ID   MCH_RAT                 Reviewed;         165 AA.
AC   P14200;
DT   01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1990, sequence version 1.
DT   04-NOV-2026, entry version 144.
DE   RecName: Full=Pro-MCH;
DE   Contains:
DE     RecName: Full=Neuropeptide-glycine-glutamic acid;
DE              Short=NGE;
DE              Short=Neuropeptide G-E;
DE   Contains:
DE     RecName: Full=Neuropeptide-glutamic acid-isoleucine;
DE              Short=NEI;
DE              Short=Neuropeptide E-I;
DE   Contains:
DE     RecName: Full=Melanin-concentrating hormone;
DE              Short=MCH;
DE   Flags: Precursor;
GN   Name=Pmch {ECO:0000312|RGD:3358}; Synonyms=Mch;
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 [MRNA].
RC   TISSUE=Hypothalamus;
RX   PubMed=2477226; DOI=10.1210/endo-125-4-2056;
RA   Nahon J.-L., Presse F., Bittencourt J.C., Sawchenko P.E., Vale W.;
RT   "The rat melanin-concentrating hormone messenger ribonucleic acid encodes
RT   multiple putative neuropeptides coexpressed in the dorsolateral
RT   hypothalamus.";
RL   Endocrinology 125:2056-2065(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2261081; DOI=10.1089/dna.1990.9.637;
RA   Thompson R.C., Watson S.J.;
RT   "Nucleotide sequence and tissue-specific expression of the rat melanin
RT   concentrating hormone gene.";
RL   DNA Cell Biol. 9:637-645(1990).
RN   [3]
RP   PROTEIN SEQUENCE OF 147-165.
RC   TISSUE=Hypothalamus;
RX   PubMed=2759038; DOI=10.1210/endo-125-3-1660;
RA   Vaughan J.M., Fischer W.H., Hoeger C., Rivier J., Vale W.;
RT   "Characterization of melanin-concentrating hormone from rat hypothalamus.";
RL   Endocrinology 125:1660-1665(1989).
RN   [4]
RP   TISSUE SPECIFICITY.
RC   STRAIN=Sprague-Dawley, and Wistar;
RX   PubMed=7783849; DOI=10.1159/000126857;
RA   Hervieu G., Nahon J.-L.;
RT   "Pro-melanin concentrating hormone messenger ribonucleic acid and peptides
RT   expression in peripheral tissues of the rat.";
RL   Neuroendocrinology 61:348-364(1995).
RN   [5]
RP   TISSUE SPECIFICITY.
RX   PubMed=8593803; DOI=10.1210/endo.137.2.8593803;
RA   Hervieu G., Volant K., Grishina O., Descroix-Vagne M., Nahon J.-L.;
RT   "Similarities in cellular expression and functions of melanin-concentrating
RT   hormone and atrial natriuretic factor in the rat digestive tract.";
RL   Endocrinology 137:561-571(1996).
RN   [6]
RP   TISSUE SPECIFICITY.
RX   PubMed=7617126; DOI=10.1159/000126872;
RA   Takahashi K., Suzuki H., Totsune K., Murakami O., Satoh F., Sone M.,
RA   Sasano H., Mouri T., Shibahara S.;
RT   "Melanin-concentrating hormone in human and rat.";
RL   Neuroendocrinology 61:493-498(1995).
RN   [7]
RP   PROTEOLYTIC PROCESSING, AMIDATION AT ILE-143, AND SUBCELLULAR LOCATION.
RX   PubMed=1327720; DOI=10.1210/endo.131.4.1327720;
RA   Parkes D., Vale W.;
RT   "Secretion of melanin-concentrating hormone and neuropeptide-EI from
RT   cultured rat hypothalamic cells.";
RL   Endocrinology 131:1826-1831(1992).
RN   [8]
RP   PROTEOLYTIC PROCESSING.
RX   PubMed=10037747; DOI=10.1074/jbc.274.10.6536;
RA   Viale A., Ortola C., Hervieu G., Furuta M., Barbero P., Steiner D.F.,
RA   Seidah N.G., Nahon J.-L.;
RT   "Cellular localization and role of prohormone convertases in the processing
RT   of pro-melanin concentrating hormone in mammals.";
RL   J. Biol. Chem. 274:6536-6545(1999).
RN   [9]
RP   FUNCTION OF NEI.
RX   PubMed=7647772; DOI=10.1111/j.1365-2826.1995.tb00761.x;
RA   Bluet-Pajot M.T., Presse F., Voko Z., Hoeger C., Mounier F., Epelbaum J.,
RA   Nahon J.-L.;
RT   "Neuropeptide-E-I antagonizes the action of melanin-concentrating hormone
RT   on stress-induced release of adrenocorticotropin in the rat.";
RL   J. Neuroendocrinol. 7:297-303(1995).
RN   [10]
RP   FUNCTION OF MCH AND NEI.
RX   PubMed=9145426; DOI=10.1016/s0196-9781(96)00327-0;
RA   Sanchez M., Baker B.I., Celis M.;
RT   "Melanin-concentrating hormone (MCH) antagonizes the effects of alpha-MSH
RT   and neuropeptide E-I on grooming and locomotor activities in the rat.";
RL   Peptides 18:393-396(1997).
RN   [11]
RP   FUNCTION OF NEI.
RX   PubMed=9700748; DOI=10.1016/s0196-9781(98)00045-x;
RA   Gonzalez M.I., Baker B.I., Hole D.R., Wilson C.A.;
RT   "Behavioral effects of neuropeptide E-I (NEI) in the female rat:
RT   interactions with alpha-MSH, MCH and dopamine.";
RL   Peptides 19:1007-1016(1998).
RN   [12]
RP   FUNCTION OF NEI.
RX   PubMed=9809645; DOI=10.1016/s0196-9781(98)00076-x;
RA   Kistler-Heer V., Schlumpf M., Lichtensteiger W.;
RT   "Melanocortin and MCH precursor-derived NEI effects on striatum-midbrain
RT   co-cultures.";
RL   Peptides 19:1317-1327(1998).
RN   [13]
RP   FUNCTION OF MCH.
RX   PubMed=9575823; DOI=10.1152/ajpendo.1998.274.4.e627;
RA   Ludwig D.S., Mountjoy K.G., Tatro J.B., Gillette J.A., Frederich R.C.,
RA   Flier J.S., Maratos-Flier E.;
RT   "Melanin-concentrating hormone: a functional melanocortin antagonist in the
RT   hypothalamus.";
RL   Am. J. Physiol. 274:E627-E633(1998).
RN   [14]
RP   FUNCTION OF MCH.
RX   PubMed=12964948; DOI=10.1186/1471-2202-4-19;
RA   Verret L., Goutagny R., Fort P., Cagnon L., Salvert D., Leger L.,
RA   Boissard R., Salin P., Peyron C., Luppi P.H.;
RT   "A role of melanin-concentrating hormone producing neurons in the central
RT   regulation of paradoxical sleep.";
RL   BMC Neurosci. 4:19-19(2003).
CC   -!- FUNCTION: [Melanin-concentrating hormone]: Neuropeptide ligand for the
CC       G protein-coupled receptor MCHR1 and MCHR2 that can activate both
CC       G(i/o)- and G(q/11)-dependent signaling pathways (By similarity). Acts
CC       as a neuromodulator in the central nervous system, promoting feeding,
CC       positive energy balance (orexigenic) and sleep (PubMed:12964948,
CC       PubMed:9575823). Inhibits stimulated ACTH release (lowering plasma
CC       glucocorticoids), consistent with a role in down-regulating
CC       hypothalamic-pituitary-adrenal (HPA) axis activity (PubMed:9575823).
CC       Functionally antagonizes melanotropin alpha (alpha-MSH), opposing its
CC       inhibitory effect on food intake and exploratory behaviors and its
CC       stimulatory effect on the HPA axis (PubMed:9145426, PubMed:9575823).
CC       Antagonizes NEI-induced behavioral effects (PubMed:9145426). May also
CC       participate in spermatocyte differentiation (By similarity).
CC       {ECO:0000250|UniProtKB:P20382, ECO:0000250|UniProtKB:P56942,
CC       ECO:0000269|PubMed:12964948, ECO:0000269|PubMed:9145426,
CC       ECO:0000269|PubMed:9575823}.
CC   -!- FUNCTION: [Neuropeptide-glutamic acid-isoleucine]: Neuropeptide that
CC       modulates stress-related neuroendocrine responses and behaviors,
CC       increasing grooming, rearing and locomotor activity (PubMed:7647772,
CC       PubMed:9145426). Stimulates ACTH secretion, functionally counteracting
CC       the ACTH-suppressing action of MCH; the underlying mechanism is not
CC       fully characterized (PubMed:7647772). Reduces dopamine and DOPAC
CC       release in the ventromedial nucleus (PubMed:9700748). Influences
CC       differentiation of neuronal processes and affects neurofilament protein
CC       content in vitro (PubMed:9809645). {ECO:0000269|PubMed:7647772,
CC       ECO:0000269|PubMed:9145426, ECO:0000269|PubMed:9700748,
CC       ECO:0000269|PubMed:9809645}.
CC   -!- SUBCELLULAR LOCATION: [Neuropeptide-glutamic acid-isoleucine]: Secreted
CC       {ECO:0000269|PubMed:1327720}.
CC   -!- SUBCELLULAR LOCATION: [Melanin-concentrating hormone]: Secreted
CC       {ECO:0000269|PubMed:1327720}.
CC   -!- TISSUE SPECIFICITY: MCH is present in all regions of the brain and in
CC       neurointermediate lobe of the pituarity gland, with highest
CC       concentrations in the hypothalamus. Also expressed to a much lesser
CC       extent in stomach, lamina propria of both duodenum and colon, ovary,
CC       thymus, pancreas, adrenal gland and testis (spermatogonia, early
CC       spermatocytes and Sertoli cells). Weak expression in heart and lung.
CC       The other peptides are expressed at least in Sertoli cells, nei being
CC       also expressed in brain, stomach and proximal duodenum. In brain
CC       exclusively mature mch and nei peptides are present. In peripheral
CC       tissues a large product, encompassing the NEI and MCH domains of the
CC       precursor, is found predominantly. At low levels fully processed MCH
CC       and NEI peptides are present in gut. No expression in peripheral blood.
CC       {ECO:0000269|PubMed:7617126, ECO:0000269|PubMed:7783849,
CC       ECO:0000269|PubMed:8593803}.
CC   -!- DEVELOPMENTAL STAGE: Expression is strongly increased in hypothalamus
CC       between postnatal days 12 and 20, to reach high constant values in
CC       adult.
CC   -!- INDUCTION: Inhibited by neurogenic stress or osmotic stress.
CC   -!- PTM: Pro-MCH is processed differentially in the brain and in peripheral
CC       organs producing two neuropeptides; NEI and MCH. A third peptide, NGE,
CC       may also be produced. Preferential processing in neurons by prohormone
CC       convertase 2 (PC2) generates NEI. MCH is generated in neurons of the
CC       lateral hypothalmic area by several prohormone convertases including
CC       PC1/3, PC2 and PC5/6. {ECO:0000269|PubMed:10037747,
CC       ECO:0000269|PubMed:1327720}.
CC   -!- SIMILARITY: Belongs to the melanin-concentrating hormone family.
CC       {ECO:0000305}.
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DR   EMBL; M29712; AAA41580.1; -; mRNA.
DR   EMBL; M62641; AAA41581.1; -; Genomic_DNA.
DR   PIR; A36237; A36237.
DR   RefSeq; NP_036757.2; NM_012625.2.
DR   AlphaFoldDB; P14200; -.
DR   FunCoup; P14200; 9.
DR   STRING; 10116.ENSRNOP00000006174; -.
DR   PaxDb; 10116-ENSRNOP00000006174; -.
DR   GeneID; 24659; -.
DR   KEGG; rno:24659; -.
DR   UCSC; RGD:3358; rat.
DR   AGR; RGD:3358; -.
DR   CTD; 5367; -.
DR   RGD; 3358; Pmch.
DR   eggNOG; ENOG502RZ12; Eukaryota.
DR   InParanoid; P14200; -.
DR   OMA; ACFQAAH; -.
DR   PhylomeDB; P14200; -.
DR   Reactome; R-RNO-375276; Peptide ligand-binding receptors.
DR   Reactome; R-RNO-416476; G alpha (q) signalling events.
DR   Reactome; R-RNO-418594; G alpha (i) signalling events.
DR   PRO; PR:P14200; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005576; C:extracellular region; IDA:RGD.
DR   GO; GO:0005634; C:nucleus; ISO:RGD.
DR   GO; GO:0045202; C:synapse; IEA:GOC.
DR   GO; GO:0030354; F:melanin-concentrating hormone activity; ISO:RGD.
DR   GO; GO:0031777; F:type 1 melanin-concentrating hormone receptor binding; IDA:RGD.
DR   GO; GO:0007268; P:chemical synaptic transmission; IEA:InterPro.
DR   GO; GO:0042756; P:drinking behavior; IDA:RGD.
DR   GO; GO:0007631; P:feeding behavior; IDA:RGD.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:RGD.
DR   GO; GO:0007595; P:lactation; IEP:RGD.
DR   GO; GO:0007611; P:learning or memory; TAS:RGD.
DR   GO; GO:0045776; P:negative regulation of blood pressure; IDA:RGD.
DR   GO; GO:0032227; P:negative regulation of synaptic transmission, dopaminergic; IDA:RGD.
DR   GO; GO:0046005; P:positive regulation of circadian sleep/wake cycle, REM sleep; IDA:RGD.
DR   GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IDA:RGD.
DR   GO; GO:0060259; P:regulation of feeding behavior; ISO:RGD.
DR   GO; GO:0002027; P:regulation of heart rate; IDA:RGD.
DR   GO; GO:0048168; P:regulation of neuronal synaptic plasticity; IMP:RGD.
DR   InterPro; IPR005456; Prepro-melanin_conc_hormone.
DR   PANTHER; PTHR12091; MELANIN-CONCENTRATING HORMONE; 1.
DR   PANTHER; PTHR12091:SF0; PRO-MCH; 1.
DR   Pfam; PF05824; Pro-MCH; 1.
DR   PRINTS; PR01641; PROMCHFAMILY.
PE   1: Evidence at protein level;
KW   Amidation; Cleavage on pair of basic residues; Direct protein sequencing;
KW   Disulfide bond; Hormone; Neuropeptide; Reference proteome; Secreted;
KW   Signal.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000255"
FT   CHAIN           22..165
FT                   /note="Pro-MCH"
FT                   /id="PRO_0000019116"
FT   PEPTIDE         110..128
FT                   /note="Neuropeptide-glycine-glutamic acid"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000019117"
FT   PEPTIDE         131..143
FT                   /note="Neuropeptide-glutamic acid-isoleucine"
FT                   /id="PRO_0000019118"
FT   PEPTIDE         147..165
FT                   /note="Melanin-concentrating hormone"
FT                   /id="PRO_0000019119"
FT   REGION          69..89
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        69..82
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         143
FT                   /note="Isoleucine amide"
FT                   /evidence="ECO:0000269|PubMed:1327720"
FT   DISULFID        153..162
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   165 AA;  18482 MW;  38E9F07693E77A05 CRC64;
     MAKMSLSSYM LMLAFSLFSH GILLSASKSI RNVEDDIVFN TFRMGKAFQK EDTAERSVVA
     PSLEGYKNDE SGFMKDDDDK TTKNTGSKQN LVTHGLPLSL AVKPYLALKG PAVFPAENGV
     QNTESTQEKR EIGDEENSAK FPIGRRDFDM LRCMLGRVYR PCWQV
//