Tag | Content |
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CPLM ID | CPLM-008685 |
UniProt Accession | |
Genbank Protein ID | |
Genbank Nucleotide ID | |
Protein Name | Death-associated protein kinase 1 |
Protein Synonyms/Alias | DAP kinase 1 |
Gene Name | DAPK1 |
Gene Synonyms/Alias | DAPK |
Created Date | July 27, 2013 |
Organism | Homo sapiens (Human) |
NCBI Taxa ID | 9606 |
Lysine Modification | Position | Peptide | Type | References |
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306 | FAARKKWKQSVRLIS | ubiquitination | [1] |
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Reference | [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments. Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA. Mol Cell Proteomics. 2013 Mar;12(3):825-31. [ PMID: 23266961] |
Functional Description | 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 Ca(2+) 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. |
Sequence Annotation | DOMAIN 13 275 Protein kinase. REPEAT 378 407 ANK 1. REPEAT 411 440 ANK 2. REPEAT 444 473 ANK 3. REPEAT 477 506 ANK 4. REPEAT 510 539 ANK 5. REPEAT 543 572 ANK 6. REPEAT 576 605 ANK 7. REPEAT 609 638 ANK 8. REPEAT 875 904 ANK 9. REPEAT 1162 1196 ANK 10. DOMAIN 1312 1396 Death. NP_BIND 19 27 ATP. NP_BIND 94 96 ATP. REGION 267 334 Calmodulin-binding. REGION 292 301 Autoinhibitory domain (By similarity). ACT_SITE 139 139 Proton acceptor (By similarity). BINDING 42 42 ATP. BINDING 100 100 ATP. BINDING 161 161 ATP. MOD_RES 289 289 Phosphoserine; by RPS6KA1 and RPS6KA3. MOD_RES 308 308 Phosphoserine; by autocatalysis. MOD_RES 333 333 Phosphoserine. MOD_RES 734 734 Phosphoserine; by MAPK1. |
Keyword | 3D-structure; Alternative splicing; ANK repeat; Apoptosis; ATP-binding; Calmodulin-binding; Complete proteome; Cytoplasm; Cytoskeleton; Kinase; Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase; Translation regulation; Ubl conjugation. |
Sequence Source | UniProt (SWISSPROT/TrEMBL); GenBank; EMBL |
Protein Length | 1430 AA |
Protein Sequence | MTVFRQENVD DYYDTGEELG SGQFAVVKKC REKSTGLQYA AKFIKKRRTK SSRRGVSRED 60 IEREVSILKE IQHPNVITLH EVYENKTDVI LILELVAGGE LFDFLAEKES LTEEEATEFL 120 KQILNGVYYL HSLQIAHFDL KPENIMLLDR NVPKPRIKII DFGLAHKIDF GNEFKNIFGT 180 PEFVAPEIVN YEPLGLEADM WSIGVITYIL LSGASPFLGD TKQETLANVS AVNYEFEDEY 240 FSNTSALAKD FIRRLLVKDP KKRMTIQDSL QHPWIKPKDT QQALSRKASA VNMEKFKKFA 300 ARKKWKQSVR LISLCQRLSR SFLSRSNMSV ARSDDTLDEE DSFVMKAIIH AINDDNVPGL 360 QHLLGSLSNY DVNQPNKHGT PPLLIAAGCG NIQILQLLIK RGSRIDVQDK GGSNAVYWAA 420 RHGHVDTLKF LSENKCPLDV KDKSGEMALH VAARYGHADV AQLLCSFGSN PNIQDKEEET 480 PLHCAAWHGY YSVAKALCEA GCNVNIKNRE GETPLLTASA RGYHDIVECL AEHGADLNAC 540 DKDGHIALHL AVRRCQMEVI KTLLSQGCFV DYQDRHGNTP LHVACKDGNM PIVVALCEAN 600 CNLDISNKYG RTPLHLAANN GILDVVRYLC LMGASVEALT TDGKTAEDLA RSEQHEHVAG 660 LLARLRKDTH RGLFIQQLRP TQNLQPRIKL KLFGHSGSGK TTLVESLKCG LLRSFFRRRR 720 PRLSSTNSSR FPPSPLASKP TVSVSINNLY PGCENVSVRS RSMMFEPGLT KGMLEVFVAP 780 THHPHCSADD QSTKAIDIQN AYLNGVGDFS VWEFSGNPVY FCCYDYFAAN DPTSIHVVVF 840 SLEEPYEIQL NQVIFWLSFL KSLVPVEEPI AFGGKLKNPL QVVLVATHAD IMNVPRPAGG 900 EFGYDKDTSL LKEIRNRFGN DLHISNKLFV LDAGASGSKD MKVLRNHLQE IRSQIVSVCP 960 PMTHLCEKII STLPSWRKLN GPNQLMSLQQ FVYDVQDQLN PLASEEDLRR IAQQLHSTGE 1020 INIMQSETVQ DVLLLDPRWL CTNVLGKLLS VETPRALHHY RGRYTVEDIQ RLVPDSDVEE 1080 LLQILDAMDI CARDLSSGTM VDVPALIKTD NLHRSWADEE DEVMVYGGVR IVPVEHLTPF 1140 PCGIFHKVQV NLCRWIHQQS TEGDADIRLW VNGCKLANRG AELLVLLVNH GQGIEVQVRG 1200 LETEKIKCCL LLDSVCSTIE NVMATTLPGL LTVKHYLSPQ QLREHHEPVM IYQPRDFFRA 1260 QTLKETSLTN TMGGYKESFS SIMCFGCHDV YSQASLGMDI HASDLNLLTR RKLSRLLDPP 1320 DPLGKDWCLL AMNLGLPDLV AKYNTSNGAP KDFLPSPLHA LLREWTTYPE STVGTLMSKL 1380 RELGRRDAAD FLLKASSVFK INLDGNGQEA YASSCNSGTS YNSISSVVSR RNSHVWNPTV 1440 |
Gene Ontology | GO:0015629; C:actin cytoskeleton; IDA:UniProtKB. GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. GO:0005524; F:ATP binding; IDA:UniProtKB. GO:0005516; F:calmodulin binding; IDA:UniProtKB. GO:0004683; F:calmodulin-dependent protein kinase activity; IDA:UniProtKB. GO:0097190; P:apoptotic signaling pathway; IMP:UniProtKB. GO:0071346; P:cellular response to interferon-gamma; IDA:UniProtKB. GO:0006917; P:induction of apoptosis; IMP:UniProtKB. GO:0007243; P:intracellular protein kinase cascade; IDA:UniProtKB. GO:0043066; P:negative regulation of apoptotic process; IEA:Compara. GO:0017148; P:negative regulation of translation; IDA:UniProtKB. GO:0046777; P:protein autophosphorylation; IDA:UniProtKB. GO:0010506; P:regulation of autophagy; TAS:UniProtKB. GO:2000310; P:regulation of N-methyl-D-aspartate selective glutamate receptor activity; ISS:UniProtKB. |
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