Reviewed, UniProtKB/Swiss-Prot P23377 (FURIN_RAT)

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
    Prohormone convertase 3

Gene names

Name:	Furin
Synonyms:	Fur, Pcsk3

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	793 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 By similarity. Binds to PACS1 which mediates TGN localization and connection to clathrin adapters.
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 By similarity.
Tissue specificity	Seems to be expressed ubiquitously.
Developmental stage	Expressed at E7 day in endoderm and mesoderm, uniformly expressed until E10, when expression is higher in heart and liver primordia. In mid- and late-gestational stages, widely expressed.
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 By similarity. 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	positive regulation of cell migration Inferred from mutant phenotype. Source: RGD positive regulation of transforming growth factor beta receptor signaling pathway Inferred from mutant phenotype. Source: RGD protein processing Inferred from direct assay. Source: RGD proteolysis Inferred from electronic annotation. Source: InterPro
Cellular component	Golgi cisterna Inferred from direct assay. Source: RGD endoplasmic reticulum membrane Inferred from direct assay. Source: RGD integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from direct assay. Source: RGD
Molecular function	calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW serine-type endopeptidase activity Inferred from mutant phenotype. Source: RGD
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_0000027032
	Chain	108 – 793	686	Furin		PRO_0000027033
Regions
	Transmembrane	715 – 735	21	Potential
	Region	758 – 761	4	Cell surface signal
	Motif	498 – 500	3	Cell attachment site Potential
	Motif	772 – 778	7	Trans Golgi network signal
	Compositional bias	556 – 705	150	Cys-rich
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	772	1	Phosphoserine; by CK2 By similarity
	Modified residue	774	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)
	P23377-1 [UniParc]. Last modified November 1, 1991. Version 1. Checksum: 87C22C345AE0A25C	FASTA	793	86,653
	10 20 30 40 50 60 MELRPWLLWV VAAAGALVLL AAEARGQKIF TNTWAVHISG GPAVADSVAR KHGFHNLGQI 70 80 90 100 110 120 FGDYYHFWHR AVTKRSLSPH RPRHSRLQRV PQVKWLEQQV AKQRAKRDVY QEPTDPKFPQ 130 140 150 160 170 180 QWYLSGVTQR DLNVKEAWAQ GFTGRGIVVS ILDDGIEKNH PDLAGNYDPG ASFDVNDQDP 190 200 210 220 230 240 DPQPRYTQMN DNRHGTRCAG EVAAVANNGV CGVGVAYNAR IGGVRMLDGE VTDAVEARSL 250 260 270 280 290 300 GLNPNHIHIY SASWGPEDDG KTVDGPARLA EEAFFRGVSQ GRGGLGSIFV WASGNGGREH 310 320 330 340 350 360 DSCNCDGYTN SIYTLSISSA TQFGNVPWYS EACSSTLATT YSSGNQNEKQ IVTTDLRQKC 370 380 390 400 410 420 TESHTGTSAS APLAAGIIAL TLEANKNLTW RDMQHLVVQT SKPAHLNAND WATNGVGRKV 430 440 450 460 470 480 SHSYGYGLLD AGAMVALAQN WTTVAPQRKC IIEILAEPKD IGKRLEVRKT VTACLGEPNH 490 500 510 520 530 540 ISRLEHVQAR LTLSYNRRGD LAIHLISPMG TRSTLLAARP HDYSADGFND WAFMTTHSWD 550 560 570 580 590 600 EDPSGEWVLE IENTSEANNY GTLTKFTLVL YGTASEGLSA PPESSGCKTL TSSQACVVCE 610 620 630 640 650 660 EGFSLHQKSC VQRCPPGFTP QVLDTHYSTE NDVEIIRASV CTPCHASCAT CQGPAPTDCL 670 680 690 700 710 720 SCPSHASLDP VEQTCSRQSQ SSRESRPQQP PPALRPEVEV EPRLRAGLAS HLPEVLAGLS 730 740 750 760 770 780 CLIIALIFGI VFLFLHRCSG FSFRGVKVYT MDRGLISYKG LPPEAWQEEC PSDSEEDEGR 790 GERTAFIKDQ SAL

References

[1]	"Sequence of the cDNA encoding rat furin, a possible propeptide-processing endoprotease." Misumi Y., Sohoda M., Ikehara Y. Nucleic Acids Res. 18:6719-6719(1990) [PubMed: 2251148] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Wistar. Tissue: Liver.
[2]	"PACS-1 defines a novel gene family of cytosolic sorting proteins required for trans-Golgi network localization." Wan L., Molloy S.S., Thomas L., Liu G., Xiang Y., Rybak S.L., Thomas G. Cell 94:205-216(1998) [PubMed: 9695949] [Abstract] Cited for: INTERACTION WITH PACS1. Tissue: Brain.

Cross-references

Sequence databases
EMBLGenBankDDBJ	X55660 mRNA. Translation: CAA39193.1.
IPI	IPI00210230.
PIR	KXRTF. S13106.
RefSeq	NP_062204.1.
UniGene	Rn.3220
3D structure databases
HSSP	HSSP built from PDB template 1P8J based on UniProtKB P23188.
SMR	P23377. Positions 109-578.
ModBase	Search...
Protein family/group databases
MEROPS	S08.071.
Proteomic databases
PRIDE	P23377.
Genome annotation databases
Ensembl	ENSRNOG00000011352. Rattus norvegicus. [Contig view]
GeneID	54281.
KEGG	rno:54281.
Organism-specific databases
RGD	3274. Furin.
Phylogenomic databases
HOVERGEN	P23377.
Enzyme and pathway databases
BRENDA	3.4.21.75. 248.
Gene expression databases
ArrayExpress	P23377.
GermOnline	ENSRNOG00000011352. Rattus norvegicus.
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. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	610854.

Entry information

Entry name

FURIN_RAT

Accession

Primary (citable) accession number: P23377

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1991
Last sequence update:	November 1, 1991
Last modified:	June 16, 2009
This is version 93 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)