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Protein

Neuroendocrine convertase 1

Gene

PCSK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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)LengthDescriptionGraphical viewFeature identifierActions
Active sitei167 – 1671Charge relay systemBy similarity
Active sitei208 – 2081Charge relay systemBy similarity
Active sitei382 – 3821Charge relay systemBy similarity

GO - Molecular functioni

GO - Biological processi

  • cell-cell signaling Source: ProtInc
  • metabolic process Source: ProtInc
  • peptide biosynthetic process Source: BHF-UCL
  • peptide hormone processing Source: Reactome
  • protein processing Source: GO_Central
  • proteolysis Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Keywords - Ligandi

Calcium

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.

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

HGNCiHGNC:8743. PCSK1.

Subcellular locationi

GO - Cellular componenti

  • extracellular space Source: BHF-UCL
  • secretory granule lumen Source: Reactome
  • transport vesicle Source: UniProtKB-SubCell
Complete GO annotation...

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti213 – 2131Missing in PC1 deficiency. 1 Publication
VAR_022777
Natural varianti307 – 3071S → 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 Publication
Corresponds to variant rs137852824 [ dbSNP | Ensembl ].
VAR_055002
Natural varianti483 – 4831G → R in PC1 deficiency; prevents processing of pro-PCSK1 and leads to its retention in the endoplasmic reticulum. 1 Publication
Corresponds to variant rs137852821 [ dbSNP | Ensembl ].
VAR_022778

Keywords - Diseasei

Disease mutation, Obesity

Organism-specific databases

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

Chemistry

ChEMBLiCHEMBL3182.
DrugBankiDB00030. Insulin Regular.
GuidetoPHARMACOLOGYi2382.

Polymorphism and mutation databases

BioMutaiPCSK1.
DMDMi116242674.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2727Sequence analysisAdd
BLAST
Propeptidei28 – 11083Sequence analysisPRO_0000027057Add
BLAST
Chaini111 – 753643Neuroendocrine convertase 1PRO_0000027058Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi173 – 1731N-linked (GlcNAc...)Sequence analysis
Disulfide bondi225 ↔ 374By similarity
Disulfide bondi317 ↔ 347By similarity
Glycosylationi401 – 4011N-linked (GlcNAc...)Sequence analysis
Disulfide bondi467 ↔ 494By similarity
Glycosylationi632 – 6321O-linked (GalNAc...)1 Publication

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

iPTMnetiP29120.
PhosphoSiteiP29120.
UniCarbKBiP29120.

Miscellaneous databases

PMAP-CutDBP29120.

Expressioni

Gene expression databases

BgeeiENSG00000175426.
CleanExiHS_PCSK1.
ExpressionAtlasiP29120. baseline and differential.
GenevisibleiP29120. HS.

Organism-specific databases

HPAiHPA048564.

Interactioni

Protein-protein interaction databases

BioGridi111151. 2 interactions.
MINTiMINT-6630348.
STRINGi9606.ENSP00000308024.

Chemistry

BindingDBiP29120.

Structurei

3D structure databases

ProteinModelPortaliP29120.
SMRiP29120. Positions 31-103, 123-595, 711-753.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini162 – 451290Peptidase S8Add
BLAST

Sequence similaritiesi

Belongs to the peptidase S8 family. Furin subfamily.Curated
Contains 1 peptidase S8 domain.Curated

Keywords - Domaini

Signal

Phylogenomic databases

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

Family and domain databases

Gene3Di2.60.120.260. 1 hit.
3.30.70.850. 1 hit.
3.40.50.200. 1 hit.
InterProiIPR008979. 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. Propept_inh.
IPR002884. PrprotnconvertsP.
IPR032815. S8_pro-domain.
[Graphical view]
PANTHERiPTHR10795. PTHR10795. 1 hit.
PfamiPF01483. P_proprotein. 1 hit.
PF00082. Peptidase_S8. 1 hit.
PF12177. Proho_convert. 1 hit.
PF16470. S8_pro-domain. 1 hit.
[Graphical view]
PRINTSiPR00723. SUBTILISIN.
SUPFAMiSSF49785. SSF49785. 1 hit.
SSF52743. SSF52743. 1 hit.
SSF54897. SSF54897. 1 hit.
PROSITEiPS00136. SUBTILASE_ASP. 1 hit.
PS00137. SUBTILASE_HIS. 1 hit.
PS00138. SUBTILASE_SER. 1 hit.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti357 – 3571S → G in CAA46031 (PubMed:1547893).Curated
Sequence conflicti370 – 3712LH → VD in BAA11133 (PubMed:8666140).Curated
Sequence conflicti617 – 6171R → G in BAH14073 (PubMed:14702039).Curated

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti80 – 801R → Q.1 Publication
Corresponds to variant rs1799904 [ dbSNP | Ensembl ].
VAR_013906
Natural varianti213 – 2131Missing in PC1 deficiency. 1 Publication
VAR_022777
Natural varianti221 – 2211N → D Associated with susceptibility to obesity; induces a 10.4% reduction of activity (P = 0.03) when compared to the wild-type enzyme. 2 Publications
Corresponds to variant rs6232 [ dbSNP | Ensembl ].
VAR_013907
Natural varianti307 – 3071S → 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 Publication
Corresponds to variant rs137852824 [ dbSNP | Ensembl ].
VAR_055002
Natural varianti483 – 4831G → R in PC1 deficiency; prevents processing of pro-PCSK1 and leads to its retention in the endoplasmic reticulum. 1 Publication
Corresponds to variant rs137852821 [ dbSNP | Ensembl ].
VAR_022778
Natural varianti665 – 6651Q → E.3 Publications
Corresponds to variant rs6234 [ dbSNP | Ensembl ].
VAR_013908
Natural varianti690 – 6901S → T.2 Publications
Corresponds to variant rs6235 [ dbSNP | Ensembl ].
VAR_013909

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 5959MERRA…YDLLG → MGKGSISFLFFS in isoform 2. 1 PublicationVSP_046100Add
BLAST

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

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliP29120.
SMRiP29120. Positions 31-103, 123-595, 711-753.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111151. 2 interactions.
MINTiMINT-6630348.
STRINGi9606.ENSP00000308024.

Chemistry

BindingDBiP29120.
ChEMBLiCHEMBL3182.
DrugBankiDB00030. Insulin Regular.
GuidetoPHARMACOLOGYi2382.

Protein family/group databases

MEROPSiS08.072.

PTM databases

iPTMnetiP29120.
PhosphoSiteiP29120.
UniCarbKBiP29120.

Polymorphism and mutation databases

BioMutaiPCSK1.
DMDMi116242674.

Proteomic databases

EPDiP29120.
PaxDbiP29120.
PeptideAtlasiP29120.
PRIDEiP29120.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi5122.
GeneCardsiPCSK1.
HGNCiHGNC:8743. PCSK1.
HPAiHPA048564.
MalaCardsiPCSK1.
MIMi162150. gene.
600955. phenotype.
612362. phenotype.
neXtProtiNX_P29120.
Orphaneti71528. Obesity due to prohormone convertase I deficiency.
PharmGKBiPA33089.
GenAtlasiSearch...

Phylogenomic databases

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

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.

Miscellaneous databases

ChiTaRSiPCSK1. human.
GeneWikiiProprotein_convertase_1.
GenomeRNAii5122.
PMAP-CutDBP29120.
PROiP29120.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000175426.
CleanExiHS_PCSK1.
ExpressionAtlasiP29120. baseline and differential.
GenevisibleiP29120. HS.

Family and domain databases

Gene3Di2.60.120.260. 1 hit.
3.30.70.850. 1 hit.
3.40.50.200. 1 hit.
InterProiIPR008979. 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. Propept_inh.
IPR002884. PrprotnconvertsP.
IPR032815. S8_pro-domain.
[Graphical view]
PANTHERiPTHR10795. PTHR10795. 1 hit.
PfamiPF01483. P_proprotein. 1 hit.
PF00082. Peptidase_S8. 1 hit.
PF12177. Proho_convert. 1 hit.
PF16470. S8_pro-domain. 1 hit.
[Graphical view]
PRINTSiPR00723. SUBTILISIN.
SUPFAMiSSF49785. SSF49785. 1 hit.
SSF52743. SSF52743. 1 hit.
SSF54897. SSF54897. 1 hit.
PROSITEiPS00136. SUBTILASE_ASP. 1 hit.
PS00137. SUBTILASE_HIS. 1 hit.
PS00138. SUBTILASE_SER. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNEC1_HUMAN
AccessioniPrimary (citable) accession number: P29120
Secondary accession number(s): B7Z8T7
, E9PHA1, P78478, Q92532
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: October 17, 2006
Last modified: September 7, 2016
This is version 165 of the entry and version 2 of the sequence. [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

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Peptidase families
    Classification of peptidase families and list of entries
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.