• Gene id: 4217

Gene Summary

• Gene Symbol: MAP3K5   Gene   UCSC   Ensembl
• Aliases: ASK1, MAPKKK5, MEKK5
• Gene name: mitogen-activated protein kinase kinase kinase 5
• Alternate names: mitogen-activated protein kinase kinase kinase 5, ASK-1, MAP/ERK kinase kinase 5, MAPK/ERK kinase kinase 5, MEK kinase 5, MEKK 5, apoptosis signal-regulating kinase 1,
• Gene location: 6q23.3 (136793097: 136557045)     Exons: 32     NC_000006.12
• Gene summary(Entrez): Mitogen-activated protein kinase (MAPK) signaling cascades include MAPK or extracellular signal-regulated kinase (ERK), MAPK kinase (MKK or MEK), and MAPK kinase kinase (MAPKKK or MEKK). MAPKK kinase/MEKK phosphorylates and activates its downstream protei
• OMIM: 602448

Protein Summary

• Protein general information: Q99683  
  • Name: Mitogen activated protein kinase kinase kinase 5 (EC 2.7.11.25) (Apoptosis signal regulating kinase 1) (ASK 1) (MAPK/ERK kinase kinase 5) (MEK kinase 5) (MEKK 5)
  • Length: 1374  
  • Mass: 154537
  • Tissue specificity: Abundantly expressed in heart and pancreas.
• Sequence:

  MSTEADEGITFSVPPFAPSGFCTIPEGGICRRGGAAAVGEGEEHQLPPPPPGSFWNVESAAAPGIGCPAATSSSS
  ATRGRGSSVGGGSRRTTVAYVINEASQGQLVVAESEALQSLREACETVGATLETLHFGKLDFGETTVLDRFYNAD
  IAVVEMSDAFRQPSLFYHLGVRESFSMANNIILYCDTNSDSLQSLKEIICQKNTMCTGNYTFVPYMITPHNKVYC
  CDSSFMKGLTELMQPNFELLLGPICLPLVDRFIQLLKVAQASSSQYFRESILNDIRKARNLYTGKELAAELARIR
  QRVDNIEVLTADIVINLLLSYRDIQDYDSIVKLVETLEKLPTFDLASHHHVKFHYAFALNRRNLPGDRAKALDIM
  IPMVQSEGQVASDMYCLVGRIYKDMFLDSNFTDTESRDHGASWFKKAFESEPTLQSGINYAVLLLAAGHQFESSF
  ELRKVGVKLSSLLGKKGNLEKLQSYWEVGFFLGASVLANDHMRVIQASEKLFKLKTPAWYLKSIVETILIYKHFV
  KLTTEQPVAKQELVDFWMDFLVEATKTDVTVVRFPVLILEPTKIYQPSYLSINNEVEEKTISIWHVLPDDKKGIH
  EWNFSASSVRGVSISKFEERCCFLYVLHNSDDFQIYFCTELHCKKFFEMVNTITEEKGRSTEEGDCESDLLEYDY
  EYDENGDRVVLGKGTYGIVYAGRDLSNQVRIAIKEIPERDSRYSQPLHEEIALHKHLKHKNIVQYLGSFSENGFI
  KIFMEQVPGGSLSALLRSKWGPLKDNEQTIGFYTKQILEGLKYLHDNQIVHRDIKGDNVLINTYSGVLKISDFGT
  SKRLAGINPCTETFTGTLQYMAPEIIDKGPRGYGKAADIWSLGCTIIEMATGKPPFYELGEPQAAMFKVGMFKVH
  PEIPESMSAEAKAFILKCFEPDPDKRACANDLLVDEFLKVSSKKKKTQPKLSALSAGSNEYLRSISLPVPVLVED
  TSSSSEYGSVSPDTELKVDPFSFKTRAKSCGERDVKGIRTLFLGIPDENFEDHSAPPSPEEKDSGFFMLRKDSER
  RATLHRILTEDQDKIVRNLMESLAQGAEEPKLKWEHITTLIASLREFVRSTDRKIIATTLSKLKLELDFDSHGIS
  QVQVVLFGFQDAVNKVLRNHNIKPHWMFALDSIIRKAVQTAITILVPELRPHFSLASESDTADQEDLDVEDDHEE
  QPSNQTVRRPQAVIEDAVATSGVSTLSSTVSHDSQSAHRSLNVQLGRMKIETNRLLEELVRKEKELQALLHRAIE
  EKDQEIKHLKLKSQPIEIPELPVFHLNSSGTNTEDSELTDWLRVNGADEDTISRFLAEDYTLLDVLYYVTRDDLK
  CLRLRGGMLCTLWKAIIDFRNKQT

• Structural information:
  • Protein Domains: (680..93-)
    (/note="Protein-kinase)
    (/evidence="ECO:0000255|PROSITE-ProRule:PRU00159"-)
  • Interpro: IPR025136  IPR011009  IPR000719  IPR017441  IPR013761   IPR008271  
  • Prosite: PS00107 PS50011 PS00108
  • PDB: 2CLQ 3VW6 4BF2 4BHN 4BIB 4BIC 4BID 4BIE 5ULM 5UOR 5UOX 5UP3 5V19 5V24 5VIL 5VIO 6E2M 6E2N 6E2O 6EJL 6OYT 6OYW
  • PDBsum: 2CLQ 3VW6 4BF2 4BHN 4BIB 4BIC 4BID 4BIE 5ULM 5UOR 5UOX 5UP3 5V19 5V24 5VIL 5VIO 6E2M 6E2N 6E2O 6EJL 6OYT 6OYW
  • DIP: 29516
  • STRING: ENSP00000351908
• Other Databases: GeneCards:  MAP3K5  Malacards:  MAP3K5

Gene ontology

GO accession	Term name	Evidence code	Go category
GO:0006468	protein phosphorylation	IDA	biological process
GO:1990604	IRE1-TRAF2-ASK1 complex	IDA	cellular component
GO:1990604	IRE1-TRAF2-ASK1 complex	IDA	cellular component
GO:0070059	intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	ISS	biological process
GO:1901216	positive regulation of neuron death	ISS	biological process
GO:0005515	protein binding	IPI	molecular function
GO:1901216	positive regulation of neuron death	IGI	biological process
GO:1902911	protein kinase complex	IDA	cellular component
GO:0034976	response to endoplasmic reticulum stress	IMP	biological process
GO:0043507	positive regulation of JUN kinase activity	IMP	biological process
GO:0046330	positive regulation of JNK cascade	ISS	biological process
GO:0004709	MAP kinase kinase kinase activity	IBA	molecular function
GO:0008631	intrinsic apoptotic signaling pathway in response to oxidative stress	IBA	biological process
GO:0000186	activation of MAPKK activity	IBA	biological process
GO:0004672	protein kinase activity	IBA	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0004672	protein kinase activity	IEA	molecular function
GO:0005524	ATP binding	IEA	molecular function
GO:0006468	protein phosphorylation	IEA	biological process
GO:0045087	innate immune response	IEA	biological process
GO:0016301	kinase activity	IEA	molecular function
GO:0002376	immune system process	IEA	biological process
GO:0016740	transferase activity	IEA	molecular function
GO:0005783	endoplasmic reticulum	IEA	cellular component
GO:0046872	metal ion binding	IEA	molecular function
GO:0005524	ATP binding	IEA	molecular function
GO:0006915	apoptotic process	IEA	biological process
GO:0005737	cytoplasm	IEA	cellular component
GO:0000166	nucleotide binding	IEA	molecular function
GO:0016310	phosphorylation	IEA	biological process
GO:0016032	viral process	IEA	biological process
GO:0004674	protein serine/threonine kinase activity	IEA	molecular function
GO:0004709	MAP kinase kinase kinase activity	TAS	molecular function
GO:0000165	MAPK cascade	TAS	biological process
GO:0007257	activation of JUN kinase activity	TAS	biological process
GO:0097190	apoptotic signaling pathway	TAS	biological process
GO:0004709	MAP kinase kinase kinase activity	IEA	molecular function
GO:0004674	protein serine/threonine kinase activity	TAS	molecular function
GO:0004674	protein serine/threonine kinase activity	TAS	molecular function
GO:0005829	cytosol	TAS	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0042802	identical protein binding	IPI	molecular function
GO:0042802	identical protein binding	IPI	molecular function
GO:0042802	identical protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:1904707	positive regulation of vascular smooth muscle cell proliferation	IEA	biological process
GO:1900745	positive regulation of p38MAPK cascade	IEA	biological process
GO:0071356	cellular response to tumor necrosis factor	IEA	biological process
GO:0042060	wound healing	IEA	biological process
GO:0010666	positive regulation of cardiac muscle cell apoptotic process	IEA	biological process
GO:0005829	cytosol	IEA	cellular component
GO:0004709	MAP kinase kinase kinase activity	IEA	molecular function
GO:0002931	response to ischemia	IEA	biological process
GO:1902170	cellular response to reactive nitrogen species	IEA	biological process
GO:0070059	intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	IEA	biological process
GO:0038066	p38MAPK cascade	IEA	biological process
GO:0010941	regulation of cell death	IEA	biological process
GO:0008631	intrinsic apoptotic signaling pathway in response to oxidative stress	IEA	biological process
GO:0004709	MAP kinase kinase kinase activity	IEA	molecular function
GO:0000187	activation of MAPK activity	IEA	biological process
GO:0072577	endothelial cell apoptotic process	IEA	biological process
GO:0043507	positive regulation of JUN kinase activity	IEA	biological process
GO:0034976	response to endoplasmic reticulum stress	IEA	biological process
GO:0009897	external side of plasma membrane	IEA	cellular component
GO:0005737	cytoplasm	IEA	cellular component
GO:0001934	positive regulation of protein phosphorylation	IEA	biological process
GO:1901216	positive regulation of neuron death	IEA	biological process
GO:0097300	programmed necrotic cell death	IEA	biological process
GO:0046330	positive regulation of JNK cascade	IEA	biological process
GO:0045663	positive regulation of myoblast differentiation	IEA	biological process
GO:0043065	positive regulation of apoptotic process	IEA	biological process
GO:0034976	response to endoplasmic reticulum stress	IEA	biological process
GO:0019901	protein kinase binding	IEA	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0019903	protein phosphatase binding	IPI	molecular function
GO:0019903	protein phosphatase binding	IPI	molecular function
GO:0043280	positive regulation of cysteine-type endopeptidase activity involved in apoptotic process	IDA	biological process
GO:0000186	activation of MAPKK activity	IDA	biological process
GO:0070301	cellular response to hydrogen peroxide	IDA	biological process
GO:0005783	endoplasmic reticulum	IEA	cellular component
GO:0005737	cytoplasm	IEA	cellular component
GO:0006468	protein phosphorylation	IDA	biological process
GO:0032991	protein-containing complex	IMP	cellular component
GO:0045893	positive regulation of transcription, DNA-templated	IDA	biological process
GO:0051403	stress-activated MAPK cascade	IDA	biological process
GO:0034198	cellular response to amino acid starvation	IDA	biological process
GO:0019904	protein domain specific binding	IPI	molecular function
GO:0004672	protein kinase activity	IDA	molecular function
GO:0008631	intrinsic apoptotic signaling pathway in response to oxidative stress	IDA	biological process
GO:0004709	MAP kinase kinase kinase activity	IDA	molecular function
GO:0000287	magnesium ion binding	IDA	molecular function
GO:0043065	positive regulation of apoptotic process	IDA	biological process
GO:0004672	protein kinase activity	IDA	molecular function
GO:0000165	MAPK cascade	IDA	biological process
GO:0005524	ATP binding	IDA	molecular function
GO:0000165	MAPK cascade	IDA	biological process
GO:0042803	protein homodimerization activity	IDA	molecular function
GO:0007254	JNK cascade	IDA	biological process
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function

KEGG pathways

Pathway id	Pathway name
hsa05010	Alzheimer disease
hsa05016	Huntington disease
hsa04010	MAPK signaling pathway
hsa05012	Parkinson disease
hsa04714	Thermogenesis
hsa04141	Protein processing in endoplasmic reticulum
hsa04530	Tight junction
hsa05017	Spinocerebellar ataxia
hsa04932	Non-alcoholic fatty liver disease
hsa05418	Fluid shear stress and atherosclerosis
hsa04210	Apoptosis
hsa04722	Neurotrophin signaling pathway
hsa04071	Sphingolipid signaling pathway
hsa04668	TNF signaling pathway
hsa05014	Amyotrophic lateral sclerosis
hsa01524	Platinum drug resistance

Diseases

Associated diseases	References
Huntington's disease	PMID:18327563
Aberrant CpGs in Low Motility Sperm	MIK: 21674046
Teratozoospermia	MIK: 17327269

PubMed references

PMID	Condition	Mutation	Ethnicity	Population details	Infertility_type	Associated_genes
17327269	Teratozoospermia			19 (6 controls, 13 cases)	Male infertility	GSE6872 analyzed by GEO2R (cutoff 1.5 fold)
21674046	Aberrant CpGs in Low Motility Sperm			18	Male infertility	GSE26881