WDR11_MOUSE
ID WDR11_MOUSE Reviewed; 1223 AA.
AC Q8K1X1; Q69ZL3; Q8C937;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=WD repeat-containing protein 11;
DE AltName: Full=Bromodomain and WD repeat-containing protein 2;
GN Name=Wdr11; Synonyms=Brwd2, Kiaa1351;
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 [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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 260-877.
RC STRAIN=C57BL/6J; TISSUE=Cerebellum;
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] OF 766-1223.
RC TISSUE=Brain;
RX PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 11:205-218(2004).
RN [4]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=20887964; DOI=10.1016/j.ajhg.2010.08.018;
RA Kim H.G., Ahn J.W., Kurth I., Ullmann R., Kim H.T., Kulharya A., Ha K.S.,
RA Itokawa Y., Meliciani I., Wenzel W., Lee D., Rosenberger G., Ozata M.,
RA Bick D.P., Sherins R.J., Nagase T., Tekin M., Kim S.H., Kim C.H.,
RA Ropers H.H., Gusella J.F., Kalscheuer V., Choi C.Y., Layman L.C.;
RT "WDR11, a WD protein that interacts with transcription factor EMX1, is
RT mutated in idiopathic hypogonadotropic hypogonadism and Kallmann
RT syndrome.";
RL Am. J. Hum. Genet. 87:465-479(2010).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-401 AND SER-405, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Liver, Lung, Pancreas, Spleen,
RC and Testis;
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 [6]
RP INTERACTION WITH TBC1D23.
RX PubMed=29084197; DOI=10.1038/ncb3627;
RA Shin J.J.H., Gillingham A.K., Begum F., Chadwick J., Munro S.;
RT "TBC1D23 is a bridging factor for endosomal vesicle capture by golgins at
RT the trans-Golgi.";
RL Nat. Cell Biol. 19:1424-1432(2017).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP SUBCELLULAR LOCATION, AND INTERACTION WITH EMX1 AND GLI3.
RX PubMed=29263200; DOI=10.15252/embr.201744632;
RA Kim Y.J., Osborn D.P., Lee J.Y., Araki M., Araki K., Mohun T.,
RA Kaensaekoski J., Brandstack N., Kim H.T., Miralles F., Kim C.H.,
RA Brown N.A., Kim H.G., Martinez-Barbera J.P., Ataliotis P., Raivio T.,
RA Layman L.C., Kim S.H.;
RT "WDR11-mediated Hedgehog signalling defects underlie a new ciliopathy
RT related to Kallmann syndrome.";
RL EMBO Rep. 19:269-289(2018).
CC -!- FUNCTION: Involved in the Hedgehog (Hh) signaling pathway, is essential
CC for normal ciliogenesis (PubMed:29263200). Regulates the proteolytic
CC processing of GLI3 and cooperates with the transcription factor EMX1 in
CC the induction of downstream Hh pathway gene expression and
CC gonadotropin-releasing hormone production (PubMed:29263200). WDR11
CC complex facilitates the tethering of Adaptor protein-1 complex (AP-1)-
CC derived vesicles. WDR11 complex acts together with TBC1D23 to
CC facilitate the golgin-mediated capture of vesicles generated using AP-1
CC (By similarity). {ECO:0000250|UniProtKB:Q9BZH6,
CC ECO:0000269|PubMed:29263200}.
CC -!- SUBUNIT: Component of the complex WDR11 composed of C17orf75, FAM91A1
CC and WDR11; FAM91A1 and WDR11 are required for proper location of the
CC complex (By similarity). Interacts with GLI3; the interaction
CC associateS EMX1 with GLI3 (PubMed:29263200). Interacts with TBC1D23;
CC this interaction may be indirect and recruits TBC1D23 to AP-1-derived
CC vesicles (PubMed:29084197). Interacts (via the N-terminal and the
CC central portion of the protein) with EMX1 (PubMed:29263200).
CC {ECO:0000250|UniProtKB:Q9BZH6, ECO:0000269|PubMed:29084197,
CC ECO:0000269|PubMed:29263200}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body
CC {ECO:0000269|PubMed:29263200}. Cytoplasm {ECO:0000269|PubMed:29263200}.
CC Nucleus {ECO:0000250|UniProtKB:Q9BZH6}. Cytoplasm, cytoskeleton, cilium
CC axoneme {ECO:0000269|PubMed:29263200}. Cytoplasmic vesicle
CC {ECO:0000250|UniProtKB:Q9BZH6}. Golgi apparatus, trans-Golgi network
CC {ECO:0000250|UniProtKB:Q9BZH6}. Note=Shuttles from the cilium to the
CC nucleus in response to Hh signaling. Might be shuttling between the
CC nucleus and the cytoplasm. {ECO:0000250|UniProtKB:Q9BZH6}.
CC -!- TISSUE SPECIFICITY: Broadly expressed in various organs including
CC brain, eye,ear, lung, heart, kideny and gonads (PubMed:29263200).
CC Cerebral cortex. The entire developing central nervous system, except
CC for the spinal cord, reveals expression. Expressed in the
CC neuroepithelium, including the diencephalic region that gives rise to
CC hypothalamic neurons. In the adult brain, intense expression is
CC restricted to the olfactory bulb, the olfaction-related piriform
CC cortex, the granule cell layer of the cerebellum, and neurons of the
CC hippocampal formation. The brain demonstrated expression scattered
CC throughout the hypothalamus, sometimes in clusters of neurons
CC (PubMed:20887964). {ECO:0000269|PubMed:20887964,
CC ECO:0000269|PubMed:29263200}.
CC -!- DEVELOPMENTAL STAGE: Expressed in embryos from 10.5. to 14.5 dpc
CC (PubMed:20887964, PubMed:29263200). In 10.5-12.5 dpc embryos, detected
CC in the vesicles of the heart, branchial arches, mesonephric duct, head
CC mesenchyme, developing eye and forebrain (PubMed:29263200). At 12.5 and
CC 14.5 dpc, high levels of expression are particularly noteworthy in the
CC developing cortex and the olfactory bulb (PubMed:20887964,
CC PubMed:29263200). {ECO:0000269|PubMed:20887964,
CC ECO:0000269|PubMed:29263200}.
CC -!- DISRUPTION PHENOTYPE: Mutants show retardation of growth and
CC development with mid-gestation embryonic lethality, delayed puberty,
CC reproductive dysfunctions and obesity. The rare mutant survivors
CC through adulthood exhibit abnormal digit separation and syndactyly, as
CC well as shortened limbs and hypoplastic skeletons with reduced or
CC absent bone mineralization. Their head show a diminutive and curved
CC nasal midline and a small lower jaw with microcephaly, closely spaced
CC eyes or single/absent eyes. They have hypothalamic gonadotropin-
CC releasing hormone (GnRH) deficiency and pituitary dysgenesis. In some
CC cases, they exhibit exencephaly. At 12.5 dpc, they also have heart
CC defects with a double-outlet right ventricle, ventricular septal
CC defects and sometimes thorcic skeletal defect and lung airway
CC abnormalities (PubMed:29263200). Mutant cells show defective
CC ciliogenesis with a significant reduction in the length of the ciliary
CC axoneme and the frequency of ciliated cells (PubMed:29263200).
CC {ECO:0000269|PubMed:29263200}.
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DR EMBL; BC037177; AAH37177.1; -; mRNA.
DR EMBL; AK043051; BAC31449.2; -; mRNA.
DR EMBL; AK173155; BAD32433.1; -; mRNA.
DR CCDS; CCDS40155.1; -.
DR RefSeq; NP_758459.2; NM_172255.3.
DR AlphaFoldDB; Q8K1X1; -.
DR BioGRID; 228899; 20.
DR IntAct; Q8K1X1; 2.
DR MINT; Q8K1X1; -.
DR STRING; 10090.ENSMUSP00000081567; -.
DR iPTMnet; Q8K1X1; -.
DR PhosphoSitePlus; Q8K1X1; -.
DR EPD; Q8K1X1; -.
DR jPOST; Q8K1X1; -.
DR MaxQB; Q8K1X1; -.
DR PaxDb; Q8K1X1; -.
DR PRIDE; Q8K1X1; -.
DR ProteomicsDB; 299968; -.
DR DNASU; 207425; -.
DR GeneID; 207425; -.
DR KEGG; mmu:207425; -.
DR CTD; 55717; -.
DR MGI; MGI:1920230; Wdr11.
DR eggNOG; KOG1912; Eukaryota.
DR InParanoid; Q8K1X1; -.
DR OrthoDB; 617629at2759; -.
DR PhylomeDB; Q8K1X1; -.
DR Reactome; R-MMU-9013407; RHOH GTPase cycle.
DR BioGRID-ORCS; 207425; 4 hits in 73 CRISPR screens.
DR ChiTaRS; Wdr11; mouse.
DR PRO; PR:Q8K1X1; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q8K1X1; protein.
DR GO; GO:0005930; C:axoneme; IDA:UniProtKB.
DR GO; GO:0036064; C:ciliary basal body; IDA:UniProtKB.
DR GO; GO:0005929; C:cilium; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0015630; C:microtubule cytoskeleton; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005802; C:trans-Golgi network; ISS:UniProtKB.
DR GO; GO:0060271; P:cilium assembly; IDA:UniProtKB.
DR GO; GO:0060322; P:head development; IMP:UniProtKB.
DR GO; GO:0007507; P:heart development; IMP:UniProtKB.
DR GO; GO:0006886; P:intracellular protein transport; ISS:UniProtKB.
DR GO; GO:0035264; P:multicellular organism growth; IMP:UniProtKB.
DR GO; GO:0008589; P:regulation of smoothened signaling pathway; IDA:UniProtKB.
DR GO; GO:0099041; P:vesicle tethering to Golgi; ISS:UniProtKB.
DR Gene3D; 2.130.10.10; -; 3.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR InterPro; IPR039694; WDR11.
DR PANTHER; PTHR14593; PTHR14593; 1.
DR SMART; SM00320; WD40; 6.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 2.
PE 1: Evidence at protein level;
KW Cell projection; Cytoplasm; Cytoplasmic vesicle; Cytoskeleton;
KW Golgi apparatus; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW WD repeat.
FT CHAIN 1..1223
FT /note="WD repeat-containing protein 11"
FT /id="PRO_0000309846"
FT REPEAT 59..108
FT /note="WD 1"
FT REPEAT 111..154
FT /note="WD 2"
FT REPEAT 354..393
FT /note="WD 3"
FT REPEAT 470..509
FT /note="WD 4"
FT REPEAT 565..604
FT /note="WD 5"
FT REPEAT 707..744
FT /note="WD 6"
FT REPEAT 746..786
FT /note="WD 7"
FT REPEAT 792..830
FT /note="WD 8"
FT REPEAT 892..939
FT /note="WD 9"
FT MOD_RES 205
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BZH6"
FT MOD_RES 209
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BZH6"
FT MOD_RES 401
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 405
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CONFLICT 482
FT /note="T -> M (in Ref. 2; BAC31449)"
FT /evidence="ECO:0000305"
FT CONFLICT 766..780
FT /note="IAMYNDGAEVWDTKE -> SRMVKDFIFCQSFLQ (in Ref. 3;
FT BAD32433)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1223 AA; 135937 MW; D8C945901E2C245E CRC64;
MLPYTVNFKV SARTLTGALN AHNKAAVDWG WQGLIAYGCH SLVVVIDSNT AQTLQVLEKH
KADIVKVRWA RENYHHNIGS PYCLRLASAD VTGKIIVWDV AAGVAQCEIQ EHVKPIQDVQ
WLWNQDASRD LLLAIHPPNY IVLWNADTGT KLWKKSYADN ILSFSFDPFD PSHLTLLTSE
GIVFISDFSP SKPPSGPGKK VYISSPHSSP AHNKLAAATG AKKALNKVKI LITQEKPSAD
FVALNDCLQL AYLPSKRNHM LLLYPREILI LDLEVNQTVG VIAIERTGVP FLQVIPCSQR
DGLFCLHENG CITLRVRRSY NSICTTSNDE PDLDPVQELT YDLRSQCDAI RVTKTVRPFS
MVCCPVNENA AALIVSDGRV MIWELKSAVC SRNARNSSGV SPLYSPVSFC GIPGGVLQNK
LPDLSLDNMI GQSAIAGEEH PKGSILQEVH LKFLLTGLLS GLPSPQFAIR MCPPLTTKNI
KTYQPLLAVG TSNGSVLVYH LTSGLLHKEL SVHSCEVKGI EWTSLTSFLS FAASTPNNMG
LVRNELQLVD LPTGRSTAFR GDRGNDESPI EMIKVSHLKQ YLAVVFKDKP LELWDIRTCT
LLREMSKSFP AITALEWSPS HNLKSLRKKQ LATREAMARQ TVVSDAELGA VESSVISLLQ
EAESKAELSQ NISAREHFVF TDNDGQVYHL TVEGNSVKDS ARIPPDGSMG SITCIAWKGD
TLVLGDMDGN LNFWDLKARV SRGIPTHRSW VRKIRFAPGK GNQKLIAMYN DGAEVWDTKE
VQMVSSLRSG RNVTFRILDV DWCTSDKVIL ASDDGCIRVL EMSMKSTCFR MDEQELVEPV
WCPYLLVPRA ALALKAFLLH QPWNGRYSLD ISHIDYPENE EIKTLLQEQL HALSNDIKKL
LLDPDFSLLQ RCLLVSRLYG DESELHFWTV AAHYLHSLSQ AKSGDTVVTK EGAPKDRLSN
PLDICYDVLC ENTYFQKFQL ERVNLQEVKR STYDHTRKCT DQLLLLGQTD RAVQLLLETS
ADNQHYYCDS LKACLVTTVT SSGPSQSTIK LVATNMIANG KLAEGVQLLC LIDKAADACR
YLQTYGEWNR AAWLAKVRLN SEECADVLKR WVDHLCSPQV NQKSKALLVL LSLGCFVSVA
ETLHSMRYFD RAALFVEACL KYGAFEVSED TEKLIAAIYA DYARSLKSLG FRQGAVRFAS
KAGAAGRDLL NELGSTKEEL TES
