NEC1_MOUSE
ID NEC1_MOUSE Reviewed; 753 AA.
AC P63239; P21662; P22546;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Neuroendocrine convertase 1;
DE Short=NEC 1;
DE EC=3.4.21.93;
DE AltName: Full=Furin homolog;
DE AltName: Full=PC3;
DE AltName: Full=Prohormone convertase 1;
DE AltName: Full=Propeptide-processing protease;
DE AltName: Full=Proprotein convertase 1;
DE Short=PC1;
DE Flags: Precursor;
GN Name=Pcsk1; Synonyms=Att-1, Nec-1, Nec1;
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=1862107; DOI=10.1073/pnas.88.15.6834;
RA Korner J., Chun J., Harter D., Axel R.;
RT "Isolation and functional expression of a mammalian prohormone processing
RT enzyme, murine prohormone convertase 1.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:6834-6838(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=LAF1;
RX PubMed=1657897; DOI=10.1093/oxfordjournals.jbchem.a123461;
RA Nakayama K., Hosaka M., Hatsuzawa K., Murakami K.;
RT "Cloning and functional expression of a novel endoprotease involved in
RT prohormone processing at dibasic sites.";
RL J. Biochem. 109:803-806(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Pituitary;
RX PubMed=2017186; DOI=10.1210/mend-5-1-111;
RA Seidah N.G., Marcinkiewicz M., Benjannet S., Gaspar L., Beaubien G.,
RA Mattei M.-G., Lazure C., Mbikay M., Chretien M.;
RT "Cloning and primary sequence of a mouse candidate prohormone convertase
RT PC1 homologous to PC2, Furin, and Kex2: distinct chromosomal localization
RT and messenger RNA distribution in brain and pituitary compared to PC2.";
RL Mol. Endocrinol. 5:111-122(1991).
RN [4]
RP PROTEIN SEQUENCE OF 111-120.
RC TISSUE=Ovary;
RX PubMed=8449925; DOI=10.1016/s0021-9258(18)53365-2;
RA Zhou Y., Lindberg I.;
RT "Purification and characterization of the prohormone convertase PC1(PC3).";
RL J. Biol. Chem. 268:5615-5623(1993).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 214-478.
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 [6]
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 [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16384863; DOI=10.1210/en.2005-1373;
RA Creemers J.W., Pritchard L.E., Gyte A., Le Rouzic P., Meulemans S.,
RA Wardlaw S.L., Zhu X., Steiner D.F., Davies N., Armstrong D., Lawrence C.B.,
RA Luckman S.M., Schmitz C.A., Davies R.A., Brennand J.C., White A.;
RT "Agouti-related protein is posttranslationally cleaved by proprotein
RT convertase 1 to generate agouti-related protein (AGRP)83-132: interaction
RT between AGRP83-132 and melanocortin receptors cannot be influenced by
RT syndecan-3.";
RL Endocrinology 147:1621-1631(2006).
RN [8]
RP STRUCTURE BY NMR OF 28-110.
RX PubMed=12095256; DOI=10.1016/s0022-2836(02)00543-0;
RA Tangrea M.A., Bryan P.N., Sari N., Orban J.;
RT "Solution structure of the pro-hormone convertase 1 pro-domain from Mus
RT musculus.";
RL J. Mol. Biol. 320:801-812(2002).
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:0000269|PubMed:16384863}.
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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 5.5-6.5.;
CC -!- INTERACTION:
CC P63239; P63239: Pcsk1; NbExp=2; IntAct=EBI-15770815, EBI-15770815;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle.
CC Note=Localized in the secretion granules.
CC -!- DISRUPTION PHENOTYPE: Increase in unprocessed AGRP.
CC {ECO:0000269|PubMed:16384863}.
CC -!- SIMILARITY: Belongs to the peptidase S8 family. Furin subfamily.
CC {ECO:0000305}.
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DR EMBL; M69196; AAA39732.1; -; mRNA.
DR EMBL; X57088; CAA40368.1; -; mRNA.
DR EMBL; M58589; AAA39894.1; -; mRNA.
DR EMBL; M55668; AAA39375.1; ALT_SEQ; mRNA.
DR CCDS; CCDS26649.1; -.
DR PIR; JX0171; KXMSC1.
DR RefSeq; NP_038656.1; NM_013628.2.
DR RefSeq; XP_006517216.1; XM_006517153.2.
DR RefSeq; XP_006517217.1; XM_006517154.3.
DR RefSeq; XP_006517218.1; XM_006517155.2.
DR PDB; 1KN6; NMR; -; A=28-110.
DR PDB; 2KDT; NMR; -; A=711-753.
DR PDB; 2KE3; NMR; -; A=711-753.
DR PDBsum; 1KN6; -.
DR PDBsum; 2KDT; -.
DR PDBsum; 2KE3; -.
DR AlphaFoldDB; P63239; -.
DR BMRB; P63239; -.
DR SMR; P63239; -.
DR BioGRID; 202057; 4.
DR DIP; DIP-48841N; -.
DR STRING; 10090.ENSMUSP00000022075; -.
DR MEROPS; S08.072; -.
DR GlyGen; P63239; 2 sites.
DR iPTMnet; P63239; -.
DR PhosphoSitePlus; P63239; -.
DR PaxDb; P63239; -.
DR PeptideAtlas; P63239; -.
DR PRIDE; P63239; -.
DR ProteomicsDB; 253052; -.
DR Antibodypedia; 13091; 178 antibodies from 31 providers.
DR DNASU; 18548; -.
DR Ensembl; ENSMUST00000022075; ENSMUSP00000022075; ENSMUSG00000021587.
DR GeneID; 18548; -.
DR KEGG; mmu:18548; -.
DR UCSC; uc007rfs.1; mouse.
DR CTD; 5122; -.
DR MGI; MGI:97511; Pcsk1.
DR VEuPathDB; HostDB:ENSMUSG00000021587; -.
DR eggNOG; KOG3525; Eukaryota.
DR GeneTree; ENSGT00940000157385; -.
DR HOGENOM; CLU_002976_4_1_1; -.
DR InParanoid; P63239; -.
DR OMA; YYLFKHK; -.
DR OrthoDB; 473018at2759; -.
DR PhylomeDB; P63239; -.
DR TreeFam; TF314277; -.
DR BRENDA; 3.4.21.93; 3474.
DR Reactome; R-MMU-209952; Peptide hormone biosynthesis.
DR Reactome; R-MMU-422085; Synthesis, secretion, and deacylation of Ghrelin.
DR BioGRID-ORCS; 18548; 2 hits in 74 CRISPR screens.
DR EvolutionaryTrace; P63239; -.
DR PRO; PR:P63239; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; P63239; protein.
DR Bgee; ENSMUSG00000021587; Expressed in supraoptic nucleus and 73 other tissues.
DR ExpressionAtlas; P63239; baseline and differential.
DR Genevisible; P63239; MM.
DR GO; GO:0043679; C:axon terminus; ISO:MGI.
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:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0043204; C:perikaryon; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005791; C:rough endoplasmic reticulum; ISO:MGI.
DR GO; GO:0030141; C:secretory granule; ISO:MGI.
DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
DR GO; GO:0005802; C:trans-Golgi network; ISO:MGI.
DR GO; GO:0030133; C:transport vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0004175; F:endopeptidase activity; IDA:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:BHF-UCL.
DR GO; GO:0022008; P:neurogenesis; IEA:Ensembl.
DR GO; GO:0031016; P:pancreas development; IEA:Ensembl.
DR GO; GO:0043043; P:peptide biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0016486; P:peptide hormone processing; IDA:BHF-UCL.
DR GO; GO:0021983; P:pituitary gland development; IEA:Ensembl.
DR GO; GO:0050714; P:positive regulation of protein secretion; ISO:MGI.
DR GO; GO:0016540; P:protein autoprocessing; ISO:MGI.
DR GO; GO:0016485; P:protein processing; IDA:BHF-UCL.
DR GO; GO:0048678; P:response to axon injury; IEA:Ensembl.
DR GO; GO:0051592; P:response to calcium ion; IEA:Ensembl.
DR GO; GO:0010157; P:response to chlorate; IEA:Ensembl.
DR GO; GO:0070542; P:response to fatty acid; IEA:Ensembl.
DR GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
DR GO; GO:0009749; P:response to glucose; IEA:Ensembl.
DR GO; GO:0070555; P:response to interleukin-1; IEA:Ensembl.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0043278; P:response to morphine; IEA:Ensembl.
DR GO; GO:0031667; P:response to nutrient levels; IEA:Ensembl.
DR GO; GO:0043434; P:response to peptide hormone; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
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 1: Evidence at protein level;
KW 3D-structure; Calcium; Cleavage on pair of basic residues;
KW Cytoplasmic vesicle; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Hydrolase; Protease; Reference proteome; Serine protease;
KW Signal; Zymogen.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT PROPEP 28..110
FT /evidence="ECO:0000255"
FT /id="PRO_0000027059"
FT CHAIN 111..753
FT /note="Neuroendocrine convertase 1"
FT /id="PRO_0000027060"
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 633..663
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 633..657
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 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 112
FT /note="V -> F (in Ref. 2; CAA40368)"
FT /evidence="ECO:0000305"
FT CONFLICT 117
FT /note="A -> P (in Ref. 2; CAA40368)"
FT /evidence="ECO:0000305"
FT CONFLICT 122
FT /note="N -> T (in Ref. 2; CAA40368)"
FT /evidence="ECO:0000305"
FT CONFLICT 128
FT /note="Q -> H (in Ref. 2; CAA40368)"
FT /evidence="ECO:0000305"
FT CONFLICT 282
FT /note="R -> K (in Ref. 2; CAA40368)"
FT /evidence="ECO:0000305"
FT CONFLICT 330
FT /note="S -> L (in Ref. 3; AAA39375)"
FT /evidence="ECO:0000305"
FT CONFLICT 732
FT /note="K -> E (in Ref. 2; CAA40368)"
FT /evidence="ECO:0000305"
FT STRAND 35..38
FT /evidence="ECO:0007829|PDB:1KN6"
FT HELIX 43..53
FT /evidence="ECO:0007829|PDB:1KN6"
FT STRAND 62..65
FT /evidence="ECO:0007829|PDB:1KN6"
FT STRAND 67..71
FT /evidence="ECO:0007829|PDB:1KN6"
FT STRAND 77..79
FT /evidence="ECO:0007829|PDB:1KN6"
FT HELIX 89..94
FT /evidence="ECO:0007829|PDB:1KN6"
FT STRAND 97..100
FT /evidence="ECO:0007829|PDB:1KN6"
FT STRAND 713..716
FT /evidence="ECO:0007829|PDB:2KDT"
FT STRAND 718..721
FT /evidence="ECO:0007829|PDB:2KE3"
FT HELIX 722..726
FT /evidence="ECO:0007829|PDB:2KDT"
FT TURN 727..730
FT /evidence="ECO:0007829|PDB:2KDT"
FT HELIX 741..748
FT /evidence="ECO:0007829|PDB:2KDT"
FT TURN 749..751
FT /evidence="ECO:0007829|PDB:2KDT"
SQ SEQUENCE 753 AA; 84174 MW; 04239C7B6385382E CRC64;
MEQRGWTLQC TAFAFFCVWC ALNSVKAKRQ FVNEWAAEIP GGQEAASAIA EELGYDLLGQ
IGSLENHYLF KHKSHPRRSR RSALHITKRL SDDDRVTWAE QQYEKERSKR SVQKDSALDL
FNDPMWNQQW YLQDTRMTAA LPKLDLHVIP VWEKGITGKG VVITVLDDGL EWNHTDIYAN
YDPEASYDFN DNDHDPFPRY DLTNENKHGT RCAGEIAMQA NNHKCGVGVA YNSKVGGIRM
LDGIVTDAIE ASSIGFNPGH VDIYSASWGP NDDGKTVEGP GRLAQKAFEY GVKQGRQGKG
SIFVWASGNG GRQGDNCDCD GYTDSIYTIS ISSASQQGLS PWYAEKCSST LATSYSSGDY
TDQRITSADL HNDCTETHTG TSASAPLAAG IFALALEANP NLTWRDMQHL VVWTSEYDPL
ASNPGWKKNG AGLMVNSRFG FGLLNAKALV DLADPRTWRN VPEKKECVVK DNNFEPRALK
ANGEVIVEIP TRACEGQENA IKSLEHVQFE ATIEYSRRGD LHVTLTSAVG TSTVLLAERE
RDTSPNGFKN WDFMSVHTWG ENPVGTWTLK ITDMSGRMQN EGRIVNWKLI LHGTSSQPEH
MKQPRVYTSY NTVQNDRRGV EKMVNVVEKR PTQKSLNGNL LVPKNSSSSN VEGRRDEQVQ
GTPSKAMLRL LQSAFSKNAL SKQSPKKSPS AKLSIPYESF YEALEKLNKP SKLEGSEDSL
YSDYVDVFYN TKPYKHRDDR LLQALMDILN EEN
