L2GL1_MOUSE
ID L2GL1_MOUSE Reviewed; 1036 AA.
AC Q80Y17; Q61856; Q7TNV3; Q8BN92;
DT 18-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Lethal(2) giant larvae protein homolog 1;
DE Short=LLGL;
DE AltName: Full=Mgl-1;
DE AltName: Full=Mlgl;
GN Name=Llgl1; Synonyms=Llglh;
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].
RC STRAIN=ICR;
RX PubMed=8103190; DOI=10.1038/365069a0;
RA Tomotsune D., Shoji H., Wakamatsu Y., Kondoh H., Takahashi N.;
RT "A mouse homologue of the Drosophila tumour-suppressor gene l(2)gl
RT controlled by Hox-C8 in vivo.";
RL Nature 365:69-72(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Eye, and Osteoclast;
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 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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain, and Olfactory epithelium;
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 [5]
RP INTERACTION WITH PARD6A, AND PHOSPHORYLATION.
RX PubMed=12629547; DOI=10.1038/ncb948;
RA Plant P.J., Fawcett J.P., Lin D.C., Holdorf A.D., Binns K., Kulkarni S.,
RA Pawson T.;
RT "A polarity complex of mPar-6 and atypical PKC binds, phosphorylates and
RT regulates mammalian Lgl.";
RL Nat. Cell Biol. 5:301-308(2003).
RN [6]
RP INTERACTION WITH STX4A.
RX PubMed=11809830; DOI=10.1091/mbc.01-10-0496;
RA Musch A., Cohen D., Yeaman C., Nelson W.J., Rodriguez-Boulan E.,
RA Brennwald P.J.;
RT "Mammalian homolog of Drosophila tumor suppressor lethal (2) giant larvae
RT interacts with basolateral exocytic machinery in Madin-Darby canine kidney
RT cells.";
RL Mol. Biol. Cell 13:158-168(2002).
RN [7]
RP DISRUPTION PHENOTYPE.
RX PubMed=15037549; DOI=10.1101/gad.1178004;
RA Klezovitch O., Fernandez T.E., Tapscott S.J., Vasioukhin V.;
RT "Loss of cell polarity causes severe brain dysplasia in Lgl1 knockout
RT mice.";
RL Genes Dev. 18:559-571(2004).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-957, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-964; SER-982 AND SER-989, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Lung, 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).
CC -!- FUNCTION: Cortical cytoskeleton protein found in a complex involved in
CC maintaining cell polarity and epithelial integrity. Involved in the
CC regulation of mitotic spindle orientation, proliferation,
CC differentiation and tissue organization of neuroepithelial cells.
CC Involved in axonogenesis through RAB10 activation thereby regulating
CC vesicular membrane trafficking toward the axonal plasma membrane.
CC -!- SUBUNIT: Associated with nonmuscle myosin II heavy chain. Interacts
CC with PRKCI/aPKC, PARD6B/Par-6 and PARD6A (By similarity). Interacts
CC with STX4A. Interacts with RAB10 (GDP-bound form); the interaction is
CC direct and promotes RAB10 association with membranes and activation
CC through competition with the Rab inhibitor GDI1. Interacts with DCAF1
CC (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Early endosome membrane {ECO:0000250}. Golgi
CC apparatus, trans-Golgi network membrane {ECO:0000250}. Golgi apparatus
CC membrane {ECO:0000250}. Cell projection, axon {ECO:0000250}. Cytoplasm,
CC cytoskeleton {ECO:0000250}. Note=Localized to the lateral membrane
CC during the polarization and formation cell-cell contacts. Enriched in
CC developing axons (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylated by PRKCI on at least one of the following Ser
CC residues: Ser 654, Ser-658, Ser-662, Ser-669 and Ser-672.
CC Phosphorylation is important for appropriated cell polarization.
CC {ECO:0000269|PubMed:12629547}.
CC -!- DISRUPTION PHENOTYPE: Mice exhibit disorganization and disruption of
CC the apical junctional complex, resulting in hyper-proliferation of
CC neuroblasts and brain dysplasia. Loss of Lgl1 in mice results in
CC formation of neuroepithelial rosette-like structures, similar to the
CC neuroblastic rosettes in human primitive neuroectodermal tumors. The
CC newborn Lgl1(-/-) pups develop severe hydrocephalus and die neonatally.
CC Due to the loss of mitotic spindle orientation, a large proportion of
CC Lgl1(-/-) neural progenitor cells fails to exit the cell cycle and
CC differentiate, and, instead, continues to proliferate and dies by
CC apoptosis. Dividing Lgl1(-/-) cells are unable to asymmetrically
CC localize the Notch inhibitor Numb, and the resulting failure of
CC asymmetric cell divisions may be responsible for the hyperproliferation
CC and the lack of differentiation. {ECO:0000269|PubMed:15037549}.
CC -!- SIMILARITY: Belongs to the WD repeat L(2)GL family. {ECO:0000305}.
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DR EMBL; D16141; BAA03712.1; -; mRNA.
DR EMBL; AK084386; BAC39171.1; -; mRNA.
DR EMBL; AK159412; BAE35062.1; -; mRNA.
DR EMBL; AL596215; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC050913; AAH50913.1; -; mRNA.
DR EMBL; BC055399; AAH55399.1; -; mRNA.
DR CCDS; CCDS48813.1; -.
DR PIR; S36758; S36758.
DR RefSeq; NP_001152876.1; NM_001159404.1.
DR RefSeq; NP_001152877.1; NM_001159405.1.
DR RefSeq; NP_032528.1; NM_008502.2.
DR AlphaFoldDB; Q80Y17; -.
DR SMR; Q80Y17; -.
DR BioGRID; 201173; 13.
DR CORUM; Q80Y17; -.
DR IntAct; Q80Y17; 1.
DR MINT; Q80Y17; -.
DR STRING; 10090.ENSMUSP00000060749; -.
DR iPTMnet; Q80Y17; -.
DR PhosphoSitePlus; Q80Y17; -.
DR SwissPalm; Q80Y17; -.
DR jPOST; Q80Y17; -.
DR MaxQB; Q80Y17; -.
DR PaxDb; Q80Y17; -.
DR PeptideAtlas; Q80Y17; -.
DR PRIDE; Q80Y17; -.
DR ProteomicsDB; 264902; -.
DR Antibodypedia; 13463; 197 antibodies from 25 providers.
DR DNASU; 16897; -.
DR Ensembl; ENSMUST00000108719; ENSMUSP00000104359; ENSMUSG00000020536.
DR GeneID; 16897; -.
DR KEGG; mmu:16897; -.
DR UCSC; uc007jge.2; mouse.
DR CTD; 3996; -.
DR MGI; MGI:102682; Llgl1.
DR VEuPathDB; HostDB:ENSMUSG00000020536; -.
DR eggNOG; KOG1983; Eukaryota.
DR GeneTree; ENSGT00950000182906; -.
DR HOGENOM; CLU_005214_0_0_1; -.
DR InParanoid; Q80Y17; -.
DR OMA; HACTILI; -.
DR OrthoDB; 122541at2759; -.
DR PhylomeDB; Q80Y17; -.
DR TreeFam; TF314585; -.
DR BioGRID-ORCS; 16897; 4 hits in 77 CRISPR screens.
DR ChiTaRS; Llgl1; mouse.
DR PRO; PR:Q80Y17; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q80Y17; protein.
DR Bgee; ENSMUSG00000020536; Expressed in medial ganglionic eminence and 263 other tissues.
DR ExpressionAtlas; Q80Y17; baseline and differential.
DR Genevisible; Q80Y17; MM.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:MGI.
DR GO; GO:0030864; C:cortical actin cytoskeleton; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005856; C:cytoskeleton; IDA:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; ISS:UniProtKB.
DR GO; GO:0000137; C:Golgi cis cisterna; ISS:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0035748; C:myelin sheath abaxonal region; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0032588; C:trans-Golgi network membrane; ISS:UniProtKB.
DR GO; GO:0005096; F:GTPase activator activity; ISS:UniProtKB.
DR GO; GO:0045159; F:myosin II binding; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0031267; F:small GTPase binding; ISO:MGI.
DR GO; GO:0007409; P:axonogenesis; ISS:UniProtKB.
DR GO; GO:0007420; P:brain development; TAS:UniProtKB.
DR GO; GO:0030866; P:cortical actin cytoskeleton organization; ISO:MGI.
DR GO; GO:0051294; P:establishment of spindle orientation; IBA:GO_Central.
DR GO; GO:0006887; P:exocytosis; IEA:UniProtKB-KW.
DR GO; GO:0006893; P:Golgi to plasma membrane transport; ISS:UniProtKB.
DR GO; GO:0035090; P:maintenance of apical/basal cell polarity; IMP:MGI.
DR GO; GO:0065003; P:protein-containing complex assembly; ISO:MGI.
DR GO; GO:0032878; P:regulation of establishment or maintenance of cell polarity; IBA:GO_Central.
DR GO; GO:0008593; P:regulation of Notch signaling pathway; IBA:GO_Central.
DR GO; GO:0050708; P:regulation of protein secretion; IBA:GO_Central.
DR Gene3D; 2.130.10.10; -; 2.
DR InterPro; IPR000664; Lethal2_giant.
DR InterPro; IPR013905; Lgl_C_dom.
DR InterPro; IPR013577; LLGL2.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR Pfam; PF08596; Lgl_C; 1.
DR Pfam; PF08366; LLGL; 1.
DR PRINTS; PR00962; LETHAL2GIANT.
DR SMART; SM00320; WD40; 5.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 2.
DR PROSITE; PS50082; WD_REPEATS_2; 1.
PE 1: Evidence at protein level;
KW Cell projection; Cytoplasm; Cytoskeleton; Endosome; Exocytosis;
KW Golgi apparatus; Membrane; Phosphoprotein; Reference proteome; Repeat;
KW WD repeat.
FT CHAIN 1..1036
FT /note="Lethal(2) giant larvae protein homolog 1"
FT /id="PRO_0000232726"
FT REPEAT 38..71
FT /note="WD 1"
FT REPEAT 78..119
FT /note="WD 2"
FT REPEAT 139..175
FT /note="WD 3"
FT REPEAT 199..233
FT /note="WD 4"
FT REPEAT 239..271
FT /note="WD 5"
FT REPEAT 289..331
FT /note="WD 6"
FT REPEAT 339..373
FT /note="WD 7"
FT REPEAT 395..473
FT /note="WD 8"
FT REPEAT 517..592
FT /note="WD 9"
FT REPEAT 601..662
FT /note="WD 10"
FT REPEAT 722..782
FT /note="WD 11"
FT REPEAT 791..843
FT /note="WD 12"
FT REPEAT 848..901
FT /note="WD 13"
FT REPEAT 915..938
FT /note="WD 14"
FT REGION 667..688
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 980..1002
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 662
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15334"
FT MOD_RES 957
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17525332"
FT MOD_RES 964
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 982
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 989
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CONFLICT 321
FT /note="C -> F (in Ref. 2; BAC39171)"
FT /evidence="ECO:0000305"
FT CONFLICT 684..685
FT /note="Missing (in Ref. 1; BAA03712)"
FT /evidence="ECO:0000305"
FT CONFLICT 1036
FT /note="G -> GSPEDSEKNLRNLEADDACRAYTLLIK (in Ref. 4;
FT AAH55399)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1036 AA; 112618 MW; 715EFC11A45CD001 CRC64;
MMKFRFRRQG ADPQREKLKQ ELFAFHKTVE HGFPNQPSAL AFDPELRIMA IGTRSGAVKI
YGAPGVEFTG LHRDAATVTQ MHFLPGQGRL LTLLDDSSLH LWEIIHHNGC AHLEEGLSFH
PPSRPSFDNA SFPASLTRVT VVLLVAGNTA ALGTESGSIF FLDVATLALL EGQTLSPDVV
LRSVPDDYRC GKALGPVESL QGHLQDPSKI LIGYSRGLLV IWSQATQSVD NVFLGNQQLE
SLCWGRDGSS IISSHSDGSY AIWSTDTGSP PTLQPTVVTT PYGPFPCKAI NKILWRSCES
GDHFIIFSGG MPRASYGDRH CVSVLRAETL VTLDFTSRVI DFFTVHSTQP EDECDNPQAL
AVLLEEELVV LDLQTPGWPA VPAPYLAPLH SSAITCSAHV ANVPSKLWAR IVSAGEQQSP
QPASSALSWP ITGGRNLAQE PSQRGLLLTG HEDGTVRFWD ASGVALRPLY KLSTAGLFQT
DCEHADSLAQ AVEDDWPPFR KVGCFDPYSD DPRLGIQKVA LCKYTAQMVV AGTAGQVLVL
ELSEVPAEHA VSVANVDLLQ DREGFTWKGH ERLNPHTGLL PWPAGFQPRM LIQCLPPAAV
TAVTLHAEWS LVAFGTSHGF GLFDYQRKSP VLARCTLHPN DSLAMEGPLS RVKSLKKSLR
QSFRRIRKSR VSGKKRTPAA SSKLQEANAQ LAEQTCPHDL EMTPVQRRIE PRSADDSLSG
VVRCLYFADT FLRDATHHGP TMWAGTNSGS VFAYALEVPA ATAGGEKRPE QAVEAVLGKE
VQLMHRAPVV AIAVLDGRGR PLPEPYEASR DLAQAPDMQG GHAVLIASEE QFKVFTLPKV
SAKTKFKLTA HEGCRVRKVA LATFASVMSE DYAETCLACL TNLGDVHVFS VPGLRPQVHY
SCIRKEDISG IASCVFTRHG QGFYLISPSE FERFSLSARN ITEPLCSLDI SWPQNATQPR
LQESPKLSQA NGTRDIILAP ESCEGSPSSA HSKRADTMEP PEAALSPVSI DSAASGDTML
DTTGDVTVEY VKDFLG
