UniProtKB - Q9NRM7 (LATS2_HUMAN)
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Protein
Serine/threonine-protein kinase LATS2
Gene
LATS2
Organism
Homo sapiens (Human)
Status
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 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.5 Publications
Catalytic activityi
ATP + a protein = ADP + a phosphoprotein.1 Publication
Cofactori
Sites
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Binding sitei | 697 | ATPPROSITE-ProRule annotation1 Publication | 1 | |
| Active sitei | 791 | Proton acceptorPROSITE-ProRule annotationBy similarity | 1 |
Regions
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Nucleotide bindingi | 674 – 782 | ATPPROSITE-ProRule annotationBy similarityAdd BLAST | 109 |
GO - Molecular functioni
- ATP binding Source: UniProtKB
- metal ion binding Source: UniProtKB-KW
- protein serine/threonine kinase activity Source: UniProtKB
GO - Biological processi
- cell division Source: UniProtKB-KW
- cellular protein localization Source: Ensembl
- G1/S transition of mitotic cell cycle Source: UniProtKB
- hippo signaling Source: BHF-UCL
- hormone-mediated signaling pathway Source: UniProtKB
- inner cell mass cell fate commitment Source: Ensembl
- inner cell mass cellular morphogenesis Source: Ensembl
- intracellular signal transduction Source: UniProtKB
- keratinocyte differentiation Source: Ensembl
- negative regulation of canonical Wnt signaling pathway Source: BHF-UCL
- negative regulation of cyclin-dependent protein serine/threonine kinase activity Source: UniProtKB
- peptidyl-serine phosphorylation Source: GO_Central
- positive regulation of apoptotic process Source: GO_Central
- protein phosphorylation Source: UniProtKB
- regulation of organ growth Source: GO_Central
Keywordsi
| Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
| Biological process | Cell cycle, Cell division, Mitosis |
| Ligand | ATP-binding, Magnesium, Metal-binding, Nucleotide-binding |
Enzyme and pathway databases
| Reactomei | R-HSA-2028269. Signaling by Hippo. |
| SignaLinki | Q9NRM7. |
| SIGNORi | Q9NRM7. |
Names & Taxonomyi
| Protein namesi | 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 Warts-like kinase |
| Gene namesi | |
| Organismi | Homo sapiens (Human) |
| Taxonomic identifieri | 9606 [NCBI] |
| Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
| Proteomesi |
|
Organism-specific databases
| HGNCi | HGNC:6515. LATS2. |
Subcellular locationi
- Cytoplasm › cytoskeleton › microtubule organizing center › centrosome
- Cytoplasm
- Cytoplasm › cytoskeleton › spindle pole
- Nucleus
Note: Colocalizes with AURKA at the centrosomes during interphase, early prophase and cytokinesis. Migrates to the spindle poles during mitosis, and to the midbody during cytokinesis. Translocates to the nucleus upon mitotic stress by nocodazole treatment.
GO - Cellular componenti
- cytosol Source: HPA
- microtubule organizing center Source: HPA
- nucleus Source: MGI
- spindle pole Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, Cytoskeleton, NucleusPathology & Biotechi
Mutagenesis
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Mutagenesisi | 83 | S → C: Fails to localize at the centromere during interphase. 1 Publication | 1 | |
| Mutagenesisi | 83 | S → E: Fails to localize at the centromere during interphase. 1 Publication | 1 | |
| Mutagenesisi | 697 | K → A: Loss of kinase activity, autophosphorylation and tumor suppressor activity. 2 Publications | 1 | |
| Mutagenesisi | 872 | S → A: Loss of tumor suppressor activity. 1 Publication | 1 |
Keywords - Diseasei
Tumor suppressorOrganism-specific databases
| DisGeNETi | 26524. |
| OpenTargetsi | ENSG00000150457. |
| PharmGKBi | PA30302. |
Chemistry databases
| ChEMBLi | CHEMBL5907. |
| GuidetoPHARMACOLOGYi | 1516. |
Polymorphism and mutation databases
| BioMutai | LATS2. |
| DMDMi | 212276441. |
PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| ChainiPRO_0000086234 | 1 – 1088 | Serine/threonine-protein kinase LATS2Add BLAST | 1088 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Modified residuei | 83 | Phosphoserine; by AURKA1 Publication | 1 | |
| Modified residuei | 279 | PhosphothreonineCombined sources | 1 | |
| Modified residuei | 380 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 576 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 1041 | Phosphothreonine1 Publication | 1 |
Post-translational modificationi
Autophosphorylated and phosphorylated during M-phase and the G1/S-phase of the cell cycle. Phosphorylated and activated by STK3/MST2.3 Publications
Keywords - PTMi
PhosphoproteinProteomic databases
| EPDi | Q9NRM7. |
| MaxQBi | Q9NRM7. |
| PaxDbi | Q9NRM7. |
| PeptideAtlasi | Q9NRM7. |
| PRIDEi | Q9NRM7. |
PTM databases
| iPTMneti | Q9NRM7. |
| PhosphoSitePlusi | Q9NRM7. |
Expressioni
Tissue specificityi
Expressed at high levels in heart and skeletal muscle and at lower levels in all other tissues examined.2 Publications
Gene expression databases
| Bgeei | ENSG00000150457. |
| CleanExi | HS_LATS2. |
| ExpressionAtlasi | Q9NRM7. baseline and differential. |
| Genevisiblei | Q9NRM7. HS. |
Organism-specific databases
| HPAi | HPA039191. HPA049037. |
Interactioni
Subunit structurei
Interacts with and is phosphorylated by AURKA. Binds to AR. 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. Interacts with LIMD1, WTIP and AJUBA. Interacts with SNAI1.7 Publications
Binary interactionsi
Protein-protein interaction databases
| BioGridi | 117727. 160 interactors. |
| DIPi | DIP-43883N. |
| IntActi | Q9NRM7. 13 interactors. |
| MINTi | MINT-1772003. |
| STRINGi | 9606.ENSP00000372035. |
Chemistry databases
| BindingDBi | Q9NRM7. |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Helixi | 74 – 84 | Combined sources | 11 | |
| Helixi | 85 – 87 | Combined sources | 3 |
3D structure databases
| Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
| 4ZRI | X-ray | 2.70 | C/D | 68-99 | [»] | |
| ProteinModelPortali | Q9NRM7. | |||||
| SMRi | Q9NRM7. | |||||
| ModBasei | Search... | |||||
| MobiDBi | Search... | |||||
Family & Domainsi
Domains and Repeats
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Domaini | 98 – 139 | UBAPROSITE-ProRule annotationAdd BLAST | 42 | |
| Domaini | 668 – 973 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 306 | |
| Domaini | 974 – 1052 | AGC-kinase C-terminalAdd BLAST | 79 |
Motif
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Motifi | 515 – 518 | PPxY motif | 4 |
Sequence similaritiesi
Phylogenomic databases
| eggNOGi | KOG0605. Eukaryota. ENOG410XQC0. LUCA. |
| GeneTreei | ENSGT00760000118994. |
| HOGENOMi | HOG000040002. |
| HOVERGENi | HBG052311. |
| InParanoidi | Q9NRM7. |
| KOi | K08791. |
| OMAi | RCPPPPY. |
| OrthoDBi | EOG091G028J. |
| PhylomeDBi | Q9NRM7. |
| TreeFami | TF351549. |
Family and domain databases
| InterProi | View protein in InterPro IPR000961. AGC-kinase_C. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_dom. IPR017441. Protein_kinase_ATP_BS. IPR008271. Ser/Thr_kinase_AS. IPR015940. UBA. IPR009060. UBA-like. |
| Pfami | View protein in Pfam PF00069. Pkinase. 2 hits. |
| SMARTi | View protein in SMART SM00133. S_TK_X. 1 hit. SM00220. S_TKc. 1 hit. |
| SUPFAMi | SSF46934. SSF46934. 1 hit. SSF56112. SSF56112. 2 hits. |
| PROSITEi | View protein in 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. |
Sequencei
Sequence statusi: Complete.
Q9NRM7-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MRPKTFPATT YSGNSRQRLQ EIREGLKQPS KSSVQGLPAG PNSDTSLDAK
60 70 80 90 100
VLGSKDATRQ QQQMRATPKF GPYQKALREI RYSLLPFANE SGTSAAAEVN
110 120 130 140 150
RQMLQELVNA GCDQEMAGRA LKQTGSRSIE AALEYISKMG YLDPRNEQIV
160 170 180 190 200
RVIKQTSPGK GLMPTPVTRR PSFEGTGDSF ASYHQLSGTP YEGPSFGADG
210 220 230 240 250
PTALEEMPRP YVDYLFPGVG PHGPGHQHQH PPKGYGASVE AAGAHFPLQG
260 270 280 290 300
AHYGRPHLLV PGEPLGYGVQ RSPSFQSKTP PETGGYASLP TKGQGGPPGA
310 320 330 340 350
GLAFPPPAAG LYVPHPHHKQ AGPAAHQLHV LGSRSQVFAS DSPPQSLLTP
360 370 380 390 400
SRNSLNVDLY ELGSTSVQQW PAATLARRDS LQKPGLEAPP RAHVAFRPDC
410 420 430 440 450
PVPSRTNSFN SHQPRPGPPG KAEPSLPAPN TVTAVTAAHI LHPVKSVRVL
460 470 480 490 500
RPEPQTAVGP SHPAWVPAPA PAPAPAPAPA AEGLDAKEEH ALALGGAGAF
510 520 530 540 550
PLDVEYGGPD RRCPPPPYPK HLLLRSKSEQ YDLDSLCAGM EQSLRAGPNE
560 570 580 590 600
PEGGDKSRKS AKGDKGGKDK KQIQTSPVPV RKNSRDEEKR ESRIKSYSPY
610 620 630 640 650
AFKFFMEQHV ENVIKTYQQK VNRRLQLEQE MAKAGLCEAE QEQMRKILYQ
660 670 680 690 700
KESNYNRLKR AKMDKSMFVK IKTLGIGAFG EVCLACKVDT HALYAMKTLR
710 720 730 740 750
KKDVLNRNQV AHVKAERDIL AEADNEWVVK LYYSFQDKDS LYFVMDYIPG
760 770 780 790 800
GDMMSLLIRM EVFPEHLARF YIAELTLAIE SVHKMGFIHR DIKPDNILID
810 820 830 840 850
LDGHIKLTDF GLCTGFRWTH NSKYYQKGSH VRQDSMEPSD LWDDVSNCRC
860 870 880 890 900
GDRLKTLEQR ARKQHQRCLA HSLVGTPNYI APEVLLRKGY TQLCDWWSVG
910 920 930 940 950
VILFEMLVGQ PPFLAPTPTE TQLKVINWEN TLHIPAQVKL SPEARDLITK
960 970 980 990 1000
LCCSADHRLG RNGADDLKAH PFFSAIDFSS DIRKQPAPYV PTISHPMDTS
1010 1020 1030 1040 1050
NFDPVDEESP WNDASEGSTK AWDTLTSPNN KHPEHAFYEF TFRRFFDDNG
1060 1070 1080
YPFRCPKPSG AEASQAESSD LESSDLVDQT EGCQPVYV
Sequence cautioni
Experimental Info
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Sequence conflicti | 59 – 61 | RQQ → SSK in BAA92381 (PubMed:10673337).Curated | 3 | |
| Sequence conflicti | 436 | T → S in BAA92381 (PubMed:10673337).Curated | 1 | |
| Sequence conflicti | 711 | A → V in AAF80561 (PubMed:10871863).Curated | 1 | |
| Sequence conflicti | 868 | C → S in BAA92381 (PubMed:10673337).Curated | 1 |
Natural variant
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_040669 | 40 | G → E in a lung adenocarcinoma sample; somatic mutation. 1 Publication | 1 | |
| Natural variantiVAR_040670 | 91 | S → L1 PublicationCorresponds to variant dbSNP:rs55842804Ensembl. | 1 | |
| Natural variantiVAR_019789 | 324 | A → V1 PublicationCorresponds to variant dbSNP:rs558614Ensembl. | 1 | |
| Natural variantiVAR_047077 | 363 | G → S. Corresponds to variant dbSNP:rs2770928Ensembl. | 1 | |
| Natural variantiVAR_040671 | 799 | I → V1 PublicationCorresponds to variant dbSNP:rs35368391Ensembl. | 1 | |
| Natural variantiVAR_040672 | 1014 | A → G1 PublicationCorresponds to variant dbSNP:rs45523141Ensembl. | 1 | |
| Natural variantiVAR_040673 | 1025 | L → P1 PublicationCorresponds to variant dbSNP:rs56116059Ensembl. | 1 |
Sequence databases
| Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF207547 mRNA. Translation: AAF80561.1. AK314235 mRNA. Translation: BAG36905.1. AL161613, AL356285 Genomic DNA. Translation: CAH71526.1. AL356285, AL161613 Genomic DNA. Translation: CAI15861.1. CH471075 Genomic DNA. Translation: EAX08286.1. AB028019 mRNA. Translation: BAA92381.1. Frameshift. |
| CCDSi | CCDS9294.1. |
| RefSeqi | NP_055387.2. NM_014572.2. XP_005266399.1. XM_005266342.1. |
| UniGenei | Hs.78960. |
Genome annotation databases
| Ensembli | ENST00000382592; ENSP00000372035; ENSG00000150457. |
| GeneIDi | 26524. |
| KEGGi | hsa:26524. |
| UCSCi | uc001unr.6. human. |
Keywords - Coding sequence diversityi
PolymorphismSimilar 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 one 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. |
Entry informationi
| Entry namei | LATS2_HUMAN | |
| Accessioni | Q9NRM7Primary (citable) accession number: Q9NRM7 Secondary accession number(s): B1AM47, Q9P2X1 | |
| Entry historyi | Integrated into UniProtKB/Swiss-Prot: | September 27, 2004 |
| Last sequence update: | November 4, 2008 | |
| Last modified: | June 7, 2017 | |
| This is version 160 of the entry and version 2 of the sequence. See complete history. | ||
| Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
| Annotation program | Chordata Protein Annotation Program | |
| Disclaimer | Any 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 proteomeDocuments
- Human chromosome 13
Human chromosome 13: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - Human and mouse protein kinases
Human and mouse protein kinases: classification and index - SIMILARITY comments
Index of protein domains and families
