FAP Protein, 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 protein is a type II transmembrane serine protease and a factor that regulates mitosis. It is essential for cell proliferation and is also involved in tissue remodeling. FAP is associated with various human diseases, including fibrosis, arthritis, atherosclerosis, autoimmune diseases, metabolic disorders, and cancer. In most cases, the elevation of FAP expression is correlated with disease progression and increased severity^[1].
(1) Fibrosis: Elevated FAP levels play a crucial role in the fibrosis process of organs such as the liver, lungs, and colon. In idiopathic pulmonary fibrosis (Idiopathic Pulmonary Fibrosis, IPF), FAP has dual functions, as it can promote fibrosis but may also inhibit fibrosis by facilitating the degradation of excessively deposited extracellular matrix. FAP is also associated with fibrosis in keloids and Crohn's disease^[2].
(2) Arthritis: FAP expression is increased in osteoarthritis (Osteoarthritis, OA) and rheumatoid arthritis (Rheumatoid Arthritis, RA), where it is involved in cartilage degradation and synovial inflammation^[3].
(3) Cardiovascular Diseases: Upregulated FAP expression is associated with atherosclerosis (Atherosclerosis) and myocardial infarction (Myocardial Infarction, MI) and may increase the risk of plaque rupture^[4].
(4) Metabolic Disorders: FAP influences metabolism by cleaving fibroblast growth factor 21 (FGF21). Inhibition of FAP can elevate FGF21 levels, improving obesity and metabolic health^[5].
(5) Tumors: FAP is typically highly expressed in the stroma of cancers, including multiple myeloma, breast cancer, lung cancer, and gastrointestinal cancer, and can serve as a marker for cancer-associated fibroblasts (CAFs). FAP affects tumor growth through various mechanisms, including promoting proliferation, invasion, angiogenesis, epithelial-mesenchymal transition, stem cell promotion, immune suppression, and drug resistance^[6].
FAP can lead to increased cell proliferation and migration by activating the PI3K/AKT and SHH/GLI signaling pathways. Overexpression of FAP reduces the phosphorylation of focal adhesion kinase (FAK), which plays a role in signal transduction at integrin aggregation points. The reduction in FAK phosphorylation may be related to decreased cell adhesion and motility. FAP can also activate the uPAR-mediated FAK-Src-STAT3 pathway, promoting the expression of the immunosuppressive cytokine CCL2 and enhancing immune suppression^[7][8].

Reduced expression of FAP (Human) (via siRNA knockdown) can inhibit the epithelial-mesenchymal transition (EMT) process in oral squamous cell carcinoma cell lines (KB cells and Tca-8113 cells) and increase the expression of epithelial cell adhesion protein (E-cadherin), thereby suppressing cancer cell proliferation and metastasis^[9].
FAP (Human) can be induced by TNFα in human aortic smooth muscle cells (HASMC) and degrades type I collagen in the thin-cap fibroatheromata^[10].
Reduced expression of FAP (Human) (via siRNA knockdown) can significantly decrease the invasion and proliferation of prostate cancer cells (DU145) and promote their apoptosis^[11].

The reduction of FAP (Human) expression has an inhibitory effect on tumor growth in a xenograft mouse model (constructed by subcutaneously injecting DU145 cells into mice and knocking down FAP expression in DU145 cells)^[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.

Solution

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]