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P29120 (NEC1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 146. 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 1

Short name=NEC 1
EC=3.4.21.93
Alternative name(s):
Prohormone convertase 1
Proprotein convertase 1
Short name=PC1
Gene names
Name:PCSK1
Synonyms:NEC1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length753 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein 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. Substrates include POMC, renin, enkephalin, dynorphin, somatostatin and insulin.

Catalytic activity

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

Cofactor

Calcium.

Subcellular location

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

Post-translational modification

O-glycosylated. Ref.7

Polymorphism

Genetic variations in PCSK1 define the body mass index quantitative trait locus 12 (BMIQ12) [MIM:612362]. Variance in body mass index is a susceptibility factor for obesity.

Involvement in disease

Proprotein convertase 1 deficiency (PC1 deficiency) [MIM:600955]: Characterized by obesity, hypogonadism, hypoadrenalism, reactive hypoglycemia as well as marked small-intestinal absorptive dysfunction It is due to impaired processing of prohormones.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Sequence similarities

Belongs to the peptidase S8 family. Furin subfamily.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P29120-1)

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: P29120-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-59: MERRAWSLQCTAFVLFCAWCALNSAKAKRQFVNEWAAEIPGGPEAASAIAEELGYDLLG → MGKGSISFLFFS
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2727 Potential
Propeptide28 – 11083 Potential
PRO_0000027057
Chain111 – 753643Neuroendocrine convertase 1
PRO_0000027058

Regions

Region122 – 410289Catalytic
Region739 – 75113Amphipathic Potential

Sites

Active site1671Charge relay system By similarity
Active site2081Charge relay system By similarity
Active site3821Charge relay system By similarity

Amino acid modifications

Glycosylation1731N-linked (GlcNAc...) Potential
Glycosylation4011N-linked (GlcNAc...) Potential
Glycosylation6321O-linked (GalNAc...) Ref.7
Disulfide bond225 ↔ 374 By similarity
Disulfide bond317 ↔ 347 By similarity
Disulfide bond467 ↔ 494 By similarity

Natural variations

Alternative sequence1 – 5959MERRA…YDLLG → MGKGSISFLFFS in isoform 2.
VSP_046100
Natural variant801R → Q. Ref.3
Corresponds to variant rs1799904 [ dbSNP | Ensembl ].
VAR_013906
Natural variant2131Missing in PC1 deficiency. Ref.11
VAR_022777
Natural variant2211N → D Associated with susceptibility to obesity; induces a 10.4% reduction of activity (P = 0.03) when compared to the wild-type enzyme. Ref.9 Ref.13
Corresponds to variant rs6232 [ dbSNP | Ensembl ].
VAR_013907
Natural variant3071S → 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. Ref.12
VAR_055002
Natural variant4831G → R in PC1 deficiency; prevents processing of pro-PCSK1 and leads to its retention in the endoplasmic reticulum. Ref.8
VAR_022778
Natural variant6651Q → E. Ref.3 Ref.9 Ref.12
Corresponds to variant rs6234 [ dbSNP | Ensembl ].
VAR_013908
Natural variant6901S → T. Ref.9 Ref.12
Corresponds to variant rs6235 [ dbSNP | Ensembl ].
VAR_013909

Experimental info

Sequence conflict3571S → G in CAA46031. Ref.1
Sequence conflict370 – 3712LH → VD in BAA11133. Ref.3
Sequence conflict6171R → G in BAH14073. Ref.4

Sequences

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

Last modified October 17, 2006. Version 2.
Checksum: D3CBD1B92093A208

FASTA75384,152
        10         20         30         40         50         60 
MERRAWSLQC TAFVLFCAWC ALNSAKAKRQ FVNEWAAEIP GGPEAASAIA EELGYDLLGQ 

        70         80         90        100        110        120 
IGSLENHYLF KHKNHPRRSR RSAFHITKRL SDDDRVIWAE QQYEKERSKR SALRDSALNL 

       130        140        150        160        170        180 
FNDPMWNQQW YLQDTRMTAA LPKLDLHVIP VWQKGITGKG VVITVLDDGL EWNHTDIYAN 

       190        200        210        220        230        240 
YDPEASYDFN DNDHDPFPRY DPTNENKHGT RCAGEIAMQA NNHKCGVGVA YNSKVGGIRM 

       250        260        270        280        290        300 
LDGIVTDAIE ASSIGFNPGH VDIYSASWGP NDDGKTVEGP GRLAQKAFEY GVKQGRQGKG 

       310        320        330        340        350        360 
SIFVWASGNG GRQGDNCDCD GYTDSIYTIS ISSASQQGLS PWYAEKCSST LATSYSSGDY 

       370        380        390        400        410        420 
TDQRITSADL HNDCTETHTG TSASAPLAAG IFALALEANP NLTWRDMQHL VVWTSEYDPL 

       430        440        450        460        470        480 
ANNPGWKKNG AGLMVNSRFG FGLLNAKALV DLADPRTWRS VPEKKECVVK DNDFEPRALK 

       490        500        510        520        530        540 
ANGEVIIEIP TRACEGQENA IKSLEHVQFE ATIEYSRRGD LHVTLTSAAG TSTVLLAERE 

       550        560        570        580        590        600 
RDTSPNGFKN WDFMSVHTWG ENPIGTWTLR ITDMSGRIQN EGRIVNWKLI LHGTSSQPEH 

       610        620        630        640        650        660 
MKQPRVYTSY NTVQNDRRGV EKMVDPGEEQ PTQENPKENT LVSKSPSSSS VGGRRDELEE 

       670        680        690        700        710        720 
GAPSQAMLRL LQSAFSKNSP PKQSPKKSPS AKLNIPYENF YEALEKLNKP SQLKDSEDSL 

       730        740        750 
YNDYVDVFYN TKPYKHRDDR LLQALVDILN EEN 

« Hide

Isoform 2 [UniParc].

Checksum: F082971DADE9EAAC
Show »

FASTA70679,010

References

« Hide 'large scale' references
[1]"Expression in human lung tumor cells of the proprotein processing enzyme PC1/PC3. Cloning and primary sequence of a 5 kb cDNA."
Creemers J.W.M., Roebroek A.J.M., van de Ven W.J.M.
FEBS Lett. 300:82-88(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"The cDNA sequence of the human pro-hormone and pro-protein convertase PC1."
Seidah N.G., Hamelin J., Gaspar A.M., Day R., Chretien M.
DNA Cell Biol. 11:283-289(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]"Human prohormone convertase 3 gene: exon-intron organization and molecular scanning for mutations in Japanese subjects with NIDDM."
Ohagi S., Sakaguchi H., Sanke T., Tatsuta H., Hanabusa T., Nanjo K.
Diabetes 45:897-901(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLN-80 AND GLU-665.
[4]"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] (ISOFORM 2).
Tissue: Trachea.
[5]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"Neuroendocrine-specific expression of the human prohormone convertase 1 gene. Hormonal regulation of transcription through distinct cAMP response elements."
Jansen E.
J. Biol. Chem. 270:15391-15397(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-60.
[7]"LC-MS/MS characterization of O-glycosylation sites and glycan structures of human cerebrospinal fluid glycoproteins."
Halim A., Ruetschi U., Larson G., Nilsson J.
J. Proteome Res. 12:573-584(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT THR-632, IDENTIFICATION BY MASS SPECTROMETRY.
[8]"Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene."
Jackson R.S., Creemers J.W., Ohagi S., Raffin-Sanson M.-L., Sanders L., Montague C.T., Hutton J.C., O'Rahilly S.
Nat. Genet. 16:303-306(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PC1 DEFICIENCY ARG-483.
[9]"Characterization of single-nucleotide polymorphisms in coding regions of human genes."
Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.
Nat. Genet. 22:231-238(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ASP-221; GLU-665 AND THR-690.
[10]Erratum
Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.
Nat. Genet. 23:373-373(1999)
[11]"Small-intestinal dysfunction accompanies the complex endocrinopathy of human proprotein convertase 1 deficiency."
Jackson R.S., Creemers J.W., Farooqi I.S., Raffin-Sanson M.-L., Varro A., Dockray G.J., Holst J.J., Brubaker P.L., Corvol P., Polonsky K.S., Ostrega D., Becker K.L., Bertagna X., Hutton J.C., White A., Dattani M.T., Hussain K., Middleton S.J. expand/collapse author list , Nicole T.M., Milla P.J., Lindley K.J., O'Rahilly S.
J. Clin. Invest. 112:1550-1560(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PC1 DEFICIENCY ALA-213 DEL.
[12]"Hyperphagia and early-onset obesity due to a novel homozygous missense mutation in prohormone convertase 1/3."
Farooqi I.S., Volders K., Stanhope R., Heuschkel R., White A., Lank E., Keogh J., O'Rahilly S., Creemers J.W.M.
J. Clin. Endocrinol. Metab. 92:3369-3373(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PC1 DEFICIENCY LEU-307, CHARACTERIZATION OF VARIANT PC1 DEFICIENCY LEU-307, VARIANTS GLU-665 AND THR-690.
[13]"Common nonsynonymous variants in PCSK1 confer risk of obesity."
Benzinou M., Creemers J.W.M., Choquet H., Lobbens S., Dina C., Durand E., Guerardel A., Boutin P., Jouret B., Heude B., Balkau B., Tichet J., Marre M., Potoczna N., Horber F., Le Stunff C., Czernichow S., Sandbaek A. expand/collapse author list , Lauritzen T., Borch-Johnsen K., Andersen G., Kiess W., Koerner A., Kovacs P., Jacobson P., Carlsson L.M.S., Walley A.J., Joergensen T., Hansen T., Pedersen O., Meyre D., Froguel P.
Nat. Genet. 40:943-945(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ASP-221, CHARACTERIZATION OF VARIANT ASP-221, ASSOCIATION WITH SUSCEPTIBILITY TO OBESITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS4081.1. [P29120-1]
CCDS54881.1. [P29120-2]
PIRKXHUC1. S21106.
RefSeqNP_000430.3. NM_000439.4. [P29120-1]
NP_001171346.1. NM_001177875.1. [P29120-2]
UniGeneHs.78977.

3D structure databases

ProteinModelPortalP29120.
SMRP29120. Positions 31-103, 123-597, 711-753.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111151. 4 interactions.
MINTMINT-6630348.
STRING9606.ENSP00000308024.

Chemistry

BindingDBP29120.
ChEMBLCHEMBL3182.
DrugBankDB00047. Insulin Glargine recombinant.
DB00046. Insulin Lyspro recombinant.
DB00030. Insulin recombinant.
DB00071. Insulin, porcine.

Protein family/group databases

MEROPSS08.072.

PTM databases

PhosphoSiteP29120.

Polymorphism databases

DMDM116242674.

Proteomic databases

PaxDbP29120.
PRIDEP29120.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000311106; ENSP00000308024; ENSG00000175426. [P29120-1]
ENST00000508626; ENSP00000421600; ENSG00000175426. [P29120-2]
GeneID5122.
KEGGhsa:5122.
UCSCuc003kls.2. human. [P29120-1]

Organism-specific databases

CTD5122.
GeneCardsGC05M095751.
HGNCHGNC:8743. PCSK1.
HPAHPA048564.
MIM162150. gene.
600955. phenotype.
612362. phenotype.
neXtProtNX_P29120.
Orphanet71528. Obesity due to prohormone convertase I deficiency.
PharmGKBPA33089.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG4935.
HOGENOMHOG000192536.
HOVERGENHBG008705.
InParanoidP29120.
KOK01359.
OMANNPGWKK.
OrthoDBEOG7BW0JD.
PhylomeDBP29120.
TreeFamTF314277.

Enzyme and pathway databases

ReactomeREACT_17015. Metabolism of proteins.
SignaLinkP29120.

Gene expression databases

ArrayExpressP29120.
BgeeP29120.
CleanExHS_PCSK1.
GenevestigatorP29120.

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.
IPR022005. Proho_convert.
IPR009020. Prot_inh_propept.
IPR002884. PrprotnconvertsP.
[Graphical view]
PANTHERPTHR10795. PTHR10795. 1 hit.
PfamPF01483. P_proprotein. 1 hit.
PF00082. Peptidase_S8. 1 hit.
PF12177. Proho_convert. 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

ChiTaRSPCSK1. human.
GeneWikiProprotein_convertase_1.
GenomeRNAi5122.
NextBio19750.
PMAP-CutDBP29120.
PROP29120.
SOURCESearch...

Entry information

Entry nameNEC1_HUMAN
AccessionPrimary (citable) accession number: P29120
Secondary accession number(s): B7Z8T7 expand/collapse secondary AC list , E9PHA1, P78478, Q92532
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: October 17, 2006
Last modified: July 9, 2014
This is version 146 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 5

Human chromosome 5: entries, gene names and cross-references to MIM