Protein:ATP2A2 |
Protein Summary |
 Gene summary |
| Gene name: ATP2A2 | ASpdb.0 ID: 488 | Gene | Gene symbol | ATP2A2 | Gene ID | 488 |
| Gene name | ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 |
| Synonyms | ATP2B|DAR|DD|SERCA2 |
| Cytomap | 12q24.11 |
| Type of gene | protein-coding |
| Description | sarcoplasmic/endoplasmic reticulum calcium ATPase 2ATPase Ca++ transporting cardiac muscle slow twitch 2ATPase, Ca++ dependent, slow-twitch, cardiac muscle-2SR Ca(2+)-ATPase 2calcium pump 2cardiac Ca2+ ATPaseendoplasmic reticulum class 1/2 Ca(2+) AT |
| Modification date | 20240413 |
| UniProtAcc | P16615 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | ATP2A2 | GO:0000045 | autophagosome assembly | 28890335 |
| Gene | ATP2A2 | GO:0005388 | P-type calcium transporter activity | 16402920 |
| Gene | ATP2A2 | GO:0005509 | calcium ion binding | 16402920 |
| Gene | ATP2A2 | GO:0005783 | endoplasmic reticulum | 16081076|30188326 |
| Gene | ATP2A2 | GO:0005789 | endoplasmic reticulum membrane | 11402072|32973183 |
| Gene | ATP2A2 | GO:0016020 | membrane | 22375059 |
| Gene | ATP2A2 | GO:0016240 | autophagosome membrane docking | 28890335 |
| Gene | ATP2A2 | GO:0016529 | sarcoplasmic reticulum | 12804600 |
| Gene | ATP2A2 | GO:0032469 | endoplasmic reticulum calcium ion homeostasis | 16402920 |
| Gene | ATP2A2 | GO:0032470 | positive regulation of endoplasmic reticulum calcium ion concentration | 16402920 |
| Gene | ATP2A2 | GO:0070588 | calcium ion transmembrane transport | 16402920|28890335 |
| Gene | ATP2A2 | GO:0086036 | regulation of cardiac muscle cell membrane potential | 16402920 |
| Gene | ATP2A2 | GO:0086039 | P-type calcium transporter activity involved in regulation of cardiac muscle cell membrane potential | 16402920|28890335 |
| Gene | ATP2A2 | GO:0140056 | organelle localization by membrane tethering | 28890335 |
| Gene | ATP2A2 | GO:1903515 | calcium ion transport from cytosol to endoplasmic reticulum | 16402920 |
| Gene | ATP2A2 | GO:1990036 | calcium ion import into sarcoplasmic reticulum | 16402920 |
| Gene | ATP2A2 | GO:1990456 | mitochondrion-endoplasmic reticulum membrane tethering | 28890335 |
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 |
| P16615-1 | P16615-1_6lly_A.pdb | 6LLY | EM | 2.8 | A | 1 | 1042 |
| 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 |
| P16615 | ATP2A2 | P16615-1 | P16615-2 | 1042 | 997 | 994 | 1042 | Substitution | GKECVQPATKSCSFSACTDGISWPFVLLIMPLVIWVYSTDTNFSDMFWS | AILE | 994 | 997 |
| P16615 | ATP2A2 | P16615-1 | P16615-3 | 1042 | 999 | 994 | 1042 | Substitution | GKECVQPATKSCSFSACTDGISWPFVLLIMPLVIWVYSTDTNFSDMFWS | VLSSEL | 994 | 999 |
| P16615 | ATP2A2 | P16615-1 | P16615-4 | 1042 | 1015 | 155 | 181 | Deletion | none | none | 154 | 154 |
| P16615 | ATP2A2 | P16615-1 | P16615-5 | 1042 | 997 | 994 | 1042 | Substitution | GKECVQPATKSCSFSACTDGISWPFVLLIMPLVIWVYSTDTNFSDMFWS | DIIK | 994 | 997 |
| Multiple sequence alignment of our canonical and alternatively spliced ATP2A2 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of ATP2A2 |
| UniProt-id | ENSG | ENST | ENSP |
| P16615-1 | ENSG00000174437.18 | ENST00000539276.7 | ENSP00000440045.2 |
| P16615-2 | ENSG00000174437.18 | ENST00000308664.10 | ENSP00000311186.6 |
| UniProt-id | NM ID | NP ID |
| P16615-1 | NM_170665.3 | NP_733765.1 |
| P16615-2 | NM_001681.3 | NP_001672.1 |
| P16615-3 | XM_011538402.2 | XP_011536704.1 |
| Amino acid sequences of our canonical and alternatively spliced ATP2A2 |
| accession_id | Protein sequence |
| P16615-1 | MENAHTKTVEEVLGHFGVNESTGLSLEQVKKLKERWGSNELPAEEGKTLLELVIEQFEDLLVRILLLAACISFVLAWFEEGEETITAFVE PFVILLILVANAIVGVWQERNAENAIEALKEYEPEMGKVYRQDRKSVQRIKAKDIVPGDIVEIAVGDKVPADIRLTSIKSTTLRVDQSIL TGESVSVIKHTDPVPDPRAVNQDKKNMLFSGTNIAAGKAMGVVVATGVNTEIGKIRDEMVATEQERTPLQQKLDEFGEQLSKVISLICIA VWIINIGHFNDPVHGGSWIRGAIYYFKIAVALAVAAIPEGLPAVITTCLALGTRRMAKKNAIVRSLPSVETLGCTSVICSDKTGTLTTNQ MSVCRMFILDRVEGDTCSLNEFTITGSTYAPIGEVHKDDKPVNCHQYDGLVELATICALCNDSALDYNEAKGVYEKVGEATETALTCLVE KMNVFDTELKGLSKIERANACNSVIKQLMKKEFTLEFSRDRKSMSVYCTPNKPSRTSMSKMFVKGAPEGVIDRCTHIRVGSTKVPMTSGV KQKIMSVIREWGSGSDTLRCLALATHDNPLRREEMHLEDSANFIKYETNLTFVGCVGMLDPPRIEVASSVKLCRQAGIRVIMITGDNKGT AVAICRRIGIFGQDEDVTSKAFTGREFDELNPSAQRDACLNARCFARVEPSHKSKIVEFLQSFDEITAMTGDGVNDAPALKKAEIGIAMG SGTAVAKTASEMVLADDNFSTIVAAVEEGRAIYNNMKQFIRYLISSNVGEVVCIFLTAALGFPEALIPVQLLWVNLVTDGLPATALGFNP PDLDIMNKPPRNPKEPLISGWLFFRYLAIGCYVGAATVGAAAWWFIAADGGPRVSFYQLSHFLQCKEDNPDFEGVDCAIFESPYPMTMAL SVLVTIEMCNALNSLSENQSLLRMPPWENIWLVGSICLSMSLHFLILYVEPLPLIFQITPLNVTQWLMVLKISLPVILMDETLKFVARNY |
| P16615-2 | MENAHTKTVEEVLGHFGVNESTGLSLEQVKKLKERWGSNELPAEEGKTLLELVIEQFEDLLVRILLLAACISFVLAWFEEGEETITAFVE PFVILLILVANAIVGVWQERNAENAIEALKEYEPEMGKVYRQDRKSVQRIKAKDIVPGDIVEIAVGDKVPADIRLTSIKSTTLRVDQSIL TGESVSVIKHTDPVPDPRAVNQDKKNMLFSGTNIAAGKAMGVVVATGVNTEIGKIRDEMVATEQERTPLQQKLDEFGEQLSKVISLICIA VWIINIGHFNDPVHGGSWIRGAIYYFKIAVALAVAAIPEGLPAVITTCLALGTRRMAKKNAIVRSLPSVETLGCTSVICSDKTGTLTTNQ MSVCRMFILDRVEGDTCSLNEFTITGSTYAPIGEVHKDDKPVNCHQYDGLVELATICALCNDSALDYNEAKGVYEKVGEATETALTCLVE KMNVFDTELKGLSKIERANACNSVIKQLMKKEFTLEFSRDRKSMSVYCTPNKPSRTSMSKMFVKGAPEGVIDRCTHIRVGSTKVPMTSGV KQKIMSVIREWGSGSDTLRCLALATHDNPLRREEMHLEDSANFIKYETNLTFVGCVGMLDPPRIEVASSVKLCRQAGIRVIMITGDNKGT AVAICRRIGIFGQDEDVTSKAFTGREFDELNPSAQRDACLNARCFARVEPSHKSKIVEFLQSFDEITAMTGDGVNDAPALKKAEIGIAMG SGTAVAKTASEMVLADDNFSTIVAAVEEGRAIYNNMKQFIRYLISSNVGEVVCIFLTAALGFPEALIPVQLLWVNLVTDGLPATALGFNP PDLDIMNKPPRNPKEPLISGWLFFRYLAIGCYVGAATVGAAAWWFIAADGGPRVSFYQLSHFLQCKEDNPDFEGVDCAIFESPYPMTMAL SVLVTIEMCNALNSLSENQSLLRMPPWENIWLVGSICLSMSLHFLILYVEPLPLIFQITPLNVTQWLMVLKISLPVILMDETLKFVARNY |
| P16615-3 | MENAHTKTVEEVLGHFGVNESTGLSLEQVKKLKERWGSNELPAEEGKTLLELVIEQFEDLLVRILLLAACISFVLAWFEEGEETITAFVE PFVILLILVANAIVGVWQERNAENAIEALKEYEPEMGKVYRQDRKSVQRIKAKDIVPGDIVEIAVGDKVPADIRLTSIKSTTLRVDQSIL TGESVSVIKHTDPVPDPRAVNQDKKNMLFSGTNIAAGKAMGVVVATGVNTEIGKIRDEMVATEQERTPLQQKLDEFGEQLSKVISLICIA VWIINIGHFNDPVHGGSWIRGAIYYFKIAVALAVAAIPEGLPAVITTCLALGTRRMAKKNAIVRSLPSVETLGCTSVICSDKTGTLTTNQ MSVCRMFILDRVEGDTCSLNEFTITGSTYAPIGEVHKDDKPVNCHQYDGLVELATICALCNDSALDYNEAKGVYEKVGEATETALTCLVE KMNVFDTELKGLSKIERANACNSVIKQLMKKEFTLEFSRDRKSMSVYCTPNKPSRTSMSKMFVKGAPEGVIDRCTHIRVGSTKVPMTSGV KQKIMSVIREWGSGSDTLRCLALATHDNPLRREEMHLEDSANFIKYETNLTFVGCVGMLDPPRIEVASSVKLCRQAGIRVIMITGDNKGT AVAICRRIGIFGQDEDVTSKAFTGREFDELNPSAQRDACLNARCFARVEPSHKSKIVEFLQSFDEITAMTGDGVNDAPALKKAEIGIAMG SGTAVAKTASEMVLADDNFSTIVAAVEEGRAIYNNMKQFIRYLISSNVGEVVCIFLTAALGFPEALIPVQLLWVNLVTDGLPATALGFNP PDLDIMNKPPRNPKEPLISGWLFFRYLAIGCYVGAATVGAAAWWFIAADGGPRVSFYQLSHFLQCKEDNPDFEGVDCAIFESPYPMTMAL SVLVTIEMCNALNSLSENQSLLRMPPWENIWLVGSICLSMSLHFLILYVEPLPLIFQITPLNVTQWLMVLKISLPVILMDETLKFVARNY |
| P16615-4 | MENAHTKTVEEVLGHFGVNESTGLSLEQVKKLKERWGSNELPAEEGKTLLELVIEQFEDLLVRILLLAACISFVLAWFEEGEETITAFVE PFVILLILVANAIVGVWQERNAENAIEALKEYEPEMGKVYRQDRKSVQRIKAKDIVPGDIVEIAGESVSVIKHTDPVPDPRAVNQDKKNM LFSGTNIAAGKAMGVVVATGVNTEIGKIRDEMVATEQERTPLQQKLDEFGEQLSKVISLICIAVWIINIGHFNDPVHGGSWIRGAIYYFK IAVALAVAAIPEGLPAVITTCLALGTRRMAKKNAIVRSLPSVETLGCTSVICSDKTGTLTTNQMSVCRMFILDRVEGDTCSLNEFTITGS TYAPIGEVHKDDKPVNCHQYDGLVELATICALCNDSALDYNEAKGVYEKVGEATETALTCLVEKMNVFDTELKGLSKIERANACNSVIKQ LMKKEFTLEFSRDRKSMSVYCTPNKPSRTSMSKMFVKGAPEGVIDRCTHIRVGSTKVPMTSGVKQKIMSVIREWGSGSDTLRCLALATHD NPLRREEMHLEDSANFIKYETNLTFVGCVGMLDPPRIEVASSVKLCRQAGIRVIMITGDNKGTAVAICRRIGIFGQDEDVTSKAFTGREF DELNPSAQRDACLNARCFARVEPSHKSKIVEFLQSFDEITAMTGDGVNDAPALKKAEIGIAMGSGTAVAKTASEMVLADDNFSTIVAAVE EGRAIYNNMKQFIRYLISSNVGEVVCIFLTAALGFPEALIPVQLLWVNLVTDGLPATALGFNPPDLDIMNKPPRNPKEPLISGWLFFRYL AIGCYVGAATVGAAAWWFIAADGGPRVSFYQLSHFLQCKEDNPDFEGVDCAIFESPYPMTMALSVLVTIEMCNALNSLSENQSLLRMPPW ENIWLVGSICLSMSLHFLILYVEPLPLIFQITPLNVTQWLMVLKISLPVILMDETLKFVARNYLEPGKECVQPATKSCSFSACTDGISWP |
| P16615-5 | MENAHTKTVEEVLGHFGVNESTGLSLEQVKKLKERWGSNELPAEEGKTLLELVIEQFEDLLVRILLLAACISFVLAWFEEGEETITAFVE PFVILLILVANAIVGVWQERNAENAIEALKEYEPEMGKVYRQDRKSVQRIKAKDIVPGDIVEIAVGDKVPADIRLTSIKSTTLRVDQSIL TGESVSVIKHTDPVPDPRAVNQDKKNMLFSGTNIAAGKAMGVVVATGVNTEIGKIRDEMVATEQERTPLQQKLDEFGEQLSKVISLICIA VWIINIGHFNDPVHGGSWIRGAIYYFKIAVALAVAAIPEGLPAVITTCLALGTRRMAKKNAIVRSLPSVETLGCTSVICSDKTGTLTTNQ MSVCRMFILDRVEGDTCSLNEFTITGSTYAPIGEVHKDDKPVNCHQYDGLVELATICALCNDSALDYNEAKGVYEKVGEATETALTCLVE KMNVFDTELKGLSKIERANACNSVIKQLMKKEFTLEFSRDRKSMSVYCTPNKPSRTSMSKMFVKGAPEGVIDRCTHIRVGSTKVPMTSGV KQKIMSVIREWGSGSDTLRCLALATHDNPLRREEMHLEDSANFIKYETNLTFVGCVGMLDPPRIEVASSVKLCRQAGIRVIMITGDNKGT AVAICRRIGIFGQDEDVTSKAFTGREFDELNPSAQRDACLNARCFARVEPSHKSKIVEFLQSFDEITAMTGDGVNDAPALKKAEIGIAMG SGTAVAKTASEMVLADDNFSTIVAAVEEGRAIYNNMKQFIRYLISSNVGEVVCIFLTAALGFPEALIPVQLLWVNLVTDGLPATALGFNP PDLDIMNKPPRNPKEPLISGWLFFRYLAIGCYVGAATVGAAAWWFIAADGGPRVSFYQLSHFLQCKEDNPDFEGVDCAIFESPYPMTMAL SVLVTIEMCNALNSLSENQSLLRMPPWENIWLVGSICLSMSLHFLILYVEPLPLIFQITPLNVTQWLMVLKISLPVILMDETLKFVARNY |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| ATP2A2 (go to UniProt):P16615 |
| 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 |
| P16615 | Topological domain | 111 | 253 | Note=Cytoplasmic;Ontology_term=ECO:0000305;evidence=ECO:0000305 | Type=Deletion;Start=155;End=181 |
| P16615 | Topological domain | 985 | 1042 | Note=Cytoplasmic;Ontology_term=ECO:0000305;evidence=ECO:0000305 | Type=Substitution;Start=994;End=1042 |
| P16615 | Topological domain | 985 | 1042 | Note=Cytoplasmic;Ontology_term=ECO:0000305;evidence=ECO:0000305 | Type=Substitution;Start=994;End=1042 |
| P16615 | Topological domain | 985 | 1042 | Note=Cytoplasmic;Ontology_term=ECO:0000305;evidence=ECO:0000305 | Type=Substitution;Start=994;End=1042 |
| P16615 | Region | 788 | 1042 | Note=Interaction with TMEM64 and PDIA3;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:O55143 | Type=Substitution;Start=994;End=1042 |
| P16615 | Region | 788 | 1042 | Note=Interaction with TMEM64 and PDIA3;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:O55143 | Type=Substitution;Start=994;End=1042 |
| P16615 | Region | 788 | 1042 | Note=Interaction with TMEM64 and PDIA3;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:O55143 | Type=Substitution;Start=994;End=1042 |
Gene Isoform Structures and Expression Levels for ATP2A2 |
| Gene structures of our canonical and alternative spliced genes of ATP2A2 * 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 P16615-1 |
| 3D view using mol* of P16615-2 |
| 3D view using mol* of P16615-3 |
| 3D view using mol* of P16615-4 |
| 3D view using mol* of P16615-5 |
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 P16615-1 |
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| pLDDT distribution across the protein length of P16615-2 |
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| pLDDT distribution across the protein length of P16615-3 |
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| pLDDT distribution across the protein length of P16615-4 |
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| pLDDT distribution across the protein length of P16615-5 |
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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 P16615-1 |
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| Ramachandran plot of P16615-2 |
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| Ramachandran plot of P16615-4 |
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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 |
| P16615-1 | 1.052 | 179 | 1.093 | 596.477 | 0.621 | 0.724 | 0.934 | 0.622 | 0.864 | 0.72 | 1.994 | 72,74,75,76,78,79,83,86,87,89,90,91,293,294,297,77 7,782,783,784,785,787,788,789,848,851,852,855,869, 872,873,875,887,890,891,893,895,896,953,954,955,95 7,958,959,960 |
| P16615-2 | 1.109 | 178 | 1.164 | 644.497 | 0.539 | 0.775 | 0.942 | 1.303 | 0.739 | 1.763 | 2.66 | 55,56,59,60,61,62,65,96,97,98,100,101,102,104,105, 108,246,249,250,253,254,256,257,258,307,308,309,31 0,311,312,313,315,316,319,336,337,760,796,827 |
| P16615-3 | 1.06 | 400 | 1.094 | 1301.342 | 0.543 | 0.75 | 0.932 | 0.829 | 0.909 | 0.913 | 1.447 | 44,47,52,55,56,57,59,60,61,62,65,96,97,98,100,101, 102,104,105,107,108,109,110,111,112,113,114,115,11 6,239,240,242,243,244,245,246,247,248,249,250,251, 253,254,256,257,258,307,308,309,311,312,313,314,31 5,316,319,320,334,335,336,337,338,691,711,712,713, 714,728,729,730,731,760,764,796,800,801,804,827 |
| P16615-4 | 1.034 | 445 | 1.062 | 1392.237 | 0.551 | 0.727 | 0.909 | 0.63 | 0.964 | 0.654 | 1.783 | 43,44,46,47,48,49,52,55,56,59,60,61,62,65,97,98,10 1,102,104,105,107,108,109,110,111,112,113,114,115, 116,117,120,215,216,217,218,219,220,221,222,223,22 4,225,226,227,229,230,231,280,281,282,284,285,288, 289,292,293,296,307,308,309,310,311,664,667,668,66 9,684,685,686,687,701,702,703,704,733,737,796,797, 800 |
| P16615-5 | 1.095 | 211 | 1.173 | 770.035 | 0.622 | 0.711 | 0.85 | 1.337 | 0.593 | 2.254 | 3.575 | 55,56,57,59,60,61,62,65,96,97,98,100,101,102,104,1 05,108,246,249,250,253,254,256,257,258,307,308,309 ,311,312,313,314,315,316,317,319,336,337,796,800,8 01,804,805,808,931,935,938 |
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 P16615-1_P16615-1_6lly_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P16615-1_6lly_A_P16615-2.pdb |
| 3D view using mol* of P16615-1_6lly_A_P16615-3.pdb |
| 3D view using mol* of P16615-1_6lly_A_P16615-4.pdb |
| 3D view using mol* of P16615-1_6lly_A_P16615-5.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P16615-1_P16615-2.pdb |
| 3D view using mol* of P16615-1_P16615-3.pdb |
| 3D view using mol* of P16615-1_P16615-4.pdb |
| 3D view using mol* of P16615-1_P16615-5.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P16615-1_vs_P16615-2.png |
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| ./stats/secondary_structure/figure/P16615-1_vs_P16615-3.png |
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| ./stats/secondary_structure/figure/P16615-1_vs_P16615-4.png |
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| ./stats/secondary_structure/figure/P16615-1_vs_P16615-5.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P16615-1_vs_P16615-2.png |
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| ./stats/relative_asa/P16615-1_vs_P16615-3.png |
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| ./stats/relative_asa/P16615-1_vs_P16615-4.png |
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| ./stats/relative_asa/P16615-1_vs_P16615-5.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| P16615 | Region | 788 | 1042 | Note=Interaction with TMEM64 and PDIA3;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:O55143 | Type=Substitution;Start=994;End=1042 |
| P16615 | Region | 788 | 1042 | Note=Interaction with TMEM64 and PDIA3;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:O55143 | Type=Substitution;Start=994;End=1042 |
| P16615 | Region | 788 | 1042 | Note=Interaction with TMEM64 and PDIA3;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:O55143 | Type=Substitution;Start=994;End=1042 |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to ATP2A2 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P16615 | ATP2A2 | DB06157 | Istaroxime | investigational |
Related Diseases to ATP2A2 |
| Previous studies relating to the alternative splicing of ATP2A2 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| ATP2A2 | 12925205 | Mutations in the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase isoform cause Darier's disease. | Darier's disease is an autosomal dominantly inherited skin disorder, characterized by loss of adhesion between epidermal cells and abnormal keratinization. ATP2A2 encoding the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA)2 has been identified as the defective gene in Darier's disease. All mutations previously reported occur in the region of ATP2A2 encoding both SERCA2a and SERCA2b isoforms. These isoforms result from alternative splicing of exon 20, with SERCA2b being the major isoform expressed in the epidermis. In this report, we studied a family affected with Darier's disease and identified a deletion (2993delTG) in a region of exon 20 of ATP2A2, which is specific for SERCA2b. This heterozygous mutation predicts a frameshift with a premature termination codon (PTC+32aa) in the eleventh transmembrane domain of SERCA2b. It segregates with the disease phenotype in the family members tested, and functional analysis shows a drastic reduction of the expression of the mutated protein in comparison with the wild-type SERCA2b. Our result suggests that the mutated allele causes the disease phenotype through loss of function of SERCA2b isoform. This finding indicates that SERCA2b plays a key role in the biology of the epidermis, and its defects are sufficient to cause Darier's disease. | D007644 | Darier Disease |
| ATP2A2 | 15972723 | Altered mRNA splicing of the skeletal muscle ryanodine receptor and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase in myotonic dystrophy type 1. | Myotonic dystrophy type 1 (DM1) is a debilitating multisystemic disorder caused by a CTG repeat expansion in the DMPK gene. Aberrant splicing of several genes has been reported to contribute to some symptoms of DM1, but the cause of muscle weakness in DM1 and elevated Ca2+ concentrations in cultured DM muscle cells is unknown. Here, we investigated the alternative splicing of mRNAs of two major proteins of the sarcoplasmic reticulum, the ryanodine receptor 1 (RyR1) and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) 1 or 2. The fetal variants, ASI(-) of RyR1 which lacks residue 3481-3485, and SERCA1b which differs at the C-terminal were significantly increased in skeletal muscles from DM1 patients and the transgenic mouse model of DM1 (HSA(LR)). In addition, a novel variant of SERCA2 was significantly decreased in DM1 patients. The total amount of mRNA for RyR1, SERCA1 and SERCA2 in DM1 and the expression levels of their proteins in HSA(LR) mice were not significantly different. However, heterologous expression of ASI(-) in cultured cells showed decreased affinity for [3H]ryanodine but similar Ca2+ dependency, and decreased channel activity in single-channel recording when compared with wild-type (WT) RyR1. In support of this, RyR1-knockout myotubes expressing ASI(-) exhibited a decreased incidence of Ca2+ oscillations during caffeine exposure compared with that observed for myotubes expressing WT-RyR1. We suggest that aberrant splicing of RyR1 and SERCA1 mRNAs might contribute to impaired Ca2+ homeostasis in DM1 muscle. | D009223 | Myotonic Dystrophy |
| ATP2A2 | 24711643 | Identifying biological pathways that underlie primordial short stature using network analysis. | Mutations in CUL7, OBSL1 and CCDC8, leading to disordered ubiquitination, cause one of the commonest primordial growth disorders, 3-M syndrome. This condition is associated with i) abnormal p53 function, ii) GH and/or IGF1 resistance, which may relate to failure to recycle signalling molecules, and iii) cellular IGF2 deficiency. However the exact molecular mechanisms that may link these abnormalities generating growth restriction remain undefined. In this study, we have used immunoprecipitation/mass spectrometry and transcriptomic studies to generate a 3-M 'interactome', to define key cellular pathways and biological functions associated with growth failure seen in 3-M. We identified 189 proteins which interacted with CUL7, OBSL1 and CCDC8, from which a network including 176 of these proteins was generated. To strengthen the association to 3-M syndrome, these proteins were compared with an inferred network generated from the genes that were differentially expressed in 3-M fibroblasts compared with controls. This resulted in a final 3-M network of 131 proteins, with the most significant biological pathway within the network being mRNA splicing/processing. We have shown using an exogenous insulin receptor (INSR) minigene system that alternative splicing of exon 11 is significantly changed in HEK293 cells with altered expression of CUL7, OBSL1 and CCDC8 and in 3-M fibroblasts. The net result is a reduction in the expression of the mitogenic INSR isoform in 3-M syndrome. From these preliminary data, we hypothesise that disordered ubiquitination could result in aberrant mRNA splicing in 3-M; however, further investigation is required to determine whether this contributes to growth failure. | D004392 | Dwarfism |
| ATP2A2 | 24711643 | Identifying biological pathways that underlie primordial short stature using network analysis. | Mutations in CUL7, OBSL1 and CCDC8, leading to disordered ubiquitination, cause one of the commonest primordial growth disorders, 3-M syndrome. This condition is associated with i) abnormal p53 function, ii) GH and/or IGF1 resistance, which may relate to failure to recycle signalling molecules, and iii) cellular IGF2 deficiency. However the exact molecular mechanisms that may link these abnormalities generating growth restriction remain undefined. In this study, we have used immunoprecipitation/mass spectrometry and transcriptomic studies to generate a 3-M 'interactome', to define key cellular pathways and biological functions associated with growth failure seen in 3-M. We identified 189 proteins which interacted with CUL7, OBSL1 and CCDC8, from which a network including 176 of these proteins was generated. To strengthen the association to 3-M syndrome, these proteins were compared with an inferred network generated from the genes that were differentially expressed in 3-M fibroblasts compared with controls. This resulted in a final 3-M network of 131 proteins, with the most significant biological pathway within the network being mRNA splicing/processing. We have shown using an exogenous insulin receptor (INSR) minigene system that alternative splicing of exon 11 is significantly changed in HEK293 cells with altered expression of CUL7, OBSL1 and CCDC8 and in 3-M fibroblasts. The net result is a reduction in the expression of the mitogenic INSR isoform in 3-M syndrome. From these preliminary data, we hypothesise that disordered ubiquitination could result in aberrant mRNA splicing in 3-M; however, further investigation is required to determine whether this contributes to growth failure. | D006130 | Growth Disorders |
| ATP2A2 | 24711643 | Identifying biological pathways that underlie primordial short stature using network analysis. | Mutations in CUL7, OBSL1 and CCDC8, leading to disordered ubiquitination, cause one of the commonest primordial growth disorders, 3-M syndrome. This condition is associated with i) abnormal p53 function, ii) GH and/or IGF1 resistance, which may relate to failure to recycle signalling molecules, and iii) cellular IGF2 deficiency. However the exact molecular mechanisms that may link these abnormalities generating growth restriction remain undefined. In this study, we have used immunoprecipitation/mass spectrometry and transcriptomic studies to generate a 3-M 'interactome', to define key cellular pathways and biological functions associated with growth failure seen in 3-M. We identified 189 proteins which interacted with CUL7, OBSL1 and CCDC8, from which a network including 176 of these proteins was generated. To strengthen the association to 3-M syndrome, these proteins were compared with an inferred network generated from the genes that were differentially expressed in 3-M fibroblasts compared with controls. This resulted in a final 3-M network of 131 proteins, with the most significant biological pathway within the network being mRNA splicing/processing. We have shown using an exogenous insulin receptor (INSR) minigene system that alternative splicing of exon 11 is significantly changed in HEK293 cells with altered expression of CUL7, OBSL1 and CCDC8 and in 3-M fibroblasts. The net result is a reduction in the expression of the mitogenic INSR isoform in 3-M syndrome. From these preliminary data, we hypothesise that disordered ubiquitination could result in aberrant mRNA splicing in 3-M; however, further investigation is required to determine whether this contributes to growth failure. | D009123 | Muscle Hypotonia |
Clinically important variants in ATP2A2 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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