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Q12884 (SEPR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 143. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Seprase

EC=3.4.21.-
Alternative name(s):
170 kDa melanoma membrane-bound gelatinase
Fibroblast activation protein alpha
Integral membrane serine protease
Gene names
Name:FAP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length760 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

In association with DPP4 is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM. May have a role in tissue remodeling during development and wound healing, and may contribute to invasiveness in malignant cancers. Ref.10

Catalytic activity

Degrades gelatin and heat-denatured type I and type IV collagen, but not native type I or type IV collagen. Does not cleave laminin, fibronectin, fibrin or casein.

Subunit structure

Homodimer, or heterodimer with DPP4. The monomer is inactive. Ref.10 Ref.11

Subcellular location

Cell membrane; Single-pass type II membrane protein. Cell projectionlamellipodium membrane; Single-pass type II membrane protein. Cell projectioninvadopodium membrane; Single-pass type II membrane protein. Note: Found in cell surface lamellipodia, invadopodia and on shed vesicles. Colocalized with DPP4 in invadopodia and lamellipodia 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. Ref.10

Tissue specificity

Fibroblast specific.

Induction

In fibroblasts at times and sites of tissue remodeling during development, tissue repair, and carcinogenesis.

Post-translational modification

N-glycosylated. Ref.11

The N-terminus may be blocked.

Sequence similarities

Belongs to the peptidase S9B family.

Ontologies

Keywords
   Cellular componentCell junction
Cell membrane
Cell projection
Membrane
   Coding sequence diversityAlternative splicing
   DomainSignal-anchor
Transmembrane
Transmembrane helix
   Molecular functionHydrolase
Protease
Serine protease
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processendothelial cell migration

Inferred from direct assay Ref.10. Source: UniProtKB

negative regulation of extracellular matrix disassembly

Inferred from direct assay Ref.10. Source: UniProtKB

proteolysis

Inferred from electronic annotation. Source: UniProtKB-KW

regulation of fibrinolysis

Inferred by curator PubMed 17317851. Source: BHF-UCL

   Cellular_componentcell junction

Inferred from electronic annotation. Source: UniProtKB-KW

extracellular space

Inferred from direct assay PubMed 17317851. Source: BHF-UCL

integral component of membrane

Non-traceable author statement Ref.3. Source: UniProtKB

invadopodium membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

lamellipodium

Inferred from direct assay Ref.10Ref.3. Source: UniProtKB

lamellipodium membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functiondipeptidyl-peptidase activity

Non-traceable author statement Ref.1. Source: UniProtKB

metalloendopeptidase activity

Traceable author statement Ref.3. Source: UniProtKB

protein homodimerization activity

Non-traceable author statement Ref.2. Source: UniProtKB

serine-type endopeptidase activity

Inferred from electronic annotation. Source: InterPro

serine-type peptidase activity

Inferred from direct assay Ref.10. Source: UniProtKB

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q12884-1)

Also known as: L;

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.
Note: Major isoform.
Isoform 2 (identifier: Q12884-2)

Also known as: S; Truncated;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 760760Seprase
PRO_0000122424

Regions

Topological domain1 – 44Cytoplasmic Potential
Transmembrane5 – 2521Helical; Signal-anchor for type II membrane protein; Potential
Topological domain26 – 760735Extracellular Potential

Sites

Active site6241Charge relay system Ref.11
Active site7021Charge relay system Ref.11
Active site7341Charge relay system Ref.11
Binding site2031Substrate
Binding site2041Substrate

Amino acid modifications

Glycosylation491N-linked (GlcNAc...) Ref.11
Glycosylation921N-linked (GlcNAc...) Ref.11
Glycosylation991N-linked (GlcNAc...) Ref.9
Glycosylation2271N-linked (GlcNAc...) Ref.9 Ref.11
Glycosylation3141N-linked (GlcNAc...) Ref.11
Glycosylation6791N-linked (GlcNAc...) Potential
Disulfide bond321 ↔ 332 Ref.11
Disulfide bond438 ↔ 441 Ref.11
Disulfide bond448 ↔ 466 Ref.11
Disulfide bond643 ↔ 755 Ref.11

Natural variations

Alternative sequence1 – 521521Missing in isoform 2.
VSP_005367

Experimental info

Sequence conflict2071A → P in AAB49652. Ref.1
Sequence conflict2291T → K in AAB49652. Ref.1
Sequence conflict3541T → R in AAB49652. Ref.1

Secondary structure

................................................................................................................................................ 760
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (L) [UniParc].

Last modified March 23, 2010. Version 5.
Checksum: 7FF817B5A4F75142

FASTA76087,713
        10         20         30         40         50         60 
MKTWVKIVFG VATSAVLALL VMCIVLRPSR VHNSEENTMR ALTLKDILNG TFSYKTFFPN 

        70         80         90        100        110        120 
WISGQEYLHQ SADNNIVLYN IETGQSYTIL SNRTMKSVNA SNYGLSPDRQ FVYLESDYSK 

       130        140        150        160        170        180 
LWRYSYTATY YIYDLSNGEF VRGNELPRPI QYLCWSPVGS KLAYVYQNNI YLKQRPGDPP 

       190        200        210        220        230        240 
FQITFNGREN KIFNGIPDWV YEEEMLATKY ALWWSPNGKF LAYAEFNDTD IPVIAYSYYG 

       250        260        270        280        290        300 
DEQYPRTINI PYPKAGAKNP VVRIFIIDTT YPAYVGPQEV PVPAMIASSD YYFSWLTWVT 

       310        320        330        340        350        360 
DERVCLQWLK RVQNVSVLSI CDFREDWQTW DCPKTQEHIE ESRTGWAGGF FVSTPVFSYD 

       370        380        390        400        410        420 
AISYYKIFSD KDGYKHIHYI KDTVENAIQI TSGKWEAINI FRVTQDSLFY SSNEFEEYPG 

       430        440        450        460        470        480 
RRNIYRISIG SYPPSKKCVT CHLRKERCQY YTASFSDYAK YYALVCYGPG IPISTLHDGR 

       490        500        510        520        530        540 
TDQEIKILEE NKELENALKN IQLPKEEIKK LEVDEITLWY KMILPPQFDR SKKYPLLIQV 

       550        560        570        580        590        600 
YGGPCSQSVR SVFAVNWISY LASKEGMVIA LVDGRGTAFQ GDKLLYAVYR KLGVYEVEDQ 

       610        620        630        640        650        660 
ITAVRKFIEM GFIDEKRIAI WGWSYGGYVS SLALASGTGL FKCGIAVAPV SSWEYYASVY 

       670        680        690        700        710        720 
TERFMGLPTK DDNLEHYKNS TVMARAEYFR NVDYLLIHGT ADDNVHFQNS AQIAKALVNA 

       730        740        750        760 
QVDFQAMWYS DQNHGLSGLS TNHLYTHMTH FLKQCFSLSD 

« Hide

Isoform 2 (S) (Truncated) [UniParc].

Checksum: 853731E1DF446AC6
Show »

FASTA23926,954

References

« Hide 'large scale' references
[1]"Molecular cloning of fibroblast activation protein alpha, a member of the serine protease family selectively expressed in stromal fibroblasts of epithelial cancers."
Scanlan M.J., Raj B.K.M., Calvo B., Garin-Chesa P., Sanz-Moncasi M.P., Healey J.H., Old L.J., Rettig W.J.
Proc. Natl. Acad. Sci. U.S.A. 91:5657-5661(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Fibroblast.
[2]"Molecular cloning of seprase: a serine integral membrane protease from human melanoma."
Goldstein L.A., Ghersi G., Pineiro-Sanchez M.L., Salamone M., Yeh Y., Flessate D., Chen W.-T.
Biochim. Biophys. Acta 1361:11-19(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Melanoma.
[3]"Identification of the 170-kDa melanoma membrane-bound gelatinase (seprase) as a serine integral membrane protease."
Pineiro-Sanchez M.L., Goldstein L.A., Dodt J., Howard L., Yeh Y., Chen W.-T.
J. Biol. Chem. 272:7595-7601(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 220-229; 461-472 AND 511-518.
Tissue: Melanoma.
[4]"Identification of an alternatively spliced seprase mRNA that encodes a novel intracellular isoform."
Goldstein L.A., Chen W.-T.
J. Biol. Chem. 275:2554-2559(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Melanoma.
[5]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Placenta.
[8]"Fibroblast activation protein: purification, epitope mapping and induction by growth factors."
Rettig W.J., Su S.L., Fortunato S.R., Scanlan M.J., Raj B.K.M., Garin-Chesa P., Healey J.H., Old L.J.
Int. J. Cancer 58:385-392(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 192-208; 220-240 AND 510-521.
[9]"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-99 AND ASN-227.
Tissue: Plasma.
[10]"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."
Ghersi G., Zhao Q., Salamone M., Yeh Y., Zucker S., Chen W.T.
Cancer Res. 66:4652-4661(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, HETERODIMERIZATION, SUBCELLULAR LOCATION.
[11]"Structural and kinetic analysis of the substrate specificity of human fibroblast activation protein alpha."
Aertgeerts K., Levin I., Shi L., Snell G.P., Jennings A., Prasad G.S., Zhang Y., Kraus M.L., Salakian S., Sridhar V., Wijnands R., Tennant M.G.
J. Biol. Chem. 280:19441-19444(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 39-757, SUBUNIT, DISULFIDE BONDS, ACTIVE SITE, GLYCOSYLATION AT ASN-49; ASN-92; ASN-227 AND ASN-314.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_004451.2. NM_004460.2.
UniGeneHs.654370.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1Z68X-ray2.60A/B39-757[»]
ProteinModelPortalQ12884.
SMRQ12884. Positions 39-757.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108485. 4 interactions.
IntActQ12884. 10 interactions.
MINTMINT-4778828.
STRING9606.ENSP00000188790.

Chemistry

ChEMBLCHEMBL4683.

Protein family/group databases

MEROPSS09.007.

PTM databases

PhosphoSiteQ12884.

Polymorphism databases

DMDM292495099.

Proteomic databases

PaxDbQ12884.
PRIDEQ12884.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000188790; ENSP00000188790; ENSG00000078098. [Q12884-1]
GeneID2191.
KEGGhsa:2191.
UCSCuc002ucd.3. human. [Q12884-1]
uc010fpc.3. human. [Q12884-2]

Organism-specific databases

CTD2191.
GeneCardsGC02M163027.
H-InvDBHIX0002548.
HGNCHGNC:3590. FAP.
HPAHPA059739.
MIM600403. gene.
neXtProtNX_Q12884.
PharmGKBPA28003.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1506.
HOGENOMHOG000231875.
HOVERGENHBG005527.
InParanoidQ12884.
KOK08674.
OMARRNELPR.
OrthoDBEOG761BT2.
PhylomeDBQ12884.
TreeFamTF313309.

Gene expression databases

ArrayExpressQ12884.
BgeeQ12884.
CleanExHS_FAP.
GenevestigatorQ12884.

Family and domain databases

InterProIPR002471. Pept_S9_AS.
IPR001375. Peptidase_S9.
IPR002469. Peptidase_S9B.
[Graphical view]
PfamPF00930. DPPIV_N. 1 hit.
PF00326. Peptidase_S9. 1 hit.
[Graphical view]
PROSITEPS00708. PRO_ENDOPEP_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSFAP. human.
EvolutionaryTraceQ12884.
GeneWikiFibroblast_activation_protein,_alpha.
GenomeRNAi2191.
NextBio8851.
PROQ12884.
SOURCESearch...

Entry information

Entry nameSEPR_HUMAN
AccessionPrimary (citable) accession number: Q12884
Secondary accession number(s): O00199 expand/collapse secondary AC list , Q53TP5, Q86Z29, Q99998, Q9UID4
Entry history
Integrated into UniProtKB/Swiss-Prot: March 5, 2002
Last sequence update: March 23, 2010
Last modified: March 19, 2014
This is version 143 of the entry and version 5 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM