LATS1_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: LATS1_MOUSE
• UniProt AC: Q8BYR2
• Protein Name: Serine/threonine-protein kinase LATS1
• Gene Name: Lats1 {ECO:0000312|EMBL:AAD16883.1}
• Organism: Mus musculus (Mouse).
• Sequence Length: 1129
• Subcellular Localization: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, cytoskeleton, spindle. Localizes to the centrosomes throughout interphase but migrates to the mitotic apparatus, including spindle pole bodies, mitotic spindle, and midbod
• Protein Description: 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..
• Protein Sequence: MKRGEKPEGYRQMRPKTFPASNYPGSSRQMLQEIRESLRNLSKPSDASKAEHNLNKMSTEDPRQVRNPPKFGTHHKALQEIRNSLLPFANETSSSRSPSEVNPQMFQDLQAAGFDEDMVIQALQKTNNRSIEAAVEFISKMSYQDPRREQMSAAAARPINATMKPGNVQHSINRKQSWKGSKESLVPQRHGPSLGENVVYRSESPNSQADVGRPLSGSGIAAFAQAHPSNGQRVNPPPPPQVRSVTPPPPPRGQTPPPRGTTPPPPSWEPSSQTKRYSGNMEYVISRISPVPPGAWQEGYPPPPLTTSPMNPPSQAQRAISSVPVGRQPIIMQSTSKFNFTPGRPGVQNGGGQSDFIVHQNVPTGSVTRQPPPPYPLTPANGQSPSALQTGASAAPPSFANGNVPQSMMVPNRNSHNMELYNINVPGLQTAWPQSSSAPAQSSPSGGHEIPTWQPNIPVRSNSFNNPLGSRASHSANSQPSATTVTAITPAPIQQPVKSMRVLKPELQTALAPTHPSWMPQPVQTVQPTPFSEGTASSVPVIPPVAEAPSYQGPPPPYPKHLLHQNPSVPPYESVSKPCKDEQPSLPKEDDSEKSADSGDSGDKEKKQITTSPITVRKNKKDEERRESRIQSYSPQAFKFFMEQHVENVLKSHQQRLHRKKQLENEMMRVGLSQDAQDQMRKMLCQKESNYIRLKRAKMDKSMFVKIKTLGIGAFGEVCLARKVDTKALYATKTLRKKDVLLRNQVAHVKAERDILAEADNEWVVRLYYSFQDKDNLYFVMDYIPGGDMMSLLIRMGIFPENLARFYIAELTCAVESVHKMGFIHRDIKPDNILIDRDGHIKLTDFGLCTGFRWTHDSKYYQSGDHPRQDSMDFSNEWGDPSNCRCGDRLKPLERRAARQHQRCLAHSLVGTPNYIAPEVLLRTGYTQLCDWWSVGVILFEMLVGQPPFLAQTPLETQMKVINWQTSLHIPPQAKLSPEASDLIIKLCRGPEDRLGKNGADEIKAHPFFKTIDFSSDLRQQSASYIPKITHPTDTSNFDPVDPDKLWSDGSEEENISDTLNGWYKNGKHPEHAFYEFTFRRFFDDNGYPYNYPKPIEYEYIHSQGSEQQSDEDDQHTSSDGNNRDLVYV

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
17	Phosphorylation	YRQMRPKTFPASNYP CCCCCCCCCCCCCCC	37.22	25619855
21	Phosphorylation	RPKTFPASNYPGSSR CCCCCCCCCCCCCHH	36.81	25619855
23	Phosphorylation	KTFPASNYPGSSRQM CCCCCCCCCCCHHHH	13.38	25619855
26	Phosphorylation	PASNYPGSSRQMLQE CCCCCCCCHHHHHHH	20.17	25619855
27	Phosphorylation	ASNYPGSSRQMLQEI CCCCCCCHHHHHHHH	32.23	25619855
37	Phosphorylation	MLQEIRESLRNLSKP HHHHHHHHHHHCCCC	23.84	-
48	Phosphorylation	LSKPSDASKAEHNLN CCCCCHHHHHHHHHH	37.07	29109428
84	Phosphorylation	ALQEIRNSLLPFANE HHHHHHHHHHHHCCC	22.79	26824392
93	Phosphorylation	LPFANETSSSRSPSE HHHCCCCCCCCCHHH	21.82	18779572
171	Phosphorylation	KPGNVQHSINRKQSW CCCCCCCCCCCCCCC	12.41	23375375
177	Phosphorylation	HSINRKQSWKGSKES CCCCCCCCCCCCHHH	33.52	23684622
181	Phosphorylation	RKQSWKGSKESLVPQ CCCCCCCCHHHCCCC	29.53	21743459
184	Phosphorylation	SWKGSKESLVPQRHG CCCCCHHHCCCCCCC	38.10	28066266
202	Phosphorylation	GENVVYRSESPNSQA CCCCEECCCCCCCCC	25.41	23984901
204	Phosphorylation	NVVYRSESPNSQADV CCEECCCCCCCCCCC	30.54	22817900
207	Phosphorylation	YRSESPNSQADVGRP ECCCCCCCCCCCCCC	30.08	21659605
216	Phosphorylation	ADVGRPLSGSGIAAF CCCCCCCCCCHHHHH	33.33	21659605
218	Phosphorylation	VGRPLSGSGIAAFAQ CCCCCCCCHHHHHHH	24.53	19060867
229	Phosphorylation	AFAQAHPSNGQRVNP HHHHCCCCCCCCCCC	43.66	25777480
244	Phosphorylation	PPPPQVRSVTPPPPP CCCCCCCCCCCCCCC	31.33	28066266
246	Phosphorylation	PPQVRSVTPPPPPRG CCCCCCCCCCCCCCC	31.18	26824392
255	Phosphorylation	PPPPRGQTPPPRGTT CCCCCCCCCCCCCCC	40.35	25263469
261	Phosphorylation	QTPPPRGTTPPPPSW CCCCCCCCCCCCCCC	37.09	25619855
262	Phosphorylation	TPPPRGTTPPPPSWE CCCCCCCCCCCCCCC	36.30	25619855
267	Phosphorylation	GTTPPPPSWEPSSQT CCCCCCCCCCCCCCC	50.25	25619855
271	Phosphorylation	PPPSWEPSSQTKRYS CCCCCCCCCCCEECC	24.46	25619855
272	Phosphorylation	PPSWEPSSQTKRYSG CCCCCCCCCCEECCC	53.21	25619855
274	Phosphorylation	SWEPSSQTKRYSGNM CCCCCCCCEECCCCC	21.31	25619855
277	Phosphorylation	PSSQTKRYSGNMEYV CCCCCEECCCCCEEE	23.61	25521595
278	Phosphorylation	SSQTKRYSGNMEYVI CCCCEECCCCCEEEE	27.94	26824392
283	Phosphorylation	RYSGNMEYVISRISP ECCCCCEEEEEEEEC	7.72	28066266
461	Phosphorylation	QPNIPVRSNSFNNPL CCCCCCCCCCCCCCC	36.74	25521595
463	Phosphorylation	NIPVRSNSFNNPLGS CCCCCCCCCCCCCCC	30.51	27087446
470	Phosphorylation	SFNNPLGSRASHSAN CCCCCCCCCCCCCCC	32.15	25619855
610	Phosphorylation	DKEKKQITTSPITVR HHHHCCCCCCCEEEE	20.80	26745281
611	Phosphorylation	KEKKQITTSPITVRK HHHCCCCCCCEEEEC	33.85	23684622
612	Phosphorylation	EKKQITTSPITVRKN HHCCCCCCCEEEECC	12.98	25521595
615	Phosphorylation	QITTSPITVRKNKKD CCCCCCEEEECCCCH	20.03	25521595
673	Phosphorylation	EMMRVGLSQDAQDQM HHHHHCCCHHHHHHH	21.78	-
682	Acetylation	DAQDQMRKMLCQKES HHHHHHHHHHHHHHH	30.77	15620171
908	Phosphorylation	HQRCLAHSLVGTPNY HHHHHHHHCCCCCCC	21.10	23984901
912	Phosphorylation	LAHSLVGTPNYIAPE HHHHCCCCCCCCCHH	10.81	23984901
915	Phosphorylation	SLVGTPNYIAPEVLL HCCCCCCCCCHHHHH	10.32	23984901
1078	Phosphorylation	EHAFYEFTFRRFFDD CCCEEEEEEHHHCCC	12.32	-
1098	Phosphorylation	NYPKPIEYEYIHSQG CCCCCEEEEEECCCC	18.10	23684622
1100	Phosphorylation	PKPIEYEYIHSQGSE CCCEEEEEECCCCCC	11.75	23684622
1106	Phosphorylation	EYIHSQGSEQQSDED EEECCCCCCCCCCCC	25.29	23684622
1110	Phosphorylation	SQGSEQQSDEDDQHT CCCCCCCCCCCCCCC	42.53	23608596

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
463	S	Phosphorylation	Kinase	NUAK1	Q641K5	Uniprot
463	S	Phosphorylation	Kinase	NUAK2	Q8BZN4	Uniprot
908	S	Phosphorylation	Kinase	MST2	Q9JI10	Uniprot
1078	T	Phosphorylation	Kinase	MST2	Q9JI10	Uniprot
-	K	Ubiquitination	E3 ubiquitin ligase	mahj	Q9W2F2	PMID:31170139

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
463	S	Phosphorylation	Phosphorylation at Ser-463 by NUAK1 and NUAK2 leads to decreased protein level and is required to regulate cellular senescence and cellular ploidy (By similarity).	17242355
908	S	Phosphorylation	Phosphorylated by STK3/MST2 at Ser-908 and Thr-1078, which results in its activation (By similarity).	-
1078	T	Phosphorylation	Phosphorylated by STK3/MST2 at Ser-908 and Thr-1078, which results in its activation (By similarity).	-

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of LATS1_MOUSE !!

Protein-Protein Interaction

Oops, there are no PPI records of LATS1_MOUSE !!

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.

Related Literatures of Post-Translational Modification

Phosphorylation

"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).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-246, AND MASSSPECTROMETRY.
PubMed: 19144319