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Protein

Death-associated protein kinase 2

Gene

Dapk2

Organism
Mus musculus (Mouse)
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. Capable of regulating both type I apoptotic and type II autophagic cell deaths signal. The former involves caspase activation, chromatin and mitochondrial condensation while the latter involves caspase-independent cell death in conjunction with accumulation of mature autophagic vesicles, plasma membrane blebs, and nuclear condensation without DNA degradation. Mediator of anoikis and a suppressor of beta-catenin-dependent anchorage-independent growth of malignant epithelial cells. May play a role in granulocytic maturation (By similarity).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei52 – 521ATP1 PublicationPROSITE-ProRule annotation
Active sitei149 – 1491Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi29 – 379ATP1 PublicationPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB
  2. calmodulin binding Source: UniProtKB
  3. calmodulin-dependent protein kinase activity Source: GO_Central
  4. identical protein binding Source: MGI

GO - Biological processi

  1. anoikis Source: MGI
  2. intracellular signal transduction Source: UniProtKB
  3. protein phosphorylation Source: UniProtKB
  4. regulation of apoptotic process Source: GO_Central
  5. 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

ReactomeiREACT_252543. Role of DCC in regulating apoptosis.

Names & Taxonomyi

Protein namesi
Recommended name:
Death-associated protein kinase 2 (EC:2.7.11.1)
Short name:
DAP kinase 2
Alternative name(s):
DAP-kinase-related protein 1
Short name:
DRP-1
Gene namesi
Name:Dapk2
OrganismiMus musculus (Mouse)Imported
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 9

Organism-specific databases

MGIiMGI:1341297. Dapk2.

Subcellular locationi

Cytoplasm By similarity. Cytoplasmic vesicleautophagosome lumen By similarity

GO - Cellular componenti

  1. autophagic vacuole lumen Source: UniProtKB-SubCell
  2. cytoplasm Source: UniProtKB
  3. cytoplasmic vesicle Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoplasmic vesicle

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 370370Death-associated protein kinase 2PRO_0000085913Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei299 – 2991Phosphoserine1 Publication
Modified residuei318 – 3181Phosphoserine; by autocatalysisBy similarity
Modified residuei349 – 3491Phosphoserine1 Publication

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

MaxQBiQ8VDF3.
PaxDbiQ8VDF3.
PRIDEiQ8VDF3.

PTM databases

PhosphoSiteiQ8VDF3.

Expressioni

Tissue specificityi

Isoform 1 is found in the adult brain while isoform 2 is expressed in brains of embryos and young mice (at protein level).1 Publication

Gene expression databases

BgeeiQ8VDF3.
CleanExiMM_DAPK2.
GenevestigatoriQ8VDF3.

Interactioni

Subunit structurei

Homodimer in its autoinhibited state. Active as monomer.1 Publication

Protein-protein interaction databases

BioGridi199051. 1 interaction.
STRINGi10090.ENSMUSP00000034944.

Structurei

Secondary structure

1
370
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi19 – 213Combined sources
Beta strandi23 – 3210Combined sources
Beta strandi35 – 428Combined sources
Turni43 – 453Combined sources
Beta strandi48 – 569Combined sources
Beta strandi59 – 613Combined sources
Beta strandi63 – 664Combined sources
Helixi68 – 7811Combined sources
Beta strandi89 – 946Combined sources
Beta strandi96 – 1049Combined sources
Helixi111 – 1155Combined sources
Helixi123 – 14220Combined sources
Helixi152 – 1543Combined sources
Beta strandi155 – 1584Combined sources
Beta strandi162 – 1643Combined sources
Beta strandi167 – 1693Combined sources
Helixi191 – 1933Combined sources
Helixi196 – 1994Combined sources
Helixi207 – 22216Combined sources
Helixi232 – 2409Combined sources
Helixi248 – 2514Combined sources
Helixi256 – 26510Combined sources
Turni270 – 2723Combined sources
Helixi276 – 2805Combined sources
Turni283 – 2853Combined sources
Helixi290 – 2978Combined sources
Helixi303 – 3097Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2YA9X-ray2.30A/B11-370[»]
2YAAX-ray2.30A/B11-370[»]
2YABX-ray1.90A/B11-370[»]
ProteinModelPortaliQ8VDF3.
SMRiQ8VDF3. Positions 13-311.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8VDF3.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini23 – 285263Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni287 – 35468Calmodulin-bindingBy similarityAdd
BLAST
Regioni292 – 30110Autoinhibitory domain

Domaini

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

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118877.
HOGENOMiHOG000233016.
HOVERGENiHBG100551.
InParanoidiQ8VDF3.
KOiK08803.
OMAiCNHLSRS.
OrthoDBiEOG7QZGBH.
PhylomeDBiQ8VDF3.
TreeFamiTF314166.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR020675. Myosin_light_ch_kinase-rel.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR22964. PTHR22964. 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. Align

Isoform 1 (identifier: Q8VDF3-1) [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
MVQASMRSPN METFKQQKVE DFYDIGEELG SGQFAIVKKC REKSTGLEYA
60 70 80 90 100
AKFIKKRQSR ASRRGVCREE IEREVSILRQ VLHPNIITLH 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 RHPWITPVDT QQAMVRRESV
310 320 330 340 350
VNLENFKKQY VRRRWKLSFS IVSLCNHLTR SLMKKVHLRT SEDLRNCESD
360 370
TEENIARRKA LHPRRRSSTS
Length:370
Mass (Da):42,778
Last modified:March 1, 2002 - v1
Checksum:i7BF8577140B5F883
GO
Isoform 2 (identifier: Q8VDF3-2) [UniParc]FASTAAdd to Basket

Also known as: Beta

The sequence of this isoform differs from the canonical sequence as follows:
     286-370: TPVDTQQAMV...LHPRRRSSTS → SKGEARAPEQ...AEEVLAGLSL

Show »
Length:489
Mass (Da):56,035
Checksum:iDB08AE634C47ABFC
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti89 – 891L → R in AAC35002. (PubMed:10629061)Curated
Sequence conflicti90 – 901H → Q in BAA88064. (PubMed:10376525)Curated
Sequence conflicti270 – 2701T → P in AAC35002. (PubMed:10629061)Curated
Sequence conflicti341 – 3411S → I in AAC35002. (PubMed:10629061)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei286 – 37085TPVDT…RSSTS → SKGEARAPEQWKAQPAQLKT KRLREYTLKCHSSMPPNNTY VNFERFAHVVEDVARVDKGC RALAGAHDTLQDDVESLVSI YNEKEAWYREENENARHNLS QLKYEYRKVESLKKLLREDI QATGASLGGVARKLDHLQAQ FETLRQQLSADIQWMQELVG IFQLESENTDSHSLGFMFHR DPSESLSELLNRSHAEEVLA GLSL in isoform 2. CuratedVSP_042058Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB018002 mRNA. Translation: BAA88064.1.
BC022165 mRNA. Translation: AAH22165.1.
AF052942 mRNA. Translation: AAC35002.1.
CCDSiCCDS23303.1. [Q8VDF3-1]
RefSeqiNP_034149.2. NM_010019.3. [Q8VDF3-1]
UniGeneiMm.304472.
Mm.335252.

Genome annotation databases

EnsembliENSMUST00000034944; ENSMUSP00000034944; ENSMUSG00000032380. [Q8VDF3-1]
GeneIDi13143.
KEGGimmu:13143.
UCSCiuc009qen.2. mouse. [Q8VDF3-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB018002 mRNA. Translation: BAA88064.1.
BC022165 mRNA. Translation: AAH22165.1.
AF052942 mRNA. Translation: AAC35002.1.
CCDSiCCDS23303.1. [Q8VDF3-1]
RefSeqiNP_034149.2. NM_010019.3. [Q8VDF3-1]
UniGeneiMm.304472.
Mm.335252.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2YA9X-ray2.30A/B11-370[»]
2YAAX-ray2.30A/B11-370[»]
2YABX-ray1.90A/B11-370[»]
ProteinModelPortaliQ8VDF3.
SMRiQ8VDF3. Positions 13-311.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199051. 1 interaction.
STRINGi10090.ENSMUSP00000034944.

PTM databases

PhosphoSiteiQ8VDF3.

Proteomic databases

MaxQBiQ8VDF3.
PaxDbiQ8VDF3.
PRIDEiQ8VDF3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000034944; ENSMUSP00000034944; ENSMUSG00000032380. [Q8VDF3-1]
GeneIDi13143.
KEGGimmu:13143.
UCSCiuc009qen.2. mouse. [Q8VDF3-1]

Organism-specific databases

CTDi23604.
MGIiMGI:1341297. Dapk2.

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118877.
HOGENOMiHOG000233016.
HOVERGENiHBG100551.
InParanoidiQ8VDF3.
KOiK08803.
OMAiCNHLSRS.
OrthoDBiEOG7QZGBH.
PhylomeDBiQ8VDF3.
TreeFamiTF314166.

Enzyme and pathway databases

ReactomeiREACT_252543. Role of DCC in regulating apoptosis.

Miscellaneous databases

EvolutionaryTraceiQ8VDF3.
NextBioi283226.
PROiQ8VDF3.
SOURCEiSearch...

Gene expression databases

BgeeiQ8VDF3.
CleanExiMM_DAPK2.
GenevestigatoriQ8VDF3.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR020675. Myosin_light_ch_kinase-rel.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR22964. PTHR22964. 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...

Publicationsi

« Hide 'large scale' publications
  1. "Death-associated protein kinase 2 is a new calcium/calmodulin-dependent protein kinase that signals apoptosis through its catalytic activity."
    Kawai T., Nomura F., Hoshino K., Copeland N.G., Gilbert D.J., Jenkins N.A., Akira S.
    Oncogene 18:3471-3480(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  3. "Death-associated protein kinase-related protein 1, a novel serine/threonine kinase involved in apoptosis."
    Inbal B., Shani G., Cohen O., Kissil J.L., Kimchi A.
    Mol. Cell. Biol. 20:1044-1054(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 68-370.
  4. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-299 AND SER-349, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  5. "New modularity of DAP-kinases: alternative splicing of the DRP-1 gene produces a ZIPk-like isoform."
    Shoval Y., Berissi H., Kimchi A., Pietrokovski S.
    PLoS ONE 6:E17344-E17344(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: ALTERNATIVE SPLICING (ISOFORM 2), TISSUE SPECIFICITY.
  6. "Structure of the dimeric autoinhibited conformation of DAPK2, a pro-apoptotic protein kinase."
    Patel A.K., Yadav R.P., Majava V., Kursula I., Kursula P.
    J. Mol. Biol. 409:369-383(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 11-370 IN COMPLEX WITH AMP AND ATP, SUBUNIT, ENZYME REGULATION, AUTOINHIBITORY DOMAIN.

Entry informationi

Entry nameiDAPK2_MOUSE
AccessioniPrimary (citable) accession number: Q8VDF3
Secondary accession number(s): O88861, Q9QYM4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 28, 2003
Last sequence update: March 1, 2002
Last modified: February 4, 2015
This is version 119 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.