MCH_RAT
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 25-MAY-2022, entry version 134.
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; 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, AND AMIDATION AT ILE-143.
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 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 [11]
RP FUNCTION OF MCH AND 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).
CC -!- FUNCTION: MCH inhibits ACTH secretion at the end of the light on period
CC which corresponds to the peak of the circadian rhythm in ACTH. Inhibits
CC also stress induced ACTH release during the light off period of the
CC cycle. Involved as a neurotransmitter or neuromodulator in a broad
CC array of neuronal functions. Stimulates sexual behavior when injected
CC into the ventromedial nucleus, this effect is antagonized by NEI. In
CC the medial preoptic area, stimulates anxiety and sexual behavior.
CC Antagonizes inhibitory effect of melanotropin alpha on exploration
CC behavior.
CC -!- FUNCTION: NEI can influence differentiation of neuronal processes in
CC brain neurons. Affects the content of neurofilament protein in
CC neuritogenesis (in vitro). May also be a neuromodulatory factor. In
CC behavioral tests, it stimulates exploration and anxiety when injected
CC into the ventromedial nucleus. Also stimulates grooming, locomotion and
CC rearing. May antagonize the inhibitory effect of mch on ACTH release.
CC Reduces dopamine and dopac release in the ventromedial nucleus.
CC -!- SUBCELLULAR LOCATION: Secreted.
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_036757.1; NM_012625.1.
DR AlphaFoldDB; P14200; -.
DR STRING; 10116.ENSRNOP00000006174; -.
DR PaxDb; P14200; -.
DR GeneID; 24659; -.
DR KEGG; rno:24659; -.
DR UCSC; RGD:3358; rat.
DR CTD; 5367; -.
DR RGD; 3358; Pmch.
DR eggNOG; ENOG502RZ12; Eukaryota.
DR InParanoid; P14200; -.
DR OrthoDB; 355941at2759; -.
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:0005615; C:extracellular space; 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; IEA:InterPro.
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:0042593; P:glucose homeostasis; IDA: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:0007218; P:neuropeptide signaling pathway; IEA:UniProtKB-KW.
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:0002027; P:regulation of heart rate; IDA:RGD.
DR GO; GO:0048168; P:regulation of neuronal synaptic plasticity; IMP:RGD.
DR GO; GO:0009409; P:response to cold; IMP:RGD.
DR InterPro; IPR005456; Prepro-melanin_conc_hormone.
DR PANTHER; PTHR12091; PTHR12091; 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..84
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
