NEC1_RAT
ID NEC1_RAT Reviewed; 752 AA.
AC P28840;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-1992, sequence version 1.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Neuroendocrine convertase 1;
DE Short=NEC 1;
DE EC=3.4.21.93;
DE AltName: Full=Prohormone convertase 1;
DE AltName: Full=Proprotein convertase 1;
DE Short=PC1;
DE Flags: Precursor;
GN Name=Pcsk1; Synonyms=Bdp, Nec-1, Nec1;
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).
CC -!- FUNCTION: Involved in the processing of hormone and other protein
CC precursors at sites comprised of pairs of basic amino acid residues.
CC Substrates include POMC, renin, enkephalin, dynorphin, somatostatin,
CC insulin and AGRP. {ECO:0000250|UniProtKB:P63239}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of protein hormones, neuropeptides and renin from
CC their precursors, generally by hydrolysis of -Lys-Arg-|- bonds.;
CC EC=3.4.21.93;
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle.
CC Note=Localized in the secretion granules.
CC -!- SIMILARITY: Belongs to the peptidase S8 family. Furin subfamily.
CC {ECO:0000305}.
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DR EMBL; M76705; AAA40945.1; -; mRNA.
DR EMBL; M83745; AAA41476.1; -; mRNA.
DR PIR; A41556; KXRTC1.
DR RefSeq; NP_058787.1; NM_017091.2.
DR AlphaFoldDB; P28840; -.
DR SMR; P28840; -.
DR STRING; 10116.ENSRNOP00000015185; -.
DR MEROPS; S08.072; -.
DR GlyGen; P28840; 3 sites.
DR PhosphoSitePlus; P28840; -.
DR PaxDb; P28840; -.
DR PRIDE; P28840; -.
DR Ensembl; ENSRNOT00000015185; ENSRNOP00000015185; ENSRNOG00000011107.
DR GeneID; 25204; -.
DR KEGG; rno:25204; -.
DR UCSC; RGD:3272; rat.
DR CTD; 5122; -.
DR RGD; 3272; Pcsk1.
DR eggNOG; KOG3525; Eukaryota.
DR GeneTree; ENSGT00940000157385; -.
DR HOGENOM; CLU_002976_4_1_1; -.
DR InParanoid; P28840; -.
DR OMA; YYLFKHK; -.
DR OrthoDB; 473018at2759; -.
DR PhylomeDB; P28840; -.
DR TreeFam; TF314277; -.
DR Reactome; R-RNO-209952; Peptide hormone biosynthesis.
DR Reactome; R-RNO-422085; Synthesis, secretion, and deacylation of Ghrelin.
DR PRO; PR:P28840; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000011107; Expressed in frontal cortex and 12 other tissues.
DR Genevisible; P28840; RN.
DR GO; GO:0043679; C:axon terminus; IDA:RGD.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0043204; C:perikaryon; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0005791; C:rough endoplasmic reticulum; IDA:RGD.
DR GO; GO:0030141; C:secretory granule; IDA:RGD.
DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
DR GO; GO:0005802; C:trans-Golgi network; IDA:RGD.
DR GO; GO:0030133; C:transport vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0004175; F:endopeptidase activity; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0004252; F:serine-type endopeptidase activity; ISO:RGD.
DR GO; GO:0022008; P:neurogenesis; IEP:RGD.
DR GO; GO:0031016; P:pancreas development; IEP:RGD.
DR GO; GO:0043043; P:peptide biosynthetic process; ISO:RGD.
DR GO; GO:0016486; P:peptide hormone processing; IDA:RGD.
DR GO; GO:0021983; P:pituitary gland development; IEP:RGD.
DR GO; GO:0050714; P:positive regulation of protein secretion; IDA:RGD.
DR GO; GO:0016540; P:protein autoprocessing; IMP:RGD.
DR GO; GO:0016485; P:protein processing; IMP:RGD.
DR GO; GO:0048678; P:response to axon injury; IEP:RGD.
DR GO; GO:0051592; P:response to calcium ion; IEP:RGD.
DR GO; GO:0010157; P:response to chlorate; IEP:RGD.
DR GO; GO:0070542; P:response to fatty acid; IEP:RGD.
DR GO; GO:0051384; P:response to glucocorticoid; IEP:RGD.
DR GO; GO:0009749; P:response to glucose; IEP:RGD.
DR GO; GO:0010035; P:response to inorganic substance; IEP:RGD.
DR GO; GO:0070555; P:response to interleukin-1; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0043278; P:response to morphine; IEP:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0043434; P:response to peptide hormone; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP: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; IPR022005; Proho_convert.
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; PF12177; Proho_convert; 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 2: Evidence at transcript level;
KW Calcium; Cleavage on pair of basic residues; Cytoplasmic vesicle;
KW Disulfide bond; Glycoprotein; Hydrolase; Protease; Reference proteome;
KW Serine protease; Signal; Zymogen.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT PROPEP 28..110
FT /evidence="ECO:0000255"
FT /id="PRO_0000027063"
FT CHAIN 111..752
FT /note="Neuroendocrine convertase 1"
FT /id="PRO_0000027064"
FT DOMAIN 129..450
FT /note="Peptidase S8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT DOMAIN 460..597
FT /note="P/Homo B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01173"
FT REGION 631..662
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 631..648
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 167
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 208
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 382
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT CARBOHYD 173
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 401
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 645
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 225..374
FT /evidence="ECO:0000250"
FT DISULFID 317..347
FT /evidence="ECO:0000250"
FT DISULFID 467..494
FT /evidence="ECO:0000250"
FT CONFLICT 366
FT /note="T -> TT (in Ref. 2; AAA41476)"
FT /evidence="ECO:0000305"
FT CONFLICT 514
FT /note="E -> A (in Ref. 2; AAA41476)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 752 AA; 84121 MW; F630AD830A076DED CRC64;
MKQRGWTLQC TAFTLFCVWC ALNSVKAKRQ FVNEWAAEIH GGPEAASAIA EELGYDLLGQ
IGSLENHYLF KHKNHPRRSR RSALHITKRL SDDDRVIWAE QQYEKERRKR SVPRDSALNL
FNDPMWNQQW YLQDTRMTAS LPKLDLHVIP VWQKGITGKG VVITVLDDGL EWNHTDIYAN
YDPEASYDFN DNDHDPFPRY DPTNENKHGT RCAGEIAMQA NNHKCGVGVA YNSKVGGIRM
LDGIVTDAIE ASSIGFNPGH VDIYSASWGP NDDGKTVEGP GRLAQKAFEY GVKQGRQGKG
SIFVWASGNG GRQGDNCDCD GYTDSIYTIS ISSASQQGLS PWYAEKCSST LATSYSSGDY
TDQRITSADL HNDCTETHTG TSASAPLAAG IFALALEANP NLTWRDMQHL VVWTSEYDPL
ANNPGWKKNG AGLMVNSRFG FGLLNAKALV DLADPRTWRN VPEKKECIIK DNNFEPRALK
ANGEVIVEIP TRACEGQENA INSLEHVQFE ATIEYSRRGD LHVTLTSAAG TSTVLLAERE
RDTSPNGFKN WDFMSVHTWG ENPVGTWTLK VTDMSGRMQN EGRIVNWKLI LHGTSSQPEH
MKQPRVYTSY NTVQNDRRGV EKMVNVVEEK PTQNSLNGNL LVPKNSSSSS VEDRRDEQVQ
GAPSKAMLRL LQSAFSKNTP SKQSSKIPSA KLSVPYEGLY EALEKLNKPS QLEDSEDSLY
SDYVDVFYNT KPYKHRDDRL LQALMDILNE KN
