Protein:AFF4 |
Protein Summary |
 Gene summary |
| Gene name: AFF4 | ASpdb.0 ID: 27125 | Gene | Gene symbol | AFF4 | Gene ID | 27125 |
| Gene name | ALF transcription elongation factor 4 |
| Synonyms | AF5Q31|CHOPS|MCEF |
| Cytomap | 5q31.1 |
| Type of gene | protein-coding |
| Description | AF4/FMR2 family member 4ALL1-fused gene from chromosome 5q31 proteinmajor CDK9 elongation factor-associated protein |
| Modification date | 20240305 |
| UniProtAcc | Q9UHB7 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | AFF4 | GO:0001650 | fibrillar center | - |
| Gene | AFF4 | GO:0005654 | nucleoplasm | - |
| Gene | AFF4 | GO:0008023 | transcription elongation factor complex | 22195968 |
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 |
| Q9UHB7-1 | Q9UHB7-1_6r80_A.pdb | 6R80 | X-ray | 2.2 | A | 901 | 1162 |
| 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 |
| Q9UHB7 | AFF4 | Q9UHB7-1 | Q9UHB7-2 | 1163 | 900 | 880 | 900 | Substitution | EKAPSSSSNCPPSAPTLDSSK | VKCWGPGAFENHSTCHVTFPG | 880 | 900 |
| Q9UHB7 | AFF4 | Q9UHB7-1 | Q9UHB7-2 | 1163 | 900 | 901 | 1163 | Deletion | none | none | 900 | 900 |
| Q9UHB7 | AFF4 | Q9UHB7-1 | Q9UHB7-3 | 1163 | 353 | 351 | 353 | Substitution | ESQ | VSK | 351 | 353 |
| Q9UHB7 | AFF4 | Q9UHB7-1 | Q9UHB7-3 | 1163 | 353 | 354 | 1163 | Deletion | none | none | 353 | 353 |
| Multiple sequence alignment of our canonical and alternatively spliced AFF4 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of AFF4 |
| UniProt-id | ENSG | ENST | ENSP |
| Q9UHB7-1 | ENSG00000072364.13 | ENST00000265343.10 | ENSP00000265343.5 |
| Q9UHB7-2 | ENSG00000072364.13 | ENST00000378595.7 | ENSP00000367858.3 |
| UniProt-id | NM ID | NP ID |
| Q9UHB7-1 | NM_014423.3 | NP_055238.1 |
| Q9UHB7-1 | XM_005271963.4 | XP_005272020.1 |
| Amino acid sequences of our canonical and alternatively spliced AFF4 |
| accession_id | Protein sequence |
| Q9UHB7-1 | MNREDRNVLRMKERERRNQEIQQGEDAFPPSSPLFAEPYKVTSKEDKLSSRIQSMLGNYDEMKDFIGDRSIPKLVAIPKPTVPPSADEKS NPNFFEQRHGGSHQSSKWTPVGPAPSTSQSQKRSSGLQSGHSSQRTSAGSSSGTNSSGQRHDRESYNNSGSSSRKKGQHGSEHSKSRSSS PGKPQAVSSLNSSHSRSHGNDHHSKEHQRSKSPRDPDANWDSPSRVPFSSGQHSTQSFPPSLMSKSNSMLQKPTAYVRPMDGQESMEPKL SSEHYSSQSHGNSMTELKPSSKAHLTKLKIPSQPLDASASGDVSCVDEILKEMTHSWPPPLTAIHTPCKTEPSKFPFPTKESQQSNFGTG EQKRYNPSKTSNGHQSKSMLKDDLKLSSSEDSDGEQDCDKTMPRSTPGSNSEPSHHNSEGADNSRDDSSSHSGSESSSGSDSESESSSSD SEANEPSQSASPEPEPPPTNKWQLDNWLNKVNPHKVSPASSVDSNIPSSQGYKKEGREQGTGNSYTDTSGPKETSSATPGRDSKTIQKGS ESGRGRQKSPAQSDSTTQRRTVGKKQPKKAEKAAAEEPRGGLKIESETPVDLASSMPSSRHKAATKGSRKPNIKKESKSSPRPTAEKKKY KSTSKSSQKSREIIETDTSSSDSDESESLPPSSQTPKYPESNRTPVKPSSVEEEDSFFRQRMFSPMEEKELLSPLSEPDDRYPLIVKIDL NLLTRIPGKPYKETEPPKGEKKNVPEKHTREAQKQASEKVSNKGKRKHKNEDDNRASESKKPKTEDKNSAGHKPSSNRESSKQSAAKEKD LLPSPAGPVPSKDPKTEHGSRKRTISQSSSLKSSSNSNKETSGSSKNSSSTSKQKKTEGKTSSSSKEVKEKAPSSSSNCPPSAPTLDSSK PRRTKLVFDDRNYSADHYLQEAKKLKHNADALSDRFEKAVYYLDAVVSFIECGNALEKNAQESKSPFPMYSETVDLIKYTMKLKNYLAPD ATAADKRLTVLCLRCESLLYLRLFKLKKENALKYSKTLTEHLKNSYNNSQAPSPGLGSKAVGMPSPVSPKLSPGNSGNYSSGASSASASG |
| Q9UHB7-2 | MNREDRNVLRMKERERRNQEIQQGEDAFPPSSPLFAEPYKVTSKEDKLSSRIQSMLGNYDEMKDFIGDRSIPKLVAIPKPTVPPSADEKS NPNFFEQRHGGSHQSSKWTPVGPAPSTSQSQKRSSGLQSGHSSQRTSAGSSSGTNSSGQRHDRESYNNSGSSSRKKGQHGSEHSKSRSSS PGKPQAVSSLNSSHSRSHGNDHHSKEHQRSKSPRDPDANWDSPSRVPFSSGQHSTQSFPPSLMSKSNSMLQKPTAYVRPMDGQESMEPKL SSEHYSSQSHGNSMTELKPSSKAHLTKLKIPSQPLDASASGDVSCVDEILKEMTHSWPPPLTAIHTPCKTEPSKFPFPTKESQQSNFGTG EQKRYNPSKTSNGHQSKSMLKDDLKLSSSEDSDGEQDCDKTMPRSTPGSNSEPSHHNSEGADNSRDDSSSHSGSESSSGSDSESESSSSD SEANEPSQSASPEPEPPPTNKWQLDNWLNKVNPHKVSPASSVDSNIPSSQGYKKEGREQGTGNSYTDTSGPKETSSATPGRDSKTIQKGS ESGRGRQKSPAQSDSTTQRRTVGKKQPKKAEKAAAEEPRGGLKIESETPVDLASSMPSSRHKAATKGSRKPNIKKESKSSPRPTAEKKKY KSTSKSSQKSREIIETDTSSSDSDESESLPPSSQTPKYPESNRTPVKPSSVEEEDSFFRQRMFSPMEEKELLSPLSEPDDRYPLIVKIDL NLLTRIPGKPYKETEPPKGEKKNVPEKHTREAQKQASEKVSNKGKRKHKNEDDNRASESKKPKTEDKNSAGHKPSSNRESSKQSAAKEKD LLPSPAGPVPSKDPKTEHGSRKRTISQSSSLKSSSNSNKETSGSSKNSSSTSKQKKTEGKTSSSSKEVKVKCWGPGAFENHSTCHVTFPG |
| Q9UHB7-3 | MNREDRNVLRMKERERRNQEIQQGEDAFPPSSPLFAEPYKVTSKEDKLSSRIQSMLGNYDEMKDFIGDRSIPKLVAIPKPTVPPSADEKS NPNFFEQRHGGSHQSSKWTPVGPAPSTSQSQKRSSGLQSGHSSQRTSAGSSSGTNSSGQRHDRESYNNSGSSSRKKGQHGSEHSKSRSSS PGKPQAVSSLNSSHSRSHGNDHHSKEHQRSKSPRDPDANWDSPSRVPFSSGQHSTQSFPPSLMSKSNSMLQKPTAYVRPMDGQESMEPKL |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| AFF4 (go to UniProt):Q9UHB7 |
| 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 |
| Q9UHB7 | Region | 324 | 904 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Substitution;Start=880;End=900 |
| Q9UHB7 | Region | 324 | 904 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=901;End=1163 |
| Q9UHB7 | Region | 324 | 904 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Substitution;Start=351;End=353 |
| Q9UHB7 | Region | 324 | 904 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=354;End=1163 |
| Q9UHB7 | Region | 1034 | 1073 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=901;End=1163 |
| Q9UHB7 | Region | 1034 | 1073 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=354;End=1163 |
| Q9UHB7 | Compositional bias | 346 | 375 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Substitution;Start=351;End=353 |
| Q9UHB7 | Compositional bias | 346 | 375 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=354;End=1163 |
| Q9UHB7 | Compositional bias | 376 | 400 | Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=354;End=1163 |
| Q9UHB7 | Compositional bias | 402 | 417 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=354;End=1163 |
| Q9UHB7 | Compositional bias | 430 | 459 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=354;End=1163 |
| Q9UHB7 | Compositional bias | 483 | 560 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=354;End=1163 |
| Q9UHB7 | Compositional bias | 567 | 584 | Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=354;End=1163 |
| Q9UHB7 | Compositional bias | 609 | 648 | Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=354;End=1163 |
| Q9UHB7 | Compositional bias | 653 | 676 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=354;End=1163 |
| Q9UHB7 | Compositional bias | 677 | 706 | Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=354;End=1163 |
| Q9UHB7 | Compositional bias | 731 | 793 | Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=354;End=1163 |
| Q9UHB7 | Compositional bias | 833 | 868 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=354;End=1163 |
| Q9UHB7 | Compositional bias | 878 | 899 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Substitution;Start=880;End=900 |
| Q9UHB7 | Compositional bias | 878 | 899 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=354;End=1163 |
| Q9UHB7 | Compositional bias | 1059 | 1073 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=901;End=1163 |
| Q9UHB7 | Compositional bias | 1059 | 1073 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=354;End=1163 |
Gene Isoform Structures and Expression Levels for AFF4 |
| Gene structures of our canonical and alternative spliced genes of AFF4 * 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 Q9UHB7-1 |
| 3D view using mol* of Q9UHB7-2 |
| 3D view using mol* of Q9UHB7-3 |
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 Q9UHB7-1 |
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| pLDDT distribution across the protein length of Q9UHB7-2 |
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| pLDDT distribution across the protein length of Q9UHB7-3 |
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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 Q9UHB7-1 |
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| Ramachandran plot of Q9UHB7-2 |
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| Ramachandran plot of Q9UHB7-3 |
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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 |
| Q9UHB7-1 | 1.057 | 214 | 1.122 | 663.362 | 0.598 | 0.686 | 0.854 | 0.922 | 0.704 | 1.309 | 1.807 | 320,323,324,683,684,685,686,687,688,689,691,692,96 7,971,974,975,978,981,982,985,986,987,1003,1006,10 10,1013,1101,1102,1103,1104,1105,1107,1108,1109,11 11,1112,1115,1116,1119 |
| Q9UHB7-2 | 0.671 | 41 | 0.625 | 83.349 | 0.568 | 0.597 | 0.843 | 0.392 | 1.027 | 0.382 | 0.931 | 41,42,43,44,49,52,53,56,57,58,59,60,62
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| Q9UHB7-3 | 0.828 | 66 | 0.833 | 144.403 | 0.588 | 0.608 | 0.935 | 0.592 | 0.908 | 0.652 | 0.911 | 328,329,330,331,332,333,334,335,338,339,340,342,34 3,344,345,347 |
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 Q9UHB7-1_Q9UHB7-1_6r80_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 Q9UHB7-1_6r80_A_Q9UHB7-2.pdb |
| 3D view using mol* of Q9UHB7-1_6r80_A_Q9UHB7-3.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of Q9UHB7-1_Q9UHB7-2.pdb |
| 3D view using mol* of Q9UHB7-1_Q9UHB7-3.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/Q9UHB7-1_vs_Q9UHB7-2.png |
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| ./stats/secondary_structure/figure/Q9UHB7-1_vs_Q9UHB7-3.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/Q9UHB7-1_vs_Q9UHB7-2.png |
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| ./stats/relative_asa/Q9UHB7-1_vs_Q9UHB7-3.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 AFF4 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
Related Diseases to AFF4 |
| Previous studies relating to the alternative splicing of AFF4 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| AFF4 | 21330300 | Functional characterization of the AFF (AF4/FMR2) family of RNA-binding proteins: insights into the molecular pathology of FRAXE intellectual disability. | The AFF (AF4/FMR2) family of genes includes four members: AFF1/AF4, AFF2/FMR2, AFF3/LAF4 and AFF4/AF5q31. AFF2/FMR2 is silenced in FRAXE intellectual disability, while the other three members have been reported to form fusion genes as a consequence of chromosome translocations with the myeloid/lymphoid or mixed lineage leukemia (MLL) gene in acute lymphoblastic leukemias (ALLs). All AFF proteins are localized in the nucleus and their role as transcriptional activators with a positive action on RNA elongation was primarily studied. We have recently shown that AFF2/FMR2 localizes to nuclear speckles, subnuclear structures considered as storage/modification sites of pre-mRNA splicing factors, and modulates alternative splicing via the interaction with the G-quadruplex RNA-forming structure. We show here that similarly to AFF2/FMR2, AFF3/LAF4 and AFF4/AF5q31 localize to nuclear speckles and are able to bind RNA, having a high apparent affinity for the G-quadruplex structure. Interestingly, AFF3/LAF4 and AFF4/AF5q31, like AFF2/FMR2, modulate, in vivo, the splicing efficiency of a mini-gene containing a G-quadruplex structure in one alternatively spliced exon. Furthermore, we observed that the overexpression of AFF2/3/4 interferes with the organization and/or biogenesis of nuclear speckles. These findings fit well with our observation that enlarged nuclear speckles are present in FRAXE fibroblasts. Furthermore, our findings suggest functional redundancy among the AFF family members in the regulation of splicing and transcription. It is possible that other members of the AFF family compensate for the loss of AFF2/FMR2 activity and as such explain the relatively mild to borderline phenotype observed in FRAXE patients. | D005600 | Fragile X Syndrome |
Clinically important variants in AFF4 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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