基因總覽
SNCA 是蛋白質編碼基因，其產物 synuclein alpha 屬於 synuclein 家族，是神經元中的蛋白質。它可呈現可溶性單體，也可形成同源四聚體；細胞內單體與四聚體會動態並存。蛋白質序列中有一段由四個重複單元構成的區域，另有一段被註記為無序區。這些基本特徵提供了認識 synuclein alpha 分子形式與序列組成的背景；其在突觸活動中的具體作用另見功能說明。
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 |
|---|---|---|
| ENST00000394991 ★ | 89,724,099–89,837,161 | 6 |
| ENST00000673902 | 89,700,345–89,837,660 | 7 |
| ENST00000618500 | 89,724,099–89,836,245 | 5 |
| ENST00000420646 | 89,724,099–89,837,139 | 5 |
| ENST00000336904 | 89,724,099–89,838,321 | 6 |
| ENST00001133508 | 89,724,099–89,837,660 | 6 |
| ENST00000394989 | 89,724,105–89,837,660 | 5 |
| ENST00000673718 | 89,724,115–89,837,660 | 8 |
| ENST00000674129 | 89,725,343–89,837,660 | 8 |
| ENST00000965187 | 89,725,519–89,837,189 | 6 |
| ENST00000889660 | 89,725,536–89,836,262 | 6 |
| ENST00000345009 | 89,725,884–89,836,947 | 4 |
顯示 12/38 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
synuclein alpha 參與神經元的突觸活動，與突觸囊泡運輸及後續神經傳遞物質釋放有關。它在突觸囊泡胞吐過程中具有作用，且其不同分子狀態對應不同功能：作為單體時，可促進囊泡進入預備狀態、囊泡融合，以及胞吐融合孔擴大。研究描述的機制之一，是增加局部微區域的 Ca(2+) 釋放；這對增強 ATP 誘發的胞吐而言是必要的。
synuclein alpha 也能在多聚體、膜結合狀態下發揮分子伴護功能。它與 cysteine string protein-alpha/DNAJC5 協同，協助突觸前質膜處的 SNARE（Soluble NSF Attachment Protein REceptors）融合組件正確折疊。此伴護作用有助於在老化過程中維持正常的 SNARE 複合體組裝；來源特別指出，這是維持相關組裝狀態的一項功能。
此外，synuclein alpha 與 dopamine transporter（DAT1）相關聯，並藉由調節 DAT1 活性參與多巴胺神經傳遞的調控。這一作用與其在突觸囊泡胞吐及 SNARE 組件折疊方面的角色不同，顯示來源所述功能涵蓋突觸囊泡釋放和多巴胺訊號調節等面向；現有資料未進一步說明這些作用之間的先後或因果關係。
Promoter 與基因調控
>SNCA ENST00000394991 GRCh38 chr4:89837061-89838161 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 AAGGGGGTGTCAATTCTGAGGGCAACGAGAATCAGAAGTCAGAAAGGTGAGTGGTGTGTAGCATCTCCCT TTCAGAAGGGGCTGAAGAAGAAATTGGATATGATGGTCCGGTAGGCTAAATCACGCTGGATTTGTCTCCC AGATAAAGGGAGGTCTGCAAAGTAAGTCCCATTTCTAGAGCGAAAAGCCTTAGGACCGCTTGTTTTAGAC GGCTGGGGAATATTTATTCCTTGTTCCACTGATGGGAAAATCAGCGTCTGGCAGGCGCTGATTGGTGGAA AGGAAAATGGTGATAGTGGCGTGGAAAGAGGATTTGCTGAGCCTTCTCCTGCCTCCTCAACCTGTGACTC TTCCTTAGTAGTCTCCCTTTCACCCTCAGGACCCTTTCCGGCTCTTCCTAGATTAAGAGCAAACGAAAAC CTTGAAGATATTTGAACTAAAGCGACCCCTAACGTTGTAACCTGTGACCGTGATTAAATTTCAGCGATGC GAGGGCAAAGCGCTCTCGGCGGTGCGGTGTGAGCCACCTCCCGGCGCTGCCTGTCTCCTCCAGCAGCTCC CCAAGGGATAGGCTCTGCCCTTGGTGGTCGACCCTCAGGCCCTCGGCTCTCCCAGGGCGACTCTGACGAG GGGTAGGGGGTGGTCCCCGGGAGGACCCAGAGGAAAGGCGGGGACAAGAAGGGAGGGGAAGGGGAAAGAG GAAGAGGCATCATCCCTAGCCCAACCGCTCCCGATCTCCACAAGAGTGCTCGTGACCCTAAACTTAACGT GAGGCGCAAAAGCGCCCCCACTTTCCCGCCTTGCGCGGCCAGGCAGGCGGCTGGAGTTGATGGCTCACCC CGCGCCCCCTGCCCCATCCCCATCCGAGATAGGGACGAGGAGCACGCTGCAGGGAAAGCAGCGAGCGCCG GGAGAGGGGCGGGCAGAAGCGCTGACAAATCAGCGGTGGGGGCGGAGAGCCGAGGAGAAGGAGAAGGAGG AGGACTAGGAGGAGGAGGACGGCGACGACCAGAAGGGGCCCAAGAGAGGGGGCGAGCGACCGAGCGCCGC GACGCGGAAGTGAGGTGCGTGCGGGCTGCAGCGCAGACCCCGGCCCGGCCC
EPDnew 實驗支持 promoter／TSS · 3 筆
| EPDnew ID | TSS（1-based） | 股向 | 來源顯示區間 |
|---|---|---|---|
| SNCA_3 ↗ | 4:89,835,626 | 負股 | 89,835,616–89,835,675 |
| SNCA_1 ↗ | 4:89,837,161 | 負股 | 89,837,151–89,837,210 |
| SNCA_2 ↗ | 4:89,838,304 | 負股 | 89,838,294–89,838,353 |
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
ENSR4_5R5HWD · CTCF_binding_site · 89835555–89835576 · regulatory
ENSR4_84MBHH · enhancer · 89836030–89836202 · regulatory
ENSR4_84MBHL · promoter · 89836203–89836434 · regulatory
ENSR4_BMSD7 · enhancer · 89836435–89836965 · regulatory
ENSR4_5R5J4G · CTCF_binding_site · 89836649–89836670 · regulatory
ENSR4_BMSDB · promoter · 89836966–89837800 · regulatory
ENSR4_5R5J9C · CTCF_binding_site · 89837703–89837724 · regulatory
ENSR4_779M4K · promoter · 89838305–89838421 · regulatory
· motif · 89835557–89835573 · motif
· motif · 89836651–89836667 · motif
· motif · 89837705–89837721 · motif
蛋白質結構域與序列
參考蛋白質長度：140 aa
synuclein alpha 長 140 個胺基酸，屬於 synuclein 家族。其第 20–67 位胺基酸區段包含四個串聯重複單元，其中第三個單元標示為近似區段。第 100–140 位胺基酸被註記為無序區；此區段亦與 SERF1A 互作相關。
蛋白質三維結構
細胞內定位
synuclein alpha 記錄於細胞質、膜、細胞核、突觸、分泌區域及軸突細胞突起；在多巴胺神經元中亦有膜結合形式。 它與 SEPTIN4 在多巴胺神經元軸突末端共定位，尤見於軸突膨大處；此共定位描述屬於 By similarity。
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；Synapse；Cell projection, axon。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 164 個夥伴
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- ABL1P00519 · UniProt INTERACTION · 3 experiments · 3 筆來源紀錄
- ANKRD13DQ6ZTN6-2 · UniProt INTERACTION · 3 experiments
- AP2B1P63010-2 · UniProt INTERACTION · 3 experiments
- AP3B1O00203 · UniProt INTERACTION · 3 experiments
- APOA1P02647 · UniProt INTERACTION · 3 experiments
- APOEP02649 · UniProt INTERACTION · 11 experiments
- APPP05067 · UniProt INTERACTION · 6 experiments
- ARFGAP1Q8N6T3-3 · UniProt INTERACTION · 3 experiments
- ARFGAP3Q9NP61 · UniProt INTERACTION · 3 experiments
- ARL16Q0P5N6 · UniProt INTERACTION · 3 experiments
- ASB13Q8WXK3 · UniProt INTERACTION · 3 experiments
- ATF3P18847 · UniProt INTERACTION · 3 experiments
- ATG10Q9H0Y0 · UniProt INTERACTION · 3 experiments
- BAG6P46379-2 · UniProt INTERACTION · 3 experiments
- BAXQ07812 · UniProt INTERACTION · 4 experiments
- BCL2L1Q07817 · UniProt INTERACTION · 3 experiments
- BIRC5O15392 · UniProt INTERACTION · 3 experiments
- BRK1Q8WUW1 · UniProt INTERACTION · 3 experiments
- C6orf141Q5SZD1 · UniProt INTERACTION · 3 experiments
- CALM3P62158 · UniProt INTERACTION · 3 experiments
- CAMKK1Q8N5S9-2 · UniProt INTERACTION · 3 experiments
- CASP6P55212 · UniProt INTERACTION · 3 experiments
- CENPVQ7Z7K6 · UniProt INTERACTION · 4 experiments
- CHMP1AQ9HD42 · UniProt INTERACTION · 3 experiments
synuclein alpha 可形成可溶性單體及同源四聚體；細胞內兩者會動態共存，四聚體被描述為維持恆定狀態的重要形式。互作對象包括 SNARE 組件 VAMP2、SNAP25，相關互作有助於 SNARE 複合體組裝與完整性；也包括 RPH3A、RAB3A、CALM1、磷脂酶 D、組蛋白及 STXBP1。與 synphilin-1/SNCAIP 的 N 端互作會促進細胞質內 SNCA 包涵體形成；與 SERF1A 互作會促進 SNCA 聚集。來源另述及與 UCHL1、SEPTIN4 的互作，但標示為 By similarity。與 DDX10 互作則會造成 DDX10 錯位至核質及細胞質包涵體。
疾病與遺傳關聯
SNCA 的基因變異與常染色體顯性 Parkinson disease 1、Parkinson disease 4 及 Lewy body dementia 有關；來源將這些疾病描述為由影響該基因的變異所致。SNCA 異常聚合形成的纖維亦與多種神經退化性疾病相關，並是 Lewy body 包涵體的重要成分；在 Alzheimer disease 類澱粉斑中，SNCA 纖維聚集體則是主要的非 A-beta 成分。此類聚集體也見於神經退化伴腦鐵累積第 1 型的類 Lewy body 神經元包涵體、膠細胞包涵體及軸突球狀體。
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 · 7 筆
| 功能面向 | 功能敘述 | 證據類型 | 可查核來源 |
|---|---|---|---|
| 功能 | synuclein alpha 是神經元蛋白質，參與突觸囊泡運輸與神經傳遞物質釋放。作為單體時，它促進囊泡預備、融合及胞吐融合孔擴大，並透過增加局部微區域 Ca(2+) 釋放來增強 ATP 誘發的胞吐。它也能在多聚體膜結合狀態下，與 cysteine string protein-alpha/DNAJC5 協同協助突觸前膜 SNARE 組件折疊，支持老化期間正常的 SNARE 複合體組裝；另透過與 DAT1 結合調節其活性，參與多巴胺神經傳遞。 | 含實驗來源 | 證據與來源Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release. Participates as a monomer in synaptic vesicle exocytosis by enhancing vesicle priming, fusion and dilation of exocytotic fusion pores. Mechanistically, acts by increasing local Ca(2+) release from microdomains which is essential for the enhancement of ATP-induced exocytosis. Also acts as a molecular chaperone in its multimeric membrane-bound state, assisting in the folding of synaptic fusion components called SNAREs (Soluble NSF Attachment Protein REceptors) at presynaptic plasma membrane in conjunction with cysteine string protein-alpha/DNAJC5. This chaperone activity is important to sustain normal SNARE-complex assembly during aging. Also plays a role in the regulation of the dopamine neurotransmission by associating with the dopamine transporter (DAT1) and thereby modulating its activity PMID 20798282 ↗ · PMID 26442590 ↗ · PMID 28288128 ↗ · PMID 30404828 ↗ |
| 交互作用 | synuclein alpha 可呈可溶性單體或同源四聚體，細胞內兩者動態共存，四聚體對維持恆定狀態重要。它與 UCHL1、磷脂酶 D、組蛋白、CALM1、RPH3A、RAB3A、SEPTIN4、VAMP2、SNAP25、STXBP1、SERF1A、DDX10 及 synphilin-1/SNCAIP 互作；與 VAMP2、SNAP25 的互作有助 SNARE 複合體組裝與完整性。synphilin-1/SNCAIP、SERF1A 相關互作促進 SNCA 包涵體形成或聚集；STXBP1 互作控制自我複製聚集，DDX10 互作則導致 DDX10 錯位。UCHL1、SEPTIN4 互作標示為 By similarity。 | 含實驗來源 | 證據與來源Soluble monomer. Homotetramer. A dynamic intracellular population of tetramers and monomers coexists normally and the tetramer plays an essential role in maintaining homeostasis. Interacts with UCHL1 (By similarity). Interacts with phospholipase D and histones. Interacts (via N-terminus) with synphilin-1/SNCAIP; this interaction promotes formation of SNCA inclusions in the cytoplasm. Interacts with CALM1. Interacts with STXBP1; this interaction controls SNCA self-replicating aggregation. Interacts with SNARE components VAMP2 and SNAP25; these interactions allows SNARE complex assembly and integrity. Interacts with RPH3A and RAB3A. Interacts with SERF1A; this interaction promotes the aggregation of SNCA. Interacts with SEPTIN4 (By similarity). Interacts with DDX10; this interaction causes DDX10 mislocalization to the nucleoplasm and cytoplasmic inclusions PMID 15207266 ↗ · PMID 19762560 ↗ · PMID 20798282 ↗ · PMID 21841800 ↗ · PMID 22854022 ↗ · PMID 23607618 ↗ · PMID 27597756 ↗ · PMID 31034892 ↗ · PMID 33657088 ↗ |
| 細胞定位 | synuclein alpha 記錄於細胞質、膜、細胞核、突觸、分泌區域及軸突細胞突起；在多巴胺神經元中為膜結合形式。它與 SEPTIN4 在多巴胺神經元軸突末端共定位，尤其見於軸突膨大處；此共定位資訊標示為 By similarity。 | 含實驗來源 | 證據與來源Cytoplasm; Membrane; Nucleus; Synapse; Secreted; Cell projection, axon; Membrane-bound in dopaminergic neurons. Expressed and colocalized with SEPTIN4 in dopaminergic axon terminals, especially at the varicosities (By similarity) PMID 19762560 ↗ · PMID 24936070 ↗ · PMID 25561023 ↗ · PMID 26442590 ↗ · PMID 31034892 ↗ · PMID 33657088 ↗ · PMID 12859192 ↗ · PMID 15282274 ↗ |
| 疾病關聯 | SNCA 的基因改變若導致異常聚合成纖維，與多種神經退化性疾病（synucleinopathies）相關。SNCA 纖維聚集體是 Alzheimer disease 類澱粉斑中主要的非 A-beta 成分，也是 Lewy body 包涵體的重要成分；此外，亦見於神經退化伴腦鐵累積第 1 型中的類 Lewy body 神經元包涵體、膠細胞包涵體及軸突球狀體。 | 資料庫紀錄 | 證據與來源Genetic alterations of SNCA resulting in aberrant polymerization into fibrils, are associated with several neurodegenerative diseases (synucleinopathies). SNCA fibrillar aggregates represent the major non A-beta component of Alzheimer disease amyloid plaque, and a major component of Lewy body inclusions. They are also found within Lewy body (LB)-like intraneuronal inclusions, glial inclusions and axonal spheroids in neurodegeneration with brain iron accumulation type 1 |
| 疾病關聯 | Parkinson disease 1 為常染色體顯性疾病，來源指出由影響 SNCA 的變異所致。此複雜神經退化疾病可有動作遲緩、靜止性震顫、肌肉僵硬、姿勢不穩、自主神經功能異常、肌張力不全性痙攣及失智；病理包括黑質多巴胺神經元流失及存活神經元內的 Lewy bodies。疾病通常在 50 歲後發病，也有早發病例；多數病例為散發性，部分患者有家族史，家族型通常較早發病並伴非典型臨床特徵。 | 含實驗來源 | 證據與來源Parkinson disease 1, autosomal dominant PARK1 A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia. The pathology of Parkinson disease involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. The disease is progressive and usually manifests after the age of 50 years, although early-onset cases (before 50 years) are known. The majority of the cases are sporadic suggesting a multifactorial etiology based on environmental and genetic factors. However, some patients present with a positive family history for the disease. Familial forms of the disease usually begin at earlier ages and are associated with atypical clinical features. The disease is caused by variants affecting the gene represented in this entry MIM: 168601 PMID 14755719 ↗ · PMID 23427326 ↗ · PMID 23457019 ↗ · PMID 24936070 ↗ · PMID 25561023 ↗ · PMID 9197268 ↗ · PMID 9462735 ↗ |
| 疾病關聯 | Parkinson disease 4 為常染色體顯性疾病，來源指出由影響 SNCA 的變異所致。其臨床表現範圍從典型 Parkinson disease 到 Lewy body dementia，可包括靜止性震顫、僵硬、姿勢不穩、動作遲緩、失智、廣泛 Lewy body 病理、自主神經功能異常、幻覺及妄想。 | 資料庫紀錄 | 證據與來源Parkinson disease 4, autosomal dominant PARK4 A complex neurodegenerative disorder with manifestations ranging from typical Parkinson disease to dementia with Lewy bodies. Clinical features include parkinsonian symptoms (resting tremor, rigidity, postural instability and bradykinesia), dementia, diffuse Lewy body pathology, autonomic dysfunction, hallucinations and paranoia. The disease is caused by variants affecting the gene represented in this entry MIM: 605543 |
| 疾病關聯 | Lewy body dementia 是神經退化性疾病，特徵包括認知受損並進展為失智、帕金森症、認知功能波動、視覺幻覺、跌倒、暈厥發作及對神經安定藥物敏感。腦幹或皮質神經元內的 Lewy bodies 是必要病理特徵；患者也可能有海馬與新皮質老年斑，有時數量足以符合 Alzheimer disease 診斷標準。來源指出此病由影響 SNCA 的變異所致。 | 含實驗來源 | 證據與來源Dementia, Lewy body DLB A neurodegenerative disorder characterized by mental impairment leading to dementia, parkinsonism, fluctuating cognitive function, visual hallucinations, falls, syncopal episodes, and sensitivity to neuroleptic medication. Brainstem or cortical intraneuronal accumulations of aggregated proteins (Lewy bodies) are the only essential pathologic features. Patients may also have hippocampal and neocortical senile plaques, sometimes in sufficient number to fulfill the diagnostic criteria for Alzheimer disease. The disease is caused by variants affecting the gene represented in this entry MIM: 127750 PMID 14755719 ↗ |
核酸與蛋白質序列
GGCGACGACCAGAAGGGGCCCAAGAGAGGGGGCGAGCGAC40CGAGCGCCGCGACGCGGAAGTGAGGTGCGTGCGGGCTGCA80GCGCAGACCCCGGCCCGGCCCCTCCGAGAGCGTCCTGGGC120GCTCCCTCACGCCTTGCCTTCAAGCCTTCTGCCTTTCCAC160CCTCGTGAGCGGAGAACTGGGAGTGGCCATTCGACGACAG200TGTGGTGTAAAGGAATTCATTAGCCATGGATGTATTCATG240AAAGGACTTTCAAAGGCCAAGGAGGGAGTTGTGGCTGCTG280CTGAGAAAACCAAACAGGGTGTGGCAGAAGCAGCAGGAAA320GACAAAAGAGGGTGTTCTCTATGTAGGCTCCAAAACCAAG360GAGGGAGTGGTGCATGGTGTGGCAACAGTGGCTGAGAAGA400CCAAAGAGCAAGTGACAAATGTTGGAGGAGCAGTGGTGAC440GGGTGTGACAGCAGTAGCCCAGAAGACAGTGGAGGGAGCA480GGGAGCATTGCAGCAGCCACTGGCTTTGTCAAAAAGGACC520AGTTGGGCAAGAATGAAGAAGGAGCCCCACAGGAAGGAAT560TCTGGAAGATATGCCTGTGGATCCTGACAATGAGGCTTAT600GAAATGCCTTCTGAGGAAGGGTATCAAGACTACGAACCTG640AAGCCTAAGAAATATCTTTGCTCCCAGTTTCTTGAGATCT680GCTGACAGATGTTCCATCCTGTACAAGTGCTCAGTTCCAA720TGTGCCCAGTCATGACATTTCTCAAAGTTTTTACAGTGTA760TCTCGAAGTCTTCCATCAGCAGTGATTGAAGTATCTGTAC800CTGCCCCCACTCAGCATTTCGGTGCTTCCCTTTCACTGAA840GTGAATACATGGTAGCAGGGTCTTTGTGTGCTGTGGATTT880TGTGGCTTCAATCTACGATGTTAAAACAAATTAAAAACAC920CTAAGTGACTACCACTTATTTCTAAATCCTCACTATTTTT960cDNA 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。