MCH_HUMAN
ID MCH_HUMAN Reviewed; 165 AA.
AC P20382; Q16044; Q8WVG0;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 3.
DT 03-AUG-2022, entry version 174.
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 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].
RC TISSUE=Hypothalamus;
RX PubMed=2149166; DOI=10.1210/mend-4-4-632;
RA Presse F., Nahon J.-L., Fischer W.H., Vale W.;
RT "Structure of the human melanin concentrating hormone mRNA.";
RL Mol. Endocrinol. 4:632-637(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Mammary cancer;
RX PubMed=8326825; DOI=10.1016/0169-328x(93)90093-5;
RA Breton C., Schorpp M., Nahon J.-L.;
RT "Isolation and characterization of the human melanin-concentrating hormone
RT gene and a variant gene.";
RL Brain Res. Mol. Brain Res. 18:297-310(1993).
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=Brain;
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 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 [6]
RP TISSUE SPECIFICITY.
RX PubMed=9191099; DOI=10.1016/s0169-328x(97)00018-1;
RA Viale A., Zhixing Y., Breton C., Pedeutour F., Coquerel A., Jordan D.,
RA Nahon J.-L.;
RT "The melanin-concentrating hormone gene in human: flanking region analysis,
RT fine chromosome mapping, and tissue-specific expression.";
RL Brain Res. Mol. Brain Res. 46:243-255(1997).
CC -!- FUNCTION: MCH may act as a neurotransmitter or neuromodulator in a
CC broad array of neuronal functions directed toward the regulation of
CC goal-directed behavior, such as food intake, and general arousal. May
CC also have a role in spermatocyte differentiation.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in lateral hypothalamus,
CC also detected in pallidum, neocortex and cerebellum. Also found in
CC thymus, brown adipose tissue, duodenum and testis (spermatogonia, early
CC spermatocytes and Sertoli cells). No expression in peripheral blood. In
CC brain exclusively mature MCH and NEI peptides are present. In
CC peripheral tissues a large product, encompassing the NEI and MCH
CC domains of the precursor, is found predominantly.
CC {ECO:0000269|PubMed:9191099}.
CC -!- PTM: Differentially processed in the brain and in peripheral organs
CC producing two neuropeptides; NEI and MCH. A third peptide, NGE, may
CC 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 -!- SIMILARITY: Belongs to the melanin-concentrating hormone family.
CC {ECO:0000305}.
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DR EMBL; M57703; AAA63214.1; -; mRNA.
DR EMBL; S63697; AAB27493.1; -; Genomic_DNA.
DR EMBL; CH471054; EAW97693.1; -; Genomic_DNA.
DR EMBL; BC018048; AAH18048.1; -; mRNA.
DR CCDS; CCDS31885.1; -.
DR PIR; I52634; I52634.
DR RefSeq; NP_002665.2; NM_002674.3.
DR AlphaFoldDB; P20382; -.
DR BioGRID; 111380; 18.
DR STRING; 9606.ENSP00000332225; -.
DR BioMuta; PMCH; -.
DR DMDM; 229462960; -.
DR MassIVE; P20382; -.
DR PaxDb; P20382; -.
DR PeptideAtlas; P20382; -.
DR PRIDE; P20382; -.
DR ProteomicsDB; 53758; -.
DR Antibodypedia; 18038; 156 antibodies from 25 providers.
DR DNASU; 5367; -.
DR Ensembl; ENST00000329406.5; ENSP00000332225.4; ENSG00000183395.5.
DR GeneID; 5367; -.
DR KEGG; hsa:5367; -.
DR MANE-Select; ENST00000329406.5; ENSP00000332225.4; NM_002674.4; NP_002665.2.
DR UCSC; uc001tjl.4; human.
DR CTD; 5367; -.
DR DisGeNET; 5367; -.
DR GeneCards; PMCH; -.
DR HGNC; HGNC:9109; PMCH.
DR HPA; ENSG00000183395; Tissue enriched (brain).
DR MIM; 176795; gene.
DR neXtProt; NX_P20382; -.
DR OpenTargets; ENSG00000183395; -.
DR PharmGKB; PA33435; -.
DR VEuPathDB; HostDB:ENSG00000183395; -.
DR eggNOG; ENOG502RZ12; Eukaryota.
DR GeneTree; ENSGT00390000004984; -.
DR HOGENOM; CLU_1610172_0_0_1; -.
DR InParanoid; P20382; -.
DR OMA; NTFRMGK; -.
DR OrthoDB; 1451976at2759; -.
DR PhylomeDB; P20382; -.
DR TreeFam; TF330944; -.
DR PathwayCommons; P20382; -.
DR Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR Reactome; R-HSA-416476; G alpha (q) signalling events.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR SignaLink; P20382; -.
DR SIGNOR; P20382; -.
DR BioGRID-ORCS; 5367; 13 hits in 1036 CRISPR screens.
DR GenomeRNAi; 5367; -.
DR Pharos; P20382; Tbio.
DR PRO; PR:P20382; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P20382; protein.
DR Bgee; ENSG00000183395; Expressed in hypothalamus and 117 other tissues.
DR Genevisible; P20382; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
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; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0007268; P:chemical synaptic transmission; IEA:InterPro.
DR GO; GO:0007631; P:feeding behavior; ISS:UniProtKB.
DR GO; GO:0007218; P:neuropeptide signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0007283; P:spermatogenesis; IEA:UniProtKB-KW.
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; Developmental protein;
KW Differentiation; Disulfide bond; Hormone; Neuropeptide; Reference proteome;
KW Secreted; Signal; Spermatogenesis.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..165
FT /note="Pro-MCH"
FT /id="PRO_0000019104"
FT PEPTIDE 110..128
FT /note="Neuropeptide-glycine-glutamic acid"
FT /evidence="ECO:0000255"
FT /id="PRO_0000019105"
FT PEPTIDE 131..143
FT /note="Neuropeptide-glutamic acid-isoleucine"
FT /id="PRO_0000019106"
FT PEPTIDE 147..165
FT /note="Melanin-concentrating hormone"
FT /id="PRO_0000019107"
FT MOD_RES 143
FT /note="Isoleucine amide"
FT /evidence="ECO:0000250"
FT DISULFID 153..162
FT /evidence="ECO:0000250"
FT CONFLICT 42
FT /note="F -> S (in Ref. 2; AAB27493)"
FT /evidence="ECO:0000305"
FT CONFLICT 104..106
FT /note="PYL -> GYQ (in Ref. 1; AAA63214)"
FT /evidence="ECO:0000305"
FT CONFLICT 113
FT /note="A -> D (in Ref. 1; AAA63214)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 165 AA; 18679 MW; 2339E8938EBEC499 CRC64;
MAKMNLSSYI LILTFSLFSQ GILLSASKSI RNLDDDMVFN TFRLGKGFQK EDTAEKSVIA
PSLEQYKNDE SSFMNEEENK VSKNTGSKHN FLNHGLPLNL AIKPYLALKG SVAFPAENGV
QNTESTQEKR EIGDEENSAK FPIGRRDFDM LRCMLGRVYR PCWQV
