ADPRHL2

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ADPRHL2
HARH3 H2BS7mar.png
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

2FOZ, 2FP0, 2G4K

Identifikatori
AliasiADPRS
Vanjski ID-jeviOMIM: 610624 MGI: 2140364 HomoloGene: 9863 GeneCards: ADPRS
Lokacija gena (čovjek)
Hromosom 1 (čovjek)
Hrom.Hromosom 1 (čovjek)[1]
Hromosom 1 (čovjek)
Genomska lokacija za ADPRHL2
Genomska lokacija za ADPRHL2
Bend1p34.3Početak36,088,892 bp[1]
Kraj36,093,932 bp[1]
Ontologija gena
Molekularna funkcija hydrolase activity
metal ion binding
poly(ADP-ribose) glycohydrolase activity
Ćelijska komponenta citoplazma
mitohondrija
Jedro
Nukleoplazma
nuclear body
mitochondrial matrix
Biološki proces cellular response to superoxide
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez
Ensembl
UniProt
RefSeq (mRNK)

NM_017825

NM_133883

RefSeq (bjelančevina)

NP_060295

NP_598644

Lokacija (UCSC)Chr 1: 36.09 – 36.09 Mbn/a
PubMed pretraga[2][3]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

(ADP-ribozil)hidrolaza 3 (ARH3 ili ADPRS) jest enzim koji je kod ljudi kodiran genom ADPRHL2 sa hromosoma 1.[4][5][6][7]

Amiokiselininska sekvenca[uredi | uredi izvor]

Dužina polipeptidnog lanca je 363 aminokiseline, a molekulska težina 38.947 Da.[8]

1020304050
MAAAAMAAAAGGGAGAARSLSRFRGCLAGALLGDCVGSFYEAHDTVDLTS
VLRHVQSLEPDPGTPGSERTEALYYTDDTAMARALVQSLLAKEAFDEVDM
AHRFAQEYKKDPDRGYGAGVVTVFKKLLNPKCRDVFEPARAQFNGKGSYG
NGGAMRVAGISLAYSSVQDVQKFARLSAQLTHASSLGYNGAILQALAVHL
ALQGESSSEHFLKQLLGHMEDLEGDAQSVLDARELGMEERPYSSRLKKIG
ELLDQASVTREEVVSELGNGIAAFESVPTAIYCFLRCMEPDPEIPSAFNS
LQRTLIYSISLGGDTDTIATMAGAIAGAYYGMDQVPESWQQSCEGYEETD
ILAQSLHRVFQKS

Funkcija[uredi | uredi izvor]

Ovaj enzim preokreće posttranslacijsko dodavanje ADP-riboze serinskim ostacima proteina, kao dio odgovora na oštećenje DNK.[9][10] Takođe je poznato da enzim cijepa poli(ADP-riboza) polimere, 1''-O-acetil-ADP-ribozu i alfa-NAD+[10][11][6][12][13]

Klinički značaj[uredi | uredi izvor]

Mutacije gubitka funkcije u genu ADPRHL2 rezultiraju nedavno definiranim poremećajem koji se naziva neurodegeneracija uzrokovana stresom u djetinjstvu s varijabilnom ataksijom i napadima (CONDSIAS; OMIM: 618170).[14][15][16][17][18][19] CONDSIAS je autosomno recesivni poremećaj čiji je odgovarajući gen (ADPRHL2) mapiran na hromosomu 1, sekvenca p35.3-p34.1. Fenotipovi ovog poremećaja su prijavljeni kao neurodegeneracija, varijabilna ataksija i napadi, tremor, nistagmus, problemi s ravnotežom, cerebelarna, kičmenomoždinska i cerebralna atrofija, oštećenje sluha i povremeno gubitak sluha, ptoza, oftalmoplegija, disartrija, mišićna slabost, aksonska dismetrija i fascikulacija jezika.[14][16] Čini se da su simptomi i težina poremećaja različiti kod pacijenata i ponekad dovode do rane smrti u djetinjstvu. Drugim riječima, iako stariji pacijenti imaju većinu gore navedenih simptoma, mlađi doživljavaju gubitak razvojnih prekretnica i smrt u ranom djetinjstvu.[15]

Reference[uredi | uredi izvor]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000116863 - Ensembl, maj 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Gene symbol report | HUGO Gene Nomenclature Committee".
  5. ^ Glowacki G, Braren R, Firner K, Nissen M, Kühl M, Reche P, et al. (juli 2002). "The family of toxin-related ecto-ADP-ribosyltransferases in humans and the mouse". Protein Science. 11 (7): 1657–70. doi:10.1110/ps.0200602. PMC 2373659. PMID 12070318.
  6. ^ a b Oka S, Kato J, Moss J (januar 2006). "Identification and characterization of a mammalian 39-kDa poly(ADP-ribose) glycohydrolase". The Journal of Biological Chemistry. 281 (2): 705–13. doi:10.1074/jbc.M510290200. PMID 16278211.
  7. ^ "Entrez Gene: ADPRHL2 ADP-ribosylhydrolase like 2".
  8. ^ "UniProt, Q9NX46" (jezik: engleski). Pristupljeno 21. 11. 2021.
  9. ^ Fontana P, Bonfiglio JJ, Palazzo L, Bartlett E, Matic I, Ahel I (juni 2017). "Serine ADP-ribosylation reversal by the hydrolase ARH3". eLife. 6. doi:10.7554/eLife.28533. PMC 5552275. PMID 28650317.
  10. ^ a b Rack JG, Palazzo L, Ahel I (mart 2020). "(ADP-ribosyl)hydrolases: structure, function, and biology". Genes & Development. 34 (5–6): 263–284. doi:10.1101/gad.334631.119. PMC 7050489. PMID 32029451.
  11. ^ Stevens LA, Kato J, Kasamatsu A, Oda H, Lee DY, Moss J (decembar 2019). "The ARH and Macrodomain Families of α-ADP-ribose-acceptor Hydrolases Catalyze α-NAD+ Hydrolysis". ACS Chemical Biology. 14 (12): 2576–2584. doi:10.1021/acschembio.9b00429. PMC 8388552 Provjerite vrijednost parametra |pmc= (pomoć). PMID 31599159.
  12. ^ Ono T, Kasamatsu A, Oka S, Moss J (novembar 2006). "The 39-kDa poly(ADP-ribose) glycohydrolase ARH3 hydrolyzes O-acetyl-ADP-ribose, a product of the Sir2 family of acetyl-histone deacetylases". Proceedings of the National Academy of Sciences of the United States of America. 103 (45): 16687–91. Bibcode:2006PNAS..10316687O. doi:10.1073/pnas.0607911103. PMC 1636516. PMID 17075046.
  13. ^ Rack JG, Liu Q, Zorzini V, Voorneveld J, Ariza A, Honarmand Ebrahimi K, et al. (juli 2021). "Mechanistic insights into the three steps of poly(ADP-ribosylation) reversal". Nature Communications. 12 (1): 4581. Bibcode:2021NatCo..12.4581R. doi:10.1038/s41467-021-24723-3. PMC 8319183 Provjerite vrijednost parametra |pmc= (pomoć). PMID 34321462 Provjerite vrijednost parametra |pmid= (pomoć).
  14. ^ a b Ghosh SG, Becker K, Huang H, Dixon-Salazar T, Chai G, Salpietro V, et al. (septembar 2018). "Biallelic Mutations in ADPRHL2, Encoding ADP-Ribosylhydrolase 3, Lead to a Degenerative Pediatric Stress-Induced Epileptic Ataxia Syndrome". American Journal of Human Genetics. 103 (3): 431–439. doi:10.1016/j.ajhg.2018.07.010. PMC 6128219. PMID 30100084.
  15. ^ a b Aryan H, Razmara E, Farhud D, Zarif-Yeganeh M, Zokaei S, Hassani SA, et al. (august 2020). "Novel imaging and clinical phenotypes of CONDSIAS disorder caused by a homozygous frameshift variant of ADPRHL2: a case report". BMC Neurology. 20 (1): 291. doi:10.1186/s12883-020-01873-3. PMC 7397971. PMID 32746785.
  16. ^ a b Danhauser K, Alhaddad B, Makowski C, Piekutowska-Abramczuk D, Syrbe S, Gomez-Ospina N, et al. (novembar 2018). "Bi-allelic ADPRHL2 Mutations Cause Neurodegeneration with Developmental Delay, Ataxia, and Axonal Neuropathy". American Journal of Human Genetics. 103 (5): 817–825. doi:10.1016/j.ajhg.2018.10.005. PMC 6218634. PMID 30401461.
  17. ^ Beijer D, Agnew T, Rack JG, Prokhorova E, Deconinck T, Ceulemans B, et al. (novembar 2021). "Biallelic ADPRHL2 mutations in complex neuropathy affect ADP ribosylation and DNA damage response". Life Science Alliance. 4 (11): e202101057. doi:10.26508/lsa.202101057. PMC 8424258 Provjerite vrijednost parametra |pmc= (pomoć). PMID 34479984 Provjerite vrijednost parametra |pmid= (pomoć).
  18. ^ Mishra B, Fatima S, Agarwal A, Radhakrishnan DM, Garg A, Srivastava AK (januar 2021). "Dystonia and Myelopathy in a Case of Stress-Induced Childhood-Onset Neurodegeneration with Ataxia and Seizures (CONDSIAS)". Movement Disorders Clinical Practice. 8 (1): 156–158. doi:10.1002/mdc3.13125. PMC 7780941. PMID 33426173. Provjerite vrijednost datuma u parametru: |pmc-embargo-date= (pomoć)
  19. ^ Hanzlikova H, Prokhorova E, Krejcikova K, Cihlarova Z, Kalasova I, Kubovciak J, et al. (juli 2020). "Pathogenic ARH3 mutations result in ADP-ribose chromatin scars during DNA strand break repair". Nature Communications. 11 (1): 3391. Bibcode:2020NatCo..11.3391H. doi:10.1038/s41467-020-17069-9. PMC 7341855. PMID 32636369.

Dopunska literatura[uredi | uredi izvor]

Vanjski linkovi[uredi | uredi izvor]