P23188 (FURIN_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Furin
EC=3.4.21.75

Alternative name(s):
Dibasic-processing enzyme
Paired basic amino acid residue-cleaving enzyme
Short name=PACE
Prohormone convertase 3

Gene names

Name:	Furin
Synonyms:	Fur, Pcsk3

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

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

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	Binds 2 calcium ions per subunit.
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 By similarity. Ref.5
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.
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 Transmembrane helix
Ligand	Calcium Metal-binding
Molecular function	Hydrolase Protease Serine protease
PTM	Autocatalytic cleavage Cleavage on pair of basic residues Disulfide bond Glycoprotein Phosphoprotein Zymogen
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	early endosome Traceable author statement. Source: MGI endoplasmic reticulum lumen Traceable author statement. Source: Reactome extracellular space Inferred from Biological aspect of Ancestor. Source: RefGenome integral to membrane Traceable author statement. Source: MGI plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell trans-Golgi network transport vesicle membrane Traceable author statement. Source: MGI
Molecular function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW serine-type endopeptidase activity Inferred from Biological aspect of Ancestor. Source: RefGenome
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_0000027030

Chain

108 – 793

686

Furin

PRO_0000027031

Regions

Transmembrane

715 – 735

21

Helical; Potential

Region

109 – 445

337

Catalytic

Region

446 – 578

133

P-domain

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

Active site

194

1

Charge relay system

Active site

368

1

Charge relay system

Metal binding

115

1

Calcium 1

Metal binding

162

1

Calcium 1

Metal binding

208

1

Calcium 1

Metal binding

258

1

Calcium 2

Metal binding

301

1

Calcium 2

Metal binding

331

1

Calcium 2

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...)

Glycosylation

440

1

N-linked (GlcNAc...)

Glycosylation

553

1

N-linked (GlcNAc...) Potential

Disulfide bond

211 ↔ 360

Disulfide bond

303 ↔ 333

Disulfide bond

450 ↔ 474

Experimental info

Sequence conflict

746

1

V → M in CAA37988. Ref.1

Secondary structure

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793

Helix Strand Turn

Details...

Helix

118 – 120

3

Turn

122 – 124

3

Helix

135 – 139

5

Beta strand

148 – 154

7

Turn

161 – 163

3

Helix

164 – 166

3

Helix

169 – 171

3

Turn

175 – 178

4

Helix

194 – 203

10

Beta strand

206 – 211

6

Turn

215 – 218

4

Beta strand

219 – 225

7

Beta strand

227 – 229

3

Helix

233 – 240

8

Turn

244 – 246

3

Beta strand

249 – 252

4

Beta strand

259 – 261

3

Helix

268 – 280

13

Helix

282 – 284

3

Beta strand

288 – 292

5

Helix

297 – 299

3

Helix

303 – 305

3

Turn

307 – 310

4

Beta strand

314 – 320

7

Beta strand

338 – 341

4

Beta strand

351 – 355

5

Turn

356 – 358

3

Beta strand

359 – 364

6

Helix

367 – 384

18

Helix

390 – 400

11

Beta strand

419 – 421

3

Turn

422 – 424

3

Helix

431 – 438

8

Beta strand

448 – 455

8

Beta strand

464 – 471

8

Beta strand

482 – 496

15

Helix

498 – 500

3

Beta strand

501 – 506

6

Beta strand

512 – 516

5

Beta strand

528 – 535

8

Turn

537 – 540

4

Beta strand

545 – 553

9

Beta strand

555 – 557

3

Beta strand

561 – 573

13

Sequences

	Sequence		Length	Mass (Da)
	P23188 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: 0F120C2DE2E1A431	FASTA	793	86,772
	10 20 30 40 50 60 MELRSWLLWV VAAAGAVVLL AADAQGQKIF TNTWAVHIPG GPAVADRVAQ KHGFHNLGQI 70 80 90 100 110 120 FGDYYHFWHR AVTKRSLSPH RPRHSRLQRE PQVKWLEQQV AKRRAKRDVY QEPTDPKFPQ 130 140 150 160 170 180 QWYLSGVTQR DLNVKEAWAQ GFTGHGIVVS 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 SKPAHLNADD WATNGVGRKV 430 440 450 460 470 480 SHSYGYGLLD AGAMVALAQN WTTVAPQRKC IVEILVEPKD IGKRLEVRKA VTACLGEPNH 490 500 510 520 530 540 ITRLEHVQAR LTLSYNRRGD LAIHLISPMG TRSTLLAARP HDYSADGFND WAFMTTHSWD 550 560 570 580 590 600 EDPAGEWVLE IENTSEANNY GTLTKFTLVL YGTAPEGLST PPESSGCKTL TSSQACVVCE 610 620 630 640 650 660 EGYSLHQKSC VQHCPPGFIP QVLDTHYSTE NDVEIIRASV CTPCHASCAT CQGPAPTDCL 670 680 690 700 710 720 SCPSHASLDP VEQTCSRQSQ SSRESRPQQQ PPALRPEVEM EPRLQAGLAS HLPEVLAGLS 730 740 750 760 770 780 CLIIVLIFGI VFLFLHRCSG FSFRGVKVYT MDRGLISYKG LPPEAWQEEC PSDSEEDEGR 790 GERTAFIKDQ SAL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure and expression of mouse furin, a yeast Kex2-related protease. Lack of processing of coexpressed prorenin in GH4C1 cells." Hatsuzawa K., Hosaka M., Nakagawa T., Nagase M., Shoda A., Murakami K., Nakayama K. J. Biol. Chem. 265:22075-22078(1990) [PubMed: 2266110] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Cloning and functional expression of a 4.3 kbp mouse fur cDNA: evidence for differential expression." Creemers J.W.M., Roebroek A.J.M., van den Ouweland A.M.W., van Duijnhoven H.L.P., van de Ven W.J.M. Life Sci. Adv. (Mol. Biol.) 11:127-138(1992) Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[3]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Eye.
[5]	"Cytoskeletal protein ABP-280 directs the intracellular trafficking of furin and modulates proprotein processing in the endocytic pathway." Liu G., Thomas L., Warren R.A., Enns C.A., Cunningham C.C., Hartwig J.H., Thomas G. J. Cell Biol. 139:1719-1733(1997) [PubMed: 9412467] [Abstract] Cited for: INTERACTION WITH FLNA.
[6]	"The crystal structure of the proprotein processing proteinase furin explains its stringent specificity." Henrich S., Cameron A., Bourenkov G.P., Kiefersauer R., Huber R., Lindberg I., Bode W., Than M.E. Nat. Struct. Biol. 10:520-526(2003) [PubMed: 12794637] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 108-578 IN COMPLEX WITH INHIBITOR.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X54056 mRNA. Translation: CAA37988.1.
L26489 mRNA. Translation: AAA37643.1.
CH466543 Genomic DNA. Translation: EDL06988.1.
BC048234 mRNA. Translation: AAH48234.1.

IPI

IPI00314624.

PIR

KXMSF. A23679.

RefSeq

NP_001074923.1. NM_001081454.1.
NP_035176.1. NM_011046.2.

UniGene

Mm.5241.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1P8J	X-ray	2.60	A/B/C/D/E/F/G/H	108-578	[»]

ProteinModelPortal

P23188.

SMR

P23188. Positions 30-100, 109-578, 594-681.

ModBase

Search...

Protein-protein interaction databases

STRING

P23188.

Protein family/group databases

MEROPS

S08.071.

PTM databases

PhosphoSite

P23188.

Proteomic databases

PRIDE

P23188.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000107362; ENSMUSP00000102985; ENSMUSG00000030530.
ENSMUST00000120753; ENSMUSP00000113793; ENSMUSG00000030530.
ENSMUST00000122232; ENSMUSP00000113370; ENSMUSG00000030530.

GeneID

18550.

KEGG

mmu:18550.

Organism-specific databases

CTD

5045.

MGI

MGI:97513. Furin.

Phylogenomic databases

eggNOG

roNOG10014.

HOGENOM

HBG715943.

HOVERGEN

HBG008705.

InParanoid

P23188.

OrthoDB

EOG4ZW59M.

PhylomeDB

P23188.

Enzyme and pathway databases

Reactome

REACT_115202. Signal Transduction.

Gene expression databases

ArrayExpress

P23188.

Bgee

P23188.

CleanEx

MM_FURIN.

Genevestigator

P23188.

GermOnline

ENSMUSG00000030530. Mus musculus.

Family and domain databases

InterPro

IPR006212. Furin_repeat.
IPR008979. Galactose-bd-like.
IPR009030. Growth_fac_rcpt.
IPR000209. Peptidase_S8/S53.
IPR023827. Peptidase_S8_Asp-AS.
IPR022398. Peptidase_S8_His-AS.
IPR023828. Peptidase_S8_Ser-AS.
IPR015500. Peptidase_S8_subtilisin-rel.
IPR009020. Prot_inh_propept.
IPR002884. PrprotnconvertsP.
[Graphical view]

Gene3D

G3DSA:3.40.50.200. Pept_S8_S53. 1 hit.

KO

K01349.

PANTHER

PTHR10795. SubtilSerProt. 1 hit.

Pfam

PF01483. P_proprotein. 1 hit.
PF00082. Peptidase_S8. 1 hit.
[Graphical view]

PRINTS

PR00723. SUBTILISIN.

SMART

SM00261. FU. 2 hits.
[Graphical view]

SUPFAM

SSF49785. Gal_bind_like. 1 hit.
SSF57184. Grow_fac_recept. 1 hit.
SSF52743. Pept_S8_S53. 1 hit.
SSF54897. Prot_inh_propept. 1 hit.

PROSITE

PS00136. SUBTILASE_ASP. 1 hit.
PS00137. SUBTILASE_HIS. 1 hit.
PS00138. SUBTILASE_SER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

SOURCE

Search...

Entry information

Entry name

FURIN_MOUSE

Accession

Primary (citable) accession number: P23188
Secondary accession number(s): Q6GTN6

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1991
Last sequence update:	July 27, 2011
Last modified:	November 16, 2011
This is version 121 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program