Reviewed, UniProtKB/Swiss-Prot O95835 (LATS1_HUMAN)

Names and origin

Protein names

Recommended name:
    Serine/threonine-protein kinase LATS1
    EC=2.7.11.1
Alternative name(s):
    Large tumor suppressor homolog 1
    WARTS protein kinase
      Short name=h-warts

Gene names

Name:	LATS1
Synonyms:	WARTS

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1130 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Tumor suppressor which plays a critical role in maintenance of ploidy through its actions in both mitotic progression and the G1 tetraploidy checkpoint. Negatively regulates G2/M transition by down-regulating CDC2 kinase activity. Involved in the control of p53 expression. Affects cytokinesis by regulating actin polymerization through negative modulation of LIMK1. May also play a role in endocrine function.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium.
Subunit structure	Complexes with CDC2 in early mitosis. LATS1-associated CDC2 has no mitotic cyclin partner and no apparent kinase activity. Binds phosphorylated ZYX, locating this protein to the mitotic spindle and suggesting a role for actin regulatory proteins during mitosis. Binds to and colocalizes with LIMK1 at the actomyosin contractile ring during cytokinesis.
Subcellular location	Centrosome. Note= Localizes to the centrosomes throughout interphase but migrates to the mitotic apparatus, including spindle pole bodies, mitotic spindle, and midbody, during mitosis.
Tissue specificity	Expressed in all adult tissues examined except for lung and kidney.
Post-translational modification	Autophosphorylated and phosphorylated during M-phase of the cell cycle. Phosphorylated by STK3 at Ser-909 and Thr-1079, which results in its activation. Phosphorylated upon DNA damage, probably by ATM or ATR.
Sequence similarities	Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. Contains 1 AGC-kinase C-terminal domain. Contains 1 protein kinase domain. Contains 1 UBA domain.

Ontologies

Keywords
Biological process	Cell cycle Cell division Mitosis
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Anti-oncogene Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	G2/M transition of mitotic cell cycle Ref.5 Inferred from direct assay. Source: UniProtKB cell division Inferred from electronic annotation. Source: UniProtKB-KW hormone-mediated signaling Inferred from sequence or structural similarity. Source: UniProtKB mitosis Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of cyclin-dependent protein kinase activity Ref.1 Inferred from direct assay. Source: UniProtKB protein amino acid phosphorylation Ref.2 Inferred from direct assay. Source: UniProtKB regulation of actin filament polymerization Ref.6 Inferred from direct assay. Source: UniProtKB sister chromatid segregation Ref.5 Inferred from direct assay. Source: UniProtKB
Cellular component	centrosome Inferred from electronic annotation. Source: UniProtKB-SubCell spindle pole Ref.2 Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Ref.2 Inferred from direct assay. Source: UniProtKB magnesium ion binding Ref.2 Inferred from direct assay. Source: UniProtKB protein kinase binding Ref.6 Inferred from physical interaction. Source: UniProtKB protein serine/threonine kinase activity Ref.2 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDC2	P06493	1	EBI-444209,EBI-444308
LIMK1	P53667	3	EBI-444209,EBI-444403
ZYX	Q15942	3	EBI-444209,EBI-444225

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O95835-1)

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 2 (identifier: O95835-2)

The sequence of this isoform differs from the canonical sequence as follows:
     672-690: GLSQDAQDQMRKMLCQKES → KPFKMSIFILNHLFAWCLF
     691-1130: Missing.

Notes: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1130	1130	Serine/threonine-protein kinase LATS1		PRO_0000086232
Regions
	Domain	100 – 141	42	UBA
	Domain	705 – 1010	306	Protein kinase
	Domain	1011 – 1090	80	AGC-kinase C-terminal
	Nucleotide binding	711 – 719	9	ATP By similarity
Sites
	Active site	828	1	Proton acceptor By similarity
	Binding site	734	1	ATP
Amino acid modifications
	Modified residue	244	1	Phosphoserine
	Modified residue	277	1	Phosphotyrosine
	Modified residue	464	1	Phosphoserine By similarity
	Modified residue	674	1	Phosphoserine
	Modified residue	909	1	Phosphoserine; by STK3
	Modified residue	1079	1	Phosphothreonine; by STK3
Natural variations
	Alternative sequence	672 – 690	19	GLSQD…CQKES → KPFKMSIFILNHLFAWCLF in isoform 2.		VSP_051604
	Alternative sequence	691 – 1130	440	Missing in isoform 2.		VSP_051605
	Natural variant	96	1	R → W		VAR_040660
	Natural variant	204	1	S → G		VAR_040661
	Natural variant	237	1	P → Q		VAR_040662
	Natural variant	370	1	R → W		VAR_040663
	Natural variant	531	1	P → S		VAR_040664
	Natural variant	641	1	F → L		VAR_040665
	Natural variant	669	1	M → I in a lung adenocarcinoma sample; somatic mutation.		VAR_040666
	Natural variant	806	1	R → P in a lung large cell carcinoma sample; somatic mutation.		VAR_040667
	Natural variant	1000	1	G → S		VAR_040668
Experimental info
	Mutagenesis	734	1	K → A: Loss of kinase activity, autophosphorylation, increased ploidy, prolonged duration of mitosis and lack of p53 expression

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: 11CFBCD8FD87DCD8	FASTA	1,130	126,870
	10 20 30 40 50 60 MKRSEKPEGY RQMRPKTFPA SNYTVSSRQM LQEIRESLRN LSKPSDAAKA EHNMSKMSTE 70 80 90 100 110 120 DPRQVRNPPK FGTHHKALQE IRNSLLPFAN ETNSSRSTSE VNPQMLQDLQ AAGFDEDMVI 130 140 150 160 170 180 QALQKTNNRS IEAAIEFISK MSYQDPRREQ MAAAAARPIN ASMKPGNVQQ SVNRKQSWKG 190 200 210 220 230 240 SKESLVPQRH GPPLGESVAY HSESPNSQTD VGRPLSGSGI SAFVQAHPSN GQRVNPPPPP 250 260 270 280 290 300 QVRSVTPPPP PRGQTPPPRG TTPPPPSWEP NSQTKRYSGN MEYVISRISP VPPGAWQEGY 310 320 330 340 350 360 PPPPLNTSPM NPPNQGQRGI SSVPVGRQPI IMQSSSKFNF PSGRPGMQNG TGQTDFMIHQ 370 380 390 400 410 420 NVVPAGTVNR QPPPPYPLTA ANGQSPSALQ TGGSAAPSSY TNGSIPQSMM VPNRNSHNME 430 440 450 460 470 480 LYNISVPGLQ TNWPQSSSAP AQSSPSSGHE IPTWQPNIPV RSNSFNNPLG NRASHSANSQ 490 500 510 520 530 540 PSATTVTAIT PAPIQQPVKS MRVLKPELQT ALAPTHPSWI PQPIQTVQPS PFPEGTASNV 550 560 570 580 590 600 TVMPPVAEAP NYQGPPPPYP KHLLHQNPSV PPYESISKPS KEDQPSLPKE DESEKSYENV 610 620 630 640 650 660 DSGDKEKKQI TTSPITVRKN KKDEERRESR IQSYSPQAFK FFMEQHVENV LKSHQQRLHR 670 680 690 700 710 720 KKQLENEMMR VGLSQDAQDQ MRKMLCQKES NYIRLKRAKM DKSMFVKIKT LGIGAFGEVC 730 740 750 760 770 780 LARKVDTKAL YATKTLRKKD VLLRNQVAHV KAERDILAEA DNEWVVRLYY SFQDKDNLYF 790 800 810 820 830 840 VMDYIPGGDM MSLLIRMGIF PESLARFYIA ELTCAVESVH KMGFIHRDIK PDNILIDRDG 850 860 870 880 890 900 HIKLTDFGLC TGFRWTHDSK YYQSGDHPRQ DSMDFSNEWG DPSSCRCGDR LKPLERRAAR 910 920 930 940 950 960 QHQRCLAHSL VGTPNYIAPE VLLRTGYTQL CDWWSVGVIL FEMLVGQPPF LAQTPLETQM 970 980 990 1000 1010 1020 KVINWQTSLH IPPQAKLSPE ASDLIIKLCR GPEDRLGKNG ADEIKAHPFF KTIDFSSDLR 1030 1040 1050 1060 1070 1080 QQSASYIPKI THPTDTSNFD PVDPDKLWSD DNEEENVNDT LNGWYKNGKH PEHAFYEFTF 1090 1100 1110 1120 1130 RRFFDDNGYP YNYPKPIEYE YINSQGSEQQ SDEDDQNTGS EIKNRDLVYV
	Isoform 2 [UniParc]. Checksum: 7154097947DF44E8		690	76,193
	10 20 30 40 50 60 MKRSEKPEGY RQMRPKTFPA SNYTVSSRQM LQEIRESLRN LSKPSDAAKA EHNMSKMSTE 70 80 90 100 110 120 DPRQVRNPPK FGTHHKALQE IRNSLLPFAN ETNSSRSTSE VNPQMLQDLQ AAGFDEDMVI 130 140 150 160 170 180 QALQKTNNRS IEAAIEFISK MSYQDPRREQ MAAAAARPIN ASMKPGNVQQ SVNRKQSWKG 190 200 210 220 230 240 SKESLVPQRH GPPLGESVAY HSESPNSQTD VGRPLSGSGI SAFVQAHPSN GQRVNPPPPP 250 260 270 280 290 300 QVRSVTPPPP PRGQTPPPRG TTPPPPSWEP NSQTKRYSGN MEYVISRISP VPPGAWQEGY 310 320 330 340 350 360 PPPPLNTSPM NPPNQGQRGI SSVPVGRQPI IMQSSSKFNF PSGRPGMQNG TGQTDFMIHQ 370 380 390 400 410 420 NVVPAGTVNR QPPPPYPLTA ANGQSPSALQ TGGSAAPSSY TNGSIPQSMM VPNRNSHNME 430 440 450 460 470 480 LYNISVPGLQ TNWPQSSSAP AQSSPSSGHE IPTWQPNIPV RSNSFNNPLG NRASHSANSQ 490 500 510 520 530 540 PSATTVTAIT PAPIQQPVKS MRVLKPELQT ALAPTHPSWI PQPIQTVQPS PFPEGTASNV 550 560 570 580 590 600 TVMPPVAEAP NYQGPPPPYP KHLLHQNPSV PPYESISKPS KEDQPSLPKE DESEKSYENV 610 620 630 640 650 660 DSGDKEKKQI TTSPITVRKN KKDEERRESR IQSYSPQAFK FFMEQHVENV LKSHQQRLHR 670 680 690 KKQLENEMMR VKPFKMSIFI LNHLFAWCLF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human homologue of the Drosophila melanogaster lats tumour suppressor modulates CDC2 activity." Tao W., Zhang S., Turenchalk G.S., Stewart R.A., St John M.A., Chen W., Xu T. Nat. Genet. 21:177-181(1999) [PubMed: 9988268] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PHOSPHORYLATION, INTERACTION WITH CDC2. Tissue: Fetal brain.
[2]	"A human homolog of Drosophila warts tumor suppressor, h-warts, localized to mitotic apparatus and specifically phosphorylated during mitosis." Nishiyama Y., Hirota T., Morisaki T., Hara T., Marumoto T., Iida S., Makino K., Yamamoto H., Hiraoka T., Kitamura N., Saya H. FEBS Lett. 459:159-165(1999) [PubMed: 10518011] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, PHOSPHORYLATION.
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Endometrium.
[4]	"Zyxin, a regulator of actin filament assembly, targets the mitotic apparatus by interacting with h-warts/LATS1 tumor suppressor." Hirota T., Morisaki T., Nishiyama Y., Marumoto T., Tada K., Hara T., Masuko N., Inagaki M., Hatakeyama K., Saya H. J. Cell Biol. 149:1073-1086(2000) [PubMed: 10831611] [Abstract] Cited for: FUNCTION, INTERACTION WITH ZYX.
[5]	"Tumor suppressor WARTS ensures genomic integrity by regulating both mitotic progression and G1 tetraploidy checkpoint function." Iida S., Hirota T., Morisaki T., Marumoto T., Hara T., Kuninaka S., Honda S., Kosai K., Kawasuji M., Pallas D.C., Saya H. Oncogene 23:5266-5274(2004) [PubMed: 15122335] [Abstract] Cited for: FUNCTION, AUTOPHOSPHORYLATION, MUTAGENESIS OF LYS-734.
[6]	"LATS1 tumour suppressor affects cytokinesis by inhibiting LIMK1." Yang X., Yu K., Hao Y., Li D.-M., Stewart R.A., Insogna K.L., Xu T. Nat. Cell Biol. 6:609-617(2004) [PubMed: 15220930] [Abstract] Cited for: FUNCTION, INTERACTION WITH LIMK1.
[7]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-244, MASS SPECTROMETRY. Tissue: Epithelium.
[8]	"The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1." Chan E.H.Y., Nousiainen M., Chalamalasetty R.B., Schaefer A., Nigg E.A., Sillje H.H.W. Oncogene 24:2076-2086(2005) [PubMed: 15688006] [Abstract] Cited for: PHOSPHORYLATION AT SER-909 AND THR-1079.
[9]	"Tyrosine phosphorylated Par3 regulates epithelial tight junction assembly promoted by EGFR signaling." Wang Y., Du D., Fang L., Yang G., Zhang C., Zeng R., Ullrich A., Lottspeich F., Chen Z. EMBO J. 25:5058-5070(2006) [PubMed: 17053785] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-277, MASS SPECTROMETRY.
[10]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-674, MASS SPECTROMETRY.
[11]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] TRP-96; GLY-204; GLN-237; TRP-370; SER-531; LEU-641; ILE-669; PRO-806 AND SER-1000.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF104413 mRNA. Translation: AAD16882.1. AF164041 mRNA. Translation: AAD50272.1. BC002767 mRNA. Translation: AAH02767.1.
RefSeq	NP_004681.1.
UniGene	Hs.549084
3D structure databases
HSSP	HSSP built from PDB template 1GZK based on UniProtKB P31751.
ModBase	Search...
Protein-protein interaction databases
IntAct	O95835.
PTM databases
PhosphoSite	O95835.
Genome annotation databases
Ensembl	ENSG00000131023. Homo sapiens. [Contig view]
GeneID	9113.
KEGG	hsa:9113.
Organism-specific databases
H-InvDB	HIX0025025.
HGNC	HGNC:6514. LATS1.
MIM	603473. gene.
PharmGKB	PA30301.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	O95835.
HOVERGEN	O95835.
Gene expression databases
ArrayExpress	O95835.
CleanEx	HS_LATS1.
GermOnline	ENSG00000131023. Homo sapiens.
Family and domain databases
InterPro	IPR000961. Pkinase_C. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_bd_CS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. IPR002290. Ser_thr_pkinase. IPR000449. UBA/transl_elong_EF1B_N. IPR015940. UBA/transl_elong_EF1B_N_euk. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. PF00433. Pkinase_C. 1 hit. PF00627. UBA. 1 hit. [Graphical view]
ProDom	PD000001. Prot_kinase. 2 hits. [Graphical view] [Entries sharing at least one domain]
SMART	SM00133. S_TK_X. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
PROSITE	PS51285. AGC_KINASE_CTER. 1 hit. PS00107. PROTEIN_KINASE_ATP. False negative. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. PS50030. UBA. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	34157.
SOURCE	Search...

Entry information

Entry name

LATS1_HUMAN

Accession

Primary (citable) accession number: O95835
Secondary accession number(s): Q6PKD0

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 27, 2004
Last sequence update:	May 1, 1999
Last modified:	November 25, 2008
This is version 76 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)