SEPR_BOVIN
ID SEPR_BOVIN Reviewed; 760 AA.
AC A5D7B7;
DT 29-OCT-2014, integrated into UniProtKB/Swiss-Prot.
DT 12-JUN-2007, sequence version 1.
DT 03-AUG-2022, entry version 98.
DE RecName: Full=Prolyl endopeptidase FAP {ECO:0000250|UniProtKB:Q12884};
DE EC=3.4.21.26 {ECO:0000269|PubMed:15313476};
DE AltName: Full=Dipeptidyl peptidase FAP {ECO:0000250|UniProtKB:Q12884};
DE EC=3.4.14.5 {ECO:0000250|UniProtKB:Q12884};
DE AltName: Full=Fibroblast activation protein alpha {ECO:0000250|UniProtKB:Q12884};
DE Short=FAPalpha {ECO:0000250|UniProtKB:Q12884};
DE AltName: Full=Gelatine degradation protease FAP {ECO:0000250|UniProtKB:Q12884};
DE EC=3.4.21.- {ECO:0000250|UniProtKB:Q12884};
DE AltName: Full=Integral membrane serine protease {ECO:0000250|UniProtKB:Q12884};
DE AltName: Full=Post-proline cleaving enzyme {ECO:0000305};
DE AltName: Full=Serine integral membrane protease {ECO:0000250|UniProtKB:Q12884};
DE Short=SIMP {ECO:0000250|UniProtKB:Q12884};
DE AltName: Full=Surface-expressed protease {ECO:0000250|UniProtKB:Q12884};
DE Short=Seprase {ECO:0000250|UniProtKB:Q12884};
DE AltName: Full=Z-Pro-prolinal insensitive peptidase {ECO:0000303|PubMed:15313476};
DE Short=ZIP {ECO:0000303|PubMed:15313476};
DE Contains:
DE RecName: Full=Antiplasmin-cleaving enzyme FAP, soluble form {ECO:0000250|UniProtKB:Q12884};
DE Short=APCE {ECO:0000250|UniProtKB:Q12884};
DE EC=3.4.14.5 {ECO:0000250|UniProtKB:Q12884};
DE EC=3.4.21.- {ECO:0000250|UniProtKB:Q12884};
DE EC=3.4.21.26 {ECO:0000250|UniProtKB:Q12884};
GN Name=FAP {ECO:0000250|UniProtKB:Q12884, ECO:0000312|EMBL:AAI40498.1,
GN ECO:0000312|Ensembl:ENSBTAP00000010702};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Hereford {ECO:0000312|EMBL:DAAA02004416};
RX PubMed=19393038; DOI=10.1186/gb-2009-10-4-r42;
RA Zimin A.V., Delcher A.L., Florea L., Kelley D.R., Schatz M.C., Puiu D.,
RA Hanrahan F., Pertea G., Van Tassell C.P., Sonstegard T.S., Marcais G.,
RA Roberts M., Subramanian P., Yorke J.A., Salzberg S.L.;
RT "A whole-genome assembly of the domestic cow, Bos taurus.";
RL Genome Biol. 10:R42.01-R42.10(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford {ECO:0000312|EMBL:AAI40498.1}; TISSUE=Ascending colon;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PARTIAL PROTEIN SEQUENCE, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND ACTIVITY REGULATION.
RX PubMed=15313476; DOI=10.1016/j.biocel.2004.05.006;
RA Collins P.J., McMahon G., O'Brien P., O'Connor B.;
RT "Purification, identification and characterisation of seprase from bovine
RT serum.";
RL Int. J. Biochem. Cell Biol. 36:2320-2333(2004).
CC -!- FUNCTION: Cell surface glycoprotein serine protease that participates
CC in extracellular matrix degradation and involved in many cellular
CC processes including tissue remodeling, fibrosis, wound healing,
CC inflammation and tumor growth. Both plasma membrane and soluble forms
CC exhibit post-proline cleaving endopeptidase activity, with a marked
CC preference for Ala/Ser-Gly-Pro-Ser/Asn/Ala consensus sequences, on
CC substrate such as alpha-2-antiplasmin SERPINF2 and SPRY2. Degrade also
CC gelatin, heat-denatured type I collagen, but not native collagen type I
CC and IV, vibronectin, tenascin, laminin, fibronectin, fibrin or casein.
CC Also has dipeptidyl peptidase activity, exhibiting the ability to
CC hydrolyze the prolyl bond two residues from the N-terminus of synthetic
CC dipeptide substrates provided that the penultimate residue is proline,
CC with a preference for Ala-Pro, Ile-Pro, Gly-Pro, Arg-Pro and Pro-Pro.
CC Natural neuropeptide hormones for dipeptidyl peptidase are the
CC neuropeptide Y (NPY), peptide YY (PYY), substance P (TAC1) and brain
CC natriuretic peptide 32 (NPPB). The plasma membrane form, in association
CC with either DPP4, PLAUR or integrins, is involved in the pericellular
CC proteolysis of the extracellular matrix (ECM), and hence promotes cell
CC adhesion, migration and invasion through the ECM. Plays a role in
CC tissue remodeling during development and wound healing. Participates in
CC the cell invasiveness towards the ECM in malignant melanoma cancers.
CC Enhances tumor growth progression by increasing angiogenesis, collagen
CC fiber degradation and apoptosis and by reducing antitumor response of
CC the immune system. Promotes glioma cell invasion through the brain
CC parenchyma by degrading the proteoglycan brevican. Acts as a tumor
CC suppressor in melanocytic cells through regulation of cell
CC proliferation and survival in a serine protease activity-independent
CC manner. {ECO:0000250|UniProtKB:Q12884, ECO:0000269|PubMed:15313476}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of an N-terminal dipeptide, Xaa-Yaa-|-Zaa-, from a
CC polypeptide, preferentially when Yaa is Pro, provided Zaa is neither
CC Pro nor hydroxyproline.; EC=3.4.14.5;
CC Evidence={ECO:0000250|UniProtKB:Q12884, ECO:0000255|PROSITE-
CC ProRule:PRU10084};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of Pro-|-Xaa >> Ala-|-Xaa in oligopeptides.;
CC EC=3.4.21.26; Evidence={ECO:0000269|PubMed:15313476};
CC -!- ACTIVITY REGULATION: Gelatinase activity is inhibited by serine-
CC protease inhibitors, such as phenylmethylsulfonyl fluoride (PMSF), 4-
CC (2-aminoethyl)-benzenesulfonyl fluoride hydrochloride (AEBSF), 4-
CC amidino phenylsulfonyl fluoride (APSF) and diisopropyl fluorophosphate
CC (DFP), N-ethylmaleimide (NEM) and phenylmethylsulfonyl fluoride (PMSF).
CC Dipeptidyl peptidase activity is inhibited by 2,2'-azino-bis(3-
CC ethylbenzthiazoline-6-sulfonic acid), diisopropylfluorophosphate (DFP).
CC Prolyl endopeptidase activity is inhibited by the boronic acid peptide
CC Ac-Gly-BoroPro, Ac-Gly-Pro-chloromethyl ketone and Thr-Ser-Gly-
CC chloromethyl ketone. {ECO:0000250|UniProtKB:Q12884,
CC ECO:0000269|PubMed:15313476}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.270 mM for Gly-Pro (Prolyl endopeptidase activity)
CC {ECO:0000269|PubMed:15313476};
CC KM=0.206 mM for Gly-Pro-Phe-His (Prolyl endopeptidase activity)
CC {ECO:0000269|PubMed:15313476};
CC -!- SUBUNIT: Homodimer; homodimerization is required for activity of both
CC plasma membrane and soluble forms. The monomer is inactive. Heterodimer
CC with DPP4. Interacts with PLAUR; the interaction occurs at the cell
CC surface of invadopodia membranes. Interacts with ITGB1. Interacts with
CC ITGA3. Associates with integrin alpha-3/beta-1; the association occurs
CC in a collagen-dependent manner at the cell surface of invadopodia
CC membranes. {ECO:0000250|UniProtKB:Q12884}.
CC -!- SUBCELLULAR LOCATION: [Prolyl endopeptidase FAP]: Cell surface
CC {ECO:0000250|UniProtKB:Q12884}. Cell membrane
CC {ECO:0000250|UniProtKB:Q12884}; Single-pass type II membrane protein
CC {ECO:0000255}. Cell projection, lamellipodium membrane
CC {ECO:0000250|UniProtKB:Q12884}; Single-pass type II membrane protein
CC {ECO:0000255}. Cell projection, invadopodium membrane
CC {ECO:0000250|UniProtKB:Q12884}; Single-pass type II membrane protein
CC {ECO:0000255}. Cell projection, ruffle membrane
CC {ECO:0000250|UniProtKB:Q12884}; Single-pass type II membrane protein
CC {ECO:0000255}. Membrane {ECO:0000250|UniProtKB:Q12884}; Single-pass
CC type II membrane protein {ECO:0000255}. Note=Localized on cell surface
CC with lamellipodia and invadopodia membranes and on shed vesicles.
CC Colocalized with DPP4 at invadopodia and lamellipodia membranes of
CC migratory activated endothelial cells in collagenous matrix.
CC Colocalized with DPP4 on endothelial cells of capillary-like
CC microvessels but not large vessels within invasive breast ductal
CC carcinoma. Anchored and enriched preferentially by integrin alpha-
CC 3/beta-1 at invadopodia, plasma membrane protrusions that correspond to
CC sites of cell invasion, in a collagen-dependent manner. Localized at
CC plasma and ruffle membranes in a collagen-independent manner.
CC Colocalized with PLAUR preferentially at the cell surface of
CC invadopodia membranes in a cytoskeleton-, integrin- and vitronectin-
CC dependent manner. Concentrated at invadopodia membranes, specialized
CC protrusions of the ventral plasma membrane in a fibrobectin-dependent
CC manner. Colocalizes with extracellular components (ECM), such as
CC collagen fibers and fibronectin. {ECO:0000250|UniProtKB:Q12884}.
CC -!- SUBCELLULAR LOCATION: [Antiplasmin-cleaving enzyme FAP, soluble form]:
CC Secreted {ECO:0000250|UniProtKB:Q12884}. Note=Found in blood plasma and
CC serum. {ECO:0000250|UniProtKB:Q12884}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q12884}.
CC -!- PTM: The N-terminus may be blocked. {ECO:0000250|UniProtKB:Q12884}.
CC -!- SIMILARITY: Belongs to the peptidase S9B family. {ECO:0000305}.
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DR EMBL; DAAA02004416; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC140497; AAI40498.1; -; mRNA.
DR RefSeq; NP_001091470.1; NM_001098001.1.
DR AlphaFoldDB; A5D7B7; -.
DR SMR; A5D7B7; -.
DR STRING; 9913.ENSBTAP00000010702; -.
DR BindingDB; A5D7B7; -.
DR ChEMBL; CHEMBL3734641; -.
DR ESTHER; bovin-a5d7b7; DPP4N_Peptidase_S9.
DR MEROPS; S09.007; -.
DR PaxDb; A5D7B7; -.
DR Ensembl; ENSBTAT00000010702; ENSBTAP00000010702; ENSBTAG00000008140.
DR GeneID; 508882; -.
DR KEGG; bta:508882; -.
DR CTD; 2191; -.
DR VEuPathDB; HostDB:ENSBTAG00000008140; -.
DR VGNC; VGNC:28862; FAP.
DR eggNOG; KOG2100; Eukaryota.
DR GeneTree; ENSGT00940000160454; -.
DR HOGENOM; CLU_006105_4_3_1; -.
DR InParanoid; A5D7B7; -.
DR OMA; MRTPQEN; -.
DR OrthoDB; 269253at2759; -.
DR TreeFam; TF313309; -.
DR SABIO-RK; A5D7B7; -.
DR Proteomes; UP000009136; Chromosome 2.
DR Bgee; ENSBTAG00000008140; Expressed in uterine horn and 84 other tissues.
DR ExpressionAtlas; A5D7B7; baseline and differential.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0045177; C:apical part of cell; IEA:Ensembl.
DR GO; GO:0045178; C:basal part of cell; IEA:Ensembl.
DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; IEA:Ensembl.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031258; C:lamellipodium membrane; IEA:UniProtKB-SubCell.
DR GO; GO:1905368; C:peptidase complex; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0008239; F:dipeptidyl-peptidase activity; IBA:GO_Central.
DR GO; GO:0005178; F:integrin binding; IEA:Ensembl.
DR GO; GO:0002020; F:protease binding; IEA:Ensembl.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0043542; P:endothelial cell migration; IEA:Ensembl.
DR GO; GO:1902362; P:melanocyte apoptotic process; IEA:Ensembl.
DR GO; GO:0097325; P:melanocyte proliferation; IEA:Ensembl.
DR GO; GO:0060244; P:negative regulation of cell proliferation involved in contact inhibition; IEA:Ensembl.
DR GO; GO:0010716; P:negative regulation of extracellular matrix disassembly; IEA:Ensembl.
DR GO; GO:1900119; P:positive regulation of execution phase of apoptosis; IEA:Ensembl.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IEA:Ensembl.
DR GO; GO:0051726; P:regulation of cell cycle; IEA:Ensembl.
DR GO; GO:0010710; P:regulation of collagen catabolic process; IEA:Ensembl.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR031245; FAP-alpha.
DR InterPro; IPR002471; Pept_S9_AS.
DR InterPro; IPR001375; Peptidase_S9.
DR InterPro; IPR002469; Peptidase_S9B_N.
DR PANTHER; PTHR11731:SF136; PTHR11731:SF136; 1.
DR Pfam; PF00930; DPPIV_N; 1.
DR Pfam; PF00326; Peptidase_S9; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
PE 1: Evidence at protein level;
KW Angiogenesis; Apoptosis; Cell adhesion; Cell junction; Cell membrane;
KW Cell projection; Cleavage on pair of basic residues; Coiled coil;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Hydrolase;
KW Membrane; Protease; Reference proteome; Secreted; Serine protease;
KW Signal-anchor; Transmembrane; Transmembrane helix.
FT CHAIN 1..760
FT /note="Prolyl endopeptidase FAP"
FT /evidence="ECO:0000250|UniProtKB:Q12884"
FT /id="PRO_0000430645"
FT CHAIN 24..760
FT /note="Antiplasmin-cleaving enzyme FAP, soluble form"
FT /evidence="ECO:0000250|UniProtKB:Q12884"
FT /id="PRO_0000430646"
FT TOPO_DOM 1..4
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q12884, ECO:0000255"
FT TRANSMEM 5..25
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 26..760
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q12884, ECO:0000255"
FT COILED 481..512
FT /evidence="ECO:0000255"
FT ACT_SITE 624
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:Q12884,
FT ECO:0000255|PROSITE-ProRule:PRU10084"
FT ACT_SITE 702
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:Q12884"
FT ACT_SITE 734
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:Q12884"
FT BINDING 203
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q12884"
FT BINDING 204
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q12884"
FT SITE 23..24
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:Q12884"
FT CARBOHYD 49
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q12884,
FT ECO:0000255|PROSITE-ProRule:PRU10084"
FT CARBOHYD 92
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q12884,
FT ECO:0000255|PROSITE-ProRule:PRU10084"
FT CARBOHYD 99
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q12884,
FT ECO:0000255|PROSITE-ProRule:PRU10084"
FT CARBOHYD 227
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q12884,
FT ECO:0000255|PROSITE-ProRule:PRU10084"
FT CARBOHYD 314
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q12884,
FT ECO:0000255|PROSITE-ProRule:PRU10084"
FT CARBOHYD 679
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10084"
FT DISULFID 321..332
FT /evidence="ECO:0000250|UniProtKB:Q12884"
FT DISULFID 438..441
FT /evidence="ECO:0000250|UniProtKB:Q12884"
FT DISULFID 448..466
FT /evidence="ECO:0000250|UniProtKB:Q12884"
FT DISULFID 643..755
FT /evidence="ECO:0000250|UniProtKB:Q12884"
SQ SEQUENCE 760 AA; 87734 MW; 94E57F1252BEA933 CRC64;
MKTWLKIVFG VATSAVLALL VMCIVLRPSR VHNSEESTTR ALTLKDILNG TFSYKTFFPN
WISGQEYLHQ STDNNVVFYN IETGESYTIL SNTTMKSVNA SNYGLSPDRQ FAYLESDYSK
LWRYSYTATY HIYDLTNGEF IRRNELPRPI QYLCWSPVGS KLAYVYQNNI YLKQRPEDPP
FQITYNGKEN KIFNGIPDWV YEEEMLATKY ALWWSPNGKF LAYAEFNDTE IPVIAYSYYG
DEQYPRTINI PYPKAGAKNP VVRIFIIDAT YPEHIGPREV PVPAMIASSD YYFSWLTWVT
DDRICLQWLK RIQNVSVLST CDFREDWQTW NCPKTQEHIE ESRTGWAGGF FVSTPVFSHD
TISYYKIFSD KDGYKHIHYI RDTVENAIQI TSGKWEAINI FRVTQDSLFY SSNEFEGYPG
RRNIYRISIG SHSPSKKCIT CHLRKKRCQY YTASFSDYAK YYALVCYGPG LPISTLHDGR
TDQEIKILED NKELENALKN IQLPKEEIKK LKVDDITLWY KMILPPQFDK SKKYPLLIQV
YGGPCSQSVR SIFAVSWISY LASKEGIVIA LVDGRGTAFQ GDKLLYAVYR KLGVYEVEDQ
ITAVRKFIEM GFIDEKRIAI WGWSYGGYVS SLALASGTGL FKCGIAVAPV SSWEYYASIY
TERFMGLPTK DDNLKHYKNS TVMARAEYFR NVDYLLIHGT ADDNVHFQNS AQIAKALVNA
QVDFQAMWYS DQNHGLSGLS TKHLYTHMTH FLKQCFSLSD
