OCA2
P-protein, znan i kao transporterski melanocitno-specifični protein ili homolog proteina za razblaživanje boje ružičastih očiju je protein koji je kod ljudi kodiran genom okulokutanog albinizma II (OCA2).[5] Smatra se da je P-protein integralni membranski protein koji je uključen u transport malih molekula, posebno tirozina – prekursora melanina. Određene mutacije u OCA2 rezultiraju tipom 2 okulokutanog albinizma.[5] OCA2 kodira ljudski homolog gena p (razblaživanje boje ružičastih očiju) miša.
Ljudski OCA2 gen nalazi se na dugom kraku (q) hromozoma 15, tačnije od baznog para 28,000.020 do baznog para 28,344.457 hromosoma 15.
Aminokiselinska sekvenca
urediDužina polipeptidnog lanca je 838 aminokiselina, a molekulska težina 92.850 Da.[6]
10 | 20 | 30 | 40 | 50 | ||||
---|---|---|---|---|---|---|---|---|
MHLEGRDGRR | YPGAPAVELL | QTSVPSGLAE | LVAGKRRLPR | GAGGADPSHS | ||||
CPRGAAGQSS | WAPAGQEFAS | FLTKGRSHSS | LPQMSSSRSK | DSCFTENTPL | ||||
LRNSLQEKGS | RCIPVYHPEF | ITAEESWEDS | SADWERRYLL | SREVSGLSAS | ||||
ASSEKGDLLD | SPHIRLRLSK | LRRCVQWLKV | MGLFAFVVLC | SILFSLYPDQ | ||||
GKLWQLLALS | PLENYSVNLS | SHVDSTLLQV | DLAGALVASG | PSRPGREEHI | ||||
VVELTQADAL | GSRWRRPQQV | THNWTVYLNP | RRSEHSVMSR | TFEVLTRETV | ||||
SISIRASLQQ | TQAVPLLMAH | QYLRGSVETQ | VTIATAILAG | VYALIIFEIV | ||||
HRTLAAMLGS | LAALAALAVI | GDRPSLTHVV | EWIDFETLAL | LFGMMILVAI | ||||
FSETGFFDYC | AVKAYRLSRG | RVWAMIIMLC | LIAAVLSAFL | DNVTTMLLFT | ||||
PVTIRLCEVL | NLDPRQVLIA | EVIFTNIGGA | ATAIGDPPNV | IIVSNQELRK | ||||
MGLDFAGFTA | HMFIGICLVL | LVCFPLLRLL | YWNRKLYNKE | PSEIVELKHE | ||||
IHVWRLTAQR | ISPASREETA | VRRLLLGKVL | ALEHLLARRL | HTFHRQISQE | ||||
DKNWETNIQE | LQKKHRISDG | ILLAKCLTVL | GFVIFMFFLN | SFVPGIHLDL | ||||
GWIAILGAIW | LLILADIHDF | EIILHRVEWA | TLLFFAALFV | LMEALAHLHL | ||||
IEYVGEQTAL | LIKMVPEEQR | LIAAIVLVVW | VSALASSLID | NIPFTATMIP | ||||
VLLNLSHDPE | VGLPAPPLMY | ALAFGACLGG | NGTLIGASAN | VVCAGIAEQH | ||||
GYGFSFMEFF | RLGFPMMVVS | CTVGMCYLLV | AHVVVGWN |
- Simboli
Funkcija
urediOCA2 kodira upute za izradu proteina koji se naziva P-protein koji se nalazi u melanocitima, specijaliziranim ćelijama koje proizvode melanin i u ćelijama pigmentnog epitela mrežnjače. Melanin je odgovoran za kontrolu boje kože, kose i očiju. Štaviše, melanin se nalazi u tkivu očne mrežnjače osetljivom na svetlost koje ima ulogu u normalnom vidu.
Tačna funkcija P-proteina je nepoznata, ali utvrđeno je da je neophodan za normalno boje kože, očiju i kose ; vjerovatno uključen je u proizvodnju melanina. Ovaj gen glavna je odrednica boje očiju, ovisno o količini proizvodnje melanina u stromi dužice (velike količine daju smeđe oči, a malo ili nimalo melanina uzrokuje nijanse plavih očiju).
Klinički značaj
urediMutacije u genu OCA2 uzrokuju poremećaj u normalnoj proizvodnji melanina; stoga uzrokuje probleme sa vidom i smanjuje boju kose, kože i očiju. Okulokutani albinizam uzrokovan mutacijama u OCA2 genu naziva se okulokutani albinizam tip 2. Prevalencija OCA tipa 2 procjenjuje se na 1/ 38.000 – 1 / 40.000 u većini populacija širom svijeta, s većom prevalencijom u afričkoj populaciji, od 1/3.900 – 1/1.500.[7] Ostale bolesti povezane s delecijom gena OCA2 su Angelmanov sindrom (svijetla kosa i svijetla koža) i Prader-Willijev sindrom (neobično svijetla kosa i svijetla koža). Uz oba ova sindroma, delecija se često javlja kod osoba sa bilo kojim sindromom.[8][9]
Mutacija gena HERC2, uz OCA2, koja utiče na ekspresiju OCA2 u ljudskom irisu, pronađena je zajednička za gotovo sve ljude sa plavim očima. Pretpostavlja se da svi plavooki ljudi dijele jednog zajedničkog pretka s kojim je nastala mutacija.[10][11][12]
His615Arg alel OCA2 uključen je u svijetli ton kože, a izvedeni alel s visokim frekvencijama,ograničen je na Istočnu Aziju, s najvišim frekvencijama u Istočnoj Aziji (49-63%), srednje frekventan u Jugoistočnoj Aziji, a najniže u zapadnoj Kini i nekim populacijama istočne Evrope.[13][14]
Reference
uredi- ^ a b c ENSG00000277361 GRCh38: Ensembl release 89: ENSG00000104044, ENSG00000277361 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030450 - 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.
- ^ a b "Entrez Gene: OCA2 oculocutaneous albinism II (pink-eye dilution homolog, mouse)". Pristupljeno 12. 3. 2015.
- ^ "UniProt, Q04671". Pristupljeno 16. 7. 2021.
- ^ Hayashi, Masahiro; Suzuki, Tamio (april 2013). "Oculocutaneous albinism type 2". Orphanet. Pristupljeno 9. 11. 2014.
- ^ "OCA2 - oculocutaneous albinism II". Genetics Home Reference - Your guide to understanding genetic conditions. U.S. National Library of Medicine. Pristupljeno 30. 3. 2013.
- ^ "Don't it make your brown eyes blue?". Understanding Genetics. Understanding Genetics. Arhivirano s originala, 12. 5. 2018. Pristupljeno 30. 3. 2013.
- ^ Bryner J (31. 1. 2008). "Here's what made those brown eyes blue". Health News. NBC News. Arhivirano s originala, 23. 9. 2020. Pristupljeno 6. 11. 2008.; Bryner J (31. 1. 2008). "One Common Ancestor Behind Blue Eyes". LiveScience. Imaginova Corp. Pristupljeno 6. 11. 2008.; "Blue-eyed humans have a single, common ancestor". News. University of Copenhagen. 30. 1. 2008. Arhivirano s originala, 2. 7. 2013. Pristupljeno 6. 11. 2008.
- ^ Eiberg H, Troelsen J, Nielsen M, Mikkelsen A, Mengel-From J, Kjaer KW, Hansen L (2008). "Blue eye color in humans may be caused by a perfectly associated founder mutation in a regulatory element located within the HERC2 gene inhibiting OCA2 expression". Hum. Genet. 123 (2): 177–87. doi:10.1007/s00439-007-0460-x. PMID 18172690. S2CID 9886658.
- ^ Sturm RA, Duffy DL, Zhao ZZ, Leite FP, Stark MS, Hayward NK, Martin NG, Montgomery GW (2008). "A single SNP in an evolutionary conserved region within intron 86 of the HERC2 gene determines human blue-brown eye color". Am. J. Hum. Genet. 82 (2): 424–31. doi:10.1016/j.ajhg.2007.11.005. PMC 2427173. PMID 18252222.
- ^ Donnelly MP, Paschou P, Grigorenko E, Gurwitz D, Barta C, Lu RB, Zhukova OV, Kim JJ, Siniscalco M, New M, Li H, Kajuna SL, Manolopoulos VG, Speed WC, Pakstis AJ, Kidd JR, Kidd KK (2012). "A global view of the OCA2-HERC2 region and pigmentation". Hum. Genet. 131 (5): 683–96. doi:10.1007/s00439-011-1110-x. PMC 3325407. PMID 22065085.
- ^ Edwards M, Bigham A, Tan J, Li S, Gozdzik A, Ross K, Jin L, Parra EJ (2010). "Association of the OCA2 polymorphism His615Arg with melanin content in east Asian populations: further evidence of convergent evolution of skin pigmentation". PLOS Genet. 6 (3): e1000867. doi:10.1371/journal.pgen.1000867. PMC 2832666. PMID 20221248.
Dopunska literatura
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