Protein-coding gene in humans
| MAP4K2 |
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| Identifiers |
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| Aliases | MAP4K2, BL44, GCK, RAB8IP, mitogen-activated protein kinase kinase kinase kinase 2 |
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| External IDs | OMIM: 603166; MGI: 1346883; HomoloGene: 3370; GeneCards: MAP4K2; OMA:MAP4K2 - orthologs |
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| Gene location (Human) |
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 | | Chr. | Chromosome 11 (human)[1] |
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| | Band | 11q13.1 | Start | 64,784,918 bp[1] |
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| End | 64,803,241 bp[1] |
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| Gene location (Mouse) |
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 | | Chr. | Chromosome 19 (mouse)[2] |
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| | Band | 19|19 A | Start | 6,391,165 bp[2] |
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| End | 6,405,645 bp[2] |
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| RNA expression pattern |
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| Bgee | | Human | Mouse (ortholog) |
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| Top expressed in | - granulocyte
- spleen
- right lung
- monocyte
- right hemisphere of cerebellum
- lymph node
- gonad
- right frontal lobe
- upper lobe of left lung
- prefrontal cortex
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| | Top expressed in | - granulocyte
- thymus
- cerebellum
- spleen
- cerebellar cortex
- neural layer of retina
- hypothalamus
- striatum of neuraxis
- primary visual cortex
- superior frontal gyrus
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| | More reference expression data |
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| BioGPS |  | | More reference expression data |
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| Gene ontology |
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| Molecular function | - transferase activity
- nucleotide binding
- protein kinase activity
- mitogen-activated protein kinase kinase kinase binding
- kinase activity
- protein serine/threonine kinase activity
- protein binding
- ATP binding
- MAP kinase kinase kinase kinase activity
| | Cellular component | - Golgi apparatus
- membrane
- Golgi membrane
- plasma membrane
- basolateral plasma membrane
- cytoplasm
| | Biological process | - intracellular signal transduction
- vesicle targeting
- phosphorylation
- immune system process
- positive regulation of JNK cascade
- protein phosphorylation
- JNK cascade
- immune response
- innate immune response
- regulation of mitotic cell cycle
- regulation of apoptotic process
- signal transduction
- stress-activated protein kinase signaling cascade
- activation of protein kinase activity
| | Sources:Amigo / QuickGO |
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| Orthologs |
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| Species | Human | Mouse |
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| Entrez | | |
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| Ensembl | | |
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| UniProt | | |
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| RefSeq (mRNA) | | |
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| RefSeq (protein) | | |
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| Location (UCSC) | Chr 11: 64.78 – 64.8 Mb | Chr 19: 6.39 – 6.41 Mb |
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| PubMed search | [3] | [4] |
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| Wikidata |
| View/Edit Human | View/Edit Mouse |
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Mitogen-activated protein kinase kinase kinase kinase 2 is an enzyme that in humans is encoded by the MAP4K2 gene.[5][6]
Function
The protein encoded by this gene is a member of the serine/threonine protein kinase family. Although this kinase is found in many tissues, its expression in lymphoid follicles is restricted to the cells of germinal centre, where it may participate in B-cell differentiation. This kinase can be activated by TNF-alpha, and has been shown to specifically activate MAP kinases. This kinase is also found to interact with TNF receptor-associated factor 2 (TRAF2), which is involved in the activation of MAP3K1/MEKK1.[6] A recent study showed that MAP4K2 is a direct kinase of LATS1/2 and thus regulates the Hippo pathway effectors YAP and TAZ.[7][8]
Interactions
MAP4K2 has been shown to interact with RAB8A[9] and TRAF2.[10]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000168067 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024948 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Katz P, Whalen G, Kehrl JH (Jun 1994). "Differential expression of a novel protein kinase in human B lymphocytes. Preferential localization in the germinal center". The Journal of Biological Chemistry. 269 (24): 16802–9. doi:10.1016/S0021-9258(19)89463-2. PMID 7515885.
- ^ a b "Entrez Gene: MAP4K2 mitogen-activated protein kinase kinase kinase kinase 2".
- ^ Meng, Zhipeng; Moroishi, Toshiro; Guan, Kun-Liang (2016-01-01). "Mechanisms of Hippo pathway regulation". Genes & Development. 30 (1): 1–17. doi:10.1101/gad.274027.115. ISSN 0890-9369. PMC 4701972. PMID 26728553.
- ^ Meng, Zhipeng; Moroishi, Toshiro; Mottier-Pavie, Violaine; Plouffe, Steven W.; Hansen, Carsten G.; Hong, Audrey W.; Park, Hyun Woo; Mo, Jung-Soon; Lu, Wenqi (2015-10-05). "MAP4K family kinases act in parallel to MST1/2 to activate LATS1/2 in the Hippo pathway". Nature Communications. 6: 8357. Bibcode:2015NatCo...6.8357M. doi:10.1038/ncomms9357. PMC 4600732. PMID 26437443.
- ^ Ren M, Zeng J, De Lemos-Chiarandini C, Rosenfeld M, Adesnik M, Sabatini DD (May 1996). "In its active form, the GTP-binding protein rab8 interacts with a stress-activated protein kinase". Proceedings of the National Academy of Sciences of the United States of America. 93 (10): 5151–5. Bibcode:1996PNAS...93.5151R. doi:10.1073/pnas.93.10.5151. PMC 39423. PMID 8643544.
- ^ Yuasa T, Ohno S, Kehrl JH, Kyriakis JM (Aug 1998). "Tumor necrosis factor signaling to stress-activated protein kinase (SAPK)/Jun NH2-terminal kinase (JNK) and p38. Germinal center kinase couples TRAF2 to mitogen-activated protein kinase/ERK kinase kinase 1 and SAPK while receptor interacting protein associates with a mitogen-activated protein kinase kinase kinase upstream of MKK6 and p38". The Journal of Biological Chemistry. 273 (35): 22681–92. doi:10.1074/jbc.273.35.22681. PMID 9712898.
Further reading
- Vionnet N, Stoffel M, Takeda J, Yasuda K, Bell GI, Zouali H, Lesage S, Velho G, Iris F, Passa P (Apr 1992). "Nonsense mutation in the glucokinase gene causes early-onset non-insulin-dependent diabetes mellitus". Nature. 356 (6371): 721–2. Bibcode:1992Natur.356..721V. doi:10.1038/356721a0. PMID 1570017. S2CID 4310834.
- Matsutani A, Janssen R, Donis-Keller H, Permutt MA (Feb 1992). "A polymorphic (CA)n repeat element maps the human glucokinase gene (GCK) to chromosome 7p". Genomics. 12 (2): 319–25. doi:10.1016/0888-7543(92)90380-B. PMID 1740341.
- Pombo CM, Kehrl JH, Sánchez I, Katz P, Avruch J, Zon LI, Woodgett JR, Force T, Kyriakis JM (Oct 1995). "Activation of the SAPK pathway by the human STE20 homologue germinal centre kinase". Nature. 377 (6551): 750–4. Bibcode:1995Natur.377..750P. doi:10.1038/377750a0. PMID 7477268. S2CID 4328522.
- Ren M, Zeng J, De Lemos-Chiarandini C, Rosenfeld M, Adesnik M, Sabatini DD (May 1996). "In its active form, the GTP-binding protein rab8 interacts with a stress-activated protein kinase". Proceedings of the National Academy of Sciences of the United States of America. 93 (10): 5151–5. Bibcode:1996PNAS...93.5151R. doi:10.1073/pnas.93.10.5151. PMC 39423. PMID 8643544.
- Guru SC, Agarwal SK, Manickam P, Olufemi SE, Crabtree JS, Weisemann JM, Kester MB, Kim YS, Wang Y, Emmert-Buck MR, Liotta LA, Spiegel AM, Boguski MS, Roe BA, Collins FS, Marx SJ, Burns L, Chandrasekharappa SC (Jul 1997). "A transcript map for the 2.8-Mb region containing the multiple endocrine neoplasia type 1 locus". Genome Research. 7 (7): 725–35. doi:10.1101/gr.7.7.725. PMC 310681. PMID 9253601.
- Yuasa T, Ohno S, Kehrl JH, Kyriakis JM (Aug 1998). "Tumor necrosis factor signaling to stress-activated protein kinase (SAPK)/Jun NH2-terminal kinase (JNK) and p38. Germinal center kinase couples TRAF2 to mitogen-activated protein kinase/ERK kinase kinase 1 and SAPK while receptor interacting protein associates with a mitogen-activated protein kinase kinase kinase upstream of MKK6 and p38". The Journal of Biological Chemistry. 273 (35): 22681–92. doi:10.1074/jbc.273.35.22681. PMID 9712898.
- Chadee DN, Yuasa T, Kyriakis JM (Feb 2002). "Direct activation of mitogen-activated protein kinase kinase kinase MEKK1 by the Ste20p homologue GCK and the adapter protein TRAF2". Molecular and Cellular Biology. 22 (3): 737–49. doi:10.1128/MCB.22.3.737-749.2002. PMC 133545. PMID 11784851.
- Wissing J, Jänsch L, Nimtz M, Dieterich G, Hornberger R, Kéri G, Wehland J, Daub H (Mar 2007). "Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry". Molecular & Cellular Proteomics. 6 (3): 537–47. doi:10.1074/mcp.T600062-MCP200. hdl:10033/19756. PMID 17192257.
