SPXN1_DANRE
ID SPXN1_DANRE Reviewed; 102 AA.
AC F1QQI2;
DT 03-SEP-2014, integrated into UniProtKB/Swiss-Prot.
DT 03-MAY-2011, sequence version 1.
DT 03-AUG-2022, entry version 47.
DE RecName: Full=Spexin prohormone 1 {ECO:0000305};
DE AltName: Full=Neuropeptide Q {ECO:0000303|PubMed:29116147};
DE AltName: Full=Spexin hormone {ECO:0000305};
DE Contains:
DE RecName: Full=Spexin-1 {ECO:0000303|PubMed:24517231};
DE AltName: Full=Spexin-14 {ECO:0000303|PubMed:24517231};
DE Flags: Precursor;
GN Name=spx; Synonyms=si:dkey-13i19.7;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=23623870; DOI=10.1016/j.mce.2013.04.008;
RA Liu Y., Li S., Qi X., Zhou W., Liu X., Lin H., Zhang Y., Cheng C.H.;
RT "A novel neuropeptide in suppressing luteinizing hormone release in
RT goldfish, Carassius auratus.";
RL Mol. Cell. Endocrinol. 374:65-72(2013).
RN [3]
RP FUNCTION (SPEXIN-1), AND TISSUE SPECIFICITY.
RX PubMed=24517231; DOI=10.1210/en.2013-2106;
RA Kim D.K., Yun S., Son G.H., Hwang J.I., Park C.R., Kim J.I., Kim K.,
RA Vaudry H., Seong J.Y.;
RT "Coevolution of the spexin/galanin/kisspeptin family: Spexin activates
RT galanin receptor type II and III.";
RL Endocrinology 155:1864-1873(2014).
RN [4]
RP FUNCTION, AND MUTAGENESIS OF 27-ALA--TYR-102.
RX PubMed=29116147; DOI=10.1038/s41598-017-15138-6;
RA Zheng B., Li S., Liu Y., Li Y., Chen H., Tang H., Liu X., Lin H., Zhang Y.,
RA Cheng C.H.K.;
RT "Spexin Suppress Food Intake in Zebrafish: Evidence from Gene Knockout
RT Study.";
RL Sci. Rep. 7:14643-14643(2017).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=31474838; DOI=10.3389/fncir.2019.00053;
RA Jeong I., Kim E., Seong J.Y., Park H.C.;
RT "Overexpression of Spexin 1 in the Dorsal Habenula Reduces Anxiety in
RT Zebrafish.";
RL Front. Neural Circuits 13:53-53(2019).
RN [6]
RP DEVELOPMENTAL STAGE.
RX PubMed=30903017; DOI=10.1038/s41598-019-41431-7;
RA Kim E., Jeong I., Chung A.Y., Kim S., Kwon S.H., Seong J.Y., Park H.C.;
RT "Distribution and neuronal circuit of spexin 1/2 neurons in the zebrafish
RT CNS.";
RL Sci. Rep. 9:5025-5025(2019).
CC -!- FUNCTION: Plays a role in the regulation of food intake and energy
CC metabolism (PubMed:29116147). May also be involved in suppressing the
CC anxiety response by promoting the expression of serotonin-related genes
CC such as fev, tph2 and slc6a4a (PubMed:31474838).
CC {ECO:0000269|PubMed:29116147, ECO:0000269|PubMed:31474838}.
CC -!- FUNCTION: [Spexin-1]: Acts as a ligand for galanin receptors galr2a and
CC galr2b (PubMed:24517231). Brain administration of the peptide inhibits
CC food consumption and elevates levels of glucose, triacylglycerol and
CC cholesterol in the serum (PubMed:29116147). Likely to control food
CC intake by regulating appetite related genes which includes the negative
CC regulation of the orexigenic factor agrp (PubMed:29116147). By
CC controlling food intake it may act as a satiety factor in energy
CC metabolism (PubMed:29116147). {ECO:0000269|PubMed:24517231,
CC ECO:0000269|PubMed:29116147}.
CC -!- SUBCELLULAR LOCATION: [Spexin-1]: Secreted
CC {ECO:0000250|UniProtKB:Q9BT56}. Secreted, extracellular space
CC {ECO:0000250|UniProtKB:Q9BT56}. Cytoplasmic vesicle, secretory vesicle
CC {ECO:0000250|UniProtKB:Q9BT56}.
CC -!- TISSUE SPECIFICITY: Mainly expressed in the brain and ovary
CC (PubMed:23623870, PubMed:24517231). Detected bilaterally in the adult
CC brainstem (PubMed:30903017). Expressed in neurons in the dorsal
CC habenula (dHb) (PubMed:31474838, PubMed:30903017). In the dHb some
CC neurons project into the interpeduncular nucleus (IPN) where expression
CC often overlaps with galr2a and galr2b (PubMed:31474838,
CC PubMed:30903017). Weakly expressed in the liver, intestine, kidney,
CC heart and gill (PubMed:23623870). {ECO:0000269|PubMed:23623870,
CC ECO:0000269|PubMed:24517231, ECO:0000269|PubMed:30903017,
CC ECO:0000269|PubMed:31474838}.
CC -!- DEVELOPMENTAL STAGE: In embryos, first detected at the 1 cell stage but
CC disappears by the 2 cell stage (PubMed:30903017). Expressed again from
CC 24 hours post fertilization (hpf) (PubMed:30903017). At 24 hours post
CC fertilization (hpf), detected in a few cells in the embryo hindbrain
CC (PubMed:30903017). In larvae, expressed in the neurons and nerve fibers
CC of the midbrain tegmentum and hindbrain (PubMed:30903017). In the
CC hindbrain, expressed in reticulospinal neurons with spinal projections
CC (PubMed:30903017). Axons of hindbrain neurons project into the dorsal
CC spinal cord where expression often overlaps with galr2b
CC (PubMed:30903017). In larvae, not detected in the hypothalamus and not
CC detected outside of the brain (PubMed:30903017).
CC {ECO:0000269|PubMed:30903017}.
CC -!- INDUCTION: Up-regulated during folliculogenesis.
CC {ECO:0000269|PubMed:23623870}.
CC -!- SIMILARITY: Belongs to the spexin family. {ECO:0000305}.
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DR EMBL; BX649476; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_005164831.1; XM_005164774.3.
DR AlphaFoldDB; F1QQI2; -.
DR STRING; 7955.ENSDARP00000073885; -.
DR PaxDb; F1QQI2; -.
DR Ensembl; ENSDART00000079429; ENSDARP00000073885; ENSDARG00000056859.
DR GeneID; 101882535; -.
DR KEGG; dre:101882535; -.
DR CTD; 80763; -.
DR ZFIN; ZDB-GENE-041210-158; spx.
DR eggNOG; ENOG502SAD1; Eukaryota.
DR GeneTree; ENSGT00390000012501; -.
DR HOGENOM; CLU_169090_0_0_1; -.
DR InParanoid; F1QQI2; -.
DR OMA; LETRSHN; -.
DR OrthoDB; 1579616at2759; -.
DR TreeFam; TF333402; -.
DR PRO; PR:F1QQI2; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 4.
DR Bgee; ENSDARG00000056859; Expressed in nucleus of thalamus and 16 other tissues.
DR ExpressionAtlas; F1QQI2; baseline.
DR GO; GO:0031045; C:dense core granule; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0030133; C:transport vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0005184; F:neuropeptide hormone activity; ISS:UniProtKB.
DR GO; GO:0031765; F:type 2 galanin receptor binding; ISS:UniProtKB.
DR GO; GO:0031766; F:type 3 galanin receptor binding; ISS:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; IMP:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; IMP:UniProtKB.
DR GO; GO:0044539; P:long-chain fatty acid import into cell; ISS:UniProtKB.
DR GO; GO:0032099; P:negative regulation of appetite; ISS:UniProtKB.
DR GO; GO:1903999; P:negative regulation of eating behavior; IMP:ZFIN.
DR GO; GO:0010459; P:negative regulation of heart rate; ISS:UniProtKB.
DR GO; GO:0035814; P:negative regulation of renal sodium excretion; ISS:UniProtKB.
DR GO; GO:1904306; P:positive regulation of gastro-intestinal system smooth muscle contraction; ISS:UniProtKB.
DR GO; GO:0003084; P:positive regulation of systemic arterial blood pressure; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0051930; P:regulation of sensory perception of pain; ISS:UniProtKB.
DR GO; GO:0070328; P:triglyceride homeostasis; IMP:UniProtKB.
DR InterPro; IPR028126; Spexin.
DR PANTHER; PTHR28590; PTHR28590; 1.
DR Pfam; PF15171; Spexin; 1.
PE 1: Evidence at protein level;
KW Amidation; Cleavage on pair of basic residues; Cytoplasmic vesicle;
KW Hormone; Reference proteome; Secreted; Signal.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..102
FT /note="Spexin prohormone 1"
FT /id="PRO_0000430232"
FT PROPEP 27..35
FT /evidence="ECO:0000250"
FT /id="PRO_0000430233"
FT PEPTIDE 36..49
FT /note="Spexin-1"
FT /id="PRO_0000430234"
FT PROPEP 50..102
FT /evidence="ECO:0000250"
FT /id="PRO_0000430235"
FT SITE 35..36
FT /note="Cleavage; by prohormone convertase 2"
FT /evidence="ECO:0000250"
FT MOD_RES 49
FT /note="Glutamine amide"
FT /evidence="ECO:0000250"
FT MUTAGEN 27..102
FT /note="APKGSFQRRNWTPQAMLYLKGTQGRRFVSEDRNEGDLYDTIRLESRSQNTEN
FT LSISKAAAFLLNILQQARDEDEPY->IPRAVFSVGIGHPKLCYI: Increased
FT food intake and elevated levels of glucose, triacylglycerol
FT and cholesterol in serum. Expression levels of agrp in the
FT hypothalamus, are significantly up-regulated in fed and
FT unfed mutants. However at 3 hours post feeding, agrp levels
FT continue to increase in fed mutants but decrease in unfed
FT mutants. No effect on puberty onset, gamete maturation,
FT body weight, body fat percentage and standard length."
FT /evidence="ECO:0000269|PubMed:29116147"
SQ SEQUENCE 102 AA; 11681 MW; 5105863C38C517A1 CRC64;
MKDLRTLAAY ALALLLLATF VSHSWSAPKG SFQRRNWTPQ AMLYLKGTQG RRFVSEDRNE
GDLYDTIRLE SRSQNTENLS ISKAAAFLLN ILQQARDEDE PY
