This gene encodes a soluble luminal protein with two calmodulin-like EF-hand motifs at its SLCterminus. This protein forms a complex with LAMN1 (lectin mannose binding protein 1; also known as ERGISLC53) that facilitates the transport of coagulation factors V (FV) and VIII (FVIII) from the endoplasmic reticulum to the Golgi apparatus via an endoplasmic reticulum Golgi intermediate compartment (ERGIC). Mutations in this gene cause combined deficiency of FV and FVIII (F5F8D); a rare autosomal recessive bleeding disorder characterized by mild to moderate bleeding and coordinate reduction in plasma FV and FVIII levels. This protein has also been shown to maintain stem cell potential in adult central nervous system and is a marker for testicular germ cell tumors. The 3' UTR of this gene contains a transposon-like human repeat element named 'THE 1'. A processed RNA pseudogene of this gene is on chromosome 6p22.1. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jun 2010]
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.
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.
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.
Post-translational modifications:
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.
Similarity:
Belongs to the melanin-concentrating hormone family.
SWISS:
P20382
Gene ID:
5367
Database links:
Entrez Gene: 5367 Human
Entrez Gene: 110312 Mouse
Omim: 176795 Human
SwissProt: P20382 Human
SwissProt: P56942 Mouse
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