Reviewed, UniProtKB/Swiss-Prot O43293 (DAPK3_HUMAN)

Names and origin

Protein names

Recommended 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
    ZIP-kinase

Gene names

Name:	DAPK3
Synonyms:	ZIPK

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	454 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Serine/threonine kinase which acts as a positive regulator of apoptosis. Phosphorylates histone H3 on 'Thr-11' at centromeres during mitosis. Ref.2 Ref.5 Ref.6
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. Ref.2
Cofactor	Magnesium. Ref.2
Subunit structure	Homodimer or forms heterodimers with ATF4. 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. Interacts with AATF and CDC5L. Ref.5 UniProtKB O54784
Subcellular location	Nucleus. CytoplasmBy similarity. Note= Relocates to the cytoplasm on binding PAWR where the complex appears to interact with actin filaments By similarity. Associates to centromeres from prophase to anaphase.
Sequence similarities	Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. DAP kinase subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Chromatin regulator Kinase Serine/threonine-protein kinase Transferase
Technical term	3D-structure
Gene Ontology (GO)
Biological process	chromatin modification Inferred from electronic annotation. Source: UniProtKB-KW induction of apoptosis Ref.1 Ref.5 Inferred from mutant phenotype. Source: UniProtKB protein amino acid phosphorylation Ref.2 Inferred from direct assay. Source: UniProtKB protein kinase cascade Ref.2 Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW nucleus Ref.1 Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	ATP binding Ref.2 Inferred from direct assay. Source: UniProtKB protein binding Ref.5 Inferred from physical interaction. Source: IntAct protein serine/threonine kinase activity Ref.2 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DAXX	Q9UER7	1	EBI-77293,EBI-77321
Daxx	O35613	1	EBI-77293,EBI-77304	From a different organism.
PAWR	Q96IZ0	1	EBI-77293,EBI-595869

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 454

454

Death-associated protein kinase 3

PRO_0000085914

Regions

Domain

13 – 275

263

Protein kinase

Nucleotide binding

19 – 27

9

ATP By similarity UniProtKB P53355

Region

395 – 454

60

Interaction with CDC5L By similarity

Sites

Active site

139

1

Proton acceptor By similarity UniProtKB P53355

Binding site

42

1

ATP By similarity UniProtKB P53355

Natural variations

Natural variant

112

1

T → M in a colorectal adenocarcinoma sample; somatic mutation. Ref.8

VAR_040438

Natural variant

161

1

D → N in an ovarian mucinous carcinoma sample; somatic mutation. Ref.8

VAR_040439

Natural variant

216

1

P → S in a lung neuroendocrine carcinoma sample; somatic mutation. Ref.8

VAR_040440

Secondary structure

1

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454

Helix Strand Turn

Details...

Helix

9 – 12

4

Beta strand

13 – 21

9

Beta strand

23 – 32

10

Turn

33 – 35

3

Beta strand

38 – 46

9

Beta strand

53 – 56

4

Helix

58 – 70

13

Beta strand

79 – 84

6

Beta strand

86 – 94

9

Helix

101 – 108

8

Helix

113 – 132

20

Helix

142 – 144

3

Beta strand

145 – 148

4

Beta strand

150 – 154

5

Beta strand

157 – 159

3

Helix

181 – 183

3

Helix

186 – 189

4

Helix

197 – 212

16

Helix

222 – 230

9

Helix

238 – 241

4

Helix

246 – 253

8

Helix

260 – 262

3

Helix

266 – 271

6

Helix

273 – 280

8

Sequences

	Sequence		Length	Mass (Da)
	O43293-1 [UniParc]. Last modified June 1, 1998. Version 1. Checksum: 56773008A6A61CF0	FASTA	454	52,536
	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

References

	« Hide 'large scale' referencesShow '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: 9488481] [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: 10356987] [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. , 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: 14702039] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[5]	"ZIP kinase triggers apoptosis from nuclear PML oncogenic domains." Kawai T., Akira S., Reed J.C. Mol. Cell. Biol. 23:6174-6186(2003) [PubMed: 12917339] [Abstract] Cited for: FUNCTION, INTERACTION WITH DAXX AND PAWR.
[6]	"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: 12560483] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[7]	"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.
[8]	"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. , 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: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] MET-112; ASN-161 AND SER-216.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

RefSeq

NP_001339.1.

UniGene

Hs.631844

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1YRP	X-ray	3.10	A/B	1-277	[»]
2J90	X-ray	2.00	A/B	9-289	[»]
3BHY	X-ray	1.24	A	9-289	[»]
3BQR	X-ray	1.75	A	9-289	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

O43293. 4 interactions.

PTM databases

PhosphoSite

O43293.

Proteomic databases

PRIDE

O43293.

Genome annotation databases

Ensembl

ENSG00000167657. Homo sapiens. [Contig view]

GeneID

1613.

KEGG

hsa:1613.

Organism-specific databases

GeneCards

GC19M003909.

H-InvDB

HIX0014650.

HGNC

HGNC:2676. DAPK3.

MIM

603289. gene.

PharmGKB

PA27144.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

O43293.

HOVERGEN

O43293.

Gene expression databases

ArrayExpress

O43293.

CleanEx

HS_DAPK3.

GermOnline

ENSG00000167657. Homo sapiens.

Family and domain databases

InterPro

IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_bd_CS.
IPR017442. Se/Thr_pkinase-rel.
IPR008271. Ser_thr_pkin_AS.
IPR002290. Ser_thr_pkinase.
[Graphical view]

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

ProDom

PD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00220. S_TKc. 1 hit.
[Graphical view]

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

LinkHub

O43293.

NextBio

6630.

SOURCE

Search...

Entry information

<

Entry name	DAPK3_HUMAN
Accession	Primary (citable) accession number: O43293 Secondary accession number(s): A0AVN4, B3KQE2
Entry history