Protein:HSP90AA1 |
Protein Summary |
 Gene summary |
| Gene name: HSP90AA1 | ASpdb.0 ID: 3320 | Gene | Gene symbol | HSP90AA1 | Gene ID | 3320 |
| Gene name | heat shock protein 90 alpha family class A member 1 |
| Synonyms | EL52|HEL-S-65p|HSP86|HSP89A|HSP90A|HSP90N|HSPC1|HSPCA|HSPCAL1|HSPCAL4|HSPN|Hsp103|Hsp89|Hsp90|LAP-2|LAP2 |
| Cytomap | 14q32.31 |
| Type of gene | protein-coding |
| Description | heat shock protein HSP 90-alphaHSP 86LPS-associated protein 2epididymis luminal secretory protein 52epididymis secretory sperm binding protein Li 65pheat shock 86 kDaheat shock 90kD protein 1, alphaheat shock 90kD protein 1, alpha-like 4heat shock |
| Modification date | 20240407 |
| UniProtAcc | P07900 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | HSP90AA1 | GO:0001934 | positive regulation of protein phosphorylation | 19363271 |
| Gene | HSP90AA1 | GO:0002218 | activation of innate immune response | 20628368 |
| Gene | HSP90AA1 | GO:0002230 | positive regulation of defense response to virus by host | 20628368 |
| Gene | HSP90AA1 | GO:0005524 | ATP binding | 27353360 |
| Gene | HSP90AA1 | GO:0005654 | nucleoplasm | - |
| Gene | HSP90AA1 | GO:0005737 | cytoplasm | 10791971 |
| Gene | HSP90AA1 | GO:0005739 | mitochondrion | 25609812 |
| Gene | HSP90AA1 | GO:0005829 | cytosol | - |
| Gene | HSP90AA1 | GO:0007004 | telomere maintenance via telomerase | 10197982 |
| Gene | HSP90AA1 | GO:0016887 | ATP hydrolysis activity | 15937123|29127155 |
| Gene | HSP90AA1 | GO:0030235 | nitric-oxide synthase regulator activity | 15937123 |
| Gene | HSP90AA1 | GO:0030911 | TPR domain binding | 9660753 |
| Gene | HSP90AA1 | GO:0031396 | regulation of protein ubiquitination | 16809764 |
| Gene | HSP90AA1 | GO:0032273 | positive regulation of protein polymerization | 19363271 |
| Gene | HSP90AA1 | GO:0032728 | positive regulation of interferon-beta production | 20628368 |
| Gene | HSP90AA1 | GO:0032991 | protein-containing complex | 23349634 |
| Gene | HSP90AA1 | GO:0042802 | identical protein binding | 29127155 |
| Gene | HSP90AA1 | GO:0042803 | protein homodimerization activity | 29127155 |
| Gene | HSP90AA1 | GO:0042981 | regulation of apoptotic process | 25609812 |
| Gene | HSP90AA1 | GO:0045040 | protein insertion into mitochondrial outer membrane | 15644312 |
| Gene | HSP90AA1 | GO:0051131 | chaperone-mediated protein complex assembly | 15644312 |
| Gene | HSP90AA1 | GO:0051973 | positive regulation of telomerase activity | 10197982 |
| Gene | HSP90AA1 | GO:0098586 | cellular response to virus | 25609812 |
| Gene | HSP90AA1 | GO:1902949 | positive regulation of tau-protein kinase activity | 19363271 |
| Gene | HSP90AA1 | GO:1905323 | telomerase holoenzyme complex assembly | 10197982 |
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 |
| P07900-1 | P07900-1_3q6m_B.pdb | 3Q6M | X-ray | 3.0 | B | 294 | 699 |
| 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 |
| P07900 | HSP90AA1 | P07900-1 | P07900-2 | 732 | 854 | 1 | 1 | Substitution | M | MPPCSGGDGSTPPGPSLRDRDCPAQSAEYPRDRLDPRPGSPSEASSPPFLRSRAPVNWYQEKAQVFLWHLMVSGSTTLLCLWKQPFHVSAFPVTASLAFRQSQGAGQHLYKDLQPFILLRLLM | 1 | 123 |
| Multiple sequence alignment of our canonical and alternatively spliced HSP90AA1 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of HSP90AA1 |
| UniProt-id | ENSG | ENST | ENSP |
| P07900-1 | ENSG00000080824.19 | ENST00000216281.13 | ENSP00000216281.8 |
| P07900-2 | ENSG00000080824.19 | ENST00000334701.11 | ENSP00000335153.7 |
| UniProt-id | NM ID | NP ID |
| P07900-1 | NM_005348.3 | NP_005339.3 |
| P07900-2 | NM_001017963.2 | NP_001017963.2 |
| Amino acid sequences of our canonical and alternatively spliced HSP90AA1 |
| accession_id | Protein sequence |
| P07900-1 | MPEETQTQDQPMEEEEVETFAFQAEIAQLMSLIINTFYSNKEIFLRELISNSSDALDKIRYESLTDPSKLDSGKELHINLIPNKQDRTLT IVDTGIGMTKADLINNLGTIAKSGTKAFMEALQAGADISMIGQFGVGFYSAYLVAEKVTVITKHNDDEQYAWESSAGGSFTVRTDTGEPM GRGTKVILHLKEDQTEYLEERRIKEIVKKHSQFIGYPITLFVEKERDKEVSDDEAEEKEDKEEEKEKEEKESEDKPEIEDVGSDEEEEKK DGDKKKKKKIKEKYIDQEELNKTKPIWTRNPDDITNEEYGEFYKSLTNDWEDHLAVKHFSVEGQLEFRALLFVPRRAPFDLFENRKKKNN IKLYVRRVFIMDNCEELIPEYLNFIRGVVDSEDLPLNISREMLQQSKILKVIRKNLVKKCLELFTELAEDKENYKKFYEQFSKNIKLGIH EDSQNRKKLSELLRYYTSASGDEMVSLKDYCTRMKENQKHIYYITGETKDQVANSAFVERLRKHGLEVIYMIEPIDEYCVQQLKEFEGKT LVSVTKEGLELPEDEEEKKKQEEKKTKFENLCKIMKDILEKKVEKVVVSNRLVTSPCCIVTSTYGWTANMERIMKAQALRDNSTMGYMAA KKHLEINPDHSIIETLRQKAEADKNDKSVKDLVILLYETALLSSGFSLEDPQTHANRIYRMIKLGLGIDEDDPTADDTSAAVTEEMPPLE |
| P07900-2 | MPPCSGGDGSTPPGPSLRDRDCPAQSAEYPRDRLDPRPGSPSEASSPPFLRSRAPVNWYQEKAQVFLWHLMVSGSTTLLCLWKQPFHVSA FPVTASLAFRQSQGAGQHLYKDLQPFILLRLLMPEETQTQDQPMEEEEVETFAFQAEIAQLMSLIINTFYSNKEIFLRELISNSSDALDK IRYESLTDPSKLDSGKELHINLIPNKQDRTLTIVDTGIGMTKADLINNLGTIAKSGTKAFMEALQAGADISMIGQFGVGFYSAYLVAEKV TVITKHNDDEQYAWESSAGGSFTVRTDTGEPMGRGTKVILHLKEDQTEYLEERRIKEIVKKHSQFIGYPITLFVEKERDKEVSDDEAEEK EDKEEEKEKEEKESEDKPEIEDVGSDEEEEKKDGDKKKKKKIKEKYIDQEELNKTKPIWTRNPDDITNEEYGEFYKSLTNDWEDHLAVKH FSVEGQLEFRALLFVPRRAPFDLFENRKKKNNIKLYVRRVFIMDNCEELIPEYLNFIRGVVDSEDLPLNISREMLQQSKILKVIRKNLVK KCLELFTELAEDKENYKKFYEQFSKNIKLGIHEDSQNRKKLSELLRYYTSASGDEMVSLKDYCTRMKENQKHIYYITGETKDQVANSAFV ERLRKHGLEVIYMIEPIDEYCVQQLKEFEGKTLVSVTKEGLELPEDEEEKKKQEEKKTKFENLCKIMKDILEKKVEKVVVSNRLVTSPCC IVTSTYGWTANMERIMKAQALRDNSTMGYMAAKKHLEINPDHSIIETLRQKAEADKNDKSVKDLVILLYETALLSSGFSLEDPQTHANRI |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| HSP90AA1 (go to UniProt):P07900 |
| 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 |
Gene Isoform Structures and Expression Levels for HSP90AA1 |
| Gene structures of our canonical and alternative spliced genes of HSP90AA1 * 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 P07900-1 |
| 3D view using mol* of P07900-2 |
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 P07900-1 |
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| pLDDT distribution across the protein length of P07900-2 |
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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 P07900-1 |
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| Ramachandran plot of P07900-2 |
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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 |
| P07900-1 | 1.111 | 221 | 1.051 | 383.131 | 0.374 | 0.864 | 1.113 | 0.823 | 1.25 | 0.658 | 0.608 | 38,47,48,51,52,54,55,58,91,93,95,96,97,98,102,106, 107,109,112,113,114,115,117,118,132,134,135,136,13 7,138,139,150,154,183,184,186,398,400 |
| P07900-2 | 1.12 | 221 | 1.041 | 381.416 | 0.332 | 0.878 | 1.159 | 0.912 | 1.305 | 0.699 | 0.497 | 169,170,172,173,174,176,177,180,184,213,215,218,21 9,220,224,228,229,234,235,236,237,239,240,253,254, 256,257,258,259,260,261,272,276,306,308,522 |
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 P07900-1_P07900-1_3q6m_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 P07900-1_3q6m_B_P07900-2.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P07900-1_P07900-2.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P07900-1_vs_P07900-2.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P07900-1_vs_P07900-2.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 HSP90AA1 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P07900 | HSP90AA1 | DB06957 | 4-CHLORO-6-(4-{4-[4-(METHYLSULFONYL)BENZYL]PIPERAZIN-1-YL}-1H-PYRAZOL-5-YL)BENZENE-1,3-DIOL | experimental | |
| P07900 | HSP90AA1 | DB07317 | (3E)-3-[(phenylamino)methylidene]dihydrofuran-2(3H)-one | experimental | |
| P07900 | HSP90AA1 | DB07319 | 6-(3-BROMO-2-NAPHTHYL)-1,3,5-TRIAZINE-2,4-DIAMINE | experimental | |
| P07900 | HSP90AA1 | DB00615 | Rifabutin | approved, investigational | other/unknown |
| P07900 | HSP90AA1 | DB06958 | 5-(5-CHLORO-2,4-DIHYDROXYPHENYL)-N-ETHYL-4-PIPERAZIN-1-YL-1H-PYRAZOLE-3-CARBOXAMIDE | experimental | |
| P07900 | HSP90AA1 | DB07502 | 4-bromo-6-(6-hydroxy-1,2-benzisoxazol-3-yl)benzene-1,3-diol | experimental | |
| P07900 | HSP90AA1 | DB04254 | 8-Benzo[1,3]Dioxol-,5-Ylmethyl-9-Butyl-2-Fluoro-9h-Purin-6-Ylamine | experimental | |
| P07900 | HSP90AA1 | DB03093 | 8-(2,5-Dimethoxy-Benzyl)-2-Fluoro-9h-Purin-6-Ylamine | experimental | |
| P07900 | HSP90AA1 | DB02550 | 8-(2-Chloro-3,4,5-Trimethoxy-Benzyl)-2-Fluoro-9-Pent-4-Ylnyl-9h-Purin-6-Ylamine | experimental | |
| P07900 | HSP90AA1 | DB08197 | (5E,7S)-2-amino-7-(4-fluoro-2-pyridin-3-ylphenyl)-4-methyl-7,8-dihydroquinazolin-5(6H)-one oxime | experimental | |
| P07900 | HSP90AA1 | DB06956 | N-(4-ACETYLPHENYL)-5-(5-CHLORO-2,4-DIHYDROXYPHENYL)-1H-PYRAZOLE-4-CARBOXAMIDE | experimental | |
| P07900 | HSP90AA1 | DB02754 | 9-Butyl-8-(3,4,5-Trimethoxybenzyl)-9h-Purin-6-Amine | experimental | |
| P07900 | HSP90AA1 | DB07601 | 4-chloro-6-{5-[(2-morpholin-4-ylethyl)amino]-1,2-benzisoxazol-3-yl}benzene-1,3-diol | experimental | |
| P07900 | HSP90AA1 | DB08442 | 4-{[(2R)-2-(2-methylphenyl)pyrrolidin-1-yl]carbonyl}benzene-1,3-diol | experimental | |
| P07900 | HSP90AA1 | DB02359 | 9-Butyl-8-(2,5-Dimethoxy-Benzyl)-9h-Purin-6-Ylamine | experimental | |
| P07900 | HSP90AA1 | DB08436 | 8-BENZO[1,3]DIOXOL-,5-YLMETHYL-9-BUTYL-9H- | experimental | |
| P07900 | HSP90AA1 | DB06961 | 5-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-[4-(morpholin-4-ylmethyl)phenyl]isoxazole-3-carboxamide | experimental | |
| P07900 | HSP90AA1 | DB08194 | 4-methyl-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidin-2-amine | experimental | |
| P07900 | HSP90AA1 | DB07495 | 5-(5-CHLORO-2,4-DIHYDROXYPHENYL)-N-ETHYL-4-(4-METHOXYPHENYL)-1H-PYRAZOLE-3-CARBOXAMIDE | experimental | |
| P07900 | HSP90AA1 | DB02840 | 4-(1,3-Benzodioxol-5-Yl)-5-(5-Ethyl-2,4-Dihydroxyphenyl)-2h-Pyrazole-3-Carboxylic Acid | experimental | |
| P07900 | HSP90AA1 | DB04588 | N-[4-(AMINOSULFONYL)BENZYL]-5-(5-CHLORO-2,4-DIHYDROXYPHENYL)-1H-PYRAZOLE-4-CARBOXAMIDE | experimental | |
| P07900 | HSP90AA1 | DB06969 | 2-amino-4-[2,4-dichloro-5-(2-pyrrolidin-1-ylethoxy)phenyl]-N-ethylthieno[2,3-d]pyrimidine-6-carboxamide | experimental | |
| P07900 | HSP90AA1 | DB02424 | Geldanamycin | experimental, investigational | |
| P07900 | HSP90AA1 | DB03137 | 8-(2,5-Dimethoxy-Benzyl)-2-Fluoro-9-Pent-9h-Purin-6-Ylamine | experimental | |
| P07900 | HSP90AA1 | DB06964 | 5-(5-CHLORO-2,4-DIHYDROXYPHENYL)-N-ETHYL-4-(4-METHOXYPHENYL)ISOXAZOLE-3-CARBOXAMIDE | experimental | |
| P07900 | HSP90AA1 | DB04505 | 8-(2-Chloro-3,4,5-Trimethoxy-Benzyl)-9-Pent-4-Ylnyl-9h-Purin-6-Ylamine | experimental | |
| P07900 | HSP90AA1 | DB08443 | 2-(1H-pyrrol-1-ylcarbonyl)benzene-1,3,5-triol | experimental | |
| P07900 | HSP90AA1 | DB07594 | CCT-018159 | experimental | |
| P07900 | HSP90AA1 | DB08789 | 2-AMINO-4-(2,4-DICHLOROPHENYL)-N-ETHYLTHIENO[2,3-D]PYRIMIDINE-6-CARBOXAMIDE | experimental | |
| P07900 | HSP90AA1 | DB07877 | 8-(6-BROMO-BENZO[1,3]DIOXOL-5-YLSULFANYL)-9-(3-ISOPROPYLAMINO-PROPYL)-ADENINE | experimental | |
| P07900 | HSP90AA1 | DB09130 | Copper | approved, investigational | |
| P07900 | HSP90AA1 | DB07325 | N-[(2-AMINO-6-METHYLPYRIMIDIN-4-YL)METHYL]-3-{[(E)-(2-OXODIHYDROFURAN-3(2H)-YLIDENE)METHYL]AMINO}BENZENESULFONAMIDE | experimental | |
| P07900 | HSP90AA1 | DB12442 | Alvespimycin | investigational | inhibitor |
| P07900 | HSP90AA1 | DB08557 | 2-[(2-methoxyethyl)amino]-4-(4-oxo-1,2,3,4-tetrahydro-9H-carbazol-9-yl)benzamide | experimental | |
| P07900 | HSP90AA1 | DB03504 | 9-Butyl-8-(2-Chloro-3,4,5-Trimethoxy-Benzyl)-9h-Purin-6-Ylamine | experimental | |
| P07900 | HSP90AA1 | DB06070 | SNX-5422 | investigational | |
| P07900 | HSP90AA1 | DB07100 | 4-CHLORO-6-(4-PIPERAZIN-1-YL-1H-PYRAZOL-5-YL)BENZENE-1,3-DIOL | experimental | |
| P07900 | HSP90AA1 | DB00716 | Nedocromil | approved, investigational | |
| P07900 | HSP90AA1 | DB03899 | 9-Butyl-8-(4-Methoxybenzyl)-9h-Purin-6-Amine | experimental | |
| P07900 | HSP90AA1 | DB03809 | 9-Butyl-8-(3-Methoxybenzyl)-9h-Purin-6-Amine | experimental | |
| P07900 | HSP90AA1 | DB08788 | 3,6-DIAMINO-5-CYANO-4-(4-ETHOXYPHENYL)THIENO[2,3-B]PYRIDINE-2-CARBOXAMIDE | experimental | |
| P07900 | HSP90AA1 | DB03749 | 4-(1h-Imidazol-4-Yl)-3-(5-Ethyl-2,4-Dihydroxy-Phenyl)-1h-Pyrazole | experimental | |
| P07900 | HSP90AA1 | DB08787 | 4-(2,4-dichlorophenyl)-5-phenyldiazenyl-pyrimidin-2-amine | experimental | |
| P07900 | HSP90AA1 | DB08786 | 4-(2-methoxyethoxy)-6-methylpyrimidin-2-amine | experimental | |
| P07900 | HSP90AA1 | DB09221 | Polaprezinc | experimental | agonist |
| P07900 | HSP90AA1 | DB04216 | Quercetin | experimental, investigational | |
| P07900 | HSP90AA1 | DB07324 | 3-({2-[(2-AMINO-6-METHYLPYRIMIDIN-4-YL)ETHYNYL]BENZYL}AMINO)-1,3-OXAZOL-2(3H)-ONE | experimental | |
| P07900 | HSP90AA1 | DB04054 | 9-Butyl-8-(2,5-Dimethoxy-Benzyl)-2-Fluoro-9h-Purin-6-Ylamine | experimental | |
| P07900 | HSP90AA1 | DB05134 | Tanespimycin | investigational |
Related Diseases to HSP90AA1 |
| Previous studies relating to the alternative splicing of HSP90AA1 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| HSP90AA1 | 25024377 | The differential regulation of human ACT1 isoforms by Hsp90 in IL-17 signaling. | IL-17 is a proinflammatory cytokine implicated in the pathogenesis of autoimmune diseases including psoriasis. ACT1 is an essential adaptor molecule in the IL-17 signaling pathway. A missense single nucleotide polymorphism (rs33980500; SNP-D10N) that resulted in the substitution of an asparagine for an aspartic acid at position 10 of ACT1 (ACT1-D10N) is associated with psoriasis susceptibility. Due to alternative splicing in humans, SNP-D10N encodes two mutated ACT1 proteins, ACT1-D10N and ACT1-D19N. Although both ACT1 isoforms are Hsp90 client proteins, the nine additional amino acids in ACT1-D19N provide an additional Hsp90 binding site that is absent in ACT1-D10N. Therefore, whereas ACT1-D10N is a dead protein that is unable to transduce IL-17 signals for gene expression, ACT1-D19N is fully responsive to IL-17. Intriguingly, the two ACT1 isoforms are differentially expressed in ACT1(D10N/D10N) fibroblasts and T cells. Fibroblasts express both isoforms equally, enabling ACT1-D19N to compensate for the loss of ACT1-D10N function. ACT1(D10N/D10N) T cells, however, express predominantly ACT1-D10N. Lacking this compensatory mechanism, ACT1(D10N/D10N) T cells behave like ACT1-deficient T cells, exhibiting a dysregulated and hyperactive Th17 phenotype with overproduction of IL-22 and IL-17. The hyperactive Th17 response combined with fully responsive fibroblasts likely synergized to contribute to psoriasis susceptibility in SNP-D10N patients. | D020022 | Genetic Predisposition to Disease |
| HSP90AA1 | 25024377 | The differential regulation of human ACT1 isoforms by Hsp90 in IL-17 signaling. | IL-17 is a proinflammatory cytokine implicated in the pathogenesis of autoimmune diseases including psoriasis. ACT1 is an essential adaptor molecule in the IL-17 signaling pathway. A missense single nucleotide polymorphism (rs33980500; SNP-D10N) that resulted in the substitution of an asparagine for an aspartic acid at position 10 of ACT1 (ACT1-D10N) is associated with psoriasis susceptibility. Due to alternative splicing in humans, SNP-D10N encodes two mutated ACT1 proteins, ACT1-D10N and ACT1-D19N. Although both ACT1 isoforms are Hsp90 client proteins, the nine additional amino acids in ACT1-D19N provide an additional Hsp90 binding site that is absent in ACT1-D10N. Therefore, whereas ACT1-D10N is a dead protein that is unable to transduce IL-17 signals for gene expression, ACT1-D19N is fully responsive to IL-17. Intriguingly, the two ACT1 isoforms are differentially expressed in ACT1(D10N/D10N) fibroblasts and T cells. Fibroblasts express both isoforms equally, enabling ACT1-D19N to compensate for the loss of ACT1-D10N function. ACT1(D10N/D10N) T cells, however, express predominantly ACT1-D10N. Lacking this compensatory mechanism, ACT1(D10N/D10N) T cells behave like ACT1-deficient T cells, exhibiting a dysregulated and hyperactive Th17 phenotype with overproduction of IL-22 and IL-17. The hyperactive Th17 response combined with fully responsive fibroblasts likely synergized to contribute to psoriasis susceptibility in SNP-D10N patients. | D011565 | Psoriasis |
Clinically important variants in HSP90AA1 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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