ABCAC_MOUSE
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 03-AUG-2022, entry version 81.
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 GlyGen; E9Q876; 39 sites.
DR iPTMnet; E9Q876; -.
DR PhosphoSitePlus; E9Q876; -.
DR PaxDb; E9Q876; -.
DR PRIDE; E9Q876; -.
DR ProteomicsDB; 324613; -.
DR Antibodypedia; 34220; 143 antibodies from 26 providers.
DR DNASU; 74591; -.
DR Ensembl; ENSMUST00000087268; ENSMUSP00000084523; ENSMUSG00000050296.
DR GeneID; 74591; -.
DR KEGG; mmu:74591; -.
DR UCSC; uc011wmq.1; mouse.
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; MPTKYCK; -.
DR OrthoDB; 131191at2759; -.
DR PhylomeDB; E9Q876; -.
DR TreeFam; TF105191; -.
DR Reactome; R-MMU-1369062; ABC transporters in lipid homeostasis.
DR BioGRID-ORCS; 74591; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Abca12; mouse.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; E9Q876; protein.
DR Bgee; ENSMUSG00000050296; Expressed in esophagus and 25 other tissues.
DR Genevisible; E9Q876; MM.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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: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 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 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
