MID2

MID2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesMID2, FXY2, MRX101, RNF60, TRIM1, midline 2, XLID101
External IDsOMIM: 300204; MGI: 1344333; HomoloGene: 8028; GeneCards: MID2; OMA:MID2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_012216
NM_052817
NM_001382751
NM_001382752

NM_011845
NM_001358366
NM_001358367

RefSeq (protein)

NP_036348
NP_438112
NP_001369680
NP_001369681

NP_035975
NP_001345295
NP_001345296
NP_001390295

Location (UCSC)Chr X: 107.83 – 107.93 MbChr X: 139.57 – 139.67 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

Function

[edit]

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

[edit]

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 LRRK2853–981.[11] MID2 (TRIM1) recruits LRRK2 to the microtubule cytoskeleton where MID2 (TRIM1) ubiquitinates LRRK2 targeting it for proteasomal degradation.[11]

References

[edit]
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000080561Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000000266Ensembl, 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. ^ 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.
  6. ^ a b "Entrez Gene: MID2 midline 2".
  7. ^ 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.
  8. ^ 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.
  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.
  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.
  11. ^ 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.

Further reading

[edit]