MAPK8IP2

MAPK8IP2
Identifiers
Aliases	MAPK8IP2 , IB-2, IB2, JIP2, PRKM8IPL, mitogen-activated protein kinase 8 interacting protein 2
External IDs	OMIM: 607755; MGI: 1926555; HomoloGene: 8201; GeneCards: MAPK8IP2; OMA:MAPK8IP2 - orthologs
Gene location (Human) Chr. Chromosome 22 (human) [1] Band 22q13.33 Start 50,600,793 bp [1] End 50,613,981 bp [1]
Gene location (Mouse) Chr. Chromosome 15 (mouse) [2] Band 15|15 E3 Start 89,338,116 bp [2] End 89,348,671 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Brodmann area 10 right hemisphere of cerebellum right frontal lobe paraflocculus of cerebellum amygdala frontal pole cingulate gyrus anterior cingulate cortex dorsolateral prefrontal cortex Brodmann area 9 Top expressed in supraoptic nucleus central gray substance of midbrain dentate gyrus of hippocampal formation granule cell visual cortex pontine nuclei primary visual cortex facial motor nucleus anterior horn of spinal cord nucleus of stria terminalis motor neuron More reference expression data BioGPS More reference expression data
Gene ontology Molecular function amyloid-beta binding structural molecule activity protein kinase activator activity protein binding kinesin binding protein kinase binding MAP-kinase scaffold activity protein-containing complex binding Cellular component cytoplasm soma intracellular anatomical structure postsynaptic density protein-containing complex Biological process dendrite morphogenesis regulation of signaling receptor activity signal complex assembly mating behavior behavioral fear response MAPK cascade regulation of AMPA receptor activity nonassociative learning regulation of NMDA receptor activity JNK cascade regulation of JNK cascade excitatory postsynaptic potential social behavior regulation of synaptic transmission, glutamatergic positive regulation of stress-activated MAPK cascade activation of protein kinase activity negative regulation of apoptotic signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 23542 60597 Ensembl ENSG00000008735 ENSMUSG00000022619 UniProt Q13387 Q9ERE9 RefSeq (mRNA) NM_012324 NM_016431 NM_139124 NM_021921 RefSeq (protein) NP_036456 NP_068740 Location (UCSC) Chr 22: 50.6 – 50.61 Mb Chr 15: 89.34 – 89.35 Mb PubMed search [3] [4]
Wikidata
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C-jun-amino-terminal kinase-interacting protein 2 is a protein or the name of the gene that encodes it. ^{[5] [6]} The gene is also known as Islet-Brain-2 (IB2).

This protein is highly expressed in the brain and is almost always deleted in Phelan-McDermid syndrome (PMS). MAPK8IP2 appears to regulate the ratio of AMPA receptors to NMDA receptors at glutamate synapses, ^[7] and thus may be an important contributor to the intellectual dysfunction and related neurological manifestations characteristic of PMS.

The protein encoded by this gene is closely related to MAPK8IP1/IB1/JIP-1, a scaffold protein that is involved in the c-Jun amino-terminal kinase signaling pathway. This protein is expressed in brain and pancreatic cells. It has been shown to interact with, and regulate the activity of MAPK8/JNK1, and MAP2K7/MKK7 kinases. This protein thus is thought to function as a regulator of signal transduction by protein kinase cascade in brain and pancreatic beta-cells. Alternatively spliced transcript variants encoding distinct isoforms have been reported for this gene. ^[6]

Interactions

MAPK8IP2 has been shown to interact with MAP3K10, ^[5] Mitogen-activated protein kinase 9, ^[5] LRP2, ^{[8] [9]} LRP1, ^[8] MAPK8IP3, ^[10] MAP3K12, ^[5] MAPK8IP1, ^[5] MAP2K7 ^{[5] [11]} and MAP3K11. ^[5]

References

1. GRCh38: Ensembl release 89: ENSG00000008735 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000022619 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Yasuda J, Whitmarsh AJ, Cavanagh J, Sharma M, Davis RJ (February 2000). "The JIP Group of Mitogen-Activated Protein Kinase Scaffold Proteins". Mol Cell Biol. 19 (10): 7245–54. doi:10.1128/mcb.19.10.7245. PMC   84717 . PMID   10490659.
6. "Entrez Gene: MAPK8IP2 mitogen-activated protein kinase 8 interacting protein 2".
7. Giza J, et al. (2010). "Behavioral and cerebellar transmission deficits in mice lacking the autism-linked gene islet brain-2". J. Neurosci. 30 (44): 14805–16. doi:10.1523/JNEUROSCI.1161-10.2010. PMC   3200367 . PMID   21048139.
8. Gotthardt M, Trommsdorff M, Nevitt M F, Shelton J, Richardson J A, Stockinger W, Nimpf J, Herz J (August 2000). "Interactions of the low density lipoprotein receptor gene family with cytosolic adaptor and scaffold proteins suggest diverse biological functions in cellular communication and signal transduction". J. Biol. Chem. 275 (33): 25616–24. doi: 10.1074/jbc.M000955200 . ISSN   0021-9258. PMID   10827173.
9. Petersen HH, Hilpert Jan, Militz Daniel, Zandler Valerie, Jacobsen Christian, Roebroek Anton J M, Willnow Thomas E (February 2003). "Functional interaction of megalin with the megalinbinding protein (MegBP), a novel tetratrico peptide repeat-containing adaptor molecule". J. Cell Sci. 116 (Pt 3): 453–61. doi: 10.1242/jcs.00243 . ISSN   0021-9533. PMID   12508107.
10. Kelkar N, Gupta S, Dickens M, Davis R J (February 2000). "Interaction of a Mitogen-Activated Protein Kinase Signaling Module with the Neuronal Protein JIP3". Mol. Cell. Biol. 20 (3): 1030–43. doi:10.1128/MCB.20.3.1030-1043.2000. ISSN   0270-7306. PMC   85220 . PMID   10629060.
11. Negri S, Oberson A, Steinmann M, Sauser C, Nicod P, Waeber G, Schorderet D F, Bonny C (March 2000). "cDNA cloning and mapping of a novel islet-brain/JNK-interacting protein". Genomics. 64 (3): 324–30. doi:10.1006/geno.2000.6129. ISSN   0888-7543. PMID   10756100.

Further reading

• Andersson B, Wentland MA, Ricafrente JY, et al. (1996). "A "double adaptor" method for improved shotgun library construction". Anal. Biochem. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID   8619474.
• Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi: 10.1101/gr.6.9.791 . PMID   8889548.
• Yu W, Andersson B, Worley KC, et al. (1997). "Large-Scale Concatenation cDNA Sequencing". Genome Res. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC   139146 . PMID   9110174.
• Dunham I, Shimizu N, Roe BA, et al. (1999). "The DNA sequence of human chromosome 22". Nature. 402 (6761): 489–95. Bibcode:1999Natur.402..489D. doi: 10.1038/990031 . PMID   10591208.
• Kelkar N, Gupta S, Dickens M, Davis RJ (2000). "Interaction of a Mitogen-Activated Protein Kinase Signaling Module with the Neuronal Protein JIP3". Mol. Cell. Biol. 20 (3): 1030–43. doi:10.1128/MCB.20.3.1030-1043.2000. PMC   85220 . PMID   10629060.
• Negri S, Oberson A, Steinmann M, et al. (2000). "cDNA cloning and mapping of a novel islet-brain/JNK-interacting protein". Genomics. 64 (3): 324–30. doi:10.1006/geno.2000.6129. PMID   10756100.
• Gotthardt M, Trommsdorff M, Nevitt MF, et al. (2000). "Interactions of the low density lipoprotein receptor gene family with cytosolic adaptor and scaffold proteins suggest diverse biological functions in cellular communication and signal transduction". J. Biol. Chem. 275 (33): 25616–24. doi: 10.1074/jbc.M000955200 . PMID   10827173.
• Schoorlemmer J, Goldfarb M (2001). "Fibroblast growth factor homologous factors are intracellular signaling proteins". Curr. Biol. 11 (10): 793–7. Bibcode:2001CBio...11..793S. doi:10.1016/S0960-9822(01)00232-9. PMC   3216481 . PMID   11378392.
• Taru H, Kirino Y, Suzuki T (2002). "Differential roles of JIP scaffold proteins in the modulation of amyloid precursor protein metabolism". J. Biol. Chem. 277 (30): 27567–74. doi: 10.1074/jbc.M203713200 . PMID   12023290.
• Buchsbaum RJ, Connolly BA, Feig LA (2002). "Interaction of Rac Exchange Factors Tiam1 and Ras-GRF1 with a Scaffold for the p38 Mitogen-Activated Protein Kinase Cascade". Mol. Cell. Biol. 22 (12): 4073–85. doi:10.1128/MCB.22.12.4073-4085.2002. PMC   133864 . PMID   12024021.
• Schoorlemmer J, Goldfarb M (2003). "Fibroblast growth factor homologous factors and the islet brain-2 scaffold protein regulate activation of a stress-activated protein kinase". J. Biol. Chem. 277 (51): 49111–9. doi: 10.1074/jbc.M205520200 . PMC   4266389 . PMID   12244047.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Willoughby EA, Perkins GR, Collins MK, Whitmarsh AJ (2003). "The JNK-interacting protein-1 scaffold protein targets MAPK phosphatase-7 to dephosphorylate JNK". J. Biol. Chem. 278 (12): 10731–6. doi: 10.1074/jbc.M207324200 . PMID   12524447.
• Collins JE, Goward ME, Cole CG, et al. (2003). "Reevaluating Human Gene Annotation: A Second-Generation Analysis of Chromosome 22". Genome Res. 13 (1): 27–36. doi:10.1101/gr.695703. PMC   430954 . PMID   12529303.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC   528928 . PMID   15489334.
• Kristensen O, Guenat S, Dar I, et al. (2006). "A unique set of SH3–SH3 interactions controls IB1 homodimerization". EMBO J. 25 (4): 785–97. doi:10.1038/sj.emboj.7600982. PMC   1383563 . PMID   16456539.