MTNA_HUMAN
ID MTNA_HUMAN Reviewed; 369 AA.
AC Q9BV20; Q8NDC9;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Methylthioribose-1-phosphate isomerase {ECO:0000255|HAMAP-Rule:MF_03119};
DE Short=M1Pi {ECO:0000255|HAMAP-Rule:MF_03119};
DE Short=MTR-1-P isomerase {ECO:0000255|HAMAP-Rule:MF_03119};
DE EC=5.3.1.23 {ECO:0000255|HAMAP-Rule:MF_03119};
DE AltName: Full=Mediator of RhoA-dependent invasion;
DE AltName: Full=S-methyl-5-thioribose-1-phosphate isomerase {ECO:0000255|HAMAP-Rule:MF_03119};
DE AltName: Full=Translation initiation factor eIF-2B subunit alpha/beta/delta-like protein {ECO:0000255|HAMAP-Rule:MF_03119};
GN Name=MRI1 {ECO:0000255|HAMAP-Rule:MF_03119}; Synonyms=MRDI;
GN ORFNames=UNQ6390/PRO21135;
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 1).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, ACTIVE SITE, INDUCTION BY
RP RHOA, SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-168 AND ASP-248.
RX PubMed=19620624; DOI=10.1074/mcp.m900178-mcp200;
RA Kabuyama Y., Litman E.S., Templeton P.D., Metzner S.I., Witze E.S.,
RA Argast G.M., Langer S.J., Polvinen K., Shellman Y., Chan D., Shabb J.B.,
RA Fitzpatrick J.E., Resing K.A., Sousa M.C., Ahn N.G.;
RT "A mediator of Rho-dependent invasion moonlights as a methionine salvage
RT enzyme.";
RL Mol. Cell. Proteomics 8:2308-2320(2009).
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 ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [9]
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).
CC -!- FUNCTION: Catalyzes the interconversion of methylthioribose-1-phosphate
CC (MTR-1-P) into methylthioribulose-1-phosphate (MTRu-1-P). Independently
CC from catalytic activity, promotes cell invasion in response to
CC constitutive RhoA activation by promoting FAK tyrosine phosphorylation
CC and stress fiber turnover. {ECO:0000255|HAMAP-Rule:MF_03119,
CC ECO:0000269|PubMed:19620624}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-methyl-5-thio-alpha-D-ribose 1-phosphate = S-methyl-5-thio-
CC D-ribulose 1-phosphate; Xref=Rhea:RHEA:19989, ChEBI:CHEBI:58533,
CC ChEBI:CHEBI:58548; EC=5.3.1.23; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_03119};
CC -!- PATHWAY: Amino-acid biosynthesis; L-methionine biosynthesis via salvage
CC pathway; L-methionine from S-methyl-5-thio-alpha-D-ribose 1-phosphate:
CC step 1/6. {ECO:0000255|HAMAP-Rule:MF_03119}.
CC -!- INTERACTION:
CC Q9BV20; P46379-2: BAG6; NbExp=3; IntAct=EBI-747381, EBI-10988864;
CC Q9BV20; P55212: CASP6; NbExp=3; IntAct=EBI-747381, EBI-718729;
CC Q9BV20; Q9Y2V7: COG6; NbExp=3; IntAct=EBI-747381, EBI-3866319;
CC Q9BV20; Q9Y624: F11R; NbExp=3; IntAct=EBI-747381, EBI-742600;
CC Q9BV20; P13473-2: LAMP2; NbExp=3; IntAct=EBI-747381, EBI-21591415;
CC Q9BV20; Q9BV20: MRI1; NbExp=7; IntAct=EBI-747381, EBI-747381;
CC Q9BV20; Q9BVL2: NUP58; NbExp=3; IntAct=EBI-747381, EBI-2811583;
CC Q9BV20; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-747381, EBI-79165;
CC Q9BV20; Q9H8W4: PLEKHF2; NbExp=3; IntAct=EBI-747381, EBI-742388;
CC Q9BV20; O75400-2: PRPF40A; NbExp=3; IntAct=EBI-747381, EBI-5280197;
CC Q9BV20; Q9Y371: SH3GLB1; NbExp=3; IntAct=EBI-747381, EBI-2623095;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|HAMAP-Rule:MF_03119,
CC ECO:0000269|PubMed:19620624}. Cytoplasm {ECO:0000255|HAMAP-
CC Rule:MF_03119, ECO:0000269|PubMed:19620624}. Cell projection
CC {ECO:0000269|PubMed:19620624}. Note=Primarily nuclear, but cytoplasmic
CC in cancer cells, with enrichment at leading edge of the plasma membrane
CC in late stage tumor cells.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9BV20-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BV20-2; Sequence=VSP_030935;
CC -!- INDUCTION: By RhoA activation in cancer cells (at protein level).
CC {ECO:0000269|PubMed:19620624}.
CC -!- SIMILARITY: Belongs to the eIF-2B alpha/beta/delta subunits family.
CC MtnA subfamily. {ECO:0000255|HAMAP-Rule:MF_03119}.
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DR EMBL; AY358176; AAQ88543.1; -; mRNA.
DR EMBL; AL834276; CAD38951.1; -; mRNA.
DR EMBL; CH471106; EAW84370.1; -; Genomic_DNA.
DR EMBL; CH471106; EAW84371.1; -; Genomic_DNA.
DR EMBL; BC001703; AAH01703.1; -; mRNA.
DR CCDS; CCDS12297.1; -. [Q9BV20-2]
DR CCDS; CCDS32923.1; -. [Q9BV20-1]
DR RefSeq; NP_001026897.1; NM_001031727.3. [Q9BV20-1]
DR RefSeq; NP_001316501.1; NM_001329572.1.
DR RefSeq; NP_115661.1; NM_032285.3. [Q9BV20-2]
DR PDB; 4LDQ; X-ray; 2.50 A; A/B=1-369.
DR PDB; 4LDR; X-ray; 2.29 A; A/B=1-369.
DR PDBsum; 4LDQ; -.
DR PDBsum; 4LDR; -.
DR AlphaFoldDB; Q9BV20; -.
DR SMR; Q9BV20; -.
DR BioGRID; 123973; 19.
DR IntAct; Q9BV20; 17.
DR MINT; Q9BV20; -.
DR STRING; 9606.ENSP00000040663; -.
DR GlyGen; Q9BV20; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9BV20; -.
DR MetOSite; Q9BV20; -.
DR PhosphoSitePlus; Q9BV20; -.
DR BioMuta; MRI1; -.
DR DMDM; 74733279; -.
DR EPD; Q9BV20; -.
DR jPOST; Q9BV20; -.
DR MassIVE; Q9BV20; -.
DR MaxQB; Q9BV20; -.
DR PaxDb; Q9BV20; -.
DR PeptideAtlas; Q9BV20; -.
DR PRIDE; Q9BV20; -.
DR ProteomicsDB; 79152; -. [Q9BV20-1]
DR ProteomicsDB; 79153; -. [Q9BV20-2]
DR Antibodypedia; 26489; 235 antibodies from 26 providers.
DR DNASU; 84245; -.
DR Ensembl; ENST00000040663.8; ENSP00000040663.5; ENSG00000037757.14. [Q9BV20-1]
DR Ensembl; ENST00000319545.12; ENSP00000314871.7; ENSG00000037757.14. [Q9BV20-2]
DR GeneID; 84245; -.
DR KEGG; hsa:84245; -.
DR MANE-Select; ENST00000040663.8; ENSP00000040663.5; NM_001031727.4; NP_001026897.1.
DR UCSC; uc002mxe.4; human. [Q9BV20-1]
DR CTD; 84245; -.
DR DisGeNET; 84245; -.
DR GeneCards; MRI1; -.
DR HGNC; HGNC:28469; MRI1.
DR HPA; ENSG00000037757; Low tissue specificity.
DR MIM; 615105; gene.
DR neXtProt; NX_Q9BV20; -.
DR OpenTargets; ENSG00000037757; -.
DR PharmGKB; PA164723110; -.
DR VEuPathDB; HostDB:ENSG00000037757; -.
DR eggNOG; KOG1468; Eukaryota.
DR GeneTree; ENSGT00390000013732; -.
DR HOGENOM; CLU_016218_1_3_1; -.
DR InParanoid; Q9BV20; -.
DR OMA; RLWVDET; -.
DR OrthoDB; 1410886at2759; -.
DR PhylomeDB; Q9BV20; -.
DR TreeFam; TF300852; -.
DR BRENDA; 5.3.1.23; 2681.
DR PathwayCommons; Q9BV20; -.
DR Reactome; R-HSA-1237112; Methionine salvage pathway.
DR SignaLink; Q9BV20; -.
DR UniPathway; UPA00904; UER00874.
DR BioGRID-ORCS; 84245; 16 hits in 1078 CRISPR screens.
DR ChiTaRS; MRI1; human.
DR GeneWiki; MGC3207; -.
DR GenomeRNAi; 84245; -.
DR Pharos; Q9BV20; Tbio.
DR PRO; PR:Q9BV20; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9BV20; protein.
DR Bgee; ENSG00000037757; Expressed in buccal mucosa cell and 109 other tissues.
DR Genevisible; Q9BV20; HS.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0001650; C:fibrillar center; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046523; F:S-methyl-5-thioribose-1-phosphate isomerase activity; IBA:GO_Central.
DR GO; GO:0019509; P:L-methionine salvage from methylthioadenosine; IBA:GO_Central.
DR GO; GO:0019284; P:L-methionine salvage from S-adenosylmethionine; IEA:UniProtKB-UniRule.
DR Gene3D; 1.20.120.420; -; 1.
DR Gene3D; 3.40.50.10470; -; 1.
DR HAMAP; MF_01678; Salvage_MtnA; 1.
DR InterPro; IPR000649; IF-2B-related.
DR InterPro; IPR005251; IF-M1Pi.
DR InterPro; IPR042529; IF_2B-like_C.
DR InterPro; IPR011559; Initiation_fac_2B_a/b/d.
DR InterPro; IPR027363; M1Pi_N.
DR InterPro; IPR037171; NagB/RpiA_transferase-like.
DR Pfam; PF01008; IF-2B; 1.
DR SUPFAM; SSF100950; SSF100950; 1.
DR TIGRFAMs; TIGR00524; eIF-2B_rel; 1.
DR TIGRFAMs; TIGR00512; salvage_mtnA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Amino-acid biosynthesis;
KW Cell projection; Cytoplasm; Isomerase; Methionine biosynthesis; Nucleus;
KW Reference proteome.
FT CHAIN 1..369
FT /note="Methylthioribose-1-phosphate isomerase"
FT /id="PRO_0000317325"
FT ACT_SITE 248
FT /note="Proton donor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03119,
FT ECO:0000269|PubMed:19620624"
FT SITE 168
FT /note="Transition state stabilizer"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT VAR_SEQ 125..200
FT /note="VICCTEDMLEKDLRDNRSIGDLGARHLLERVAPSGGKVTVLTHCNTGALATA
FT GYGTALGVIRSLHSLGRLEHAFCT -> RETELCEHWEEHTRQRELPLRGPLGGTVL
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_030935"
FT VARIANT 235
FT /note="M -> V (in dbSNP:rs35098252)"
FT /id="VAR_059253"
FT VARIANT 319
FT /note="G -> A (in dbSNP:rs10402855)"
FT /id="VAR_059254"
FT MUTAGEN 168
FT /note="C->S: Abolishes enzymatic activity."
FT /evidence="ECO:0000269|PubMed:19620624"
FT MUTAGEN 248
FT /note="D->A: Abolishes enzymatic activity."
FT /evidence="ECO:0000269|PubMed:19620624"
FT STRAND 5..9
FT /evidence="ECO:0007829|PDB:4LDR"
FT STRAND 12..16
FT /evidence="ECO:0007829|PDB:4LDR"
FT HELIX 18..20
FT /evidence="ECO:0007829|PDB:4LDR"
FT TURN 21..23
FT /evidence="ECO:0007829|PDB:4LDR"
FT STRAND 27..30
FT /evidence="ECO:0007829|PDB:4LDR"
FT HELIX 33..41
FT /evidence="ECO:0007829|PDB:4LDR"
FT HELIX 48..63
FT /evidence="ECO:0007829|PDB:4LDR"
FT TURN 64..66
FT /evidence="ECO:0007829|PDB:4LDR"
FT STRAND 70..72
FT /evidence="ECO:0007829|PDB:4LDR"
FT HELIX 73..87
FT /evidence="ECO:0007829|PDB:4LDR"
FT HELIX 95..112
FT /evidence="ECO:0007829|PDB:4LDR"
FT HELIX 118..155
FT /evidence="ECO:0007829|PDB:4LDR"
FT STRAND 162..166
FT /evidence="ECO:0007829|PDB:4LDR"
FT TURN 172..174
FT /evidence="ECO:0007829|PDB:4LDR"
FT STRAND 175..178
FT /evidence="ECO:0007829|PDB:4LDR"
FT HELIX 181..190
FT /evidence="ECO:0007829|PDB:4LDR"
FT STRAND 194..200
FT /evidence="ECO:0007829|PDB:4LDR"
FT TURN 203..206
FT /evidence="ECO:0007829|PDB:4LDR"
FT HELIX 207..210
FT /evidence="ECO:0007829|PDB:4LDR"
FT HELIX 212..218
FT /evidence="ECO:0007829|PDB:4LDR"
FT STRAND 223..226
FT /evidence="ECO:0007829|PDB:4LDR"
FT HELIX 228..230
FT /evidence="ECO:0007829|PDB:4LDR"
FT HELIX 231..237
FT /evidence="ECO:0007829|PDB:4LDR"
FT STRAND 242..245
FT /evidence="ECO:0007829|PDB:4LDR"
FT STRAND 248..251
FT /evidence="ECO:0007829|PDB:4LDR"
FT STRAND 256..259
FT /evidence="ECO:0007829|PDB:4LDR"
FT HELIX 262..271
FT /evidence="ECO:0007829|PDB:4LDR"
FT STRAND 276..279
FT /evidence="ECO:0007829|PDB:4LDR"
FT HELIX 282..284
FT /evidence="ECO:0007829|PDB:4LDR"
FT HELIX 292..294
FT /evidence="ECO:0007829|PDB:4LDR"
FT HELIX 303..306
FT /evidence="ECO:0007829|PDB:4LDR"
FT STRAND 323..328
FT /evidence="ECO:0007829|PDB:4LDR"
FT HELIX 330..332
FT /evidence="ECO:0007829|PDB:4LDR"
FT STRAND 335..339
FT /evidence="ECO:0007829|PDB:4LDR"
FT STRAND 342..344
FT /evidence="ECO:0007829|PDB:4LDR"
FT HELIX 346..348
FT /evidence="ECO:0007829|PDB:4LDR"
FT HELIX 349..353
FT /evidence="ECO:0007829|PDB:4LDR"
SQ SEQUENCE 369 AA; 39150 MW; A6A1B5EC76632F4F CRC64;
MTLEAIRYSR GSLQILDQLL LPKQSRYEAV GSVHQAWEAI RAMKVRGAPA IALVGCLSLA
VELQAGAGGP GLAALVAFVR DKLSFLVTAR PTAVNMARAA RDLADVAARE AEREGATEEA
VRERVICCTE DMLEKDLRDN RSIGDLGARH LLERVAPSGG KVTVLTHCNT GALATAGYGT
ALGVIRSLHS LGRLEHAFCT ETRPYNQGAR LTAFELVYEQ IPATLITDSM VAAAMAHRGV
SAVVVGADRV VANGDTANKV GTYQLAIVAK HHGIPFYVAA PSSSCDLRLE TGKEIIIEER
PGQELTDVNG VRIAAPGIGV WNPAFDVTPH DLITGGIITE LGVFAPEELR TALTTTISSR
DGTLDGPQM
