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Q8VDF3 (DAPK2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
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to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Death-associated protein kinase 2
Short name=DAP kinase 2
EC=2.7.11.1
Alternative name(s):
DAP-kinase-related protein 1
Short name=DRP-1
Gene names
Name:Dapk2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length370 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. UniProtKB P53355 UniProtKB Q9UIK4

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium By similarity. UniProtKB P53355

Enzyme regulation

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. Ref.7

Subunit structure

Homodimer in its autoinhibited state. Active as monomer. Ref.7

Subcellular location

Cytoplasm By similarity. Cytoplasmic vesicle › autophagosome lumen By similarity UniProtKB Q9UIK4.

Tissue specificity

Isoform 1 is found in the adult brain while isoform 2 is expressed in brains of embryos and young mice (at protein level). Ref.6

Domain

The autoinhibitory domain sterically blocks the substrate peptide-binding site by making both hydrophobic and electrostatic contacts with the kinase core. Ref.7

Post-translational modification

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

Sequence similarities

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. DAP kinase subfamily.

Contains 1 protein kinase domain.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8VDF3-1)

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.
Isoform 2 (identifier: Q8VDF3-2)

Also known as: Beta;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 370370Death-associated protein kinase 2
PRO_0000085913

Regions

Domain23 – 285263Protein kinase
Nucleotide binding29 – 379ATP UniProtKB P53355
Region287 – 35468Calmodulin-binding By similarity UniProtKB P53355
Region292 – 30110Autoinhibitory domain

Sites

Active site1491Proton acceptor By similarity UniProtKB P53355
Binding site521ATP UniProtKB P53355

Amino acid modifications

Modified residue2991Phosphoserine Ref.5
Modified residue3181Phosphoserine; by autocatalysis By similarity UniProtKB P53355
Modified residue3491Phosphoserine Ref.4

Natural variations

Alternative sequence286 – 37085TPVDT…RSSTS → SKGEARAPEQWKAQPAQLKT KRLREYTLKCHSSMPPNNTY VNFERFAHVVEDVARVDKGC RALAGAHDTLQDDVESLVSI YNEKEAWYREENENARHNLS QLKYEYRKVESLKKLLREDI QATGASLGGVARKLDHLQAQ FETLRQQLSADIQWMQELVG IFQLESENTDSHSLGFMFHR DPSESLSELLNRSHAEEVLA GLSL in isoform 2.
VSP_042058

Experimental info

Sequence conflict891L → R in AAC35002. Ref.3
Sequence conflict901H → Q in BAA88064. Ref.1
Sequence conflict2701T → P in AAC35002. Ref.3
Sequence conflict3411S → I in AAC35002. Ref.3

Secondary structure

1 ..................................................... 370
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Alpha) [UniParc].

Last modified March 1, 2002. Version 1.
Checksum: 7BF8577140B5F883

FASTA37042,778
        10         20         30         40         50         60 
MVQASMRSPN METFKQQKVE DFYDIGEELG SGQFAIVKKC REKSTGLEYA AKFIKKRQSR 

        70         80         90        100        110        120 
ASRRGVCREE IEREVSILRQ VLHPNIITLH DVYENRTDVV LILELVSGGE LFDFLAQKES 

       130        140        150        160        170        180 
LSEEEATSFI KQILDGVNYL HTKKIAHFDL KPENIMLLDK NIPIPHIKLI DFGLAHEIED 

       190        200        210        220        230        240 
GVEFKNIFGT PEFVAPEIVN YEPLGLEADM WSIGVITYIL LSGASPFLGD TKQETLANIT 

       250        260        270        280        290        300 
AVSYDFDEEF FSQTSELAKD FIRKLLVKET RKRLTIQEAL RHPWITPVDT QQAMVRRESV 

       310        320        330        340        350        360 
VNLENFKKQY VRRRWKLSFS IVSLCNHLTR SLMKKVHLRT SEDLRNCESD TEENIARRKA 

       370 
LHPRRRSSTS

« Hide

Isoform 2 (Beta) [UniParc].

Checksum: DB08AE634C47ABFC
Show »

FASTA48956,035

References

« Hide 'large scale' references
[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]"Protein phosphorylation and expression profiling by Yin-yang multidimensional liquid chromatography (Yin-yang MDLC) mass spectrometry."
Dai J., Jin W.-H., Sheng Q.-H., Shieh C.-H., Wu J.-R., Zeng R.
J. Proteome Res. 6:250-262(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-349, MASS SPECTROMETRY.
Tissue: Liver.
[5]"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry."
Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M.
J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-299, MASS SPECTROMETRY.
Tissue: Melanoma.
[6]"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.
[7]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AB018002 mRNA. Translation: BAA88064.1.
BC022165 mRNA. Translation: AAH22165.1.
AF052942 mRNA. Translation: AAC35002.1.
IPIIPI00123234.
RefSeqNP_034149.2. NM_010019.3.
UniGeneMm.304472.
Mm.335252.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2YA9X-ray2.30A/B11-370[»]
2YAAX-ray2.30A/B11-370[»]
2YABX-ray1.90A/B11-370[»]
ProteinModelPortalQ8VDF3.
SMRQ8VDF3. Positions 13-311.
ModBaseSearch...

Protein-protein interaction databases

STRING10090.ENSMUSP00000034944.

PTM databases

PhosphoSiteQ8VDF3.

Proteomic databases

PaxDbQ8VDF3.
PRIDEQ8VDF3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000034944; ENSMUSP00000034944; ENSMUSG00000032380.
GeneID13143.
KEGGmmu:13143.
UCSCuc009qen.2. mouse.

Organism-specific databases

CTD23604.
MGIMGI:1341297. Dapk2.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00680000099521.
HOGENOMHOG000233016.
HOVERGENHBG100551.
InParanoidQ8VDF3.
KOK08803.
OMAYARRRWK.
OrthoDBEOG4894MS.

Enzyme and pathway databases

ReactomeREACT_100962. Apoptosis.

Gene expression databases

BgeeQ8VDF3.
CleanExMM_DAPK2.
GenevestigatorQ8VDF3.
GermOnlineENSMUSG00000032380. Mus musculus.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR020675. Myosin_light_ch_kinase-rel.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERPTHR22964. PTHR22964. 1 hit.
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. Kinase_like. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ8VDF3.
NextBio283226.
SOURCESearch...

Entry information

Entry nameDAPK2_MOUSE
AccessionPrimary (citable) accession number: Q8VDF3
Secondary accession number(s): O88861, Q9QYM4
Entry history
Integrated into UniProtKB/Swiss-Prot: November 28, 2003
Last sequence update: March 1, 2002
Last modified: April 3, 2013
This is version 103 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents