MTLN_HUMAN
ID MTLN_HUMAN Reviewed; 56 AA.
AC Q8NCU8;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 10-OCT-2018, sequence version 2.
DT 03-AUG-2022, entry version 90.
DE RecName: Full=Mitoregulin {ECO:0000303|PubMed:29949756, ECO:0000312|HGNC:HGNC:27339};
DE AltName: Full=Micropeptide in mitochondria {ECO:0000250|UniProtKB:Q8BT35};
DE AltName: Full=Micropeptide regulator of beta-oxidation {ECO:0000250|UniProtKB:Q8BT35};
DE AltName: Full=Small integral membrane protein 37 {ECO:0000312|HGNC:HGNC:27339};
DE AltName: Full=lncRNA-encoded micropeptide {ECO:0000250|UniProtKB:Q8BT35};
GN Name=MTLN {ECO:0000303|PubMed:29949756, ECO:0000312|HGNC:HGNC:27339};
GN Synonyms=LEMP {ECO:0000250|UniProtKB:Q8BT35},
GN LINC00116 {ECO:0000312|HGNC:HGNC:27339},
GN MOXI {ECO:0000250|UniProtKB:Q8BT35}, MPM {ECO:0000250|UniProtKB:Q8BT35},
GN NCRNA00116 {ECO:0000312|HGNC:HGNC:27339},
GN SMIM37 {ECO:0000312|HGNC:HGNC:27339};
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 [LARGE SCALE MRNA] (ISOFORM LONG).
RC TISSUE=Eye;
RA Guo J.H., Yu L.;
RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
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 [3]
RP MASS SPECTROMETRY, AND CLEAVAGE OF INITIATOR METHIONINE (ISOFORM SHORT).
RX PubMed=23305238; DOI=10.1021/ac3031527;
RA Catherman A.D., Li M., Tran J.C., Durbin K.R., Compton P.D., Early B.P.,
RA Thomas P.M., Kelleher N.L.;
RT "Top down proteomics of human membrane proteins from enriched mitochondrial
RT fractions.";
RL Anal. Chem. 85:1880-1888(2013).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [5]
RP FUNCTION.
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 [6]
RP FUNCTION, INTERACTION WITH ATP5B AND HADHB, DEVELOPMENTAL STAGE, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
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 (By similarity). Increases mitochondrial membrane potential
CC while decreasing mitochondrial reactive oxygen species
CC (PubMed:29949756). Increases mitochondrial respiration rate
CC (PubMed:29949756). Increased mitochondrial respiratory activity
CC promotes myogenic differentiation which facilitates muscle growth and
CC regeneration (By similarity). Increases mitochondrial calcium retention
CC capacity (PubMed:29949756). Plays a role in maintenance of cellular
CC lipid composition through its interaction with cytochrome b5 reductase
CC CYB5R3 which is required for mitochondrial respiratory complex I
CC activity (By similarity). Interacts with the mitochondrial
CC trifunctional enzyme complex (MTE) and enhances fatty acid beta-
CC oxidation (PubMed:32243843). Not required for MTE formation or
CC stability (By similarity). Modulates triglyceride clearance in
CC adipocytes through its role in regulating fatty acid beta-oxidation and
CC lipolysis (PubMed:32243843). {ECO:0000250|UniProtKB:Q8BT35,
CC ECO:0000269|PubMed:29949756, ECO:0000269|PubMed:32243843}.
CC -!- SUBUNIT: Interacts with mitochondrial trifunctional enzyme, a
CC heterotetrameric complex composed of 2 HADHA subunits and 2 HADHB
CC subunits (PubMed:32243843). 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 (By similarity). Interacts with ATP synthase subunit
CC ATP5F1B/ATP5B (PubMed:32243843). {ECO:0000250|UniProtKB:Q8BT35,
CC ECO:0000269|PubMed:32243843}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:Q8BT35}; Single-pass membrane protein
CC {ECO:0000305}. Note=Preferentially binds to cardiolipin relative to
CC other common cell membrane lipids. {ECO:0000250|UniProtKB:Q8BT35}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=Short;
CC IsoId=Q8NCU8-2; Sequence=Displayed;
CC Name=Long;
CC IsoId=Q8NCU8-1; Sequence=VSP_059832;
CC -!- DEVELOPMENTAL STAGE: Levels increase throughout adipogenesis.
CC {ECO:0000269|PubMed:32243843}.
CC -!- MASS SPECTROMETRY: Mass=6391.6; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:23305238};
CC -!- SIMILARITY: Belongs to the mitoregulin family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF504645; AAM28196.1; -; mRNA.
DR EMBL; CH878608; EAW50629.1; -; Genomic_DNA.
DR AlphaFoldDB; Q8NCU8; -.
DR SMR; Q8NCU8; -.
DR STRING; 9606.ENSP00000485216; -.
DR iPTMnet; Q8NCU8; -.
DR PhosphoSitePlus; Q8NCU8; -.
DR BioMuta; LINC00116; -.
DR EPD; Q8NCU8; -.
DR jPOST; Q8NCU8; -.
DR MassIVE; Q8NCU8; -.
DR PeptideAtlas; Q8NCU8; -.
DR PRIDE; Q8NCU8; -.
DR ProteomicsDB; 72950; -. [Q8NCU8-1]
DR TopDownProteomics; Q8NCU8-1; -. [Q8NCU8-1]
DR Ensembl; ENST00000414416.2; ENSP00000485216.1; ENSG00000175701.11. [Q8NCU8-1]
DR Ensembl; ENST00000426713.1; ENSP00000485373.1; ENSG00000175701.11. [Q8NCU8-2]
DR Ensembl; ENST00000611969.5; ENSP00000485064.1; ENSG00000175701.11. [Q8NCU8-2]
DR MANE-Select; ENST00000611969.5; ENSP00000485064.1; NM_001384134.1; NP_001371063.1.
DR UCSC; uc002tfq.3; human. [Q8NCU8-2]
DR GeneCards; MTLN; -.
DR HGNC; HGNC:27339; MTLN.
DR HPA; ENSG00000175701; Tissue enhanced (skeletal).
DR neXtProt; NX_Q8NCU8; -.
DR OpenTargets; ENSG00000175701; -.
DR VEuPathDB; HostDB:ENSG00000175701; -.
DR eggNOG; ENOG502S9AW; Eukaryota.
DR GeneTree; ENSGT00390000007551; -.
DR HOGENOM; CLU_1921930_0_0_1; -.
DR InParanoid; Q8NCU8; -.
DR OMA; EMLWGFR; -.
DR PhylomeDB; Q8NCU8; -.
DR SignaLink; Q8NCU8; -.
DR ChiTaRS; LINC00116; human.
DR Pharos; Q8NCU8; Tbio.
DR PRO; PR:Q8NCU8; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q8NCU8; protein.
DR Bgee; ENSG00000175701; Expressed in hindlimb stylopod muscle and 167 other tissues.
DR ExpressionAtlas; Q8NCU8; baseline and differential.
DR Genevisible; Q8NCU8; HS.
DR GO; GO:0031305; C:integral component of mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0044255; P:cellular lipid metabolic process; ISS:UniProtKB.
DR GO; GO:0045333; P:cellular respiration; ISS:UniProtKB.
DR GO; GO:0006635; P:fatty acid beta-oxidation; IMP:UniProtKB.
DR GO; GO:0032000; P:positive regulation of fatty acid beta-oxidation; ISS:UniProtKB.
DR GO; GO:0010918; P:positive regulation of mitochondrial membrane potential; IDA:UniProtKB.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; ISS:UniProtKB.
DR GO; GO:0051284; P:positive regulation of sequestering of calcium ion; IDA:UniProtKB.
DR GO; GO:0051146; P:striated muscle cell differentiation; ISS:UniProtKB.
DR GO; GO:0070328; P:triglyceride homeostasis; IMP:UniProtKB.
DR InterPro; IPR038778; Mtln.
DR PANTHER; PTHR37154; PTHR37154; 1.
PE 1: Evidence at protein level;
KW Alternative initiation; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:23305238"
FT CHAIN 2..56
FT /note="Mitoregulin"
FT /id="PRO_0000337006"
FT TOPO_DOM 2..9
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000250|UniProtKB:Q8BT35"
FT TRANSMEM 10..27
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 28..56
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000250|UniProtKB:Q8BT35"
FT VAR_SEQ 1
FT /note="M -> MLANDVRHQQEMWGFRKVEGGVVQSLGKSSVEGETDGTISEFREIQR
FT LAAFASFLSHAPPLNARRLLTPPPRRRPRCTPAAAM (in isoform Long)"
FT /evidence="ECO:0000305"
FT /id="VSP_059832"
SQ SEQUENCE 56 AA; 6527 MW; A838723AD9527A11 CRC64;
MADVSERTLQ LSVLVAFASG VLLGWQANRL RRRYLDWRKR RLQDKLAATQ KKLDLA
