dbPTM

NUAK1_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	NUAK1_HUMAN
UniProt AC	O60285
Protein Name	NUAK family SNF1-like kinase 1
Gene Name	NUAK1
Organism	Homo sapiens (Human).
Sequence Length	661
Subcellular Localization	Nucleus . Cytoplasm .
Protein Description	Serine/threonine-protein kinase involved in various processes such as cell adhesion, regulation of cell ploidy and senescence, cell proliferation and tumor progression. Phosphorylates ATM, CASP6, LATS1, PPP1R12A and p53/TP53. Acts as a regulator of cellular senescence and cellular ploidy by mediating phosphorylation of 'Ser-464' of LATS1, thereby controlling its stability. Controls cell adhesion by regulating activity of the myosin protein phosphatase 1 (PP1) complex. Acts by mediating phosphorylation of PPP1R12A subunit of myosin PP1: phosphorylated PPP1R12A then interacts with 14-3-3, leading to reduced dephosphorylation of myosin MLC2 by myosin PP1. May be involved in DNA damage response: phosphorylates p53/TP53 at 'Ser-15' and 'Ser-392' and is recruited to the CDKN1A/WAF1 promoter to participate to transcription activation by p53/TP53. May also act as a tumor malignancy-associated factor by promoting tumor invasion and metastasis under regulation and phosphorylation by AKT1. Suppresses Fas-induced apoptosis by mediating phosphorylation of CASP6, thereby suppressing the activation of the caspase and the subsequent cleavage of CFLAR. Regulates UV radiation-induced DNA damage response mediated by CDKN1A. In association with STK11, phosphorylates CDKN1A in response to UV radiation and contributes to its degradation which is necessary for optimal DNA repair. [PubMed: 25329316]
Protein Sequence	MEGAAAPVAGDRPDLGLGAPGSPREAVAGATAALEPRKPHGVKRHHHKHNLKHRYELQETLGKGTYGKVKRATERFSGRVVAIKSIRKDKIKDEQDMVHIRREIEIMSSLNHPHIISIYEVFENKDKIVIIMEYASKGELYDYISERRRLSERETRHFFRQIVSAVHYCHKNGVVHRDLKLENILLDDNCNIKIADFGLSNLYQKDKFLQTFCGSPLYASPEIVNGRPYRGPEVDSWALGVLLYTLVYGTMPFDGFDHKNLIRQISSGEYREPTQPSDARGLIRWMLMVNPDRRATIEDIANHWWVNWGYKSSVCDCDALHDSESPLLARIIDWHHRSTGLQADTEAKMKGLAKPTTSEVMLERQRSLKKSKKENDFAQSGQDAVPESPSKLSSKRPKGILKKRSNSEHRSHSTGFIEGVVGPALPSTFKMEQDLCRTGVLLPSSPEAEVPGKLSPKQSATMPKKGILKKTQQRESGYYSSPERSESSELLDSNDVMGSSIPSPSPPDPARVTSHSLSCRRKGILKHSSKYSAGTMDPALVSPEMPTLESLSEPGVPAEGLSRSYSRPSSVISDDSVLSSDSFDLLDLQENRPARQRIRSCVSAENFLQIQDFEGLQNRPRPQYLKRYRNRLADSSFSLLTDMDDVTQVYKQALEICSKLN

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
1	Acetylation	-------MEGAAAPV -------CCCCCCCC	10.93	19369195
22	Phosphorylation	LGLGAPGSPREAVAG CCCCCCCCHHHHHHC	21.52	26329039
134	Phosphorylation	KIVIIMEYASKGELY EEEEEEEECCCCCHH	9.97	29083192
136	Phosphorylation	VIIMEYASKGELYDY EEEEEECCCCCHHHH	40.05	29083192
141	Phosphorylation	YASKGELYDYISERR ECCCCCHHHHHHHHH	11.46	-
143	Phosphorylation	SKGELYDYISERRRL CCCCHHHHHHHHHCC	7.87	-
145	Phosphorylation	GELYDYISERRRLSE CCHHHHHHHHHCCCH	20.87	-
200	Phosphorylation	KIADFGLSNLYQKDK EEECCCHHHHHCCCH	25.76	29523821
203	Phosphorylation	DFGLSNLYQKDKFLQ CCCHHHHHCCCHHHH	20.12	29523821
211	Phosphorylation	QKDKFLQTFCGSPLY CCCHHHHHHCCCCCC	24.04	14976552
266	Phosphorylation	KNLIRQISSGEYREP HHHHHHHHCCCCCCC	24.77	27251275
267	Phosphorylation	NLIRQISSGEYREPT HHHHHHHCCCCCCCC	36.95	27251275
284	Methylation	SDARGLIRWMLMVNP CCHHHHHHHHHHCCC	20.14	24151209
323	Phosphorylation	DCDALHDSESPLLAR CHHHCCCCCCHHHHH	29.26	24076635
325	Phosphorylation	DALHDSESPLLARII HHCCCCCCHHHHHHH	25.46	27251275
356	Phosphorylation	MKGLAKPTTSEVMLE HCCCCCCCHHHHHHH	42.10	-
388	Phosphorylation	GQDAVPESPSKLSSK CCCCCCCCCCHHCCC	28.53	22777824
390	Phosphorylation	DAVPESPSKLSSKRP CCCCCCCCHHCCCCC	56.35	27251275
411	Phosphorylation	RSNSEHRSHSTGFIE CCCCCCCCCCCCCCC	24.56	28450419
413	Phosphorylation	NSEHRSHSTGFIEGV CCCCCCCCCCCCCCC	31.32	28450419
414	Phosphorylation	SEHRSHSTGFIEGVV CCCCCCCCCCCCCCC	30.59	22468782
427	Phosphorylation	VVGPALPSTFKMEQD CCCCCCCCCCCCCCH	47.53	22468782
428	Phosphorylation	VGPALPSTFKMEQDL CCCCCCCCCCCCCHH	25.90	22468782
438	Phosphorylation	MEQDLCRTGVLLPSS CCCHHHHCCCCCCCC	30.55	25072903
444	Phosphorylation	RTGVLLPSSPEAEVP HCCCCCCCCCCCCCC	59.50	30266825
445	Phosphorylation	TGVLLPSSPEAEVPG CCCCCCCCCCCCCCC	25.48	30266825
455	Phosphorylation	AEVPGKLSPKQSATM CCCCCCCCHHHCCCC	33.27	30266825
459	Phosphorylation	GKLSPKQSATMPKKG CCCCHHHCCCCCCCC	31.65	-
461	Phosphorylation	LSPKQSATMPKKGIL CCHHHCCCCCCCCCC	38.97	22798277
476	Phosphorylation	KKTQQRESGYYSSPE HHHHHCCCCCCCCCC	33.99	-
480	Phosphorylation	QRESGYYSSPERSES HCCCCCCCCCCCCCC	30.82	-
481	Phosphorylation	RESGYYSSPERSESS CCCCCCCCCCCCCCC	18.05	25307156
499	Phosphorylation	DSNDVMGSSIPSPSP CCCCCCCCCCCCCCC	13.65	-
505	Phosphorylation	GSSIPSPSPPDPARV CCCCCCCCCCCHHHH	54.10	24076635
516	Phosphorylation	PARVTSHSLSCRRKG HHHHCCCHHHHHHCC	23.03	-
518	Phosphorylation	RVTSHSLSCRRKGIL HHCCCHHHHHHCCHH	14.48	27251275
532	Phosphorylation	LKHSSKYSAGTMDPA HHCCCCCCCCCCCHH	24.78	29523821
535	Phosphorylation	SSKYSAGTMDPALVS CCCCCCCCCCHHHCC	20.37	29523821
542	Phosphorylation	TMDPALVSPEMPTLE CCCHHHCCCCCCCCH	18.92	29523821
547	Phosphorylation	LVSPEMPTLESLSEP HCCCCCCCCHHHCCC	41.68	29523821
550	Phosphorylation	PEMPTLESLSEPGVP CCCCCCHHHCCCCCC	40.06	29523821
562	Phosphorylation	GVPAEGLSRSYSRPS CCCCCCCCCCCCCCC	30.00	20068231
564	Phosphorylation	PAEGLSRSYSRPSSV CCCCCCCCCCCCCCC	24.88	20068231
565	Phosphorylation	AEGLSRSYSRPSSVI CCCCCCCCCCCCCCC	13.95	20068231
566	Phosphorylation	EGLSRSYSRPSSVIS CCCCCCCCCCCCCCC	38.67	21406692
569	Phosphorylation	SRSYSRPSSVISDDS CCCCCCCCCCCCCCC	35.81	27251275
570	Phosphorylation	RSYSRPSSVISDDSV CCCCCCCCCCCCCCC	26.59	27251275
600	Phosphorylation	PARQRIRSCVSAENF HHHHHHHHHHCHHHC	19.25	14976552
603	Phosphorylation	QRIRSCVSAENFLQI HHHHHHHCHHHCHHC	33.90	24501219
635	Phosphorylation	YRNRLADSSFSLLTD HHHHHCCCCCHHCCC	27.89	29523821
636	Phosphorylation	RNRLADSSFSLLTDM HHHHCCCCCHHCCCH	21.28	29523821
638	Phosphorylation	RLADSSFSLLTDMDD HHCCCCCHHCCCHHH	25.15	24719451

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
211	T	Phosphorylation	Kinase	STK38L	Q9Y2H1	GPS
211	T	Phosphorylation	Kinase	STK11	Q15831	PhosphoELM
445	S	Phosphorylation	Kinase	CDK1	P06493	PSP
476	S	Phosphorylation	Kinase	PLK1	P53350	PSP
480	S	Phosphorylation	Kinase	PLK1	P53350	PSP
600	S	Phosphorylation	Kinase	AKT1	P31749	Uniprot
600	S	Phosphorylation	Kinase	AKT-FAMILY	-	GPS
600	S	Phosphorylation	Kinase	PKB_GROUP	-	PhosphoELM

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
29	K	Phosphorylation	18254724
Ubiquitinated with 'Lys-29'- and 'Lys-33'-linked polyubiquitins which appear to impede LKB1-mediated phosphorylation.
29	K	ubiquitylation	18254724
Ubiquitinated with 'Lys-29'- and 'Lys-33'-linked polyubiquitins which appear to impede LKB1-mediated phosphorylation.
211	T	Phosphorylation	14976552
Phosphorylated at Thr-211 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39.

Disease-associated PTM Sites based on SAP

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

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of NUAK1_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
KPRA_HUMAN	PRPSAP1	physical	17353931
K2C1B_HUMAN	KRT77	physical	17353931
S10A8_HUMAN	S100A8	physical	17353931
KAP0_HUMAN	PRKAR1A	physical	17353931
S10A9_HUMAN	S100A9	physical	17353931
USP9X_HUMAN	USP9X	physical	18254724
A4_HUMAN	APP	physical	21832049
LATS1_HUMAN	LATS1	physical	19927127
USP9X_HUMAN	USP9X	physical	24785407
MYPT1_HUMAN	PPP1R12A	physical	24785407
MYPT2_HUMAN	PPP1R12B	physical	24785407
PP12C_HUMAN	PPP1R12C	physical	24785407
PP1B_HUMAN	PPP1CB	physical	24785407
SKP1_HUMAN	SKP1	physical	24785407
FBW1A_HUMAN	BTRC	physical	24785407
FBW1B_HUMAN	FBXW11	physical	24785407
CUL1_HUMAN	CUL1	physical	24785407
PLK1_HUMAN	PLK1	physical	24785407
SRRM2_HUMAN	SRRM2	physical	25852190
FBW1A_HUMAN	BTRC	physical	28514442
FBW1B_HUMAN	FBXW11	physical	28514442

Drug and Disease Associations

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

Regulatory Network of NUAK1_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Large-scale proteomics analysis of the human kinome."; Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,Mann M., Daub H.; Mol. Cell. Proteomics 8:1751-1764(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-22; THR-211; SER-388;SER-444; SER-445 AND SER-455, AND MASS SPECTROMETRY.	19369195 [Abstract]
"Identification of a novel protein kinase mediating Akt survivalsignaling to the ATM protein."; Suzuki A., Kusakai G., Kishimoto A., Lu J., Ogura T., Lavin M.F.,Esumi H.; J. Biol. Chem. 278:48-53(2003). Cited for: FUNCTION, INTERACTION WITH PKB, PHOSPHORYLATION AT SER-600 BY PKB, ANDMUTAGENESIS OF SER-600.	12409306 [Abstract]
"New roles for the LKB1-NUAK pathway in controlling myosin phosphatasecomplexes and cell adhesion."; Zagorska A., Deak M., Campbell D.G., Banerjee S., Hirano M.,Aizawa S., Prescott A.R., Alessi D.R.; Sci. Signal. 3:RA25-RA25(2010). Cited for: FUNCTION, INTERACTION WITH PPP1CB, DOMAIN GILK, MUTAGENESIS OF400-ILE-LEU-401, AND PHOSPHORYLATION AT THR-211.	20354225 [Abstract]
"LKB1 is a master kinase that activates 13 kinases of the AMPKsubfamily, including MARK/PAR-1."; Lizcano J.M., Goeransson O., Toth R., Deak M., Morrice N.A.,Boudeau J., Hawley S.A., Udd L., Maekelae T.P., Hardie D.G.,Alessi D.R.; EMBO J. 23:833-843(2004). Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ENZYME REGULATION,PHOSPHORYLATION AT THR-211, AND MUTAGENESIS OF THR-211.	14976552 [Abstract]

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