The Eukaryote Linear Motif resource for Functional Sites in Proteins
Accession:
Functional site class:
LATS kinase phosphorylation motif
Functional site description:
The LATS/NDR kinases are an evolutionarily conserved subfamily of the basophilic AGC kinases. The two mammalian Large Tumor suppressors, LATS1/2, are collectively referred as LATS and are highly conserved within their orthologous sets. LATS kinases were initially identified in Drosophila and named WARTS. The LATS act as key components of the Hippo-LATS pathway. At the core of this pathway in flies is the Ste-20-like kinase, Hpo which phosphorylates and activates the NDR family kinase Lats/Warts in complex with Mats/dMOB1. The active Mats/Lats complex then in turn phosphorylates their downstream effectors and inhibits their activity as transcriptional co activators in drosophila. Studies have shown that this pathway is highly conserved in mammals. The LATS phosphorylation site comprises a serine/threonine residue with a histidine at -5 position.
ELM Description:
The mammalian tumour suppressors LATS1 and 2 are basophilic AGC group kinases involved in the Hippo pathway. Orthologues of LATS kinases are conserved in animals, fungi and slime moulds. Some known substrates of LATS like YAP1, WWTR1 and SSD1 have multiple LATS phosphorylation sites, which has helped to define the sequence motif at the target site. The LATS kinases prefer to phosphorylate peptide sequences in which the target serine/threonine residue is preceded by positively charged residues. These positively charged residues nicely fill the negative pocket in the catalytic domain of LATS. They match the consensus sequence Hx[RK]xx[ST]. Although the consensus sequence is similar to other AGC kinases, the LATS family is the only family which requires histidine at -5 position which shows the specificity of LATS phosphorylation.
Pattern: H.[KR]..([ST])[^P]
Pattern Probability: 0.0004776
Present in taxons: Fungi Metazoa Mycetozoa
Interaction Domains:
o See 23 Instances for MOD_LATS_1
o Abstract
The NDR/LATS kinase constitute a subfamily of the AGC group of protein kinases found in metazoa, fungi and slime moulds (Avruch,2012). Members of the NDR/LATS kinases family have been implicated in a variety of biological processes ranging from cell division and morphology to apoptosis and tumor suppression (Zhao,2010). The mammalian genome encodes four members of the NDR/LATS family: NDR1, NDR2, LATS1 and LATS2. In S. cerevisiae, Dbf2p and Cbk1p have been identified as orthologous to the NDR/LATS kinases. The corresponding kinases in S. pombe are Orb6 and Sid2. In Drosophila they are known as Tricornered and Warts/Lats. In C. elegans Sax1 and Lats are the NDR/LATS kinases (Cornils,2011). Due to the expansion of LATS kinase isoforms and the number of their interacting partners, the complexity and the functional diversity seems to be increased in higher eukaryotes.
LATS1/LATS2 are primarily considered as central players in the Hippo tumour suppressor pathway, however they also participate in a range of other signalling pathways. (Zhao,2010). The core of the Hippo pathway consists of Hpo, Wts, Sav and Mats. Hippo (Hpo) is a Ste20 family protein kinase that complexes with the regulatory scaffold protein Salvador (Sav). The Hpo/Sav complex then phosphorylates and activates Warts (Wts). Wts has an activating subunit Mats. The active Wts/Mats complex then in turn phosphorylates the transcriptional co-activators Yorkie (Yki) in flies, and YAP and TAZ in mammals. Phosphorylation of these transcriptional co-activators leads to their association with 14-3-3 family proteins, cytoplasmic retention and inactivation (Zhao,2007). In the presence of active CK1 kinase, LATS1/2 mediated phosphorylation of YAP also leads to the recruitment of the beta-TRCP SCF E3 ligase thereby triggering the subsequent proteasomal degradation of YAP (Zhao,2010). The LATS kinases prefer to phosphorylate a peptide sequence in which the target serine/threonine residue is preceded by positively charged residues. Some of the LATS substrate proteins possess multiple sites for phosphorylation, each matching the consensus sequence Hx[RK]xx[ST]. Although the consensus sequence is similar to other AGC kinases, the LATS kinases are the only family which requires histidine at -5 position.
o 8 selected references:

o 8 GO-Terms:

o 23 Instances for MOD_LATS_1
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Acc., Gene-, NameStartEndSubsequenceLogic#Ev.OrganismNotes
P46937-2 YAP1
YAP1_HUMAN
56 62 AGHQIVHVRGDSETDLEALF TP 4 Homo sapiens (Human)
2 
P46937-2 YAP1
YAP1_HUMAN
104 110 PPEPKSHSRQASTDAGTAGA TP 4 Homo sapiens (Human)
2 
P46937-2 YAP1
YAP1_HUMAN
122 128 GALTPQHVRAHSSPASLQLG TP 5 Homo sapiens (Human)
2 
P46937-2 YAP1
YAP1_HUMAN
159 165 ATPTAQHLRQSSFEIPDDVP TP 4 Homo sapiens (Human)
2 
P46937-2 YAP1
YAP1_HUMAN
376 382 LNSGTYHSRDESTDSGLSMS TP 4 Homo sapiens (Human)
2 
1 
O95863 SNAI1
SNAI1_HUMAN
198 204 PWLLQGHVRTHTGEKPFSCP FP 5 Homo sapiens (Human)
Q9GZV5 WWTR1
WWTR1_HUMAN
61 67 EPDSGSHSRQSSTDSSGGHP TP 3 Homo sapiens (Human)
2 
Q9GZV5 WWTR1
WWTR1_HUMAN
84 90 LAGGAQHVRSHSSPASLQLG TP 4 Homo sapiens (Human)
2 
Q9GZV5 WWTR1
WWTR1_HUMAN
112 118 PAQQHAHLRQQSYDVTDELP TP 3 Homo sapiens (Human)
2 
Q9GZV5 WWTR1
WWTR1_HUMAN
306 312 LNGGPYHSREQSTDSGLGLG TP 3 Homo sapiens (Human)
2 
Q96KQ4 PPP1R13B
ASPP1_HUMAN
378 384 IASNAAHGRSKSANDGNWPT TP 2 Homo sapiens (Human)
2 
Q45VV3 yki
YORKI_DROME
163 169 SRLAIHHSRARSSPASLQQN TP 2 Drosophila melanogaster (Fruit fly)
2 
P21192 ACE2
ACE2_YEAST
117 123 KKSMSSHKRGLSGTAIFGFL TP 5 Saccharomyces cerevisiae S288c
2 
P21192 ACE2
ACE2_YEAST
132 138 IFGFLGHNKTLSISSLQQSI TP 4 Saccharomyces cerevisiae S288c
2 
Q59U10 BCR1
BCR1_CANAL
186 192 SEHLARHKRKHTGERPFTCP FP 4 Candida albicans SC5314
Q59U10 BCR1
BCR1_CANAL
551 557 YQQNSFHQRQSSVVSDFSIF TP 4 Candida albicans SC5314
P24276 SSD1
SSD1_YEAST
37 43 KQIHVAHRRSQSELTNLMIE TP 2 Saccharomyces cerevisiae S288c
2 
P24276 SSD1
SSD1_YEAST
121 127 GSRSRTHSRNNSGYYHNSYD TP 2 Saccharomyces cerevisiae S288c
2 
P24276 SSD1
SSD1_YEAST
147 153 NPGSNSHRKTSSQSSIYGHS TP 2 Saccharomyces cerevisiae S288c
2 
P24276 SSD1
SSD1_YEAST
159 165 QSSIYGHSRRHSLGLNEAKK TP 2 Saccharomyces cerevisiae S288c
2 
P24276 SSD1
SSD1_YEAST
223 229 PNAHQGHRRATSNLSPPSFK TP 2 Saccharomyces cerevisiae S288c
2 
P24276 SSD1
SSD1_YEAST
256 262 IATSSTHRRSKTRNNEYSPG TP 2 Saccharomyces cerevisiae S288c
2 
Q96J02 ITCH
ITCH_HUMAN
80 86 TPVSKLHFRVWSHQTLKSDV FP 1 Homo sapiens (Human)
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