PNKD
| Paroxysmal nonkinesigenic dyskinesia | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||||||
| Symbols | PNKD ; BRP17; DYT8; FKSG19; FPD1; KIPP1184; MR-1; MR1; PDC; PKND1; TAHCCP2 | ||||||||||||
| External IDs | OMIM: 609023 MGI: 1930773 HomoloGene: 75045 GeneCards: PNKD Gene | ||||||||||||
| EC number | 3.1.2.6 | ||||||||||||
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| Orthologs | |||||||||||||
| Species | Human | Mouse | |||||||||||
| Entrez | 25953 | 56695 | |||||||||||
| Ensembl | ENSG00000127838 | ENSMUSG00000026179 | |||||||||||
| UniProt | Q8N490 | Q69ZP3 | |||||||||||
| RefSeq (mRNA) | NM_001077399 | NM_001039509 | |||||||||||
| RefSeq (protein) | NP_001070867 | NP_001034598 | |||||||||||
| Location (UCSC) |
Chr 2: 218.27 – 218.35 Mb |
Chr 1: 74.28 – 74.35 Mb | |||||||||||
| PubMed search | |||||||||||||
PNKD is the abbreviation for a human neurological movement disorder paroxysmal nonkinesiogenic dyskinesia. Like many other human genetics disorders, PNKD also refers to the disease, the disease gene and the encoded protein. (PNKD) is a protein that in humans is encoded by the PNKD gene.[1][2] Alternative splicing results in the transcription of three isoforms. The mouse ortholog is called brain protein 17 (Brp17).
Function
The function of PNKD proteins are unknown but the long and medium isoforms of PNKD contain a conserved β-lactamase domain which suggest it may function as an enzyme. The closest mammalian homolog to PNKD is HAGH, an enzyme involves in a two-step reaction to hydrolyze SLG and produce D-lactic acid and reduced GSH. However, the hydrolytic activity of PNKD is minimal.[3]
The long form of PNKD is neuronal specific and encodes a synaptic protein that localizes dominantly to the pre-synaptic membrane. Post-synaptic area and vesicular structure also occasionally has PNKD long form. PNKD long form interacts with pre-synaptic protein RIM and inhibits synaptic exocytosis. PNKD with disease mutations is less effective in inhibition thus the synaptic release is increased. This would cause excessive neurotransmitter release in the brain and maybe the root cause for triggering epilepsy in PNKD patients.[4]
Clinical significance
Point mutations in PNKD exon 1 cause an inherited neurological movement disorder in human, paroxysmal non-kinesigenic dyskinesia.[2]
References
- ↑ Fink JK, Rainer S, Wilkowski J, Jones SM, Kume A, Hedera P, Albin R, Mathay J, Girbach L, Varvil T, Otterud B, Leppert M (Jul 1996). "Paroxysmal dystonic choreoathetosis: tight linkage to chromosome 2q". American Journal of Human Genetics 59 (1): 140–5. PMC 1915128. PMID 8659518.
- 1 2 "Entrez Gene: PNKD paroxysmal nonkinesiogenic dyskinesia".
- ↑ Shen Y, Lee HY, Rawson J, Ojha S, Babbitt P, Fu YH, Ptácek LJ (2011). "Mutations in PNKD causing paroxysmal dyskinesia alters protein cleavage and stability". Hum. Mol. Genet. 20 (12): 2322–32. doi:10.1093/hmg/ddr125. PMC 3098736. PMID 21487022.
- ↑ Shen Y, Ge W, Li Y, Hirano A, Lee HY, Rohlmann A, Missler M, Tsien R, Jan L, Fu YH, Ptacek LJ (17 February 2015). "Protein mutated in paroxysmal dyskinesia interacts with the active zone protein RIM and suppresses synaptic vesicle exocytosis". Proceedings of the National Academy of Sciences: 201501364. doi:10.1073/pnas.1501364112.