dbPTM

DAPK1_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	DAPK1_HUMAN
UniProt AC	P53355
Protein Name	Death-associated protein kinase 1
Gene Name	DAPK1
Organism	Homo sapiens (Human).
Sequence Length	1430
Subcellular Localization	Isoform 1: Cytoplasm. Cytoplasm, cytoskeleton. Colocalizes with MAP1B in the microtubules and cortical actin fibers. Isoform 2: Cytoplasm. Cytoplasm, cytoskeleton.
Protein Description	Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Regulates both type I apoptotic and type II autophagic cell deaths signal, depending on the cellular setting. The former is caspase-dependent, while the latter is caspase-independent and is characterized by the accumulation of autophagic vesicles. Phosphorylates PIN1 resulting in inhibition of its catalytic activity, nuclear localization, and cellular function. Phosphorylates TPM1, enhancing stress fiber formation in endothelial cells. Phosphorylates STX1A and significantly decreases its binding to STXBP1. Phosphorylates PRKD1 and regulates JNK signaling by binding and activating PRKD1 under oxidative stress. Phosphorylates BECN1, reducing its interaction with BCL2 and BCL2L1 and promoting the induction of autophagy. Phosphorylates TSC2, disrupting the TSC1-TSC2 complex and stimulating mTORC1 activity in a growth factor-dependent pathway. Phosphorylates RPS6, MYL9 and DAPK3. Acts as a signaling amplifier of NMDA receptors at extrasynaptic sites for mediating brain damage in stroke. Cerebral ischemia recruits DAPK1 into the NMDA receptor complex and it phosphorylates GRINB at Ser-1303 inducing injurious Ca(2+) influx through NMDA receptor channels, resulting in an irreversible neuronal death. Required together with DAPK3 for phosphorylation of RPL13A upon interferon-gamma activation which is causing RPL13A involvement in transcript-selective translation inhibition.; Isoform 2 cannot induce apoptosis but can induce membrane blebbing..
Protein Sequence	MTVFRQENVDDYYDTGEELGSGQFAVVKKCREKSTGLQYAAKFIKKRRTKSSRRGVSREDIEREVSILKEIQHPNVITLHEVYENKTDVILILELVAGGELFDFLAEKESLTEEEATEFLKQILNGVYYLHSLQIAHFDLKPENIMLLDRNVPKPRIKIIDFGLAHKIDFGNEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANVSAVNYEFEDEYFSNTSALAKDFIRRLLVKDPKKRMTIQDSLQHPWIKPKDTQQALSRKASAVNMEKFKKFAARKKWKQSVRLISLCQRLSRSFLSRSNMSVARSDDTLDEEDSFVMKAIIHAINDDNVPGLQHLLGSLSNYDVNQPNKHGTPPLLIAAGCGNIQILQLLIKRGSRIDVQDKGGSNAVYWAARHGHVDTLKFLSENKCPLDVKDKSGEMALHVAARYGHADVAQLLCSFGSNPNIQDKEEETPLHCAAWHGYYSVAKALCEAGCNVNIKNREGETPLLTASARGYHDIVECLAEHGADLNACDKDGHIALHLAVRRCQMEVIKTLLSQGCFVDYQDRHGNTPLHVACKDGNMPIVVALCEANCNLDISNKYGRTPLHLAANNGILDVVRYLCLMGASVEALTTDGKTAEDLARSEQHEHVAGLLARLRKDTHRGLFIQQLRPTQNLQPRIKLKLFGHSGSGKTTLVESLKCGLLRSFFRRRRPRLSSTNSSRFPPSPLASKPTVSVSINNLYPGCENVSVRSRSMMFEPGLTKGMLEVFVAPTHHPHCSADDQSTKAIDIQNAYLNGVGDFSVWEFSGNPVYFCCYDYFAANDPTSIHVVVFSLEEPYEIQLNQVIFWLSFLKSLVPVEEPIAFGGKLKNPLQVVLVATHADIMNVPRPAGGEFGYDKDTSLLKEIRNRFGNDLHISNKLFVLDAGASGSKDMKVLRNHLQEIRSQIVSVCPPMTHLCEKIISTLPSWRKLNGPNQLMSLQQFVYDVQDQLNPLASEEDLRRIAQQLHSTGEINIMQSETVQDVLLLDPRWLCTNVLGKLLSVETPRALHHYRGRYTVEDIQRLVPDSDVEELLQILDAMDICARDLSSGTMVDVPALIKTDNLHRSWADEEDEVMVYGGVRIVPVEHLTPFPCGIFHKVQVNLCRWIHQQSTEGDADIRLWVNGCKLANRGAELLVLLVNHGQGIEVQVRGLETEKIKCCLLLDSVCSTIENVMATTLPGLLTVKHYLSPQQLREHHEPVMIYQPRDFFRAQTLKETSLTNTMGGYKESFSSIMCFGCHDVYSQASLGMDIHASDLNLLTRRKLSRLLDPPDPLGKDWCLLAMNLGLPDLVAKYNTSNGAPKDFLPSPLHALLREWTTYPESTVGTLMSKLRELGRRDAADFLLKASSVFKINLDGNGQEAYASSCNSGTSYNSISSVVSR

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Phosphorylation	------MTVFRQENV ------CCCCCCCCC	39.39	24719451
12	Phosphorylation	RQENVDDYYDTGEEL CCCCCCCCCCCCCCC	9.97	22817900
13	Phosphorylation	QENVDDYYDTGEELG CCCCCCCCCCCCCCC	17.64	22817900
15	Phosphorylation	NVDDYYDTGEELGSG CCCCCCCCCCCCCCC	30.30	-
39	Phosphorylation	EKSTGLQYAAKFIKK HHCHHHHHHHHHHHH	17.36	-
57	Phosphorylation	KSSRRGVSREDIERE CCCCCCCCHHHHHHH	32.54	-
66	Phosphorylation	EDIEREVSILKEIQH HHHHHHHHHHHHCCC	19.90	24719451
112	Phosphorylation	LAEKESLTEEEATEF HHHHCCCCHHHHHHH	51.10	-
180	Phosphorylation	EFKNIFGTPEFVAPE HHHHHHCCCCCCCCC	14.64	15611134
289	Phosphorylation	QALSRKASAVNMEKF HHHHHHHHHCCHHHH	35.47	26657352
295	Acetylation	ASAVNMEKFKKFAAR HHHCCHHHHHHHHHH	52.28	7481375
297	Acetylation	AVNMEKFKKFAARKK HCCHHHHHHHHHHHH	59.03	7481385
306	Ubiquitination	FAARKKWKQSVRLIS HHHHHHHHHHHHHHH	41.39	-
306 (in isoform 3)	Ubiquitination	-	41.39	-
306	Ubiquitination	FAARKKWKQSVRLIS HHHHHHHHHHHHHHH	41.39	-
308	Phosphorylation	ARKKWKQSVRLISLC HHHHHHHHHHHHHHH	12.89	17056602
313	Phosphorylation	KQSVRLISLCQRLSR HHHHHHHHHHHHHHH	27.90	24117733
319	Phosphorylation	ISLCQRLSRSFLSRS HHHHHHHHHHHHHCC	28.24	23403867
321	Phosphorylation	LCQRLSRSFLSRSNM HHHHHHHHHHHCCCC	27.45	22617229
324	Phosphorylation	RLSRSFLSRSNMSVA HHHHHHHHCCCCCCC	31.49	21406692
326	Phosphorylation	SRSFLSRSNMSVARS HHHHHHCCCCCCCCC	33.24	27422710
329	Phosphorylation	FLSRSNMSVARSDDT HHHCCCCCCCCCCCC	19.51	21406692
333	Phosphorylation	SNMSVARSDDTLDEE CCCCCCCCCCCCCHH	30.05	27499020
336	Phosphorylation	SVARSDDTLDEEDSF CCCCCCCCCCHHHHH	40.89	23403867
342	Phosphorylation	DTLDEEDSFVMKAII CCCCHHHHHHHHHHH	24.03	30108239
366	Phosphorylation	GLQHLLGSLSNYDVN CHHHHHHHHCCCCCC	28.70	26657352
368	Phosphorylation	QHLLGSLSNYDVNQP HHHHHHHCCCCCCCC	34.73	28348404
410	Ubiquitination	SRIDVQDKGGSNAVY CCEEEECCCCCCHHH	48.34	-
435	Ubiquitination	LKFLSENKCPLDVKD HHHHCCCCCCCCCCC	32.93	-
490	Phosphorylation	HCAAWHGYYSVAKAL CHHHHHHHHHHHHHH	4.62	17803936
491	Phosphorylation	CAAWHGYYSVAKALC HHHHHHHHHHHHHHH	10.97	17803936
606	Phosphorylation	ANCNLDISNKYGRTP CCCCCCCCCCCCCCH	27.25	-
609	Phosphorylation	NLDISNKYGRTPLHL CCCCCCCCCCCHHHH	18.98	26434776
612	Phosphorylation	ISNKYGRTPLHLAAN CCCCCCCCHHHHHHC	26.32	26434776
628	Phosphorylation	GILDVVRYLCLMGAS CHHHHHHHHHHCCCC	7.08	26434776
635	Phosphorylation	YLCLMGASVEALTTD HHHHCCCCCHHHCCC	18.11	26434776
640	Phosphorylation	GASVEALTTDGKTAE CCCCHHHCCCCCCHH	29.86	26434776
641	Phosphorylation	ASVEALTTDGKTAED CCCHHHCCCCCCHHH	43.54	26434776
691	Ubiquitination	LQPRIKLKLFGHSGS CCCCEEEEEECCCCC	36.45	-
696	Phosphorylation	KLKLFGHSGSGKTTL EEEEECCCCCCCCHH	34.73	25003641
698	Phosphorylation	KLFGHSGSGKTTLVE EEECCCCCCCCHHHH	39.88	23401153
714	Phosphorylation	LKCGLLRSFFRRRRP HHHHHHHHHHHHCCC	28.80	24719451
724	Phosphorylation	RRRRPRLSSTNSSRF HHCCCCCCCCCCCCC	36.07	-
725	Phosphorylation	RRRPRLSSTNSSRFP HCCCCCCCCCCCCCC	35.88	-
728	Phosphorylation	PRLSSTNSSRFPPSP CCCCCCCCCCCCCCC	23.99	28509920
734	Phosphorylation	NSSRFPPSPLASKPT CCCCCCCCCCCCCCE	32.55	15616583
736	Phosphorylation	SRFPPSPLASKPTVS CCCCCCCCCCCCEEE	11.17	15616583
745	Phosphorylation	SKPTVSVSINNLYPG CCCEEEEEECCCCCC	16.46	24114839
750	Phosphorylation	SVSINNLYPGCENVS EEEECCCCCCCCCEE	10.33	24114839
757	Phosphorylation	YPGCENVSVRSRSMM CCCCCCEEECCCCHH	24.32	24114839
762	Phosphorylation	NVSVRSRSMMFEPGL CEEECCCCHHCCCCC	18.82	28857561
858	Phosphorylation	NQVIFWLSFLKSLVP HHHHHHHHHHHHHCC	21.09	24719451
875	Ubiquitination	EPIAFGGKLKNPLQV CCCCCCCCCCCCCEE	57.58	-
906	Ubiquitination	GGEFGYDKDTSLLKE CCCCCCCCCHHHHHH	55.19	-
909	Phosphorylation	FGYDKDTSLLKEIRN CCCCCCHHHHHHHHH	41.67	24719451
912	Ubiquitination	DKDTSLLKEIRNRFG CCCHHHHHHHHHHHC	57.28	-
939	Ubiquitination	DAGASGSKDMKVLRN ECCCCCCHHHHHHHH	66.42	-
975	Phosphorylation	KIISTLPSWRKLNGP HHHHHCCHHHHCCCH	42.50	26091039
1050	Phosphorylation	NVLGKLLSVETPRAL HHHHHHHCCCCHHHH	28.48	23403867
1053	Phosphorylation	GKLLSVETPRALHHY HHHHCCCCHHHHCCC	18.87	28857561
1060	Phosphorylation	TPRALHHYRGRYTVE CHHHHCCCCCCCCHH	12.19	-
1115	Phosphorylation	KTDNLHRSWADEEDE ECCCCCCCCCCCCCC	18.83	22210691
1266	Phosphorylation	RAQTLKETSLTNTMG HCCCCCCCCCCCCCC	27.70	-
1267	Phosphorylation	AQTLKETSLTNTMGG CCCCCCCCCCCCCCC	34.00	-
1269	Phosphorylation	TLKETSLTNTMGGYK CCCCCCCCCCCCCCH	28.54	-
1421	Phosphorylation	SCNSGTSYNSISSVV HCCCCCCCCCCHHHC	16.87	25332170
1425	Phosphorylation	GTSYNSISSVVSR-- CCCCCCCHHHCCC--	19.53	25332170

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
289	S	Phosphorylation	Kinase	DAPK1	P53355	PSP
289	S	Phosphorylation	Kinase	P90RSK	Q15418	PSP
289	S	Phosphorylation	Kinase	KS6A3	P51812	PhosphoELM
289	S	Phosphorylation	Kinase	ERK-SUBFAMILY	-	GPS
289	S	Phosphorylation	Kinase	RSK-SUBFAMILY	-	GPS
289	S	Phosphorylation	Kinase	RSK_GROUP	-	PhosphoELM
308	S	Phosphorylation	Kinase	DAPK1	P53355	PSP
308	S	Phosphorylation	Kinase	DAPK-FAMILY	-	GPS
308	S	Phosphorylation	Kinase	DAPK_GROUP	-	PhosphoELM
313	S	Phosphorylation	Kinase	DAPK1	P53355	GPS
490	Y	Phosphorylation	Kinase	SRC	P12931	PSP
491	Y	Phosphorylation	Kinase	SRC	P12931	PSP
734	S	Phosphorylation	Kinase	ERK2	P28482	PSP
734	S	Phosphorylation	Kinase	MAPK3	P27361	GPS
736	S	Phosphorylation	Kinase	MK01	P28482	PhosphoELM
-	K	Ubiquitination	E3 ubiquitin ligase	MIB1	Q86YT6	PMID:12351649
-	K	Ubiquitination	E3 ubiquitin ligase	KLHL20	Q9Y2M5	PMID:20389280
-	K	Ubiquitination	E3 ubiquitin ligase	STUB1	Q9UNE7	PMID:17324930

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
289	S	Phosphorylation	16213824
In response to mitogenic stimulation (PMA or EGF), phosphorylated at Ser-289; phosphorylation suppresses DAPK1 pro-apoptotic function.
308	S	Phosphorylation	11579085
Autophosphorylation at Ser-308 inhibits its catalytic activity.
308	S	Phosphorylation	11579085
Endoplasmic-stress can cause dephosphorylation at Ser-308.
734	S	Phosphorylation	15616583
Phosphorylation at Ser-734 by MAPK1 increases its catalytic activity and promotes cytoplasmic retention of MAPK1.

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 DAPK1_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
P53_HUMAN	TP53	physical	17339337
HS90A_HUMAN	HSP90AA1	physical	17324930
F10A1_HUMAN	ST13	physical	17324930
CCDB1_HUMAN	CCNDBP1	physical	17324930
KLH20_HUMAN	KLHL20	physical	20389280
CUL3_HUMAN	CUL3	physical	20389280
DAPK1_HUMAN	DAPK1	physical	19712061
LRRK2_HUMAN	LRRK2	physical	19712061
LRRK1_HUMAN	LRRK1	physical	19712061
DAPK1_HUMAN	DAPK1	physical	20103772
MK03_HUMAN	MAPK3	physical	15616583
MK01_HUMAN	MAPK1	physical	15616583
ML12B_HUMAN	MYL12B	physical	15616583
DAPK1_HUMAN	DAPK1	physical	19180116
BECN1_HUMAN	BECN1	physical	19180116
MIB1_MOUSE	Mib1	physical	12351649
2ABD_HUMAN	PPP2R2D	physical	20220139
2A5A_HUMAN	PPP2R5A	physical	20220139
DAPK1_HUMAN	DAPK1	physical	20220139
ACTC_HUMAN	ACTC1	physical	25852190
TTLL3_HUMAN	TTLL3	physical	25852190
BAG2_HUMAN	BAG2	physical	25852190
CAZA2_HUMAN	CAPZA2	physical	25852190
CAPZB_HUMAN	CAPZB	physical	25852190
COR1C_HUMAN	CORO1C	physical	25852190
DDX5_HUMAN	DDX5	physical	25852190
EF2_HUMAN	EEF2	physical	25852190
GILT_HUMAN	IFI30	physical	25852190
MYO1B_HUMAN	MYO1B	physical	25852190
MYO1D_HUMAN	MYO1D	physical	25852190
SVIL_HUMAN	SVIL	physical	25852190
TMOD3_HUMAN	TMOD3	physical	25852190
TPM3_HUMAN	TPM3	physical	25852190
TWF1_HUMAN	TWF1	physical	25852190
TSC2_HUMAN	TSC2	physical	21134130
UNC5A_HUMAN	UNC5A	physical	15729359
UNC5B_HUMAN	UNC5B	physical	15729359
UNC5C_HUMAN	UNC5C	physical	15729359

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 DAPK1_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Control of death-associated protein kinase (DAPK) activity byphosphorylation and proteasomal degradation."; Jin Y., Blue E.K., Gallagher P.J.; J. Biol. Chem. 281:39033-39040(2006). Cited for: ALTERNATIVE SPLICING (ISOFORM 3), AUTOPHOSPHORYLATION AT SER-308,DEPHOSPHORYLATION, AND ENZYME REGULATION.	17056602 [Abstract]
"The dependence receptor UNC5H2 mediates apoptosis through DAP-kinase."; Llambi F., Lourenco F.C., Gozuacik D., Guix C., Pays L., Del Rio G.,Kimchi A., Mehlen P.; EMBO J. 24:1192-1201(2005). Cited for: AUTOPHOSPHORYLATION AT SER-308, ENZYME REGULATION, AND INTERACTIONWITH UNC5B.	15729359 [Abstract]
"Bidirectional signals transduced by DAPK-ERK interaction promote theapoptotic effect of DAPK."; Chen C.H., Wang W.J., Kuo J.C., Tsai H.C., Lin J.R., Chang Z.F.,Chen R.H.; EMBO J. 24:294-304(2005). Cited for: PHOSPHORYLATION AT SER-734, AND INTERACTION WITH MAPK1 AND MAPK3.	15616583 [Abstract]
"The tumor suppressor DAP kinase is a target of RSK-mediated survivalsignaling."; Anjum R., Roux P.P., Ballif B.A., Gygi S.P., Blenis J.; Curr. Biol. 15:1762-1767(2005). Cited for: PHOSPHORYLATION AT SER-289.	16213824 [Abstract]
"The pro-apoptotic function of death-associated protein kinase iscontrolled by a unique inhibitory autophosphorylation-basedmechanism."; Shohat G., Spivak-Kroizman T., Cohen O., Bialik S., Shani G.,Berissi H., Eisenstein M., Kimchi A.; J. Biol. Chem. 276:47460-47467(2001). Cited for: FUNCTION, ENZYME REGULATION, MUTAGENESIS OF LYS-42; SER-308 ANDSER-313, AND PHOSPHORYLATION AT SER-308.	11579085 [Abstract]

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