TISIDB

Summary
Symbol	FAP
Name	fibroblast activation protein, alpha
Aliases	seprase; DPPIVA; 170 kDa melanoma membrane-bound gelatinase; FAPalpha; dipeptidyl peptidase FAP; gelatine de ......
Chromosomal Location	2q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Prolyl endopeptidase FAP: Cell surface Cell membrane Single-pass type II membrane protein Cell projection, lamellipodium membrane Single-pass type II membrane protein Cell projection, invadopodium membrane Single-pass type II membrane protein Cell projection, ruffle membrane Single-pass type II membrane protein Membrane Single-pass type II membrane protein Note=Localized on cell surface with lamellipodia and invadopodia membranes and on shed vesicles. Colocalized with DPP4 at invadopodia and lamellipodia membranes of migratory activated endothelial cells in collagenous matrix. Colocalized with DPP4 on endothelial cells of capillary-like microvessels but not large vessels within invasive breast ductal carcinoma. Anchored and enriched preferentially by integrin alpha-3/beta-1 at invadopodia, plasma membrane protrusions that correspond to sites of cell invasion, in a collagen-dependent manner. Localized at plasma and ruffle membranes in a collagen-independent manner. Colocalized with PLAUR preferentially at the cell surface of invadopodia membranes in a cytoskeleton-, integrin- and vitronectin-dependent manner. Concentrated at invadopodia membranes, specialized protrusions of the ventral plasma membrane in a fibrobectin-dependent manner. Colocalizes with extracellular components (ECM), such as collagen fibers and fibronectin. ; SUBCELLULAR LOCATION: Antiplasmin-cleaving enzyme FAP, soluble form: Secreted Note=Found in blood plasma and serum. ; SUBCELLULAR LOCATION: Isoform 2: Cytoplasm
Domain	PF00930 Dipeptidyl peptidase IV (DPP IV) N-terminal region PF00326 Prolyl oligopeptidase family
Function	Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammation and tumor growth. Both plasma membrane and soluble forms exhibit post-proline cleaving endopeptidase activity, with a marked preference for Ala/Ser-Gly-Pro-Ser/Asn/Ala consensus sequences, on substrate such as alpha-2-antiplasmin SERPINF2 and SPRY2 (PubMed:14751930, PubMed:16223769, PubMed:16480718, PubMed:16410248, PubMed:17381073, PubMed:18095711, PubMed:21288888, PubMed:24371721). Degrade also gelatin, heat-denatured type I collagen, but not native collagen type I and IV, vibronectin, tenascin, laminin, fibronectin, fibrin or casein (PubMed:9065413, PubMed:2172980, PubMed:7923219, PubMed:10347120, PubMed:10455171, PubMed:12376466, PubMed:16223769, PubMed:16651416, PubMed:18095711). Have also dipeptidyl peptidase activity, exhibiting the ability to hydrolyze the prolyl bond two residues from the N-terminus of synthetic dipeptide substrates provided that the penultimate residue is proline, with a preference for Ala-Pro, Ile-Pro, Gly-Pro, Arg-Pro and Pro-Pro (PubMed:10347120, PubMed:10593948, PubMed:16175601, PubMed:16223769, PubMed:16651416, PubMed:16410248, PubMed:17381073, PubMed:21314817, PubMed:24371721, PubMed:24717288). Natural neuropeptide hormones for dipeptidyl peptidase are the neuropeptide Y (NPY), peptide YY (PYY), substance P (TAC1) and brain natriuretic peptide 32 (NPPB) (PubMed:21314817). The plasma membrane form, in association with either DPP4, PLAUR or integrins, is involved in the pericellular proteolysis of the extracellular matrix (ECM), and hence promotes cell adhesion, migration and invasion through the ECM. Plays a role in tissue remodeling during development and wound healing. Participates in the cell invasiveness towards the ECM in malignant melanoma cancers. Enhances tumor growth progression by increasing angiogenesis, collagen fiber degradation and apoptosis and by reducing antitumor response of the immune system. Promotes glioma cell invasion through the brain parenchyma by degrading the proteoglycan brevican. Acts as a tumor suppressor in melanocytic cells through regulation of cell proliferation and survival in a serine protease activity-independent manner.

> Gene Ontology [ TOP ]
Biological Process	GO:0001525 angiogenesis GO:0001667 ameboidal-type cell migration GO:0007050 cell cycle arrest GO:0007596 blood coagulation GO:0007599 hemostasis GO:0009894 regulation of catabolic process GO:0010631 epithelial cell migration GO:0010710 regulation of collagen catabolic process GO:0010712 regulation of collagen metabolic process GO:0010715 regulation of extracellular matrix disassembly GO:0010716 negative regulation of extracellular matrix disassembly GO:0022617 extracellular matrix disassembly GO:0030193 regulation of blood coagulation GO:0030195 negative regulation of blood coagulation GO:0030198 extracellular matrix organization GO:0030574 collagen catabolic process GO:0032102 negative regulation of response to external stimulus GO:0032963 collagen metabolic process GO:0042730 fibrinolysis GO:0043062 extracellular structure organization GO:0043542 endothelial cell migration GO:0044236 multicellular organism metabolic process GO:0044243 multicellular organism catabolic process GO:0044246 regulation of multicellular organismal metabolic process GO:0044259 multicellular organismal macromolecule metabolic process GO:0045786 negative regulation of cell cycle GO:0045787 positive regulation of cell cycle GO:0048514 blood vessel morphogenesis GO:0050673 epithelial cell proliferation GO:0050817 coagulation GO:0050818 regulation of coagulation GO:0050819 negative regulation of coagulation GO:0050878 regulation of body fluid levels GO:0051917 regulation of fibrinolysis GO:0060242 contact inhibition GO:0060244 negative regulation of cell proliferation involved in contact inhibition GO:0061041 regulation of wound healing GO:0061045 negative regulation of wound healing GO:0071156 regulation of cell cycle arrest GO:0071158 positive regulation of cell cycle arrest GO:0071850 mitotic cell cycle arrest GO:0090068 positive regulation of cell cycle process GO:0090130 tissue migration GO:0090132 epithelium migration GO:0097194 execution phase of apoptosis GO:0097325 melanocyte proliferation GO:1900046 regulation of hemostasis GO:1900047 negative regulation of hemostasis GO:1900117 regulation of execution phase of apoptosis GO:1900119 positive regulation of execution phase of apoptosis GO:1902362 melanocyte apoptotic process GO:1903034 regulation of response to wounding GO:1903035 negative regulation of response to wounding GO:1903053 regulation of extracellular matrix organization GO:1903054 negative regulation of extracellular matrix organization
Molecular Function	GO:0002020 protease binding GO:0004175 endopeptidase activity GO:0004177 aminopeptidase activity GO:0004222 metalloendopeptidase activity GO:0004252 serine-type endopeptidase activity GO:0005178 integrin binding GO:0008236 serine-type peptidase activity GO:0008237 metallopeptidase activity GO:0008238 exopeptidase activity GO:0008239 dipeptidyl-peptidase activity GO:0017171 serine hydrolase activity GO:0050839 cell adhesion molecule binding
Cellular Component	GO:0001726 ruffle GO:0005924 cell-substrate adherens junction GO:0005925 focal adhesion GO:0030027 lamellipodium GO:0030055 cell-substrate junction GO:0031252 cell leading edge GO:0031253 cell projection membrane GO:0031256 leading edge membrane GO:0031258 lamellipodium membrane GO:0032587 ruffle membrane GO:0045177 apical part of cell GO:0045178 basal part of cell GO:0071437 invadopodium GO:0071438 invadopodium membrane

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	-

Summary
Symbol	FAP
Name	fibroblast activation protein, alpha
Aliases	seprase; DPPIVA; 170 kDa melanoma membrane-bound gelatinase; FAPalpha; dipeptidyl peptidase FAP; gelatine de ......
Chromosomal Location	2q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between FAP and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

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Literatures describing the relation between FAP and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
27216177	Hepatocellular Carcinoma	Inhibit immunity (T cell function)	In a murine liver tumor model, we found that FAP(+)CAFs were a major source of CCL2 and that fibroblastic STAT3-CCL2 signaling in this setting promoted tumor growth by enhancing recruitment of myeloid-derived suppressor cells (MDSC).
23732988	Lung Carcinoma	Promote immunity (T cell function); essential for immunotherapy	Fibroblast activation protein-α (FAP), a type 2 dipeptidyl peptidase, is expressed on CAFs in a majority of solid tumors making it an attractive immunotherapeutic target. In an established A549 lung cancer model, adoptive transfer of FAP-specific T cells significantly reduced FAP-positive stromal cells, with a concomitant decrease in tumor growth. Combining these FAP-specific T cells with T cells that targeted the EphA2 antigen on the A549 cancer cells themselves significantly enhanced overall antitumor activity and conferred a survival advantage compared to either alone. Our study underscores the value of co-targeting both CAFs and cancer cells to increase the benefits of T-cell immunotherapy for solid tumors.
29626119	breast carcinoma	Inhibit immunity	Fibroblast activation protein (FAP) is overexpressed in cancer associated fibroblasts and is involved in a variety of tumor promoting activities such as matrix remodeling, angiogenesis, chemotherapy resistance and immunosuppression.
24277834	Pancreatic Ductal Adenocarcinoma	Inhibit immunity; Resistant to immunotherapy	Immune control of PDA growth was achieved, however, by depleting carcinoma-associated fibroblasts (CAFs) that express fibroblast activation protein (FAP). The depletion of the FAP(+) stromal cell also uncovered the antitumor effects of α-CTLA-4 and α-PD-L1, indicating that its immune suppressive activity accounts for the failure of these T-cell checkpoint antagonists.

Summary
Symbol	FAP
Name	fibroblast activation protein, alpha
Aliases	seprase; DPPIVA; 170 kDa melanoma membrane-bound gelatinase; FAPalpha; dipeptidyl peptidase FAP; gelatine de ......
Chromosomal Location	2q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of FAP in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	FAP
Name	fibroblast activation protein, alpha
Aliases	seprase; DPPIVA; 170 kDa melanoma membrane-bound gelatinase; FAPalpha; dipeptidyl peptidase FAP; gelatine de ......
Chromosomal Location	2q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of FAP in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-1.446	0.0126
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-2.17	0.221
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.9	0.437
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-1.341	0.00482
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-1.494	0.356
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-1.146	0.581
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.282	0.677
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.588	0.693
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.004	0.998
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.735	0.646
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	2.209	0.288
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.356	0.178

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of FAP in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	7.4	6.8	0.6	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	7.4	8.5	-1.1	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	22.2	0	22.2	0.12
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	50	0	50	0.109
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	FAP
Name	fibroblast activation protein, alpha
Aliases	seprase; DPPIVA; 170 kDa melanoma membrane-bound gelatinase; FAPalpha; dipeptidyl peptidase FAP; gelatine de ......
Chromosomal Location	2q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of FAP. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	FAP
Name	fibroblast activation protein, alpha
Aliases	seprase; DPPIVA; 170 kDa melanoma membrane-bound gelatinase; FAPalpha; dipeptidyl peptidase FAP; gelatine de ......
Chromosomal Location	2q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of FAP. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by FAP. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	FAP
Name	fibroblast activation protein, alpha
Aliases	seprase; DPPIVA; 170 kDa melanoma membrane-bound gelatinase; FAPalpha; dipeptidyl peptidase FAP; gelatine de ......
Chromosomal Location	2q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of FAP. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	FAP
Name	fibroblast activation protein, alpha
Aliases	seprase; DPPIVA; 170 kDa melanoma membrane-bound gelatinase; FAPalpha; dipeptidyl peptidase FAP; gelatine de ......
Chromosomal Location	2q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of FAP expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	FAP
Name	fibroblast activation protein, alpha
Aliases	seprase; DPPIVA; 170 kDa melanoma membrane-bound gelatinase; FAPalpha; dipeptidyl peptidase FAP; gelatine de ......
Chromosomal Location	2q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between FAP and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	FAP
Name	fibroblast activation protein, alpha
Aliases	seprase; DPPIVA; 170 kDa melanoma membrane-bound gelatinase; FAPalpha; dipeptidyl peptidase FAP; gelatine de ......
Chromosomal Location	2q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting FAP collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

Browse FAP