ABCAC_HUMAN
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 03-AUG-2022, entry version 169.
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";
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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; 7.
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 GlyGen; Q86UK0; 35 sites.
DR iPTMnet; Q86UK0; -.
DR PhosphoSitePlus; Q86UK0; -.
DR BioMuta; ABCA12; -.
DR DMDM; 269849713; -.
DR EPD; Q86UK0; -.
DR jPOST; Q86UK0; -.
DR MassIVE; Q86UK0; -.
DR MaxQB; Q86UK0; -.
DR PaxDb; Q86UK0; -.
DR PeptideAtlas; Q86UK0; -.
DR PRIDE; Q86UK0; -.
DR ProteomicsDB; 69821; -. [Q86UK0-1]
DR ProteomicsDB; 69822; -. [Q86UK0-2]
DR Antibodypedia; 34220; 143 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 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 non-bullous 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; MPTKYCK; -.
DR OrthoDB; 131191at2759; -.
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 1067 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 tissues.
DR ExpressionAtlas; Q86UK0; baseline and differential.
DR Genevisible; Q86UK0; HS.
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:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
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: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 Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR003439; ABC_transporter-like_ATP-bd.
DR InterPro; IPR017871; ABC_transporter-like_CS.
DR InterPro; IPR026082; ABCA.
DR InterPro; IPR030371; ABCA12.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR19229; PTHR19229; 1.
DR PANTHER; PTHR19229:SF29; PTHR19229:SF29; 1.
DR Pfam; PF00005; ABC_tran; 2.
DR SMART; SM00382; AAA; 2.
DR SUPFAM; SSF52540; SSF52540; 2.
DR PROSITE; PS00211; ABC_TRANSPORTER_1; 1.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 2.
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; unknown pathological
FT 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; unknown pathological
FT 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
