Peripheral myelin protein 22

Source: Wikipedia, the free encyclopedia.
PMP22
Identifiers
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl

ENSG00000109099

ENSMUSG00000018217

UniProt

Q01453

P16646

RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)Chr 17: 15.23 – 15.27 MbChr 11: 63.02 – 63.05 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Peripheral myelin protein 22 (PMP22), also called Growth arrest-specific protein 3 (GAS-3), is a protein which in humans is encoded by the PMP22 gene. Mutations in PMP22 cause changes in the expression of peripheral myelin protein 22 which can result in several neuropathies.

PMP22 is a 22

myelin sheath, a protective fatty layer that provides electrical insulation for the neuronal axon.[5] The level of PMP22 expression is relatively low in the central nervous system of adults.[6]

Like other membrane proteins, newly translated PMP22 protein is temporarily sequestered to the

plasma membrane of the cell.[5]

Structure and function

In humans, the PMP22 gene is located on

transmembrane domains, two extracellular loops (ECL1 and ECL2), and one intracellular loop.[9] Exon 2 codes for the first transmembrane domain, located on the N-terminus of the PMP22 protein. Exon 3 codes for the first extracellular loop. Exon 4 corresponds to the second transmembrane domain and half of the third. Exon 5 is responsible for the rest of the third and the fourth transmembrane domain, the second extracellular loop, and the 3' UTR.[8] ECL1 has been suggested to mediate a homophilic interaction between two PMP22 proteins, whereas ECL2 has been shown to mediate a heterophilic interaction between PMP22 protein and Myelin protein zero (MPZ).[6]

Although the PMP22 mechanism of action in myelinating Schwann cells is not fully known, it plays an essential role in the formation and maintenance of compact myelin.

cell-cycle regulation. PMP22 is detectable in non-neural tissues, where its expression has been shown to serve as growth-arrest-specific (gas-3) function.[5]

Gene-dosage

Improper

gene deletion) results in HNPP.[10] Point mutations in PMP22 can result in CMT1E.[6] Gene duplication of PMP22 is the most common genetic cause of CMT;[11][12] up to half of all cases confirmed by a genetic diagnosis are caused by a 1.4 Mb duplication on chromosome 17, which contains the PMP22 gene.[13] Overproduction of PMP22 results in defects in multiple signaling pathways and dysfunction of transcriptional factors like KNOX20, SOX10 and EGR2.[5]

Interactions and Regulation

PMP22 has been found to interact with several different factors, some of which regulate expression. Peripheral myelin protein 22 has been shown to interact with myelin protein zero, with the proteins forming complexes in myelin.[14] Transcription factors SOX10 and EGR2 have been found to increase the expression of PMP22 through a super-enhancer upstream of the gene.[13] TEAD1 and YAP/TAZ (of the hippo signaling pathway) have been found to bind at the enhancers, with studies showing a decrease in PMP22 expression with the knockdown of these factors. Additionally, PKC activators and HDAC inhibitors have been characterized as regulators of PMP22, as well as microRNAs such as miR-29a and miR-381.[13]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000109099 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000018217 – 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. ^
    S2CID 40080925
    .
  6. ^
    PMID 23224996
    .
  7. PMID 12119418
    .
  8. ^
    PMID 36217151
    .
  9. S2CID 31130790
    .
  10. S2CID 23911870
    .
  11. S2CID 205309846
    .
  12. S2CID 25129077
    .
  13. ^
    PMID 31586623
    .
  14. PMID 10212299
    .

Further reading

External links
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