Protein:MCL1 |
Protein Summary |
 Gene summary |
| Gene name: MCL1 | ASpdb.0 ID: 4170 | Gene | Gene symbol | MCL1 | Gene ID | 4170 |
| Gene name | MCL1 apoptosis regulator, BCL2 family member |
| Synonyms | BCL2L3|EAT|MCL1-ES|MCL1L|MCL1S|Mcl-1|TM|bcl2-L-3|mcl1/EAT |
| Cytomap | 1q21.2 |
| Type of gene | protein-coding |
| Description | induced myeloid leukemia cell differentiation protein Mcl-1BCL2 family apoptosis regulatorMCL1, BCL2 family apoptosis regulatorbcl-2-like protein 3bcl-2-related protein EAT/mcl1myeloid cell leukemia 1myeloid cell leukemia ESmyeloid cell leukemia se |
| Modification date | 20240411 |
| UniProtAcc | Q07820 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | MCL1 | GO:0005634 | nucleus | 20467439 |
| Gene | MCL1 | GO:0005739 | mitochondrion | 7896880 |
| Gene | MCL1 | GO:0016020 | membrane | 7896880 |
| Gene | MCL1 | GO:0034097 | response to cytokine | 9184696 |
| Gene | MCL1 | GO:0043065 | positive regulation of apoptotic process | 21132008 |
| Gene | MCL1 | GO:0043066 | negative regulation of apoptotic process | 20041405 |
| Gene | MCL1 | GO:0097136 | Bcl-2 family protein complex | 21199865 |
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 |
| Q07820-1 | Q07820-1_6oqd_A.pdb | 6OQD | X-ray | 1.48 | A | 171 | 326 |
| 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 |
| Q07820 | MCL1 | Q07820-1 | Q07820-2 | 350 | 271 | 231 | 271 | Substitution | MLRKLDIKNEDDVKSLSRVMIHVFSDGVTNWGRIVTLISFG | WVCGVLPCRGPRRWHQECAAGFCRCCWSRSWFGISNKIALL | 231 | 271 |
| Q07820 | MCL1 | Q07820-1 | Q07820-2 | 350 | 271 | 272 | 350 | Deletion | none | none | 271 | 271 |
| Multiple sequence alignment of our canonical and alternatively spliced MCL1 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of MCL1 |
| UniProt-id | ENSG | ENST | ENSP |
| Q07820-1 | ENSG00000143384.14 | ENST00000369026.3 | ENSP00000358022.2 |
| Q07820-1 | ENSG00000143384.14 | ENST00000678770.1 | ENSP00000502859.1 |
| Q07820-2 | ENSG00000143384.14 | ENST00000307940.3 | ENSP00000309973.3 |
| UniProt-id | NM ID | NP ID |
| Q07820-1 | NM_021960.4 | NP_068779.1 |
| Q07820-2 | NM_182763.2 | NP_877495.1 |
| Amino acid sequences of our canonical and alternatively spliced MCL1 |
| accession_id | Protein sequence |
| Q07820-1 | MFGLKRNAVIGLNLYCGGAGLGAGSGGATRPGGRLLATEKEASARREIGGGEAGAVIGGSAGASPPSTLTPDSRRVARPPPIGAEVPDVT ATPARLLFFAPTRRAAPLEEMEAPAADAIMSPEEELDGYEPEPLGKRPAVLPLLELVGESGNNTSTDGSLPSTPPPAEEEEDELYRQSLE IISRYLREQATGAKDTKPMGRSGATSRKALETLRRVGDGVQRNHETAFQGMLRKLDIKNEDDVKSLSRVMIHVFSDGVTNWGRIVTLISF |
| Q07820-2 | MFGLKRNAVIGLNLYCGGAGLGAGSGGATRPGGRLLATEKEASARREIGGGEAGAVIGGSAGASPPSTLTPDSRRVARPPPIGAEVPDVT ATPARLLFFAPTRRAAPLEEMEAPAADAIMSPEEELDGYEPEPLGKRPAVLPLLELVGESGNNTSTDGSLPSTPPPAEEEEDELYRQSLE IISRYLREQATGAKDTKPMGRSGATSRKALETLRRVGDGVQRNHETAFQGWVCGVLPCRGPRRWHQECAAGFCRCCWSRSWFGISNKIAL |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| MCL1 (go to UniProt):Q07820 |
| 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 |
| Q07820 | Transmembrane | 328 | 348 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=272;End=350 |
| Q07820 | Motif | 252 | 272 | Note=BH1 | Type=Substitution;Start=231;End=271 |
| Q07820 | Motif | 252 | 272 | Note=BH1 | Type=Deletion;Start=272;End=350 |
| Q07820 | Motif | 304 | 319 | Note=BH2 | Type=Deletion;Start=272;End=350 |
Gene Isoform Structures and Expression Levels for MCL1 |
| Gene structures of our canonical and alternative spliced genes of MCL1 * 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 Q07820-1 |
| 3D view using mol* of Q07820-2 |
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 Q07820-1 |
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| pLDDT distribution across the protein length of Q07820-2 |
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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 Q07820-1 |
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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 |
| Q07820-1 | 1.063 | 92 | 1.1 | 210.945 | 0.468 | 0.771 | 1.042 | 1.115 | 0.81 | 1.377 | 1.356 | 11,12,13,14,252,253,255,256,258,260,262,263,266,26 7,331,334,335,337,338,339,341 |
| Q07820-2 | 1.096 | 309 | 1.182 | 758.716 | 0.551 | 0.698 | 0.926 | 1.509 | 0.543 | 2.782 | 1.185 | 14,186,188,189,192,194,214,217,218,220,221,222,224 ,225,227,228,229,231,232,233,236,237,238,239,240,2 44,245,247,248,249,251,252,253,254,255,256,257,259 ,260,261,264,265,268 |
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 Q07820-1_Q07820-1_6oqd_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 Q07820-1_6oqd_A_Q07820-2.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of Q07820-1_Q07820-2.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/Q07820-1_vs_Q07820-2.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/Q07820-1_vs_Q07820-2.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 MCL1 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
Related Diseases to MCL1 |
| Previous studies relating to the alternative splicing of MCL1 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| MCL1 | 19369967 | Modification of alternative splicing of Mcl-1 pre-mRNA using antisense morpholino oligonucleotides induces apoptosis in basal cell carcinoma cells. | Myeloid cell leukemia-1 (Mcl-1, Mcl-1L) is an anti-apoptotic protein of the Bcl-2 family that acts as a critical molecule in apoptosis control. Mcl-1 pre-mRNA can undergo alternative splicing to yield the short isoform, Mcl-1S, which resembles BH3-only pro-apoptotic proteins and induces apoptosis. Overexpression of Mcl-1 may play a role in various human tumors, and Mcl-1 may serve as a target in cancer therapy. In this study, we found an imbalance between the expression levels of Mcl-1L and Mcl-1S in the skin basal cell carcinoma (BCC) cell line when compared with primary keratinocytes. We showed that overexpression of Mcl-1S induces apoptosis in BCC cells. Finally, we showed that Mcl-1 antisense morpholino oligonucleotides (AMOs) can specifically target Mcl-1 pre-mRNA and shift the splicing pattern from Mcl-1L to Mcl-1S mRNA and protein. This shift increases the level of pro-apoptotic Mcl-1S and reduces the level of anti-apoptotic Mcl-1L, which induces apoptosis in BCC cells and AGS cells, a human gastric adenocarcinoma epithelial cell line. Thus, this report provides a strategy for cancer therapy in which AMOs change the alternative splicing pattern of Mcl-1 pre-mRNA and thereby induce apoptosis. | D000230 | Adenocarcinoma |
| MCL1 | 19369967 | Modification of alternative splicing of Mcl-1 pre-mRNA using antisense morpholino oligonucleotides induces apoptosis in basal cell carcinoma cells. | Myeloid cell leukemia-1 (Mcl-1, Mcl-1L) is an anti-apoptotic protein of the Bcl-2 family that acts as a critical molecule in apoptosis control. Mcl-1 pre-mRNA can undergo alternative splicing to yield the short isoform, Mcl-1S, which resembles BH3-only pro-apoptotic proteins and induces apoptosis. Overexpression of Mcl-1 may play a role in various human tumors, and Mcl-1 may serve as a target in cancer therapy. In this study, we found an imbalance between the expression levels of Mcl-1L and Mcl-1S in the skin basal cell carcinoma (BCC) cell line when compared with primary keratinocytes. We showed that overexpression of Mcl-1S induces apoptosis in BCC cells. Finally, we showed that Mcl-1 antisense morpholino oligonucleotides (AMOs) can specifically target Mcl-1 pre-mRNA and shift the splicing pattern from Mcl-1L to Mcl-1S mRNA and protein. This shift increases the level of pro-apoptotic Mcl-1S and reduces the level of anti-apoptotic Mcl-1L, which induces apoptosis in BCC cells and AGS cells, a human gastric adenocarcinoma epithelial cell line. Thus, this report provides a strategy for cancer therapy in which AMOs change the alternative splicing pattern of Mcl-1 pre-mRNA and thereby induce apoptosis. | D002280 | Carcinoma, Basal Cell |
| MCL1 | 19369967 | Modification of alternative splicing of Mcl-1 pre-mRNA using antisense morpholino oligonucleotides induces apoptosis in basal cell carcinoma cells. | Myeloid cell leukemia-1 (Mcl-1, Mcl-1L) is an anti-apoptotic protein of the Bcl-2 family that acts as a critical molecule in apoptosis control. Mcl-1 pre-mRNA can undergo alternative splicing to yield the short isoform, Mcl-1S, which resembles BH3-only pro-apoptotic proteins and induces apoptosis. Overexpression of Mcl-1 may play a role in various human tumors, and Mcl-1 may serve as a target in cancer therapy. In this study, we found an imbalance between the expression levels of Mcl-1L and Mcl-1S in the skin basal cell carcinoma (BCC) cell line when compared with primary keratinocytes. We showed that overexpression of Mcl-1S induces apoptosis in BCC cells. Finally, we showed that Mcl-1 antisense morpholino oligonucleotides (AMOs) can specifically target Mcl-1 pre-mRNA and shift the splicing pattern from Mcl-1L to Mcl-1S mRNA and protein. This shift increases the level of pro-apoptotic Mcl-1S and reduces the level of anti-apoptotic Mcl-1L, which induces apoptosis in BCC cells and AGS cells, a human gastric adenocarcinoma epithelial cell line. Thus, this report provides a strategy for cancer therapy in which AMOs change the alternative splicing pattern of Mcl-1 pre-mRNA and thereby induce apoptosis. | D012878 | Skin Neoplasms |
| MCL1 | 19369967 | Modification of alternative splicing of Mcl-1 pre-mRNA using antisense morpholino oligonucleotides induces apoptosis in basal cell carcinoma cells. | Myeloid cell leukemia-1 (Mcl-1, Mcl-1L) is an anti-apoptotic protein of the Bcl-2 family that acts as a critical molecule in apoptosis control. Mcl-1 pre-mRNA can undergo alternative splicing to yield the short isoform, Mcl-1S, which resembles BH3-only pro-apoptotic proteins and induces apoptosis. Overexpression of Mcl-1 may play a role in various human tumors, and Mcl-1 may serve as a target in cancer therapy. In this study, we found an imbalance between the expression levels of Mcl-1L and Mcl-1S in the skin basal cell carcinoma (BCC) cell line when compared with primary keratinocytes. We showed that overexpression of Mcl-1S induces apoptosis in BCC cells. Finally, we showed that Mcl-1 antisense morpholino oligonucleotides (AMOs) can specifically target Mcl-1 pre-mRNA and shift the splicing pattern from Mcl-1L to Mcl-1S mRNA and protein. This shift increases the level of pro-apoptotic Mcl-1S and reduces the level of anti-apoptotic Mcl-1L, which induces apoptosis in BCC cells and AGS cells, a human gastric adenocarcinoma epithelial cell line. Thus, this report provides a strategy for cancer therapy in which AMOs change the alternative splicing pattern of Mcl-1 pre-mRNA and thereby induce apoptosis. | D013274 | Stomach Neoplasms |
Clinically important variants in MCL1 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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