UniProtKB - Q80YE7 (DAPK1_MOUSE)
(max 400 entries)x
Your basket is currently empty. i
Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)
Protein
Death-associated protein kinase 1
Gene
Dapk1
Organism
Mus musculus (Mouse)
Status
Functioni
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 Ca2+ 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.By similarity4 Publications
Catalytic activityi
ATP + a protein = ADP + a phosphoprotein.
Cofactori
Mg2+1 Publication
Enzyme regulationi
Activated by Ca2+/calmodulin. Regulated by a locking mechanism, involving autophosphorylation at Ser-308 and calmodulin binding. In the inactive state, Ser-308 is phosphorylated. Activation involves its dephosphorylation and a release-of-autoinhibition mechanism where binding of calmodulin induces a conformational change that relieves the steric block of the active site by the autoinhibitory domain. Activity is modulated by UNC5B and NTN1. UNC5B activates it by inhibiting the phosphorylation at Ser-308, whereas NTN1 inhibits UNC5B-mediated activation of DAPK1. Endoplasmic-stress activates by causing Ser-308 dephosphorylation.2 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 42 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 139 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 19 – 27 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB
- calmodulin binding Source: UniProtKB
- calmodulin-dependent protein kinase activity Source: MGI
- GTP binding Source: UniProtKB-KW
- identical protein binding Source: MGI
- protein kinase activity Source: MGI
- syntaxin-1 binding Source: MGI
GO - Biological processi
- apoptotic process Source: MGI
- apoptotic signaling pathway Source: MGI
- cellular response to hydroperoxide Source: MGI
- cellular response to interferon-gamma Source: UniProtKB
- extrinsic apoptotic signaling pathway via death domain receptors Source: MGI
- intracellular signal transduction Source: UniProtKB
- negative regulation of apoptotic process Source: UniProtKB
- negative regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: MGI
- negative regulation of translation Source: MGI
- positive regulation of autophagy Source: MGI
- positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: MGI
- protein autophosphorylation Source: MGI
- protein phosphorylation Source: UniProtKB
- regulation of NMDA receptor activity Source: UniProtKB
Keywordsi
Molecular function | Calmodulin-binding, Kinase, Serine/threonine-protein kinase, Transferase |
Biological process | Apoptosis, Translation regulation |
Ligand | ATP-binding, GTP-binding, Nucleotide-binding |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:Dapk1 |
Organismi | Mus musculus (Mouse)Imported |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1916885. Dapk1. |
Subcellular locationi
Pathology & Biotechi
Disruption phenotypei
Mice are protected against cerebral ischemic neuronal death.1 Publication
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000085911 | 1 – 1442 | Death-associated protein kinase 1Add BLAST | 1442 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 289 | Phosphoserine; by RPS6KA1 and RPS6KA3By similarity | 1 | |
Modified residuei | 308 | Phosphoserine; by autocatalysis2 Publications | 1 | |
Modified residuei | 319 | PhosphoserineBy similarity | 1 | |
Modified residuei | 333 | PhosphoserineCombined sources | 1 | |
Modified residuei | 734 | Phosphoserine; by MAPK1By similarity | 1 | |
Modified residuei | 1115 | PhosphoserineCombined sources | 1 | |
Modified residuei | 1433 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Ubiquitinated by the BCR(KLHL20) E3 ubiquitin ligase complex, leading to its degradation by the proteasome.By similarity
In response to mitogenic stimulation (PMA or EGF), phosphorylated at Ser-289; phosphorylation suppresses DAPK1 pro-apoptotic function. Autophosphorylation at Ser-308 inhibits its catalytic activity. Phosphorylation at Ser-734 by MAPK1 increases its catalytic activity and promotes cytoplasmic retention of MAPK1. Endoplasmic-stress can cause dephosphorylation at Ser-308.2 Publications
Keywords - PTMi
Phosphoprotein, Ubl conjugationProteomic databases
PaxDbi | Q80YE7. |
PeptideAtlasi | Q80YE7. |
PRIDEi | Q80YE7. |
PTM databases
iPTMneti | Q80YE7. |
PhosphoSitePlusi | Q80YE7. |
Expressioni
Tissue specificityi
High levels in bladder, uterus, vas deferens, lung, liver and kidney.1 Publication
Gene expression databases
Bgeei | ENSMUSG00000021559. |
CleanExi | MM_DAPK1. |
Genevisiblei | Q80YE7. MM. |
Interactioni
Subunit structurei
Interacts with KLHL20. Interacts (via death domain) with MAPK1 and MAPK3. Interacts with MAP1B (via N-terminus). Interacts with PRKD1 in an oxidative stress-regulated manner. Interacts with PIN1, PDCD6, BECN1, TSC2 and STX1A (By similarity). Interacts (via death domain) with UNC5B (via death domain). Interacts with GRINB.By similarity2 Publications
Binary interactionsi
With | Entry | #Exp. | IntAct | Notes |
---|---|---|---|---|
Grin2b | Q01097 | 8 | EBI-2584874,EBI-400125 |
GO - Molecular functioni
- calmodulin binding Source: UniProtKB
- identical protein binding Source: MGI
- syntaxin-1 binding Source: MGI
Protein-protein interaction databases
BioGridi | 213581. 7 interactors. |
IntActi | Q80YE7. 4 interactors. |
STRINGi | 10090.ENSMUSP00000040825. |
Structurei
3D structure databases
ProteinModelPortali | Q80YE7. |
SMRi | Q80YE7. |
ModBasei | Search... |
MobiDBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 13 – 275 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 263 | |
Repeati | 378 – 407 | ANK 1CuratedAdd BLAST | 30 | |
Repeati | 411 – 440 | ANK 2CuratedAdd BLAST | 30 | |
Repeati | 444 – 473 | ANK 3CuratedAdd BLAST | 30 | |
Repeati | 477 – 506 | ANK 4CuratedAdd BLAST | 30 | |
Repeati | 510 – 539 | ANK 5CuratedAdd BLAST | 30 | |
Repeati | 543 – 572 | ANK 6CuratedAdd BLAST | 30 | |
Repeati | 576 – 605 | ANK 7CuratedAdd BLAST | 30 | |
Repeati | 609 – 638 | ANK 8CuratedAdd BLAST | 30 | |
Domaini | 681 – 955 | RocPROSITE-ProRule annotationAdd BLAST | 275 | |
Repeati | 875 – 904 | ANK 9CuratedAdd BLAST | 30 | |
Repeati | 1164 – 1196 | ANK 10CuratedAdd BLAST | 33 | |
Domaini | 1312 – 1396 | DeathPROSITE-ProRule annotationAdd BLAST | 85 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 267 – 334 | Calmodulin-bindingBy similarityAdd BLAST | 68 | |
Regioni | 292 – 301 | Autoinhibitory domainBy similarity | 10 |
Domaini
The autoinhibitory domain sterically blocks the substrate peptide-binding site by making both hydrophobic and electrostatic contacts with the kinase core.
Sequence similaritiesi
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. DAP kinase subfamily.Curated
Keywords - Domaini
ANK repeat, RepeatPhylogenomic databases
eggNOGi | KOG0032. Eukaryota. ENOG410XRMJ. LUCA. |
GeneTreei | ENSGT00760000118877. |
HOGENOMi | HOG000082489. |
HOVERGENi | HBG051296. |
InParanoidi | Q80YE7. |
KOi | K08803. |
OMAi | CQMEVIK. |
OrthoDBi | EOG091G0J2O. |
PhylomeDBi | Q80YE7. |
TreeFami | TF314166. |
Family and domain databases
CDDi | cd00204. ANK. 3 hits. |
Gene3Di | 1.25.40.20. 3 hits. |
InterProi | View protein in InterPro IPR002110. Ankyrin_rpt. IPR020683. Ankyrin_rpt-contain_dom. IPR036770. Ankyrin_rpt-contain_sf. IPR020676. DAPK1. IPR011029. DEATH-like_dom_sf. IPR000488. Death_domain. IPR011009. Kinase-like_dom_sf. IPR027417. P-loop_NTPase. IPR000719. Prot_kinase_dom. IPR017441. Protein_kinase_ATP_BS. IPR020859. ROC_dom. IPR008271. Ser/Thr_kinase_AS. |
PANTHERi | PTHR44619. PTHR44619. 1 hit. |
Pfami | View protein in Pfam PF12796. Ank_2. 2 hits. PF00531. Death. 1 hit. PF00069. Pkinase. 1 hit. |
PRINTSi | PR01415. ANKYRIN. |
SMARTi | View protein in SMART SM00248. ANK. 9 hits. SM00005. DEATH. 1 hit. SM00220. S_TKc. 1 hit. |
SUPFAMi | SSF47986. SSF47986. 1 hit. SSF48403. SSF48403. 1 hit. SSF52540. SSF52540. 2 hits. SSF56112. SSF56112. 1 hit. |
PROSITEi | View protein in PROSITE PS50297. ANK_REP_REGION. 1 hit. PS50088. ANK_REPEAT. 7 hits. PS50017. DEATH_DOMAIN. 1 hit. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. PS51424. ROC. 1 hit. |
s (2)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basket
Isoform 1Curated (identifier: Q80YE7-1) [UniParc]FASTAAdd to basket
Also known as: Beta
This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
10 20 30 40 50
MTVFRQENVD DYYDTGEELG SGQFAVVKKC REKSTGLQYA AKFIKKRRTK
60 70 80 90 100
SSRRGVSRED IEREVSILKE IRHPNVITLH EVYENKTDVI LILELVAGGE
110 120 130 140 150
LFDFLAEKES LTEEEATEFL KQILSGVYYL HSLQIAHFDL KPENIMLLDR
160 170 180 190 200
NVPKPRIKII DFGLAHKIDF GNEFKNIFGT PEFVAPEIVN YEPLGLEADM
210 220 230 240 250
WSIGVITYIL LSGASPFLGD TKQETLANVS AVNYDFEEEF FRNTSTLAKD
260 270 280 290 300
FIRRLLVKDP KKRMTIQDSL QHPWIKPKDT QQALSRKASA VNMEKFKKFA
310 320 330 340 350
ARKKWKQSVR LISLCQRLSR SFLSRSNMSV ARSDDTLDEE DSFVMKAIIH
360 370 380 390 400
AINDDNVPGL QHLLGSLSSY DVNQPNKHGT PPLLIAAGCG NIQMLQLLIK
410 420 430 440 450
RGSRIDVQDK GGSNAIYWAS RHGHVDTLKF LNENKCPLDV KDKSGETALH
460 470 480 490 500
VAARYGHADV VQLLCSFGSN PDFQDKEEET PLHCAAWHGY YSVAKALCEV
510 520 530 540 550
GCNVNIKNRE GETPLLTASA RGYHDIVECL AEHGADLNAS DKDGHIALHL
560 570 580 590 600
AVRRCQMEVI KTLLGHGSFV DFQDRHGNTP LHVACKDGSA PIVVALCEAS
610 620 630 640 650
CNLDISNKYG RTPLHLAANN GILDVVRYLC LMGANVEALT SDGKTAEDLA
660 670 680 690 700
KAEQHEHVAG LLARLRKDTH RGLFIQQLRP TQNLQPRIKL KLFGHSGSGK
710 720 730 740 750
STLVESLKCG LLRSFFRRRR PRLSSTNSTR FPPSPLAAKP TVSVSINNLY
760 770 780 790 800
PGCENVSVRS RSMMFEPGLT KGMLEVFVAP SHHLHCSTDD QSTKAIDIQN
810 820 830 840 850
AYLNGVGDFS VWEFSGNPVY FCCYDYFAAN DPTSIHIIVF SLEEPYEIQL
860 870 880 890 900
NQVIFWLSFL KSLVPVEEPI AFGGKLKNPL RVVLVATHAD IMNIPRPAGG
910 920 930 940 950
EFGYDKDTSL LKEIRNRFGN DLHVSNKLFV LDAGASGSKD IKVLRNHLQE
960 970 980 990 1000
IRSQIVSGCS PMTHLCEKII STLPSWRKLN GPNQLMSLQQ FVYDVQDQLN
1010 1020 1030 1040 1050
PLASEDDLRR IAQQLHSTGE INIMQSETVQ DVLLLDPRWL CTNVLGKLLS
1060 1070 1080 1090 1100
VETPRALHHY RGRYTMEDIQ RLVPDSDVEE LLQILDAMDI CARDLSSGTM
1110 1120 1130 1140 1150
VDIPALIKTD SLQRSWADEE DEVMVYGGVR IVPVEHLTPF PCGIFHKVQV
1160 1170 1180 1190 1200
NLCRWIHQQS AEGDADIRLW VSGCRIANRG AELLVLLVNH GQGIEVQVRG
1210 1220 1230 1240 1250
LETEKIKCCL LLDSVCSTIE TVMATTLPGL LTVKHYLSPQ QLREHHEPVM
1260 1270 1280 1290 1300
VYQPRDFFRA QTLKESSLTN TMGGYKESFS SITCFGCHDV YSQASLGMDI
1310 1320 1330 1340 1350
HASDLSLLTR RKLSRLLDPP DPMGKDWCLL AMNLGLPDMV AKHNVNNRAS
1360 1370 1380 1390 1400
RDFLPSPVHA LLQEWTSYPE STVGILISKL RELGRRDAAD FLLKASSVFK
1410 1420 1430 1440
INLDGNGQEA YASSCNSGTS YNSISSVVSR RDSHAWTPLY DL
Sequence cautioni
The sequence AAH21490 differs from that shown. Reason: Erroneous initiation.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 354 | D → N in CAA65762 (Ref. 2) Curated | 1 | |
Sequence conflicti | 441 | K → Q in AAH57317 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 441 | K → Q in AAH60161 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 461 | V → A in CAA65762 (Ref. 2) Curated | 1 | |
Sequence conflicti | 960 | S → P in CAA65762 (Ref. 2) Curated | 1 | |
Sequence conflicti | 1000 | N → T in CAA65762 (Ref. 2) Curated | 1 | |
Sequence conflicti | 1038 – 1042 | RWLCT → PMALH in CAA65762 (Ref. 2) Curated | 5 | |
Sequence conflicti | 1105 | A → V in AAO91934 (PubMed:11485996).Curated | 1 | |
Sequence conflicti | 1105 | A → V in AAO91935 (PubMed:11485996).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_050629 | 1431 – 1442 | Missing in isoform 2. 4 PublicationsAdd BLAST | 12 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY245540 mRNA. Translation: AAO91934.2. AY245541 mRNA. Translation: AAO91935.1. X97048 mRNA. Translation: CAA65762.1. BC021490 mRNA. Translation: AAH21490.1. Different initiation. BC026671 mRNA. Translation: AAH26671.1. BC057317 mRNA. Translation: AAH57317.1. BC060161 mRNA. Translation: AAH60161.1. AK013153 mRNA. Translation: BAB28681.1. |
CCDSi | CCDS26581.1. [Q80YE7-2] |
RefSeqi | NP_001272846.1. NM_001285917.1. [Q80YE7-1] NP_083929.2. NM_029653.3. [Q80YE7-2] NP_598823.1. NM_134062.2. [Q80YE7-2] XP_006517433.1. XM_006517370.3. [Q80YE7-1] |
UniGenei | Mm.24103. |
Genome annotation databases
Ensembli | ENSMUST00000044083; ENSMUSP00000040825; ENSMUSG00000021559. [Q80YE7-2] ENSMUST00000077453; ENSMUSP00000076666; ENSMUSG00000021559. [Q80YE7-2] ENSMUST00000226059; ENSMUSP00000153607; ENSMUSG00000021559. [Q80YE7-1] |
GeneIDi | 69635. |
KEGGi | mmu:69635. |
UCSCi | uc007qvm.2. mouse. [Q80YE7-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Entry informationi
Entry namei | DAPK1_MOUSE | |
Accessioni | Q80YE7Primary (citable) accession number: Q80YE7 Secondary accession number(s): Q80YE6 Q9JJP7 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 28, 2003 |
Last sequence update: | November 28, 2003 | |
Last modified: | March 28, 2018 | |
This is version 153 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |