dbPTM

DAPK3_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	DAPK3_HUMAN
UniProt AC	O43293
Protein Name	Death-associated protein kinase 3
Gene Name	DAPK3
Organism	Homo sapiens (Human).
Sequence Length	454
Subcellular Localization	Nucleus . Cytoplasm . Predominantly localizes to the cytoplasm but can shuttle between the nucleus and cytoplasm cytoplasmic localization is promoted by phosphorylation at Thr-299 and involves Rho/Rock signaling. Isoform 1: Nucleus . Cytoplasm . I
Protein Description	Serine/threonine kinase which is involved in the regulation of apoptosis, autophagy, transcription, translation and actin cytoskeleton reorganization. Involved in the regulation of smooth muscle contraction. Regulates both type I (caspase-dependent) apoptotic and type II (caspase-independent) autophagic cell deaths signal, depending on the cellular setting. Involved in regulation of starvation-induced autophagy. Regulates myosin phosphorylation in both smooth muscle and non-muscle cells. In smooth muscle, regulates myosin either directly by phosphorylating MYL12B and MYL9 or through inhibition of smooth muscle myosin phosphatase (SMPP1M) via phosphorylation of PPP1R12A; the inhibition of SMPP1M functions to enhance muscle responsiveness to Ca(2+) and promote a contractile state. Phosphorylates MYL12B in non-muscle cells leading to reorganization of actin cytoskeleton. Isoform 2 can phosphorylate myosin, PPP1R12A and MYL12B. Overexpression leads to condensation of actin stress fibers into thick bundles. Involved in actin filament focal adhesion dynamics. The function in both reorganization of actin cytoskeleton and focal adhesion dissolution is modulated by RhoD. Positively regulates canonical Wnt/beta-catenin signaling through interaction with NLK and TCF7L2. Phosphorylates RPL13A on 'Ser-77' upon interferon-gamma activation which is causing RPL13A release from the ribosome, RPL13A association with the GAIT complex and its subsequent involvement in transcript-selective translation inhibition. Enhances transcription from AR-responsive promoters in a hormone- and kinase-dependent manner. Involved in regulation of cell cycle progression and cell proliferation. May be a tumor suppressor..
Protein Sequence	MSTFRQEDVEDHYEMGEELGSGQFAIVRKCRQKGTGKEYAAKFIKKRRLSSSRRGVSREEIEREVNILREIRHPNIITLHDIFENKTDVVLILELVSGGELFDFLAEKESLTEDEATQFLKQILDGVHYLHSKRIAHFDLKPENIMLLDKNVPNPRIKLIDFGIAHKIEAGNEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGETKQETLTNISAVNYDFDEEYFSNTSELAKDFIRRLLVKDPKRRMTIAQSLEHSWIKAIRRRNVRGEDSGRKPERRRLKTTRLKEYTIKSHSSLPPNNSYADFERFSKVLEEAAAAEEGLRELQRSRRLCHEDVEALAAIYEEKEAWYREESDSLGQDLRRLRQELLKTEALKRQAQEEAKGALLGTSGLKRRFSRLENRYEALAKQVASEMRFVQDLVRALEQEKLQGVECGLR

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
37	Methylation	CRQKGTGKEYAAKFI HHHCCCCHHHHHHHH	47.60	-
39	Phosphorylation	QKGTGKEYAAKFIKK HCCCCHHHHHHHHHH	18.49	-
50	Phosphorylation	FIKKRRLSSSRRGVS HHHHHCCCCCCCCCC	25.18	18239682
110	Phosphorylation	DFLAEKESLTEDEAT HHHHHHHCCCHHHHH	52.22	21406692
112	Phosphorylation	LAEKESLTEDEATQF HHHHHCCCHHHHHHH	51.15	21406692
117	Phosphorylation	SLTEDEATQFLKQIL CCCHHHHHHHHHHHH	20.15	21406692
121	Ubiquitination	DEATQFLKQILDGVH HHHHHHHHHHHHHHH	36.26	-
133	Ubiquitination	GVHYLHSKRIAHFDL HHHHHHHCCEEECCC	36.76	-
141	Ubiquitination	RIAHFDLKPENIMLL CEEECCCCHHHEEEE	52.72	-
150	Ubiquitination	ENIMLLDKNVPNPRI HHEEEECCCCCCCCE	60.87	-
167	Ubiquitination	IDFGIAHKIEAGNEF EEHHHHHEECCCCCH	32.97	21906983
180	Phosphorylation	EFKNIFGTPEFVAPE CHHHCCCCCCCCCCC	14.64	15611134
225	Phosphorylation	LGETKQETLTNISAV CCCCCCHHHHHCEEE	36.07	15611134
265	Phosphorylation	KDPKRRMTIAQSLEH CCHHHCCCHHHHHHH	16.02	18239682
276	Ubiquitination	SLEHSWIKAIRRRNV HHHHHHHHHHHHCCC	31.35	-
299	Phosphorylation	PERRRLKTTRLKEYT CCHHHCCCCCCCEEE	23.03	15611134
300	Phosphorylation	ERRRLKTTRLKEYTI CHHHCCCCCCCEEEC	32.20	26074081
303	Ubiquitination	RLKTTRLKEYTIKSH HCCCCCCCEEECCCC	45.44	-
305	Phosphorylation	KTTRLKEYTIKSHSS CCCCCCEEECCCCCC	16.51	28152594
306	Phosphorylation	TTRLKEYTIKSHSSL CCCCCEEECCCCCCC	24.03	28152594
308	Ubiquitination	RLKEYTIKSHSSLPP CCCEEECCCCCCCCC	34.02	-
309	Phosphorylation	LKEYTIKSHSSLPPN CCEEECCCCCCCCCC	25.42	23927012
311	Phosphorylation	EYTIKSHSSLPPNNS EEECCCCCCCCCCCC	40.43	23927012
312	Phosphorylation	YTIKSHSSLPPNNSY EECCCCCCCCCCCCH	39.20	23927012
318	Phosphorylation	SSLPPNNSYADFERF CCCCCCCCHHHHHHH	28.47	23403867
319	Phosphorylation	SLPPNNSYADFERFS CCCCCCCHHHHHHHH	16.59	23403867
326	Phosphorylation	YADFERFSKVLEEAA HHHHHHHHHHHHHHH	28.24	15611134
327	Ubiquitination	ADFERFSKVLEEAAA HHHHHHHHHHHHHHH	48.40	21906983
363	Ubiquitination	LAAIYEEKEAWYREE HHHHHHHHHHHHHHC	40.57	-
387	Ubiquitination	RLRQELLKTEALKRQ HHHHHHHHHHHHHHH	57.87	-
388	Phosphorylation	LRQELLKTEALKRQA HHHHHHHHHHHHHHH	26.85	-
400	Ubiquitination	RQAQEEAKGALLGTS HHHHHHHHHHHHCCH	48.25	-
406	Phosphorylation	AKGALLGTSGLKRRF HHHHHHCCHHHHHHH	21.42	28555341
407	Phosphorylation	KGALLGTSGLKRRFS HHHHHCCHHHHHHHH	40.09	25159151
410	Ubiquitination	LLGTSGLKRRFSRLE HHCCHHHHHHHHHHH	45.08	-
414	Phosphorylation	SGLKRRFSRLENRYE HHHHHHHHHHHHHHH	33.86	29214152
425	Ubiquitination	NRYEALAKQVASEMR HHHHHHHHHHHHHHH	46.27	21906983
429	Phosphorylation	ALAKQVASEMRFVQD HHHHHHHHHHHHHHH	32.82	28348404
445	Ubiquitination	VRALEQEKLQGVECG HHHHHHHHHCCCCCC	45.89	-
454	Methylation	QGVECGLR------- CCCCCCCC-------	29.76	-

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
50	S	Phosphorylation	Kinase	DAPK2	Q9UIK4	GPS
180	T	Phosphorylation	Kinase	DAPK3	O43293	PSP
225	T	Phosphorylation	Kinase	DAPK3	O43293	PSP
265	T	Phosphorylation	Kinase	ROCK1	Q13464	Uniprot
265	T	Phosphorylation	Kinase	DAPK3	O43293	PSP
265	T	Phosphorylation	Kinase	DAPK2	Q9UIK4	GPS
299	T	Phosphorylation	Kinase	DAPK1	P53355	Uniprot
299	T	Phosphorylation	Kinase	ROCK1	Q13464	Uniprot
299	T	Phosphorylation	Kinase	DAPK3	O43293	PSP
299	T	Phosphorylation	Kinase	DAPK2	Q9UIK4	GPS
306	T	Phosphorylation	Kinase	DAPK2	Q9UIK4	GPS
306	T	Phosphorylation	Kinase	DAPK3	O43293	PSP
309	S	Phosphorylation	Kinase	DAPK1	P53355	Uniprot
311	S	Phosphorylation	Kinase	DAPK3	O43293	PSP
311	S	Phosphorylation	Kinase	DAPK2	Q9UIK4	GPS
311	S	Phosphorylation	Kinase	DAPK1	P53355	Uniprot
312	S	Phosphorylation	Kinase	DAPK1	P53355	Uniprot
318	S	Phosphorylation	Kinase	DAPK1	P53355	Uniprot
326	S	Phosphorylation	Kinase	DAPK1	P53355	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
180	T	Phosphorylation	15611134
Phosphorylation at Thr-180, Thr-225 and Thr-265 is essential for activity.
225	T	Phosphorylation	15611134
Phosphorylation at Thr-180, Thr-225 and Thr-265 is essential for activity.
265	T	Phosphorylation	15611134
Phosphorylation at Thr-180, Thr-225 and Thr-265 is essential for activity.
299	T	Phosphorylation	15367680
The phosphorylated form is localized in the cytoplasm promoted by phosphorylation at Thr-299; nuclear translocation or retention is maximal when it is not phosphorylated.

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 DAPK3_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
DAXX_HUMAN	DAXX	physical	12917339
PAWR_HUMAN	PAWR	physical	12917339
ATF4_MOUSE	Atf4	physical	9488481
GRB14_HUMAN	GRB14	physical	12242277
KPCZ_HUMAN	PRKCZ	physical	12242277
CDN1A_HUMAN	CDKN1A	physical	15001356
DAPK3_HUMAN	DAPK3	physical	15001356
MDM2_HUMAN	MDM2	physical	15001356
P53_HUMAN	TP53	physical	15001356
CHK2_HUMAN	CHEK2	physical	15001356
PAWR_HUMAN	PAWR	physical	15001356
TCP1L_HUMAN	TCP10L	physical	21988832
CU077_HUMAN	TCP10L	physical	21988832
RL34_HUMAN	RPL34	physical	21988832
DAPK3_HUMAN	DAPK3	physical	23146908
ANDR_HUMAN	AR	physical	23146908
MDM2_HUMAN	MDM2	physical	23146908
DAPK3_HUMAN	DAPK3	physical	18082144

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 DAPK3_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Regulation of zipper-interacting protein kinase activity in vitro andin vivo by multisite phosphorylation."; Graves P.R., Winkfield K.M., Haystead T.A.; J. Biol. Chem. 280:9363-9374(2005). Cited for: PHOSPHORYLATION AT THR-180; THR-225; THR-265; THR-299; THR-306 ANDSER-311, AND ENZYME REGULATION.	15611134 [Abstract]
"Activation segment dimerization: a mechanism for kinaseautophosphorylation of non-consensus sites."; Pike A.C., Rellos P., Niesen F.H., Turnbull A., Oliver A.W.,Parker S.A., Turk B.E., Pearl L.H., Knapp S.; EMBO J. 27:704-714(2008). Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 9-289 IN COMPLEX WITHPYRIDONE 6, ENZYME REGULATION, SUBUNIT, AND PHOSPHORYLATION AT SER-50AND THR-265.	18239682 [Abstract]
"Death-associated protein kinase phosphorylates ZIP kinase, forming aunique kinase hierarchy to activate its cell death functions."; Shani G., Marash L., Gozuacik D., Bialik S., Teitelbaum L., Shohat G.,Kimchi A.; Mol. Cell. Biol. 24:8611-8626(2004). Cited for: FUNCTION, PHOSPHORYLATION AT THR-299; SER-309; SER-311; SER-312;SER-318 AND SER-326, INTERACTION WITH DAPK1, AND SUBCELLULAR LOCATION.	15367680 [Abstract]
"Phosphorylation-dependent control of ZIPK nuclear import is speciesspecific."; Weitzel D.H., Chambers J., Haystead T.A.; Cell. Signal. 23:297-303(2011). Cited for: PHOSPHORYLATION AT THR-299, AND SUBCELLULAR LOCATION.	20854903 [Abstract]
"ROCK1 phosphorylates and activates zipper-interacting proteinkinase."; Hagerty L., Weitzel D.H., Chambers J., Fortner C.N., Brush M.H.,Loiselle D., Hosoya H., Haystead T.A.; J. Biol. Chem. 282:4884-4893(2007). Cited for: FUNCTION, ENZYME REGULATION, AUTOPHOSPHORYLATION, PHOSPHORYLATION ATTHR-180; THR-265 AND THR-299, AND MUTAGENESIS OF LYS-42; ASP-161;THR-225; THR-265 AND THR-299.	17158456 [Abstract]
"Phosphorylation of threonine-265 in zipper-interacting protein kinaseplays an important role in its activity and is induced by IL-6 familycytokines."; Sato N., Kamada N., Muromoto R., Kawai T., Sugiyama K., Watanabe T.,Imoto S., Sekine Y., Ohbayashi N., Ishida M., Akira S., Matsuda T.; Immunol. Lett. 103:127-134(2006). Cited for: PHOSPHORYLATION AT THR-265.	16325270 [Abstract]

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