基因總覽
SKP1(S-phase kinase associated protein 1)是蛋白質編碼基因,產物屬於 SKP1 family。它是多種蛋白質泛素連接酶複合體的重要組成,尤其見於以 SKP1、CUL1 與 F-box 蛋白構成的 SCF 複合體。SKP1在其中擔任連接角色,協助組合複合體的不同成分;而各複合體所含的 F-box 蛋白不同,底物辨識範圍也隨之改變。除 SCF 複合體外,SKP1亦是 Cul7-RING(FBXW8) 與 Cul1-RING(FBXL4) 泛素連接酶複合體的核心成分。這些組合使 SKP1參與多種蛋白質調控途徑;其具體作用取決於所處的複合體及其底物辨識成分。
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 |
|---|---|---|
| ENST00000353411 ★ | 134,148,935–134,176,950 | 6 |
| ENST00001128131 | 134,145,693–134,177,258 | 6 |
| ENST00000986185 | 134,145,709–134,177,258 | 7 |
| ENST00001104973 | 134,146,155–134,177,258 | 8 |
| ENST00001104974 | 134,147,004–134,177,258 | 7 |
| ENST00001135163 | 134,148,935–134,177,258 | 6 |
| ENST00001104975 | 134,152,451–134,177,258 | 6 |
| ENST00000880996 | 134,155,960–134,176,977 | 5 |
| ENST00000934648 | 134,156,391–134,177,258 | 6 |
| ENST00000934649 | 134,156,395–134,177,258 | 6 |
| ENST00001037625 | 134,156,395–134,177,258 | 6 |
| ENST00000934650 | 134,156,428–134,177,258 | 5 |
顯示 12/40 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
SKP1的主要功能是作為泛素連接酶複合體的組成與連接元件。於 SCF(SKP1-CUL1-F-box protein)複合體中,它連結 F-box 蛋白與 CUL1;F-box 蛋白負責辨識底物,因此不同 F-box 蛋白可使 SCF複合體作用於不同標的。此類複合體介導蛋白質泛素化,所涉及的生物過程包括細胞週期進程、訊息傳遞與轉錄調控。
不同 SCF組合所辨識的底物涵蓋多種蛋白質。例如,SCF(BTRC)與SCF(FBXW11)可促進CTNNB1泛素化,並參與Wnt訊息傳遞;SCF(SKP2)促進已磷酸化的CDKN1B/p27kip泛素化,並參與G1/S轉換調控。SCF(FBXW7)作用於cyclin E及由NOTCH1釋出的細胞內結構域NICD;SCF(FBXL3)與SCF(FBXL21)則作用於CRY1和CRY2。另有多種SCF組合分別促進不同標的的泛素化,顯示底物選擇性主要隨F-box蛋白而異;部分標的在來源中以「可能」描述,並非確定指認。
部分泛素化與後續蛋白質降解相連。例如,SCF(BTRC)在NFKBIA的Lys-21與Lys-22促進泛素化;NFKBIA降解後,與其相關的NFKB1-RELA二聚體得以轉位至細胞核並活化轉錄。SKP1也作為Cul7-RING(FBXW8)複合體的核心成分,參與標的蛋白的泛素化及其後續蛋白酶體降解;在Cul1-RING(FBXL4)複合體中,則促進BNIP3與BNI3L的泛素化及後續降解。SKP1因此透過不同複合體的組成,參與多類蛋白質命運與細胞調控過程。
Promoter 與基因調控
>SKP1 ENST00000353411 GRCh38 chr5:134176850-134177950 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 GGGTGGGGCTTTCAGACTACTCCCTTTCCTTTACAGCTGGCTTCATTCCATCGACCTCATCAAAGCCTTC CTGGGAGCACCCTAGAGAAGAGTTACGTCCAGGCCGGGCCCTGGCTGCCTGGTTCACGGCGGAATCCCCA GCACCACGCCTCGCACGTCGGGCTCAAAGCATGTTTAGTGAAGGAGTAGGTACCTACTGCTAGATGGAGC CATCTCTCTAGACTTGGGGTTTCCCTATAACGATGGCTATGTTTGGCATGGAAGCCTCTTTAGAAGTCAA TAGTAGGAAATAAGGGCTAACAGCACCTAATTGTGGAGTAAGGTTCAAATCCTAGCTCTGCCACTTAACC GTTCCGAACCTGTTCCCTCACTGCAGAGGCGAAAAGGCTAACACTATTTCACCTCGGAGGGTTACCGTGG AGAATGGAAGCTGGACAAGCTGTATCAGTTCAGTAGTAAAACACACACACACAAGCGCCCCACCCCCACC CCACCCCACCCCAGGAATGAACACACACACCCGCGCGCGCACATACACCTCAGGAATGAACACACGCGCG TACACACACACGCAGCCCCCCCCAGGAGTGAACACACACACACACGCCCCGTTCTGTTGTTCCCAGGAAC ACACACAGAGACGCACACACTCGCCCGGTTTTGTTTTTTCCAGGCTTTTTAACTGGGGTCTTTCACTCGG CTTAGGGCACCGCTGCCTGAAAGACCTTTCTAGGCCAGTCGGGGTCCGGCACCCAGTTGACGAGACAGCG CGGCGCTTTCAGAGCTGGGGAGAGGCGAAAACTCTTCCGGCCCCCCGATCCCCCGGCCAGCCGCCCCCGG CAGCTCCTTGCCGCCTCCCGGCCTGGGCCCGCCCAGCCGTTCTCGGCCTGCCGTCAGGCGATCTCGGCGG CCAGCCCAGCCGCGATGTGACGCCGCGCGCCCCGGGGTCCTCGGCGCCTGCGCCCTCTCCTATAAAGCAG ACGCCGCGCCGCGCTGCGACGCTGTAGTGGCTTCGTCTTCGGTTTTTCTCTTCCTTCGCTAACGCCTCCC GGCTCTCGTCAGCCTCCCGCCGGCCGTCTCCTTAACACCGAACACCGTGAG
EPDnew 實驗支持 promoter/TSS · 1 筆
| EPDnew ID | TSS(1-based) | 股向 | 來源顯示區間 |
|---|---|---|---|
| SKP1_1 ↗ | 5:134,176,950 | 負股 | 134,176,940–134,176,999 |
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
ENSR5_CHBH2 · enhancer · 134174965–134176708 · regulatory
ENSR5_BZLZ7 · promoter · 134176709–134177454 · regulatory
ENSR5_536K52Q · CTCF_binding_site · 134176974–134176995 · regulatory
ENSR5_536K569 · CTCF_binding_site · 134177738–134177759 · regulatory
· motif · 134175011–134175024 · motif
· motif · 134175011–134175024 · motif
· motif · 134175631–134175642 · motif
· motif · 134176772–134176787 · motif
· motif · 134176779–134176787 · motif
· motif · 134176976–134176992 · motif
· motif · 134177055–134177070 · motif
· motif · 134177740–134177756 · motif
蛋白質結構域與序列
參考蛋白質長度:163 aa
SKP1蛋白長163個胺基酸,屬於SKP1 family。第63至83位胺基酸區段註記為無序區;第104至163位則是與F-box proteins之F-box domain互作的區域。這些區段註解描述了蛋白質序列中的特徵與互作區域。
蛋白質三維結構
細胞內定位
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
- ANKRD36BP1Q96IX9 · UniProt INTERACTION · 3 experiments
- APIPQ96GX9 · UniProt INTERACTION · 3 experiments
- ATXN1P54253 · UniProt INTERACTION · 6 experiments
- BTRCQ9Y297 · UniProt INTERACTION · 25 experiments
- CCNFP41002 · UniProt INTERACTION · 10 experiments · 2 筆來源紀錄
- CDKN1AP38936 · UniProt INTERACTION · 3 experiments
- CUL1Q13616 · UniProt INTERACTION · 21 experiments
- FBXL12Q9NXK8 · UniProt INTERACTION · 11 experiments
- FBXL14Q8N1E6 · UniProt INTERACTION · 7 experiments
- FBXL17Q9UF56 · UniProt INTERACTION · 17 experiments
- FBXL2Q9UKC9 · UniProt INTERACTION · 14 experiments
- FBXL20Q96IG2 · UniProt INTERACTION · 8 experiments
- FBXL22Q6P050 · UniProt INTERACTION · 7 experiments
- FBXL5Q9UKA1 · UniProt INTERACTION · 15 experiments
- FBXL6Q8N531 · UniProt INTERACTION · 4 experiments
- FBXL8Q96CD0 · UniProt INTERACTION · 18 experiments
- FBXO11Q86XK2 · UniProt INTERACTION · 12 experiments · 2 筆來源紀錄
- FBXO17Q96EF6 · UniProt INTERACTION · 20 experiments
- FBXO2Q9UK22 · UniProt INTERACTION · 15 experiments
- FBXO21O94952 · UniProt INTERACTION · 11 experiments
- FBXO22Q8NEZ5 · UniProt INTERACTION · 11 experiments
- FBXO25Q8TCJ0-3 · UniProt INTERACTION · 4 experiments
- FBXO27Q8NI29 · UniProt INTERACTION · 3 experiments
- FBXO28Q9NVF7 · UniProt INTERACTION · 15 experiments
- FBXO3Q9UK99 · UniProt INTERACTION · 13 experiments
SKP1可與KDM2B形成異二聚體;SKP1-KDM2B複合體再與PCGF1-BCORL異二聚體互作,形成PRC1.1。它也是多種SCF複合體的成分,與不同F-box蛋白及CUL1、RBX1共同組成複合體;亦見於Cul7-RING(FBXW8)與Cul1-RING(FBXL4)複合體。另有來源記載SKP1與CEP68、NOTCH2、BCORL1等互作。微生物感染條件下,SKP1與vaccinia virus蛋白C9L互作。
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 · 4 筆
| 功能面向 | 功能敘述 | 證據類型 | 可查核來源 |
|---|---|---|---|
| 功能 | SKP1是SCF及其他泛素連接酶複合體的核心或必要成分,在SCF中連結F-box底物辨識蛋白與CUL1。不同F-box蛋白使複合體辨識不同標的,參與細胞週期、訊息傳遞與轉錄調控;部分標的及作用以可能性描述。特定複合體可促進標的泛素化,並與蛋白酶體降解或轉錄活化相關。 | 含實驗來源 | 證據與來源Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1. The functional specificity of the SCF complex depends on the F-box protein as substrate recognition component. SCF(BTRC) and SCF(FBXW11) direct ubiquitination of CTNNB1 and participate in Wnt signaling. SCF(FBXW11) directs ubiquitination of phosphorylated NFKBIA. SCF(BTRC) directs ubiquitination of NFKBIB, NFKBIE, ATF4, SMAD3, SMAD4, CDC25A, FBXO5, CEP68 and probably NFKB2. SCF(SKP2) directs ubiquitination of phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. SCF(SKP2) directs ubiquitination of ORC1, CDT1, RBL2, ELF4, CDKN1A, RAG2, FOXO1A, and probably MYC and TAL1. SCF(FBXW7) directs ubiquitination of cyclin E, NOTCH1 released notch intracellular domain (NICD), and probably PSEN1. SCF(FBXW2) directs ubiquitination of GCM1. SCF(FBXO32) directs ubiquitination of MYOD1. SCF(FBXO7) directs ubiquitination of BIRC2 and DLGAP5. SCF(FBXO33) directs ubiquitination of YBX1. SCF(FBXO11) directs ubiquitination of BCL6 and DTL but does not seem to direct ubiquitination of TP53. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(CCNF) directs ubiquitination of CCP110. SCF(FBXL3) and SCF(FBXL21) direct ubiquitination of CRY1 and CRY2. SCF(FBXO9) directs ubiquitination of TTI1 and TELO2. SCF(FBXO10) directs ubiquitination of BCL2. Core component of the Cul7-RING(FBXW8) ubiquitin ligase complex, which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Also acts as a core component of the Cul1-RING(FBXL4) ubiquitin ligase complex, which mediates the ubiquitination and subsequent proteasomal degradation of BNIP3 and BNI3L PMID 16209941 ↗ · PMID 20181953 ↗ · PMID 22113614 ↗ · PMID 23431138 ↗ · PMID 25704143 ↗ · PMID 28727686 ↗ · PMID 35982156 ↗ · PMID 36896912 ↗ |
| 分子活性 | SKP1相關的活動類別包括蛋白質修飾,具體列為蛋白質泛素化。 | 資料庫紀錄 | |
| 交互作用 | SKP1與KDM2B形成異二聚體,該複合體可再與PCGF1-BCORL異二聚體組成PRC1.1。SKP1亦參與多種SCF及其他泛素連接酶複合體,並與多種F-box蛋白、CUL1、RBX1等共同組成複合體;另記載其與CEP68、NOTCH2、BCORL1等互作,以及SKP1-KDM2A和SKP1-KDM2B複合體與UBB互作。 | 含實驗來源 | 證據與來源Interacts with KDM2B, forming heterodimers. The KDM2B-SKP1 heterodimeric complex interacts with the PCGF1-BCORL heterodimeric complex to form a homotetrameric polycomb repression complex 1 (PRC1.1). Component of multiple SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complexes formed of CUL1, SKP1, RBX1 and a variable F-box domain-containing protein as substrate-specific subunit. Component of the SCF(FBXW11) complex containing FBXW11. Component of the SCF(SKP2) complex containing SKP2, in which it interacts directly with SKP1, SKP2 and RBX1. Component of the SCF(FBXW2) complex containing FBXW2. Component of the SCF(FBXO32) complex containing FBXO32. Component of the probable SCF(FBXO7) complex containing FBXO7. Component of the SCF(FBXO10) complex containing FBXO10. Component of the SCF(FBXO11) complex containing FBXO11. Component of the SCF(FBXO25) complex containing FBXO25. Component of the SCF(FBXO33) complex containing FBXO33. Component of the probable SCF(FBXO4) complex containing FBXO4. Component of the SCF(FBXO44) complex, composed of SKP1, CUL1 and FBXO44. Component of the SCF(BTRC) complex, composed of SKP1, CUL1 and BTRC. This complex binds phosphorylated NFKBIA. Part of a SCF complex consisting of CUL1, RBX1, SKP1 and FBXO2. Component of a SCF(SKP2)-like complex containing CUL1, SKP1, TRIM21 and SKP2. Component of the SCF(FBXO17) complex, composed of SKP1, CUL1 and FBXO17. Component of the SCF(FBXO27) complex, composed of SKP1, CUL1 and FBXO27. Component of the SCF(CCNF) complex consisting of CUL1, RBX1, SKP1 and CCNF. Component of the SCF(FBXL3) complex composed of CUL1, SKP1, RBX1 and FBXL3. Component of the SCF(FBXL21) complex composed of CUL1, SKP1, RBX1 and FBXL21. Component of the SCF(FBXO9) complex composed of CUL1, SKP1, RBX1 and FBXO9. Component of the SCF(FBXW7) complex composed of CUL1, SKP1, RBX1 and FBXW7. Component of the SCF(FBXO31) complex composed of CUL1, SKP1, RBX1 and FBXO31. Component of the SCF(FBXW15) complex composed of CUL1, SKP1, RBX1 and FBXW15 (By similarity). Component of the SCF(FBXL2) complex composed of CUL1, SKP1, RBX1 and FBXL2. Interacts with CEP68. Interacts with NOTCH2. Interacts with FBXW15 (By similarity). The SKP1-KDM2A and SKP1-KDM2B complexes interact with UBB. Component of the Cul7-RING(FBXW8) complex consisting of CUL7, RBX1, SKP1 and FBXW8; within the complex interacts with FBXW8. Interacts with BCORL1. Interacts with FBXL4 PMID 11389839 ↗ · PMID 12481031 ↗ · PMID 12820959 ↗ · PMID 16209941 ↗ · PMID 16880511 ↗ · PMID 17389369 ↗ · PMID 17434132 ↗ · PMID 18203720 ↗ · PMID 20181953 ↗ · PMID 20596027 ↗ · PMID 22113614 ↗ · PMID 23431138 ↗ · PMID 25503564 ↗ · PMID 27568929 ↗ · PMID 28727686 ↗ · PMID 29149593 ↗ · PMID 30033217 ↗ · PMID 31209342 ↗ · PMID 31413110 ↗ · PMID 35982156 ↗ · PMID 36896912 ↗ · PMID 38342987 ↗ · PMID 39880951 ↗ |
| 交互作用 | 在微生物感染條件下,SKP1與vaccinia virus蛋白C9L互作。 | 含實驗來源 |
核酸與蛋白質序列
GCTGTAGTGGCTTCGTCTTCGGTTTTTCTCTTCCTTCGCT40AACGCCTCCCGGCTCTCGTCAGCCTCCCGCCGGCCGTCTC80CTTAACACCGAACACCATGCCTTCAATTAAGTTGCAGAGT120TCTGATGGAGAGATATTTGAAGTTGATGTGGAAATTGCCA160AACAATCTGTGACTATTAAGACCATGTTGGAAGATTTGGG200AATGGATGATGAAGGAGATGATGACCCAGTTCCTCTACCA240AATGTGAATGCAGCAATATTAAAAAAGGTCATTCAGTGGT280GCACCCACCACAAGGATGACCCTCCTCCTCCTGAAGATGA320TGAGAACAAAGAAAAGCGAACAGATGATATCCCTGTTTGG360GACCAAGAATTCCTGAAAGTTGACCAAGGAACACTTTTTG400AACTCATTCTGGCTGCAAACTACTTAGACATCAAAGGTTT440GCTTGATGTTACATGCAAGACTGTTGCCAATATGATCAAG480GGGAAAACTCCTGAGGAGATTCGCAAGACCTTCAATATCA520AAAATGACTTTACTGAAGAGGAGGAAGCCCAGGTACGCAA560AGAGAACCAGTGGTGTGAAGAGAAGTGAAATGTTGTGCCT600GACACTGTAACACTGTAAGGATTGTTCCAAATACTAGTTG640CACTGCTCTGTTTATAATTGTTAATATTAGACAAACAGTA680GACAAATGCAGCAGCAAGTCAATTGTATTAGCAGAATATT720GTCCTCATTGCATGTGTAGTTTGAGCACAGATCCCAAACC760TTACGGCCAAGTTTCTTCTAGTATGATGGAAAGTTTCTTT800TTTCTTTGCTCTGAATAAAACTGAACTGTGGGTTCTCTAT840AAGTGGCATTTTGGGCTTTCCCTCTTTTTTGTAAAGCAAT880GTCTGCCTAGTTTATTGTCCAGTTAACTTTAGTGACCTTT920TAAAAGTTGGCATTGTAAATAAAACAACTTGCAAAAAAGT960cDNA 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。