Reviewed, UniProtKB/Swiss-Prot Q28193 (FURIN_BOVIN)

Names and origin

Protein names

Recommended name:
    Furin
    EC=3.4.21.75
Alternative name(s):
    Paired basic amino acid residue-cleaving enzyme
      Short name=PACE
    Dibasic-processing enzyme
    Trans Golgi network protease furin

Gene names

Name:	FURIN
Synonyms:	FUR, PACE

Organism

Bos taurus (Bovine)

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

Protein attributes

Sequence length	797 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Furin is likely to represent the ubiquitous endoprotease activity within constitutive secretory pathways and capable of cleavage at the RX(K/R)R consensus motif.
Catalytic activity	Release of mature proteins from their proproteins by cleavage of -Arg-Xaa-Yaa-Arg-|-Zaa- bonds, where Xaa can be any amino acid and Yaa is Arg or Lys. Releases albumin, complement component C3 and vWF from their respective precursors.
Cofactor	Calcium By similarity.
Enzyme regulation	Could be inhibited by the not secondly cleaved propeptide.
Subunit structure	Interacts with FLNA. Binds to PACS1 which mediates TGN localization and connection to clathrin adapters By similarity.
Subcellular location	Golgi apparatus › trans-Golgi network membrane; Single-pass type I membrane protein. Cell membrane; Single-pass type I membrane protein. Note: Shuttles between the trans-Golgi network and the cell surface. Propeptide cleavage is a prerequisite for exit of furin molecules out of the endoplasmic reticulum (ER). A second cleavage within the propeptide occurs in the trans Golgi network (TGN), followed by the release of the propeptide and the activation of furin.
Tissue specificity	Seems to be expressed ubiquitously.
Domain	Contains a cytoplasmic domain responsible for its TGN localization and recycling from the cell surface.
Post-translational modification	The inhibition peptide, which plays the role of an intramolecular chaperone, is autocatalytically removed in the endoplasmic reticulum (ER) and remains non-covalently bound to furin as a potent autoinhibitor. Following transport to the trans Golgi, a second cleavage within the inhibition propeptide results in propeptide dissociation and furin activation. Phosphorylation is required for TGN localization of the endoprotease. In vivo, exists as di-, mono- and non-phosphorylated forms By similarity.
Sequence similarities	Belongs to the peptidase S8 family. Furin subfamily. Contains 1 homo B/P domain.

Ontologies

Keywords
Cellular component	Cell membrane Golgi apparatus Membrane
Domain	Signal Transmembrane
Ligand	Calcium Metal-binding
Molecular function	Hydrolase Protease Serine protease
PTM	Autocatalytic cleavage Cleavage on pair of basic residues Disulfide bond Glycoprotein Phosphoprotein Zymogen
Gene Ontology (GO)
Biological process	proteolysis Inferred from electronic annotation. Source: InterPro
Cellular component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 24	24	Potential
	Propeptide	25 – 107	83	Inhibition peptide By similarity		PRO_0000027026
	Chain	108 – 797	690	Furin		PRO_0000027027
Regions
	Transmembrane	719 – 741	23	Potential
	Region	762 – 765	4	Cell surface signal
	Motif	498 – 500	3	Cell attachment site Potential
	Motif	776 – 782	7	Trans Golgi network signal
	Compositional bias	556 – 708	153	Cys-rich
	Compositional bias	690 – 698	9	Poly-Pro
Sites
	Active site	153	1	Charge relay system By similarity
	Active site	194	1	Charge relay system By similarity
	Active site	368	1	Charge relay system By similarity
	Metal binding	115	1	Calcium 1 By similarity
	Metal binding	162	1	Calcium 1 By similarity
	Metal binding	208	1	Calcium 1 By similarity
	Metal binding	258	1	Calcium 2 By similarity
	Metal binding	301	1	Calcium 2 By similarity
	Metal binding	331	1	Calcium 2 By similarity
	Site	75 – 76	2	Cleavage, second; by autolysis By similarity
	Site	107 – 108	2	Cleavage, first; by autolysis By similarity
Amino acid modifications
	Modified residue	776	1	Phosphoserine; by CK2 By similarity
	Modified residue	778	1	Phosphoserine; by CK2 By similarity
	Glycosylation	387	1	N-linked (GlcNAc...) Potential
	Glycosylation	440	1	N-linked (GlcNAc...) Potential
	Glycosylation	553	1	N-linked (GlcNAc...) Potential
	Disulfide bond	211 ↔ 360		By similarity
	Disulfide bond	303 ↔ 333		By similarity
	Disulfide bond	450 ↔ 474		By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q28193-1 [UniParc]. Last modified November 1, 1997. Version 1. Checksum: 466F28EC0246C3D2	FASTA	797	87,251
	10 20 30 40 50 60 MELRPWLFWV VAAAGALVLL VADARGEKVF TNTWAVHIPG GPAVADRVAR KHGFLNLGQI 70 80 90 100 110 120 FGDYYHFWHR AVTKRSLSPH RLGHNRLQRE PQVKWLEQQV AKRRAKRDIY QEPTDPKFPQ 130 140 150 160 170 180 QWYLSGVTQR DLNVKEAWAQ GYTGRGIVVS ILDDGIEKNH PDLAGNYDPG ASFDVNDQDP 190 200 210 220 230 240 DPQPRYTQMN DNRHGTRCAG EVAAVANNGV CGVGVAYNAR IGGVRMLDGE VTDAVEARSL 250 260 270 280 290 300 GLNPNHIHIY SASWGPEDDG KTVDGPAHLA EEAFFRGVSQ GRGGLGSIFV WASGNGGREH 310 320 330 340 350 360 DSCNCDGYTN SIYTLSISSA TQFGNVPWYS EACSSTLATT YSSGNQNEKQ IVTTDLRQKC 370 380 390 400 410 420 TESHTGTSAF APLAAGIIAL TLEANKNLTW RDMQHLVVRT SKPAHLNAND WATNGVGRKV 430 440 450 460 470 480 SHSYGYGLLD AGAMVALAQN WTTVAPQRKC TIDILTEPKD IGKRLEVRKT VTACLGEPSH 490 500 510 520 530 540 ITRLEHAQAR LTLSYNRRGD LAIHLVSPMG TRSTLLAARP HDYSADGFND WAFMTTHSWD 550 560 570 580 590 600 EDPSGEWVLE IENTSEANNY GTLTKFTLVL YGTAPEGLPT PPESIGCKTL TSSQACVVCE 610 620 630 640 650 660 EGFSLHQKNC VQHCPPGFAP QVLDTHYSTE NDVEIIRASV CTPCHASCAT CQGPAPTDCL 670 680 690 700 710 720 SCPSHASLDP VEQTCSRQSQ SSRESHQQQP PPPPRPPPAE VATEPRLRAD LLPSHLPEVV 730 740 750 760 770 780 AGLSCAFIVL VFVTVFLVLQ LRSGFSFRGV KVYTMDRGLI SYKGLPPEAW QEECPSDSEE 790 DEGRGERTAF IKDQSAL

References

[1]

"Maturation of the trans-Golgi network protease furin: compartmentalization of propeptide removal, substrate cleavage, and COOH-terminal truncation." Vey M., Schaefer W., Berghoefer S., Klenk H., Garten W. J. Cell Biol. 127:1829-1842(1994) [PubMed: 7806563] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEOLYTIC PROCESSING. Tissue: Kidney.

Cross-references

Sequence databases
EMBLGenBankDDBJ	X75956 mRNA. Translation: CAA53569.1.
IPI	IPI00685701.
PIR	I46044.
RefSeq	NP_776561.1.
UniGene	Bt.21338
3D structure databases
HSSP	HSSP built from PDB template 1P8J based on UniProtKB P23188.
SMR	Q28193. Positions 109-578.
ModBase	Search...
Protein family/group databases
MEROPS	S08.071.
Genome annotation databases
Ensembl	ENSBTAG00000002939. Bos taurus. [Contig view]
GeneID	281374.
KEGG	bta:281374.
Phylogenomic databases
HOVERGEN	Q28193.
Enzyme and pathway databases
BRENDA	3.4.21.75. 251.
Family and domain databases
InterPro	IPR006212. Furin_repeat. IPR000209. Pept_S8_S53. IPR015500. Peptidase_S8_subtilisin-rel. IPR002884. PrprotnconvertsP. [Graphical view]
Gene3D	G3DSA:3.40.50.200. Pept_S8_S53. 1 hit.
PANTHER	PTHR10795. SubtilSerProt. 1 hit.
Pfam	PF01483. P_proprotein. 1 hit. PF00082. Peptidase_S8. 1 hit. [Graphical view]
PRINTS	PR00723. SUBTILISIN.
ProDom	PD000717. PrprotnconvertsP. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00261. FU. 2 hits. [Graphical view]
PROSITE	PS00136. SUBTILASE_ASP. 1 hit. PS00137. SUBTILASE_HIS. 1 hit. PS00138. SUBTILASE_SER. False negative. [Graphical view]
ProtoNet	Search...
Other Resources
PMAP-CutDB	Q28193.

Entry information

Entry name

FURIN_BOVIN

Accession

Primary (citable) accession number: Q28193

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	June 16, 2009
This is version 82 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)