VGF_HUMAN
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 03-AUG-2022, entry version 142.
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=VGF-derived peptide TLQP-21;
DE Contains:
DE RecName: Full=VGF-derived peptide TLQP-62;
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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 of
RT 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., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., 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., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA 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., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., 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 project:
RT 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 electron
RT transfer dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 12:700-709(2013).
RN [6]
RP REVIEW ON FUNCTION, PYROGLUTAMATE FORMATION AT GLN-310, SUBCELLULAR
RP 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 phosphoproteome.";
RL Cell 161:1619-1632(2015).
RN [8]
RP INTERACTION WITH HSPA8 (VGF-DERIVED PEPTIDE TLQP-21).
RX PubMed=28934328; DOI=10.1371/journal.pone.0185176;
RA Akhter S., Chakraborty S., Moutinho D., Alvarez-Coiradas E., Rosa I.,
RA Vinuela J., Dominguez E., Garcia A., Requena J.R.;
RT "The human VGF-derived bioactive peptide TLQP-21 binds heat shock 71 kDa
RT protein 8 (HSPA8)on the surface of SH-SY5Y cells.";
RL PLoS ONE 12:E0185176-E0185176(2017).
CC -!- FUNCTION: [Neurosecretory protein VGF]: Secreted polyprotein that is
CC packaged and proteolytically processed by prohormone convertases PCSK1
CC and PCSK2 in a cell-type-specific manner (By similarity). VGF and
CC peptides derived from its processing play many roles in neurogenesis
CC and neuroplasticity associated with learning, memory, depression and
CC chronic pain (By similarity). {ECO:0000250|UniProtKB:P20156,
CC ECO:0000250|UniProtKB:Q0VGU4}.
CC -!- FUNCTION: [Neuroendocrine regulatory peptide-1]: Plays a role in the
CC control of body fluid homeostasis by regulating vasopressin release.
CC Suppresses presynaptic glutamatergic neurons connected to vasopressin
CC neurons. {ECO:0000250|UniProtKB:P20156}.
CC -!- FUNCTION: [Neuroendocrine regulatory peptide-2]: Plays a role in the
CC control of body fluid homeostasis by regulating vasopressin release.
CC Activates GABAergic interneurons which are inhibitory neurons of the
CC nervous system and thereby suppresses presynaptic glutamatergic neurons
CC (By similarity). Stimulates also feeding behavior in an orexin-
CC dependent manner in the hypothalamus (By similarity). Functions as a
CC positive regulator for the activation of orexin neurons resulting in
CC elevated gastric acid secretion and gastric emptying (By similarity).
CC {ECO:0000250|UniProtKB:P20156}.
CC -!- FUNCTION: [VGF-derived peptide TLQP-21]: Secreted multifunctional
CC neuropeptide that binds to different cell receptors and thereby plays
CC multiple physiological roles including modulation of energy
CC expenditure, pain, response to stress, gastric regulation, glucose
CC homeostasis as well as lipolysis (By similarity). Activates the G-
CC protein-coupled receptor C3AR1 via a folding-upon-binding mechanism
CC leading to enhanced lipolysis in adipocytes (By similarity). Interacts
CC with C1QBP receptor in macrophages and microglia causing increased
CC levels of intracellular calcium and hypersensitivity (By similarity).
CC {ECO:0000250|UniProtKB:P20156, ECO:0000250|UniProtKB:Q0VGU4}.
CC -!- FUNCTION: [VGF-derived peptide TLQP-62]: Plays a role in the regulation
CC of memory formation and depression-related behaviors potentially by
CC influencing synaptic plasticity and neurogenesis. Induces acute and
CC transient activation of the NTRK2/TRKB receptor and subsequent CREB
CC phosphorylation (By similarity). Induces also insulin secretion in
CC insulinoma cells by increasing intracellular calcium mobilization (By
CC similarity). {ECO:0000250|UniProtKB:Q0VGU4}.
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 -!- SUBUNIT: [VGF-derived peptide TLQP-21]: Interacts with HSPA8 on cell
CC membrane (PubMed:28934328). Interacts with C3AR1 (By similarity).
CC Interacts with C1QBP (By similarity). {ECO:0000250|UniProtKB:P20156,
CC ECO:0000250|UniProtKB:Q0VGU4, ECO:0000269|PubMed:28934328}.
CC -!- SUBCELLULAR LOCATION: [Neurosecretory protein VGF]: Secreted
CC {ECO:0000269|PubMed:19194657}. Cytoplasmic vesicle, secretory vesicle
CC {ECO:0000269|PubMed:19194657}. Note=Stored in secretory vesicles and
CC then secreted, NERP peptides colocalize with vasopressin in the storage
CC granules of hypothalamus.
CC -!- TISSUE SPECIFICITY: Central and peripheral nervous systems, synthesized
CC 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 PDB; 7D13; NMR; -; A=310-347.
DR PDB; 7D16; NMR; -; A=310-347.
DR PDBsum; 7D13; -.
DR PDBsum; 7D16; -.
DR AlphaFoldDB; O15240; -.
DR SMR; O15240; -.
DR BioGRID; 113268; 32.
DR IntAct; O15240; 4.
DR STRING; 9606.ENSP00000249330; -.
DR GlyGen; O15240; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O15240; -.
DR PhosphoSitePlus; O15240; -.
DR BioMuta; VGF; -.
DR EPD; O15240; -.
DR jPOST; O15240; -.
DR MassIVE; O15240; -.
DR MaxQB; O15240; -.
DR PaxDb; O15240; -.
DR PeptideAtlas; O15240; -.
DR PRIDE; O15240; -.
DR ProteomicsDB; 48531; -.
DR Antibodypedia; 30974; 373 antibodies from 35 providers.
DR DNASU; 7425; -.
DR Ensembl; ENST00000249330.3; ENSP00000249330.2; ENSG00000128564.8.
DR Ensembl; ENST00000445482.2; ENSP00000400884.2; ENSG00000128564.8.
DR GeneID; 7425; -.
DR KEGG; hsa:7425; -.
DR MANE-Select; ENST00000249330.3; ENSP00000249330.2; NM_003378.4; NP_003369.2.
DR UCSC; uc003uxx.5; human.
DR CTD; 7425; -.
DR DisGeNET; 7425; -.
DR GeneCards; VGF; -.
DR HGNC; HGNC:12684; VGF.
DR HPA; ENSG00000128564; Tissue enriched (brain).
DR MIM; 602186; gene.
DR neXtProt; NX_O15240; -.
DR OpenTargets; ENSG00000128564; -.
DR PharmGKB; PA37305; -.
DR VEuPathDB; HostDB:ENSG00000128564; -.
DR eggNOG; ENOG502S5N4; Eukaryota.
DR GeneTree; ENSGT00390000017745; -.
DR HOGENOM; CLU_030654_0_0_1; -.
DR InParanoid; O15240; -.
DR OMA; EMPGHRR; -.
DR OrthoDB; 1064302at2759; -.
DR PhylomeDB; O15240; -.
DR TreeFam; TF338498; -.
DR PathwayCommons; O15240; -.
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 Reactome; R-HSA-9031628; NGF-stimulated transcription.
DR SignaLink; O15240; -.
DR BioGRID-ORCS; 7425; 12 hits in 1068 CRISPR screens.
DR GenomeRNAi; 7425; -.
DR Pharos; O15240; Tbio.
DR PRO; PR:O15240; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; O15240; protein.
DR Bgee; ENSG00000128564; Expressed in superior frontal gyrus and 78 other tissues.
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:0043005; C:neuron projection; IEA:Ensembl.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0030667; C:secretory granule membrane; IEA:Ensembl.
DR GO; GO:0045202; C:synapse; IEA:Ensembl.
DR GO; GO:0030133; C:transport vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0005179; F:hormone activity; IBA:GO_Central.
DR GO; GO:0005184; F:neuropeptide hormone activity; IEA:Ensembl.
DR GO; GO:0033500; P:carbohydrate homeostasis; IBA:GO_Central.
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:0043084; P:penile erection; IEA:Ensembl.
DR GO; GO:0048168; P:regulation of neuronal synaptic plasticity; IEA:Ensembl.
DR GO; GO:0048167; P:regulation of synaptic plasticity; IBA:GO_Central.
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 3D-structure; Amidation; Antibiotic; Antimicrobial;
KW Cleavage on pair of basic residues; Cytoplasmic vesicle;
KW Direct protein sequencing; Growth factor; Phosphoprotein;
KW Pyrrolidone carboxylic acid; Reference proteome; Secreted; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..615
FT /note="Neurosecretory protein VGF"
FT /id="PRO_0000022655"
FT PEPTIDE 281..306
FT /note="Neuroendocrine regulatory peptide-1"
FT /id="PRO_0000403364"
FT PEPTIDE 310..347
FT /note="Neuroendocrine regulatory peptide-2"
FT /id="PRO_0000403365"
FT PEPTIDE 554..615
FT /note="VGF-derived peptide TLQP-62"
FT /id="PRO_0000446626"
FT PEPTIDE 554..577
FT /note="Antimicrobial peptide VGF[554-577]"
FT /id="PRO_0000422072"
FT PEPTIDE 554..574
FT /note="VGF-derived peptide TLQP-21"
FT /id="PRO_0000446627"
FT REGION 22..201
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 218..257
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 342..600
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 130..145
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 166..196
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 351..379
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 392..435
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 436..451
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 468..488
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 489..517
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 524..539
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 558..572
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 578..600
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 310
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:19194657"
FT MOD_RES 420
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 424
FT /note="Phosphothreonine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 577
FT /note="Proline amide"
FT /evidence="ECO:0000269|PubMed:23250050"
FT CONFLICT 129..131
FT /note="PES -> AGE (in Ref. 1; CAA73210)"
FT /evidence="ECO:0000305"
FT CONFLICT 282
FT /note="P -> A (in Ref. 1; CAA73210)"
FT /evidence="ECO:0000305"
FT CONFLICT 387
FT /note="E -> EA (in Ref. 1; CAA73210)"
FT /evidence="ECO:0000305"
FT CONFLICT 393
FT /note="E -> D (in Ref. 1; CAA73210)"
FT /evidence="ECO:0000305"
FT CONFLICT 481
FT /note="K -> N (in Ref. 1; CAA73210)"
FT /evidence="ECO:0000305"
FT CONFLICT 485
FT /note="N -> K (in Ref. 1; CAA73210)"
FT /evidence="ECO:0000305"
FT CONFLICT 512..515
FT /note="APAP -> PPS (in Ref. 1; CAA73210)"
FT /evidence="ECO:0000305"
FT CONFLICT 585..586
FT /note="RA -> HAQ (in Ref. 1; CAA73210)"
FT /evidence="ECO:0000305"
FT HELIX 311..345
FT /evidence="ECO:0007829|PDB:7D13"
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
