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 2

Gene

DAPK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Enzyme 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
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  • anoikis Source: UniProtKB
  • apoptotic process Source: UniProtKB
  • intracellular signal transduction Source: UniProtKB
  • neutrophil migration Source: Ensembl
  • positive regulation of eosinophil chemotaxis Source: UniProtKB
  • positive regulation of neutrophil chemotaxis Source: UniProtKB
  • protein autophosphorylation Source: UniProtKB
  • protein phosphorylation Source: UniProtKB
  • regulation of apoptotic process Source: UniProtKB
  • regulation of autophagy Source: UniProtKB
  • regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis

Keywords - Ligandi

ATP-binding, Calmodulin-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS00508-MONOMER.
ReactomeiR-HSA-418889. Ligand-independent caspase activation via DCC.
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

HGNCiHGNC:2675. DAPK2.

Subcellular locationi

GO - Cellular componenti

  • autophagosome lumen Source: UniProtKB-SubCell
  • cytoplasm Source: UniProtKB
  • cytoplasmic vesicle Source: UniProtKB-KW
Complete GO annotation...

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.
GuidetoPHARMACOLOGYi2003.

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.

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.
CleanExiHS_DAPK2.
ExpressionAtlasiQ9UIK4. baseline and differential.
GenevisibleiQ9UIK4. HS.

Organism-specific databases

HPAiCAB009520.

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

WithEntry#Exp.IntActNotes
itself4EBI-77154,EBI-77154
ATF4P188482EBI-9693115,EBI-492498
FAM9BQ8IZU03EBI-77154,EBI-10175124

GO - Molecular functioni

  • calmodulin binding Source: UniProtKB

Protein-protein interaction databases

BioGridi117137. 8 interactors.
IntActiQ9UIK4. 7 interactors.
STRINGi9606.ENSP00000261891.

Chemistry databases

BindingDBiQ9UIK4.

Structurei

Secondary structure

1370
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi19 – 22Combined sources4
Beta strandi23 – 31Combined sources9
Beta strandi33 – 42Combined sources10
Turni43 – 45Combined sources3
Beta strandi48 – 56Combined sources9
Beta strandi58 – 61Combined sources4
Beta strandi63 – 66Combined sources4
Helixi68 – 80Combined sources13
Beta strandi89 – 94Combined sources6
Beta strandi96 – 103Combined sources8
Helixi111 – 116Combined sources6
Helixi123 – 142Combined sources20
Beta strandi144 – 146Combined sources3
Helixi152 – 154Combined sources3
Beta strandi155 – 158Combined sources4
Beta strandi162 – 164Combined sources3
Beta strandi167 – 169Combined sources3
Helixi191 – 193Combined sources3
Helixi196 – 199Combined sources4
Helixi207 – 222Combined sources16
Helixi232 – 240Combined sources9
Helixi248 – 251Combined sources4
Helixi256 – 263Combined sources8
Turni270 – 272Combined sources3
Helixi276 – 281Combined sources6
Turni283 – 285Combined sources3
Helixi290 – 298Combined sources9
Helixi303 – 312Combined sources10
Helixi314 – 328Combined sources15

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...

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

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0032. Eukaryota.
ENOG410XRMJ. LUCA.
GeneTreeiENSGT00760000118877.
HOGENOMiHOG000233016.
HOVERGENiHBG100551.
InParanoidiQ9UIK4.
KOiK08803.
OMAiNLRNCES.
PhylomeDBiQ9UIK4.
TreeFamiTF314166.

Family and domain databases

InterProiIPR020636. Ca/CaM-dep_Ca-dep_prot_Kinase.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR24347. PTHR24347. 1 hit.
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

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

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 → W.1 PublicationCorresponds to variant rs56047843dbSNPEnsembl.1
Natural variantiVAR_040437271R → W.1 PublicationCorresponds to variant rs34270163dbSNPEnsembl.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]
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

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]
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. 7 interactors.
STRINGi9606.ENSP00000261891.

Chemistry databases

BindingDBiQ9UIK4.
ChEMBLiCHEMBL3123.
GuidetoPHARMACOLOGYi2003.

PTM databases

iPTMnetiQ9UIK4.
PhosphoSitePlusiQ9UIK4.

Polymorphism and mutation databases

BioMutaiDAPK2.
DMDMi38605084.

Proteomic databases

EPDiQ9UIK4.
PaxDbiQ9UIK4.
PeptideAtlasiQ9UIK4.
PRIDEiQ9UIK4.

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.
GeneCardsiDAPK2.
HGNCiHGNC:2675. DAPK2.
HPAiCAB009520.
MIMi616567. gene.
neXtProtiNX_Q9UIK4.
OpenTargetsiENSG00000035664.
PharmGKBiPA27143.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0032. Eukaryota.
ENOG410XRMJ. LUCA.
GeneTreeiENSGT00760000118877.
HOGENOMiHOG000233016.
HOVERGENiHBG100551.
InParanoidiQ9UIK4.
KOiK08803.
OMAiNLRNCES.
PhylomeDBiQ9UIK4.
TreeFamiTF314166.

Enzyme and pathway databases

BioCyciZFISH:HS00508-MONOMER.
ReactomeiR-HSA-418889. Ligand-independent caspase activation via DCC.
SignaLinkiQ9UIK4.
SIGNORiQ9UIK4.

Miscellaneous databases

ChiTaRSiDAPK2. human.
EvolutionaryTraceiQ9UIK4.
GeneWikiiDAPK2.
GenomeRNAii23604.
PROiQ9UIK4.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000035664.
CleanExiHS_DAPK2.
ExpressionAtlasiQ9UIK4. baseline and differential.
GenevisibleiQ9UIK4. HS.

Family and domain databases

InterProiIPR020636. Ca/CaM-dep_Ca-dep_prot_Kinase.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR24347. PTHR24347. 1 hit.
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDAPK2_HUMAN
AccessioniPrimary (citable) accession number: Q9UIK4
Secondary accession number(s): E9JGM7, O75892, Q24JS1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 28, 2003
Last sequence update: May 1, 2000
Last modified: November 2, 2016
This is version 158 of the entry and version 1 of the sequence. [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 chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.