dbPTM

DAPK1_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	DAPK1_MOUSE
UniProt AC	Q80YE7
Protein Name	Death-associated protein kinase 1
Gene Name	Dapk1
Organism	Mus musculus (Mouse).
Sequence Length	1442
Subcellular Localization
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 (By similarity). 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..
Protein Sequence	MTVFRQENVDDYYDTGEELGSGQFAVVKKCREKSTGLQYAAKFIKKRRTKSSRRGVSREDIEREVSILKEIRHPNVITLHEVYENKTDVILILELVAGGELFDFLAEKESLTEEEATEFLKQILSGVYYLHSLQIAHFDLKPENIMLLDRNVPKPRIKIIDFGLAHKIDFGNEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANVSAVNYDFEEEFFRNTSTLAKDFIRRLLVKDPKKRMTIQDSLQHPWIKPKDTQQALSRKASAVNMEKFKKFAARKKWKQSVRLISLCQRLSRSFLSRSNMSVARSDDTLDEEDSFVMKAIIHAINDDNVPGLQHLLGSLSSYDVNQPNKHGTPPLLIAAGCGNIQMLQLLIKRGSRIDVQDKGGSNAIYWASRHGHVDTLKFLNENKCPLDVKDKSGETALHVAARYGHADVVQLLCSFGSNPDFQDKEEETPLHCAAWHGYYSVAKALCEVGCNVNIKNREGETPLLTASARGYHDIVECLAEHGADLNASDKDGHIALHLAVRRCQMEVIKTLLGHGSFVDFQDRHGNTPLHVACKDGSAPIVVALCEASCNLDISNKYGRTPLHLAANNGILDVVRYLCLMGANVEALTSDGKTAEDLAKAEQHEHVAGLLARLRKDTHRGLFIQQLRPTQNLQPRIKLKLFGHSGSGKSTLVESLKCGLLRSFFRRRRPRLSSTNSTRFPPSPLAAKPTVSVSINNLYPGCENVSVRSRSMMFEPGLTKGMLEVFVAPSHHLHCSTDDQSTKAIDIQNAYLNGVGDFSVWEFSGNPVYFCCYDYFAANDPTSIHIIVFSLEEPYEIQLNQVIFWLSFLKSLVPVEEPIAFGGKLKNPLRVVLVATHADIMNIPRPAGGEFGYDKDTSLLKEIRNRFGNDLHVSNKLFVLDAGASGSKDIKVLRNHLQEIRSQIVSGCSPMTHLCEKIISTLPSWRKLNGPNQLMSLQQFVYDVQDQLNPLASEDDLRRIAQQLHSTGEINIMQSETVQDVLLLDPRWLCTNVLGKLLSVETPRALHHYRGRYTMEDIQRLVPDSDVEELLQILDAMDICARDLSSGTMVDIPALIKTDSLQRSWADEEDEVMVYGGVRIVPVEHLTPFPCGIFHKVQVNLCRWIHQQSAEGDADIRLWVSGCRIANRGAELLVLLVNHGQGIEVQVRGLETEKIKCCLLLDSVCSTIETVMATTLPGLLTVKHYLSPQQLREHHEPVMVYQPRDFFRAQTLKESSLTNTMGGYKESFSSITCFGCHDVYSQASLGMDIHASDLSLLTRRKLSRLLDPPDPMGKDWCLLAMNLGLPDMVAKHNVNNRASRDFLPSPVHALLQEWTSYPESTVGILISKLRELGRRDAADFLLKASSVFKINLDGNGQEAYASSCNSGTSYNSISSVVSRRDSHAWTPLYDL

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
285	Phosphorylation	KDTQQALSRKASAVN HHHHHHHHHHHHHCC	34.45	20531401
289	Phosphorylation	QALSRKASAVNMEKF HHHHHHHHHCCHHHH	35.47	22324799
308	Phosphorylation	ARKKWKQSVRLISLC HHHHHHHHHHHHHHH	12.89	18806755
313	Phosphorylation	KQSVRLISLCQRLSR HHHHHHHHHHHHHHH	27.90	23737553
319	Phosphorylation	ISLCQRLSRSFLSRS HHHHHHHHHHHHHCC	28.24	26824392
321	Phosphorylation	LCQRLSRSFLSRSNM HHHHHHHHHHHCCCC	27.45	23737553
324	Phosphorylation	RLSRSFLSRSNMSVA HHHHHHHHCCCCCCC	31.49	23737553
326	Phosphorylation	SRSFLSRSNMSVARS HHHHHHCCCCCCCCC	33.24	22817900
329	Phosphorylation	FLSRSNMSVARSDDT HHHCCCCCCCCCCCC	19.51	30635358
333	Phosphorylation	SNMSVARSDDTLDEE CCCCCCCCCCCCCHH	30.05	25521595
336	Phosphorylation	SVARSDDTLDEEDSF CCCCCCCCCCHHHHH	40.89	21149613
342	Phosphorylation	DTLDEEDSFVMKAII CCCCHHHHHHHHHHH	24.03	30635358
345	Oxidation	DEEDSFVMKAIIHAI CHHHHHHHHHHHHHH	1.98	17242355
366	Phosphorylation	GLQHLLGSLSSYDVN CHHHHHHCHHCCCCC	25.66	26643407
368	Phosphorylation	QHLLGSLSSYDVNQP HHHHHCHHCCCCCCC	28.66	26824392
369	Phosphorylation	HLLGSLSSYDVNQPN HHHHCHHCCCCCCCC	30.55	26643407
370	Phosphorylation	LLGSLSSYDVNQPNK HHHCHHCCCCCCCCC	22.12	26643407
455	Phosphorylation	ALHVAARYGHADVVQ HHHHHHHHCCHHHHH	14.45	21454597
469	Phosphorylation	QLLCSFGSNPDFQDK HHHHHCCCCCCCCCC	43.08	21454597
696	Phosphorylation	KLKLFGHSGSGKSTL EEEEECCCCCCHHHH	34.73	25367039
698	Phosphorylation	KLFGHSGSGKSTLVE EEECCCCCCHHHHHH	46.17	29550500
701	Phosphorylation	GHSGSGKSTLVESLK CCCCCCHHHHHHHHH	30.42	21454597
706	Phosphorylation	GKSTLVESLKCGLLR CHHHHHHHHHHHHHH	26.16	21454597
708	Ubiquitination	STLVESLKCGLLRSF HHHHHHHHHHHHHHH	35.22	22790023
725	Phosphorylation	RRRPRLSSTNSTRFP HCCCCCCCCCCCCCC	35.88	20531401
734	Phosphorylation	NSTRFPPSPLAAKPT CCCCCCCCCCCCCCE	32.55	-
760	Phosphorylation	CENVSVRSRSMMFEP CCCEEECCCCHHCCC	26.93	26643407
762	Phosphorylation	NVSVRSRSMMFEPGL CEEECCCCHHCCCCC	18.82	25521595
875	Ubiquitination	EPIAFGGKLKNPLRV CCCCCCCCCCCCEEE	57.58	22790023
912	Ubiquitination	DKDTSLLKEIRNRFG CCCHHHHHHHHHHHC	57.28	22790023
939	Ubiquitination	DAGASGSKDIKVLRN ECCCCCCHHHHHHHH	67.98	22790023
942	Ubiquitination	ASGSKDIKVLRNHLQ CCCCHHHHHHHHHHH	45.40	22790023
1004	Phosphorylation	DQLNPLASEDDLRRI HHHHCCCCHHHHHHH	49.60	29109428
1053	Phosphorylation	GKLLSVETPRALHHY HHHHCCCCHHHHHCC	18.87	20531401
1108	Ubiquitination	VDIPALIKTDSLQRS EECCCEEECCCCCCC	47.32	22790023
1115	Phosphorylation	KTDSLQRSWADEEDE ECCCCCCCCCCCCCC	17.41	22817900
1226	O-linked_Glycosylation	IETVMATTLPGLLTV HHHHHHHCCCCCCHH	22.78	30016717
1232	O-linked_Glycosylation	TTLPGLLTVKHYLSP HCCCCCCHHEECCCH	32.33	30016717
1433	Phosphorylation	SVVSRRDSHAWTPLY HHHHCCCCCCCCCCC	17.19	16141072
1437	Phosphorylation	RRDSHAWTPLYDL-- CCCCCCCCCCCCC--	12.28	26643407

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	RPS6KA1	P18653	Uniprot
289	S	Phosphorylation	Kinase	RPS6KA3	P18654	Uniprot
308	S	Phosphorylation	Kinase	DAPK1	P53355	PSP
308	S	Phosphorylation	Kinase	DAPK1	Q80YE7	PSP
734	S	Phosphorylation	Kinase	MAPK1	P63085	Uniprot
-	K	Ubiquitination	E3 ubiquitin ligase	Mib1	Q80SY4	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
289	S	Phosphorylation	20141836
In response to mitogenic stimulation (PMA or EGF), phosphorylated at Ser-289; phosphorylation suppresses DAPK1 pro-apoptotic function.
308	S	Phosphorylation	15729359
Autophosphorylation at Ser-308 inhibits its catalytic activity.
308	S	Phosphorylation	15729359
Endoplasmic-stress can cause dephosphorylation at Ser-308.
734	S	Phosphorylation	20141836
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_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference	Domain-Domain Interactions
P53_MOUSE	Trp53	physical	25139875

Drug and Disease Associations

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

Regulatory Network of DAPK1_MOUSE

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"DAPK1 interaction with NMDA receptor NR2B subunits mediates braindamage in stroke."; Tu W., Xu X., Peng L., Zhong X., Zhang W., Soundarapandian M.M.,Balel C., Wang M., Jia N., Zhang W., Lew F., Chan S.L., Chen Y.,Lu Y.; Cell 140:222-234(2010). Cited for: FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITHGRIN2B, AUTOPHOSPHORYLATION AT SER-308, AND DISRUPTION PHENOTYPE.	20141836 [Abstract]
"DAP-kinase is a mediator of endoplasmic reticulum stress-inducedcaspase activation and autophagic cell death."; Gozuacik D., Bialik S., Raveh T., Mitou G., Shohat G., Sabanay H.,Mizushima N., Yoshimori T., Kimchi A.; Cell Death Differ. 15:1875-1886(2008). Cited for: FUNCTION, DEPHOSPHORYLATION AT SER-308, AND ENZYME REGULATION.	18806755 [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]

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