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Protein

Serine/threonine-protein kinase LATS1

Gene

LATS1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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. Plays a role in mammary gland epithelial cells differentiation, both through the Hippo signaling pathway and the intracellular estrogen receptor signaling pathway by promoting the degradation of ESR1 (PubMed:28068668).7 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.2 Publications

Cofactori

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei734ATPPROSITE-ProRule annotation1 Publication1
Active sitei828Proton acceptorPROSITE-ProRule annotationBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi711 – 719ATPPROSITE-ProRule annotationBy similarity9

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • estrogen receptor binding Source: UniProtKB
  • magnesium ion binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processCell cycle, Cell division, Mitosis
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-2028269 Signaling by Hippo
SignaLinkiO95835
SIGNORiO95835

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
Short name:
h-warts
Gene namesi
Name:LATS1Imported
Synonyms:WARTSImported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000131023.12
HGNCiHGNC:6514 LATS1
MIMi603473 gene
neXtProtiNX_O95835

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi464S → A: Abolishes phosphorylation by NUAK1 and NUAK2. 1 Publication1
Mutagenesisi559Y → F: Loss of interaction with YAP1. 1 Publication1
Mutagenesisi734K → A: Loss of kinase activity, autophosphorylation, increased ploidy, prolonged duration of mitosis and lack of p53 expression. 1 Publication1

Keywords - Diseasei

Tumor suppressor

Organism-specific databases

DisGeNETi9113
OpenTargetsiENSG00000131023
PharmGKBiPA30301

Chemistry databases

ChEMBLiCHEMBL6167

Polymorphism and mutation databases

BioMutaiLATS1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000862321 – 1130Serine/threonine-protein kinase LATS1Add BLAST1130

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei246PhosphothreonineCombined sources1
Modified residuei278PhosphoserineCombined sources1
Modified residuei464Phosphoserine; by NUAK1 and NUAK2Combined sources1 Publication1
Modified residuei613PhosphoserineCombined sources1
Modified residuei674PhosphoserineCombined sources1
Modified residuei909Phosphoserine; by STK3/MST21 Publication1
Modified residuei1079Phosphothreonine; by STK3/MST22 Publications1

Post-translational modificationi

Autophosphorylated and phosphorylated during M-phase of the cell cycle. Phosphorylated by STK3/MST2 at Ser-909 and Thr-1079, which results in its activation. Phosphorylation at Ser-464 by NUAK1 and NUAK2 leads to decreased protein level and is required to regulate cellular senescence and cellular ploidy.4 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO95835
MaxQBiO95835
PaxDbiO95835
PeptideAtlasiO95835
PRIDEiO95835
ProteomicsDBi51081
51082 [O95835-2]

PTM databases

iPTMnetiO95835
PhosphoSitePlusiO95835

Expressioni

Tissue specificityi

Expressed in all adult tissues examined except for lung and kidney.1 Publication

Gene expression databases

BgeeiENSG00000131023 Expressed in 208 organ(s), highest expression level in tibia
CleanExiHS_LATS1
ExpressionAtlasiO95835 baseline and differential
GenevisibleiO95835 HS

Organism-specific databases

HPAiHPA031804

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. Interacts with LIMD1, WTIP and AJUBA. Interacts with ESR1, DCAF1 and DCAF13; probably recruits DCAF1 and DCAF13 to ESR1 to promote ESR1 ubiquitination and ubiquitin-mediated proteasomal degradation (PubMed:28068668). Interacts with STK3/MST2; this interaction is inhibited in the presence of DLG5 (PubMed:28087714). Interacts with SCRIB in the presence of DLG5 (PubMed:28169360).9 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114563, 111 interactors
CORUMiO95835
DIPiDIP-31516N
IntActiO95835, 51 interactors
MINTiO95835
STRINGi9606.ENSP00000253339

Chemistry databases

BindingDBiO95835

Structurei

Secondary structure

11130
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO95835
SMRiO95835
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini100 – 141UBAPROSITE-ProRule annotationAdd BLAST42
Domaini705 – 1010Protein kinasePROSITE-ProRule annotationAdd BLAST306
Domaini1011 – 1090AGC-kinase C-terminalAdd BLAST80

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni526 – 655Interaction with YAP11 PublicationAdd BLAST130

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi373 – 376PPxY motif 14
Motifi556 – 559PPxY motif 24

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0605 Eukaryota
ENOG410XQC0 LUCA
GeneTreeiENSGT00760000118994
HOGENOMiHOG000040002
HOVERGENiHBG052311
InParanoidiO95835
KOiK08791
OMAiEDDQHTG
OrthoDBiEOG091G028J
PhylomeDBiO95835
TreeFamiTF351549

Family and domain databases

InterProiView protein in InterPro
IPR000961 AGC-kinase_C
IPR011009 Kinase-like_dom_sf
IPR028741 LATS1
IPR000719 Prot_kinase_dom
IPR008271 Ser/Thr_kinase_AS
IPR015940 UBA
IPR009060 UBA-like_sf
PANTHERiPTHR24356:SF138 PTHR24356:SF138, 1 hit
PfamiView protein in Pfam
PF00069 Pkinase, 2 hits
PF00627 UBA, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF46934 SSF46934, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS51285 AGC_KINASE_CTER, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
PS50030 UBA, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 11 Publication (identifier: O95835-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MKRSEKPEGY RQMRPKTFPA SNYTVSSRQM LQEIRESLRN LSKPSDAAKA
60 70 80 90 100
EHNMSKMSTE DPRQVRNPPK FGTHHKALQE IRNSLLPFAN ETNSSRSTSE
110 120 130 140 150
VNPQMLQDLQ AAGFDEDMVI QALQKTNNRS IEAAIEFISK MSYQDPRREQ
160 170 180 190 200
MAAAAARPIN ASMKPGNVQQ SVNRKQSWKG SKESLVPQRH GPPLGESVAY
210 220 230 240 250
HSESPNSQTD VGRPLSGSGI SAFVQAHPSN GQRVNPPPPP QVRSVTPPPP
260 270 280 290 300
PRGQTPPPRG TTPPPPSWEP NSQTKRYSGN MEYVISRISP VPPGAWQEGY
310 320 330 340 350
PPPPLNTSPM NPPNQGQRGI SSVPVGRQPI IMQSSSKFNF PSGRPGMQNG
360 370 380 390 400
TGQTDFMIHQ NVVPAGTVNR QPPPPYPLTA ANGQSPSALQ TGGSAAPSSY
410 420 430 440 450
TNGSIPQSMM VPNRNSHNME LYNISVPGLQ TNWPQSSSAP AQSSPSSGHE
460 470 480 490 500
IPTWQPNIPV RSNSFNNPLG NRASHSANSQ PSATTVTAIT PAPIQQPVKS
510 520 530 540 550
MRVLKPELQT ALAPTHPSWI PQPIQTVQPS PFPEGTASNV TVMPPVAEAP
560 570 580 590 600
NYQGPPPPYP KHLLHQNPSV PPYESISKPS KEDQPSLPKE DESEKSYENV
610 620 630 640 650
DSGDKEKKQI TTSPITVRKN KKDEERRESR IQSYSPQAFK FFMEQHVENV
660 670 680 690 700
LKSHQQRLHR KKQLENEMMR VGLSQDAQDQ MRKMLCQKES NYIRLKRAKM
710 720 730 740 750
DKSMFVKIKT LGIGAFGEVC LARKVDTKAL YATKTLRKKD VLLRNQVAHV
760 770 780 790 800
KAERDILAEA DNEWVVRLYY SFQDKDNLYF VMDYIPGGDM MSLLIRMGIF
810 820 830 840 850
PESLARFYIA ELTCAVESVH KMGFIHRDIK PDNILIDRDG HIKLTDFGLC
860 870 880 890 900
TGFRWTHDSK YYQSGDHPRQ DSMDFSNEWG DPSSCRCGDR LKPLERRAAR
910 920 930 940 950
QHQRCLAHSL VGTPNYIAPE VLLRTGYTQL CDWWSVGVIL FEMLVGQPPF
960 970 980 990 1000
LAQTPLETQM KVINWQTSLH IPPQAKLSPE ASDLIIKLCR GPEDRLGKNG
1010 1020 1030 1040 1050
ADEIKAHPFF KTIDFSSDLR QQSASYIPKI THPTDTSNFD PVDPDKLWSD
1060 1070 1080 1090 1100
DNEEENVNDT LNGWYKNGKH PEHAFYEFTF RRFFDDNGYP YNYPKPIEYE
1110 1120 1130
YINSQGSEQQ SDEDDQNTGS EIKNRDLVYV
Length:1,130
Mass (Da):126,870
Last modified:May 1, 1999 - v1
Checksum:i11CFBCD8FD87DCD8
GO
Isoform 2Curated (identifier: O95835-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     672-690: GLSQDAQDQMRKMLCQKES → KPFKMSIFILNHLFAWCLF
     691-1130: Missing.

Note: No experimental confirmation available.Curated
Show »
Length:690
Mass (Da):76,193
Checksum:i7154097947DF44E8
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q6PJG3Q6PJG3_HUMAN
LATS1 protein
LATS1
135Annotation score:
H0YG09H0YG09_HUMAN
Serine/threonine-protein kinase LAT...
LATS1
200Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04066096R → W1 PublicationCorresponds to variant dbSNP:rs55945045Ensembl.1
Natural variantiVAR_040661204S → G1 PublicationCorresponds to variant dbSNP:rs34793526Ensembl.1
Natural variantiVAR_040662237P → Q1 PublicationCorresponds to variant dbSNP:rs56149740Ensembl.1
Natural variantiVAR_040663370R → W1 PublicationCorresponds to variant dbSNP:rs56348064Ensembl.1
Natural variantiVAR_040664531P → S1 PublicationCorresponds to variant dbSNP:rs55874734Ensembl.1
Natural variantiVAR_040665641F → L1 PublicationCorresponds to variant dbSNP:rs35163691Ensembl.1
Natural variantiVAR_040666669M → I in a lung adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_040667806R → P in a lung large cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_0406681000G → S1 PublicationCorresponds to variant dbSNP:rs56412005Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_051604672 – 690GLSQD…CQKES → KPFKMSIFILNHLFAWCLF in isoform 2. 1 PublicationAdd BLAST19
Alternative sequenceiVSP_051605691 – 1130Missing in isoform 2. 1 PublicationAdd BLAST440

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF104413 mRNA Translation: AAD16882.1
AF164041 mRNA Translation: AAD50272.1
BC002767 mRNA Translation: AAH02767.1
CCDSiCCDS34551.1 [O95835-1]
CCDS59040.1 [O95835-2]
RefSeqiNP_001257448.1, NM_001270519.1 [O95835-2]
NP_004681.1, NM_004690.3 [O95835-1]
UniGeneiHs.549084

Genome annotation databases

EnsembliENST00000253339; ENSP00000253339; ENSG00000131023 [O95835-1]
ENST00000392273; ENSP00000444678; ENSG00000131023 [O95835-2]
ENST00000543571; ENSP00000437550; ENSG00000131023 [O95835-1]
GeneIDi9113
KEGGihsa:9113
UCSCiuc003qmu.2 human [O95835-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF104413 mRNA Translation: AAD16882.1
AF164041 mRNA Translation: AAD50272.1
BC002767 mRNA Translation: AAH02767.1
CCDSiCCDS34551.1 [O95835-1]
CCDS59040.1 [O95835-2]
RefSeqiNP_001257448.1, NM_001270519.1 [O95835-2]
NP_004681.1, NM_004690.3 [O95835-1]
UniGeneiHs.549084

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4ZRKX-ray2.32E/F/G/H69-100[»]
5B5WX-ray2.96U622-704[»]
5BRKX-ray2.30B602-704[»]
ProteinModelPortaliO95835
SMRiO95835
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114563, 111 interactors
CORUMiO95835
DIPiDIP-31516N
IntActiO95835, 51 interactors
MINTiO95835
STRINGi9606.ENSP00000253339

Chemistry databases

BindingDBiO95835
ChEMBLiCHEMBL6167

PTM databases

iPTMnetiO95835
PhosphoSitePlusiO95835

Polymorphism and mutation databases

BioMutaiLATS1

Proteomic databases

EPDiO95835
MaxQBiO95835
PaxDbiO95835
PeptideAtlasiO95835
PRIDEiO95835
ProteomicsDBi51081
51082 [O95835-2]

Protocols and materials databases

DNASUi9113
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000253339; ENSP00000253339; ENSG00000131023 [O95835-1]
ENST00000392273; ENSP00000444678; ENSG00000131023 [O95835-2]
ENST00000543571; ENSP00000437550; ENSG00000131023 [O95835-1]
GeneIDi9113
KEGGihsa:9113
UCSCiuc003qmu.2 human [O95835-1]

Organism-specific databases

CTDi9113
DisGeNETi9113
EuPathDBiHostDB:ENSG00000131023.12
GeneCardsiLATS1
HGNCiHGNC:6514 LATS1
HPAiHPA031804
MIMi603473 gene
neXtProtiNX_O95835
OpenTargetsiENSG00000131023
PharmGKBiPA30301
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0605 Eukaryota
ENOG410XQC0 LUCA
GeneTreeiENSGT00760000118994
HOGENOMiHOG000040002
HOVERGENiHBG052311
InParanoidiO95835
KOiK08791
OMAiEDDQHTG
OrthoDBiEOG091G028J
PhylomeDBiO95835
TreeFamiTF351549

Enzyme and pathway databases

ReactomeiR-HSA-2028269 Signaling by Hippo
SignaLinkiO95835
SIGNORiO95835

Miscellaneous databases

ChiTaRSiLATS1 human
GeneWikiiLATS1
GenomeRNAii9113
PROiPR:O95835
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000131023 Expressed in 208 organ(s), highest expression level in tibia
CleanExiHS_LATS1
ExpressionAtlasiO95835 baseline and differential
GenevisibleiO95835 HS

Family and domain databases

InterProiView protein in InterPro
IPR000961 AGC-kinase_C
IPR011009 Kinase-like_dom_sf
IPR028741 LATS1
IPR000719 Prot_kinase_dom
IPR008271 Ser/Thr_kinase_AS
IPR015940 UBA
IPR009060 UBA-like_sf
PANTHERiPTHR24356:SF138 PTHR24356:SF138, 1 hit
PfamiView protein in Pfam
PF00069 Pkinase, 2 hits
PF00627 UBA, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF46934 SSF46934, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS51285 AGC_KINASE_CTER, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
PS50030 UBA, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiLATS1_HUMAN
AccessioniPrimary (citable) accession number: O95835
Secondary accession number(s): Q6PKD0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 27, 2004
Last sequence update: May 1, 1999
Last modified: November 7, 2018
This is version 181 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  7. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
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