基因總覽
VPS29 retromer complex component 是由 VPS29 基因編碼的蛋白質,屬於 VPS29 family。它是多種膜運輸複合體的組成成員,包括 retromer cargo-selective complex(CSC)與 retriever complex;也屬於由 CCC subcomplex 和 retriever subcomplex 組成的 commander complex。這些複合體參與內體膜蛋白貨物的分選與運輸。VPS29 的特色在於可置身於組成和合作夥伴不同的複合體中,因此其功能脈絡會隨複合體類型而異。
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 |
|---|---|---|
| ENST00000549578 ★ | 110,491,083–110,502,111 | 4 |
| ENST00000360579 | 110,489,728–110,502,132 | 5 |
| ENST00000552130 | 110,489,728–110,499,546 | 5 |
| ENST00000447578 | 110,489,728–110,502,078 | 5 |
| ENST00000546588 | 110,489,728–110,502,092 | 6 |
| ENST00000549970 | 110,489,728–110,502,111 | 5 |
| ENST00001008778 | 110,489,728–110,502,132 | 3 |
| ENST00001008780 | 110,489,728–110,502,132 | 4 |
| ENST00001008783 | 110,489,728–110,502,132 | 6 |
| ENST00001008786 | 110,489,728–110,502,132 | 4 |
| ENST00001024938 | 110,489,728–110,502,132 | 6 |
| ENST00001066411 | 110,489,728–110,502,132 | 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
VPS29 是內體貨物分選與回收相關複合體的成員。它參與 retriever complex,此異源三聚體與 retromer cargo-selective complex(CSC)相關,但負責不依賴 retromer 的貨物回收;例如 integrin alpha-5/beta-1(ITGA5:ITGB1)等貨物。Retriever complex 在內體中與 SNX17 協作,回收帶有 NxxY motif 的貨物,支持多種細胞表面蛋白的穩態維持;這些蛋白與細胞遷移、細胞黏附、營養供應及細胞訊號等過程相關。Retriever complex 招募至內體膜涉及 CCC 與 WASH complexes。
VPS29 也屬於 retromer CSC。CSC 被認為是 retromer 或其不同變體的核心功能組件,可避免特定跨膜貨物被錯誤送入溶酶體降解途徑。不同 retromer 變體與 sorting nexins 合作,參與不同路徑:SNX-BAR retromer 可將貨物由內體逆向運送至 trans-Golgi network(TGN),也參與內體至細胞膜的運輸與回收;SNX3-retromer 則以不同於 SNX-BAR 路徑的方式,介導 WLS 由內體逆向運送至 TGN。SNX27-retromer 被認為參與多種貨物由內體運往細胞膜及其回收。CSC 招募至內體膜涉及 RAB7A 和 SNX3,並可作為 WASH complex、TBC1D5 等蛋白的招募平台。
此外,VPS29 對 polymeric immunoglobulin receptor(pIgR-pIgA)的跨胞轉運調節有必要性,也參與 GLUT1 由內體至細胞膜的運送;後者功能依賴其與 ANKRD27 的關聯。在微生物感染情境中,CSC 介導 human papillomavirus 離開早期內體並送至 Golgi apparatus。
Promoter 與基因調控
>VPS29 ENST00000549578 GRCh38 chr12:110502011-110503111 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 CACTAAGCCCGGCTAATTTTTGTATGTTTAGTAGAGACGGGGTTTCATCATGTTGGTCAGGGTGGTCTCG AACTCCCGACCTAAGGTGATCCACCCGCCTTGGCCTCCCAAAGTGCTAGGATTACAGGCGTGAGCCACTG CACCCGGCCTAACTTCCATTTTGAAAGCGCCGTTTACAACACTAATAGTTCTTGTACATTCCATCTATTA CTGGGCTCTTTACACGCATTTCCATTTCATTGCCTCCAAACAAACTCTGTGACGAAGGTGCTGTCATTAC CCCTGTTTCCGTTTTAGAAACTGAGCCCCAAAGAGATTTAGTGACTTTTCCAAGTTCATACATTTTTAAA AATGGTAGAATCTGGGGAAAAAAAAAACCAGGTTAATGCTGTTCTCTTGGCACAAAAATACTTTTACTGT CCAAGCATTATTTTTTTCTCTCAACTCTTCCCCATGCAGTCCTCAGCATCCCGAGTTTGTGGCCCGATGG TACAACTCTATTTCCCGGATACCACCCATATTACATCTGCCTCTAAGTCACACGAGATGGGTCCTCATCC TCCCCTCAGAAGTTAACAGGGACTTGAGTGGGTGGGGCTGTGGCCAGGGCGTGCGTCCTCAGTCATTGCG CAAAAAGGCAAAGAGGAAAAATTAGACAATGGTAGGGACGACCTATTAACGTCTGCTTTTCTCTCTGCTA AATGGGAAGACAACAAAGGCCGCTCCACCTTTCACCTGACTGCCGCTCATCACGCACTTCAGCATGGCTG CCATCCGCCCTAAAAAGCAGGCTCGGAAGGCGCGCCTCAGCTCGACGGCCCAGGTGCCCGGATGTTGCCC GCGCTTTTCAAAGCTTCGCGATCTCGTCTCTGCACTCTACCACCCCGCCTCCACAAGTTCCCAAACGGCT TTACGGCGGAGAAGGGTCCGTGCGGGCCTCCGTACGGCAATTTCTGTCTCCCTCTGCTCTCATTGGTTGC GGTTAAGTGGGCGGGTCGCCGAGGAGCCTGAGGAAGAGGGCGGCGACGGTGGTGGTGACTGAGCGGAGCC CGGTGACAGGATGGTGAGGGCTGCAGTTGCGGCGACCAAGGCCTGGCTCTC
EPDnew 實驗支持 promoter/TSS · 1 筆
| EPDnew ID | TSS(1-based) | 股向 | 來源顯示區間 |
|---|---|---|---|
| VPS29_1 ↗ | 12:110,502,111 | 負股 | 110,502,101–110,502,160 |
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
ENSR12_BRX4K · enhancer · 110499024–110499535 · regulatory
ENSR12_78HFR3 · promoter · 110499536–110499636 · regulatory
ENSR12_93LT7T · promoter · 110501493–110501993 · regulatory
ENSR12_93LT82 · promoter · 110502068–110502341 · regulatory
· motif · 110499272–110499285 · motif
· motif · 110499298–110499309 · motif
· motif · 110499631–110499641 · motif
· motif · 110501599–110501608 · motif
· motif · 110501599–110501610 · motif
· motif · 110501656–110501673 · motif
· motif · 110501658–110501673 · motif
· motif · 110501663–110501674 · motif
· motif · 110501824–110501837 · motif
· motif · 110501824–110501837 · motif
· motif · 110502115–110502125 · motif
· motif · 110502127–110502135 · motif
· motif · 110502127–110502142 · motif
· motif · 110502220–110502230 · motif
· motif · 110502276–110502285 · motif
· motif · 110502478–110502487 · motif
· motif · 110502478–110502487 · motif
蛋白質結構域與序列
參考蛋白質長度:182 aa
VPS29 retromer complex component 屬於 VPS29 family。來源未提供其序列長度、結構域或其他蛋白質區域註解。
蛋白質三維結構
細胞內定位
VPS29 位於細胞質及膜相關區域,並被列於早期與晚期內體;在膜上屬周邊膜蛋白。 來源未描述不同條件下的定位改變或異構型差異。
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:Membrane。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 33 個夥伴
- TBC1D5B9A6K1 · UniProt INTERACTION · 3 experiments
- TBC1D5Q92609 · UniProt INTERACTION · 12 experiments
- VPS26AO75436 · UniProt INTERACTION · 14 experiments
- VPS35Q96QK1 · UniProt INTERACTION · 27 experiments · 2 筆來源紀錄
- VPS35LQ7Z3J2 · UniProt INTERACTION · 16 experiments
- A2MP01023 · UniProt INTERACTION · 3 experiments
- ACTBP60709 · UniProt INTERACTION · 3 experiments
- APLP1P51693 · UniProt INTERACTION · 3 experiments
- BGNP21810 · UniProt INTERACTION · 3 experiments
- BLMHQ13867 · UniProt INTERACTION · 3 experiments
- CAMK2AQ9UQM7 · UniProt INTERACTION · 3 experiments
- CASP1P29466-3 · UniProt INTERACTION · 3 experiments
- CSNK1DP48730-2 · UniProt INTERACTION · 3 experiments
- DYNC1I1O14576-2 · UniProt INTERACTION · 3 experiments
- FYNP06241 · UniProt INTERACTION · 3 experiments
- HSPD1P10809 · UniProt INTERACTION · 3 experiments
- LRP1Q07954-2 · UniProt INTERACTION · 3 experiments
- MAP3K5Q99683 · UniProt INTERACTION · 3 experiments
- NEFLI6L9F6 · UniProt INTERACTION · 3 experiments
- PARK7Q99497 · UniProt INTERACTION · 3 experiments
- PIK3R1P27986-2 · UniProt INTERACTION · 3 experiments
- PINK1Q9BXM7 · UniProt INTERACTION · 3 experiments
- PRKACAP17612 · UniProt INTERACTION · 3 experiments
- PRKCDQ05655 · UniProt INTERACTION · 3 experiments
- PRKNO60260-5 · UniProt INTERACTION · 3 experiments
VPS29 是 retriever complex 與 retromer CSC 的組成成員;在 retriever complex 中與 VPS35L 互作。它也參與 commander complex。CSC 可與不同 sorting nexins 及 WASH complex 組成具不同功能的複合體。VPS29 與 TBC1D5 互作,但在 retriever complex 中此互作會受 VPS35L 阻斷;與 SNX17 的關係則為間接互作。另有來源記載其與 VPS26A、VPS35、SNX1、SNX2、SNX3、SNX27、WASHC5、VPS26B 及 ANKRD27 互作。感染情境下,VPS29 與 human papillomavirus 16 minor capsid protein L2 的 C 端互作,與病毒衣殼由早期內體運至 Golgi apparatus 有關。
疾病與遺傳關聯
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 | VPS29 是 commander complex、retriever complex 與 retromer CSC 的組成成員,參與內體跨膜貨物回收與分選。Retriever 可回收含 NxxY motif 的貨物,並與 SNX17、CCC 及 WASH complexes 協作;不同 retromer 變體則參與貨物的 TGN 或細胞膜運輸。VPS29 亦涉及 pIgR-pIgA 跨胞轉運調節,以及依賴 ANKRD27 的 GLUT1 內體至細胞膜運送。 | 含實驗來源 | 證據與來源Component of the commander complex that is essential for endosomal recycling of transmembrane cargos; the commander complex is composed of the CCC subcomplex and the retriever subcomplex. Component of the retriever complex, which is a heterotrimeric complex related to retromer cargo-selective complex (CSC) and essential for retromer-independent retrieval and recycling of numerous cargos such as integrin alpha-5/beta-1 (ITGA5:ITGB1). Component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. The recruitment of the CSC to the endosomal membrane involves RAB7A and SNX3. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX3-retromer mediates the retrograde endosome-to-TGN transport of WLS distinct from the SNX-BAR retromer pathway. The SNX27-retromer is believed to be involved in endosome-to-plasma membrane trafficking and recycling of a broad spectrum of cargo proteins. The CSC seems to act as recruitment hub for other proteins, such as the WASH complex and TBC1D5. Required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA). In the endosomes, retriever complex drives the retrieval and recycling of NxxY-motif-containing cargo proteins by coupling to SNX17, a cargo essential for the homeostatic maintenance of numerous cell surface proteins associated with processes that include cell migration, cell adhesion, nutrient supply and cell signaling. The recruitment of the retriever complex to the endosomal membrane involves CCC and WASH complexes. Involved in GLUT1 endosome-to-plasma membrane trafficking; the function is dependent of association with ANKRD27 PMID 24856514 ↗ · PMID 28892079 ↗ · PMID 37172566 ↗ · PMID 38062209 ↗ · PMID 38459129 ↗ · PMID 39587083 ↗ · PMID 15247922 ↗ · PMID 21725319 ↗ · PMID 23563491 ↗ |
| 功能 | 在微生物感染情境中,含 VPS29 的異源三聚體 retromer cargo-selective complex(CSC)介導 human papillomavirus 離開早期內體,並將病毒送往 Golgi apparatus。 | 含實驗來源 | 證據與來源(Microbial infection) The heterotrimeric retromer cargo-selective complex (CSC) mediates the exit of human papillomavirus from the early endosome and the delivery to the Golgi apparatus PMID 25693203 ↗ |
| 交互作用 | VPS29 是由 VPS26C、VPS29 與 VPS35L 組成的異源三聚體 retriever complex 成員,並在其中與 VPS35L 互作;它也屬於 commander complex 與由 VPS26、VPS29、VPS35 組成的 retromer CSC。CSC 可與不同 sorting nexins 及 WASH complex 組合。VPS29 另與多種蛋白互作;與 SNX17 為間接互作,與 TBC1D5 的互作則會受 retriever complex 中的 VPS35L 阻斷。 | 含實驗來源 | 證據與來源Component of the commander complex consisting of the CCC subcomplex and the retriever subcomplex. Component of the heterotrimeric retriever complex formed by VPS26C, VPS29 and VPS35L; within the complex interacts with VPS35L. Component of the heterotrimeric retromer cargo-selective complex (CSC), also described as vacuolar protein sorting subcomplex (VPS), formed by VPS26 (VPS26A or VPS26B), VPS29 and VPS35. The CSC has a highly elongated structure with VPS26 and VPS29 binding independently at opposite distal ends of VPS35 as central platform (By similarity). The CSC is believed to associate with variable sorting nexins to form functionally distinct retromer complex variants. The originally described retromer complex (also called SNX-BAR retromer) is a pentamer containing the CSC and a heterodimeric membrane-deforming subcomplex formed between SNX1 or SNX2 and SNX5 or SNX6 (also called SNX-BAR subcomplex); the respective CSC and SNX-BAR subcomplexes associate with low affinity. The CSC associates with SNX3 to form a SNX3-retromer complex. The CSC associates with SNX27, the WASH complex and the SNX-BAR subcomplex to form the SNX27-retromer complex. Interacts with VPS26A, VPS35, SNX1, SNX2, SNX3, SNX27, WASHC5. Interacts with TBC1D5; this interaction is blocked by VPS35L in the retriever complex. Interacts with SNX17; the interaction is indirect; SNX17 (via its C-terminus) interacts with the retriever complex (via VPS26C and VPS35L). Interacts with VPS26B and ANKRD27 (By similarity) PMID 11102511 ↗ · PMID 16737443 ↗ · PMID 17891154 ↗ · PMID 20923837 ↗ · PMID 23331060 ↗ · PMID 23563491 ↗ · PMID 28892079 ↗ · PMID 31712251 ↗ · PMID 38062209 ↗ · PMID 38459129 ↗ · PMID 39587083 ↗ · PMID 21725319 ↗ |
| 交互作用 | 在 human papillomavirus 感染情境中,VPS29 與病毒第 16 型次要衣殼蛋白 L2 的 C 端互作;此互作介導病毒衣殼由早期內體運送至 Golgi apparatus。 | 含實驗來源 | 證據與來源(Microbial infection) Interacts with human papillomavirus 16 minor capsid protein L2 (via C-terminus); this interaction mediates the transport of the capsid from the early endosome to the Golgi apparatus PMID 25693203 ↗ |
| 細胞定位 | VPS29 的定位包括細胞質、膜周邊及內體膜周邊,並記載於早期內體與晚期內體。此定位資料未進一步說明特定條件下的變化或不同異構型的差異。 | 推論支持 | 證據與來源Cytoplasm; Membrane / Peripheral membrane protein; Endosome membrane / Peripheral membrane protein; Early endosome; Late endosome |
核酸與蛋白質序列
GAGGAGCCTGAGGAAGAGGGCGGCGACGGTGGTGGTGACT40GAGCGGAGCCCGGTGACAGGATGTTGGTGTTGGTATTAGG80AGATCTGCACATCCCACACCGGTGCAACAGTTTGCCAGCT120AAATTCAAAAAACTCCTGGTGCCAGGAAAAATTCAGCACA160TTCTCTGCACAGGAAACCTTTGCACCAAAGAGAGTTATGA200CTATCTCAAGACTCTGGCTGGTGATGTTCATATTGTGAGA240GGAGACTTCGATGAGAATCTGAATTATCCAGAACAGAAAG280TTGTGACTGTTGGACAGTTCAAAATTGGTCTGATCCATGG320ACATCAAGTTATTCCATGGGGAGATATGGCCAGCTTAGCC360CTGTTGCAGAGGCAATTTGATGTGGACATTCTTATCTCGG400GACACACACACAAATTTGAAGCATTTGAGCATGAAAATAA440ATTCTACATTAATCCAGGTTCTGCCACTGGGGCATATAAT480GCCTTGGAAACAAACATTATTCCATCATTTGTGTTGATGG520ATATCCAGGCTTCTACAGTGGTCACCTATGTGTATCAGCT560AATTGGAGATGATGTGAAAGTAGAACGAATCGAATACAAA600AAACCTTAAAGCCAGGCCTGTCTTGATGATTTTTGGTTTT640TTTTCATTGTCCTGTTGAAATCAAGTAATTAAACATTTAA680GAGCCACAAAATTGTATCACTTTTATAATATTTTGCAGTA720AAATATAATACCATCTTCTCTGTTAATACATAATTGCTCC760AAGCTTCCTGTAAACTATAAGAATATATTTAGTTTACAGT800ATATGGATTCTATGAAAAAATGTCCACAACACAGTAATTG840GTCACTTGTTAAGAAAAATTTATCCTTGTAAGTATCTTCA880AAGTTGATATTTGGAACTTTATTCCAAAAGTAGTGCATGT920GGAGAAAGAATCTAGACTTTCTTGTATACATTTTTCTCTT960cDNA 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。