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O88764

- DAPK3_RAT

UniProt

O88764 - DAPK3_RAT

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Protein

Death-associated protein kinase 3

Gene

Dapk3

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

Serine/threonine kinase which is involved in the regulation of apoptosis, autophagy, transcription, translation, actin cytoskeleton reorganization, cell motility, smooth muscle contraction, and mitosis, particularly cytokinesis. 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. Regulates myosin phosphorylation in both smooth muscle and non-muscle cells. In smooth muscle, regulates myosin either directly by phosphorylating MYL12B and MYL9 or through inhibition of smooth muscle myosin phosphatase (SMPP1M) via phosphorylation of PPP1R12A, and the inhibition of SMPP1M functions to enhance muscle responsiveness to Ca2+ and promote a contractile state. Enhances transcription from AR-responsive promoters in a hormone- and kinase-dependent manner. Phosphorylates STAT3 and enhances its transcriptional activity. Positively regulates the canonical Wnt/beta-catenin signaling through interaction with NLK and TCF7L2. Can disrupt the NLK-TCF7L2 complex thereby influencing the phosphorylation of TCF7L2 by NLK. Phosphorylates histone H3 on 'Thr-11' at centromeres during mitosis. Involved in the formation of promyelocytic leukemia protein nuclear body (PML-NB), one of many subnuclear domains in the eukaryotic cell nucleus, and which is involved in oncogenesis and viral infection. Phosphorylates RPL13A on 'Ser-77' upon interferon-gamma activation which is causing RPL13A release from the ribosome, its association with the GAIT complex and its subsequent involvement in transcript-selective translation inhibition (By similarity).By similarity

Catalytic activityi

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

Cofactori

Magnesium.2 Publications

Enzyme regulationi

Inhibited by pyridone 6 (K00225), a potent, ATP-competitive inhibitor. Phosphorylation at Thr-180, Thr-225 and Thr-265 is essential for activity. Oligomerization is required for full enzymatic activity (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei42 – 421ATPCurated
Binding sitei94 – 941InhibitorBy similarity
Binding sitei96 – 961InhibitorBy similarity
Active sitei139 – 1391Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi19 – 279ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB
  2. calmodulin-dependent protein kinase activity Source: RefGenome
  3. protein homodimerization activity Source: UniProtKB
  4. protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  1. apoptotic process Source: UniProtKB
  2. apoptotic signaling pathway Source: Ensembl
  3. cellular response to interferon-gamma Source: Ensembl
  4. chromatin modification Source: UniProtKB-KW
  5. intracellular signal transduction Source: UniProtKB
  6. negative regulation of translation Source: Ensembl
  7. neuron differentiation Source: RGD
  8. positive regulation of canonical Wnt signaling pathway Source: Ensembl
  9. positive regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: UniProtKB
  10. protein autophosphorylation Source: UniProtKB
  11. regulation of transcription, DNA-templated Source: UniProtKB-KW
  12. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator, Chromatin regulator, Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, Transcription, Transcription regulation

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Death-associated protein kinase 3 (EC:2.7.11.1)
Short name:
DAP kinase 3
Alternative name(s):
DAP-like kinase
Short name:
Dlk
MYPT1 kinase
ZIP-kinase
Gene namesi
Name:Dapk3
Synonyms:Zipk
OrganismiRattus norvegicus (Rat)Imported
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Unplaced

Organism-specific databases

RGDi621766. Dapk3.

Subcellular locationi

Nucleus. Cytoplasm. NucleusPML body By similarity. Chromosomecentromere. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome By similarity
Note: Relocates to the cytoplasm on binding PAWR where the complex appears to interact with actin filaments. Localizes to promyelocytic leukemia protein nuclear bodies (PML-NBs). Associated: with the centrosomes throughout the mitotic cell cycle, with the centromeres from prophase to anaphase and with the contractile ring during cytokinesis (By similarity).By similarity

GO - Cellular componenti

  1. chromosome, centromeric region Source: UniProtKB-KW
  2. cytoplasm Source: UniProtKB-KW
  3. cytoskeleton Source: UniProtKB-KW
  4. membrane raft Source: UniProtKB
  5. nucleus Source: UniProtKB
  6. PML body Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Centromere, Chromosome, Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi42 – 421K → A: Loss of kinase activity and of translocation into the cytoplasm. 1 Publication
Mutagenesisi294 – 2941A → T: Causes dissociation from promyelocytic leukemia oncogenic bodies and increased blebbing-inducing potency; when associated with T-300. 1 Publication
Mutagenesisi295 – 2951A → T: Causes dissociation from promyelocytic leukemia oncogenic bodies and increased blebbing-inducing potency; when associated with T-299. 1 Publication
Mutagenesisi418 – 44831Missing: Prevents binding to ATF4 but not PAWR. Add
BLAST

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 448448Death-associated protein kinase 3PRO_0000085916Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei180 – 1801PhosphothreonineBy similarity
Modified residuei225 – 2251PhosphothreonineBy similarity
Modified residuei265 – 2651Phosphothreonine; by autocatalysis and ROCK1By similarity
Modified residuei304 – 3041Phosphoserine; by DAPK1By similarity
Modified residuei306 – 3061Phosphoserine; by autocatalysis and DAPK1By similarity
Modified residuei307 – 3071Phosphoserine; by DAPK1By similarity
Modified residuei313 – 3131Phosphoserine; by DAPK1By similarity
Modified residuei321 – 3211Phosphoserine; by DAPK1By similarity

Post-translational modificationi

Ubiquitinated. Ubiquitination mediated by the UBE2D3 E3 ligase does not lead to proteasomal degradation, but influences promyelocytic leukemia protein nuclear bodies (PML-NBs) formation in the nucleus (By similarity).By similarity
The phosphorylation status is critical for its activity and its ability to oligomerize. Phosphorylation increases the trimeric form, and its dephosphorylation shifts the equilibrium towards the monomeric form. Phosphorylation at Thr-180, Thr-225 and Thr-265 is essential for activity. A species-specific loss of a key phosphorylation site in murine DAPK3 seems to direct it to the nucleus, while the presence of the 'Thr-299' site in human DAPK3 correlates with cytoplasmic localization.

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiO88764.

Expressioni

Tissue specificityi

Ubiquitously expressed in all tissue types examined. High levels in brain, heart, lung and spleen, lower expression in kidney, liver, skeletal muscle and testis. Isoform 2 is expressed in the smooth muscle.1 Publication

Gene expression databases

GenevestigatoriO88764.

Interactioni

Subunit structurei

Monomer and homotrimer. Can also exist as homodimer or form heterodimers with ATF4. Homodimerization is required for activation segment autophosphorylation. Both interactions require an intact leucine zipper domain and oligomerization is required for full enzymatic activity. Interacts with UBE2D1, UBE2D2 AND UBE2D3. Interacts with AR and this interaction is enhanced by AATF. Interacts (via leucine zipper) with TCP10L (via leucine zipper). Interacts (via kinase domain) with DAPK1 (via kinase domain). Interacts with STAT3, NLK and TCF7L2 (By similarity). Also binds to DAXX and PAWR, possibly in a ternary complex which plays a role in caspase activation. Interacts with AATF and CDC5L.By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
PawrQ626275EBI-4404236,EBI-1187240

Protein-protein interaction databases

BioGridi249061. 5 interactions.
IntActiO88764. 5 interactions.

Structurei

3D structure databases

ProteinModelPortaliO88764.
SMRiO88764. Positions 2-276.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini13 – 275263Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni161 – 20444Activation segmentBy similarityAdd
BLAST
Regioni276 – 32853Interaction with ARBy similarityAdd
BLAST
Regioni277 – 30630Interaction with MYPT1By similarityAdd
BLAST
Regioni390 – 44859Interaction with CDC5LAdd
BLAST
Regioni422 – 43615Leucine-zipperBy similarityAdd
BLAST

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000233016.
HOVERGENiHBG101549.
InParanoidiO88764.
KOiK08803.
PhylomeDBiO88764.
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: O88764-1) [UniParc]FASTAAdd to Basket

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
MSTFRQEDVE DHYEMGEELG SGQFAIVRKC QQKGTGMEYA AKFIKKRRLP
60 70 80 90 100
SSRRGVSREE IEREVSILRE IRHPNIITLH DVFENKTDVV LILELVSGGE
110 120 130 140 150
LFDFLAEKES LTEDEATQFL KQILDGVHYL HSKRIAHFDL KPENIMLLDK
160 170 180 190 200
HAASPRIKLI DFGIAHRIEA GSEFKNIFGT PEFVAPEIVN YEPLGLEADM
210 220 230 240 250
WSIGVITYIL LSGASPFLGE TKQETLTNIS AVNYDFDEEY FSSTSELAKD
260 270 280 290 300
FIRRLLVKDP KRRMTIAQSL EHSWIKVRRR EDGARKPERR RLRAARLREY
310 320 330 340 350
SLKSHSSMPR NTSYASFERF SRVLEDVAAA EQGLRELQRG RRQCRERVCA
360 370 380 390 400
LRVAAEQREA RCRDGSAGLG RDLRRLRTEL GRTEALRTRA QEEARAALLG
410 420 430 440
AGGLKRRLCR LENRYDALAA QVAAEVQFVR DLVRALEQER LQAECGVR
Length:448
Mass (Da):51,450
Last modified:November 1, 1998 - v1
Checksum:i843C0FD0BF0C1EEA
GO
Isoform 2 (identifier: O88764-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MIDSSCVPRILQKDSAMM

Show »
Length:465
Mass (Da):53,326
Checksum:i1AC035BCAB567234
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 11M → MIDSSCVPRILQKDSAMM in isoform 2. CuratedVSP_042061

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AJ006971 mRNA. Translation: CAA07360.1.
BC062076 mRNA. Translation: AAH62076.1.
RefSeqiNP_071991.1. NM_022546.1. [O88764-1]
XP_006241055.1. XM_006240993.2. [O88764-1]
UniGeneiRn.60353.

Genome annotation databases

GeneIDi64391.
KEGGirno:64391.
UCSCiRGD:621766. rat. [O88764-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AJ006971 mRNA. Translation: CAA07360.1 .
BC062076 mRNA. Translation: AAH62076.1 .
RefSeqi NP_071991.1. NM_022546.1. [O88764-1 ]
XP_006241055.1. XM_006240993.2. [O88764-1 ]
UniGenei Rn.60353.

3D structure databases

ProteinModelPortali O88764.
SMRi O88764. Positions 2-276.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 249061. 5 interactions.
IntActi O88764. 5 interactions.

Proteomic databases

PaxDbi O88764.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 64391.
KEGGi rno:64391.
UCSCi RGD:621766. rat. [O88764-1 ]

Organism-specific databases

CTDi 1613.
RGDi 621766. Dapk3.

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000233016.
HOVERGENi HBG101549.
InParanoidi O88764.
KOi K08803.
PhylomeDBi O88764.
TreeFami TF314166.

Miscellaneous databases

NextBioi 613146.
PROi O88764.

Gene expression databases

Genevestigatori O88764.

Family and domain databases

InterProi IPR011009. 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 ]
PANTHERi PTHR22964. PTHR22964. 1 hit.
Pfami PF00069. Pkinase. 1 hit.
[Graphical view ]
SMARTi SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and characterization of Dlk, a novel serine/threonine kinase that is tightly associated with chromatin and phosphorylates core histones."
    Koegel D., Ploettner O., Landsberg G., Christian S., Scheidtmann K.H.
    Oncogene 17:2645-2654(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
  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].
    Tissue: Prostate.
  3. "AATF -- a novel transcription factor that interacts with Dlk/ZIP kinase and interferes with apoptosis."
    Page G., Loedige I., Kogel D., Scheidtmann K.H.
    FEBS Lett. 462:187-191(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH AATF.
  4. "Interaction partners of Dlk/ZIP kinase: co-expression of Dlk/ZIP kinase and Par-4 results in cytoplasmic retention and apoptosis."
    Page G., Kogel D., Rangnekar V., Scheidtmann K.H.
    Oncogene 18:7265-7273(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH ATF4 AND PAWR, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-42.
  5. "Zipper-interacting protein kinase induces Ca(2+)-free smooth muscle contraction via myosin light chain phosphorylation."
    Niiro N., Ikebe M.
    J. Biol. Chem. 276:29567-29574(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: ALTERNATIVE SPLICING (ISOFORM 2), FUNCTION IN PHOSPHORYLATION OF MYL12B AND PPP1R12A.
  6. "DAP-like kinase interacts with the rat homolog of Schizosaccharomyces pombe CDC5 protein, a factor involved in pre-mRNA splicing and required for G2/M phase transition."
    Engemann H., Heinzel V., Page G., Preuss U., Scheidtmann K.H.
    Nucleic Acids Res. 30:1408-1417(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CDC5L.
  7. "ZIPK: a unique case of murine-specific divergence of a conserved vertebrate gene."
    Shoval Y., Pietrokovski S., Kimchi A.
    PLoS Genet. 3:1884-1893(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, INTERACTION WITH PAWR, MUTAGENESIS OF ALA-294 AND ALA-295.
  8. "Phosphorylation-dependent control of ZIPK nuclear import is species specific."
    Weitzel D.H., Chambers J., Haystead T.A.
    Cell. Signal. 23:297-303(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.

Entry informationi

Entry nameiDAPK3_RAT
AccessioniPrimary (citable) accession number: O88764
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 28, 2003
Last sequence update: November 1, 1998
Last modified: October 29, 2014
This is version 118 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

The murine DAPK3 protein differs from the human ortholog, losing an important phosphorylation site and displaying distinct altered cellular localization. The murine protein localizes only to the nucleus while the human protein shows both nuclear and cytoplasmic localization. A different protein interaction capacity, with an important protein partner in the apoptosis pathway (PAWR), evolved in the murine system to maintain the basic membrane blebbing function in the apoptosis pathway.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3