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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

DAPK3 Gene

protein-coding GIFtS: 64
GCID: GC19M003958

death-associated protein kinase 3

Explore 10 diseases affiliated with
DAPK3 via

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(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Death-Associated Protein Kinase 3¹ ²		MYPT1 Kinase² ³
ZIPK¹ ² ³ ⁵		EC 2.7.11.1³ ⁸
ZIP¹ ²		Dlk³
Zipper-Interacting Protein Kinase² ³		ZIP Kinase Isoform²
ZIP-Kinase¹		Dlk³
DAP Kinase 3² ³		EC 2.7.11⁸
DAP-Like Kinase² ³

External Ids:	HGNC: 2676¹	Entrez Gene: 1613²	Ensembl: ENSG00000167657⁷	OMIM: 603289⁵	UniProtKB: O43293³

Export aliases for DAPK3 gene to outside databases

Previous GC identifers: GC19M004050 GC19M003898 GC19M003909 GC19M003721

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for DAPK3:

Death-associated protein kinase 3 (DAPK3) induces morphological changes in apoptosis when overexpressed in mammalian

cells. These results suggest that DAPK3 may play a role in the induction of apoptosis. (provided by RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: DAPK3_HUMAN, O43293

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 Ca(2+) 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

Function: Isoform 2 can phosphorylate myosin, PPP1R12A and MYL12B

Gene Wiki entry for DAPK3

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000019.9 NC_018930.1 NT_011255.14

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the DAPK3 gene promoter:
Sp1 p53 NRSF form 1 c-Myb STAT3 STAT5A NRSF form 2
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): DAPK3 promoter sequence

Search SABiosciences Chromatin IP Primers for DAPK3

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat DAPK3

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 19p13.3 Ensembl cytogenetic band: 19p13.3 HGNC cytogenetic band: 19p13.3

DAPK3 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
DAPK3 gene location

GeneLoc information about chromosome 19 GeneLoc Exon Structure

GeneLoc location for GC19M003958: view genomic region (about GC identifiers)

Start:	3,958,452 bp from pter	End:	3,971,038 bp from pter
Size:	12,587 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: DAPK3_HUMAN, O43293 (See protein sequence)

Recommended Name: Death-associated protein kinase 3

Size: 454 amino acids; 52536 Da

Cofactor: Magnesium

Subunit: 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 PubMed:17953487, 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

Subcellular location: Nucleus. Cytoplasm. Nucleus, PML body. Chromosome, centromere. Cytoplasm, cytoskeleton,

centrosome. 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

Subcellular location: Isoform 2: Nucleus. Cytoplasm

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

4 PDB 3D structures from and Proteopedia for DAPK3:

1YRP (3D)

2J90 (3D)

3BHY (3D)

3BQR (3D)

Secondary accessions: A0AVN4 B3KQE2 Q05JY4

Alternative splicing: 2 isoforms: O43293-1 O43293-2 (The internal splice site between exon 8 and the 3' UTR, which yields this truncated isoform, is non-canonical)

Explore the universe of human proteins at neXtProt for DAPK3: NX_O43293

Post-translational modifications:

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 nucleus¹

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 autophosphorylation¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_O43293

4/9 DME Specific Peptides for DAPK3 (O43293) (see all 9)

IRRLLVKD

GVITYILL

GTPEFVAPE

TSELAKDFIR

DAPK3 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins: NP_001339.1

ENSEMBL proteins:

ENSP00000301264 ENSP00000442973

Reactome Protein details: O43293
Human Recombinant Protein Products:

	EMD Millipore Purified and/or Recombinant DAPK3 Protein
	Browse R&D Systems for human recombinant proteins
	Browse recombinant and purified proteins available from Enzo Life Sciences
	OriGene Purified Protein: DAPK3 Browse OriGene Protein Over-expression Lysates OriGene Custom Protein Services for DAPK3
	GenScript Custom Purified and Recombinant Proteins Services for DAPK3
	Novus Biologicals DAPK3 Proteins
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Uscn Proteins for DAPK3

Gene Ontology (GO): 5 cellular component terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000775	chromosome, centromeric region	IEA	--
GO:0005634	nucleus	ISS	--
GO:0005737	cytoplasm	IEA	--
GO:0005815	microtubule organizing center	IEA	--
GO:0016605	PML body	IEA	--

DAPK3 for ontologies About GeneDecksing

DAPK3 Antibody Products:

	Browse EMD Millipore's Extensive Line of Mono- and Polyclonal Antibodies
	R&D Systems Antibodies for DAPK3 (DAPK3/ZIPK)
	Cell Signaling Technology (CST) Antibodies for DAPK3
	OriGene Antibodies (see all 3): DAPK3 OriGene Custom Antibody Services for DAPK3
	GenScript Custom Superior Antibodies Services for DAPK3
	Novus Biologicals DAPK3 Antibodies
	Abcam antibodies for DAPK3
	Uscn Antibodies for DAPK3
	ThermoFisher Antibodies for DAPK3

Assay Products for DAPK3:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for DAPK3
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for DAPK3

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

DAPK3 for domains About GeneDecksing

5/6 InterPro domains/families (see all 6):

IPR017441 Protein_kinase_ATP_BS

IPR002290 Ser/Thr_dual-sp_kinase_dom

IPR011009 Kinase-like_dom

IPR008271 Ser/Thr_kinase_AS

IPR000719 Prot_kinase_cat_dom

Graphical View of Domain Structure for InterPro Entry O43293

ProtoNet protein and cluster: O43293

UniProtKB/Swiss-Prot: DAPK3_HUMAN, O43293

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

Similarity: Contains 1 protein kinase domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary: