Myelin regulatory factor

Mammalian protein found in Homo sapiens
MYRF
Identifiers
AliasesMYRF, C11orf9, MRF, Ndt80, pqn-47, myelin regulatory factor, 11orf9, MMERV, CUGS
External IDsOMIM: 608329 MGI: 2684944 HomoloGene: 32167 GeneCards: MYRF
Gene location (Human)
Chromosome 11 (human)
Chr.Chromosome 11 (human)[1]
Chromosome 11 (human)
Genomic location for MYRF
Genomic location for MYRF
Band11q12.2Start61,752,636 bp[1]
End61,788,518 bp[1]
Gene location (Mouse)
Chromosome 19 (mouse)
Chr.Chromosome 19 (mouse)[2]
Chromosome 19 (mouse)
Genomic location for MYRF
Genomic location for MYRF
Band19|19 AStart10,185,636 bp[2]
End10,218,112 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • middle frontal gyrus

  • inferior ganglion of vagus nerve

  • inferior olivary nucleus

  • subthalamic nucleus

  • ventral tegmental area

  • external globus pallidus

  • superior vestibular nucleus

  • retinal pigment epithelium

  • corpus callosum

  • putamen
Top expressed in
  • pyloric antrum

  • epithelium of stomach

  • mucous cell of stomach

  • motor neuron

  • yolk sac

  • abdominal wall

  • substantia nigra

  • optic nerve

  • anterior horn of spinal cord

  • superior frontal gyrus
More reference expression data
BioGPS
n/a
Gene ontology
Molecular function
  • peptidase activity
  • hydrolase activity
  • DNA binding
  • DNA-binding transcription factor activity
  • identical protein binding
  • DNA-binding transcription factor activity, RNA polymerase II-specific
  • sequence-specific DNA binding
Cellular component
  • endoplasmic reticulum membrane
  • nucleus
  • membrane
  • cytoplasm
  • integral component of membrane
  • endoplasmic reticulum
  • nucleoplasm
  • Golgi apparatus
  • cytosol
Biological process
  • positive regulation of myelination
  • oligodendrocyte differentiation
  • regulation of transcription, DNA-templated
  • proteolysis
  • central nervous system myelination
  • central nervous system myelin maintenance
  • cell differentiation
  • positive regulation of transcription, DNA-templated
  • transcription, DNA-templated
  • oligodendrocyte development
  • regulation of transcription by RNA polymerase II
  • protein autoprocessing
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

745

225908

Ensembl

ENSG00000124920

ENSMUSG00000036098

UniProt

Q9Y2G1

Q3UR85

RefSeq (mRNA)

NM_001127392
NM_013279

NM_001033481

RefSeq (protein)

NP_001120864
NP_037411

NP_001028653
NP_001391042

Location (UCSC)Chr 11: 61.75 – 61.79 MbChr 19: 10.19 – 10.22 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse
Myelin regulatory factor
Identifiers
SymbolMYRF
InterProIPR026933
Membranome237

Myelin regulatory factor (MyRF), also known as myelin gene regulatory factor (MRF), is a protein that in humans is encoded by the MYRF gene.

Orthologs

Myelin regulatory factor is encoded by the Myrf/GM98 gene in mice and by the MYRF gene in humans.[5] The family of MyRF-like-proteins also contains the orthologues pqn-47 from C. elegans and MYRFA from Dictyostelium.[6] All orthologs have a DNA-binding domain of high homology to the Saccharomyces cerevisiae protein Ndt80 (a p53-like transcription factor) and therefore likely act as a transcription factor.

Function

MyRF is a transcription factor that promotes the expression of many genes important in the production of myelin.[7] It is therefore of critical importance in the development and maintenance of myelin sheaths.[8]

The expression of MYRF is specific to mature, myelinating oligodendrocytes in the CNS.[9][10] It has been shown to be critical for the maintenance of myelin by these cells. Following ablation of MYRF the expression of myelin genes such as PLP1, MBP, MAG and MOG drops rapidly.[8] Therefore, MYRF is a key regulator and likely a direct activator of the expression of these genes.[7]

Animal models

Mice that lose MYRF during adulthood present with a severe demyelination similar to that seen in animal models of multiple sclerosis. This underlines the importance of an active renewal of proteins in the myelin sheath. Further, the activity of MYRF increases during remyelination, suggesting it has a critical role in this process.[8] Animals with repressed Myrf in a proportion of oligodendrocyte precursor cells showed a delayed functional recovery from spinal cord injury.[11]

Myrf has been shown to be significantly downregulated in a mouse model carrying the same mutation in the NPC1 protein that is underlying Niemann-Pick type C1 disease, a neurodegenerative process in which dysmyelination is a main pathogenic factor. Therefore, a disruption of oligodendrocyte formation and myelination may be the root cause of the neurological abnormalities.[12]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000124920 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000036098 – 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. ^ "MYRF". Universal Protein Resource (UniProt) Consortium. Retrieved 2012-06-13.
  6. ^ Senoo H, Wang HY, Araki T, Williams JG, Fukuzawa M (2012). "An orthologue of the Myelin-gene Regulatory Transcription Factor regulates Dictyostelium prestalk differentiation". Int. J. Dev. Biol. 56 (5): 325–32. doi:10.1387/ijdb.120030jw. PMC 3586673. PMID 22811266.
  7. ^ a b Bujalka H, Koenning M, Jackson S, Perreau VM, Pope B, Hay CM, Mitew S, Hill AF, Lu QR, Wegner M, Srinivasan R, Svaren J, Willingham M, Barres BA, Emery B (September 2013). "MYRF Is a Membrane-Associated Transcription Factor That Autoproteolytically Cleaves to Directly Activate Myelin Genes". PLOS Biol. 11 (8): e1001625. doi:10.1371/journal.pbio.1001625. PMC 3742440. PMID 23966833.
  8. ^ a b c Koenning M, Jackson S, Hay CM, Faux C, Kilpatrick TJ, Willingham M, Emery B (September 2012). "Myelin gene regulatory factor is required for maintenance of myelin and mature oligodendrocyte identity in the adult CNS". J. Neurosci. 32 (36): 12528–42. doi:10.1523/JNEUROSCI.1069-12.2012. PMC 3752083. PMID 22956843.
  9. ^ Emery B, Agalliu D, Cahoy JD, Watkins TA, Dugas JC, Mulinyawe SB, Ibrahim A, Ligon KL, Rowitch DH, Barres BA (July 2009). "Myelin gene regulatory factor is a critical transcriptional regulator required for CNS myelination". Cell. 138 (1): 172–85. doi:10.1016/j.cell.2009.04.031. PMC 2757090. PMID 19596243.
  10. ^ Cahoy JD, Emery B, Kaushal A, Foo LC, Zamanian JL, Christopherson KS, Xing Y, Lubischer JL, Krieg PA, Krupenko SA, Thompson WJ, Barres BA (January 2008). "A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function". J. Neurosci. 28 (1): 264–78. doi:10.1523/JNEUROSCI.4178-07.2008. PMC 6671143. PMID 18171944.
  11. ^ Duncan GJ, Plemel JR, Hilton BJ, Liu J, Kramer JK, Kim J, Mao S, Tetzlaff W (October 2012). Myelin gene regulatory factor knockout delays functional recovery from spinal cord injury. Neuroscience 2012. pp. S60.
  12. ^ Yan X, Lukas J, Witt M, Wree A, Hübner R, Frech M, Köhling R, Rolfs A, Luo J (December 2011). "Decreased expression of myelin gene regulatory factor in Niemann-Pick type C 1 mouse". Metab Brain Dis. 26 (4): 299–306. doi:10.1007/s11011-011-9263-9. PMID 21938520. S2CID 26878522.
  • v
  • t
  • e
(1) Basic domains
(1.1) Basic leucine zipper (bZIP)
(1.2) Basic helix-loop-helix (bHLH)
Group A
Group B
Group C
bHLH-PAS
Group D
Group E
Group F
bHLH-COE
(1.3) bHLH-ZIP
(1.4) NF-1
(1.5) RF-X
(1.6) Basic helix-span-helix (bHSH)
(2) Zinc finger DNA-binding domains
(2.1) Nuclear receptor (Cys4)
subfamily 1
subfamily 2
subfamily 3
subfamily 4
subfamily 5
subfamily 6
subfamily 0
(2.2) Other Cys4
(2.3) Cys2His2
(2.4) Cys6
(2.5) Alternating composition
(2.6) WRKY
(3) Helix-turn-helix domains
(3.1) Homeodomain
Antennapedia
ANTP class
protoHOX
Hox-like
metaHOX
NK-like
other
(3.2) Paired box
(3.3) Fork head / winged helix
(3.4) Heat shock factors
(3.5) Tryptophan clusters
(3.6) TEA domain
  • transcriptional enhancer factor
(4) β-Scaffold factors with minor groove contacts
(4.1) Rel homology region
(4.2) STAT
(4.3) p53-like
(4.4) MADS box
(4.6) TATA-binding proteins
(4.7) High-mobility group
(4.9) Grainyhead
(4.10) Cold-shock domain
(4.11) Runt
(0) Other transcription factors
(0.2) HMGI(Y)
(0.3) Pocket domain
(0.5) AP-2/EREBP-related factors
(0.6) Miscellaneous
see also transcription factor/coregulator deficiencies