基因總覽
SH3KBP1（SH3 domain containing kinase binding protein 1）是位於 X 染色體的蛋白質編碼基因，其產物屬於接頭蛋白。蛋白質長 665 個胺基酸，含有三個 SH3 domain，並有數段被註記為無序的區域。這種組成使 SH3KBP1 能參與多種蛋白質交互作用，並在不同訊息傳遞途徑中擔任調節角色。
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 |
|---|---|---|
| ENST00000397821 ★ | 19,533,977–19,887,600 | 18 |
| ENST00000379716 | 19,533,966–19,670,998 | 13 |
| ENST00000699720 | 19,533,966–19,833,153 | 18 |
| ENST00000699721 | 19,533,966–19,670,934 | 14 |
| ENST00000699723 | 19,533,966–19,799,788 | 17 |
| ENST00000699725 | 19,533,966–19,833,133 | 19 |
| ENST00000699726 | 19,533,966–19,833,201 | 18 |
| ENST00000379726 | 19,533,966–19,887,650 | 20 |
| ENST00000699668 | 19,533,966–19,887,650 | 19 |
| ENST00000699729 | 19,533,966–19,833,119 | 16 |
| ENST00000699731 | 19,533,966–19,833,133 | 18 |
| ENST00000699732 | 19,533,966–19,833,141 | 17 |
顯示 12/30 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
SH3KBP1 是調節多種訊息傳遞路徑的接頭蛋白，參與受體內吞及後續降解。當 EGFR 或 MET 等受體酪胺酸激酶受到配體刺激後，SH3KBP1 可透過與 CBL 及 endophilins 的關聯，參與受體內吞和溶酶體降解的調節。PDCD6IP 和／或 SPRY2 與 SH3KBP1 的交互作用，可能抑制其與 CBL 的關聯，並因此抑制受體內化；SH3KBP1 也參與配體依賴性的 IgE receptor 內吞調節。
在其他訊息路徑中，SH3KBP1 與磷脂醯肌醇 3-激酶的調節次單元交互作用，並依相似性資料註記可減弱該酵素活性。它可能參與細胞黏附調節，並促進 TTK2B 與 PDCD6IP 的交互作用；也可能透過與 MAP3K4 交互作用，參與 MAPK 路徑介導的細胞壓力反應調節。這些功能的部分描述帶有推論性，不能視為已確立的直接作用機制。
SH3KBP1 亦參與腫瘤壞死因子介導的細胞凋亡調節，並調控細胞形態與細胞骨架組織。來源指出，它是控制細胞形狀及移動所必需的因子，顯示其作用不僅涉及受體訊號，也關聯細胞結構與行為的調整。
在免疫細胞中，SH3KBP1 對 B 細胞活化刺激具有必要作用。此功能與其參與免疫受體及細胞訊息調節的特性相符，但來源未提供足以進一步界定其在 B 細胞活化中的具體分子步驟。
Promoter 與基因調控
>SH3KBP1 ENST00000397821 GRCh38 chrX:19887500-19888600 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 GTGGTGGTGAATGGACCCAAAACGGAGCTTCTGAATTGCCCACGAATGCCCACGGATTCCCTGTTAACAT TTTAGCGCCCACTCAAGGGTCGGCCGTCCAGGTCTGGGAGTCAGTAAGGCACAATAATGCCTGCTAGGGA GGGAGCCAGCCCTCATCTCAGCGGATTCCTGGGAACGTCAGAGCTCGGGAACATTCCTGAACACCCGAAC CGCACCTGGCCCAGGCACTGGGGCGGGGCTTAGGCGGGTCCCAGCGAGGCGATGCGTCCCCTCGGCCCCG CTGCGTCCTTCGCCCGTTTTTCCCCACGTCAGTGCCACCGCCTCCTCTGTGCGGAACTCGCACCTGGCCT GCCTGCGTTCCCACGCCCCACCGAAGGGACGCCGCGTTTCTCTCCCTTCCAAGGGACCCTTTTCCTTCCC CTCCAACAGCCCCCCGGGAAAACTCATTCCAGATTGCCTCGATGCCCCAGGGCCACCTGCCATCACCCTG GTCAGGCGTTTGGCCCCGGGCCTGCCCTGGTCTCCATCCCCAGCCCGTCCTCCACCTCTTGTCGCCCCCT CCCGCTCAGCCCCCTTCTCCTCCTTCTCCACGTGCCCCTGCACTCCCACGCCCCTCCCCCAAGAAGCCCC TCTCCTCCGGTCTCGAGGAGTCTCGCGGCACTTCCCGGGGCGTCAGCCCAGCCGCTGCGGGTGGGTGGCA GCCGCGCGGAGAGGGGTGCCTCTGGCGCGGGCGGTGAGGAGGGCGCCCAAGCCCCTCAGCCGCAGGGACG CCCCCGGCGCCTGCCCCGACGCGGCCCCGGCCCCGGCCCCGCCCCTCTCCGGCCCCGCCCCCGCCCGGCG GCCGCGCGTCCCCGGCAGGCGGAGCTGCAGGAGCCTCGCGGCAGCGCTGAGGAGGAGGGGAGAGCGGGCG GCGCGGCCGCGGCTGCCGGGCGCTGGGCTGGGCGGCGCTGTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT TTTTTTTTTTTTTTTTTTTCGCAATTTCCACTCGCGGGGAGCAGGAAACCCGGCGCAGCCGGGCGCATTG GGCCGCGATGCAACAGCAGCAGCAGGAGTCGCCCCGGGGCAGCAGCGGCAG
EPDnew 實驗支持 promoter／TSS · 2 筆
| EPDnew ID | TSS（1-based） | 股向 | 來源顯示區間 |
|---|---|---|---|
| SH3KBP1_2 ↗ | X:19,799,773 | 負股 | 19,799,763–19,799,822 |
| SH3KBP1_1 ↗ | X:19,887,600 | 負股 | 19,887,590–19,887,649 |
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
ENSRX_99W4G · enhancer · 19883790–19884270 · regulatory
ENSRX_B5XK6 · enhancer · 19886444–19887454 · regulatory
ENSRX_B5XK9 · promoter · 19887455–19888090 · regulatory
ENSRX_56NB3T · CTCF_binding_site · 19887516–19887537 · regulatory
ENSRX_56NB4T · CTCF_binding_site · 19887733–19887754 · regulatory
ENSRX_64C646 · CTCF_binding_site · 19888032–19888066 · regulatory
ENSRX_56NB97 · CTCF_binding_site · 19888666–19888687 · regulatory
ENSRX_56NBDD · CTCF_binding_site · 19889352–19889373 · regulatory
ENSRX_B5XKL · enhancer · 19889591–19890389 · regulatory
· motif · 19883639–19883652 · motif
· motif · 19884010–19884027 · motif
· motif · 19884076–19884084 · motif
· motif · 19885909–19885931 · motif
· motif · 19885909–19885931 · motif
· motif · 19887518–19887534 · motif
· motif · 19887735–19887751 · motif
· motif · 19887764–19887777 · motif
· motif · 19887770–19887783 · motif
· motif · 19887786–19887799 · motif
· motif · 19887821–19887834 · motif
· motif · 19887902–19887915 · motif
· motif · 19887987–19888000 · motif
· motif · 19888005–19888014 · motif
· motif · 19888034–19888050 · motif
· motif · 19888047–19888063 · motif
· motif · 19888160–19888173 · motif
· motif · 19888160–19888173 · motif
· motif · 19888253–19888262 · motif
· motif · 19888381–19888390 · motif
· motif · 19888631–19888640 · motif
· motif · 19888668–19888684 · motif
· motif · 19889207–19889222 · motif
· motif · 19889213–19889225 · motif
· motif · 19889215–19889222 · motif
· motif · 19889215–19889230 · motif
· motif · 19889345–19889357 · motif
· motif · 19889354–19889370 · motif
· motif · 19889528–19889540 · motif
· motif · 19889530–19889537 · motif
· motif · 19889530–19889545 · motif
· motif · 19889962–19889973 · motif
· motif · 19890325–19890336 · motif
蛋白質結構域與序列
參考蛋白質長度：665 aa
SH3KBP1 蛋白質長 665 個胺基酸，含三個 SH3 domain：SH3 1 位於第 1–58 個胺基酸，SH3 2 位於第 98–157 個胺基酸，SH3 3 位於第 267–328 個胺基酸。另有三段區域被註記為無序，分別位於第 159–200、第 328–444 及第 467–610 個胺基酸。
蛋白質三維結構
細胞內定位
SH3KBP1 位於細胞質、細胞骨架相關區域及胞質囊泡膜，也見於突觸體與焦點黏著。 它可定位於含有聚集受體的內吞囊泡，並與 ASAP1、肌動蛋白微絲及 ZFP36 共定位；在突觸體中則與 MAGI2 共定位。 EGF 刺激時，SH3KBP1 會轉移至含 EGFR 的囊泡；此轉位在 SH3KBP1 存在時受到抑制。
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：Synapse, synaptosome；Cell junction, focal adhesion。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 42 個夥伴
- ANKS1AQ49AR9 · UniProt INTERACTION · 3 experiments
- ARAP3Q8WWN8 · UniProt INTERACTION · 5 experiments
- ASAP1Q9ULH1 · UniProt INTERACTION · 14 experiments
- ASAP2O43150 · UniProt INTERACTION · 4 experiments
- CAPZA1P52907 · UniProt INTERACTION · 8 experiments
- CBLP22681 · UniProt INTERACTION · 22 experiments
- CBLBQ13191 · UniProt INTERACTION · 23 experiments · 2 筆來源紀錄
- CCDC57Q2TAC2-2 · UniProt INTERACTION · 3 experiments
- CCDC88BA6NC98 · UniProt INTERACTION · 3 experiments
- CD2P06729 · UniProt INTERACTION · 3 experiments
- CD2APQ9Y5K6 · UniProt INTERACTION · 7 experiments
- CYSRT1A8MQ03 · UniProt INTERACTION · 3 experiments
- DAB2P98082 · UniProt INTERACTION · 3 experiments
- DDNO94850 · UniProt INTERACTION · 5 experiments
- DENND2AQ9ULE3-2 · UniProt INTERACTION · 3 experiments
- DNM2P50570 · UniProt INTERACTION · 5 experiments
- GGNQ86UU5 · UniProt INTERACTION · 3 experiments
- GPRASP3Q6PI77 · UniProt INTERACTION · 5 experiments
- INPP5DQ92835 · UniProt INTERACTION · 6 experiments
- KIF1BO60333-2 · UniProt INTERACTION · 3 experiments
- KPRPQ5T749 · UniProt INTERACTION · 5 experiments
- KRTAP6-3Q3LI67 · UniProt INTERACTION · 3 experiments
- LZTS2Q9BRK4 · UniProt INTERACTION · 3 experiments
- MAP3K4Q9Y6R4 · UniProt INTERACTION · 5 experiments
- NELFAQ9H3P2 · UniProt INTERACTION · 3 experiments
SH3KBP1 可自我結合形成同源四聚體，並與多種蛋白質交互作用。其 SH3 domains 可與 endophilins 的 SH3 domain 結合；SH3KBP1 也與 CBL、CBLB、EGFR、MET 等蛋白質互作。EGF 刺激會增強 SH3KBP1 與 CBL 或 CBLB，以及 EGFR 的交互作用；PDCD6IP 則可減弱其與 CBL 的關聯。SH3KBP1、DAB2 與 clathrin heavy chain 可組成複合體，生長因子處理後 DAB2 和 clathrin 會與 SH3KBP1 分離。來源另記載其與 Chikungunya virus non-structural protein 3 的結合，並指出此互作參與病毒複製的啟動。
疾病與遺傳關聯
SH3KBP1 與免疫缺陷症 61（Immunodeficiency 61）相關。此疾病為 X 連鎖隱性原發性免疫疾病，特徵包括反覆感染及抗體生成受損；患者循環中的 B 細胞與 T 細胞數量正常，但 B 細胞本身有抗體生成缺陷。疾病嚴重程度不一，通常於幼年發病。來源指出，影響 SH3KBP1 所代表基因的變異可能造成此病；這是疾病與基因變異的關聯描述，並非宣稱所有變異皆會致病。
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 · 5 筆
| 功能面向 | 功能敘述 | 證據類型 | 可查核來源 |
|---|---|---|---|
| 功能 | SH3KBP1 是調節多種訊息傳遞路徑的接頭蛋白，參與 EGFR、MET 等受體酪胺酸激酶的配體誘導內吞與溶酶體降解；其與 CBL 的關聯可能受 PDCD6IP 和／或 SPRY2 抑制。它也參與 IgE receptor 內吞、細胞黏附、MAPK 細胞壓力反應、腫瘤壞死因子介導的細胞凋亡、細胞形態與移動調節，並對 B 細胞活化刺激具有必要作用。磷脂醯肌醇 3-激酶活性減弱的描述依相似性資料提出。 | 含實驗來源 | 證據與來源Adapter protein involved in regulating diverse signal transduction pathways. Involved in the regulation of endocytosis and lysosomal degradation of ligand-induced receptor tyrosine kinases, including EGFR and MET/hepatocyte growth factor receptor, through an association with CBL and endophilins. The association with CBL, and thus the receptor internalization, may be inhibited by an interaction with PDCD6IP and/or SPRY2. Involved in regulation of ligand-dependent endocytosis of the IgE receptor. Attenuates phosphatidylinositol 3-kinase activity by interaction with its regulatory subunit (By similarity). May be involved in regulation of cell adhesion; promotes the interaction between TTK2B and PDCD6IP. May be involved in the regulation of cellular stress response via the MAPK pathways through its interaction with MAP3K4. Is involved in modulation of tumor necrosis factor mediated apoptosis. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape and migration. Has an essential role in the stimulation of B cell activation PMID 11894095 ↗ · PMID 11894096 ↗ · PMID 12177062 ↗ · PMID 12734385 ↗ · PMID 12771190 ↗ · PMID 15090612 ↗ · PMID 15707590 ↗ · PMID 16177060 ↗ · PMID 16256071 ↗ · PMID 21275903 ↗ · PMID 21834987 ↗ · PMID 29636373 ↗ |
| 交互作用 | SH3KBP1 可自我結合形成同源四聚體，並與多種受體、訊息蛋白及 E3 泛素連接酶交互作用，包括 CBL 與 CBLB，但不與 CBLC 互作。EGF 刺激會增強其與 CBL 或 CBLB 及 EGFR 的交互作用；PDCD6IP 可減弱其與 CBL 的關聯。它透過 SH3 domains 或富含脯胺酸區域結合多種夥伴，參與受體泛素化、內吞運輸及不同蛋白質複合體的組成；部分關聯以「可能」描述，或依相似性資料推定。 | 含實驗來源 | 證據與來源Can self-associate and form homotetramers. Interacts with CD2, F-actin capping protein, PIK3R3, GRB2, EGFR, MET, BLNK, MAP3K4, PDCD6IP, SPRY2, ARHGAP17, ARHGAP27, MAGI2, CRK, BCAR1, SOS1, ASAP1, ARAP3, HIP1R, SYNJ2, INPP5D and STAP1. Interacts with E3 ubiquitin-protein ligases CBL and CBLB, but does not interact with CBLC. Two molecules of SH3KBP1 seem to bind through their respective SH3 1 domain to one molecule of CBLB. The interaction with CBL or CBLB and EGFR is increased upon EGF stimulation. The interaction with CBL is attenuated by PDCD6IP. Interacts (via SH3 domains) with ARAP1. The interaction is independent of EGF and does not affect ARAP1 GTPase-activating activity but is involved in regulating ubiquitination and endocytic trafficking of EGFR. ARAP1 competes with CBL for binding to SH3KBP1 and prevents interaction of CBL with SH3KBP1; this is likely to regulate SH3KBP1-mediated internalization of EGFR (By similarity). Interacts through its proline-rich region with the SH3 domain of endophilins SH3GL1, SH3GL2 and SH3GL3. The SH3KBP1-endophilin complex seems to associate with a complex containing the phosphorylated receptor (EGFR or MET) and phosphorylated CBL. Probably associates with ASAP1 and phosphorylated EGFR. Probably part of a complex consisting of at least SH3KBP1, ASAP1 and ARAP3. Interacts with focal adhesion kinases PTK2/FAK1 and PTK2B/PYK2, probably as a dimer. Interacts with DAB2 and probably associates with chathrin through its interaction with DAB2. Part of a complex consisting of SH3KBP1, DAB2, and clathrin heavy chain. DAB2 and clathrin dissociate from SH3KBP1 following growth factor treatment, enabling interaction with CBL. Interacts with DDN and probably associates with MAGI2 through its interaction with DDN. Interacts with the SH3 domains of SRC tyrosine-protein kinases SRC, LCK, LYN, FGR, FYN and HCK. Interacts with TRADD, BIRC2, TRAF1, TRAF2 and TNFR1, and the association with a TNFR1-associated complex upon stimulation with TNF seems to be mediated by SRC. Interacts (via SH3 domains) with SHKBP1 (via PXXXPR motifs) (By similarity). Interaction with CBL is abolished in the presence of SHKBP1 (By similarity). Interacts (via SH3 domains) with ZFP36 (via extreme C-terminal region). Interacts with MAP3K4; this interaction enhances the association with ZFP36 PMID 10679202 ↗ · PMID 11071869 ↗ · PMID 11894095 ↗ · PMID 11894096 ↗ · PMID 12177062 ↗ · PMID 12690097 ↗ · PMID 12771190 ↗ · PMID 14596919 ↗ · PMID 15090612 ↗ · PMID 15456872 ↗ · PMID 15707590 ↗ · PMID 15962011 ↗ · PMID 16228008 ↗ · PMID 16256071 ↗ · PMID 16678097 ↗ · PMID 16751601 ↗ · PMID 16895919 ↗ · PMID 20221403 ↗ · PMID 21275903 ↗ |
| 交互作用 | 在微生物感染情境中，SH3KBP1 透過其 SH3 domains 與 Chikungunya virus non-structural protein 3 的 C 端交互作用；此結合參與病毒複製的啟動。 | 含實驗來源 | 證據與來源(Microbial infection) Interacts (via SH3 domains) with Chikungunya virus non-structural protein 3 (via C-terminus); this interaction plays a role in initiation of viral replication PMID 31493651 ↗ |
| 細胞定位 | SH3KBP1 分布於細胞質、細胞骨架相關區域、胞質囊泡膜、突觸體及焦點黏著，並位於含有聚集受體的內吞囊泡。它與 ASAP1、肌動蛋白微絲、MAGI2 及 ZFP36 共定位。EGF 刺激時，其轉移至含 EGFR 囊泡的過程，在 SH3KBP1 存在時受到抑制；部分定位敘述依相似性資料提出。 | 含實驗來源 | 證據與來源Cytoplasm; Cytoplasm, cytoskeleton; Cytoplasmic vesicle membrane / Peripheral membrane protein; Synapse, synaptosome; Cell junction, focal adhesion; Localized in endocytic vesicles containing clustered receptors. Colocalizes with ASAP1 in vesicular structures. Colocalized with actin microfilaments and focal adhesions (By similarity). Colocalized with MAGI2 in synaptosomes. Translocation to EGFR containing vesicles upon EGF stimulation is inhibited in the presence of SH3KBP1 (By similarity). Colocalizes with ZFP36 in the cytoplasm PMID 20221403 ↗ |
| 疾病關聯 | 免疫缺陷症 61 是 X 連鎖隱性原發性免疫疾病，患者反覆感染且抗體生成受損；循環 B、T 細胞數量正常，但 B 細胞有內在的抗體生成缺陷。疾病嚴重程度不一，於幼年發病。影響 SH3KBP1 所代表基因的變異可能造成此病。 | 含實驗來源 | 證據與來源Immunodeficiency 61 IMD61 An X-linked recessive primary immunologic disorder characterized by recurrent infections due to impaired antibody production. Affected individuals have normal numbers of circulating B and T cells, but B cells have an intrinsic defect in antibody production. Disease severity is variable and onset is in early childhood. The disease may be caused by variants affecting the gene represented in this entry MIM: 300310 PMID 29636373 ↗ |
核酸與蛋白質序列
GCAATTTCCACTCGCGGGGAGCAGGAAACCCGGCGCAGCC40GGGCGCATTGGGCCGCGATGCAACAGCAGCAGCAGGAGTC80GCCCCGGGGCAGCAGCGGCAGCAGCAGCAGAGGCAGCAGC120GGGCGGCGCTGAGCCGCCGCCGCCGCCACTGAGGAAGAAG160CCGGCCCAGCCGCCGCCGCGTCCGGACCCTCGCGCCTGGA200TCCCAGCGCCCCGATCCCGGCGCCCCAACCCCCACGCCCG240CCTCCGCCAACTTTCACGCTGCCTCGGCGGCCCGGCCCGG280CTCGACGCCAATGGTGGAGGCCATAGTGGAGTTTGACTAC320CAGGCCCAGCACGATGATGAGCTGACGATCAGCGTGGGTG360AAATCATCACCAACATCAGGAAGGAGGATGGAGGCTGGTG400GGAGGGACAGATCAACGGCAGGAGAGGTTTGTTCCCTGAC440AACTTTGTAAGAGAAATAAAGAAAGAGATGAAGAAAGACC480CTCTCACCAACAAAGCTCCAGAAAAGCCCCTGCACGAAGT520GCCCAGTGGAAACTCTTTGCTGTCTTCTGAAACGATTTTA560AGAACCAATAAGAGAGGCGAGCGACGGAGGCGCCGGTGCC600AGGTGGCATTCAGCTACCTGCCCCAGAATGACGATGAACT640TGAGCTGAAAGTTGGCGACATCATAGAGGTGGTAGGAGAG680GTAGAGGAAGGATGGTGGGAAGGTGTTCTCAACGGGAAGA720CTGGAATGTTTCCTTCCAACTTCATCAAGGAGCTGTCAGG760GGAGTCGGATGAGCTTGGCATTTCCCAGGATGAGCAGCTA800TCCAAGTCAAGTTTAAGGGAAACCACAGGCTCCGAGAGTG840ATGGGGGTGACTCAAGCAGCACCAAGTCTGAAGGTGCCAA880CGGGACAGTGGCAACTGCAGCAATCCAGCCCAAGAAAGTT920AAGGGAGTGGGCTTTGGAGACATTTTCAAAGACAAGCCAA960cDNA 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。