Q8BYR2 (LATS1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

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

Gene names

Name:	Lats1
Synonyms:	Warts

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1129 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Negative regulator of YAP1 in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. Acts as a 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 CDK1 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 By similarity. Ref.4
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. UniProtKB O95835
Cofactor	Magnesium By similarity. UniProtKB O95835
Subunit structure	Complexes with CDK1 in early mitosis. LATS1-associated CDK1 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. Interacts (via PPxY motif 2) with YAP1 (via WW domains). Interacts with MOB1A and MOB1B By similarity. Interacts with LIMD1, WTIP and AJUBA By similarity.
Subcellular location	Cytoplasm › cytoskeleton › centrosome By similarity. Cytoplasm › cytoskeleton › spindle By similarity. Note: Localizes to the centrosomes throughout interphase but migrates to the mitotic apparatus, including spindle pole bodies, mitotic spindle, and midbody, during mitosis By similarity.
Post-translational modification	Autophosphorylated and phosphorylated during M-phase of the cell cycle. Phosphorylated by STK3/MST2 at Ser-908 and Thr-1078, which results in its activation. UniProtKB O95835
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
Cellular component	Cytoplasm Cytoskeleton
Disease	Tumor suppressor
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G2/M transition of mitotic cell cycle Inferred from sequence or structural similarity. Source: UniProtKB cell division Inferred from electronic annotation. Source: UniProtKB-KW cellular protein localization Inferred from genetic interaction PubMed 19289085. Source: MGI cytoplasmic sequestering of protein Inferred from electronic annotation. Source: Compara hippo signaling cascade Inferred from genetic interaction PubMed 18369314. Source: MGI hormone-mediated signaling pathway Inferred from direct assay Ref.4. Source: UniProtKB keratinocyte differentiation Inferred from genetic interaction PubMed 18369314. Source: MGI mitosis Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of canonical Wnt receptor signaling pathway Inferred from electronic annotation. Source: Compara negative regulation of cyclin-dependent protein serine/threonine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of peptidyl-serine phosphorylation Inferred from electronic annotation. Source: Compara regulation of actin filament polymerization Inferred from sequence or structural similarity. Source: UniProtKB sister chromatid segregation Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW microtubule organizing center Inferred from electronic annotation. Source: UniProtKB-SubCell spindle pole Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	ATP binding Inferred from sequence or structural similarity. Source: UniProtKB magnesium ion binding Inferred from sequence or structural similarity. Source: UniProtKB protein serine/threonine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1129	1129	Serine/threonine-protein kinase LATS1		PRO_0000086233
Regions
	Domain	100 – 141	42	UBA
	Domain	704 – 1009	306	Protein kinase
	Domain	1010 – 1089	80	AGC-kinase C-terminal
	Nucleotide binding	710 – 718	9	ATP By similarity UniProtKB P22612
	Region	525 – 654	130	Interaction with YAP1 By similarity
	Motif	372 – 375	4	PPxY motif 1
	Motif	555 – 558	4	PPxY motif 2
Sites
	Active site	827	1	Proton acceptor By similarity UniProtKB P22612
	Binding site	733	1	ATP By similarity UniProtKB O95835
Amino acid modifications
	Modified residue	246	1	Phosphothreonine Ref.6
	Modified residue	278	1	Phosphoserine By similarity
	Modified residue	463	1	Phosphoserine; by NUAK1 and NUAK2 Probable
	Modified residue	673	1	Phosphoserine By similarity
	Modified residue	908	1	Phosphoserine; by STK3/MST2 By similarity
	Modified residue	1078	1	Phosphothreonine; by STK3/MST2 By similarity
Experimental info
	Sequence conflict	940	1	F → C in AAD16883. Ref.3
	Sequence conflict	963	1	N → I in AAD16883. Ref.3
	Sequence conflict	1061	1	N → S in AAD16883. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q8BYR2 [UniParc]. Last modified July 27, 2011. Version 3. Checksum: FCDC2EC8BC2FF2DE	FASTA	1,129	126,258
	10 20 30 40 50 60 MKRGEKPEGY RQMRPKTFPA SNYPGSSRQM LQEIRESLRN LSKPSDASKA EHNLNKMSTE 70 80 90 100 110 120 DPRQVRNPPK FGTHHKALQE IRNSLLPFAN ETSSSRSPSE VNPQMFQDLQ AAGFDEDMVI 130 140 150 160 170 180 QALQKTNNRS IEAAVEFISK MSYQDPRREQ MSAAAARPIN ATMKPGNVQH SINRKQSWKG 190 200 210 220 230 240 SKESLVPQRH GPSLGENVVY RSESPNSQAD VGRPLSGSGI AAFAQAHPSN GQRVNPPPPP 250 260 270 280 290 300 QVRSVTPPPP PRGQTPPPRG TTPPPPSWEP SSQTKRYSGN MEYVISRISP VPPGAWQEGY 310 320 330 340 350 360 PPPPLTTSPM NPPSQAQRAI SSVPVGRQPI IMQSTSKFNF TPGRPGVQNG GGQSDFIVHQ 370 380 390 400 410 420 NVPTGSVTRQ PPPPYPLTPA NGQSPSALQT GASAAPPSFA NGNVPQSMMV PNRNSHNMEL 430 440 450 460 470 480 YNINVPGLQT AWPQSSSAPA QSSPSGGHEI PTWQPNIPVR SNSFNNPLGS RASHSANSQP 490 500 510 520 530 540 SATTVTAITP APIQQPVKSM RVLKPELQTA LAPTHPSWMP QPVQTVQPTP FSEGTASSVP 550 560 570 580 590 600 VIPPVAEAPS YQGPPPPYPK HLLHQNPSVP PYESVSKPCK DEQPSLPKED DSEKSADSGD 610 620 630 640 650 660 SGDKEKKQIT TSPITVRKNK KDEERRESRI QSYSPQAFKF FMEQHVENVL KSHQQRLHRK 670 680 690 700 710 720 KQLENEMMRV GLSQDAQDQM RKMLCQKESN YIRLKRAKMD KSMFVKIKTL GIGAFGEVCL 730 740 750 760 770 780 ARKVDTKALY ATKTLRKKDV LLRNQVAHVK AERDILAEAD NEWVVRLYYS FQDKDNLYFV 790 800 810 820 830 840 MDYIPGGDMM SLLIRMGIFP ENLARFYIAE LTCAVESVHK MGFIHRDIKP DNILIDRDGH 850 860 870 880 890 900 IKLTDFGLCT GFRWTHDSKY YQSGDHPRQD SMDFSNEWGD PSNCRCGDRL KPLERRAARQ 910 920 930 940 950 960 HQRCLAHSLV GTPNYIAPEV LLRTGYTQLC DWWSVGVILF EMLVGQPPFL AQTPLETQMK 970 980 990 1000 1010 1020 VINWQTSLHI PPQAKLSPEA SDLIIKLCRG PEDRLGKNGA DEIKAHPFFK TIDFSSDLRQ 1030 1040 1050 1060 1070 1080 QSASYIPKIT HPTDTSNFDP VDPDKLWSDG SEEENISDTL NGWYKNGKHP EHAFYEFTFR 1090 1100 1110 1120 RFFDDNGYPY NYPKPIEYEY IHSQGSEQQS DEDDQHTSSD GNNRDLVYV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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]. Tissue: Brain.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-602. Strain: C57BL/6J. Tissue: Hypothalamus.
[3]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 168-1129. Tissue: Brain.
[4]	"Mice deficient of Lats1 develop soft-tissue sarcomas, ovarian tumours and pituitary dysfunction." St John M.A., Tao W., Fei X., Fukumoto R., Carcangiu M.L., Brownstein D.G., Parlow A.F., McGrath J., Xu T. Nat. Genet. 21:182-186(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[5]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-463, MASS SPECTROMETRY. Tissue: Liver.
[6]	"The phagosomal proteome in interferon-gamma-activated macrophages." Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P. Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-246, MASS SPECTROMETRY. Tissue: Macrophage.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	BC158092 mRNA. Translation: AAI58093.1. BC158123 mRNA. Translation: AAI58124.1. AK038612 mRNA. Translation: BAC30063.1. AF104414 mRNA. Translation: AAD16883.1.
IPI	IPI00408940.
RefSeq	NP_034820.1. NM_010690.1.
UniGene	Mm.34083.
3D structure databases
ProteinModelPortal	Q8BYR2.
SMR	Q8BYR2. Positions 95-142, 625-1118.
ModBase	Search...
PTM databases
PhosphoSite	Q8BYR2.
Proteomic databases
PaxDb	Q8BYR2.
PRIDE	Q8BYR2.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000040043; ENSMUSP00000041915; ENSMUSG00000040021. ENSMUST00000165952; ENSMUSP00000132078; ENSMUSG00000040021.
GeneID	16798.
KEGG	mmu:16798.
Organism-specific databases
CTD	9113.
MGI	MGI:1333883. Lats1.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00700000104041.
HOGENOM	HOG000040002.
HOVERGEN	HBG052311.
InParanoid	B2RY46.
KO	K08791.
OMA	RYSGNME.
OrthoDB	EOG40GCQ5.
Gene expression databases
Bgee	Q8BYR2.
CleanEx	MM_LATS1.
Genevestigator	Q8BYR2.
GermOnline	ENSMUSG00000040021. Mus musculus.
Family and domain databases
InterPro	IPR000961. AGC-kinase_C. IPR011009. Kinase-like_dom. IPR017892. Pkinase_C. IPR000719. Prot_kinase_cat_dom. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. IPR009060. UBA-like. IPR000449. UBA/transl_elong_EF1B_N. IPR015940. UBA/transl_elong_EF1B_N_euk. [Graphical view]
Pfam	PF00069. Pkinase. 2 hits. PF00433. Pkinase_C. 1 hit. PF00627. UBA. 1 hit. [Graphical view]
SMART	SM00133. S_TK_X. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit. SSF46934. UBA_like. 1 hit.
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
NextBio	290674.
SOURCE	Search...

Entry information

Entry name

LATS1_MOUSE

Accession

Primary (citable) accession number: Q8BYR2
Secondary accession number(s): B2RY46, Q9Z0W4

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 27, 2004
Last sequence update:	July 27, 2011
Last modified:	May 1, 2013
This is version 106 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program