OCA2

OCA2
Identifikatori
Aliasi	OCA2
Vanjski ID-jevi	OMIM: 611409 MGI: 97454 HomoloGene: 37281 GeneCards: OCA2
Lokacija gena (čovjek)
Hrom.	Hromosom 15 (čovjek)
Kraj	28,099,315 bp
Lokacija gena (miš)
Hrom.	Hromosom 7 (miš)
Kraj	56,186,266 bp
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
	4948
	18431
	ENSG00000104044; ENSG00000277361
	ENSMUSG00000030450
	Q04671
	Q62052
	NM_000275; NM_001300984
	NM_021879
	NP_000266; NP_001287913
	NP_068679
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

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

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

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

^ ^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

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

Commons logo

Commons ima datoteke na temu: OCA2

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

[refGRCh38Ensembl-1] ENSG00000277361 GRCh38: Ensembl release 89: ENSG00000104044, ENSG00000277361 - Ensembl, maj 2017

[refGRCm38Ensembl-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.

[entrez-5] "Entrez Gene: OCA2 oculocutaneous albinism II (pink-eye dilution homolog, mouse)". Pristupljeno 12. 3. 2015.

[UniProt-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.

[OCA2_blue_eyes_press-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.

[pmid18172690-11] 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.

[pmid18252222-12] 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.

[pmid22065085-13] 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.

[Edwards_2010-14] 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.

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