FAP 蛋白, Human (HEK293, His)

FAP protein is a transmembrane serine protease that plays multiple roles in cell proliferation, fibrosis, wound healing, inflammation, and tumor growth by activating signaling pathways such as PI3K/AKT, SHH/GLI, and FAK-Src-STAT3. FAP Protein, Human (HEK293, His) is a recombinant protein expressed by HEK293, with an N-terminal His tag, and consists of 735 amino acids (L26-D760)^{[1][2][3][4][5][6][7][8][9][10][11]}.

FAP 蛋白是一种 II 型跨膜丝氨酸蛋白酶，同时也是一种调节有丝分裂的因子，对细胞增殖是必需的，也参与组织重塑。FAP 与多种人类疾病有关，包括纤维化、关节炎、动脉粥样硬化、自身免疫性疾病、代谢疾病和癌症。多数情况下 FAP 表达水平的上升与疾病的进展和严重程度增加有关^[1]。
(1) 纤维化：FAP 水平升高在肝、肺、结肠等器官的纤维化过程中发挥重要作用，特发性肺纤维化（Idiopathic Pulmonary Fibrosis, IPF）中的FAP 具有双重作用，既能促进纤维化，也可能通过促进过度沉积的细胞外基质降解来抑制纤维化。FAP还与瘢痕疙瘩和克罗恩病相关的纤维化有关^[2]。
(2) 关节炎：FAP在骨关节炎 (Osteoarthritis, OA) 和类风湿性关节炎 (Rheumatoid Arthritis, RA) 中表达增加，参与软骨退化和滑膜炎症^[3]。
(3) 心血管疾病：FAP 表达水平上调与动脉粥样硬化 (Atherosclerosis) 和心肌梗死 (Myocardial Infarction, MI) 有关，可能增加斑块破裂风险^[4]。
(4) 代谢性疾病：FAP通过切割成纤维细胞生长因子21 (FGF21) 影响代谢，抑制FAP可提升FGF21水平，改善肥胖和代谢健康^[5]。
(5) 肿瘤： FAP通常在癌症的基质中高度表达，包括骨髓瘤、乳腺癌、肺癌和胃肠道癌，可作为癌症相关成纤维细胞 (CAFs) 的标志物。FAP 通过多种机制影响肿瘤生长，包括促进增殖、侵袭、血管生成、上皮间充质转化、干细胞促进、免疫抑制和耐药性^[6]。
FAP可通过激活 PI3K/AKT 和 SHH/GLI 信号通路，导致细胞增殖和迁移增加。FAP 过表达减少局部黏附酪氨酸激酶 (FAK) 磷酸化， FAK 在整合素聚集点发挥信号转导作用，FAK 磷酸化减少可能与细胞的附着和运动能力下降有关。FAP还可以激活通过 uPAR 介导的FAK-Src-STAT3 通路调节，促进免疫抑制细胞因子 CCL2 表达，强化免疫抑制^[7][8]。

FAP (Human) 表达量降低 (通过 siRNA 敲低) 可抑制口腔鳞状细胞癌细胞系 (KB 细胞和 Tca-8113 细胞) 中上皮-间质的转化过程，并增加上皮细胞间粘附蛋白 (E-cadherin) 的表达，从而抑制癌细胞增殖和转移^[9]。
FAP (Human) 可在在人主动脉平滑肌细胞 (HASMC) 由 TNFα 诱导，并在其薄帽纤维粥样斑块中促进降 I 型胶原降解^[10]。
FAP (Human) 表达的降低 (通过 siRNA 敲低) 可以显著减少前列腺癌细胞 (DU145) 细胞侵袭、增殖，并促进其凋亡^[11]。

FAP (Human) 表达的降低在肿瘤异种移植小鼠模型 (通过皮下注射 DU145 细胞构建小鼠模型，在 DU145 细胞中通过 DU145 敲低 FAP 表达量) 中对肿瘤生长具有抑制作用^[10]。

Measured by its ability to convert the substrate benzyloxycarbonyl-Gly-Pro-7-amido-4-methylcoumarin (Z-GP-AMC) to Z-Gly-Pro and 7-amino-4-methylcoumarin (AMC). The specific activity is >3884 pmol/min/μg.

Human

HEK293

N-8*His

Q12884-1 (L26-D760)

2191  [NCBI]

LRPSRVHNSEENTMRALTLKDILNGTFSYKTFFPNWISGQEYLHQSADNNIVLYNIETGQSYTILSNRTMKSVNASNYGLSPDRQFVYLESDYSKLWRYSYTATYYIYDLSNGEFVRGNELPRPIQYLCWSPVGSKLAYVYQNNIYLKQRPGDPPFQITFNGRENKIFNGIPDWVYEEEMLATKYALWWSPNGKFLAYAEFNDTDIPVIAYSYYGDEQYPRTINIPYPKAGAKNPVVRIFIIDTTYPAYVGPQEVPVPAMIASSDYYFSWLTWVTDERVCLQWLKRVQNVSVLSICDFREDWQTWDCPKTQEHIEESRTGWAGGFFVSTPVFSYDAISYYKIFSDKDGYKHIHYIKDTVENAIQITSGKWEAINIFRVTQDSLFYSSNEFEEYPGRRNIYRISIGSYPPSKKCVTCHLRKERCQYYTASFSDYAKYYALVCYGPGIPISTLHDGRTDQEIKILEENKELENALKNIQLPKEEIKKLEVDEITLWYKMILPPQFDRSKKYPLLIQVYGGPCSQSVRSVFAVNWISYLASKEGMVIALVDGRGTAFQGDKLLYAVYRKLGVYEVEDQITAVRKFIEMGFIDEKRIAIWGWSYGGYVSSLALASGTGLFKCGIAVAPVSSWEYYASVYTERFMGLPTKDDNLEHYKNSTVMARAEYFRNVDYLLIHGTADDNVHFQNSAQIAKALVNAQVDFQAMWYSDQNHGLSGLSTNHLYTHMTHFLKQCFSLSD

Approximately 85-100 kDa due to the glycosylation.

• 
  Greater than 95% as determined by reducing SDS-PAGE.

溶液

Supplied as a 0.2 μm filtered solution of 20 mM Tris-HCl, 150 mM NaCl, 20% Glycerol, pH 8.0.

<1 EU/μg, determined by LAL method.

Stored at -80°C for 1 year. It is stable at -20°C for 3 months after opening. It is recommended to freeze aliquots at -80°C for extended storage. Avoid repeated freeze-thaw cycles.

Shipping with dry ice.

• [1]. Fitzgerald AA, et al. The role of fibroblast activation protein in health and malignancy. Cancer Metastasis Rev. 2020 Sep;39(3):783-803.  [Content Brief]

  [2]. Dienus K, et al. Increased expression of fibroblast activation protein-alpha in keloid fibroblasts: implications for development of a novel treatment option. Arch Dermatol Res. 2010 Dec;302(10):725-31.  [Content Brief]

  [3]. Wäldele S, et al. Deficiency of fibroblast activation protein alpha ameliorates cartilage destruction in inflammatory destructive arthritis. Arthritis Res Ther. 2015 Jan 20;17(1):12.  [Content Brief]

  [4]. Uitte de Willige S, et al. Plasma levels of soluble fibroblast activation protein in arterial thrombosis: determinants and cleavage of its substrate alpha-2-antiplasmin. Int J Cardiol. 2015 Jan 15;178:105-10.  [Content Brief]

  [5]. Dunshee DR, et al. Fibroblast Activation Protein Cleaves and Inactivates Fibroblast Growth Factor 21. J Biol Chem. 2016 Mar 11;291(11):5986-5996.  [Content Brief]

  [6]. Mai W, et al. Comprehensive analysis of the oncogenic and immunological role of FAP and identification of the ceRNA network in human cancers. Aging (Albany NY). 2023 May 9;15(9):3738-3758.  [Content Brief]

  [7]. Jia J, et al. FAP-α (Fibroblast activation protein-α) is involved in the control of human breast cancer cell line growth and motility via the FAK pathway. BMC Cell Biol. 2014 May 21;15:16.  [Content Brief]

  [8]. Yang X, et al. FAP Promotes Immunosuppression by Cancer-Associated Fibroblasts in the Tumor Microenvironment via STAT3-CCL2 Signaling. Cancer Res. 2016 Jul 15;76(14):4124-35.  [Content Brief]

  [9]. Wang H, et al. Downregulation of FAP suppresses cell proliferation and metastasis through PTEN/PI3K/AKT and Ras-ERK signaling in oral squamous cell carcinoma. Cell Death Dis. 2014 Apr 10;5(4):e1155.  [Content Brief]

  [10]. Brokopp CE, et al. Fibroblast activation protein is induced by inflammation and degrades type I collagen in thin-cap fibroatheromata. Eur Heart J. 2011 Nov;32(21):2713-22.  [Content Brief]

  [11]. An J, et al. Fibroblast activation protein-alpha knockdown suppresses prostate cancer cell invasion and proliferation. Histol Histopathol. 2022 Jun;37(6):597-607.  [Content Brief]