演化之聲
THE SOUND OF EVOLUTION
Human Gene AtlasHOMO SAPIENS
HUMAN PROTEIN-CODING GENE

SIRT2SIR2L

sirtuin 2

SIRT2 是 NAD 依賴型去乙醯化酶,作用於組蛋白、α-tubulin 與多種調控蛋白,參與細胞週期、染色質調節及代謝等過程。

Homo sapiens19q13.2UniProt Q8IXJ6
OFFICIAL SYMBOL
SIRT2
CHROMOSOME
19
UNIPROT
Q8IXJ6
PDB / ALPHAFOLD
9DPD
01 / GENE OVERVIEW

基因總覽

sirtuin 2 是由 SIRT2 編碼的蛋白質,屬於 sirtuin 家族的 Class I subfamily。其酵素活性依賴 NAD,可移除蛋白質 lysine 殘基上的乙醯基,也能處理其他 lysine acyl 基團。已知作用對象包括 histone、α-tubulin,以及多種轉錄因子與其他調控蛋白。SIRT2 的功能涵蓋細胞週期、基因組穩定性、微管動態、細胞分化、代謝與自噬等不同面向。其作用不只限於單一細胞區室或一類底物,且可隨細胞週期階段與生理條件而變化。部分異構型的去乙醯化活性也有差異:來源指出其中一種異構型至少對已知 SIRT2 標的缺乏去乙醯化活性。

Official symbol
SIRT2
Gene name
sirtuin 2
Organism
Homo sapiens
Gene type
Protein coding
HGNC ID
HGNC:10886
UniProt
Q8IXJ6
02 / NOMENCLATURE

基因異名與舊稱

Alternative gene names & synonyms
SIR2L

異名取自 HGNC,可能包含歷史名稱;蛋白質名稱以 UniProt 註解為準。

03 / GENOMIC CONTEXT

染色體位置與基因結構

Chromosome 1919q13.2
chr19 · 58,617,616 bp · GRCh38chr19p13.3 · 1–6900000 · gnegchr19p13.2 · 6900001–12600000 · gpos25chr19p13.13 · 12600001–13800000 · gnegchr19p13.12 · 13800001–16100000 · gpos25chr19p13.11 · 16100001–19900000 · gnegchr19p12 · 19900001–24200000 · gvarchr19p11 · 24200001–26200000 · acenchr19q11 · 26200001–28100000 · acenchr19q12 · 28100001–31900000 · gvarchr19q13.11 · 31900001–35100000 · gnegchr19q13.12 · 35100001–37800000 · gpos25chr19q13.13 · 37800001–38200000 · gnegchr19q13.2 · 38200001–42900000 · gpos25chr19q13.31 · 42900001–44700000 · gnegchr19q13.32 · 44700001–47500000 · gpos25chr19q13.33 · 47500001–50900000 · gnegchr19q13.41 · 50900001–53100000 · gpos25chr19q13.42 · 53100001–55800000 · gnegchr19q13.43 · 55800001–58617616 · gpos25SIRT2pq1 bp58,617,616 bp
GRCh38 / 1-based inclusiveDirection: reverse strand (−)
Genomic coordinates
chr19:38,878,555–38,900,501
Gene span
21,947 bp
Strand
Reverse (−)
Gene assembly
GRCh38
查看實際轉錄本與 exon 註解
TranscriptGenomic coordinatesExons
ENST00000249396 ★38,878,560–38,899,61816
ENST0000035893138,878,555–38,899,86213
ENST0000039208138,878,555–38,899,86215
ENST0000087214538,878,555–38,900,50114
ENST0000087214638,878,555–38,899,86216
ENST0000087214738,878,555–38,899,86216
ENST0000087214838,878,555–38,899,86213
ENST0000087215038,878,555–38,899,86214
ENST0000087215138,878,555–38,899,86215
ENST0000094183738,878,555–38,899,86215
ENST0000112024338,878,555–38,899,86215
ENST0000112024438,878,555–38,899,58315

顯示 12/21 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。

04 / BIOLOGICAL FUNCTION

分子功能與生物學過程

SIRT2 利用 NAD 催化蛋白質去乙醯化,底物包括組蛋白、α-tubulin,以及多種轉錄因子和調控蛋白;此反應同時產生 nicotinamide 與乙醯化的 ADP-ribose 產物。它也可移除 lysine 上的 benzoyl、methacryl 與長鏈脂肪醯基,因而具有去醯化作用。這些修飾使 SIRT2 能影響染色質狀態、細胞骨架與基因表現,但不同底物及細胞情境下的作用並不相同。

在細胞週期中,SIRT2 參與避免細胞在微管受壓時過早進入有絲分裂的 antephase checkpoint,並藉由去乙醯化 CDC20 與 FZR1,正向調節 APC/C 活性,促進有絲分裂進程。細胞由 G2 進入 M 期至中期時,SIRT2 去乙醯化 histone H4 的 Lys-16,讓 KMT5A 得以沉積 H4K20me1,並與後續 H4K20me2、H4K20me3 的形成及染色質緊密化相關;它也在 G2/M 轉換時去乙醯化 histone H3 的 Lys-57。感染 Listeria monocytogenes 時,SIRT2 在 MET 與 PI3K/Akt 依賴的條件下去乙醯化 histone H3 Lys-18,抑制轉錄活性,並促進感染晚期進程。

SIRT2 對 α-tubulin Lys-40 的去乙醯化與微管功能相關,來源指出此作用涉及神經元移動、少突膠質細胞突起形成,以及非神經細胞增殖。其活性亦與細胞黏附、遷移及神經突生長有關;G1/S 特異性 cyclin E-CDK2 複合體在 Ser-368 磷酸化 SIRT2,會使其對 α-tubulin 的去乙醯化失活。卵母細胞減數分裂期間,SIRT2 可能透過影響微管動態與 kinetochore 功能,參與紡錘體組裝和染色體排列。

在代謝方面,低營養時 SIRT2 可去乙醯化並穩定 PCK1 活性,參與血糖恆定;它也能活化 G6PD,促進 pentose phosphate pathway 產生細胞質 NADPH,以應對氧化損傷。SIRT2 另與抑制脂肪生成、促進脂解及調節自噬相關;氧化壓力或血清缺乏時,它去乙醯化 FOXO1,負向調節 FOXO1 介導的自噬。除此之外,SIRT2 可調節多種轉錄因子的活性或穩定性,例如抑制 RELA、p53/TP53、EP300 與 HIF1A 相關的轉錄作用。這些作用顯示其功能涉及多條細胞調節路徑,並依底物與環境而異。

05 / GENE REGULATION

Promoter 與基因調控

到

以 TSS = 0 為基準:負數為上游、正數為下游,包含起點與終點。每次最多取得 100,000 bp。

TSS: 38899618 · 負股
依所選 TSS 來源,取得指定上、下游範圍的基因組序列。
擷取區間依所選 TSS 計算;調控註解與實驗支持的 TSS 可在下方查閱。
>SIRT2 ENST00000249396 GRCh38 chr19:38899518-38900618 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
CTTAGAGTCAGGGACCAAGTATTAATTTCGGAAATCAAACTCTAGGGCTCAAATCGGGAACTAAGAATCA
AAGATCATATTTGGAGGTTAGAAGTCAGGAGAAGCCACAGTTCTAACAGAAGTCTCAGGACTGGAGTCAG
GTTTGGGTATCAGTGGATACAATGTGGATTCCAGGAGCTGAGAATCATAGTTCAAGAAAAGAAGGTAAGA
AATGATTGGGTTAGGATCATAGCTAGATAGAAGATTGGTTTTGTTAAAAGTTAGGACTCGGGGGTTAGAG
GTCAGGAAGTTCAGCATCGGAAGTCAGATTTAGGAGTATGAGGTTAGGAAGCCTCAGGGATCAGAGATTA
ATGAGGAATGTGACGCCGGGTCCTAGGGCTCCGTTTGGCAGCCTAAGGTTCACTCACGTGTCCCCATCCT
CAGTGACGTAGCCGAAGACGAGGGGAGCCCACGACAGCCCCGGGCCCAACTCCGCGCCCAACCCAGGTCC
TCCGGGGGCCGCTGCGTCCGGACCCAGGGAGCCCAGGCCGCTGTCGCACCATTCATCTGCGTCGGCAGCT
TTTCCCAAGCACGCGACCCCAGCCATGGCCCCCGCCGCCTCAGGGGCCCCCCGCAGTCGCCCGCCTGTAG
CTGGGCTTTGCCGGGAGTTCTGGAGCTTCCGCCCTGCGGGAAATTCCCCACCACGCCCCCTGATTCACCC
AATGATAATATGCTGAATCGCTCACACCCCGCCCTCGTACTGCATCCTGACCAATCAGAGTATTCGGGAG
GACTACAACTCTCTAGCCGTTCCCACATTTTCCGGGCGCCCTTTACCAACATGGCTGCTGACGCCACGCC
TTCTGGGACTCGTAGTCCGGTCCTCGCGCGCTTTCTTACCTAACTGGGGCGCTCTGGGTGTTGTACGAAA
GCGCGTCTGCGGCCGCAATGTCTGCTGAGAGTTGTAGTTCTGTGCCCTATCACGGCCACTCCCATTTCTG
GTGCCGTCACGGGACAGAGCAGTCGGTGACAGGACAGAGCAGTCGGTGACGGGACACAGTGGTTGGTGAC
GGGACAGAGCGGTCGGTGACAGCCTCAAGGGCTTCAGCACCGCGCCCATGG
SIRT2 位於負股。上下游依轉錄方向計算,序列一律以該方向的 5′→3′ 顯示;負股會取得反向互補序列。
EPDnew 實驗支持 promoter/TSS · 0 筆

封存資料的查詢區間內未找到名稱與股向相符的紀錄;不代表此基因沒有 promoter。

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

ENSR19_B9PFR · enhancer · 38898807–38899607 · regulatory

ENSR19_749QHQ · promoter · 38899608–38899710 · regulatory

ENSR19_835TQG · enhancer · 38899711–38899851 · regulatory

ENSR19_835TQJ · promoter · 38899852–38899979 · regulatory

· motif · 38895938–38895947 · motif

· motif · 38895938–38895947 · motif

· motif · 38896022–38896033 · motif

· motif · 38899258–38899270 · motif

· motif · 38899627–38899640 · motif

· motif · 38899644–38899654 · motif

· motif · 38899883–38899893 · motif

· motif · 38899929–38899939 · motif

· motif · 38900207–38900216 · motif

· motif · 38900207–38900216 · motif

· motif · 38900331–38900343 · motif

· motif · 38900334–38900341 · motif

· motif · 38900334–38900349 · motif

· motif · 38900335–38900348 · motif

· motif · 38900522–38900535 · motif

· motif · 38904545–38904557 · motif

· motif · 38904548–38904555 · motif

SIRT2 表現會隨代謝與環境條件改變:低葡萄糖及缺氧後再氧合壓力會使其上調,高葡萄糖則使其下調;trichostatin A 也會使 SIRT2 上調。數種腫瘤中,組蛋白去乙醯化與 SIRT2 下調相關。

序列擷取依所選 TSS 與相對範圍計算;該區間的調控功能需參照相應的實驗證據。
06 / PROTEIN ANATOMY

蛋白質結構域與序列

參考蛋白質長度:389 aa

1 aa389 aa結構域功能區域基序
依 Q8IXJ6 的 UniProt 殘基座標與蛋白質長度繪製;結構域、DNA 結合區、功能區域與基序分列,重疊註解分行顯示。區域色彩區分類型,並非活性或信心分數。

SIRT2 蛋白長 389 個胺基酸,屬於 sirtuin 家族 Class I subfamily。其 sirtuin 型去乙醯化酶結構域位於第 57–338 位胺基酸。蛋白 N 端第 1–34 位與 C 端第 351–389 位皆標註為無序區;第 41–51 位含有核輸出訊號。每個次單元結合 1 個鋅離子。

結構域Deacetylase sirtuin-type57–338 aa
功能區域Disordered1–34 aa
功能區域Disordered351–389 aa
基序Nuclear export signal41–51 aa
07 / STRUCTURAL BIOLOGY

蛋白質三維結構

自動載入 · 可拖曳旋轉與縮放
正在載入 PDB · 9DPD…

PDB · 9DPD

EM · 3.87 A · C=1-389

查看原始結構紀錄 ↗

實驗模型;依序列位置著色,可能只覆蓋局部區域。

08 / SUBCELLULAR LOCALIZATION

細胞內定位

動物細胞結構與蛋白質定位細胞膜包圍細胞質;細胞核內有核仁,粗面內質網鄰接核膜,粒線體含內膜摺疊,高基氏體由堆疊扁平囊組成。深綠色圓點依來源註解標記定位,器官大小與數量為示意。圓點數量不表示含量;未繪示構造列於圖旁文字。 細胞質 細胞膜 粗面內質網與核糖體 細胞核與核膜 核仁 粒線體:外膜與含摺疊的內膜 高基氏體與運輸囊泡 胞內體、溶體與其他囊泡(示意)
定位:Nucleus;Cytoplasm, perinuclear region;Cytoplasm;Cytoplasm, cytoskeleton;Cytoplasm, cytoskeleton, microtubule organizing center, centrosome;Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole;Cytoplasm, cytoskeleton, spindle;Midbody;Chromosome;Perikaryon;Cell projection;Cell projection, growth cone;Myelin membrane

SIRT2 在細胞週期大部分時間位於細胞質;G2/M 轉換與有絲分裂期間則可轉至染色質,並參與 histone H4 Lys-16 去乙醯化。 它可在細胞質與細胞核間穿梭,Listeria monocytogenes 感染時會移至細胞核及染色質。 異構型 1、2 主要位於細胞質,異構型 5 則主要位於細胞核。

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:Midbody;Chromosome;Perikaryon;Cell projection;Cell projection, growth cone;Myelin 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。

09 / PROTEIN NETWORK

交互作用與訊號網絡

圖中 8 個夥伴 · 最多顯示 50 個
SIR2LSIRT2BUB1BCDC14BG6PDKAT2BRELASHANK3CDC20FZR1
來源支持的結構/直接結合關係其他來源關係紀錄

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 8 個夥伴
第 1 頁

查看 UniProt 完整互作來源 ↗

SIRT2 與 CDC20、FOXO3、FZR1 等蛋白有互作;亦與 MAPK1/ERK2、MAPK3/ERK1 互作,後兩者的互作可增加 SIRT2 穩定性與去乙醯化活性。SIRT2 形成同源三聚體。異構型 1、2 可與 HDAC6 互作,該互作有助於此複合體接觸 α-tubulin;來源據此指出兩者可能構成參與細胞骨架去乙醯化的大型複合體。SIRT2 也與 FOXO1、RELA、EP300、KMT5A 等互作;其中與 KMT5A 的直接互作可刺激其組蛋白甲基轉移酶活性,且在 H₂O₂ 誘發的氧化壓力下增加。

10 / HUMAN HEALTH

疾病與遺傳關聯

目前未取得此類註解。
個別變異的臨床意義取決於其證據;基因層級的疾病關聯不能套用至所有變異。
11 / CONTEXTUAL FUNCTIONAL EVIDENCE MATRIX

Contextual Functional Evidence Matrix

功能證據與細胞情境矩陣

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。

15 筆功能證據/註解
目前尚無同時具備實驗情境與干預/量測資訊的證據列。可查核的功能敘述列於「功能註解總覽」,空白實驗欄位不以推測補齊。
功能註解總覽 · 15 筆
功能面向功能敘述證據類型可查核來源
功能SIRT2 是 NAD 依賴型蛋白質去乙醯化酶,可作用於 histone、α-tubulin 及多種蛋白質,包括關鍵轉錄因子。它參與細胞週期、基因組穩定性、微管動態、細胞分化、代謝與自噬;另涉及 APC/C 調節、組蛋白修飾、葡萄糖代謝、氧化壓力反應及轉錄調控。它也能移除 lysine 上的 benzoyl、methacryl 與長鏈脂肪醯基。含實驗來源
證據與來源

NAD-dependent protein deacetylase, which deacetylates internal lysines on histone and alpha-tubulin as well as many other proteins such as key transcription factors. Participates in the modulation of multiple and diverse biological processes such as cell cycle control, genomic integrity, microtubule dynamics, cell differentiation, metabolic networks, and autophagy. Plays a major role in the control of cell cycle progression and genomic stability. Functions in the antephase checkpoint preventing precocious mitotic entry in response to microtubule stress agents, and hence allowing proper inheritance of chromosomes. Positively regulates the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase complex activity by deacetylating CDC20 and FZR1, then allowing progression through mitosis. Associates both with chromatin at transcriptional start sites (TSSs) and enhancers of active genes. Plays a role in cell cycle and chromatin compaction through epigenetic modulation of the regulation of histone H4 'Lys-20' methylation (H4K20me1) during early mitosis. Specifically deacetylates histone H4 at 'Lys-16' (H4K16ac) between the G2/M transition and metaphase enabling H4K20me1 deposition by KMT5A leading to ulterior levels of H4K20me2 and H4K20me3 deposition throughout cell cycle, and mitotic S-phase progression. Deacetylates KMT5A modulating KMT5A chromatin localization during the mitotic stress response. Also deacetylates histone H3 at 'Lys-57' (H3K56ac) during the mitotic G2/M transition. Upon bacterium Listeria monocytogenes infection, deacetylates 'Lys-18' of histone H3 in a receptor tyrosine kinase MET- and PI3K/Akt-dependent manner, thereby inhibiting transcriptional activity and promoting late stages of listeria infection. During oocyte meiosis progression, may deacetylate histone H4 at 'Lys-16' (H4K16ac) and alpha-tubulin, regulating spindle assembly and chromosome alignment by influencing microtubule dynamics and kinetochore function. Deacetylates histone H4 at 'Lys-16' (H4K16ac) at the VEGFA promoter and thereby contributes to regulate expression of VEGFA, a key regulator of angiogenesis. Deacetylates alpha-tubulin at 'Lys-40' and hence controls neuronal motility, oligodendroglial cell arbor projection processes and proliferation of non-neuronal cells. Phosphorylation at Ser-368 by a G1/S-specific cyclin E-CDK2 complex inactivates SIRT2-mediated alpha-tubulin deacetylation, negatively regulating cell adhesion, cell migration and neurite outgrowth during neuronal differentiation. Deacetylates PARD3 and participates in the regulation of Schwann cell peripheral myelination formation during early postnatal development and during postinjury remyelination. Involved in several cellular metabolic pathways. Plays a role in the regulation of blood glucose homeostasis by deacetylating and stabilizing phosphoenolpyruvate carboxykinase PCK1 activity in response to low nutrient availability. Acts as a key regulator in the pentose phosphate pathway (PPP) by deacetylating and activating the glucose-6-phosphate G6PD enzyme, and therefore, stimulates the production of cytosolic NADPH to counteract oxidative damage. Maintains energy homeostasis in response to nutrient deprivation as well as energy expenditure by inhibiting adipogenesis and promoting lipolysis. Attenuates adipocyte differentiation by deacetylating and promoting FOXO1 interaction to PPARG and subsequent repression of PPARG-dependent transcriptional activity. Plays a role in the regulation of lysosome-mediated degradation of protein aggregates by autophagy in neuronal cells. Deacetylates FOXO1 in response to oxidative stress or serum deprivation, thereby negatively regulating FOXO1-mediated autophagy. Deacetylates a broad range of transcription factors and co-regulators regulating target gene expression. Deacetylates transcriptional factor FOXO3 stimulating the ubiquitin ligase SCF(SKP2)-mediated FOXO3 ubiquitination and degradation (By similarity). Deacetylates HIF1A and therefore promotes HIF1A degradation and inhibition of HIF1A transcriptional activity in tumor cells in response to hypoxia. Deacetylates RELA in the cytoplasm inhibiting NF-kappaB-dependent transcription activation upon TNF stimulation. Inhibits transcriptional activation by deacetylating p53/TP53 and EP300. Also deacetylates EIF5A. In addition to protein deacetylase activity, also acts as a protein-lysine deacylase by recognizing other acyl groups: catalyzes removal of N(6)-benzoyl (benzoyl) and N(6)-methacryl (methacryl) acyl groups from lysine residues, leading to histone debenzoylation and demethacrylation, respectively. Functions as a negative regulator on oxidative stress-tolerance in response to anoxia-reoxygenation conditions. Plays a role as tumor suppressor. In addition to protein deacetylase activity, also has activity toward long-chain fatty acyl groups and mediates protein-lysine demyristoylation and depalmitoylation of target proteins, such as ARF6 and KRAS, thereby regulating their association with membranes

PMID 12620231 ↗ · PMID 12697818 ↗ · PMID 16648462 ↗ · PMID 16909107 ↗ · PMID 17488717 ↗ · PMID 17574768 ↗ · PMID 17726514 ↗ · PMID 18249187 ↗ · PMID 18332217 ↗ · PMID 18640115 ↗ · PMID 18722353 ↗ · PMID 18995842 ↗ · PMID 19282667 ↗ · PMID 20543840 ↗ · PMID 20587414 ↗ · PMID 21081649 ↗ · PMID 21726808 ↗ · PMID 21949390 ↗ · PMID 22014574 ↗ · PMID 22771473 ↗ · PMID 22819792 ↗ · PMID 23468428 ↗ · PMID 23908241 ↗ · PMID 23932781 ↗ · PMID 24177535 ↗ · PMID 24681946 ↗ · PMID 24769394 ↗ · PMID 24940000 ↗ · PMID 25704306 ↗

開啟資料庫紀錄 ↗

功能SIRT2 可去乙醯化 EP300、α-tubulin,以及 histone H3 和 H4。這筆註解列出其作用底物,但沒有進一步說明作用條件、細胞系統或相應的生物學結果。含實驗來源
證據與來源

Deacetylates EP300, alpha-tubulin and histone H3 and H4

PMID 24177535 ↗

開啟資料庫紀錄 ↗

功能此筆功能註解指出,SIRT2 缺乏去乙醯化活性;此限制至少適用於已知的 SIRT2 標的。資料未在此項敘述中指出涉及的標的、異構型或實驗情境,因此不宜將此描述延伸至所有底物或條件。含實驗來源
證據與來源

Lacks deacetylation activity, at least toward known SIRT2 targets

PMID 24177535 ↗

開啟資料庫紀錄 ↗

分子活性N(6)-acetyl-L-lysyl-[protein] + NAD(+) + H2O = 2''-O-acetyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein]含實驗來源
證據與來源

N(6)-acetyl-L-lysyl-[protein] + NAD(+) + H2O = 2''-O-acetyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein]

PMID 11483616 ↗ · PMID 11812793 ↗ · PMID 16648462 ↗ · PMID 18722353 ↗ · PMID 24177535 ↗ · PMID 24389023 ↗ · PMID 24940000 ↗ · PMID 25672491 ↗

開啟資料庫紀錄 ↗

分子活性N(6)-benzoyl-L-lysyl-[protein] + NAD(+) + H2O = 2''-O-benzoyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein]含實驗來源
證據與來源

N(6)-benzoyl-L-lysyl-[protein] + NAD(+) + H2O = 2''-O-benzoyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein]

PMID 30154464 ↗

開啟資料庫紀錄 ↗

分子活性N(6)-methacrylyl-L-lysyl-[protein] + NAD(+) + H2O = 2''-O-methacrylyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein]含實驗來源
證據與來源

N(6)-methacrylyl-L-lysyl-[protein] + NAD(+) + H2O = 2''-O-methacrylyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein]

PMID 34961760 ↗

開啟資料庫紀錄 ↗

分子活性N(6)-tetradecanoyl-L-lysyl-[protein] + NAD(+) + H2O = 2''-O-tetradecanoyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein]含實驗來源
證據與來源

N(6)-tetradecanoyl-L-lysyl-[protein] + NAD(+) + H2O = 2''-O-tetradecanoyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein]

PMID 25704306 ↗ · PMID 32103017 ↗

開啟資料庫紀錄 ↗

分子活性N(6)-hexadecanoyl-L-lysyl-[protein] + NAD(+) + H2O = 2''-O-hexadecanoyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein]含實驗來源
證據與來源

N(6)-hexadecanoyl-L-lysyl-[protein] + NAD(+) + H2O = 2''-O-hexadecanoyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein]

PMID 29239724 ↗

開啟資料庫紀錄 ↗

分子活性每個 SIRT2 蛋白次單元結合 1 個鋅離子。此註解描述的是鋅離子與次單元的數量關係,沒有提供其結合位置或對蛋白功能的影響。資料庫紀錄
證據與來源

Binds 1 zinc ion per subunit.

開啟資料庫紀錄 ↗

交互作用SIRT2 與 CDC20、FOXO3、FZR1、FOXO1、RELA、KMT5A、G6PD、EP300 等多種蛋白互作,並可形成同源三聚體。異構型 1、2 與 HDAC6 的互作有助於複合體接觸 α-tubulin;與 FOXO1 的互作在血清缺乏或氧化壓力時中斷。其與 KMT5A 的互作可刺激組蛋白甲基轉移酶活性,並在 H₂O₂ 誘發的氧化壓力下增加。含實驗來源
證據與來源

Interacts with CDC20, FOXO3 and FZR1. Associates with microtubules in primary cortical mature neurons (By similarity). Homotrimer. Isoform 1 and isoform 2 interact (via both phosphorylated, unphosphorylated, active or inactive forms) with HDAC6; the interaction is necessary for the complex to interact with alpha-tubulin, suggesting that these proteins belong to a large complex that deacetylates the cytoskeleton. Interacts with FOXO1; the interaction is disrupted upon serum-starvation or oxidative stress, leading to increased level of acetylated FOXO1 and induction of autophagy. Interacts with RELA; the interaction occurs in the cytoplasm and is increased in a TNF-dependent manner. Interacts with HOXA10; the interaction is direct. Interacts with YWHAB and YWHAG; the interactions occur in a AKT-dependent manner and increase SIRT2-dependent TP53 deacetylation. Interacts with MAPK1/ERK2 and MAPK3/ERK1; the interactions increase SIRT2 stability and deacetylation activity. Interacts (phosphorylated form) with KMT5A isoform 2; the interaction is direct, stimulates KMT5A-mediated methyltransferase activity on histone at 'Lys-20' (H4K20me1) and is increased in a H(2)O(2)-induced oxidative stress-dependent manner. Interacts with G6PD; the interaction is enhanced by H(2)O(2) treatment. Interacts with a G1/S-specific cyclin E-CDK2 complex. Interacts with AURKA, CDK5R1 (p35 form) and CDK5 and HIF1A. Isoform 1, isoform 2 and isoform 5 interact (via C-terminus region) with EP300. Interacts with the tRNA ligase SARS1; recruited to the VEGFA promoter via interaction with SARS1. Interacts with BEX4; negatively regulates alpha-tubulin deacetylation by SIRT2

PMID 11427894 ↗ · PMID 12620231 ↗ · PMID 15213244 ↗ · PMID 16648462 ↗ · PMID 17726514 ↗ · PMID 18249187 ↗ · PMID 18332217 ↗ · PMID 18722353 ↗ · PMID 20543840 ↗ · PMID 21081649 ↗ · PMID 21949390 ↗ · PMID 23454361 ↗ · PMID 23468428 ↗ · PMID 23806683 ↗ · PMID 24177535 ↗ · PMID 24389023 ↗ · PMID 24681946 ↗ · PMID 24769394 ↗ · PMID 24940000 ↗ · PMID 27512957 ↗

開啟資料庫紀錄 ↗

細胞定位SIRT2 可位於細胞核、細胞質及多種細胞骨架相關區域,並在細胞質與細胞核之間穿梭。大多數細胞週期階段它位於細胞質,G2/M 轉換與有絲分裂時則與染色質相關;Listeria monocytogenes 感染時會移至細胞核及染色質。它也在特定細胞情境中與微管、紡錘體、中體、神經突起及髓鞘區域共定位。含實驗來源
證據與來源

Nucleus; Cytoplasm, perinuclear region; Cytoplasm; Cytoplasm, cytoskeleton; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole; Cytoplasm, cytoskeleton, spindle; Midbody; Chromosome; Perikaryon; Cell projection; Cell projection, growth cone; Myelin membrane; Localizes in the cytoplasm during most of the cell cycle except in the G2/M transition and during mitosis, where it is localized in association with chromatin and induces deacetylation of histone at 'Lys-16' (H4K16ac). Colocalizes with KMT5A at mitotic foci. Colocalizes with CDK1 at centrosome during prophase and splindle fibers during metaphase. Colocalizes with Aurora kinase AURKA at centrosome during early prophase and in the centrioles and growing mitotic spindle throughout metaphase. Colocalizes with Aurora kinase AURKB during cytokinesis with the midbody. Colocalizes with microtubules. Detected in perinuclear foci that may be aggresomes containing misfolded, ubiquitinated proteins (By similarity). Shuttles between the cytoplasm and the nucleus through the CRM1 export pathway. Colocalizes with EP300 in the nucleus. Translocates to the nucleus and chromatin upon bacterium Listeria monocytogenes infection in interphase cells. Deacetylates FOXO3 in the cytoplasm (By similarity). Colocalizes with PLP1 in internodal regions, at paranodal axoglial junction and Schmidt-Lanterman incisures of myelin sheath (By similarity). Colocalizes with CDK5R1 in the perikaryon, neurites and growth cone of hippocampal neurons (By similarity). Colocalizes with alpha-tubulin in neuronal growth cone (By similarity). Localizes in the cytoplasm and nucleus of germinal vesicle (GV) stage oocytes (By similarity). Colocalizes with alpha-tubulin on the meiotic spindle as the oocytes enter into metaphase, and also during meiotic anaphase and telophase, especially with the midbody (By similarity). Colocalizes with PARD3 in internodal region of axons (By similarity). Colocalizes with acetylated alpha-tubulin in cell projection processes during primary oligodendrocyte precursor (OLP) differentiation (By similarity)

PMID 12697818 ↗ · PMID 16079181 ↗ · PMID 16648462 ↗ · PMID 17726514 ↗ · PMID 20543840 ↗ · PMID 23908241 ↗ · PMID 24177535 ↗ · PMID 24681946 ↗ · PMID 12620231 ↗ · PMID 17488717 ↗ · PMID 23468428 ↗

開啟資料庫紀錄 ↗

細胞定位SIRT2 異構型 1 可位於細胞質與細胞核,但主要位於細胞質。此筆註解說明其主要定位偏向細胞質,並未提供在不同細胞條件下定位改變的描述。含實驗來源
證據與來源

Isoform 1; Cytoplasm; Nucleus; Predominantly localized in the cytoplasmic

PMID 24177535 ↗

開啟資料庫紀錄 ↗

細胞定位SIRT2 異構型 2 可位於細胞質與細胞核,但主要位於細胞質。此筆註解說明其主要定位偏向細胞質,並未提供在不同細胞條件下定位改變的描述。含實驗來源
證據與來源

Isoform 2; Cytoplasm; Nucleus; Predominantly localized in the cytoplasmic

PMID 24177535 ↗

開啟資料庫紀錄 ↗

細胞定位SIRT2 異構型 5 可位於細胞質與細胞核,但主要位於細胞核。此筆註解顯示其主要定位與異構型 1、2 不同,並未提供造成此差異的條件或機制。含實驗來源
證據與來源

Isoform 5; Cytoplasm; Nucleus; Predominantly localized in the nucleus

PMID 24177535 ↗

開啟資料庫紀錄 ↗

調控SIRT2 在低葡萄糖與缺氧後再氧合壓力下上調,也會受 trichostatin A 誘導;高葡萄糖則使其下調。數種腫瘤中,組蛋白去乙醯化與 SIRT2 下調相關。這些敘述描述表現量與條件的關聯,未指出更進一步的調控機制。含實驗來源
證據與來源

Up-regulated in response to low levels of glucose and anoxia-reoxygenation stress. Up-regulated by trichostatin A. Down-regulated in response to high levels of glucose. Down-regulated by histone deacetylation in several tumors

PMID 16909107 ↗ · PMID 18640115 ↗ · PMID 21726808 ↗

開啟資料庫紀錄 ↗

情境矩陣 0 筆 · 一般功能註解 15 筆。互作清單與機器格式紀錄不列入本區。
證據分項判讀,不加總為單一可信度分數。「含實驗來源」依資料庫證據標記辨識;未逐篇核對原始方法的紀錄,不宣稱已完成實驗審查。
12 / SEQUENCE EXPLORER

核酸與蛋白質序列

完整轉錄本 · UTR / CDS 著色 · FASTA
ENST00000249396 · 1,862 nt · GRCh38
依 Ensembl exon 註解拼接的 GRCh38 參考序列,保留非編碼區。
1AGTCGGTGACAGGACAGAGCAGTCGGTGACGGGACACAGT40
41GGTTGGTGACGGGACAGAGCGGTCGGTGACAGCCTCAAGG80
81GCTTCAGCACCGCGCCCATGGCAGAGCCAGACCCCTCTCA120
121CCCTCTGGAGACCCAGGCAGGGAAGGTGCAGGAGGCTCAG160
161GACTCAGATTCAGACTCTGAGGGAGGAGCCGCTGGTGGAG200
201AAGCAGACATGGACTTCCTGCGGAACTTATTCTCCCAGAC240
241GCTCAGCCTGGGCAGCCAGAAGGAGCGTCTGCTGGACGAG280
281CTGACCTTGGAAGGGGTGGCCCGGTACATGCAGAGCGAAC320
321GCTGTCGCAGAGTCATCTGTTTGGTGGGAGCTGGAATCTC360
361CACATCCGCAGGCATCCCCGACTTTCGCTCTCCATCCACC400
401GGCCTCTATGACAACCTAGAGAAGTACCATCTTCCCTACC440
441CAGAGGCCATCTTTGAGATCAGCTATTTCAAGAAACATCC480
481GGAACCCTTCTTCGCCCTCGCCAAGGAACTCTATCCTGGG520
521CAGTTCAAGCCAACCATCTGTCACTACTTCATGCGCCTGC560
561TGAAGGACAAGGGGCTACTCCTGCGCTGCTACACGCAGAA600
601CATAGATACCCTGGAGCGAATAGCCGGGCTGGAACAGGAG640
641GACTTGGTGGAGGCGCACGGCACCTTCTACACATCACACT680
681GCGTCAGCGCCAGCTGCCGGCACGAATACCCGCTAAGCTG720
721GATGAAAGAGAAGATCTTCTCTGAGGTGACGCCCAAGTGT760
761GAAGACTGTCAGAGCCTGGTGAAGCCTGATATCGTCTTTT800
801TTGGTGAGAGCCTCCCAGCGCGTTTCTTCTCCTGTATGCA840
841GTCAGACTTCCTGAAGGTGGACCTCCTCCTGGTCATGGGT880
881ACCTCCTTGCAGGTGCAGCCCTTTGCCTCCCTCATCAGCA920
921AGGCACCCCTCTCCACCCCTCGCCTGCTCATCAACAAGGA960

cDNA 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。