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Protein

Lethal(2) giant larvae protein homolog 1

Gene

LLGL1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

GO - Molecular functioni

  1. protein kinase binding Source: UniProtKB
  2. Rab GTPase activator activity Source: UniProtKB
  3. structural molecule activity Source: ProtInc

GO - Biological processi

  1. axonogenesis Source: UniProtKB
  2. cortical actin cytoskeleton organization Source: UniProtKB
  3. exocytosis Source: UniProtKB-KW
  4. Golgi to plasma membrane transport Source: UniProtKB
  5. maintenance of apical/basal cell polarity Source: Ensembl
  6. positive regulation of Rab GTPase activity Source: GOC
  7. protein complex assembly Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Exocytosis

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:LLGL1
Synonyms:DLG4, HUGL, HUGL1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:6628. LLGL1.

Subcellular locationi

Early endosome membrane By similarity. Golgi apparatustrans-Golgi network membrane By similarity. Golgi apparatus membrane By similarity. Cell projectionaxon By similarity. Cytoplasmcytoskeleton 2 Publications
Note: Localized to the lateral membrane during the polarization and formation cell-cell contacts. Enriched in developping axons (By similarity).By similarity

GO - Cellular componenti

  1. axon Source: UniProtKB-SubCell
  2. cortical actin cytoskeleton Source: UniProtKB
  3. cytoplasm Source: UniProtKB
  4. cytoskeleton Source: ProtInc
  5. early endosome membrane Source: UniProtKB
  6. Golgi cis cisterna Source: UniProtKB
  7. Golgi membrane Source: UniProtKB-SubCell
  8. myelin sheath abaxonal region Source: Ensembl
  9. trans-Golgi network membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell projection, Cytoplasm, Cytoskeleton, Endosome, Golgi apparatus, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA30396.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10641064Lethal(2) giant larvae protein homolog 1PRO_0000232725Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei663 – 6631Phosphoserine1 Publication
Modified residuei958 – 9581PhosphothreonineBy similarity

Post-translational modificationi

Phosphorylated at least at Ser-663 by PRKCI.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ15334.
PaxDbiQ15334.
PRIDEiQ15334.

PTM databases

PhosphoSiteiQ15334.

Expressioni

Tissue specificityi

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.3 Publications

Gene expression databases

BgeeiQ15334.
CleanExiHS_DLG4.
HS_LLGL1.
ExpressionAtlasiQ15334. baseline and differential.
GenevestigatoriQ15334.

Organism-specific databases

HPAiHPA022924.
HPA023569.

Interactioni

Subunit structurei

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.By similarity3 Publications

Protein-protein interaction databases

BioGridi110183. 15 interactions.
IntActiQ15334. 25 interactions.
MINTiMINT-1387867.
STRINGi9606.ENSP00000321537.

Structurei

3D structure databases

ProteinModelPortaliQ15334.
SMRiQ15334. Positions 437-465, 517-544.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati38 – 7134WD 1Add
BLAST
Repeati78 – 11942WD 2Add
BLAST
Repeati139 – 17638WD 3Add
BLAST
Repeati200 – 23435WD 4Add
BLAST
Repeati240 – 27233WD 5Add
BLAST
Repeati290 – 33243WD 6Add
BLAST
Repeati340 – 37435WD 7Add
BLAST
Repeati396 – 47479WD 8Add
BLAST
Repeati518 – 59376WD 9Add
BLAST
Repeati602 – 66362WD 10Add
BLAST
Repeati723 – 78361WD 11Add
BLAST
Repeati792 – 84453WD 12Add
BLAST
Repeati849 – 90254WD 13Add
BLAST
Repeati916 – 93924WD 14Add
BLAST

Sequence similaritiesi

Belongs to the WD repeat L(2)GL family.Curated
Contains 14 WD repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiNOG289584.
GeneTreeiENSGT00390000000018.
HOGENOMiHOG000115700.
HOVERGENiHBG052711.
InParanoidiQ15334.
KOiK06094.
OMAiVTLHAEW.
OrthoDBiEOG79W94C.
PhylomeDBiQ15334.
TreeFamiTF314585.

Family and domain databases

Gene3Di2.130.10.10. 3 hits.
InterProiIPR000664. Lethal2_giant.
IPR013577. LLGL2.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
[Graphical view]
PfamiPF08366. LLGL. 1 hit.
[Graphical view]
PRINTSiPR00962. LETHAL2GIANT.
SMARTiSM00320. WD40. 5 hits.
[Graphical view]
SUPFAMiSSF50978. SSF50978. 4 hits.
PROSITEiPS00678. WD_REPEATS_1. 2 hits.
PS50082. WD_REPEATS_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q15334-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MMKFRFRRQG ADPQREKLKQ ELFAFNKTVE HGFPNQPSAL AFDPELRIMA
60 70 80 90 100
IGTRSGAVKI YGAPGVEFTG LHRDAATVTQ MHFLTGQGRL LSLLDDSSLH
110 120 130 140 150
LWEIVHHNGC AHLEEALSFQ LPSRPGFDGA SAPLSLTRVT VVLLVAASDI
160 170 180 190 200
AALGTEGSSV FFLDVTTLTL LEGQTLAPGE VLRSVPDDYR CGKALGPVES
210 220 230 240 250
LQGHLRDPTK ILIGYSRGLL VIWNQASQCV DHIFLGNQQL ESLCWGRDSS
260 270 280 290 300
TVVSSHSDGS YAVWSVDAGS FPTLQPTVAT TPYGPFPCKA INKILWRNCE
310 320 330 340 350
SGGHFIIFSG GMPRASYGDR HCVSVLRAET LVTLDFTSRI IDFFTVHSTR
360 370 380 390 400
PEDEFDDPQA LAVLLEEELV VLDLQTPGWP AVPAPYLAPL HSSAITCSAH
410 420 430 440 450
VASVPAKLWA RIVSAGEQQS PQPVSSALSW PITGGRNLAQ EPSQRGLLLT
460 470 480 490 500
GHEDGTVRFW DASGVALRPL YKLSTAGLFQ TDCEHADSLA QAAEDDWPPF
510 520 530 540 550
RKVGCFDPYS DDPRLGVQKV ALCKYTAQMV VAGTAGQVLV LELSDVPVEQ
560 570 580 590 600
AVSVAIIDLL QDREGFTWKG HERLSPRTGP LPWPAGFQPR VLVQCLPPAA
610 620 630 640 650
VTAVTLHTEW SLVAFGTSHG FGLFDYQRKS PVLARCTLHP NDSLAMEGPL
660 670 680 690 700
SRVKSLKKSL RQSFRRIRKS RVSGKKRAAN ASSKLQEANA QLAEQACPHD
710 720 730 740 750
VEMTPVQRRI EPRSADDSLS GVVRCLYFAD TFLRDGAHHG PTMWAGTNSG
760 770 780 790 800
SVFAYALEVP AAAVGGEKRP EQAVEAVLGK EVQLMHRAPV VAIAVLDGRG
810 820 830 840 850
RPLPEPYEAS RDLAQAPDMQ GGHAVLIASE EQFKVFTLPK VSAKTKFKLT
860 870 880 890 900
AHEGCRVRKV ALATFASVAC EDYAETCLAC LTNLGDVHVF SVPGLRPQVH
910 920 930 940 950
YSCIRKEDIS GIASCVFTRH GQGFYLISPS EFERFSLSAR NITEPLCSLD
960 970 980 990 1000
INWPRDATQA SYRIRESPKL SQANGTPSIL LAPQSLDGSP DPAHSMGPDT
1010 1020 1030 1040 1050
PEPPEAALSP MSIDSATSAD TTLDTTGDVT VEDVKDFLGS SEESEKNLRN
1060
LAEDEAHACA ILIK
Length:1,064
Mass (Da):115,418
Last modified:September 21, 2009 - v3
Checksum:i9318D6736934E4D5
GO

Sequence cautioni

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. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti5 – 51R → P in CAA60130 (PubMed:7542763).Curated
Sequence conflicti152 – 1521A → G in BAA19516 (PubMed:8565641).Curated
Sequence conflicti159 – 1591S → SS in CAA60130 (PubMed:7542763).Curated
Sequence conflicti194 – 1941A → D in CAA60130 (PubMed:7542763).Curated
Sequence conflicti206 – 2061R → Q in CAA60130 (PubMed:7542763).Curated
Sequence conflicti216 – 2161S → D in BAA19516 (PubMed:8565641).Curated
Sequence conflicti223 – 2231W → R in CAA60130 (PubMed:7542763).Curated
Sequence conflicti226 – 2272AS → SR in BAA19516 (PubMed:8565641).Curated
Sequence conflicti337 – 3382TS → HF in CAA60130 (PubMed:7542763).Curated
Sequence conflicti400 – 4001H → Y in BAA19516 (PubMed:8565641).Curated
Sequence conflicti486 – 4861A → S in CAA60130 (PubMed:7542763).Curated
Sequence conflicti580 – 5801P → L in CAA60130 (PubMed:7542763).Curated
Sequence conflicti588 – 5881Q → L in BAA19516 (PubMed:8565641).Curated
Sequence conflicti590 – 5901R → C in CAA60130 (PubMed:7542763).Curated
Sequence conflicti624 – 6296FDYQRK → L in CAA60130 (PubMed:7542763).Curated
Sequence conflicti686 – 6861Q → L in BAA19516 (PubMed:8565641).Curated
Sequence conflicti781 – 7822EV → KE in BAA19516 (PubMed:8565641).Curated
Sequence conflicti782 – 7821V → L in CAA60130 (PubMed:7542763).Curated
Sequence conflicti799 – 7991Missing in CAA60130 (PubMed:7542763).Curated
Sequence conflicti818 – 8181D → H in CAA60130 (PubMed:7542763).Curated
Sequence conflicti860 – 8601V → VV in CAA60130 (PubMed:7542763).Curated
Sequence conflicti871 – 8711E → R in BAA19516 (PubMed:8565641).Curated
Sequence conflicti894 – 8941Missing in BAA19516 (PubMed:8565641).Curated
Sequence conflicti898 – 8981Q → E in CAA60130 (PubMed:7542763).Curated
Sequence conflicti945 – 9451P → G in CAA60130 (PubMed:7542763).Curated
Sequence conflicti1060 – 10645AILIK → CI in CAA60130 (PubMed:7542763).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti148 – 1481S → G.3 Publications
Corresponds to variant rs2290505 [ dbSNP | Ensembl ].
VAR_058710
Natural varianti550 – 5501Q → H.1 Publication
Corresponds to variant rs1063683 [ dbSNP | Ensembl ].
VAR_058711

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X86371 mRNA. Translation: CAA60130.1.
D50550 mRNA. Translation: BAA19516.1. Frameshift.
BC028037 mRNA. Translation: AAH28037.1.
BC151838 mRNA. Translation: AAI51839.1.
CCDSiCCDS32586.1.
PIRiI38171.
RefSeqiNP_004131.3. NM_004140.3.
UniGeneiHs.513983.

Genome annotation databases

EnsembliENST00000316843; ENSP00000321537; ENSG00000131899.
GeneIDi3996.
KEGGihsa:3996.
UCSCiuc002gsp.3. human.

Polymorphism databases

DMDMi259016343.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X86371 mRNA. Translation: CAA60130.1.
D50550 mRNA. Translation: BAA19516.1. Frameshift.
BC028037 mRNA. Translation: AAH28037.1.
BC151838 mRNA. Translation: AAI51839.1.
CCDSiCCDS32586.1.
PIRiI38171.
RefSeqiNP_004131.3. NM_004140.3.
UniGeneiHs.513983.

3D structure databases

ProteinModelPortaliQ15334.
SMRiQ15334. Positions 437-465, 517-544.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110183. 15 interactions.
IntActiQ15334. 25 interactions.
MINTiMINT-1387867.
STRINGi9606.ENSP00000321537.

PTM databases

PhosphoSiteiQ15334.

Polymorphism databases

DMDMi259016343.

Proteomic databases

MaxQBiQ15334.
PaxDbiQ15334.
PRIDEiQ15334.

Protocols and materials databases

DNASUi3996.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000316843; ENSP00000321537; ENSG00000131899.
GeneIDi3996.
KEGGihsa:3996.
UCSCiuc002gsp.3. human.

Organism-specific databases

CTDi3996.
GeneCardsiGC17P018128.
HGNCiHGNC:6628. LLGL1.
HPAiHPA022924.
HPA023569.
MIMi600966. gene.
neXtProtiNX_Q15334.
PharmGKBiPA30396.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG289584.
GeneTreeiENSGT00390000000018.
HOGENOMiHOG000115700.
HOVERGENiHBG052711.
InParanoidiQ15334.
KOiK06094.
OMAiVTLHAEW.
OrthoDBiEOG79W94C.
PhylomeDBiQ15334.
TreeFamiTF314585.

Miscellaneous databases

GeneWikiiLLGL1.
GenomeRNAii3996.
NextBioi15682.
PROiQ15334.
SOURCEiSearch...

Gene expression databases

BgeeiQ15334.
CleanExiHS_DLG4.
HS_LLGL1.
ExpressionAtlasiQ15334. baseline and differential.
GenevestigatoriQ15334.

Family and domain databases

Gene3Di2.130.10.10. 3 hits.
InterProiIPR000664. Lethal2_giant.
IPR013577. LLGL2.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
[Graphical view]
PfamiPF08366. LLGL. 1 hit.
[Graphical view]
PRINTSiPR00962. LETHAL2GIANT.
SMARTiSM00320. WD40. 5 hits.
[Graphical view]
SUPFAMiSSF50978. SSF50978. 4 hits.
PROSITEiPS00678. WD_REPEATS_1. 2 hits.
PS50082. WD_REPEATS_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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(1994) [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(1995) [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(2003) [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(2002) [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(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY.
  6. Cited for: FUNCTION, TISSUE SPECIFICITY, INVOLVEMENT IN COLORECTAL CANCER AND MELANOMA.
  7. 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(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiL2GL1_HUMAN
AccessioniPrimary (citable) accession number: Q15334
Secondary accession number(s): A7MBM7
, O00188, Q58F11, Q86UK6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 17, 2006
Last sequence update: September 21, 2009
Last modified: March 3, 2015
This is version 120 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

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.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.