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Protein

Neuroendocrine convertase 2

Gene

PCSK2

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. Responsible for the release of glucagon from proglucagon in pancreatic A cells.2 Publications

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

  • protein-containing complex binding Source: Ensembl
  • serine-type endopeptidase activity Source: BHF-UCL

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Serine protease

Enzyme and pathway databases

ReactomeiR-HSA-264876 Insulin processing
SignaLinkiP16519
SIGNORiP16519

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

EuPathDBiHostDB:ENSG00000125851.9
HGNCiHGNC:8744 PCSK2
MIMi162151 gene
neXtProtiNX_P16519

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, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi5126
OpenTargetsiENSG00000125851
PharmGKBiPA33091

Chemistry databases

ChEMBLiCHEMBL2433
DrugBankiDB00030 Insulin Human
DB00071 Insulin Pork
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...) asparagineSequence analysis1
Disulfide bondi468 ↔ 494By similarity
Glycosylationi514N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi524N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

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

Proteomic databases

PaxDbiP16519
PeptideAtlasiP16519
PRIDEiP16519
ProteomicsDBi53377
53378 [P16519-2]

PTM databases

GlyConnecti1551
iPTMnetiP16519
PhosphoSitePlusiP16519

Expressioni

Gene expression databases

BgeeiENSG00000125851 Expressed in 162 organ(s), highest expression level in islet of Langerhans
CleanExiHS_PCSK2
GenevisibleiP16519 HS

Organism-specific databases

HPAiHPA049627

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
Domaini461 – 597P/Homo BPROSITE-ProRule annotationAdd BLAST137

Sequence similaritiesi

Belongs to the peptidase S8 family. Furin subfamily.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3525 Eukaryota
KOG3526 Eukaryota
COG1404 LUCA
COG4935 LUCA
GeneTreeiENSGT00750000117358
HOGENOMiHOG000192536
HOVERGENiHBG008705
InParanoidiP16519
KOiK01360
OMAiPQRGVLK
OrthoDBiEOG091G05HI
PhylomeDBiP16519
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
IPR032815 S8_pro-domain
IPR038466 S8_pro-domain_sf
PfamiView protein in Pfam
PF01483 P_proprotein, 1 hit
PF00082 Peptidase_S8, 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 (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

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_07973077A → D Rare polymorphism; no effect on secretion; no effect on proglucagon processing. 1 PublicationCorresponds to variant dbSNP:rs201718679Ensembl.1
Natural variantiVAR_069075244P → Q1 PublicationCorresponds to variant dbSNP:rs17854040Ensembl.1
Natural variantiVAR_079731267A → T Rare polymorphism; decreased secretion; reduced proglucagon processing. 1 PublicationCorresponds to variant dbSNP:rs144151196Ensembl.1
Natural variantiVAR_036548424D → N in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs780820865Ensembl.1
Natural variantiVAR_079732430R → W Rare polymorphism; no effect on secretion; no effect on proglucagon processing. 1 PublicationCorresponds to variant dbSNP:rs200711626Ensembl.1
Natural variantiVAR_069076484K → E1 PublicationCorresponds to variant dbSNP:rs17857236Ensembl.1
Natural variantiVAR_079733525M → V Rare polymorphism; no effect on secretion; no effect on proglucagon processing. 1 PublicationCorresponds to variant dbSNP:rs139619496Ensembl.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
AL031664 Genomic DNA No translation available.
AL031675 Genomic DNA No translation available.
AL121779 Genomic DNA No translation available.
AL359511 Genomic DNA No translation available.
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

Similar proteinsi

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
AL031664 Genomic DNA No translation available.
AL031675 Genomic DNA No translation available.
AL121779 Genomic DNA No translation available.
AL359511 Genomic DNA No translation available.
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 Human
DB00071 Insulin Pork
GuidetoPHARMACOLOGYi2383

Protein family/group databases

MEROPSiS08.073

PTM databases

GlyConnecti1551
iPTMnetiP16519
PhosphoSitePlusiP16519

Polymorphism and mutation databases

BioMutaiPCSK2
DMDMi13124785

Proteomic databases

PaxDbiP16519
PeptideAtlasiP16519
PRIDEiP16519
ProteomicsDBi53377
53378 [P16519-2]

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
EuPathDBiHostDB:ENSG00000125851.9
GeneCardsiPCSK2
HGNCiHGNC:8744 PCSK2
HPAiHPA049627
MIMi162151 gene
neXtProtiNX_P16519
OpenTargetsiENSG00000125851
PharmGKBiPA33091
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

ReactomeiR-HSA-264876 Insulin processing
SignaLinkiP16519
SIGNORiP16519

Miscellaneous databases

ChiTaRSiPCSK2 human
GeneWikiiProprotein_convertase_2
GenomeRNAii5126
PROiPR:P16519
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000125851 Expressed in 162 organ(s), highest expression level in islet of Langerhans
CleanExiHS_PCSK2
GenevisibleiP16519 HS

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
IPR032815 S8_pro-domain
IPR038466 S8_pro-domain_sf
PfamiView protein in Pfam
PF01483 P_proprotein, 1 hit
PF00082 Peptidase_S8, 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
ProtoNetiSearch...

Entry informationi

Entry nameiNEC2_HUMAN
AccessioniPrimary (citable) accession number: P16519
Secondary accession number(s): B1ANH9
, B4DFQ3, Q14927, Q5JYQ1, Q8IWA8, Q9NQG3, Q9NUG1, Q9UJC6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: February 21, 2001
Last modified: October 10, 2018
This is version 181 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

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Peptidase families
    Classification of peptidase families and list of entries
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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