P97321 (SEPR_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Seprase
EC=3.4.21.-

Alternative name(s):
Fibroblast activation protein alpha
Integral membrane serine protease

Gene names

Name:

Fap

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	761 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript 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 By similarity. May have a role in tissue remodeling during development and wound healing, and contribute to invasiveness in malignant cancers.
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 By similarity.
Subcellular location	Cell membrane; Single-pass type II membrane protein By similarity. Cell projection › lamellipodium membrane; Single-pass type II membrane protein By similarity. Cell projection › invadopodium membrane; Single-pass type II membrane protein By similarity. 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 By similarity.
Tissue specificity	Detected in fibroblasts, in placenta, uterus, embryos from day 7-19 and in newborn mice (P1).
Sequence similarities	Belongs to the peptidase S9B family.

Ontologies

Keywords
Cellular component	Cell junction Cell membrane Cell projection Membrane
Coding sequence diversity	Alternative splicing
Domain	Signal-anchor Transmembrane Transmembrane helix
Molecular function	Hydrolase Protease Serine protease
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	endothelial cell migration Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of extracellular matrix disassembly Inferred from sequence or structural similarity. Source: UniProtKB proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW extracellular space Inferred from electronic annotation. Source: Compara integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW invadopodium membrane Inferred from electronic annotation. Source: UniProtKB-SubCell lamellipodium Inferred from sequence or structural similarity. Source: UniProtKB lamellipodium membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro serine-type peptidase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P97321-1)

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.

Isoform 2 (identifier: P97321-2)

The sequence of this isoform differs from the canonical sequence as follows:
     31-35: Missing.

Isoform 3 (identifier: P97321-3)

The sequence of this isoform differs from the canonical sequence as follows:
     31-63: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 761	761	Seprase		PRO_0000122425
Regions
	Topological domain	1 – 4	4	Cytoplasmic Potential
	Transmembrane	5 – 25	21	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	26 – 761	736	Extracellular Potential
Sites
	Active site	624	1	Charge relay system By similarity
	Active site	702	1	Charge relay system By similarity
	Active site	734	1	Charge relay system By similarity
	Binding site	203	1	Substrate By similarity
	Binding site	204	1	Substrate By similarity
Amino acid modifications
	Glycosylation	49	1	N-linked (GlcNAc...) Potential
	Glycosylation	92	1	N-linked (GlcNAc...) Potential
	Glycosylation	99	1	N-linked (GlcNAc...) Potential
	Glycosylation	227	1	N-linked (GlcNAc...) Potential
	Glycosylation	314	1	N-linked (GlcNAc...) Potential
	Glycosylation	679	1	N-linked (GlcNAc...) Potential
	Disulfide bond	321 ↔ 332		By similarity
	Disulfide bond	438 ↔ 441		By similarity
	Disulfide bond	448 ↔ 466		By similarity
	Disulfide bond	643 ↔ 756		By similarity
Natural variations
	Alternative sequence	31 – 63	33	Missing in isoform 3.		VSP_005369
	Alternative sequence	31 – 35	5	Missing in isoform 2.		VSP_005368
Experimental info
	Sequence conflict	737	1	S → L in AAH19190. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: 9174C3AEDA213B25	FASTA	761	87,945
	10 20 30 40 50 60 MKTWLKTVFG VTTLAALALV VICIVLRPSR VYKPEGNTKR ALTLKDILNG TFSYKTYFPN 70 80 90 100 110 120 WISEQEYLHQ SEDDNIVFYN IETRESYIIL SNSTMKSVNA TDYGLSPDRQ FVYLESDYSK 130 140 150 160 170 180 LWRYSYTATY YIYDLQNGEF VRGYELPRPI QYLCWSPVGS KLAYVYQNNI YLKQRPGDPP 190 200 210 220 230 240 FQITYTGREN RIFNGIPDWV YEEEMLATKY ALWWSPDGKF LAYVEFNDSD IPIIAYSYYG 250 260 270 280 290 300 DGQYPRTINI PYPKAGAKNP VVRVFIVDTT YPHHVGPMEV PVPEMIASSD YYFSWLTWVS 310 320 330 340 350 360 SERVCLQWLK RVQNVSVLSI CDFREDWHAW ECPKNQEHVE ESRTGWAGGF FVSTPAFSQD 370 380 390 400 410 420 ATSYYKIFSD KDGYKHIHYI KDTVENAIQI TSGKWEAIYI FRVTQDSLFY SSNEFEGYPG 430 440 450 460 470 480 RRNIYRISIG NSPPSKKCVT CHLRKERCQY YTASFSYKAK YYALVCYGPG LPISTLHDGR 490 500 510 520 530 540 TDQEIQVLEE NKELENSLRN IQLPKVEIKK LKDGGLTFWY KMILPPQFDR SKKYPLLIQV 550 560 570 580 590 600 YGGPCSQSVK SVFAVNWITY LASKEGIVIA LVDGRGTAFQ GDKFLHAVYR KLGVYEVEDQ 610 620 630 640 650 660 LTAVRKFIEM GFIDEERIAI WGWSYGGYVS SLALASGTGL FKCGIAVAPV SSWEYYASIY 670 680 690 700 710 720 SERFMGLPTK DDNLEHYKNS TVMARAEYFR NVDYLLIHGT ADDNVHFQNS AQIAKALVNA 730 740 750 760 QVDFQAMWYS DQNHGISSGR SQNHLYTHMT HFLKQCFSLS D
	Isoform 2 [UniParc]. Checksum: BE2A232BCEFD0C64	FASTA	756	87,328
	10 20 30 40 50 60 MKTWLKTVFG VTTLAALALV VICIVLRPSR GNTKRALTLK DILNGTFSYK TYFPNWISEQ 70 80 90 100 110 120 EYLHQSEDDN IVFYNIETRE SYIILSNSTM KSVNATDYGL SPDRQFVYLE SDYSKLWRYS 130 140 150 160 170 180 YTATYYIYDL QNGEFVRGYE LPRPIQYLCW SPVGSKLAYV YQNNIYLKQR PGDPPFQITY 190 200 210 220 230 240 TGRENRIFNG IPDWVYEEEM LATKYALWWS PDGKFLAYVE FNDSDIPIIA YSYYGDGQYP 250 260 270 280 290 300 RTINIPYPKA GAKNPVVRVF IVDTTYPHHV GPMEVPVPEM IASSDYYFSW LTWVSSERVC 310 320 330 340 350 360 LQWLKRVQNV SVLSICDFRE DWHAWECPKN QEHVEESRTG WAGGFFVSTP AFSQDATSYY 370 380 390 400 410 420 KIFSDKDGYK HIHYIKDTVE NAIQITSGKW EAIYIFRVTQ DSLFYSSNEF EGYPGRRNIY 430 440 450 460 470 480 RISIGNSPPS KKCVTCHLRK ERCQYYTASF SYKAKYYALV CYGPGLPIST LHDGRTDQEI 490 500 510 520 530 540 QVLEENKELE NSLRNIQLPK VEIKKLKDGG LTFWYKMILP PQFDRSKKYP LLIQVYGGPC 550 560 570 580 590 600 SQSVKSVFAV NWITYLASKE GIVIALVDGR GTAFQGDKFL HAVYRKLGVY EVEDQLTAVR 610 620 630 640 650 660 KFIEMGFIDE ERIAIWGWSY GGYVSSLALA SGTGLFKCGI AVAPVSSWEY YASIYSERFM 670 680 690 700 710 720 GLPTKDDNLE HYKNSTVMAR AEYFRNVDYL LIHGTADDNV HFQNSAQIAK ALVNAQVDFQ 730 740 750 AMWYSDQNHG ISSGRSQNHL YTHMTHFLKQ CFSLSD
	Isoform 3 [UniParc]. Checksum: 4436F2EC1C4B1BDA	FASTA	728	84,096
	10 20 30 40 50 60 MKTWLKTVFG VTTLAALALV VICIVLRPSR EQEYLHQSED DNIVFYNIET RESYIILSNS 70 80 90 100 110 120 TMKSVNATDY GLSPDRQFVY LESDYSKLWR YSYTATYYIY DLQNGEFVRG YELPRPIQYL 130 140 150 160 170 180 CWSPVGSKLA YVYQNNIYLK QRPGDPPFQI TYTGRENRIF NGIPDWVYEE EMLATKYALW 190 200 210 220 230 240 WSPDGKFLAY VEFNDSDIPI IAYSYYGDGQ YPRTINIPYP KAGAKNPVVR VFIVDTTYPH 250 260 270 280 290 300 HVGPMEVPVP EMIASSDYYF SWLTWVSSER VCLQWLKRVQ NVSVLSICDF REDWHAWECP 310 320 330 340 350 360 KNQEHVEESR TGWAGGFFVS TPAFSQDATS YYKIFSDKDG YKHIHYIKDT VENAIQITSG 370 380 390 400 410 420 KWEAIYIFRV TQDSLFYSSN EFEGYPGRRN IYRISIGNSP PSKKCVTCHL RKERCQYYTA 430 440 450 460 470 480 SFSYKAKYYA LVCYGPGLPI STLHDGRTDQ EIQVLEENKE LENSLRNIQL PKVEIKKLKD 490 500 510 520 530 540 GGLTFWYKMI LPPQFDRSKK YPLLIQVYGG PCSQSVKSVF AVNWITYLAS KEGIVIALVD 550 560 570 580 590 600 GRGTAFQGDK FLHAVYRKLG VYEVEDQLTA VRKFIEMGFI DEERIAIWGW SYGGYVSSLA 610 620 630 640 650 660 LASGTGLFKC GIAVAPVSSW EYYASIYSER FMGLPTKDDN LEHYKNSTVM ARAEYFRNVD 670 680 690 700 710 720 YLLIHGTADD NVHFQNSAQI AKALVNAQVD FQAMWYSDQN HGISSGRSQN HLYTHMTHFL KQCFSLSD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mouse fibroblast activation protein: molecular cloning, alternative splicing and expression in the reactive stroma of epithelial cancers." Niedermeyer J., Scanlan M.J., Garin-Chesa P., Daiber C., Fiebig H.H., Old L.J., Rettig W.J., Schnapp A. Int. J. Cancer 71:383-389(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3). Strain: BALB/c. Tissue: Embryo.
[2]	"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: Mammary gland.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	Y10007 mRNA. Translation: CAA71116.1. BC019190 mRNA. Translation: AAH19190.1.
IPI	IPI00123925. IPI00227000. IPI00227001.
RefSeq	NP_032012.1. NM_007986.2.
UniGene	Mm.41816.
3D structure databases
ProteinModelPortal	P97321.
SMR	P97321. Positions 40-758.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-4997001.
Protein family/group databases
MEROPS	S09.007.
PTM databases
PhosphoSite	P97321.
Proteomic databases
PaxDb	P97321.
PRIDE	P97321.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000000402; ENSMUSP00000000402; ENSMUSG00000000392. ENSMUST00000102732; ENSMUSP00000099793; ENSMUSG00000000392. ENSMUST00000174448; ENSMUSP00000134386; ENSMUSG00000000392.
GeneID	14089.
KEGG	mmu:14089.
UCSC	uc008jvk.1. mouse. uc008jvl.1. mouse.
Organism-specific databases
CTD	2191.
MGI	MGI:109608. Fap.
Phylogenomic databases
eggNOG	COG1506.
GeneTree	ENSGT00530000062751.
HOGENOM	HOG000231875.
HOVERGEN	HBG005527.
InParanoid	P97321.
KO	K08674.
OMA	LSTKHLY.
OrthoDB	EOG4CVG69.
Gene expression databases
ArrayExpress	P97321.
Bgee	P97321.
CleanEx	MM_FAP.
Genevestigator	P97321.
GermOnline	ENSMUSG00000000392. Mus musculus.
Family and domain databases
InterPro	IPR002471. Pept_S9_AS. IPR001375. Peptidase_S9. IPR002469. Peptidase_S9B. [Graphical view]
Pfam	PF00930. DPPIV_N. 1 hit. PF00326. Peptidase_S9. 1 hit. [Graphical view]
PROSITE	PS00708. PRO_ENDOPEP_SER. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL5769.
NextBio	285126.
SOURCE	Search...

Entry information

Entry name

SEPR_MOUSE

Accession

Primary (citable) accession number: P97321

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 5, 2002
Last sequence update:	May 1, 1997
Last modified:	May 29, 2013
This is version 112 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program