基因總覽
RUVBL1(RuvB like AAA ATPase 1)是蛋白質編碼基因,產生屬於 RuvB 家族的 AAA ATPase。其蛋白質可形成環狀寡聚體,並作為多種大型蛋白質複合體的組成部分;這些複合體涵蓋染色質重塑、組蛋白修飾與轉錄相關工作。RUVBL1 也與 RUVBL2共同組成環狀結構,並出現在 NuA4、INO80、SWR1-like、R2TP 與 PAQosome 等複合體中。其家族歸屬與多樣的複合體組成,構成理解此蛋白質基本性質的主要線索。
基因異名與舊稱
異名取自 HGNC,可能包含歷史名稱;蛋白質名稱以 UniProt 註解為準。
染色體位置與基因結構
查看實際轉錄本與 exon 註解
| Transcript | Genomic coordinates | Exons |
|---|---|---|
| ENST00000322623 ★ | 128,080,810–128,123,812 | 11 |
| ENST00000464873 | 128,063,024–128,153,914 | 10 |
| ENST00000998655 | 128,063,024–128,123,837 | 11 |
| ENST00000998656 | 128,063,024–128,123,837 | 12 |
| ENST00001038551 | 128,063,024–128,123,837 | 10 |
| ENST00000472125 | 128,064,782–128,101,619 | 5 |
| ENST00000881248 | 128,064,782–128,123,837 | 12 |
| ENST00001139140 | 128,080,810–128,123,837 | 11 |
| ENST00000931761 | 128,080,955–128,123,837 | 11 |
| ENST00000881253 | 128,080,956–128,123,837 | 9 |
| ENST00000998661 | 128,080,958–128,123,837 | 12 |
| ENST00001084223 | 128,080,959–128,123,837 | 11 |
顯示 12/25 個蛋白質編碼轉錄本;canonical 優先。
帶型與著絲點依 Ensembl 座標繪製;核染色體長度以 GRCh38 第 1 號染色體為共同尺度。黃色標記表示本基因位置,細小區間加粗以利辨識;實際基因長度與 exon 見下方資料。
分子功能與生物學過程
RUVBL1 具有受單股 DNA 刺激的 ATPase 活性,也能以 ATP 為能量進行 3′ 至 5′ 方向的 DNA 解旋。資料指出,六聚化可能是 ATP 水解的重要條件;環狀結構中相鄰次單元也共同促成 ATPase 活性。ATP 水解反應為 ATP 與水生成 ADP、磷酸及氫離子。
RUVBL1 是 NuA4 組蛋白乙醯轉移酶複合體的組成部分。NuA4 主要透過乙醯化核小體中的組蛋白 H4 與 H2A,促進特定基因的轉錄活化。這些修飾可能改變核小體與 DNA 的作用,也可能促進修飾後組蛋白和其他正向調節轉錄的蛋白質互動。NuA4 可能參與多種轉錄程序,包括致癌基因或原癌基因介導的生長誘導、腫瘤抑制因子介導的生長停滯與複製性衰老、細胞凋亡及 DNA 修復。RUVBL1、RUVBL2 與 EP400 的結合,似乎至少部分提供 NuA4 的 ATPase 與解旋酶活性;NuA4 被招募至 DNA 損傷位置時,也可能直接參與修復。
在染色質重塑方面,RUVBL1 是 SWR1-like 複合體的組成部分,該複合體特異性介導核小體中組蛋白 H2A.Z/H2AZ1 的移除。RUVBL1 也被提出是 INO80 染色質重塑複合體的核心組成部分;INO80 具有受 DNA 與核小體活化的 ATPase 活性,並可催化 ATP 依賴性的核小體滑動。
RUVBL1 對 MYC 介導的致癌轉化具有必要作用,並可調節 LEF1/TCF1-CTNNB1 複合體所促進的轉錄活化。資料亦指出 RUVBL1 對細胞增殖不可或缺。另有較不確定的描述指出,RUVBL1 可能在細胞表面結合 plasminogen,並增強 plasminogen 活化;此項作用仍以可能性表述。
Promoter 與基因調控
>RUVBL1 ENST00000322623 GRCh38 chr3:128123712-128124812 strand=-1 5′→3′ 相對 TSS:-1000 到 +100 bp;1101 bp 依轉錄本 TSS 擷取的基因組序列;TSS = 0,兩端包含,未驗證為 promoter CATCACCTTCATGATGCCTTCCCTGGCTCTCCAGGCTGTTCCGGGGGCTTCTGCTCTGGTCTTCTCGCCA CCTGGGTGTACCTGTCTCAGCACATCTCACGTTGCAAGTTTTCTAAGCAAGAAGTAAACGCATCAAGACT TTTATCCCTGTATCCCCAGTGCATTGTGGTGTCTGGCTCGTGTTTGTTGAACGGATGGATGGATGGATGG CAAGTACAATTGTGGTGCAGGTTGTGCTAATATCATTATGAAACCTGAAGGGACAATTTGCTGGCTGATT GTCTCAGCTGGAGTCATGGGACGTGATGAGCATTATTATATAGGTTTTGAAGCCTGAAGATTTCTAGTTC TGATTATTTGTGATGCTTTCTTGGGCGGATGGGCCTCTTTCCGCTTGTTTGTAGCTGCATGCGTAATTAC ACTACCTTACAGGGCTGTGGAATTTTGAAAACTGCAAAATGTTATTTACAGTCAACTGAACTCAGCAGGA ACCTTATCTCTCGGTGGAGGATGGAGGATAGAAGCAGGGGAAGACAATTCCACGGAAACGGTGGTGGGTT GAGCTGGGCCTTTCCAGGGAGATGCAAAGGTATGGGAGTCAGAAAACATTGGTTAGTAACCAATCCCAGT TTAAGCTCTGAACCTCAGTTCTTCTGTTTCCAAAACGGAAATAATAACTTGAGATTTGCGTAAGAGTATG ACGTTCAAATGTGCTAATGGATAGGACGGAAGGATTAGGAGTGGTACCCGGGGGCCACTGCCTCGTGCAA CGCCCCAGCCCTAGATCAAATCCGGGGCGTGGTCCCACTGTGCTCCCGACCCCAGCCTCGGCAGGAAGCG CCGGCTACGGGGGAAGCCAACCCGGAGACACAGACGGAAGTGGGTGACCGGAGCTCTAGCAGCAGCCGCG ATGGGCGCAGCCGTGAGCCTATGGAGAGCGGAGGTGTTCCCGCTTCCACCAATGGAAAGCCGGTCTAGGC GGGCCTTTGCAAATTGCCCTAGTAACGGCCGCATGGTAACTCAGGCGCCGGGCGCACTGTCCTAGCTGCT GGTTTTCCACGCTGGTTTTAGCTCCCGGCGTCTGCAAAATGAAGATTGAGG
EPDnew 實驗支持 promoter/TSS · 1 筆
| EPDnew ID | TSS(1-based) | 股向 | 來源顯示區間 |
|---|---|---|---|
| RUVBL1_1 ↗ | 3:128,123,812 | 負股 | 128,123,802–128,123,861 |
EPDnew human v006 · UCSC hg38,GRCh38/hg38,透過 UCSC 取得。TSS 具有 CAGE/RAMPAGE 等實驗資料支持;任意擷取的上下游區間仍需另行判讀調控功能,不能視為整段皆經功能驗證。
EPD 封存狀態 ↗ · UCSC 資料說明 ↗ · EPD team, SIB Swiss Institute of Bioinformatics; UCSC Genome Browser · CC BY 4.0
查看已取得的調控/motif 註解
ENSR3_93TT3X · promoter · 128123802–128124302 · regulatory
· motif · 128122157–128122170 · motif
· motif · 128122236–128122249 · motif
· motif · 128122251–128122264 · motif
· motif · 128123470–128123480 · motif
· motif · 128123806–128123821 · motif
· motif · 128123806–128123821 · motif
· motif · 128123893–128123910 · motif
· motif · 128123931–128123940 · motif
· motif · 128123931–128123942 · motif
· motif · 128123931–128123942 · motif
· motif · 128124010–128124020 · motif
· motif · 128124140–128124149 · motif
· motif · 128124140–128124151 · motif
· motif · 128124140–128124151 · motif
蛋白質結構域與序列
蛋白質三維結構
細胞內定位
RUVBL1 主要位於細胞核,與核基質或核質相關,也可見於細胞質及細胞膜。 其位置會隨有絲分裂階段改變:前期與前中期可見於中心體及分枝微管紡錘體;核膜解體後聚集於中心體和微管蛋白聚合處,之後依序出現在微管交錯區、極性微管重疊處,並於子細胞染色體去凝縮位置再次出現。
深綠色圓點:來源記載的蛋白質定位;數量不表示含量。
未繪示構造:Membrane;Dynein axonemal particle。這些構造未在通用細胞圖中標點,仍保留來源定位名稱。
動物細胞結構示意;器官大小與數量不按比例。點選細胞構造可查看定位註解。
交互作用與訊號網絡
拖曳節點後放開可帶動位置變化;點選夥伴查看證據。位置與連線長度不代表結合強度,圖中未推定夥伴彼此之間的關係。
更多交互作用夥伴 · 已取得 18 個夥伴
- CTNNB1P35222 · UniProt INTERACTION · 3 experiments
- DKC1O60832 · UniProt INTERACTION · 10 experiments
- ECDO95905 · UniProt INTERACTION · 8 experiments
- INVSQ9Y283 · UniProt INTERACTION · 2 experiments
- IQCB1Q15051 · UniProt INTERACTION · 2 experiments
- KAT5Q92993 · UniProt INTERACTION · 10 experiments
- NPHP1O15259 · UniProt INTERACTION · 2 experiments
- NPHP3Q7Z494 · UniProt INTERACTION · 2 experiments
- NPHP4O75161 · UniProt INTERACTION · 2 experiments
- OFD1O75665 · UniProt INTERACTION · 3 experiments
- RUVBL2Q9Y230 · UniProt INTERACTION · 41 experiments
- TERTO14746 · UniProt INTERACTION · 11 experiments
- TP53P04637 · UniProt INTERACTION · 10 experiments
- UBE2IP63279 · UniProt INTERACTION · 3 experiments
- VPS72Q15906 · UniProt INTERACTION · 12 experiments
- YY1P25490 · UniProt INTERACTION · 11 experiments
- ZNHIT2Q9UHR6 · UniProt INTERACTION · 10 experiments
- I79_017133G3I183 · UniProt INTERACTION · 2 experiments
RUVBL1 可形成同源六聚環,也能與 RUVBL2 組成由兩個堆疊六聚環構成的十二聚體;但各六聚環的寡聚狀態尚未確定。寡聚化可能調節核酸結合,而核酸結合也可能影響十二聚體組裝。RUVBL1 直接與 EP400 互作,並是 NuA4、INO80、SWR1-like、R2TP 及 PAQosome 等複合體的組成部分;它也可與 MYC 的轉錄活化區互作。與 DHX34 互作會改變複合體中 RUVBL2 的 N 端構形,並使複合體失去核苷酸結合能力及 ATP 水解能力。微生物感染時,RUVBL1 與腮腺炎病毒 L polymerase 互作,該互作可調節病毒轉錄。
疾病與遺傳關聯
Contextual Functional Evidence Matrix
矩陣以「功能主張」為列,以細胞情境、干預條件、量測結果與證據來源為欄,方便比較同一功能在不同條件下的支持情形。只有含情境與實驗資訊的紀錄會列入矩陣;一般功能註解另列於下方。
功能註解總覽 · 5 筆
| 功能面向 | 功能敘述 | 證據類型 | 可查核來源 |
|---|---|---|---|
| 功能 | RUVBL1 具有受單股 DNA 刺激的 ATPase 活性,以及 ATP 依賴、方向為 3′ 至 5′ 的 DNA 解旋酶活性;六聚化被認為對 ATP 水解至關重要,環狀結構中的相鄰次單元也參與 ATPase 活性。它是 NuA4、SWR1-like 與 INO80 等染色質相關複合體的組成部分,涉及組蛋白乙醯化、核小體重塑、轉錄調控及 DNA 修復。RUVBL1 對 MYC 介導的致癌轉化及細胞增殖具有重要作用,也可調節 LEF1/TCF1-CTNNB1 複合體的轉錄活化;其可能在細胞表面結合 plasminogen 並促進其活化。 | 含實驗來源 | 證據與來源Possesses single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase (3' to 5') activity; hexamerization is thought to be critical for ATP hydrolysis and adjacent subunits in the ring-like structure contribute to the ATPase activity. Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome-DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage. Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome. Proposed core component of the chromatin remodeling INO80 complex which exhibits DNA- and nucleosome-activated ATPase activity and catalyzes ATP-dependent nucleosome sliding. Plays an essential role in oncogenic transformation by MYC and also modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex. Essential for cell proliferation. May be able to bind plasminogen at cell surface and enhance plasminogen activation PMID 10882073 ↗ · PMID 11027681 ↗ · PMID 14506706 ↗ · PMID 14966270 ↗ · PMID 16014379 ↗ · PMID 16230350 ↗ · PMID 17157868 ↗ · PMID 21303910 ↗ · PMID 24463511 ↗ · PMID 33205750 ↗ |
| 分子活性 | ATP + H2O = ADP + phosphate + H(+) | 含實驗來源 | |
| 交互作用 | RUVBL1 可形成同源六聚環,並可與 RUVBL2 組成由兩個堆疊六聚環構成的十二聚體,但在兩者等莫耳存在時,各六聚環的寡聚狀態仍不清楚;寡聚化與核酸結合可能彼此影響。它與 MYC 轉錄活化區及 EP400 互作,也參與 RNA polymerase II holoenzyme、NuA4、INO80、SWR1-like、R2TP、PAQosome 等複合體,並與多種其他蛋白質互作或共同組成複合體。DHX34 造成 RUVBL2 N 端構形改變,進而使複合體喪失核苷酸結合及 ATP 水解能力。 | 含實驗來源 | 證據與來源Forms homohexameric rings. Can form a dodecamer with RUVBL2 made of two stacked hexameric rings; however, even though RUVBL1 and RUVBL2 are present in equimolar ratio, the oligomeric status of each hexamer is not known. Oligomerization may regulate binding to nucleic acids and conversely, binding to nucleic acids may affect the dodecameric assembly. Interaction of the complex with DHX34 results in conformational changes of the N-terminus of the RUVBL2 subunits, resulting in loss of nucleotide binding ability and ATP hydrolysis of the complex. Interacts with the transcriptional activation domain of MYC. Component of the RNA polymerase II holoenzyme complex. May also act to bridge the LEF1/TCF1-CTNNB1 complex and TBP. Component of the NuA4 histone acetyltransferase complex which contains the catalytic subunit KAT5/TIP60 and the subunits EP400, TRRAP/PAF400, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, ING3, actin, ACTL6A/BAF53A, MORF4L1/MRG15, MORF4L2/MRGX, MRGBP, YEATS4/GAS41, VPS72/YL1 and MEAF6. The NuA4 complex interacts with MYC and the adenovirus E1A protein. RUVBL1 interacts with EP400. Component of a NuA4-related complex which contains EP400, TRRAP/PAF400, SRCAP, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, actin, ACTL6A/BAF53A, VPS72 and YEATS4/GAS41. Component of the BAF53 complex, at least composed of ACTL6A/BAF53A, RUVBL1/TIP49, SMARCA2/BRM, and TRRAP/PAF400. Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BACC1, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, MYST1/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Associates with alpha and gamma tubulins, particularly during metaphase and early anaphase. Interacts with NPAT. Component of the chromatin-remodeling INO80 complex; specifically part of a complex module associated with the helicase ATP-binding and the helicase C-terminal domain of INO80. Interacts with IGHMBP2. Interacts with OFD1. Interacts with HINT1. Component of a complex with USP49 and PSMC5. Component of a SWR1-like complex. Component of the R2TP complex composed at least of RUVBL1, RUVBL2, RPAP3 and PIHD1. Component of the PAQosome complex which is responsible for the biogenesis of several protein complexes and which consists of R2TP complex members RUVBL1, RUVBL2, RPAP3 and PIH1D1, URI complex members PFDN2, PFDN6, PDRG1, UXT and URI1 as well as ASDURF, POLR2E and DNAAF10/WDR92. Interacts with PIH1D1. Interacts with ITFG1. Interacts with WAC; WAC positively regulates MTOR activity by promoting the assembly of the TTT complex composed of TELO2, TTI1 and TTI2 and the RUVBL complex composed of RUVBL1 and RUVBL2 into the TTT-RUVBL complex which leads to the dimerization of the mTORC1 complex and its subsequent activation. The RUVBL1/RUVBL2 complex interacts with ZNHIT1 (via HIT-type zinc finger), ZNHIT3 (via HIT-type zinc finger), ZNHIT6 (via HIT-type zinc finger) and DDX59/ZNHIT5 (via HIT-type zinc finger) in the presence of ADP. Interacts with NOPCHAP1; the interaction is direct and disrupted upon ATP binding. Interacts with SMG1. Interacts with NOP2, NOP56 and NUFIP1 PMID 10428817 ↗ · PMID 10882073 ↗ · PMID 10966108 ↗ · PMID 11839798 ↗ · PMID 12963728 ↗ · PMID 14506706 ↗ · PMID 14966270 ↗ · PMID 15960975 ↗ · PMID 16014379 ↗ · PMID 16230350 ↗ · PMID 17060327 ↗ · PMID 17157868 ↗ · PMID 17636026 ↗ · PMID 17761535 ↗ · PMID 17967892 ↗ · PMID 18026119 ↗ · PMID 19299493 ↗ · PMID 20864032 ↗ · PMID 21303910 ↗ · PMID 23824326 ↗ · PMID 24463511 ↗ · PMID 25437307 ↗ · PMID 26812014 ↗ · PMID 28561026 ↗ · PMID 30337683 ↗ · PMID 31738558 ↗ · PMID 33205750 ↗ · PMID 33367824 ↗ · PMID 36161484 ↗ |
| 交互作用 | 在微生物感染情境下,RUVBL1 與腮腺炎病毒 L polymerase 互作;此互作會調節病毒轉錄。 | 含實驗來源 | 證據與來源(Microbial infection) Interacts with Mumps L polymerase; this interaction regulates the viral transcription PMID 31121004 ↗ |
| 細胞定位 | RUVBL1 主要位於細胞核的核基質或核質,也可出現在細胞質及細胞膜。其定位隨有絲分裂進程變動:前期與前中期位於中心體及分枝微管紡錘體;核膜解體後聚集於中心體和微管蛋白聚合位置;中期至末期靠近中心體,後於後期聚集於微管交錯區、末期位於極性微管重疊處,並在子細胞染色體去凝縮位置再次出現。 | 含實驗來源 | 證據與來源Nucleus matrix; Nucleus, nucleoplasm; Cytoplasm; Membrane; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Dynein axonemal particle; Mainly localized in the nucleus, associated with nuclear matrix or in the nuclear cytosol, although it is also present in the cytoplasm and associated with the cell membranes. In prophase and prometaphase it is located at the centrosome and the branching microtubule spindles. After mitotic nuclear membrane disintigration it accumulates at the centrosome and sites of tubulin polymerization. As cells pass through metaphase and into telophase it is located close to the centrosome at the early phase of tubulin polymerization. In anaphase it accumulates at the zone of tubule interdigitation. In telophase it is found at polar tubule overlap, and it reappears at the site of chromosomal decondensation in the daughter cells PMID 11027681 ↗ |
核酸與蛋白質序列
AGTAACGGCCGCATGGTAACTCAGGCGCCGGGCGCACTGT40CCTAGCTGCTGGTTTTCCACGCTGGTTTTAGCTCCCGGCG80TCTGCAAAATGAAGATTGAGGAGGTGAAGAGCACTACGAA120GACGCAGCGCATCGCCTCCCACAGCCACGTGAAAGGGCTG160GGGCTGGACGAGAGCGGCTTGGCCAAGCAGGCGGCCTCAG200GGCTTGTGGGCCAGGAGAACGCGCGAGAGGCATGTGGCGT240CATAGTAGAATTAATCAAAAGCAAGAAAATGGCTGGAAGA280GCTGTCTTGTTGGCAGGACCTCCTGGAACTGGCAAGACAG320CTCTGGCTCTGGCTATTGCTCAGGAGCTGGGTAGTAAGGT360CCCCTTCTGCCCAATGGTGGGGAGTGAAGTTTACTCAACT400GAGATCAAGAAGACAGAGGTGCTGATGGAGAACTTCCGCA440GGGCCATTGGGCTGCGAATAAAGGAGACCAAGGAAGTTTA480TGAAGGTGAAGTCACAGAGCTAACTCCGTGTGAGACAGAG520AATCCCATGGGAGGATATGGCAAAACCATTAGCCATGTGA560TCATAGGACTCAAAACAGCCAAAGGAACCAAACAGTTGAA600ACTGGACCCCAGCATTTTTGAAAGTTTGCAGAAAGAGCGA640GTAGAAGCTGGAGATGTGATTTACATTGAAGCCAACAGTG680GGGCCGTGAAGAGGCAGGGCAGGTGTGATACCTATGCCAC720AGAATTCGACCTTGAAGCTGAAGAGTATGTCCCCTTGCCA760AAAGGGGATGTGCACAAAAAGAAAGAAATCATCCAAGATG800TGACCTTGCATGACTTGGATGTGGCTAATGCGCGGCCCCA840GGGGGGACAAGATATCCTGTCCATGATGGGCCAGCTAATG880AAGCCAAAGAAGACAGAAATCACAGACAAACTTCGAGGGG920AGATTAATAAGGTGGTGAACAAGTACATCGACCAGGGCAT960cDNA 使用 DNA 字母 T;mRNA 模式改以 U 顯示。轉錄本保留已註解的非編碼區,未另外加入 poly(A) 尾;非編碼 RNA 的參考轉錄本也可能仍需後續加工。數字為所選序列的 1-based 位置。長序列以黃色捲軸瀏覽,可複製或下載完整轉錄本與蛋白質;基因組 DNA 隨捲動取得所需範圍。