MTX2_HUMAN
ID MTX2_HUMAN Reviewed; 263 AA.
AC O75431; A8JZZ4; Q53S50; Q53SQ2; Q5M7Z6; Q8IZ68;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Metaxin-2;
DE AltName: Full=Mitochondrial outer membrane import complex protein 2;
GN Name=MTX2;
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), INTERACTION WITH MTX1, SUBCELLULAR
RP LOCATION, AND FUNCTION.
RX PubMed=10381257;
RX DOI=10.1002/(sici)1097-4644(19990701)74:1<11::aid-jcb2>3.0.co;2-v;
RA Armstrong L.C., Saenz A.J., Bornstein P.;
RT "Metaxin 1 interacts with metaxin 2, a novel related protein associated
RT with the mammalian mitochondrial outer membrane.";
RL J. Cell. Biochem. 74:11-22(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Thymus;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Testis;
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
RP INTERACTION WITH THE MINOS/MITOS COMPLEX.
RX PubMed=22114354; DOI=10.1091/mbc.e11-09-0774;
RA Alkhaja A.K., Jans D.C., Nikolov M., Vukotic M., Lytovchenko O.,
RA Ludewig F., Schliebs W., Riedel D., Urlaub H., Jakobs S., Deckers M.;
RT "MINOS1 is a conserved component of mitofilin complexes and required for
RT mitochondrial function and cristae organization.";
RL Mol. Biol. Cell 23:247-257(2012).
RN [8]
RP INTERACTION WITH THE MICOS COMPLEX, AND SUBCELLULAR LOCATION.
RX PubMed=25997101; DOI=10.7554/elife.06265;
RA Guarani V., McNeill E.M., Paulo J.A., Huttlin E.L., Froehlich F.,
RA Gygi S.P., Van Vactor D., Harper J.W.;
RT "QIL1 is a novel mitochondrial protein required for MICOS complex stability
RT and cristae morphology.";
RL Elife 4:0-0(2015).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [10]
RP INVOLVEMENT IN MDPS.
RX PubMed=32917887; DOI=10.1038/s41467-020-18146-9;
RA Elouej S., Harhouri K., Le Mao M., Baujat G., Nampoothiri S., Kayserili H.,
RA Menabawy N.A., Selim L., Paneque A.L., Kubisch C., Lessel D.,
RA Rubinsztajn R., Charar C., Bartoli C., Airault C., Deleuze J.F., Roetig A.,
RA Bauer P., Pereira C., Loh A., Escande-Beillard N., Muchir A., Martino L.,
RA Gruenbaum Y., Lee S.H., Manivet P., Lenaers G., Reversade B., Levy N.,
RA De Sandre-Giovannoli A.;
RT "Loss of MTX2 causes mandibuloacral dysplasia and links mitochondrial
RT dysfunction to altered nuclear morphology.";
RL Nat. Commun. 11:4589-4589(2020).
CC -!- FUNCTION: Involved in transport of proteins into the mitochondrion.
CC {ECO:0000269|PubMed:10381257}.
CC -!- SUBUNIT: Interacts with MTX1/metaxin-1. Associates with the
CC mitochondrial contact site and cristae organizing system (MICOS)
CC complex, composed of at least MICOS10/MIC10, CHCHD3/MIC19,
CC CHCHD6/MIC25, APOOL/MIC27, IMMT/MIC60, APOO/MIC23/MIC26 and QIL1/MIC13.
CC This complex was also known under the names MINOS or MitOS complex. The
CC MICOS complex associates with mitochondrial outer membrane proteins
CC SAMM50, MTX1 and MTX2 (together described as components of the
CC mitochondrial outer membrane sorting assembly machinery (SAM) complex)
CC and DNAJC11, mitochondrial inner membrane protein TMEM11 and with
CC HSPA9. The MICOS and SAM complexes together with DNAJC11 are part of a
CC large protein complex spanning both membranes termed the mitochondrial
CC intermembrane space bridging (MIB) complex.
CC {ECO:0000269|PubMed:10381257, ECO:0000269|PubMed:22114354,
CC ECO:0000269|PubMed:25997101}.
CC -!- INTERACTION:
CC O75431; Q9BXJ5: C1QTNF2; NbExp=3; IntAct=EBI-7415268, EBI-2817707;
CC O75431; Q8N6L0: KASH5; NbExp=6; IntAct=EBI-7415268, EBI-749265;
CC O75431; Q15669: RHOH; NbExp=3; IntAct=EBI-7415268, EBI-1244971;
CC O75431; O75478: TADA2A; NbExp=3; IntAct=EBI-7415268, EBI-742268;
CC O75431; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-7415268, EBI-947187;
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000269|PubMed:10381257}. Mitochondrion
CC {ECO:0000269|PubMed:25997101}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O75431-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O75431-2; Sequence=VSP_054468;
CC -!- DISEASE: Mandibuloacral dysplasia progeroid syndrome (MDPS)
CC [MIM:619127]: A form of mandibuloacral dysplasia, a rare progeroid
CC disorder with clinical and genetic heterogeneity, characterized by
CC growth retardation, craniofacial dysmorphic features due to distal bone
CC resorption, musculoskeletal and skin abnormalities associated with
CC lipodystrophy. MDPS is an autosomal recessive disorder. Clinical
CC features include poor growth, osteoporosis, osteopenia, acroosteolysis
CC of distal phalanges, arterial calcification, renal glomerulosclerosis
CC and severe hypertension. {ECO:0000269|PubMed:32917887}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the metaxin family. {ECO:0000305}.
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DR EMBL; AF053551; AAC25105.1; -; mRNA.
DR EMBL; AK289359; BAF82048.1; -; mRNA.
DR EMBL; AK303564; BAG64587.1; -; mRNA.
DR EMBL; AC016739; AAY14795.1; -; Genomic_DNA.
DR EMBL; AC073069; AAX93188.1; -; Genomic_DNA.
DR EMBL; CH471058; EAX11076.1; -; Genomic_DNA.
DR EMBL; CH471058; EAX11078.1; -; Genomic_DNA.
DR EMBL; BC017271; AAH17271.1; -; mRNA.
DR EMBL; BC067831; AAH67831.1; -; mRNA.
DR EMBL; BC088359; AAH88359.1; -; mRNA.
DR CCDS; CCDS2272.1; -. [O75431-1]
DR RefSeq; NP_001006636.1; NM_001006635.2. [O75431-2]
DR RefSeq; NP_001306026.1; NM_001319097.1.
DR RefSeq; NP_001306027.1; NM_001319098.1.
DR RefSeq; NP_006545.1; NM_006554.4. [O75431-1]
DR AlphaFoldDB; O75431; -.
DR SMR; O75431; -.
DR BioGRID; 115894; 180.
DR ComplexPortal; CPX-6133; SAM mitochondrial sorting and assembly machinery complex.
DR CORUM; O75431; -.
DR IntAct; O75431; 45.
DR MINT; O75431; -.
DR STRING; 9606.ENSP00000249442; -.
DR iPTMnet; O75431; -.
DR PhosphoSitePlus; O75431; -.
DR SwissPalm; O75431; -.
DR BioMuta; MTX2; -.
DR EPD; O75431; -.
DR jPOST; O75431; -.
DR MassIVE; O75431; -.
DR MaxQB; O75431; -.
DR PaxDb; O75431; -.
DR PeptideAtlas; O75431; -.
DR PRIDE; O75431; -.
DR ProteomicsDB; 50001; -. [O75431-1]
DR ProteomicsDB; 71282; -.
DR TopDownProteomics; O75431-1; -. [O75431-1]
DR Antibodypedia; 33917; 184 antibodies from 26 providers.
DR DNASU; 10651; -.
DR Ensembl; ENST00000249442.11; ENSP00000249442.6; ENSG00000128654.14. [O75431-1]
DR GeneID; 10651; -.
DR KEGG; hsa:10651; -.
DR MANE-Select; ENST00000249442.11; ENSP00000249442.6; NM_006554.5; NP_006545.1.
DR UCSC; uc002ukx.4; human. [O75431-1]
DR CTD; 10651; -.
DR DisGeNET; 10651; -.
DR GeneCards; MTX2; -.
DR HGNC; HGNC:7506; MTX2.
DR HPA; ENSG00000128654; Low tissue specificity.
DR MalaCards; MTX2; -.
DR MIM; 608555; gene.
DR MIM; 619127; phenotype.
DR neXtProt; NX_O75431; -.
DR OpenTargets; ENSG00000128654; -.
DR Orphanet; 90153; Mandibuloacral dysplasia with type A lipodystrophy.
DR PharmGKB; PA31308; -.
DR VEuPathDB; HostDB:ENSG00000128654; -.
DR eggNOG; KOG3027; Eukaryota.
DR GeneTree; ENSGT00950000182919; -.
DR InParanoid; O75431; -.
DR OMA; PWPENAA; -.
DR OrthoDB; 1219712at2759; -.
DR PhylomeDB; O75431; -.
DR TreeFam; TF313422; -.
DR PathwayCommons; O75431; -.
DR Reactome; R-HSA-1268020; Mitochondrial protein import.
DR Reactome; R-HSA-8949613; Cristae formation.
DR SignaLink; O75431; -.
DR SIGNOR; O75431; -.
DR BioGRID-ORCS; 10651; 60 hits in 1075 CRISPR screens.
DR ChiTaRS; MTX2; human.
DR GenomeRNAi; 10651; -.
DR Pharos; O75431; Tbio.
DR PRO; PR:O75431; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; O75431; protein.
DR Bgee; ENSG00000128654; Expressed in hindlimb stylopod muscle and 195 other tissues.
DR ExpressionAtlas; O75431; baseline and differential.
DR Genevisible; O75431; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0140275; C:MIB complex; HDA:UniProtKB.
DR GO; GO:0005741; C:mitochondrial outer membrane; TAS:ProtInc.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0001401; C:SAM complex; IPI:ComplexPortal.
DR GO; GO:0007007; P:inner mitochondrial membrane organization; IC:UniProtKB.
DR GO; GO:0006839; P:mitochondrial transport; IMP:UniProtKB.
DR GO; GO:0007005; P:mitochondrion organization; IBA:GO_Central.
DR GO; GO:0045040; P:protein insertion into mitochondrial outer membrane; IC:ComplexPortal.
DR InterPro; IPR036282; Glutathione-S-Trfase_C_sf.
DR InterPro; IPR040079; Glutathione_S-Trfase.
DR InterPro; IPR033468; Metaxin_GST.
DR InterPro; IPR019564; Sam37/metaxin_N.
DR Pfam; PF17171; GST_C_6; 1.
DR Pfam; PF10568; Tom37; 1.
DR SFLD; SFLDS00019; Glutathione_Transferase_(cytos; 1.
DR SUPFAM; SSF47616; SSF47616; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Membrane; Mitochondrion;
KW Mitochondrion outer membrane; Protein transport; Reference proteome;
KW Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:25944712"
FT CHAIN 2..263
FT /note="Metaxin-2"
FT /id="PRO_0000220995"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:25944712"
FT VAR_SEQ 1..13
FT /note="MSLVAEAFVSQIA -> MYI (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_054468"
SQ SEQUENCE 263 AA; 29763 MW; 3A2EF476F1C78465 CRC64;
MSLVAEAFVS QIAAAEPWPE NATLYQQLKG EQILLSDNAA SLAVQAFLQM CNLPIKVVCR
ANAEYMSPSG KVPFIHVGNQ VVSELGPIVQ FVKAKGHSLS DGLEEVQKAE MKAYMELVNN
MLLTAELYLQ WCDEATVGEI THARYGSPYP WPLNHILAYQ KQWEVKRKMK AIGWGKKTLD
QVLEDVDQCC QALSQRLGTQ PYFFNKQPTE LDALVFGHLY TILTTQLTND ELSEKVKNYS
NLLAFCRRIE QHYFEDRGKG RLS
