基因總覽
TGFB3 編碼 transforming growth factor beta 3，屬於 TGF-beta 家族。其前體經加工後形成 Latency-associated peptide（LAP）與 Transforming growth factor beta-3 兩條鏈，分別構成調節部分與活性部分。兩鏈可非共價結合，使活性鏈在細胞外基質中維持潛伏狀態；因此，這個蛋白質的成熟與活性不只涉及前體加工，也受到後續調控。
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 |
|---|---|---|
| ENST00000238682 ★ | 75,958,097–75,981,995 | 7 |
| ENST00000556674 | 75,958,066–75,983,026 | 8 |
| ENST00000858792 | 75,958,066–75,982,570 | 8 |
| ENST00000858793 | 75,958,066–75,982,525 | 8 |
| ENST00000858794 | 75,958,066–75,982,525 | 8 |
| ENST00000858795 | 75,958,066–75,982,525 | 8 |
| ENST00000858796 | 75,958,066–75,981,998 | 7 |
| ENST00000858797 | 75,958,066–75,981,998 | 6 |
| ENST00000911430 | 75,958,066–75,982,524 | 8 |
| ENST00000964914 | 75,958,066–75,983,026 | 8 |
| ENST00000964915 | 75,958,066–75,983,026 | 8 |
| ENST00000964916 | 75,958,066–75,981,998 | 5 |
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
Transforming growth factor beta-3 參與胚胎發育與細胞分化，並在次級腭發育等過程中具有必要作用；這些功能描述依據相似性推定。其活化涉及多個階段：前體在 Golgi apparatus 經切割後，形成 LAP 與 Transforming growth factor beta-3 鏈，兩者仍以非共價方式連結，使活性鏈在細胞外基質中維持不活化狀態。
LAP 除了與活性鏈結合，也可與 LTBP1、LRRC32/GARP 等細胞外環境分子互動，協助調節 Transforming growth factor beta-3 的活化，並在細胞外環境中維持其潛伏狀態。這些調控機制同樣是依相似性推定。
integrins 與 LAP 結合後會使 LAP 鏈構形變形，促使活性 Transforming growth factor beta-3 從 LAP 釋出。釋出的蛋白質接著與 TGF-beta receptors TGFBR1 和 TGFBR2 結合，由受體傳遞訊號。資料描述的是活化與訊號傳遞的步驟，未進一步詳述下游訊號內容。
Promoter 與基因調控
>TGFB3 ENST00000238682 GRCh38 chr14:75981895-75982995 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 AGGCCTAGAGGTTCGGGCCGAGAAGAGGAGCGAAAGCACAGAGCCGACTTCCCCTCACCCATCTGGGAAA TGGGCTCGGGCCAACTGCTGACTTCGCGCTCGCTGGCGCAGCTCCCTGCGGAGACCTCGGCGGGGAGGGA GGCTGAACATCTGGATGACATTTCTGCGAGAGCGGCTCCGGAGCGGCGGTCGGGGAGGGAGAGGTGCGCT CGTGCGCACGTCGGGCCGGGAGGGAGGCGATTCCTCGGGGCCTGGGTCTTGTTTTTCTCGCTCTCTACCG CAGCCCCTTCTCCCGCCCCTCAGCCCCCACCCCGCAGCCCCCAGCCCCCGAGCCTCCCCGGCTCCCGACC AGCCGAGCTCCTTCACTGGCGGCCTCGCCTCGCCAGAGGGCACCCTCGATCTTCCGGAAAACGCCACCAT TTTTCACTGCCCCTGGAGCGTCTCCAGGCTTCTGCCCGCCTCCCGACTCCGATCTTGTCAATGAAGAATC GGGCCAGGATCGCCGCGGAGCGGACGCCGACCCTCCGACCCGGCTCGCAGGCTGGGAGTCCCCTCTGCGA GGCTGGCATGGCCGCCCCTACCGGGTCCCGCGCCCTCTGCGGACCCTGCCCCGGGTTGGGCCTGGCCCGC GGGCGGCCCCGGGACCGGGGGACCAGGAGGGAGAGTAGACGCGGGCCGCGGACGGCGCGGACTGACAGCT GGCGAGAGGGCGCCGGGGCTGGGGGAAAGGGAGGGAGGGGGCTCATCGGAGTAACTTTCCAGAAAAACAG CCAACGTGTGGCAGGAGTGATTCCAAGAGGGGAAAAAAAGTTCAGCTACCACGTCGAACGAGAGGACTCG CAAAGTATTTTTCAAAAGGGCTCGGCTTTTCCTGTGCCTGTTTAAAACATTAACATCGTGCAGCAAAAGA GGCTGCGTGCGCTGGTCCCTCCCTCCCCCACCCCAGGCCAGAGACGTCATGGGAGGGAGGTATAAAATTT CAGCAGAGAGAAATAGAGAAAGCAGTGTGTGTGCATGTGTGTGTGTGTGAGAGAGAGAGGGAGAGGAGCG AGAGGGAGAGGGAGAGGGAGAGAGAGAAAGGGAGGGAAGCAGAGAGTCAAG
EPDnew 實驗支持 promoter／TSS · 2 筆
| EPDnew ID | TSS（1-based） | 股向 | 來源顯示區間 |
|---|---|---|---|
| TGFB3_1 ↗ | 14:75,981,007 | 負股 | 75,980,997–75,981,056 |
| TGFB3_2 ↗ | 14:75,981,160 | 負股 | 75,981,150–75,981,209 |
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
蛋白質結構域與序列
參考蛋白質長度：412 aa
TGFB3 前體長 412 個胺基酸，N 端第 1–23 位標註為訊號胜肽；第 261–263 位則有細胞附著位點（cell attachment site）註解。該蛋白質屬於 TGF-beta 家族。
蛋白質三維結構
細胞內定位
LAP 會分泌至細胞外空間與細胞外基質；Transforming growth factor beta-3 鏈則標註為分泌型。 來源未描述兩者因條件或異構型而有不同定位。
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。
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 1 個夥伴
- TGFBR2P37173 · UniProt INTERACTION · 8 experiments
LAP 與 Transforming growth factor beta-3 鏈以非共價方式結合，維持後者的潛伏狀態；LAP 也可與 LRRC32/GARP 及 integrins 互動，分別涉及活化調節及活性鏈釋出。LAP 與 Transforming growth factor beta-3 各自可形成雙硫鍵連結的同源二聚體。活化的 Transforming growth factor beta-3 與 TGFBR1、TGFBR2 結合並促成訊號傳遞。另有與 ASPN 互作的記錄，但來源未說明其作用方式。
疾病與遺傳關聯
來源列出 TGFB3 變異與家族性致心律不整性右心室發育不良 1（ARVD1）及 Loeys-Dietz syndrome 5（LDS5）的疾病關聯，並記載這些疾病由影響該基因的變異所致。ARVD1 是先天性心臟病，可見脂肪與纖維組織浸潤右心室、心肌細胞減少及心室性和上心室性心律不整。LDS5 屬 Loeys-Dietz syndrome；其描述包括動脈迂曲與動脈瘤、眼距過寬、分叉懸雍垂或腭裂，也可能有二尖瓣疾病、骨骼過度生長、頸椎不穩及馬蹄內翻足。LDS5 患者未見顯著主動脈或動脈迂曲，且缺乏早發性主動脈剝離的強力證據。
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 · 8 筆
| 功能面向 | 功能敘述 | 證據類型 | 可查核來源 |
|---|---|---|---|
| 功能 | Transforming growth factor beta-3 proprotein 是前體，會形成 Latency-associated peptide（LAP）鏈與 Transforming growth factor beta-3 鏈；兩者分別構成 TGF-beta-3 的調節部分與活性部分。 | 推論支持 | 證據與來源Transforming growth factor beta-3 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-3 (TGF-beta-3) chains, which constitute the regulatory and active subunit of TGF-beta-3, respectively |
| 功能 | Transforming growth factor beta-3 鏈在細胞外基質儲存期間須維持潛伏狀態。LAP 與該鏈非共價結合，並透過與 LTBP1、LRRC32/GARP 等細胞外環境分子的互動調節活化；integrins 結合則使 LAP 鏈變形，促使活性鏈釋出。以上機制依相似性推定。 | 推論支持 | 證據與來源Required to maintain the Transforming growth factor beta-3 (TGF-beta-3) chain in a latent state during storage in extracellular matrix (By similarity). Associates non-covalently with TGF-beta-3 and regulates its activation via interaction with 'milieu molecules', such as LTBP1 and LRRC32/GARP, that control activation of TGF-beta-3 (By similarity). Interaction with integrins results in distortion of the Latency-associated peptide chain and subsequent release of the active TGF-beta-3 (By similarity) |
| 功能 | Transforming growth factor beta-3 依相似性推定可調節胚胎發育與細胞分化，並參與次級腭發育。前體在 Golgi apparatus 切割後，LAP 與活性鏈仍非共價結合，使活性鏈在細胞外基質中保持不活化；LAP 與 LTBP1、LRRC32/GARP 等分子互動並調控活化。integrins 結合使 LAP 變形並釋出活性鏈，後者再結合 TGFBR1、TGFBR2 傳遞訊號。 | 推論支持 | 證據與來源Transforming growth factor beta-3: Multifunctional protein that regulates embryogenesis and cell differentiation and is required in various processes such as secondary palate development (By similarity). Activation into mature form follows different steps: following cleavage of the proprotein in the Golgi apparatus, Latency-associated peptide (LAP) and Transforming growth factor beta-3 (TGF-beta-3) chains remain non-covalently linked rendering TGF-beta-3 inactive during storage in extracellular matrix (By similarity). At the same time, LAP chain interacts with 'milieu molecules', such as LTBP1 and LRRC32/GARP that control activation of TGF-beta-3 and maintain it in a latent state during storage in extracellular milieus (By similarity). TGF-beta-3 is released from LAP by integrins: integrin-binding results in distortion of the LAP chain and subsequent release of the active TGF-beta-3 (By similarity). Once activated following release of LAP, TGF-beta-3 acts by binding to TGF-beta receptors (TGFBR1 and TGFBR2), which transduce signal (By similarity) |
| 交互作用 | LAP 與 Transforming growth factor beta-3 各自可形成雙硫鍵連結的同源二聚體；兩鏈之間以非共價方式結合，使活性鏈維持潛伏。LAP 與 LRRC32/GARP、integrins 互動，涉及活化調節及活性鏈釋出；Transforming growth factor beta-3 與 TGFBR1、TGFBR2 結合以傳遞訊號，另記載與 ASPN 互作。 | 含實驗來源 | 證據與來源Interacts with ASPN. Latency-associated peptide: Homodimer; disulfide-linked. Latency-associated peptide: Interacts with Transforming growth factor beta-3 (TGF-beta-3) chain; interaction is non-covalent and maintains (TGF-beta-3) in a latent state (By similarity). Latency-associated peptide: Interacts with LRRC32/GARP; leading to regulate activation of TGF-beta-3 and promote epithelial fusion during palate development (By similarity). Latency-associated peptide: Interacts (via cell attachment site) with integrins, leading to release of the active TGF-beta-3 (By similarity). Transforming growth factor beta-3: Homodimer; disulfide-linked. Transforming growth factor beta-3: Interacts with TGF-beta receptors (TGFBR1 and TGFBR2), leading to signal transduction (By similarity) PMID 8819159 ↗ |
| 細胞定位 | Latency-associated peptide 會分泌至細胞外空間及細胞外基質。 | 推論支持 | |
| 細胞定位 | Transforming growth factor beta-3 鏈標註為分泌型。 | 推論支持 | |
| 疾病關聯 | 家族性致心律不整性右心室發育不良 1（ARVD1）是先天性心臟病，特徵包括脂肪與纖維組織浸潤右心室、心肌細胞減少，並導致心室性及上心室性心律不整。來源將此病因歸於影響該基因的變異。 | 含實驗來源 | 證據與來源Arrhythmogenic right ventricular dysplasia, familial, 1 ARVD1 A congenital heart disease characterized by infiltration of adipose and fibrous tissue into the right ventricle and loss of myocardial cells, resulting in ventricular and supraventricular arrhythmias. The disease is caused by variants affecting the gene represented in this entry MIM: 107970 PMID 15639475 ↗ |
| 疾病關聯 | Loeys-Dietz syndrome 5（LDS5）是 Loeys-Dietz syndrome 的一型，可有動脈迂曲與動脈瘤、眼距過寬、分叉懸雍垂或腭裂；其他表現包括二尖瓣疾病、骨骼過度生長、頸椎不穩及馬蹄內翻足。患者未見顯著主動脈或動脈迂曲，且沒有早發性主動脈剝離的強力證據。來源將疾病歸因於影響該基因的變異。 | 含實驗來源 | 證據與來源Loeys-Dietz syndrome 5 LDS5 A form of Loeys-Dietz syndrome, a syndrome with widespread systemic involvement characterized by arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. LDS5 additional variable features include mitral valve disease, skeletal overgrowth, cervical spine instability, and clubfoot deformity. LDS5 patients do not manifest remarkable aortic or arterial tortuosity, and there is no strong evidence for early aortic dissection. The disease is caused by variants affecting the gene represented in this entry MIM: 615582 PMID 23824657 ↗ |
核酸與蛋白質序列
AGCAGTGTGTGTGCATGTGTGTGTGTGTGAGAGAGAGAGG40GAGAGGAGCGAGAGGGAGAGGGAGAGGGAGAGAGAGAAAG80GGAGGGAAGCAGAGAGTCAAGTCCAAGGGAATGAGCGAGA120GAGGCAGAGACAGGGGAAGAGGCGTGCGAGAGAAGGAATA160ACAGCTTTCCGGAGCAGGCGTGCCGTGAACTGGCTTCTAT200TTTATTTTATTTTTTTCTCCTTTTTATTTTTTAAAGAGAA240GCAGGGGACAGAAGCAATGGCCGAGGCAGAAGACAAGCCG280AGGTGCTGGTGACCCTGGGCGTCTGAGTGGATGATTGGGG320CTGCTGCGCTCAGAGGCCTGCCTCCCTGCCTTCCAATGCA360TATAACCCCACACCCCAGCCAATGAAGACGAGAGGCAGCG400TGAACAAAGTCATTTAGAAAGCCCCCGAGGAAGTGTAAAC440AAAAGAGAAAGCATGAATGGAGTGCCTGAGAGACAAGTGT480GTCCTGTACTGCCCCCACCTTTAGCTGGGCCAGCAACTGC520CCGGCCCTGCTTCTCCCCACCTACTCACTGGTGATCTTTT560TTTTTTTACTTTTTTTTCCCTTTTCTTTTCCATTCTCTTT600TCTTATTTTCTTTCAAGGCAAGGCAAGGATTTTGATTTTG640GGACCCAGCCATGGTCCTTCTGCTTCTTCTTTAAAATACC680CACTTTCTCCCCATCGCCAAGCGGCGTTTGGCAATATCAG720ATATCCACTCTATTTATTTTTACCTAAGGAAAAACTCCAG760CTCCCTTCCCACTCCCAGCTGCCTTGCCACCCCTCCCAGC800CCTCTGCTTGCCCTCCACCTGGCCTGCTGGGAGTCAGAGC840CCAGCAAAACCTGTTTAGACACATGGACAAGAATCCCAGC880GCTACAAGGCACACAGTCCGCTTCTTCGTCCTCAGGGTTG920CCAGCGCTTCCTGGAAGTCCTGAAGCTCTCGCAGTGCAGT960cDNA 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。