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Protein

Prolyl endopeptidase FAP

Gene

FAP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.By similarity21 Publications

Catalytic activityi

Hydrolysis of Pro-|-Xaa >> Ala-|-Xaa in oligopeptides.7 Publications
Release of an N-terminal dipeptide, Xaa-Yaa-|-Zaa-, from a polypeptide, preferentially when Yaa is Pro, provided Zaa is neither Pro nor hydroxyproline.PROSITE-ProRule annotation10 Publications

Enzyme regulationi

Gelatinase activity is inhibited by serine-protease inhibitors, such as phenylmethylsulfonyl fluoride (PMSF), 4-(2-aminoethyl)-benzenesulfonyl fluoride hydrochloride (AEBSF), 4-amidino phenylsulfonyl fluoride (APSF) and diisopropyl fluorophosphate (DFP), N-ethylmaleimide (NEM) and phenylmethylsulfonyl fluoride (PMSF). Dipeptidyl peptidase activity is inhibited by 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid), diisopropylfluorophosphate (DFP). Prolyl endopeptidase activity is inhibited by the boronic acid peptide Ac-Gly-BoroPro, Ac-Gly-Pro-chloromethyl ketone and Thr-Ser-Gly-chloromethyl ketone.6 Publications

Kineticsi

  1. KM=0.46 mM for Ala-Pro (Dipeptidyl peptidase activity)1 Publication
  2. KM=0.9 mM for Lys-Pro (Dipeptidyl peptidase activity)1 Publication
  3. KM=1.15 mM for Gly-Pro (Dipeptidyl peptidase activity)1 Publication
  4. KM=0.25 mM for Gly-Pro (Dipeptidyl peptidase activity)1 Publication
  5. KM=0.24 mM for Ala-Pro (Dipeptidyl peptidase activity)1 Publication
  6. KM=0.10 mM for Ile-Pro (Dipeptidyl peptidase activity)1 Publication
  7. KM=0.24 mM for Phe-Pro (Dipeptidyl peptidase activity)1 Publication
  8. KM=0.24 mM for Gly-Pro (Dipeptidyl peptidase activity)1 Publication
  9. KM=0.33 mM for Ac-Gly-Pro (Prolyl endopeptidase activity)2 Publications
  10. KM=1.3 µM for Thr-Ser-Gly-Pro-Asn-Gln (Prolyl endopeptidase activity)1 Publication
  11. KM=2.2 µM for Ala-Ser-Gly-Pro-Asn-Gln (Prolyl endopeptidase activity)1 Publication
  12. KM=0.7 µM for Thr-Ala-Gly-Pro-Asn-Gln (Prolyl endopeptidase activity)1 Publication
  13. KM=1.9 µM for Thr-Ser-Gly-Pro-Ser-Gln (Prolyl endopeptidase activity)1 Publication
  14. KM=2.2 µM for Thr-Ser-Gly-Pro-Asn-Ser (Prolyl endopeptidase activity)1 Publication
  15. KM=4.3 µM for Ala-Ser-Gly-Pro-Ser-Ser (Prolyl endopeptidase activity)1 Publication
  16. KM=0.101 mM for Gly-Pro (FAP form, prolyl endopeptidase activity)1 Publication
  17. KM=0.124 mM for Gly-Pro (Antiplasmin-cleaving enzyme FAP soluble form, prolyl endopeptidase activity)1 Publication
  18. KM=0.323 mM for Gly-Pro (FAP form, dipeptidyl peptidase activity)1 Publication
  19. KM=0.272 mM for Gly-Pro (Antiplasmin-cleaving enzyme FAP soluble form, dipeptidyl peptidase activity)1 Publication
  20. KM=0.029 mM for Arg-Gly-Thr-Ser-Gly-Pro-Asn-Gln-Glu-Gln-Glu (FAP form, prolyl endopeptidase activity)1 Publication
  21. KM=0.026 mM for Arg-Gly-Thr-Ser-Gly-Pro-Asn-Gln-Glu-Gln-Glu (Antiplasmin-cleaving enzyme FAP soluble form, prolyl endopeptidase activity)1 Publication

    pH dependencei

    Optimum pH is 6-8.4 for gelatinase activity. At pH lower than 5 inhibited gelatinase activity.2 Publications

    Temperature dependencei

    Optimum temperature is 37 degrees Celsius for gelatinase activity. Temperatures above 50 degrees Celsius inhibit gelatinase activity.2 Publications

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei203Substrate1 Publication1
    Binding sitei204Substrate1 Publication1
    Active sitei624Charge relay systemPROSITE-ProRule annotation1 Publication1
    Active sitei702Charge relay system1 Publication1
    Active sitei734Charge relay system1 Publication1

    GO - Molecular functioni

    • dipeptidyl-peptidase activity Source: UniProtKB
    • endopeptidase activity Source: BHF-UCL
    • integrin binding Source: UniProtKB
    • metalloendopeptidase activity Source: UniProtKB
    • peptidase activity Source: UniProtKB
    • protease binding Source: BHF-UCL
    • protein dimerization activity Source: UniProtKB
    • protein homodimerization activity Source: UniProtKB
    • serine-type endopeptidase activity Source: UniProtKB
    • serine-type peptidase activity Source: UniProtKB

    GO - Biological processi

    • angiogenesis Source: UniProtKB-KW
    • cell adhesion Source: UniProtKB-KW
    • endothelial cell migration Source: UniProtKB
    • melanocyte apoptotic process Source: UniProtKB
    • melanocyte proliferation Source: UniProtKB
    • mitotic cell cycle arrest Source: UniProtKB
    • negative regulation of cell proliferation involved in contact inhibition Source: UniProtKB
    • negative regulation of extracellular matrix disassembly Source: UniProtKB
    • negative regulation of extracellular matrix organization Source: UniProtKB
    • positive regulation of cell cycle arrest Source: UniProtKB
    • positive regulation of execution phase of apoptosis Source: UniProtKB
    • proteolysis Source: UniProtKB
    • proteolysis involved in cellular protein catabolic process Source: UniProtKB
    • regulation of collagen catabolic process Source: UniProtKB
    • regulation of fibrinolysis Source: BHF-UCL
    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase, Protease, Serine protease

    Keywords - Biological processi

    Angiogenesis, Apoptosis, Cell adhesion

    Enzyme and pathway databases

    BioCyciZFISH:ENSG00000078098-MONOMER.
    BRENDAi3.4.21.B28. 2681.

    Protein family/group databases

    ESTHERihuman-FAP. DPP4N_Peptidase_S9.
    MEROPSiS09.007.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Prolyl endopeptidase FAPCurated (EC:3.4.21.261 Publication)
    Alternative name(s):
    170 kDa melanoma membrane-bound gelatinase2 Publications
    Dipeptidyl peptidase FAPCurated (EC:3.4.14.51 Publication)
    Fibroblast activation protein alpha1 Publication
    Short name:
    FAPalphaBy similarity
    Gelatine degradation protease FAPCurated (EC:3.4.21.-1 Publication)
    Integral membrane serine protease1 Publication
    Post-proline cleaving enzymeCurated
    Serine integral membrane protease1 Publication
    Short name:
    SIMP1 Publication
    Surface-expressed protease1 Publication
    Short name:
    Seprase1 Publication
    Cleaved into the following chain:
    Antiplasmin-cleaving enzyme FAP, soluble form1 Publication (EC:3.4.14.52 Publications, EC:3.4.21.-2 Publications, EC:3.4.21.262 Publications)
    Short name:
    APCE1 Publication
    Gene namesi
    Name:FAPImported
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:3590. FAP.

    Subcellular locationi

    Prolyl endopeptidase FAP :
    Antiplasmin-cleaving enzyme FAP, soluble form :
    Isoform 2 :
    • Cytoplasm 1 Publication

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Topological domaini1 – 4Cytoplasmic1 PublicationSequence analysis4
    Transmembranei5 – 25Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
    Topological domaini26 – 760Extracellular1 PublicationSequence analysisAdd BLAST735

    GO - Cellular componenti

    • apical part of cell Source: Ensembl
    • basal part of cell Source: Ensembl
    • cell surface Source: UniProtKB
    • cytoplasm Source: UniProtKB-SubCell
    • extracellular space Source: BHF-UCL
    • focal adhesion Source: UniProtKB
    • integral component of membrane Source: UniProtKB
    • invadopodium membrane Source: UniProtKB
    • lamellipodium Source: UniProtKB
    • lamellipodium membrane Source: UniProtKB-SubCell
    • plasma membrane Source: UniProtKB
    • ruffle membrane Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Cell junction, Cell membrane, Cell projection, Cytoplasm, Membrane, Secreted

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi123R → A, M or E: Reduces dipeptidyl peptidase and endopeptidase activities. 1 Publication1
    Mutagenesisi203E → A, D or Q: Reduces dipeptidyl peptidase and endopeptidase activities. Does not inhibit cell adhesion, migration and invasion. Inhibits dipeptidyl peptidase and endopeptidase activities; when associated with A-204. 2 Publications1
    Mutagenesisi204E → A, D or Q: Reduces dipeptidyl peptidase and endopeptidase activities. Does not inhibit cell adhesion, migration and invasion. Inhibits dipeptidyl peptidase and endopeptidase activities; when associated with A-203. 2 Publications1
    Mutagenesisi624S → A: Reduces dipeptidyl peptidase and gelatinolytic activities. Does not inhibit cell adhesion, migration and invasion. 2 Publications1
    Mutagenesisi656Y → F: Reduces dipeptidyl peptidase and endopeptidase activities. 1 Publication1
    Mutagenesisi657A → D or N: Inhibits endopeptidase activity. Increases dipeptidyl peptidase activity. 1 Publication1
    Mutagenesisi657A → F or V: Reduces dipeptidyl peptidase and endopeptidase activities. 1 Publication1
    Mutagenesisi657A → Q: Inhibits endopeptidase activity. No change in dipeptidyl peptidase activity. 1 Publication1
    Mutagenesisi657A → S or T: Reduces strongly endopeptidase activity. No change in dipeptidyl peptidase activity. 1 Publication1
    Mutagenesisi704N → A: Reduces dipeptidyl peptidase and endopeptidase activities. 1 Publication1

    Organism-specific databases

    DisGeNETi2191.
    OpenTargetsiENSG00000078098.
    PharmGKBiPA28003.

    Chemistry databases

    ChEMBLiCHEMBL4683.
    GuidetoPHARMACOLOGYi2365.

    Polymorphism and mutation databases

    BioMutaiFAP.
    DMDMi292495099.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001224241 – 760Prolyl endopeptidase FAPCuratedAdd BLAST760
    ChainiPRO_000043064324 – 760Antiplasmin-cleaving enzyme FAP, soluble form1 PublicationAdd BLAST737

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Glycosylationi49N-linked (GlcNAc...)PROSITE-ProRule annotation1 Publication1
    Glycosylationi92N-linked (GlcNAc...)PROSITE-ProRule annotation1 Publication1
    Glycosylationi99N-linked (GlcNAc...)PROSITE-ProRule annotation1 Publication1
    Glycosylationi227N-linked (GlcNAc...)PROSITE-ProRule annotation2 Publications1
    Glycosylationi314N-linked (GlcNAc...)PROSITE-ProRule annotation1 Publication1
    Disulfide bondi321 ↔ 3321 Publication
    Disulfide bondi438 ↔ 4411 Publication
    Disulfide bondi448 ↔ 4661 Publication
    Disulfide bondi643 ↔ 7551 Publication
    Glycosylationi679N-linked (GlcNAc...)PROSITE-ProRule annotation1

    Post-translational modificationi

    N-glycosylated.4 Publications
    The N-terminus may be blocked.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sitei23 – 24Cleavage1 Publication2

    Keywords - PTMi

    Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

    Proteomic databases

    PaxDbiQ12884.
    PeptideAtlasiQ12884.
    PRIDEiQ12884.

    PTM databases

    iPTMnetiQ12884.
    PhosphoSitePlusiQ12884.
    SwissPalmiQ12884.

    Expressioni

    Tissue specificityi

    Expressed in adipose tissue. Expressed in the dermal fibroblasts in the fetal skin. Expressed in the granulation tissue of healing wounds and on reactive stromal fibroblast in epithelial cancers. Expressed in activated fibroblast-like synoviocytes from inflamed synovial tissues. Expressed in activated hepatic stellate cells (HSC) and myofibroblasts from cirrhotic liver, but not detected in normal liver. Expressed in glioma cells (at protein level). Expressed in glioblastomas and glioma cells. Isoform 1 and isoform 2 are expressed in melanoma, carcinoma and fibroblast cell lines.8 Publications

    Inductioni

    In fibroblasts at times and sites of tissue remodeling during development, tissue repair and carcinogenesis. Up-regulated upon tumor stem cell differentiation. Up-regulated by transforming growth factor-beta, 12-O-tetradecanoyl phorbol-13-acetate and retinoids.2 Publications

    Gene expression databases

    BgeeiENSG00000078098.
    CleanExiHS_FAP.
    ExpressionAtlasiQ12884. baseline and differential.
    GenevisibleiQ12884. HS.

    Organism-specific databases

    HPAiHPA059739.

    Interactioni

    Subunit structurei

    Homodimer; homodimerization is required for activity of both plasma membrane and soluble forms. The monomer is inactive. Heterodimer with DPP4. Interacts with PLAUR; the interaction occurs at the cell surface of invadopodia membranes. Interacts with ITGB1. Interacts with ITGA3. Associates with integrin alpha-3/beta-1; the association occurs in a collagen-dependent manner at the cell surface of invadopodia membranes.7 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    GCGP012754EBI-4319803,EBI-7629173
    VIPP012822EBI-4319803,EBI-751454

    GO - Molecular functioni

    • integrin binding Source: UniProtKB
    • protease binding Source: BHF-UCL
    • protein dimerization activity Source: UniProtKB
    • protein homodimerization activity Source: UniProtKB

    Protein-protein interaction databases

    BioGridi108485. 15 interactors.
    IntActiQ12884. 10 interactors.
    MINTiMINT-4778828.
    STRINGi9606.ENSP00000188790.

    Chemistry databases

    BindingDBiQ12884.

    Structurei

    Secondary structure

    1760
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi44 – 49Combined sources6
    Turni50 – 52Combined sources3
    Beta strandi60 – 70Combined sources11
    Beta strandi76 – 83Combined sources8
    Beta strandi86 – 90Combined sources5
    Helixi92 – 96Combined sources5
    Turni97 – 99Combined sources3
    Beta strandi101 – 105Combined sources5
    Beta strandi109 – 120Combined sources12
    Beta strandi122 – 124Combined sources3
    Beta strandi126 – 134Combined sources9
    Turni135 – 138Combined sources4
    Beta strandi148 – 150Combined sources3
    Beta strandi153 – 155Combined sources3
    Beta strandi162 – 166Combined sources5
    Beta strandi169 – 175Combined sources7
    Turni189 – 191Combined sources3
    Beta strandi192 – 196Combined sources5
    Helixi199 – 204Combined sources6
    Beta strandi212 – 214Combined sources3
    Beta strandi218 – 227Combined sources10
    Beta strandi233 – 238Combined sources6
    Beta strandi241 – 244Combined sources4
    Beta strandi246 – 251Combined sources6
    Beta strandi261 – 270Combined sources10
    Helixi272 – 275Combined sources4
    Helixi284 – 287Combined sources4
    Beta strandi291 – 312Combined sources22
    Beta strandi315 – 323Combined sources9
    Beta strandi325 – 331Combined sources7
    Helixi334 – 336Combined sources3
    Beta strandi337 – 341Combined sources5
    Beta strandi343 – 345Combined sources3
    Beta strandi347 – 351Combined sources5
    Beta strandi364 – 369Combined sources6
    Beta strandi375 – 382Combined sources8
    Beta strandi393 – 395Combined sources3
    Beta strandi397 – 403Combined sources7
    Beta strandi405 – 413Combined sources9
    Helixi415 – 417Combined sources3
    Beta strandi422 – 428Combined sources7
    Beta strandi430 – 433Combined sources4
    Beta strandi436 – 440Combined sources5
    Turni441 – 447Combined sources7
    Beta strandi450 – 455Combined sources6
    Helixi457 – 459Combined sources3
    Beta strandi460 – 466Combined sources7
    Beta strandi469 – 471Combined sources3
    Beta strandi473 – 477Combined sources5
    Beta strandi479 – 481Combined sources3
    Beta strandi484 – 489Combined sources6
    Helixi492 – 497Combined sources6
    Beta strandi505 – 513Combined sources9
    Beta strandi516 – 524Combined sources9
    Beta strandi530 – 532Combined sources3
    Beta strandi534 – 540Combined sources7
    Helixi557 – 563Combined sources7
    Beta strandi568 – 573Combined sources6
    Beta strandi577 – 580Combined sources4
    Helixi582 – 585Combined sources4
    Helixi586 – 588Combined sources3
    Helixi594 – 608Combined sources15
    Beta strandi613 – 623Combined sources11
    Helixi625 – 634Combined sources10
    Beta strandi637 – 639Combined sources3
    Beta strandi642 – 648Combined sources7
    Turni653 – 655Combined sources3
    Helixi658 – 665Combined sources8
    Turni670 – 673Combined sources4
    Helixi674 – 679Combined sources6
    Helixi683 – 689Combined sources7
    Beta strandi692 – 699Combined sources8
    Beta strandi703 – 705Combined sources3
    Helixi708 – 719Combined sources12
    Beta strandi725 – 729Combined sources5
    Helixi739 – 756Combined sources18

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1Z68X-ray2.60A/B39-757[»]
    ProteinModelPortaliQ12884.
    SMRiQ12884.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ12884.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the peptidase S9B family.Curated

    Keywords - Domaini

    Signal-anchor, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG2100. Eukaryota.
    COG1506. LUCA.
    GeneTreeiENSGT00760000119233.
    HOGENOMiHOG000231875.
    HOVERGENiHBG005527.
    InParanoidiQ12884.
    KOiK08674.
    OMAiKHLYTHM.
    OrthoDBiEOG091G0BU5.
    PhylomeDBiQ12884.
    TreeFamiTF313309.

    Family and domain databases

    Gene3Di2.140.10.30. 1 hit.
    3.40.50.1820. 1 hit.
    InterProiIPR029058. AB_hydrolase.
    IPR002471. Pept_S9_AS.
    IPR001375. Peptidase_S9.
    IPR002469. Peptidase_S9B_N.
    [Graphical view]
    PfamiPF00930. DPPIV_N. 1 hit.
    PF00326. Peptidase_S9. 1 hit.
    [Graphical view]
    SUPFAMiSSF53474. SSF53474. 1 hit.

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q12884-1) [UniParc]FASTAAdd to basket
    Also known as: L, seprase-I1 Publication

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MKTWVKIVFG VATSAVLALL VMCIVLRPSR VHNSEENTMR ALTLKDILNG
    60 70 80 90 100
    TFSYKTFFPN WISGQEYLHQ SADNNIVLYN IETGQSYTIL SNRTMKSVNA
    110 120 130 140 150
    SNYGLSPDRQ FVYLESDYSK LWRYSYTATY YIYDLSNGEF VRGNELPRPI
    160 170 180 190 200
    QYLCWSPVGS KLAYVYQNNI YLKQRPGDPP FQITFNGREN KIFNGIPDWV
    210 220 230 240 250
    YEEEMLATKY ALWWSPNGKF LAYAEFNDTD IPVIAYSYYG DEQYPRTINI
    260 270 280 290 300
    PYPKAGAKNP VVRIFIIDTT YPAYVGPQEV PVPAMIASSD YYFSWLTWVT
    310 320 330 340 350
    DERVCLQWLK RVQNVSVLSI CDFREDWQTW DCPKTQEHIE ESRTGWAGGF
    360 370 380 390 400
    FVSTPVFSYD AISYYKIFSD KDGYKHIHYI KDTVENAIQI TSGKWEAINI
    410 420 430 440 450
    FRVTQDSLFY SSNEFEEYPG RRNIYRISIG SYPPSKKCVT CHLRKERCQY
    460 470 480 490 500
    YTASFSDYAK YYALVCYGPG IPISTLHDGR TDQEIKILEE NKELENALKN
    510 520 530 540 550
    IQLPKEEIKK LEVDEITLWY KMILPPQFDR SKKYPLLIQV YGGPCSQSVR
    560 570 580 590 600
    SVFAVNWISY LASKEGMVIA LVDGRGTAFQ GDKLLYAVYR KLGVYEVEDQ
    610 620 630 640 650
    ITAVRKFIEM GFIDEKRIAI WGWSYGGYVS SLALASGTGL FKCGIAVAPV
    660 670 680 690 700
    SSWEYYASVY TERFMGLPTK DDNLEHYKNS TVMARAEYFR NVDYLLIHGT
    710 720 730 740 750
    ADDNVHFQNS AQIAKALVNA QVDFQAMWYS DQNHGLSGLS TNHLYTHMTH
    760
    FLKQCFSLSD
    Note: Major isoform.
    Length:760
    Mass (Da):87,713
    Last modified:March 23, 2010 - v5
    Checksum:i7FF817B5A4F75142
    GO
    Isoform 21 Publication (identifier: Q12884-2) [UniParc]FASTAAdd to basket
    Also known as: S, Truncated, seprase-s1 Publication

    The sequence of this isoform differs from the canonical sequence as follows:
         1-521: Missing.

    Note: Upstream open reading frames ORF(s)-containing region inhibits the translation of its downstream ORF.1 Publication
    Show »
    Length:239
    Mass (Da):26,954
    Checksum:i853731E1DF446AC6
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti207A → P in AAB49652 (PubMed:7911242).Curated1
    Sequence conflicti229T → K in AAB49652 (PubMed:7911242).Curated1
    Sequence conflicti354T → R in AAB49652 (PubMed:7911242).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_071264363S → L Decreased plasma membrane expression; loss of homodimerization and dipeptidyl peptidase activity; mislocalized with the calnexin in the endoplasmic reticulum; causes induction of the unfolded protein response (UPR). 2 PublicationsCorresponds to variant rs762738740dbSNPEnsembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0053671 – 521Missing in isoform 2. 1 PublicationAdd BLAST521

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U09278 mRNA. Translation: AAB49652.1.
    U76833 mRNA. Translation: AAC51668.1.
    AF007822 mRNA. Translation: AAF21600.1.
    AC007750 Genomic DNA. Translation: AAY24205.1.
    CH471058 Genomic DNA. Translation: EAX11353.1.
    BC026250 mRNA. Translation: AAH26250.1.
    CCDSiCCDS33311.1. [Q12884-1]
    RefSeqiNP_001278736.1. NM_001291807.1.
    NP_004451.2. NM_004460.3. [Q12884-1]
    UniGeneiHs.654370.

    Genome annotation databases

    EnsembliENST00000188790; ENSP00000188790; ENSG00000078098. [Q12884-1]
    GeneIDi2191.
    KEGGihsa:2191.
    UCSCiuc002ucd.3. human. [Q12884-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U09278 mRNA. Translation: AAB49652.1.
    U76833 mRNA. Translation: AAC51668.1.
    AF007822 mRNA. Translation: AAF21600.1.
    AC007750 Genomic DNA. Translation: AAY24205.1.
    CH471058 Genomic DNA. Translation: EAX11353.1.
    BC026250 mRNA. Translation: AAH26250.1.
    CCDSiCCDS33311.1. [Q12884-1]
    RefSeqiNP_001278736.1. NM_001291807.1.
    NP_004451.2. NM_004460.3. [Q12884-1]
    UniGeneiHs.654370.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1Z68X-ray2.60A/B39-757[»]
    ProteinModelPortaliQ12884.
    SMRiQ12884.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi108485. 15 interactors.
    IntActiQ12884. 10 interactors.
    MINTiMINT-4778828.
    STRINGi9606.ENSP00000188790.

    Chemistry databases

    BindingDBiQ12884.
    ChEMBLiCHEMBL4683.
    GuidetoPHARMACOLOGYi2365.

    Protein family/group databases

    ESTHERihuman-FAP. DPP4N_Peptidase_S9.
    MEROPSiS09.007.

    PTM databases

    iPTMnetiQ12884.
    PhosphoSitePlusiQ12884.
    SwissPalmiQ12884.

    Polymorphism and mutation databases

    BioMutaiFAP.
    DMDMi292495099.

    Proteomic databases

    PaxDbiQ12884.
    PeptideAtlasiQ12884.
    PRIDEiQ12884.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000188790; ENSP00000188790; ENSG00000078098. [Q12884-1]
    GeneIDi2191.
    KEGGihsa:2191.
    UCSCiuc002ucd.3. human. [Q12884-1]

    Organism-specific databases

    CTDi2191.
    DisGeNETi2191.
    GeneCardsiFAP.
    H-InvDBHIX0002548.
    HGNCiHGNC:3590. FAP.
    HPAiHPA059739.
    MIMi600403. gene.
    neXtProtiNX_Q12884.
    OpenTargetsiENSG00000078098.
    PharmGKBiPA28003.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG2100. Eukaryota.
    COG1506. LUCA.
    GeneTreeiENSGT00760000119233.
    HOGENOMiHOG000231875.
    HOVERGENiHBG005527.
    InParanoidiQ12884.
    KOiK08674.
    OMAiKHLYTHM.
    OrthoDBiEOG091G0BU5.
    PhylomeDBiQ12884.
    TreeFamiTF313309.

    Enzyme and pathway databases

    BioCyciZFISH:ENSG00000078098-MONOMER.
    BRENDAi3.4.21.B28. 2681.

    Miscellaneous databases

    ChiTaRSiFAP. human.
    EvolutionaryTraceiQ12884.
    GeneWikiiFibroblast_activation_protein,_alpha.
    GenomeRNAii2191.
    PROiQ12884.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000078098.
    CleanExiHS_FAP.
    ExpressionAtlasiQ12884. baseline and differential.
    GenevisibleiQ12884. HS.

    Family and domain databases

    Gene3Di2.140.10.30. 1 hit.
    3.40.50.1820. 1 hit.
    InterProiIPR029058. AB_hydrolase.
    IPR002471. Pept_S9_AS.
    IPR001375. Peptidase_S9.
    IPR002469. Peptidase_S9B_N.
    [Graphical view]
    PfamiPF00930. DPPIV_N. 1 hit.
    PF00326. Peptidase_S9. 1 hit.
    [Graphical view]
    SUPFAMiSSF53474. SSF53474. 1 hit.
    ProtoNetiSearch...

    Entry informationi

    Entry nameiSEPR_HUMAN
    AccessioniPrimary (citable) accession number: Q12884
    Secondary accession number(s): O00199
    , Q53TP5, Q86Z29, Q99998, Q9UID4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 5, 2002
    Last sequence update: March 23, 2010
    Last modified: November 2, 2016
    This is version 166 of the entry and version 5 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 2
      Human chromosome 2: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Peptidase families
      Classification of peptidase families and list of entries
    7. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.