NEC2_RAT
ID NEC2_RAT Reviewed; 637 AA.
AC P28841;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-1992, sequence version 1.
DT 03-AUG-2022, entry version 172.
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, Rpc2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1791845; DOI=10.1210/mend-5-12-2014;
RA Bloomquist B.T., Eipper B.A., Mains R.E.;
RT "Prohormone-converting enzymes: regulation and evaluation of function using
RT antisense RNA.";
RL Mol. Endocrinol. 5:2014-2024(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1954888; DOI=10.1210/endo-129-6-3053;
RA Hakes D.J., Birch N.P., Mezey A., Dixon J.E.;
RT "Isolation of two complementary deoxyribonucleic acid clones from a rat
RT insulinoma cell line based on similarities to Kex2 and furin sequences and
RT the specific localization of each transcript to endocrine and
RT neuroendocrine tissues in rats.";
RL Endocrinology 129:3053-3063(1991).
RN [3]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-523, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24090084; DOI=10.1021/pr400783j;
RA Parker B.L., Thaysen-Andersen M., Solis N., Scott N.E., Larsen M.R.,
RA Graham M.E., Packer N.H., Cordwell S.J.;
RT "Site-specific glycan-peptide analysis for determination of N-glycoproteome
RT heterogeneity.";
RL J. Proteome Res. 12:5791-5800(2013).
CC -!- FUNCTION: Involved in the processing of hormone and other protein
CC precursors at sites comprised of pairs of basic amino acid residues.
CC Responsible for the release of glucagon from proglucagon in pancreatic
CC A cells (By similarity). {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 -!- INTERACTION:
CC P28841; P27682: Scg5; NbExp=4; IntAct=EBI-988244, EBI-988232;
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; M76706; AAA40946.1; -; mRNA.
DR EMBL; M83746; AAA41477.1; -; mRNA.
DR PIR; B41556; KXRTC2.
DR RefSeq; NP_036878.1; NM_012746.1.
DR AlphaFoldDB; P28841; -.
DR SMR; P28841; -.
DR BioGRID; 247192; 2.
DR IntAct; P28841; 3.
DR STRING; 10116.ENSRNOP00000007249; -.
DR MEROPS; S08.073; -.
DR GlyGen; P28841; 3 sites, 5 N-linked glycans (1 site).
DR iPTMnet; P28841; -.
DR PhosphoSitePlus; P28841; -.
DR PaxDb; P28841; -.
DR PRIDE; P28841; -.
DR Ensembl; ENSRNOT00000007249; ENSRNOP00000007249; ENSRNOG00000005438.
DR GeneID; 25121; -.
DR KEGG; rno:25121; -.
DR UCSC; RGD:3273; rat.
DR CTD; 5126; -.
DR RGD; 3273; Pcsk2.
DR eggNOG; KOG3526; Eukaryota.
DR GeneTree; ENSGT00940000156965; -.
DR HOGENOM; CLU_002976_4_4_1; -.
DR InParanoid; P28841; -.
DR OMA; PFMTDVI; -.
DR OrthoDB; 308083at2759; -.
DR PhylomeDB; P28841; -.
DR TreeFam; TF314277; -.
DR BRENDA; 3.4.21.94; 5301.
DR PRO; PR:P28841; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000005438; Expressed in frontal cortex and 8 other tissues.
DR Genevisible; P28841; RN.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0043204; C:perikaryon; IDA:RGD.
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; ISO:RGD.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IMP:BHF-UCL.
DR GO; GO:0034230; P:enkephalin processing; ISO:RGD.
DR GO; GO:0030070; P:insulin processing; ISO:RGD.
DR GO; GO:0034231; P:islet amyloid polypeptide processing; IMP:BHF-UCL.
DR GO; GO:0007399; P:nervous system development; ISO:RGD.
DR GO; GO:0016486; P:peptide hormone processing; IMP:RGD.
DR GO; GO:0016540; P:protein autoprocessing; ISO:RGD.
DR GO; GO:0016485; P:protein processing; IMP:RGD.
DR GO; GO:0006508; P:proteolysis; ISO:RGD.
DR CDD; cd04059; Peptidases_S8_Protein_convertases_Kexins_Furin-like; 1.
DR Gene3D; 3.30.70.850; -; 1.
DR Gene3D; 3.40.50.200; -; 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 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; SSF49785; 1.
DR SUPFAM; SSF52743; SSF52743; 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_0000027071"
FT CHAIN 109..637
FT /note="Neuroendocrine convertase 2"
FT /id="PRO_0000027072"
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:0007744|PubMed:24090084"
FT DISULFID 224..375
FT /evidence="ECO:0000250"
FT DISULFID 316..346
FT /evidence="ECO:0000250"
FT DISULFID 467..493
FT /evidence="ECO:0000250"
FT CONFLICT 320
FT /note="G -> GI (in Ref. 2; AAA41477)"
FT /evidence="ECO:0000305"
FT CONFLICT 342
FT /note="Y -> H (in Ref. 2; AAA41477)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 637 AA; 70753 MW; 45DCB85B2CDA4B19 CRC64;
MEGGCGSQWK AAGLLFCVMV FASAERPVFT NHFLVELHKD GEEEARQVAA EHGFGVRKLP
FAEGLYHFYH NGLAKAKRRR SLHHKRQLER DPRIKMALQQ EGFDRKKRGY RDINEIDINM
NDPLFTKQWY LFNTGQADGT PGLDLNVAEA WELGYTGKGV TIGIMDDGID YLHPDLAYNY
NSDASYDFSS NDPYPYPRYT DDWFNSHGTR CAGEVSAAAS NNICGVGVAY NSKVAGIRML
DQPFMTDIIE ASSISHMPQL IDIYSASWGP TDNGKTVDGP RELTLQAMAD GVNKGRGGKG
SIYVWASGDG GSYDDCNCDG YASSMWTISI NSAINDGRTA LYDESCSSTL ASTFSNGRKR
NPEAGVATTD LYGNCTLRHS GTSAAAPEAA GVFALALEAN VDLTWRDMQH LTVLTSKRNQ
LHDEVHQWRR NGVGLEFNHL FGYGVLDAGA MVKMAKDWKT VPERFHCVGG SVQNPEKIPP
TGKLVLTLQT NACEGKENFV RYLEHVQAVI TVNATRRGDL NINMTSPMGT KSILLSRRPR
DDDSKVGFDK WPFMTTHTWG EDARGTWTLE LGFVGSAPQK GLLKEWTLML HGTQSAPYID
QVVRDYQSKL AMSKKQELEE ELDEAVERSL QSILRKN
