基因總覽
transforming growth factor beta receptor 2 是一種蛋白質激酶超家族中的跨膜受體，屬於 TKL Ser/Thr protein kinase family 的 TGFB receptor subfamily。蛋白質具有單次跨膜的第一型膜蛋白架構：胞外區負責接觸配體，跨膜區連接細胞內的蛋白質激酶區域。它與 TGFBR1 共同構成辨識 TGFB1、TGFB2 與 TGFB3 的受體；其主要角色是接收細胞外的 TGF-beta 訊號並將訊息傳入細胞。
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 |
|---|---|---|
| ENST00000295754 ★ | 30,606,601–30,694,142 | 7 |
| ENST00000714389 | 30,606,478–30,694,249 | 7 |
| ENST00000714390 | 30,606,494–30,694,249 | 7 |
| ENST00000714391 | 30,606,495–30,694,249 | 8 |
| ENST00000359013 | 30,606,585–30,694,249 | 8 |
| ENST00000894724 | 30,606,585–30,694,249 | 5 |
| ENST00000941788 | 30,606,585–30,694,249 | 7 |
| ENST00000941789 | 30,606,585–30,694,249 | 7 |
| ENST00001144391 | 30,606,601–30,694,249 | 7 |
顯示 9/9 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
TGFBR2 是具有受體活性的跨膜絲胺酸／蘇胺酸激酶，與 TGFBR1 一同參與 TGFB1、TGFB2、TGFB3 的訊號傳遞。來源指出，TGFBR2 可在不需其他受體參與的情況下，以皮莫耳（picomolar）親和力結合這三種配體；另一項功能註解則指出，TGFBR2 與 TGFBR1 共同形成對這些細胞激素具專一性的受體。
Promoter 與基因調控
>TGFBR2 ENST00000295754 GRCh38 chr3:30605601-30606701 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 CATGTACACCAGGAATGTCTTGGGCAAATCTGGTTGCCCTAGCAAGAAAGGAAATTTGAAAGTTTATACT GTTCTGCTCCCATGTTACCCCGTTTGCACATGAGAGGGTAAGTATTCTCTTTCTTCACCTGCATTAAGGG AATAAAAGCACAAGCATTCAGGTGACTCCCAACCCACTTTTAATTTTACAGTTTCTGCTATACTCTATAC ATTCTGAAAATTACATTTCCCACCACTATCACTTCGTGATAGGTGATCATTTACAATTACTCACTGACTC AGTCCCGGGAAGAGGCGGTGCAAAATGGGACGCTCTATCCAGGTGCTCATTAGAAATGCAGAATCTCTGC CTGCCTCCTAGACCTACTGAATTAGAATCTGCATTTTTAAATAAGATTTCCAGGTGATCAATATGTACAT TAAAACTTGAGAAAAACCTCTAGACTTCGACCTAAAGAAAAACATTTTACAACTTGACAGTGTATGCACA TACATACATGCATATAGACACAACTGAAGCACAAATTTAATGAAGTAGAATTTACCGTTACTATTTTATT TGGGAAAGAAATGTGCTCGCGACTCAATAGATTGGAGTATTCACTCCTGGATCTCAACTTGCAATTTGAA AACGCATCTCTAAAGCACCTAGGAGCAATCTGAAGAAAGCTGAGGGGAGGCGGCAGATGTTCTGATCTAC TAGGGAAAACGTGGACGTTTTCTGTTGTTACTTTGTGAACTGTGTGCACTTAGTCATTCTTGAGTAAATA CTTGGAGCGAGGAACTCCTGAGTGGTGTGGGAGGGCGGTGAGGGGCAGCTGAAAGTCGGCCAAAGCTCTC GGAGGGGCTGGTCTAGGAAACATGATTGGCAGCTACGAGAGAGCTAGGGGCTGGACGTCGAGGAGAGGGA GAAGGCTCTCGGGCGGAGAGAGGTCCTGCCCAGCTGTTGGCGAGGAGTTTCCTGTTTCCCCCGCAGCGCT GAGTTGAAGTTGAGTGAGTCACTCGCGCGCACGGAGCGACGACACCCCCGCGCGTGCACCCGCTCGGGAC AGGAGCCGGACTCCTGTGCAGCTTCCCTCGGCCGCCGGGGGCCTCCCCGCG
EPDnew 實驗支持 promoter／TSS · 2 筆
| EPDnew ID | TSS（1-based） | 股向 | 來源顯示區間 |
|---|---|---|---|
| TGFBR2_2 ↗ | 3:30,606,500 | 正股 | 30,606,451–30,606,510 |
| TGFBR2_1 ↗ | 3:30,606,601 | 正股 | 30,606,552–30,606,611 |
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_9G5Z3 · enhancer · 30602955–30603277 · regulatory
ENSR3_D3HZX · enhancer · 30604079–30606282 · regulatory
ENSR3_9G622 · promoter · 30606283–30606611 · regulatory
ENSR3_9G627 · promoter · 30606831–30607331 · regulatory
ENSR3_9G62C · enhancer · 30607332–30607796 · regulatory
ENSR3_B842B · enhancer · 30608236–30609029 · regulatory
ENSR3_9G63C · enhancer · 30610796–30611303 · regulatory
· motif · 30603080–30603097 · motif
· motif · 30603126–30603148 · motif
· motif · 30603126–30603148 · motif
· motif · 30603163–30603171 · motif
· motif · 30603442–30603454 · motif
· motif · 30604296–30604309 · motif
· motif · 30604296–30604309 · motif
· motif · 30604670–30604681 · motif
· motif · 30606039–30606054 · motif
· motif · 30606443–30606453 · motif
· motif · 30606594–30606602 · motif
蛋白質結構域與序列
參考蛋白質長度：567 aa
TGFBR2 蛋白質長 567 個胺基酸，N 端訊號肽位於第 1–22 個胺基酸；第 23–166 位為胞外區，第 167–187 位為螺旋型跨膜區，第 188–567 位為細胞質區。蛋白質激酶結構域位於第 244–544 位；第 439–567 位則足以與 CLU 互作。
蛋白質三維結構
細胞內定位
主要型態是細胞膜上的單次跨膜第一型膜蛋白，亦被註記位於膜筏。 另有 Isoform 3 被註記為分泌型；此定位描述適用於該異構型，不應與主要型態的膜定位混為一談。
深綠色圓點：來源記載的蛋白質定位；數量不表示含量。
細胞外定位：圓點散佈於細胞周圍，與細胞膜保持距離。
未繪示構造：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 73 個夥伴
- AK2P54819 · UniProt INTERACTION · 3 experiments
- AP1S1P61966-2 · UniProt INTERACTION · 3 experiments
- ARFGAP3Q9NP61 · UniProt INTERACTION · 3 experiments
- ATG13O75143-2 · UniProt INTERACTION · 3 experiments
- ATP2A3Q93084-2 · UniProt INTERACTION · 3 experiments
- ATXN1P54253 · UniProt INTERACTION · 3 experiments
- ATXN3P54252 · UniProt INTERACTION · 3 experiments
- ATXN3Q4VBR4 · UniProt INTERACTION · 3 experiments
- BAHD1Q8TBE0 · UniProt INTERACTION · 3 experiments
- C1orf216Q8TAB5 · UniProt INTERACTION · 3 experiments
- CCT6AP40227 · UniProt INTERACTION · 3 experiments
- CDH1P12830 · UniProt INTERACTION · 3 experiments
- COL25A1Q8NE08 · UniProt INTERACTION · 3 experiments
- CSNK1DP48730-2 · UniProt INTERACTION · 3 experiments
- DAXXQ9UER7 · UniProt INTERACTION · 2 experiments
- DDX19BQ9UMR2 · UniProt INTERACTION · 3 experiments
- DNASE1L1P49184 · UniProt INTERACTION · 3 experiments
- DPYSL4O14531 · UniProt INTERACTION · 3 experiments
- ELAVL4P26378-2 · UniProt INTERACTION · 3 experiments
- ETS2P15036 · UniProt INTERACTION · 3 experiments
- GNAO1P09471 · UniProt INTERACTION · 3 experiments
- GPM6AP51674 · UniProt INTERACTION · 3 experiments
- HTTP42858 · UniProt INTERACTION · 3 experiments
- IDH1O75874 · UniProt INTERACTION · 3 experiments
- INO80CQ6PI98 · UniProt INTERACTION · 3 experiments
TGFBR2 可形成同源二聚體；另有註記指出其同源二聚體以二硫鍵連結。配體參與時，TGFB1、TGFB2 或 TGFB3 的同源二聚體可與兩個 TGFBR1–TGFBR2 異源二聚體組成異源六聚體受體複合體。TGFBR2 也與 TSC22D1、DAXX、DYNLT4、ZFYVE9、SCUBE3、VPS39 和 CLU 有互作註記；其中 SCUBE3 可與其互作並使其活化，ZFYVE9 則會將 SMAD2、SMAD3 招募至 TGF-beta 受體。
疾病與遺傳關聯
TGFBR2 的變異與多種疾病相關。來源將影響此基因的變異列為遺傳性非息肉症大腸直腸癌第 6 型（HNPCC6）及食道癌的致病因素。Loeys-Dietz syndrome 2（LDS2）亦與影響此基因的變異相關；其中 TGFBR2 的 Cys-460 與 His-460 突變曾被報告與胸主動脈瘤及剝離相關。來源並指出，這類表現曾以胸主動脈瘤第 3 型稱呼；由於部分帶有這些突變者也有降主動脈及其他動脈的疾病或動脈瘤，OMIM 將其視為 LDS2。
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 · 12 筆
| 功能面向 | 功能敘述 | 證據類型 | 可查核來源 |
|---|---|---|---|
| 功能 | TGFBR2 是跨膜絲胺酸／蘇胺酸激酶，與 TGFBR1 共同形成辨識 TGFB1、TGFB2、TGFB3 的受體。配體結合後，受體複合體中的 TGFBR2 磷酸化並活化 TGFBR1；接續的 SMAD2、SMAD4 路徑調節 TGF-beta 相關基因轉錄。此受體也參與非典型、非 SMAD 依賴的訊號傳遞，並關聯多種生理與病理過程。 | 含實驗來源 | 證據與來源Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, 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 thus regulates 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 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 PMID 7774578 ↗ |
| 功能 | TGFBR2 具有受 transforming growth factor beta 活化的受體活性；此註解描述其受體功能，未提供額外的作用條件或下游結果。 | 含實驗來源 | |
| 功能 | TGFBR2 能以皮莫耳親和力範圍結合 TGFB1、TGFB2 與 TGFB3，且不需要其他受體參與。來源也指出，TGFBR2 會阻斷 TGFB1 對 SMAD2 和 SMAD3 的活化；此處保留原註解所述的阻斷方向。 | 含實驗來源 | 證據與來源Binds TGFB1, TGFB2 and TGFB3 in the picomolar affinity range without the participation of additional receptors. Blocks activation of SMAD2 and SMAD3 by TGFB1 PMID 34568316 ↗ |
| 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 | TGFBR2 可形成同源二聚體；在配體參與時，TGFB1、TGFB2 或 TGFB3 的同源二聚體與兩個 TGFBR1–TGFBR2 異源二聚體組成異源六聚體，受體與配體的親和力可能影響組裝動力學及不同 TGFB 的生物活性。另有多種蛋白質互作註記，包括 TSC22D1、DAXX、DYNLT4、ZFYVE9、SCUBE3、VPS39 與 CLU；部分互作具有來源列明的調控或配體條件。 | 含實驗來源 | 證據與來源Homodimer. 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 TGFRB1 and TGFRB2 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 DAXX. Interacts with DYNLT4. Interacts with ZFYVE9; ZFYVE9 recruits SMAD2 and SMAD3 to the TGF-beta receptor. Interacts with and is activated by SCUBE3; this interaction does not affect TGFB1-binding to TGFBR2. Interacts with VPS39; this interaction is independent of the receptor kinase activity and of the presence of TGF-beta. Interacts with CLU PMID 11483955 ↗ · PMID 11850637 ↗ · PMID 12941698 ↗ · PMID 16982625 ↗ · PMID 18243111 ↗ · PMID 20207738 ↗ · PMID 21441952 ↗ · PMID 21791611 ↗ · PMID 8555189 ↗ · PMID 9865696 ↗ |
| 交互作用 | TGFBR2 可形成以二硫鍵連結的同源二聚體。此項互作註記未提供其他複合體、條件或功能結果。 | 含實驗來源 | |
| 細胞定位 | TGFBR2 被註記位於細胞膜，屬單次跨膜第一型膜蛋白；來源也列出膜筏定位。此筆資料未描述定位改變的條件或異構型差異。 | 含實驗來源 | 證據與來源Cell membrane / Single-pass type I membrane protein; Membrane raft PMID 1310899 ↗ · PMID 25893292 ↗ |
| 細胞定位 | Isoform 3; Secreted | 含實驗來源 | |
| 疾病關聯 | 影響 TGFBR2 的變異與常染色體顯性遺傳的遺傳性非息肉症大腸直腸癌第 6 型（HNPCC6）相關。疾病涉及早發性大腸直腸癌家族傾向，也可能伴隨胃腸道、泌尿道及女性生殖道的腸外腫瘤；來源亦描述其臨床分型與 Amsterdam 診斷準則。 | 含實驗來源 | 證據與來源Hereditary non-polyposis colorectal cancer 6 HNPCC6 An autosomal dominant disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early-onset colorectal carcinoma (CRC) and extra-colonic tumors of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world. Clinically, HNPCC is often divided into two subgroups. Type I is characterized by hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II is characterized by increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPCC is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term 'suspected HNPCC' or 'incomplete HNPCC' can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected. The disease is caused by variants affecting the gene represented in this entry MIM: 614331 PMID 9590282 ↗ |
| 疾病關聯 | 影響 TGFBR2 的變異與食道癌相關。食道癌為食道的惡性腫瘤，常見類型包括食道鱗狀細胞癌及腺癌；來源指出，此病通常到晚期、難以治癒時才被發現。 | 含實驗來源 | 證據與來源Esophageal cancer ESCR A malignancy of the esophagus. The most common types are esophageal squamous cell carcinoma and adenocarcinoma. Cancer of the esophagus remains a devastating disease because it is usually not detected until it has progressed to an advanced incurable stage. The disease is caused by variants affecting the gene represented in this entry MIM: 133239 PMID 10789724 ↗ |
| 疾病關聯 | 影響 TGFBR2 的變異與 Loeys-Dietz syndrome 2（LDS2）相關，表徵包括動脈迂曲與動脈瘤、眼距過寬及分叉懸雍垂或顎裂。Cys-460、His-460 突變曾被報告與胸主動脈瘤及剝離相關；來源並說明，因部分患者也有降主動脈及其他動脈病變，OMIM 將該表現納入 LDS2。 | 含實驗來源 | 證據與來源Loeys-Dietz syndrome 2 LDS2 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. TGFBR2 mutations Cys-460 and His-460 have been reported to be associated with thoracic aortic aneurysms and dissection (TAAD). This phenotype, also known as thoracic aortic aneurysms type 3 (AAT3), is distinguised from LDS2 by having aneurysms restricted to thoracic aorta. As individuals carrying these mutations also exhibit descending aortic disease and aneurysms of other arteries, they have been considered as LDS2 by the OMIM resource MIM: 610168 PMID 16027248 ↗ · PMID 15235604 ↗ · PMID 15731757 ↗ · PMID 16251899 ↗ · PMID 19533785 ↗ · PMID 19883511 ↗ · PMID 20101701 ↗ · PMID 20358619 ↗ · PMID 21949523 ↗ · PMID 22113417 ↗ |
核酸與蛋白質序列
ACTCGCGCGCACGGAGCGACGACACCCCCGCGCGTGCACC40CGCTCGGGACAGGAGCCGGACTCCTGTGCAGCTTCCCTCG80GCCGCCGGGGGCCTCCCCGCGCCTCGCCGGCCTCCAGGCC120CCCTCCTGGCTGGCGAGCGGGCGCCACATCTGGCCCGCAC160ATCTGCGCTGCCGGCCCGGCGCGGGGTCCGGAGAGGGCGC200GGCGCGGAGGCGCAGCCAGGGGTCCGGGAAGGCGCCGTCC240GCTGCGCTGGGGGCTCGGTCTATGACGAGCAGCGGGGTCT280GCCATGGGTCGGGGGCTGCTCAGGGGCCTGTGGCCGCTGC320ACATCGTCCTGTGGACGCGTATCGCCAGCACGATCCCACC360GCACGTTCAGAAGTCGGTTAATAACGACATGATAGTCACT400GACAACAACGGTGCAGTCAAGTTTCCACAACTGTGTAAAT440TTTGTGATGTGAGATTTTCCACCTGTGACAACCAGAAATC480CTGCATGAGCAACTGCAGCATCACCTCCATCTGTGAGAAG520CCACAGGAAGTCTGTGTGGCTGTATGGAGAAAGAATGACG560AGAACATAACACTAGAGACAGTTTGCCATGACCCCAAGCT600CCCCTACCATGACTTTATTCTGGAAGATGCTGCTTCTCCA640AAGTGCATTATGAAGGAAAAAAAAAAGCCTGGTGAGACTT680TCTTCATGTGTTCCTGTAGCTCTGATGAGTGCAATGACAA720CATCATCTTCTCAGAAGAATATAACACCAGCAATCCTGAC760TTGTTGCTAGTCATATTTCAAGTGACAGGCATCAGCCTCC800TGCCACCACTGGGAGTTGCCATATCTGTCATCATCATCTT840CTACTGCTACCGCGTTAACCGGCAGCAGAAGCTGAGTTCA880ACCTGGGAAACCGGCAAGACGCGGAAGCTCATGGAGTTCA920GCGAGCACTGTGCCATCATCCTGGAAGATGACCGCTCTGA960cDNA 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。