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O43293 (DAPK3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 134. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Death-associated protein kinase 3

Short name=DAP kinase 3
EC=2.7.11.1
Alternative name(s):
DAP-like kinase
Short name=Dlk
MYPT1 kinase
Zipper-interacting protein kinase
Short name=ZIP-kinase
Gene names
Name:DAPK3
Synonyms:ZIPK
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length454 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.2 Ref.5 Ref.7 Ref.8 Ref.9 Ref.10 Ref.12 Ref.17 Ref.20 Ref.21 Ref.23 Ref.24

Isoform 2 can phosphorylate myosin, PPP1R12A and MYL12B. Ref.2 Ref.5 Ref.7 Ref.8 Ref.9 Ref.10 Ref.12 Ref.17 Ref.20 Ref.21 Ref.23 Ref.24

Catalytic activity

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

Cofactor

Magnesium. Ref.2

Enzyme regulation

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. Ref.11 Ref.14 Ref.17

Subunit structure

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. Also binds to DAXX and PAWR, possibly in a ternary complex which plays a role in caspase activation. According to Ref.18, does not interact with PARW. Interacts with AATF, CDC5L, 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. Isoform 1 and isoform 2 can interact with myosin and PPP1R12A. Ref.5 Ref.7 Ref.9 Ref.11 Ref.12 Ref.13 Ref.18 Ref.20 Ref.21 Ref.23 Ref.24

Subcellular location

Nucleus. Cytoplasm. NucleusPML body. Chromosomecentromere. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome. Note: The phosphorylated form is anchored in the cytoplasm and/or prevented from being shuttled to the nucleus, whereas nuclear translocation or retention is maximal when it is not phosphorylated. Phosphorylation at Thr-299 promotes cytoplasmic localization. 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. Ref.5 Ref.6 Ref.8 Ref.9 Ref.13 Ref.18 Ref.20 Ref.22

Isoform 2: Nucleus. Cytoplasm Ref.5 Ref.6 Ref.8 Ref.9 Ref.13 Ref.18 Ref.20 Ref.22.

Tissue specificity

Isoform 2 is expressed in the bladder smooth muscle. Ref.5

Post-translational modification

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.

The phosphorylation status is critical for: its intracellular localization, ability to oligomerize and its activity. The phosphorylated form is anchored in the cytoplasm and/or prevented from being shuttled to the nucleus, whereas nuclear translocation or retention is maximal when it is not phosphorylated. 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. Phosphorylation at Thr-299 promotes cytoplasmic localization. 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. Both isoform 1 and isoform 2 can undergo autophosphorylation. Ref.5 Ref.9 Ref.11 Ref.14 Ref.16 Ref.17 Ref.22

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.

Sequence similarities

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

Contains 1 protein kinase domain.

Biophysicochemical properties

Kinetic parameters:

KM=12 µM for myosin (isoform 2) Ref.5

KM=6.2 µM for myosin (isoform 1)

KM=73 µM for MYL12B (isoform 2)

KM=10.4 µM for MYL12B (isoform 1)

Vmax=248 nmol/min/mg enzyme toward myosin (isoform 2)

Vmax=120 nmol/min/mg enzyme toward myosin (isoform 1)

Vmax=1.3 µmol/min/mg enzyme toward MYL12B (isoform 2)

Vmax=271 nmol/min/mg enzyme toward MYL12B (isoform 1)

Ontologies

Keywords
   Biological processApoptosis
Transcription
Transcription regulation
Translation regulation
   Cellular componentCentromere
Chromosome
Cytoplasm
Cytoskeleton
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandATP-binding
Nucleotide-binding
   Molecular functionActivator
Chromatin regulator
Kinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic process

Inferred from direct assay PubMed 10580117. Source: UniProtKB

apoptotic signaling pathway

Inferred from electronic annotation. Source: Ensembl

cellular response to interferon-gamma

Inferred from direct assay Ref.10. Source: UniProtKB

chromatin modification

Inferred from electronic annotation. Source: UniProtKB-KW

cytokinesis

Traceable author statement. Source: UniProtKB

intracellular signal transduction

Inferred from direct assay Ref.2. Source: UniProtKB

negative regulation of translation

Inferred from direct assay Ref.10. Source: UniProtKB

neuron differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of canonical Wnt signaling pathway

Inferred from mutant phenotype Ref.23. Source: UniProtKB

positive regulation of extrinsic apoptotic signaling pathway in absence of ligand

Inferred from electronic annotation. Source: Ensembl

protein autophosphorylation

Inferred from direct assay Ref.11. Source: UniProtKB

protein phosphorylation

Inferred from direct assay Ref.2. Source: UniProtKB

regulation of actin cytoskeleton reorganization

Traceable author statement. Source: UniProtKB

regulation of apoptotic process

Traceable author statement Ref.15. Source: UniProtKB

regulation of autophagy

Traceable author statement Ref.15. Source: UniProtKB

regulation of cell motility

Traceable author statement. Source: UniProtKB

regulation of mitosis

Traceable author statement. Source: UniProtKB

regulation of smooth muscle contraction

Traceable author statement. Source: UniProtKB

regulation of transcription, DNA-templated

Traceable author statement. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentPML body

Inferred from electronic annotation. Source: UniProtKB-SubCell

chromosome, centromeric region

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

microtubule organizing center

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionATP binding

Inferred from direct assay Ref.2. Source: UniProtKB

calmodulin-dependent protein kinase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

identical protein binding

Inferred from physical interaction Ref.11. Source: IntAct

leucine zipper domain binding

Inferred from physical interaction PubMed 10580117. Source: UniProtKB

protein homodimerization activity

Inferred from direct assay Ref.11. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from direct assay Ref.2Ref.11. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

itself2EBI-77293,EBI-77293

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O43293-1)

Also known as: ZIPK-L;

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: O43293-2)

Also known as: ZIPK-S;

The sequence of this isoform differs from the canonical sequence as follows:
     313-322: LPPNNSYADF → ASPIVAPVDA
     323-454: Missing.
Note: The internal splice site between exon 8 and the 3' UTR, which yields this truncated isoform, is non-canonical.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 454454Death-associated protein kinase 3
PRO_0000085914

Regions

Domain13 – 275263Protein kinase
Nucleotide binding19 – 279ATP By similarity UniProtKB P53355
Region161 – 20444Activation segment By similarity
Region276 – 33358Interaction with AR
Region278 – 31134Interaction with MYPT1
Region395 – 45460Interaction with CDC5L By similarity
Region427 – 44115Leucine-zipper

Sites

Active site1391Proton acceptor By similarity UniProtKB P53355
Binding site421ATP Probable UniProtKB P53355
Binding site941Inhibitor
Binding site961Inhibitor

Amino acid modifications

Modified residue501Phosphoserine; by autocatalysis Ref.11
Modified residue1801Phosphothreonine Ref.14 Ref.17
Modified residue2251Phosphothreonine Ref.14
Modified residue2651Phosphothreonine; by autocatalysis and ROCK1 Ref.11 Ref.14 Ref.16 Ref.17
Modified residue2991Phosphothreonine; by autocatalysis, DAPK1 and ROCK1 Ref.9 Ref.14 Ref.17 Ref.22
Modified residue3061Phosphothreonine; by autocatalysis Ref.14
Modified residue3091Phosphoserine; by DAPK1 Ref.9
Modified residue3111Phosphoserine; by autocatalysis and DAPK1 Ref.9 Ref.14
Modified residue3121Phosphoserine; by DAPK1 Ref.9
Modified residue3181Phosphoserine; by DAPK1 Ref.9
Modified residue3261Phosphoserine; by DAPK1 Ref.9

Natural variations

Alternative sequence313 – 32210LPPNNSYADF → ASPIVAPVDA in isoform 2.
VSP_042059
Alternative sequence323 – 454132Missing in isoform 2.
VSP_042060
Natural variant1121T → M in a colorectal adenocarcinoma sample; somatic mutation. Ref.26
VAR_040438
Natural variant1611D → N in an ovarian mucinous carcinoma sample; somatic mutation. Ref.26
VAR_040439
Natural variant2161P → S in a lung neuroendocrine carcinoma sample; somatic mutation. Ref.26
VAR_040440

Experimental info

Mutagenesis421K → A: Loss of kinase activity at low concentrations of ATP. Ref.17
Mutagenesis1611D → A: Loss of kinase activity. Ref.17
Mutagenesis2251T → A: Loss of kinase activity. Ref.17
Mutagenesis2651T → A: Loss of phosphorylation by ROCK1, catalytically inactive. Ref.17
Mutagenesis2991T → A: Loss of phosphorylation by ROCK1. Ref.17

Secondary structure

................................................ 454
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (ZIPK-L) [UniParc].

Last modified June 1, 1998. Version 1.
Checksum: 56773008A6A61CF0

FASTA45452,536
        10         20         30         40         50         60 
MSTFRQEDVE DHYEMGEELG SGQFAIVRKC RQKGTGKEYA AKFIKKRRLS SSRRGVSREE 

        70         80         90        100        110        120 
IEREVNILRE IRHPNIITLH DIFENKTDVV LILELVSGGE LFDFLAEKES LTEDEATQFL 

       130        140        150        160        170        180 
KQILDGVHYL HSKRIAHFDL KPENIMLLDK NVPNPRIKLI DFGIAHKIEA GNEFKNIFGT 

       190        200        210        220        230        240 
PEFVAPEIVN YEPLGLEADM WSIGVITYIL LSGASPFLGE TKQETLTNIS AVNYDFDEEY 

       250        260        270        280        290        300 
FSNTSELAKD FIRRLLVKDP KRRMTIAQSL EHSWIKAIRR RNVRGEDSGR KPERRRLKTT 

       310        320        330        340        350        360 
RLKEYTIKSH SSLPPNNSYA DFERFSKVLE EAAAAEEGLR ELQRSRRLCH EDVEALAAIY 

       370        380        390        400        410        420 
EEKEAWYREE SDSLGQDLRR LRQELLKTEA LKRQAQEEAK GALLGTSGLK RRFSRLENRY 

       430        440        450 
EALAKQVASE MRFVQDLVRA LEQEKLQGVE CGLR 

« Hide

Isoform 2 (ZIPK-S) [UniParc].

Checksum: 616983FE83F8DDA6
Show »

FASTA32237,048

References

« Hide 'large scale' references
[1]"ZIP kinase, a novel serine/threonine kinase which mediates apoptosis."
Kawai T., Matsumoto M., Takeda K., Sanjo H., Akira S.
Mol. Cell. Biol. 18:1642-1651(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"ZIP kinase identified as a novel myosin regulatory light chain kinase in HeLa cells."
Murata-Hori M., Suizu F., Iwasaki T., Kikuchi A., Hosoya H.
FEBS Lett. 451:81-84(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
Tissue: Cervix carcinoma.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]"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: Brain.
[5]"Novel ZIP kinase isoform lacks leucine zipper."
Takamoto N., Komatsu S., Komaba S., Niiro N., Ikebe M.
Arch. Biochem. Biophys. 456:194-203(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 165-454 (ISOFORM 2), ALTERNATIVE SPLICING, FUNCTION IN PHOSPHORYLATION OF MYOSIN; PPP1R12A AND MYL12B, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, INTERACTION WITH PPP1R12A AND MYOSIN, AUTOPHOSPHORYLATION, TISSUE SPECIFICITY.
Tissue: Urinary bladder.
[6]"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.
[7]"ZIP kinase triggers apoptosis from nuclear PML oncogenic domains."
Kawai T., Akira S., Reed J.C.
Mol. Cell. Biol. 23:6174-6186(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH DAXX AND PAWR.
[8]"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.
[9]"Death-associated protein kinase phosphorylates ZIP kinase, forming a unique kinase hierarchy to activate its cell death functions."
Shani G., Marash L., Gozuacik D., Bialik S., Teitelbaum L., Shohat G., Kimchi A.
Mol. Cell. Biol. 24:8611-8626(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION AT THR-299; SER-309; SER-311; SER-312; SER-318 AND SER-326, INTERACTION WITH DAPK1, SUBCELLULAR LOCATION.
[10]"DAPK-ZIPK-L13a axis constitutes a negative-feedback module regulating inflammatory gene expression."
Mukhopadhyay R., Ray P.S., Arif A., Brady A.K., Kinter M., Fox P.L.
Mol. Cell 32:371-382(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"Activation segment dimerization: a mechanism for kinase autophosphorylation of non-consensus sites."
Pike A.C., Rellos P., Niesen F.H., Turnbull A., Oliver A.W., Parker S.A., Turk B.E., Pearl L.H., Knapp S.
EMBO J. 27:704-714(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 9-289 IN COMPLEX WITH PYRIDONE 6, ENZYME REGULATION, SUBUNIT, PHOSPHORYLATION AT SER-50 AND THR-265.
[12]"Physical and functional interactions between STAT3 and ZIP kinase."
Sato N., Kawai T., Sugiyama K., Muromoto R., Imoto S., Sekine Y., Ishida M., Akira S., Matsuda T.
Int. Immunol. 17:1543-1552(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF STAT3, INTERACTION WITH STAT3.
[13]"TCP10L is expressed specifically in spermatogenic cells and binds to death associated protein kinase-3."
Yu H., Jiang D., Guo Z., Saiyin H., Guo J., Wang X., Yu L.
Int. J. Androl. 28:163-170(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TCP10L, SUBCELLULAR LOCATION.
[14]"Regulation of zipper-interacting protein kinase activity in vitro and in vivo by multisite phosphorylation."
Graves P.R., Winkfield K.M., Haystead T.A.
J. Biol. Chem. 280:9363-9374(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-180; THR-225; THR-265; THR-299; THR-306 AND SER-311, ENZYME REGULATION.
[15]"The death-associated protein kinases: structure, function, and beyond."
Bialik S., Kimchi A.
Annu. Rev. Biochem. 75:189-210(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[16]"Phosphorylation of threonine-265 in zipper-interacting protein kinase plays an important role in its activity and is induced by IL-6 family cytokines."
Sato N., Kamada N., Muromoto R., Kawai T., Sugiyama K., Watanabe T., Imoto S., Sekine Y., Ohbayashi N., Ishida M., Akira S., Matsuda T.
Immunol. Lett. 103:127-134(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-265.
[17]"ROCK1 phosphorylates and activates zipper-interacting protein kinase."
Hagerty L., Weitzel D.H., Chambers J., Fortner C.N., Brush M.H., Loiselle D., Hosoya H., Haystead T.A.
J. Biol. Chem. 282:4884-4893(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION, AUTOPHOSPHORYLATION, PHOSPHORYLATION AT THR-180; THR-265 AND THR-299, MUTAGENESIS OF LYS-42; ASP-161; THR-225; THR-265 AND THR-299.
[18]"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, ABSENCE OF INTERACTION WITH PARW.
[19]"Dlk/ZIP kinase, a novel Ser/Thr-specific protein kinase with multiple functions."
Scheidtmann K.H.
Signal Transduct. 7:248-259(2007)
Cited for: REVIEW ON FUNCTION.
[20]"Physical and functional interactions between ZIP kinase and UbcH5."
Ohbayashi N., Okada K., Kawakami S., Togi S., Sato N., Ikeda O., Kamitani S., Muromoto R., Sekine Y., Kawai T., Akira S., Matsuda T.
Biochem. Biophys. Res. Commun. 372:708-712(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH UBE2D1; UBE2D2 AND UBE2D3, FUNCTION, SUBCELLULAR LOCATION.
[21]"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, INTERACTION WITH AR.
[22]"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: PHOSPHORYLATION AT THR-299, SUBCELLULAR LOCATION.
[23]"Zipper-interacting protein kinase (ZIPK) modulates canonical Wnt/beta-catenin signaling through interaction with Nemo-like kinase and T-cell factor 4 (NLK/TCF4)."
Togi S., Ikeda O., Kamitani S., Nakasuji M., Sekine Y., Muromoto R., Nanbo A., Oritani K., Kawai T., Akira S., Matsuda T.
J. Biol. Chem. 286:19170-19177(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH NLK AND TCF7L2.
[24]"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: FUNCTION, INTERACTION WITH ATF4.
[25]"Crystal structure of human ZIP kinase."
Kursula P., Vahokoski J., Wilmanns M.
Submitted (JUN-2006) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 1-277.
[26]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] MET-112; ASN-161 AND SER-216.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB007144 mRNA. Translation: BAA24955.1.
AB022341 mRNA. Translation: BAA81746.1.
AK074799 mRNA. Translation: BAG52004.1.
BC126430 mRNA. Translation: AAI26431.1.
BC126432 mRNA. Translation: AAI26433.1.
AB265224 mRNA. Translation: BAF34614.1.
CCDSCCDS12116.1. [O43293-1]
RefSeqNP_001339.1. NM_001348.1. [O43293-1]
XP_005259565.1. XM_005259508.1. [O43293-1]
XP_005259566.1. XM_005259509.1. [O43293-1]
UniGeneHs.631844.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1YRPX-ray3.10A/B1-277[»]
2J90X-ray2.00A/B9-289[»]
3BHYX-ray1.24A9-289[»]
3BQRX-ray1.75A9-289[»]
ProteinModelPortalO43293.
SMRO43293. Positions 2-277.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107983. 18 interactions.
IntActO43293. 8 interactions.
MINTMINT-6505325.
STRING9606.ENSP00000301264.

Chemistry

BindingDBO43293.
ChEMBLCHEMBL2468.
GuidetoPHARMACOLOGY2004.

PTM databases

PhosphoSiteO43293.

Proteomic databases

MaxQBO43293.
PaxDbO43293.
PRIDEO43293.

Protocols and materials databases

DNASU1613.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000301264; ENSP00000301264; ENSG00000167657. [O43293-1]
ENST00000545797; ENSP00000442973; ENSG00000167657. [O43293-1]
GeneID1613.
KEGGhsa:1613.
UCSCuc002lzc.1. human. [O43293-1]

Organism-specific databases

CTD1613.
GeneCardsGC19M003958.
HGNCHGNC:2676. DAPK3.
HPAHPA028569.
MIM603289. gene.
neXtProtNX_O43293.
PharmGKBPA27144.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233016.
HOVERGENHBG101549.
InParanoidO43293.
KOK08803.
OMALENRYEV.
OrthoDBEOG7QZGBH.
PhylomeDBO43293.
TreeFamTF314166.

Enzyme and pathway databases

ReactomeREACT_578. Apoptosis.
SignaLinkO43293.

Gene expression databases

ArrayExpressO43293.
BgeeO43293.
CleanExHS_DAPK3.
GenevestigatorO43293.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR020675. Myosin_light_ch_kinase-rel.
IPR000719. Prot_kinase_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. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSDAPK3. human.
EvolutionaryTraceO43293.
GeneWikiDAPK3.
GenomeRNAi1613.
NextBio6630.
PROO43293.
SOURCESearch...

Entry information

Entry nameDAPK3_HUMAN
AccessionPrimary (citable) accession number: O43293
Secondary accession number(s): A0AVN4, B3KQE2, Q05JY4
Entry history
Integrated into UniProtKB/Swiss-Prot: November 28, 2003
Last sequence update: June 1, 1998
Last modified: July 9, 2014
This is version 134 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM