DBT (gen)
Mitohondrijska lipoamid-aciltransferazna komponenta razgranatolančanog kompleksa alfa-keto kisele dehidrogenaze jest enzim koji je kod ljudi kodiran genom DBT sa hromosoma 1.[5][6][7]
Amiokiselininska sekvenca[uredi | uredi izvor]
Dužina polipeptidnog lanca je 482 aminokiselina, a molekulska težina 53.487 Da.[8]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MAAVRMLRTW | SRNAGKLICV | RYFQTCGNVH | VLKPNYVCFF | GYPSFKYSHP | ||||
| HHFLKTTAAL | RGQVVQFKLS | DIGEGIREVT | VKEWYVKEGD | TVSQFDSICE | ||||
| VQSDKASVTI | TSRYDGVIKK | LYYNLDDIAY | VGKPLVDIET | EALKDSEEDV | ||||
| VETPAVSHDE | HTHQEIKGRK | TLATPAVRRL | AMENNIKLSE | VVGSGKDGRI | ||||
| LKEDILNYLE | KQTGAILPPS | PKVEIMPPPP | KPKDMTVPIL | VSKPPVFTGK | ||||
| DKTEPIKGFQ | KAMVKTMSAA | LKIPHFGYCD | EIDLTELVKL | REELKPIAFA | ||||
| RGIKLSFMPF | FLKAASLGLL | QFPILNASVD | ENCQNITYKA | SHNIGIAMDT | ||||
| EQGLIVPNVK | NVQICSIFDI | ATELNRLQKL | GSVGQLSTTD | LTGGTFTLSN | ||||
| IGSIGGTFAK | PVIMPPEVAI | GALGSIKAIP | RFNQKGEVYK | AQIMNVSWSA | ||||
| DHRVIDGATM | SRFSNLWKSY | LENPAFMLLD | LK |
Funkcija[uredi | uredi izvor]
Kompleks dehidrogenaze razgranatog lanca alfa-keto kiseline (BCKD) je unutrašnji mitohondrijski enzimski kompleks koji je uključen u razgradnju aminokiselina razgranatog lanca izoleucina, leucina i valina. Smatra se da je BCKD kompleks sastavljen od jezgra od 24 transacilazne (E2) podjedinice i pridružene dekarboksilaze (E1), dehidrogenaze (E3) i regulatornih podjedinica. Ovaj gen kodira transacilaznu (E2) podjedinicu. Mutacije u ovom genu rezultiraju bolešću s urinom boje javorovog sirupa, tip 2. Opisanw su alternativno prerađene varijante transkripta, ali njihova biološka valjanost nije utvrđena.[7]
Reference[uredi | uredi izvor]
- ^ a b c GRCh38: Ensembl release 89: ENSG00000137992 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000000340 - Ensembl, maj 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.
- ^ Lau KS, Chuang JL, Herring WJ, Danner DJ, Cox RP, Chuang DT (Dec 1992). "The complete cDNA sequence for dihydrolipoyl transacylase (E2) of human branched-chain alpha-keto acid dehydrogenase complex". Biochim Biophys Acta. 1132 (3): 319–21. doi:10.1016/0167-4781(92)90169-z. PMID 1420314.
- ^ Lau KS, Herring WJ, Chuang JL, McKean M, Danner DJ, Cox RP, Chuang DT (Dec 1992). "Structure of the gene encoding dihydrolipoyl transacylase (E2) component of human branched chain alpha-keto acid dehydrogenase complex and characterization of an E2 pseudogene". J Biol Chem. 267 (33): 24090–6. doi:10.1016/S0021-9258(18)35950-7. PMID 1429740.
- ^ a b "Entrez Gene: DBT dihydrolipoamide branched chain transacylase E2".
- ^ "UniProt, P11182" (jezik: engleski). Pristupljeno 24. 11. 2021.
Dopunska literatura[uredi | uredi izvor]
- Patel MS, Harris RA (1995). "Mammalian alpha-keto acid dehydrogenase complexes: gene regulation and genetic defects". FASEB J. 9 (12): 1164–72. doi:10.1096/fasebj.9.12.7672509. PMID 7672509. S2CID 25326935.
- Popov KM, Zhao Y, Shimomura Y, et al. (1992). "Branched-chain alpha-ketoacid dehydrogenase kinase. Molecular cloning, expression, and sequence similarity with histidine protein kinases". J. Biol. Chem. 267 (19): 13127–30. doi:10.1016/S0021-9258(18)42179-5. PMID 1377677.
- Fisher CW, Lau KS, Fisher CR, et al. (1991). "A 17-bp insertion and a Phe215----Cys missense mutation in the dihydrolipoyl transacylase (E2) mRNA from a thiamine-responsive maple syrup urine disease patient WG-34". Biochem. Biophys. Res. Commun. 174 (2): 804–9. doi:10.1016/0006-291X(91)91489-Y. PMID 1847055.
- Zneimer SM, Lau KS, Eddy RL, et al. (1991). "Regional assignment of two genes of the human branched-chain alpha-keto acid dehydrogenase complex: the E1 beta gene (BCKDHB) to chromosome 6p21-22 and the E2 gene (DBT) to chromosome 1p31". Genomics. 10 (3): 740–7. doi:10.1016/0888-7543(91)90458-Q. PMID 1889817.
- Chuang DT, Fisher CW, Lau KS, et al. (1991). "Maple syrup urine disease: domain structure, mutations and exon skipping in the dihydrolipoyl transacylase (E2) component of the branched-chain alpha-keto acid dehydrogenase complex". Mol. Biol. Med. 8 (1): 49–63. PMID 1943690.
- Herring WJ, Litwer S, Weber JL, Danner DJ (1991). "Molecular genetic basis of maple syrup urine disease in a family with two defective alleles for branched chain acyltransferase and localization of the gene to human chromosome 1". Am. J. Hum. Genet. 48 (2): 342–50. PMC 1683011. PMID 1990841.
- Lau KS, Lee J, Fisher CW, et al. (1991). "Premature termination of transcription and alternative splicing in the human transacylase (E2) gene of the branched-chain alpha-ketoacid dehydrogenase complex". FEBS Lett. 279 (2): 229–32. doi:10.1016/0014-5793(91)80155-V. PMID 2001734.
- Mitsubuchi H, Nobukuni Y, Akaboshi I, et al. (1991). "Maple syrup urine disease caused by a partial deletion in the inner E2 core domain of the branched chain alpha-keto acid dehydrogenase complex due to aberrant splicing. A single base deletion at a 5'-splice donor site of an intron of the E2 gene disrupts the consensus sequence in this region". J. Clin. Invest. 87 (4): 1207–11. doi:10.1172/JCI115120. PMC 295137. PMID 2010537.
- Danner DJ, Litwer S, Herring WJ, Pruckler J (1989). "Construction and nucleotide sequence of a cDNA encoding the full-length preprotein for human branched chain acyltransferase". J. Biol. Chem. 264 (13): 7742–6. doi:10.1016/S0021-9258(18)83297-5. PMID 2708389.
- Nobukuni Y, Mitsubuchi H, Endo F, Matsuda I (1989). "Complete primary structure of the transacylase (E2b) subunit of the human branched chain alpha-keto acid dehydrogenase complex". Biochem. Biophys. Res. Commun. 161 (3): 1035–41. doi:10.1016/0006-291X(89)91347-8. PMID 2742576.
- Lau KS, Griffin TA, Hu CW, Chuang DT (1988). "Conservation of primary structure in the lipoyl-bearing and dihydrolipoyl dehydrogenase binding domains of mammalian branched-chain alpha-keto acid dehydrogenase complex: molecular cloning of human and bovine transacylase (E2) cDNAs". Biochemistry. 27 (6): 1972–81. doi:10.1021/bi00406a025. PMID 2837277.
- Litwer S, Danner DJ (1985). "Identification of a cDNA clone in lambda gt11 for the transacylase component of branched chain ketoacid dehydrogenase". Biochem. Biophys. Res. Commun. 131 (2): 961–7. doi:10.1016/0006-291X(85)91333-6. PMID 2932110.
- Litwer S, Danner DJ (1988). "Mitochondrial import and processing of an in vitro synthesized human prebranched chain acyltransferase fragment". Am. J. Hum. Genet. 43 (5): 764–9. PMC 1715554. PMID 3189339.
- Hummel KB, Litwer S, Bradford AP, et al. (1988). "Nucleotide sequence of a cDNA for branched chain acyltransferase with analysis of the deduced protein structure". J. Biol. Chem. 263 (13): 6165–8. doi:10.1016/S0021-9258(18)68766-6. PMID 3245861.
- Chuang DT, Niu WL, Cox RP (1982). "Activities of branched-chain 2-oxo acid dehydrogenase and its components in skin fibroblasts from normal and classical-maple-syrup-urine-disease subjects". Biochem. J. 200 (1): 59–67. doi:10.1042/bj2000059. PMC 1163502. PMID 6895847.
- Wynn RM, Kochi H, Cox RP, Chuang DT (1994). "Differential processing of human and rat E1 alpha precursors of the branched-chain alpha-keto acid dehydrogenase complex caused by an N-terminal proline in the rat sequence". Biochim. Biophys. Acta. 1201 (1): 125–8. doi:10.1016/0304-4165(94)90161-9. PMID 7918575.
- Fisher CW, Fisher CR, Chuang JL, et al. (1993). "Occurrence of a 2-bp (AT) deletion allele and a nonsense (G-to-T) mutant allele at the E2 (DBT) locus of six patients with maple syrup urine disease: multiple-exon skipping as a secondary effect of the mutations". Am. J. Hum. Genet. 52 (2): 414–24. PMC 1682180. PMID 8430702.