MTLN_MOUSE
ID MTLN_MOUSE Reviewed; 56 AA.
AC Q8BT35;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 97.
DE RecName: Full=Mitoregulin {ECO:0000303|PubMed:29949756};
DE AltName: Full=Micropeptide in mitochondria {ECO:0000303|PubMed:31296841};
DE AltName: Full=Micropeptide regulator of beta-oxidation {ECO:0000303|PubMed:29949755};
DE AltName: Full=Small integral membrane protein 37 {ECO:0000250|UniProtKB:Q8NCU8};
DE AltName: Full=lncRNA-encoded micropeptide {ECO:0000303|PubMed:32393776};
GN Name=Mtln {ECO:0000303|PubMed:29949756};
GN Synonyms=Lemp {ECO:0000303|PubMed:32393776},
GN Moxi {ECO:0000303|PubMed:29949755}, Mpm {ECO:0000303|PubMed:31296841},
GN Smim37 {ECO:0000250|UniProtKB:Q8NCU8};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo, and Kidney;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
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 [3]
RP PROTEIN SEQUENCE OF 2-11 AND 17-30, IDENTIFICATION BY MASS SPECTROMETRY,
RP FUNCTION, INTERACTION WITH HADHA AND HADHB, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=29949755; DOI=10.1016/j.celrep.2018.05.058;
RA Makarewich C.A., Baskin K.K., Munir A.Z., Bezprozvannaya S., Sharma G.,
RA Khemtong C., Shah A.M., McAnally J.R., Malloy C.R., Szweda L.I.,
RA Bassel-Duby R., Olson E.N.;
RT "MOXI Is a Mitochondrial Micropeptide That Enhances Fatty Acid beta-
RT Oxidation.";
RL Cell Rep. 23:3701-3709(2018).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE,
RP AND TOPOLOGY.
RX PubMed=29949756; DOI=10.1016/j.celrep.2018.06.002;
RA Stein C.S., Jadiya P., Zhang X., McLendon J.M., Abouassaly G.M.,
RA Witmer N.H., Anderson E.J., Elrod J.W., Boudreau R.L.;
RT "Mitoregulin: a lncRNA-encoded microprotein that supports mitochondrial
RT supercomplexes and respiratory efficiency.";
RL Cell Rep. 23:3710-3720(2018).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=31296841; DOI=10.1038/s41419-019-1767-y;
RA Lin Y.F., Xiao M.H., Chen H.X., Meng Y., Zhao N., Yang L., Tang H.,
RA Wang J.L., Liu X., Zhu Y., Zhuang S.M.;
RT "A novel mitochondrial micropeptide MPM enhances mitochondrial respiratory
RT activity and promotes myogenic differentiation.";
RL Cell Death Dis. 10:528-528(2019).
RN [6]
RP FUNCTION, INTERACTION WITH CYB5R3, AND SUBCELLULAR LOCATION.
RX PubMed=30796188; DOI=10.1073/pnas.1809105116;
RA Chugunova A., Loseva E., Mazin P., Mitina A., Navalayeu T., Bilan D.,
RA Vishnyakova P., Marey M., Golovina A., Serebryakova M., Pletnev P.,
RA Rubtsova M., Mair W., Vanyushkina A., Khaitovich P., Belousov V.,
RA Vysokikh M., Sergiev P., Dontsova O.;
RT "LINC00116 codes for a mitochondrial peptide linking respiration and lipid
RT metabolism.";
RL Proc. Natl. Acad. Sci. U.S.A. 116:4940-4945(2019).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=32393776; DOI=10.1038/s41419-020-2570-5;
RA Wang L., Fan J., Han L., Qi H., Wang Y., Wang H., Chen S., Du L., Li S.,
RA Zhang Y., Tang W., Ge G., Pan W., Hu P., Cheng H.;
RT "The micropeptide LEMP plays an evolutionarily conserved role in
RT myogenesis.";
RL Cell Death Dis. 11:357-357(2020).
RN [8]
RP FUNCTION.
RX PubMed=32243843; DOI=10.1016/j.stemcr.2020.03.002;
RA Friesen M., Warren C.R., Yu H., Toyohara T., Ding Q., Florido M.H.C.,
RA Sayre C., Pope B.D., Goff L.A., Rinn J.L., Cowan C.A.;
RT "Mitoregulin Controls beta-Oxidation in Human and Mouse Adipocytes.";
RL Stem Cell Reports 14:590-602(2020).
CC -!- FUNCTION: Positively regulates mitochondrial complex assembly and/or
CC stability (PubMed:29949756). Increases mitochondrial membrane potential
CC while decreasing mitochondrial reactive oxygen species (By similarity).
CC Increases mitochondrial respiration rate (PubMed:31296841). Increased
CC mitochondrial respiratory activity promotes myogenic differentiation
CC which facilitates muscle growth and regeneration (PubMed:31296841,
CC PubMed:32393776). Increases mitochondrial calcium retention capacity
CC (PubMed:29949756). Plays a role in maintenance of cellular lipid
CC composition through its interaction with cytochrome b5 reductase CYB5R3
CC which is required for mitochondrial respiratory complex I activity
CC (PubMed:30796188). Interacts with the mitochondrial trifunctional
CC enzyme complex (MTE) and enhances fatty acid beta-oxidation
CC (PubMed:29949755, PubMed:32243843). Not required for MTE formation or
CC stability (PubMed:29949755). Modulates triglyceride clearance in
CC adipocytes through its role in regulating fatty acid beta-oxidation and
CC lipolysis (PubMed:32243843). {ECO:0000250|UniProtKB:Q8NCU8,
CC ECO:0000269|PubMed:29949755, ECO:0000269|PubMed:29949756,
CC ECO:0000269|PubMed:30796188, ECO:0000269|PubMed:31296841,
CC ECO:0000269|PubMed:32243843, ECO:0000269|PubMed:32393776}.
CC -!- SUBUNIT: Interacts with mitochondrial trifunctional enzyme, a
CC heterotetrameric complex composed of 2 HADHA subunits and 2 HADHB
CC subunits (PubMed:29949755). Interacts with cytochrome b5 reductase
CC CYB5R3; the interaction is required to maintain cellular lipid
CC composition and leads to stimulation of mitochondrial respiratory
CC complex I activity (PubMed:31296841). Interacts with ATP synthase
CC subunit ATP5F1B/ATP5B (By similarity). {ECO:0000250|UniProtKB:Q8NCU8,
CC ECO:0000269|PubMed:29949755, ECO:0000269|PubMed:31296841}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:29949755, ECO:0000269|PubMed:29949756,
CC ECO:0000269|PubMed:30796188, ECO:0000269|PubMed:31296841,
CC ECO:0000269|PubMed:32393776}; Single-pass membrane protein
CC {ECO:0000305}. Note=Preferentially binds to cardiolipin relative to
CC other common cell membrane lipids. {ECO:0000269|PubMed:29949756}.
CC -!- TISSUE SPECIFICITY: Enriched in heart and skeletal muscle (at protein
CC level) (PubMed:29949755, PubMed:29949756, PubMed:31296841). Also
CC enriched in adipose tissue with lower levels detected in liver,
CC pancreas and brain (at protein level) (PubMed:29949756). Higher levels
CC in differentiated myotubes than in satellite cells (PubMed:32393776).
CC {ECO:0000269|PubMed:29949755, ECO:0000269|PubMed:29949756,
CC ECO:0000269|PubMed:31296841, ECO:0000269|PubMed:32393776}.
CC -!- DEVELOPMENTAL STAGE: Levels increase after birth and remain high at
CC postnatal days 14 and 21. {ECO:0000269|PubMed:31296841}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype (PubMed:29949756). Mutants
CC are viable and develop normally with no overt phenotypes later in life
CC (PubMed:29949756). In the fed state, no effect on mitochondrial
CC respiratory activities in cardiac or skeletal muscle fibers but, in
CC fasted mutants, skeletal muscle fibers and left ventricular fibers show
CC significantly lower rates of maximal fatty acid oxidation relative to
CC wild-type controls (PubMed:29949756). Left ventricular fibers also show
CC reduced mitochondrial calcium retention capacity (PubMed:29949756).
CC Aberrant distribution of respiratory chain complex I (CI) with distinct
CC loss of a high-molecular weight supercomplex and concomitant increase
CC in free or disassembled CI-associated complexes (PubMed:29949756).
CC Severely decreased presence of dimers of the mitochondrial 2-
CC oxoglutarate dehydrogenase OGDH and the mitochondrial acyl-CoA
CC dehydrogenase ACAD9 (PubMed:29949756). Significantly altered
CC distribution of the mitochondrial acyl-CoA dehydrogenase ACADVL/VLCAD
CC (PubMed:29949756). Impaired muscle formation, muscle weakness and
CC impaired muscle regeneration due to defects in satellite cell
CC differention (PubMed:32393776). {ECO:0000269|PubMed:29949756,
CC ECO:0000269|PubMed:32393776}.
CC -!- SIMILARITY: Belongs to the mitoregulin family. {ECO:0000305}.
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DR EMBL; AK027942; BAC25674.1; -; mRNA.
DR EMBL; AK165423; BAE38178.1; -; mRNA.
DR EMBL; BC116797; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC116799; -; NOT_ANNOTATED_CDS; mRNA.
DR AlphaFoldDB; Q8BT35; -.
DR SMR; Q8BT35; -.
DR STRING; 10090.ENSMUSP00000141107; -.
DR PeptideAtlas; Q8BT35; -.
DR PRIDE; Q8BT35; -.
DR Ensembl; ENSMUST00000135091; ENSMUSP00000141107; ENSMUSG00000051319.
DR MGI; MGI:1915135; Mtln.
DR VEuPathDB; HostDB:ENSMUSG00000051319; -.
DR eggNOG; ENOG502S9AW; Eukaryota.
DR GeneTree; ENSGT00390000007551; -.
DR HOGENOM; CLU_198667_0_0_1; -.
DR InParanoid; Q8BT35; -.
DR OMA; FVAGWQA; -.
DR ChiTaRS; Mtln; mouse.
DR PRO; PR:Q8BT35; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q8BT35; protein.
DR Bgee; ENSMUSG00000051319; Expressed in interventricular septum and 228 other tissues.
DR Genevisible; Q8BT35; MM.
DR GO; GO:0031305; C:integral component of mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0044255; P:cellular lipid metabolic process; IMP:UniProtKB.
DR GO; GO:0045333; P:cellular respiration; IMP:UniProtKB.
DR GO; GO:0006635; P:fatty acid beta-oxidation; ISS:UniProtKB.
DR GO; GO:0032000; P:positive regulation of fatty acid beta-oxidation; IMP:UniProtKB.
DR GO; GO:0010918; P:positive regulation of mitochondrial membrane potential; ISS:UniProtKB.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; IMP:UniProtKB.
DR GO; GO:0051284; P:positive regulation of sequestering of calcium ion; IDA:UniProtKB.
DR GO; GO:0051146; P:striated muscle cell differentiation; IMP:UniProtKB.
DR GO; GO:0070328; P:triglyceride homeostasis; ISS:UniProtKB.
DR InterPro; IPR038778; Mtln.
DR PANTHER; PTHR37154; PTHR37154; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q8NCU8"
FT CHAIN 2..56
FT /note="Mitoregulin"
FT /id="PRO_0000337007"
FT TOPO_DOM 2..9
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305|PubMed:29949756"
FT TRANSMEM 10..27
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 28..56
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305|PubMed:29949756"
SQ SEQUENCE 56 AA; 6529 MW; 1459668592AF46E2 CRC64;
MADVSERTLQ VSVLVAFASG VVLGWQANRL RRRYLDWRKR RLQDKLATTQ KKLDLA
