Affinage

FAP

Prolyl endopeptidase FAP · UniProt Q12884

Round 2 corrected
Length
760 aa
Mass
87.7 kDa
Annotated
2026-04-28
130 papers in source corpus 23 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FAP is a type II transmembrane serine protease that functions as an obligate homodimer with dual enzymatic activities—dipeptidyl peptidase IV-like exopeptidase and post-prolyl endopeptidase—both dependent on a single catalytic serine (S624), with endopeptidase specificity over DPPIV conferred by Ala657 in the active-site pocket (PMID:15809306, PMID:10593948). FAP cleaves physiological substrates including type I collagen (cooperating with MMPs to facilitate collagen catabolism and Endo180-mediated internalization), α2-antiplasmin (regulating fibrinolysis), FGF21 (controlling metabolic homeostasis), and BNP (modulating post-ischemic angiogenesis), with obligate substrate dependence confirmed by epistasis experiments in FGF21-KO and Nppb-KO mice (PMID:26663085, PMID:16223769, PMID:26797127, PMID:36756875). Beyond its protease function, FAP exerts non-enzymatic signaling roles: it activates STAT3 via a uPAR–FAK–Src–JAK2 cascade in cancer-associated fibroblasts to drive CCL2-dependent MDSC recruitment, promotes M2 macrophage polarization through FN1–integrin α5β1–FAK–AKT–STAT3 signaling, and mediates CCL8-dependent proinflammatory macrophage recruitment in adipose tissue (PMID:27216177, PMID:40263422, PMID:38100414). FAP forms a functional complex with DPPIV/CD26 at invadopodia and associates with α3β1 integrin in a collagen-dependent manner to mediate ECM degradation and tumor cell invasion (PMID:12023964, PMID:10455171).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1994 High

    Molecular cloning established FAP as a type II membrane serine protease with homology to DPPIV and revealed that FAP and CD26/DPPIV form heteromeric complexes on the cell surface, providing the first molecular identity for the fibroblast activation protein.

    Evidence Expression cloning in COS-1 cells with immunochemical co-expression analysis

    PMID:7911242

    Open questions at the time
    • Enzymatic activity not yet characterized
    • Physiological substrates unknown
    • In vivo function not addressed
  2. 1997 High

    Demonstration that seprase and FAP are identical proteins and that gelatinase activity requires the homodimeric form resolved a key structural prerequisite for catalytic function.

    Evidence Purification, RT-PCR cloning, [³H]DFP active-site labeling, and dissociation experiments in COS-7 cells

    PMID:9065413 PMID:9247085

    Open questions at the time
    • Specific cleavage sites not mapped
    • Dimerization interface not structurally defined
    • Endopeptidase versus exopeptidase activity not distinguished
  3. 1999 High

    Mutagenesis of the catalytic serine showed that a single active site governs both DPPIV-like exopeptidase and collagenolytic endopeptidase activities, and collagen-dependent recruitment of FAP to invadopodia via α3β1 integrin provided a spatial mechanism for ECM degradation at the invasion front.

    Evidence S→A mutagenesis with in vitro collagen/gelatin degradation assays; co-IP showing collagen-dependent α3β1 integrin–FAP complex at invadopodia

    PMID:10455171 PMID:10593948

    Open questions at the time
    • Structural basis for dual activity unknown
    • In vivo collagenolytic role not tested
    • No physiological substrates beyond gelatin/collagen identified
  4. 2002 High

    Isolation of a functional FAP–DPPIV protease complex at invadopodia demonstrated that the two related proteases cooperate in gelatin degradation and cell migration, establishing a composite proteolytic unit for ECM invasion.

    Evidence Co-IP of FAP–DPPIV complex, gelatinase activity assays with serine protease inhibitors and anti-gelatin-binding antibodies, wound-closure migration assays

    PMID:12023964 PMID:16651416

    Open questions at the time
    • Relative contribution of each protease to invasion unclear
    • Stoichiometry and regulation of complex assembly unresolved
  5. 2005 High

    The crystal structure of FAP revealed that a single residue difference (Ala657 vs. Asp663 in DPPIV) governs endopeptidase specificity, and identification of α2-antiplasmin as a physiological substrate linked soluble FAP to fibrinolysis regulation.

    Evidence X-ray crystallography with A657D kinetic analysis; comparative biochemistry of APCE/FAP showing cleavage of α2-antiplasmin at defined sites

    PMID:15809306 PMID:16223769

    Open questions at the time
    • Physiological relevance of α2-antiplasmin cleavage in vivo not confirmed in genetic models
    • Structural basis for collagen recognition not resolved
  6. 2005 Medium

    Overexpression studies in hepatic stellate cells demonstrated that FAP promotes adhesion, migration, and invasion through non-enzymatic mechanisms independent of its protease activity, expanding FAP's functional repertoire beyond catalysis.

    Evidence GFP-FAP overexpression with enzyme-dead controls in LX-2 cells; adhesion, migration, and invasion assays; MMP-2/CD44/integrin-β1 expression changes

    PMID:16175601

    Open questions at the time
    • Mechanism of non-enzymatic signaling not defined
    • Overexpression system may not reflect physiological levels
    • No identification of the non-enzymatic binding partner
  7. 2011 Medium

    FAP's enzymatic remodeling of 3D extracellular matrix was shown to organize collagen/fibronectin fibers into parallel orientations that promote directional tumor cell invasion via β1-integrin/FAK signaling, linking FAP catalytic activity to a mechanistic ECM-guided invasion program.

    Evidence Tetracycline-inducible FAP expression, 3D matrix fiber orientation analysis, FAP enzymatic inhibitor rescue, β1-integrin/FAK Western blot

    PMID:21668992

    Open questions at the time
    • Specific ECM cleavage products driving fiber reorganization unidentified
    • In vivo validation of fiber-orientation phenotype lacking
  8. 2015 High

    Genetic and pharmacological studies in fibrosis models revealed that FAP processes MMP-generated collagen fragments to promote Endo180-mediated collagen internalization, establishing an in vivo collagen catabolic function; concurrently, TGF-β1/SMAD2/3 was identified as the upstream inducer of FAP expression in cardiac fibroblasts.

    Evidence FAP-KO mice in bleomycin/irradiation fibrosis models with viral rescue; TGF-β1 stimulation with SMAD2/3 siRNA and pharmacological inhibitors in cardiac fibroblasts

    PMID:26319660 PMID:26663085

    Open questions at the time
    • Precise collagen fragment cleavage sites in vivo unmapped
    • Contribution of soluble vs. membrane FAP in fibrosis not distinguished
  9. 2016 High

    FGF21 was established as a key physiological substrate through convergent evidence from FAP inhibitor treatment, immunodepletion, Fap-KO mice, and primate dosing, with FGF21-KO epistasis confirming it as the obligate mediator of FAP's metabolic effects; separately, TM domain mutagenesis defined the small-X3-small dimerization motif required for protease activity and surface trafficking.

    Evidence In vitro cleavage, selective FAP inhibitor in cynomolgus monkeys, FGF21-KO epistasis in obese mice; AraTM bacterial dimerization assay with TM point mutations

    PMID:26797127 PMID:27155568 PMID:27689014

    Open questions at the time
    • Full spectrum of FAP-regulated metabolic pathways beyond FGF21 unclear
    • Structural model of the TM dimer interface at atomic resolution lacking
  10. 2016 Medium

    FAP was placed upstream of STAT3 activation via a uPAR–FAK–Src–JAK2 signaling cascade in cancer-associated fibroblasts, driving CCL2-dependent MDSC recruitment—demonstrating a non-enzymatic immunomodulatory function validated by Ccr2-KO epistasis in vivo.

    Evidence FAP overexpression in fibroblasts with FAK/Src/JAK2 inhibitors, STAT3 reporter, murine liver tumor model, Ccr2-KO mice

    PMID:27216177

    Open questions at the time
    • Whether protease activity contributes to STAT3 activation not formally excluded
    • Generalizability beyond hepatocellular carcinoma model not established
  11. 2023 High

    BNP was identified as a novel FAP substrate mediating post-ischemic angiogenesis, with FAP inhibition improving cardiac function after MI in a BNP- and NPR1-dependent manner, establishing a cardiovascular axis for FAP protease activity; in parallel, macrophage-specific FAP deletion revealed a CCL8-dependent role in adipose tissue inflammation and metabolic regulation.

    Evidence FAP-KO and pharmacological inhibition in mouse MI model with Nppb-KO and Npr1-KO epistasis; macrophage-specific FAP-KO on HFD with CCL8 overexpression rescue

    PMID:36756875 PMID:38100414

    Open questions at the time
    • BNP cleavage site(s) by FAP not precisely mapped
    • Relative contribution of membrane vs. soluble FAP to BNP inactivation in vivo unknown
    • CCL8 transcriptional regulation by FAP mechanism uncharacterized
  12. 2025 Medium

    FAP+ CAF-derived fibronectin 1 was shown to drive M2 macrophage polarization via integrin α5β1–FAK–AKT–STAT3 signaling, revealing a paracrine mechanism by which FAP shapes the immunosuppressive tumor microenvironment.

    Evidence scRNA-seq, co-culture with conditioned medium, Cilengitide and integrin-blocking antibody treatment, mouse tumor models

    PMID:40263422

    Open questions at the time
    • Whether FAP enzymatic activity is required for FN1 upregulation not tested
    • Single tumor type (breast cancer) limits generalizability

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include the full substrate repertoire of FAP in vivo, the structural basis for collagen and BNP recognition, the molecular mechanism by which FAP exerts non-enzymatic signaling functions, and whether membrane-bound and soluble FAP have distinct physiological roles.
  • No co-crystal structure with any physiological substrate
  • Membrane vs. soluble FAP contributions not genetically separated in vivo
  • Non-enzymatic signaling mechanism molecularly undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 8 GO:0016787 hydrolase activity 5
Localization
GO:0005886 plasma membrane 5 GO:0031012 extracellular matrix 2 GO:0005576 extracellular region 1
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-1474244 Extracellular matrix organization 3 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-1430728 Metabolism 2
Partners
DPP4DPP9FN1ITGA3ITGB1MPRIPUPAR
Complex memberships
FAP homodimerFAP-DPPIV/CD26 heteromeric complex

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 FAP (fibroblast activation protein alpha) was identified as a type II integral membrane protein with a large extracellular domain, sharing 48% amino acid sequence identity with CD26/DPPIV and conserving three catalytic serine protease domains. Immunochemical analysis of COS-1 cells co-expressing FAP and CD26 revealed that the two molecules form heteromeric cell surface complexes, identifying CD26 as the previously described FAP-associated protein FAP-beta. Expression cloning in COS-1 cells, immunochemical co-expression analysis, sequence analysis Proceedings of the National Academy of Sciences of the United States of America High 7911242
1997 Seprase (the 170-kDa melanoma membrane-bound gelatinase) was identified as identical to FAP-alpha; it is a homodimer of N-glycosylated 97-kDa subunits. Proteolytic (gelatinase) activity requires the dimeric form and is abolished upon dissociation into 97-kDa subunits. The active site serine was confirmed by affinity labeling with [³H]diisopropyl fluorophosphate, and activity was blocked by serine-protease inhibitors, establishing FAP/seprase as a serine integral membrane protease. Protein purification, reverse transcription-PCR cloning, COS-7 cell transfection, [³H]DFP affinity labeling, serine protease inhibitor assays, dissociation experiments The Journal of biological chemistry High 9065413 9247085
1999 FAP exhibits both dipeptidyl peptidase IV activity and a collagenolytic/gelatinolytic endopeptidase activity capable of degrading gelatin and type I collagen. Mutation of the putative catalytic serine residue to alanine abolishes both enzymatic activities. FAP enzyme activity was detected in human cancerous tissues but not in matched normal tissues using an immunocapture assay, demonstrating it is active as a cell surface-bound collagenase in tumor stroma. Recombinant protein expression, active-site serine-to-alanine mutagenesis, in vitro collagen/gelatin degradation assays, immunocapture enzyme activity assay on tissue extracts The Journal of biological chemistry High 10593948
1999 Type I collagen substratum induces the association of α3β1 integrin with seprase/FAP as a complex at invadopodia of aggressive tumor cells. In the absence of collagen, α3β1 integrin and seprase exist as non-associating membrane proteins, establishing that integrin serves as a collagen-dependent docking protein for FAP at sites of cell invasion. Co-immunoprecipitation, immunofluorescence localization at invadopodia, collagen-dependent association assay The Journal of biological chemistry Medium 10455171
2002 FAP/seprase and DPPIV form a functional protease complex at invadopodia of migratory fibroblasts that is required for cell invasion and migration on collagenous matrix. This complex elicits both gelatin-binding and gelatinase activities localized at invadopodia; serine protease inhibitors block the gelatinase activity and gelatin degradation, and antibodies to the gelatin-binding domain of DPPIV reduce degradation without affecting adhesion. Co-immunoprecipitation of seprase-DPPIV complex, gelatinase activity assays, serine protease inhibitor blocking, antibody neutralization, wound-closure migration assays The Journal of biological chemistry High 12023964 16651416
2005 The crystal structure of FAP-alpha apoenzyme was solved at high resolution, revealing a DPPIV-like fold with an alpha/beta-hydrolase domain and an eight-bladed beta-propeller domain. A critical difference from DPPIV is Ala657 in FAP (vs. Asp663 in DPPIV) within the active site, which reduces acidity in the substrate-binding pocket and explains FAP's lower affinity for N-terminal amines and its endopeptidase activity. The FAP/A657D mutant showed ~60-fold increased catalytic efficiency for dipeptide substrates and ~350-fold reduced efficiency for endopeptidase substrates, confirming Ala657 as the molecular determinant of substrate specificity. X-ray crystallography (apoenzyme structure), kinetic analysis of wild-type and A657D mutant FAP, comparison with DPPIV crystal structure The Journal of biological chemistry High 15809306
2005 Circulating antiplasmin-cleaving enzyme (APCE) is a soluble form of FAP. APCE and recombinant FAP are homodimers with identical pH optima, extinction coefficients, tryptic peptide sequences, and antibody cross-reactivity. Both cleave α2-antiplasmin at Pro3-Leu4 and Pro12-Asn13 bonds, with ~16-fold higher kcat/Km for the Pro12-Asn13 site, identifying Met-α2-antiplasmin as a physiological substrate of FAP and establishing a role for soluble FAP in fibrinolysis. Comparative biochemical characterization of APCE and recombinant FAP, kinetic analysis of cleavage site preferences, tryptic peptide sequencing, antibody cross-reactivity Blood High 16223769
2005 FAP overexpression in LX-2 human hepatic stellate cells increased cell adhesion and migration on extracellular matrix proteins (collagen-I, fibronectin, Matrigel) and enhanced invasion across transwells, and also enhanced staurosporine-induced apoptosis. Importantly, the enzymatic activity of FAP was not required for these functions (non-enzymatic role). FAP overexpression increased MMP-2 and CD44 expression and reduced integrin-β1 expression. GFP-FAP fusion protein overexpression in LX-2 and HEK293T cells, adhesion assays, transwell migration/invasion assays, Western blot for downstream targets, enzyme-activity-dead controls Hepatology Medium 16175601
2011 FAP enzymatically remodels extracellular matrix by modulating fibronectin and collagen fiber organization and protein levels in a 3D matrix system. FAP-dependent architectural alterations of the ECM promote pancreatic cancer cell invasion along parallel fiber orientations (enhanced directionality and velocity), and this phenotype is reversed by inhibition of FAP enzymatic activity during matrix production. The FAP+ matrix-induced tumor invasion phenotype is β1-integrin/FAK mediated. Tetracycline-inducible FAP overexpression, 3D in vivo-like matrix system, fiber orientation analysis, time-lapse invasion assays, FAP enzymatic inhibitor treatment, Western blot for β1-integrin/FAK BMC cancer Medium 21668992
2015 FAP directly participates in collagen catabolism in concert with MMPs. In two mouse models of pulmonary fibrosis (bleomycin and thoracic irradiation), FAP-deficient mice showed increased mortality and lung fibrosis, with accumulation of intermediate-sized collagen fragments consistent with FAP mediating proteolytic processing of MMP-derived collagen cleavage products. FAP-mediated collagen processing increased collagen internalization (via Endo180 receptor) without altering receptor expression; pharmacological FAP inhibition decreased collagen internalization; restoration of FAP expression in FAP-deficient mouse lungs normalized collagen content. FAP-knockout mouse models, two independent fibrosis models, lung ECM analysis, in vitro collagen processing assays, pharmacological FAP inhibition, viral rescue (FAP re-expression in KO lungs), hydroxyproline quantification The Journal of biological chemistry High 26663085
2015 FAP triggers induction of a cancer-associated fibroblast subset with an inflammatory phenotype via persistent activation of STAT3 through a uPAR-dependent FAK-Src-JAK2 signaling pathway. Enforcing FAP expression in normal fibroblasts was sufficient to activate STAT3 and upregulate CCL2, which promoted recruitment of myeloid-derived suppressor cells (MDSCs) via CCR2. FAP+-CAF-mediated tumor promotion and MDSC recruitment was abrogated in Ccr2-deficient mice. FAP overexpression in normal fibroblasts, signaling pathway inhibitors (FAK, Src, JAK2), STAT3 reporter assays, murine liver tumor model, Ccr2-deficient mice, CCL2 ELISA Cancer research Medium 27216177
2016 FAP cleaves and inactivates fibroblast growth factor 21 (FGF21). A selective FAP chemical inhibitor, FAP immunodepletion, or genetic Fap deletion stabilized recombinant human FGF21 in serum. Administration of a selective FAP inhibitor acutely increased circulating intact FGF21 levels in cynomolgus monkeys, establishing FGF21 as a physiological substrate of FAP. In vitro cleavage assays with purified FAP, selective FAP inhibitor treatment, immunodepletion of FAP from serum, Fap-knockout mice, in vivo FAP inhibitor dosing in monkeys with intact FGF21 quantification The Journal of biological chemistry High 26797127
2016 Pharmacological FAP inhibition (using talabostat) in diet-induced obese mice led to decreased body weight, reduced food intake, improved glucose tolerance and insulin sensitivity, and elevated plasma FGF21 levels. FAP inhibition showed no metabolic effect in FGF21-knockout obese animals, and in vitro FAP was shown to degrade human FGF21 at both termini in the absence of inhibitor, confirming FGF21 as the critical substrate mediating FAP's metabolic role. In vitro FGF21 degradation assay with purified FAP and inhibitor, diet-induced obese mouse model, FGF21-knockout mice, talabostat pharmacological intervention, metabolic phenotyping Molecular metabolism High 27689014
2016 Specific interfacial residues in the FAP transmembrane (TM) domain (G10, S14, A18, forming a small-X3-small motif) are required for FAP homodimerization. Mutations G10L, S14L, and A18L reduced FAP TM-CYTO dimerization as measured by the AraTM bacterial assay, while off-interface residues showed no change. The G10L mutation significantly decreased FAP endopeptidase activity by more than 25% and reduced cell-surface versus intracellular FAP expression, linking TM-mediated dimerization to both protease activity and proper trafficking. AraTM bacterial dimerization assay, site-directed mutagenesis of TM interface residues, endopeptidase activity assays, cell-surface vs. intracellular expression quantification Biochimica et biophysica acta Medium 27155568
2015 FAP expression in activated cardiac fibroblasts after myocardial infarction is induced by TGF-β1 via the canonical SMAD2/SMAD3 pathway (blocked by TGFbR1 inhibitor SB431542, MAPK inhibitor U0126, and siRNA targeting SMAD2/SMAD3). FAP depletion in fibroblasts reduced migratory capacity (Boyden chamber assay) without affecting proliferation, and FAP exhibited gelatinase activity by gelatin zymography, indicating roles in cardiac wound healing and remodeling. TGF-β1 stimulation of human cardiac fibroblasts, TGFbR1 inhibitor, MAPK inhibitor, SMAD2/3 siRNA knockdown, modified Boyden-chamber migration assay, BrdU proliferation assay, gelatin zymography Journal of molecular and cellular cardiology Medium 26319660
2023 BNP (brain natriuretic peptide) is a novel physiological substrate of FAP that mediates post-ischemic angiogenesis. FAP degrades BNP to inhibit vascular endothelial cell migration and tube formation. Genetic or pharmacological inhibition of FAP in mice increased angiogenesis in the peri-infarct zone after myocardial infarction and improved cardiac function. The cardioprotective effect of FAP inhibition was abolished in mice deficient in Nppb (encoding pre-proBNP) or Npr1 (encoding the BNP receptor), establishing BNP as the obligate mediator. In vitro BNP cleavage assay, endothelial cell migration and tube formation assays, FAP genetic KO and pharmacological inhibition in mouse MI model, Nppb-KO and Npr1-KO epistasis, echocardiography, histological analysis, RNA-sequencing Circulation research High 36756875
2014 FAP silencing in oral squamous cell carcinoma (OSCC) cells inhibited growth and metastasis in vitro and in vivo; mechanistically, FAP knockdown inactivated PTEN/PI3K/AKT and Ras-ERK signaling. The inhibitory effects of FAP knockdown on proliferation and metastasis were rescued by PTEN silencing, placing FAP upstream of PTEN/PI3K/AKT in OSCC. FAP siRNA knockdown, in vitro proliferation/migration/invasion assays, xenograft mouse models, Western blot for PI3K/AKT and Ras-ERK pathway components, PTEN rescue experiment Cell death & disease Medium 24722280
2020 FAP overexpression in oral squamous cell carcinoma induces epithelial-mesenchymal transition (EMT) by down-regulating DPP9 (dipeptidyl peptidase 9). FAP was identified as interacting intracellularly with DPP9 by immunoprecipitation-mass spectrometry. DPP9 overexpression reversed the FAP-induced proliferation, migration, invasion, and EMT, establishing a FAP→DPP9 suppression axis. This mechanism is non-enzymatic (FAP promotes EMT by reducing DPP9, not via its protease activity). Immunoprecipitation-mass spectrometry (IP-MS) to identify FAP interactors, FAP overexpression, DPP9 knockdown/overexpression, in vitro and in vivo functional assays OncoTargets and therapy Medium 32273729
2023 FAP in adipose tissue macrophages (ATM) specifically mediates CCL8 chemokine expression, contributing to recruitment of proinflammatory monocyte-derived macrophages in obese adipose tissue. Macrophage-specific FAP deficiency protected mice from diet-induced obesity and improved insulin resistance; CCL8 overexpression restored metabolic phenotypes in FAP-deficient mice, establishing CCL8 as the downstream effector. FAP-deficient ATMs also showed decreased monoamine oxidase expression, leading to elevated norepinephrine and increased lipolysis. Macrophage-specific FAP knockout mice, high-fat diet model, CCL8 overexpression rescue, flow cytometry, norepinephrine measurement, monoamine oxidase expression analysis Proceedings of the National Academy of Sciences of the United States of America Medium 38100414
2023 FAP promotes metastasis and chemoresistance in mucinous colorectal adenocarcinoma by interacting with MPRIP (myosin phosphatase Rho-interacting protein) and regulating the Rho/Hippo/YAP signaling pathway, leading to TAM recruitment and M2 macrophage polarization. MPRIP was identified as a direct FAP-interacting protein. Co-immunoprecipitation identifying MPRIP as FAP interactor, FAP overexpression/knockdown, in vitro and in vivo functional assays, Rho/Hippo/YAP pathway analysis, macrophage polarization assays iScience Low 37213233
2025 FAP+ cancer-associated fibroblasts in breast cancer secrete high levels of fibronectin 1 (FN1), which engages integrin α5β1 on macrophages to activate FAK-AKT-STAT3 signaling, driving M2-like macrophage polarization. Pharmacological disruption of FN1-integrin α5β1 signaling with Cilengitide reprogrammed the tumor immune landscape and suppressed tumor growth in mouse models. scRNA-seq, co-culture experiments, FAP+ CAF conditioned medium, integrin α5β1 blocking antibody and Cilengitide treatment, Western blot for FAK-AKT-STAT3 pathway, in vivo mouse tumor models Oncogene Medium 40263422

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science (New York, N.Y.) 1669 1651563
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2012 A census of human soluble protein complexes. Cell 689 22939629
2022 Single-cell and spatial analysis reveal interaction of FAP+ fibroblasts and SPP1+ macrophages in colorectal cancer. Nature communications 675 35365629
1995 FAP-1: a protein tyrosine phosphatase that associates with Fas. Science (New York, N.Y.) 668 7536343
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2016 FAP Promotes Immunosuppression by Cancer-Associated Fibroblasts in the Tumor Microenvironment via STAT3-CCL2 Signaling. Cancer research 603 27216177
1994 Molecular cloning of fibroblast activation protein alpha, a member of the serine protease family selectively expressed in stromal fibroblasts of epithelial cancers. Proceedings of the National Academy of Sciences of the United States of America 501 7911242
1999 Fibroblast activation protein, a dual specificity serine protease expressed in reactive human tumor stromal fibroblasts. The Journal of biological chemistry 495 10593948
2011 Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for β-Pix in negative regulation of focal adhesion maturation. Nature cell biology 490 21423176
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2015 Tumor-Promoting Desmoplasia Is Disrupted by Depleting FAP-Expressing Stromal Cells. Cancer research 413 25979873
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2014 Understanding fibroblast activation protein (FAP): substrates, activities, expression and targeting for cancer therapy. Proteomics. Clinical applications 382 24470260
2005 Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. Journal of proteome research 350 16335952
1994 Familial adenomatous polyposis (FAP): frequency, penetrance, and mutation rate. Human mutation 339 8199592
2003 The multifunctional or moonlighting protein CD26/DPPIV. European journal of cell biology 266 12647932
2006 Correlations between mutation site in APC and phenotype of familial adenomatous polyposis (FAP): a review of the literature. Critical reviews in oncology/hematology 257 17064931
2011 FAP-overexpressing fibroblasts produce an extracellular matrix that enhances invasive velocity and directionality of pancreatic cancer cells. BMC cancer 254 21668992
2005 Structural and kinetic analysis of the substrate specificity of human fibroblast activation protein alpha. The Journal of biological chemistry 244 15809306
2012 Rationale behind targeting fibroblast activation protein-expressing carcinoma-associated fibroblasts as a novel chemotherapeutic strategy. Molecular cancer therapeutics 229 22323494
2014 Extended structure-activity relationship and pharmacokinetic investigation of (4-quinolinoyl)glycyl-2-cyanopyrrolidine inhibitors of fibroblast activation protein (FAP). Journal of medicinal chemistry 220 24617858
2008 Fibroblast activation protein and its relationship to clinical outcome in pancreatic adenocarcinoma. Pancreas 201 18665076
2015 Fibroblast activation protein alpha expression identifies activated fibroblasts after myocardial infarction. Journal of molecular and cellular cardiology 194 26319660
2015 Fibroblast activation protein overexpression and clinical implications in solid tumors: a meta-analysis. PloS one 193 25775399
1999 A novel protease-docking function of integrin at invadopodia. The Journal of biological chemistry 189 10455171
2013 Autophagy variation within a cell population determines cell fate through selective degradation of Fap-1. Nature cell biology 185 24316673
2016 Sixty years of transthyretin familial amyloid polyneuropathy (TTR-FAP) in Europe: where are we now? A European network approach to defining the epidemiology and management patterns for TTR-FAP. Current opinion in neurology 172 26734951
2005 Antiplasmin-cleaving enzyme is a soluble form of fibroblast activation protein. Blood 168 16223769
2012 Targeting carcinoma-associated fibroblasts within the tumor stroma with a fibroblast activation protein-activated prodrug. Journal of the National Cancer Institute 164 22911669
2012 Expression of fibroblast activation protein in human pancreatic adenocarcinoma and its clinicopathological significance. World journal of gastroenterology 163 22371645
2014 Downregulation of FAP suppresses cell proliferation and metastasis through PTEN/PI3K/AKT and Ras-ERK signaling in oral squamous cell carcinoma. Cell death & disease 160 24722280
2005 Fibroblast activation protein increases apoptosis, cell adhesion, and migration by the LX-2 human stellate cell line. Hepatology (Baltimore, Md.) 159 16175601
2018 FAP Delineates Heterogeneous and Functionally Divergent Stromal Cells in Immune-Excluded Breast Tumors. Cancer immunology research 156 30266714
2013 High intratumoral expression of fibroblast activation protein (FAP) in colon cancer is associated with poorer patient prognosis. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 145 23328994
2002 Regulation of fibroblast migration on collagenous matrix by a cell surface peptidase complex. The Journal of biological chemistry 142 12023964
2006 The protease complex consisting of dipeptidyl peptidase IV and seprase plays a role in the migration and invasion of human endothelial cells in collagenous matrices. Cancer research 134 16651416
1997 Identification of the 170-kDa melanoma membrane-bound gelatinase (seprase) as a serine integral membrane protease. The Journal of biological chemistry 131 9065413
2017 Features of dipeptidyl peptidase IV (DPP-IV) inhibitory peptides from dietary proteins. Journal of food biochemistry 130 31353485
2016 Fibroblast Activation Protein Cleaves and Inactivates Fibroblast Growth Factor 21. The Journal of biological chemistry 130 26797127
1997 Molecular cloning of seprase: a serine integral membrane protease from human melanoma. Biochimica et biophysica acta 128 9247085
2006 Doxycycline disrupts transthyretin amyloid: evidence from studies in a FAP transgenic mice model. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 123 16449795
2002 Intrahepatic expression of the hepatic stellate cell marker fibroblast activation protein correlates with the degree of fibrosis in hepatitis C virus infection. Liver 123 12028401
2021 FAP and FAPI-PET/CT in Malignant and Non-Malignant Diseases: A Perfect Symbiosis? Cancers 121 34638433
2021 Simlukafusp alfa (FAP-IL2v) immunocytokine is a versatile combination partner for cancer immunotherapy. mAbs 100 33974508
2015 Fibroblast Activation Protein (FAP) Accelerates Collagen Degradation and Clearance from Lungs in Mice. The Journal of biological chemistry 99 26663085
2020 Targeting fibroblast activation protein (FAP): next generation PET radiotracers using squaramide coupled bifunctional DOTA and DATA5m chelators. EJNMMI radiopharmacy and chemistry 95 32728930
2003 FAP-1 association with Fas (Apo-1) inhibits Fas expression on the cell surface. Molecular and cellular biology 88 12724420
2021 Translational imaging of the fibroblast activation protein (FAP) using the new ligand [68Ga]Ga-OncoFAP-DOTAGA. European journal of nuclear medicine and molecular imaging 82 34957527
2023 Targeting fibroblast activation protein (FAP): advances in CAR-T cell, antibody, and vaccine in cancer immunotherapy. Drug delivery and translational research 73 36840906
2020 High Expression of FAP in Colorectal Cancer Is Associated With Angiogenesis and Immunoregulation Processes. Frontiers in oncology 73 32733792
2015 Specific inhibition of fibroblast activation protein (FAP)-alpha prevents tumor progression in vitro. Advances in medical sciences 73 26057860
2006 The genetics of FAP and FAP-like syndromes. Familial cancer 71 16998667
2021 Radioligands Targeting Fibroblast Activation Protein (FAP). Cancers 69 34830898
2008 "You're one of us now": young people describe their experiences of predictive genetic testing for Huntington disease (HD) and familial adenomatous polyposis (FAP). American journal of medical genetics. Part C, Seminars in medical genetics 69 18189288
2016 Fibroblast activation protein (FAP) as a novel metabolic target. Molecular metabolism 67 27689014
2023 Inhibition of Fap Promotes Cardiac Repair by Stabilizing BNP. Circulation research 62 36756875
2000 Dipeptidyl peptidase IV (DPPIV) inhibits cellular invasion of melanoma cells. Clinical & experimental metastasis 59 11467771
2002 Protein-tyrosine phosphatase PTPL1/FAP-1 triggers apoptosis in human breast cancer cells. The Journal of biological chemistry 56 12354757
2022 A Dimeric FAP-Targeting Small-Molecule Radioconjugate with High and Prolonged Tumor Uptake. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 53 35589404
2023 Novel Generation of FAP Inhibitor-Based Homodimers for Improved Application in Radiotheranostics. Cancers 52 36980775
2017 Gastric tumours in FAP. Familial cancer 50 28271232
2014 DPPIV (CD26) as a novel stem cell marker in Ph+ chronic myeloid leukaemia. European journal of clinical investigation 49 25371066
2019 Novel Small Molecule-Derived, Highly Selective Substrates for Fibroblast Activation Protein (FAP). ACS medicinal chemistry letters 45 31413802
2016 DPPIV/CD26: a tumor suppressor or a marker of malignancy? Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 45 26943912
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