Reviewed, UniProtKB/Swiss-Prot P16519 (NEC2_HUMAN)

Names and origin

Protein names

Recommended name:
    Neuroendocrine convertase 2
      Short name=NEC 2
    EC=3.4.21.94
Alternative name(s):
    Prohormone convertase 2
    Proprotein convertase 2
      Short name=PC2
    KEX2-like endoprotease 2

Gene names

Name:	PCSK2
Synonyms:	NEC2

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	638 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.
Catalytic activity	Release of protein hormones and neuropeptides from their precursors, generally by hydrolysis of -Lys-Arg-|- bonds.
Subcellular location	Cytoplasmic vesicle › secretory vesicle. Note: Localized in the secretion granules.
Sequence similarities	Belongs to the peptidase S8 family. Furin subfamily.

Ontologies

Keywords
Cellular component	Cytoplasmic vesicle
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Hydrolase Protease Serine protease
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Zymogen
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	enkephalin processing Inferred from sequence or structural similarity. Source: UniProtKB insulin processing Inferred from direct assay. Source: UniProtKB islet amyloid polypeptide processing Inferred from sequence or structural similarity. Source: UniProtKB proteolysis Inferred from direct assay. Source: UniProtKB
Cellular component	extracellular space Inferred from direct assay. Source: UniProtKB membrane Inferred from direct assay. Source: UniProtKB secretory granule Inferred from electronic annotation. Source: UniProtKB-SubCell soluble fraction Inferred from direct assay. Source: UniProtKB
Molecular function	protein binding Inferred from physical interaction. Source: UniProtKB serine-type endopeptidase activity Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 25	25	Potential
	Propeptide	26 – 109	84	Potential		PRO_0000027065
	Chain	110 – 638	529	Neuroendocrine convertase 2		PRO_0000027066
Regions
	Region	122 – 415	294	Catalytic
Sites
	Active site	167	1	Charge relay system By similarity
	Active site	208	1	Charge relay system By similarity
	Active site	384	1	Charge relay system By similarity
Amino acid modifications
	Glycosylation	375	1	N-linked (GlcNAc...) Potential
	Glycosylation	514	1	N-linked (GlcNAc...) Potential
	Glycosylation	524	1	N-linked (GlcNAc...) Potential
	Disulfide bond	225 ↔ 376		By similarity
	Disulfide bond	317 ↔ 347		By similarity
	Disulfide bond	468 ↔ 494		By similarity
Natural variations
	Natural variant	424	1	D → N in a colorectal cancer sample; somatic mutation. Ref.6		VAR_036548
Experimental info
	Sequence conflict	283 – 284	2	EL → DV in AAA60032. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P16519-1 [UniParc]. Last modified February 21, 2001. Version 2. Checksum: 323623FBDA6086B2	FASTA	638	70,565
	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

References

	« Hide 'large scale' referencesShow '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: 2154467] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. 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: 1594602] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Placenta.
[3]	"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. , 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: 11780052] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[5]	"Analysis of the gene encoding human PC2, a prohormone processing enzyme." Ohagi S., Yoshida H., Nanjo K. Nippon Rinsho 52:2544-2549(1994) [PubMed: 7983775] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-8.
[6]	"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. , 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: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ASN-424.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	J05252 mRNA. Translation: AAA60032.1. M95971 , M95960, M95961, M95962, M95963, M95964, M95965, M95966, M95967, M95968, M95969, M95970 Genomic DNA. Translation: AAA59919.1. 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. BC005815 mRNA. Translation: AAH05815.1. S75955 Genomic DNA. Translation: AAD14202.1.
IPI	IPI00029131.
PIR	KXHUC2. A45382.
RefSeq	NP_002585.2.
UniGene	Hs.315186
3D structure databases
HSSP	HSSP built from PDB template 1P8J based on UniProtKB P23188.
ModBase	Search...
Protein-protein interaction databases
STRING	P16519.
Protein family/group databases
MEROPS	S08.073.
Proteomic databases
PRIDE	P16519.
Genome annotation databases
Ensembl	ENST00000262545; ENSP00000262545; ENSG00000125851; Homo sapiens. [Genome view] ENST00000377899; ENSP00000367131; ENSG00000125851; Homo sapiens. [Genome view]
GeneID	5126.
KEGG	hsa:5126.
UCSC	uc002wpm.1. human.
Organism-specific databases
CTD	5126.
GeneCards	GC20P017155.
H-InvDB	HIX0015657.
HGNC	HGNC:8744. PCSK2.
MIM	162151. gene.
PharmGKB	PA33091.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P16519.
HOVERGEN	P16519.
OMA	NYNADAS.
Enzyme and pathway databases
BRENDA	3.4.21.94. 247.
Reactome	REACT_15380. Diabetes pathways.
Gene expression databases
ArrayExpress	P16519.
Bgee	P16519.
CleanEx	HS_PCSK2.
Genevestigator	P16519.
GermOnline	ENSG00000125851. Homo sapiens.
Family and domain databases
InterPro	IPR000209. Peptidase_S8/S53. IPR015500. Peptidase_S8_subtilisin-rel. IPR002884. PrprotnconvertsP. [Graphical view]
Gene3D	G3DSA:3.40.50.200. Pept_S8_S53. 1 hit.
PANTHER	PTHR10795. SubtilSerProt. 1 hit.
Pfam	PF01483. P_proprotein. 1 hit. PF00082. Peptidase_S8. 1 hit. [Graphical view]
PRINTS	PR00723. SUBTILISIN.
ProDom	PD000717. PrprotnconvertsP. 1 hit. [Graphical view] [Entries sharing at least one domain]
PROSITE	PS00136. SUBTILASE_ASP. 1 hit. PS00137. SUBTILASE_HIS. 1 hit. PS00138. SUBTILASE_SER. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00047. Insulin Glargine recombinant. DB00046. Insulin Lyspro recombinant. DB00030. Insulin recombinant. DB00071. Insulin, porcine.
NextBio	19758.
SOURCE	Search...

Entry information

Entry name

NEC2_HUMAN

Accession

Primary (citable) accession number: P16519
Secondary accession number(s): Q14927 , Q9NQG3, Q9NUG1, Q9UJC6

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	February 21, 2001
Last modified:	November 3, 2009
This is version 104 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.