SPXN_RAT
ID SPXN_RAT Reviewed; 116 AA.
AC M0R8L2; Q6TXE0;
DT 03-SEP-2014, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2013, sequence version 1.
DT 03-AUG-2022, entry version 38.
DE RecName: Full=Spexin;
DE AltName: Full=Liver regeneration-related protein LRRGT00060;
DE AltName: Full=NPQ;
DE AltName: Full=Neuropeptide Q;
DE AltName: Full=Spexin hormone;
DE Contains:
DE RecName: Full=Spexin-1;
DE Contains:
DE RecName: Full=Spexin-2;
DE AltName: Full=NPQ 53-70;
DE Flags: Precursor;
GN Name=SPX;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE (ISOFORM 2).
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RA Xu C.S., Chang C.F., Han H.P., Wang G.P., Chai L.Q., Yuan J.Y., Yang K.J.,
RA Zhao L.F., Ma H., Wang L., Wang S.F., Xing X.K., Shen G.M., Shi J.B.,
RA Rahman S., Wang Q.N., Zhang J.B.;
RT "Liver regeneration after PH.";
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=19132080; DOI=10.1371/journal.pcbi.1000258;
RA Sonmez K., Zaveri N.T., Kerman I.A., Burke S., Neal C.R., Xie X.,
RA Watson S.J., Toll L.;
RT "Evolutionary sequence modeling for discovery of peptide hormones.";
RL PLoS Comput. Biol. 5:E1000258-E1000258(2009).
RN [4]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=20530460; DOI=10.1369/jhc.2010.956300;
RA Porzionato A., Rucinski M., Macchi V., Stecco C., Malendowicz L.K.,
RA De Caro R.;
RT "Spexin expression in normal rat tissues.";
RL J. Histochem. Cytochem. 58:825-837(2010).
RN [5]
RP FUNCTION, INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=20045034; DOI=10.1016/j.peptides.2009.12.025;
RA Rucinski M., Porzionato A., Ziolkowska A., Szyszka M., Macchi V.,
RA De Caro R., Malendowicz L.K.;
RT "Expression of the spexin gene in the rat adrenal gland and evidences
RT suggesting that spexin inhibits adrenocortical cell proliferation.";
RL Peptides 31:676-682(2010).
RN [6]
RP INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=23080164; DOI=10.1007/978-94-007-4584-1_29;
RA Porzionato A., Rucinski M., Macchi V., Stecco C., Sarasin G., Sfriso M.M.,
RA Di Giulio C., Malendowicz L.K., De Caro R.;
RT "Spexin is expressed in the carotid body and is upregulated by postnatal
RT hyperoxia exposure.";
RL Adv. Exp. Med. Biol. 758:207-213(2012).
RN [7]
RP FUNCTION (SPEXIN AND SPEXIN-2).
RX PubMed=22038051; DOI=10.1096/fj.11-192831;
RA Toll L., Khroyan T.V., Sonmez K., Ozawa A., Lindberg I., McLaughlin J.P.,
RA Eans S.O., Shahien A.A., Kapusta D.R.;
RT "Peptides derived from the prohormone proNPQ/spexin are potent central
RT modulators of cardiovascular and renal function and nociception.";
RL FASEB J. 26:947-954(2012).
RN [8]
RP FUNCTION (SPEXIN-1), AND INDUCTION.
RX PubMed=24550067; DOI=10.1002/oby.20725;
RA Walewski J.L., Ge F., Lobdell H. IV, Levin N., Schwartz G.J.,
RA Vasselli J.R., Pomp A., Dakin G., Berk P.D.;
RT "Spexin is a novel human peptide that reduces adipocyte uptake of long
RT chain fatty acids and causes weight loss in rodents with diet-induced
RT obesity.";
RL Obesity 22:1643-1652(2014).
CC -!- FUNCTION: Plays a role as a central modulator of cardiovascular and
CC renal function and nociception. Also plays a role in energy metabolism
CC and storage. Inhibits adrenocortical cell proliferation with minor
CC stimulation on corticosteroid release (PubMed:20045034,
CC PubMed:22038051). {ECO:0000269|PubMed:20045034,
CC ECO:0000269|PubMed:22038051}.
CC -!- FUNCTION: [Spexin-1]: Acts as a ligand for galanin receptors GALR2 and
CC GALR3 (By similarity). Intracerebroventricular administration of the
CC peptide induces an increase in arterial blood pressure, a decrease in
CC both heart rate and renal excretion and delayed natriuresis.
CC Intraventricular administration of the peptide induces antinociceptive
CC activity. Intraperitoneal administration of the peptide induces a
CC reduction in food consumption and body weight. Inhibits long chain
CC fatty acid uptake into adipocytes. Also induces contraction of
CC muscarinic-like stomach smooth muscles (PubMed:24550067). {ECO:0000250,
CC ECO:0000269|PubMed:24550067}.
CC -!- FUNCTION: [Spexin-2]: Intracerebroventricular administration of the
CC peptide induces a decrease in heart rate, but no change in arterial
CC pressure, and an increase in urine flow rate. Intraventricular
CC administration of the peptide induces antinociceptive activity
CC (PubMed:22038051). {ECO:0000269|PubMed:22038051}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}. Secreted, extracellular
CC space {ECO:0000250}. Cytoplasmic vesicle, secretory vesicle
CC {ECO:0000250}. Note=Secreted via the classical ER/Golgi-dependent
CC pathway into the extracellular medium largely as a full-length protein
CC without the signal peptide, and not as a hydrolyzed and amidated
CC peptide. Localized extracellularly surrounding the villous
CC trophoblastic cells. Detected in the serum (By similarity).
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=M0R8L2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=M0R8L2-2; Sequence=VSP_055872;
CC -!- TISSUE SPECIFICITY: Widely expressed; predominantly expressed in
CC epithelial cells in the skin, respiratory, digestive, urinary and
CC reproductive systems, retina, adrenal gland and various brain regions.
CC In the adrenal gland, expressed in parenchymal cells of the cortex and
CC in ganglionic cells and intermingled cortical cells of the medulla.
CC Expressed in the type I glomic cells within the carotid body (at
CC protein level). Widely expressed. Strongly expressed in esophagus,
CC liver, pancreas, kidney, brain, hypothalamus, thyroid and ovary.
CC Expressed in the zona glomerulosa (ZG) and zona fasciculata/reticularis
CC (ZF/R) of the adrenal gland. Also expressed in stomach, lung, skeletal
CC muscle, heart, uterus, spleen, adrenal gland and testis. Weakly
CC expressed in small intestine, thymus, urinary bladder and
CC adenohypophysis. In the brain, is expressed in the Barrington's
CC nucleus, with lesser amount in the ventrolateral caudal periaqueductal
CC gray (PAG) and in the mesopontine tegmentum.
CC {ECO:0000269|PubMed:19132080, ECO:0000269|PubMed:20045034,
CC ECO:0000269|PubMed:20530460, ECO:0000269|PubMed:23080164}.
CC -!- INDUCTION: Up-regulated by enucleation-induced adrenocortical
CC regeneration (at protein level). Up-regulated by dexamethasone (DX)
CC treatment. Down-regulated by adrenocorticotropic hormone (ACTH)
CC treatment. Up-regulated by hypoxia in the carotid body.
CC {ECO:0000269|PubMed:20045034, ECO:0000269|PubMed:23080164,
CC ECO:0000269|PubMed:24550067}.
CC -!- SIMILARITY: Belongs to the spexin family. {ECO:0000305}.
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DR EMBL; AABR06034154; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06034155; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06034156; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06034157; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06034158; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AY383715; AAQ96273.1; -; mRNA.
DR RefSeq; NP_001077402.2; NM_001083933.3. [M0R8L2-1]
DR AlphaFoldDB; M0R8L2; -.
DR SMR; M0R8L2; -.
DR STRING; 10116.ENSRNOP00000037793; -.
DR PaxDb; M0R8L2; -.
DR Ensembl; ENSRNOT00000087378; ENSRNOP00000071461; ENSRNOG00000053700. [M0R8L2-1]
DR GeneID; 691138; -.
DR KEGG; rno:691138; -.
DR UCSC; RGD:1587448; rat.
DR CTD; 80763; -.
DR RGD; 1587448; Spx.
DR GeneTree; ENSGT00390000012501; -.
DR HOGENOM; CLU_169090_0_0_1; -.
DR OMA; LETRSHN; -.
DR OrthoDB; 1579616at2759; -.
DR TreeFam; TF333402; -.
DR PRO; PR:M0R8L2; -.
DR Proteomes; UP000002494; Chromosome 4.
DR Bgee; ENSRNOG00000053700; Expressed in cerebellum and 2 other tissues.
DR ExpressionAtlas; M0R8L2; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0031045; C:dense core granule; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISS: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:0044539; P:long-chain fatty acid import into cell; IDA:UniProtKB.
DR GO; GO:0032099; P:negative regulation of appetite; IDA:UniProtKB.
DR GO; GO:0010459; P:negative regulation of heart rate; IDA:UniProtKB.
DR GO; GO:0035814; P:negative regulation of renal sodium excretion; IDA: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; IDA: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; IDA:UniProtKB.
DR InterPro; IPR028126; Spexin.
DR PANTHER; PTHR28590; PTHR28590; 1.
DR Pfam; PF15171; Spexin; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Amidation; Cleavage on pair of basic residues;
KW Cytoplasmic vesicle; Hormone; Reference proteome; Secreted; Signal.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..116
FT /note="Spexin"
FT /id="PRO_0000430222"
FT PROPEP 27..35
FT /evidence="ECO:0000250"
FT /id="PRO_0000430223"
FT PEPTIDE 36..49
FT /note="Spexin-1"
FT /id="PRO_0000430224"
FT PROPEP 50..116
FT /evidence="ECO:0000250"
FT /id="PRO_0000430225"
FT PEPTIDE 53..70
FT /note="Spexin-2"
FT /id="PRO_0000430226"
FT PROPEP 74..116
FT /evidence="ECO:0000250"
FT /id="PRO_0000430227"
FT REGION 56..75
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 35..36
FT /note="Cleavage; by prohormone convertase 2"
FT /evidence="ECO:0000250"
FT SITE 52..53
FT /note="Cleavage; by prohormone convertase 2"
FT /evidence="ECO:0000250"
FT SITE 72..73
FT /note="Cleavage; by prohormone convertase 2"
FT /evidence="ECO:0000250"
FT MOD_RES 49
FT /note="Glutamine amide"
FT /evidence="ECO:0000250"
FT VAR_SEQ 71..116
FT /note="RRNPNLQLLTLPEAAALFLASLEKPQKDEGGDFDKSKLLEDRRFYW -> MN
FT EVVDRKLLMFKTCIFTWELLTSTHAHGLAHLCRMSNHFVHNAGQRKEKEGKGQRGRGGE
FT TVKLKEEEEEEEEEEEEEEEEEEEEEEEEEEEEEEEEEAKT (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_055872"
SQ SEQUENCE 116 AA; 13083 MW; 62C63F80765E53BD CRC64;
MKGPSILAVA ALALLLVLSV LENSSGAPQR LSEKRNWTPQ AMLYLKGAQG HRFISDQSRR
KELADRPPPE RRNPNLQLLT LPEAAALFLA SLEKPQKDEG GDFDKSKLLE DRRFYW
