Protein:RUNX2 |
Protein Summary |
 Gene summary |
| Gene name: RUNX2 | ASpdb.0 ID: 860 | Gene | Gene symbol | RUNX2 | Gene ID | 860 |
| Gene name | RUNX family transcription factor 2 |
| Synonyms | AML3|CBF-alpha-1|CBFA1|CCD|CCD1|CLCD|OSF-2|OSF2|PEA2aA|PEBP2aA |
| Cytomap | 6p21.1 |
| Type of gene | protein-coding |
| Description | runt-related transcription factor 2PEA2-alpha APEBP2-alpha ASL3-3 enhancer factor 1 alpha A subunitSL3/AKV core-binding factor alpha A subunitacute myeloid leukemia 3 proteincore-binding factor, runt domain, alpha subunit 1oncogene AML-3osteoblast |
| Modification date | 20240407 |
| UniProtAcc | Q13950 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | RUNX2 | GO:0005634 | nucleus | 28505335|28738062 |
| Gene | RUNX2 | GO:0005654 | nucleoplasm | - |
| Gene | RUNX2 | GO:0045892 | negative regulation of DNA-templated transcription | 11965546 |
| Gene | RUNX2 | GO:0045893 | positive regulation of DNA-templated transcription | 11965546 |
| Gene | RUNX2 | GO:1990837 | sequence-specific double-stranded DNA binding | 28473536 |
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 |
| Q13950-1 | Q13950-1_6vg8_D.pdb | 6VG8 | X-ray | 4.31 | D | 111 | 230 |
| 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 |
| Q13950 | RUNX2 | Q13950-1 | Q13950-2 | 521 | 507 | 1 | 19 | Substitution | MASNSLFSTVTPCQQNFFW | MRIPV | 1 | 5 |
| Q13950 | RUNX2 | Q13950-1 | Q13950-3 | 521 | 499 | 341 | 362 | Deletion | none | none | 340 | 340 |
| Multiple sequence alignment of our canonical and alternatively spliced RUNX2 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of RUNX2 |
| UniProt-id | ENSG | ENST | ENSP |
| Q13950-1 | ENSG00000124813.23 | ENST00000371438.5 | ENSP00000360493.1 |
| Q13950-1 | ENSG00000124813.23 | ENST00000647337.2 | ENSP00000495497.1 |
| Q13950-2 | ENSG00000124813.23 | ENST00000359524.7 | ENSP00000352514.5 |
| Q13950-3 | ENSG00000124813.23 | ENST00000371432.7 | ENSP00000360486.4 |
| Q13950-3 | ENSG00000124813.23 | ENST00000371436.10 | ENSP00000360491.6 |
| UniProt-id | NM ID | NP ID |
| Q13950-1 | NM_001024630.3 | NP_001019801.3 |
| Q13950-3 | NM_001015051.3 | NP_001015051.3 |
| Amino acid sequences of our canonical and alternatively spliced RUNX2 |
| accession_id | Protein sequence |
| Q13950-1 | MASNSLFSTVTPCQQNFFWDPSTSRRFSPPSSSLQPGKMSDVSPVVAAQQQQQQQQQQQQQQQQQQQQQQQEAAAAAAAAAAAAAAAAAV PRLRPPHDNRTMVEIIADHPAELVRTDSPNFLCSVLPSHWRCNKTLPVAFKVVALGEVPDGTVVTVMAGNDENYSAELRNASAVMKNQVA RFNDLRFVGRSGRGKSFTLTITVFTNPPQVATYHRAIKVTVDGPREPRRHRQKLDDSKPSLFSDRLSDLGRIPHPSMRVGVPPQNPRPSL NSAPSPFNPQGQSQITDPRQAQSSPPWSYDQSYPSYLSQMTSPSIHSTTPLSSTRGTGLPAITDVPRRISDDDTATSDFCLWPSTLSKKS QAGASELGPFSDPRQFPSISSLTESRFSNPRMHYPATFTYTPPVTSGMSLGMSATTHYHTYLPPPYPGSSQSQSGPFQTSSTPYLYYGTS |
| Q13950-2 | MRIPVDPSTSRRFSPPSSSLQPGKMSDVSPVVAAQQQQQQQQQQQQQQQQQQQQQQQEAAAAAAAAAAAAAAAAAVPRLRPPHDNRTMVE IIADHPAELVRTDSPNFLCSVLPSHWRCNKTLPVAFKVVALGEVPDGTVVTVMAGNDENYSAELRNASAVMKNQVARFNDLRFVGRSGRG KSFTLTITVFTNPPQVATYHRAIKVTVDGPREPRRHRQKLDDSKPSLFSDRLSDLGRIPHPSMRVGVPPQNPRPSLNSAPSPFNPQGQSQ ITDPRQAQSSPPWSYDQSYPSYLSQMTSPSIHSTTPLSSTRGTGLPAITDVPRRISDDDTATSDFCLWPSTLSKKSQAGASELGPFSDPR QFPSISSLTESRFSNPRMHYPATFTYTPPVTSGMSLGMSATTHYHTYLPPPYPGSSQSQSGPFQTSSTPYLYYGTSSGSYQFPMVPGGDR |
| Q13950-3 | MASNSLFSTVTPCQQNFFWDPSTSRRFSPPSSSLQPGKMSDVSPVVAAQQQQQQQQQQQQQQQQQQQQQQQEAAAAAAAAAAAAAAAAAV PRLRPPHDNRTMVEIIADHPAELVRTDSPNFLCSVLPSHWRCNKTLPVAFKVVALGEVPDGTVVTVMAGNDENYSAELRNASAVMKNQVA RFNDLRFVGRSGRGKSFTLTITVFTNPPQVATYHRAIKVTVDGPREPRRHRQKLDDSKPSLFSDRLSDLGRIPHPSMRVGVPPQNPRPSL NSAPSPFNPQGQSQITDPRQAQSSPPWSYDQSYPSYLSQMTSPSIHSTTPLSSTRGTGLPAITDVPRRISGASELGPFSDPRQFPSISSL TESRFSNPRMHYPATFTYTPPVTSGMSLGMSATTHYHTYLPPPYPGSSQSQSGPFQTSSTPYLYYGTSSGSYQFPMVPGGDRSPSRMLPP |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| RUNX2 (go to UniProt):Q13950 |
| 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 |
| Q13950 | Region | 18 | 59 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Substitution;Start=1;End=19 |
| Q13950 | Region | 336 | 439 | Note=Interaction with KAT6A;Ontology_term=ECO:0000250;evidence=ECO:0000250 | Type=Deletion;Start=341;End=362 |
Gene Isoform Structures and Expression Levels for RUNX2 |
| Gene structures of our canonical and alternative spliced genes of RUNX2 * 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 Q13950-1 |
| 3D view using mol* of Q13950-2 |
| 3D view using mol* of Q13950-3 |
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 Q13950-1 |
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| pLDDT distribution across the protein length of Q13950-2 |
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| pLDDT distribution across the protein length of Q13950-3 |
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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 Q13950-1 |
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| Ramachandran plot of Q13950-2 |
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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 |
| Q13950-1 | 0.856 | 82 | 0.871 | 216.776 | 0.708 | 0.572 | 0.732 | 0.281 | 0.991 | 0.283 | 0.628 | 83,86,87,96,97,98,99,100,101,102,105,120,143,144,1 45,146,147,148,149,150,176,177,178,179 |
| Q13950-2 | 0.994 | 279 | 1.047 | 658.903 | 0.577 | 0.626 | 0.856 | 0.762 | 0.822 | 0.927 | 0.909 | 65,66,68,69,70,72,73,74,76,77,78,79,80,82,83,84,85 ,86,91,95,98,99,125,127,129,130,131,132,133,134,13 5,136,137,158,159,160,161,162,163,164,165,166,167, 168,169,170 |
| Q13950-3 | 0.983 | 111 | 1.011 | 268.569 | 0.498 | 0.66 | 0.933 | 0.593 | 0.997 | 0.595 | 0.795 | 94,95,96,97,98,99,100,105,108,109,112,113,141,143, 144,145,146,147,148,149,150,175,176,177,178,179 |
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 Q13950-1_Q13950-1_6vg8_D.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of Q13950-1_6vg8_D_Q13950-2.pdb |
| 3D view using mol* of Q13950-1_6vg8_D_Q13950-3.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of Q13950-1_Q13950-2.pdb |
| 3D view using mol* of Q13950-1_Q13950-3.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/Q13950-1_vs_Q13950-2.png |
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| ./stats/secondary_structure/figure/Q13950-1_vs_Q13950-3.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/Q13950-1_vs_Q13950-2.png |
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| ./stats/relative_asa/Q13950-1_vs_Q13950-3.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Q13950 | Region | 336 | 439 | Note=Interaction with KAT6A;Ontology_term=ECO:0000250;evidence=ECO:0000250 | Type=Deletion;Start=341;End=362 |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to RUNX2 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
Related Diseases to RUNX2 |
| Previous studies relating to the alternative splicing of RUNX2 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| RUNX2 | 15225881 | Conservation and expression of an alternative 3' exon of Runx2 encoding a novel proline-rich C-terminal domain. | The Runx2 (Cbfa1, Aml3, PEBP2alphaA) gene plays an essential role in bone development and is one of a three-member family of closely related genes that encode the alpha-chain DNA binding components of the heterodimeric core binding factor complex. While all three mammalian Runx genes share a complex dual promoter structure (P1, P2) and display alternative splicing, a distinctive feature of Runx2 is the potential to encode larger isoforms in which the C-terminal domain encoded by the standard 3' terminal exon (exon 6) is replaced by an extended 200-201 amino acid C-terminal sequence including an extensive proline-rich domain and a C-terminal amphipathic helix. We report that the novel exon that gives rise to these variants (exon 6.1) is located over 100 kb downstream of exon 6 in the mouse, rat and human genomes. Exon 6.1 spans a CpG-rich island, and human/rodent conservation is evident through the coding sequence and the 3' untranslated region (UTR). Reverse transcriptase polymerase chain reaction (RT-PCR) and blot hybridisation analyses reveal that exon 6.1 is utilised at low levels in all mouse tissues and cell lines that express Runx2, regardless of which promoter is active, giving Runx2 the potential to encode more than 12 distinct isoforms. RT-PCR analysis of human RUNX2 exon 6.1 expression shows that utilisation of this exon is also conserved. In vitro transcription/translation of cDNAs encoding several exon 6.1 isoforms reveals that the novel Runx proteins are able to bind specifically to canonical Runx DNA target sequences. Antibodies raised to the unique C-terminal domain were shown to be reactive by immunoprecipitation and immunoblot assay, and were used in confocal immunofluorescence microscopy to reveal low level cytoplasmic staining in osteosarcoma and lymphoma cells that express high levels of Runx2 mRNA. However, reactive protein could not be detected in immunoblots of extracts from either cell type, suggesting that these proteins are unstable in lymphoid and osteosarcoma cells. In conclusion, the conservation and widespread utilisation of Runx2 exon 6.1 suggest that its encoded isoforms play an as yet undetermined role in mammalian development. | D008223 | Lymphoma |
| RUNX2 | 15225881 | Conservation and expression of an alternative 3' exon of Runx2 encoding a novel proline-rich C-terminal domain. | The Runx2 (Cbfa1, Aml3, PEBP2alphaA) gene plays an essential role in bone development and is one of a three-member family of closely related genes that encode the alpha-chain DNA binding components of the heterodimeric core binding factor complex. While all three mammalian Runx genes share a complex dual promoter structure (P1, P2) and display alternative splicing, a distinctive feature of Runx2 is the potential to encode larger isoforms in which the C-terminal domain encoded by the standard 3' terminal exon (exon 6) is replaced by an extended 200-201 amino acid C-terminal sequence including an extensive proline-rich domain and a C-terminal amphipathic helix. We report that the novel exon that gives rise to these variants (exon 6.1) is located over 100 kb downstream of exon 6 in the mouse, rat and human genomes. Exon 6.1 spans a CpG-rich island, and human/rodent conservation is evident through the coding sequence and the 3' untranslated region (UTR). Reverse transcriptase polymerase chain reaction (RT-PCR) and blot hybridisation analyses reveal that exon 6.1 is utilised at low levels in all mouse tissues and cell lines that express Runx2, regardless of which promoter is active, giving Runx2 the potential to encode more than 12 distinct isoforms. RT-PCR analysis of human RUNX2 exon 6.1 expression shows that utilisation of this exon is also conserved. In vitro transcription/translation of cDNAs encoding several exon 6.1 isoforms reveals that the novel Runx proteins are able to bind specifically to canonical Runx DNA target sequences. Antibodies raised to the unique C-terminal domain were shown to be reactive by immunoprecipitation and immunoblot assay, and were used in confocal immunofluorescence microscopy to reveal low level cytoplasmic staining in osteosarcoma and lymphoma cells that express high levels of Runx2 mRNA. However, reactive protein could not be detected in immunoblots of extracts from either cell type, suggesting that these proteins are unstable in lymphoid and osteosarcoma cells. In conclusion, the conservation and widespread utilisation of Runx2 exon 6.1 suggest that its encoded isoforms play an as yet undetermined role in mammalian development. | D012516 | Osteosarcoma |
Clinically important variants in RUNX2 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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