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Protein

Death-associated protein kinase 2

Gene

DAPK2

Organism
Homo sapiens (Human)
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 death signals, 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. Acts as a mediator of anoikis and a suppressor of beta-catenin-dependent anchorage-independent growth of malignant epithelial cells. May play a role in granulocytic maturation (PubMed:17347302). Regulates granulocytic motility by controlling cell spreading and polarization (PubMed:24163421).3 Publications
Isoform 2 is not regulated by calmodulin. It can phosphorylate MYL9. It can induce membrane blebbing and autophagic cell death.

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.2 Publications

Cofactori

Mg2+3 Publications

Activity regulationi

Activated by Ca2+/calmodulin. Regulated by a double locking mechanism, involving autophosphorylation at Ser-318, calmodulin binding, and dimerization. In the inactive state, Ser-318 is phosphorylated, and the kinase is dimeric. Activation involves: dephosphorylation at Ser-318, release-of-autoinhibition mechanism where calmodulin binding induces a conformational change that relieves the steric block of the active site by the autoinhibitory domain, and generation of the monomeric active form of the kinase.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei52ATPPROSITE-ProRule annotation2 Publications1
Active sitei149Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi29 – 37ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • calmodulin binding Source: UniProtKB
  • identical protein binding Source: IntAct
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-418889 via Dependence Receptors in the absence of ligand
SignaLinkiQ9UIK4
SIGNORiQ9UIK4

Names & Taxonomyi

Protein namesi
Recommended name:
Death-associated protein kinase 2 (EC:2.7.11.12 Publications)
Short name:
DAP kinase 2
Alternative name(s):
DAP-kinase-related protein 1
Short name:
DRP-1
Gene namesi
Name:DAPK2
OrganismiHomo sapiens (Human)Imported
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

EuPathDBiHostDB:ENSG00000035664.11
HGNCiHGNC:2675 DAPK2
MIMi616567 gene
neXtProtiNX_Q9UIK4

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

Keywords - Cellular componenti

Cytoplasm, Cytoplasmic vesicle

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi52K → A: Loss of activity, apoptotic function and of autophosphorylation. 3 Publications1
Mutagenesisi299 – 330Missing : Loss of ca(2+)-calmodulin binding, increase in activity, loss of autophosphorylation. Add BLAST32
Mutagenesisi299S → A: No effect on Ca(2+)-calmodulin independent phosphorylation or apoptotic activity. 1 Publication1
Mutagenesisi318S → A: Loss of Ca(2+)-calmodulin independent phosphorylation, increase in apoptotic activity. 1 Publication1
Mutagenesisi318S → D: Abolishes apoptotic activity. 1 Publication1
Mutagenesisi320S → A: No effect on Ca(2+)-calmodulin independent phosphorylation or apoptotic activity. 1 Publication1
Mutagenesisi323S → A: No effect on Ca(2+)-calmodulin independent phosphorylation or apoptotic activity. 1 Publication1
Mutagenesisi329T → A: No effect on Ca(2+)-calmodulin independent phosphorylation or apoptotic activity. 1 Publication1
Mutagenesisi367S → A: No effect on interaction with YWHAE. 1 Publication1
Mutagenesisi368S → A: No effect on interaction with YWHAE. 1 Publication1
Mutagenesisi369T → A: Interaction with YWHAE is reduced. 1 Publication1
Mutagenesisi370S → A: Interaction with YWHAE is increased. 1 Publication1

Organism-specific databases

DisGeNETi23604
OpenTargetsiENSG00000035664
PharmGKBiPA27143

Chemistry databases

ChEMBLiCHEMBL3123

Polymorphism and mutation databases

BioMutaiDAPK2
DMDMi38605084

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000859121 – 370Death-associated protein kinase 2Add BLAST370

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei299PhosphoserineCombined sources1
Modified residuei318Phosphoserine; by autocatalysis1 Publication1
Modified residuei349PhosphoserineCombined sources1
Modified residuei369Phosphothreonine; by PKB/AKT11 Publication1

Post-translational modificationi

Autophosphorylation at Ser-318 inhibits its catalytic activity. Dephosphorylated at Ser-318 in response to activated Fas and TNF-alpha receptors.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9UIK4
PaxDbiQ9UIK4
PeptideAtlasiQ9UIK4
PRIDEiQ9UIK4
ProteomicsDBi84537
84538 [Q9UIK4-2]

PTM databases

iPTMnetiQ9UIK4
PhosphoSitePlusiQ9UIK4

Expressioni

Tissue specificityi

Expressed in neutrophils and eosinophils (PubMed:24163421). Isoform 2 is expressed in embryonic stem cells (at protein level). Isoform 1 is ubiquitously expressed in all tissue types examined with high levels in heart, lung and skeletal muscle.4 Publications

Inductioni

Up-regulated during granulocytic maturation (PubMed:17347302, PubMed:24163421).2 Publications

Gene expression databases

BgeeiENSG00000035664 Expressed in 210 organ(s), highest expression level in right lobe of thyroid gland
CleanExiHS_DAPK2
ExpressionAtlasiQ9UIK4 baseline and differential
GenevisibleiQ9UIK4 HS

Organism-specific databases

HPAiHPA071581

Interactioni

Subunit structurei

Homodimer in its autoinhibited state. Active as monomer (By similarity). Isoform 2 but not isoform 1 can interact with ATF4. Interacts with 14-3-3 proteins YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ and SFN; the interaction requires DAPK2 phosphorylation at Thr-369 and suppresses DAPK2 kinase activity and DAPK2-induced apoptosis (PubMed:26047703).By similarity1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi117137, 8 interactors
IntActiQ9UIK4, 8 interactors
STRINGi9606.ENSP00000261891

Chemistry databases

BindingDBiQ9UIK4

Structurei

Secondary structure

1370
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9UIK4
SMRiQ9UIK4
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UIK4

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini23 – 285Protein kinasePROSITE-ProRule annotationAdd BLAST263

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni277 – 344Calmodulin-bindingAdd 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.By similarity

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0032 Eukaryota
ENOG410XRMJ LUCA
GeneTreeiENSGT00760000118877
HOGENOMiHOG000233016
HOVERGENiHBG100551
InParanoidiQ9UIK4
KOiK08803
OMAiCNHLSRS
PhylomeDBiQ9UIK4
TreeFamiTF314166

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 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 4 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9UIK4-1) [UniParc]FASTAAdd to basket
Also known as: Alpha

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
MFQASMRSPN MEPFKQQKVE DFYDIGEELG SGQFAIVKKC REKSTGLEYA
60 70 80 90 100
AKFIKKRQSR ASRRGVSREE IEREVSILRQ VLHHNVITLH DVYENRTDVV
110 120 130 140 150
LILELVSGGE LFDFLAQKES LSEEEATSFI KQILDGVNYL HTKKIAHFDL
160 170 180 190 200
KPENIMLLDK NIPIPHIKLI DFGLAHEIED GVEFKNIFGT PEFVAPEIVN
210 220 230 240 250
YEPLGLEADM WSIGVITYIL LSGASPFLGD TKQETLANIT AVSYDFDEEF
260 270 280 290 300
FSQTSELAKD FIRKLLVKET RKRLTIQEAL RHPWITPVDN QQAMVRRESV
310 320 330 340 350
VNLENFRKQY VRRRWKLSFS IVSLCNHLTR SLMKKVHLRP DEDLRNCESD
360 370
TEEDIARRKA LHPRRRSSTS
Length:370
Mass (Da):42,898
Last modified:May 1, 2000 - v1
Checksum:i035E914BBCD881A2
GO
Isoform 2 (identifier: Q9UIK4-2) [UniParc]FASTAAdd to basket
Also known as: Beta

The sequence of this isoform differs from the canonical sequence as follows:
     287-370: PVDNQQAMVR...LHPRRRSSTS → SKGEGRAPEQ...TEEFLAGWKL

Note: Contains a leucine zipper at positions 434-451.
Show »
Length:488
Mass (Da):55,931
Checksum:i34F716A709C569B8
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YKW8H0YKW8_HUMAN
Death-associated protein kinase 2
DAPK2
80Annotation score:
H0YLP5H0YLP5_HUMAN
Death-associated protein kinase 2
DAPK2
88Annotation score:
H0YMK1H0YMK1_HUMAN
Death-associated protein kinase 2
DAPK2
91Annotation score:
H0YL86H0YL86_HUMAN
Death-associated protein kinase 2
DAPK2
48Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti241A → S in AAC35001 (PubMed:10629061).Curated1
Sequence conflicti253Q → H in AAC35001 (PubMed:10629061).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04043660R → W1 PublicationCorresponds to variant dbSNP:rs56047843Ensembl.1
Natural variantiVAR_040437271R → W1 PublicationCorresponds to variant dbSNP:rs34270163Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_042057287 – 370PVDNQ…RSSTS → SKGEGRAPEQRKTEPTQLKT KHLREYTLKCHSSMPPNNSY VNFERFACVVEDVARVDLGC RALVEAHDTIQDDVEALVSI FNEKEAWYREENESARHDLS QLRYEFRKVESLKKLLREDI QATGCSLGSMARKLDHLQAQ FEILRQELSADLQWIQELVG SFQLESGSSEGLGSTFYQDT SESLSELLSRSCTEEFLAGW KL in isoform 2. 1 PublicationAdd BLAST84

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB018001 mRNA Translation: BAA88063.1
AF052941 mRNA Translation: AAC35001.1
GU056176 mRNA Translation: ADD83109.1
AC015914 Genomic DNA No translation available.
AC021541 Genomic DNA No translation available.
BC114506 mRNA Translation: AAI14507.1
CCDSiCCDS10188.1 [Q9UIK4-1]
CCDS86463.1 [Q9UIK4-2]
RefSeqiNP_055141.2, NM_014326.3 [Q9UIK4-1]
XP_011519718.1, XM_011521416.2 [Q9UIK4-2]
UniGeneiHs.237886

Genome annotation databases

EnsembliENST00000261891; ENSP00000261891; ENSG00000035664 [Q9UIK4-1]
ENST00000457488; ENSP00000408277; ENSG00000035664 [Q9UIK4-1]
ENST00000558069; ENSP00000453235; ENSG00000035664 [Q9UIK4-2]
ENST00000612884; ENSP00000484390; ENSG00000035664 [Q9UIK4-2]
GeneIDi23604
KEGGihsa:23604
UCSCiuc002amr.4 human [Q9UIK4-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB018001 mRNA Translation: BAA88063.1
AF052941 mRNA Translation: AAC35001.1
GU056176 mRNA Translation: ADD83109.1
AC015914 Genomic DNA No translation available.
AC021541 Genomic DNA No translation available.
BC114506 mRNA Translation: AAI14507.1
CCDSiCCDS10188.1 [Q9UIK4-1]
CCDS86463.1 [Q9UIK4-2]
RefSeqiNP_055141.2, NM_014326.3 [Q9UIK4-1]
XP_011519718.1, XM_011521416.2 [Q9UIK4-2]
UniGeneiHs.237886

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1WMKX-ray3.60A/B/C/D/E/F/G/H11-330[»]
1WRZX-ray2.00B312-330[»]
1Z9XX-ray3.93A/B/C11-330[»]
1ZUZX-ray1.91B312-330[»]
1ZWSX-ray2.90A/B/C/D/E/F/G/H11-297[»]
2A27X-ray3.00A/B/C/D/E/F/G/H11-330[»]
2A2AX-ray1.47A/B/C/D11-330[»]
2CKEX-ray2.80A/B/C/D11-330[»]
ProteinModelPortaliQ9UIK4
SMRiQ9UIK4
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117137, 8 interactors
IntActiQ9UIK4, 8 interactors
STRINGi9606.ENSP00000261891

Chemistry databases

BindingDBiQ9UIK4
ChEMBLiCHEMBL3123

PTM databases

iPTMnetiQ9UIK4
PhosphoSitePlusiQ9UIK4

Polymorphism and mutation databases

BioMutaiDAPK2
DMDMi38605084

Proteomic databases

EPDiQ9UIK4
PaxDbiQ9UIK4
PeptideAtlasiQ9UIK4
PRIDEiQ9UIK4
ProteomicsDBi84537
84538 [Q9UIK4-2]

Protocols and materials databases

DNASUi23604
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000261891; ENSP00000261891; ENSG00000035664 [Q9UIK4-1]
ENST00000457488; ENSP00000408277; ENSG00000035664 [Q9UIK4-1]
ENST00000558069; ENSP00000453235; ENSG00000035664 [Q9UIK4-2]
ENST00000612884; ENSP00000484390; ENSG00000035664 [Q9UIK4-2]
GeneIDi23604
KEGGihsa:23604
UCSCiuc002amr.4 human [Q9UIK4-1]

Organism-specific databases

CTDi23604
DisGeNETi23604
EuPathDBiHostDB:ENSG00000035664.11
GeneCardsiDAPK2
HGNCiHGNC:2675 DAPK2
HPAiHPA071581
MIMi616567 gene
neXtProtiNX_Q9UIK4
OpenTargetsiENSG00000035664
PharmGKBiPA27143
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0032 Eukaryota
ENOG410XRMJ LUCA
GeneTreeiENSGT00760000118877
HOGENOMiHOG000233016
HOVERGENiHBG100551
InParanoidiQ9UIK4
KOiK08803
OMAiCNHLSRS
PhylomeDBiQ9UIK4
TreeFamiTF314166

Enzyme and pathway databases

ReactomeiR-HSA-418889 via Dependence Receptors in the absence of ligand
SignaLinkiQ9UIK4
SIGNORiQ9UIK4

Miscellaneous databases

ChiTaRSiDAPK2 human
EvolutionaryTraceiQ9UIK4
GeneWikiiDAPK2
GenomeRNAii23604
PROiPR:Q9UIK4
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000035664 Expressed in 210 organ(s), highest expression level in right lobe of thyroid gland
CleanExiHS_DAPK2
ExpressionAtlasiQ9UIK4 baseline and differential
GenevisibleiQ9UIK4 HS

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiDAPK2_HUMAN
AccessioniPrimary (citable) accession number: Q9UIK4
Secondary accession number(s): E9JGM7, O75892, Q24JS1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 28, 2003
Last sequence update: May 1, 2000
Last modified: September 12, 2018
This is version 167 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  6. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  7. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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