ID   VGF_HUMAN               Reviewed;         615 AA.
AC   O15240; Q9UDW8;
DT   27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT   23-SEP-2008, sequence version 2.
DT   13-FEB-2019, entry version 126.
DE   RecName: Full=Neurosecretory protein VGF;
DE   Contains:
DE     RecName: Full=Neuroendocrine regulatory peptide-1;
DE              Short=NERP-1;
DE   Contains:
DE     RecName: Full=Neuroendocrine regulatory peptide-2;
DE              Short=NERP-2;
DE   Contains:
DE     RecName: Full=Antimicrobial peptide VGF[554-577];
DE   Flags: Precursor;
GN   Name=VGF;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   TISSUE=Placenta;
RX   PubMed=9344675; DOI=10.1006/geno.1997.4945;
RA   Canu N., Possenti R., Ricco A.S., Rocchi M., Levi A.;
RT   "Cloning, structural organization analysis and chromosomal assignment
RT   of the human gene for neurosecretory protein VGF.";
RL   Genomics 45:443-446(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12853948; DOI=10.1038/nature01782;
RA   Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA   Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R.,
RA   Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
RA   Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
RA   Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
RA   Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
RA   Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
RA   Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
RA   Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
RA   Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
RA   Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
RA   Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
RA   Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
RA   Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA   Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K.,
RA   Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
RA   Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
RA   Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
RA   Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
RA   Waterston R.H., Wilson R.K.;
RT   "The DNA sequence of human chromosome 7.";
RL   Nature 424:157-164(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=PNS;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   PROTEIN SEQUENCE OF 554-577, FUNCTION, AND AMIDATION AT PRO-577.
RX   PubMed=23250050; DOI=10.1074/mcp.M112.017400;
RA   Sasaki K., Osaki T., Minamino N.;
RT   "Large-scale identification of endogenous secretory peptides using
RT   electron transfer dissociation mass spectrometry.";
RL   Mol. Cell. Proteomics 12:700-709(2013).
RN   [6]
RP   FUNCTION OF PEPTIDES NERP-1 AND NERP-2, PYROGLUTAMATE FORMATION AT
RP   GLN-310, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=19194657; DOI=10.1007/s00018-009-8796-0;
RA   Toshinai K., Nakazato M.;
RT   "Neuroendocrine regulatory peptide-1 and -2: novel bioactive peptides
RT   processed from VGF.";
RL   Cell. Mol. Life Sci. 66:1939-1945(2009).
RN   [7]
RP   PHOSPHORYLATION AT SER-420 AND THR-424.
RX   PubMed=26091039; DOI=10.1016/j.cell.2015.05.028;
RA   Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J.,
RA   Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N.,
RA   Pinna L.A., Pagliarini D.J., Dixon J.E.;
RT   "A single kinase generates the majority of the secreted
RT   phosphoproteome.";
RL   Cell 161:1619-1632(2015).
CC   -!- FUNCTION: May be involved in the regulation of cell-cell
CC       interactions or in synatogenesis during the maturation of the
CC       nervous system. {ECO:0000250}.
CC   -!- FUNCTION: NERP peptides are involved in the control of body fluid
CC       homeostasis by regulating vasopressin release.
CC       {ECO:0000269|PubMed:19194657}.
CC   -!- FUNCTION: Antimicrobial peptide VGF[554-577]: Has bactericidal
CC       activity against M. luteus, and antifungal activity against P.
CC       Pastoris. {ECO:0000269|PubMed:23250050}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:19194657}.
CC       Cytoplasmic vesicle, secretory vesicle
CC       {ECO:0000269|PubMed:19194657}. Note=Stored in secretory vesicles
CC       and then secreted, NERP peptides colocalize with vasopressin in
CC       the storage granules of hypothalamus.
CC   -!- TISSUE SPECIFICITY: Central and peripheral nervous systems,
CC       synthesized exclusively in neuronal and neuroendocrine cells.
CC       {ECO:0000269|PubMed:19194657}.
CC   -!- PTM: Multiple peptides are derived from VGF, with activities in
CC       synaptic plasticity, antidepression, penile erection, autonomic
CC       activation, and increases in energy expenditure. {ECO:0000250}.
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DR   EMBL; Y12661; CAA73210.1; -; Genomic_DNA.
DR   EMBL; AC004876; AAD45830.1; -; Genomic_DNA.
DR   EMBL; CH471197; EAW50201.1; -; Genomic_DNA.
DR   EMBL; BC063835; AAH63835.1; -; mRNA.
DR   CCDS; CCDS5712.1; -.
DR   RefSeq; NP_003369.2; NM_003378.3.
DR   RefSeq; XP_005250618.1; XM_005250561.4.
DR   RefSeq; XP_011514851.1; XM_011516549.2.
DR   RefSeq; XP_016868068.1; XM_017012579.1.
DR   UniGene; Hs.587325; -.
DR   ProteinModelPortal; O15240; -.
DR   SMR; O15240; -.
DR   BioGrid; 113268; 5.
DR   IntAct; O15240; 3.
DR   STRING; 9606.ENSP00000249330; -.
DR   iPTMnet; O15240; -.
DR   PhosphoSitePlus; O15240; -.
DR   BioMuta; VGF; -.
DR   EPD; O15240; -.
DR   jPOST; O15240; -.
DR   MaxQB; O15240; -.
DR   PaxDb; O15240; -.
DR   PeptideAtlas; O15240; -.
DR   PRIDE; O15240; -.
DR   ProteomicsDB; 48531; -.
DR   Ensembl; ENST00000249330; ENSP00000249330; ENSG00000128564.
DR   Ensembl; ENST00000445482; ENSP00000400884; ENSG00000128564.
DR   GeneID; 7425; -.
DR   KEGG; hsa:7425; -.
DR   UCSC; uc003uxx.5; human.
DR   CTD; 7425; -.
DR   DisGeNET; 7425; -.
DR   EuPathDB; HostDB:ENSG00000128564.6; -.
DR   GeneCards; VGF; -.
DR   HGNC; HGNC:12684; VGF.
DR   HPA; HPA055177; -.
DR   HPA; HPA072505; -.
DR   MIM; 602186; gene.
DR   neXtProt; NX_O15240; -.
DR   OpenTargets; ENSG00000128564; -.
DR   PharmGKB; PA37305; -.
DR   eggNOG; ENOG410IKTZ; Eukaryota.
DR   eggNOG; ENOG410YR85; LUCA.
DR   GeneTree; ENSGT00390000017745; -.
DR   HOGENOM; HOG000120127; -.
DR   HOVERGEN; HBG006806; -.
DR   InParanoid; O15240; -.
DR   OMA; YIRPRTL; -.
DR   OrthoDB; 1064302at2759; -.
DR   PhylomeDB; O15240; -.
DR   TreeFam; TF338498; -.
DR   Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR   Reactome; R-HSA-8957275; Post-translational protein phosphorylation.
DR   GenomeRNAi; 7425; -.
DR   PRO; PR:O15240; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   Bgee; ENSG00000128564; Expressed in 140 organ(s), highest expression level in hypothalamus.
DR   ExpressionAtlas; O15240; baseline and differential.
DR   Genevisible; O15240; HS.
DR   GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR   GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR   GO; GO:0030133; C:transport vesicle; IEA:UniProtKB-SubCell.
DR   GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR   GO; GO:0005184; F:neuropeptide hormone activity; IEA:Ensembl.
DR   GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome.
DR   GO; GO:0042742; P:defense response to bacterium; IEA:UniProtKB-KW.
DR   GO; GO:0006091; P:generation of precursor metabolites and energy; IEA:Ensembl.
DR   GO; GO:0042593; P:glucose homeostasis; IEA:Ensembl.
DR   GO; GO:0030073; P:insulin secretion; IEA:Ensembl.
DR   GO; GO:0001541; P:ovarian follicle development; IEA:Ensembl.
DR   GO; GO:0043687; P:post-translational protein modification; TAS:Reactome.
DR   GO; GO:0051591; P:response to cAMP; IEP:UniProtKB.
DR   GO; GO:0009409; P:response to cold; IEA:Ensembl.
DR   GO; GO:0002021; P:response to dietary excess; IEA:Ensembl.
DR   GO; GO:0032868; P:response to insulin; IEA:Ensembl.
DR   GO; GO:0019953; P:sexual reproduction; IEA:Ensembl.
DR   InterPro; IPR026128; VGF.
DR   PANTHER; PTHR15159; PTHR15159; 1.
PE   1: Evidence at protein level;
KW   Amidation; Antibiotic; Antimicrobial;
KW   Cleavage on pair of basic residues; Complete proteome;
KW   Cytoplasmic vesicle; Direct protein sequencing; Growth factor;
KW   Phosphoprotein; Pyrrolidone carboxylic acid; Reference proteome;
KW   Secreted; Signal.
FT   SIGNAL        1     22       {ECO:0000255}.
FT   CHAIN        23    615       Neurosecretory protein VGF.
FT                                /FTId=PRO_0000022655.
FT   PEPTIDE     281    306       Neuroendocrine regulatory peptide-1.
FT                                /FTId=PRO_0000403364.
FT   PEPTIDE     310    347       Neuroendocrine regulatory peptide-2.
FT                                /FTId=PRO_0000403365.
FT   PEPTIDE     554    577       Antimicrobial peptide VGF[554-577].
FT                                /FTId=PRO_0000422072.
FT   COMPBIAS    353    447       Asp/Glu-rich (acidic).
FT   MOD_RES     310    310       Pyrrolidone carboxylic acid.
FT                                {ECO:0000269|PubMed:19194657}.
FT   MOD_RES     420    420       Phosphoserine; by FAM20C.
FT                                {ECO:0000269|PubMed:26091039}.
FT   MOD_RES     424    424       Phosphothreonine; by FAM20C.
FT                                {ECO:0000269|PubMed:26091039}.
FT   MOD_RES     577    577       Proline amide.
FT                                {ECO:0000269|PubMed:23250050}.
FT   CONFLICT    129    131       PES -> AGE (in Ref. 1; CAA73210).
FT                                {ECO:0000305}.
FT   CONFLICT    282    282       P -> A (in Ref. 1; CAA73210).
FT                                {ECO:0000305}.
FT   CONFLICT    387    387       E -> EA (in Ref. 1; CAA73210).
FT                                {ECO:0000305}.
FT   CONFLICT    393    393       E -> D (in Ref. 1; CAA73210).
FT                                {ECO:0000305}.
FT   CONFLICT    481    481       K -> N (in Ref. 1; CAA73210).
FT                                {ECO:0000305}.
FT   CONFLICT    485    485       N -> K (in Ref. 1; CAA73210).
FT                                {ECO:0000305}.
FT   CONFLICT    512    515       APAP -> PPS (in Ref. 1; CAA73210).
FT                                {ECO:0000305}.
FT   CONFLICT    585    586       RA -> HAQ (in Ref. 1; CAA73210).
FT                                {ECO:0000305}.
SQ   SEQUENCE   615 AA;  67258 MW;  198097C5622AC087 CRC64;
     MKALRLSASA LFCLLLINGL GAAPPGRPEA QPPPLSSEHK EPVAGDAVPG PKDGSAPEVR
     GARNSEPQDE GELFQGVDPR ALAAVLLQAL DRPASPPAPS GSQQGPEEEA AEALLTETVR
     SQTHSLPAPE SPEPAAPPRP QTPENGPEAS DPSEELEALA SLLQELRDFS PSSAKRQQET
     AAAETETRTH TLTRVNLESP GPERVWRASW GEFQARVPER APLPPPAPSQ FQARMPDSGP
     LPETHKFGEG VSSPKTHLGE ALAPLSKAYQ GVAAPFPKAR RPESALLGGS EAGERLLQQG
     LAQVEAGRRQ AEATRQAAAQ EERLADLASD LLLQYLLQGG ARQRGLGGRG LQEAAEERES
     AREEEEAEQE RRGGEERVGE EDEEAAEAEA EAEEAERARQ NALLFAEEED GEAGAEDKRS
     QEETPGHRRK EAEGTEEGGE EEDDEEMDPQ TIDSLIELST KLHLPADDVV SIIEEVEEKR
     KRKKNAPPEP VPPPRAAPAP THVRSPQPPP PAPAPARDEL PDWNEVLPPW DREEDEVYPP
     GPYHPFPNYI RPRTLQPPSA LRRRHYHHAL PPSRHYPGRE AQARRAQEEA EAEERRLQEQ
     EELENYIEHV LLRRP
//