P63239 (NEC1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Neuroendocrine convertase 1
Short name=NEC 1
EC=3.4.21.93

Alternative name(s):
Furin homolog
PC3
Prohormone convertase 1
Propeptide-processing protease
Proprotein convertase 1
Short name=PC1

Gene names

Name:	Pcsk1
Synonyms:	Att-1, Nec-1, Nec1

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	753 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	Involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues. Substrates include POMC, renin, enkephalin, dynorphin, somatostatin and insulin.
Catalytic activity	Release of protein hormones, neuropeptides and renin from their precursors, generally by hydrolysis of -Lys-Arg-|- bonds.
Cofactor	Calcium.
Subcellular location	Cytoplasmic vesicle › secretory vesicle. Note: Localized in the secretion granules.
Sequence similarities	Belongs to the peptidase S8 family. Furin subfamily.
Biophysicochemical properties	pH dependence: Optimum pH is 5.5-6.5.

Ontologies

Keywords
Cellular component	Cytoplasmic vesicle
Domain	Signal
Ligand	Calcium
Molecular function	Hydrolase Protease Serine protease
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	peptide biosynthetic process Inferred from direct assay PubMed 8262946. Source: BHF-UCL peptide hormone processing Inferred from direct assay PubMed 8262946PubMed 9242664. Source: BHF-UCL proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	Golgi apparatus Inferred from Biological aspect of Ancestor. Source: RefGenome endoplasmic reticulum lumen Traceable author statement. Source: Reactome extracellular space Inferred from direct assay PubMed 8397508. Source: BHF-UCL secretory granule Traceable author statement. Source: Reactome transport vesicle Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	serine-type endopeptidase activity Inferred from direct assay PubMed 8262946. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 27

27

Potential

Propeptide

28 – 110

83

Potential

PRO_0000027059

Chain

111 – 753

643

Neuroendocrine convertase 1

PRO_0000027060

Regions

Region

122 – 410

289

Catalytic

Region

739 – 751

13

Amphipathic Potential

Sites

Active site

167

1

Charge relay system By similarity

Active site

208

1

Charge relay system By similarity

Active site

382

1

Charge relay system By similarity

Amino acid modifications

Glycosylation

401

1

N-linked (GlcNAc...) Potential

Glycosylation

645

1

N-linked (GlcNAc...) Potential

Disulfide bond

225 ↔ 374

By similarity

Disulfide bond

317 ↔ 347

By similarity

Disulfide bond

467 ↔ 494

By similarity

Experimental info

Sequence conflict

112

1

V → F in CAA40368. Ref.2

Sequence conflict

117

1

A → P in CAA40368. Ref.2

Sequence conflict

122

1

N → T in CAA40368. Ref.2

Sequence conflict

128

1

Q → H in CAA40368. Ref.2

Sequence conflict

282

1

R → K in CAA40368. Ref.2

Sequence conflict

330

1

S → L in AAA39375. Ref.3

Sequence conflict

732

1

K → E in CAA40368. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

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.

.

.

.

.

.

.

.

.

.

.

.

.

753

Helix Strand Turn

Details...

Beta strand

35 – 38

4

Helix

43 – 53

11

Beta strand

62 – 65

4

Beta strand

67 – 71

5

Beta strand

77 – 79

3

Helix

89 – 94

6

Beta strand

97 – 100

4

Beta strand

713 – 716

4

Beta strand

718 – 721

4

Helix

722 – 726

5

Turn

727 – 730

4

Helix

741 – 748

8

Turn

749 – 751

3

Sequences

	Sequence		Length	Mass (Da)
	P63239 [UniParc]. Last modified October 11, 2004. Version 1. Checksum: 04239C7B6385382E	FASTA	753	84,174
	10 20 30 40 50 60 MEQRGWTLQC TAFAFFCVWC ALNSVKAKRQ FVNEWAAEIP GGQEAASAIA EELGYDLLGQ 70 80 90 100 110 120 IGSLENHYLF KHKSHPRRSR RSALHITKRL SDDDRVTWAE QQYEKERSKR SVQKDSALDL 130 140 150 160 170 180 FNDPMWNQQW YLQDTRMTAA LPKLDLHVIP VWEKGITGKG VVITVLDDGL EWNHTDIYAN 190 200 210 220 230 240 YDPEASYDFN DNDHDPFPRY DLTNENKHGT RCAGEIAMQA NNHKCGVGVA YNSKVGGIRM 250 260 270 280 290 300 LDGIVTDAIE ASSIGFNPGH VDIYSASWGP NDDGKTVEGP GRLAQKAFEY GVKQGRQGKG 310 320 330 340 350 360 SIFVWASGNG GRQGDNCDCD GYTDSIYTIS ISSASQQGLS PWYAEKCSST LATSYSSGDY 370 380 390 400 410 420 TDQRITSADL HNDCTETHTG TSASAPLAAG IFALALEANP NLTWRDMQHL VVWTSEYDPL 430 440 450 460 470 480 ASNPGWKKNG AGLMVNSRFG FGLLNAKALV DLADPRTWRN VPEKKECVVK DNNFEPRALK 490 500 510 520 530 540 ANGEVIVEIP TRACEGQENA IKSLEHVQFE ATIEYSRRGD LHVTLTSAVG TSTVLLAERE 550 560 570 580 590 600 RDTSPNGFKN WDFMSVHTWG ENPVGTWTLK ITDMSGRMQN EGRIVNWKLI LHGTSSQPEH 610 620 630 640 650 660 MKQPRVYTSY NTVQNDRRGV EKMVNVVEKR PTQKSLNGNL LVPKNSSSSN VEGRRDEQVQ 670 680 690 700 710 720 GTPSKAMLRL LQSAFSKNAL SKQSPKKSPS AKLSIPYESF YEALEKLNKP SKLEGSEDSL 730 740 750 YSDYVDVFYN TKPYKHRDDR LLQALMDILN EEN

References

[1]	"Isolation and functional expression of a mammalian prohormone processing enzyme, murine prohormone convertase 1." Korner J., Chun J., Harter D., Axel R. Proc. Natl. Acad. Sci. U.S.A. 88:6834-6838(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Pituitary.
[2]	"Cloning and functional expression of a novel endoprotease involved in prohormone processing at dibasic sites." Nakayama K., Hosaka M., Hatsuzawa K., Murakami K. J. Biochem. 109:803-806(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: LAF1.
[3]	"Cloning and primary sequence of a mouse candidate prohormone convertase PC1 homologous to PC2, Furin, and Kex2: distinct chromosomal localization and messenger RNA distribution in brain and pituitary compared to PC2." Seidah N.G., Marcinkiewicz M., Benjannet S., Gaspar L., Beaubien G., Mattei M.-G., Lazure C., Mbikay M., Chretien M. Mol. Endocrinol. 5:111-122(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: BALB/c. Tissue: Pituitary.
[4]	"Purification and characterization of the prohormone convertase PC1(PC3)." Zhou Y., Lindberg I. J. Biol. Chem. 268:5615-5623(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 111-120. Tissue: Ovary.
[5]	"cDNA sequence of two distinct pituitary proteins homologous to Kex2 and furin gene products: tissue-specific mRNAs encoding candidates for pro-hormone processing proteinases." Seidah N.G., Gaspar L., Mion P., Marcinkiewicz M., Mbikay M., Chretien M. DNA Cell Biol. 9:415-424(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 214-478. Tissue: Pituitary.
[6]	Erratum Seidah N.G., Gaspar L., Mion P., Marcinkiewicz M., Mbikay M., Chretien M. DNA Cell Biol. 9:789-789(1990) [PubMed] [Europe PMC] [Abstract]
[7]	"Solution structure of the pro-hormone convertase 1 pro-domain from Mus musculus." Tangrea M.A., Bryan P.N., Sari N., Orban J. J. Mol. Biol. 320:801-812(2002) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 28-110.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M69196 mRNA. Translation: AAA39732.1.
X57088 mRNA. Translation: CAA40368.1.
M58589 mRNA. Translation: AAA39894.1.
M55668 mRNA. Translation: AAA39375.1. Sequence problems.

IPI

IPI00470989.

PIR

KXMSC1. JX0171.

RefSeq

NP_038656.1. NM_013628.2.

UniGene

Mm.1333.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1KN6	NMR	-	A	28-110	[»]
2KDT	NMR	-	A	711-753	[»]
2KE3	NMR	-	A	711-753	[»]

ProteinModelPortal

P63239.

SMR

P63239. Positions 31-103, 123-597, 711-753.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-48841N.

Protein family/group databases

MEROPS

S08.072.

PTM databases

PhosphoSite

P63239.

Proteomic databases

PaxDb

P63239.

PRIDE

P63239.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000022075; ENSMUSP00000022075; ENSMUSG00000021587.

GeneID

18548.

KEGG

mmu:18548.

Organism-specific databases

CTD

5122.

MGI

MGI:97511. Pcsk1.

Phylogenomic databases

eggNOG

COG4935.

HOGENOM

HOG000192536.

HOVERGEN

HBG008705.

InParanoid

P63239.

KO

K01359.

OMA

NNPGWKK.

OrthoDB

EOG4K3KVR.

Enzyme and pathway databases

Reactome

REACT_112621. Metabolism.
REACT_115202. Signal Transduction.

Gene expression databases

ArrayExpress

P63239.

Bgee

P63239.

CleanEx

MM_PCSK1.

Genevestigator

P63239.

GermOnline

ENSMUSG00000021587. Mus musculus.

Family and domain databases

Gene3D

3.40.50.200. 1 hit.

InterPro

IPR008979. Galactose-bd-like.
IPR000209. Peptidase_S8/S53_dom.
IPR023827. Peptidase_S8_Asp-AS.
IPR022398. Peptidase_S8_His-AS.
IPR023828. Peptidase_S8_Ser-AS.
IPR015500. Peptidase_S8_subtilisin-rel.
IPR022005. Proho_convert.
IPR009020. Prot_inh_propept.
IPR002884. PrprotnconvertsP.
[Graphical view]

PANTHER

PTHR10795. PTHR10795. 1 hit.

Pfam

PF01483. P_proprotein. 1 hit.
PF00082. Peptidase_S8. 1 hit.
PF12177. Proho_convert. 1 hit.
[Graphical view]

PRINTS

PR00723. SUBTILISIN.

SUPFAM

SSF49785. Gal_bind_like. 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

EvolutionaryTrace

P63239.

NextBio

294338.

PMAP-CutDB

P63239.

SOURCE

Search...

Entry information

Entry name

NEC1_MOUSE

Accession

Primary (citable) accession number: P63239
Secondary accession number(s): P21662, P22546

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 11, 2004
Last sequence update:	October 11, 2004
Last modified:	May 1, 2013
This is version 85 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program