基因總覽
S100 calcium binding protein A9 是蛋白質編碼基因，產物屬於 S-100 family，具有結合鈣與鋅的能力。S100A9 常與 S100A8 組成異源二聚體或異源四聚體，形成 calprotectin（S100A8/A9）；也可形成同源二聚體。此蛋白質在細胞內與細胞外均有功能，涉及發炎過程及免疫反應。其結構包含兩個 EF-hand 區域，另有一段被註解為無序區域。
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 |
|---|---|---|
| ENST00000368738 ★ | 153,357,854–153,361,023 | 3 |
| ENST00000872632 | 153,357,767–153,361,036 | 3 |
| ENST00000872633 | 153,357,767–153,361,036 | 3 |
| ENST00000970306 | 153,357,767–153,361,027 | 3 |
| ENST00001097955 | 153,357,767–153,361,028 | 3 |
| ENST00001097958 | 153,357,767–153,361,036 | 3 |
| ENST00001097959 | 153,357,767–153,361,027 | 3 |
| ENST00001097960 | 153,357,767–153,361,036 | 3 |
| ENST00001097961 | 153,357,767–153,361,027 | 3 |
| ENST00001097962 | 153,357,767–153,361,028 | 3 |
| ENST00001144880 | 153,357,767–153,361,036 | 3 |
| ENST00001097956 | 153,357,822–153,361,036 | 3 |
顯示 12/16 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
S100A9 主要參與發炎調節與免疫反應，且多以 calprotectin（S100A8/A9）形式發揮細胞內外作用。在中性球中，它可促進趨化與黏附，並透過活化 SYK、PI3K/AKT 和 ERK1/2 增強吞噬作用及殺菌能力；也能以 MAPK 依賴的方式促進脫顆粒。它亦與 CD69 一同參與調節性 T 細胞分化。
在細胞內，S100A9 有助於白血球花生四烯酸的運輸與代謝，並參與吞噬細胞遷移時微管依賴的細胞骨架調節。它也協助活化中性球 NADPH 氧化酶：促進酵素複合體在細胞膜組裝，並將其必要輔因子花生四烯酸轉交至複合體；S100A8 則可直接結合 NCF2/P67PHOX，協助組裝過程。
在細胞外，S100A9 具有促發炎、抗微生物、清除氧化物及誘導細胞死亡等作用。作為警報素或危險相關分子模式（DAMP），它可結合 TLR4 與 AGER 等模式辨識受體，活化 MAP-kinase 和 NF-kappa-B 訊號，放大促發炎反應，並促進白血球募集、細胞激素與趨化因子生成，以及白血球黏附和遷移。它對細菌與真菌具有抗微生物作用，可能藉由螯合微生物生長所需的 Zn(2+) 達成。
S100A9 也能影響細胞存活與組織損傷。它可透過活性氧引發粒線體與溶酶體之間的訊號交互作用，並涉及 BNIP3，促進自噬與細胞凋亡；另一方面，也可經由 ITGAM/ITGB、TLR4 與 MEK-ERK 訊號抑制中性球凋亡。其清除氧化物的作用可限制過度組織損傷。另有研究提出，S100A9 具有轉亞硝基化酶活性：在氧化修飾 LDL 誘導的條件下，可能將 NO 基團由 NOS2/iNOS 經自身 S-亞硝基化的 Cys-3 轉移至 GAPDH 的 Cys-247；相關複合體也被提出可依序列基序選擇性修飾其他靶蛋白。
Promoter 與基因調控
>S100A9 ENST00000368738 GRCh38 chr1:153356854-153357954 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 CTGTGGAGTAGGGGAAGGGCACTCCTGGGGTGGCAAGGTGGGAGGTGGGCCCTGTGTTCCCACAGTGGGC AGGGAGGTAGTGAAAGGGAAGCTGGCCGGACAGGCAGGGCCATTCCAAGAGGGCTTTGTGCGCAGGGCTA AGCCAAGCTTTCTCCATAGGCAATGGGGAGCAACTGGAGGTTCGTAGCAGGAGAAGGACACATCTTGCCC ACCAGGAGGCTAAGTAAAAACAGTTGTCTCCCAAGTTATAAGTTCCTGGAACCCTTGCTGGGAGCAGGAT TTAGAAAAATGATGCTGAGAGATGCTAGAAACATATTCGCCCTGAGGCTCTCTCACTCAGACTGCAAGAG GAAGGTATCATCAGAATTGCCCTTAACCAGGAACCAGAATAGCTGGGTCCCCTTCCTGCCAAGTCAGCAA CCAGCTATGTGACCTTGCTCAGGTCCATCTCCGGGTGTCAGTTTCTTCATCTACAATGCAAGAGGGTTGC CCACCTCTGAGAACCCTTCTAACCCCAAATCTCACCCTATGAATCTAAGAACACCAACCCCTCGCCATCC TAAGTATCACAGAGCCAGGCAAGCATGGGTGAGAGCTCAGACCATCCTTGTTGGACTAAAAGGAAGGGGC AGACTGCCCATGGGGGGCAGCCGAGAGGGTCAGGCCCCCATAGGTCCTCAGCCTGCTTCAACCTCAAAGG GGATGGGGGGCTGAGTGGTGCCAGAGGAGCAGCAGGCTCGCTCGGGGAGAGTAGGGCCTTAGGATAGAAG GGAAATGAACTAAACAACCAGCTTCCTCCCAAACCAGTTTCAGGCCAGGGCTGGGAATTTCACAAAAAAG CAGAAGGCGCTCTGTGAACATTTCCTGCCCCGCCCCAGCCCCCTTCCTGGCAGCATTACCACACTGCTCA CCTGTGAAGCAATCTTCCGGAGACAGGGCCAAAGGGCCAAGTGCCCCAGTCAGGAGCTGCCTATAAATGC CGAGCCTGCACAGCTCTGGCAAACACTCTGTGTGGCTCCTCGGCTTTGGTAAGTGAGCTGCCAGCTTCCC CAGGCAGAAGCCTGCCTGCCGATTCCTTCTTTCCTTCCCTGACCCAACTTC
EPDnew 實驗支持 promoter／TSS · 2 筆
| EPDnew ID | TSS（1-based） | 股向 | 來源顯示區間 |
|---|---|---|---|
| S100A9_1 ↗ | 1:153,357,854 | 正股 | 153,357,805–153,357,864 |
| S100A9_2 ↗ | 1:153,358,260 | 正股 | 153,358,211–153,358,270 |
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
ENSR1_948TFW · enhancer · 153352500–153352920 · regulatory
ENSR1_948TG7 · enhancer · 153353633–153354014 · regulatory
ENSR1_53C3W86 · CTCF_binding_site · 153353763–153353784 · regulatory
ENSR1_B35FPT · enhancer · 153355393–153355975 · regulatory
ENSR1_53C3WJW · CTCF_binding_site · 153355653–153355674 · regulatory
ENSR1_948TH7 · enhancer · 153357054–153357470 · regulatory
ENSR1_948THB · promoter · 153357497–153357864 · regulatory
ENSR1_53C3WWC · CTCF_binding_site · 153357686–153357707 · regulatory
ENSR1_7C2GZL · enhancer · 153357865–153357985 · regulatory
· motif · 153352866–153352879 · motif
· motif · 153352866–153352879 · motif
· motif · 153353765–153353781 · motif
· motif · 153355655–153355671 · motif
· motif · 153357141–153357152 · motif
· motif · 153357259–153357273 · motif
· motif · 153357259–153357273 · motif
· motif · 153357688–153357704 · motif
· motif · 153357788–153357802 · motif
· motif · 153359907–153359922 · motif
· motif · 153359912–153359924 · motif
· motif · 153360017–153360029 · motif
· motif · 153360019–153360026 · motif
· motif · 153360041–153360054 · motif
· motif · 153360426–153360441 · motif
蛋白質結構域與序列
參考蛋白質長度：114 aa
S100A9 屬於 S-100 family，蛋白質長 114 個胺基酸。其序列含兩個 EF-hand 區域：EF-hand 1 位於第 12–47 個胺基酸，EF-hand 2 位於第 54–89 個胺基酸；第 93–114 個胺基酸則被註解為無序區域。
蛋白質三維結構
細胞內定位
細胞內鈣濃度升高時，會由細胞質轉移至細胞骨架與細胞膜。 中性球活化或單核球黏附於內皮細胞時，S100A9 可經由微管介導的替代途徑分泌。
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。
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 10 個夥伴
- AQP1P29972 · UniProt INTERACTION · 2 experiments
- AQP9O43315 · UniProt INTERACTION · 2 experiments
- ARRB1P49407 · UniProt INTERACTION · 2 experiments
- ARRB2P32121 · UniProt INTERACTION · 2 experiments
- CD33P20138 · UniProt INTERACTION · 5 experiments
- MAGEA1P43355 · UniProt INTERACTION · 3 experiments
- MAGEA3P43357 · UniProt INTERACTION · 3 experiments
- MAGEA6P43360 · UniProt INTERACTION · 3 experiments
- S100A8P05109 · UniProt INTERACTION · 7 experiments
- S100BP04271 · UniProt INTERACTION · 3 experiments
S100A9 可形成同源二聚體，但較常與 S100A8 組成 calprotectin 異源二聚體或異源四聚體。S100A9 與 AGER 及由 TLR4、LY96 組成的異源二聚體複合體有交互作用；與後者的交互作用發生於有鈣和／或鋅離子時。calprotectin 亦與微管、CEACAM3、ANXA6、NCF2/P67PHOX、RAC1、RAC2、CYBA、CYBB、NOS2 和 CD69 等分子互作，其中與 NOS2 可形成 iNOS-S100A8/A9 轉亞硝基化酶複合體。另有記載指出，S100A9 與 ATP2A2 的關係為相似性推定。
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 · 3 筆
| 功能面向 | 功能敘述 | 證據類型 | 可查核來源 |
|---|---|---|---|
| 功能 | S100A9 是可結合鈣與鋅的蛋白質，參與發炎與免疫調節；可促進中性球趨化、黏附、吞噬、殺菌及脫顆粒。它常與 S100A8 組成 calprotectin，參與細胞內外多種作用，包括花生四烯酸運輸、細胞骨架調節及 NADPH 氧化酶活化。細胞外作用涵蓋促發炎、抗微生物、清除氧化物與調節細胞死亡；部分抗菌機制被認為可能涉及螯合鋅。另有轉亞硝基化功能的研究提案。 | 含實驗來源 | 證據與來源S100A9 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. It can induce neutrophil chemotaxis, adhesion, can increase the bactericidal activity of neutrophils by promoting phagocytosis via activation of SYK, PI3K/AKT, and ERK1/2 and can induce degranulation of neutrophils by a MAPK-dependent mechanism. Predominantly found as calprotectin (S100A8/A9) which has a wide plethora of intra- and extracellular functions. The intracellular functions include: facilitating leukocyte arachidonic acid trafficking and metabolism, modulation of the tubulin-dependent cytoskeleton during migration of phagocytes and activation of the neutrophilic NADPH-oxidase. Also participates in regulatory T-cell differentiation together with CD69. Activates NADPH-oxidase by facilitating the enzyme complex assembly at the cell membrane, transferring arachidonic acid, an essential cofactor, to the enzyme complex and S100A8 contributes to the enzyme assembly by directly binding to NCF2/P67PHOX. The extracellular functions involve pro-inflammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities. Its pro-inflammatory activity includes recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration. Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and stimulates innate immune cells via binding to pattern recognition receptors such as Toll-like receptor 4 (TLR4) and receptor for advanced glycation endproducts (AGER). Binding to TLR4 and AGER activates the MAP-kinase and NF-kappa-B signaling pathways resulting in the amplification of the pro-inflammatory cascade. Has antimicrobial activity towards bacteria and fungi and exerts its antimicrobial activity probably via chelation of Zn(2+) which is essential for microbial growth. Can induce cell death via autophagy and apoptosis and this occurs through the cross-talk of mitochondria and lysosomes via reactive oxygen species (ROS) and the process involves BNIP3. Can regulate neutrophil number and apoptosis by an anti-apoptotic effect; regulates cell survival via ITGAM/ITGB and TLR4 and a signaling mechanism involving MEK-ERK. Its role as an oxidant scavenger has a protective role in preventing exaggerated tissue damage by scavenging oxidants. Can act as a potent amplifier of inflammation in autoimmunity as well as in cancer development and tumor spread. Has transnitrosylase activity; in oxidatively-modified low-densitity lipoprotein (LDL(ox))-induced S-nitrosylation of GAPDH on 'Cys-247' proposed to transfer the NO moiety from NOS2/iNOS to GAPDH via its own S-nitrosylated Cys-3. The iNOS-S100A8/A9 transnitrosylase complex is proposed to also direct selective inflammatory stimulus-dependent S-nitrosylation of multiple targets such as ANXA5, EZR, MSN and VIM by recognizing a [IL]-x-C-x-x-[DE] motif PMID 12626582 ↗ · PMID 15331440 ↗ · PMID 15598812 ↗ · PMID 15642721 ↗ · PMID 16258195 ↗ · PMID 19087201 ↗ · PMID 19122197 ↗ · PMID 19402754 ↗ · PMID 19534726 ↗ · PMID 19935772 ↗ · PMID 20103766 ↗ · PMID 21325622 ↗ · PMID 21487906 ↗ · PMID 22363402 ↗ · PMID 22804476 ↗ · PMID 22808130 ↗ · PMID 25417112 ↗ · PMID 26296369 ↗ · PMID 8423249 ↗ · PMID 21912088 ↗ · PMID 22489132 ↗ |
| 交互作用 | S100A9 可形成同源二聚體，但較常與 S100A8 組成 calprotectin 異源二聚體或異源四聚體。其互作對象包括 AGER、TLR4/LY96 複合體、amyloid-beta protein 40 及 quinoline-3-carboxamides；與 TLR4/LY96 及後者的結合涉及鈣和／或鋅離子。calprotectin 也與多種細胞骨架及 NADPH 氧化酶相關蛋白互作，並可與 NOS2 組成受 LDL(ox) 誘導的轉亞硝基化酶複合體。 | 含實驗來源 | 證據與來源Homodimer. Preferentially exists as a heterodimer or heterotetramer with S100A8 known as calprotectin (S100A8/A9). S100A9 interacts with ATP2A2 (By similarity). S100A9 interacts with AGER, and with the heterodimeric complex formed by TLR4 and LY96 in the presence of calcium and/or zinc ions. S100A9 binds quinoline-3-carboxamides in the presence of calcium and/or zinc ions. S100A9 interacts with amyloid-beta protein 40. Calprotectin (S100A8/9) interacts with CEACAM3 and tubulin filaments in a calcium-dependent manner. Heterotetrameric calprotectin (S100A8/A9) interacts with ANXA6 and associates with tubulin filaments in activated monocytes. Calprotectin (S100A8/9) interacts with NCF2/P67PHOX, RAC1, RAC2, CYBA and CYBB. Calprotectin (S100A8/9) interacts with NOS2 to form the iNOS-S100A8/A9 transnitrosylase complex; induced by LDL(ox). Calprotectin (S100A8/9) interacts with CD69 PMID 11708798 ↗ · PMID 11851337 ↗ · PMID 15642721 ↗ · PMID 16258195 ↗ · PMID 17553524 ↗ · PMID 18786929 ↗ · PMID 19087201 ↗ · PMID 19122197 ↗ · PMID 19402754 ↗ · PMID 22457725 ↗ · PMID 22808130 ↗ · PMID 25417112 ↗ · PMID 26296369 ↗ · PMID 8423249 ↗ · PMID 9083090 ↗ |
| 細胞定位 | S100A9 主要位於細胞質，也可見於細胞骨架、細胞膜周邊或分泌狀態。細胞內鈣濃度升高時，蛋白質會從細胞質轉移至細胞骨架和細胞膜；中性球活化或單核球黏附內皮細胞時，則可經微管介導的替代途徑分泌。 | 含實驗來源 | 證據與來源Secreted; Cytoplasm; Cytoplasm, cytoskeleton; Cell membrane / Peripheral membrane protein; Predominantly localized in the cytoplasm. Upon elevation of the intracellular calcium level, translocated from the cytoplasm to the cytoskeleton and the cell membrane. Upon neutrophil activation or endothelial adhesion of monocytes, is secreted via a microtubule-mediated, alternative pathway PMID 15598812 ↗ · PMID 8423249 ↗ · PMID 22489132 ↗ · PMID 9083090 ↗ · PMID 18786929 ↗ |
核酸與蛋白質序列
AAACACTCTGTGTGGCTCCTCGGCTTTGACAGAGTGCAAG40ACGATGACTTGCAAAATGTCGCAGCTGGAACGCAACATAG80AGACCATCATCAACACCTTCCACCAATACTCTGTGAAGCT120GGGGCACCCAGACACCCTGAACCAGGGGGAATTCAAAGAG160CTGGTGCGAAAAGATCTGCAAAATTTTCTCAAGAAGGAGA200ATAAGAATGAAAAGGTCATAGAACACATCATGGAGGACCT240GGACACAAATGCAGACAAGCAGCTGAGCTTCGAGGAGTTC280ATCATGCTGATGGCGAGGCTAACCTGGGCCTCCCACGAGA320AGATGCACGAGGGTGACGAGGGCCCTGGCCACCACCATAA360GCCAGGCCTCGGGGAGGGCACCCCCTAAGACCACAGTGGC400CAAGATCACAGTGGCCACGGCCACGGCCACAGTCATGGTG440GCCACGGCCACAGCCACTAATCAGGAGGCCAGGCCACCCT480GCCTCTACCCAACCAGGGCCCCGGGGCCTGTTATGTCAAA520CTGTCTTGGCTGTGGGGCTAGGGGCTGGGGCCAAATAAAG560TCTCTTCCTCCAA573cDNA 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。