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Protein

Serine/threonine-protein kinase LATS1

Gene

Lats1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.By similarity

Cofactori

Mg2+By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei733 – 7331ATPPROSITE-ProRule annotationBy similarity
Active sitei827 – 8271Proton acceptorPROSITE-ProRule annotationBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi710 – 7189ATPPROSITE-ProRule annotationBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Cell cycle, Cell division, Mitosis

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_301726. Signaling by Hippo.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase LATS1 (EC:2.7.11.1)
Alternative name(s):
Large tumor suppressor homolog 1
WARTS protein kinase
Gene namesi
Name:Lats1Imported
Synonyms:WartsBy similarity
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1333883. Lats1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton

Pathology & Biotechi

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11291129Serine/threonine-protein kinase LATS1PRO_0000086233Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei246 – 2461Phosphothreonine1 Publication
Modified residuei278 – 2781PhosphoserineBy similarity
Modified residuei463 – 4631Phosphoserine; by NUAK1 and NUAK22 Publications
Modified residuei612 – 6121Phosphoserine1 Publication
Modified residuei673 – 6731PhosphoserineBy similarity
Modified residuei908 – 9081Phosphoserine; by STK3/MST2By similarity
Modified residuei1078 – 10781Phosphothreonine; by STK3/MST2By similarity

Post-translational modificationi

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.

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ8BYR2.
PaxDbiQ8BYR2.
PRIDEiQ8BYR2.

PTM databases

PhosphoSiteiQ8BYR2.

Expressioni

Gene expression databases

BgeeiQ8BYR2.
CleanExiMM_LATS1.
GenevestigatoriQ8BYR2.

Interactioni

Subunit structurei

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).By similarity

Protein-protein interaction databases

BioGridi201113. 1 interaction.
DIPiDIP-47647N.
IntActiQ8BYR2. 1 interaction.

Structurei

3D structure databases

ProteinModelPortaliQ8BYR2.
SMRiQ8BYR2. Positions 95-142, 625-1118.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini100 – 14142UBAPROSITE-ProRule annotationAdd
BLAST
Domaini704 – 1009306Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini1010 – 108980AGC-kinase C-terminalAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni525 – 654130Interaction with YAP1By similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi372 – 3754PPxY motif 1
Motifi555 – 5584PPxY motif 2

Sequence similaritiesi

Contains 1 AGC-kinase C-terminal domain.Curated
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 UBA domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118994.
HOGENOMiHOG000040002.
HOVERGENiHBG052311.
InParanoidiQ8BYR2.
KOiK08791.
OMAiWQTSLHI.
OrthoDBiEOG7BZVS1.
TreeFamiTF351549.

Family and domain databases

InterProiIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR028741. LATS1/Warts.
IPR000719. Prot_kinase_dom.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
IPR009060. UBA-like.
IPR015940. UBA/transl_elong_EF1B_N_euk.
IPR000449. UBA/Ts_N.
[Graphical view]
PANTHERiPTHR24356:SF138. PTHR24356:SF138. 1 hit.
PfamiPF00069. Pkinase. 2 hits.
PF00627. UBA. 1 hit.
[Graphical view]
SMARTiSM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF46934. SSF46934. 1 hit.
SSF56112. SSF56112. 2 hits.
PROSITEiPS51285. AGC_KINASE_CTER. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50030. UBA. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8BYR2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKRGEKPEGY RQMRPKTFPA SNYPGSSRQM LQEIRESLRN LSKPSDASKA
60 70 80 90 100
EHNLNKMSTE DPRQVRNPPK FGTHHKALQE IRNSLLPFAN ETSSSRSPSE
110 120 130 140 150
VNPQMFQDLQ AAGFDEDMVI QALQKTNNRS IEAAVEFISK MSYQDPRREQ
160 170 180 190 200
MSAAAARPIN ATMKPGNVQH SINRKQSWKG SKESLVPQRH GPSLGENVVY
210 220 230 240 250
RSESPNSQAD VGRPLSGSGI AAFAQAHPSN GQRVNPPPPP QVRSVTPPPP
260 270 280 290 300
PRGQTPPPRG TTPPPPSWEP SSQTKRYSGN MEYVISRISP VPPGAWQEGY
310 320 330 340 350
PPPPLTTSPM NPPSQAQRAI SSVPVGRQPI IMQSTSKFNF TPGRPGVQNG
360 370 380 390 400
GGQSDFIVHQ NVPTGSVTRQ PPPPYPLTPA NGQSPSALQT GASAAPPSFA
410 420 430 440 450
NGNVPQSMMV PNRNSHNMEL YNINVPGLQT AWPQSSSAPA QSSPSGGHEI
460 470 480 490 500
PTWQPNIPVR SNSFNNPLGS RASHSANSQP SATTVTAITP APIQQPVKSM
510 520 530 540 550
RVLKPELQTA LAPTHPSWMP QPVQTVQPTP FSEGTASSVP VIPPVAEAPS
560 570 580 590 600
YQGPPPPYPK HLLHQNPSVP PYESVSKPCK DEQPSLPKED DSEKSADSGD
610 620 630 640 650
SGDKEKKQIT TSPITVRKNK KDEERRESRI QSYSPQAFKF FMEQHVENVL
660 670 680 690 700
KSHQQRLHRK KQLENEMMRV GLSQDAQDQM RKMLCQKESN YIRLKRAKMD
710 720 730 740 750
KSMFVKIKTL GIGAFGEVCL ARKVDTKALY ATKTLRKKDV LLRNQVAHVK
760 770 780 790 800
AERDILAEAD NEWVVRLYYS FQDKDNLYFV MDYIPGGDMM SLLIRMGIFP
810 820 830 840 850
ENLARFYIAE LTCAVESVHK MGFIHRDIKP DNILIDRDGH IKLTDFGLCT
860 870 880 890 900
GFRWTHDSKY YQSGDHPRQD SMDFSNEWGD PSNCRCGDRL KPLERRAARQ
910 920 930 940 950
HQRCLAHSLV GTPNYIAPEV LLRTGYTQLC DWWSVGVILF EMLVGQPPFL
960 970 980 990 1000
AQTPLETQMK VINWQTSLHI PPQAKLSPEA SDLIIKLCRG PEDRLGKNGA
1010 1020 1030 1040 1050
DEIKAHPFFK TIDFSSDLRQ QSASYIPKIT HPTDTSNFDP VDPDKLWSDG
1060 1070 1080 1090 1100
SEEENISDTL NGWYKNGKHP EHAFYEFTFR RFFDDNGYPY NYPKPIEYEY
1110 1120
IHSQGSEQQS DEDDQHTSSD GNNRDLVYV
Length:1,129
Mass (Da):126,258
Last modified:July 27, 2011 - v3
Checksum:iFCDC2EC8BC2FF2DE
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti940 – 9401F → C in AAD16883 (PubMed:9988268).Curated
Sequence conflicti963 – 9631N → I in AAD16883 (PubMed:9988268).Curated
Sequence conflicti1061 – 10611N → S in AAD16883 (PubMed:9988268).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC158092 mRNA. Translation: AAI58093.1.
BC158123 mRNA. Translation: AAI58124.1.
AK038612 mRNA. Translation: BAC30063.1.
AF104414 mRNA. Translation: AAD16883.1.
CCDSiCCDS48494.1.
RefSeqiNP_034820.1. NM_010690.1.
UniGeneiMm.34083.

Genome annotation databases

EnsembliENSMUST00000040043; ENSMUSP00000041915; ENSMUSG00000040021.
ENSMUST00000165952; ENSMUSP00000132078; ENSMUSG00000040021.
GeneIDi16798.
KEGGimmu:16798.
UCSCiuc007eig.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC158092 mRNA. Translation: AAI58093.1.
BC158123 mRNA. Translation: AAI58124.1.
AK038612 mRNA. Translation: BAC30063.1.
AF104414 mRNA. Translation: AAD16883.1.
CCDSiCCDS48494.1.
RefSeqiNP_034820.1. NM_010690.1.
UniGeneiMm.34083.

3D structure databases

ProteinModelPortaliQ8BYR2.
SMRiQ8BYR2. Positions 95-142, 625-1118.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201113. 1 interaction.
DIPiDIP-47647N.
IntActiQ8BYR2. 1 interaction.

PTM databases

PhosphoSiteiQ8BYR2.

Proteomic databases

MaxQBiQ8BYR2.
PaxDbiQ8BYR2.
PRIDEiQ8BYR2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000040043; ENSMUSP00000041915; ENSMUSG00000040021.
ENSMUST00000165952; ENSMUSP00000132078; ENSMUSG00000040021.
GeneIDi16798.
KEGGimmu:16798.
UCSCiuc007eig.2. mouse.

Organism-specific databases

CTDi9113.
MGIiMGI:1333883. Lats1.

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118994.
HOGENOMiHOG000040002.
HOVERGENiHBG052311.
InParanoidiQ8BYR2.
KOiK08791.
OMAiWQTSLHI.
OrthoDBiEOG7BZVS1.
TreeFamiTF351549.

Enzyme and pathway databases

ReactomeiREACT_301726. Signaling by Hippo.

Miscellaneous databases

NextBioi290674.
PROiQ8BYR2.
SOURCEiSearch...

Gene expression databases

BgeeiQ8BYR2.
CleanExiMM_LATS1.
GenevestigatoriQ8BYR2.

Family and domain databases

InterProiIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR028741. LATS1/Warts.
IPR000719. Prot_kinase_dom.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
IPR009060. UBA-like.
IPR015940. UBA/transl_elong_EF1B_N_euk.
IPR000449. UBA/Ts_N.
[Graphical view]
PANTHERiPTHR24356:SF138. PTHR24356:SF138. 1 hit.
PfamiPF00069. Pkinase. 2 hits.
PF00627. UBA. 1 hit.
[Graphical view]
SMARTiSM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF46934. SSF46934. 1 hit.
SSF56112. SSF56112. 2 hits.
PROSITEiPS51285. AGC_KINASE_CTER. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50030. UBA. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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: BrainImported.
  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. 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].

Entry informationi

Entry nameiLATS1_MOUSE
AccessioniPrimary (citable) accession number: Q8BYR2
Secondary accession number(s): B2RY46, Q9Z0W4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 27, 2004
Last sequence update: July 27, 2011
Last modified: April 1, 2015
This is version 126 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.