基因總覽
SMARCA5 是蛋白質編碼基因，產物英文名稱為 SNF2 related chromatin remodeling ATPase 5，屬於 SNF2/RAD54 helicase family 的 ISWI subfamily。此蛋白質是多種 ISWI 染色質重塑複合體的催化次單元，能以 ATP 水解提供核小體重塑所需的能量。其主要角色是參與染色質中核小體的組織與重新配置，讓 DNA 在染色質結構中的可及性受到調節。不同複合體成員會影響其催化活性及核小體移動特性，因此 SMARCA5 的作用方式會隨所屬複合體而異。
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 |
|---|---|---|
| ENST00000283131 ★ | 143,513,702–143,557,486 | 24 |
| ENST00000885350 | 143,513,445–143,557,486 | 23 |
| ENST00000913619 | 143,513,445–143,557,486 | 24 |
| ENST00000913620 | 143,513,445–143,557,486 | 22 |
| ENST00000913621 | 143,513,445–143,557,486 | 23 |
| ENST00000940951 | 143,513,445–143,557,486 | 24 |
| ENST00000940952 | 143,513,445–143,557,486 | 25 |
| ENST00000940953 | 143,513,445–143,557,486 | 24 |
| ENST00000940954 | 143,513,445–143,557,486 | 23 |
| ENST00000940955 | 143,513,445–143,557,486 | 23 |
| ENST00000940956 | 143,513,445–143,557,486 | 22 |
| ENST00001077283 | 143,513,445–143,557,486 | 24 |
顯示 12/16 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
SMARCA5 具有 ATP 依賴性的核小體重塑活性，能水解 ATP，並在 ISWI 染色質重塑複合體中移動 DNA 上的 histone octamer。依複合體組成不同，核小體可沿 DNA 模板重新定位；含 BAZ1A/ACF1、BAZ1B/WSTF、BAZ2A/TIP5 或 BAZ2B 的複合體能調節核小體間距，並可使單一核小體以 ATP 依賴方式移向 DNA 模板中央。含 CECR2 或 RSF1 的複合體則不具將單一核小體移至中央的能力。此類重塑有助於形成有序核小體排列，並促進 DNA 複製、轉錄及修復等 DNA 模板依賴過程中的 DNA 可及性；此作用可能需要完整的 histone H4 尾端。
SMARCA5 也參與特定複合體所執行的染色質整理。與 RSF1 一同結合核心 histone，並為 RSF-5 複合體組裝規則的核小體陣列所需。它是 WICH-5 複合體的重要成分，該複合體可移動核小體，將不規則染色質重新整理為規則核小體陣列。SMARCA5 與 BAZ1A/ACF1 共同參與 S 期周著絲粒異染色質的複製，並涉及複製期間染色質結構的維持。
不同複合體亦將 SMARCA5 的功能連結至轉錄調控。WICH-5 參與多種基因的轉錄及 RNA polymerase I 轉錄；在 B-WICH 複合體中，SMARCA5 與 RNA polymerase III 轉錄有關。它可能透過將 SIN3/HDAC1 corepressor 複合體募集至 rDNA 啟動子，參與抑制 RNA polymerase I 依賴的 rDNA 轉錄；此項描述為相似性推論。NoRC-5 則透過募集 histone 修飾酵素與 DNA methyltransferases，使部分 rDNA 沉默並形成異染色質。另有資料指出 SMARCA5 介導 histone H2AX 在 Tyr-142 的磷酸化。
Promoter 與基因調控
>SMARCA5 ENST00000283131 GRCh38 chr4:143512702-143513802 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 CACAAGGCCCTTAAGCTGCATTGAAGGCTGCCTAAGGCAGTATACAAAATCAGTGCTGAATATTTGTTAA CACTTAAGGAGAATGTACGTTTTAATTTTCATGTTTGATGCTTGGGGAAAAGATTACATCGCACCACCTA TCTTCCCCATATATTGATTATTCGTGTTTCTCACTTCCATGGTAGTGTGCACGTTATTTGCTTAACTTTG GCATATAAATTCAGAAGAAATATCATTTAACTCTGTGCCTAAGGAGGGTATTTAGAAATAACCGACGCAG CTAACATGAGAAGGCAAAAAAAAAAAAAAAGAAAAAAGAAAAAAATCACACTAACGGACTTTTTTTTTTT TTCTAACAACAAAAAACCGTGAGACTTCACTTGGGGTAACCATAACGTCGTCAAGGCTGTGGCGTCACGC CTCTAAGCGGATACGGCAGAAGTTTTGGGGCCAGACACAAGACTTCCAAGTTTGAATGGGCAGCGCAAAA CCCAGACAAGTTTTCCGGTAGTGCCGCCAACCCCTGTCAGGCACAGAAGACACAGCGAGAACCGTGAGCC GTTACGAAAGCCTAAAACACTGAGCTCGCGTCCTGCCAAGCAGCAGGCGCACAAACCTACACCTCCGAGC GCTCCCTGGAGGTCCCGCCCACTCTTCTCTCCCGAGCCGGCTAGAGATCTGGAAGAGGGCGGGCCAAGGG TGAGGAGGGCAGTATGCGCATGCGCGCTCAGGACCCAGTCAGTGAGCCAATAAGGAATCTCGCGAGTGTT GAAAGTCGGTGGCGTAGGTCGTCGTCCTGGATGCTGGCGAGATAGATGTTATCTTCCAGAGGAAGAGGAG GAGGCGGCGAAGCGTTTTCCCAGCCTCAGTCTCTCTTTCGTTTTCCTTTTCCCTTCCCCCAACCCTCCGC CCTTCTCTAAATCAGCCGGCCTTCCTTGACCTCAGTGACCCGTCTGGCCCCGCCCACCCTCGTCGACGTG ATTCCCGCCGTGAGGTAAGCGCCGGTGGAACCTAGAGCCCCGCGGAAGAGCAGAACGTTTGGGAGTGTGC AGCTCCTGGGCCCGGCTCAGGCCCGTCGCGGAGGCGCGGCGCAGGGGAGCG
EPDnew 實驗支持 promoter／TSS · 2 筆
| EPDnew ID | TSS（1-based） | 股向 | 來源顯示區間 |
|---|---|---|---|
| SMARCA5_1 ↗ | 4:143,513,463 | 正股 | 143,513,414–143,513,473 |
| SMARCA5_2 ↗ | 4:143,513,708 | 正股 | 143,513,659–143,513,718 |
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
ENSR4_538QDS9 · CTCF_binding_site · 143512829–143512850 · regulatory
ENSR4_944XZT · promoter · 143513212–143513712 · regulatory
ENSR4_538QDX8 · CTCF_binding_site · 143513469–143513490 · regulatory
ENSR4_944Z29 · promoter · 143514625–143515125 · regulatory
· motif · 143510228–143510241 · motif
· motif · 143510228–143510241 · motif
· motif · 143512831–143512847 · motif
· motif · 143513107–143513122 · motif
· motif · 143513391–143513404 · motif
· motif · 143513398–143513413 · motif
· motif · 143513416–143513427 · motif
· motif · 143513416–143513427 · motif
· motif · 143513471–143513487 · motif
· motif · 143513568–143513588 · motif
· motif · 143513574–143513594 · motif
· motif · 143513580–143513600 · motif
· motif · 143513634–143513646 · motif
· motif · 143513637–143513644 · motif
· motif · 143513658–143513668 · motif
· motif · 143514043–143514060 · motif
· motif · 143514622–143514632 · motif
· motif · 143517973–143517986 · motif
· motif · 143517973–143517986 · motif
蛋白質結構域與序列
參考蛋白質長度：1052 aa
SNF2 related chromatin remodeling ATPase 5 長 1,052 個胺基酸，屬於 SNF2/RAD54 helicase family 的 ISWI subfamily。蛋白質含 Helicase ATP-binding domain、Helicase C-terminal domain，以及兩個 SANT domain；另註有 DEAH box motif。序列兩端分別有預測為無序的區域：第 1–83 位及第 1,015–1,052 位。
蛋白質三維結構
細胞內定位
SMARCA5 位於細胞核及染色體，並可定位於有絲分裂染色體。 其位置會隨細胞週期與情境改變：S 期與 PCNA 同位於複製焦點，晚期 S 期則與 BAZ1B/WSTF 同位於複製焦點；與 SIRT6 互作後，SMARCA5 會被募集至 DNA 損傷位置。
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：Chromosome。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 5 個夥伴
- BAZ1AQ9NRL2 · UniProt INTERACTION · 4 experiments
- BAZ1BQ9UIG0 · UniProt INTERACTION · 8 experiments
- BPTFQ12830 · UniProt INTERACTION · 2 experiments
- H4C9P62805 · UniProt INTERACTION · 2 experiments
- RSF1Q96T23 · UniProt INTERACTION · 6 experiments
SMARCA5 是 ACF-5、CHRAC、WICH-5、NoRC-5、BRF-5、NURF-5、CERF-5、RSF-5 與 B-WICH 等 ISWI 複合體的成分，並在多個複合體中與其搭檔直接或以來源所述方式互作。與 BAZ1A/ACF1 的直接互作有助於核小體滑動；CHRAC1–POLE3 異二聚體可與 SMARCA5–BAZ1A/ACF1 配合增強滑動活性，但不會增強 ACF-5 的滑動活性。SMARCA5 亦直接互作 RAD21、HDAC2、RBBP4 與 CHD4，並與 PCNA、BEND3 及 SIRT6 互作。感染情境下，另有與 JC virus small t antigen 及 Epstein Barr virus（EBV）裂解期轉換蛋白 BZLF1 的互作紀錄。
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 · 6 筆
| 功能面向 | 功能敘述 | 證據類型 | 可查核來源 |
|---|---|---|---|
| 功能 | SMARCA5 是具內在 ATP 依賴性核小體重塑活性的 ATPase，也是多種 ISWI 複合體的催化次單元，可移動核小體並調節其排列，使 DNA 在複製、轉錄與修復等過程中較易被接近；此作用可能需要完整 histone H4 尾端。複合體組成會影響核小體滑動能力。SMARCA5 另參與異染色質複製、染色質結構維持及多種 RNA polymerase 轉錄調控；部分 rDNA 沉默與 histone H2AX 磷酸化描述屬相似性推論。 | 含實驗來源 | 證據與來源ATPase that possesses intrinsic ATP-dependent nucleosome-remodeling activity. Catalytic subunit of ISWI chromatin-remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair; this may require intact histone H4 tails. Within the ISWI chromatin-remodeling complexes, slides edge- and center-positioned histone octamers away from their original location on the DNA template. Catalytic activity and histone octamer sliding propensity is regulated and determined by components of the ISWI chromatin-remodeling complexes. The BAZ1A/ACF1-, BAZ1B/WSTF-, BAZ2A/TIP5- and BAZ2B-containing ISWI chromatin-remodeling complexes regulate the spacing of nucleosomes along the chromatin and have the ability to slide mononucleosomes to the center of a DNA template in an ATP-dependent manner. The CECR2- and RSF1-containing ISWI chromatin-remodeling complexes do not have the ability to slide mononucleosomes to the center of a DNA template. Binds to core histones together with RSF1, and is required for the assembly of regular nucleosome arrays by the RSF-5 ISWI chromatin-remodeling complex. Involved in DNA replication and together with BAZ1A/ACF1 is required for replication of pericentric heterochromatin in S-phase. Probably plays a role in repression of RNA polymerase I dependent transcription of the rDNA locus, through the recruitment of the SIN3/HDAC1 corepressor complex to the rDNA promoter (By similarity). Essential component of the WICH-5 ISWI chromatin-remodeling complex (also called the WICH complex), a chromatin-remodeling complex that mobilizes nucleosomes and reconfigures irregular chromatin to a regular nucleosomal array structure. The WICH-5 ISWI chromatin-remodeling complex regulates the transcription of various genes, has a role in RNA polymerase I transcription (By similarity). Within the B-WICH complex has a role in RNA polymerase III transcription. Mediates the histone H2AX phosphorylation at 'Tyr-142', and is involved in the maintenance of chromatin structures during DNA replication processes (By similarity). Essential component of NoRC-5 ISWI chromatin-remodeling complex, a complex that mediates silencing of a fraction of rDNA by recruiting histone-modifying enzymes and DNA methyltransferases, leading to heterochromatin formation and transcriptional silencing (By similarity) PMID 10880450 ↗ · PMID 11980720 ↗ · PMID 12198550 ↗ · PMID 12434153 ↗ · PMID 12972596 ↗ · PMID 14759371 ↗ · PMID 15543136 ↗ · PMID 16603771 ↗ · PMID 23911928 ↗ · PMID 28801535 ↗ |
| 分子活性 | ATP + H2O = ADP + phosphate + H(+) | 含實驗來源 | |
| 交互作用 | SMARCA5 參與多種 ISWI 染色質重塑複合體，並與各複合體搭檔互作。與 BAZ1A/ACF1 的直接互作可支持核小體滑動；在 CHRAC 中，POLE3-CHRAC1 異二聚體直接與 SMARCA5 及 BAZ1A/ACF1 配合，增強核小體滑動，但不會增強 ACF-5 的滑動活性。SMARCA5 亦與 RAD21、NuRD 成分 HDAC2、RBBP4、CHD4、PCNA、BEND3 及 SIRT6 互作；部分複合體成員組成與互作描述來自相似性證據。 | 含實驗來源 | 證據與來源Component of the ACF-5 ISWI chromatin-remodeling complex (also called the ACF/WCRF complex) at least composed of SMARCA5/SNF2H and BAZ1A/ACF1, which regulates the spacing of histone octamers on the DNA template to facilitate access to DNA. Within the complex interacts with BAZ1A/ACF1; the interaction is direct and is required to slide nucleosomes from end to center positions on a DNA template in an ATP-dependent manner. Component of the CHRAC ISWI chromatin-remodeling complex at least composed of SMARCA5/SNF2H, BAZ1A/ACF1, CHRAC1 and POLE3; the complex preferentially binds DNA through the CHRAC1-POLE3 heterodimer and possesses ATP-dependent nucleosome-remodeling activity. Within the complex interacts with BAZ1A/ACF1; the interaction is direct and promotes the interaction with the POLE3-CHRAC1 heterodimer. Within the complex interacts with the POLE3-CHRAC1 heterodimer; the interaction is direct and enhances nucleosome sliding activity by the SMARCA5/SNF2H and BAZ1A/ACF1 interaction. Neither POLE3 nor CHRAC1 enhances nucleosome sliding activity of the ACF-5 ISWI chromatin remodeling complex. Component of the WICH-5 ISWI chromatin-remodeling complex (also called the WICH complex) at least composed of SMARCA5/SNF2H and BAZ1B/WSTF, which regulates the spacing of histone octamers on the DNA template to facilitate access to DNA. Within the complex interacts with BAZ1B/WSTF. Component of the NoRC-5 ISWI chromatin-remodeling complex (also called the NoRC chromatin-remodeling complex) at least composed of SMARCA5/SNF2H and BAZ2A/TIP5; the complex suppresses rDNA transcription by a combination of nucleosome remodeling, histone deacetylation, and DNA methylation. Within the complex interacts with BAZ2A/TIP5. Within the complex interacts with HDAC1 (By similarity). Component of the BRF-5 ISWI chromatin-remodeling complex at least composed of SMARCA5/SNF2H and BAZ2B. Within the complex interacts with BAZ2B. Component of the NURF-5 ISWI chromatin-remodeling complex at least composed of SMARCA5/SNF2H and BPTF. Within the complex interacts with BPFT. Component of the CERF-5 ISWI chromatin-remodeling complex at least composed of SMARCA5/SNF2H and CECR2. LUZP1 is detected as part of the CERF-5 complex in embryonic stem cells where it is involved in complex stabilization but is not detected in the complex in the testis (By similarity). Within the complex interacts with CECR2. Component of the RSF-5 ISWI chromatin-remodeling complex (also called the RSF complex) at least composed of SMARCA5/SNF2H and RSF1. Within the complex interacts with RSF1. Interacts with the cohesin complex component RAD21; the interaction is direct. Interacts with the NuRD complex components HDAC2, RBBP4 and CHD4; the interactions are direct. Interacts with PCNA. Component of the B-WICH complex, at least composed of SMARCA5/SNF2H, BAZ1B/WSTF, SF3B1, DEK, MYO1C, ERCC6, MYBBP1A and DDX21 which positively regulates RNA polymerase III transcription. Interacts with MYO1C (By similarity). Interacts with BEND3. Interacts with SIRT6; promoting recruitment to DNA damage sites PMID 10880450 ↗ · PMID 11980720 ↗ · PMID 12198550 ↗ · PMID 12434153 ↗ · PMID 12972596 ↗ · PMID 14759371 ↗ · PMID 15543136 ↗ · PMID 16603771 ↗ · PMID 23911928 ↗ · PMID 26100909 ↗ · PMID 28801535 ↗ |
| 交互作用 | 在微生物感染情境中，SMARCA5 與 JC virus small t antigen 有互作紀錄；此筆敘述未提供互作效果或進一步的功能說明。 | 含實驗來源 | |
| 交互作用 | 在微生物感染情境中，SMARCA5 與 Epstein Barr virus（EBV）裂解期轉換蛋白 BZLF1 互作。此互作參與 BZLF1 活化早期病毒裂解基因的過程。 | 含實驗來源 | 證據與來源(Microbial infection) Interacts with Epstein Barr virus (EBV) lytic switch protein BZLF1; this interaction participates to the activation of early lytic viral genes by BZLF1 PMID 30926617 ↗ |
| 細胞定位 | SMARCA5 位於細胞核與染色體，並出現在有絲分裂染色體上；它在細胞核與 RSF1 共定位。S 期時，SMARCA5 與 PCNA 位於複製焦點，晚期 S 期則與 BAZ1B/WSTF 共定位。與 SIRT6 互作後，SMARCA5 會被募集至 DNA 損傷位置。 | 含實驗來源 | 證據與來源Nucleus; Chromosome; Localizes to mitotic chromosomes. Co-localizes with RSF1 in the nucleus. Co-localizes with PCNA at replication foci during S phase. Co-localizes with BAZ1B/WSTF at replication foci during late-S phase. Recruited to DNA damage sites following interaction with SIRT6 PMID 12434153 ↗ · PMID 12972596 ↗ · PMID 15543136 ↗ · PMID 33092197 ↗ · PMID 23911928 ↗ |
核酸與蛋白質序列
GCCGGTGGAACCTAGAGCCCCGCGGAAGAGCAGAACGTTT40GGGAGTGTGCAGCTCCTGGGCCCGGCTCAGGCCCGTCGCG80GAGGCGCGGCGCAGGGGAGCGCTCGGGTGGGAGTCTCGCT120CCTCCACCAGTTTATTGCGACGTAGCATCCAGGCCTAGGC160CTCCCCGTCCATCCCCGCCGGACTCGGGCCTCTGGCAGCA200GCGGGTGACGCAGACGGAACATCATGTCGTCCGCGGCCGA240GCCTCCGCCACCCCCGCCTCCCGAGAGCGCGCCTTCCAAG280CCCGCAGCCTCGATCGCCAGCGGCGGGAGCAACAGCAGCA320ACAAAGGCGGCCCCGAAGGCGTCGCGGCGCAGGCGGTTGC360GTCTGCGGCCAGCGCTGGTCCCGCAGACGCCGAGATGGAG400GAAATATTTGATGATGCGTCACCTGGAAAGCAAAAGGAAA440TCCAAGAACCAGATCCTACCTATGAAGAAAAAATGCAAAC480TGACCGGGCAAATAGATTCGAGTATTTATTAAAGCAGACA520GAACTTTTTGCACATTTCATTCAACCTGCTGCTCAGAAGA560CTCCAACTTCACCTTTGAAGATGAAACCAGGGCGCCCACG600AATAAAAAAAGATGAGAAGCAGAACTTACTATCCGTTGGC640GATTACCGACACCGTAGAACAGAGCAAGAGGAGGATGAAG680AGCTATTAACAGAAAGCTCCAAAGCAACCAATGTTTGCAC720TCGATTTGAAGACTCTCCATCGTATGTAAAATGGGGTAAA760CTGAGAGATTATCAGGTCCGAGGATTAAACTGGCTCATTT800CTTTGTATGAGAATGGCATCAATGGTATCCTTGCAGATGA840AATGGGCCTAGGAAAGACTCTTCAAACAATTTCTCTTCTT880GGGTACATGAAACATTATAGAAACATTCCTGGGCCTCATA920TGGTTTTGGTTCCTAAGTCTACATTACACAACTGGATGAG960cDNA 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。