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NPVF_HUMAN
ID   NPVF_HUMAN              Reviewed;         196 AA.
AC   Q9HCQ7; A4D164; Q7LE27; Q96PI9;
DT   10-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT   23-FEB-2022, sequence version 3.
DT   03-AUG-2022, entry version 136.
DE   RecName: Full=Pro-FMRFamide-related neuropeptide VF;
DE   Contains:
DE     RecName: Full=Neuropeptide NPSF;
DE   Contains:
DE     RecName: Full=Neuropeptide RFRP-1;
DE   Contains:
DE     RecName: Full=Neuropeptide RFRP-2;
DE   Contains:
DE     RecName: Full=Neuropeptide NPVF;
DE     AltName: Full=Neuropeptide RFRP-3;
DE   Flags: Precursor;
GN   Name=NPVF; Synonyms=C7orf9, RFRP;
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 [MRNA] (ISOFORM 1), SYNTHESIS OF RFRP-1; RFRP-2 AND
RP   NPVF, AND FUNCTION.
RC   TISSUE=Fetal brain;
RX   PubMed=11025660; DOI=10.1038/35036326;
RA   Hinuma S., Shintani Y., Fukusumi S., Iijima N., Matsumoto Y., Hosoya M.,
RA   Fujii R., Watanabe T., Kikuchi K., Terao Y., Yano T., Yamamoto T.,
RA   Kawamata Y., Habata Y., Asada M., Kitada C., Kurokawa T., Onda H.,
RA   Nishimura O., Tanaka M., Ibata Y., Fujino M.;
RT   "New neuropeptides containing carboxy-terminal RFamide and their receptor
RT   in mammals.";
RL   Nat. Cell Biol. 2:703-708(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX   PubMed=11481330; DOI=10.1074/jbc.m105308200;
RA   Liu Q., Guan X.-M., Martin W.J., McDonald T.P., Clements M.K., Jiang Q.,
RA   Zeng Z., Jacobson M., Williams D.L. Jr., Yu H., Bomford D., Figueroa D.,
RA   Mallee J., Wang R., Evans J., Gould R., Austin C.P.;
RT   "Identification and characterization of novel mammalian neuropeptide FF-
RT   like peptides that attenuate morphine-induced antinociception.";
RL   J. Biol. Chem. 276:36961-36969(2001).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), TISSUE SPECIFICITY,
RP   AND VARIANT GLY-42.
RC   TISSUE=Retina;
RX   PubMed=11951088;
RA   Schulz H.L., Stoehr H., White K., van Driel M.A., Hoyng C.B., Cremers F.,
RA   Weber B.H.F.;
RT   "Genomic structure and assessment of the retinally expressed RFamide-
RT   related peptide gene in dominant cystoid macular dystrophy.";
RL   Mol. Vis. 8:67-71(2002).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ILE-32.
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   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12690205; DOI=10.1126/science.1083423;
RA   Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA   Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA   Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA   Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA   Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA   Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA   Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA   Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA   Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA   Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA   Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA   Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA   Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA   Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA   Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA   Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA   Adams M.D., Tsui L.-C.;
RT   "Human chromosome 7: DNA sequence and biology.";
RL   Science 300:767-772(2003).
RN   [6]
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   [7]
RP   PROTEIN SEQUENCE OF 81-92 AND 124-131, AMIDATION AT PHE-92 AND PHE-131,
RP   FUNCTION, TISSUE SPECIFICITY, AND MASS SPECTROMETRY.
RX   PubMed=20027225; DOI=10.1371/journal.pone.0008400;
RA   Ubuka T., Morgan K., Pawson A.J., Osugi T., Chowdhury V.S., Minakata H.,
RA   Tsutsui K., Millar R.P., Bentley G.E.;
RT   "Identification of human GnIH homologs, RFRP-1 and RFRP-3, and the cognate
RT   receptor, GPR147 in the human hypothalamic pituitary axis.";
RL   PLoS ONE 4:E8400-E8400(2009).
CC   -!- FUNCTION: Neuropeptide RFRP-1 acts as a potent negative regulator of
CC       gonadotropin synthesis and secretion. Neuropeptides NPSF and NPVF
CC       efficiently inhibit forskolin-induced production of cAMP, but RFRP-2
CC       shows no inhibitory activity. Neuropeptide RFRP-1 induces secretion of
CC       prolactin in rats. Neuropeptide NPVF blocks morphine-induced analgesia.
CC       {ECO:0000269|PubMed:11025660, ECO:0000269|PubMed:20027225}.
CC   -!- INTERACTION:
CC       Q9HCQ7; O43765: SGTA; NbExp=3; IntAct=EBI-1753111, EBI-347996;
CC       Q9HCQ7; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-1753111, EBI-947187;
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q9HCQ7-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9HCQ7-2; Sequence=VSP_039962;
CC   -!- TISSUE SPECIFICITY: Isoform 1 is specifically expressed in the retina.
CC       Neuropeptides RFRP-1 and NPVF are detected in the hypothalamus.
CC       {ECO:0000269|PubMed:11951088, ECO:0000269|PubMed:20027225}.
CC   -!- MASS SPECTROMETRY: [Neuropeptide RFRP-1]: Mass=1428.85; Method=MALDI;
CC       Evidence={ECO:0000269|PubMed:20027225};
CC   -!- MASS SPECTROMETRY: [Neuropeptide NPVF]: Mass=969.56; Method=MALDI;
CC       Evidence={ECO:0000269|PubMed:20027225};
CC   -!- SIMILARITY: Belongs to the FARP (FMRFamide related peptide) family.
CC       {ECO:0000305}.
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DR   EMBL; AB040290; BAB17674.1; -; mRNA.
DR   EMBL; AF330057; AAK94201.1; -; mRNA.
DR   EMBL; AF440392; AAL90453.1; -; mRNA.
DR   EMBL; AF440395; AAL90458.1; -; Genomic_DNA.
DR   EMBL; AF440393; AAL90458.1; JOINED; Genomic_DNA.
DR   EMBL; AF440394; AAL90458.1; JOINED; Genomic_DNA.
DR   EMBL; AC004129; AAP22339.1; -; Genomic_DNA.
DR   EMBL; CH236948; EAL24237.1; -; Genomic_DNA.
DR   EMBL; CH471073; EAW93830.1; -; Genomic_DNA.
DR   CCDS; CCDS5395.1; -. [Q9HCQ7-1]
DR   RefSeq; NP_071433.3; NM_022150.3.
DR   AlphaFoldDB; Q9HCQ7; -.
DR   BioGRID; 122068; 17.
DR   IntAct; Q9HCQ7; 5.
DR   STRING; 9606.ENSP00000222674; -.
DR   iPTMnet; Q9HCQ7; -.
DR   PhosphoSitePlus; Q9HCQ7; -.
DR   BioMuta; NPVF; -.
DR   DMDM; 311033508; -.
DR   MassIVE; Q9HCQ7; -.
DR   PaxDb; Q9HCQ7; -.
DR   PeptideAtlas; Q9HCQ7; -.
DR   PRIDE; Q9HCQ7; -.
DR   ProteomicsDB; 81787; -. [Q9HCQ7-1]
DR   ProteomicsDB; 81788; -. [Q9HCQ7-2]
DR   Antibodypedia; 50012; 28 antibodies from 9 providers.
DR   DNASU; 64111; -.
DR   Ensembl; ENST00000222674.2; ENSP00000222674.2; ENSG00000105954.2. [Q9HCQ7-1]
DR   GeneID; 64111; -.
DR   KEGG; hsa:64111; -.
DR   MANE-Select; ENST00000222674.2; ENSP00000222674.2; NM_022150.3; NP_071433.3.
DR   UCSC; uc003sxo.4; human. [Q9HCQ7-1]
DR   CTD; 64111; -.
DR   DisGeNET; 64111; -.
DR   GeneCards; NPVF; -.
DR   HGNC; HGNC:13782; NPVF.
DR   HPA; ENSG00000105954; Tissue enriched (retina).
DR   MIM; 616984; gene.
DR   neXtProt; NX_Q9HCQ7; -.
DR   OpenTargets; ENSG00000105954; -.
DR   PharmGKB; PA162398161; -.
DR   VEuPathDB; HostDB:ENSG00000105954; -.
DR   eggNOG; ENOG502S5H9; Eukaryota.
DR   GeneTree; ENSGT00390000003271; -.
DR   HOGENOM; CLU_120051_0_0_1; -.
DR   InParanoid; Q9HCQ7; -.
DR   OrthoDB; 1553087at2759; -.
DR   PhylomeDB; Q9HCQ7; -.
DR   TreeFam; TF330935; -.
DR   PathwayCommons; Q9HCQ7; -.
DR   SignaLink; Q9HCQ7; -.
DR   BioGRID-ORCS; 64111; 13 hits in 1055 CRISPR screens.
DR   GenomeRNAi; 64111; -.
DR   Pharos; Q9HCQ7; Tdark.
DR   PRO; PR:Q9HCQ7; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   RNAct; Q9HCQ7; protein.
DR   Bgee; ENSG00000105954; Expressed in hypothalamus and 11 other tissues.
DR   Genevisible; Q9HCQ7; HS.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR   GO; GO:0032277; P:negative regulation of gonadotropin secretion; IDA:UniProtKB.
DR   GO; GO:0007218; P:neuropeptide signaling pathway; IBA:GO_Central.
DR   InterPro; IPR026297; FMRFamide-related/fGRP.
DR   PANTHER; PTHR14403; PTHR14403; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Amidation; Cleavage on pair of basic residues;
KW   Direct protein sequencing; Neuropeptide; Reference proteome; Secreted;
KW   Signal.
FT   SIGNAL          1..26
FT                   /evidence="ECO:0000255"
FT   PROPEP          27..55
FT                   /id="PRO_0000009920"
FT   PEPTIDE         56..92
FT                   /note="Neuropeptide NPSF"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000009921"
FT   PEPTIDE         81..92
FT                   /note="Neuropeptide RFRP-1"
FT                   /id="PRO_0000401171"
FT   PROPEP          95..99
FT                   /id="PRO_0000009922"
FT   PEPTIDE         101..112
FT                   /note="Neuropeptide RFRP-2"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000009923"
FT   PROPEP          115..121
FT                   /id="PRO_0000009924"
FT   PEPTIDE         124..131
FT                   /note="Neuropeptide NPVF"
FT                   /id="PRO_0000009925"
FT   PROPEP          134..196
FT                   /id="PRO_0000009926"
FT   MOD_RES         92
FT                   /note="Phenylalanine amide"
FT                   /evidence="ECO:0000269|PubMed:20027225"
FT   MOD_RES         131
FT                   /note="Phenylalanine amide"
FT                   /evidence="ECO:0000269|PubMed:20027225"
FT   VAR_SEQ         181..196
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:11481330"
FT                   /id="VSP_039962"
FT   VARIANT         32
FT                   /note="M -> I (in dbSNP:rs886354)"
FT                   /evidence="ECO:0000269|PubMed:12853948"
FT                   /id="VAR_014073"
FT   VARIANT         42
FT                   /note="D -> G (in dbSNP:rs877834)"
FT                   /evidence="ECO:0000269|PubMed:11951088"
FT                   /id="VAR_014074"
FT   VARIANT         121
FT                   /note="V -> M (in dbSNP:rs3213641)"
FT                   /id="VAR_030644"
SQ   SEQUENCE   196 AA;  22327 MW;  332248B927702198 CRC64;
     MEIISSKLFI LLTLATSSLL TSNIFCADEL VMSNLHSKEN YDKYSEPRGY PKGERSLNFE
     ELKDWGPKNV IKMSTPAVNK MPHSFANLPL RFGRNVQEER SAGATANLPL RSGRNMEVSL
     VRRVPNLPQR FGRTTTAKSV CRMLSDLCQG SMHSPCANDL FYSMTCQHQE IQNPDQKQSR
     RLLFKKIDDA ELKQEK
 
 
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