基因總覽
TGFBR1 是蛋白質編碼基因，產物為 transforming growth factor beta receptor 1。此蛋白屬於蛋白質激酶超家族中的 TKL Ser/Thr protein kinase family，並歸入 TGFB receptor subfamily；它是跨膜絲胺酸／蘇胺酸激酶受體。TGFBR1 與 TGFBR2 協同構成 TGFB1、TGFB2 和 TGFB3 的受體。其受體性質使其能在細胞表面接收細胞外訊號，並將訊號傳至細胞內。蛋白質具有細胞外區段、單次跨膜區段及細胞質區段，後者包含 GS domain 與 protein kinase domain。
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 |
|---|---|---|
| ENST00000374994 ★ | 99,105,113–99,154,192 | 9 |
| ENST00000547314 | 99,104,038–99,154,192 | 9 |
| ENST00000552573 | 99,104,070–99,154,192 | 9 |
| ENST00000698941 | 99,105,037–99,154,192 | 9 |
| ENST00000714345 | 99,105,078–99,154,192 | 9 |
| ENST00000374990 | 99,105,078–99,154,192 | 8 |
| ENST00000714348 | 99,105,078–99,154,192 | 9 |
| ENST00000552516 | 99,105,078–99,154,192 | 9 |
| ENST00000858563 | 99,105,078–99,154,192 | 7 |
| ENST00000858564 | 99,105,078–99,154,192 | 6 |
| ENST00000937285 | 99,105,078–99,154,192 | 8 |
| ENST00000937286 | 99,105,078–99,154,192 | 8 |
顯示 12/20 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
TGFBR1 與 TGFBR2 組成 TGFB1、TGFB2 和 TGFB3 的受體，將細胞表面的訊號傳入細胞質。配體二聚體與兩個 TGFBR1、兩個 TGFBR2 形成受體複合體後，持續具活性的 TGFBR2 會磷酸化並活化 TGFBR1。這使 TGFBR1 能將受體複合體接收到的訊號往下傳遞。
在典型的 SMAD 依賴性路徑中，活化的 TGFBR1 磷酸化 SMAD2。SMAD2 隨後離開受體，與 SMAD4 結合；形成的複合體轉移至細胞核，調節受 TGFB 調控基因的轉錄。這條訊號路徑使細胞外的 TGFB 訊號得以影響基因表現。
TGFBR1 也參與非典型、非 SMAD 依賴性訊號。其一是促進 TRAF6 自體泛素化，進而造成 MAP3K7 泛素化與活化，並觸發細胞凋亡。另一途徑則透過磷酸化並活化 PARD6A，調節上皮細胞向間質細胞轉化。
來源指出，TGFBR1 傳遞的 TGFB 訊號涉及多種生理與病理過程，包括上皮細胞與造血細胞的細胞週期停滯、間質細胞增殖與分化的調控、傷口癒合、細胞外基質生成、免疫抑制及致癌作用。這些過程涵蓋細胞生長、組織反應與疾病相關變化；資料並未將各項過程限定為單一組織或情境。
Promoter 與基因調控
>TGFBR1 ENST00000374994 GRCh38 chr9:99104113-99105213 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 GGAGCGTCTCGCAGTAAATTAGGAATTCAGAATGAAAACGTAGAGTTTATTTGGGTTTTTAGTGACACCT CAGGATTATTATACAGCAGTGTCAGACACAGCTCAAAGTAATGATGACTGCTCCCCCTCCGCCCCGCGGG AGCTGGGTGCTAAGAAGGGGGAACCCCTCCTTTGAGGGGTTGGGGTGGGGATCCTCCCTTTCCAACCTGG ATCGGGAAGGGGTTTGAGAGGAGTGCGGCTTGGATCCCCATCCTGGATCTGTGCTGGAGGGAGGCGGGAG GCTATTTGGGGGTGTGTTTGGGCTCAGGATCTGGGTCTGACGCTGGGATCTGAGGACTTTCTGGGTTTGG AACTGGGTGGGGGAGCTGGGTTTGGGGTGACCGCTGGGAGCAGGAGGAAATAGGAGAGTGAGTCGCATGT GAAGGGCACTGAGGAGGGATCTTCGGGGGAATGCTGAAGTTGATGCGTGGACTTGGAGAGGGGAAGTTGA AGTGGATGCAGGGGCCTGGCGCTGCAGCGGATCTGGGTGGCATGTGCTGGGATTGCCAATGCGGAGCTGT GAATGGGGTCAGGGTGGGGCTGAGGCAGTACCAGATCTTCCGCGCCTAGAGGAGGTTAGAAGAAAAGAGC GTCGAACGGCCACAGCCTTTTTCCGAAAGAGACTCACACAGACACACCCATCGCTCTACCCGGCCCTCCG GGGCTAGCGGCTGAGCGGTGCTGGGGCTGGCAGACCCCGCCCCCACGCGGCCTCTCGGAGCCGGGAGCCG ATCGGGCCGGGGCTGGGGTCTGGCGGCCCAGCCCCCGGGGAGCGTGGGGCGTGGCCAGAAACCGGCGCTC GCGGCTGCGGATTGGCTGCCTGGCGGGCCCGCAGGCGGGGCTCCCGGCTGGGTCCCGCTTGGCAGCTCGC GGCGGCGGGGAGGCGGGGCCGGCGGGAGCCCGGCAGCCAATGGACGCGCGTCCTCCGAGCAGTTACAAAG GGCCGGAGCGAGGCCGCCGCGGCGGCTAGGGAGGTGGGGCGAGGCGAGGTTTGCTGGGGTGAGGCAGCGG CGCGGCCGGGCCGGGCCGGGCCACAGGCGGTGGCGGCGGGACCATGGAGGC
EPDnew 實驗支持 promoter／TSS · 2 筆
| EPDnew ID | TSS（1-based） | 股向 | 來源顯示區間 |
|---|---|---|---|
| TGFBR1_1 ↗ | 9:99,105,116 | 正股 | 99,105,067–99,105,126 |
| TGFBR1_2 ↗ | 9:99,105,242 | 正股 | 99,105,193–99,105,252 |
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
ENSR9_93GC3P · enhancer · 99103089–99103546 · regulatory
ENSR9_BPN34 · promoter · 99104547–99105160 · regulatory
ENSR9_5TBD9R · CTCF_binding_site · 99104846–99104867 · regulatory
ENSR9_CCSJ5 · enhancer · 99105161–99106437 · regulatory
ENSR9_5TBDCL · CTCF_binding_site · 99105238–99105259 · regulatory
ENSR9_BPN3D · enhancer · 99106746–99107283 · regulatory
ENSR9_93GC52 · enhancer · 99107510–99108014 · regulatory
ENSR9_93GC5K · enhancer · 99109514–99109901 · regulatory
· motif · 99104677–99104684 · motif
· motif · 99104810–99104825 · motif
· motif · 99104848–99104864 · motif
· motif · 99104912–99104925 · motif
· motif · 99104912–99104925 · motif
· motif · 99105003–99105019 · motif
· motif · 99105240–99105256 · motif
· motif · 99105388–99105401 · motif
· motif · 99105471–99105479 · motif
· motif · 99105471–99105486 · motif
· motif · 99105484–99105497 · motif
· motif · 99105560–99105573 · motif
· motif · 99105560–99105573 · motif
· motif · 99105619–99105632 · motif
· motif · 99105684–99105697 · motif
· motif · 99105769–99105786 · motif
· motif · 99105771–99105786 · motif
· motif · 99108780–99108791 · motif
蛋白質結構域與序列
參考蛋白質長度：503 aa
transforming growth factor beta receptor 1 長 503 個胺基酸，具有訊號胜肽、細胞外區段、螺旋型跨膜區段及細胞質區段。細胞質部分含 GS domain 與 protein kinase domain，另有 FKBP1A-binding motif。蛋白質歸屬於 TKL Ser/Thr protein kinase family 及 TGFB receptor subfamily。
蛋白質三維結構
細胞內定位
TGFBR1 是單次跨膜的第一型膜蛋白，定位於細胞膜與細胞表面，也見於細胞緊密連接及膜筏。 資料未提供定位隨條件改變或不同異構型之間差異的描述。
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：Cell junction, tight junction；Cell surface；Membrane raft。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
- FKBP1AP62942 · UniProt INTERACTION · 2 experiments
- TGFB1P01137 · UniProt INTERACTION · 2 experiments
- YWHAZP63104 · UniProt INTERACTION · 4 experiments
- Q99IB8Q99IB8 · UniProt INTERACTION · 5 experiments
- LRG1P02750 · UniProt INTERACTION · 6 experiments
TGFBR1 可形成同源二聚體，也能與 TGFBR2 組成異源二聚體；配體二聚體參與組裝時，形成含兩個 TGFBR1 與兩個 TGFBR2 的受體－配體六聚體。它亦與 TSC22D1、CD109、FKBP1A、SMAD2、SMAD3、TRAF6、MAP3K7、PARD6A 等蛋白互作。這些互作具有不同關係：例如 FKBP1A 結合未磷酸化的 TGFBR1 並維持其非活化狀態；TRAF6 與 MAP3K7 的互作則涉及 MAP3K7 活化。TSC22D1、TGFBR1 與 TGFBR2 可構成複合體，其與 TSC22D1 的互作受 SMAD7 抑制、受 TGFB1 促進。
疾病與遺傳關聯
影響 TGFBR1 的基因變異與 Loeys-Dietz syndrome 1（LDS1）相關。此症候群可有動脈迂曲與動脈瘤、眼距過寬及分叉舌垂或顎裂等表現，亦可能伴隨關節鬆弛、易瘀青、皮膚與妊娠相關併發症。TGFBR1 的 Gln-487 突變曾被報告與胸主動脈瘤及剝離相關；但此表現是否應界定為僅限胸主動脈的胸主動脈瘤類型 5，仍不明確。影響此基因的變異也與多發性自癒性鱗狀上皮瘤相關，患者可出現多處皮膚腫瘤，腫瘤常自行消退並留下凹陷性疤痕。
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 | TGFBR1 是跨膜絲胺酸／蘇胺酸激酶，與 TGFBR2 共同接收 TGFB1、TGFB2、TGFB3 訊號。配體二聚體組成含兩個 TGFBR1 與兩個 TGFBR2 的受體複合體後，TGFBR2 磷酸化並活化 TGFBR1；其後可經 SMAD2、SMAD4 調節基因轉錄，也參與非 SMAD 訊號，包括促進 TRAF6、MAP3K7 活化以觸發細胞凋亡，以及透過 PARD6A 調節上皮間質轉化。 | 含實驗來源 | 證據與來源Transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine kinase receptor, TGFBR2, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways. For instance, TGFBR1 induces TRAF6 autoubiquitination which in turn results in MAP3K7 ubiquitination and activation to trigger apoptosis. Also regulates epithelial to mesenchymal transition through a SMAD-independent signaling pathway through PARD6A phosphorylation and activation PMID 15761148 ↗ · PMID 16754747 ↗ · PMID 18758450 ↗ · PMID 33914044 ↗ · PMID 7774578 ↗ · PMID 8752209 ↗ · PMID 8980228 ↗ · PMID 9346908 ↗ |
| 分子活性 | L-threonyl-[receptor-protein] + ATP = O-phospho-L-threonyl-[receptor-protein] + ADP + H(+) | 資料庫紀錄 | 證據與來源L-threonyl-[receptor-protein] + ATP = O-phospho-L-threonyl-[receptor-protein] + ADP + H(+) |
| 分子活性 | L-seryl-[receptor-protein] + ATP = O-phospho-L-seryl-[receptor-protein] + ADP + H(+) | 資料庫紀錄 | |
| 交互作用 | TGFBR1 可形成同源二聚體，並與 TGFBR2 及 TGFB 配體二聚體組成受體－配體異源六聚體；不同受體對配體的親和力可能影響組裝速度及不同 TGFB 配體的生物活性。它與多種蛋白互作，部分互作受配體或其他蛋白調節，例如 TGFB1 促進、SMAD7 抑制其與 TSC22D1 的互作；未磷酸化 TGFBR1 與 FKBP1A 結合可維持非活化狀態。 | 含實驗來源 | 證據與來源Homodimer; in the endoplasmic reticulum but also at the cell membrane. Heterohexamer; TGFB1, TGFB2 and TGFB3 homodimeric ligands assemble a functional receptor composed of two TGFBR1 and TGFBR2 heterodimers to form a ligand-receptor heterohexamer. The respective affinity of TGBRB1 and TGFBR2 for the ligands may modulate the kinetics of assembly of the receptor and may explain the different biological activities of TGFB1, TGFB2 and TGFB3. Component of a complex composed of TSC22D1 (via N-terminus), TGFBR1 and TGFBR2; the interaction between TSC22D1 and TGFBR1 is inhibited by SMAD7 and promoted by TGFB1. Interacts with CD109; inhibits TGF-beta receptor activation in keratinocytes. Interacts with RBPMS. Interacts (unphosphorylated) with FKBP1A; prevents TGFBR1 phosphorylation by TGFBR2 and stabilizes it in the inactive conformation. Interacts with SMAD2, SMAD3 and ZFYVE9; ZFYVE9 recruits SMAD2 and SMAD3 to the TGF-beta receptor. Interacts with TRAF6 and MAP3K7; induces MAP3K7 activation by TRAF6. Interacts with PARD6A; involved in TGF-beta induced epithelial to mesenchymal transition. Interacts with NEDD4L. Interacts with SMAD7, SMURF1 and SMURF2; SMAD7 recruits NEDD4L, SMURF1 and SMURF2 to the TGF-beta receptor. Interacts with USP15 and VPS39. Interacts with SDCBP (via C-terminus). Interacts with CAV1 and this interaction is impaired in the presence of SDCBP. Interacts with APPL1; interaction is TGF beta dependent; mediates trafficking of the TGFBR1 from the endosomes to the nucleus via microtubules in a TRAF6-dependent manner. Interacts with GPR50; this interaction promotes the constitutive activation of SMAD signaling pathway PMID 10025408 ↗ · PMID 11163210 ↗ · PMID 11278251 ↗ · PMID 11583628 ↗ · PMID 12941698 ↗ · PMID 15177479 ↗ · PMID 15317461 ↗ · PMID 15496141 ↗ · PMID 15761148 ↗ · PMID 16754747 ↗ · PMID 17099224 ↗ · PMID 18243111 ↗ · PMID 18758450 ↗ · PMID 20207738 ↗ · PMID 21791611 ↗ · PMID 25893292 ↗ · PMID 26583432 ↗ · PMID 29572483 ↗ · PMID 7774578 ↗ · PMID 8980228 ↗ · PMID 9233797 ↗ · PMID 9311995 ↗ · PMID 9346908 ↗ · PMID 9865696 ↗ |
| 細胞定位 | TGFBR1 為單次跨膜的第一型膜蛋白，定位記錄包括細胞膜、細胞表面、細胞緊密連接及膜筏。 | 含實驗來源 | 證據與來源Cell membrane / Single-pass type I membrane protein; Cell junction, tight junction; Cell surface; Membrane raft PMID 21791611 ↗ · PMID 25893292 ↗ · PMID 9472030 ↗ · PMID 15761148 ↗ |
| 疾病關聯 | 影響 TGFBR1 的變異與 Loeys-Dietz syndrome 1（LDS1）相關，該症可有動脈迂曲與動脈瘤、眼距過寬、分叉舌垂或顎裂等表現。Gln-487 突變曾被報告與胸主動脈瘤及剝離相關，但此表現是否符合僅限胸主動脈的胸主動脈瘤類型 5，仍不明確，因此相關個案在 OMIM 資源中列為 LDS1。 | 含實驗來源 | 證據與來源Loeys-Dietz syndrome 1 LDS1 An aortic aneurysm syndrome with widespread systemic involvement, characterized by arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. Physical findings include prominent joint laxity, easy bruising, wide and atrophic scars, velvety and translucent skin with easily visible veins, spontaneous rupture of the spleen or bowel, and catastrophic complications of pregnancy, including rupture of the gravid uterus and the arteries, either during pregnancy or in the immediate postpartum period. Some patients have craniosynostosis, exotropy, micrognathia and retrognathia, structural brain abnormalities, and intellectual deficit. The disease is caused by variants affecting the gene represented in this entry. TGFBR1 mutation Gln-487 has been reported to be associated with thoracic aortic aneurysms and dissection (TAAD). This phenotype, also known as thoracic aortic aneurysms type 5 (AAT5), is distinguised from LDS1 by having aneurysms restricted to thoracic aorta. It is unclear, however, if this condition is fulfilled in individuals bearing Gln-487 mutation, that is why they are considered as LDS1 by the OMIM resource MIM: 609192 PMID 16791849 ↗ · PMID 15731757 ↗ · PMID 16596670 ↗ · PMID 16928994 ↗ · PMID 19883511 ↗ · PMID 22113417 ↗ |
| 疾病關聯 | 影響 TGFBR1 的變異與多發性自癒性鱗狀上皮瘤相關。此疾病會形成多處皮膚腫瘤，常見於日照部位；腫瘤可局部侵犯，並在數月內自行消退，留下凹陷性疤痕。 | 含實驗來源 | 證據與來源Multiple self-healing squamous epithelioma MSSE A disorder characterized by multiple skin tumors that undergo spontaneous regression. Tumors appear most often on sun-exposed regions, are locally invasive, and undergo spontaneous resolution over a period of months leaving pitted scars. The disease is caused by variants affecting the gene represented in this entry MIM: 132800 PMID 21358634 ↗ |
核酸與蛋白質序列
GGCGGCTAGGGAGGTGGGGCGAGGCGAGGTTTGCTGGGGT40GAGGCAGCGGCGCGGCCGGGCCGGGCCGGGCCACAGGCGG80TGGCGGCGGGACCATGGAGGCGGCGGTCGCTGCTCCGCGT120CCCCGGCTGCTCCTCCTCGTGCTGGCGGCGGCGGCGGCGG160CGGCGGCGGCGCTGCTCCCGGGGGCGACGGCGTTACAGTG200TTTCTGCCACCTCTGTACAAAAGACAATTTTACTTGTGTG240ACAGATGGGCTCTGCTTTGTCTCTGTCACAGAGACCACAG280ACAAAGTTATACACAACAGCATGTGTATAGCTGAAATTGA320CTTAATTCCTCGAGATAGGCCGTTTGTATGTGCACCCTCT360TCAAAAACTGGGTCTGTGACTACAACATATTGCTGCAATC400AGGACCATTGCAATAAAATAGAACTTCCAACTACTGTAAA440GTCATCACCTGGCCTTGGTCCTGTGGAACTGGCAGCTGTC480ATTGCTGGACCAGTGTGCTTCGTCTGCATCTCACTCATGT520TGATGGTCTATATCTGCCACAACCGCACTGTCATTCACCA560TCGAGTGCCAAATGAAGAGGACCCTTCATTAGATCGCCCT600TTTATTTCAGAGGGTACTACGTTGAAAGACTTAATTTATG640ATATGACAACGTCAGGTTCTGGCTCAGGTTTACCATTGCT680TGTTCAGAGAACAATTGCGAGAACTATTGTGTTACAAGAA720AGCATTGGCAAAGGTCGATTTGGAGAAGTTTGGAGAGGAA760AGTGGCGGGGAGAAGAAGTTGCTGTTAAGATATTCTCCTC800TAGAGAAGAACGTTCGTGGTTCCGTGAGGCAGAGATTTAT840CAAACTGTAATGTTACGTCATGAAAACATCCTGGGATTTA880TAGCAGCAGACAATAAAGACAATGGTACTTGGACTCAGCT920CTGGTTGGTGTCAGATTATCATGAGCATGGATCCCTTTTT960cDNA 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。