Protein:ATP7A |
Protein Summary |
 Gene summary |
| Gene name: ATP7A | ASpdb.0 ID: 538 | Gene | Gene symbol | ATP7A | Gene ID | 538 |
| Gene name | ATPase copper transporting alpha |
| Synonyms | DSMAX|HMNX|MK|MNK|SMAX3 |
| Cytomap | Xq21.1 |
| Type of gene | protein-coding |
| Description | copper-transporting ATPase 1ATPase, Cu++ transporting, alpha polypeptideCu++-transporting P-type ATPaseMenkes disease-associated proteincopper pump 1 |
| Modification date | 20240305 |
| UniProtAcc | Q04656 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | ATP7A | GO:0005507 | copper ion binding | 15670166 |
| Gene | ATP7A | GO:0005524 | ATP binding | 19917612 |
| Gene | ATP7A | GO:0005770 | late endosome | 8943055 |
| Gene | ATP7A | GO:0005794 | Golgi apparatus | 9467005 |
| Gene | ATP7A | GO:0005802 | trans-Golgi network | 8943055|12812980 |
| Gene | ATP7A | GO:0005886 | plasma membrane | 12812980 |
| Gene | ATP7A | GO:0016323 | basolateral plasma membrane | 16397091 |
| Gene | ATP7A | GO:0032767 | copper-dependent protein binding | 31283225 |
| Gene | ATP7A | GO:0048471 | perinuclear region of cytoplasm | 8943055|10567439|16397091 |
| Gene | ATP7A | GO:0060003 | copper ion export | 10419525 |
| Gene | ATP7A | GO:0140581 | P-type monovalent copper transporter activity | 10419525 |
| Gene | ATP7A | GO:1903136 | cuprous ion binding | 31283225 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| Q04656-1 | Q04656-1_3cjk_B.pdb | 3CJK | X-ray | 1.8 | B | 7 | 77 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| Q04656 | ATP7A | Q04656-1 | Q04656-4 | 1500 | 503 | 42 | 1038 | Deletion | none | none | 41 | 41 |
| Q04656 | ATP7A | Q04656-1 | Q04656-6 | 1500 | 103 | 1 | 1 | Substitution | M | MRKLSIRKRDNNLLKECNEEIK | 1 | 22 |
| Q04656 | ATP7A | Q04656-1 | Q04656-6 | 1500 | 103 | 53 | 81 | Substitution | DPKLQTPKTLQEAIDDMGFDAVIHNPDPL | AHWFGFAALDGICSNGCFICFCSTFFSSL | 74 | 102 |
| Q04656 | ATP7A | Q04656-1 | Q04656-6 | 1500 | 103 | 82 | 1499 | Deletion | none | none | 102 | 102 |
| Multiple sequence alignment of our canonical and alternatively spliced ATP7A |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of ATP7A |
| UniProt-id | ENSG | ENST | ENSP |
| Q04656-1 | ENSG00000165240.22 | ENST00000341514.11 | ENSP00000345728.6 |
| Q04656-1 | ENSG00000165240.22 | ENST00000685264.1 | ENSP00000510136.1 |
| Q04656-1 | ENSG00000165240.22 | ENST00000686133.1 | ENSP00000509233.1 |
| Q04656-1 | ENSG00000165240.22 | ENST00000687086.1 | ENSP00000509566.1 |
| UniProt-id | NM ID | NP ID |
| Q04656-1 | NM_000052.6 | NP_000043.4 |
| Amino acid sequences of our canonical and alternatively spliced ATP7A |
| accession_id | Protein sequence |
| Q04656-1 | MDPSMGVNSVTISVEGMTCNSCVWTIEQQIGKVNGVHHIKVSLEEKNATIIYDPKLQTPKTLQEAIDDMGFDAVIHNPDPLPVLTDTLFL TVTASLTLPWDHIQSTLLKTKGVTDIKIYPQKRTVAVTIIPSIVNANQIKELVPELSLDTGTLEKKSGACEDHSMAQAGEVVLKMKVEGM TCHSCTSTIEGKIGKLQGVQRIKVSLDNQEATIVYQPHLISVEEMKKQIEAMGFPAFVKKQPKYLKLGAIDVERLKNTPVKSSEGSQQRS PSYTNDSTATFIIDGMHCKSCVSNIESTLSALQYVSSIVVSLENRSAIVKYNASSVTPESLRKAIEAVSPGLYRVSITSEVESTSNSPSS SSLQKIPLNVVSQPLTQETVINIDGMTCNSCVQSIEGVISKKPGVKSIRVSLANSNGTVEYDPLLTSPETLRGAIEDMGFDATLSDTNEP LVVIAQPSSEMPLLTSTNEFYTKGMTPVQDKEEGKNSSKCYIQVTGMTCASCVANIERNLRREEGIYSILVALMAGKAEVRYNPAVIQPP MIAEFIRELGFGATVIENADEGDGVLELVVRGMTCASCVHKIESSLTKHRGILYCSVALATNKAHIKYDPEIIGPRDIIHTIESLGFEAS LVKKDRSASHLDHKREIRQWRRSFLVSLFFCIPVMGLMIYMMVMDHHFATLHHNQNMSKEEMINLHSSMFLERQILPGLSVMNLLSFLLC VPVQFFGGWYFYIQAYKALKHKTANMDVLIVLATTIAFAYSLIILLVAMYERAKVNPITFFDTPPMLFVFIALGRWLEHIAKGKTSEALA KLISLQATEATIVTLDSDNILLSEEQVDVELVQRGDIIKVVPGGKFPVDGRVIEGHSMVDESLITGEAMPVAKKPGSTVIAGSINQNGSL LICATHVGADTTLSQIVKLVEEAQTSKAPIQQFADKLSGYFVPFIVFVSIATLLVWIVIGFLNFEIVETYFPGYNRSISRTETIIRFAFQ ASITVLCIACPCSLGLATPTAVMVGTGVGAQNGILIKGGEPLEMAHKVKVVVFDKTGTITHGTPVVNQVKVLTESNRISHHKILAIVGTA ESNSEHPLGTAITKYCKQELDTETLGTCIDFQVVPGCGISCKVTNIEGLLHKNNWNIEDNNIKNASLVQIDASNEQSSTSSSMIIDAQIS NALNAQQYKVLIGNREWMIRNGLVINNDVNDFMTEHERKGRTAVLVAVDDELCGLIAIADTVKPEAELAIHILKSMGLEVVLMTGDNSKT ARSIASQVGITKVFAEVLPSHKVAKVKQLQEEGKRVAMVGDGINDSPALAMANVGIAIGTGTDVAIEAADVVLIRNDLLDVVASIDLSRK TVKRIRINFVFALIYNLVGIPIAAGVFMPIGLVLQPWMGSAAMAASSVSVVLSSLFLKLYRKPTYESYELPARSQIGQKSPSEISVHVGI |
| Q04656-4 | MDPSMGVNSVTISVEGMTCNSCVWTIEQQIGKVNGVHHIKVKVVVFDKTGTITHGTPVVNQVKVLTESNRISHHKILAIVGTAESNSEHP LGTAITKYCKQELDTETLGTCIDFQVVPGCGISCKVTNIEGLLHKNNWNIEDNNIKNASLVQIDASNEQSSTSSSMIIDAQISNALNAQQ YKVLIGNREWMIRNGLVINNDVNDFMTEHERKGRTAVLVAVDDELCGLIAIADTVKPEAELAIHILKSMGLEVVLMTGDNSKTARSIASQ VGITKVFAEVLPSHKVAKVKQLQEEGKRVAMVGDGINDSPALAMANVGIAIGTGTDVAIEAADVVLIRNDLLDVVASIDLSRKTVKRIRI NFVFALIYNLVGIPIAAGVFMPIGLVLQPWMGSAAMAASSVSVVLSSLFLKLYRKPTYESYELPARSQIGQKSPSEISVHVGIDDTSRNS |
| Q04656-6 | MRKLSIRKRDNNLLKECNEEIKDPSMGVNSVTISVEGMTCNSCVWTIEQQIGKVNGVHHIKVSLEEKNATIIYAHWFGFAALDGICSNGC |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| ATP7A (go to UniProt):Q04656 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Q04656 | Topological domain | 1 | 653 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=42;End=1038 |
| Q04656 | Topological domain | 1 | 653 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Substitution;Start=1;End=1 |
| Q04656 | Topological domain | 1 | 653 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Substitution;Start=53;End=81 |
| Q04656 | Topological domain | 1 | 653 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=82;End=1499 |
| Q04656 | Transmembrane | 654 | 675 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=42;End=1038 |
| Q04656 | Transmembrane | 654 | 675 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=82;End=1499 |
| Q04656 | Topological domain | 676 | 714 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=42;End=1038 |
| Q04656 | Topological domain | 676 | 714 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=82;End=1499 |
| Q04656 | Transmembrane | 715 | 734 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=42;End=1038 |
| Q04656 | Transmembrane | 715 | 734 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=82;End=1499 |
| Q04656 | Topological domain | 735 | 741 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=42;End=1038 |
| Q04656 | Topological domain | 735 | 741 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=82;End=1499 |
| Q04656 | Transmembrane | 742 | 762 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=42;End=1038 |
| Q04656 | Transmembrane | 742 | 762 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=82;End=1499 |
| Q04656 | Topological domain | 763 | 781 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=42;End=1038 |
| Q04656 | Topological domain | 763 | 781 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=82;End=1499 |
| Q04656 | Transmembrane | 782 | 802 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=42;End=1038 |
| Q04656 | Transmembrane | 782 | 802 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=82;End=1499 |
| Q04656 | Topological domain | 803 | 936 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=42;End=1038 |
| Q04656 | Topological domain | 803 | 936 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=82;End=1499 |
| Q04656 | Transmembrane | 937 | 959 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=42;End=1038 |
| Q04656 | Transmembrane | 937 | 959 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=82;End=1499 |
| Q04656 | Topological domain | 960 | 989 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=42;End=1038 |
| Q04656 | Topological domain | 960 | 989 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=82;End=1499 |
| Q04656 | Transmembrane | 990 | 1011 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=42;End=1038 |
| Q04656 | Transmembrane | 990 | 1011 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=82;End=1499 |
| Q04656 | Topological domain | 1012 | 1356 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=42;End=1038 |
| Q04656 | Topological domain | 1012 | 1356 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=82;End=1499 |
| Q04656 | Transmembrane | 1357 | 1374 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=82;End=1499 |
| Q04656 | Topological domain | 1375 | 1385 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=82;End=1499 |
| Q04656 | Transmembrane | 1386 | 1405 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=82;End=1499 |
| Q04656 | Topological domain | 1406 | 1500 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=82;End=1499 |
| Q04656 | Domain | 8 | 74 | Note=HMA 1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00280 | Type=Deletion;Start=42;End=1038 |
| Q04656 | Domain | 8 | 74 | Note=HMA 1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00280 | Type=Substitution;Start=53;End=81 |
| Q04656 | Domain | 85 | 151 | Note=HMA 2;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00280 | Type=Deletion;Start=42;End=1038 |
| Q04656 | Domain | 85 | 151 | Note=HMA 2;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00280 | Type=Deletion;Start=82;End=1499 |
| Q04656 | Domain | 171 | 237 | Note=HMA 3;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00280 | Type=Deletion;Start=42;End=1038 |
| Q04656 | Domain | 171 | 237 | Note=HMA 3;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00280 | Type=Deletion;Start=82;End=1499 |
| Q04656 | Domain | 277 | 343 | Note=HMA 4;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00280 | Type=Deletion;Start=42;End=1038 |
| Q04656 | Domain | 277 | 343 | Note=HMA 4;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00280 | Type=Deletion;Start=82;End=1499 |
| Q04656 | Domain | 377 | 443 | Note=HMA 5;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00280 | Type=Deletion;Start=42;End=1038 |
| Q04656 | Domain | 377 | 443 | Note=HMA 5;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00280 | Type=Deletion;Start=82;End=1499 |
| Q04656 | Domain | 488 | 554 | Note=HMA 6;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00280 | Type=Deletion;Start=42;End=1038 |
| Q04656 | Domain | 488 | 554 | Note=HMA 6;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00280 | Type=Deletion;Start=82;End=1499 |
| Q04656 | Domain | 564 | 630 | Note=HMA 7;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00280 | Type=Deletion;Start=42;End=1038 |
| Q04656 | Domain | 564 | 630 | Note=HMA 7;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00280 | Type=Deletion;Start=82;End=1499 |
| Q04656 | Region | 1486 | 1500 | Note=PDZD11-binding | Type=Deletion;Start=82;End=1499 |
| Q04656 | Motif | 1467 | 1468 | Note=Endocytosis signal;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:Q64430 | Type=Deletion;Start=82;End=1499 |
| Q04656 | Motif | 1487 | 1488 | Note=Endocytosis signal;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:Q64430 | Type=Deletion;Start=82;End=1499 |
Gene Isoform Structures and Expression Levels for ATP7A |
| Gene structures of our canonical and alternative spliced genes of ATP7A * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of Q04656-1 |
| 3D view using mol* of Q04656-4 |
| 3D view using mol* of Q04656-6 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of Q04656-1 |
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| pLDDT distribution across the protein length of Q04656-4 |
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| pLDDT distribution across the protein length of Q04656-6 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of Q04656-1 |
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| Ramachandran plot of Q04656-4 |
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| Ramachandran plot of Q04656-6 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| Q04656-1 | 1.047 | 472 | 1.01 | 1071.532 | 0.473 | 0.769 | 1.008 | 0.403 | 1.201 | 0.335 | 0.665 | 494,495,496,497,498,499,500,501,503,504,505,507,50 8,509,511,522,523,524,526,639,640,642,643,644,645, 646,649,650,652,653,656,657,726,727,729,730,731,73 4,741,743,744,745,746,747,791,794,795,798,799,802, 920,923,924,925,926,927,928,931,932,934,935,936,93 8,939,942,943,1002,1004,1005,1006,1008,1009,1010,1 012,1013,1016,1028,1029,1393,1394,1397 |
| Q04656-4 | 1.014 | 318 | 1.054 | 851.669 | 0.607 | 0.677 | 0.891 | 0.763 | 0.896 | 0.851 | 0.87 | 48,57,60,84,87,88,89,90,91,92,95,114,116,117,118,1 19,120,121,122,185,186,187,206,210,211,212,213,214 ,215,216,217,231,232,233,234,235,236,237,239,240,2 41,243,244,245,247,248,260,262,263,265,266,267,268 ,269,270,271,272,273,274,418,421,422,424,425,426,4 28,429,430,431,432,433,434,436,437 |
| Q04656-6 | 1.026 | 115 | 1.085 | 303.555 | 0.638 | 0.656 | 0.803 | 0.502 | 0.762 | 0.659 | 0.913 | 9,11,14,15,16,17,18,19,20,21,28,30,32,34,59,61,63, 66,68,70,72 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of Q04656-1_Q04656-1_3cjk_B.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of Q04656-1_3cjk_B_Q04656-4.pdb |
| 3D view using mol* of Q04656-1_3cjk_B_Q04656-6.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of Q04656-1_Q04656-4.pdb |
| 3D view using mol* of Q04656-1_Q04656-6.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/Q04656-1_vs_Q04656-4.png |
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| ./stats/secondary_structure/figure/Q04656-1_vs_Q04656-6.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/Q04656-1_vs_Q04656-4.png |
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| ./stats/relative_asa/Q04656-1_vs_Q04656-6.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to ATP7A |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
Related Diseases to ATP7A |
| Previous studies relating to the alternative splicing of ATP7A and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| ATP7A | 9693104 | Multiple transcripts coding for the menkes gene: evidence for alternative splicing of Menkes mRNA. | We isolated cDNA fragments from four human cell lines that had sequences for the Menkes Cu-transporting ATPase (ATP7A). Primers designed to generate a 4.8 kb cDNA with the complete open reading frame generated a 1.9 kb cDNA in addition to the expected 4.8 kb product. Sequence analysis revealed that the 1.9 kb cDNA encoded one of the six Cu-binding sites and two of the eight transmembrane domains of ATP7A. Stop and start codons were also present. More striking, however, was an unusual union between exons 2 and 16 that retained an in-frame reference to exon 23. The 1.9 kb cDNA thus appeared to be a truncated Menkes mRNA that coded for an ATP7A variant that lacked exons 3-15. A 530 bp probe specific for exon 23 that avoided sequences in the exon 3-15 region hybridized to a 5.5 kb band on Northern blot analysis. Western blotting provided immunochemical evidence for the presence of both a 170 kDa and a 57 kDa protein with ATP7A sequences in detergent extracts of Caco-2 and induced BeWo cells. Extracts from non-induced BeWo cells, which lack the capacity to express the Menkes gene (MNK), showed neither protein. In a cell-free reticulocyte lysate, a plasmid containing the 1.9 kb cDNA insert directed the synthesis of a 59 kDa protein with antigenic properties of ATP7A. These studies provide evidence that non-Menkes cells have the capacity to synthesize more than one MNK mRNA. The one characterized in this report codes for a 57-59 kDa protein that lacks the core structure of the ATP7A protein. The smaller variant could be an alternative spliced form of MNK mRNA. | D007706 | Menkes Kinky Hair Syndrome |
Clinically important variants in ATP7A |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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