基因總覽
MAP1LC3B(microtubule associated protein 1 light chain 3 beta)是蛋白質編碼基因,產物屬於 ATG8 家族,具有泛素樣修飾因子的性質。其名稱反映與 microtubule associated protein 1 light chain 3 相關的身分;來源所述的主要角色則與自噬相關。蛋白質會以不同形式參與相關膜結構:膜結合形式 LC3-II 可與自噬膜結合。這些家族與基本性質構成理解 MAP1LC3B 產物的基礎;其在特定細胞條件下的作用方式另見功能說明。
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 |
|---|---|---|
| ENST00000268607 ★ | 87,392,336–87,404,774 | 4 |
| ENST00000650688 | 87,383,953–87,404,779 | 5 |
| ENST00000565788 | 87,392,029–87,402,609 | 3 |
| ENST00000880068 | 87,392,029–87,405,090 | 4 |
| ENST00000936306 | 87,392,029–87,404,771 | 4 |
| ENST00000960545 | 87,392,029–87,404,779 | 4 |
| ENST00001139637 | 87,392,029–87,404,779 | 4 |
顯示 7/7 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
MAP1LC3B 產物參與自噬體形成,是自噬相關膜結構的泛素樣修飾因子。LC3 類蛋白參與吞噬泡膜延伸;相較之下,GABARAP/GATE-16 亞家族對自噬體成熟的較後階段至關重要,顯示不同 ATG8 家族成員在自噬體形成與成熟過程中所涉階段有所不同。
在粒線體自噬中,MAP1LC3B 有助於調節粒線體的數量與品質,使粒線體維持在滿足細胞能量需求的基礎水平,並避免過量 ROS 產生。細胞受壓力且粒線體發生分裂時,MAP1LC3B 可結合 C-18 ceramides,並將自噬溶酶體錨定於粒線體外膜,協助清除受損粒線體。
MAP1LC3B 也參與初級纖毛形成:它透過自噬途徑移除 centriolar satellites 上的 OFD1。在營養壓力下,MAP1LC3B 與內質網自噬受體 TEX264 作用,參與將內質網的特定亞區域重塑為自噬體;這些自噬體之後與溶酶體融合,促進內質網周轉。
營養壓力下,MAP1LC3B 會直接將輔因子 JMY 招募至吞噬泡膜表面,促進 JMY 的 actin 成核活性及自噬體生合成。這些作用連結膜結構形成、受損細胞成分清除與細胞內胞器周轉;來源所述的效果均依上述自噬或營養、細胞壓力條件而定。
Promoter 與基因調控
>MAP1LC3B ENST00000268607 GRCh38 chr16:87391336-87392436 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 CCTACAGAGACACATTGGCCACAGGCTGAGGTGGGCAATAGCAACCAAATATCGCATGGTGGTTTACGCA CTGCAGCCCATTTGGAGTCCTCAAATATGACTGCCCTTTCACAGATGAGTCTGAGACTCAAAAACTGTCA CTAGCGTAAGGTTGTCCAGCGAGTTTAGTGGCTGGGAGGCTGAGGGGTAGACAGGGCGGCTAGCGATGTG GGGCAGGCCTGGCAGTCGCCACAGACGACCTAACGGTAGGAAAATCTTACAGCCACCAGGAGAGTTCCAG GCGCCGCGGCAGGGGGACTGGGAGAGGGGACTGCGCCCAGAATGAAGGCTCGGGACAAAAGCAGTTGCGC AAACGCGCCAAGGCTGGGCGTCGAGTGACCGCGGGCGGAGGTCACCAGCGGCCACTCCCCGGAAGCCACC CACGGACCACGCGCGCCCCTGCACGCAGAGGGGGCCAGGGCTCCACGGGCGAGCGGCGACCCTGCCTCCC GGAGACGGCGCGGCCTGCCCTGCGCGCCTCAGCCCCGGGTGCCGGCGTCTCGGGCAGCACCACCAAGTCT CTCTGGAGGGGAAAGGATGGTCGGATTTGCCCCATGTCCCTTCCTCTGACCCCTCCCTCAAGAGTGCCCC GGGACACCCCGCCTGTGGCTCAGCCTCCCCCGCCCCGCGCTGCCATCTCCTCAGGGCCGGGCAGCAGGCT CCCGAGCGCCCACAGACCCGGGGTGCGGCCCAGCCCACAACCGTCACCTCAGGGGCCTCAGGCGCCCAGC GGTGCTGGGCGGGGCTGGGGCACGACCGGGAGCATGCGCAGAGCGCGCGTTTCGCCCATCGCGCACGCGC ACACACCTGCTCCGCCCCCACGCTGCGTGCCGCTGCTGGGTTCCGCCACGCCCGTCATGGCGGCGGCCCC GGCCGGCTCTGGCCCCGCCCCTCGGTGACGCGTCGCGAGTCACCTGACCAGGCTGCGGGCTGAGGAGATA CAAGGGAAGTGGCTATCGCCAGAGTCGGATTCGCCGCCGCAGCAGCCGCCGCCCCCGGGAGCCGCCGGGA CCCTCGCGTCGTCGCCGCCGCCGCCGCCCAGATCCCTGCACCATGCCGTCG
EPDnew 實驗支持 promoter/TSS · 1 筆
| EPDnew ID | TSS(1-based) | 股向 | 來源顯示區間 |
|---|---|---|---|
| MAP1LC3B_1 ↗ | 16:87,392,336 | 正股 | 87,392,287–87,392,346 |
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
ENSR16_CBN5H · enhancer · 87387722–87389006 · regulatory
ENSR16_5QJZ8M · CTCF_binding_site · 87388110–87388131 · regulatory
ENSR16_84KD3K · enhancer · 87389290–87389507 · regulatory
ENSR16_939NK3 · promoter · 87391844–87392346 · regulatory
ENSR16_CBN5S · enhancer · 87392347–87393860 · regulatory
ENSR16_BMC9W · enhancer · 87394304–87394917 · regulatory
· motif · 87387719–87387731 · motif
· motif · 87388000–87388022 · motif
· motif · 87388000–87388022 · motif
· motif · 87388112–87388128 · motif
· motif · 87388227–87388240 · motif
· motif · 87388227–87388240 · motif
· motif · 87388284–87388297 · motif
· motif · 87388284–87388297 · motif
· motif · 87388753–87388764 · motif
· motif · 87391135–87391150 · motif
· motif · 87391679–87391688 · motif
· motif · 87391721–87391733 · motif
· motif · 87391750–87391763 · motif
· motif · 87391938–87391950 · motif
· motif · 87391941–87391948 · motif
· motif · 87392110–87392120 · motif
· motif · 87392134–87392145 · motif
· motif · 87392134–87392145 · motif
· motif · 87392138–87392154 · motif
· motif · 87392138–87392154 · motif
· motif · 87392165–87392176 · motif
· motif · 87392165–87392176 · motif
· motif · 87392177–87392186 · motif
· motif · 87392184–87392194 · motif
· motif · 87392220–87392230 · motif
· motif · 87392230–87392240 · motif
· motif · 87392257–87392267 · motif
· motif · 87392349–87392366 · motif
· motif · 87392824–87392837 · motif
· motif · 87394224–87394236 · motif
· motif · 87394353–87394375 · motif
蛋白質結構域與序列
蛋白質三維結構
細胞內定位
膜結合形式 LC3-II 可定位於自噬膜;在 Parkin 介導的粒線體自噬期間,LC3-II 也會與粒線體內膜同位。 此外,MAP1LC3B 產物可沿纖毛軸絲呈離散點狀分布。
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:Endomembrane system。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 64 個夥伴
- APPP05067 · UniProt INTERACTION · 3 experiments
- ATG13O75143 · UniProt INTERACTION · 5 experiments
- ATG16L1Q676U5 · UniProt INTERACTION · 2 experiments
- ATG2AQ2TAZ0 · UniProt INTERACTION · 2 experiments
- ATG3Q9NT62 · UniProt INTERACTION · 8 experiments
- ATG4BQ9Y4P1 · UniProt INTERACTION · 15 experiments
- ATG5Q9H1Y0 · UniProt INTERACTION · 2 experiments
- ATG7O95352 · UniProt INTERACTION · 7 experiments
- BRCA2P51587 · UniProt INTERACTION · 2 experiments
- BUB1O43683 · UniProt INTERACTION · 2 experiments
- CAV1Q03135 · UniProt INTERACTION · 2 experiments
- CHATP28329-3 · UniProt INTERACTION · 3 experiments
- CLINT1Q14677 · UniProt INTERACTION · 2 experiments
- CTNNB1P35222 · UniProt INTERACTION · 5 experiments
- DYNC1I1O14576-2 · UniProt INTERACTION · 3 experiments
- FGFR3P22607 · UniProt INTERACTION · 3 experiments
- FUNDC1Q8IVP5 · UniProt INTERACTION · 8 experiments
- FYCO1Q9BQS8 · UniProt INTERACTION · 9 experiments
- GORASP2Q9H8Y8 · UniProt INTERACTION · 6 experiments
- GRNP28799 · UniProt INTERACTION · 3 experiments
- HADHAP40939 · UniProt INTERACTION · 4 experiments
- HSPA1AP0DMV8 · UniProt INTERACTION · 3 experiments
- IPO5O00410 · UniProt INTERACTION · 2 experiments
- IRGQQ8WZA9 · UniProt INTERACTION · 4 experiments
- KBTBD6Q86V97 · UniProt INTERACTION · 6 experiments
MAP1LC3B 與多種自噬相關蛋白有交互作用,包括直接結合 SQSTM1;此結合可使其被招募至含多泛素化蛋白聚集物的包涵體,並與包涵體經自噬降解相關。它也與 TEX264、JMY 等蛋白作用;其中營養壓力下招募 JMY 可促進其成核活性。另有資料指出 LC3-II 在 Parkin 介導的粒線體損傷後與 PHB、PHB2 作用。MAP1LC3B 亦可與 MAP1A 或 MAP1B 重鏈相關聯;另有與 UBQLN1、UBQLN2 同處複合體的報告。這些結合或複合體關係不應一概視為相同作用。
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 | MAP1LC3B 產物參與自噬體形成及粒線體自噬,可協助調節粒線體數量與品質。細胞受壓力且粒線體分裂時,它結合 C-18 ceramides 並錨定自噬溶酶體以清除受損粒線體;也參與初級纖毛形成、營養壓力下的內質網周轉,以及 JMY 活性與自噬體生合成。 | 含實驗來源 | 證據與來源Ubiquitin-like modifier involved in formation of autophagosomal vacuoles (autophagosomes). Plays a role in mitophagy which contributes to regulate mitochondrial quantity and quality by eliminating the mitochondria to a basal level to fulfill cellular energy requirements and preventing excess ROS production. In response to cellular stress and upon mitochondria fission, binds C-18 ceramides and anchors autophagolysosomes to outer mitochondrial membranes to eliminate damaged mitochondria. While LC3s are involved in elongation of the phagophore membrane, the GABARAP/GATE-16 subfamily is essential for a later stage in autophagosome maturation. Promotes primary ciliogenesis by removing OFD1 from centriolar satellites via the autophagic pathway. Through its interaction with the reticulophagy receptor TEX264, participates in the remodeling of subdomains of the endoplasmic reticulum into autophagosomes upon nutrient stress, which then fuse with lysosomes for endoplasmic reticulum turnover. Upon nutrient stress, directly recruits cofactor JMY to the phagophore membrane surfaces and promotes JMY's actin nucleation activity and autophagosome biogenesis during autophagy PMID 20418806 ↗ · PMID 22922758 ↗ · PMID 23209295 ↗ · PMID 24089205 ↗ · PMID 28017329 ↗ · PMID 30420355 ↗ · PMID 31006537 ↗ · PMID 31006538 ↗ |
| 交互作用 | MAP1LC3B 與多種蛋白質有交互作用,包含 SQSTM1、TEX264、JMY、PHB 與 PHB2;部分作用具有特定條件或功能結果,例如 SQSTM1 促進其至蛋白聚集物包涵體的招募,JMY 的成核活性可被促進。它也與 MAP1A 或 MAP1B 重鏈相關聯,並曾被報告與 UBQLN1、UBQLN2 同處複合體。 | 含實驗來源 | 證據與來源3 different light chains, LC1 (a cleavage product of MAP1B), LC2 (a cleavage product of MAP1A) and LC3 (produced by one of the MAP1LC3 genes), can associate with the MAP1A or MAP1B heavy chains (By similarity). Interacts at microtubules with CABP1 (via EF-hands 1 and 2) but not with calmodulin. Interacts with FYCO1 (via C-terminus). Interacts with TP53INP1 and TP53INP2. Interacts with TBC1D25. Directly interacts with SQSTM1; this interaction leads to MAP1LC3B recruitment to inclusion bodies containing polyubiquitinated protein aggregates and to inclusion body degradation by autophagy. Interacts with ATG4B, MAPK15 and BNIP3. Interacts with MAPB1, KEAP1, PCM1, OFD1, CEP131, and TECPR2. Interacts with TBC1D5. Found in a complex with UBQLN1 and UBQLN2. Interacts with UBQLN4 (via STI1 1 and 2 domains). Interacts with UBQLN1 in the presence of UBQLN4. Interacts with ATG13. Interacts with reticulophagy regulators RETREG1, RETREG2 and RETREG3. No interaction, or very weak, with WDFY3. Interacts with PLCL1; the interaction inhibits autophagosome formation (By similarity). Interacts with TRIM16. Interacts with CRY1 and PER2 (By similarity). Interacts with the reticulophagy receptor TEX264. Membrane-bound form LC3-II interacts with PHB and PHB2; the interaction takes place upon Parkin-mediated mitochondrial damage. Interacts with PJVK; the interaction is direct (By similarity). Interacts with KBTBD6 and KBTBD7; the interaction is direct. Interacts with AMBRA1 (via LIR motif). Interacts with JMY; the interaction results in the activation of JYM's nucleation activity in the cytoplasm. Interacts with MOAP1 (via LIR motif). Interacts with TAX1BP1. Interacts with IRGM. Interacts with STX17. Interacts (the lipidate and non-lipidated LC3 form) with DNM2; this interaction mediates recycling endosome scission leading to autophagosome release. Interacts with IRGQ. Interacts with UBAC2 PMID 15095872 ↗ · PMID 17580304 ↗ · PMID 18524774 ↗ · PMID 20100911 ↗ · PMID 20529957 ↗ · PMID 20562859 ↗ · PMID 21383079 ↗ · PMID 22354992 ↗ · PMID 22470510 ↗ · PMID 22948227 ↗ · PMID 23209295 ↗ · PMID 23459205 ↗ · PMID 24089205 ↗ · PMID 24290141 ↗ · PMID 24668264 ↗ · PMID 25215947 ↗ · PMID 25684205 ↗ · PMID 26040720 ↗ · PMID 28017329 ↗ · PMID 29420192 ↗ · PMID 30143514 ↗ · PMID 30420355 ↗ · PMID 31006537 ↗ · PMID 31006538 ↗ · PMID 32315611 ↗ · PMID 33783314 ↗ · PMID 34338405 ↗ · PMID 39284914 ↗ |
| 交互作用 | 在 Hantaan hantavirus 感染情境中,MAP1LC3B 與病毒 glycoprotein N 交互作用。此交互作用與病毒誘發的粒線體自噬性降解相關,並連帶造成宿主 MAVS 降解及 type I interferon(IFN)反應受到抑制。 | 含實驗來源 | 證據與來源(Microbial infection) Interacts with Hantaan hantavirus glycoprotein N; this interaction contributes to the virus-induced degradation of mitochondria by autophagy, which leads to degradation of host MAVS and inhibition of type I interferon (IFN) responses PMID 31091447 ↗ |
| 交互作用 | 在 Hantaan hantavirus 感染情境中,MAP1LC3B 與病毒 nucleoprotein 交互作用;此交互作用可阻止病毒誘發的自噬分解病毒 glycoprotein N。 | 含實驗來源 | 證據與來源(Microbial infection) Interacts with Hantaan hantavirus nucleoprotein; this interaction prevents the breakdown of the viral glycoprotein N by virus-triggered autophagy PMID 31091447 ↗ |
| 細胞定位 | LC3-II 可結合自噬膜;在 Parkin 介導的粒線體自噬期間,它與粒線體內膜同位。MAP1LC3B 產物也可沿纖毛軸絲呈離散點狀定位,顯示其定位會依相關膜結構或細胞構造而異。 | 含實驗來源 | 證據與來源Cytoplasmic vesicle, autophagosome membrane / Lipid-anchor; Endomembrane system / Lipid-anchor; Mitochondrion membrane / Lipid-anchor; Cytoplasm, cytoskeleton; Cytoplasmic vesicle; LC3-II binds to the autophagic membranes. LC3-II localizes with the mitochondrial inner membrane during Parkin-mediated mitophagy. Also localizes to discrete punctae along the ciliary axoneme PMID 17580304 ↗ · PMID 20529957 ↗ · PMID 22311637 ↗ · PMID 23459205 ↗ · PMID 31315929 ↗ · PMID 33499712 ↗ · PMID 15187094 ↗ · PMID 29458288 ↗ · PMID 12740394 ↗ · PMID 25215947 ↗ · PMID 28017329 ↗ · PMID 30420355 ↗ |
核酸與蛋白質序列
AGAGTCGGATTCGCCGCCGCAGCAGCCGCCGCCCCCGGGA40GCCGCCGGGACCCTCGCGTCGTCGCCGCCGCCGCCGCCCA80GATCCCTGCACCATGCCGTCGGAGAAGACCTTCAAGCAGC120GCCGCACCTTCGAACAAAGAGTAGAAGATGTCCGACTTAT160TCGAGAGCAGCATCCAACCAAAATCCCGGTGATAATAGAA200CGATACAAGGGTGAGAAGCAGCTTCCTGTTCTGGATAAAA240CAAAGTTCCTTGTACCTGACCATGTCAACATGAGTGAGCT280CATCAAGATAATTAGAAGGCGCTTACAGCTCAATGCTAAT320CAGGCCTTCTTCCTGTTGGTGAACGGACACAGCATGGTCA360GCGTCTCCACACCAATCTCAGAGGTGTATGAGAGTGAGAA400AGATGAAGATGGATTCCTGTACATGGTCTATGCCTCCCAG440GAGACGTTCGGGATGAAATTGTCAGTGTAAAACCAGAAAA480AATGCAGCTCTTCTAGAATTGTTTAAACCCTTACCAAGGA520AAAAAAAGGGATGTTACCAACTGAGATCGATCAGTTCATC560CAATCACAGATCATGAAACAGTAGTGTTCCCACCTAGGAG600TGTTAGGAAGTTGTGTTTGTGTTTCAAGCAGAAAAACTGA640GCTCCAAGTGAGCACATTCAGCTTTGGAAACTATATTATT680TAATGTAGGCTAGCTTGTTTTCAAATTTTAAAAGTTTAAA720AATAAAATACTTTGCATTCTAAGTTGCCAATAAAATAGAC760CTTCAAGTTATTTTAATGCTCTTTTCTCACTAATAGGAAC800TTGTAATTCCAGCAGTAATTTAAAGGCTTTCAGAGAGACC840CTGAGTCTTCTCTTCAGGTTCACAAAACCCGCCGCCTTTT880TGGGTAGAAGTTTTCTACTCAGCTAGAGAGATCTCCCTAA920GAGGATCTTTAGGCCTGAGTTGTGAAGCGCAACCCCCGCA960cDNA 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。