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ABCA12
Identifikatori
Aliasi	ABCA12
Vanjski ID-jevi	OMIM: 607800 MGI: 2676312 HomoloGene: 45441 GeneCards: ABCA12
Lokacija gena (čovjek)
Hrom.	Hromosom 2 (čovjek)
Kraj	215,138,626 bp
Lokacija gena (miš)
Hrom.	Hromosom 1 (miš)
Kraj	71,454,069 bp
Ontologija gena
Molekularna funkcija	• nucleotide binding; • transporter activity; • apolipoprotein A-I receptor binding; • ATPase activity; • GO:0001948, GO:0016582 vezivanje za proteine; • signaling receptor binding; • ATP binding; • ATPase-coupled lipid transmembrane transporter activity; • lipid transporter activity; • ATPase-coupled transmembrane transporter activity;
Ćelijska komponenta	• citoplazma; • integral component of membrane; • citosol; • membrana; • ćelijska membrana; • epidermal lamellar body; • intracellular membrane-bounded organelle;
Biološki proces	• surfactant homeostasis; • lipid transport; • ceramide transport; • establishment of skin barrier; • secretion by cell; • phospholipid efflux; • keratinization; • cellular homeostasis; • keratinocyte differentiation; • positive regulation of cholesterol efflux; • positive regulation of protein localization to cell surface; • lipid homeostasis; • regulated exocytosis; • lung alveolus development; • protein localization to plasma membrane; • transmembrane transport;
	Izvori:Amigo / QuickGO
Ortolozi
	26154
	74591
	ENSG00000144452
	ENSMUSG00000050296
	Q86UK0
	E9Q876
	NM_015657; NM_173076
	NM_175210
	NP_056472; NP_775099
	NP_780419
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Član 12 potporodice A ATP-vezujuće kasete znan I kao transporter 12 ATP-vezujuće kasete jest protein koji je kod ljudi kodiran genom ABCA12 sa hromosoma 2.^[5]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 2.595 aminokiselina, a molekulska težina 293.237 Da.^[6]

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

ABCA12 pripada grupi gena koji se nazivaju porodica ATP-vezujuća kaseta, koji stvara proteine za transport molekula kroz ćelijsku membranu. ABCA12 gen aktivan je u nekim tipovima ćelija kože i u tkivima nekoliko drugih organa, kao što su sjemenici, placenta, pluća, želudac i fetusni mozak i jetra. Čini se da je ovaj protein neophodan za normalan razvoj kože, koja predstavlja barijeru između tijela i okoline. On transportuje epidermozid, glukozilceramid, iz keratinocita stratum corneum epiderme.^[7]

Gen ABCA12 nalazi se na dugom (q) kraku hromosoma 2 između pozicija 34 i 35, od bp 215,621.772 do baznog para 215,828.656.

Klinički značaj

Ihtioza tipa harlekin

Poznato je da nekoliko mutacija gena ABCA12 uzrokuje ihtiozu tipa harlekin.^[8] Predviđa se da će većina ovih mutacija dovesti do odsustva proteina ABCA12 ili proizvodnje izuzetno male verzije proteina koja ne može pravilno transportirati lipide. Gubitak funkcionalnog proteina ABCA12 uzrokuje brojne probleme u razvoju epiderme prije i nakon rođenja. Abnormalnosti u transportu lipida sprečavaju kožu da formira efikasnu barijeru i dovode do tvrdih, debelih ljuski karakterističnih za ihtiozu harlekin.

Lamelna ihtioza tip 2

Mutacije u genu ABCA12 također uzrokuju još jedan teški poremećaj kože, lamelnu ihtiozu tip 2.^[9]^[10] Ljudi s ovim poremećajem imaju crvenu, ljuskavu kožu nalik pločama koja pokriva većinu tijela. Mutacije ABCA12 koje uzrokuju ovaj poremećaj zamjenjuju jednu aminokiselinu (građevni blok proteina) za drugu aminokiselinu u proteinu ABCA12. Ove mutacije se gotovo uvijek javljaju u važnoj funkcionalnoj regiji proteina (regiji koja se vezuje za ATP, molekul ukoji opskrbljuje energiju za hemijske reakcije). Promjene u strukturi proteina ABCA12 vjerovatno narušavaju njegovu sposobnost transporta lipida, što utiče na razvoj kože prije i nakon rođenja.

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000144452 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000050296 - 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.
^ "Entrez Gene: ATP-binding cassette".
^ "UniProt, Q86UK0" (jezik: engleski). Pristupljeno 15. 11. 2021.
^ Y. Ishibashi; A. Kohyama-Koganeya; Y. Hirabayashi (2013). "New insights on glucosylated lipids: Metabolism and functions". Biochim. Biophys. Acta. 1831 (9): 1475–1485. doi:10.1016/j.bbalip.2013.06.001. PMID 23770033.
^ Kelsell DP, Norgett EE, Unsworth H, et al. (maj 2005). "Mutations in ABCA12 underlie the severe congenital skin disease harlequin ichthyosis". Am. J. Hum. Genet. 76 (5): 794–803. doi:10.1086/429844. PMC 1199369. PMID 15756637.
^ Annilo T, Shulenin S, Chen ZQ, Arnould I, Prades C, Lemoine C, Maintoux-Larois C, Devaud C, Dean M, Denefle P, Rosier M (2002). "Identification and characterization of a novel ABCA subfamily member, ABCA12, located in the lamellar ichthyosis region on 2q34". Cytogenet Genome Res. 98 (2–3): 169–76. doi:10.1159/000069811. PMID 12697999. S2CID 28012695.
^ Lefevre C, Audebert S, Jobard F, Bouadjar B, Lakhdar H, Boughdene-Stambouli O, Blanchet-Bardon C, Heilig R, Foglio M, Weissenbach J, Lathrop M, Prud'homme JF, Fischer J (2003). "Mutations in the transporter ABCA12 are associated with lamellar ichthyosis type 2". Hum Mol Genet. 12 (18): 2369–78. doi:10.1093/hmg/ddg235. PMID 12915478.

Dopunska literatura

Lefévre C, Audebert S, Jobard F, Bouadjar B, Lakhdar H, Boughdene-Stambouli O, Blanchet-Bardon C, Heilig R, Foglio M, Weissenbach J, Lathrop M, Prud'homme JF, Fischer J (septembar 2003). "Mutations in the transporter ABCA12 are associated with lamellar ichthyosis type 2". Hum. Mol. Genet. 12 (18): 2369–78. doi:10.1093/hmg/ddg235. PMID 12915478.*Sakai K, Akiyama M, Sugiyama-Nakagiri Y, et al. (2007). "Localization of ABCA12 from Golgi apparatus to lamellar granules in human upper epidermal keratinocytes". Exp. Dermatol. 16 (11): 920–6. doi:10.1111/j.1600-0625.2007.00614.x. PMID 17927575. S2CID 23836833.
Thomas AC, Tattersall D, Norgett EE, et al. (2009). "Premature terminal differentiation and a reduction in specific proteases associated with loss of ABCA12 in Harlequin ichthyosis". Am. J. Pathol. 174 (3): 970–8. doi:10.2353/ajpath.2009.080860. PMC 2665756. PMID 19179616.
Yamanaka Y, Akiyama M, Sugiyama-Nakagiri Y, et al. (2007). "Expression of the keratinocyte lipid transporter ABCA12 in developing and reconstituted human epidermis". Am. J. Pathol. 171 (1): 43–52. doi:10.2353/ajpath.2007.061207. PMC 1941601. PMID 17591952.
Thomas AC, Sinclair C, Mahmud N, et al. (2008). "Novel and recurring ABCA12 mutations associated with harlequin ichthyosis: implications for prenatal diagnosis". Br. J. Dermatol. 158 (3): 611–3. doi:10.1111/j.1365-2133.2007.08277.x. PMID 17986308. S2CID 10098614.
Rose JE, Behm FM, Drgon T, et al. (2010). "Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score". Mol. Med. 16 (7–8): 247–53. doi:10.2119/molmed.2009.00159. PMC 2896464. PMID 20379614.
Dean M, Rzhetsky A, Allikmets R (2001). "The human ATP-binding cassette (ABC) transporter superfamily". Genome Res. 11 (7): 1156–66. doi:10.1101/gr.184901 (neaktivno 31. 10. 2021). PMID 11435397.CS1 održavanje: DOI nije aktivan od 2021 (link)
Jiang YJ, Lu B, Kim P, et al. (2008). "PPAR and LXR activators regulate ABCA12 expression in human keratinocytes". J. Invest. Dermatol. 128 (1): 104–9. doi:10.1038/sj.jid.5700944. PMID 17611579.
Ohkubo T, Shibata N, Ohnuma T, et al. (2005). "No genetic association between ATP binding cassette proteins and Japanese sporadic Alzheimer's disease". Dement Geriatr Cogn Disord. 20 (2–3): 95–8. doi:10.1159/000086473. PMID 15980630. S2CID 25370003.
Jiang YJ, Uchida Y, Lu B, et al. (2009). "Ceramide stimulates ABCA12 expression via peroxisome proliferator-activated receptor {delta} in human keratinocytes". J. Biol. Chem. 284 (28): 18942–52. doi:10.1074/jbc.M109.006973. PMC 2707228. PMID 19429679.
Annilo T, Shulenin S, Chen ZQ, et al. (2002). "Identification and characterization of a novel ABCA subfamily member, ABCA12, located in the lamellar ichthyosis region on 2q34". Cytogenet. Genome Res. 98 (2–3): 169–76. doi:10.1159/000069811. PMID 12697999. S2CID 28012695.
Akiyama M, Sugiyama-Nakagiri Y, Sakai K, et al. (2005). "Mutations in lipid transporter ABCA12 in harlequin ichthyosis and functional recovery by corrective gene transfer". J. Clin. Invest. 115 (7): 1777–84. doi:10.1172/JCI24834. PMC 1159149. PMID 16007253.
Parmentier L, Clepet C, Boughdene-Stambouli O, et al. (1999). "Lamellar ichthyosis: further narrowing, physical and expression mapping of the chromosome 2 candidate locus". Eur. J. Hum. Genet. 7 (1): 77–87. doi:10.1038/sj.ejhg.5200271. PMID 10094194. S2CID 17929356.
Kelsell DP, Norgett EE, Unsworth H, et al. (2005). "Mutations in ABCA12 underlie the severe congenital skin disease harlequin ichthyosis". Am. J. Hum. Genet. 76 (5): 794–803. doi:10.1086/429844. PMC 1199369. PMID 15756637.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039. S2CID 21903526.
Mammalian Gene Collection Program Team; Strausberg, R. L.; Feingold, E. A.; Grouse, L. H.; et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proceedings of the National Academy of Sciences of the United States of America. 99 (26): 16899–16903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Natsuga K, Akiyama M, Kato N, et al. (2007). "Novel ABCA12 mutations identified in two cases of non-bullous congenital ichthyosiform erythroderma associated with multiple skin malignant neoplasia". J. Invest. Dermatol. 127 (11): 2669–73. doi:10.1038/sj.jid.5700885. hdl:2115/32351. PMID 17508018.
Sakai K, Akiyama M, Yanagi T, et al. (2009). "ABCA12 is a major causative gene for non-bullous congenital ichthyosiform erythroderma". J. Invest. Dermatol. 129 (9): 2306–9. doi:10.1038/jid.2009.23. PMID 19262603.
Allikmets R, Gerrard B, Hutchinson A, Dean M (1996). "Characterization of the human ABC superfamily: isolation and mapping of 21 new genes using the expressed sequence tags database". Hum. Mol. Genet. 5 (10): 1649–55. doi:10.1093/hmg/5.10.1649. PMID 8894702.
Thomas AC, Cullup T, Norgett EE, et al. (2006). "ABCA12 is the major harlequin ichthyosis gene". J. Invest. Dermatol. 126 (11): 2408–13. doi:10.1038/sj.jid.5700455. PMID 16902423.

Vanjski linkovi

GeneCard
ABCA12 protein, human na US National Library of Medicine Medical Subject Headings (MeSH)
ABCA12 lokacija ljudskog genoma UCSC Genome Browser.

ABCA12 detalji ljudskog genoma u UCSC Genome Browser.

10	20	30	40	50
MASLFHQLQI	LVWKNWLGVK	RQPLWTLVLI	LWPVIIFIIL	AITRTKFPPT
AKPTCYLAPR	NLPSTGFFPF	LQTLLCDTDS	KCKDTPYGPQ	DLLRRKGIDD
ALFKDSEILR	KSSNLDKDSS	LSFQSTQVPE	RRHASLATVF	PSPSSDLEIP
GTYTFNGSQV	LARILGLEKL	LKQNSTSEDI	RRELCDSYSG	YIVDDAFSWT
FLGRNVFNKF	CLSNMTLLES	SLQELNKQFS	QLSSDPNNQK	IVFQEIVRML
SFFSQVQEQK	AVWQLLSSFP	NVFQNDTSLS	NLFDVLRKAN	SVLLVVQKVY
PRFATNEGFR	TLQKSVKHLL	YTLDSPAQGD	SDNITHVWNE	DDGQTLSPSS
LAAQLLILEN	FEDALLNISA	NSPYIPYLAC	VRNVTDSLAR	GSPENLRLLQ
STIRFKKSFL	RNGSYEDYFP	PVPEVLKSKL	SQLRNLTELL	CESETFSLIE
KSCQLSDMSF	GSLCEESEFD	LQLLEAAELG	TEIAASLLYH	DNVISKKVRD
LLTGDPSKIN	LNMDQFLEQA	LQMNYLENIT	QLIPIIEAML	HVNNSADASE
KPGQLLEMFK	NVEELKEDLR	RTTGMSNRTI	DKLLAIPIPD	NRAEIISQVF
WLHSCDTNIT	TPKLEDAMKE	FCNLSLSERS	RQSYLIGLTL	LHYLNIYNFT
YKVFFPRKDQ	KPVEKMMELF	IRLKEILNQM	ASGTHPLLDK	MRSLKQMHLP
RSVPLTQAMY	RSNRMNTPQG	SFSTISQALC	SQGITTEYLT	AMLPSSQRPK
GNHTKDFLTY	KLTKEQIASK	YGIPINSTPF	CFSLYKDIIN	MPAGPVIWAF
LKPMLLGRIL	YAPYNPVTKA	IMEKSNVTLR	QLAELREKSQ	EWMDKSPLFM
NSFHLLNQAI	PMLQNTLRNP	FVQVFVKFSV	GLDAVELLKQ	IDELDILRLK
LENNIDIIDQ	LNTLSSLTVN	ISSCVLYDRI	QAAKTIDEME	REAKRLYKSN
ELFGSVIFKL	PSNRSWHRGY	DSGNVFLPPV	IKYTIRMSLK	TAQTTRSLRT
KIWAPGPHNS	PSHNQIYGRA	FIYLQDSIER	AIIELQTGRN	SQEIAVQVQA
IPYPCFMKDN	FLTSVSYSLP	IVLMVAWVVF	IAAFVKKLVY	EKDLRLHEYM
KMMGVNSCSH	FFAWLIESVG	FLLVTIVILI	IILKFGNILP	KTNGFILFLY
FSDYSFSVIA	MSYLISVFFN	NTNIAALIGS	LIYIIAFFPF	IVLVTVENEL
SYVLKVFMSL	LSPTAFSYAS	QYIARYEEQG	IGLQWENMYT	SPVQDDTTSF
GWLCCLILAD	SFIYFLIAWY	VRNVFPGTYG	MAAPWYFPIL	PSYWKERFGC
AEVKPEKSNG	LMFTNIMMQN	TNPSASPEYM	FSSNIEPEPK	DLTVGVALHG
VTKIYGSKVA	VDNLNLNFYE	GHITSLLGPN	GAGKTTTISM	LTGLFGASAG
TIFVYGKDIK	TDLHTVRKNM	GVCMQHDVLF	SYLTTKEHLL	LYGSIKVPHW
TKKQLHEEVK	RTLKDTGLYS	HRHKRVGTLS	GGMKRKLSIS	IALIGGSRVV
ILDEPSTGVD	PCSRRSIWDV	ISKNKTARTI	ILSTHHLDEA	EVLSDRIAFL
EQGGLRCCGS	PFYLKEAFGD	GYHLTLTKKK	SPNLNANAVC	DTMAVTAMIQ
SHLPEAYLKE	DIGGELVYVL	PPFSTKVSGA	YLSLLRALDN	GMGDLNIGCY
GISDTTVEEV	FLNLTKESQK	NSAMSLEHLT	QKKIGNSNAN	GISTPDDLSV
SSSNFTDRDD	KILTRGERLD	GFGLLLKKIM	AILIKRFHHT	RRNWKGLIAQ
VILPIVFVTT	AMGLGTLRNS	SNSYPEIQIS	PSLYGTSEQT	AFYANYHPST
EALVSAMWDF	PGIDNMCLNT	SDLQCLNKDS	LEKWNTSGEP	ITNFGVCSCS
ENVQECPKFN	YSPPHRRTYS	SQVIYNLTGQ	RVENYLISTA	NEFVQKRYGG
WSFGLPLTKD	LRFDITGVPA	NRTLAKVWYD	PEGYHSLPAY	LNSLNNFLLR
VNMSKYDAAR	HGIIMYSHPY	PGVQDQEQAT	ISSLIDILVA	LSILMGYSVT
TASFVTYVVR	EHQTKAKQLQ	HISGIGVTCY	WVTNFIYDMV	FYLVPVAFSI
GIIAIFKLPA	FYSENNLGAV	SLLLLLFGYA	TFSWMYLLAG	LFHETGMAFI
TYVCVNLFFG	INSIVSLSVV	YFLSKEKPND	PTLELISETL	KRIFLIFPQF
CFGYGLIELS	QQQSVLDFLK	AYGVEYPNET	FEMNKLGAMF	VALVSQGTMF
FSLRLLINES	LIKKLRLFFR	KFNSSHVRET	IDEDEDVRAE	RLRVESGAAE
FDLVQLYCLT	KTYQLIHKKI	IAVNNISIGI	PAGECFGLLG	VNGAGKTTIF
KMLTGDIIPS	SGNILIRNKT	GSLGHVDSHS	SLVGYCPQED	ALDDLVTVEE
HLYFYARVHG	IPEKDIKETV	HKLLRRLHLM	PFKDRATSMC	SYGTKRKLST
ALALIGKPSI	LLLDEPSSGM	DPKSKRHLWK	IISEEVQNKC	SVILTSHSME
ECEALCTRLA	IMVNGKFQCI	GSLQHIKSRF	GRGFTVKVHL	KNNKVTMETL
TKFMQLHFPK	TYLKDQHLSM	LEYHVPVTAG	GVANIFDLLE	TNKTALNITN
FLVSQTTLEE	VFINFAKDQK	SYETADTSSQ	GSTISVDSQD	DQMES