基因總覽
RHD 是蛋白質編碼基因,產物 Rh blood group D antigen 為紅血球膜蛋白,屬於 ammonium transporter(TC 2.A.49)家族的 Rh subfamily。其蛋白序列長 417 個胺基酸,具有多段跨膜螺旋,符合多次穿膜膜蛋白的特徵。文獻將 Rh polypeptide 描述為紅血球膜中的整合性蛋白,並指出它是 Rh 抗原相關的大分子複合體成員之一。這些特性構成其膜蛋白身分;其可能的膜內作用及脂肪酸修飾情形,另見功能說明。
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 |
|---|---|---|
| ENST00000328664 ★ | 25,272,509–25,330,445 | 10 |
| ENST00000648012 | 25,272,439–25,329,161 | 9 |
| ENST00000622561 | 25,272,439–25,330,445 | 11 |
| ENST00000454452 | 25,272,439–25,330,445 | 7 |
| ENST00001103186 | 25,272,439–25,330,445 | 10 |
| ENST00001145213 | 25,272,439–25,330,445 | 10 |
| ENST00000342055 | 25,272,548–25,329,211 | 9 |
| ENST00000357542 | 25,272,548–25,329,211 | 8 |
| ENST00000417538 | 25,272,548–25,329,211 | 8 |
| ENST00000423810 | 25,272,548–25,329,211 | 10 |
| ENST00000568195 | 25,272,548–25,329,211 | 9 |
顯示 11/11 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
RHD 產物 Rh blood group D antigen 的功能尚未完全確定。資料指出它可能是紅血球膜寡聚複合體的一部分,而該複合體可能具有運輸或通道功能;這項描述仍屬可能性,不能視為已確立的特定運輸底物或機制。
早期研究著重於 Rh polypeptide 的脂肪酸修飾。以完整人類紅血球進行的實驗中,加入放射性標記的棕櫚酸後,可在 Rh(D) 陰性與陽性紅血球膜中觀察到約 32,000 Da 的標記蛋白;陽性細胞中的該蛋白可由 anti-D 沉澱。缺少 Rh 抗原的 Rhmod 紅血球膜則未見相似標記。研究結果支持 Rh polypeptide 可接受脂肪酸醯化,且修飾不依賴蛋白質合成;以未標記棕櫚酸追蹤時,標記可完全逆轉,符合紅血球膜中醯化與去醯化的動態過程。
後續體外研究以人類或其他哺乳類紅血球製備的 inside-out 膜囊泡進行分析,發現 ATP 與 CoA 存在時,Rh polypeptide 主要接受棕櫚酸標記,也可接受肉豆蔻酸或油酸。相較之下,完整人類紅血球較偏好摻入棕櫚酸。試劑處理與胰蛋白酶消化結果顯示,多個位於脂雙層細胞質側附近的巰基可能被棕櫚醯化;與 Rh 抗原性相關的外側巰基則未被標記。
在去污劑溶解的膜樣本中,已棕櫚醯化的 Rh polypeptide 呈現約 170,000 Da 的表觀分子量,研究者因此提出它可能處於大分子複合體中。脂肪酸轉移在膜囊泡經高溫處理或以 Triton X-100 溶解後仍可觀察到,該體外結果被解讀為修飾具有選擇性,但作用機制可能不依賴酵素。這些研究描繪了 Rh polypeptide 的膜內修飾與複合體關聯,尚未釐清其與所推測運輸或通道功能之間的直接關係。
Promoter 與基因調控
>RHD ENST00000328664 GRCh38 chr1:25271509-25272609 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 GAAAATAAGGAAACTCCAATTCCTTCCTTCTTTTCTTCCTCTTTCATCTCTTCCTCCCTCTCTACATCCC TCTCTCTCTTCCTTCCTTCCTCGACACTTACCATGTACCAGACCTTCTGCCAGGCACATGGATGGGAGCA CAGGGGAAGTTGGCTGCAGGGTTAGAACTAAGTCCCAAGCCCCCTAAAGCTCATGCCAGGGGACTGGACT GTCCAGTACTGAGGGATGGGGATGCTGAGGCTGGTGGCCTTCCTCAAATGCACTGTAGTGCCCCAGGCAG AGTCCTGGGCTGCCCTGTGAGGAGGTGACCAGAGGTAGAGCAACTTCACCCTAAGGCTGGATCAGGATCC CCTCCAGGTTTTTACTAGAGCCAAACCCACATCTCCTTTCTCTTCTGCCACCCCCCCTTAAAATGCTTAG AAACACATAGATTTAAATACAAATTCAAATGTAAGTAATTTCAACTGTGTAACTATGAGGAGTCAGTTCT ACGTGGGTCCTATCTGTATCCTCCCCAGGGCTCAGCTCCATTCTTTGCTTTCATTCATTCTCATTCAATA CATTGTTGTTAAGAGCTCACTGGGTGCCCTCTCTGTCATGTAGTAAGGTTTTAAAAAGAAAGCCTCTTCT GAGCTTCAGTTTCCTTATTCATAAAATAGGAGTATTGATCCATTCCTTGCTTTTCTTACAAGGATATGCT GAAGATGACTGAAGTACAGAGTAAAGAAGGATTATGTTTGGGTGTCAAAGGAATAGAATGCCCTCTTTCA AACTGAGCACAGCAGGAACCTGTAACAGGAACACAGCAACTTGTTGAATGAATGACAATATTGGAAAACA TACATTTCCTCCCCTCCCCATCATAGTCCCTCTGCTTCCGTGTTAACTCCATAGAGAGGCCAGCACAACC AGCCTTGCAGCCTGAGATAAGGCCTTTGGCGGGTGTCTCCCCTATCGCTCCCTCAAGCCCTCAAGTAGGT GTTGGAGAGAGGGGTGATGCCTGGTGCTGGTGGAACCCCTGCACAGAGACGGACACAGGATGAGCTCTAA GTACCCGCGGTCTGTCCGGCGCTGCCTGCCCCTCTGGGCCCTAACACTGGA
EPDnew 實驗支持 promoter/TSS · 2 筆
| EPDnew ID | TSS(1-based) | 股向 | 來源顯示區間 |
|---|---|---|---|
| RHD_2 ↗ | 1:25,272,399 | 正股 | 25,272,350–25,272,409 |
| RHD_1 ↗ | 1:25,272,509 | 正股 | 25,272,460–25,272,519 |
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
ENSR1_C4HNR · enhancer · 25266386–25268318 · regulatory
ENSR1_8Q3N8 · promoter · 25272274–25272519 · regulatory
· motif · 25267628–25267643 · motif
· motif · 25267901–25267912 · motif
· motif · 25267901–25267912 · motif
· motif · 25267922–25267939 · motif
· motif · 25267974–25267985 · motif
· motif · 25267974–25267985 · motif
· motif · 25268010–25268019 · motif
· motif · 25268161–25268174 · motif
· motif · 25272433–25272439 · motif
蛋白質結構域與序列
參考蛋白質長度:417 aa
Rh blood group D antigen 長 417 個胺基酸,序列註解包含 11 段螺旋型跨膜區域,分布於蛋白質不同位置。這種多次穿膜的結構特徵與其紅血球膜蛋白身分相符;家族分類為 ammonium transporter(TC 2.A.49)家族的 Rh subfamily。
蛋白質三維結構
細胞內定位
Rh blood group D antigen 定位於細胞膜,屬多次穿膜蛋白。 輸入資料未提供可區分的定位變化條件、異構型差異或動態資訊。
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。
更多交互作用夥伴 · 已取得 7 個夥伴
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- TMEM237Q96Q45-2 · UniProt INTERACTION · 3 experiments
已取得的互作紀錄列於上方網絡與資料卡。
疾病與遺傳關聯
RHD 變異與 RhD 相關胎兒及新生兒溶血病有關。此病發生於缺乏 Rh 血型 D 抗原的母親接觸 RhD 陽性胎兒紅血球後;母體產生的抗體可穿過胎盤並破壞胎兒紅血球。來源將疾病歸因於影響 RHD 的變異,但未提供特定變異或風險量化資料。
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 · 5 筆
| 功能面向 | 功能敘述 | 證據類型 | 可查核來源 |
|---|---|---|---|
| 功能 | Rh blood group D antigen 可能參與紅血球膜寡聚複合體;該複合體可能具有運輸或通道功能。來源以可能性描述此角色,未指出具體運輸物質或已確立的作用機制。 | 資料庫紀錄 | 證據與來源May be part of an oligomeric complex which is likely to have a transport or channel function in the erythrocyte membrane |
| 細胞定位 | Rh blood group D antigen 位於細胞膜,並被註記為多次穿膜蛋白。 | 含實驗來源 | |
| 疾病關聯 | RhD 相關胎兒及新生兒溶血病發生於缺乏 RhD 抗原的母親接觸 RhD 陽性胎兒紅血球後;母體抗體可穿過胎盤並破壞胎兒紅血球。來源指出影響 RHD 的基因變異會造成此病。 | 含實驗來源 | 證據與來源Hemolytic disease of fetus and newborn, RH-induced HDFNRH A disease that occurs in pregnancies in which mothers who lack the D antigen (RhD) of the Rh blood group have been exposed to the RhD-positive red cells of the fetus. The resulting maternal autoantibodies cross the placenta and destroy fetal red cells. The disease is caused by variants affecting the gene represented in this entry MIM: 619462 PMID 10805260 ↗ |
| 功能 | Incubation of [3H]palmitic acid, ATP, and CoA with inside-out membrane vesicles prepared from human or other mammalian red cells resulted in nearly exclusive 3H-palmitoylation of the Mr = 32,000 Rh polypeptides. [3H]Palmitic, [3H]myristic, and [3H]oleic acids were comparably esterified onto Rh polypeptides in inside-out membrane vesicles in the presence of ATP and CoA, although [3H]palmitic acid was preferentially incorporated by intact human red cells. Experiments using sulfhydryl reagents or tryptic digestions suggested that multiple sulfhydryl groups on the Rh polypeptides located near the cytoplasmic leaflet of the lipid bilayer were 3H-palmitoylated; the exofacial sulfhydryl group essen | 文獻摘要 | 證據與來源Incubation of [3H]palmitic acid, ATP, and CoA with inside-out membrane vesicles prepared from human or other mammalian red cells resulted in nearly exclusive 3H-palmitoylation of the Mr = 32,000 Rh polypeptides. [3H]Palmitic, [3H]myristic, and [3H]oleic acids were comparably esterified onto Rh polypeptides in inside-out membrane vesicles in the presence of ATP and CoA, although [3H]palmitic acid was preferentially incorporated by intact human red cells. Experiments using sulfhydryl reagents or tryptic digestions suggested that multiple sulfhydryl groups on the Rh polypeptides located near the cytoplasmic leaflet of the lipid bilayer were 3H-palmitoylated; the exofacial sulfhydryl group essential for Rh antigenic reactivity was not 3H-palmitoylated. Transfer of fatty acid from [14C]palmitoyl-CoA to sites on the Rh polypeptides occurred even after previous incubation of inside-out membrane vesicles at 95 degrees C or after solubilization of inside-out membrane vesicles in Triton X-100. Hydrodynamic analyses of Triton X-100-solubilized membranes surprisingly demonstrated that 3H-palmitoylated Rh polypeptides behaved as a protein of apparent Mr = 170,000. These in vitro studies suggest that palmitoylation of Rh polypeptides occurs within a macromolecular complex by a highly selective but possibly nonenzymatic mechanism. PMID 1544931 ↗Mammalian red cell membrane Rh polypeptides are selectively palmitoylated subunits of a macromolecular complex. · cc by |
| 功能 | 人類紅血球實驗顯示,Rh polypeptide 可接受脂肪酸醯化。放射性棕櫚酸標記出現在 Rh(D) 陰性與陽性細胞的約 32,000 Da 蛋白,陽性細胞中的蛋白可由 anti-D 沉澱;缺少 Rh 抗原的 Rhmod 細胞未見相似標記。結果支持棕櫚酸透過硫酯鍵醯化,修飾不依賴蛋白質合成,且可由未標記棕櫚酸追蹤而完全逆轉。 | 文獻摘要 | 證據與來源The erythrocyte Rh antigens contain an Mr = 32,000 integral protein which is thought to contribute in some way to the organization of surrounding phospholipid. To search for possible fatty acid acylation of the Rh polypeptide, intact human erythrocytes were incubated with [3H]palmitic acid prior to preparation of membranes and sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography. Several membrane proteins were labeled, but none corresponded to the glycophorins or membrane proteins 1-8. An Mr = 32,000 band was prominently labeled on Rh (D)-negative and -positive erythrocytes and could be precipitated from the latter with anti-D. No similar protein was labeled on membranes from Rhmod erythrocytes, a rare phenotype lacking Rh antigens. Labeling of the Rh polypeptide most likely represents palmitic acid acylation through thioester linkages. The 3H label was not extracted with chloroform/methanol, but was quantitatively eluted with hydroxylamine and co-chromatographed with palmitohydroxamate and free palmitate by thin layer chromatography. The fatty acid acylations occurred independent of protein synthesis and were completely reversed by chase with unlabeled palmitate. It is concluded that the Rh polypeptide is fatty acid-acylated, being a major substrate of an acylation-deacylation mechanism associated with the erythrocyte membrane. PMID 3142870 ↗The Rh polypeptide is a major fatty acid-acylated erythrocyte membrane protein. · cc by |
核酸與蛋白質序列
CTGGTGCTGGTGGAACCCCTGCACAGAGACGGACACAGGA40TGAGCTCTAAGTACCCGCGGTCTGTCCGGCGCTGCCTGCC80CCTCTGGGCCCTAACACTGGAAGCAGCTCTCATTCTCCTC120TTCTATTTTTTTACCCACTATGACGCTTCCTTAGAGGATC160AAAAGGGGCTCGTGGCATCCTATCAAGTTGGCCAAGATCT200GACCGTGATGGCGGCCATTGGCTTGGGCTTCCTCACCTCG240AGTTTCCGGAGACACAGCTGGAGCAGTGTGGCCTTCAACC280TCTTCATGCTGGCGCTTGGTGTGCAGTGGGCAATCCTGCT320GGACGGCTTCCTGAGCCAGTTCCCTTCTGGGAAGGTGGTC360ATCACACTGTTCAGTATTCGGCTGGCCACCATGAGTGCTT400TGTCGGTGCTGATCTCAGTGGATGCTGTCTTGGGGAAGGT440CAACTTGGCGCAGTTGGTGGTGATGGTGCTGGTGGAGGTG480ACAGCTTTAGGCAACCTGAGGATGGTCATCAGTAATATCT520TCAACACAGACTACCACATGAACATGATGCACATCTACGT560GTTCGCAGCCTATTTTGGGCTGTCTGTGGCCTGGTGCCTG600CCAAAGCCTCTACCCGAGGGAACGGAGGATAAAGATCAGA640CAGCAACGATACCCAGTTTGTCTGCCATGCTGGGCGCCCT680CTTCTTGTGGATGTTCTGGCCAAGTTTCAACTCTGCTCTG720CTGAGAAGTCCAATCGAAAGGAAGAATGCCGTGTTCAACA760CCTACTATGCTGTAGCAGTCAGCGTGGTGACAGCCATCTC800AGGGTCATCCTTGGCTCACCCCCAAGGGAAGATCAGCAAG840ACTTATGTGCACAGTGCGGTGTTGGCAGGAGGCGTGGCTG880TGGGTACCTCGTGTCACCTGATCCCTTCTCCGTGGCTTGC920CATGGTGCTGGGTCTTGTGGCTGGGCTGATCTCCGTCGGG960cDNA 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。