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Protein

Neuroendocrine convertase 2

Gene

PCSK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues. Responsible for the release of glucagon from proglucagon in pancreatic A cells.1 Publication

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei167Charge relay systemBy similarity1
Active sitei208Charge relay systemBy similarity1
Active sitei384Charge relay systemBy similarity1

GO - Molecular functioni

  • serine-type endopeptidase activity Source: BHF-UCL

GO - Biological processi

  • enkephalin processing Source: BHF-UCL
  • insulin processing Source: BHF-UCL
  • islet amyloid polypeptide processing Source: BHF-UCL
  • nervous system development Source: Ensembl
  • protein autoprocessing Source: Ensembl
  • proteolysis Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Enzyme and pathway databases

BioCyciZFISH:HS04957-MONOMER.
ReactomeiR-HSA-264876. Insulin processing.
SignaLinkiP16519.

Protein family/group databases

MEROPSiS08.073.

Names & Taxonomyi

Protein namesi
Recommended name:
Neuroendocrine convertase 2 (EC:3.4.21.94)
Short name:
NEC 2
Alternative name(s):
KEX2-like endoprotease 2
Prohormone convertase 2
Proprotein convertase 2
Short name:
PC2
Gene namesi
Name:PCSK2
Synonyms:NEC2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:8744. PCSK2.

Subcellular locationi

GO - Cellular componenti

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

Keywords - Cellular componenti

Cytoplasmic vesicle

Pathology & Biotechi

Organism-specific databases

DisGeNETi5126.
OpenTargetsiENSG00000125851.
PharmGKBiPA33091.

Chemistry databases

ChEMBLiCHEMBL2433.
DrugBankiDB00030. Insulin Regular.
GuidetoPHARMACOLOGYi2383.

Polymorphism and mutation databases

BioMutaiPCSK2.
DMDMi13124785.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 25Sequence analysisAdd BLAST25
PropeptideiPRO_000002706526 – 109Sequence analysisAdd BLAST84
ChainiPRO_0000027066110 – 638Neuroendocrine convertase 2Add BLAST529

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi225 ↔ 376By similarity
Disulfide bondi317 ↔ 347By similarity
Glycosylationi375N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi468 ↔ 494By similarity
Glycosylationi514N-linked (GlcNAc...)Sequence analysis1
Glycosylationi524N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

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

Proteomic databases

PaxDbiP16519.
PeptideAtlasiP16519.
PRIDEiP16519.

PTM databases

iPTMnetiP16519.
PhosphoSitePlusiP16519.

Expressioni

Gene expression databases

BgeeiENSG00000125851.
CleanExiHS_PCSK2.
GenevisibleiP16519. HS.

Organism-specific databases

HPAiHPA048851.
HPA049627.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000262545.

Chemistry databases

BindingDBiP16519.

Structurei

3D structure databases

ProteinModelPortaliP16519.
SMRiP16519.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini162 – 453Peptidase S8Add BLAST292

Sequence similaritiesi

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

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3525. Eukaryota.
KOG3526. Eukaryota.
COG1404. LUCA.
COG4935. LUCA.
GeneTreeiENSGT00750000117358.
HOGENOMiHOG000192536.
HOVERGENiHBG008705.
InParanoidiP16519.
KOiK01360.
OMAiDAFPYPR.
OrthoDBiEOG091G05HI.
PhylomeDBiP16519.
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.
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.
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 (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P16519-1) [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
MKGGCVSQWK AAAGFLFCVM VFASAERPVF TNHFLVELHK GGEDKARQVA
60 70 80 90 100
AEHGFGVRKL PFAEGLYHFY HNGLAKAKRR RSLHHKQQLE RDPRVKMALQ
110 120 130 140 150
QEGFDRKKRG YRDINEIDIN MNDPLFTKQW YLINTGQADG TPGLDLNVAE
160 170 180 190 200
AWELGYTGKG VTIGIMDDGI DYLHPDLASN YNAEASYDFS SNDPYPYPRY
210 220 230 240 250
TDDWFNSHGT RCAGEVSAAA NNNICGVGVA YNSKVAGIRM LDQPFMTDII
260 270 280 290 300
EASSISHMPQ LIDIYSASWG PTDNGKTVDG PRELTLQAMA DGVNKGRGGK
310 320 330 340 350
GSIYVWASGD GGSYDDCNCD GYASSMWTIS INSAINDGRT ALYDESCSST
360 370 380 390 400
LASTFSNGRK RNPEAGVATT DLYGNCTLRH SGTSAAAPEA AGVFALALEA
410 420 430 440 450
NLGLTWRDMQ HLTVLTSKRN QLHDEVHQWR RNGVGLEFNH LFGYGVLDAG
460 470 480 490 500
AMVKMAKDWK TVPERFHCVG GSVQDPEKIP STGKLVLTLT TDACEGKENF
510 520 530 540 550
VRYLEHVQAV ITVNATRRGD LNINMTSPMG TKSILLSRRP RDDDSKVGFD
560 570 580 590 600
KWPFMTTHTW GEDARGTWTL ELGFVGSAPQ KGVLKEWTLM LHGTQSAPYI
610 620 630
DQVVRDYQSK LAMSKKEELE EELDEAVERS LKSILNKN
Length:638
Mass (Da):70,565
Last modified:February 21, 2001 - v2
Checksum:i323623FBDA6086B2
GO
Isoform 2 (identifier: P16519-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     60-94: Missing.

Note: No experimental confirmation available.
Show »
Length:603
Mass (Da):66,312
Checksum:i7D25259EECDA94EE
GO
Isoform 3 (identifier: P16519-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-19: Missing.

Note: No experimental confirmation available.
Show »
Length:619
Mass (Da):68,580
Checksum:iFCC1B2B87F1A5B71
GO

Sequence cautioni

The sequence CAA21069 differs from that shown. Reason: Erroneous initiation.Curated
The sequence CAB89428 differs from that shown. Reason: Erroneous initiation.Curated
The sequence CAB96732 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti283 – 284EL → DV in AAA60032 (PubMed:2154467).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069075244P → Q.1 PublicationCorresponds to variant rs17854040dbSNPEnsembl.1
Natural variantiVAR_036548424D → N in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant rs780820865dbSNPEnsembl.1
Natural variantiVAR_069076484K → E.1 PublicationCorresponds to variant rs17857236dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0458731 – 19Missing in isoform 3. 1 PublicationAdd BLAST19
Alternative sequenceiVSP_04335860 – 94Missing in isoform 2. 1 PublicationAdd BLAST35

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J05252 mRNA. Translation: AAA60032.1.
M95971
, M95960, M95961, M95962, M95963, M95964, M95965, M95966, M95967, M95968, M95969, M95970 Genomic DNA. Translation: AAA59919.1.
AK294200 mRNA. Translation: BAG57514.1.
AK312341 mRNA. Translation: BAG35262.1.
AL031675
, AL031664, AL121779, AL359511 Genomic DNA. Translation: CAA21069.2. Different initiation.
AL031664
, AL031675, AL121779, AL359511 Genomic DNA. Translation: CAB89428.2. Different initiation.
AL121779
, AL031664, AL031675, AL359511 Genomic DNA. Translation: CAB96732.2. Different initiation.
AL359511
, AL031664, AL031675, AL121779 Genomic DNA. Translation: CAC34957.2.
AL121779
, AL031664, AL031675, AL359511 Genomic DNA. Translation: CAI19155.1.
AL359511
, AL031664, AL031675, AL121779 Genomic DNA. Translation: CAI20085.1.
AL031664
, AL031675, AL121779, AL359511 Genomic DNA. Translation: CAI21690.1.
AL031675
, AL031664, AL121779, AL359511 Genomic DNA. Translation: CAI22648.1.
CH471133 Genomic DNA. Translation: EAX10279.1.
CH471133 Genomic DNA. Translation: EAX10280.1.
CH471133 Genomic DNA. Translation: EAX10281.1.
BC005815 mRNA. Translation: AAH05815.1.
BC040546 mRNA. Translation: AAH40546.1.
S75955 Genomic DNA. Translation: AAD14202.1.
CCDSiCCDS13125.1. [P16519-1]
CCDS56179.1. [P16519-2]
CCDS56180.1. [P16519-3]
PIRiA45382. KXHUC2.
RefSeqiNP_001188457.1. NM_001201528.1. [P16519-3]
NP_001188458.1. NM_001201529.2. [P16519-2]
NP_002585.2. NM_002594.4. [P16519-1]
UniGeneiHs.315186.

Genome annotation databases

EnsembliENST00000262545; ENSP00000262545; ENSG00000125851. [P16519-1]
ENST00000377899; ENSP00000367131; ENSG00000125851. [P16519-3]
ENST00000536609; ENSP00000437458; ENSG00000125851. [P16519-2]
GeneIDi5126.
KEGGihsa:5126.
UCSCiuc002wpl.4. human. [P16519-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J05252 mRNA. Translation: AAA60032.1.
M95971
, M95960, M95961, M95962, M95963, M95964, M95965, M95966, M95967, M95968, M95969, M95970 Genomic DNA. Translation: AAA59919.1.
AK294200 mRNA. Translation: BAG57514.1.
AK312341 mRNA. Translation: BAG35262.1.
AL031675
, AL031664, AL121779, AL359511 Genomic DNA. Translation: CAA21069.2. Different initiation.
AL031664
, AL031675, AL121779, AL359511 Genomic DNA. Translation: CAB89428.2. Different initiation.
AL121779
, AL031664, AL031675, AL359511 Genomic DNA. Translation: CAB96732.2. Different initiation.
AL359511
, AL031664, AL031675, AL121779 Genomic DNA. Translation: CAC34957.2.
AL121779
, AL031664, AL031675, AL359511 Genomic DNA. Translation: CAI19155.1.
AL359511
, AL031664, AL031675, AL121779 Genomic DNA. Translation: CAI20085.1.
AL031664
, AL031675, AL121779, AL359511 Genomic DNA. Translation: CAI21690.1.
AL031675
, AL031664, AL121779, AL359511 Genomic DNA. Translation: CAI22648.1.
CH471133 Genomic DNA. Translation: EAX10279.1.
CH471133 Genomic DNA. Translation: EAX10280.1.
CH471133 Genomic DNA. Translation: EAX10281.1.
BC005815 mRNA. Translation: AAH05815.1.
BC040546 mRNA. Translation: AAH40546.1.
S75955 Genomic DNA. Translation: AAD14202.1.
CCDSiCCDS13125.1. [P16519-1]
CCDS56179.1. [P16519-2]
CCDS56180.1. [P16519-3]
PIRiA45382. KXHUC2.
RefSeqiNP_001188457.1. NM_001201528.1. [P16519-3]
NP_001188458.1. NM_001201529.2. [P16519-2]
NP_002585.2. NM_002594.4. [P16519-1]
UniGeneiHs.315186.

3D structure databases

ProteinModelPortaliP16519.
SMRiP16519.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000262545.

Chemistry databases

BindingDBiP16519.
ChEMBLiCHEMBL2433.
DrugBankiDB00030. Insulin Regular.
GuidetoPHARMACOLOGYi2383.

Protein family/group databases

MEROPSiS08.073.

PTM databases

iPTMnetiP16519.
PhosphoSitePlusiP16519.

Polymorphism and mutation databases

BioMutaiPCSK2.
DMDMi13124785.

Proteomic databases

PaxDbiP16519.
PeptideAtlasiP16519.
PRIDEiP16519.

Protocols and materials databases

DNASUi5126.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262545; ENSP00000262545; ENSG00000125851. [P16519-1]
ENST00000377899; ENSP00000367131; ENSG00000125851. [P16519-3]
ENST00000536609; ENSP00000437458; ENSG00000125851. [P16519-2]
GeneIDi5126.
KEGGihsa:5126.
UCSCiuc002wpl.4. human. [P16519-1]

Organism-specific databases

CTDi5126.
DisGeNETi5126.
GeneCardsiPCSK2.
HGNCiHGNC:8744. PCSK2.
HPAiHPA048851.
HPA049627.
MIMi162151. gene.
neXtProtiNX_P16519.
OpenTargetsiENSG00000125851.
PharmGKBiPA33091.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3525. Eukaryota.
KOG3526. Eukaryota.
COG1404. LUCA.
COG4935. LUCA.
GeneTreeiENSGT00750000117358.
HOGENOMiHOG000192536.
HOVERGENiHBG008705.
InParanoidiP16519.
KOiK01360.
OMAiDAFPYPR.
OrthoDBiEOG091G05HI.
PhylomeDBiP16519.
TreeFamiTF314277.

Enzyme and pathway databases

BioCyciZFISH:HS04957-MONOMER.
ReactomeiR-HSA-264876. Insulin processing.
SignaLinkiP16519.

Miscellaneous databases

ChiTaRSiPCSK2. human.
GeneWikiiProprotein_convertase_2.
GenomeRNAii5126.
PROiP16519.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000125851.
CleanExiHS_PCSK2.
GenevisibleiP16519. 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.
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.
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 nameiNEC2_HUMAN
AccessioniPrimary (citable) accession number: P16519
Secondary accession number(s): B1ANH9
, B4DFQ3, Q14927, Q5JYQ1, Q8IWA8, Q9NQG3, Q9NUG1, Q9UJC6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: February 21, 2001
Last modified: November 2, 2016
This is version 167 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 20
    Human chromosome 20: 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.