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Protein

Neuroendocrine convertase 1

Gene

PCSK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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, insulin and AGRP.By similarity

Catalytic activityi

Release of protein hormones, neuropeptides and renin from their precursors, generally by hydrolysis of -Lys-Arg-|- bonds.

Cofactori

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei167Charge relay systemBy similarity1
Active sitei208Charge relay systemBy similarity1
Active sitei382Charge relay systemBy similarity1

GO - Molecular functioni

GO - Biological processi

  • cell-cell signaling Source: ProtInc
  • peptide biosynthetic process Source: BHF-UCL
  • peptide hormone processing Source: Reactome
  • proteolysis Source: ProtInc

Keywordsi

Molecular functionHydrolase, Protease, Serine protease
LigandCalcium

Enzyme and pathway databases

ReactomeiR-HSA-209952 Peptide hormone biosynthesis
R-HSA-264876 Insulin processing
R-HSA-381771 Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)
R-HSA-400511 Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP)
R-HSA-422085 Synthesis, secretion, and deacylation of Ghrelin
SignaLinkiP29120
SIGNORiP29120

Protein family/group databases

MEROPSiS08.072

Names & Taxonomyi

Protein namesi
Recommended name:
Neuroendocrine convertase 1 (EC:3.4.21.93)
Short name:
NEC 1
Alternative name(s):
Prohormone convertase 1
Proprotein convertase 1
Short name:
PC1
Gene namesi
Name:PCSK1
Synonyms:NEC1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000175426.10
HGNCiHGNC:8743 PCSK1
MIMi162150 gene
neXtProtiNX_P29120

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasmic vesicle

Pathology & Biotechi

Involvement in diseasei

Proprotein convertase 1 deficiency (PC1 deficiency)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionCharacterized by obesity, hypogonadism, hypoadrenalism, reactive hypoglycemia as well as marked small-intestinal absorptive dysfunction It is due to impaired processing of prohormones.
See also OMIM:600955
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_022777213Missing in PC1 deficiency. 1 Publication1
Natural variantiVAR_055002307S → L in PC1 deficiency; in vitro the mutation markedly impairs the catalytic activity of the enzyme; however intracellular trafficking of this mutant enzyme appears normal; retains some autocatalytic activity even though it is completely inactive on other substrates. 1 PublicationCorresponds to variant dbSNP:rs137852824EnsemblClinVar.1
Natural variantiVAR_022778483G → R in PC1 deficiency; prevents processing of pro-PCSK1 and leads to its retention in the endoplasmic reticulum. 1 PublicationCorresponds to variant dbSNP:rs137852821EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Obesity

Organism-specific databases

DisGeNETi5122
MalaCardsiPCSK1
MIMi600955 phenotype
612362 phenotype
OpenTargetsiENSG00000175426
Orphaneti71528 Obesity due to prohormone convertase I deficiency
PharmGKBiPA33089

Chemistry databases

ChEMBLiCHEMBL3182
DrugBankiDB00030 Insulin Human
DB00071 Insulin Pork
GuidetoPHARMACOLOGYi2382

Polymorphism and mutation databases

BioMutaiPCSK1
DMDMi116242674

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 27Sequence analysisAdd BLAST27
PropeptideiPRO_000002705728 – 110Sequence analysisAdd BLAST83
ChainiPRO_0000027058111 – 753Neuroendocrine convertase 1Add BLAST643

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi173N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi225 ↔ 374By similarity
Disulfide bondi317 ↔ 347By similarity
Glycosylationi401N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi467 ↔ 494By similarity
Glycosylationi632O-linked (GalNAc...) threonine1 Publication1

Post-translational modificationi

O-glycosylated.1 Publication

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

EPDiP29120
PaxDbiP29120
PeptideAtlasiP29120
PRIDEiP29120

PTM databases

GlyConnecti673
iPTMnetiP29120
PhosphoSitePlusiP29120
UniCarbKBiP29120

Miscellaneous databases

PMAP-CutDBP29120

Expressioni

Gene expression databases

BgeeiENSG00000175426
CleanExiHS_PCSK1
ExpressionAtlasiP29120 baseline and differential
GenevisibleiP29120 HS

Organism-specific databases

HPAiHPA048564

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111151, 8 interactors
IntActiP29120, 1 interactor
STRINGi9606.ENSP00000308024

Chemistry databases

BindingDBiP29120

Structurei

3D structure databases

ProteinModelPortaliP29120
SMRiP29120
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini162 – 451Peptidase S8Add BLAST290
Domaini460 – 597P/Homo BPROSITE-ProRule annotationAdd BLAST138

Sequence similaritiesi

Belongs to the peptidase S8 family. Furin subfamily.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3525 Eukaryota
COG1404 LUCA
COG4935 LUCA
GeneTreeiENSGT00750000117358
HOGENOMiHOG000192536
HOVERGENiHBG008705
InParanoidiP29120
KOiK01359
OMAiFEPRALK
OrthoDBiEOG091G05HI
PhylomeDBiP29120
TreeFamiTF314277

Family and domain databases

CDDicd04059 Peptidases_S8_Protein_converta, 1 hit
Gene3Di2.60.120.260, 1 hit
3.30.70.850, 1 hit
3.40.50.200, 1 hit
InterProiView protein in InterPro
IPR008979 Galactose-bd-like_sf
IPR034182 Kexin/furin
IPR002884 P_dom
IPR000209 Peptidase_S8/S53_dom
IPR036852 Peptidase_S8/S53_dom_sf
IPR023827 Peptidase_S8_Asp-AS
IPR022398 Peptidase_S8_His-AS
IPR023828 Peptidase_S8_Ser-AS
IPR015500 Peptidase_S8_subtilisin-rel
IPR022005 Proho_convert
IPR032815 S8_pro-domain
IPR038466 S8_pro-domain_sf
PfamiView protein in Pfam
PF01483 P_proprotein, 1 hit
PF00082 Peptidase_S8, 1 hit
PF12177 Proho_convert, 1 hit
PF16470 S8_pro-domain, 1 hit
PRINTSiPR00723 SUBTILISIN
SUPFAMiSSF49785 SSF49785, 1 hit
SSF52743 SSF52743, 1 hit
PROSITEiView protein in PROSITE
PS51829 P_HOMO_B, 1 hit
PS00136 SUBTILASE_ASP, 1 hit
PS00137 SUBTILASE_HIS, 1 hit
PS00138 SUBTILASE_SER, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P29120-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MERRAWSLQC TAFVLFCAWC ALNSAKAKRQ FVNEWAAEIP GGPEAASAIA
60 70 80 90 100
EELGYDLLGQ IGSLENHYLF KHKNHPRRSR RSAFHITKRL SDDDRVIWAE
110 120 130 140 150
QQYEKERSKR SALRDSALNL FNDPMWNQQW YLQDTRMTAA LPKLDLHVIP
160 170 180 190 200
VWQKGITGKG VVITVLDDGL EWNHTDIYAN YDPEASYDFN DNDHDPFPRY
210 220 230 240 250
DPTNENKHGT RCAGEIAMQA NNHKCGVGVA YNSKVGGIRM LDGIVTDAIE
260 270 280 290 300
ASSIGFNPGH VDIYSASWGP NDDGKTVEGP GRLAQKAFEY GVKQGRQGKG
310 320 330 340 350
SIFVWASGNG GRQGDNCDCD GYTDSIYTIS ISSASQQGLS PWYAEKCSST
360 370 380 390 400
LATSYSSGDY TDQRITSADL HNDCTETHTG TSASAPLAAG IFALALEANP
410 420 430 440 450
NLTWRDMQHL VVWTSEYDPL ANNPGWKKNG AGLMVNSRFG FGLLNAKALV
460 470 480 490 500
DLADPRTWRS VPEKKECVVK DNDFEPRALK ANGEVIIEIP TRACEGQENA
510 520 530 540 550
IKSLEHVQFE ATIEYSRRGD LHVTLTSAAG TSTVLLAERE RDTSPNGFKN
560 570 580 590 600
WDFMSVHTWG ENPIGTWTLR ITDMSGRIQN EGRIVNWKLI LHGTSSQPEH
610 620 630 640 650
MKQPRVYTSY NTVQNDRRGV EKMVDPGEEQ PTQENPKENT LVSKSPSSSS
660 670 680 690 700
VGGRRDELEE GAPSQAMLRL LQSAFSKNSP PKQSPKKSPS AKLNIPYENF
710 720 730 740 750
YEALEKLNKP SQLKDSEDSL YNDYVDVFYN TKPYKHRDDR LLQALVDILN

EEN
Length:753
Mass (Da):84,152
Last modified:October 17, 2006 - v2
Checksum:iD3CBD1B92093A208
GO
Isoform 2 (identifier: P29120-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-59: MERRAWSLQCTAFVLFCAWCALNSAKAKRQFVNEWAAEIPGGPEAASAIAEELGYDLLG → MGKGSISFLFFS

Note: No experimental confirmation available.
Show »
Length:706
Mass (Da):79,010
Checksum:iF082971DADE9EAAC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti357S → G in CAA46031 (PubMed:1547893).Curated1
Sequence conflicti370 – 371LH → VD in BAA11133 (PubMed:8666140).Curated2
Sequence conflicti617R → G in BAH14073 (PubMed:14702039).Curated1

Polymorphismi

Genetic variations in PCSK1 define the body mass index quantitative trait locus 12 (BMIQ12) [MIMi:612362]. Variance in body mass index is a susceptibility factor for obesity.1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01390680R → Q1 PublicationCorresponds to variant dbSNP:rs1799904Ensembl.1
Natural variantiVAR_022777213Missing in PC1 deficiency. 1 Publication1
Natural variantiVAR_013907221N → D Associated with susceptibility to obesity; induces a 10.4% reduction of activity (P = 0.03) when compared to the wild-type enzyme. 2 PublicationsCorresponds to variant dbSNP:rs6232EnsemblClinVar.1
Natural variantiVAR_055002307S → L in PC1 deficiency; in vitro the mutation markedly impairs the catalytic activity of the enzyme; however intracellular trafficking of this mutant enzyme appears normal; retains some autocatalytic activity even though it is completely inactive on other substrates. 1 PublicationCorresponds to variant dbSNP:rs137852824EnsemblClinVar.1
Natural variantiVAR_022778483G → R in PC1 deficiency; prevents processing of pro-PCSK1 and leads to its retention in the endoplasmic reticulum. 1 PublicationCorresponds to variant dbSNP:rs137852821EnsemblClinVar.1
Natural variantiVAR_013908665Q → E3 PublicationsCorresponds to variant dbSNP:rs6234EnsemblClinVar.1
Natural variantiVAR_013909690S → T2 PublicationsCorresponds to variant dbSNP:rs6235EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0461001 – 59MERRA…YDLLG → MGKGSISFLFFS in isoform 2. 1 PublicationAdd BLAST59

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X64810 mRNA Translation: CAA46031.1
M90753 mRNA Translation: AAA59918.1
D73407 Genomic DNA Translation: BAA11133.1
AK303888 mRNA Translation: BAH14073.1
AC008951 Genomic DNA No translation available.
AC108107 Genomic DNA No translation available.
U24128 Genomic DNA Translation: AAA73788.1
CCDSiCCDS4081.1 [P29120-1]
CCDS54881.1 [P29120-2]
PIRiS21106 KXHUC1
RefSeqiNP_000430.3, NM_000439.4 [P29120-1]
NP_001171346.1, NM_001177875.1 [P29120-2]
UniGeneiHs.78977

Genome annotation databases

EnsembliENST00000311106; ENSP00000308024; ENSG00000175426 [P29120-1]
ENST00000508626; ENSP00000421600; ENSG00000175426 [P29120-2]
GeneIDi5122
KEGGihsa:5122
UCSCiuc003kls.3 human [P29120-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNEC1_HUMAN
AccessioniPrimary (citable) accession number: P29120
Secondary accession number(s): B7Z8T7
, E9PHA1, P78478, Q92532
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: October 17, 2006
Last modified: April 25, 2018
This is version 179 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health