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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 and actin cytoskeleton reorganization. Regulates both type I (caspase-dependent) apoptotic and type II (caspase-independent) autophagic cell deaths signal, depending on the cellular setting. Involved in formation of promyelocytic leukemia protein nuclear body (PML-NB). Involved in apoptosis involving PAWR which mediates cytoplasmic relocation; in vitro phosphorylates PAWR. Phosphorylates MYL12B in non-muscle cells leading to reorganization of actin cytoskeleton such as in regulation of cell polarity and cell migration. Positively regulates canonical Wnt/beta-catenin signaling through interaction with NLK and TCF7L2; disrupts the NLK-TCF7L2 complex thereby influencing the phosphorylation of TCF7L2 by NLK. Phosphorylates RPL13A on 'Ser-77' upon interferon-gamma activation which is causing RPL13A release from the ribosome, RPL13A association with the GAIT complex and its subsequent involvement in transcript-selective translation inhibition (By similarity). Phosphorylates STAT3 and enhances its transcriptional activity (By similarity). Enhances transcription from AR-responsive promoters in a hormone- and kinase-dependent manner. Phosphorylates histone H3 on 'Thr-11' at centromeres during mitosis.By similarity6 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.4 Publications

Cofactori

Mg2+2 Publications

Enzyme regulationi

A sequential activation is proposed: autophosphorylation at consensus sites is leading to dimerization of the catalytic domain and activation segment exchange (producing an active confirmation of both kinase modules in trans) followed by phosphorylation at Thr-180 in the activation segment and at other regulatory sites (Probable). Phosphorylation at Thr-180, Thr-225 and Thr-265 is essential for activity. Inhibited by pyridone 6 (K00225), a potent, ATP-competitive inhibitor. Phosphorylation at Thr-180, Thr-225 and Thr-265 is essential for 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:2.7.11.14 Publications)
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 5 Publications. NucleusPML body 1 Publication. Cytoplasm 1 Publication. Cytoplasmcytoskeletonmicrotubule organizing center 1 Publication. Chromosomecentromere 2 Publications. Cytoplasmcytoskeleton 1 Publication
Note: Predominantly localized to the nucleus. Relocates to the cytoplasm on binding PAWR where the complex appears to interact with actin filaments (Probable). Associated with the centrosomes throughout the mitotic cell cycle, with the centromeres from prophase to anaphase and with the contractile ring during cytokinesis.2 Publications1 Publication

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, loss of PAWR-linked translocation into the cytoplasm; maintains nuclear localization but loss of localization to PML-NB. 2 Publications
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
Mutagenesisi406 – 4072RR → AL: Cytoplasmic localization. 1 Publication

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; alternateBy similarity
Modified residuei265 – 2651Phosphothreonine; by ROCK1; alteranteBy 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 kinase activity, oligomerization and intracellular localization. Phosphorylation at Thr-180, Thr-225 and Thr-265 is essential for activity. The phosphorylated form is localized in the cytoplasm and nuclear translocation or retention is maximal when it is not phosphorylated. Phosphorylation increases the trimeric form, and its dephosphorylation favors a kinase-inactive monomeric form.By similarity

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

Homooligomer in its kinase-active form (homotrimers and homodimers are reported); monomeric in its kinase-inactive form. Homodimerization is required for activation segment autophosphorylation (By similarity). Interacts with DAXX, ATF4, NLK, TCF7L2, UBE2D1, UBE2D2, UBE2D3 and CDC5L. Interacts with PAWR; also demonstrated in aorta smooth muscle cells indicative for the cytoskeletal targeting function of PAWR. Interacts with AR; enhanced by AATF.By similarity6 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
Regioni390 – 44859Interaction with CDC5L1 PublicationAdd
BLAST
Regioni418 – 44831Required for interaction with ATF4 but not with PAWR1 PublicationAdd
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:
EMBLi
GenBanki
DDBJi
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]
XP_008763351.1. XM_008765129.1. [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:
EMBLi
GenBanki
DDBJi
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 ]
XP_008763351.1. XM_008765129.1. [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, CATALYTIC ACTIVITY, 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. "C-terminal truncation of Dlk/ZIP kinase leads to abrogation of nuclear transport and high apoptotic activity."
    Koegel D., Bierbaum H., Preuss U., Scheidtmann K.H.
    Oncogene 18:7212-7218(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF 406-ARG-ARG-407.
  5. "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 IN APOPTOSIS, CATALYTIC ACTIVITY, INTERACTION WITH ATF4 AND PAWR, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-42.
  6. "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, CATALYTIC ACTIVITY.
  7. "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.
  8. "DAP-like kinase, a member of the death-associated protein kinase family, associates with centrosomes, centromers, and the contractile ring during mitosis."
    Preuss U., Bierbaum H., Buchenau P., Scheidtmann K.H.
    Eur. J. Cell Biol. 82:447-459(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  9. "Novel mitosis-specific phosphorylation of histone H3 at Thr11 mediated by Dlk/ZIP kinase."
    Preuss U., Landsberg G., Scheidtmann K.H.
    Nucleic Acids Res. 31:878-885(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  10. "ZIP kinase is responsible for the phosphorylation of myosin II and necessary for cell motility in mammalian fibroblasts."
    Komatsu S., Ikebe M.
    J. Cell Biol. 165:243-254(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF MYL12B, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY.
  11. "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.
  12. "ZIP kinase plays a crucial role in androgen receptor-mediated transcription."
    Leister P., Felten A., Chasan A.I., Scheidtmann K.H.
    Oncogene 27:3292-3300(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN ANDROGEN RECEPTOR-MEDIATED TRANSCRIPTION, INTERACTION WITH AR.
  13. "The pro-apoptotic protein Par-4 facilitates vascular contractility by cytoskeletal targeting of ZIPK."
    Vetterkind S., Morgan K.G.
    J. Cell. Mol. Med. 13:887-895(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PAWR.
  14. "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: November 26, 2014
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

Miscellaneous

A species-specific loss of a key phosphorylation site in murine DAPK3 seems to direct it mainly to the nucleus which is proposed to be compensated by the interaction with PAWR to maintain at least the cytoplasmic basic membrane blebbing function in the apoptosis pathway.1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3