EKS-HOS-00395

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-HOS-00395

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
STE/STE11	364.5	1.9E-108	682	938	257

Status

Reviewed

Ensembl Protein

ENSP00000351908

UniProt Accession

Q99683; Q5THN3; Q99461;

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

MAP3K5; ASK1, MAPKKK5, MEKK5;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSG00000197442	ENSP00000348104	ENST00000355845
ENSG00000197442	ENSP00000351908	ENST00000359015

Organism

Homo sapiens

Functional Description

Serine/threonine kinase which acts as an essentialcomponent 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).

Protein Length

1374

Protein Sequence
(FASTA)

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

Nucleotide Sequence
(FASTA)

ATGAGCACGG AGGCGGACGA GGGCATCACT TTCTCTGTGC CACCCTTCGC CCCCTCGGGC 60

TTCTGCACCA TCCCCGAGGG CGGCATCTGC AGGAGGGGAG GAGCGGCGGC GGTGGGCGAG 120

GGCGAGGAGC ACCAGCTGCC ACCGCCGCCG CCGGGCAGCT TCTGGAACGT GGAGAGCGCC 180

GCTGCCCCTG GCATCGGTTG TCCGGCGGCC ACCTCCTCGA GCAGTGCCAC CCGAGGCCGG 240

GGCAGCTCTG TTGGCGGGGG CAGCCGACGG ACCACGGTGG CATATGTGAT CAACGAAGCG 300

AGCCAAGGGC AACTGGTGGT GGCCGAGAGC GAGGCCCTGC AGAGCTTGCG GGAGGCGTGC 360

GAGACAGTGG GCGCCACCCT GGAAACCCTG CATTTTGGGA AACTCGACTT TGGAGAAACC 420

ACCGTGCTGG ACCGCTTTTA CAATGCAGAT ATTGCGGTGG TGGAGATGAG CGATGCCTTC 480

CGGCAGCCGT CCTTGTTTTA CCACCTTGGG GTGAGAGAAA GTTTCAGCAT GGCCAACAAC 540

ATCATCCTCT ACTGTGATAC TAACTCGGAC TCTCTGCAGT CACTGAAGGA AATAATTTGC 600

CAGAAGAATA CTATGTGCAC TGGGAACTAC ACCTTTGTTC CTTACATGAT AACTCCACAT 660

AACAAAGTCT ACTGCTGTGA CAGCAGCTTC ATGAAGGGGT TGACAGAGCT CATGCAACCG 720

AACTTCGAGC TGCTTCTTGG ACCCATCTGC TTACCTCTTG TGGATCGTTT TATTCAACTT 780

TTGAAGGTGG CACAAGCAAG TTCTAGCCAG TACTTCCGGG AATCTATACT CAATGACATC 840

AGGAAAGCTC GTAATTTATA CACTGGTAAA GAATTGGCAG CTGAGTTGGC AAGAATTCGG 900

CAGCGAGTAG ATAATATCGA AGTCTTGACA GCAGATATTG TCATAAATCT GTTACTTTCC 960

TACAGAGATA TCCAGGACTA TGATTCTATT GTGAAGCTGG TAGAGACTTT AGAAAAACTG 1020

CCAACCTTTG ATTTGGCCTC CCATCACCAT GTGAAGTTTC ATTATGCATT TGCACTGAAT 1080

AGGAGAAATC TCCCTGGTGA CAGAGCAAAA GCTCTTGATA TTATGATTCC CATGGTGCAA 1140

AGCGAAGGAC AAGTTGCTTC AGATATGTAT TGCCTAGTTG GTCGAATCTA CAAAGATATG 1200

TTTTTGGACT CTAATTTCAC GGACACTGAA AGCAGAGACC ATGGAGCTTC TTGGTTCAAA 1260

AAGGCATTTG AATCTGAGCC AACACTACAG TCAGGAATTA ATTATGCGGT CCTCCTCCTG 1320

GCAGCTGGAC ACCAGTTTGA ATCTTCCTTT GAGCTCCGGA AAGTTGGGGT GAAGCTAAGT 1380

AGTCTTCTTG GTAAAAAGGG AAACTTGGAA AAACTCCAGA GCTACTGGGA AGTTGGATTT 1440

TTTCTGGGGG CCAGCGTCCT AGCCAATGAC CACATGAGAG TCATTCAAGC ATCTGAAAAG 1500

CTTTTTAAAC TGAAGACACC AGCATGGTAC CTCAAGTCTA TTGTAGAGAC AATTTTAATA 1560

TATAAGCATT TTGTGAAACT GACCACAGAA CAGCCTGTGG CCAAGCAAGA ACTTGTGGAC 1620

TTTTGGATGG ATTTCCTGGT CGAGGCCACA AAGACAGATG TTACTGTGGT TAGGTTTCCA 1680

GTATTAATAT TAGAACCAAC CAAAATCTAT CAACCTTCTT ATTTGTCTAT CAACAATGAA 1740

GTTGAGGAAA AGACAATCTC TATTTGGCAC GTGCTTCCTG ATGACAAGAA AGGTATACAT 1800

GAGTGGAATT TTAGTGCCTC TTCTGTCAGG GGAGTGAGTA TTTCTAAATT TGAAGAAAGA 1860

TGCTGCTTTC TTTATGTGCT TCACAATTCT GATGATTTCC AAATCTATTT CTGTACAGAA 1920

CTTCATTGTA AAAAGTTTTT TGAGATGGTG AACACCATTA CCGAAGAGAA GGGGAGAAGC 1980

ACAGAGGAAG GAGACTGTGA AAGTGACTTG CTGGAGTATG ACTATGAATA TGATGAAAAT 2040

GGTGACAGAG TCGTTTTAGG AAAAGGCACT TATGGGATAG TCTACGCAGG TCGGGACTTG 2100

AGCAACCAAG TCAGAATTGC TATTAAGGAA ATCCCAGAGA GAGACAGCAG ATACTCTCAG 2160

CCCCTGCATG AAGAAATAGC ATTGCATAAA CACCTGAAGC ACAAAAATAT TGTCCAGTAT 2220

CTGGGCTCTT TCAGTGAGAA TGGTTTCATT AAAATCTTCA TGGAGCAGGT CCCTGGAGGA 2280

AGTCTTTCTG CTCTCCTTCG TTCCAAATGG GGTCCATTAA AAGACAATGA GCAAACAATT 2340

GGCTTTTATA CAAAGCAAAT ACTGGAAGGA TTAAAATATC TCCATGACAA TCAGATAGTT 2400

CACCGGGACA TAAAGGGTGA CAATGTGTTG ATTAATACCT ACAGTGGTGT TCTCAAGATC 2460

TCTGACTTCG GAACATCAAA GAGGCTTGCT GGCATAAACC CCTGTACTGA AACTTTTACT 2520

GGTACCCTCC AGTATATGGC ACCAGAAATA ATAGATAAAG GACCAAGAGG CTACGGAAAA 2580

GCAGCAGACA TCTGGTCTCT GGGCTGTACA ATCATTGAAA TGGCCACAGG AAAACCCCCA 2640

TTTTATGAAC TGGGAGAACC ACAAGCAGCT ATGTTCAAGG TGGGAATGTT TAAAGTCCAC 2700

CCTGAGATCC CAGAGTCCAT GTCTGCAGAG GCCAAGGCAT TCATACTGAA ATGTTTTGAA 2760

CCAGATCCTG ACAAGAGAGC CTGTGCTAAC GACTTGCTTG TTGATGAGTT TTTAAAAGTT 2820

TCAAGCAAAA AGAAAAAGAC ACAACCTAAG CTTTCAGCTC TTTCAGCTGG ATCAAATGAA 2880

TATCTCAGGA GTATATCCTT GCCGGTACCT GTGCTGGTGG AGGACACCAG CAGCAGCAGT 2940

GAGTACGGCT CAGTTTCACC CGACACGGAG TTGAAAGTGG ACCCCTTCTC TTTCAAAACA 3000

AGAGCCAAGT CCTGCGGAGA AAGAGATGTC AAGGGAATTC GGACACTCTT TTTGGGCATT 3060

CCAGATGAGA ATTTTGAAGA TCACAGTGCT CCTCCTTCCC CTGAAGAAAA AGATTCTGGA 3120

TTCTTCATGC TGAGGAAGGA CAGTGAGAGG CGAGCTACCC TTCACAGGAT CCTGACGGAA 3180

GACCAAGACA AAATTGTGAG AAACCTAATG GAATCTTTAG CTCAGGGGGC TGAAGAACCG 3240

AAACTAAAAT GGGAACACAT CACAACCCTC ATTGCAAGCC TCAGAGAATT TGTGAGATCC 3300

ACTGACCGAA AAATCATAGC CACCACACTG TCAAAGCTGA AACTGGAGCT GGACTTCGAC 3360

AGCCATGGCA TTAGCCAAGT CCAGGTGGTA CTCTTTGGTT TTCAAGATGC TGTCAATAAA 3420

GTTCTTCGGA ATCATAACAT CAAGCCGCAC TGGATGTTTG CCTTAGACAG TATCATTCGG 3480

AAGGCGGTAC AGACAGCCAT TACCATCCTG GTTCCAGAAC TAAGGCCACA TTTCAGCCTT 3540

GCATCTGAGA GTGATACTGC TGATCAAGAA GACTTGGATG TAGAAGATGA CCATGAGGAA 3600

CAGCCTTCAA ATCAAACTGT CCGAAGACCT CAGGCTGTCA TTGAAGATGC TGTGGCTACC 3660

TCAGGCGTGA GCACGCTCAG TTCTACTGTG TCTCATGATT CCCAGAGTGC TCACCGGTCA 3720

CTGAATGTAC AGCTTGGAAG GATGAAAATA GAAACCAATA GATTACTGGA AGAATTGGTT 3780

CGGAAAGAGA AAGAATTACA AGCACTCCTT CATCGAGCTA TTGAAGAAAA AGACCAAGAA 3840

ATTAAACACC TGAAGCTTAA GTCCCAACCC ATAGAAATTC CTGAATTGCC TGTATTTCAT 3900

CTAAATTCTT CTGGCACAAA TACTGAAGAT TCTGAACTTA CCGACTGGCT GAGAGTGAAT 3960

GGAGCTGATG AAGACACTAT AAGCCGGTTT TTGGCTGAAG ATTATACACT ATTGGATGTT 4020

CTCTACTATG TTACACGTGA TGACTTAAAA TGCTTGAGAC TAAGGGGAGG GATGCTGTGC 4080

ACACTGTGGA AGGCTATCAT TGACTTTCGA AACAAACAGA CTTGA 4125

Domain Profile

S: 3     krevigkGsfgsvyaaldvdtgellavKeveikpekksekkevkalkeEikllkelkHen  62

         +r v+gkG++g vya++d++++ ++a+Ke+   pe++s+  ++++l+eEi+l+k+lkH+n

Q: 682   DRVVLGKGTYGIVYAGRDLSNQVRIAIKEI---PERDSR--YSQPLHEEIALHKHLKHKN  736

         5789**************************...888775..9******************

S: 63    ivkyyGveveeeelkiflEyvegGslsslle.kygkle..esvikkytkqileglayLHe  119

         iv+y+G+ +e++ +kif+E+v+gGsls+ll+ k+g+l+  e++i +ytkqilegl+yLH+

Q: 737   IVQYLGSFSENGFIKIFMEQVPGGSLSALLRsKWGPLKdnEQTIGFYTKQILEGLKYLHD  796

         *******************************9*****9999*******************

S: 120   kkivHRDiKgaNillds.sgvvklsDFGaskrlaelntkaaelesltGtlaymaPEvikk  178

         ++ivHRDiKg+N+l+++ sgv+k+sDFG+skrla +n++   +e++tGtl+ymaPE+i+k

Q: 797   NQIVHRDIKGDNVLINTySGVLKISDFGTSKRLAGINPC---TETFTGTLQYMAPEIIDK  853

         ***************************************...8*****************

S: 179   kekgygrkaDiWslgcvviemltgkrPfaeldeelaimfkvgakktkPeipeklseegkd  238

         + +gyg++aDiWslgc++iem+tgk+Pf el+e++a+mfkvg+ k++Peipe++s+e+k+

Q: 854   GPRGYGKAADIWSLGCTIIEMATGKPPFYELGEPQAAMFKVGMFKVHPEIPESMSAEAKA  913

         ************************************************************

S: 239   flekcleldpkkrpsaeeLLkhefl  263

         f+ kc+e dp+kr++a++LL +efl

Q: 914   FILKCFEPDPDKRACANDLLVDEFL  938

         **********************996

Domain Sequence
(FASTA)

DRVVLGKGTY GIVYAGRDLS NQVRIAIKEI PERDSRYSQP LHEEIALHKH LKHKNIVQYL 60

GSFSENGFIK IFMEQVPGGS LSALLRSKWG PLKDNEQTIG FYTKQILEGL KYLHDNQIVH 120

RDIKGDNVLI NTYSGVLKIS DFGTSKRLAG INPCTETFTG TLQYMAPEII DKGPRGYGKA 180

ADIWSLGCTI IEMATGKPPF YELGEPQAAM FKVGMFKVHP EIPESMSAEA KAFILKCFEP 240

DPDKRACAND LLVDEFL 257

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

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Anolis carolinensis"; ?>Bos taurus"; ?>Caenorhabditis elegans"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Danio rerio"; ?>Drosophila melanogaster"; ?>Equus caballus"; ?>Felis catus"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Monodelphis domestica"; ?>Mus musculus"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Nomascus leucogenys"; ?>Oreochromis niloticus"; ?>Ornithorhynchus anatinus"; ?>Oryctolagus cuniculus"; ?>Oryzias latipes"; ?>Otolemur garnettii"; ?>Pelodiscus sinensis"; ?>Pongo abelii"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Sus scrofa"; ?>Taeniopygia guttata"; ?>Takifugu rubripes"; ?>Tetraodon nigroviridis"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0005783	; C:endoplasmic reticulum
GO:0005524	; F:ATP binding
GO:0008656	; F:cysteine-type endopeptidase activator activity involved in apoptotic process
GO:0000287	; F:magnesium ion binding
GO:0004709	; F:MAP kinase kinase kinase activity
GO:0042803	; F:protein homodimerization activity
GO:0007257	; P:activation of JUN kinase activity
GO:0070301	; P:cellular response to hydrogen peroxide
GO:0010421	; P:hydrogen peroxide-mediated programmed cell death
GO:0045087	; P:innate immune response
GO:0008631	; P:intrinsic apoptotic signaling pathway in response to oxidative stress
GO:0043065	; P:positive regulation of apoptotic process
GO:0019048	; P:virus-host interaction

KEGG

hsa:4217

;

InterPros

IPR025136	; DUF4071.
IPR011009	; Kinase-like_dom.
IPR000719	; Prot_kinase_cat_dom.
IPR017441	; Protein_kinase_ATP_BS.
IPR013761	; SAM/pointed.
IPR002290	; Ser/Thr_dual-sp_kinase_dom.
IPR008271	; Ser/Thr_kinase_AS.

Pfam

PF13281	; DUF4071; 1.
PF00069	; Pkinase; 1.

SMARTs

SM00220

; S_TKc; 1.

Prosites

PS00107	; PROTEIN_KINASE_ATP; 1.
PS50011	; PROTEIN_KINASE_DOM; 1.
PS00108	; PROTEIN_KINASE_ST; 1.

Prints

Created Date

20-Feb-2013