MRS2_HUMAN
ID MRS2_HUMAN Reviewed; 443 AA.
AC Q9HD23; A8K4U3; B3KNN2; B4DQL2; Q5T3Y1; Q6NTG4; Q96KF8; Q9BVP1;
DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Magnesium transporter MRS2 homolog, mitochondrial;
DE AltName: Full=MRS2-like protein;
DE Flags: Precursor;
GN Name=MRS2; Synonyms=HPT, MRS2L;
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] (ISOFORM 1), NUCLEOTIDE SEQUENCE [GENOMIC DNA]
RP OF 241-278, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11401429; DOI=10.1006/geno.2000.6407;
RA Zsurka G., Gregan J., Schweyen R.J.;
RT "The human mitochondrial Mrs2 protein functionally substitutes for its
RT yeast homologue, a candidate magnesium transporter.";
RL Genomics 72:158-168(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Bosma T.J., MacDiarmid C.W., Gardner R.C.;
RT "Putative mammalian magnesium transporters.";
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 4).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Lung, and Lymph;
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 [7]
RP FUNCTION.
RX PubMed=18384665; DOI=10.1111/j.1582-4934.2008.00328.x;
RA Piskacek M., Zotova L., Zsurka G., Schweyen R.J.;
RT "Conditional knockdown of hMRS2 results in loss of mitochondrial Mg(2+)
RT uptake and cell death.";
RL J. Cell. Mol. Med. 13:693-700(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
CC -!- FUNCTION: Magnesium transporter that mediates the influx of magnesium
CC into the mitochondrial matrix (PubMed:11401429, PubMed:18384665).
CC Required for normal expression of the mitochondrial respiratory complex
CC I subunits (PubMed:18384665). {ECO:0000269|PubMed:11401429,
CC ECO:0000269|PubMed:18384665}.
CC -!- INTERACTION:
CC Q9HD23-2; Q969G2: LHX4; NbExp=3; IntAct=EBI-13374520, EBI-2865388;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:11401429, ECO:0000305|PubMed:18384665}; Multi-pass
CC membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9HD23-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9HD23-2; Sequence=VSP_016209, VSP_016210;
CC Name=3;
CC IsoId=Q9HD23-3; Sequence=VSP_016207, VSP_016208;
CC Name=4;
CC IsoId=Q9HD23-4; Sequence=VSP_055287;
CC -!- MISCELLANEOUS: Has the ability to complement a deletion of MRS2 in
CC S.cerevisiae and partly restore mitochondrial magnesium concentrations.
CC -!- SIMILARITY: Belongs to the CorA metal ion transporter (MIT) (TC 1.A.35)
CC family. {ECO:0000305}.
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DR EMBL; AF293076; AAK38615.1; -; mRNA.
DR EMBL; AF293078; AAK38617.1; -; Genomic_DNA.
DR EMBL; AF288288; AAG01170.1; -; mRNA.
DR EMBL; AK054587; BAG51394.1; -; mRNA.
DR EMBL; AK291058; BAF83747.1; -; mRNA.
DR EMBL; AK298849; BAG60974.1; -; mRNA.
DR EMBL; AL359713; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471087; EAW55445.1; -; Genomic_DNA.
DR EMBL; CH471087; EAW55446.1; -; Genomic_DNA.
DR EMBL; BC001028; AAH01028.2; -; mRNA.
DR EMBL; BC069009; AAH69009.1; -; mRNA.
DR CCDS; CCDS4552.1; -. [Q9HD23-1]
DR CCDS; CCDS69055.1; -. [Q9HD23-4]
DR CCDS; CCDS75408.1; -. [Q9HD23-2]
DR RefSeq; NP_001273193.1; NM_001286264.1. [Q9HD23-4]
DR RefSeq; NP_001273194.1; NM_001286265.1. [Q9HD23-2]
DR RefSeq; NP_001273195.1; NM_001286266.1.
DR RefSeq; NP_065713.1; NM_020662.3. [Q9HD23-1]
DR AlphaFoldDB; Q9HD23; -.
DR SMR; Q9HD23; -.
DR BioGRID; 121498; 86.
DR IntAct; Q9HD23; 37.
DR MINT; Q9HD23; -.
DR STRING; 9606.ENSP00000399585; -.
DR DrugBank; DB14513; Magnesium.
DR TCDB; 1.A.35.5.7; the cora metal ion transporter (mit) family.
DR iPTMnet; Q9HD23; -.
DR PhosphoSitePlus; Q9HD23; -.
DR BioMuta; MRS2; -.
DR DMDM; 74752816; -.
DR EPD; Q9HD23; -.
DR jPOST; Q9HD23; -.
DR MassIVE; Q9HD23; -.
DR MaxQB; Q9HD23; -.
DR PaxDb; Q9HD23; -.
DR PeptideAtlas; Q9HD23; -.
DR PRIDE; Q9HD23; -.
DR ProteomicsDB; 4888; -.
DR ProteomicsDB; 81814; -. [Q9HD23-1]
DR ProteomicsDB; 81815; -. [Q9HD23-2]
DR ProteomicsDB; 81816; -. [Q9HD23-3]
DR Antibodypedia; 25267; 58 antibodies from 14 providers.
DR DNASU; 57380; -.
DR Ensembl; ENST00000378353.5; ENSP00000367604.1; ENSG00000124532.15. [Q9HD23-2]
DR Ensembl; ENST00000378386.8; ENSP00000367637.3; ENSG00000124532.15. [Q9HD23-1]
DR Ensembl; ENST00000443868.6; ENSP00000399585.2; ENSG00000124532.15. [Q9HD23-4]
DR GeneID; 57380; -.
DR KEGG; hsa:57380; -.
DR MANE-Select; ENST00000378386.8; ENSP00000367637.3; NM_020662.4; NP_065713.1.
DR UCSC; uc003nea.5; human. [Q9HD23-1]
DR CTD; 57380; -.
DR DisGeNET; 57380; -.
DR GeneCards; MRS2; -.
DR HGNC; HGNC:13785; MRS2.
DR HPA; ENSG00000124532; Low tissue specificity.
DR MIM; 619307; gene.
DR neXtProt; NX_Q9HD23; -.
DR OpenTargets; ENSG00000124532; -.
DR PharmGKB; PA162396189; -.
DR VEuPathDB; HostDB:ENSG00000124532; -.
DR eggNOG; KOG2662; Eukaryota.
DR GeneTree; ENSGT00390000009988; -.
DR HOGENOM; CLU_047261_0_0_1; -.
DR InParanoid; Q9HD23; -.
DR OMA; TRNNCII; -.
DR OrthoDB; 1363588at2759; -.
DR PhylomeDB; Q9HD23; -.
DR TreeFam; TF328433; -.
DR PathwayCommons; Q9HD23; -.
DR Reactome; R-HSA-5223345; Miscellaneous transport and binding events.
DR SignaLink; Q9HD23; -.
DR BioGRID-ORCS; 57380; 20 hits in 1082 CRISPR screens.
DR ChiTaRS; MRS2; human.
DR GeneWiki; MRS2L; -.
DR GenomeRNAi; 57380; -.
DR Pharos; Q9HD23; Tbio.
DR PRO; PR:Q9HD23; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9HD23; protein.
DR Bgee; ENSG00000124532; Expressed in biceps brachii and 200 other tissues.
DR ExpressionAtlas; Q9HD23; baseline and differential.
DR Genevisible; Q9HD23; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0015095; F:magnesium ion transmembrane transporter activity; IMP:UniProtKB.
DR GO; GO:0015693; P:magnesium ion transport; IBA:GO_Central.
DR GO; GO:0045016; P:mitochondrial magnesium ion transmembrane transport; IMP:UniProtKB.
DR GO; GO:0055085; P:transmembrane transport; TAS:Reactome.
DR CDD; cd12823; Mrs2_Mfm1p-like; 1.
DR InterPro; IPR039204; MRS2-like.
DR PANTHER; PTHR13890; PTHR13890; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Ion transport; Magnesium; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Reference proteome; Transit peptide;
KW Transmembrane; Transmembrane helix; Transport.
FT TRANSIT 1..49
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 50..443
FT /note="Magnesium transporter MRS2 homolog, mitochondrial"
FT /id="PRO_0000042837"
FT TOPO_DOM 50..339
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000255"
FT TRANSMEM 340..360
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 361..372
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255"
FT TRANSMEM 373..393
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 394..443
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000255"
FT VAR_SEQ 101..117
FT /note="ERKKTELYQELGLQARD -> VFESCDNSRVSSDIRLS (in isoform
FT 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_016207"
FT VAR_SEQ 118..443
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_016208"
FT VAR_SEQ 139..159
FT /note="YLKAVITPECLLILDYRNLNL -> KYSLLLESVASILQNSVSFMERQT
FT (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055287"
FT VAR_SEQ 408
FT /note="M -> V (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_016209"
FT VAR_SEQ 409..443
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_016210"
FT VARIANT 35
FT /note="P -> S (in dbSNP:rs2295651)"
FT /id="VAR_023782"
FT VARIANT 412
FT /note="P -> S (in dbSNP:rs35261004)"
FT /id="VAR_061129"
SQ SEQUENCE 443 AA; 50318 MW; 396EEFB64A8BB14F CRC64;
MECLRSLPCL LPRAMRLPRR TLCALALDVT SVGPPVAACG RRANLIGRSR AAQLCGPDRL
RVAGEVHRFR TSDVSQATLA SVAPVFTVTK FDKQGNVTSF ERKKTELYQE LGLQARDLRF
QHVMSITVRN NRIIMRMEYL KAVITPECLL ILDYRNLNLE QWLFRELPSQ LSGEGQLVTY
PLPFEFRAIE ALLQYWINTL QGKLSILQPL ILETLDALVD PKHSSVDRSK LHILLQNGKS
LSELETDIKI FKESILEILD EEELLEELCV SKWSDPQVFE KSSAGIDHAE EMELLLENYY
RLADDLSNAA RELRVLIDDS QSIIFINLDS HRNVMMRLNL QLTMGTFSLS LFGLMGVAFG
MNLESSLEED HRIFWLITGI MFMGSGLIWR RLLSFLGRQL EAPLPPMMAS LPKKTLLADR
SMELKNSLRL DGLGSGRSIL TNR
