ID NEC2_MOUSE Reviewed; 637 AA.
AC P21661; Q80WU1;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1991, sequence version 1.
DT 27-MAR-2024, entry version 201.
DE RecName: Full=Neuroendocrine convertase 2;
DE Short=NEC 2;
DE EC=3.4.21.94;
DE AltName: Full=KEX2-like endoprotease 2;
DE AltName: Full=Prohormone convertase 2;
DE AltName: Full=Proprotein convertase 2;
DE Short=PC2;
DE Flags: Precursor;
GN Name=Pcsk2; Synonyms=Nec-2, Nec2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Pituitary;
RX PubMed=2169760; DOI=10.1089/dna.1990.9.415;
RA Seidah N.G., Gaspar L., Mion P., Marcinkiewicz M., Mbikay M., Chretien M.;
RT "cDNA sequence of two distinct pituitary proteins homologous to Kex2 and
RT furin gene products: tissue-specific mRNAs encoding candidates for pro-
RT hormone processing proteinases.";
RL DNA Cell Biol. 9:415-424(1990).
RN [2]
RP ERRATUM OF PUBMED:2169760.
RX PubMed=2264933; DOI=10.1089/dna.1990.9.789;
RA Seidah N.G., Gaspar L., Mion P., Marcinkiewicz M., Mbikay M., Chretien M.;
RL DNA Cell Biol. 9:789-789(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Serine endopeptidase which is involved in the processing of
CC hormone and other protein precursors at sites comprised of pairs of
CC basic amino acid residues. Responsible for the release of glucagon from
CC proglucagon in pancreatic A cells (By similarity).
CC {ECO:0000250|UniProtKB:P16519}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of protein hormones and neuropeptides from their
CC precursors, generally by hydrolysis of -Lys-Arg-|- bonds.;
CC EC=3.4.21.94;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle
CC {ECO:0000250|UniProtKB:P16519}. Secreted
CC {ECO:0000250|UniProtKB:P16519}. Note=Localized in the secretion
CC granules. {ECO:0000250|UniProtKB:P16519}.
CC -!- SIMILARITY: Belongs to the peptidase S8 family. Furin subfamily.
CC {ECO:0000305}.
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DR EMBL; M55669; AAA39376.1; -; mRNA.
DR EMBL; BC052013; AAH52013.2; -; mRNA.
DR EMBL; BC057348; AAH57348.1; -; mRNA.
DR CCDS; CCDS16810.1; -.
DR PIR; B35571; KXMSC2.
DR RefSeq; NP_032818.1; NM_008792.4.
DR AlphaFoldDB; P21661; -.
DR SMR; P21661; -.
DR BioGRID; 202058; 7.
DR STRING; 10090.ENSMUSP00000028905; -.
DR MEROPS; S08.073; -.
DR GlyConnect; 2546; 7 N-Linked glycans (3 sites).
DR GlyCosmos; P21661; 3 sites, 7 glycans.
DR GlyGen; P21661; 3 sites, 7 N-linked glycans (3 sites).
DR iPTMnet; P21661; -.
DR PhosphoSitePlus; P21661; -.
DR SwissPalm; P21661; -.
DR PaxDb; 10090-ENSMUSP00000028905; -.
DR PeptideAtlas; P21661; -.
DR ProteomicsDB; 252799; -.
DR Antibodypedia; 9205; 242 antibodies from 33 providers.
DR DNASU; 18549; -.
DR Ensembl; ENSMUST00000028905.10; ENSMUSP00000028905.10; ENSMUSG00000027419.10.
DR GeneID; 18549; -.
DR KEGG; mmu:18549; -.
DR UCSC; uc008mqf.2; mouse.
DR AGR; MGI:97512; -.
DR CTD; 5126; -.
DR MGI; MGI:97512; Pcsk2.
DR VEuPathDB; HostDB:ENSMUSG00000027419; -.
DR eggNOG; KOG3526; Eukaryota.
DR GeneTree; ENSGT00940000156965; -.
DR HOGENOM; CLU_002976_4_4_1; -.
DR InParanoid; P21661; -.
DR OMA; LAKQWHS; -.
DR OrthoDB; 5474719at2759; -.
DR PhylomeDB; P21661; -.
DR TreeFam; TF314277; -.
DR BRENDA; 3.4.21.94; 3474.
DR BioGRID-ORCS; 18549; 3 hits in 78 CRISPR screens.
DR ChiTaRS; Pcsk2; mouse.
DR PRO; PR:P21661; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P21661; Protein.
DR Bgee; ENSMUSG00000027419; Expressed in islet of Langerhans and 116 other cell types or tissues.
DR ExpressionAtlas; P21661; baseline and differential.
DR Genevisible; P21661; MM.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0043204; C:perikaryon; ISO:MGI.
DR GO; GO:0030141; C:secretory granule; IDA:MGI.
DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
DR GO; GO:0030133; C:transport vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0004175; F:endopeptidase activity; IDA:BHF-UCL.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:BHF-UCL.
DR GO; GO:0034230; P:enkephalin processing; IDA:BHF-UCL.
DR GO; GO:0030070; P:insulin processing; IMP:MGI.
DR GO; GO:0034231; P:islet amyloid polypeptide processing; ISO:MGI.
DR GO; GO:0007399; P:nervous system development; IEP:HGNC-UCL.
DR GO; GO:0016486; P:peptide hormone processing; IDA:BHF-UCL.
DR GO; GO:0016540; P:protein autoprocessing; IDA:HGNC-UCL.
DR GO; GO:0016485; P:protein processing; IDA:BHF-UCL.
DR GO; GO:0006508; P:proteolysis; IMP:MGI.
DR CDD; cd04059; Peptidases_S8_Protein_convertases_Kexins_Furin-like; 1.
DR Gene3D; 2.60.120.260; Galactose-binding domain-like; 1.
DR Gene3D; 3.30.70.850; Peptidase S8, pro-domain; 1.
DR Gene3D; 3.40.50.200; Peptidase S8/S53 domain; 1.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR InterPro; IPR034182; Kexin/furin.
DR InterPro; IPR002884; P_dom.
DR InterPro; IPR000209; Peptidase_S8/S53_dom.
DR InterPro; IPR036852; Peptidase_S8/S53_dom_sf.
DR InterPro; IPR023827; Peptidase_S8_Asp-AS.
DR InterPro; IPR022398; Peptidase_S8_His-AS.
DR InterPro; IPR023828; Peptidase_S8_Ser-AS.
DR InterPro; IPR015500; Peptidase_S8_subtilisin-rel.
DR InterPro; IPR032815; S8_pro-domain.
DR InterPro; IPR038466; S8_pro-domain_sf.
DR PANTHER; PTHR42884:SF13; NEUROENDOCRINE CONVERTASE 2; 1.
DR PANTHER; PTHR42884; PROPROTEIN CONVERTASE SUBTILISIN/KEXIN-RELATED; 1.
DR Pfam; PF01483; P_proprotein; 1.
DR Pfam; PF00082; Peptidase_S8; 1.
DR Pfam; PF16470; S8_pro-domain; 1.
DR PRINTS; PR00723; SUBTILISIN.
DR SUPFAM; SSF49785; Galactose-binding domain-like; 1.
DR SUPFAM; SSF54897; Protease propeptides/inhibitors; 1.
DR SUPFAM; SSF52743; Subtilisin-like; 1.
DR PROSITE; PS51829; P_HOMO_B; 1.
DR PROSITE; PS51892; SUBTILASE; 1.
DR PROSITE; PS00136; SUBTILASE_ASP; 1.
DR PROSITE; PS00137; SUBTILASE_HIS; 1.
DR PROSITE; PS00138; SUBTILASE_SER; 1.
PE 1: Evidence at protein level;
KW Cleavage on pair of basic residues; Cytoplasmic vesicle; Disulfide bond;
KW Glycoprotein; Hydrolase; Protease; Reference proteome; Secreted;
KW Serine protease; Signal; Zymogen.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT PROPEP 25..108
FT /evidence="ECO:0000255"
FT /id="PRO_0000027067"
FT CHAIN 109..637
FT /note="Neuroendocrine convertase 2"
FT /id="PRO_0000027068"
FT DOMAIN 128..452
FT /note="Peptidase S8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT DOMAIN 460..596
FT /note="P/Homo B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01173"
FT ACT_SITE 166
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 207
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 383
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT CARBOHYD 374
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 513
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 523
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 224..375
FT /evidence="ECO:0000250|UniProtKB:P23188"
FT DISULFID 316..346
FT /evidence="ECO:0000250|UniProtKB:P23188"
FT DISULFID 467..493
FT /evidence="ECO:0000250|UniProtKB:P23188"
SQ SEQUENCE 637 AA; 70785 MW; B69F2DCCD00FB0E6 CRC64;
MEGGCGSQWK AAGFLFCVMV FASAERPVFT NHFLVELHKD GEEEARQVAA EHGFGVRKLP
FAEGLYHFYH NGLAKAKRRR SLHHKRQLER DPRIKMALQQ EGFDRKKRGY RDINEIDINM
NDPLFTKQWY LFNTGQADGT PGLDLNVAEA WELGYTGKGV TIGIMDDGID YLHPDLAYNY
NADASYDFSS NDPYPYPRYT DDWFNSHGTR CAGEVSAAAS NNICGVGVAY NSKVAGIRML
DQPFMTDIIE ASSISHMPQL IDIYSASWGP TDNGKTVDGP RELTLQAMAD GVNKGRGGKG
SIYVWASGDG GSYDDCNCDG YASSMWTISI NSAINDGRTA LYDESCSSTL ASTFSNGRKR
NPEAGVATTD LYGNCTLRHS GTSAAAPEAA GVFALALEAN LDLTWRDMQH LTVLTSKRNQ
LHDEVHQWRR NGVGLEFNHL FGYGVLDAGA MVKMAKDWKT VPERFHCVGG SVQNPEKIPP
TGKLVLTLKT NACEGKENFV RYLEHVQAVI TVNATRRGDL NINMTSPMGT KSILLSRRPR
DDDSKVGFDK WPFMTTHTWG EDARGTWTLE LGFVGSAPQK GLLKEWTLML HGTQSAPYID
QVVRDYQSKL AMSKKQELEE ELDEAVERSL QSILRKN
//
