ID   ABCAC_MOUSE             Reviewed;        2595 AA.
AC   E9Q876;
DT   02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT   05-APR-2011, sequence version 1.
DT   27-MAR-2024, entry version 90.
DE   RecName: Full=Glucosylceramide transporter ABCA12 {ECO:0000305};
DE            EC=7.6.2.1 {ECO:0000250|UniProtKB:Q86UK0};
DE   AltName: Full=ATP-binding cassette sub-family A member 12 {ECO:0000305};
GN   Name=Abca12 {ECO:0000312|MGI:MGI:2676312};
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [2]
RP   DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND FUNCTION.
RX   PubMed=18632686; DOI=10.1093/hmg/ddn204;
RA   Yanagi T., Akiyama M., Nishihara H., Sakai K., Nishie W., Tanaka S.,
RA   Shimizu H.;
RT   "Harlequin ichthyosis model mouse reveals alveolar collapse and severe
RT   fetal skin barrier defects.";
RL   Hum. Mol. Genet. 17:3075-3083(2008).
RN   [3]
RP   DISRUPTION PHENOTYPE, AND FUNCTION.
RX   PubMed=18957418; DOI=10.1074/jbc.m807377200;
RA   Zuo Y., Zhuang D.Z., Han R., Isaac G., Tobin J.J., McKee M., Welti R.,
RA   Brissette J.L., Fitzgerald M.L., Freeman M.W.;
RT   "ABCA12 maintains the epidermal lipid permeability barrier by facilitating
RT   formation of ceramide linoleic esters.";
RL   J. Biol. Chem. 283:36624-36635(2008).
RN   [4]
RP   MUTAGENESIS OF GLY-1996, AND FUNCTION.
RX   PubMed=18802465; DOI=10.1371/journal.pgen.1000192;
RA   Smyth I., Hacking D.F., Hilton A.A., Mukhamedova N., Meikle P.J., Ellis S.,
RA   Satterley K., Slattery K., Collinge J.E., de Graaf C.A., Bahlo M.,
RA   Sviridov D., Kile B.T., Hilton D.J.;
RT   "A mouse model of harlequin ichthyosis delineates a key role for Abca12 in
RT   lipid homeostasis.";
RL   PLoS Genet. 4:e1000192-e1000192(2008).
RN   [5]
RP   FUNCTION.
RX   PubMed=20489143; DOI=10.2353/ajpath.2010.091120;
RA   Yanagi T., Akiyama M., Nishihara H., Ishikawa J., Sakai K., Miyamura Y.,
RA   Naoe A., Kitahara T., Tanaka S., Shimizu H.;
RT   "Self-improvement of keratinocyte differentiation defects during skin
RT   maturation in ABCA12-deficient harlequin ichthyosis model mice.";
RL   Am. J. Pathol. 177:106-118(2010).
RN   [6]
RP   FUNCTION, AND INTERACTION WITH NR1H2 AND ABCA1.
RX   PubMed=23931754; DOI=10.1016/j.cmet.2013.07.003;
RA   Fu Y., Mukhamedova N., Ip S., D'Souza W., Henley K.J., DiTommaso T.,
RA   Kesani R., Ditiatkovski M., Jones L., Lane R.M., Jennings G., Smyth I.M.,
RA   Kile B.T., Sviridov D.;
RT   "ABCA12 regulates ABCA1-dependent cholesterol efflux from macrophages and
RT   the development of atherosclerosis.";
RL   Cell Metab. 18:225-238(2013).
RN   [7]
RP   TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND FUNCTION.
RX   PubMed=24293640; DOI=10.1194/jlr.m044941;
RA   Haller J.F., Cavallaro P., Hernandez N.J., Dolat L., Soscia S.J., Welti R.,
RA   Grabowski G.A., Fitzgerald M.L., Freeman M.W.;
RT   "Endogenous beta-glucocerebrosidase activity in Abca12-/- epidermis
RT   elevates ceramide levels after topical lipid application but does not
RT   restore barrier function.";
RL   J. Lipid Res. 55:493-503(2014).
RN   [8]
RP   FUNCTION, AND MUTAGENESIS OF 1388-ILE--ARG-1461.
RX   PubMed=27551807; DOI=10.1371/journal.pone.0161465;
RA   Zhang L., Ferreyros M., Feng W., Hupe M., Crumrine D.A., Chen J.,
RA   Elias P.M., Holleran W.M., Niswander L., Hohl D., Williams T.,
RA   Torchia E.C., Roop D.R.;
RT   "Defects in Stratum Corneum Desquamation Are the Predominant Effect of
RT   Impaired ABCA12 Function in a Novel Mouse Model of Harlequin Ichthyosis.";
RL   PLoS ONE 11:e0161465-e0161465(2016).
RN   [9]
RP   TISSUE SPECIFICITY, AND FUNCTION.
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   [10]
RP   INDUCTION.
RX   PubMed=32873425; DOI=10.1016/j.jdermsci.2020.08.010;
RA   Teramura T., Nomura T.;
RT   "Acute skin barrier disruption alters the secretion of lamellar bodies via
RT   the multilayered expression of ABCA12.";
RL   J. Dermatol. Sci. 100:50-57(2020).
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:18957418, PubMed:27551807, PubMed:24293640, PubMed:20489143,
CC       PubMed:18802465). In the meantime, participates in the transport of the
CC       lamellar granules-associated proteolytic enzymes, in turn regulates
CC       desquamation and keratinocyte differentiation (PubMed:27551807,
CC       PubMed:20489143). 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 (PubMed:18802465, PubMed:23931754). Plays pleiotropic roles in
CC       regulating glucose stimulated insulin secretion from beta cells,
CC       regulating the morphology and fusion of insulin granules, lipid raft
CC       abundance and the actin cytoskeleton (PubMed:32072744). Also involved
CC       in lung surfactant biogenesis (PubMed:18632686).
CC       {ECO:0000269|PubMed:18632686, ECO:0000269|PubMed:18802465,
CC       ECO:0000269|PubMed:18957418, ECO:0000269|PubMed:20489143,
CC       ECO:0000269|PubMed:23931754, ECO:0000269|PubMed:24293640,
CC       ECO:0000269|PubMed:27551807, ECO:0000269|PubMed:32072744}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + H2O + phospholipidSide 1 = ADP + phosphate +
CC         phospholipidSide 2.; EC=7.6.2.1;
CC         Evidence={ECO:0000250|UniProtKB:Q86UK0};
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:0000250|UniProtKB:Q86UK0};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66661;
CC         Evidence={ECO:0000250|UniProtKB:Q86UK0};
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:0000269|PubMed:23931754}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle membrane
CC       {ECO:0000250|UniProtKB:Q86UK0}; Multi-pass membrane protein
CC       {ECO:0000250|UniProtKB:Q86UK0}. Golgi apparatus membrane
CC       {ECO:0000250|UniProtKB:Q86UK0}. Note=Localizes in the limiting membrane
CC       of the lamellar granules (LGs). Trafficks from the Golgi apparatus to
CC       the lamellar granules (LGs) at the cell periphery in the uppermost
CC       granular layer keratinocytes where ABCA12-positive LGs fuse with the
CC       keratinocyte-cell membrane to secrete their lipid content to the
CC       extracellular space of the stratum corneum. Co-localizes through the
CC       Golgi apparatus to the cell periphery with glucosylceramide.
CC       {ECO:0000250|UniProtKB:Q86UK0}.
CC   -!- TISSUE SPECIFICITY: Expressed in a number of other tissues besides
CC       skin, including heart, intestine, stomach, and kidney
CC       (PubMed:24293640). Expressed mainly in the granular layer of the skin
CC       (PubMed:18632686). Expressed in lung (PubMed:18632686). Expressed in
CC       alpha and beta cells of pancreatic islets (PubMed:32072744).
CC       {ECO:0000269|PubMed:18632686, ECO:0000269|PubMed:24293640,
CC       ECO:0000269|PubMed:32072744}.
CC   -!- DEVELOPMENTAL STAGE: At 18.5 dpc highly expressed in the epidermis, and
CC       weakly in the stomach. {ECO:0000269|PubMed:24293640}.
CC   -!- INDUCTION: Up-regulated during barrier recovery.
CC       {ECO:0000269|PubMed:32873425}.
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   -!- DISRUPTION PHENOTYPE: Homozygous knockout mice for Abca12 are born with
CC       a thickened epidermis and die shortly after birth, as water rapidly
CC       evaporates from their skin (PubMed:18957418). In a mouse model for
CC       harlequin ichthyosis (HI), homozygous knockout mice are smaller and die
CC       within a few hours and their entire body are covered of erythematous
CC       skin, making their skin less flexible. The entire skin surface is
CC       covered with thick scales and some mice develop skin fissures and
CC       eversions of the lips (eclabium). At 18.5 dpc, fetuses develop taut and
CC       shiny skin without normal skin folds and show contractures of the
CC       limbs. The lungs of the present model mice show signs of alveolar
CC       collapse (PubMed:18632686). {ECO:0000269|PubMed:18632686,
CC       ECO:0000269|PubMed:18957418}.
CC   -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCA family.
CC       {ECO:0000305}.
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DR   EMBL; AC107789; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC138589; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS48286.1; -.
DR   RefSeq; NP_780419.2; NM_175210.3.
DR   AlphaFoldDB; E9Q876; -.
DR   SMR; E9Q876; -.
DR   STRING; 10090.ENSMUSP00000084523; -.
DR   GlyCosmos; E9Q876; 39 sites, No reported glycans.
DR   GlyGen; E9Q876; 39 sites.
DR   iPTMnet; E9Q876; -.
DR   PhosphoSitePlus; E9Q876; -.
DR   PaxDb; 10090-ENSMUSP00000084523; -.
DR   ProteomicsDB; 324613; -.
DR   Antibodypedia; 34220; 152 antibodies from 26 providers.
DR   DNASU; 74591; -.
DR   Ensembl; ENSMUST00000087268.7; ENSMUSP00000084523.6; ENSMUSG00000050296.15.
DR   GeneID; 74591; -.
DR   KEGG; mmu:74591; -.
DR   UCSC; uc011wmq.1; mouse.
DR   AGR; MGI:2676312; -.
DR   CTD; 26154; -.
DR   MGI; MGI:2676312; Abca12.
DR   VEuPathDB; HostDB:ENSMUSG00000050296; -.
DR   eggNOG; KOG0059; Eukaryota.
DR   GeneTree; ENSGT00940000157295; -.
DR   HOGENOM; CLU_000604_19_7_1; -.
DR   InParanoid; E9Q876; -.
DR   OMA; TYIVREH; -.
DR   OrthoDB; 6951at2759; -.
DR   PhylomeDB; E9Q876; -.
DR   TreeFam; TF105191; -.
DR   Reactome; R-MMU-1369062; ABC transporters in lipid homeostasis.
DR   BioGRID-ORCS; 74591; 2 hits in 80 CRISPR screens.
DR   ChiTaRS; Abca12; mouse.
DR   PRO; PR:E9Q876; -.
DR   Proteomes; UP000000589; Chromosome 1.
DR   RNAct; E9Q876; Protein.
DR   Bgee; ENSMUSG00000050296; Expressed in esophagus and 27 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR   GO; GO:0005829; C:cytosol; IDA:MGI.
DR   GO; GO:0097209; C:epidermal lamellar body; ISO:MGI.
DR   GO; GO:0097234; C:epidermal lamellar body membrane; ISS:UniProtKB.
DR   GO; GO:0000139; C:Golgi membrane; ISS:UniProtKB.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR   GO; GO:0005743; C:mitochondrial inner membrane; HDA:MGI.
DR   GO; GO:0005886; C:plasma membrane; ISO:MGI.
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; ISO:MGI.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
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:0042626; F:ATPase-coupled transmembrane transporter activity; IBA:GO_Central.
DR   GO; GO:0005319; F:lipid transporter activity; ISO:MGI.
DR   GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR   GO; GO:0006672; P:ceramide metabolic process; IMP:UniProtKB.
DR   GO; GO:0035627; P:ceramide transport; IMP:UniProtKB.
DR   GO; GO:0033344; P:cholesterol efflux; IMP:MGI.
DR   GO; GO:0003336; P:corneocyte desquamation; IMP:UniProtKB.
DR   GO; GO:0051649; P:establishment of localization in cell; IMP:MGI.
DR   GO; GO:0061436; P:establishment of skin barrier; IMP:UniProtKB.
DR   GO; GO:0006886; P:intracellular protein transport; ISS:UniProtKB.
DR   GO; GO:0031424; P:keratinization; IMP:MGI.
DR   GO; GO:0030216; P:keratinocyte differentiation; IMP:MGI.
DR   GO; GO:0055088; P:lipid homeostasis; IMP:MGI.
DR   GO; GO:0006869; P:lipid transport; ISO:MGI.
DR   GO; GO:0048286; P:lung alveolus development; IMP:MGI.
DR   GO; GO:0033700; P:phospholipid efflux; ISO:MGI.
DR   GO; GO:0010875; P:positive regulation of cholesterol efflux; IMP:MGI.
DR   GO; GO:0032379; P:positive regulation of intracellular lipid transport; IMP:UniProtKB.
DR   GO; GO:2000010; P:positive regulation of protein localization to cell surface; IMP:MGI.
DR   GO; GO:0072659; P:protein localization to plasma membrane; ISO:MGI.
DR   GO; GO:0045055; P:regulated exocytosis; ISO:MGI.
DR   GO; GO:0061178; P:regulation of insulin secretion involved in cellular response to glucose stimulus; IMP:UniProtKB.
DR   GO; GO:0045616; P:regulation of keratinocyte differentiation; IMP:UniProtKB.
DR   GO; GO:0032940; P:secretion by cell; ISO:MGI.
DR   GO; GO:0043129; P:surfactant homeostasis; IMP:MGI.
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; E9Q876; MM.
PE   1: Evidence at protein level;
KW   ATP-binding; Cytoplasmic vesicle; Glycoprotein; Golgi apparatus;
KW   Lipid transport; Membrane; Nucleotide-binding; Reference proteome; Repeat;
KW   Translocase; Transmembrane; Transmembrane helix; Transport.
FT   CHAIN           1..2595
FT                   /note="Glucosylceramide transporter ABCA12"
FT                   /id="PRO_0000452550"
FT   TRANSMEM        23..43
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1062..1082
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1109..1129
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1142..1162
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1171..1191
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1197..1217
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1247..1267
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        2143..2163
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          109..143
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1672..1703
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2575..2595
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        115..139
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         1378..1385
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT   BINDING         2290..2297
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT   CARBOHYD        120
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
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        331
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        365
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        381
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        410
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        433
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        455
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        526
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        541
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        574
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        605
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        645
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        749
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        773
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        812
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        823
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        854
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        917
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        960
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        1167
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        1319
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        1673
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        1686
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        1690
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        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        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   MUTAGEN         1388..1461
FT                   /note="ISMLTGLFGATAGTIFVYGKDIKTDLNTVRKNMGVCMQHDVLFSYLTTKEHL
FT                   LLYGSIKVPHWTKTQLHEEVKR->M: In a mouse model for harlequin
FT                   ichthyosis (HI), smooth skin (smsk) mutant mice show a
FT                   pronounced perinatal lethal skin phenotype in 25% of the
FT                   offspring and newborn mutant pups die within a few hours
FT                   after birth, and appear severely dehydrated with dry
FT                   cracking skin. Smsk homozygous mutants embryos show a
FT                   normal appearance at 14.5 dpc, but at 16.5 dpc develop a
FT                   partial absence of normal skin folds around the trunk and
FT                   limbs, and by 18.5 dpc develop a taut, thick skin and limb
FT                   contractures."
FT                   /evidence="ECO:0000269|PubMed:27551807"
FT   MUTAGEN         1996
FT                   /note="G->D: In a mouse model for harlequin ichthyosis
FT                   (HI), homozygous mice are embryonic lethal but occasionally
FT                   pups are found in the first few hours after birth but die
FT                   and are severely dehydrated and fail to suckle normally.
FT                   Homozygous pups show hallmarks of HI desease including
FT                   hyperkeratosis, abnormal extracellular lipid lamellae and
FT                   defects in cornified envelope processing. At 14.5 dpc and
FT                   15.5 dpc homozygous embryos appear normal; however from
FT                   16.5 dpc onwards they are characterized by an absence of
FT                   normal skin folds around the trunk and limbs. As
FT                   development progressed, embryos develop a taut, thick
FT                   epidermis and multiple contractures affecting the limbs.
FT                   Late stage embryos are smaller."
FT                   /evidence="ECO:0000269|PubMed:18802465"
SQ   SEQUENCE   2595 AA;  292592 MW;  17D651731EC35D05 CRC64;
     MASQFHQLRI LVWKNWLGVK RQPLWTLVLI LWPVIIFIIL AITRTKFPPT AKPTCYLAPR
     NLPSAGFFPF LQTLLCDTDS KCKDTPYGPR DLLRRKGIDG PLFKESEILK KPSNPKRDSN
     LSLRSTQVPE RSHTSLATVP PRPSYDLEGT GTENFNGSQL LTRILGLEKL LKQNSTPEDI
     RRELCESYPG YTADYAFSWV TLGKNVFNKF CLSNMTLLES SLQELKYQVS QMSSDPDNQK
     RVFRGLVQVL SFFSQVQQQR EVWQLLSSLP DVFQNGTSLS SLFGVLQKAN RVLLVVQKVY
     PRVQTDEGFS TLQKSVKHLL NTLDSPMQGD NSTHAWSDDD EQTLSPSSLA AQLLILENFE
     DAILNISSNS PYSPYLACVR NMTDNLAKGS PDNLKLLQST IHFRKSFLQN GSSEDSFPPF
     LEILKSKLSQ LRNLTELLCE SETFSSIKKS CQFSNMSFER LCEDHAFHVQ LIEAAELGTD
     LTTGLLYHDN IISAKLRGLL TGDPSKINLN VDWLLEQALQ MNYLENITRL IPTVEAMLHV
     NTSADASEKP GQLREMFKNI DLLKEDLRAI GMSNTSIDKL LAIPIPDNRA EIISRVFWLH
     SCDTNVTNPK LEDAMKEFCK LPLPERSHQS YLIGLTLLHY LDIYNFTYKV FFPRKDQKPM
     ERMMELFIKL REILNQLASG THPLLDKMRS LRQMHLPRSV PLTQAMYRNT RMNSPAGSFS
     TISQALCSQG ITTEYLTAML PSSQKPKGNH TKDFLTYKLT KEEIASKYGI PLNATPFCFS
     LYKDIINMPA GPVIWAFLKP MLLGKILYSP YNPTTKAIME KSNVTLRQLA ELREKSQEWM
     DKSPIFMNSF HLLNQTIPML QNTLRNPFVQ VFVKFSVGLD AVELLKQIDD LDVLRLKLVN
     NIDIIDQLNT LSSLTVNISS CVLYDRIQAS DTVEEMETVA EQLYKSNELF GSVIFKLPSN
     GSLHRGFDPE KVSLPPIVRY TIRMSLKTAQ TTRSIRTKIW APGPHNSPSH NQIYGRAFIY
     LQDSIERAII ELQTGRNSQE VAVQVQAVPY PCFMKDNFLT SVSYSLPIVL MVAWVVFIAA
     FVKKLVYEKD LRLHEYMKMM GVNSCSHFFA WLIESIGFLL VTIAILIVIL KFGNILPKTN
     GFILFLYFSD YSFSVIAMSY LISVFFNNTN IAALIGSLIY VIAFFPFIVL VTVEDELSYV
     IKVFMSLLSP TAFSYASQYI ARYEEQGVGL QWENMYKSPV QDDTTSFGWL CCLILADSFI
     YFFIAWYVRN VFPGTYGMAA PWYFPILPSY WKERFGCAEV KHEKSNGLMF TNIMMQNTNP
     SASKTSPDCA FPSNIEPEPK DLQVGVALHG VTKIYGSKTA VENLNLNFYE GHITSLLGPN
     GAGKTTTISM LTGLFGATAG TIFVYGKDIK TDLNTVRKNM GVCMQHDVLF SYLTTKEHLL
     LYGSIKVPHW TKTQLHEEVK RTLKDTGLYS HRHKRVGTLS GGMKRKLSIS IALIGGSRVV
     ILDEPSTGVD PCSRRSIWDV ISKNKTARTI ILSTHHLDEA EVLSDRIAFL EQGGLRCCGS
     PFYLKEAFGD GYHLTLTKKK SPNLDTNAIC DTVAVTAMIQ SHLPEAYLKE DIGGELVYVL
     PPFSTKVSGA YLSLLRALDK GMGKLNIGCY GISDTTVEEV FLNLTKDSQK SSNMSLEHLT
     QRKVGNPSAN GTSTPDDLSV SSSNFTDRDD KVLTRSEKLE GFGLLLKKIM AILIKRFHHT
     RRNWKGLIAQ VILPIVFVAT AMGLGTLRDS SNSYPEIMIS PSIYGTSEQT AFYANFDPST
     SGLVSALWNF PGIDNVCLNT SDLQCLKKDD LGKWNTSGEA IDNFGVCSCS DNVQECPKFN
     YHPPHRRTYS SQVIYNLTGK HMENYLITTA NHFVQKRYGG WSFGMKLTND LRFDVTAVPD
     NRTLAKVWYD PEGYHSLPAY LNSLNNFLLR VNMSEYDAAR HGIIMYSHPY PGVQDQEQAT
     ISSLIDILVA LSILMGYSVT TASFVTYIVR EHQTKAKQLQ HISGIGVTCY WVTNFIYDMV
     FYLVPVAFSI GVIAIFKLPA FYSGNNLGAV SLLLLLFGYA TFSWMYLLAG LFHETGMAFI
     TYVCVNLFFG INSIVSLSVV YFLSKEKPND PTLELISETL KRIFLIFPQF CFGYGLIELS
     QQQAVLDFLK AYGVEYPSET FEMDKLGAMF VALVSQGTMF FLLRLLINEW LIKKLRLFFR
     KFTSSPIMET VDEDEDVRAE RFRVESGAAE FDLVQLHRLT KTYQLIHKKI IAVNNISLGI
     PAGECFGLLG VNGAGKTTIF KMLTGDIIPS SGNILIRNKS GSLGHVDSHS SLVGYCPQED
     ALDDLVTVEE HLYFYARVHG IPEKDIKDTV HKLLRRLHLM AYKDRSTSMC SYGTKRKLST
     ALALIGKPSI LLLDEPSSGM DPKSKRHLWR IISEEVQNKC SVILTSHSME ECEALCTRLA
     IMVNGRFQCI GSLQHIKSRF GRGFTVKVHL KNNKVSMETL TKFMQLHFPK TYLKDQHLSM
     LEYHVPVTAG GVANIFDLLE TNKTALNITN FLVSQTTLEE VFINFAKDQK SYENVDTSSQ
     GSTISVDSQE DQLDS
//