• Gene id: 9448

Gene Summary

• Gene Symbol: MAP4K4   Gene   UCSC   Ensembl
• Aliases: FLH21957, HEL-S-31, HGK, MEKKK4, NIK
• Gene name: mitogen-activated protein kinase kinase kinase kinase 4
• Alternate names: mitogen-activated protein kinase kinase kinase kinase 4, HPK/GCK-like kinase HGK, MAPK/ERK kinase kinase kinase 4, MEK kinase kinase 4, Ste20 group protein kinase HGK, epididymis secretory protein Li 31, hepatocyte progenitor kinase-like/germinal center kinase-,
• Gene location: 2q11.2 (101697702: 101894689)     Exons: 33     NC_000002.12
• Gene summary(Entrez): The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase has been shown to specifically activate MAPK8/JNK. The activation of MAPK8 by this kinase is found to be inhibited by the dominant-negative mutants of
• OMIM: 604666

Protein Summary

• Protein general information: O95819  
  • Name: Mitogen activated protein kinase kinase kinase kinase 4 (EC 2.7.11.1) (HPK/GCK like kinase HGK) (MAPK/ERK kinase kinase kinase 4) (MEK kinase kinase 4) (MEKKK 4) (Nck interacting kinase)
  • Length: 1239  
  • Mass: 142101
  • Tissue specificity: Widely expressed. Isoform 5 is abundant in the brain. Isoform 4 is predominant in the liver, skeletal muscle and placenta. {ECO
• Sequence:

  MANDSPAKSLVDIDLSSLRDPAGIFELVEVVGNGTYGQVYKGRHVKTGQLAAIKVMDVTEDEEEEIKLEINMLKK
  YSHHRNIATYYGAFIKKSPPGHDDQLWLVMEFCGAGSITDLVKNTKGNTLKEDWIAYISREILRGLAHLHIHHVI
  HRDIKGQNVLLTENAEVKLVDFGVSAQLDRTVGRRNTFIGTPYWMAPEVIACDENPDATYDYRSDLWSCGITAIE
  MAEGAPPLCDMHPMRALFLIPRNPPPRLKSKKWSKKFFSFIEGCLVKNYMQRPSTEQLLKHPFIRDQPNERQVRI
  QLKDHIDRTRKKRGEKDETEYEYSGSEEEEEEVPEQEGEPSSIVNVPGESTLRRDFLRLQQENKERSEALRRQQL
  LQEQQLREQEEYKRQLLAERQKRIEQQKEQRRRLEEQQRREREARRQQEREQRRREQEEKRRLEELERRRKEEEE
  RRRAEEEKRRVEREQEYIRRQLEEEQRHLEVLQQQLLQEQAMLLECRWREMEEHRQAERLQRQLQQEQAYLLSLQ
  HDHRRPHPQHSQQPPPPQQERSKPSFHAPEPKAHYEPADRAREVEDRFRKTNHSSPEAQSKQTGRVLEPPVPSRS
  ESFSNGNSESVHPALQRPAEPQVPVRTTSRSPVLSRRDSPLQGSGQQNSQAGQRNSTSIEPRLLWERVEKLVPRP
  GSGSSSGSSNSGSQPGSHPGSQSGSGERFRVRSSSKSEGSPSQRLENAVKKPEDKKEVFRPLKPADLTALAKELR
  AVEDVRPPHKVTDYSSSSEESGTTDEEDDDVEQEGADESTSGPEDTRAASSLNLSNGETESVKTMIVHDDVESEP
  AMTPSKEGTLIVRQTQSASSTLQKHKSSSSFTPFIDPRLLQISPSSGTTVTSVVGFSCDGMRPEAIRQDPTRKGS
  VVNVNPTNTRPQSDTPEIRKYKKRFNSEILCAALWGVNLLVGTESGLMLLDRSGQGKVYPLINRRRFQQMDVLEG
  LNVLVTISGKKDKLRVYYLSWLRNKILHNDPEVEKKQGWTTVGDLEGCVHYKVVKYERIKFLVIALKSSVEVYAW
  APKPYHKFMAFKSFGELVHKPLLVDLTVEEGQRLKVIYGSCAGFHAVDVDSGSVYDIYLPTHIQCSIKPHAIIIL
  PNTDGMELLVCYEDEGVYVNTYGRITKDVVLQWGEMPTSVAYIRSNQTMGWGEKAIEIRSVETGHLDGVFMHKRA
  QRLKFLCERNDKVFFASVRSGGSSQVYFMTLGRTSLLSW

• Structural information:
  • Protein Domains: (25..28-)
    (/note="Protein-kinase)
    (/evidence="ECO:0000255|PROSITE-ProRule:PRU00159-)
    (926..121-)
    (/note="CNH-)
    (/evidence="ECO:0000255|PROSITE-ProRule:PRU00795"-)
  • Interpro: IPR001180  IPR011009  IPR000719  IPR017441  IPR008271  
  • Prosite: PS50219 PS00107 PS50011 PS00108
  • PDB: 4OBO 4OBP 4OBQ 4RVT 4U3Y 4U3Z 4U40 4U41 4U42 4U43 4U44 4U45 4ZK5 4ZP5 5DI1 5J95 5W5Q
  • PDBsum: 4OBO 4OBP 4OBQ 4RVT 4U3Y 4U3Z 4U40 4U41 4U42 4U43 4U44 4U45 4ZK5 4ZP5 5DI1 5J95 5W5Q
  • STRING: ENSP00000343658
• Other Databases: GeneCards:  MAP4K4  Malacards:  MAP4K4

Gene ontology

GO accession	Term name	Evidence code	Go category
GO:0008017	microtubule binding	IDA	molecular function
GO:0005925	focal adhesion	IDA	cellular component
GO:0120183	positive regulation of focal adhesion disassembly	ISS	biological process
GO:0043547	positive regulation of GTPase activity	ISS	biological process
GO:0001953	negative regulation of cell-matrix adhesion	NAS	biological process
GO:0030335	positive regulation of cell migration	IMP	biological process
GO:0051549	positive regulation of keratinocyte migration	ISS	biological process
GO:0051894	positive regulation of focal adhesion assembly	ISS	biological process
GO:0032014	positive regulation of ARF protein signal transduction	ISS	biological process
GO:0004111	creatine kinase activity	IDA	molecular function
GO:0043066	negative regulation of apoptotic process	IMP	biological process
GO:0023014	signal transduction by protein phosphorylation	IBA	biological process
GO:0031098	stress-activated protein kinase signaling cascade	IBA	biological process
GO:0004674	protein serine/threonine kinase activity	IBA	molecular function
GO:0005737	cytoplasm	IBA	cellular component
GO:0007346	regulation of mitotic cell cycle	IBA	biological process
GO:0032147	activation of protein kinase activity	IBA	biological process
GO:0048812	neuron projection morphogenesis	IBA	biological process
GO:0046328	regulation of JNK cascade	IDA	biological process
GO:0005737	cytoplasm	IDA	cellular component
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:0016740	transferase activity	IEA	molecular function
GO:0016301	kinase activity	IEA	molecular function
GO:0016310	phosphorylation	IEA	biological process
GO:0000166	nucleotide binding	IEA	molecular function
GO:0005737	cytoplasm	IEA	cellular component
GO:0004674	protein serine/threonine kinase activity	IEA	molecular function
GO:0005524	ATP binding	IEA	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005737	cytoplasm	IEA	cellular component
GO:0006468	protein phosphorylation	IDA	biological process
GO:0004674	protein serine/threonine kinase activity	IDA	molecular function
GO:0035556	intracellular signal transduction	IDA	biological process
GO:0005524	ATP binding	IDA	molecular function
GO:0030033	microvillus assembly	IMP	NOT|biological process

KEGG pathways

Pathway id	Pathway name
hsa04010	MAPK signaling pathway

Diseases

Associated diseases	References
Cryptorchidism	MIK: 28606200
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)
28606200	Cryptorchidism			Monozgotic twins (1 control, I cwith cryptorchidism)	Male infertility	MeDIP-Seq