Q86UK0Q53QE2Q53S55Q8IZW6Q96JT3Q9Y4M5ABCAC_HUMANGlucosylceramide transporter ABCA127.6.2.1ATP-binding cassette sub-family A member 12ATP-binding cassette transporter 12ATP-binding cassette 12ABCA12ABC12Homo sapiensHumanEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomoIdentification and characterization of a novel ABCA subfamily member, ABCA12, located in the lamellar ichthyosis region on 2q34.NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)TISSUE SPECIFICITYVARIANT THR-777A retinal cDNA for the ATP-binding cassette transporter ABCA12.NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)VARIANT THR-777Generation and annotation of the DNA sequences of human chromosomes 2 and 4.NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]Cloning of a novel ABC transporter (ABCA12) tentatively involved in lipid homeostatis.NUCLEOTIDE SEQUENCE [MRNA] OF 221-2595VARIANT THR-777The full-ORF clone resource of the German cDNA consortium.NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2400-2595Mutations in lipid transporter ABCA12 in harlequin ichthyosis and functional recovery by corrective gene transfer.TISSUE SPECIFICITYINDUCTIONSUBCELLULAR LOCATIONFUNCTIONVARIANTS ARCI4B 434-ARG--SER-2595 DEL; THR-1385 DEL AND 1950-ARG--SER-2595 DELCATALYTIC ACTIVITYExpression of the keratinocyte lipid transporter ABCA12 in developing and reconstituted human epidermis.DEVELOPMENTAL STAGETISSUE SPECIFICITYINDUCTIONLocalization of ABCA12 from Golgi apparatus to lamellar granules in human upper epidermal keratinocytes.TISSUE SPECIFICITYSUBCELLULAR LOCATIONFUNCTIONPPAR and LXR activators regulate ABCA12 expression in human keratinocytes.INDUCTIONPremature terminal differentiation and a reduction in specific proteases associated with loss of ABCA12 in Harlequin ichthyosis.TISSUE SPECIFICITYFUNCTIONCeramide stimulates ABCA12 expression via peroxisome proliferator-activated receptor {delta} in human keratinocytes.INDUCTIONABCA12 dysfunction causes a disorder in glucosylceramide accumulation during keratinocyte differentiation.FUNCTIONCATALYTIC ACTIVITYABCA12 regulates insulin secretion from beta-cells.TISSUE SPECIFICITYABCA12 mutations and autosomal recessive congenital ichthyosis: a review of genotype/phenotype correlations and of pathogenetic concepts.REVIEW ON VARIANTSINVOLVEMENT IN ARCIMutations in the transporter ABCA12 are associated with lamellar ichthyosis type 2.VARIANTS ARCI4A SER-1380; GLU-1381; HIS-1514; LYS-1539 AND SER-1651Mutations in ABCA12 underlie the severe congenital skin disease harlequin ichthyosis.VARIANT ASN-2365Compound heterozygous mutations including a de novo missense mutation in ABCA12 led to a case of harlequin ichthyosis with moderate clinical severity.VARIANT ARCI4B ASN-387ABCA12 is the major harlequin ichthyosis gene.VARIANT ARCI4B ARG-1179Novel ABCA12 mutations identified in two cases of non-bullous congenital ichthyosiform erythroderma associated with multiple skin malignant neoplasia.VARIANTS ARCI4A PRO-345 AND THR-1494Novel compound heterozygous nonsense and missense ABCA12 mutations lead to nonbullous congenital ichthyosiform erythroderma.VARIANT ARCI4A ASP-1136Core signaling pathways in human pancreatic cancers revealed by global genomic analyses.VARIANT [LARGE SCALE ANALYSIS] VAL-476ABCA12 is a major causative gene for non-bullous congenital ichthyosiform erythroderma.VARIANTS ARCI4A SER-1235; HIS-1514; LEU-1798 AND LYS-1980Non-bullous congenital ichthyosiform erythroderma associated with homozygosity for a novel missense mutation in an ATP binding domain of ABCA12.VARIANT ARCI4A VAL-1559Transports lipids such as glucosylceramides from the outer to the inner leaflet of lamellar granules (LGs) membrane, whereby the lipids are finally transported to the keratinocyte periphery via the trans-Golgi network and LGs and released to the apical surface of the granular keratinocytes to form lipid lamellae in the stratum corneum of the epidermis, which is essential for skin barrier function (PubMed:16007253, PubMed:20869849). In the meantime, participates in the transport of the lamellar granules-associated proteolytic enzymes, in turn regulates desquamation and keratinocyte differentiation (PubMed:19179616). Furthermore, is essential for the regulation of cellular cholesterol homeostasis by regulating ABCA1-dependent cholesterol efflux from macrophages through interaction with NR1H2 and ABCA1 (By similarity). Plays pleiotropic roles in regulating glucose stimulated insulin secretion from beta cells, regulating the morphology and fusion of insulin granules, lipid raft abundance and the actin cytoskeleton (By similarity). Also involved in lung surfactant biogenesis (By similarity).ATP + H2O + phospholipidSide 1 = ADP + phosphate + phospholipidSide 2.ATP + beta-D-glucosylceramide(in) + H2O = ADP + beta-D-glucosylceramide(out) + H(+) + phosphateInteracts with NR1H2 and ABCA1; this interaction is required for ABCA1 localization to the cell surface and is necessary for its normal activity and stability.Q86UK0O95477false4Cytoplasmic vesicleSecretory vesicle membraneMulti-pass membrane proteinGolgi apparatus membraneLocalizes in the limiting membrane of the lamellar granules (LGs) (PubMed:17927575). Trafficks from the Golgi apparatus to the lamellar granules (LGs) at the cell periphery in the uppermost granular layer keratinocytes where ABCA12-positive LGs fuse with the keratinocyte-cell membrane to secrete their lipid content to the extracellular space of the stratum corneum (PubMed:16007253, PubMed:17927575). Co-localizes through the Golgi apparatus to the cell periphery with glucosylceramide (PubMed:17927575).Q86UK0-11Q86UK0-22Additional isoforms seem to exist.Mainly expressed in the stomach, placenta, testis and fetal brain (PubMed:12697999). Expressed in the upper epidermal layers, mainly the granular layers, of skin (PubMed:16007253, PubMed:17591952, PubMed:17927575). Expressed throughout the normal interfollicular epidermis with prominent expression in the stratum granulosum (PubMed:19179616). Expressed in alpha and beta cells of pancreatic islets (PubMed:32072744).At about 6 to 9 weeks estimated gestational age (EGA), expressed in the periderm during the early period when the two-layered epidermis form. At 10 to 13 weeks EGA, expressed in the entire epidermis with high expression in periderm until to 14 to 22 weeks EGA.Up-regulated during keratinization (PubMed:16007253). Up-regulated after 15 weeks estimated gestational age (EGA) (PubMed:17591952). Highly up-regulated by PPARG activators such as ciglitazone, troglitazone, and the PPARD activator GW 0742 in time- and dose-dependent manner but independently of keratinocyte differentiation. In addition, modestly up-regulated by the NR1H3 and NR1H2 activator TO901317 in an keratinocyte differentiation-independent manner (PubMed:17611579). Up-regulated by N-(hexanoyl)sphing-4-enine in a time- and dose-dependent manner or by glucosyltransferase inhibitors, ceramidase inhibitors and sphingomyelin synthase inhibitors that increase endogenous ceramide levels and induce ABCA12 expression via the PPARD signaling pathway (PubMed:19429679). Up-regulated by N-acetylsphingosine in a time- and dose-dependent manner via the PPARD signaling pathway (Probable).Multifunctional polypeptide with two homologous halves, each containing a hydrophobic membrane-anchoring domain and an ATP binding cassette (ABC) domain.Ichthyosis, congenital, autosomal recessive 4A
ARCI4A
A form of autosomal recessive congenital ichthyosis, a disorder of keratinization with abnormal differentiation and desquamation of the epidermis, resulting in abnormal skin scaling over the whole body. The main skin phenotypes are lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur. Lamellar ichthyosis is a condition often associated with an embedment in a collodion-like membrane at birth; skin scales later develop, covering the entire body surface. Non-bullous congenital ichthyosiform erythroderma characterized by fine whitish scaling on an erythrodermal background; larger brownish scales are present on the buttocks, neck and legs.The disease is caused by variants affecting the gene represented in this entry.Ichthyosis, congenital, autosomal recessive 4B
ARCI4B
A rare, very severe form of congenital ichthyosis, in which the neonate is born with a thick covering of armor-like scales. The skin dries out to form hard diamond-shaped plaques separated by fissures, resembling 'armor plating'. The normal facial features are severely affected, with distortion of the lips (eclabion), eyelids (ectropion), ears, and nostrils. Affected babies are often born prematurely and rarely survive the perinatal period. Babies who survive into infancy and beyond develop skin changes resembling severe non-bullous congenital ichthyosiform erythroderma.The disease is caused by variants affecting the gene represented in this entry.Belongs to the ABC transporter superfamily. ABCA family.Database for mutations in ABC proteinsAlternative splicingATP-bindingCytoplasmic vesicleDisease variantGlycoproteinGolgi apparatusIchthyosisLipid transportMembraneNucleotide-bindingReference proteomeRepeatTranslocaseTransmembraneTransmembrane helixTransportATPATPLLYTLDSPAQMFTYIKIITSWCNHQRRGTPSNSTAVEGSTGDGRWSGDNSGEITRHEKRCGVGSPLTKEKDNYDYHNDYHMASLFHQLQILVWKNWLGVKRQPLWTLVLILWPVIIFIILAITRTKFPPTAKPTCYLAPRNLPSTGFFPFLQTLLCDTDSKCKDTPYGPQDLLRRKGIDDALFKDSEILRKSSNLDKDSSLSFQSTQVPERRHASLATVFPSPSSDLEIPGTYTFNGSQVLARILGLEKLLKQNSTSEDIRRELCDSYSGYIVDDAFSWTFLGRNVFNKFCLSNMTLLESSLQELNKQFSQLSSDPNNQKIVFQEIVRMLSFFSQVQEQKAVWQLLSSFPNVFQNDTSLSNLFDVLRKANSVLLVVQKVYPRFATNEGFRTLQKSVKHLLYTLDSPAQGDSDNITHVWNEDDGQTLSPSSLAAQLLILENFEDALLNISANSPYIPYLACVRNVTDSLARGSPENLRLLQSTIRFKKSFLRNGSYEDYFPPVPEVLKSKLSQLRNLTELLCESETFSLIEKSCQLSDMSFGSLCEESEFDLQLLEAAELGTEIAASLLYHDNVISKKVRDLLTGDPSKINLNMDQFLEQALQMNYLENITQLIPIIEAMLHVNNSADASEKPGQLLEMFKNVEELKEDLRRTTGMSNRTIDKLLAIPIPDNRAEIISQVFWLHSCDTNITTPKLEDAMKEFCNLSLSERSRQSYLIGLTLLHYLNIYNFTYKVFFPRKDQKPVEKMMELFIRLKEILNQMASGTHPLLDKMRSLKQMHLPRSVPLTQAMYRSNRMNTPQGSFSTISQALCSQGITTEYLTAMLPSSQRPKGNHTKDFLTYKLTKEQIASKYGIPINSTPFCFSLYKDIINMPAGPVIWAFLKPMLLGRILYAPYNPVTKAIMEKSNVTLRQLAELREKSQEWMDKSPLFMNSFHLLNQAIPMLQNTLRNPFVQVFVKFSVGLDAVELLKQIDELDILRLKLENNIDIIDQLNTLSSLTVNISSCVLYDRIQAAKTIDEMEREAKRLYKSNELFGSVIFKLPSNRSWHRGYDSGNVFLPPVIKYTIRMSLKTAQTTRSLRTKIWAPGPHNSPSHNQIYGRAFIYLQDSIERAIIELQTGRNSQEIAVQVQAIPYPCFMKDNFLTSVSYSLPIVLMVAWVVFIAAFVKKLVYEKDLRLHEYMKMMGVNSCSHFFAWLIESVGFLLVTIVILIIILKFGNILPKTNGFILFLYFSDYSFSVIAMSYLISVFFNNTNIAALIGSLIYIIAFFPFIVLVTVENELSYVLKVFMSLLSPTAFSYASQYIARYEEQGIGLQWENMYTSPVQDDTTSFGWLCCLILADSFIYFLIAWYVRNVFPGTYGMAAPWYFPILPSYWKERFGCAEVKPEKSNGLMFTNIMMQNTNPSASPEYMFSSNIEPEPKDLTVGVALHGVTKIYGSKVAVDNLNLNFYEGHITSLLGPNGAGKTTTISMLTGLFGASAGTIFVYGKDIKTDLHTVRKNMGVCMQHDVLFSYLTTKEHLLLYGSIKVPHWTKKQLHEEVKRTLKDTGLYSHRHKRVGTLSGGMKRKLSISIALIGGSRVVILDEPSTGVDPCSRRSIWDVISKNKTARTIILSTHHLDEAEVLSDRIAFLEQGGLRCCGSPFYLKEAFGDGYHLTLTKKKSPNLNANAVCDTMAVTAMIQSHLPEAYLKEDIGGELVYVLPPFSTKVSGAYLSLLRALDNGMGDLNIGCYGISDTTVEEVFLNLTKESQKNSAMSLEHLTQKKIGNSNANGISTPDDLSVSSSNFTDRDDKILTRGERLDGFGLLLKKIMAILIKRFHHTRRNWKGLIAQVILPIVFVTTAMGLGTLRNSSNSYPEIQISPSLYGTSEQTAFYANYHPSTEALVSAMWDFPGIDNMCLNTSDLQCLNKDSLEKWNTSGEPITNFGVCSCSENVQECPKFNYSPPHRRTYSSQVIYNLTGQRVENYLISTANEFVQKRYGGWSFGLPLTKDLRFDITGVPANRTLAKVWYDPEGYHSLPAYLNSLNNFLLRVNMSKYDAARHGIIMYSHPYPGVQDQEQATISSLIDILVALSILMGYSVTTASFVTYVVREHQTKAKQLQHISGIGVTCYWVTNFIYDMVFYLVPVAFSIGIIAIFKLPAFYSENNLGAVSLLLLLFGYATFSWMYLLAGLFHETGMAFITYVCVNLFFGINSIVSLSVVYFLSKEKPNDPTLELISETLKRIFLIFPQFCFGYGLIELSQQQSVLDFLKAYGVEYPNETFEMNKLGAMFVALVSQGTMFFSLRLLINESLIKKLRLFFRKFNSSHVRETIDEDEDVRAERLRVESGAAEFDLVQLYCLTKTYQLIHKKIIAVNNISIGIPAGECFGLLGVNGAGKTTIFKMLTGDIIPSSGNILIRNKTGSLGHVDSHSSLVGYCPQEDALDDLVTVEEHLYFYARVHGIPEKDIKETVHKLLRRLHLMPFKDRATSMCSYGTKRKLSTALALIGKPSILLLDEPSSGMDPKSKRHLWKIISEEVQNKCSVILTSHSMEECEALCTRLAIMVNGKFQCIGSLQHIKSRFGRGFTVKVHLKNNKVTMETLTKFMQLHFPKTYLKDQHLSMLEYHVPVTAGGVANIFDLLETNKTALNITNFLVSQTTLEEVFINFAKDQKSYETADTSSQGSTISVDSQDDQMES
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