LRWD1_MOUSE
ID LRWD1_MOUSE Reviewed; 648 AA.
AC Q8BUI3; D3Z2P9; Q3TIG2; Q8BKI3; Q9DBW4;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Leucine-rich repeat and WD repeat-containing protein 1;
DE AltName: Full=ORC-associated protein;
DE Short=ORCA;
DE AltName: Full=Origin recognition complex-associated protein;
GN Name=LRWD1; Synonyms=Orca;
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=BALB/cJ, C57BL/6J, and NOD; TISSUE=Eye, Lung, and Thymus;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Colon;
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 TISSUE SPECIFICITY.
RX PubMed=17074343; DOI=10.1016/j.fertnstert.2006.04.039;
RA Lin Y.H., Lin Y.M., Teng Y.N., Hsieh T.Y., Lin Y.S., Kuo P.L.;
RT "Identification of ten novel genes involved in human spermatogenesis by
RT microarray analysis of testicular tissue.";
RL Fertil. Steril. 86:1650-1658(2006).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=20180869; DOI=10.1111/j.1365-2605.2009.01038.x;
RA Teng Y.N., Liao M.H., Lin Y.B., Kuo P.L., Kuo T.Y.;
RT "Expression of lrwd1 in mouse testis and its centrosomal localization.";
RL Int. J. Androl. 33:832-840(2010).
RN [6]
RP FUNCTION.
RX PubMed=22427655; DOI=10.1074/jbc.m111.337980;
RA Chan K.M., Zhang Z.;
RT "Leucine-rich repeat and WD repeat-containing protein 1 is recruited to
RT pericentric heterochromatin by trimethylated lysine 9 of histone H3 and
RT maintains heterochromatin silencing.";
RL J. Biol. Chem. 287:15024-15033(2012).
CC -!- FUNCTION: Required for G1/S transition. Recruits and stabilizes the
CC origin recognition complex (ORC) onto chromatin during G1 to establish
CC pre-replication complex (preRC) and to heterochromatic sites in post-
CC replicated cells. Binds a combination of DNA and histone methylation
CC repressive marks on heterochromatin. Binds histone H3 and H4
CC trimethylation marks H3K9me3, H3K27me3 and H4K20me3 in a cooperative
CC manner with DNA methylation (By similarity). Required for silencing of
CC major satellite repeats. May be important ORC2, ORC3 and ORC4
CC stability. {ECO:0000250, ECO:0000269|PubMed:22427655}.
CC -!- SUBUNIT: Integral component of the ORC complex (By similarity).
CC Directly interacts with CDT1, GMNN and ORC2. Interacts with ORC2 only
CC when non-ubiquitinated; this interaction prevents LRWD1 ubiquitination
CC and degradation. Some of these interactions are regulated in a cell-
CC cycle dependent manner. Interaction with ORC1 occurs predominantly
CC during G1. Association with phosphorylated ORC1 during mitosis is not
CC efficient. Interaction with CDT1 occurs during G1 phase, as well as
CC during mitosis with phosphorylated CDT1. Interaction with GMNN occurs
CC from G1/S to mitosis. Interaction with ORC2 is observed throughout the
CC cell cycle. The stoichiometry of the ORCA/ORC/CDT1/GMNN complex is
CC 1:1:1:2 (By similarity). Interacts with CUL4A and DDB1; this
CC interaction may lead to ubiquitination (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9UFC0}.
CC Chromosome, centromere {ECO:0000250|UniProtKB:Q9UFC0}. Chromosome,
CC telomere {ECO:0000250|UniProtKB:Q9UFC0}. Cytoplasm, cytoskeleton,
CC microtubule organizing center, centrosome
CC {ECO:0000269|PubMed:20180869}. Chromosome, centromere, kinetochore
CC {ECO:0000250|UniProtKB:Q9UFC0}. Note=Localizes to heterochromatin
CC during G1 phase. Restricted to centromeres or telomeres as cells
CC progress though S phase. When cells enter mitosis, relocalizes to
CC centromeres. Recruitment to pericentric heterochromatin largely depends
CC on the presence of H3K9me3. {ECO:0000250|UniProtKB:Q9UFC0}.
CC -!- TISSUE SPECIFICITY: Testis-specific. {ECO:0000269|PubMed:17074343}.
CC -!- DOMAIN: The entire WD repeat region is required for the interaction
CC with ORC, CDT1 and GMNN, as well as for association with chromatin and
CC for binding to histone H3 and H4 trimethylation marks H3K9me3 and
CC H4K20me3 (By similarity). Centrosomal localization requires additional
CC conformation. {ECO:0000250}.
CC -!- PTM: Ubiquitinated; undergoes 'Lys-48'-linked polyubiquitination
CC leading to proteasomal degradation. Ubiquitination occurs within the WD
CC repeats at the end of the G1 phase. Ubiquitination may be catalyzed by
CC the CUL4-DDB1 E3 ubiquitin-protein ligase complex and other E3 ligases
CC (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the LRWD1 family. {ECO:0000305}.
CC -!- CAUTION: Reported to be testis-specific (PubMed:20180869). However the
CC transcript is found in many tissues, suggesting that the protein is
CC present in many tissues. {ECO:0000305|PubMed:20180869}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB23500.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
CC Sequence=BAC34810.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
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DR EMBL; AK004717; BAB23500.1; ALT_SEQ; mRNA.
DR EMBL; AK051910; BAC34810.1; ALT_SEQ; mRNA.
DR EMBL; AK084948; BAC39318.1; -; mRNA.
DR EMBL; AK153976; BAE32292.1; -; mRNA.
DR EMBL; AK167020; BAE39194.1; -; mRNA.
DR EMBL; AK167868; BAE39884.1; -; mRNA.
DR EMBL; AC087420; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC048397; AAH48397.1; -; mRNA.
DR CCDS; CCDS51666.1; -.
DR RefSeq; NP_082167.2; NM_027891.4.
DR AlphaFoldDB; Q8BUI3; -.
DR BioGRID; 214889; 3.
DR STRING; 10090.ENSMUSP00000006301; -.
DR iPTMnet; Q8BUI3; -.
DR PhosphoSitePlus; Q8BUI3; -.
DR EPD; Q8BUI3; -.
DR MaxQB; Q8BUI3; -.
DR PaxDb; Q8BUI3; -.
DR PeptideAtlas; Q8BUI3; -.
DR PRIDE; Q8BUI3; -.
DR ProteomicsDB; 292375; -.
DR Antibodypedia; 16796; 113 antibodies from 22 providers.
DR DNASU; 71735; -.
DR Ensembl; ENSMUST00000006301; ENSMUSP00000006301; ENSMUSG00000029703.
DR GeneID; 71735; -.
DR KEGG; mmu:71735; -.
DR UCSC; uc008zzx.2; mouse.
DR CTD; 222229; -.
DR MGI; MGI:1918985; Lrwd1.
DR VEuPathDB; HostDB:ENSMUSG00000029703; -.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000154248; -.
DR HOGENOM; CLU_022994_0_0_1; -.
DR InParanoid; Q8BUI3; -.
DR OMA; CPEQYLL; -.
DR OrthoDB; 810613at2759; -.
DR PhylomeDB; Q8BUI3; -.
DR TreeFam; TF329554; -.
DR BioGRID-ORCS; 71735; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Lrwd1; mouse.
DR PRO; PR:Q8BUI3; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q8BUI3; protein.
DR Bgee; ENSMUSG00000029703; Expressed in seminiferous tubule of testis and 256 other tissues.
DR ExpressionAtlas; Q8BUI3; baseline and differential.
DR Genevisible; Q8BUI3; MM.
DR GO; GO:0000781; C:chromosome, telomeric region; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0000776; C:kinetochore; ISS:UniProtKB.
DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR GO; GO:0005664; C:nuclear origin of replication recognition complex; ISS:UniProtKB.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005721; C:pericentric heterochromatin; ISS:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0008327; F:methyl-CpG binding; ISS:UniProtKB.
DR GO; GO:0035064; F:methylated histone binding; ISS:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; ISS:UniProtKB.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-KW.
DR GO; GO:0071169; P:establishment of protein localization to chromatin; ISS:UniProtKB.
DR Gene3D; 2.130.10.10; -; 1.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR025875; Leu-rich_rpt_4.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
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 Pfam; PF12799; LRR_4; 1.
DR Pfam; PF00400; WD40; 1.
DR SMART; SM00369; LRR_TYP; 2.
DR SMART; SM00320; WD40; 4.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS51450; LRR; 3.
DR PROSITE; PS00678; WD_REPEATS_1; 1.
DR PROSITE; PS50082; WD_REPEATS_2; 1.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 2: Evidence at transcript level;
KW Centromere; Chromatin regulator; Chromosome; Cytoplasm; Cytoskeleton;
KW DNA replication; Kinetochore; Leucine-rich repeat; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Telomere; Ubl conjugation; WD repeat.
FT CHAIN 1..648
FT /note="Leucine-rich repeat and WD repeat-containing protein
FT 1"
FT /id="PRO_0000310995"
FT REPEAT 22..43
FT /note="LRR 1"
FT REPEAT 48..69
FT /note="LRR 2"
FT REPEAT 70..91
FT /note="LRR 3"
FT REPEAT 92..113
FT /note="LRR 4"
FT REPEAT 392..432
FT /note="WD 1"
FT REPEAT 443..482
FT /note="WD 2"
FT REPEAT 497..536
FT /note="WD 3"
FT REPEAT 541..592
FT /note="WD 4"
FT REPEAT 616..648
FT /note="WD 5"
FT REGION 214..262
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 259
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UFC0"
SQ SEQUENCE 648 AA; 71594 MW; 1DEDF520FCB24BCA CRC64;
MAPLTPQLLL QRGRPKTDKL GKIQSLNLSG LQLLSEHLDP NLLGRLKKLR ELDLSNNLLE
TLPANLGLSH LRILRCTNNQ LGDVTALHQF PELEELNLEG NPFLTVSDNL KVSFLLPKLR
KVNGKDTAST CSQVENLDRE LMDRVTAHWQ KFIATVSPEE ETDKVRADFM RSAVRDVCYG
PESLIEFTQW RVRMIAEELV ASGGAQVQDA KVPVEHPQAA GASKFRAREV ASKRPGKDPV
TLPPSKRVRA LPPAQAEGSP MGADGGQAAL HLEPLHFLQC HSRNNSPKDL ETQLWACAFE
PAREEGHSRA TSQTVATCGG EAVCVIDCQT GLVLHKYKVP GEEFFSVAWT ALTVVTQAGH
KKRWNMLAAA GLRGMVRLLH VRAGFCCSVI RAHKKAIATL CFSPSHETHL FTASYDKRII
LWDIGVPNQD YKFQASQLLT LNCGSVPLRL CPVATCPDDF LLAGCEGGCY CWDVRLDQPQ
KQRVCEVNFI FSEDSKVSGQ RVDGLAFVNE DVVASKGSGQ GTIYLWSWSQ TWAGRGRQSV
LPVVILVRLQ WSPTNLAYFS LSTCPGKNLV LCGDEEGSVW IYDVEHLLKE PPQATTLQPP
TQILKWPQPT ALGQPVTKTM INTVVANAAF TYLTALTDSN IVSIWRRC
