MID2

MID2
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2DJA, 2DMK
Identifiers
Aliases	MID2, FXY2, MRX101, RNF60, TRIM1, midline 2, XLID101
External IDs	OMIM: 300204; MGI: 1344333; HomoloGene: 8028; GeneCards: MID2; OMA:MID2 - orthologs
Gene location (Human)
Chr.	X chromosome (human)
End	107,931,637 bp
Gene location (Mouse)
Chr.	X chromosome (mouse)
End	139,668,464 bp
RNA expression pattern
	Top expressed in
	tibialis anterior muscle; ; islet of Langerhans; ; cartilage tissue; ; muscle of thigh; ; smooth muscle tissue; ; gastrocnemius muscle; ; skin of thigh; ; pancreatic ductal cell; ; popliteal artery; ; tibial arteries;
	Top expressed in
	lateral nasal prominence; ; medial nasal prominence; ; left lung lobe; ; supraoptic nucleus; ; female urethra; ; superior frontal gyrus; ; dentate gyrus of hippocampal formation granule cell; ; genital tubercle; ; ascending aorta; ; cerebellar cortex;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	protein homodimerization activity; microtubule binding; zinc ion binding; metal ion binding; phosphoprotein binding; protein binding; protein heterodimerization activity; identical protein binding; transferase activity;
Cellular component	cytoplasm; intracellular anatomical structure; microtubule; extracellular exosome; cytoskeleton;
Biological process	positive regulation of autophagy; positive regulation of DNA-binding transcription factor activity; protein localization to microtubule; positive regulation of NF-kappaB transcription factor activity; protein ubiquitination; positive regulation of I-kappaB kinase/NF-kappaB signaling; innate immune response; negative regulation of viral transcription; negative regulation of viral entry into host cell;
	Sources:Amigo / QuickGO
Orthologs
	11043
	23947
	ENSG00000080561
	ENSMUSG00000000266
	Q9UJV3
	Q9QUS6
	NM_012216; NM_052817; NM_001382751; NM_001382752
	NM_011845; NM_001358366; NM_001358367
	NP_036348; NP_438112; NP_001369680; NP_001369681
	NP_035975; NP_001345295; NP_001345296; NP_001390295
	Wikidata
View/Edit Human	View/Edit Mouse

Midline-2 is a protein that in humans is encoded by the MID2 gene.^[5]^[6]

Function

The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein localizes to microtubular structures in the cytoplasm. Its function has not been identified. Alternate splicing of this gene results in two transcript variants encoding different isoforms.^[6]

Recent reports indicate the involvement of MID2 in cytokinesis ^[7]^[8].MID2 (TRIM1) ubiquitinates Sperm-associated antigen 5 (Astrin) on K409, further promoting its degradation and proper cytokinesis.^[8] In contrary, depletion of MID2 (TRIM1) stabilizes Sperm-associated antigen 5 (Astrin) whose inappropriate accumulation at the midbody triggers cytokinetic arrest, multinucleated cells, and cell death.^[7]^[8]

Interactions

MID2 has been shown to interact with MID1.^[9]^[10]

MID2 (TRIM1) interacts with Leucine-rich repeat kinase 2 (LRRK2), which is often subject to missense mutations in familial Parkinson's disease (PD).^[11] MID2 (TRIM1) specifically binds to the flexible regulatory loop of LRRK2_853–981.^[11] MID2 (TRIM1) recruits LRRK2 to the microtubule cytoskeleton where MID2 (TRIM1) ubiquitinates LRRK2 targeting it for proteasomal degradation.^[11]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000080561 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000000266 – 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.
^ Buchner G, Montini E, Andolfi G, Quaderi N, Cainarca S, Messali S, et al. (August 1999). "MID2, a homologue of the Opitz syndrome gene MID1: similarities in subcellular localization and differences in expression during development". Human Molecular Genetics. 8 (8): 1397–1407. doi:10.1093/hmg/8.8.1397. PMID 10400986.
^ ^a ^b "Entrez Gene: MID2 midline 2".
^ ^a ^b Zanchetta ME, Meroni G (2019-03-19). "Emerging Roles of the TRIM E3 Ubiquitin Ligases MID1 and MID2 in Cytokinesis". Frontiers in Physiology. 10: 274. doi:10.3389/fphys.2019.00274. PMC 6433704. PMID 30941058.
^ ^a ^b ^c Gholkar AA, Senese S, Lo YC, Vides E, Contreras E, Hodara E, et al. (January 2016). "The X-Linked-Intellectual-Disability-Associated Ubiquitin Ligase Mid2 Interacts with Astrin and Regulates Astrin Levels to Promote Cell Division". Cell Reports. 14 (2): 180–188. doi:10.1016/j.celrep.2015.12.035. PMC 4724641. PMID 26748699.
^ Reymond A, Meroni G, Fantozzi A, Merla G, Cairo S, Luzi L, et al. (May 2001). "The tripartite motif family identifies cell compartments". The EMBO Journal. 20 (9): 2140–2151. doi:10.1093/emboj/20.9.2140. PMC 125245. PMID 11331580.
^ Short KM, Hopwood B, Yi Z, Cox TC (2002). "MID1 and MID2 homo- and heterodimerise to tether the rapamycin-sensitive PP2A regulatory subunit, alpha 4, to microtubules: implications for the clinical variability of X-linked Opitz GBBB syndrome and other developmental disorders". BMC Cell Biology. 3: 1. doi:10.1186/1471-2121-3-1. PMC 64779. PMID 11806752.
^ ^a ^b ^c Stormo AE, Shavarebi F, FitzGibbon M, Earley EM, Ahrendt H, Lum LS, et al. (April 2022). "The E3 ligase TRIM1 ubiquitinates LRRK2 and controls its localization, degradation, and toxicity". The Journal of Cell Biology. 221 (4): e202010065. doi:10.1083/jcb.202010065. PMC 8919618. PMID 35266954.

Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, et al. (May 2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): 801–814. doi:10.1016/j.cell.2006.03.032. PMID 16713569.
Jehee FS, Rosenberg C, Krepischi-Santos AC, Kok F, Knijnenburg J, Froyen G, et al. (December 2005). "An Xq22.3 duplication detected by comparative genomic hybridization microarray (Array-CGH) defines a new locus (FGS5) for FG syndrome". American Journal of Medical Genetics. Part A. 139 (3): 221–226. doi:10.1002/ajmg.a.30991. PMID 16283679. S2CID 37197250.
Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–1178. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
Yap MW, Nisole S, Lynch C, Stoye JP (July 2004). "Trim5alpha protein restricts both HIV-1 and murine leukemia virus". Proceedings of the National Academy of Sciences of the United States of America. 101 (29): 10786–10791. Bibcode:2004PNAS..10110786Y. doi:10.1073/pnas.0402876101. PMC 490012. PMID 15249690.
Short KM, Hopwood B, Yi Z, Cox TC (2002). "MID1 and MID2 homo- and heterodimerise to tether the rapamycin-sensitive PP2A regulatory subunit, alpha 4, to microtubules: implications for the clinical variability of X-linked Opitz GBBB syndrome and other developmental disorders". BMC Cell Biology. 3: 1. doi:10.1186/1471-2121-3-1. PMC 64779. PMID 11806752.
Reymond A, Meroni G, Fantozzi A, Merla G, Cairo S, Luzi L, et al. (May 2001). "The tripartite motif family identifies cell compartments". The EMBO Journal. 20 (9): 2140–2151. doi:10.1093/emboj/20.9.2140. PMC 125245. PMID 11331580.
Perry J, Short KM, Romer JT, Swift S, Cox TC, Ashworth A (December 1999). "FXY2/MID2, a gene related to the X-linked Opitz syndrome gene FXY/MID1, maps to Xq22 and encodes a FNIII domain-containing protein that associates with microtubules". Genomics. 62 (3): 385–394. doi:10.1006/geno.1999.6043. PMID 10644436.
Cainarca S, Messali S, Ballabio A, Meroni G (August 1999). "Functional characterization of the Opitz syndrome gene product (midin): evidence for homodimerization and association with microtubules throughout the cell cycle". Human Molecular Genetics. 8 (8): 1387–1396. doi:10.1093/hmg/8.8.1387. PMID 10400985.

This article on a gene on the human X chromosome and/or its associated protein is a stub. You can help Wikipedia by expanding it.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000080561 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000000266 – 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.

[pmid10400986-5] Buchner G, Montini E, Andolfi G, Quaderi N, Cainarca S, Messali S, et al. (August 1999). "MID2, a homologue of the Opitz syndrome gene MID1: similarities in subcellular localization and differences in expression during development". Human Molecular Genetics. 8 (8): 1397–1407. doi:10.1093/hmg/8.8.1397. PMID 10400986.

[entrez-6] "Entrez Gene: MID2 midline 2".

[:0-7] Zanchetta ME, Meroni G (2019-03-19). "Emerging Roles of the TRIM E3 Ubiquitin Ligases MID1 and MID2 in Cytokinesis". Frontiers in Physiology. 10: 274. doi:10.3389/fphys.2019.00274. PMC 6433704. PMID 30941058.

[:1-8] Gholkar AA, Senese S, Lo YC, Vides E, Contreras E, Hodara E, et al. (January 2016). "The X-Linked-Intellectual-Disability-Associated Ubiquitin Ligase Mid2 Interacts with Astrin and Regulates Astrin Levels to Promote Cell Division". Cell Reports. 14 (2): 180–188. doi:10.1016/j.celrep.2015.12.035. PMC 4724641. PMID 26748699.

[pmid11331580-9] Reymond A, Meroni G, Fantozzi A, Merla G, Cairo S, Luzi L, et al. (May 2001). "The tripartite motif family identifies cell compartments". The EMBO Journal. 20 (9): 2140–2151. doi:10.1093/emboj/20.9.2140. PMC 125245. PMID 11331580.

[pmid11806752-10] Short KM, Hopwood B, Yi Z, Cox TC (2002). "MID1 and MID2 homo- and heterodimerise to tether the rapamycin-sensitive PP2A regulatory subunit, alpha 4, to microtubules: implications for the clinical variability of X-linked Opitz GBBB syndrome and other developmental disorders". BMC Cell Biology. 3: 1. doi:10.1186/1471-2121-3-1. PMC 64779. PMID 11806752.

[:2-11] Stormo AE, Shavarebi F, FitzGibbon M, Earley EM, Ahrendt H, Lum LS, et al. (April 2022). "The E3 ligase TRIM1 ubiquitinates LRRK2 and controls its localization, degradation, and toxicity". The Journal of Cell Biology. 221 (4): e202010065. doi:10.1083/jcb.202010065. PMC 8919618. PMID 35266954.

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MID2

Function

Interactions

References

Further reading