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 27-MAR-2024, entry version 169. 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}. 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; 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 PDB; 8IP3; EM; 2.60 A; A/B/C/D/E=1-443. DR PDB; 8IP4; EM; 2.70 A; A/B/C/D/E=1-443. DR PDB; 8IP5; EM; 2.50 A; A/B/C/D/E=1-443. DR PDB; 8IP6; EM; 2.90 A; A/B/C/D/E=1-443. DR PDB; 8TUL; EM; 2.80 A; A/B/C/D/E=1-443. DR PDB; 8TUP; EM; 3.30 A; A/B/C/D/E=1-443. DR PDBsum; 8IP3; -. DR PDBsum; 8IP4; -. DR PDBsum; 8IP5; -. DR PDBsum; 8IP6; -. DR PDBsum; 8TUL; -. DR PDBsum; 8TUP; -. DR AlphaFoldDB; Q9HD23; -. DR EMDB; EMD-35630; -. DR EMDB; EMD-35631; -. DR EMDB; EMD-35632; -. DR EMDB; EMD-35633; -. DR EMDB; EMD-41624; -. DR EMDB; EMD-41628; -. DR EMDB; EMD-41629; -. DR EMDB; EMD-41630; -. DR SMR; Q9HD23; -. DR BioGRID; 121498; 88. 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; 9606-ENSP00000399585; -. DR PeptideAtlas; Q9HD23; -. DR ProteomicsDB; 4888; -. DR ProteomicsDB; 81814; -. [Q9HD23-1] DR ProteomicsDB; 81815; -. [Q9HD23-2] DR ProteomicsDB; 81816; -. [Q9HD23-3] DR Pumba; Q9HD23; -. DR Antibodypedia; 25267; 72 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 AGR; HGNC:13785; -. 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; QWLPVPE; -. DR OrthoDB; 73031at2759; -. 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 1155 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 202 other cell types or tissues. DR ExpressionAtlas; Q9HD23; baseline and differential. 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:0006089; P:lactate metabolic process; IEA:Ensembl. 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 Gene3D; 2.40.128.330; -; 1. DR Gene3D; 1.20.58.340; Magnesium transport protein CorA, transmembrane region; 1. DR InterPro; IPR039204; MRS2-like. DR PANTHER; PTHR13890:SF26; MAGNESIUM TRANSPORTER MRS2 HOMOLOG, MITOCHONDRIAL; 1. DR PANTHER; PTHR13890; RNA SPLICING PROTEIN MRS2, MITOCHONDRIAL; 1. DR Genevisible; Q9HD23; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Ion transport; Magnesium; Membrane; KW Mitochondrion; Mitochondrion inner membrane; Reference proteome; KW Transit peptide; 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" FT STRAND 85..92 FT /evidence="ECO:0007829|PDB:8IP5" FT STRAND 97..103 FT /evidence="ECO:0007829|PDB:8IP5" FT HELIX 104..111 FT /evidence="ECO:0007829|PDB:8IP5" FT HELIX 115..118 FT /evidence="ECO:0007829|PDB:8IP5" FT STRAND 122..129 FT /evidence="ECO:0007829|PDB:8IP5" FT STRAND 132..137 FT /evidence="ECO:0007829|PDB:8IP5" FT STRAND 140..144 FT /evidence="ECO:0007829|PDB:8IP5" FT STRAND 146..153 FT /evidence="ECO:0007829|PDB:8IP5" FT TURN 155..158 FT /evidence="ECO:0007829|PDB:8IP5" FT HELIX 160..172 FT /evidence="ECO:0007829|PDB:8IP5" FT STRAND 173..176 FT /evidence="ECO:0007829|PDB:8IP4" FT STRAND 180..182 FT /evidence="ECO:0007829|PDB:8IP5" FT HELIX 184..218 FT /evidence="ECO:0007829|PDB:8IP5" FT STRAND 223..225 FT /evidence="ECO:0007829|PDB:8TUP" FT HELIX 228..260 FT /evidence="ECO:0007829|PDB:8IP5" FT HELIX 262..268 FT /evidence="ECO:0007829|PDB:8IP5" FT HELIX 270..274 FT /evidence="ECO:0007829|PDB:8IP5" FT HELIX 276..282 FT /evidence="ECO:0007829|PDB:8IP5" FT STRAND 283..285 FT /evidence="ECO:0007829|PDB:8IP5" FT HELIX 288..358 FT /evidence="ECO:0007829|PDB:8IP5" FT STRAND 361..363 FT /evidence="ECO:0007829|PDB:8IP3" FT STRAND 366..369 FT /evidence="ECO:0007829|PDB:8IP3" FT HELIX 372..400 FT /evidence="ECO:0007829|PDB:8IP5" 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 //