Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Death-associated protein kinase 1

Gene

Dapk1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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

Activity 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 keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei42ATPPROSITE-ProRule annotation1
Active sitei139Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi19 – 27ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionCalmodulin-binding, Kinase, Serine/threonine-protein kinase, Transferase
Biological processApoptosis, Translation regulation
LigandATP-binding, GTP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Death-associated protein kinase 1 (EC:2.7.11.1)
Short name:
DAP kinase 1
Gene namesi
Name:Dapk1
OrganismiMus musculus (Mouse)Imported
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 13

Organism-specific databases

MGIiMGI:1916885 Dapk1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Disruption phenotypei

Mice are protected against cerebral ischemic neuronal death.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000859111 – 1442Death-associated protein kinase 1Add BLAST1442

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei289Phosphoserine; by RPS6KA1 and RPS6KA3By similarity1
Modified residuei308Phosphoserine; by autocatalysis2 Publications1
Modified residuei319PhosphoserineBy similarity1
Modified residuei333PhosphoserineCombined sources1
Modified residuei734Phosphoserine; by MAPK1By similarity1
Modified residuei1115PhosphoserineCombined sources1
Modified residuei1433PhosphoserineCombined sources1

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 conjugation

Proteomic databases

PaxDbiQ80YE7
PeptideAtlasiQ80YE7
PRIDEiQ80YE7

PTM databases

iPTMnetiQ80YE7
PhosphoSitePlusiQ80YE7

Expressioni

Tissue specificityi

High levels in bladder, uterus, vas deferens, lung, liver and kidney.1 Publication

Gene expression databases

BgeeiENSMUSG00000021559 Expressed in 268 organ(s), highest expression level in cochlea
CleanExiMM_DAPK1
ExpressionAtlasiQ80YE7 baseline and differential
GenevisibleiQ80YE7 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

WithEntry#Exp.IntActNotes
Grin2bQ010978EBI-2584874,EBI-400125

GO - Molecular functioni

Protein-protein interaction databases

BioGridi213581, 7 interactors
ComplexPortaliCPX-106 DAPK1 - calmodulin complex
IntActiQ80YE7, 5 interactors
STRINGi10090.ENSMUSP00000040825

Structurei

3D structure databases

ProteinModelPortaliQ80YE7
SMRiQ80YE7
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini13 – 275Protein kinasePROSITE-ProRule annotationAdd BLAST263
Repeati378 – 407ANK 1CuratedAdd BLAST30
Repeati411 – 440ANK 2CuratedAdd BLAST30
Repeati444 – 473ANK 3CuratedAdd BLAST30
Repeati477 – 506ANK 4CuratedAdd BLAST30
Repeati510 – 539ANK 5CuratedAdd BLAST30
Repeati543 – 572ANK 6CuratedAdd BLAST30
Repeati576 – 605ANK 7CuratedAdd BLAST30
Repeati609 – 638ANK 8CuratedAdd BLAST30
Domaini681 – 955RocPROSITE-ProRule annotationAdd BLAST275
Repeati875 – 904ANK 9CuratedAdd BLAST30
Repeati1164 – 1196ANK 10CuratedAdd BLAST33
Domaini1312 – 1396DeathPROSITE-ProRule annotationAdd BLAST85

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni267 – 334Calmodulin-bindingBy similarityAdd BLAST68
Regioni292 – 301Autoinhibitory domainBy similarity10

Domaini

The autoinhibitory domain sterically blocks the substrate peptide-binding site by making both hydrophobic and electrostatic contacts with the kinase core.

Sequence similaritiesi

Keywords - Domaini

ANK repeat, Repeat

Phylogenomic databases

eggNOGiKOG0032 Eukaryota
ENOG410XRMJ LUCA
GeneTreeiENSGT00760000118877
HOGENOMiHOG000082489
HOVERGENiHBG051296
InParanoidiQ80YE7
KOiK08803
OMAiNTMGGYR
OrthoDBiEOG091G0J2O
PhylomeDBiQ80YE7
TreeFamiTF314166

Family and domain databases

CDDicd00204 ANK, 3 hits
Gene3Di1.25.40.20, 3 hits
InterProiView 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
PANTHERiPTHR44619 PTHR44619, 1 hit
PfamiView protein in Pfam
PF12796 Ank_2, 2 hits
PF00531 Death, 1 hit
PF00069 Pkinase, 1 hit
PRINTSiPR01415 ANKYRIN
SMARTiView protein in SMART
SM00248 ANK, 9 hits
SM00005 DEATH, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF47986 SSF47986, 1 hit
SSF48403 SSF48403, 1 hit
SSF52540 SSF52540, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView 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

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

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.

« Hide
        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
Length:1,442
Mass (Da):161,442
Last modified:November 28, 2003 - v3
Checksum:i243A14D7C6598F63
GO
Isoform 2Curated (identifier: Q80YE7-2) [UniParc]FASTAAdd to basket
Also known as: Alpha

The sequence of this isoform differs from the canonical sequence as follows:
     1431-1442: Missing.

Show »
Length:1,430
Mass (Da):159,986
Checksum:iFB5B401603C273D9
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A286YDD8A0A286YDD8_MOUSE
Death-associated protein kinase 1
Dapk1
15Annotation score:

Sequence cautioni

The sequence AAH21490 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti354D → N in CAA65762 (Ref. 2) Curated1
Sequence conflicti441K → Q in AAH57317 (PubMed:15489334).Curated1
Sequence conflicti441K → Q in AAH60161 (PubMed:15489334).Curated1
Sequence conflicti461V → A in CAA65762 (Ref. 2) Curated1
Sequence conflicti960S → P in CAA65762 (Ref. 2) Curated1
Sequence conflicti1000N → T in CAA65762 (Ref. 2) Curated1
Sequence conflicti1038 – 1042RWLCT → PMALH in CAA65762 (Ref. 2) Curated5
Sequence conflicti1105A → V in AAO91934 (PubMed:11485996).Curated1
Sequence conflicti1105A → V in AAO91935 (PubMed:11485996).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0506291431 – 1442Missing in isoform 2. 4 PublicationsAdd BLAST12

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
CCDSiCCDS26581.1 [Q80YE7-2]
RefSeqiNP_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]
UniGeneiMm.24103

Genome annotation databases

EnsembliENSMUST00000044083; ENSMUSP00000040825; ENSMUSG00000021559 [Q80YE7-2]
ENSMUST00000077453; ENSMUSP00000076666; ENSMUSG00000021559 [Q80YE7-2]
ENSMUST00000226059; ENSMUSP00000153607; ENSMUSG00000021559 [Q80YE7-1]
GeneIDi69635
KEGGimmu:69635
UCSCiuc007qvm.2 mouse [Q80YE7-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

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
CCDSiCCDS26581.1 [Q80YE7-2]
RefSeqiNP_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]
UniGeneiMm.24103

3D structure databases

ProteinModelPortaliQ80YE7
SMRiQ80YE7
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi213581, 7 interactors
ComplexPortaliCPX-106 DAPK1 - calmodulin complex
IntActiQ80YE7, 5 interactors
STRINGi10090.ENSMUSP00000040825

PTM databases

iPTMnetiQ80YE7
PhosphoSitePlusiQ80YE7

Proteomic databases

PaxDbiQ80YE7
PeptideAtlasiQ80YE7
PRIDEiQ80YE7

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000044083; ENSMUSP00000040825; ENSMUSG00000021559 [Q80YE7-2]
ENSMUST00000077453; ENSMUSP00000076666; ENSMUSG00000021559 [Q80YE7-2]
ENSMUST00000226059; ENSMUSP00000153607; ENSMUSG00000021559 [Q80YE7-1]
GeneIDi69635
KEGGimmu:69635
UCSCiuc007qvm.2 mouse [Q80YE7-1]

Organism-specific databases

CTDi1612
MGIiMGI:1916885 Dapk1

Phylogenomic databases

eggNOGiKOG0032 Eukaryota
ENOG410XRMJ LUCA
GeneTreeiENSGT00760000118877
HOGENOMiHOG000082489
HOVERGENiHBG051296
InParanoidiQ80YE7
KOiK08803
OMAiNTMGGYR
OrthoDBiEOG091G0J2O
PhylomeDBiQ80YE7
TreeFamiTF314166

Miscellaneous databases

PROiPR:Q80YE7
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000021559 Expressed in 268 organ(s), highest expression level in cochlea
CleanExiMM_DAPK1
ExpressionAtlasiQ80YE7 baseline and differential
GenevisibleiQ80YE7 MM

Family and domain databases

CDDicd00204 ANK, 3 hits
Gene3Di1.25.40.20, 3 hits
InterProiView 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
PANTHERiPTHR44619 PTHR44619, 1 hit
PfamiView protein in Pfam
PF12796 Ank_2, 2 hits
PF00531 Death, 1 hit
PF00069 Pkinase, 1 hit
PRINTSiPR01415 ANKYRIN
SMARTiView protein in SMART
SM00248 ANK, 9 hits
SM00005 DEATH, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF47986 SSF47986, 1 hit
SSF48403 SSF48403, 1 hit
SSF52540 SSF52540, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView 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
ProtoNetiSearch...

Entry informationi

Entry nameiDAPK1_MOUSE
AccessioniPrimary (citable) accession number: Q80YE7
Secondary accession number(s): Q80YE6
, Q8R341, Q8VDN6, Q9CSD4, Q9JJP7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 28, 2003
Last sequence update: November 28, 2003
Last modified: November 7, 2018
This is version 158 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again