ID   SPXN_HUMAN              Reviewed;         116 AA.
AC   Q9BT56; B3KND6;
DT   27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2001, sequence version 1.
DT   24-JAN-2024, entry version 130.
DE   RecName: Full=Spexin;
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; Synonyms=C12orf39;
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], AND 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   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Embryo;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
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=Uterus;
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   FUNCTION (SPEXIN-1), SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=17284679; DOI=10.1101/gr.5755407;
RA   Mirabeau O., Perlas E., Severini C., Audero E., Gascuel O., Possenti R.,
RA   Birney E., Rosenthal N., Gross C.;
RT   "Identification of novel peptide hormones in the human proteome by hidden
RT   Markov model screening.";
RL   Genome Res. 17:320-327(2007).
RN   [6]
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=19193193; DOI=10.1042/bsr20080156;
RA   Wan B., Wang X.R., Zhou Y.B., Zhang X., Huo K., Han Z.G.;
RT   "C12ORF39, a novel secreted prot ein with a typical amidation processing
RT   signal.";
RL   Biosci. Rep. 30:1-10(2010).
RN   [7]
RP   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   [8]
RP   PROTEOLYTIC PROCESSING (SPEXIN-1 AND SPEXIN-2), AND AMIDATION AT GLN-49.
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   [9]
RP   FUNCTION (SPEXIN-1), AND PHYLOGENY.
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   [10]
RP   SUBCELLULAR LOCATION, 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 (By similarity). {ECO:0000250}.
CC   -!- FUNCTION: [Spexin-1]: Acts as a ligand for galanin receptors GALR2 and
CC       GALR3 (PubMed:17284679, PubMed:24517231). Intracerebroventricular
CC       administration of the peptide induces an increase in arterial blood
CC       pressure, a decrease in both heart rate and renal excretion and delayed
CC       natriuresis. Intraventricular administration of the peptide induces
CC       antinociceptive activity. Also induces contraction of muscarinic-like
CC       stomach smooth muscles. Intraperitoneal administration of the peptide
CC       induces a reduction in food consumption and body weight. Inhibits long
CC       chain fatty acid uptake into adipocytes (By similarity). {ECO:0000250,
CC       ECO:0000269|PubMed:17284679, ECO:0000269|PubMed:24517231}.
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 (By
CC       similarity). {ECO:0000250}.
CC   -!- INTERACTION:
CC       Q9BT56; Q6IN84: MRM1; NbExp=3; IntAct=EBI-17975052, EBI-5454865;
CC   -!- SUBCELLULAR LOCATION: Secreted. Secreted, extracellular space.
CC       Cytoplasmic vesicle, secretory vesicle. Note=Secreted via the classical
CC       ER/Golgi-dependent pathway into the extracellular medium largely as a
CC       full-length protein without the signal peptide, and not as a hydrolyzed
CC       and amidated peptide (PubMed:19193193, PubMed:17284679). Localized
CC       extracellularly surrounding the villous trophoblastic cells. Detected
CC       in the serum.
CC   -!- TISSUE SPECIFICITY: Expressed in the type I glomic cells within the
CC       carotid body (at protein level). Expressed predominantly in pancreas,
CC       testis, kidney, brain and placenta. Expressed in submucosal layer of
CC       esophagus and stomach fundus. {ECO:0000269|PubMed:17284679,
CC       ECO:0000269|PubMed:19132080, ECO:0000269|PubMed:19193193,
CC       ECO:0000269|PubMed:23080164}.
CC   -!- INDUCTION: Down-regulated in omental and subcutaneous fat of obese
CC       subjects. {ECO:0000269|PubMed:24550067}.
CC   -!- SIMILARITY: Belongs to the spexin family. {ECO:0000305}.
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DR   EMBL; AK027273; BAG51298.1; -; mRNA.
DR   EMBL; AK075342; BAG52117.1; -; mRNA.
DR   EMBL; CH471094; EAW96444.1; -; Genomic_DNA.
DR   EMBL; BC004336; AAH04336.1; -; mRNA.
DR   CCDS; CCDS31757.1; -.
DR   RefSeq; NP_085049.1; NM_030572.3.
DR   PDB; 7XJL; EM; 3.50 A; A=36-49.
DR   PDBsum; 7XJL; -.
DR   AlphaFoldDB; Q9BT56; -.
DR   SMR; Q9BT56; -.
DR   BioGRID; 123297; 34.
DR   IntAct; Q9BT56; 1.
DR   STRING; 9606.ENSP00000256969; -.
DR   BioMuta; SPX; -.
DR   jPOST; Q9BT56; -.
DR   MassIVE; Q9BT56; -.
DR   PaxDb; 9606-ENSP00000256969; -.
DR   PeptideAtlas; Q9BT56; -.
DR   ProteomicsDB; 78952; -.
DR   Antibodypedia; 2438; 27 antibodies from 11 providers.
DR   DNASU; 80763; -.
DR   Ensembl; ENST00000256969.7; ENSP00000256969.2; ENSG00000134548.11.
DR   GeneID; 80763; -.
DR   KEGG; hsa:80763; -.
DR   MANE-Select; ENST00000256969.7; ENSP00000256969.2; NM_030572.4; NP_085049.1.
DR   UCSC; uc001rfa.2; human.
DR   AGR; HGNC:28139; -.
DR   CTD; 80763; -.
DR   DisGeNET; 80763; -.
DR   GeneCards; SPX; -.
DR   HGNC; HGNC:28139; SPX.
DR   HPA; ENSG00000134548; Tissue enriched (adipose).
DR   MIM; 619246; gene.
DR   neXtProt; NX_Q9BT56; -.
DR   OpenTargets; ENSG00000134548; -.
DR   PharmGKB; PA143485369; -.
DR   VEuPathDB; HostDB:ENSG00000134548; -.
DR   eggNOG; ENOG502SAD1; Eukaryota.
DR   GeneTree; ENSGT00390000012501; -.
DR   HOGENOM; CLU_169090_0_0_1; -.
DR   InParanoid; Q9BT56; -.
DR   OMA; LETRSHN; -.
DR   OrthoDB; 4588475at2759; -.
DR   PhylomeDB; Q9BT56; -.
DR   TreeFam; TF333402; -.
DR   PathwayCommons; Q9BT56; -.
DR   SignaLink; Q9BT56; -.
DR   SIGNOR; Q9BT56; -.
DR   BioGRID-ORCS; 80763; 13 hits in 1143 CRISPR screens.
DR   GenomeRNAi; 80763; -.
DR   Pharos; Q9BT56; Tbio.
DR   PRO; PR:Q9BT56; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   RNAct; Q9BT56; Protein.
DR   Bgee; ENSG00000134548; Expressed in body of pancreas and 138 other cell types or tissues.
DR   ExpressionAtlas; Q9BT56; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0031045; C:dense core granule; IDA:UniProtKB.
DR   GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR   GO; GO:0030133; C:transport vesicle; IEA:UniProtKB-SubCell.
DR   GO; GO:0005184; F:neuropeptide hormone activity; 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: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; IMP:UniProtKB.
DR   GO; GO:0003084; P:positive regulation of systemic arterial blood pressure; ISS:UniProtKB.
DR   GO; GO:0051930; P:regulation of sensory perception of pain; ISS:UniProtKB.
DR   InterPro; IPR028126; Spexin.
DR   PANTHER; PTHR28590; SPEXIN; 1.
DR   PANTHER; PTHR28590:SF1; SPEXIN; 1.
DR   Pfam; PF15171; Spexin; 1.
DR   Genevisible; Q9BT56; HS.
PE   1: Evidence at protein level;
KW   3D-structure; 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_0000430213"
FT   PROPEP          27..35
FT                   /id="PRO_0000363216"
FT   PEPTIDE         36..49
FT                   /note="Spexin-1"
FT                   /id="PRO_0000042159"
FT   PROPEP          50..116
FT                   /id="PRO_0000363217"
FT   PEPTIDE         53..70
FT                   /note="Spexin-2"
FT                   /id="PRO_0000430214"
FT   PROPEP          74..116
FT                   /id="PRO_0000430215"
FT   REGION          55..77
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        55..69
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            35..36
FT                   /note="Cleavage; by prohormone convertase 2"
FT   SITE            52..53
FT                   /note="Cleavage; by prohormone convertase 2"
FT   SITE            72..73
FT                   /note="Cleavage; by prohormone convertase 2"
FT   MOD_RES         49
FT                   /note="Glutamine amide"
FT                   /evidence="ECO:0000269|PubMed:22038051"
FT   HELIX           39..46
FT                   /evidence="ECO:0007829|PDB:7XJL"
SQ   SEQUENCE   116 AA;  13302 MW;  CCBC3E7BD22E357E CRC64;
     MKGLRSLAAT TLALFLVFVF LGNSSCAPQR LLERRNWTPQ AMLYLKGAQG RRFISDQSRR
     KDLSDRPLPE RRSPNPQLLT IPEAATILLA SLQKSPEDEE KNFDQTRFLE DSLLNW
//