VGF_MOUSE
ID VGF_MOUSE Reviewed; 617 AA.
AC Q0VGU4;
DT 10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2006, sequence version 1.
DT 03-AUG-2022, entry version 122.
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 Flags: Precursor;
GN Name=Vgf {ECO:0000312|MGI:MGI:1343180};
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [4]
RP DISRUPTION PHENOTYPE, AND FUNCTION (NEUROSECRETORY PROTEIN VGF).
RX PubMed=19863797; DOI=10.1186/1472-6793-9-19;
RA Watson E., Fargali S., Okamoto H., Sadahiro M., Gordon R.E.,
RA Chakraborty T., Sleeman M.W., Salton S.R.;
RT "Analysis of knockout mice suggests a role for VGF in the control of fat
RT storage and energy expenditure.";
RL BMC Physiol. 9:19-19(2009).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION (VGF-DERIVED PEPTIDE TLQP-21), AND TISSUE SPECIFICITY (VGF-DERIVED
RP PEPTIDE TLQP-21).
RX PubMed=22289198; DOI=10.1016/j.bbr.2012.01.038;
RA Razzoli M., Bo E., Pascucci T., Pavone F., D'Amato F.R., Cero C.,
RA Sanghez V., Dadomo H., Palanza P., Parmigiani S., Ceresini G.,
RA Puglisi-Allegra S., Porta M., Panzica G.C., Moles A., Possenti R.,
RA Bartolomucci A.;
RT "Implication of the VGF-derived peptide TLQP-21 in mouse acute and chronic
RT stress responses.";
RL Behav. Brain Res. 229:333-339(2012).
RN [7]
RP FUNCTION (VGF-DERIVED PEPTIDE TLQP-21), INTERACTION WITH C3AR1 (VGF-DERIVED
RP PEPTIDE TLQP-21), AND MUTAGENESIS OF ARG-576.
RX PubMed=25456411; DOI=10.1016/j.str.2014.10.001;
RA Cero C., Vostrikov V.V., Verardi R., Severini C., Gopinath T., Braun P.D.,
RA Sassano M.F., Gurney A., Roth B.L., Vulchanova L., Possenti R., Veglia G.,
RA Bartolomucci A.;
RT "The TLQP-21 peptide activates the G-protein-coupled receptor C3aR1 via a
RT folding-upon-binding mechanism.";
RL Structure 22:1744-1753(2014).
RN [8]
RP FUNCTION (VGF-DERIVED PEPTIDE TLQP-62).
RX PubMed=25917832; DOI=10.1530/jme-14-0313;
RA Petrocchi-Passeri P., Cero C., Cutarelli A., Frank C., Severini C.,
RA Bartolomucci A., Possenti R.;
RT "The VGF-derived peptide TLQP-62 modulates insulin secretion and glucose
RT homeostasis.";
RL J. Mol. Endocrinol. 54:227-239(2015).
RN [9]
RP FUNCTION (VGF-DERIVED PEPTIDE TLQP-62), AND FUNCTION (NEUROSECRETORY
RP PROTEIN VGF).
RX PubMed=26180209; DOI=10.1523/jneurosci.0584-15.2015;
RA Lin W.J., Jiang C., Sadahiro M., Bozdagi O., Vulchanova L., Alberini C.M.,
RA Salton S.R.;
RT "VGF and Its C-Terminal Peptide TLQP-62 Regulate Memory Formation in
RT Hippocampus via a BDNF-TrkB-Dependent Mechanism.";
RL J. Neurosci. 35:10343-10356(2015).
RN [10]
RP FUNCTION (VGF-DERIVED PEPTIDE TLQP-62), AND FUNCTION (NEUROSECRETORY
RP PROTEIN VGF).
RX PubMed=30504797; DOI=10.1038/s41386-018-0277-4;
RA Jiang C., Lin W.J., Labonte B., Tamminga C.A., Turecki G., Nestler E.J.,
RA Russo S.J., Salton S.R.;
RT "VGF and its C-terminal peptide TLQP-62 in ventromedial prefrontal cortex
RT regulate depression-related behaviors and the response to ketamine.";
RL Neuropsychopharmacology 44:971-981(2019).
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 (PubMed:19863797, PubMed:26180209, PubMed:30504797).
CC {ECO:0000250|UniProtKB:P20156, ECO:0000269|PubMed:19863797,
CC ECO:0000269|PubMed:26180209, ECO:0000269|PubMed:30504797}.
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-1]: 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 peptide that interacts with different receptors and thereby plays
CC multiple physiological roles including modulation of energy
CC expenditure, pain, response to stress, gastric regulation as well as
CC lipolysis (PubMed:22289198, PubMed:25456411). Activates the G-protein-
CC coupled receptor C3AR1 via a folding-upon-binding mechanism leading to
CC enhanced lipolysis in adipocytes (PubMed:25456411). Interacts with
CC gC1qR receptor in macrophages and microglia causing increased levels of
CC intracellular calcium and hypersensitivity (By similarity).
CC {ECO:0000250|UniProtKB:P20156, ECO:0000269|PubMed:22289198,
CC ECO:0000269|PubMed:25456411}.
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 (PubMed:26180209, PubMed:30504797). Induces also
CC insulin secretion in insulinoma cells by increasing intracellular
CC calcium mobilization (PubMed:25917832). {ECO:0000269|PubMed:25917832,
CC ECO:0000269|PubMed:26180209, ECO:0000269|PubMed:30504797}.
CC -!- SUBUNIT: [VGF-derived peptide TLQP-21]: Interacts with HSPA8 on cell
CC membrane (By similarity). Interacts with C3AR1 (PubMed:25456411).
CC Interacts with C1QBP (By similarity). {ECO:0000250|UniProtKB:O15240,
CC ECO:0000250|UniProtKB:P20156, ECO:0000269|PubMed:25456411}.
CC -!- SUBCELLULAR LOCATION: [Neurosecretory protein VGF]: Secreted
CC {ECO:0000250|UniProtKB:O15240}. Cytoplasmic vesicle, secretory vesicle
CC {ECO:0000250|UniProtKB:O15240}. Note=Stored in secretory vesicles and
CC then secreted, NERP peptides colocalize with vasopressin in the storage
CC granules of hypothalamus. {ECO:0000250|UniProtKB:O15240}.
CC -!- DISRUPTION PHENOTYPE: VGF-deficiency produces a lean, hypermetabolic
CC mouse that is resistant to diet and genetically-induced obesity.
CC {ECO:0000269|PubMed:19863797}.
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DR EMBL; AC147986; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466529; EDL19290.1; -; Genomic_DNA.
DR EMBL; BC085134; AAH85134.1; -; mRNA.
DR EMBL; BC138553; AAI38554.1; -; mRNA.
DR EMBL; BC138554; AAI38555.1; -; mRNA.
DR CCDS; CCDS19760.1; -.
DR RefSeq; NP_001034474.1; NM_001039385.1.
DR RefSeq; XP_006504497.1; XM_006504434.2.
DR RefSeq; XP_006504498.1; XM_006504435.1.
DR RefSeq; XP_006504499.1; XM_006504436.2.
DR RefSeq; XP_006504500.1; XM_006504437.2.
DR RefSeq; XP_006504501.1; XM_006504438.2.
DR RefSeq; XP_006504502.1; XM_006504439.2.
DR RefSeq; XP_006504503.1; XM_006504440.1.
DR RefSeq; XP_017176427.1; XM_017320938.1.
DR RefSeq; XP_017176428.1; XM_017320939.1.
DR AlphaFoldDB; Q0VGU4; -.
DR SMR; Q0VGU4; -.
DR IntAct; Q0VGU4; 2.
DR STRING; 10090.ENSMUSP00000140815; -.
DR iPTMnet; Q0VGU4; -.
DR PhosphoSitePlus; Q0VGU4; -.
DR MaxQB; Q0VGU4; -.
DR PaxDb; Q0VGU4; -.
DR PeptideAtlas; Q0VGU4; -.
DR PRIDE; Q0VGU4; -.
DR ProteomicsDB; 338956; -.
DR Antibodypedia; 30974; 373 antibodies from 35 providers.
DR Ensembl; ENSMUST00000041543; ENSMUSP00000048273; ENSMUSG00000037428.
DR Ensembl; ENSMUST00000186451; ENSMUSP00000140735; ENSMUSG00000037428.
DR Ensembl; ENSMUST00000190827; ENSMUSP00000140815; ENSMUSG00000037428.
DR GeneID; 381677; -.
DR KEGG; mmu:381677; -.
DR UCSC; uc009abl.1; mouse.
DR CTD; 7425; -.
DR MGI; MGI:1343180; Vgf.
DR VEuPathDB; HostDB:ENSMUSG00000037428; -.
DR eggNOG; ENOG502S5N4; Eukaryota.
DR GeneTree; ENSGT00390000017745; -.
DR HOGENOM; CLU_030654_0_0_1; -.
DR InParanoid; Q0VGU4; -.
DR OMA; EMPGHRR; -.
DR OrthoDB; 1064302at2759; -.
DR PhylomeDB; Q0VGU4; -.
DR TreeFam; TF338498; -.
DR Reactome; R-MMU-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-MMU-8957275; Post-translational protein phosphorylation.
DR BioGRID-ORCS; 381677; 3 hits in 75 CRISPR screens.
DR PRO; PR:Q0VGU4; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q0VGU4; protein.
DR Bgee; ENSMUSG00000037428; Expressed in suprachiasmatic nucleus and 74 other tissues.
DR ExpressionAtlas; Q0VGU4; baseline and differential.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:MGI.
DR GO; GO:0005576; C:extracellular region; TAS:MGI.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0030667; C:secretory granule membrane; ISO:MGI.
DR GO; GO:0045202; C:synapse; ISO:MGI.
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; IMP:MGI.
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; IMP:MGI.
DR GO; GO:0042593; P:glucose homeostasis; IMP:MGI.
DR GO; GO:0030073; P:insulin secretion; IGI:MGI.
DR GO; GO:0001541; P:ovarian follicle development; IMP:MGI.
DR GO; GO:0043084; P:penile erection; ISO:MGI.
DR GO; GO:0048168; P:regulation of neuronal synaptic plasticity; ISO:MGI.
DR GO; GO:0048167; P:regulation of synaptic plasticity; IBA:GO_Central.
DR GO; GO:0051591; P:response to cAMP; IEA:Ensembl.
DR GO; GO:0009409; P:response to cold; IDA:MGI.
DR GO; GO:0002021; P:response to dietary excess; IDA:MGI.
DR GO; GO:0032868; P:response to insulin; IMP:MGI.
DR GO; GO:0019953; P:sexual reproduction; IMP:MGI.
DR InterPro; IPR026128; VGF.
DR PANTHER; PTHR15159; PTHR15159; 1.
PE 1: Evidence at protein level;
KW Amidation; Antibiotic; Antimicrobial; Cleavage on pair of basic residues;
KW Coiled coil; Cytoplasmic vesicle; Growth factor; Phosphoprotein;
KW Pyrrolidone carboxylic acid; Reference proteome; Secreted; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..617
FT /note="Neurosecretory protein VGF"
FT /evidence="ECO:0000255"
FT /id="PRO_5015097006"
FT PEPTIDE 284..309
FT /note="Neuroendocrine regulatory peptide-1"
FT /evidence="ECO:0000250|UniProtKB:P20156"
FT /id="PRO_0000446628"
FT PEPTIDE 313..350
FT /note="Neuroendocrine regulatory peptide-2"
FT /evidence="ECO:0000250|UniProtKB:P20156"
FT /id="PRO_0000446629"
FT PEPTIDE 556..617
FT /note="VGF-derived peptide TLQP-62"
FT /evidence="ECO:0000269|PubMed:25917832"
FT /id="PRO_0000446630"
FT PEPTIDE 556..576
FT /note="VGF-derived peptide TLQP-21"
FT /evidence="ECO:0000269|PubMed:22289198"
FT /id="PRO_0000446631"
FT REGION 29..75
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 93..204
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 239..262
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 345..599
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 46..61
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 169..199
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 349..378
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 379..394
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 395..438
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 439..455
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 472..492
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 493..520
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 526..541
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 574..599
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 313
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000250|UniProtKB:O15240"
FT MOD_RES 423
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O15240"
FT MUTAGEN 576
FT /note="R->A: Complete loss of lipolytic function."
FT /evidence="ECO:0000269|PubMed:25456411"
SQ SEQUENCE 617 AA; 68232 MW; 97E3598E7932EDE5 CRC64;
MKTFTLPASV LFCFLLLIQG LGAAPPGRPD VFPPPLSSEH NGQVAEDAVS RPKDDGVPEV
RAARNPEPQD QGELFQGVDP RALASVLLQA LDRPASPPSV PGGSQQGTPE EAAEALLTES
VRSQTHSLPA PEIQAPAVAP PRPQTQDRDP EEDDRSEELE ALASLLQELR DFSPSNAKRQ
QETAAAETET RTHTLTRVNL ESPGPERVWR ASWGEFQARV PERAPLPPPV PSQFQARMSE
SAPLPETHQF GEGVSSPKTH LGETLTPLSK AYQSLGGPFP KVRRLEGSFL GGSEAGERLL
QQGLAQVEAG RRQAEATRQA AAQEERLADL ASDLLLQYLL QGGARQRDLG GRELQETQQE
RENEREEEAE QERRGGGEDD VGEEDEEAAE AEAEAEEAER ARQNALLFAE EEDGEAGAED
KRSQEEAPGH RRKDAEGAEE GGEEDDDDEE MDPQTIDSLI ELSTKLHLPA DDVVSIIEEV
EEKRKRKKNA PPEPVPPPRA APAPTHVRSP QPPPPAPARD ELPDWNEVLP PWDREEDEVF
PPGPYHPFPN YIRPRTLQPP ASSRRRHFHH ALPPARHHPD LEAQARRAQE EADAEERRLQ
EQEELENYIE HVLLHRP
