P14200 (MCH_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Pro-MCH

Cleaved into the following 3 chains:

1. Neuropeptide-glycine-glutamic acid
   Short name=NGE
   Short name=Neuropeptide G-E
2. Neuropeptide-glutamic acid-isoleucine
   Short name=NEI
   Short name=Neuropeptide E-I
3. Melanin-concentrating hormone
   Short name=MCH

Gene names

Name:	Pmch
Synonyms:	Mch

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	165 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	MCH inhibits ACTH secretion at the end of the light on period which corresponds to the peak of the circadian rhythm in ACTH. Inhibits also stress induced ACTH release during the light off period of the cycle. Involved as a neurotransmitter or neuromodulator in a broad array of neuronal functions. Stimulates sexual behavior when injected into the ventromedial nucleus, this effect is antagonized by NEI. In the medial preoptic area, stimulates anxiety and sexual behavior. Antagonizes inhibitory effect of melanotropin alpha on exploration behavior. Ref.9 Ref.10 Ref.11 NEI can influence differentiation of neuronal processes in brain neurons. Affects the content of neurofilament protein in neuritogenesis (in vitro). May also be a neuromodulatory factor. In behavioral tests, it stimulates exploration and anxiety when injected into the ventromedial nucleus. Also stimulates grooming, locomotion and rearing. May antagonize the inhibitory effect of mch on ACTH release. Reduces dopamine and dopac release in the ventromedial nucleus. Ref.9 Ref.10 Ref.11
Subcellular location	Secreted.
Tissue specificity	MCH is present in all regions of the brain and in neurointermediate lobe of the pituarity gland, with highest concentrations in the hypothalamus. Also expressed to a much lesser extent in stomach, lamina propria of both duodenum and colon, ovary, thymus, pancreas, adrenal gland and testis (spermatogonia, early spermatocytes and Sertoli cells). Weak expression in heart and lung. The other peptides are expressed at least in Sertoli cells, nei being also expressed in brain, stomach and proximal duodenum. In brain exclusively mature mch and nei peptides are present. In peripheral tissues a large product, encompassing the NEI and MCH domains of the precursor, is found predominantly. At low levels fully processed MCH and NEI peptides are present in gut. No expression in peripheral blood. Ref.4 Ref.5 Ref.6
Developmental stage	Expression is strongly increased in hypothalamus between postnatal days 12 and 20, to reach high constant values in adult.
Induction	Inhibited by neurogenic stress or osmotic stress.
Post-translational modification	Pro-MCH is processed differentially in the brain and in peripheral organs producing two neuropeptides; NEI and MCH. A third peptide, NGE, may also be produced. Preferential processing in neurons by prohormone convertase 2 (PC2) generates NEI. MCH is generated in neurons of the lateral hypothalmic area by several prohormone convertases including PC1/3, PC2 and PC5/6.
Sequence similarities	Belongs to the melanin-concentrating hormone family.

Ontologies

Keywords
Cellular component	Secreted
Domain	Signal
Molecular function	Hormone Neuropeptide
PTM	Amidation Cleavage on pair of basic residues Disulfide bond
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	drinking behavior Inferred from direct assay PubMed 17188345. Source: RGD elevation of cytosolic calcium ion concentration Inferred from direct assay PubMed 10559938. Source: RGD glucose homeostasis Inferred from direct assay PubMed 16002548. Source: RGD lactation Inferred from expression pattern PubMed 14962080. Source: RGD learning or memory Traceable author statement PubMed 11814630. Source: RGD negative regulation of blood pressure Inferred from direct assay PubMed 17045349. Source: RGD negative regulation of synaptic transmission, dopaminergic Inferred from direct assay PubMed 15555641. Source: RGD neuropeptide signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of circadian sleep/wake cycle, REM sleep Inferred from direct assay PubMed 12964948. Source: RGD regulation of heart rate Inferred from direct assay PubMed 17045349. Source: RGD regulation of neuronal synaptic plasticity Inferred from mutant phenotype PubMed 11814630. Source: RGD response to cold Inferred from mutant phenotype PubMed 12960043. Source: RGD synaptic transmission Inferred from electronic annotation. Source: InterPro
Cellular_component	extracellular space Inferred from direct assay PubMed 11483240. Source: RGD
Molecular_function	type 1 melanin-concentrating hormone receptor binding Inferred from direct assay PubMed 10421367. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Potential
	Chain	22 – 165	144	Pro-MCH		PRO_0000019116
	Peptide	110 – 128	19	Neuropeptide-glycine-glutamic acid Potential		PRO_0000019117
	Peptide	131 – 143	13	Neuropeptide-glutamic acid-isoleucine		PRO_0000019118
	Peptide	147 – 165	19	Melanin-concentrating hormone Ref.3		PRO_0000019119
Amino acid modifications
	Modified residue	143	1	Isoleucine amide Ref.7
	Disulfide bond	153 ↔ 162		By similarity

Sequences

	Sequence		Length	Mass (Da)
	P14200 [UniParc]. Last modified January 1, 1990. Version 1. Checksum: 38E9F07693E77A05	FASTA	165	18,482
	10 20 30 40 50 60 MAKMSLSSYM LMLAFSLFSH GILLSASKSI RNVEDDIVFN TFRMGKAFQK EDTAERSVVA 70 80 90 100 110 120 PSLEGYKNDE SGFMKDDDDK TTKNTGSKQN LVTHGLPLSL AVKPYLALKG PAVFPAENGV 130 140 150 160 QNTESTQEKR EIGDEENSAK FPIGRRDFDM LRCMLGRVYR PCWQV

References

[1]	"The rat melanin-concentrating hormone messenger ribonucleic acid encodes multiple putative neuropeptides coexpressed in the dorsolateral hypothalamus." Nahon J.-L., Presse F., Bittencourt J.C., Sawchenko P.E., Vale W. Endocrinology 125:2056-2065(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Hypothalamus.
[2]	"Nucleotide sequence and tissue-specific expression of the rat melanin concentrating hormone gene." Thompson R.C., Watson S.J. DNA Cell Biol. 9:637-645(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Characterization of melanin-concentrating hormone from rat hypothalamus." Vaughan J.M., Fischer W.H., Hoeger C., Rivier J., Vale W. Endocrinology 125:1660-1665(1989) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 147-165. Tissue: Hypothalamus.
[4]	"Pro-melanin concentrating hormone messenger ribonucleic acid and peptides expression in peripheral tissues of the rat." Hervieu G., Nahon J.-L. Neuroendocrinology 61:348-364(1995) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY. Strain: Sprague-Dawley and Wistar.
[5]	"Similarities in cellular expression and functions of melanin-concentrating hormone and atrial natriuretic factor in the rat digestive tract." Hervieu G., Volant K., Grishina O., Descroix-Vagne M., Nahon J.-L. Endocrinology 137:561-571(1996) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[6]	"Melanin-concentrating hormone in human and rat." Takahashi K., Suzuki H., Totsune K., Murakami O., Satoh F., Sone M., Sasano H., Mouri T., Shibahara S. Neuroendocrinology 61:493-498(1995) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[7]	"Secretion of melanin-concentrating hormone and neuropeptide-EI from cultured rat hypothalamic cells." Parkes D., Vale W. Endocrinology 131:1826-1831(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING, AMIDATION AT ILE-143.
[8]	"Cellular localization and role of prohormone convertases in the processing of pro-melanin concentrating hormone in mammals." Viale A., Ortola C., Hervieu G., Furuta M., Barbero P., Steiner D.F., Seidah N.G., Nahon J.-L. J. Biol. Chem. 274:6536-6545(1999) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING.
[9]	"Neuropeptide-E-I antagonizes the action of melanin-concentrating hormone on stress-induced release of adrenocorticotropin in the rat." Bluet-Pajot M.T., Presse F., Voko Z., Hoeger C., Mounier F., Epelbaum J., Nahon J.-L. J. Neuroendocrinol. 7:297-303(1995) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION OF NEI.
[10]	"Behavioral effects of neuropeptide E-I (NEI) in the female rat: interactions with alpha-MSH, MCH and dopamine." Gonzalez M.I., Baker B.I., Hole D.R., Wilson C.A. Peptides 19:1007-1016(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION OF NEI.
[11]	"Melanocortin and MCH precursor-derived NEI effects on striatum-midbrain co-cultures." Kistler-Heer V., Schlumpf M., Lichtensteiger W. Peptides 19:1317-1327(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION OF MCH AND NEI.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M29712 mRNA. Translation: AAA41580.1. M62641 Genomic DNA. Translation: AAA41581.1.
IPI	IPI00203169.
PIR	A36237.
RefSeq	NP_036757.1. NM_012625.1.
UniGene	Rn.9675.
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	10116.ENSRNOP00000006174.
Proteomic databases
PRIDE	P14200.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	24659.
KEGG	rno:24659.
UCSC	RGD:3358. rat.
Organism-specific databases
CTD	5367.
RGD	3358. Pmch.
Phylogenomic databases
eggNOG	NOG42445.
HOGENOM	HOG000230520.
HOVERGEN	HBG052429.
InParanoid	P14200.
KO	K05229.
OrthoDB	EOG46MBM5.
Gene expression databases
Genevestigator	P14200.
GermOnline	ENSRNOG00000004632. Rattus norvegicus.
Family and domain databases
InterPro	IPR005456. Prepro-melanin_conc_hormone. [Graphical view]
PANTHER	PTHR12091. PTHR12091. 1 hit.
Pfam	PF05824. Pro-MCH. 1 hit. [Graphical view]
PRINTS	PR01641. PROMCHFAMILY.
ProtoNet	Search...
Other
NextBio	604010.
PMAP-CutDB	P14200.

Entry information

Entry name

MCH_RAT

Accession

Primary (citable) accession number: P14200

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	January 1, 1990
Last modified:	April 3, 2013
This is version 104 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program