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Q7TSJ6 (LATS2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 116. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1042 AA.
Sequence statusComplete.
Protein existenceEvidence 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

Cytoplasmcytoskeletonmicrotubule organizing centercentrosome. Cytoplasm. Cytoplasmcytoskeletonspindle pole. Nucleus By similarity. Note: Colocalizes 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 processCell cycle
Cell division
Mitosis
   Cellular componentCytoplasm
Cytoskeleton
Nucleus
   DiseaseTumor suppressor
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG1/S transition of mitotic cell cycle

Inferred from direct assay Ref.4. Source: UniProtKB

cellular protein localization

Inferred from direct assay PubMed 19289085. Source: MGI

hippo signaling

Inferred from genetic interaction PubMed 18369314. Source: MGI

hormone-mediated signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

intracellular signal transduction

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 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

protein phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of organ growth

Inferred from mutant phenotype PubMed 21512031. Source: MGI

   Cellular_componentcytoplasm

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_functionATP 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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10421042Serine/threonine-protein kinase LATS2
PRO_0000086235

Regions

Domain97 – 13842UBA
Domain626 – 931306Protein kinase
Domain932 – 101079AGC-kinase C-terminal
Nucleotide binding632 – 6409ATP By similarity UniProtKB P22612
Motif472 – 4754PPxY motif

Sites

Active site7491Proton acceptor By similarity UniProtKB P22612
Binding site6551ATP By similarity UniProtKB Q9NRM7

Amino acid modifications

Modified residue821Phosphoserine; by AURKA By similarity UniProtKB Q9NRM7
Modified residue2671Phosphothreonine By similarity
Modified residue9991Phosphothreonine By similarity

Experimental info

Sequence conflict1841Q → R in BAA92380. Ref.1
Sequence conflict2791Q → R in BAC26704. Ref.2
Sequence conflict5491E → K in BAC26704. Ref.2
Sequence conflict5891M → V in BAA92380. Ref.1

Secondary structure

....... 1042
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q7TSJ6 [UniParc].

Last modified October 1, 2003. Version 1.
Checksum: 7E0E73A73DB954C0

FASTA1,042115,472
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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.
RefSeqNP_056586.2. NM_015771.2.
UniGeneMm.347899.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2COSNMR-A98-138[»]
ProteinModelPortalQ7TSJ6.
SMRQ7TSJ6. Positions 91-138, 614-1002.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ7TSJ6. 124 interactions.
MINTMINT-4100233.

PTM databases

PhosphoSiteQ7TSJ6.

Proteomic databases

PaxDbQ7TSJ6.
PRIDEQ7TSJ6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000022531; ENSMUSP00000022531; ENSMUSG00000021959.
GeneID50523.
KEGGmmu:50523.
UCSCuc007udk.1. mouse.

Organism-specific databases

CTD26524.
MGIMGI:1354386. Lats2.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00750000117422.
HOGENOMHOG000040002.
HOVERGENHBG052311.
InParanoidQ7TSJ6.
KOK08791.
OMAGSHIRQD.
PhylomeDBQ7TSJ6.
TreeFamTF351549.

Gene expression databases

ArrayExpressQ7TSJ6.
BgeeQ7TSJ6.
CleanExMM_LATS2.
GenevestigatorQ7TSJ6.

Family and domain databases

InterProIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_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.
IPR028742. Warts/LATS2.
[Graphical view]
PANTHERPTHR24356:SF2. PTHR24356:SF2. 1 hit.
PfamPF00069. Pkinase. 2 hits.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
SMARTSM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF46934. SSF46934. 1 hit.
SSF56112. SSF56112. 2 hits.
PROSITEPS51285. 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]
ProtoNetSearch...

Other

ChiTaRSLATS2. mouse.
EvolutionaryTraceQ7TSJ6.
NextBio307518.
PROQ7TSJ6.
SOURCESearch...

Entry information

Entry nameLATS2_MOUSE
AccessionPrimary (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: April 16, 2014
This is version 116 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot