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.

U čovjeka, OCA2 gen nalazi se na dugom (q) kraku hromosoma 15 između položaja 12 i 13.1

OCA2
Identifikatori
Aliasi	OCA2
Vanjski ID-jevi	OMIM: 611409 MGI: 97454 HomoloGene: 37281 GeneCards: OCA2
Lokacija gena (čovjek) Hrom. Hromosom 15 (čovjek)[1] Bend 15q12-q13.1 Početak 27,754,875 bp[1] Kraj 28,099,315 bp[1]
Lokacija gena (miš) Hrom. Hromosom 7 (miš)[2] Bend 7 B5|7 33.44 cM Početak 55,889,508 bp[2] Kraj 56,186,266 bp[2]
Obrazac RNK ekspresije Više referentnih podataka o ekspresiji
Ontologija gena Molekularna funkcija • transporter activity • L-tyrosine transmembrane transporter activity • GO:0001948, GO:0016582 vezivanje za proteine Ćelijska komponenta • endoplasmic reticulum membrane • lysosomal membrane • endosome membrane • membrana • citoplazma • melanosome membrane • integral component of membrane Biološki proces • eye pigment biosynthetic process • pigmentation • developmental pigmentation • melanin biosynthetic process • Ćelijska proliferacija • transmembrane transport • spermatid development • melanocyte differentiation • tyrosine transport Izvori:Amigo / QuickGO
Ortolozi
Vrste	Čovjek	Miš
Entrez	4948	18431
Ensembl	ENSG00000104044 ENSG00000277361	ENSMUSG00000030450
UniProt	Q04671	Q62052
RefSeq (mRNK)	NM_000275 NM_001300984	NM_021879
RefSeq (bjelančevina)	NP_000266 NP_001287913	NP_068679
Lokacija (UCSC)	Chr 15: 27.75 – 28.1 Mb	Chr 7: 55.89 – 56.19 Mb
PubMed pretraga	[3]	[4]
Wikipodaci
Pogledaj/uredi – čovjek Pogledaj/uredi – miš

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.

Raspon ekspreaije gena OCA2

Aminokiselinska sekvenca

Dužina 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

C: Cistein
D: Asparaginska kiselina
E: Glutaminska kiselina
F: Fenilalanin
G: Glicin
H: Histidin
I: Izoleucin
K: Lizin
L: Leucin
M: Metionin
N: Asparagin
P: Prolin
Q: Glutamin
R: Arginin
S: Serin
T: Treonin
V: Valin
W: Triptofan
Y: Tirozin

Funkcija

OCA2 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

Mutacije 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

1. ENSG00000277361 GRCh38: Ensembl release 89: ENSG00000104044, ENSG00000277361 - Ensembl, maj 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000030450 - Ensembl, maj 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. "Entrez Gene: OCA2 oculocutaneous albinism II (pink-eye dilution homolog, mouse)". Pristupljeno 12. 3. 2015.
6. "UniProt, Q04671". Pristupljeno 16. 7. 2021.
7. Hayashi, Masahiro; Suzuki, Tamio (april 2013). "Oculocutaneous albinism type 2". Orphanet. Pristupljeno 9. 11. 2014.
8. "OCA2 - oculocutaneous albinism II". Genetics Home Reference - Your guide to understanding genetic conditions. U.S. National Library of Medicine. Pristupljeno 30. 3. 2013.
9. "Don't it make your brown eyes blue?". Understanding Genetics. Understanding Genetics. Arhivirano s originala, 12. 5. 2018. Pristupljeno 30. 3. 2013.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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

• Oetting WS, King RA (1999). "Molecular basis of albinism: mutations and polymorphisms of pigmentation genes associated with albinism". Hum. Mutat. 13 (2): 99–115. doi:10.1002/(SICI)1098-1004(1999)13:2<99::AID-HUMU2>3.0.CO;2-C. PMID 10094567.
• Brilliant MH (2001). "The mouse p (pink-eyed dilution) and human P genes, oculocutaneous albinism type 2 (OCA2), and melanosomal pH". Pigment Cell Res. 14 (2): 86–93. doi:10.1034/j.1600-0749.2001.140203.x. PMID 11310796.
• Ramsay M, Colman MA, Stevens G, Zwane E, Kromberg J, Farrall M, Jenkins T (1992). "The tyrosinase-positive oculocutaneous albinism locus maps to chromosome 15q11.2-q12". Am. J. Hum. Genet. 51 (4): 879–84. PMC 1682821. PMID 1415228.
• Gardner JM, Nakatsu Y, Gondo Y, Lee S, Lyon MF, King RA, Brilliant MH (1992). "The mouse pink-eyed dilution gene: association with human Prader-Willi and Angelman syndromes". Science. 257 (5073): 1121–4. Bibcode:1992Sci...257.1121G. doi:10.1126/science.257.5073.1121. PMID 1509264. S2CID 5800811.
• Ludowese CJ, Thompson KJ, Sekhon GS, Pauli RM (1991). "Absence of predictable phenotypic expression in proximal 15q duplications". Clin. Genet. 40 (3): 194–201. doi:10.1111/j.1399-0004.1991.tb03076.x. PMID 1773534. S2CID 28419032.
• Lee ST, Nicholls RD, Jong MT, Fukai K, Spritz RA (1995). "Organization and sequence of the human P gene and identification of a new family of transport proteins". Genomics. 26 (2): 354–63. doi:10.1016/0888-7543(95)80220-G. PMID 7601462.
• Spritz RA, Fukai K, Holmes SA, Luande J (1995). "Frequent intragenic deletion of the P gene in Tanzanian patients with type II oculocutaneous albinism (OCA2)". Am. J. Hum. Genet. 56 (6): 1320–3. PMC 1801108. PMID 7762554.
• Lee ST, Nicholls RD, Schnur RE, Guida LC, Lu-Kuo J, Spinner NB, Zackai EH, Spritz RA (1994). "Diverse mutations of the P gene among African-Americans with type II (tyrosinase-positive) oculocutaneous albinism (OCA2)". Hum. Mol. Genet. 3 (11): 2047–51. PMID 7874125.
• Durham-Pierre D, Gardner JM, Nakatsu Y, King RA, Francke U, Ching A, Aquaron R, del Marmol V, Brilliant MH (1994). "African origin of an intragenic deletion of the human P gene in tyrosinase positive oculocutaneous albinism". Nat. Genet. 7 (2): 176–9. doi:10.1038/ng0694-176. PMID 7920637. S2CID 6185436.
• Lee ST, Nicholls RD, Bundey S, Laxova R, Musarella M, Spritz RA (1994). "Mutations of the P gene in oculocutaneous albinism, ocular albinism, and Prader-Willi syndrome plus albinism". N. Engl. J. Med. 330 (8): 529–34. doi:10.1056/NEJM199402243300803. PMID 8302318.
• Rinchik EM, Bultman SJ, Horsthemke B, Lee ST, Strunk KM, Spritz RA, Avidano KM, Jong MT, Nicholls RD (1993). "A gene for the mouse pink-eyed dilution locus and for human type II oculocutaneous albinism". Nature. 361 (6407): 72–6. Bibcode:1993Natur.361...72R. doi:10.1038/361072a0. PMID 8421497. S2CID 21794972.
• Spritz RA, Lee ST, Fukai K, Brondum-Nielsen K, Chitayat D, Lipson MH, Musarella MA, Rosenmann A, Weleber RG (1997). "Novel mutations of the P gene in type II oculocutaneous albinism (OCA2)". Hum. Mutat. 10 (2): 175–7. doi:10.1002/(SICI)1098-1004(1997)10:2<175::AID-HUMU12>3.0.CO;2-X. PMID 9259203.
• Kerr R, Stevens G, Manga P, Salm S, John P, Haw T, Ramsay M (2000). "Identification of P gene mutations in individuals with oculocutaneous albinism in sub-Saharan Africa". Hum. Mutat. 15 (2): 166–72. doi:10.1002/(SICI)1098-1004(200002)15:2<166::AID-HUMU5>3.0.CO;2-Z. PMID 10649493.
• Oetting WS, Gardner JM, Fryer JP, Ching A, Durham-Pierre D, King RA, Brilliant MH (1998). "Mutations of the human P gene associated with Type II oculocutaneous albinism (OCA2). Mutations in brief no. 205. Online". Hum. Mutat. 12 (6): 434. doi:10.1002/(SICI)1098-1004(1998)12:6<434::AID-HUMU16>3.0.CO;2-7. PMID 10671067.
• Passmore LA, Kaesmann-Kellner B, Weber BH (1999). "Novel and recurrent mutations in the tyrosinase gene and the P gene in the German albino population". Hum. Genet. 105 (3): 200–10. doi:10.1007/s004390051090. PMID 10987646.
• Manga P, Kromberg J, Turner A, Jenkins T, Ramsay M (2001). "In Southern Africa, brown oculocutaneous albinism (BOCA) maps to the OCA2 locus on chromosome 15q: P-gene mutations identified". Am. J. Hum. Genet. 68 (3): 782–7. doi:10.1086/318800. PMC 1274491. PMID 11179026.
• Manga P, Orlow SJ (2001). "Inverse correlation between pink-eyed dilution protein expression and induction of melanogenesis by bafilomycin A1". Pigment Cell Res. 14 (5): 362–7. doi:10.1034/j.1600-0749.2001.140508.x. PMID 11601658.
• Toyofuku K, Valencia JC, Kushimoto T, Costin GE, Virador VM, Vieira WD, Ferrans VJ, Hearing VJ (2002). "The etiology of oculocutaneous albinism (OCA) type II: the pink protein modulates the processing and transport of tyrosinase". Pigment Cell Res. 15 (3): 217–24. doi:10.1034/j.1600-0749.2002.02007.x. PMID 12028586.

Vanjski linkovi

• GeneReviews/NCBI/NIH/UW entry on Oculocutaneous Albinism Type 2