Q7TSJ6 (LATS2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase LATS2
EC=2.7.11.1

Alternative name(s):
Kinase phosphorylated during mitosis protein
Large tumor suppressor homolog 2
Serine/threonine-protein kinase kpm

Gene names

Name:

Lats2

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	1042 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 LATS2 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 centrosome duplication, maintenance of mitotic fidelity and genomic stability. Negatively regulates G1/S transition by down-regulating cyclin E/CDK2 kinase activity. Negative regulator of the androgen receptor. Phosphorylates SNAI1 in the nucleus leading to its nuclear retention and stabilization, which enhances its epithelial-mesenchymal transition and tumor cell invasion/migration activities. This tumor-promoting activity is independent of its effects upon YAP1 or WWTR1/TAZ By similarity. Ref.4
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. UniProtKB Q9NRM7
Cofactor	Magnesium By similarity. UniProtKB Q9NRM7
Subunit structure	Interacts with and is phosphorylated by AURKA. Binds to AR By similarity. Interacts with AJUBA during mitosis and this complex regulates organization of the spindle apparatus through recruitment of gamma-tubulin to the centrosome. Interacts (via PPxY motif) with YAP1 (via WW domains). Interacts with MOB1A and MOB1B By similarity. Interacts with LIMD1, WTIP and AJUBA By similarity. Interacts with SNAI1 By similarity.
Subcellular location	Cytoplasm › cytoskeleton › centrosome. Cytoplasm. Cytoplasm › cytoskeleton › spindle pole. Nucleus By similarity. Note: Co-localizes with AURKA at the centrosomes during interphase, early prophase and cytokinesis By similarity. Migrates to the spindle poles during mitosis, and to the midbody during cytokinesis. Translocates to the nucleus upon mitotic stress by nocodazole treatment By similarity. Ref.4
Tissue specificity	Expressed at high levels in ovary and testis and at lower levels in all other tissues examined. Ref.1
Post-translational modification	Autophosphorylated and phosphorylated during M-phase and the G1/S-phase of the cell cycle. Phosphorylated and activated by STK3/MST2 By similarity. UniProtKB Q9NRM7
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.
Sequence caution	The sequence BAC26704.1 differs from that shown. Reason: Frameshift at positions 970, 1025 and 1037.

Ontologies

Keywords
Biological process	Cell cycle Cell division Mitosis
Cellular component	Cytoplasm Cytoskeleton Nucleus
Disease	Tumor suppressor
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G1/S transition of mitotic cell cycle Inferred from direct assay Ref.4. Source: UniProtKB cell division Inferred from electronic annotation. Source: UniProtKB-KW cellular protein localization Inferred from direct assay PubMed 19289085. Source: MGI hippo signaling cascade Inferred from genetic interaction PubMed 18369314. Source: MGI hormone-mediated signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB intracellular protein kinase cascade Inferred from sequence or structural similarity. 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 genetic interaction PubMed 21512031. Source: MGI negative regulation of cyclin-dependent protein serine/threonine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB regulation of organ growth Inferred from mutant phenotype PubMed 21512031. Source: MGI
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell microtubule organizing center Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell spindle pole Inferred from direct assay Ref.4. Source: UniProtKB
Molecular_function	ATP binding Inferred from sequence or structural similarity. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW 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 – 1042

1042

Serine/threonine-protein kinase LATS2

PRO_0000086235

Regions

Domain

97 – 138

42

UBA

Domain

626 – 931

306

Protein kinase

Domain

932 – 1010

79

AGC-kinase C-terminal

Nucleotide binding

632 – 640

9

ATP By similarity UniProtKB P22612

Motif

472 – 475

4

PPxY motif

Sites

Active site

749

1

Proton acceptor By similarity UniProtKB P22612

Binding site

655

1

ATP By similarity UniProtKB Q9NRM7

Amino acid modifications

Modified residue

82

1

Phosphoserine; by AURKA By similarity UniProtKB Q9NRM7

Modified residue

267

1

Phosphothreonine By similarity

Modified residue

999

1

Phosphothreonine By similarity

Experimental info

Sequence conflict

184

1

Q → R in BAA92380. Ref.1

Sequence conflict

279

1

Q → R in BAC26704. Ref.2

Sequence conflict

549

1

E → K in BAC26704. Ref.2

Sequence conflict

589

1

M → V in BAA92380. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

1042

Helix Strand Turn

Details...

Helix

100 – 110

11

Helix

113 – 123

11

Helix

128 – 138

11

Sequences

	Sequence		Length	Mass (Da)
	Q7TSJ6 [UniParc]. Last modified October 1, 2003. Version 1. Checksum: 7E0E73A73DB954C0	FASTA	1,042	115,472
	10 20 30 40 50 60 MRPKTFPATT YSGNSRQRLQ EIREGLKQPS KASTQGLLVG PNSDTSLDAK VLGSKDASRQ 70 80 90 100 110 120 QQMRATPKFG PYQKALREIR YSLLPFANES GTSAAAEVNR QMLQELVNAG CDQEMAGRAL 130 140 150 160 170 180 KQTGSRSIEA ALEYISKMGY LDPRNEQIVR VIKQTSPGKG LAPTPVTRRP SFEGTGEALP 190 200 210 220 230 240 SYHQLGGANY EGPAALEEMP RQYLDFLFPG AGAGTHGAQA HQHPPKGYST AVEPSAHFPG 250 260 270 280 290 300 THYGRGHLLS EQPGYGVQRS SSFQNKTPPD AYSSMAKAQG GPPASLTFPA HAGLYTASHH 310 320 330 340 350 360 KPAATPPGAH PLHVLGTRGP TFTGESSAQA VLAPSRNSLN ADLYELGSTV PWSAAPLARR 370 380 390 400 410 420 DSLQKQGLEA SRPHVAFRAG PSRTNSFNNP QPEPSLPAPN TVTAVTAAHI LHPVKSVRVL 430 440 450 460 470 480 RPEPQTAVGP SHPAWVAAPT APATESLETK EGSAGPHPLD VDYGGSERRC PPPPYPKHLL 490 500 510 520 530 540 LPSKSEQYSV DLDSLCTSVQ QSLRGGTEQD RSDKSHKGAK GDKAGRDKKQ IQTSPVPVRK 550 560 570 580 590 600 NSRDEEKRES RIKSYSPYAF KFFMEQHVEN VIKTYQQKVS RRLQLEQEMA KAGLCEAEQE 610 620 630 640 650 660 QMRKILYQKE SNYNRLKRAK MDKSMFVKIK TLGIGAFGEV CLACKLDTHA LYAMKTLRKK 670 680 690 700 710 720 DVLNRNQVAH VKAERDILAE ADNEWVVKLY YSFQDKDSLY FVMDYIPGGD MMSLLIRMEV 730 740 750 760 770 780 FPEHLARFYI AELTLAIESV HKMGFIHRDI KPDNILIDLD GHIKLTDFGL CTGFRWTHNS 790 800 810 820 830 840 KYYQKGNHMR QDSMEPGDLW DDVSNCRCGD RLKTLEQRAQ KQHQRCLAHS LVGTPNYIAP 850 860 870 880 890 900 EVLLRKGYTQ LCDWWSVGVI LFEMLVGQPP FLAPTPTETQ LKVINWESTL HIPTQVRLSA 910 920 930 940 950 960 EARDLITKLC CAADCRLGRD GADDLKAHPF FNTIDFSRDI RKQPAPYVPT ISHPMDTSNF 970 980 990 1000 1010 1020 DPVDEESPWH EASGESAKAW DTLASPSSKH PEHAFYEFTF RRFFDDNGYP FRCPKPSEPA 1030 1040 ESADPGDADL EGAAEGCQPV YV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure, expression, and chromosome mapping of LATS2, a mammalian homologue of the Drosophila tumor suppressor gene lats/warts." Yabuta N., Fujii T., Copeland N.G., Gilbert D.J., Jenkins N.A., Nishiguchi H., Endo Y., Toji S., Tanaka H., Nishimune Y., Nojima H. Genomics 63:263-270(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Testis.
[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]. Strain: C57BL/6J. Tissue: Testis.
[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]. Strain: C57BL/6. Tissue: Brain.
[4]	"Lats2/Kpm is required for embryonic development, proliferation control and genomic integrity." McPherson J.P., Tamblyn L., Elia A., Migon E., Shehabeldin A., Matysiak-Zablocki E., Lemmers B., Salmena L., Hakem A., Fish J., Kassam F., Squire J., Bruneau B.G., Hande M.P., Hakem R. EMBO J. 23:3677-3688(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[5]	"Solution structure of RSGI RUH-038, a UBA domain from mouse LATS2 (large tumor suppressor homolog 2)." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 98-138.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB023958 mRNA. Translation: BAA92380.1.
AK029966 mRNA. Translation: BAC26704.1. Frameshift.
BC053028 mRNA. Translation: AAH53028.1.

IPI

IPI00125698.

RefSeq

NP_056586.2. NM_015771.2.

UniGene

Mm.202747.
Mm.347899.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2COS	NMR	-	A	98-138	[»]

ProteinModelPortal

Q7TSJ6.

SMR

Q7TSJ6. Positions 91-138, 614-961.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q7TSJ6. 1 interaction.

MINT

MINT-4100233.

PTM databases

PhosphoSite

Q7TSJ6.

Proteomic databases

PaxDb

Q7TSJ6.

PRIDE

Q7TSJ6.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000022531; ENSMUSP00000022531; ENSMUSG00000021959.

GeneID

50523.

KEGG

mmu:50523.

UCSC

uc007udk.1. mouse.

Organism-specific databases

CTD

26524.

MGI

MGI:1354386. Lats2.

Phylogenomic databases

eggNOG

COG0515.

GeneTree

ENSGT00700000104041.

HOGENOM

HOG000040002.

HOVERGEN

HBG052311.

InParanoid

Q7TSJ6.

KO

K08791.

OMA

RPSFEGT.

OrthoDB

EOG498V00.

Gene expression databases

ArrayExpress

Q7TSJ6.

Bgee

Q7TSJ6.

CleanEx

MM_LATS2.

Genevestigator

Q7TSJ6.

GermOnline

ENSMUSG00000021959. Mus musculus.

Family and domain databases

InterPro

IPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR009060. UBA-like.
IPR015940. UBA/transl_elong_EF1B_N_euk.
[Graphical view]

Pfam

PF00069. Pkinase. 2 hits.
PF00433. Pkinase_C. 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. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50030. UBA. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

LATS2. mouse.

EvolutionaryTrace

Q7TSJ6.

NextBio

307518.

SOURCE

Search...

Entry information

Entry name

LATS2_MOUSE

Accession

Primary (citable) accession number: Q7TSJ6
Secondary accession number(s): Q8CDJ4, Q9JMI3

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 27, 2004
Last sequence update:	October 1, 2003
Last modified:	May 1, 2013
This is version 107 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program