基因總覽
SMARCB1(SWI/SNF related BAF chromatin remodeling complex subunit B1)是蛋白質編碼基因,產物屬於 SNF5 family,也是 BAF(hSWI/SNF)染色質重塑複合體的核心組成蛋白。它參與多種 SWI/SNF 相關複合體,並出現在神經前驅細胞特異性的 npBAF 複合體及神經元特異性的 nBAF 複合體中。這些複合體可依細胞與發育階段採用不同的亞基組合。SMARCB1 蛋白長 385 個胺基酸,含有 N 端 DNA 結合區,以及兩段近似串聯重複區;其序列特徵另包含與 HIV-1 integrase、MYC 及 PPP1R15A 互作相關的區域。
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 |
|---|---|---|
| ENST00000644036 ★ | 23,786,966–23,838,009 | 9 |
| ENST00000407422 | 23,786,931–23,838,009 | 9 |
| ENST00000344921 | 23,786,931–23,838,009 | 9 |
| ENST00000263121 | 23,786,931–23,838,009 | 8 |
| ENST00000877791 | 23,786,931–23,838,009 | 9 |
| ENST00000877792 | 23,786,931–23,838,009 | 10 |
| ENST00000877794 | 23,786,931–23,838,009 | 10 |
| ENST00000877795 | 23,786,931–23,838,009 | 10 |
| ENST00000923808 | 23,786,931–23,838,009 | 9 |
| ENST00000948392 | 23,786,931–23,838,009 | 9 |
| ENST00000948393 | 23,786,931–23,838,009 | 10 |
| ENST00000992969 | 23,786,931–23,834,513 | 8 |
顯示 12/23 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
SMARCB1 是 BAF(hSWI/SNF)染色質重塑複合體的核心成分。此複合體依賴 ATP,可改變染色質構形,並參與細胞增殖與分化、細胞抗病毒活動及腫瘤形成抑制等過程。SMARCB1 在體外可刺激 SMARCA4/BRG1/BAF190A 的重塑活性,也與 CSF1 啟動子的活化有關。
BAF 複合體可形成穩定且不同於一般染色質的結構,其負超螺旋受限程度較低。來源描述,這種變化可能與多核小體陣列中最多約一半的核小體轉變為不對稱結構 altosomes 有關;每個 altosomes 由兩個組蛋白八聚體構成。這提供了複合體改變染色質組織方式的結構性說明。
在神經發育期間,神經前驅細胞退出細胞週期並分化為神經元時,染色質重塑複合體的亞基組成會轉換。具有 ACTL6A/BAF53A 與 PHF10/BAF45A 的 npBAF,會由含同源替代亞基 ACTL6B/BAF53B,以及 DPF1/BAF45B 或 DPF3/BAF45C 的 nBAF 取代。npBAF 對多能神經幹細胞的自我更新及增殖能力至關重要;nBAF 則與 CREST 一同參與調節對樹突生長重要的基因活性,此項功能註記為相似性推定。
此外,SMARCB1 與細胞週期控制相關,來源指出它可造成 G0/G1 期停滯。上述作用顯示,SMARCB1 所在的複合體與染色質調節、細胞增殖狀態及神經細胞分化過程相連;但資料並未提供這些作用間更直接的因果機制。
Promoter 與基因調控
>SMARCB1 ENST00000644036 GRCh38 chr22:23785966-23787066 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 TACAAGGCCGGGCGCAGTGGCTCACACCTGTAATCCCAGCACTTTGGGAGGCCGAGGGGGGCGGATCACG AGGTCAGGAGATCGAGACCATCCTGGCTAACATGGTGAAACCCTGTCTCTACTAAAAATACAAAAAATTA GCTGGGCGTGGTGGCGGGTGCCTGTAGTCCCAGCTACTTGGGAGGCTGAGGCAGGAGACTCCAGCCTCAA AAAAAAAAAAAAGAGTTGGGATTACAGGCATGAGCCGCTGAGCCCAGCCACAGCTGCAATTTCATTAGAT TGAACGGTGTGAAATCATCAGTAGTGGGCCACTGTTTTACTCCCTGCATTATTCAATCATGATTGCTTTC AGACTTTCATTAGTTTCACTAGCTTCGCGCTGTAAGAGCCAAGAGGCAGAGCCACAGGGCTGGGCTGCCT GGTTTCACTCCCCACTGCAGGGCTCGGTTAAGCAGAGTGTAGGCTAAGAGAGGAATGGAGAAGGTGGAAG GTGTCTCTCCCTTCCAACGCTCATCTGATGCACCAGCCAAACCAAATACCACCTGGGCCTTTGAACATTG CCAAGCCTCATCCGCTGTTGTCATTTTGCCCACCTCCACAGCTGCAGGGACAGCCGTAGGCCCGGAACTG GGATATCTCTTCCTAGGGGCCTGCCTATCTGCTCAGCTGCACTGCGTTTTAGGGGTGGGGAAGCTAAGGC ACGAGATTGGGGTCCCAAAGCATGCCCAGACCACCCAGGCTTCCAGATACTAGGTCCTCCTCCTTCAGGC CTCACTTCGTTGCTTTTCCCCTGGGCTCAGTTCCAGTCCTGGCTGTAAGACTGGGAAAGCCACTGCTTGA GTCAGGACCTCATTGGCTATTTTTGTCCGTGAGAAGTCCTCTACACCACGACTTGGGAGGCAGCCTGGGA GAAAGAGAAATTAGTCGTGGCTCCTTTAAGGGGTCCGCGGAGGCGCGCCCGGCCTTTTGTTTGAGCGGCG GCGCGCGCGTCAGCGTCAACGCCAGCGCCTGCGCACTGAGGGCGGCCTGGTCGTCGTCTGCGGCGGCGGC GGCGGCTGAGGAGCCCGGCTGAGGCGCCAGTACCCGGCCCGGTCCGCATTT
EPDnew 實驗支持 promoter/TSS · 1 筆
| EPDnew ID | TSS(1-based) | 股向 | 來源顯示區間 |
|---|---|---|---|
| SMARCB1_1 ↗ | 22:23,786,978 | 正股 | 23,786,929–23,786,988 |
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
ENSR22_8NTR8 · enhancer · 23784477–23784691 · regulatory
ENSR22_B6PGC · promoter · 23786441–23787021 · regulatory
ENSR22_B6PGG · enhancer · 23787022–23788012 · regulatory
ENSR22_8NTWB · enhancer · 23789818–23790007 · regulatory
· motif · 23784397–23784410 · motif
· motif · 23784397–23784412 · motif
· motif · 23784397–23784412 · motif
· motif · 23786969–23786980 · motif
· motif · 23786969–23786980 · motif
· motif · 23787068–23787079 · motif
· motif · 23787068–23787088 · motif
· motif · 23787074–23787094 · motif
· motif · 23787392–23787402 · motif
· motif · 23787406–23787416 · motif
· motif · 23787425–23787435 · motif
· motif · 23787607–23787620 · motif
· motif · 23787610–23787622 · motif
· motif · 23787613–23787620 · motif
· motif · 23787760–23787772 · motif
· motif · 23789327–23789339 · motif
· motif · 23789329–23789344 · motif
· motif · 23789329–23789344 · motif
· motif · 23790997–23791010 · motif
蛋白質結構域與序列
參考蛋白質長度:385 aa
SMARCB1 蛋白長 385 個胺基酸,屬於 SNF5 family。其第 1–113 位胺基酸區域具有 DNA 結合註解;第 186–319 位包含兩段近似串聯重複區,其中第 186–245 位及第 259–319 位分別標示為重複區。另有與 HIV-1 integrase 結合、MYC 結合及 PPP1R15A 互作相關的區域註解。
蛋白質三維結構
細胞內定位
SMARCB1 的細胞內定位註記為細胞核;來源未提供其他定位或定位隨條件、異構型變化的資訊。
深綠色圓點:來源記載的蛋白質定位;數量不表示含量。
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。
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SMARCB1 是 BAF、PBAF、npBAF 與 nBAF 等染色質重塑複合體的組成亞基;不同複合體的其他亞基可依發育或組織情境而異。它可結合雙股 DNA,並有多項蛋白質互作註記,包括未甲基化時的 CEBPB,以及 PIH1D1、PPP1R15A、DPF2、YWHAZ、ERCC6 和多個 FOS 家族蛋白。感染相關資料另指出,SMARCB1 在體外緊密結合 HIV-1 integrase 並刺激其 DNA 接合活性;它也與 human papillomavirus 18 E1 及 Epstein-Barr virus EBNA-2 互作。
疾病與遺傳關聯
SMARCB1 變異與多種疾病相關。Rhabdoid tumor predisposition syndrome 1 是家族性癌症易感症候群,可涉及腎臟或腎外惡性 rhabdoid tumors,以及脈絡叢癌、medulloblastoma 等中樞神經系統腫瘤;來源指出此病由影響該基因的變異造成。Schwannomatosis 1 為常染色體顯性腫瘤易感症候群,疾病易感性與該基因變異相關。Coffin-Siris syndrome 3 則由影響該基因的變異造成,可有智能障礙、粗獷臉部特徵、多毛,以及第五指指甲或指骨發育不全或缺如等表現,並曾報告常染色體顯性與隱性遺傳。
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 · 7 筆
| 功能面向 | 功能敘述 | 證據類型 | 可查核來源 |
|---|---|---|---|
| 功能 | SMARCB1 是 BAF(hSWI/SNF)複合體核心成分;該 ATP 依賴性染色質重塑複合體參與細胞增殖、分化、抗病毒活動及抑制腫瘤形成。複合體可形成較少受負超螺旋限制的穩定染色質構形,可能涉及部分核小體轉為由兩個組蛋白八聚體構成的 altosomes。SMARCB1 可於體外刺激 SMARCA4 活性,並與 CSF1 啟動子活化、細胞週期控制及 G0/G1 停滯相關。神經發育中 npBAF 轉為 nBAF,前者支持神經幹細胞自我更新與增殖,後者與 CREST 調節樹突生長相關基因。 | 含實驗來源 | 證據與來源Core component of the BAF (hSWI/SNF) complex. This ATP-dependent chromatin-remodeling complex plays important roles in cell proliferation and differentiation, in cellular antiviral activities and inhibition of tumor formation. The BAF complex is able to create a stable, altered form of chromatin that constrains fewer negative supercoils than normal. This change in supercoiling would be due to the conversion of up to one-half of the nucleosomes on polynucleosomal arrays into asymmetric structures, termed altosomes, each composed of 2 histones octamers. Stimulates in vitro the remodeling activity of SMARCA4/BRG1/BAF190A. Involved in activation of CSF1 promoter. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity). Plays a key role in cell-cycle control and causes cell cycle arrest in G0/G1 PMID 10078207 ↗ · PMID 12226744 ↗ · PMID 14604992 ↗ · PMID 16267391 ↗ · PMID 16314535 ↗ · PMID 9448295 ↗ |
| 交互作用 | SMARCB1 是 SWI/SNF-A(BAF)、SWI/SNF-B(PBAF)及相關染色質重塑複合體的組成亞基,也出現在 npBAF 與 nBAF。各複合體另含不同的催化及結構亞基,其組成可依發育和組織而異;部分列出的組成屬可能性或相似性推定。SMARCB1 可結合雙股 DNA,並與 CEBPB(未甲基化時)、PIH1D1、MYK、MAEL、PPP1R15A、DPF2、YWHAZ、ERCC6 及 FOS 家族蛋白互作。 | 含實驗來源 | 證據與來源Component of the multiprotein chromatin-remodeling complexes SWI/SNF: SWI/SNF-A (BAF), SWI/SNF-B (PBAF) and related complexes. The canonical complex contains a catalytic subunit (either SMARCA4/BRG1/BAF190A or SMARCA2/BRM/BAF190B) and at least SMARCE1, ACTL6A/BAF53, SMARCC1/BAF155, SMARCC2/BAF170, and SMARCB1/SNF5/BAF47. Other subunits specific to each of the complexes may also be present permitting several possible combinations developmentally and tissue specific (Probable). Component of the BAF complex, which includes at least actin (ACTB), ARID1A/BAF250A, ARID1B/BAF250B, SMARCA2/BRM, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, ACTL6B/BAF53B, SMARCE1/BAF57 SMARCC1/BAF155, SMARCC2/BAF170, SMARCB1/SNF5/INI1, and one or more SMARCD1/BAF60A, SMARCD2/BAF60B, or SMARCD3/BAF60C. In muscle cells, the BAF complex also contains DPF3. Component of neural progenitors-specific chromatin remodeling complex (npBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, PHF10/BAF45A, ACTL6A/BAF53A and actin. Component of neuron-specific chromatin remodeling complex (nBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, DPF1/BAF45B, DPF3/BAF45C, ACTL6B/BAF53B and actin (By similarity). Component of the SWI/SNF-B (PBAF) chromatin remodeling complex, at least composed of SMARCA4/BRG1, SMARCB1/BAF47/SNF5, ACTL6A/BAF53A or ACTL6B/BAF53B, SMARCE1/BAF57, SMARCD1/BAF60A, SMARCD2/BAF60B, perhaps SMARCD3/BAF60C, SMARCC1/BAF155, SMARCC2/BAF170, PBRM1/BAF180, ARID2/BAF200 and actin. Binds to double-stranded DNA. Interacts with CEBPB (when not methylated). Interacts with PIH1D1. Interacts with MYK and MAEL. Interacts with PPP1R15A. Interacts with DPF2. Interacts with YWHAZ. Interacts with ERCC6. Interacts with FOS, FOSB isoform 1 and 2, FOSL1 and FOSL2 (By similarity) PMID 10319872 ↗ · PMID 10490642 ↗ · PMID 12016208 ↗ · PMID 16959763 ↗ · PMID 18765789 ↗ · PMID 20111005 ↗ · PMID 20460684 ↗ · PMID 22368283 ↗ · PMID 24874740 ↗ · PMID 8895581 ↗ · PMID 22952240 ↗ · PMID 26601204 ↗ |
| 交互作用 | 在微生物感染相關資料中,SMARCB1 被報告可於體外緊密結合 human immunodeficiency virus-type 1(HIV-1)integrase,並刺激其 DNA 接合活性。它也與 human papillomavirus 18 E1 蛋白互作,並刺激該病毒複製;此外,另有與 Epstein-Barr virus 蛋白 EBNA-2 互作的註記。 | 含實驗來源 | 證據與來源(Microbial infection) Binds tightly to the human immunodeficiency virus-type 1 (HIV-1) integrase in vitro and stimulates its DNA-joining activity. Interacts with human papillomavirus 18 E1 protein to stimulate its viral replication. Interacts with Epstein-Barr virus protein EBNA-2 PMID 10365963 ↗ · PMID 8709224 ↗ |
| 細胞定位 | SMARCB1 的細胞內定位註記為細胞核。 | 資料庫紀錄 | |
| 疾病關聯 | Rhabdoid tumor predisposition syndrome 1 是家族性癌症易感症候群,患者可能發生腎臟或腎外惡性 rhabdoid tumors,也可能出現脈絡叢癌、medulloblastoma 及中樞神經系統原始神經外胚層腫瘤。來源指出,此疾病由影響 SMARCB1 的變異造成;rhabdoid tumors 是幼兒期侵襲性與致死性最高的惡性腫瘤。 | 含實驗來源 | 證據與來源Rhabdoid tumor predisposition syndrome 1 RTPS1 A familial cancer syndrome predisposing to renal or extrarenal malignant rhabdoid tumors and to a variety of tumors of the central nervous system, including choroid plexus carcinoma, medulloblastoma, and central primitive neuroectodermal tumors. Rhabdoid tumors are the most aggressive and lethal malignancies occurring in early childhood. The disease is caused by variants affecting the gene represented in this entry MIM: 609322 PMID 9671307 ↗ · PMID 9892189 ↗ |
| 疾病關聯 | Schwannomatosis 1 是常染色體顯性腫瘤易感症候群,特徵為顱神經、脊神經及周邊神經出現多發性良性神經鞘瘤,但不涉及前庭神經;患者也可能有多發性腦膜瘤。疾病易感性與影響 SMARCB1 的變異相關,來源未將此關聯表述為變異直接造成疾病。 | 含實驗來源 | 證據與來源Schwannomatosis 1 SWN1 An autosomal dominant tumor predisposition syndrome characterized by the development of multiple benign nerve sheath tumors called schwannomas on cranial, spinal, and peripheral nerves, without involvement of the vestibular nerve. Affected individuals may also have multiple meningiomas. Disease susceptibility is associated with variants affecting the gene represented in this entry MIM: 162091 PMID 17357086 ↗ · PMID 18072270 ↗ |
| 疾病關聯 | Coffin-Siris syndrome 3 是先天性多重異常症候群的一型,表現及遺傳背景具有廣泛差異。常見特徵包括智能障礙、粗獷臉部特徵、多毛,以及第五指指甲或指骨發育不全或缺如;其他可能表現包括多系統器官異常、餵食困難、生長不佳、眼科異常、聽力障礙與脊椎異常。來源指出此病由影響 SMARCB1 的變異造成,並曾報告顯性及隱性遺傳。 | 含實驗來源 | 證據與來源Coffin-Siris syndrome 3 CSS3 A form of Coffin-Siris syndrome, a congenital multiple malformation syndrome with broad phenotypic and genetic variability. Cardinal features are intellectual disability, coarse facial features, hypertrichosis, and hypoplastic or absent fifth digit nails or phalanges. Additional features include malformations of the cardiac, gastrointestinal, genitourinary, and/or central nervous systems. Sucking/feeding difficulties, poor growth, ophthalmologic abnormalities, hearing impairment, and spinal anomalies are common findings. Both autosomal dominant and autosomal recessive inheritance patterns have been reported. The disease is caused by variants affecting the gene represented in this entry MIM: 614608 PMID 22426308 ↗ · PMID 22726846 ↗ · PMID 23906836 ↗ · PMID 29907796 ↗ |
核酸與蛋白質序列
GCCAGCGCCTGCGCACTGAGGGCGGCCTGGTCGTCGTCTG40CGGCGGCGGCGGCGGCTGAGGAGCCCGGCTGAGGCGCCAG80TACCCGGCCCGGTCCGCATTTCGCCTTCCGGCTTCGGTTT120CCCTCGGCCCAGCACGCCCCGGCCCCGCCCCAGCCCTCCT160GATCCCTCGCAGCCCGGCTCCGGCCGCCCGCCTCTGCCGC200CGCAATGATGATGATGGCGCTGAGCAAGACCTTCGGGCAG240AAGCCCGTGAAGTTCCAGCTGGAGGACGACGGCGAGTTCT280ACATGATCGGCTCCGAGGTGGGAAACTACCTCCGTATGTT320CCGAGGTTCTCTGTACAAGAGATACCCCTCACTCTGGAGG360CGACTAGCCACTGTGGAAGAGAGGAAGAAAATAGTTGCAT400CGTCACATGGTAAAAAAACAAAACCTAACACTAAGGATCA440CGGATACACGACTCTAGCCACCAGTGTGACCCTGTTAAAA480GCCTCGGAAGTGGAAGAGATTCTGGATGGCAACGATGAGA520AGTACAAGGCTGTGTCCATCAGCACAGAGCCCCCCACCTA560CCTCAGGGAACAGAAGGCCAAGAGGAACAGCCAGTGGGTA600CCCACCCTGCCCAACAGCTCCCACCACTTAGATGCCGTGC640CATGCTCCACAACCATCAACAGGAACCGCATGGGCCGAGA680CAAGAAGAGAACCTTCCCCCTTTGCTTTGATGACCATGAC720CCAGCTGTGATCCATGAGAACGCATCTCAGCCCGAGGTGC760TGGTCCCCATCCGGCTGGACATGGAGATCGATGGGCAGAA800GCTGCGAGACGCCTTCACCTGGAACATGAATGAGAAGTTG840ATGACGCCTGAGATGTTTTCAGAAATCCTCTGTGACGATC880TGGATTTGAACCCGCTGACGTTTGTGCCAGCCATCGCCTC920TGCCATCAGACAGCAGATCGAGTCCTACCCCACGGACAGC960cDNA 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。