERACTION:
CC Q9H977-4; Q9BRQ3: NUDT22; NbExp=5; IntAct=EBI-23279779, EBI-10297093;
CC -!- SUBCELLULAR LOCATION: Vesicle {ECO:0000269|PubMed:30458214}.
CC Note=Aggregates in vesicles when cross-linked.
CC {ECO:0000269|PubMed:30458214}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=b {ECO:0000303|PubMed:29987896,
CC ECO:0000303|PubMed:30458214};
CC IsoId=Q9H977-1; Sequence=Displayed;
CC Name=3; Synonyms=c {ECO:0000303|PubMed:29987896,
CC ECO:0000303|PubMed:30458214};
CC IsoId=Q9H977-3; Sequence=VSP_060292, VSP_060294, VSP_060295;
CC Name=2; Synonyms=a {ECO:0000303|PubMed:29987896,
CC ECO:0000303|PubMed:30458214};
CC IsoId=Q9H977-4; Sequence=VSP_060293;
CC -!- TISSUE SPECIFICITY: Expressed in epithelial cells (at protein level)
CC (PubMed:29987896). Isoform 3 expression is highly increased in
CC colorectal cancer cells (PubMed:29987896).
CC {ECO:0000269|PubMed:29987896}.
CC -!- DOMAIN: WD6 repeat is required for cross-linking by TGM2.
CC {ECO:0000269|PubMed:30458214}.
CC -!- PTM: Cross-linked to tightly form both dimers and trimers by TGM2.
CC Cross-linking enhances the activation of EGF receptor-mediated
CC signaling pathway (PubMed:30458214). Cross-linking is inhibited by EGF
CC (PubMed:30458214). {ECO:0000269|PubMed:30458214}.
CC -!- PTM: Ubiquitinated. EGF increases ubiquitination.
CC {ECO:0000269|PubMed:30458214}.
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; AK023015; BAB14358.1; -; mRNA.
DR EMBL; AK222696; BAD96416.1; -; mRNA.
DR EMBL; CH471053; EAW99677.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99680.1; -; Genomic_DNA.
DR EMBL; AC005041; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC051848; AAH51848.1; -; mRNA.
DR CCDS; CCDS1940.1; -. [Q9H977-1]
DR CCDS; CCDS82473.1; -. [Q9H977-3]
DR RefSeq; NP_001307752.1; NM_001320823.1. [Q9H977-4]
DR RefSeq; NP_001307753.1; NM_001320824.1. [Q9H977-1]
DR RefSeq; NP_001307754.1; NM_001320825.1. [Q9H977-3]
DR RefSeq; NP_115494.1; NM_032118.3. [Q9H977-1]
DR AlphaFoldDB; Q9H977; -.
DR SMR; Q9H977; -.
DR BioGRID; 123853; 47.
DR IntAct; Q9H977; 23.
DR STRING; 9606.ENSP00000006526; -.
DR iPTMnet; Q9H977; -.
DR PhosphoSitePlus; Q9H977; -.
DR BioMuta; WDR54; -.
DR DMDM; 74761551; -.
DR EPD; Q9H977; -.
DR jPOST; Q9H977; -.
DR MassIVE; Q9H977; -.
DR MaxQB; Q9H977; -.
DR PaxDb; Q9H977; -.
DR PeptideAtlas; Q9H977; -.
DR PRIDE; Q9H977; -.
DR ProteomicsDB; 7498; -.
DR ProteomicsDB; 81290; -.
DR Antibodypedia; 51442; 82 antibodies from 14 providers.
DR DNASU; 84058; -.
DR Ensembl; ENST00000348227.4; ENSP00000006526.6; ENSG00000005448.17. [Q9H977-1]
DR Ensembl; ENST00000409791.5; ENSP00000387236.1; ENSG00000005448.17. [Q9H977-3]
DR GeneID; 84058; -.
DR KEGG; hsa:84058; -.
DR MANE-Select; ENST00000348227.4; ENSP00000006526.6; NM_032118.4; NP_115494.1.
DR UCSC; uc002slb.4; human. [Q9H977-1]
DR CTD; 84058; -.
DR DisGeNET; 84058; -.
DR GeneCards; WDR54; -.
DR HGNC; HGNC:25770; WDR54.
DR HPA; ENSG00000005448; Tissue enhanced (fallopian).
DR neXtProt; NX_Q9H977; -.
DR OpenTargets; ENSG00000005448; -.
DR PharmGKB; PA142670589; -.
DR VEuPathDB; HostDB:ENSG00000005448; -.
DR eggNOG; ENOG502QRUZ; Eukaryota.
DR GeneTree; ENSGT00390000014530; -.
DR HOGENOM; CLU_045688_2_0_1; -.
DR InParanoid; Q9H977; -.
DR OMA; WENYICV; -.
DR OrthoDB; 839593at2759; -.
DR PhylomeDB; Q9H977; -.
DR TreeFam; TF329316; -.
DR PathwayCommons; Q9H977; -.
DR SignaLink; Q9H977; -.
DR BioGRID-ORCS; 84058; 55 hits in 1079 CRISPR screens.
DR ChiTaRS; WDR54; human.
DR GenomeRNAi; 84058; -.
DR Pharos; Q9H977; Tdark.
DR PRO; PR:Q9H977; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9H977; protein.
DR Bgee; ENSG00000005448; Expressed in bronchial epithelial cell and 146 other tissues.
DR Genevisible; Q9H977; HS.
DR GO; GO:0031982; C:vesicle; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0002091; P:negative regulation of receptor internalization; IMP:UniProtKB.
DR GO; GO:0042058; P:regulation of epidermal growth factor receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0043408; P:regulation of MAPK cascade; 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 SMART; SM00320; WD40; 3.
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 Alternative splicing; Reference proteome; Repeat; Ubl conjugation;
KW WD repeat.
FT CHAIN 1..334
FT /note="WD repeat-containing protein 54"
FT /id="PRO_0000051415"
FT REPEAT 6..47
FT /note="WD 1"
FT REPEAT 58..99
FT /note="WD 2"
FT REPEAT 105..147
FT /note="WD 3"
FT REPEAT 155..198
FT /note="WD 4"
FT REPEAT 243..281
FT /note="WD 5"
FT REPEAT 289..333
FT /note="WD 6"
FT VAR_SEQ 1..73
FT /note="MFRWERSIPLRGSAAALCNNLSVLQLPARNLTYFGVVHGPSAQLLSAAPEGV
FT PLAQRQLHAKEGAGVSPPLIT -> MVAADLEGPYEPGVRRADLGL (in isoform
FT 3)"
FT /id="VSP_060292"
FT VAR_SEQ 1
FT /note="M -> MVAADLEGPYEPGVRM (in isoform 2)"
FT /id="VSP_060293"
FT VAR_SEQ 292..296
FT /note="VEHCH -> ATPLL (in isoform 3)"
FT /id="VSP_060294"
FT VAR_SEQ 297..334
FT /note="Missing (in isoform 3)"
FT /id="VSP_060295"
FT MUTAGEN 107
FT /note="W->A: Decreases cross-linking."
FT /evidence="ECO:0000269|PubMed:30458214"
FT MUTAGEN 196
FT /note="W->A: Slightly decreases cross-linking."
FT /evidence="ECO:0000269|PubMed:30458214"
FT MUTAGEN 221
FT /note="W->A: Decreases cross-linking."
FT /evidence="ECO:0000269|PubMed:30458214"
FT MUTAGEN 279
FT /note="W->A: Abolishes cross-linking. Decreases ERK
FT signaling pathway activation. Abolishes inhibition of EGF
FT receptor degradation after EGF stimulation."
FT /evidence="ECO:0000269|PubMed:30458214"
FT MUTAGEN 280
FT /note="K->R: Decreases cross-linking. Abolishes
FT ubiquitination."
FT /evidence="ECO:0000269|PubMed:30458214"
FT MUTAGEN 304
FT /note="Q->A: No effect on cross-linking."
FT /evidence="ECO:0000269|PubMed:30458214"
FT CONFLICT 243
FT /note="N -> D (in Ref. 2; BAD96416)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 334 AA; 35891 MW; F0B10168F9C84D34 CRC64;
MFRWERSIPL RGSAAALCNN LSVLQLPARN LTYFGVVHGP SAQLLSAAPE GVPLAQRQLH
AKEGAGVSPP LITQVHWCVL PFRVLLVLTS HRGIQMYESN GYTMVYWHAL DSGDASPVQA
VFARGIAASG HFICVGTWSG RVLVFDIPAK GPNIVLSEEL AGHQMPITDI ATEPAQGQDC
VADMVTADDS GLLCVWRSGP EFTLLTRIPG FGVPCPSVQL WQGIIAAGYG NGQVHLYEAT
TGNLHVQINA HARAICALDL ASEVGKLLSA GEDTFVHIWK LSRNPESGYI EVEHCHGECV
ADTQLCGARF CDSSGNSFAV TGYDLAEIRR FSSV
