L2GL1_HUMAN
ID L2GL1_HUMAN Reviewed; 1064 AA.
AC Q15334; A7MBM7; O00188; Q58F11; Q86UK6;
DT 18-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 22-SEP-2009, sequence version 3.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Lethal(2) giant larvae protein homolog 1;
DE Short=LLGL;
DE AltName: Full=DLG4;
DE AltName: Full=Hugl-1;
DE AltName: Full=Human homolog to the D-lgl gene protein;
GN Name=LLGL1; Synonyms=DLG4, HUGL, HUGL1;
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 [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP INTERACTION WITH MYOSIN II HEAVY CHAIN, AND VARIANTS GLY-148 AND HIS-550.
RC TISSUE=Brain;
RX PubMed=7542763;
RA Strand D.J., Unger S., Corvi R., Hartenstein K., Schenkel H., Kalmes A.,
RA Merdes G., Neumann B., Kreig-Schneider F., Coy J.F., Poustka A., Schwab M.,
RA Mechler B.;
RT "A human homologue of the Drosophila tumour suppressor gene l(2)gl maps to
RT 17p11.2-12 and codes for a cytoskeletal protein that associates with
RT nonmuscle myosin II heavy chain.";
RL Oncogene 11:291-301(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLY-148.
RC TISSUE=Brain;
RX PubMed=8565641; DOI=10.1159/000134167;
RA Koyama K., Fukushima Y., Inazawa J., Tomotsune D., Takahashi N.,
RA Nakamura Y.;
RT "The human homologue of the murine Llglh gene (LLGL) maps within the Smith-
RT Magenis syndrome region in 17p11.2.";
RL Cytogenet. Cell Genet. 72:78-82(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-148.
RC TISSUE=Fetal brain;
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 INTERACTION WITH PARD6B/PAR-6 AND PRKCI/APKC, SUBCELLULAR LOCATION, AND
RP PHOSPHORYLATION AT SER-663.
RX PubMed=12725730; DOI=10.1016/s0960-9822(03)00244-6;
RA Yamanaka T., Horikoshi Y., Sugiyama Y., Ishiyama C., Suzuki A., Hirose T.,
RA Iwamatsu A., Shinohara A., Ohno S.;
RT "Mammalian Lgl forms a protein complex with PAR-6 and aPKC independently of
RT PAR-3 to regulate epithelial cell polarity.";
RL Curr. Biol. 13:734-743(2003).
RN [5]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=15735678; DOI=10.1038/sj.onc.1208520;
RA Schimanski C.C., Schmitz G., Kashyap A., Bosserhoff A.K., Bataille F.,
RA Schafer S.C., Lehr H.A., Berger M.R., Galle P.R., Strand S., Strand D.;
RT "Reduced expression of Hugl-1, the human homologue of Drosophila tumour
RT suppressor gene lgl, contributes to progression of colorectal cancer.";
RL Oncogene 24:3100-3109(2005).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, AND INVOLVEMENT IN COLORECTAL CANCER AND
RP MELANOMA.
RX PubMed=16170365; DOI=10.1038/sj.onc.1209008;
RA Kuphal S., Wallner S., Schimanski C.C., Bataille F., Hofer P., Strand S.,
RA Strand D., Bosserhoff A.K.;
RT "Expression of Hugl-1 is strongly reduced in malignant melanoma.";
RL Oncogene 25:103-110(2006).
RN [7]
RP INTERACTION WITH DCAF1.
RX PubMed=20644714; DOI=10.1371/journal.pbio.1000422;
RA Tamori Y., Bialucha C.U., Tian A.G., Kajita M., Huang Y.C., Norman M.,
RA Harrison N., Poulton J., Ivanovitch K., Disch L., Liu T., Deng W.M.,
RA Fujita Y.;
RT "Involvement of Lgl and Mahjong/VprBP in cell competition.";
RL PLoS Biol. 8:E1000422-E1000422(2010).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
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 {ECO:0000269|PubMed:15735678, ECO:0000269|PubMed:16170365}.
CC -!- SUBUNIT: Associated with nonmuscle myosin II heavy chain. Interacts
CC with PRKCI/aPKC, PARD6B/Par-6 and PARD6A. Interacts with STX4A (By
CC similarity). 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 (By similarity).
CC Interacts with DCAF1. {ECO:0000250, ECO:0000269|PubMed:12725730,
CC ECO:0000269|PubMed:20644714, ECO:0000269|PubMed:7542763}.
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:0000269|PubMed:12725730, ECO:0000269|PubMed:7542763}.
CC Note=Localized to the lateral membrane during the polarization and
CC formation cell-cell contacts. Enriched in developing axons (By
CC similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in brain, kidney, and muscle but is
CC barely seen in heart and placenta. Down-regulated or lost in all cell
CC lines and in most of the tumor samples analyzed. Loss was associated
CC with advanced stage of the disease. {ECO:0000269|PubMed:15735678,
CC ECO:0000269|PubMed:16170365, ECO:0000269|PubMed:7542763}.
CC -!- PTM: Phosphorylated at least at Ser-663 by PRKCI.
CC {ECO:0000269|PubMed:12725730}.
CC -!- MISCELLANEOUS: Down-regulation of LLGL1 is associated with the
CC progression of colorectal cancer and melanoma. Located within the
CC Smith-Magenis syndrome region on chromosome 17; deleted in patients
CC with this syndrome.
CC -!- MISCELLANEOUS: Expression increases cell adhesion and decreases cell
CC migration. Substitutes for Drosophila l(2)gl tumor suppressor function
CC in vivo.
CC -!- SIMILARITY: Belongs to the WD repeat L(2)GL family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA19516.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; X86371; CAA60130.1; -; mRNA.
DR EMBL; D50550; BAA19516.1; ALT_FRAME; mRNA.
DR EMBL; BC028037; AAH28037.1; -; mRNA.
DR EMBL; BC151838; AAI51839.1; -; mRNA.
DR CCDS; CCDS32586.1; -.
DR PIR; I38171; I38171.
DR RefSeq; NP_004131.3; NM_004140.3.
DR AlphaFoldDB; Q15334; -.
DR SMR; Q15334; -.
DR BioGRID; 110183; 138.
DR ComplexPortal; CPX-6188; Scribble cell polarity complex, DLG5-LLGL1-SCRIB variant.
DR ComplexPortal; CPX-6189; Scribble cell polarity complex, DLG4-LLGL1-SCRIB variant.
DR ComplexPortal; CPX-6190; Scribble cell polarity complex, DLG3-LLGL1-SCRIB variant.
DR ComplexPortal; CPX-6191; Scribble cell polarity complex, DLG2-LLGL1-SCRIB variant.
DR ComplexPortal; CPX-6192; Scribble cell polarity complex, DLG1-LLGL1-SCRIB variant.
DR CORUM; Q15334; -.
DR IntAct; Q15334; 47.
DR MINT; Q15334; -.
DR STRING; 9606.ENSP00000321537; -.
DR GlyGen; Q15334; 1 site, 2 O-linked glycans (1 site).
DR iPTMnet; Q15334; -.
DR PhosphoSitePlus; Q15334; -.
DR SwissPalm; Q15334; -.
DR BioMuta; LLGL1; -.
DR DMDM; 259016343; -.
DR EPD; Q15334; -.
DR jPOST; Q15334; -.
DR MassIVE; Q15334; -.
DR MaxQB; Q15334; -.
DR PaxDb; Q15334; -.
DR PeptideAtlas; Q15334; -.
DR PRIDE; Q15334; -.
DR ProteomicsDB; 60533; -.
DR Antibodypedia; 13463; 197 antibodies from 25 providers.
DR DNASU; 3996; -.
DR Ensembl; ENST00000316843.9; ENSP00000321537.4; ENSG00000131899.12.
DR Ensembl; ENST00000640494.2; ENSP00000492144.1; ENSG00000284137.2.
DR GeneID; 3996; -.
DR KEGG; hsa:3996; -.
DR MANE-Select; ENST00000316843.9; ENSP00000321537.4; NM_004140.4; NP_004131.4.
DR UCSC; uc002gsp.4; human.
DR CTD; 3996; -.
DR DisGeNET; 3996; -.
DR GeneCards; LLGL1; -.
DR HGNC; HGNC:6628; LLGL1.
DR HPA; ENSG00000131899; Tissue enhanced (brain).
DR MIM; 600966; gene.
DR neXtProt; NX_Q15334; -.
DR OpenTargets; ENSG00000131899; -.
DR PharmGKB; PA30396; -.
DR VEuPathDB; HostDB:ENSG00000131899; -.
DR eggNOG; KOG1983; Eukaryota.
DR GeneTree; ENSGT00950000182906; -.
DR HOGENOM; CLU_005214_0_0_1; -.
DR InParanoid; Q15334; -.
DR OMA; HACTILI; -.
DR OrthoDB; 122541at2759; -.
DR PhylomeDB; Q15334; -.
DR TreeFam; TF314585; -.
DR PathwayCommons; Q15334; -.
DR SignaLink; Q15334; -.
DR SIGNOR; Q15334; -.
DR BioGRID-ORCS; 3996; 18 hits in 1082 CRISPR screens.
DR ChiTaRS; LLGL1; human.
DR GeneWiki; LLGL1; -.
DR GenomeRNAi; 3996; -.
DR Pharos; Q15334; Tbio.
DR PRO; PR:Q15334; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q15334; protein.
DR Bgee; ENSG00000131899; Expressed in C1 segment of cervical spinal cord and 93 other tissues.
DR ExpressionAtlas; Q15334; baseline and differential.
DR Genevisible; Q15334; HS.
DR GO; GO:0005912; C:adherens junction; IC:ComplexPortal.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0030864; C:cortical actin cytoskeleton; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; TAS:ProtInc.
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: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; IDA:UniProtKB.
DR GO; GO:0005198; F:structural molecule activity; TAS:ProtInc.
DR GO; GO:0007409; P:axonogenesis; ISS:UniProtKB.
DR GO; GO:0030866; P:cortical actin cytoskeleton organization; IDA:UniProtKB.
DR GO; GO:0051294; P:establishment of spindle orientation; IBA:GO_Central.
DR GO; GO:0045197; P:establishment or maintenance of epithelial cell apical/basal polarity; IC:ComplexPortal.
DR GO; GO:0006887; P:exocytosis; IEA:UniProtKB-KW.
DR GO; GO:0006893; P:Golgi to plasma membrane transport; ISS:UniProtKB.
DR GO; GO:0065003; P:protein-containing complex assembly; IDA:UniProtKB.
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; -; 1.
DR InterPro; IPR000664; Lethal2_giant.
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; PF08366; LLGL; 1.
DR Pfam; PF00400; WD40; 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..1064
FT /note="Lethal(2) giant larvae protein homolog 1"
FT /id="PRO_0000232725"
FT REPEAT 38..71
FT /note="WD 1"
FT REPEAT 78..119
FT /note="WD 2"
FT REPEAT 139..176
FT /note="WD 3"
FT REPEAT 200..234
FT /note="WD 4"
FT REPEAT 240..272
FT /note="WD 5"
FT REPEAT 290..332
FT /note="WD 6"
FT REPEAT 340..374
FT /note="WD 7"
FT REPEAT 396..474
FT /note="WD 8"
FT REPEAT 518..593
FT /note="WD 9"
FT REPEAT 602..663
FT /note="WD 10"
FT REPEAT 723..783
FT /note="WD 11"
FT REPEAT 792..844
FT /note="WD 12"
FT REPEAT 849..902
FT /note="WD 13"
FT REPEAT 916..939
FT /note="WD 14"
FT REGION 966..1010
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 966..983
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 663
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:12725730"
FT MOD_RES 958
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q80Y17"
FT MOD_RES 967
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80Y17"
FT MOD_RES 985
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80Y17"
FT VARIANT 148
FT /note="S -> G (in dbSNP:rs2290505)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:7542763, ECO:0000269|PubMed:8565641"
FT /id="VAR_058710"
FT VARIANT 550
FT /note="Q -> H (in dbSNP:rs1063683)"
FT /evidence="ECO:0000269|PubMed:7542763"
FT /id="VAR_058711"
FT CONFLICT 5
FT /note="R -> P (in Ref. 1; CAA60130)"
FT /evidence="ECO:0000305"
FT CONFLICT 152
FT /note="A -> G (in Ref. 2; BAA19516)"
FT /evidence="ECO:0000305"
FT CONFLICT 159
FT /note="S -> SS (in Ref. 1; CAA60130)"
FT /evidence="ECO:0000305"
FT CONFLICT 194
FT /note="A -> D (in Ref. 1; CAA60130)"
FT /evidence="ECO:0000305"
FT CONFLICT 206
FT /note="R -> Q (in Ref. 1; CAA60130)"
FT /evidence="ECO:0000305"
FT CONFLICT 216
FT /note="S -> D (in Ref. 2; BAA19516)"
FT /evidence="ECO:0000305"
FT CONFLICT 223
FT /note="W -> R (in Ref. 1; CAA60130)"
FT /evidence="ECO:0000305"
FT CONFLICT 226..227
FT /note="AS -> SR (in Ref. 2; BAA19516)"
FT /evidence="ECO:0000305"
FT CONFLICT 337..338
FT /note="TS -> HF (in Ref. 1; CAA60130)"
FT /evidence="ECO:0000305"
FT CONFLICT 400
FT /note="H -> Y (in Ref. 2; BAA19516)"
FT /evidence="ECO:0000305"
FT CONFLICT 486
FT /note="A -> S (in Ref. 1; CAA60130)"
FT /evidence="ECO:0000305"
FT CONFLICT 580
FT /note="P -> L (in Ref. 1; CAA60130)"
FT /evidence="ECO:0000305"
FT CONFLICT 588
FT /note="Q -> L (in Ref. 2; BAA19516)"
FT /evidence="ECO:0000305"
FT CONFLICT 590
FT /note="R -> C (in Ref. 1; CAA60130)"
FT /evidence="ECO:0000305"
FT CONFLICT 624..629
FT /note="FDYQRK -> L (in Ref. 1; CAA60130)"
FT /evidence="ECO:0000305"
FT CONFLICT 686
FT /note="Q -> L (in Ref. 2; BAA19516)"
FT /evidence="ECO:0000305"
FT CONFLICT 781..782
FT /note="EV -> KE (in Ref. 2; BAA19516)"
FT /evidence="ECO:0000305"
FT CONFLICT 782
FT /note="V -> L (in Ref. 1; CAA60130)"
FT /evidence="ECO:0000305"
FT CONFLICT 799
FT /note="Missing (in Ref. 1; CAA60130)"
FT /evidence="ECO:0000305"
FT CONFLICT 818
FT /note="D -> H (in Ref. 1; CAA60130)"
FT /evidence="ECO:0000305"
FT CONFLICT 860
FT /note="V -> VV (in Ref. 1; CAA60130)"
FT /evidence="ECO:0000305"
FT CONFLICT 871
FT /note="E -> R (in Ref. 2; BAA19516)"
FT /evidence="ECO:0000305"
FT CONFLICT 894
FT /note="Missing (in Ref. 2; BAA19516)"
FT /evidence="ECO:0000305"
FT CONFLICT 898
FT /note="Q -> E (in Ref. 1; CAA60130)"
FT /evidence="ECO:0000305"
FT CONFLICT 945
FT /note="P -> G (in Ref. 1; CAA60130)"
FT /evidence="ECO:0000305"
FT CONFLICT 1060..1064
FT /note="AILIK -> CI (in Ref. 1; CAA60130)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1064 AA; 115418 MW; 9318D6736934E4D5 CRC64;
MMKFRFRRQG ADPQREKLKQ ELFAFNKTVE HGFPNQPSAL AFDPELRIMA IGTRSGAVKI
YGAPGVEFTG LHRDAATVTQ MHFLTGQGRL LSLLDDSSLH LWEIVHHNGC AHLEEALSFQ
LPSRPGFDGA SAPLSLTRVT VVLLVAASDI AALGTEGSSV FFLDVTTLTL LEGQTLAPGE
VLRSVPDDYR CGKALGPVES LQGHLRDPTK ILIGYSRGLL VIWNQASQCV DHIFLGNQQL
ESLCWGRDSS TVVSSHSDGS YAVWSVDAGS FPTLQPTVAT TPYGPFPCKA INKILWRNCE
SGGHFIIFSG GMPRASYGDR HCVSVLRAET LVTLDFTSRI IDFFTVHSTR PEDEFDDPQA
LAVLLEEELV VLDLQTPGWP AVPAPYLAPL HSSAITCSAH VASVPAKLWA RIVSAGEQQS
PQPVSSALSW PITGGRNLAQ EPSQRGLLLT GHEDGTVRFW DASGVALRPL YKLSTAGLFQ
TDCEHADSLA QAAEDDWPPF RKVGCFDPYS DDPRLGVQKV ALCKYTAQMV VAGTAGQVLV
LELSDVPVEQ AVSVAIIDLL QDREGFTWKG HERLSPRTGP LPWPAGFQPR VLVQCLPPAA
VTAVTLHTEW SLVAFGTSHG FGLFDYQRKS PVLARCTLHP NDSLAMEGPL SRVKSLKKSL
RQSFRRIRKS RVSGKKRAAN ASSKLQEANA QLAEQACPHD VEMTPVQRRI EPRSADDSLS
GVVRCLYFAD TFLRDGAHHG PTMWAGTNSG SVFAYALEVP AAAVGGEKRP EQAVEAVLGK
EVQLMHRAPV VAIAVLDGRG RPLPEPYEAS RDLAQAPDMQ GGHAVLIASE EQFKVFTLPK
VSAKTKFKLT AHEGCRVRKV ALATFASVAC EDYAETCLAC LTNLGDVHVF SVPGLRPQVH
YSCIRKEDIS GIASCVFTRH GQGFYLISPS EFERFSLSAR NITEPLCSLD INWPRDATQA
SYRIRESPKL SQANGTPSIL LAPQSLDGSP DPAHSMGPDT PEPPEAALSP MSIDSATSAD
TTLDTTGDVT VEDVKDFLGS SEESEKNLRN LAEDEAHACA ILIK
