基因總覽
RUVBL2 是蛋白質編碼基因，產物正式名稱為 RuvB like AAA ATPase 2，屬於 RuvB 家族。它是一種具 ATPase 活性的蛋白質，也具有受單股 DNA 刺激的 ATP 水解活性，以及 ATP 依賴的 DNA 解旋酶活性。其功能與多種大型蛋白質複合體相關，包括染色質重塑及組蛋白乙醯轉移酶複合體。RUVBL2 可形成六聚環，並能與 RUVBL1 組成由兩個六聚環堆疊而成的十二聚體；不過，該十二聚體中各六聚環的寡聚狀態尚未確定。
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 |
|---|---|---|
| ENST00000595090 ★ | 48,993,887–49,015,970 | 15 |
| ENST00000888166 | 48,993,476–49,015,926 | 15 |
| ENST00000888167 | 48,993,476–49,017,868 | 13 |
| ENST00000888168 | 48,993,476–49,017,868 | 15 |
| ENST00000888170 | 48,993,476–49,017,868 | 15 |
| ENST00000940725 | 48,993,476–49,017,868 | 8 |
| ENST00000940726 | 48,993,476–49,017,868 | 15 |
| ENST00000940727 | 48,993,476–49,017,868 | 15 |
| ENST00000940728 | 48,993,476–49,017,868 | 11 |
| ENST00000940729 | 48,993,476–49,017,868 | 12 |
| ENST00000988187 | 48,993,476–49,015,925 | 15 |
| ENST00001033080 | 48,993,476–49,017,868 | 13 |
顯示 12/24 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
RUVBL2 具有 ATPase 與 DNA 解旋酶活性：單股 DNA 可刺激其 ATP 水解，而 DNA 解旋方向為 5′ 至 3′。六聚化被認為對 ATP 水解至關重要，環狀結構中相鄰的次單元也共同參與 ATPase 活性。這些性質使 RUVBL2 能參與染色質相關複合體的功能，但其在各複合體中的具體貢獻並不完全相同。
在 NuA4 組蛋白乙醯轉移酶複合體中，RUVBL2 是其組成成分。NuA4 主要透過乙醯化核小體組蛋白 H4 與 H2A，促進特定基因的轉錄活化；這種修飾可能改變核小體與 DNA 的互動，也可能促進修飾後組蛋白與其他正向調節轉錄的蛋白質結合。NuA4 可能參與致癌基因及原癌基因引起的生長誘導、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 修復等轉錄程序。RUVBL1、RUVBL2 與 EP400 的結合，似乎至少部分提供該複合體的 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 DNA 修復。
RUVBL2 也是 SWR1-like 複合體的組成成分，該複合體可特異性移除核小體中的組蛋白 H2A.Z/H2AZ1。它被提出為 INO80 染色質重塑複合體的核心成分；INO80 複合體具有受 DNA 與核小體活化的 ATPase 活性，並可依賴 ATP 推動核小體滑動。這些複合體涉及核小體狀態的調整，但來源未將所有效應單獨歸因於 RUVBL2。
在轉錄調控方面，RUVBL2 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；它也可能抑制 ATF2 的轉錄活性。此外，RUVBL2 參與內質網相關降解（ERAD）途徑，並在該途徑中負向調節內質網壓力反應基因的表現；它也可能參與調節 U5 snRNP 複合體的組成。
Promoter 與基因調控
>RUVBL2 ENST00000595090 GRCh38 chr19:48992887-48993987 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 AGGTCACAAGGGTTCCCCTAGTAGCCCCGTCCTCCTACAACTCAGAGTTCCGGGCCCCCATCCACTACTG TCCTTCTCGTCAAGGGCCCCGACGCCTGGCGTGCTCACCCTTGTTAGCCACCTCCCAGGCCACTTCGAAG AGCACTGCGTTCTCCAGGTCGAATTCATCCTCCCAGTCCTCCAGTCCTGGCAGTGAGGACATGGACAAAG TGCGGTTTAAAGGCATGGCTGGCGCAGGAAGGGGGGCTCCGGGGATCTCCAGGTAGGGACCCCGGAGGTG TCTAGGGAATGCACCAGGTAGGGTGCGGGGCCGAGTAGCTGGTGCCCGACGGGAAGCTTGCAAGACGCTC GGCTTCCTATTGCAAGACCGCACCCCTGCCCCGAAGCGTTGGGACCTAGGCAGAAGGAGGCCGCAGCGTC ACTGAGCCCACTGGCGCCCCTGCAGTGAAACCTCGCAGCCGCCAGGAGGCGGTGGCCGCCCCCCCCAGCC AGCGCCATTGGCCCACGCCCGGGGGCGGGGATTTCCGCGTGTCCTCATTGGTGGAACGGGTTGGAGTCGC TGTGTCCCGGCCCCGCCTCGGCCGTGAGACCTCCAGGGGGCGGAGCTTGCCGCTGCGCTTTACGGAAACG AGTGGCCTTCAGCTCTGTCAATCTGGAGCTGGAGGCCTCAAAGTGGGGAGGAGGAGGAGGGTGGGATAAA GAGGAAAGGAGCGTGGAGGACGTGTGGTTACTCAAAGAACAGCTAAGAATTTTGCAATCGGCCTGAGCGG GGCGGTGGTGGGGCTGAGCAAAAGGAGGAGGAGCCAGGAGACATTGGGAATGGACCCAGGAGTTCCGGAC GCCCGTCTTCCAGCGCAGCCTCGGTGGGAGGGCGGGGCATAAAGTCCCGCCACGCCCCCACAATATTTAC ATATTTATGAGGAACCATCGAGATCTTTGAAGAACCAGCTAGCCTAGAGGAGCCAGAACATCTCGCTCCT CGCGCGTTTCCGTTTCCGCTAGGACTCTGGCAGTTGGTGAGCATCATGGCAACCGTTGTAAGTGTGGGTG CATGGAGGGTGAGGAGCGAGCTAGCAGTCTCGAGTTTGAGAGAGGAGGATG
EPDnew 實驗支持 promoter／TSS · 2 筆
| EPDnew ID | TSS（1-based） | 股向 | 來源顯示區間 |
|---|---|---|---|
| RUVBL2_2 ↗ | 19:48,993,533 | 正股 | 48,993,484–48,993,543 |
| RUVBL2_1 ↗ | 19:48,993,898 | 正股 | 48,993,849–48,993,908 |
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
ENSR19_BCPHN · enhancer · 48989690–48990380 · regulatory
ENSR19_C6T92 · enhancer · 48991698–48993298 · regulatory
ENSR19_BCPJ7 · promoter · 48993299–48993897 · regulatory
ENSR19_5FJ5R3 · CTCF_binding_site · 48993341–48993362 · regulatory
ENSR19_5FJ5RN · CTCF_binding_site · 48993472–48993493 · regulatory
ENSR19_BCPJ9 · enhancer · 48993898–48994494 · regulatory
ENSR19_9PG4N · enhancer · 48997884–48998392 · regulatory
· motif · 48993096–48993104 · motif
· motif · 48993343–48993359 · motif
· motif · 48993397–48993407 · motif
· motif · 48993406–48993417 · motif
· motif · 48993406–48993417 · motif
· motif · 48993474–48993490 · motif
· motif · 48993482–48993492 · motif
· motif · 48993754–48993764 · motif
· motif · 48993775–48993785 · motif
· motif · 48993788–48993801 · motif
· motif · 48993792–48993805 · motif
· motif · 48993792–48993805 · motif
· motif · 48994737–48994746 · motif
· motif · 48994737–48994746 · motif
蛋白質結構域與序列
參考蛋白質長度：463 aa
RuvB like AAA ATPase 2 屬於 RuvB 家族。來源未提供其特定結構域、序列區段或其他蛋白質結構註解，因此不進一步描述其結構細節。
蛋白質三維結構
細胞內定位
RUVBL2 主要位於細胞核，可與核基質或核質相關；此外也存在於細胞質，並與細胞膜相關。 來源另列出 dynein axonemal particle，但未說明此定位的條件或動態變化。
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 8 個夥伴
- DNAAF19Q8IW40 · UniProt INTERACTION · 3 experiments
- DNAJB4Q9UDY4 · UniProt INTERACTION · 3 experiments
- DPCDQ9BVM2 · UniProt INTERACTION · 14 experiments
- EP400Q96L91 · UniProt INTERACTION · 6 experiments
- LNX1Q8TBB1 · UniProt INTERACTION · 6 experiments
- RUVBL1Q9Y265 · UniProt INTERACTION · 41 experiments
- YY1P25490 · UniProt INTERACTION · 11 experiments
- DpcdQ8BPA8 · UniProt INTERACTION · 2 experiments
RUVBL2 可形成同源六聚環，也可與 RUVBL1 組成十二聚體；其與 DHX34 互作會改變 RUVBL2 次單元的 N 端構形，使複合體失去核苷酸結合及 ATP 水解能力。它是 NuA4、INO80、SWR1-like、R2TP 與 PAQosome 等複合體的組成成分，並與 EP400、MYC、ATF2 等蛋白質互作。另有研究指出，感染情境下 RUVBL2 與腮腺炎病毒的 L polymerase 互作，並調節病毒轉錄。
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 | RUVBL2 具有受單股 DNA 刺激的 ATPase 活性，以及 ATP 依賴、方向為 5′ 至 3′ 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共同貢獻 ATPase 活性。它參與 NuA4、SWR1-like 與 INO80 等染色質複合體，涉及組蛋白修飾、核小體調整與轉錄調控；另與 MYC 介導的致癌轉化、ERAD 中壓力反應基因的負向調節，以及可能的 U5 snRNP 組成調節有關。 | 含實驗來源 | 證據與來源Possesses single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase (5' to 3') 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. May also inhibit the transcriptional activity of ATF2. Involved in the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway where it negatively regulates expression of ER stress response genes. May play a role in regulating the composition of the U5 snRNP complex PMID 10428817 ↗ · PMID 10882073 ↗ · PMID 11713276 ↗ · PMID 14966270 ↗ · PMID 16014379 ↗ · PMID 16230350 ↗ · PMID 17157868 ↗ · PMID 21303910 ↗ · PMID 24463511 ↗ · PMID 25652260 ↗ · PMID 28561026 ↗ · PMID 33205750 ↗ |
| 分子活性 | ATP + H2O = ADP + phosphate + H(+) | 含實驗來源 | |
| 交互作用 | RUVBL2 可形成同源六聚環，並能與 RUVBL1 組成堆疊的十二聚體，但各六聚環的寡聚狀態尚不清楚；寡聚化與核酸結合可能互相影響。DHX34 互作會改變 RUVBL2 N 端構形，造成核苷酸結合及 ATP 水解能力喪失。RUVBL2 也與 MYC、ATF2 等互作，並為多種轉錄、染色質重塑及蛋白質複合體的成員，包括 NuA4、INO80、R2TP 與 PAQosome；部分互作受 ATP 或 ADP 條件影響。 | 含實驗來源 | 證據與來源Forms homohexameric rings. Can form a dodecamer with RUVBL1 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. Interacts with ATF2. 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. RUVBL2 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. 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. 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. Interacts with IGHMBP2. Interacts with TELO2. Interacts with HINT1. 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 ITFG1. Interacts with ZMYND10. 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. Forms a complex with APPL1 and APPL2. Interacts with ZNHIT2 (via HIT-type zinc finger) in the presence of ATP or ADP; shows a stronger interaction in the presence of ADP. 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 PMID 10428817 ↗ · PMID 10882073 ↗ · PMID 10966108 ↗ · PMID 11713276 ↗ · PMID 12963728 ↗ · PMID 14966270 ↗ · PMID 15960975 ↗ · PMID 16014379 ↗ · PMID 16230350 ↗ · PMID 17157868 ↗ · PMID 17967892 ↗ · PMID 18026119 ↗ · PMID 19299493 ↗ · PMID 19433865 ↗ · PMID 20801936 ↗ · PMID 20864032 ↗ · PMID 21303910 ↗ · PMID 24463511 ↗ · PMID 25437307 ↗ · PMID 26812014 ↗ · PMID 28561026 ↗ · PMID 29601588 ↗ · PMID 31738558 ↗ · PMID 33205750 ↗ · PMID 33367824 ↗ |
| 交互作用 | 在微生物感染情境中，RUVBL2 與腮腺炎病毒的 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 | RUVBL2 主要位於細胞核，與核基質或核質相關；此外也存在於細胞質，並與細胞膜相關。來源列出的定位還包括 dynein axonemal particle，但未提供該定位的條件或動態資訊。 | 推論支持 | 證據與來源Nucleus matrix; Nucleus, nucleoplasm; Cytoplasm; Membrane; 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 |
核酸與蛋白質序列
AGGACTCTGGCAGTTGGTGAGCATCATGGCAACCGTTACA40GCCACAACCAAAGTCCCGGAGATCCGTGATGTAACAAGGA80TTGAGCGAATCGGTGCCCACTCCCACATCCGGGGACTGGG120GCTGGACGATGCCTTGGAGCCTCGGCAGGCTTCGCAAGGC160ATGGTGGGTCAGCTGGCGGCACGGCGGGCGGCTGGCGTGG200TGCTGGAGATGATCCGGGAAGGGAAGATTGCCGGTCGGGC240AGTCCTTATTGCTGGCCAGCCGGGCACGGGGAAGACGGCC280ATCGCCATGGGCATGGCGCAGGCCCTGGGCCCTGACACGC320CATTCACAGCCATCGCCGGCAGTGAAATCTTCTCCCTGGA360GATGAGCAAGACCGAGGCGCTGACGCAGGCCTTCCGGCGG400TCCATCGGCGTTCGCATCAAGGAGGAGACGGAGATCATCG440AAGGGGAGGTGGTGGAGATCCAGATTGATCGACCAGCAAC480AGGGACGGGCTCCAAGGTGGGCAAACTGACCCTCAAGACC520ACAGAGATGGAGACCATCTACGACCTGGGCACCAAGATGA560TTGAGTCCCTGACCAAGGACAAGGTCCAGGCCGGGGACGT600GATCACCATCGACAAGGCGACGGGCAAGATCTCCAAGCTG640GGCCGCTCCTTCACACGCGCCCGCGACTACGACGCTATGG680GCTCCCAGACCAAGTTCGTGCAGTGCCCAGATGGGGAGCT720CCAGAAACGCAAGGAGGTGGTGCACACCGTGTCCCTGCAC760GAGATCGACGTCATCAACTCTCGCACCCAGGGCTTCCTGG800CGCTCTTCTCAGGTGACACAGGGGAGATCAAGTCAGAAGT840CCGTGAGCAGATCAATGCCAAGGTGGCTGAGTGGCGCGAG880GAGGGCAAGGCGGAGATCATCCCTGGAGTGCTGTTCATCG920ACGAGGTCCACATGCTGGACATCGAGAGCTTCTCCTTCCT960cDNA 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。