ID ABCAC_HUMAN Reviewed; 2595 AA. AC Q86UK0; Q53QE2; Q53S55; Q8IZW6; Q96JT3; Q9Y4M5; DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot. DT 24-NOV-2009, sequence version 3. DT 27-MAR-2024, entry version 178. DE RecName: Full=Glucosylceramide transporter ABCA12 {ECO:0000305}; DE EC=7.6.2.1 {ECO:0000269|PubMed:16007253, ECO:0000269|PubMed:20869849}; DE AltName: Full=ATP-binding cassette sub-family A member 12; DE AltName: Full=ATP-binding cassette transporter 12; DE Short=ATP-binding cassette 12; GN Name=ABCA12 {ECO:0000312|HGNC:HGNC:14637}; Synonyms=ABC12; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND VARIANT RP THR-777. RC TISSUE=Placenta; RX PubMed=12697999; DOI=10.1159/000069811; RA Annilo T., Shulemin S., Chen Z.Q., Arnould I., Prades C., Lemoine C., RA Maintoux-Larois C., Devaud C., Dean M., Denefle P., Rosier M.; RT "Identification and characterization of a novel ABCA subfamily member, RT ABCA12, located in the lamellar ichthyosis region on 2q34."; RL Cytogenet. Genome Res. 98:169-176(2002). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANT THR-777. RC TISSUE=Retina; RA Bonner T.I., Moses T., Detera-Wadleigh S.; RT "A retinal cDNA for the ATP-binding cassette transporter ABCA12."; RL Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 221-2595, AND VARIANT THR-777. RA Schaap F.G., van Wijland M., Groen A.K.; RT "Cloning of a novel ABC transporter (ABCA12) tentatively involved in lipid RT homeostatis."; RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2400-2595. RC TISSUE=Testis; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [6] RP TISSUE SPECIFICITY, INDUCTION, SUBCELLULAR LOCATION, FUNCTION, VARIANTS RP ARCI4B 434-ARG--SER-2595 DEL; THR-1385 DEL AND 1950-ARG--SER-2595 DEL, AND RP CATALYTIC ACTIVITY. RX PubMed=16007253; DOI=10.1172/jci24834; RA Akiyama M., Sugiyama-Nakagiri Y., Sakai K., McMillan J.R., Goto M., RA Arita K., Tsuji-Abe Y., Tabata N., Matsuoka K., Sasaki R., Sawamura D., RA Shimizu H.; RT "Mutations in lipid transporter ABCA12 in harlequin ichthyosis and RT functional recovery by corrective gene transfer."; RL J. Clin. Invest. 115:1777-1784(2005). RN [7] RP DEVELOPMENTAL STAGE, TISSUE SPECIFICITY, AND INDUCTION. RX PubMed=17591952; DOI=10.2353/ajpath.2007.061207; RA Yamanaka Y., Akiyama M., Sugiyama-Nakagiri Y., Sakai K., Goto M., RA McMillan J.R., Ota M., Sawamura D., Shimizu H.; RT "Expression of the keratinocyte lipid transporter ABCA12 in developing and RT reconstituted human epidermis."; RL Am. J. Pathol. 171:43-52(2007). RN [8] RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND FUNCTION. RX PubMed=17927575; DOI=10.1111/j.1600-0625.2007.00614.x; RA Sakai K., Akiyama M., Sugiyama-Nakagiri Y., McMillan J.R., Sawamura D., RA Shimizu H.; RT "Localization of ABCA12 from Golgi apparatus to lamellar granules in human RT upper epidermal keratinocytes."; RL Exp. Dermatol. 16:920-926(2007). RN [9] RP INDUCTION. RX PubMed=17611579; DOI=10.1038/sj.jid.5700944; RA Jiang Y.J., Lu B., Kim P., Paragh G., Schmitz G., Elias P.M., RA Feingold K.R.; RT "PPAR and LXR activators regulate ABCA12 expression in human RT keratinocytes."; RL J. Invest. Dermatol. 128:104-109(2008). RN [10] RP TISSUE SPECIFICITY, AND FUNCTION. RX PubMed=19179616; DOI=10.2353/ajpath.2009.080860; RA Thomas A.C., Tattersall D., Norgett E.E., O'Toole E.A., Kelsell D.P.; RT "Premature terminal differentiation and a reduction in specific proteases RT associated with loss of ABCA12 in Harlequin ichthyosis."; RL Am. J. Pathol. 174:970-978(2009). RN [11] RP INDUCTION. RX PubMed=19429679; DOI=10.1074/jbc.m109.006973; RA Jiang Y.J., Uchida Y., Lu B., Kim P., Mao C., Akiyama M., Elias P.M., RA Holleran W.M., Grunfeld C., Feingold K.R.; RT "Ceramide stimulates ABCA12 expression via peroxisome proliferator- RT activated receptor {delta} in human keratinocytes."; RL J. Biol. Chem. 284:18942-18952(2009). RN [12] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=20869849; DOI=10.1016/j.jdermsci.2010.08.012; RA Mitsutake S., Suzuki C., Akiyama M., Tsuji K., Yanagi T., Shimizu H., RA Igarashi Y.; RT "ABCA12 dysfunction causes a disorder in glucosylceramide accumulation RT during keratinocyte differentiation."; RL J. Dermatol. Sci. 60:128-129(2010). RN [13] RP TISSUE SPECIFICITY. RX PubMed=32072744; DOI=10.15252/embr.201948692; RA Ursino G.M., Fu Y., Cottle D.L., Mukhamedova N., Jones L.K., Low H., RA Tham M.S., Gan W.J., Mellett N.A., Das P.P., Weir J.M., Ditiatkovski M., RA Fynch S., Thorn P., Thomas H.E., Meikle P.J., Parkington H.C., Smyth I.M., RA Sviridov D.; RT "ABCA12 regulates insulin secretion from beta-cells."; RL EMBO Rep. 21:e48692-e48692(2020). RN [14] RP REVIEW ON VARIANTS, AND INVOLVEMENT IN ARCI. RX PubMed=20672373; DOI=10.1002/humu.21326; RA Akiyama M.; RT "ABCA12 mutations and autosomal recessive congenital ichthyosis: a review RT of genotype/phenotype correlations and of pathogenetic concepts."; RL Hum. Mutat. 31:1090-1096(2010). RN [15] RP VARIANTS ARCI4A SER-1380; GLU-1381; HIS-1514; LYS-1539 AND SER-1651. RX PubMed=12915478; DOI=10.1093/hmg/ddg235; RA Lefevre C., Audebert S., Jobard F., Bouadjar B., Lakhdar H., RA Boughdene-Stambouli O., Blanchet-Bardon C., Heilig R., Foglio M., RA Weissenbach J., Lathrop M., Prud'homme J.F., Fischer J.; RT "Mutations in the transporter ABCA12 are associated with lamellar RT ichthyosis type 2."; RL Hum. Mol. Genet. 12:2369-2378(2003). RN [16] RP VARIANT ASN-2365. RX PubMed=15756637; DOI=10.1086/429844; RA Kelsell D.P., Norgett E.E., Unsworth H., Teh M.-T., Cullup T., Mein C.A., RA Dopping-Hepenstal P.J., Dale B.A., Tadini G., Fleckman P., Stephens K.G., RA Sybert V.P., Mallory S.B., North B.V., Witt D.R., Sprecher E., RA Taylor A.E.M., Ilchyshyn A., Kennedy C.T., Goodyear H., Moss C., Paige D., RA Harper J.I., Young B.D., Leigh I.M., Eady R.A.J., O'Toole E.A.; RT "Mutations in ABCA12 underlie the severe congenital skin disease harlequin RT ichthyosis."; RL Am. J. Hum. Genet. 76:794-803(2005). RN [17] RP VARIANT ARCI4B ASN-387. RX PubMed=16675967; DOI=10.1038/sj.jid.5700295; RA Akiyama M., Sakai K., Sugiyama-Nakagiri Y., Yamanaka Y., McMillan J.R., RA Sawamura D., Niizeki H., Miyagawa S., Shimizu H.; RT "Compound heterozygous mutations including a de novo missense mutation in RT ABCA12 led to a case of harlequin ichthyosis with moderate clinical RT severity."; RL J. Invest. Dermatol. 126:1518-1523(2006). RN [18] RP VARIANT ARCI4B ARG-1179. RX PubMed=16902423; DOI=10.1038/sj.jid.5700455; RA Thomas A.C., Cullup T., Norgett E.E., Hill T., Barton S., Dale B.A., RA Sprecher E., Sheridan E., Taylor A.E., Wilroy R.S., DeLozier C., RA Burrows N., Goodyear H., Fleckman P., Stephens K.G., Mehta L., Watson R.M., RA Graham R., Wolf R., Slavotinek A., Martin M., Bourn D., Mein C.A., RA O'Toole E.A., Kelsell D.P.; RT "ABCA12 is the major harlequin ichthyosis gene."; RL J. Invest. Dermatol. 126:2408-2413(2006). RN [19] RP VARIANTS ARCI4A PRO-345 AND THR-1494. RX PubMed=17508018; DOI=10.1038/sj.jid.5700885; RA Natsuga K., Akiyama M., Kato N., Sakai K., Sugiyama-Nakagiri Y., RA Nishimura M., Hata H., Abe M., Arita K., Tsuji-Abe Y., Onozuka T., RA Aoyagi S., Kodama K., Ujiie H., Tomita Y., Shimizu H.; RT "Novel ABCA12 mutations identified in two cases of non-bullous congenital RT ichthyosiform erythroderma associated with multiple skin malignant RT neoplasia."; RL J. Invest. Dermatol. 127:2669-2673(2007). RN [20] RP VARIANT ARCI4A ASP-1136. RX PubMed=18284401; DOI=10.1111/j.1365-2133.2008.08439.x; RA Akiyama M., Sakai K., Hatamochi A., Yamazaki S., McMillan J.R., Shimizu H.; RT "Novel compound heterozygous nonsense and missense ABCA12 mutations lead to RT nonbullous congenital ichthyosiform erythroderma."; RL Br. J. Dermatol. 158:864-867(2008). RN [21] RP VARIANT [LARGE SCALE ANALYSIS] VAL-476. RX PubMed=18772397; DOI=10.1126/science.1164368; RA Jones S., Zhang X., Parsons D.W., Lin J.C., Leary R.J., Angenendt P., RA Mankoo P., Carter H., Kamiyama H., Jimeno A., Hong S.M., Fu B., Lin M.T., RA Calhoun E.S., Kamiyama M., Walter K., Nikolskaya T., Nikolsky Y., RA Hartigan J., Smith D.R., Hidalgo M., Leach S.D., Klein A.P., Jaffee E.M., RA Goggins M., Maitra A., Iacobuzio-Donahue C., Eshleman J.R., Kern S.E., RA Hruban R.H., Karchin R., Papadopoulos N., Parmigiani G., Vogelstein B., RA Velculescu V.E., Kinzler K.W.; RT "Core signaling pathways in human pancreatic cancers revealed by global RT genomic analyses."; RL Science 321:1801-1806(2008). RN [22] RP VARIANTS ARCI4A SER-1235; HIS-1514; LEU-1798 AND LYS-1980. RX PubMed=19262603; DOI=10.1038/jid.2009.23; RA Sakai K., Akiyama M., Yanagi T., McMillan J.R., Suzuki T., Tsukamoto K., RA Sugiyama H., Hatano Y., Hayashitani M., Takamori K., Nakashima K., RA Shimizu H.; RT "ABCA12 is a major causative gene for non-bullous congenital ichthyosiform RT erythroderma."; RL J. Invest. Dermatol. 129:2306-2309(2009). RN [23] RP VARIANT ARCI4A VAL-1559. RX PubMed=22257947; DOI=10.1684/ejd.2011.1638; RA Nawaz S., Tariq M., Ahmad I., Malik N.A., Baig S.M., Dahl N., Klar J.; RT "Non-bullous congenital ichthyosiform erythroderma associated with RT homozygosity for a novel missense mutation in an ATP binding domain of RT ABCA12."; RL Eur. J. Dermatol. 22:178-181(2012). CC -!- FUNCTION: Transports lipids such as glucosylceramides from the outer to CC the inner leaflet of lamellar granules (LGs) membrane, whereby the CC lipids are finally transported to the keratinocyte periphery via the CC trans-Golgi network and LGs and released to the apical surface of the CC granular keratinocytes to form lipid lamellae in the stratum corneum of CC the epidermis, which is essential for skin barrier function CC (PubMed:16007253, PubMed:20869849). In the meantime, participates in CC the transport of the lamellar granules-associated proteolytic enzymes, CC in turn regulates desquamation and keratinocyte differentiation CC (PubMed:19179616). Furthermore, is essential for the regulation of CC cellular cholesterol homeostasis by regulating ABCA1-dependent CC cholesterol efflux from macrophages through interaction with NR1H2 and CC ABCA1 (By similarity). Plays pleiotropic roles in regulating glucose CC stimulated insulin secretion from beta cells, regulating the morphology CC and fusion of insulin granules, lipid raft abundance and the actin CC cytoskeleton (By similarity). Also involved in lung surfactant CC biogenesis (By similarity). {ECO:0000250|UniProtKB:E9Q876, CC ECO:0000269|PubMed:16007253, ECO:0000269|PubMed:19179616, CC ECO:0000269|PubMed:20869849}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O + phospholipidSide 1 = ADP + phosphate + CC phospholipidSide 2.; EC=7.6.2.1; CC Evidence={ECO:0000269|PubMed:16007253, ECO:0000269|PubMed:20869849}; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + beta-D-glucosylceramide(in) + H2O = ADP + beta-D- CC glucosylceramide(out) + H(+) + phosphate; Xref=Rhea:RHEA:66660, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:83264, ChEBI:CHEBI:456216; CC Evidence={ECO:0000269|PubMed:16007253, ECO:0000269|PubMed:20869849}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66661; CC Evidence={ECO:0000305|PubMed:16007253, ECO:0000305|PubMed:20869849}; CC -!- SUBUNIT: Interacts with NR1H2 and ABCA1; this interaction is required CC for ABCA1 localization to the cell surface and is necessary for its CC normal activity and stability. {ECO:0000250|UniProtKB:E9Q876}. CC -!- INTERACTION: CC Q86UK0; O95477: ABCA1; NbExp=4; IntAct=EBI-9541582, EBI-784112; CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle membrane CC {ECO:0000269|PubMed:16007253, ECO:0000269|PubMed:17927575}; Multi-pass CC membrane protein {ECO:0000305}. Golgi apparatus membrane CC {ECO:0000269|PubMed:17927575}. Note=Localizes in the limiting membrane CC of the lamellar granules (LGs) (PubMed:17927575). Trafficks from the CC Golgi apparatus to the lamellar granules (LGs) at the cell periphery in CC the uppermost granular layer keratinocytes where ABCA12-positive LGs CC fuse with the keratinocyte-cell membrane to secrete their lipid content CC to the extracellular space of the stratum corneum (PubMed:16007253, CC PubMed:17927575). Co-localizes through the Golgi apparatus to the cell CC periphery with glucosylceramide (PubMed:17927575). CC {ECO:0000269|PubMed:16007253, ECO:0000269|PubMed:17927575}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Comment=Additional isoforms seem to exist.; CC Name=1; CC IsoId=Q86UK0-1; Sequence=Displayed; CC Name=2; CC IsoId=Q86UK0-2; Sequence=VSP_011283, VSP_011284; CC -!- TISSUE SPECIFICITY: Mainly expressed in the stomach, placenta, testis CC and fetal brain (PubMed:12697999). Expressed in the upper epidermal CC layers, mainly the granular layers, of skin (PubMed:16007253, CC PubMed:17591952, PubMed:17927575). Expressed throughout the normal CC interfollicular epidermis with prominent expression in the stratum CC granulosum (PubMed:19179616). Expressed in alpha and beta cells of CC pancreatic islets (PubMed:32072744). {ECO:0000269|PubMed:12697999, CC ECO:0000269|PubMed:16007253, ECO:0000269|PubMed:17591952, CC ECO:0000269|PubMed:17927575, ECO:0000269|PubMed:19179616, CC ECO:0000269|PubMed:32072744}. CC -!- DEVELOPMENTAL STAGE: At about 6 to 9 weeks estimated gestational age CC (EGA), expressed in the periderm during the early period when the two- CC layered epidermis form. At 10 to 13 weeks EGA, expressed in the entire CC epidermis with high expression in periderm until to 14 to 22 weeks EGA. CC {ECO:0000269|PubMed:17591952}. CC -!- INDUCTION: Up-regulated during keratinization (PubMed:16007253). Up- CC regulated after 15 weeks estimated gestational age (EGA) CC (PubMed:17591952). Highly up-regulated by PPARG activators such as CC ciglitazone, troglitazone, and the PPARD activator GW 0742 in time- and CC dose-dependent manner but independently of keratinocyte CC differentiation. In addition, modestly up-regulated by the NR1H3 and CC NR1H2 activator TO901317 in an keratinocyte differentiation-independent CC manner (PubMed:17611579). Up-regulated by N-(hexanoyl)sphing-4-enine in CC a time- and dose-dependent manner or by glucosyltransferase inhibitors, CC ceramidase inhibitors and sphingomyelin synthase inhibitors that CC increase endogenous ceramide levels and induce ABCA12 expression via CC the PPARD signaling pathway (PubMed:19429679). Up-regulated by N- CC acetylsphingosine in a time- and dose-dependent manner via the PPARD CC signaling pathway (Probable). {ECO:0000269|PubMed:16007253, CC ECO:0000269|PubMed:17591952, ECO:0000269|PubMed:17611579, CC ECO:0000269|PubMed:19429679, ECO:0000305|PubMed:19429679}. CC -!- DOMAIN: Multifunctional polypeptide with two homologous halves, each CC containing a hydrophobic membrane-anchoring domain and an ATP binding CC cassette (ABC) domain. {ECO:0000250}. CC -!- DISEASE: Ichthyosis, congenital, autosomal recessive 4A (ARCI4A) CC [MIM:601277]: A form of autosomal recessive congenital ichthyosis, a CC disorder of keratinization with abnormal differentiation and CC desquamation of the epidermis, resulting in abnormal skin scaling over CC the whole body. The main skin phenotypes are lamellar ichthyosis (LI) CC and non-bullous congenital ichthyosiform erythroderma (NCIE), although CC phenotypic overlap within the same patient or among patients from the CC same family can occur. Lamellar ichthyosis is a condition often CC associated with an embedment in a collodion-like membrane at birth; CC skin scales later develop, covering the entire body surface. Non- CC bullous congenital ichthyosiform erythroderma characterized by fine CC whitish scaling on an erythrodermal background; larger brownish scales CC are present on the buttocks, neck and legs. CC {ECO:0000269|PubMed:12915478, ECO:0000269|PubMed:17508018, CC ECO:0000269|PubMed:18284401, ECO:0000269|PubMed:19262603, CC ECO:0000269|PubMed:22257947}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Ichthyosis, congenital, autosomal recessive 4B (ARCI4B) CC [MIM:242500]: A rare, very severe form of congenital ichthyosis, in CC which the neonate is born with a thick covering of armor-like scales. CC The skin dries out to form hard diamond-shaped plaques separated by CC fissures, resembling 'armor plating'. The normal facial features are CC severely affected, with distortion of the lips (eclabion), eyelids CC (ectropion), ears, and nostrils. Affected babies are often born CC prematurely and rarely survive the perinatal period. Babies who survive CC into infancy and beyond develop skin changes resembling severe non- CC bullous congenital ichthyosiform erythroderma. CC {ECO:0000269|PubMed:16007253, ECO:0000269|PubMed:16675967, CC ECO:0000269|PubMed:16902423}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCA family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAN40735.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=ABCMdb; Note=Database for mutations in ABC proteins; CC URL="http://abcm2.hegelab.org/search"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY219711; AAP21093.1; -; mRNA. DR EMBL; AY033486; AAK54355.1; -; mRNA. DR EMBL; AC072062; AAY24276.1; -; Genomic_DNA. DR EMBL; AC114780; AAY24230.1; -; Genomic_DNA. DR EMBL; AF418105; AAN40735.1; ALT_INIT; mRNA. DR EMBL; AL080207; CAB45776.1; -; mRNA. DR CCDS; CCDS33372.1; -. [Q86UK0-1] DR CCDS; CCDS33373.1; -. [Q86UK0-2] DR PIR; T12512; T12512. DR RefSeq; NP_056472.2; NM_015657.3. [Q86UK0-2] DR RefSeq; NP_775099.2; NM_173076.2. [Q86UK0-1] DR AlphaFoldDB; Q86UK0; -. DR SMR; Q86UK0; -. DR BioGRID; 117585; 9. DR IntAct; Q86UK0; 5. DR MINT; Q86UK0; -. DR STRING; 9606.ENSP00000272895; -. DR TCDB; 3.A.1.211.13; the atp-binding cassette (abc) superfamily. DR GlyCosmos; Q86UK0; 35 sites, No reported glycans. DR GlyGen; Q86UK0; 36 sites, 1 O-linked glycan (1 site). DR iPTMnet; Q86UK0; -. DR PhosphoSitePlus; Q86UK0; -. DR SwissPalm; Q86UK0; -. DR BioMuta; ABCA12; -. DR DMDM; 269849713; -. DR EPD; Q86UK0; -. DR jPOST; Q86UK0; -. DR MassIVE; Q86UK0; -. DR MaxQB; Q86UK0; -. DR PaxDb; 9606-ENSP00000272895; -. DR PeptideAtlas; Q86UK0; -. DR ProteomicsDB; 69821; -. [Q86UK0-1] DR ProteomicsDB; 69822; -. [Q86UK0-2] DR Antibodypedia; 34220; 152 antibodies from 26 providers. DR DNASU; 26154; -. DR Ensembl; ENST00000272895.12; ENSP00000272895.7; ENSG00000144452.15. [Q86UK0-1] DR Ensembl; ENST00000389661.4; ENSP00000374312.4; ENSG00000144452.15. [Q86UK0-2] DR GeneID; 26154; -. DR KEGG; hsa:26154; -. DR MANE-Select; ENST00000272895.12; ENSP00000272895.7; NM_173076.3; NP_775099.2. DR UCSC; uc002vev.4; human. [Q86UK0-1] DR AGR; HGNC:14637; -. DR CTD; 26154; -. DR DisGeNET; 26154; -. DR GeneCards; ABCA12; -. DR GeneReviews; ABCA12; -. DR HGNC; HGNC:14637; ABCA12. DR HPA; ENSG00000144452; Tissue enhanced (breast, skin). DR MalaCards; ABCA12; -. DR MIM; 242500; phenotype. DR MIM; 601277; phenotype. DR MIM; 607800; gene. DR neXtProt; NX_Q86UK0; -. DR OpenTargets; ENSG00000144452; -. DR Orphanet; 79394; Congenital ichthyosiform erythroderma. DR Orphanet; 457; Harlequin ichthyosis. DR Orphanet; 313; Lamellar ichthyosis. DR PharmGKB; PA29604; -. DR VEuPathDB; HostDB:ENSG00000144452; -. DR eggNOG; KOG0059; Eukaryota. DR GeneTree; ENSGT00940000157295; -. DR HOGENOM; CLU_000604_19_7_1; -. DR InParanoid; Q86UK0; -. DR OMA; TYIVREH; -. DR OrthoDB; 6951at2759; -. DR PhylomeDB; Q86UK0; -. DR TreeFam; TF105191; -. DR PathwayCommons; Q86UK0; -. DR Reactome; R-HSA-1369062; ABC transporters in lipid homeostasis. DR Reactome; R-HSA-5682294; Defective ABCA12 causes ARCI4B. DR SignaLink; Q86UK0; -. DR BioGRID-ORCS; 26154; 6 hits in 1147 CRISPR screens. DR ChiTaRS; ABCA12; human. DR GeneWiki; ABCA12; -. DR GenomeRNAi; 26154; -. DR Pharos; Q86UK0; Tbio. DR PRO; PR:Q86UK0; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q86UK0; Protein. DR Bgee; ENSG00000144452; Expressed in penis and 75 other cell types or tissues. DR ExpressionAtlas; Q86UK0; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL. DR GO; GO:0005829; C:cytosol; IEA:Ensembl. DR GO; GO:0097209; C:epidermal lamellar body; IDA:BHF-UCL. DR GO; GO:0097234; C:epidermal lamellar body membrane; IDA:UniProtKB. DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central. DR GO; GO:0016020; C:membrane; NAS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL. DR GO; GO:0030658; C:transport vesicle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0140359; F:ABC-type transporter activity; IEA:InterPro. DR GO; GO:0034191; F:apolipoprotein A-I receptor binding; IPI:BHF-UCL. DR GO; GO:0005524; F:ATP binding; NAS:UniProtKB. DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro. DR GO; GO:0140326; F:ATPase-coupled intramembrane lipid transporter activity; IEA:UniProtKB-EC. DR GO; GO:0034040; F:ATPase-coupled lipid transmembrane transporter activity; IC:BHF-UCL. DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; IBA:GO_Central. DR GO; GO:0005319; F:lipid transporter activity; IDA:BHF-UCL. DR GO; GO:0005102; F:signaling receptor binding; IPI:BHF-UCL. DR GO; GO:0019725; P:cellular homeostasis; NAS:UniProtKB. DR GO; GO:0006672; P:ceramide metabolic process; IDA:UniProtKB. DR GO; GO:0035627; P:ceramide transport; IDA:UniProtKB. DR GO; GO:0033344; P:cholesterol efflux; IEA:Ensembl. DR GO; GO:0003336; P:corneocyte desquamation; IMP:UniProtKB. DR GO; GO:0061436; P:establishment of skin barrier; ISS:UniProtKB. DR GO; GO:0006886; P:intracellular protein transport; IMP:UniProtKB. DR GO; GO:0031424; P:keratinization; IEA:Ensembl. DR GO; GO:0055088; P:lipid homeostasis; IEA:Ensembl. DR GO; GO:0006869; P:lipid transport; IDA:BHF-UCL. DR GO; GO:0048286; P:lung alveolus development; IEA:Ensembl. DR GO; GO:0033700; P:phospholipid efflux; IMP:BHF-UCL. DR GO; GO:0010875; P:positive regulation of cholesterol efflux; IDA:BHF-UCL. DR GO; GO:0032379; P:positive regulation of intracellular lipid transport; ISS:UniProtKB. DR GO; GO:2000010; P:positive regulation of protein localization to cell surface; IEA:Ensembl. DR GO; GO:0072659; P:protein localization to plasma membrane; IDA:BHF-UCL. DR GO; GO:0045055; P:regulated exocytosis; IMP:BHF-UCL. DR GO; GO:0061178; P:regulation of insulin secretion involved in cellular response to glucose stimulus; ISS:UniProtKB. DR GO; GO:0045616; P:regulation of keratinocyte differentiation; IMP:UniProtKB. DR GO; GO:0032940; P:secretion by cell; IMP:BHF-UCL. DR GO; GO:0043129; P:surfactant homeostasis; IEA:Ensembl. DR CDD; cd03263; ABC_subfamily_A; 2. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 2. DR InterPro; IPR003593; AAA+_ATPase. DR InterPro; IPR013525; ABC2_TM. DR InterPro; IPR003439; ABC_transporter-like_ATP-bd. DR InterPro; IPR017871; ABC_transporter-like_CS. DR InterPro; IPR026082; ABCA. DR InterPro; IPR027417; P-loop_NTPase. DR PANTHER; PTHR19229; ATP-BINDING CASSETTE TRANSPORTER SUBFAMILY A ABCA; 1. DR PANTHER; PTHR19229:SF29; GLUCOSYLCERAMIDE TRANSPORTER ABCA12; 1. DR Pfam; PF12698; ABC2_membrane_3; 2. DR Pfam; PF00005; ABC_tran; 2. DR SMART; SM00382; AAA; 2. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 2. DR PROSITE; PS00211; ABC_TRANSPORTER_1; 1. DR PROSITE; PS50893; ABC_TRANSPORTER_2; 2. DR Genevisible; Q86UK0; HS. PE 1: Evidence at protein level; KW Alternative splicing; ATP-binding; Cytoplasmic vesicle; Disease variant; KW Glycoprotein; Golgi apparatus; Ichthyosis; Lipid transport; Membrane; KW Nucleotide-binding; Reference proteome; Repeat; Translocase; Transmembrane; KW Transmembrane helix; Transport. FT CHAIN 1..2595 FT /note="Glucosylceramide transporter ABCA12" FT /id="PRO_0000093300" FT TRANSMEM 23..43 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 1065..1085 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 1112..1132 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 1145..1165 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 1174..1194 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 1200..1220 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 1250..1270 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 1747..1767 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 1979..1999 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 2035..2055 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 2072..2092 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 2103..2123 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 2187..2207 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 2270..2290 FT /note="Helical" FT /evidence="ECO:0000255" FT DOMAIN 1346..1577 FT /note="ABC transporter 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434" FT DOMAIN 2254..2489 FT /note="ABC transporter 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434" FT REGION 2571..2595 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 1378..1385 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434" FT BINDING 2290..2297 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434" FT CARBOHYD 156 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 174 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 214 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 275 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 333 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 367 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 383 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 412 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 435 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 528 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 543 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 577 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 608 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 623 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 648 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 752 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 826 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 920 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 963 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1170 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1524 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1663 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1704 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1769 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1819 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1835 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1876 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1921 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1952 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 2178 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 2208 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 2223 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 2318 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 2542 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 2547 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VAR_SEQ 1..318 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.2" FT /id="VSP_011283" FT VAR_SEQ 319..328 FT /note="LLYTLDSPAQ -> MFTYIKIITS (in isoform 2)" FT /evidence="ECO:0000303|Ref.2" FT /id="VSP_011284" FT VARIANT 199 FT /note="W -> C (in dbSNP:rs16853238)" FT /id="VAR_055473" FT VARIANT 237 FT /note="N -> H (in dbSNP:rs11890512)" FT /id="VAR_055474" FT VARIANT 274 FT /note="Q -> R (in dbSNP:rs11890468)" FT /id="VAR_055475" FT VARIANT 287 FT /note="R -> G (in dbSNP:rs11891778)" FT /id="VAR_055476" FT VARIANT 345 FT /note="T -> P (in ARCI4A; skin phenotype consistent with FT non-bullous congenital ichthyosiform erythroderma; FT dbSNP:rs1295935868)" FT /evidence="ECO:0000269|PubMed:17508018" FT /id="VAR_067075" FT VARIANT 387 FT /note="S -> N (in ARCI4B; dbSNP:rs746315995)" FT /evidence="ECO:0000269|PubMed:16675967" FT /id="VAR_067076" FT VARIANT 434..2595 FT /note="Missing (in ARCI4B)" FT /evidence="ECO:0000269|PubMed:16007253" FT /id="VAR_084428" FT VARIANT 459 FT /note="S -> T (in dbSNP:rs113112835)" FT /id="VAR_019597" FT VARIANT 476 FT /note="A -> V (in a pancreatic ductal adenocarcinoma FT sample; somatic mutation; dbSNP:rs370640837)" FT /evidence="ECO:0000269|PubMed:18772397" FT /id="VAR_062663" FT VARIANT 550 FT /note="E -> G (in dbSNP:rs16853149)" FT /id="VAR_027444" FT VARIANT 777 FT /note="S -> T (in dbSNP:rs7560008)" FT /evidence="ECO:0000269|PubMed:12697999, ECO:0000269|Ref.2, FT ECO:0000269|Ref.4" FT /id="VAR_027445" FT VARIANT 1136 FT /note="G -> D (in ARCI4A; skin phenotype consistent with FT non-bullous congenital ichthyosiform erythroderma)" FT /evidence="ECO:0000269|PubMed:18284401" FT /id="VAR_067077" FT VARIANT 1179 FT /note="G -> R (in ARCI4B; dbSNP:rs267606622)" FT /evidence="ECO:0000269|PubMed:16902423" FT /id="VAR_067078" FT VARIANT 1235 FT /note="W -> S (in ARCI4A; skin phenotype consistent with FT non-bullous congenital ichthyosiform erythroderma)" FT /evidence="ECO:0000269|PubMed:19262603" FT /id="VAR_067079" FT VARIANT 1251 FT /note="G -> D (in dbSNP:rs13414448)" FT /id="VAR_027446" FT VARIANT 1380 FT /note="N -> S (in ARCI4A; dbSNP:rs28940269)" FT /evidence="ECO:0000269|PubMed:12915478" FT /id="VAR_019598" FT VARIANT 1381 FT /note="G -> E (in ARCI4A; dbSNP:rs28940268)" FT /evidence="ECO:0000269|PubMed:12915478" FT /id="VAR_019599" FT VARIANT 1385 FT /note="Missing (in ARCI4B; uncertain significance)" FT /evidence="ECO:0000269|PubMed:16007253" FT /id="VAR_084429" FT VARIANT 1494 FT /note="I -> T (in ARCI4A; skin phenotype consistent with FT non-bullous congenital ichthyosiform erythroderma; FT dbSNP:rs1263698595)" FT /evidence="ECO:0000269|PubMed:17508018" FT /id="VAR_067080" FT VARIANT 1514 FT /note="R -> H (in ARCI4A; dbSNP:rs28940270)" FT /evidence="ECO:0000269|PubMed:12915478, FT ECO:0000269|PubMed:19262603" FT /id="VAR_019600" FT VARIANT 1539 FT /note="E -> K (in ARCI4A; dbSNP:rs28940271)" FT /evidence="ECO:0000269|PubMed:12915478" FT /id="VAR_019601" FT VARIANT 1546 FT /note="R -> C (in dbSNP:rs13401480)" FT /id="VAR_027447" FT VARIANT 1559 FT /note="G -> V (in ARCI4A; skin phenotype consistent with FT non-bullous congenital ichthyosiform erythroderma; FT dbSNP:rs1457513156)" FT /evidence="ECO:0000269|PubMed:22257947" FT /id="VAR_067081" FT VARIANT 1651 FT /note="G -> S (in ARCI4A; dbSNP:rs28940568)" FT /evidence="ECO:0000269|PubMed:12915478" FT /id="VAR_019602" FT VARIANT 1798 FT /note="P -> L (in ARCI4A; skin phenotype consistent with FT non-bullous congenital ichthyosiform erythroderma; FT dbSNP:rs181314573)" FT /evidence="ECO:0000269|PubMed:19262603" FT /id="VAR_067082" FT VARIANT 1950..2595 FT /note="Missing (in ARCI4B; uncertain significance)" FT /evidence="ECO:0000269|PubMed:16007253" FT /id="VAR_084430" FT VARIANT 1980 FT /note="T -> K (in ARCI4A; skin phenotype consistent with FT non-bullous congenital ichthyosiform erythroderma; FT dbSNP:rs763858530)" FT /evidence="ECO:0000269|PubMed:19262603" FT /id="VAR_067083" FT VARIANT 2064 FT /note="E -> K (in dbSNP:rs1213011)" FT /id="VAR_027448" FT VARIANT 2365 FT /note="D -> N (in dbSNP:rs726070)" FT /evidence="ECO:0000269|PubMed:15756637" FT /id="VAR_027449" FT CONFLICT 651 FT /note="Y -> D (in Ref. 1; AAP21093)" FT /evidence="ECO:0000305" FT CONFLICT 811 FT /note="Y -> H (in Ref. 1; AAP21093)" FT /evidence="ECO:0000305" FT CONFLICT 826 FT /note="N -> D (in Ref. 2; AAK54355)" FT /evidence="ECO:0000305" FT CONFLICT 2079 FT /note="Y -> H (in Ref. 1; AAP21093)" FT /evidence="ECO:0000305" SQ SEQUENCE 2595 AA; 293237 MW; 5B71359B642BBAE6 CRC64; 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 //