SPXN_HUMAN
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 03-AUG-2022, entry version 123.
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 and 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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
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 AlphaFoldDB; Q9BT56; -.
DR BioGRID; 123297; 34.
DR IntAct; Q9BT56; 1.
DR STRING; 9606.ENSP00000256969; -.
DR BioMuta; SPX; -.
DR jPOST; Q9BT56; -.
DR MassIVE; Q9BT56; -.
DR PaxDb; Q9BT56; -.
DR PeptideAtlas; Q9BT56; -.
DR PRIDE; Q9BT56; -.
DR ProteomicsDB; 78952; -.
DR Antibodypedia; 2438; 24 antibodies from 10 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 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; 1579616at2759; -.
DR PhylomeDB; Q9BT56; -.
DR TreeFam; TF333402; -.
DR PathwayCommons; Q9BT56; -.
DR SignaLink; Q9BT56; -.
DR SIGNOR; Q9BT56; -.
DR BioGRID-ORCS; 80763; 13 hits in 1065 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 137 other tissues.
DR ExpressionAtlas; Q9BT56; baseline and differential.
DR Genevisible; Q9BT56; HS.
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; IDA:UniProtKB.
DR GO; GO:0031765; F:type 2 galanin receptor binding; IDA:UniProtKB.
DR GO; GO:0031766; F:type 3 galanin receptor binding; IDA: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:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0051930; P:regulation of sensory perception of pain; ISS: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..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"
SQ SEQUENCE 116 AA; 13302 MW; CCBC3E7BD22E357E CRC64;
MKGLRSLAAT TLALFLVFVF LGNSSCAPQR LLERRNWTPQ AMLYLKGAQG RRFISDQSRR
KDLSDRPLPE RRSPNPQLLT IPEAATILLA SLQKSPEDEE KNFDQTRFLE DSLLNW
