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Q15334 (L2GL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 116. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Lethal(2) giant larvae protein homolog 1

Short name=LLGL
Alternative name(s):
DLG4
Hugl-1
Human homolog to the D-lgl gene protein
Gene names
Name:LLGL1
Synonyms:DLG4, HUGL, HUGL1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1064 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Cortical cytoskeleton protein found in a complex involved in maintaining cell polarity and epithelial integrity. Involved in the regulation of mitotic spindle orientation, proliferation, differentiation and tissue organization of neuroepithelial cells. Involved in axonogenesis through RAB10 activation thereby regulating vesicular membrane trafficking toward the axonal plasma membrane. Ref.5 Ref.6

Subunit structure

Associated with nonmuscle myosin II heavy chain. Interacts with PRKCI/aPKC, PARD6B/Par-6 and PARD6A. Interacts with STX4A By similarity. Interacts with RAB10 (GDP-bound form); the interaction is direct and promotes RAB10 association with membranes and activation through competition with the Rab inhibitor GDI1 By similarity. Interacts with VPRBP. Ref.1 Ref.4 Ref.7

Subcellular location

Early endosome membrane By similarity. Golgi apparatustrans-Golgi network membrane By similarity. Golgi apparatus membrane By similarity. Cell projectionaxon By similarity. Cytoplasmcytoskeleton. Note: Localized to the lateral membrane during the polarization and formation cell-cell contacts. Enriched in developping axons By similarity. Ref.1 Ref.4

Tissue specificity

Expressed in brain, kidney, and muscle but is barely seen in heart and placenta. Down-regulated or lost in all cell lines and in most of the tumor samples analyzed. Loss was associated with advanced stage of the disease. Ref.1 Ref.5 Ref.6

Post-translational modification

Phosphorylated at least at Ser-663 by PRKCI. Ref.4

Miscellaneous

Down-regulation of LLGL1 is associated with the progression of colorectal cancer and melanoma. Located within the Smith-Magenis syndrome region on chromosome 17; deleted in patients with this syndrome.

Expression increases cell adhesion and decreases cell migration. Substitutes for Drosophila l2gl tumor suppressor function in vivo.

Sequence similarities

Belongs to the WD repeat L(2)GL family.

Contains 14 WD repeats.

Sequence caution

The sequence BAA19516.1 differs from that shown. Reason: Frameshift at positions 205, 216, 737, 740, 794, 799, 866, 872, 881, 945, 968 and 1024.

Ontologies

Keywords
   Biological processExocytosis
   Cellular componentCell projection
Cytoplasm
Cytoskeleton
Endosome
Golgi apparatus
Membrane
   Coding sequence diversityPolymorphism
   DomainRepeat
WD repeat
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processGolgi to plasma membrane transport

Inferred from sequence or structural similarity. Source: UniProtKB

axonogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

cortical actin cytoskeleton organization

Inferred from direct assay Ref.1. Source: UniProtKB

exocytosis

Inferred from electronic annotation. Source: UniProtKB-KW

maintenance of apical/basal cell polarity

Inferred from electronic annotation. Source: Ensembl

positive regulation of Rab GTPase activity

Inferred from sequence or structural similarity. Source: GOC

protein complex assembly

Inferred from direct assay Ref.1. Source: UniProtKB

   Cellular_componentGolgi cis cisterna

Inferred from sequence or structural similarity. Source: UniProtKB

Golgi membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

axon

Inferred from electronic annotation. Source: UniProtKB-SubCell

cortical actin cytoskeleton

Inferred from direct assay Ref.1. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.1. Source: UniProtKB

cytoskeleton

Traceable author statement Ref.1. Source: ProtInc

early endosome membrane

Inferred from sequence or structural similarity. Source: UniProtKB

myelin sheath abaxonal region

Inferred from electronic annotation. Source: Ensembl

trans-Golgi network membrane

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionRab GTPase activator activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.1. Source: UniProtKB

protein kinase binding

Inferred from direct assay Ref.1. Source: UniProtKB

structural molecule activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10641064Lethal(2) giant larvae protein homolog 1
PRO_0000232725

Regions

Repeat38 – 7134WD 1
Repeat78 – 11942WD 2
Repeat139 – 17638WD 3
Repeat200 – 23435WD 4
Repeat240 – 27233WD 5
Repeat290 – 33243WD 6
Repeat340 – 37435WD 7
Repeat396 – 47479WD 8
Repeat518 – 59376WD 9
Repeat602 – 66362WD 10
Repeat723 – 78361WD 11
Repeat792 – 84453WD 12
Repeat849 – 90254WD 13
Repeat916 – 93924WD 14

Amino acid modifications

Modified residue6631Phosphoserine Ref.4
Modified residue9581Phosphothreonine By similarity

Natural variations

Natural variant1481S → G. Ref.1 Ref.2 Ref.3
Corresponds to variant rs2290505 [ dbSNP | Ensembl ].
VAR_058710
Natural variant5501Q → H. Ref.1
Corresponds to variant rs1063683 [ dbSNP | Ensembl ].
VAR_058711

Experimental info

Sequence conflict51R → P in CAA60130. Ref.1
Sequence conflict1521A → G in BAA19516. Ref.2
Sequence conflict1591S → SS in CAA60130. Ref.1
Sequence conflict1941A → D in CAA60130. Ref.1
Sequence conflict2061R → Q in CAA60130. Ref.1
Sequence conflict2161S → D in BAA19516. Ref.2
Sequence conflict2231W → R in CAA60130. Ref.1
Sequence conflict226 – 2272AS → SR in BAA19516. Ref.2
Sequence conflict337 – 3382TS → HF in CAA60130. Ref.1
Sequence conflict4001H → Y in BAA19516. Ref.2
Sequence conflict4861A → S in CAA60130. Ref.1
Sequence conflict5801P → L in CAA60130. Ref.1
Sequence conflict5881Q → L in BAA19516. Ref.2
Sequence conflict5901R → C in CAA60130. Ref.1
Sequence conflict624 – 6296FDYQRK → L in CAA60130. Ref.1
Sequence conflict6861Q → L in BAA19516. Ref.2
Sequence conflict781 – 7822EV → KE in BAA19516. Ref.2
Sequence conflict7821V → L in CAA60130. Ref.1
Sequence conflict7991Missing in CAA60130. Ref.1
Sequence conflict8181D → H in CAA60130. Ref.1
Sequence conflict8601V → VV in CAA60130. Ref.1
Sequence conflict8711E → R in BAA19516. Ref.2
Sequence conflict8941Missing in BAA19516. Ref.2
Sequence conflict8981Q → E in CAA60130. Ref.1
Sequence conflict9451P → G in CAA60130. Ref.1
Sequence conflict1060 – 10645AILIK → CI in CAA60130. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q15334 [UniParc].

Last modified September 22, 2009. Version 3.
Checksum: 9318D6736934E4D5

FASTA1,064115,418
        10         20         30         40         50         60 
MMKFRFRRQG ADPQREKLKQ ELFAFNKTVE HGFPNQPSAL AFDPELRIMA IGTRSGAVKI 

        70         80         90        100        110        120 
YGAPGVEFTG LHRDAATVTQ MHFLTGQGRL LSLLDDSSLH LWEIVHHNGC AHLEEALSFQ 

       130        140        150        160        170        180 
LPSRPGFDGA SAPLSLTRVT VVLLVAASDI AALGTEGSSV FFLDVTTLTL LEGQTLAPGE 

       190        200        210        220        230        240 
VLRSVPDDYR CGKALGPVES LQGHLRDPTK ILIGYSRGLL VIWNQASQCV DHIFLGNQQL 

       250        260        270        280        290        300 
ESLCWGRDSS TVVSSHSDGS YAVWSVDAGS FPTLQPTVAT TPYGPFPCKA INKILWRNCE 

       310        320        330        340        350        360 
SGGHFIIFSG GMPRASYGDR HCVSVLRAET LVTLDFTSRI IDFFTVHSTR PEDEFDDPQA 

       370        380        390        400        410        420 
LAVLLEEELV VLDLQTPGWP AVPAPYLAPL HSSAITCSAH VASVPAKLWA RIVSAGEQQS 

       430        440        450        460        470        480 
PQPVSSALSW PITGGRNLAQ EPSQRGLLLT GHEDGTVRFW DASGVALRPL YKLSTAGLFQ 

       490        500        510        520        530        540 
TDCEHADSLA QAAEDDWPPF RKVGCFDPYS DDPRLGVQKV ALCKYTAQMV VAGTAGQVLV 

       550        560        570        580        590        600 
LELSDVPVEQ AVSVAIIDLL QDREGFTWKG HERLSPRTGP LPWPAGFQPR VLVQCLPPAA 

       610        620        630        640        650        660 
VTAVTLHTEW SLVAFGTSHG FGLFDYQRKS PVLARCTLHP NDSLAMEGPL SRVKSLKKSL 

       670        680        690        700        710        720 
RQSFRRIRKS RVSGKKRAAN ASSKLQEANA QLAEQACPHD VEMTPVQRRI EPRSADDSLS 

       730        740        750        760        770        780 
GVVRCLYFAD TFLRDGAHHG PTMWAGTNSG SVFAYALEVP AAAVGGEKRP EQAVEAVLGK 

       790        800        810        820        830        840 
EVQLMHRAPV VAIAVLDGRG RPLPEPYEAS RDLAQAPDMQ GGHAVLIASE EQFKVFTLPK 

       850        860        870        880        890        900 
VSAKTKFKLT AHEGCRVRKV ALATFASVAC EDYAETCLAC LTNLGDVHVF SVPGLRPQVH 

       910        920        930        940        950        960 
YSCIRKEDIS GIASCVFTRH GQGFYLISPS EFERFSLSAR NITEPLCSLD INWPRDATQA 

       970        980        990       1000       1010       1020 
SYRIRESPKL SQANGTPSIL LAPQSLDGSP DPAHSMGPDT PEPPEAALSP MSIDSATSAD 

      1030       1040       1050       1060 
TTLDTTGDVT VEDVKDFLGS SEESEKNLRN LAEDEAHACA ILIK 

« Hide

References

« Hide 'large scale' references
[1]"A human homologue of the Drosophila tumour suppressor gene l(2)gl maps to 17p11.2-12 and codes for a cytoskeletal protein that associates with nonmuscle myosin II heavy chain."
Strand D.J., Unger S., Corvi R., Hartenstein K., Schenkel H., Kalmes A., Merdes G., Neumann B., Kreig-Schneider F., Coy J.F., Poustka A., Schwab M., Mechler B.
Oncogene 11:291-301(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH MYOSIN II HEAVY CHAIN, VARIANTS GLY-148 AND HIS-550.
Tissue: Brain.
[2]"The human homologue of the murine Llglh gene (LLGL) maps within the Smith-Magenis syndrome region in 17p11.2."
Koyama K., Fukushima Y., Inazawa J., Tomotsune D., Takahashi N., Nakamura Y.
Cytogenet. Cell Genet. 72:78-82(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLY-148.
Tissue: Brain.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLY-148.
Tissue: Fetal brain.
[4]"Mammalian Lgl forms a protein complex with PAR-6 and aPKC independently of PAR-3 to regulate epithelial cell polarity."
Yamanaka T., Horikoshi Y., Sugiyama Y., Ishiyama C., Suzuki A., Hirose T., Iwamatsu A., Shinohara A., Ohno S.
Curr. Biol. 13:734-743(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PARD6B/PAR-6 AND PRKCI/APKC, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-663.
[5]"Reduced expression of Hugl-1, the human homologue of Drosophila tumour suppressor gene lgl, contributes to progression of colorectal cancer."
Schimanski C.C., Schmitz G., Kashyap A., Bosserhoff A.K., Bataille F., Schafer S.C., Lehr H.A., Berger M.R., Galle P.R., Strand S., Strand D.
Oncogene 24:3100-3109(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[6]"Expression of Hugl-1 is strongly reduced in malignant melanoma."
Kuphal S., Wallner S., Schimanski C.C., Bataille F., Hofer P., Strand S., Strand D., Bosserhoff A.K.
Oncogene 25:103-110(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, INVOLVEMENT IN COLORECTAL CANCER AND MELANOMA.
[7]"Involvement of Lgl and Mahjong/VprBP in cell competition."
Tamori Y., Bialucha C.U., Tian A.G., Kajita M., Huang Y.C., Norman M., Harrison N., Poulton J., Ivanovitch K., Disch L., Liu T., Deng W.M., Fujita Y.
PLoS Biol. 8:E1000422-E1000422(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH VPRBP.
[8]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X86371 mRNA. Translation: CAA60130.1.
D50550 mRNA. Translation: BAA19516.1. Frameshift.
BC028037 mRNA. Translation: AAH28037.1.
BC151838 mRNA. Translation: AAI51839.1.
CCDSCCDS32586.1.
PIRI38171.
RefSeqNP_004131.3. NM_004140.3.
UniGeneHs.513983.

3D structure databases

ProteinModelPortalQ15334.
SMRQ15334. Positions 439-464.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110183. 16 interactions.
IntActQ15334. 25 interactions.
MINTMINT-1387867.
STRING9606.ENSP00000321537.

PTM databases

PhosphoSiteQ15334.

Polymorphism databases

DMDM259016343.

Proteomic databases

MaxQBQ15334.
PaxDbQ15334.
PRIDEQ15334.

Protocols and materials databases

DNASU3996.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000316843; ENSP00000321537; ENSG00000131899.
GeneID3996.
KEGGhsa:3996.
UCSCuc002gsp.3. human.

Organism-specific databases

CTD3996.
GeneCardsGC17P018128.
HGNCHGNC:6628. LLGL1.
HPAHPA022924.
HPA023569.
MIM600966. gene.
neXtProtNX_Q15334.
PharmGKBPA30396.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG289584.
HOGENOMHOG000115700.
HOVERGENHBG052711.
InParanoidQ15334.
KOK06094.
OMAVTLHAEW.
OrthoDBEOG79W94C.
PhylomeDBQ15334.
TreeFamTF314585.

Gene expression databases

ArrayExpressQ15334.
BgeeQ15334.
CleanExHS_DLG4.
HS_LLGL1.
GenevestigatorQ15334.

Family and domain databases

Gene3D2.130.10.10. 3 hits.
InterProIPR000664. Lethal2_giant.
IPR013577. LLGL2.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
[Graphical view]
PfamPF08366. LLGL. 1 hit.
[Graphical view]
PRINTSPR00962. LETHAL2GIANT.
SMARTSM00320. WD40. 5 hits.
[Graphical view]
SUPFAMSSF50978. SSF50978. 4 hits.
PROSITEPS00678. WD_REPEATS_1. 2 hits.
PS50082. WD_REPEATS_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiLLGL1.
GenomeRNAi3996.
NextBio15682.
PROQ15334.
SOURCESearch...

Entry information

Entry nameL2GL1_HUMAN
AccessionPrimary (citable) accession number: Q15334
Secondary accession number(s): A7MBM7 expand/collapse secondary AC list , O00188, Q58F11, Q86UK6
Entry history
Integrated into UniProtKB/Swiss-Prot: April 18, 2006
Last sequence update: September 22, 2009
Last modified: July 9, 2014
This is version 116 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM