| Tag | Content |
|---|
| CPLM ID | CPLM-019763 |
UniProt Accession | |
Genbank Protein ID | |
Genbank Nucleotide ID | |
Protein Name | Mitogen-activated protein kinase kinase kinase 5 |
Protein Synonyms/Alias | Apoptosis signal-regulating kinase 1; ASK-1; MAPK/ERK kinase kinase 5; MEK kinase 5; MEKK 5 |
Gene Name | MAP3K5 |
Gene Synonyms/Alias | ASK1; MAPKKK5; MEKK5 |
Created Date | July 27, 2013 |
Organism | Homo sapiens (Human) |
NCBI Taxa ID | 9606 |
Lysine Modification | Position | Peptide | Type | References |
|---|
| 535 | TTEQPVAKQELVDFW | sumoylation | [1] | | 827 | ISDFGTSKRLAGINP | ubiquitination | [2] | | 1083 | GAEEPKLKWEHITTL | sumoylation | [1] | | 1114 | ATTLSKLKLELDFDS | sumoylation | [1] |
|
Reference | [1] SUMO-1 represses apoptosis signal-regulating kinase 1 activation through physical interaction and not through covalent modification. Lee YS, Jang MS, Lee JS, Choi EJ, Kim E. EMBO Rep. 2005 Oct;6(10):949-55. [ PMID: 16142216] [2] Systematic and quantitative assessment of the ubiquitin-modified proteome. Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP. Mol Cell. 2011 Oct 21;44(2):325-40. [ PMID: 21906983] |
Functional Description | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signaling for determination of cell fate such as differentiation and survival. Plays a crucial role in the apoptosis signal transduction pathway through mitochondria-dependent caspase activation. MAP3K5/ASK1 is required for the innate immune response, which is essential for host defense against a wide range of pathogens. Mediates signal transduction of various stressors like oxidative stress as well as by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF) or lipopolysaccharide (LPS). Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K4/SEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases (JNKs). Both p38 MAPK and JNKs control the transcription factors activator protein-1 (AP-1). |
Sequence Annotation | DOMAIN 680 938 Protein kinase.
NP_BIND 686 694 ATP (By similarity).
ACT_SITE 803 803 Proton acceptor (By similarity).
BINDING 709 709 ATP.
MOD_RES 83 83 Phosphoserine; by PIM1, PKB/AKT1 and
MOD_RES 718 718 Phosphotyrosine.
MOD_RES 813 813 Phosphothreonine; by autocatalysis.
MOD_RES 838 838 Phosphothreonine; by autocatalysis, MELK
MOD_RES 842 842 Phosphothreonine; by autocatalysis.
MOD_RES 958 958 Phosphoserine.
MOD_RES 966 966 Phosphoserine.
MOD_RES 976 976 Phosphothreonine (By similarity).
MOD_RES 1029 1029 Phosphoserine.
MOD_RES 1033 1033 Phosphoserine. |
Keyword | 3D-structure; Apoptosis; ATP-binding; Coiled coil; Complete proteome; Cytoplasm; Endoplasmic reticulum; Host-virus interaction; Immunity; Innate immunity; Kinase; Magnesium; Metal-binding; Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Stress response; Transferase; Ubl conjugation. |
Sequence Source | UniProt (SWISSPROT/TrEMBL); GenBank; EMBL |
Protein Length | 1374 AA |
Protein Sequence | MSTEADEGIT FSVPPFAPSG FCTIPEGGIC RRGGAAAVGE GEEHQLPPPP PGSFWNVESA 60
AAPGIGCPAA TSSSSATRGR GSSVGGGSRR TTVAYVINEA SQGQLVVAES EALQSLREAC 120
ETVGATLETL HFGKLDFGET TVLDRFYNAD IAVVEMSDAF RQPSLFYHLG VRESFSMANN 180
IILYCDTNSD SLQSLKEIIC QKNTMCTGNY TFVPYMITPH NKVYCCDSSF MKGLTELMQP 240
NFELLLGPIC LPLVDRFIQL LKVAQASSSQ YFRESILNDI RKARNLYTGK ELAAELARIR 300
QRVDNIEVLT ADIVINLLLS YRDIQDYDSI VKLVETLEKL PTFDLASHHH VKFHYAFALN 360
RRNLPGDRAK ALDIMIPMVQ SEGQVASDMY CLVGRIYKDM FLDSNFTDTE SRDHGASWFK 420
KAFESEPTLQ SGINYAVLLL AAGHQFESSF ELRKVGVKLS SLLGKKGNLE KLQSYWEVGF 480
FLGASVLAND HMRVIQASEK LFKLKTPAWY LKSIVETILI YKHFVKLTTE QPVAKQELVD 540
FWMDFLVEAT KTDVTVVRFP VLILEPTKIY QPSYLSINNE VEEKTISIWH VLPDDKKGIH 600
EWNFSASSVR GVSISKFEER CCFLYVLHNS DDFQIYFCTE LHCKKFFEMV NTITEEKGRS 660
TEEGDCESDL LEYDYEYDEN GDRVVLGKGT YGIVYAGRDL SNQVRIAIKE IPERDSRYSQ 720
PLHEEIALHK HLKHKNIVQY LGSFSENGFI KIFMEQVPGG SLSALLRSKW GPLKDNEQTI 780
GFYTKQILEG LKYLHDNQIV HRDIKGDNVL INTYSGVLKI SDFGTSKRLA GINPCTETFT 840
GTLQYMAPEI IDKGPRGYGK AADIWSLGCT IIEMATGKPP FYELGEPQAA MFKVGMFKVH 900
PEIPESMSAE AKAFILKCFE PDPDKRACAN DLLVDEFLKV SSKKKKTQPK LSALSAGSNE 960
YLRSISLPVP VLVEDTSSSS EYGSVSPDTE LKVDPFSFKT RAKSCGERDV KGIRTLFLGI 1020
PDENFEDHSA PPSPEEKDSG FFMLRKDSER RATLHRILTE DQDKIVRNLM ESLAQGAEEP 1080
KLKWEHITTL IASLREFVRS TDRKIIATTL SKLKLELDFD SHGISQVQVV LFGFQDAVNK 1140
VLRNHNIKPH WMFALDSIIR KAVQTAITIL VPELRPHFSL ASESDTADQE DLDVEDDHEE 1200
QPSNQTVRRP QAVIEDAVAT SGVSTLSSTV SHDSQSAHRS LNVQLGRMKI ETNRLLEELV 1260
RKEKELQALL HRAIEEKDQE IKHLKLKSQP IEIPELPVFH LNSSGTNTED SELTDWLRVN 1320
GADEDTISRF LAEDYTLLDV LYYVTRDDLK CLRLRGGMLC TLWKAIIDFR NKQT 1374 |
Gene Ontology | GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell. GO:0005524; F:ATP binding; IDA:UniProtKB. GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; IDA:UniProtKB. GO:0000287; F:magnesium ion binding; IDA:UniProtKB. GO:0004709; F:MAP kinase kinase kinase activity; IDA:UniProtKB. GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. GO:0007257; P:activation of JUN kinase activity; TAS:ProtInc. GO:0070301; P:cellular response to hydrogen peroxide; IDA:BHF-UCL. GO:0045087; P:innate immune response; IEA:UniProtKB-KW. GO:0008631; P:intrinsic apoptotic signaling pathway in response to oxidative stress; IDA:UniProtKB. GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB. GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. |
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