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P16519 (NEC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 145. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Neuroendocrine convertase 2

Short name=NEC 2
EC=3.4.21.94
Alternative name(s):
KEX2-like endoprotease 2
Prohormone convertase 2
Proprotein convertase 2
Short name=PC2
Gene names
Name:PCSK2
Synonyms:NEC2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length638 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript 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. Responsible for the release of glucagon from proglucagon in pancreatic A cells. Ref.8

Catalytic activity

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

Subcellular location

Cytoplasmic vesiclesecretory vesicle. Note: Localized in the secretion granules.

Sequence similarities

Belongs to the peptidase S8 family. Furin subfamily.

Sequence caution

The sequence CAA21069.2 differs from that shown. Reason: Erroneous initiation.

The sequence CAB89428.2 differs from that shown. Reason: Erroneous initiation.

The sequence CAB96732.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Cellular componentCytoplasmic vesicle
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSignal
   Molecular functionHydrolase
Protease
Serine protease
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
Zymogen
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular protein metabolic process

Traceable author statement. Source: Reactome

embryo development

Inferred from electronic annotation. Source: Ensembl

enkephalin processing

Inferred from sequence or structural similarity. Source: BHF-UCL

insulin processing

Inferred from direct assay PubMed 7626024. Source: BHF-UCL

islet amyloid polypeptide processing

Inferred from sequence or structural similarity. Source: BHF-UCL

nervous system development

Inferred from electronic annotation. Source: Ensembl

protein autoprocessing

Inferred from electronic annotation. Source: Ensembl

proteolysis

Inferred from direct assay PubMed 7626024. Source: BHF-UCL

   Cellular_componentdendrite

Inferred from electronic annotation. Source: Ensembl

extracellular space

Inferred from direct assay PubMed 9020868. Source: BHF-UCL

membrane

Inferred from direct assay PubMed 8034613. Source: BHF-UCL

perikaryon

Inferred from electronic annotation. Source: Ensembl

secretory granule lumen

Traceable author statement. Source: Reactome

transport vesicle

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionserine-type endopeptidase activity

Inferred from direct assay PubMed 7626024. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P16519-1)

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.
Isoform 2 (identifier: P16519-2)

The sequence of this isoform differs from the canonical sequence as follows:
     60-94: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: P16519-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-19: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2525 Potential
Propeptide26 – 10984 Potential
PRO_0000027065
Chain110 – 638529Neuroendocrine convertase 2
PRO_0000027066

Regions

Region122 – 415294Catalytic

Sites

Active site1671Charge relay system By similarity
Active site2081Charge relay system By similarity
Active site3841Charge relay system By similarity

Amino acid modifications

Glycosylation3751N-linked (GlcNAc...) Potential
Glycosylation5141N-linked (GlcNAc...) Potential
Glycosylation5241N-linked (GlcNAc...) Potential
Disulfide bond225 ↔ 376 By similarity
Disulfide bond317 ↔ 347 By similarity
Disulfide bond468 ↔ 494 By similarity

Natural variations

Alternative sequence1 – 1919Missing in isoform 3.
VSP_045873
Alternative sequence60 – 9435Missing in isoform 2.
VSP_043358
Natural variant2441P → Q. Ref.6
Corresponds to variant rs17854040 [ dbSNP | Ensembl ].
VAR_069075
Natural variant4241D → N in a colorectal cancer sample; somatic mutation. Ref.9
VAR_036548
Natural variant4841K → E. Ref.6
Corresponds to variant rs17857236 [ dbSNP | Ensembl ].
VAR_069076

Experimental info

Sequence conflict283 – 2842EL → DV in AAA60032. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 21, 2001. Version 2.
Checksum: 323623FBDA6086B2

FASTA63870,565
        10         20         30         40         50         60 
MKGGCVSQWK AAAGFLFCVM VFASAERPVF TNHFLVELHK GGEDKARQVA AEHGFGVRKL 

        70         80         90        100        110        120 
PFAEGLYHFY HNGLAKAKRR RSLHHKQQLE RDPRVKMALQ QEGFDRKKRG YRDINEIDIN 

       130        140        150        160        170        180 
MNDPLFTKQW YLINTGQADG TPGLDLNVAE AWELGYTGKG VTIGIMDDGI DYLHPDLASN 

       190        200        210        220        230        240 
YNAEASYDFS SNDPYPYPRY TDDWFNSHGT RCAGEVSAAA NNNICGVGVA YNSKVAGIRM 

       250        260        270        280        290        300 
LDQPFMTDII EASSISHMPQ LIDIYSASWG PTDNGKTVDG PRELTLQAMA DGVNKGRGGK 

       310        320        330        340        350        360 
GSIYVWASGD GGSYDDCNCD GYASSMWTIS INSAINDGRT ALYDESCSST LASTFSNGRK 

       370        380        390        400        410        420 
RNPEAGVATT DLYGNCTLRH SGTSAAAPEA AGVFALALEA NLGLTWRDMQ HLTVLTSKRN 

       430        440        450        460        470        480 
QLHDEVHQWR RNGVGLEFNH LFGYGVLDAG AMVKMAKDWK TVPERFHCVG GSVQDPEKIP 

       490        500        510        520        530        540 
STGKLVLTLT TDACEGKENF VRYLEHVQAV ITVNATRRGD LNINMTSPMG TKSILLSRRP 

       550        560        570        580        590        600 
RDDDSKVGFD KWPFMTTHTW GEDARGTWTL ELGFVGSAPQ KGVLKEWTLM LHGTQSAPYI 

       610        620        630 
DQVVRDYQSK LAMSKKEELE EELDEAVERS LKSILNKN 

« Hide

Isoform 2 [UniParc].

Checksum: 7D25259EECDA94EE
Show »

FASTA60366,312
Isoform 3 [UniParc].

Checksum: FCC1B2B87F1A5B71
Show »

FASTA61968,580

References

« Hide 'large scale' references
[1]"Identification of a human insulinoma cDNA encoding a novel mammalian protein structurally related to the yeast dibasic processing protease Kex2."
Smeekens S.P., Steiner D.F.
J. Biol. Chem. 265:2997-3000(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Insulinoma.
[2]"Identification and analysis of the gene encoding human PC2, a prohormone convertase expressed in neuroendocrine tissues."
Ohagi S., Lamendola J., Lebeau M.M., Espinosa R., Takeda J., Smeekens S.P., Chan S.J., Steiner D.F.
Proc. Natl. Acad. Sci. U.S.A. 89:4977-4981(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Placenta.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Amygdala and Brain cortex.
[4]"The DNA sequence and comparative analysis of human chromosome 20."
Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. expand/collapse author list , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), VARIANTS GLN-244 AND GLU-484.
Tissue: Brain and Lung.
[7]"Analysis of the gene encoding human PC2, a prohormone processing enzyme."
Ohagi S., Yoshida H., Nanjo K.
Nippon Rinsho 52:2544-2549(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-8.
[8]"Role of the prohormone convertase PC2 in the processing of proglucagon to glucagon."
Rouille Y., Bianchi M., Irminger J.C., Halban P.A.
FEBS Lett. 413:119-123(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] ASN-424.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J05252 mRNA. Translation: AAA60032.1.
M95971 expand/collapse EMBL AC list , 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 expand/collapse EMBL AC list , AL031664, AL121779, AL359511 Genomic DNA. Translation: CAA21069.2. Different initiation.
AL031664 expand/collapse EMBL AC list , AL031675, AL121779, AL359511 Genomic DNA. Translation: CAB89428.2. Different initiation.
AL121779 expand/collapse EMBL AC list , AL031664, AL031675, AL359511 Genomic DNA. Translation: CAB96732.2. Different initiation.
AL359511 expand/collapse EMBL AC list , AL031664, AL031675, AL121779 Genomic DNA. Translation: CAC34957.2.
AL121779 expand/collapse EMBL AC list , AL031664, AL031675, AL359511 Genomic DNA. Translation: CAI19155.1.
AL359511 expand/collapse EMBL AC list , AL031664, AL031675, AL121779 Genomic DNA. Translation: CAI20085.1.
AL031664 expand/collapse EMBL AC list , AL031675, AL121779, AL359511 Genomic DNA. Translation: CAI21690.1.
AL031675 expand/collapse EMBL AC list , 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.
PIRKXHUC2. A45382.
RefSeqNP_001188457.1. NM_001201528.1.
NP_001188458.1. NM_001201529.2.
NP_002585.2. NM_002594.4.
UniGeneHs.315186.

3D structure databases

ProteinModelPortalP16519.
SMRP16519. Positions 30-102, 123-594.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000262545.

Chemistry

BindingDBP16519.
ChEMBLCHEMBL2433.
DrugBankDB00047. Insulin Glargine recombinant.
DB00046. Insulin Lyspro recombinant.
DB00030. Insulin recombinant.
DB00071. Insulin, porcine.

Protein family/group databases

MEROPSS08.073.

Polymorphism databases

DMDM13124785.

Proteomic databases

PaxDbP16519.
PRIDEP16519.

Protocols and materials databases

DNASU5126.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262545; ENSP00000262545; ENSG00000125851. [P16519-1]
ENST00000377899; ENSP00000367131; ENSG00000125851. [P16519-3]
ENST00000536609; ENSP00000437458; ENSG00000125851. [P16519-2]
GeneID5126.
KEGGhsa:5126.
UCSCuc002wpl.3. human. [P16519-1]
uc010zrm.2. human. [P16519-2]

Organism-specific databases

CTD5126.
GeneCardsGC20P017206.
HGNCHGNC:8744. PCSK2.
HPAHPA048851.
HPA049627.
MIM162151. gene.
neXtProtNX_P16519.
PharmGKBPA33091.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG4935.
HOGENOMHOG000192536.
HOVERGENHBG008705.
InParanoidP16519.
KOK01360.
OMAYHCEAGE.
OrthoDBEOG7BW0JD.
PhylomeDBP16519.
TreeFamTF314277.

Enzyme and pathway databases

ReactomeREACT_17015. Metabolism of proteins.
SignaLinkP16519.

Gene expression databases

ArrayExpressP16519.
BgeeP16519.
CleanExHS_PCSK2.
GenevestigatorP16519.

Family and domain databases

Gene3D2.60.120.260. 1 hit.
3.40.50.200. 1 hit.
InterProIPR008979. 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. Prot_inh_propept.
IPR002884. PrprotnconvertsP.
[Graphical view]
PANTHERPTHR10795. PTHR10795. 1 hit.
PfamPF01483. P_proprotein. 1 hit.
PF00082. Peptidase_S8. 1 hit.
[Graphical view]
PRINTSPR00723. SUBTILISIN.
SUPFAMSSF49785. SSF49785. 1 hit.
SSF52743. SSF52743. 1 hit.
SSF54897. SSF54897. 1 hit.
PROSITEPS00136. SUBTILASE_ASP. 1 hit.
PS00137. SUBTILASE_HIS. 1 hit.
PS00138. SUBTILASE_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiProprotein_convertase_2.
GenomeRNAi5126.
NextBio19758.
PROP16519.
SOURCESearch...

Entry information

Entry nameNEC2_HUMAN
AccessionPrimary (citable) accession number: P16519
Secondary accession number(s): B1ANH9 expand/collapse secondary AC list , B4DFQ3, Q14927, Q5JYQ1, Q8IWA8, Q9NQG3, Q9NUG1, Q9UJC6
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: February 21, 2001
Last modified: April 16, 2014
This is version 145 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 20

Human chromosome 20: entries, gene names and cross-references to MIM