基因總覽
PRDM9（PR/SET domain 9）是蛋白質編碼基因，產物為組蛋白甲基轉移酶。其蛋白質具有甲基轉移酶活性，能修飾組蛋白；來源亦指出，H3 是其可甲基化的四種核心組蛋白中，最適合且修飾程度最高的受質。這項酵素功能與 PRDM9 在減數分裂前期的角色相連，使它能參與減數分裂重組相關過程。
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 |
|---|---|---|
| ENST00000296682 ★ | 23,507,609–23,528,093 | 11 |
| ENST00000635252 | 23,443,586–23,526,498 | 11 |
| ENST00000502755 | 23,507,155–23,527,773 | 11 |
顯示 3/3 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
PRDM9 在減數分裂前期參與重組熱點的定位。它透過鋅指結構域辨識特定 DNA 序列，並在這些位置修飾組蛋白 H3；其甲基轉移酶活性可依序形成 H3K4me3 與 H3K36me3，且兩種修飾可富集於同一核小體。來源指出，這些局部修飾與 PRDM9 結合位點的雙股 DNA 斷裂形成相關，該斷裂會啟動減數分裂重組，支持減數分裂正常進行。
在組蛋白修飾方面，PRDM9 可依序單甲基化、雙甲基化及三甲基化 H3K4 與 H3K36。來源亦提及它能甲基化四種核心組蛋白，其中 H3 是最佳受質且修飾最多；此外，依相似性推定，它可單甲基化及雙甲基化 H4K20，也可三甲基化 H3K9，而雙甲基化 H3K9 是較佳受質。PRDM9 亦會進行自我甲基化。H3 的乙醯化與磷酸化則會減弱或阻止 H3 甲基化。
PRDM9 相關的組蛋白標記也與早期減數分裂前期的基因轉錄活化有關；來源將 H3K4me3 和 H3K36me3 富集描述為表觀遺傳轉錄活化的特定標記。在減數分裂進程中，結合熱點的 PRDM9 也與 DNA 雙股斷裂修復路徑、同源染色體配對及性染色體體形成相關。這些作用部分依相似性推定；來源並指出，在減數分裂前期不同階段，PRDM9 與不同蛋白質複合體的關聯有所變化。
Promoter 與基因調控
>PRDM9 ENST00000296682 GRCh38 chr5:23506609-23507709 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 GTGTCCCCAGGGCTGTGGCACGTAGCTAGGGATACCGGGGGCGGGGGGGAGATCTGTGGCTAGCACTTGA ACGGGGGAGGAGCCCCCACTCTCAGAGCACTGAGAGAGGTGAGACATTTGGGACACTGGGCAGCGAGGGA GCGAGGCATGCCTCCCTCCAGAGGGCCAGTCCAGAAAAGGGGCGACCTATGCAGCCTCTGCCCGAGGGAG CCCCGCAGCCCAGAACACCTAACAAAAGCAACGCAGGCAGCCACCAGTGATTACAGGAGGCTCCCCCAAG ACCTAGGAGCTGGTAAAGGGCTATTGCTCTCCCGTCTCACCGCAAAGCACGCCTGCGAACGCAAAGTACA AAAGAGCCTTGCTACCGGAGATAGCAGCCGTGCCTCTTAAGCACCATCTATTGGATCACGGCCCTAACTA CAACACCAAAATTGGCCAGCTAATACAACATCTGTGAAACCAAGCACAATTCACCCACACGTAAGGGTCC TGTACAGAACCCTGGCCCTCTGAAGCATCCAGAAACGAAGCCAGCTGACAATACCCAACTTACACCACAG TTAAAGGAACACCAACCCTCCCAGATGAGAATCAGTGCAAGAACTCTGGCAATTCAAAAAGACACAGTGT CCCCTTGGAAGACCCAGGCCTGCGGAGGGACGTGAGGAGCAGCCCCGACGCCCGACTCAGTCGCAAACAC CGGAGTTGGGGAAAACCAAGTAATAAAACCCTCGAAACTGCGCCTGCGCGCCGGAGGGTTACACGCAATC CCCTCTGGGAGGGGAGGGACCTTCCTCAGGGGCGGGAAGAGCCAGGCCCCTCCCCCACCTCCTGAGCCCC AAACCGGGTTGTGCCCGTGACTGACAGGCAAGGCTCCGCCCTACTCCCCGCCCATTTAGCGCCTCCTGAC TGCTGAATGGCGGGCTCGCCTTGGTCTCCGTGCTGATTGGCTGGCAGCTGTACAGCCTGGCACTTCGCCC TCCACCACATCTCACCTCCTGAGGGACTCTGAGAGAACGCCCGGCCAGGGTGAACGCCGCGGCAGGAGAG CACGGGAGATTGTGAAGAGCATGGGGAGCCTTTGTCGTGCAGCGTGAAACC
EPDnew 實驗支持 promoter／TSS · 1 筆
| EPDnew ID | TSS（1-based） | 股向 | 來源顯示區間 |
|---|---|---|---|
| PRDM9_1 ↗ | 5:23,443,529 | 正股 | 23,443,480–23,443,539 |
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_B6MXT · enhancer · 23506427–23507336 · regulatory
ENSR5_57J9NP · CTCF_binding_site · 23506996–23507017 · regulatory
ENSR5_9CBWX · promoter · 23507337–23507619 · regulatory
ENSR5_8NMSZ · enhancer · 23507620–23507761 · regulatory
· motif · 23506998–23507014 · motif
· motif · 23507493–23507503 · motif
蛋白質結構域與序列
參考蛋白質長度：894 aa
PRDM9 蛋白質長 894 個胺基酸，具有 KRAB-related 與 SET 結構域，並含多個 C2H2 型鋅指，其中一個被註記為退化型。另有一段 DNA 結合區域，以及數段預測為無序的區域。PRDM9 歸屬於 class V-like SAM-binding methyltransferase 超家族。
蛋白質三維結構
細胞內定位
PRDM9 位於細胞核與染色體。 在精母細胞發育過程中，其核內定位見於前細線期、細線期，以及早期至中期偶線期。
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：Chromosome。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。
PRDM9 可形成同源二聚體。當它結合重組熱點 DNA 時，會與 EHMT2、CDYL 互作；與 CXXC1 的互作則不負責連結熱點與雙股 DNA 斷裂機制，也非熱點辨識途徑所必需。PRDM9 還可與 EWSR1、REC8、SYCP3 及 SYCP1 形成複合體；此複合體形成需要 PRDM9 結合熱點 DNA，並依賴磷酸化的 REC8，EWSR1 透過 REC8 將 PRDM9 連接至染色體軸。此外，PRDM9 與 HELLS 互作可招募 HELLS 至減數分裂重組熱點。
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 · 10 筆
| 功能面向 | 功能敘述 | 證據類型 | 可查核來源 |
|---|---|---|---|
| 功能 | PRDM9 可甲基化組蛋白，主要作用於 H3K4 與 H3K36，並在減數分裂前期辨識特定 DNA 序列、定位重組熱點。熱點上的組蛋白修飾與雙股 DNA 斷裂形成及減數分裂重組相關；其對其他組蛋白的修飾能力及轉錄、修復等作用，部分依相似性推定。 | 含實驗來源 | 證據與來源Histone methyltransferase that sequentially mono-, di-, and tri-methylates both 'Lys-4' (H3K4) and 'Lys-36' (H3K36) of histone H3 to produce respectively trimethylated 'Lys-4' (H3K4me3) and trimethylated 'Lys-36' (H3K36me3) histone H3 and plays a key role in meiotic prophase by determining hotspot localization thereby promoting meiotic recombination. Can also methylate all four core histones with H3 being the best substrate and the most highly modified. Is also able, on one hand, to mono and di-methylate H4K20 and on other hand to trimethylate H3K9 with the di-methylated H3K9 as the best substrate (By similarity). During meiotic prophase, binds specific DNA sequences through its zinc finger domains thereby determining hotspot localization where it promotes local H3K4me3 and H3K36me3 enrichment on the same nucleosomes through its histone methyltransferase activity. Thereby promotes double-stranded breaks (DSB) formation, at this subset of PRDM9-binding sites, that initiates meiotic recombination for the proper meiotic progression (By similarity). During meiotic progression hotspot-bound PRDM9 interacts with several complexes; in early leptonema binds CDYL and EHMT2 followed by EWSR1 and CXXC1 by the end of leptonema. EWSR1 joins PRDM9 with the chromosomal axis through REC8 (By similarity). In this way, controls the DSB repair pathway, pairing of homologous chromosomes and sex body formation (By similarity). Moreover plays a central role in the transcriptional activation of genes during early meiotic prophase thanks to H3K4me3 and H3K36me3 enrichment that represents a specific tag for epigenetic transcriptional activation (By similarity). In addition performs automethylation (By similarity). Acetylation and phosphorylation of histone H3 attenuate or prevent histone H3 methylation (By similarity) PMID 18941885 ↗ · PMID 24095733 ↗ · PMID 24634223 ↗ · PMID 26833727 ↗ |
| 分子活性 | L-lysyl-[protein] + S-adenosyl-L-methionine = N(6)-methyl-L-lysyl-[protein] + S-adenosyl-L-homocysteine + H(+) | 推論支持 | 證據與來源L-lysyl-[protein] + S-adenosyl-L-methionine = N(6)-methyl-L-lysyl-[protein] + S-adenosyl-L-homocysteine + H(+) |
| 分子活性 | N(6)-methyl-L-lysyl-[protein] + S-adenosyl-L-methionine = N(6),N(6)-dimethyl-L-lysyl-[protein] + S-adenosyl-L-homocysteine + H(+) | 推論支持 | 證據與來源N(6)-methyl-L-lysyl-[protein] + S-adenosyl-L-methionine = N(6),N(6)-dimethyl-L-lysyl-[protein] + S-adenosyl-L-homocysteine + H(+) |
| 分子活性 | L-lysyl(4)-[histone H3] + 3 S-adenosyl-L-methionine = N(6),N(6),N(6)-trimethyl-L-lysyl(4)-[histone H3] + 3 S-adenosyl-L-homocysteine + 3 H(+) | 含實驗來源 | 證據與來源L-lysyl(4)-[histone H3] + 3 S-adenosyl-L-methionine = N(6),N(6),N(6)-trimethyl-L-lysyl(4)-[histone H3] + 3 S-adenosyl-L-homocysteine + 3 H(+) PMID 24095733 ↗ · PMID 24634223 ↗ · PMID 26833727 ↗ · PMID 27129774 ↗ |
| 分子活性 | L-lysyl(36)-[histone H3] + 3 S-adenosyl-L-methionine = N(6),N(6),N(6)-trimethyl-L-lysyl(36)-[histone H3] + 3 S-adenosyl-L-homocysteine + 3 H(+) | 含實驗來源 | 證據與來源L-lysyl(36)-[histone H3] + 3 S-adenosyl-L-methionine = N(6),N(6),N(6)-trimethyl-L-lysyl(36)-[histone H3] + 3 S-adenosyl-L-homocysteine + 3 H(+) PMID 24634223 ↗ · PMID 27129774 ↗ |
| 分子活性 | L-lysyl(9)-[histone H3] + 3 S-adenosyl-L-methionine = N(6),N(6),N(6)-trimethyl-L-lysyl(9)-[histone H3] + 3 S-adenosyl-L-homocysteine + 3 H(+) | 推論支持 | 證據與來源L-lysyl(9)-[histone H3] + 3 S-adenosyl-L-methionine = N(6),N(6),N(6)-trimethyl-L-lysyl(9)-[histone H3] + 3 S-adenosyl-L-homocysteine + 3 H(+) |
| 分子活性 | L-lysyl(20)-[histone H4] + S-adenosyl-L-methionine = N(6)-methyl-L-lysyl(20)-[histone H4] + S-adenosyl-L-homocysteine + H(+) | 推論支持 | 證據與來源L-lysyl(20)-[histone H4] + S-adenosyl-L-methionine = N(6)-methyl-L-lysyl(20)-[histone H4] + S-adenosyl-L-homocysteine + H(+) |
| 分子活性 | N(6)-methyl-L-lysyl(20)-[histone H4] + S-adenosyl-L-methionine = N(6),N(6)-dimethyl-L-lysyl(20)-[histone H4] + S-adenosyl-L-homocysteine + H(+) | 推論支持 | 證據與來源N(6)-methyl-L-lysyl(20)-[histone H4] + S-adenosyl-L-methionine = N(6),N(6)-dimethyl-L-lysyl(20)-[histone H4] + S-adenosyl-L-homocysteine + H(+) |
| 交互作用 | PRDM9 可形成同源二聚體，並在結合熱點 DNA 時與 EHMT2、CDYL 互作；它也與 CXXC1 互作，但此關係並非熱點辨識所必需。PRDM9 可與 EWSR1、REC8、SYCP3、SYCP1 形成依賴磷酸化 REC8 的複合體，並與 HELLS 互作以招募 HELLS 至重組熱點。 | 含實驗來源 | 證據與來源Homodimer (Ref.10). Interacts with EHMT2 and CDYL; interaction only takes place when PRDM9 is bound to hotspot DNA. Interacts with CXXC1; this interaction does not link PRDM9-activated recombination hotspot sites with DSB machinery and is not required for the hotspot recognition pathway. Forms a complex with EWSR1, REC8, SYCP3 and SYCP1; complex formation is dependent of phosphorylated form of REC8 and requires PRDM9 bound to hotspot DNA; EWSR1 joins PRDM9 with the chromosomal axis through REC8 (By similarity). Interacts with HELLS; the interaction recruits HELLS to meiotic recombination hot spots PMID 24095733 ↗ · PMID 26833727 ↗ · PMID 32001511 ↗ |
| 細胞定位 | PRDM9 定位於細胞核與染色體；在精母細胞中，其核內定位出現於前細線期、細線期及早期至中期偶線期。 | 推論支持 | 證據與來源Nucleus; Chromosome; Localizes in nuclei of pre-leptotene, leptotene, and early to mid-zygotene spermatocytes |
核酸與蛋白質序列
GAGGGACTCTGAGAGAACGCCCGGCCAGGGTGAACGCCGC40GGCAGGAGAGCACGGGAGATTGTGAAGAGCATGGGGAGCC80TTTGTCGTGCAGCGTGAAACCCTTGAGCCTTTGGCCTAGG120AGCTGGGAGACTCAGGGCCCTTCTCACACTCAGAATTGGA160GCAGGGCCTTCTAGACAGTCCCAGCACCATGAGCCCTGAA200AAGTCCCAAGAGGAGAGCCCAGAAGAAGACACAGAGAGAA240CAGAGCGGAAGCCCATGGTCAAAGATGCCTTCAAAGACAT280TTCCATATACTTCACCAAGGAAGAATGGGCAGAGATGGGA320GACTGGGAGAAAACTCGCTATAGGAATGTGAAAAGGAACT360ATAATGCACTGATTACTATAGGTCTCAGAGCCACTCGACC400AGCTTTCATGTGTCACCGAAGGCAGGCCATCAAACTCCAG440GTGGATGACACAGAAGATTCTGATGAAGAATGGACCCCTA480GGCAGCAAGTCAAACCTCCTTGGATGGCCTTAAGAGTGGA520ACAGCGTAAACACCAGAAGGGAATGCCCAAGGCGTCATTC560AGTAATGAATCTAGTTTGAAAGAATTGTCAAGAACAGCAA600ATTTACTGAATGCAAGTGGCTCAGAGCAGGCTCAGAAACC640AGTGTCCCCTTCTGGAGAAGCAAGTACCTCTGGACAGCAC680TCAAGACTAAAACTGGAACTCAGGAAGAAGGAGACTGAAA720GAAAGATGTATAGCCTGCGAGAAAGAAAGGGTCATGCATA760CAAAGAGGTCAGCGAGCCGCAGGATGATGATTACCTCTAT800TGTGAGATGTGTCAGAACTTCTTCATTGACAGCTGTGCTG840CCCATGGGCCCCCTACATTTGTAAAGGACAGTGCAGTGGA880CAAGGGGCACCCCAACCGTTCAGCCCTCAGTCTGCCCCCA920GGGCTGAGAATTGGGCCATCAGGCATCCCTCAGGCTGGGC960cDNA 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。