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P53355 (DAPK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 158. 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·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Death-associated protein kinase 1

Short name=DAP kinase 1
EC=2.7.11.1
Gene names
Name:DAPK1
Synonyms:DAPK
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1430 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. 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. Phosphorylates PIN1 resulting in inhibition of its catalytic activity, nuclear localization, and cellular function. Phosphorylates TPM1, enhancing stress fiber formation in endothelial cells. Phosphorylates STX1A and significantly decreases its binding to STXBP1. Phosphorylates PRKD1 and regulates JNK signaling by binding and activating PRKD1 under oxidative stress. Phosphorylates BECN1, reducing its interaction with BCL2 and BCL2L1 and promoting the induction of autophagy. Phosphorylates TSC2, disrupting the TSC1-TSC2 complex and stimulating mTORC1 activity in a growth factor-dependent pathway. Phosphorylates RPS6, MYL9 and DAPK3. Acts as a signaling amplifier of NMDA receptors at extrasynaptic sites for mediating brain damage in stroke. Cerebral ischemia recruits DAPK1 into the NMDA receptor complex and it phosphorylates GRINB at Ser-1303 inducing injurious Ca2+ influx through NMDA receptor channels, resulting in an irreversible neuronal death. Required together with DAPK3 for phosphorylation of RPL13A upon interferon-gamma activation which is causing RPL13A involvement in transcript-selective translation inhibition. Ref.1 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.30 Ref.31

Isoform 2 cannot induce apoptosis but can induce membrane blebbing. Ref.1 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.30 Ref.31

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium.

Enzyme regulation

Activated by Ca2+/calmodulin. Regulated by a locking mechanism, involving autophosphorylation at Ser-308 and calmodulin binding. In the inactive state, Ser-308 is phosphorylated. Activation involves its dephosphorylation and a release-of-autoinhibition mechanism where binding of calmodulin induces a conformational change that relieves the steric block of the active site by the autoinhibitory domain. Activity is modulated by UNC5B and NTN1. UNC5B activates it by inhibiting the phosphorylation at Ser-308, whereas NTN1 inhibits UNC5B-mediated activation of DAPK1. Endoplasmic-stress activates by causing Ser-308 dephosphorylation. Ref.11 Ref.18 Ref.20

Subunit structure

Interacts with KLHL20. Interacts (via death domain) with MAPK1 and MAPK3. Interacts with MAP1B (via N-terminus). Interacts (via death domain) with UNC5B (via death domain). Interacts with PRKD1 in an oxidative stress-regulated manner. Interacts with PIN1, PDCD6, BECN1, GRINB, TSC2 and STX1A. Interacts (via kinase domain) with DAPK3 (via kinase domain). Ref.13 Ref.14 Ref.15 Ref.17 Ref.18 Ref.21 Ref.24 Ref.26 Ref.27 Ref.28 Ref.30

Subcellular location

Isoform 1: Cytoplasm. Cytoplasmcytoskeleton Ref.10 Ref.12 Ref.23 Ref.24. Note: Colocalizes with MAP1B in the microtubules and cortical actin fibers. Ref.10 Ref.12 Ref.23 Ref.24

Isoform 2: Cytoplasm. Cytoplasmcytoskeleton Ref.10 Ref.12 Ref.23 Ref.24.

Tissue specificity

Isoform 2 is expressed in normal intestinal tissue as well as in colorectal carcinomas. Ref.23

Induction

Up-regulated following treatment with IFNG/IFN-gamma. Ref.1 Ref.11 Ref.18 Ref.20

Domain

The autoinhibitory domain sterically blocks the substrate peptide-binding site by making both hydrophobic and electrostatic contacts with the kinase core.

Post-translational modification

Ubiquitinated by the BCR(KLHL20) E3 ubiquitin ligase complex, leading to its degradation by the proteasome. Ref.28

Removal of the C-terminal tail of isoform 2 (corresponding to amino acids 296-337 of isoform 2)by proteolytic cleavage stimulates maximally its membrane-blebbing function.

In response to mitogenic stimulation (PMA or EGF), phosphorylated at Ser-289; phosphorylation suppresses DAPK1 pro-apoptotic function. Autophosphorylation at Ser-308 inhibits its catalytic activity. Phosphorylation at Ser-734 by MAPK1 increases its catalytic activity and promotes cytoplasmic retention of MAPK1. Endoplasmic-stress can cause dephosphorylation at Ser-308. Ref.11 Ref.16 Ref.17 Ref.18 Ref.20

Sequence similarities

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

Contains 10 ANK repeats.

Contains 1 death domain.

Contains 1 protein kinase domain.

Sequence caution

The sequence AAP35581.1 differs from that shown. Reason: Contaminating sequence. Sequence of unknown origin in the C-terminal part.

The sequence CAA53712.1 differs from that shown. Reason: Frameshift at positions 462 and 464.

Ontologies

Keywords
   Biological processApoptosis
Translation regulation
   Cellular componentCytoplasm
Cytoskeleton
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainANK repeat
Repeat
   LigandATP-binding
Calmodulin-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic process

Inferred from mutant phenotype Ref.10. Source: UniProtKB

apoptotic signaling pathway

Inferred from mutant phenotype Ref.1. Source: UniProtKB

cellular response to interferon-gamma

Inferred from direct assay Ref.25. Source: UniProtKB

extrinsic apoptotic signaling pathway via death domain receptors

Inferred from electronic annotation. Source: Ensembl

intracellular signal transduction

Inferred from direct assay Ref.10. Source: UniProtKB

negative regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of extrinsic apoptotic signaling pathway via death domain receptors

Inferred from electronic annotation. Source: Ensembl

negative regulation of translation

Inferred from direct assay Ref.25. Source: UniProtKB

positive regulation of apoptotic process

Traceable author statement. Source: Reactome

protein autophosphorylation

Inferred from direct assay Ref.10. Source: UniProtKB

protein phosphorylation

Inferred from direct assay Ref.10. Source: UniProtKB

regulation of N-methyl-D-aspartate selective glutamate receptor activity

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of apoptotic process

Traceable author statement Ref.19. Source: UniProtKB

regulation of autophagy

Traceable author statement Ref.19. Source: UniProtKB

   Cellular_componentactin cytoskeleton

Inferred from direct assay Ref.10. Source: UniProtKB

cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from direct assay Ref.10. Source: UniProtKB

calmodulin binding

Inferred from direct assay Ref.10. Source: UniProtKB

calmodulin-dependent protein kinase activity

Inferred from direct assay Ref.10. Source: UniProtKB

identical protein binding

Inferred from physical interaction Ref.26PubMed 19712061PubMed 21738225. Source: IntAct

protein kinase activity

Inferred from direct assay Ref.1. Source: MGI

protein serine/threonine kinase activity

Traceable author statement Ref.19. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P53355-1)

Also known as: Alpha;

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: P53355-2)

Also known as: s-DAPK-1;

The sequence of this isoform differs from the canonical sequence as follows:
     1-446: Missing.
     742-783: VSVSINNLYP...LEVFVAPTHH → GRNLHAGPVS...SLGLYWTLWP
     784-1430: Missing.
Isoform 3 (identifier: P53355-3)

Also known as: Beta;

The sequence of this isoform differs from the canonical sequence as follows:
     1430-1430: R → RRNSHVWNPTV

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 14301430Death-associated protein kinase 1
PRO_0000085910

Regions

Domain13 – 275263Protein kinase
Repeat378 – 40730ANK 1
Repeat411 – 44030ANK 2
Repeat444 – 47330ANK 3
Repeat477 – 50630ANK 4
Repeat510 – 53930ANK 5
Repeat543 – 57230ANK 6
Repeat576 – 60530ANK 7
Repeat609 – 63830ANK 8
Repeat875 – 90430ANK 9
Repeat1162 – 119635ANK 10
Domain1312 – 139685Death
Nucleotide binding19 – 279ATP
Nucleotide binding94 – 963ATP
Region267 – 33468Calmodulin-binding
Region292 – 30110Autoinhibitory domain By similarity

Sites

Active site1391Proton acceptor By similarity
Binding site421ATP
Binding site1001ATP
Binding site1611ATP

Amino acid modifications

Modified residue2891Phosphoserine; by RPS6KA1 and RPS6KA3 Ref.16
Modified residue3081Phosphoserine; by autocatalysis Ref.11 Ref.18 Ref.20
Modified residue3331Phosphoserine Ref.32
Modified residue7341Phosphoserine; by MAPK1 Ref.17

Natural variations

Alternative sequence1 – 446446Missing in isoform 2.
VSP_042053
Alternative sequence742 – 78342VSVSI…APTHH → GRNLHAGPVSPAGVGFRTLS FQGLGGKGVVFGSLGLYWTL WP in isoform 2.
VSP_042054
Alternative sequence784 – 1430647Missing in isoform 2.
VSP_042055
Alternative sequence14301R → RRNSHVWNPTV in isoform 3.
VSP_042056
Natural variant4161V → I. Ref.37
Corresponds to variant rs12343465 [ dbSNP | Ensembl ].
VAR_033235
Natural variant4611A → S. Ref.37
VAR_040420
Natural variant5191S → A. Ref.37
VAR_040421
Natural variant5401C → Y. Ref.37
Corresponds to variant rs56327474 [ dbSNP | Ensembl ].
VAR_040422
Natural variant5911P → L. Ref.5
VAR_060693
Natural variant6221I → M. Ref.5
Corresponds to variant rs36215047 [ dbSNP | Ensembl ].
VAR_060694
Natural variant9411M → T. Ref.37
VAR_040423
Natural variant9771R → W. Ref.37
VAR_040424
Natural variant9781K → N. Ref.37
VAR_040425
Natural variant9931Y → C. Ref.37
VAR_040426
Natural variant9941D → E. Ref.37
VAR_040427
Natural variant10051E → Q. Ref.37
VAR_040428
Natural variant10071D → Y. Ref.37
VAR_040429
Natural variant10081L → P. Ref.37
VAR_040430
Natural variant10101R → C. Ref.37
VAR_040431
Natural variant10181T → A. Ref.37
VAR_040432
Natural variant12721M → I. Ref.37
Corresponds to variant rs56169226 [ dbSNP | Ensembl ].
VAR_040433
Natural variant13461S → N. Ref.1 Ref.4 Ref.5 Ref.6 Ref.37
Corresponds to variant rs1056719 [ dbSNP | Ensembl ].
VAR_040434
Natural variant14051G → V. Ref.5 Ref.37
Corresponds to variant rs36220450 [ dbSNP | Ensembl ].
VAR_040435

Experimental info

Mutagenesis421K → A: Loss of activity, apoptotic function and of autophosphorylation. Ref.1 Ref.11
Mutagenesis2891S → A: Loss of phosphorylation and significant increase in proapoptotic activity.
Mutagenesis2891S → E: Reduction in proapoptotic activity.
Mutagenesis3081S → A: Elevated Ca(2+)-calmodulin binding and Ca(2+)-calmodulin-independent kinase activity. Increases apoptotic activity. Ref.11
Mutagenesis3081S → D: Reduced Ca(2+)-calmodulin binding and Ca(2+)-calmodulin-independent kinase activity. Decreases apoptotic activity. Ref.11
Mutagenesis3131S → A: Minimal effect on activity. Ref.11
Sequence conflict4901Y → H in BAC87163. Ref.3
Sequence conflict12171S → G in CAH18690. Ref.4

Secondary structure

............................................................... 1430
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Alpha) [UniParc].

Last modified January 11, 2011. Version 6.
Checksum: E2C4246E7C78A6D2

FASTA1,430160,046
        10         20         30         40         50         60 
MTVFRQENVD DYYDTGEELG SGQFAVVKKC REKSTGLQYA AKFIKKRRTK SSRRGVSRED 

        70         80         90        100        110        120 
IEREVSILKE IQHPNVITLH EVYENKTDVI LILELVAGGE LFDFLAEKES LTEEEATEFL 

       130        140        150        160        170        180 
KQILNGVYYL HSLQIAHFDL KPENIMLLDR NVPKPRIKII DFGLAHKIDF GNEFKNIFGT 

       190        200        210        220        230        240 
PEFVAPEIVN YEPLGLEADM WSIGVITYIL LSGASPFLGD TKQETLANVS AVNYEFEDEY 

       250        260        270        280        290        300 
FSNTSALAKD FIRRLLVKDP KKRMTIQDSL QHPWIKPKDT QQALSRKASA VNMEKFKKFA 

       310        320        330        340        350        360 
ARKKWKQSVR LISLCQRLSR SFLSRSNMSV ARSDDTLDEE DSFVMKAIIH AINDDNVPGL 

       370        380        390        400        410        420 
QHLLGSLSNY DVNQPNKHGT PPLLIAAGCG NIQILQLLIK RGSRIDVQDK GGSNAVYWAA 

       430        440        450        460        470        480 
RHGHVDTLKF LSENKCPLDV KDKSGEMALH VAARYGHADV AQLLCSFGSN PNIQDKEEET 

       490        500        510        520        530        540 
PLHCAAWHGY YSVAKALCEA GCNVNIKNRE GETPLLTASA RGYHDIVECL AEHGADLNAC 

       550        560        570        580        590        600 
DKDGHIALHL AVRRCQMEVI KTLLSQGCFV DYQDRHGNTP LHVACKDGNM PIVVALCEAN 

       610        620        630        640        650        660 
CNLDISNKYG RTPLHLAANN GILDVVRYLC LMGASVEALT TDGKTAEDLA RSEQHEHVAG 

       670        680        690        700        710        720 
LLARLRKDTH RGLFIQQLRP TQNLQPRIKL KLFGHSGSGK TTLVESLKCG LLRSFFRRRR 

       730        740        750        760        770        780 
PRLSSTNSSR FPPSPLASKP TVSVSINNLY PGCENVSVRS RSMMFEPGLT KGMLEVFVAP 

       790        800        810        820        830        840 
THHPHCSADD QSTKAIDIQN AYLNGVGDFS VWEFSGNPVY FCCYDYFAAN DPTSIHVVVF 

       850        860        870        880        890        900 
SLEEPYEIQL NQVIFWLSFL KSLVPVEEPI AFGGKLKNPL QVVLVATHAD IMNVPRPAGG 

       910        920        930        940        950        960 
EFGYDKDTSL LKEIRNRFGN DLHISNKLFV LDAGASGSKD MKVLRNHLQE IRSQIVSVCP 

       970        980        990       1000       1010       1020 
PMTHLCEKII STLPSWRKLN GPNQLMSLQQ FVYDVQDQLN PLASEEDLRR IAQQLHSTGE 

      1030       1040       1050       1060       1070       1080 
INIMQSETVQ DVLLLDPRWL CTNVLGKLLS VETPRALHHY RGRYTVEDIQ RLVPDSDVEE 

      1090       1100       1110       1120       1130       1140 
LLQILDAMDI CARDLSSGTM VDVPALIKTD NLHRSWADEE DEVMVYGGVR IVPVEHLTPF 

      1150       1160       1170       1180       1190       1200 
PCGIFHKVQV NLCRWIHQQS TEGDADIRLW VNGCKLANRG AELLVLLVNH GQGIEVQVRG 

      1210       1220       1230       1240       1250       1260 
LETEKIKCCL LLDSVCSTIE NVMATTLPGL LTVKHYLSPQ QLREHHEPVM IYQPRDFFRA 

      1270       1280       1290       1300       1310       1320 
QTLKETSLTN TMGGYKESFS SIMCFGCHDV YSQASLGMDI HASDLNLLTR RKLSRLLDPP 

      1330       1340       1350       1360       1370       1380 
DPLGKDWCLL AMNLGLPDLV AKYNTSNGAP KDFLPSPLHA LLREWTTYPE STVGTLMSKL 

      1390       1400       1410       1420       1430 
RELGRRDAAD FLLKASSVFK INLDGNGQEA YASSCNSGTS YNSISSVVSR 

« Hide

Isoform 2 (s-DAPK-1) [UniParc].

Checksum: 3BA58BA79D87E0C6
Show »

FASTA33736,765
Isoform 3 (Beta) [UniParc].

Checksum: D43BB6B6A3F0ABF9
Show »

FASTA1,440161,237

References

« Hide 'large scale' references
[1]"Identification of a novel serine/threonine kinase and a novel 15-kD protein as potential mediators of the gamma interferon-induced cell death."
Deiss L.P., Feinstein E., Berissi H., Cohen O., Kimchi A.
Genes Dev. 9:15-30(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INDUCTION, MUTAGENESIS OF LYS-42, VARIANT ASN-1346.
[2]Feinstein E.
Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION TO 164-171.
[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] (ISOFORM 2).
Tissue: Placenta.
[4]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ASN-1346.
Tissue: Amygdala.
[5]NIEHS SNPs program
Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LEU-591; MET-622; ASN-1346 AND VAL-1405.
[6]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ASN-1346.
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"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] (ISOFORM 1).
Tissue: Cerebellum.
[9]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-363.
[10]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[11]"The pro-apoptotic function of death-associated protein kinase is controlled by a unique inhibitory autophosphorylation-based mechanism."
Shohat G., Spivak-Kroizman T., Cohen O., Bialik S., Shani G., Berissi H., Eisenstein M., Kimchi A.
J. Biol. Chem. 276:47460-47467(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION, MUTAGENESIS OF LYS-42; SER-308 AND SER-313, PHOSPHORYLATION AT SER-308.
[12]"DAP kinase and DRP-1 mediate membrane blebbing and the formation of autophagic vesicles during programmed cell death."
Inbal B., Bialik S., Sabanay I., Shani G., Kimchi A.
J. Cell Biol. 157:455-468(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[13]"Ca2+-dependent phosphorylation of syntaxin-1A by the death-associated protein (DAP) kinase regulates its interaction with Munc18."
Tian J.H., Das S., Sheng Z.H.
J. Biol. Chem. 278:26265-26274(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF STX1A, INTERACTION WITH STX1A.
[14]"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 IN PHOSPHORYLATION OF DAPK3, INTERACTION WITH DAPK3.
[15]"Programmed cell death 6 (PDCD6) protein interacts with death-associated protein kinase 1 (DAPk1): additive effect on apoptosis via caspase-3 dependent pathway."
Lee J.H., Rho S.B., Chun T.
Biotechnol. Lett. 27:1011-1015(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PDCD6.
[16]"The tumor suppressor DAP kinase is a target of RSK-mediated survival signaling."
Anjum R., Roux P.P., Ballif B.A., Gygi S.P., Blenis J.
Curr. Biol. 15:1762-1767(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-289.
[17]"Bidirectional signals transduced by DAPK-ERK interaction promote the apoptotic effect of DAPK."
Chen C.H., Wang W.J., Kuo J.C., Tsai H.C., Lin J.R., Chang Z.F., Chen R.H.
EMBO J. 24:294-304(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-734, INTERACTION WITH MAPK1 AND MAPK3.
[18]"The dependence receptor UNC5H2 mediates apoptosis through DAP-kinase."
Llambi F., Lourenco F.C., Gozuacik D., Guix C., Pays L., Del Rio G., Kimchi A., Mehlen P.
EMBO J. 24:1192-1201(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: AUTOPHOSPHORYLATION AT SER-308, ENZYME REGULATION, INTERACTION WITH UNC5B.
[19]"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.
[20]"Control of death-associated protein kinase (DAPK) activity by phosphorylation and proteasomal degradation."
Jin Y., Blue E.K., Gallagher P.J.
J. Biol. Chem. 281:39033-39040(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING (ISOFORM 3), AUTOPHOSPHORYLATION AT SER-308, DEPHOSPHORYLATION, ENZYME REGULATION.
[21]"DAP kinase regulates JNK signaling by binding and activating protein kinase D under oxidative stress."
Eisenberg-Lerner A., Kimchi A.
Cell Death Differ. 14:1908-1915(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF PRKD1, INTERACTION WITH PRKD1.
[22]"DAP kinase mediates the phosphorylation of tropomyosin-1 downstream of the ERK pathway, which regulates the formation of stress fibers in response to oxidative stress."
Houle F., Poirier A., Dumaresq J., Huot J.
J. Cell Sci. 120:3666-3677(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF TPM1.
[23]"An alternative transcript from the death-associated protein kinase 1 locus encoding a small protein selectively mediates membrane blebbing."
Lin Y., Stevens C., Hrstka R., Harrison B., Fourtouna A., Pathuri S., Vojtesek B., Hupp T.
FEBS J. 275:2574-2584(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING (ISOFORM 2), PROTEOLYTIC PROCESSING, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[24]"DAPK-1 binding to a linear peptide motif in MAP1B stimulates autophagy and membrane blebbing."
Harrison B., Kraus M., Burch L., Stevens C., Craig A., Gordon-Weeks P., Hupp T.R.
J. Biol. Chem. 283:9999-10014(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MAP1B.
[25]"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.
[26]"DAP-kinase-mediated phosphorylation on the BH3 domain of beclin 1 promotes dissociation of beclin 1 from Bcl-XL and induction of autophagy."
Zalckvar E., Berissi H., Mizrachy L., Idelchuk Y., Koren I., Eisenstein M., Sabanay H., Pinkas-Kramarski R., Kimchi A.
EMBO Rep. 10:285-292(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF BECN1, INTERACTION WITH BECN1.
[27]"Peptide combinatorial libraries identify TSC2 as a death-associated protein kinase (DAPK) death domain-binding protein and reveal a stimulatory role for DAPK in mTORC1 signaling."
Stevens C., Lin Y., Harrison B., Burch L., Ridgway R.A., Sansom O., Hupp T.
J. Biol. Chem. 284:334-344(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF TSC2 AND RPS6, INTERACTION WITH TSC2.
[28]"The Cullin 3 substrate adaptor KLHL20 mediates DAPK ubiquitination to control interferon responses."
Lee Y.R., Yuan W.C., Ho H.C., Chen C.H., Shih H.M., Chen R.H.
EMBO J. 29:1748-1761(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, INTERACTION WITH KLHL20.
[29]"Death-associated protein kinase (DAPK) and signal transduction: additional roles beyond cell death."
Lin Y., Hupp T.R., Stevens C.
FEBS J. 277:48-57(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[30]"Death-associated protein kinase 1 phosphorylates Pin1 and inhibits its prolyl isomerase activity and cellular function."
Lee T.H., Chen C.H., Suizu F., Huang P., Schiene-Fischer C., Daum S., Zhang Y.J., Goate A., Chen R.H., Zhou X.Z., Lu K.P.
Mol. Cell 42:147-159(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF PIN1, INTERACTION WITH PIN1.
[31]"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.
[32]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-333, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[33]"Crystal structures of the catalytic domain of human protein kinase associated with apoptosis and tumor suppression."
Tereshko V., Teplova M., Brunzelle J., Watterson D.M., Egli M.
Nat. Struct. Biol. 8:899-907(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 2-285 IN COMPLEX WITH ATP ANALOG AND DIVALENT METAL CATION.
[34]"An aminopyridazine-based inhibitor of a pro-apoptotic protein kinase attenuates hypoxia-ischemia induced acute brain injury."
Velentza A.V., Wainwright M.S., Zasadzki M., Mirzoeva S., Schumacher A.M., Haiech J., Focia P.J., Egli M., Watterson D.M.
Bioorg. Med. Chem. Lett. 13:3465-3470(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 2-285 IN COMPLEX WITH SYNTHETIC INHIBITOR.
[35]"Complex structure of kinase domain of DAP kinase with staurosporine."
Ueda Y., Ogata H., Yamakawa A., Higuchi Y.
Submitted (APR-2006) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 1-278 IN COMPLEX WITH INHIBITORS.
[36]"Recognition of human death-associated protein kinases by calmodulin."
Kursula P., Vahokoski J., Wilmanns M.
Submitted (JUL-2006) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 302-320 IN COMPLEX WITH CALMODULIN.
[37]"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] ILE-416; SER-461; ALA-519; TYR-540; THR-941; TRP-977; ASN-978; CYS-993; GLU-994; GLN-1005; TYR-1007; PRO-1008; CYS-1010; ALA-1018; ILE-1272; ASN-1346 AND VAL-1405.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X76104 mRNA. Translation: CAA53712.1. Frameshift.
AK127855 mRNA. Translation: BAC87163.1.
CR749834 mRNA. Translation: CAH18690.1.
DQ436495 Genomic DNA. Translation: ABD96827.1.
AL160279 Genomic DNA. No translation available.
AL161787 Genomic DNA. No translation available.
AL591852 Genomic DNA. No translation available.
CH471089 Genomic DNA. Translation: EAW62727.1.
BC113660 mRNA. Translation: AAI13661.1.
BC143733 mRNA. Translation: AAI43734.1.
BT006935 mRNA. Translation: AAP35581.1. Sequence problems.
PIRI37275.
RefSeqNP_001275658.1. NM_001288729.1.
NP_001275659.1. NM_001288730.1.
NP_001275660.1. NM_001288731.1.
NP_004929.2. NM_004938.3.
UniGeneHs.380277.
Hs.693441.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1IG1X-ray1.80A2-285[»]
1JKKX-ray2.40A2-285[»]
1JKLX-ray1.62A2-285[»]
1JKSX-ray1.50A2-285[»]
1JKTX-ray3.50A/B2-285[»]
1P4FX-ray1.90A2-285[»]
1WVWX-ray2.40A1-278[»]
1WVXX-ray2.60A1-278[»]
1WVYX-ray2.80A1-278[»]
1YR5X-ray1.70B302-320[»]
2W4JX-ray1.30A1-277[»]
2W4KX-ray1.90A1-302[»]
2X0GX-ray2.20A1-334[»]
2XUUX-ray1.80A1-334[»]
2XZSX-ray2.00A/B2-312[»]
2Y0AX-ray2.60A2-304[»]
2Y4PX-ray2.65A/B/C/D1-285[»]
2Y4VX-ray1.80B302-320[»]
2YAKX-ray2.20A1-285[»]
3DFCX-ray1.90B1-285[»]
3DGKX-ray1.70A1-285[»]
3EH9X-ray1.70A2-285[»]
3EHAX-ray1.60A2-285[»]
3F5GX-ray1.85A2-285[»]
3F5UX-ray2.00A1-285[»]
3GU4X-ray1.35A1-285[»]
3GU5X-ray1.65A1-285[»]
3GU6X-ray1.49A1-285[»]
3GU7X-ray1.90A1-285[»]
3GU8X-ray1.60A1-285[»]
3GUBX-ray1.71A1-285[»]
3ZXTX-ray2.65A/B/C/D1-285[»]
4B4LX-ray1.75A1-334[»]
ProteinModelPortalP53355.
SMRP53355. Positions 3-712.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107982. 24 interactions.
IntActP53355. 17 interactions.
MINTMINT-1136108.
STRING9606.ENSP00000350785.

Chemistry

BindingDBP53355.
ChEMBLCHEMBL2558.
GuidetoPHARMACOLOGY2002.

PTM databases

PhosphoSiteP53355.

Polymorphism databases

DMDM317373595.

Proteomic databases

PaxDbP53355.
PRIDEP53355.

Protocols and materials databases

DNASU1612.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000358077; ENSP00000350785; ENSG00000196730. [P53355-1]
ENST00000408954; ENSP00000386135; ENSG00000196730. [P53355-1]
ENST00000472284; ENSP00000417076; ENSG00000196730. [P53355-1]
GeneID1612.
KEGGhsa:1612.
UCSCuc004apc.3. human. [P53355-1]
uc004apf.1. human. [P53355-2]

Organism-specific databases

CTD1612.
GeneCardsGC09P090112.
HGNCHGNC:2674. DAPK1.
HPACAB037302.
MIM600831. gene.
neXtProtNX_P53355.
PharmGKBPA27142.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0666.
HOVERGENHBG051296.
KOK08803.
OrthoDBEOG7QZGBH.
PhylomeDBP53355.
TreeFamTF314166.

Enzyme and pathway databases

BRENDA2.7.11.1. 2681.
ReactomeREACT_578. Apoptosis.
SignaLinkP53355.

Gene expression databases

ArrayExpressP53355.
BgeeP53355.
CleanExHS_DAPK1.
GenevestigatorP53355.

Family and domain databases

Gene3D1.10.533.10. 1 hit.
1.25.40.20. 1 hit.
InterProIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR011009. Kinase-like_dom.
IPR020675. Myosin_light_ch_kinase-rel.
IPR027417. P-loop_NTPase.
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.
PfamPF00023. Ank. 6 hits.
PF00531. Death. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSPR01415. ANKYRIN.
SMARTSM00248. ANK. 9 hits.
SM00005. DEATH. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF47986. SSF47986. 1 hit.
SSF48403. SSF48403. 1 hit.
SSF52540. SSF52540. 2 hits.
SSF56112. SSF56112. 1 hit.
PROSITEPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 7 hits.
PS50017. DEATH_DOMAIN. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSDAPK1. human.
EvolutionaryTraceP53355.
GeneWikiDAPK1.
GenomeRNAi1612.
NextBio6626.
PROP53355.
SOURCESearch...

Entry information

Entry nameDAPK1_HUMAN
AccessionPrimary (citable) accession number: P53355
Secondary accession number(s): B7ZLD2 expand/collapse secondary AC list , Q14CQ7, Q1W5W0, Q68CP8, Q6ZRZ3, Q9BTL8
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 11, 2011
Last modified: April 16, 2014
This is version 158 of the entry and version 6 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 9

Human chromosome 9: entries, gene names and cross-references to MIM