Gene_Locus Report

Biblio print

Add to basket

Go to basket

Tree Display

AceDB Schema

XML Display

Feedback

Gene_locus Report for: human-FAP

Homo sapiens (Human) fibroblast activation protein alpha FAPalpha, integral membrane serine protease seprase FAPA, FAP, SEPR

Comment
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. Degrade also gelatin, heat-denatured type I collagen, but not native collagen type I and IV, vibronectin, tenascin, laminin, fibronectin, fibrin or casein. FAP can 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. Natural neuropeptide hormones for dipeptidyl peptidase are the neuropeptide Y (NPY cleavage product proangiogenic FAP enhances tumor growth progression), peptide YY (PYY), substance P (TAC1) and brain natriuretic peptide 32 (NPPB). 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


Relationship
Family|DPP4N_Peptidase_S9
Block| X
Position in NCBI Life Tree|Homo sapiens
(Below N is a link to NCBI taxonomic web page and E link to ESTHER at designed phylum.)
> cellular organisms: N E > Eukaryota: N E > Opisthokonta: N E > Metazoa: N E > Eumetazoa: N E > Bilateria: N E > Deuterostomia: N E > Chordata: N E > Craniata: N E > Vertebrata: N E > Gnathostomata: N E > Teleostomi: N E > Euteleostomi: N E > Sarcopterygii: N E > Dipnotetrapodomorpha: N E > Tetrapoda: N E > Amniota: N E > Mammalia: N E > Theria: N E > Eutheria: N E > Boreoeutheria: N E > Euarchontoglires: N E > Primates: N E > Haplorrhini: N E > Simiiformes: N E > Catarrhini: N E > Hominoidea: N E > Hominidae: N E > Homininae: N E > Homo: N E > Homo sapiens: N E


Molecular evidence
Database
No mutation
2 structures: 1Z68, 6Y0F
No kinetic





1 substrate:
Z-Gly-Pro-AMC
7 inhibitors (e.g. : AEBSF, ARI-3099, DFP... more)
>3 Genbank links 4 more: U09278, U76833, AF007822
3 UniProt : Q12884, B2RD89, B4DLR2
2 Structure : 6Y0F, 1Z68
3 UniProt : Q12884, B2RD89, B4DLR2
3 Interpro : Q12884, B2RD89, B4DLR2
3 Prodom : Q12884, B2RD89, B4DLR2
3 Pfam : Q12884, B2RD89, B4DLR2
3 PIRSF : Q12884, B2RD89, B4DLR2
3 SUPERFAM : Q12884, B2RD89, B4DLR2
1 EntrezGene : 2191
1 SNP : 2191
1 UniGene : 654370
1 HUGO HGNC : 3590
1 IUPHAR : 2365
1 OMIM : 600403
1 Ensembl : ENSG00000078098
Sequence
Graphical view for this peptide sequence: human-FAP
Colored MSA for DPP4N_Peptidase_S9 (raw)
MKTWVKIVFGVATSAVLALLVMCIVLRPSRVHNSEENTMRALTLKDILNG
TFSYKTFFPNWISGQEYLHQSADNNIVLYNIETGQSYTILSNRTMKSVNA
SNYGLSPDRQFVYLESDYSKLWRYSYTATYYIYDLSNGEFVRGNELPRPI
QYLCWSPVGSKLAYVYQNNIYLKQRPGDPPFQITFNGRENKIFNGIPDWV
YEEEMLPTKYALWWSPNGKFLAYAEFNDKDIPVIAYSYYGDEQYPRTINI
PYPKAGAKNPVVRIFIIDTTYPAYVGPQEVPVPAMIASSDYYFSWLTWVT
DERVCLQWLKRVQNVSVLSICDFREDWQTWDCPKTQEHIEESRTGWAGGF
FVSRPVFSYDAISYYKIFSDKDGYKHIHYIKDTVENAIQITSGKWEAINI
FRVTQDSLFYSSNEFEEYPGRRNIYRISIGSYPPSKKCVTCHLRKERCQY
YTASFSDYAKYYALVCYGPGIPISTLHDGRTDQEIKILEENKELENALKN
IQLPKEEIKKLEVDEITLWYKMILPPQFDRSKKYPLLIQVYGGPCSQSVR
SVFAVNWISYLASKEGMVIALVDGRGTAFQGDKLLYAVYRKLGVYEVEDQ
ITAVRKFIEMGFIDEKRIAIWGWSYGGYVSSLALASGTGLFKCGIAVAPV
SSWEYYASVYTERFMGLPTKDDNLEHYKNSTVMARAEYFRNVDYLLIHGT
ADDNVHFQNSAQIAKALVNAQVDFQAMWYSDQNHGLSGLSTNHLYTHMTH
FLKQCFSLSD
Legend This sequence has been compared to family alignement (MSA)
red => minority aminoacid
blue => majority aminoacid
color intensity => conservation rate
title => sequence position(MSA position)aminoacid rate
Catalytic site
Catalytic site in the MSA

MKTWVKIVFGVATSAVLALLVMCIVLRPSRVHNSEENTMRALTLKDILNG
TFSYKTFFPNWISGQEYLHQSADNNIVLYNIETGQSYTILSNRTMKSVNA
SNYGLSPDRQFVYLESDYSKLWRYSYTATYYIYDLSNGEFVRGNELPRPI
QYLCWSPVGSKLAYVYQNNIYLKQRPGDPPFQITFNGRENKIFNGIPDWV
YEEEMLPTKYALWWSPNGKFLAYAEFNDKDIPVIAYSYYGDEQYPRTINI
PYPKAGAKNPVVRIFIIDTTYPAYVGPQEVPVPAMIASSDYYFSWLTWVT
DERVCLQWLKRVQNVSVLSICDFREDWQTWDCPKTQEHIEESRTGWAGGF
FVSRPVFSYDAISYYKIFSDKDGYKHIHYIKDTVENAIQITSGKWEAINI
FRVTQDSLFYSSNEFEEYPGRRNIYRISIGSYPPSKKCVTCHLRKERCQY
YTASFSDYAKYYALVCYGPGIPISTLHDGRTDQEIKILEENKELENALKN
IQLPKEEIKKLEVDEITLWYKMILPPQFDRSKKYPLLIQVYGGPCSQSVR
SVFAVNWISYLASKEGMVIALVDGRGTAFQGDKLLYAVYRKLGVYEVEDQ
ITAVRKFIEMGFIDEKRIAIWGWSYGGYVSSLALASGTGLFKCGIAVAPV
SSWEYYASVYTERFMGLPTKDDNLEHYKNSTVMARAEYFRNVDYLLIHGT
ADDNVHFQNSAQIAKALVNAQVDFQAMWYSDQNHGLSGLSTNHLYTHMTH
FLKQCFSLSD


References
6 more
    Title: A Single Second Shell Amino Acid Determines Affinity and Kinetics of Linagliptin Binding to Type 4 Dipeptidyl Peptidase and Fibroblast Activation Protein
    Schnapp G, Hoevels Y, Bakker RA, Schreiner P, Klein T, Nar H
    Ref: ChemMedChem, 16:630, 2021 : PubMed

            

    Title: A Tumor-Imaging Method Targeting Cancer-Associated Fibroblasts
    Loktev A, Lindner T, Mier W, Debus J, Altmann A, Jager D, Giesel F, Kratochwil C, Barthe P and Haberkorn U <1 more author(s)>
    Ref: J Nucl Med, 59:1423, 2018 : PubMed

            

    Title: Structural and kinetic analysis of the substrate specificity of human fibroblast activation protein alpha
    Aertgeerts K, Levin I, Shi L, Snell GP, Jennings A, Prasad GS, Zhang Y, Kraus ML, Salakian S and Tennant MG <2 more author(s)>
    Ref: Journal of Biological Chemistry, 280:19441, 2005 : PubMed

            


Other Papers


Send your questions or comments to :
Mail to: Nicolas Lenfant, Thierry Hotelier, Yves Bourne, Pascale Marchot and Arnaud Chatonnet.
Please cite: Lenfant 2013 Nucleic.Acids.Res. or Marchot Chatonnet 2012 Prot.Pept Lett.
For technical information about these pages see:
ESTHER Home Page and ACEDB Home Page
AcePerl Lincoln Stein Home Page
webmaster

Acknowledgements and disclaimer