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Q8BYR2 (LATS1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 115. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | 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 LATS1

EC=2.7.11.1
Alternative name(s):
Large tumor suppressor homolog 1
WARTS protein kinase
Gene names
Name:Lats1
Synonyms:Warts
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1129 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 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

Cytoplasmcytoskeletonmicrotubule organizing centercentrosome By similarity. Cytoplasmcytoskeletonspindle 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 processCell cycle
Cell division
Mitosis
   Cellular componentCytoplasm
Cytoskeleton
   DiseaseTumor suppressor
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG2/M transition of mitotic cell cycle

Inferred from sequence or structural similarity. Source: UniProtKB

cellular protein localization

Inferred from genetic interaction PubMed 19289085. Source: MGI

cytoplasmic sequestering of protein

Inferred from electronic annotation. Source: Ensembl

hippo signaling

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 signaling pathway

Inferred from electronic annotation. Source: Ensembl

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: Ensembl

protein phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

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_componentcytoplasm

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_functionATP 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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11291129Serine/threonine-protein kinase LATS1
PRO_0000086233

Regions

Domain100 – 14142UBA
Domain704 – 1009306Protein kinase
Domain1010 – 108980AGC-kinase C-terminal
Nucleotide binding710 – 7189ATP By similarity UniProtKB P22612
Region525 – 654130Interaction with YAP1 By similarity
Motif372 – 3754PPxY motif 1
Motif555 – 5584PPxY motif 2

Sites

Active site8271Proton acceptor By similarity UniProtKB P22612
Binding site7331ATP By similarity UniProtKB O95835

Amino acid modifications

Modified residue2461Phosphothreonine Ref.6
Modified residue2781Phosphoserine By similarity
Modified residue4631Phosphoserine; alternate Ref.5 Ref.6
Modified residue4631Phosphoserine; by NUAK1 and NUAK2; alternate Probable
Modified residue6121Phosphoserine Ref.6
Modified residue6731Phosphoserine By similarity
Modified residue9081Phosphoserine; by STK3/MST2 By similarity
Modified residue10781Phosphothreonine; by STK3/MST2 By similarity

Experimental info

Sequence conflict9401F → C in AAD16883. Ref.3
Sequence conflict9631N → I in AAD16883. Ref.3
Sequence conflict10611N → S in AAD16883. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q8BYR2 [UniParc].

Last modified July 27, 2011. Version 3.
Checksum: FCDC2EC8BC2FF2DE

FASTA1,129126,258
        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 

« Hide

References

« Hide '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. 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] 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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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; SER-463 AND SER-612, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+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.
RefSeqNP_034820.1. NM_010690.1.
UniGeneMm.34083.

3D structure databases

ProteinModelPortalQ8BYR2.
SMRQ8BYR2. Positions 95-142, 625-1118.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201113. 1 interaction.
IntActQ8BYR2. 1 interaction.

PTM databases

PhosphoSiteQ8BYR2.

Proteomic databases

PaxDbQ8BYR2.
PRIDEQ8BYR2.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000040043; ENSMUSP00000041915; ENSMUSG00000040021.
ENSMUST00000165952; ENSMUSP00000132078; ENSMUSG00000040021.
GeneID16798.
KEGGmmu:16798.
UCSCuc007eig.2. mouse.

Organism-specific databases

CTD9113.
MGIMGI:1333883. Lats1.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00750000117422.
HOGENOMHOG000040002.
HOVERGENHBG052311.
InParanoidB2RY46.
KOK08791.
OMAAGFDEDM.
OrthoDBEOG7BZVS1.
TreeFamTF351549.

Gene expression databases

BgeeQ8BYR2.
CleanExMM_LATS1.
GenevestigatorQ8BYR2.

Family and domain databases

InterProIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR028741. LATS1.
IPR000719. Prot_kinase_dom.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR009060. UBA-like.
IPR015940. UBA/transl_elong_EF1B_N_euk.
IPR000449. UBA/Ts_N.
[Graphical view]
PANTHERPTHR24356:SF113. PTHR24356:SF113. 1 hit.
PfamPF00069. Pkinase. 2 hits.
PF00627. UBA. 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.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50030. UBA. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio290674.
PROQ8BYR2.
SOURCESearch...

Entry information

Entry nameLATS1_MOUSE
AccessionPrimary (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: April 16, 2014
This is version 115 of the entry and version 3 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

MGD cross-references

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