Q6P1M3 (L2GL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Lethal(2) giant larvae protein homolog 2

Alternative name(s):
HGL

Gene names

Name:

LLGL2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1020 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Part of a complex with GPSM2/LGN, PRKCI/aPKC and PARD6B/Par-6, which may ensure the correct organization and orientation of bipolar spindles for normal cell division. This complex plays roles in the initial phase of the establishment of epithelial cell polarity. Ref.4
Subunit structure	Interacts with GPSM2/LGN, PRKCI/aPKC and PARD6B/Par-6. The complex is enhanced during mitosis. Ref.4 Ref.5
Subcellular location	Cytoplasm. Note: Localized in the perinuclear structure and faintly at the cell-cell contacts sites in the interphase. Localized at the cell periphery during metaphase. Cortical localization in mitotic cells. Found in the lateral region of polarized epithelial cells. Ref.4
Post-translational modification	Phosphorylated at Ser-653 by PRKCI. Phosphorylation is enhanced during cell polarization induced by calcium. Phosphorylation may occur during the cell-cell contact-induced cell polarization and may contribute to the segregation of LLGL2 from the PRKCI/aPKC and PARD6B/Par-6 complex. Ref.5
Miscellaneous	Overexpression of LLGL2 inhibits the tight junction formation.
Sequence similarities	Belongs to the WD repeat L(2)GL family. Contains 14 WD repeats.

Ontologies

Keywords
Biological process	Cell cycle Cell division Exocytosis
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat WD repeat
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW cell division Inferred from electronic annotation. Source: UniProtKB-KW exocytosis Inferred from electronic annotation. Source: UniProtKB-KW regulation of establishment or maintenance of cell polarity Inferred from direct assay Ref.5. Source: UniProtKB
Cellular_component	cytoplasm Inferred from direct assay Ref.4. Source: UniProtKB intracellular membrane-bounded organelle Inferred from direct assay. Source: HPA
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform C (identifier: Q6P1M3-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform A (identifier: Q6P1M3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     986-1020: VLKEIQSTLEGDRGSGNWRSHRAAVGCSLSNGGAE → AATGVHIEPPWGAASAMAEQSEWLSVQAAR

Note: No experimental confirmation available.

Isoform B (identifier: Q6P1M3-3)

The sequence of this isoform differs from the canonical sequence as follows:
     346-351: TFDDPY → SGVGAQ
     352-1020: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1020	1020	Lethal(2) giant larvae protein homolog 2		PRO_0000232728
Regions
	Repeat	36 – 69	34	WD 1
	Repeat	76 – 117	42	WD 2
	Repeat	132 – 169	38	WD 3
	Repeat	193 – 227	35	WD 4
	Repeat	233 – 268	36	WD 5
	Repeat	282 – 324	43	WD 6
	Repeat	332 – 366	35	WD 7
	Repeat	388 – 464	77	WD 8
	Repeat	508 – 583	76	WD 9
	Repeat	592 – 653	62	WD 10
	Repeat	713 – 769	57	WD 11
	Repeat	778 – 830	53	WD 12
	Repeat	835 – 888	54	WD 13
	Repeat	902 – 925	24	WD 14
Amino acid modifications
	Modified residue	653	1	Phosphoserine Ref.5
	Modified residue	1015	1	Phosphoserine Ref.6
Natural variations
	Alternative sequence	346 – 351	6	TFDDPY → SGVGAQ in isoform B.		VSP_017944
	Alternative sequence	352 – 1020	669	Missing in isoform B.		VSP_017945
	Alternative sequence	986 – 1020	35	VLKEI…NGGAE → AATGVHIEPPWGAASAMAEQ SEWLSVQAAR in isoform A.		VSP_017946
	Natural variant	45	1	R → H. Ref.1 Corresponds to variant rs1671036 [ dbSNP | Ensembl ].		VAR_050069
	Natural variant	479	1	F → L. Ref.3 Corresponds to variant rs1671021 [ dbSNP | Ensembl ].		VAR_050070
	Natural variant	488	1	P → L. Corresponds to variant rs35991442 [ dbSNP | Ensembl ].		VAR_050071
	Natural variant	490	1	L → P. Corresponds to variant rs1671021 [ dbSNP | Ensembl ].		VAR_050072
	Natural variant	748	1	R → H. Corresponds to variant rs35474687 [ dbSNP | Ensembl ].		VAR_034058
	Natural variant	759	1	P → S. Ref.3 Corresponds to variant rs1661715 [ dbSNP | Ensembl ].		VAR_050073
	Natural variant	790	1	P → L. Corresponds to variant rs1661714 [ dbSNP | Ensembl ].		VAR_050075
	Natural variant	1001	1	G → S. Corresponds to variant rs35886912 [ dbSNP | Ensembl ].		VAR_034059
Experimental info
	Mutagenesis	641	1	S → A: No effect on phosphorylation. Ref.5
	Mutagenesis	645	1	S → A: Decrease of phosphorylation. Ref.5
	Mutagenesis	649	1	S → A: Decrease of phosphorylation. Ref.5
	Mutagenesis	653	1	S → A: Loss of phosphorylation. Ref.5
	Mutagenesis	660	1	S → A: Decrease of phosphorylation. Ref.5
	Mutagenesis	663	1	S → A: No effect on phosphorylation. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform C [UniParc]. Last modified April 18, 2006. Version 2. Checksum: 9C36BFF9F94314B5	FASTA	1,020	113,448
	10 20 30 40 50 60 MRRFLRPGHD PVRERLKRDL FQFNKTVEHG FPHQPSALGY SPSLRILAIG TRSGAIKLYG 70 80 90 100 110 120 APGVEFMGLH QENNAVTQIH LLPGQCQLVT LLDDNSLHLW SLKVKGGASE LQEDESFTLR 130 140 150 160 170 180 GPPGAAPSAT QITVVLPHSS CELLYLGTES GNVFVVQLPA FRALEDRTIS SDAVLQRLPE 190 200 210 220 230 240 EARHRRVFEM VEALQEHPRD PNQILIGYSR GLVVIWDLQG SRVLYHFLSS QQLENIWWQR 250 260 270 280 290 300 DGRLLVSCHS DGSYCQWPVS SEAQQPEPLR SLVPYGPFPC KAITRILWLT TRQGLPFTIF 310 320 330 340 350 360 QGGMPRASYG DRHCISVIHD GQQTAFDFTS RVIGFTVLTE ADPAATFDDP YALVVLAEEE 370 380 390 400 410 420 LVVIDLQTAG WPPVQLPYLA SLHCSAITCS HHVSNIPLKL WERIIAAGSR QNAHFSTMEW 430 440 450 460 470 480 PIDGGTSLTP APPQRDLLLT GHEDGTVRFW DASGVCLRLL YKLSTVRVFL TDTDPNENFS 490 500 510 520 530 540 AQGEDEWPPL RKVGSFDPYS DDPRLGIQKI FLCKYSGYLA VAGTAGQVLV LELNDEAAEQ 550 560 570 580 590 600 AVEQVEADLL QDQEGYRWKG HERLAARSGP VRFEPGFQPF VLVQCQPPAV VTSLALHSEW 610 620 630 640 650 660 RLVAFGTSHG FGLFDHQQRR QVFVKCTLHP SDQLALEGPL SRVKSLKKSL RQSFRRMRRS 670 680 690 700 710 720 RVSSRKRHPA GPPGEAQEGS AKAERPGLQN MELAPVQRKI EARSAEDSFT GFVRTLYFAD 730 740 750 760 770 780 TYLKDSSRHC PSLWAGTNGG TIYAFSLRVP PAERRMDEPV RAEQAKEIQL MHRAPVVGIL 790 800 810 820 830 840 VLDGHSVPLP EPLEVAHDLS KSPDMQGSHQ LLVVSEEQFK VFTLPKVSAK LKLKLTALEG 850 860 870 880 890 900 SRVRRVSVAH FGSRRAEDYG EHHLAVLTNL GDIQVVSLPL LKPQVRYSCI RREDVSGIAS 910 920 930 940 950 960 CVFTKYGQGF YLISPSEFER FSLSTKWLVE PRCLVDSAET KNHRPGNGAG PKKAPSRARN 970 980 990 1000 1010 1020 SGTQSDGEEK QPGLVMERAL LSDERVLKEI QSTLEGDRGS GNWRSHRAAV GCSLSNGGAE
	Isoform A [UniParc]. Checksum: F2C96A62BAA08AE4	FASTA	1,015	112,927
	10 20 30 40 50 60 MRRFLRPGHD PVRERLKRDL FQFNKTVEHG FPHQPSALGY SPSLRILAIG TRSGAIKLYG 70 80 90 100 110 120 APGVEFMGLH QENNAVTQIH LLPGQCQLVT LLDDNSLHLW SLKVKGGASE LQEDESFTLR 130 140 150 160 170 180 GPPGAAPSAT QITVVLPHSS CELLYLGTES GNVFVVQLPA FRALEDRTIS SDAVLQRLPE 190 200 210 220 230 240 EARHRRVFEM VEALQEHPRD PNQILIGYSR GLVVIWDLQG SRVLYHFLSS QQLENIWWQR 250 260 270 280 290 300 DGRLLVSCHS DGSYCQWPVS SEAQQPEPLR SLVPYGPFPC KAITRILWLT TRQGLPFTIF 310 320 330 340 350 360 QGGMPRASYG DRHCISVIHD GQQTAFDFTS RVIGFTVLTE ADPAATFDDP YALVVLAEEE 370 380 390 400 410 420 LVVIDLQTAG WPPVQLPYLA SLHCSAITCS HHVSNIPLKL WERIIAAGSR QNAHFSTMEW 430 440 450 460 470 480 PIDGGTSLTP APPQRDLLLT GHEDGTVRFW DASGVCLRLL YKLSTVRVFL TDTDPNENFS 490 500 510 520 530 540 AQGEDEWPPL RKVGSFDPYS DDPRLGIQKI FLCKYSGYLA VAGTAGQVLV LELNDEAAEQ 550 560 570 580 590 600 AVEQVEADLL QDQEGYRWKG HERLAARSGP VRFEPGFQPF VLVQCQPPAV VTSLALHSEW 610 620 630 640 650 660 RLVAFGTSHG FGLFDHQQRR QVFVKCTLHP SDQLALEGPL SRVKSLKKSL RQSFRRMRRS 670 680 690 700 710 720 RVSSRKRHPA GPPGEAQEGS AKAERPGLQN MELAPVQRKI EARSAEDSFT GFVRTLYFAD 730 740 750 760 770 780 TYLKDSSRHC PSLWAGTNGG TIYAFSLRVP PAERRMDEPV RAEQAKEIQL MHRAPVVGIL 790 800 810 820 830 840 VLDGHSVPLP EPLEVAHDLS KSPDMQGSHQ LLVVSEEQFK VFTLPKVSAK LKLKLTALEG 850 860 870 880 890 900 SRVRRVSVAH FGSRRAEDYG EHHLAVLTNL GDIQVVSLPL LKPQVRYSCI RREDVSGIAS 910 920 930 940 950 960 CVFTKYGQGF YLISPSEFER FSLSTKWLVE PRCLVDSAET KNHRPGNGAG PKKAPSRARN 970 980 990 1000 1010 SGTQSDGEEK QPGLVMERAL LSDERAATGV HIEPPWGAAS AMAEQSEWLS VQAAR
	Isoform B [UniParc]. Checksum: 176D21EC7BA6F9D4	FASTA	351	39,141
	10 20 30 40 50 60 MRRFLRPGHD PVRERLKRDL FQFNKTVEHG FPHQPSALGY SPSLRILAIG TRSGAIKLYG 70 80 90 100 110 120 APGVEFMGLH QENNAVTQIH LLPGQCQLVT LLDDNSLHLW SLKVKGGASE LQEDESFTLR 130 140 150 160 170 180 GPPGAAPSAT QITVVLPHSS CELLYLGTES GNVFVVQLPA FRALEDRTIS SDAVLQRLPE 190 200 210 220 230 240 EARHRRVFEM VEALQEHPRD PNQILIGYSR GLVVIWDLQG SRVLYHFLSS QQLENIWWQR 250 260 270 280 290 300 DGRLLVSCHS DGSYCQWPVS SEAQQPEPLR SLVPYGPFPC KAITRILWLT TRQGLPFTIF 310 320 330 340 350 QGGMPRASYG DRHCISVIHD GQQTAFDFTS RVIGFTVLTE ADPAASGVGA Q

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A human homolog of the Drosophila 1(2) giant larvae tumor suppressor maps to 17q24-25." Wiemann S., Tommerup N., Celis J.E., Ansorge W., Leffers H. Submitted (MAY-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM C), VARIANT HIS-45.
[2]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] (ISOFORMS A AND B), VARIANTS LEU-479 AND SER-759. Tissue: Lung and Testis.
[4]	"Direct binding of Lgl2 to LGN during mitosis and its requirement for normal cell division." Yasumi M., Sakisaka T., Hoshino T., Kimura T., Sakamoto Y., Yamanaka T., Ohno S., Takai Y. J. Biol. Chem. 280:6761-6765(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GPSM2/LGN, SUBCELLULAR LOCATION, FUNCTION. Tissue: Brain.
[5]	"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, PHOSPHORYLATION AT SER-653, MUTAGENESIS OF SER-641; SER-645; SER-649; SER-653; SER-660 AND SER-663.
[6]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1015, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[7]	"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	X87342 mRNA. Translation: CAA60780.1. AC100787 Genomic DNA. No translation available. BC006503 mRNA. Translation: AAH06503.1. BC010879 mRNA. Translation: AAH10879.1. BC064994 mRNA. Translation: AAH64994.1.
IPI	IPI00465050. IPI00555972. IPI00641801.
PIR	S55474.
RefSeq	NP_001015002.1. NM_001015002.1. NP_001026973.1. NM_001031803.1. NP_004515.2. NM_004524.2.
UniGene	Hs.514477.
3D structure databases
ProteinModelPortal	Q6P1M3.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q6P1M3. 4 interactions.
STRING	9606.ENSP00000376333.
PTM databases
PhosphoSite	Q6P1M3.
Polymorphism databases
DMDM	93204600.
Proteomic databases
PaxDb	Q6P1M3.
PRIDE	Q6P1M3.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000167462; ENSP00000167462; ENSG00000073350. ENST00000375227; ENSP00000364375; ENSG00000073350. ENST00000392550; ENSP00000376333; ENSG00000073350. ENST00000578363; ENSP00000464603; ENSG00000073350.
GeneID	3993.
KEGG	hsa:3993.
UCSC	uc002jog.1. human. uc002joh.3. human. uc002joi.3. human.
Organism-specific databases
CTD	3993.
GeneCards	GC17P073521.
HGNC	HGNC:6629. LLGL2.
HPA	HPA022913.
neXtProt	NX_Q6P1M3.
PharmGKB	PA30397.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG289584.
HOGENOM	HOG000115700.
HOVERGEN	HBG052711.
InParanoid	Q6P1M3.
KO	K06094.
OMA	QCQPPAV.
Gene expression databases
ArrayExpress	Q6P1M3.
Bgee	Q6P1M3.
CleanEx	HS_LLGL2.
Genevestigator	Q6P1M3.
GermOnline	ENSG00000073350. Homo sapiens.
Family and domain databases
Gene3D	2.130.10.10. 3 hits.
InterPro	IPR000664. Lethal2_giant. IPR013577. LLGL2. IPR015943. WD40/YVTN_repeat-like_dom. IPR001680. WD40_repeat. IPR019775. WD40_repeat_CS. IPR017986. WD40_repeat_dom. [Graphical view]
Pfam	PF08366. LLGL. 1 hit. PF00400. WD40. 1 hit. [Graphical view]
PRINTS	PR00962. LETHAL2GIANT.
SMART	SM00320. WD40. 5 hits. [Graphical view]
SUPFAM	SSF50978. WD40_like. 1 hit.
PROSITE	PS00678. WD_REPEATS_1. 1 hit. PS50082. WD_REPEATS_2. 1 hit. PS50294. WD_REPEATS_REGION. False negative. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	LLGL2. human.
GenomeRNAi	3993.
NextBio	15664.

Entry information

Entry name

L2GL2_HUMAN

Accession

Primary (citable) accession number: Q6P1M3
Secondary accession number(s): Q14521, Q9BR62

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 18, 2006
Last sequence update:	April 18, 2006
Last modified:	May 1, 2013
This is version 87 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.