Reviewed, UniProtKB/Swiss-Prot Q9UIK4 (DAPK2_HUMAN)

Names and origin

Protein names

Recommended name:
    Death-associated protein kinase 2
      Short name=DAP kinase 2
    EC=2.7.11.1
Alternative name(s):
    DAP-kinase-related protein 1
      Short name=DRP-1

Gene names

Name:

DAPK2

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	370 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Calcium/calmodulin-dependent serine/threonine kinase which acts as a positive regulator of apoptosis. Ref.1 Ref.2 Ref.4
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium. Ref.1 Ref.2 Ref.4
Enzyme regulation	Negatively regulated by autophosphorylation on Ser-318. Ref.1 Ref.4 UniProtKB P53355
Subunit structure	Homodimer. Homodimerization is required for apoptotic function and is inhibited by autophosphorylation at Ser-318. Ref.2 Ref.4
Subcellular location	Cytoplasm Ref.2.
Tissue specificity	Ubiquitously expressed in all tissue types examined. High levels in heart, lung and skeletal muscle. Ref.1
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
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Calmodulin-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	apoptosis Inferred from electronic annotation. Source: UniProtKB-KW induction of apoptosis Ref.1 Ref.2 Inferred from mutant phenotype. Source: UniProtKB protein amino acid phosphorylation Ref.1 Ref.2 Inferred from direct assay. Source: UniProtKB protein kinase cascade Ref.1 Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasm Ref.1 Ref.2 Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Ref.1 Inferred from direct assay. Source: UniProtKB calmodulin binding Ref.1 Inferred from direct assay. Source: UniProtKB calmodulin-dependent protein kinase activity Ref.2 Traceable author statement. Source: ProtInc identical protein binding Ref.2 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		1	EBI-77154,EBI-77154

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 370

370

Death-associated protein kinase 2

PRO_0000085912

Regions

Domain

23 – 285

263

Protein kinase

Nucleotide binding

29 – 37

9

ATP By similarity UniProtKB P53355

Region

277 – 344

68

Calmodulin-binding Ref.1

Sites

Active site

149

1

Proton acceptor By similarity UniProtKB P53355

Binding site

52

1

ATP Ref.1 Ref.2

Amino acid modifications

Modified residue

299

1

Phosphoserine By similarity

Modified residue

318

1

Phosphoserine; by autocatalysis Ref.4

Modified residue

349

1

Phosphoserine Ref.5 Ref.6

Natural variations

Natural variant

60

1

R → W: dbSNP rs56047843. Ref.7

VAR_040436

Natural variant

271

1

R → W: dbSNP rs34270163. Ref.7

VAR_040437

Experimental info

Mutagenesis

52

1

K → A: Loss of activity, apoptotic function and of autophosphorylation. Ref.1 Ref.2 Ref.4

Mutagenesis

299 – 330

32

Missing: Loss of ca(2+)-calmodulin binding, increase in activity, loss of autophosphorylation. Ref.1 Ref.4

Mutagenesis

299

1

S → A: No effect on Ca(2+)-calmodulin independent phosphorylation or apoptotic activity. Ref.4

Mutagenesis

318

1

S → A: Loss of Ca(2+)-calmodulin independent phosphorylation, increase in apoptotic activity. Ref.4

Mutagenesis

318

1

S → D: Abolishes apoptotic activity. Ref.4

Mutagenesis

320

1

S → A: No effect on Ca(2+)-calmodulin independent phosphorylation or apoptotic activity. Ref.4

Mutagenesis

323

1

S → A: No effect on Ca(2+)-calmodulin independent phosphorylation or apoptotic activity. Ref.4

Mutagenesis

329

1

T → A: No effect on Ca(2+)-calmodulin independent phosphorylation or apoptotic activity. Ref.4

Sequence conflict

241

1

A → S in AAC35001. Ref.2

Sequence conflict

253

1

Q → H in AAC35001. Ref.2

Secondary structure

1

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370

Helix Strand Turn

Details...

Helix

19 – 22

4

Beta strand

23 – 31

9

Beta strand

33 – 42

10

Turn

43 – 45

3

Beta strand

48 – 56

9

Beta strand

58 – 61

4

Beta strand

63 – 66

4

Helix

68 – 80

13

Beta strand

89 – 94

6

Beta strand

96 – 103

8

Helix

111 – 116

6

Helix

123 – 142

20

Helix

152 – 154

3

Beta strand

155 – 158

4

Beta strand

162 – 164

3

Beta strand

167 – 169

3

Helix

191 – 193

3

Helix

196 – 199

4

Helix

207 – 222

16

Helix

232 – 240

9

Helix

248 – 251

4

Helix

256 – 263

8

Turn

270 – 272

3

Helix

276 – 281

6

Turn

283 – 285

3

Helix

290 – 298

9

Helix

303 – 312

10

Turn

320 – 324

5

Sequences

	Sequence		Length	Mass (Da)
	Q9UIK4-1 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 035E914BBCD881A2	FASTA	370	42,898
	10 20 30 40 50 60 MFQASMRSPN MEPFKQQKVE DFYDIGEELG SGQFAIVKKC REKSTGLEYA AKFIKKRQSR 70 80 90 100 110 120 ASRRGVSREE IEREVSILRQ VLHHNVITLH DVYENRTDVV LILELVSGGE LFDFLAQKES 130 140 150 160 170 180 LSEEEATSFI KQILDGVNYL HTKKIAHFDL KPENIMLLDK NIPIPHIKLI DFGLAHEIED 190 200 210 220 230 240 GVEFKNIFGT PEFVAPEIVN YEPLGLEADM WSIGVITYIL LSGASPFLGD TKQETLANIT 250 260 270 280 290 300 AVSYDFDEEF FSQTSELAKD FIRKLLVKET RKRLTIQEAL RHPWITPVDN QQAMVRRESV 310 320 330 340 350 360 VNLENFRKQY VRRRWKLSFS IVSLCNHLTR SLMKKVHLRP DEDLRNCESD TEEDIARRKA 370 LHPRRRSSTS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Death-associated protein kinase 2 is a new calcium/calmodulin-dependent protein kinase that signals apoptosis through its catalytic activity." Kawai T., Nomura F., Hoshino K., Copeland N.G., Gilbert D.J., Jenkins N.A., Akira S. Oncogene 18:3471-3480(1999) [PubMed: 10376525] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ENZYME REGULATION, TISSUE SPECIFICITY, MUTAGENESIS OF LYS-52. Tissue: Skeletal muscle.
[2]	"Death-associated protein kinase-related protein 1, a novel serine/threonine kinase involved in apoptosis." Inbal B., Shani G., Cohen O., Kissil J.L., Kimchi A. Mol. Cell. Biol. 20:1044-1054(2000) [PubMed: 10629061] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, HOMODIMERIZATION, MUTAGENESIS OF LYS-52. Tissue: Kidney.
[3]	"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].
[4]	"Autophosphorylation restrains the apoptotic activity of DRP-1 kinase by controlling dimerization and calmodulin binding." Shani G., Henis-Korenblit S., Jona G., Gileadi O., Eisenstein M., Ziv T., Admon A., Kimchi A. EMBO J. 20:1099-1113(2001) [PubMed: 11230133] [Abstract] Cited for: FUNCTION, HOMODIMERIZATION, MUTAGENESIS OF LYS-52; SER-299; SER-318; SER-320; SER-323 AND THR-329, PHOSPHORYLATION AT SER-318.
[5]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-349, MASS SPECTROMETRY. Tissue: Epithelium.
[6]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-349, MASS SPECTROMETRY.
[7]	"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] TRP-60 AND TRP-271.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB018001 mRNA. Translation: BAA88063.1.
AF052941 mRNA. Translation: AAC35001.1.
BC114506 mRNA. Translation: AAI14507.1.

IPI

IPI00033388.

RefSeq

NP_055141.2.

UniGene

Hs.237886

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WMK	X-ray	3.60	A/B/C/D/E/F/G/H	11-330	[»]
1WRZ	X-ray	2.00	B	312-330	[»]
1Z9X	X-ray	3.93	A/B/C	11-330	[»]
1ZWS	X-ray	2.90	A/B/C/D/E/F/G/H	11-297	[»]
2A27	X-ray	3.00	A/B/C/D/E/F/G/H	11-330	[»]
2A2A	X-ray	1.47	A/B/C/D	11-330	[»]
2CKE	X-ray	2.80	A/B/C/D	11-330	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9UIK4. 1 interaction.

STRING

Q9UIK4.

PTM databases

PhosphoSite

Q9UIK4.

Proteomic databases

PRIDE

Q9UIK4.

Genome annotation databases

Ensembl

ENST00000261891; ENSP00000261891; ENSG00000035664; Homo sapiens. [Genome view]
ENST00000457488; ENSP00000408277; ENSG00000035664; Homo sapiens. [Genome view]

GeneID

23604.

KEGG

hsa:23604.

UCSC

uc002amr.1. human.

Organism-specific databases

CTD

23604.

GeneCards

GC15M061986.

H-InvDB

HIX0019168.

HGNC

HGNC:2675. DAPK2.

PharmGKB

PA27143.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG05364.

HOGENOM

HBG755340.

HOVERGEN

Q9UIK4.

InParanoid

Q9UIK4.

OMA

HPWIMPV.

OrthoDB

EOG9ZW7WM.

PhylomeDB

Q9UIK4.

Enzyme and pathway databases

BRENDA

2.7.11.1. 247.

Gene expression databases

ArrayExpress

Q9UIK4.

Bgee

Q9UIK4.

CleanEx

HS_DAPK2.

Genevestigator

Q9UIK4.

GermOnline

ENSG00000035664. Homo sapiens.

Family and domain databases

InterPro

IPR020676. Death-assoc_prot_kinase.
IPR011009. Kinase-like_dom.
IPR020675. Myosin_light_chain_kin-rel.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_prot_kinase-like_dom.
IPR008271. Ser/Thr_prot_kinase_AS.
IPR002290. Ser/Thr_prot_kinase_dom.
[Graphical view]

PANTHER

PTHR22964:SF1. Death-assoc_prot_kinase. 1 hit.
PTHR22964. Myosin_light_chain_kin-rel. 1 hit.

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

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

NextBio

46296.

Entry information

Entry name

DAPK2_HUMAN

Accession

Primary (citable) accession number: Q9UIK4
Secondary accession number(s): O75892, Q24JS1

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 28, 2003
Last sequence update:	May 1, 2000
Last modified:	January 19, 2010
This is version 92 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.