AIMP2_HUMAN
ID AIMP2_HUMAN Reviewed; 320 AA.
AC Q13155; F8W950; Q75MR1; Q96CZ5; Q9P1L2;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2001, sequence version 2.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Aminoacyl tRNA synthase complex-interacting multifunctional protein 2;
DE AltName: Full=Multisynthase complex auxiliary component p38;
DE AltName: Full=Protein JTV-1;
GN Name=AIMP2; Synonyms=JTV1; ORFNames=PRO0992;
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).
RX PubMed=8666379; DOI=10.1006/geno.1995.9997;
RA Nicolaides N.C., Kinzler K.W., Vogelstein B.;
RT "Analysis of the 5' region of PMS2 reveals heterogeneous transcripts and a
RT novel overlapping gene.";
RL Genomics 29:329-334(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLY-129.
RC TISSUE=Lymph, and Placenta;
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 PROTEIN SEQUENCE OF 1-17 AND 34-58, ALTERNATIVE SPLICING, IDENTIFICATION IN
RP THE MSC COMPLEX, INTERACTION WITH TARS3, AND IDENTIFICATION BY MASS
RP SPECTROMETRY (ISOFORMS 1 AND 2).
RX PubMed=24312579; DOI=10.1371/journal.pone.0081734;
RA Kim K., Park S.J., Na S., Kim J.S., Choi H., Kim Y.K., Paek E., Lee C.;
RT "Reinvestigation of aminoacyl-tRNA synthetase core complex by affinity
RT purification-mass spectrometry reveals TARSL2 as a potential member of the
RT complex.";
RL PLoS ONE 8:E81734-E81734(2013).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 197-320.
RC TISSUE=Fetal liver;
RA Zhang C., Yu Y., Zhang S., Wei H., Zhou G., Ouyang S., Luo L., Bi J.,
RA Liu M., He F.;
RT "Functional prediction of the coding sequences of 121 new genes deduced by
RT analysis of cDNA clones from human fetal liver.";
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP INTERACTION WITH KARS1.
RX PubMed=9878398; DOI=10.1006/jmbi.1998.2316;
RA Quevillon S., Robinson J.-C., Berthonneau E., Siatecka M., Mirande M.;
RT "Macromolecular assemblage of aminoacyl-tRNA synthetases: identification of
RT protein-protein interactions and characterization of a core protein.";
RL J. Mol. Biol. 285:183-195(1999).
RN [9]
RP INTERACTION WITH FUBP1.
RX PubMed=12819782; DOI=10.1038/ng1182;
RA Kim M.J., Park B.-J., Kang Y.-S., Kim H.J., Park J.-H., Kang J.W.,
RA Lee S.W., Han J.M., Lee H.-W., Kim S.;
RT "Downregulation of FUSE-binding protein and c-myc by tRNA synthetase
RT cofactor p38 is required for lung cell differentiation.";
RL Nat. Genet. 34:330-336(2003).
RN [10]
RP INTERACTION WITH KARS1.
RX PubMed=15220430; DOI=10.1128/jvi.78.14.7553-7564.2004;
RA Halwani R., Cen S., Javanbakht H., Saadatmand J., Kim S., Shiba K.,
RA Kleiman L.;
RT "Cellular distribution of Lysyl-tRNA synthetase and its interaction with
RT Gag during human immunodeficiency virus type 1 assembly.";
RL J. Virol. 78:7553-7564(2004).
RN [11]
RP FUNCTION, INTERACTION WITH PRKN, AND UBIQUITINATION.
RX PubMed=16135753; DOI=10.1523/jneurosci.2172-05.2005;
RA Ko H.S., von Coelln R., Sriram S.R., Kim S.W., Chung K.K.K., Pletnikova O.,
RA Troncoso J., Johnson B., Saffary R., Goh E.L., Song H., Park B.-J.,
RA Kim M.J., Kim S., Dawson V.L., Dawson T.M.;
RT "Accumulation of the authentic parkin substrate aminoacyl-tRNA synthetase
RT cofactor, p38/JTV-1, leads to catecholaminergic cell death.";
RL J. Neurosci. 25:7968-7978(2005).
RN [12]
RP INTERACTION WITH KARS1.
RX PubMed=18029264; DOI=10.1016/j.bbrc.2007.11.028;
RA Guzzo C.M., Yang D.C.H.;
RT "Lysyl-tRNA synthetase interacts with EF1alpha, aspartyl-tRNA synthetase
RT and p38 in vitro.";
RL Biochem. Biophys. Res. Commun. 365:718-723(2008).
RN [13]
RP INTERACTION WITH TP53, VARIANTS VAL-92; 97-ASP--SER-99 AND SER-209, AND
RP MUTAGENESIS OF 163-GLU-ASN-164 AND 172-GLN-ASN-173.
RX PubMed=18695251; DOI=10.1073/pnas.0800297105;
RA Han J.M., Park B.-J., Park S.G., Oh Y.S., Choi S.J., Lee S.W., Hwang S.-K.,
RA Chang S.-H., Cho M.-H., Kim S.;
RT "AIMP2/p38, the scaffold for the multi-tRNA synthetase complex, responds to
RT genotoxic stresses via p53.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:11206-11211(2008).
RN [14]
RP FUNCTION, SUBUNIT, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=19131329; DOI=10.1074/jbc.m809636200;
RA Kaminska M., Havrylenko S., Decottignies P., Gillet S., Le Marechal P.,
RA Negrutskii B., Mirande M.;
RT "Dissection of the structural organization of the aminoacyl-tRNA synthetase
RT complex.";
RL J. Biol. Chem. 284:6053-6060(2009).
RN [15]
RP SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=19289464; DOI=10.1074/jbc.m900480200;
RA Kaminska M., Havrylenko S., Decottignies P., Le Marechal P., Negrutskii B.,
RA Mirande M.;
RT "Dynamic Organization of Aminoacyl-tRNA Synthetase Complexes in the
RT Cytoplasm of Human Cells.";
RL J. Biol. Chem. 284:13746-13754(2009).
RN [16]
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 [17]
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 [18] {ECO:0007744|PDB:4DPG}
RP X-RAY CRYSTALLOGRAPHY (2.84 ANGSTROMS) OF 1-48 IN COMPLEX WITH KARS1, AND
RP SUBUNIT.
RX PubMed=23159739; DOI=10.1016/j.molcel.2012.10.010;
RA Ofir-Birin Y., Fang P., Bennett S.P., Zhang H.M., Wang J., Rachmin I.,
RA Shapiro R., Song J., Dagan A., Pozo J., Kim S., Marshall A.G., Schimmel P.,
RA Yang X.L., Nechushtan H., Razin E., Guo M.;
RT "Structural switch of lysyl-tRNA synthetase between translation and
RT transcription.";
RL Mol. Cell 49:30-42(2013).
RN [19] {ECO:0007744|PDB:4YCU, ECO:0007744|PDB:4YCW}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 1-36 IN COMPLEX WITH KARS1.
RX PubMed=26074468; DOI=10.1016/j.chembiol.2015.05.007;
RA Fang P., Han H., Wang J., Chen K., Chen X., Guo M.;
RT "Structural Basis for Specific Inhibition of tRNA Synthetase by an ATP
RT Competitive Inhibitor.";
RL Chem. Biol. 22:734-744(2015).
RN [20] {ECO:0007744|PDB:5A34}
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 90-320 IN COMPLEX WITH EPRS1,
RP SUBUNIT, AND MUTAGENESIS OF ARG-215 AND ASP-238.
RX PubMed=26472928; DOI=10.1074/jbc.m115.690867;
RA Cho H.Y., Maeng S.J., Cho H.J., Choi Y.S., Chung J.M., Lee S., Kim H.K.,
RA Kim J.H., Eom C.Y., Kim Y.G., Guo M., Jung H.S., Kang B.S., Kim S.;
RT "Assembly of Multi-tRNA Synthetase Complex via Heterotetrameric Glutathione
RT Transferase-homology Domains.";
RL J. Biol. Chem. 290:29313-29328(2015).
RN [21]
RP INVOLVEMENT IN HLD17, AND VARIANT HLD17 35-TYR--LYS-320 DEL.
RX PubMed=29215095; DOI=10.1038/s10038-017-0363-1;
RA Shukla A., Das Bhowmik A., Hebbar M., Rajagopal K.V., Girisha K.M.,
RA Gupta N., Dalal A.;
RT "Homozygosity for a nonsense variant in AIMP2 is associated with a
RT progressive neurodevelopmental disorder with microcephaly, seizures, and
RT spastic quadriparesis.";
RL J. Hum. Genet. 63:19-25(2018).
CC -!- FUNCTION: Required for assembly and stability of the aminoacyl-tRNA
CC synthase complex (PubMed:19131329). Mediates ubiquitination and
CC degradation of FUBP1, a transcriptional activator of MYC, leading to
CC MYC down-regulation which is required for aveolar type II cell
CC differentiation. Blocks MDM2-mediated ubiquitination and degradation of
CC p53/TP53. Functions as a proapoptotic factor.
CC {ECO:0000269|PubMed:16135753, ECO:0000269|PubMed:19131329}.
CC -!- SUBUNIT: Part of the multisynthetase complex (MSC), a multisubunit
CC complex that groups tRNA ligases for Arg (RARS1), Asp (DARS1), Gln
CC (QARS1), Ile (IARS1), Leu (LARS1), Lys (KARS1), Met (MARS1) the
CC bifunctional ligase for Glu and Pro (EPRS1) and the auxiliary subunits
CC AIMP1/p43, AIMP2/p38 and EEF1E1/p18 (PubMed:24312579, PubMed:19131329,
CC PubMed:19289464). Interacts (via N-terminus) with KARS1
CC (PubMed:9878398, PubMed:15220430, PubMed:18029264, PubMed:23159739,
CC PubMed:26074468). Interacts with EPRS1 (PubMed:26472928). Forms a
CC linear complex that contains MARS1, EEF1E1, EPRS1 and AIMP2 that is at
CC the core of the multisubunit complex (PubMed:26472928). Binds FUBP1
CC (via C-terminus). Interacts in both its unphosphorylated and
CC phosphorylated forms with p53/TP53 (via N-terminus) in the nucleus
CC following UV irradiation. Interacts (via N-terminus) with PRKN/parkin
CC (via first RING-type domain) (PubMed:16135753). Interacts with TARS3
CC (PubMed:24312579). {ECO:0000269|PubMed:12819782,
CC ECO:0000269|PubMed:15220430, ECO:0000269|PubMed:16135753,
CC ECO:0000269|PubMed:18029264, ECO:0000269|PubMed:18695251,
CC ECO:0000269|PubMed:19131329, ECO:0000269|PubMed:19289464,
CC ECO:0000269|PubMed:23159739, ECO:0000269|PubMed:24312579,
CC ECO:0000269|PubMed:26074468, ECO:0000269|PubMed:26472928,
CC ECO:0000269|PubMed:9878398}.
CC -!- INTERACTION:
CC Q13155; Q12904: AIMP1; NbExp=4; IntAct=EBI-745226, EBI-1045802;
CC Q13155; Q12904-2: AIMP1; NbExp=5; IntAct=EBI-745226, EBI-12412735;
CC Q13155; P05067: APP; NbExp=3; IntAct=EBI-745226, EBI-77613;
CC Q13155; O75934: BCAS2; NbExp=12; IntAct=EBI-745226, EBI-1050106;
CC Q13155; Q0VDD7: BRME1; NbExp=8; IntAct=EBI-745226, EBI-741210;
CC Q13155; Q13895: BYSL; NbExp=5; IntAct=EBI-745226, EBI-358049;
CC Q13155; Q8TAB5: C1orf216; NbExp=3; IntAct=EBI-745226, EBI-747505;
CC Q13155; Q8NA61-2: CBY2; NbExp=5; IntAct=EBI-745226, EBI-11524851;
CC Q13155; Q494R4-2: CCDC153; NbExp=3; IntAct=EBI-745226, EBI-11974185;
CC Q13155; Q96L14: CEP170P1; NbExp=5; IntAct=EBI-745226, EBI-743488;
CC Q13155; P14868: DARS1; NbExp=10; IntAct=EBI-745226, EBI-358730;
CC Q13155; Q9NRI5-2: DISC1; NbExp=3; IntAct=EBI-745226, EBI-11988027;
CC Q13155; Q8IYI6: EXOC8; NbExp=5; IntAct=EBI-745226, EBI-742102;
CC Q13155; Q13643: FHL3; NbExp=13; IntAct=EBI-745226, EBI-741101;
CC Q13155; Q96AE4: FUBP1; NbExp=4; IntAct=EBI-745226, EBI-711404;
CC Q13155; P13807: GYS1; NbExp=3; IntAct=EBI-745226, EBI-740553;
CC Q13155; Q15046: KARS1; NbExp=21; IntAct=EBI-745226, EBI-356367;
CC Q13155; Q15046-1: KARS1; NbExp=2; IntAct=EBI-745226, EBI-21457670;
CC Q13155; Q15323: KRT31; NbExp=3; IntAct=EBI-745226, EBI-948001;
CC Q13155; Q14525: KRT33B; NbExp=3; IntAct=EBI-745226, EBI-1049638;
CC Q13155; O76011: KRT34; NbExp=3; IntAct=EBI-745226, EBI-1047093;
CC Q13155; O76013-2: KRT36; NbExp=3; IntAct=EBI-745226, EBI-11958506;
CC Q13155; P25791: LMO2; NbExp=3; IntAct=EBI-745226, EBI-739696;
CC Q13155; P25791-3: LMO2; NbExp=6; IntAct=EBI-745226, EBI-11959475;
CC Q13155; Q8TBB1: LNX1; NbExp=8; IntAct=EBI-745226, EBI-739832;
CC Q13155; Q9NYP9: MIS18A; NbExp=6; IntAct=EBI-745226, EBI-1104552;
CC Q13155; Q9GZM8: NDEL1; NbExp=3; IntAct=EBI-745226, EBI-928842;
CC Q13155; Q7Z6G3-2: NECAB2; NbExp=3; IntAct=EBI-745226, EBI-10172876;
CC Q13155; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-745226, EBI-741158;
CC Q13155; P22061: PCMT1; NbExp=3; IntAct=EBI-745226, EBI-353343;
CC Q13155; O15212: PFDN6; NbExp=3; IntAct=EBI-745226, EBI-356973;
CC Q13155; Q9H8W4: PLEKHF2; NbExp=3; IntAct=EBI-745226, EBI-742388;
CC Q13155; P54646: PRKAA2; NbExp=3; IntAct=EBI-745226, EBI-1383852;
CC Q13155; Q15276: RABEP1; NbExp=3; IntAct=EBI-745226, EBI-447043;
CC Q13155; P0C264: SBK3; NbExp=3; IntAct=EBI-745226, EBI-17181801;
CC Q13155; O95391: SLU7; NbExp=3; IntAct=EBI-745226, EBI-750559;
CC Q13155; Q8TC71: SPATA18; NbExp=3; IntAct=EBI-745226, EBI-11334239;
CC Q13155; Q8WWU5-7: TCP11; NbExp=3; IntAct=EBI-745226, EBI-17721485;
CC Q13155; Q9NYB0: TERF2IP; NbExp=2; IntAct=EBI-745226, EBI-750109;
CC Q13155; Q9BXU0: TEX12; NbExp=3; IntAct=EBI-745226, EBI-12090309;
CC Q13155; Q9UBB9: TFIP11; NbExp=6; IntAct=EBI-745226, EBI-1105213;
CC Q13155; P04637: TP53; NbExp=6; IntAct=EBI-745226, EBI-366083;
CC Q13155; A0A0S2Z6H0: ZGPAT; NbExp=3; IntAct=EBI-745226, EBI-16428984;
CC Q13155; Q8N5A5: ZGPAT; NbExp=3; IntAct=EBI-745226, EBI-3439227;
CC Q13155; Q8N5A5-2: ZGPAT; NbExp=12; IntAct=EBI-745226, EBI-10183064;
CC Q13155; PRO_0000038593 [P04591]: gag; Xeno; NbExp=3; IntAct=EBI-745226, EBI-6179719;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:19289464}.
CC Nucleus {ECO:0000250|UniProtKB:Q8R010}. Note=Following DNA damage,
CC dissociates from the aminoacyl-tRNA synthase complex and translocates
CC from the cytoplasm to the nucleus. {ECO:0000250|UniProtKB:Q8R010}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q13155-1; Sequence=Displayed;
CC Name=2; Synonyms=DX2 {ECO:0000303|PubMed:24312579};
CC IsoId=Q13155-2; Sequence=VSP_059914;
CC -!- PTM: Phosphorylated on serine residues in response to UV irradiation.
CC {ECO:0000250}.
CC -!- PTM: Ubiquitinated by PRKN, leading to its degradation by the
CC proteasome. Mutant PRKN fails to ubiquitinate AIMP2 efficiently,
CC allowing its accumulation which may contribute to neurodegeneration
CC associated with Parkinson disease. {ECO:0000269|PubMed:16135753}.
CC -!- DISEASE: Leukodystrophy, hypomyelinating, 17 (HLD17) [MIM:618006]: An
CC autosomal recessive neurodevelopmental disorder characterized by
CC atrophy of cerebral cortex, spinal cord and cerebellum, thin corpus
CC callosum, abnormal signals in the basal ganglia, and features
CC suggesting hypo- or demyelination observed on brain imaging. Clinical
CC manifestations include lack of development, absent speech,
CC microcephaly, spasticity, seizures, and contractures.
CC {ECO:0000269|PubMed:29215095}. Note=The disease may be caused by
CC variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Accumulates in brains affected by autosomal-recessive
CC juvenile parkinsonism, idiopathic Parkinson disease and diffuse Lewy
CC body disease.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC50391.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; U24169; AAC50391.1; ALT_FRAME; mRNA.
DR EMBL; AC005995; AAS00389.1; -; Genomic_DNA.
DR EMBL; CH236963; EAL23713.1; -; Genomic_DNA.
DR EMBL; CH878731; EAW55053.1; -; Genomic_DNA.
DR EMBL; BC002853; AAH02853.1; -; mRNA.
DR EMBL; BC010156; AAH10156.1; -; mRNA.
DR EMBL; BC013630; AAH13630.1; -; mRNA.
DR EMBL; AF116615; AAF71039.1; -; mRNA.
DR CCDS; CCDS5344.1; -. [Q13155-1]
DR CCDS; CCDS87475.1; -. [Q13155-2]
DR RefSeq; NP_001313536.1; NM_001326607.1. [Q13155-2]
DR RefSeq; NP_006294.2; NM_006303.3. [Q13155-1]
DR PDB; 4DPG; X-ray; 2.84 A; I/J/K/L=1-48.
DR PDB; 4YCU; X-ray; 2.10 A; C=1-36.
DR PDB; 4YCW; X-ray; 2.90 A; C/D/G/H=1-36.
DR PDB; 5A1N; X-ray; 2.10 A; B=90-320.
DR PDB; 5A34; X-ray; 2.60 A; B/D/F/H=90-320.
DR PDB; 5A5H; X-ray; 2.32 A; B/D/F/H=90-320.
DR PDB; 5Y6L; X-ray; 2.90 A; D=89-320.
DR PDB; 6ILD; X-ray; 1.88 A; C=1-36.
DR PDB; 6IY6; X-ray; 3.60 A; C/D/I/J=115-320.
DR PDB; 6JPV; X-ray; 2.15 A; A/B=24-32.
DR PDB; 6K39; X-ray; 1.40 A; A/B=25-32.
DR PDBsum; 4DPG; -.
DR PDBsum; 4YCU; -.
DR PDBsum; 4YCW; -.
DR PDBsum; 5A1N; -.
DR PDBsum; 5A34; -.
DR PDBsum; 5A5H; -.
DR PDBsum; 5Y6L; -.
DR PDBsum; 6ILD; -.
DR PDBsum; 6IY6; -.
DR PDBsum; 6JPV; -.
DR PDBsum; 6K39; -.
DR AlphaFoldDB; Q13155; -.
DR SMR; Q13155; -.
DR BioGRID; 113684; 232.
DR CORUM; Q13155; -.
DR DIP; DIP-34421N; -.
DR IntAct; Q13155; 99.
DR MINT; Q13155; -.
DR STRING; 9606.ENSP00000223029; -.
DR BindingDB; Q13155; -.
DR ChEMBL; CHEMBL4523285; -.
DR GlyGen; Q13155; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q13155; -.
DR PhosphoSitePlus; Q13155; -.
DR SwissPalm; Q13155; -.
DR BioMuta; AIMP2; -.
DR EPD; Q13155; -.
DR jPOST; Q13155; -.
DR MassIVE; Q13155; -.
DR MaxQB; Q13155; -.
DR PaxDb; Q13155; -.
DR PeptideAtlas; Q13155; -.
DR PRIDE; Q13155; -.
DR ProteomicsDB; 30261; -.
DR ProteomicsDB; 59195; -.
DR ABCD; Q13155; 1 sequenced antibody.
DR Antibodypedia; 11563; 214 antibodies from 32 providers.
DR DNASU; 7965; -.
DR Ensembl; ENST00000223029.8; ENSP00000223029.3; ENSG00000106305.10. [Q13155-1]
DR Ensembl; ENST00000395236.2; ENSP00000378658.2; ENSG00000106305.10. [Q13155-2]
DR GeneID; 7965; -.
DR KEGG; hsa:7965; -.
DR MANE-Select; ENST00000223029.8; ENSP00000223029.3; NM_006303.4; NP_006294.2.
DR UCSC; uc003spo.4; human. [Q13155-1]
DR CTD; 7965; -.
DR DisGeNET; 7965; -.
DR GeneCards; AIMP2; -.
DR HGNC; HGNC:20609; AIMP2.
DR HPA; ENSG00000106305; Tissue enhanced (skeletal muscle, tongue).
DR MalaCards; AIMP2; -.
DR MIM; 600859; gene.
DR MIM; 618006; phenotype.
DR neXtProt; NX_Q13155; -.
DR OpenTargets; ENSG00000106305; -.
DR PharmGKB; PA165617609; -.
DR VEuPathDB; HostDB:ENSG00000106305; -.
DR eggNOG; ENOG502QUNJ; Eukaryota.
DR GeneTree; ENSGT00390000015826; -.
DR HOGENOM; CLU_076114_0_0_1; -.
DR InParanoid; Q13155; -.
DR OMA; LCQHYRV; -.
DR OrthoDB; 1382507at2759; -.
DR PhylomeDB; Q13155; -.
DR TreeFam; TF326322; -.
DR PathwayCommons; Q13155; -.
DR Reactome; R-HSA-2408522; Selenoamino acid metabolism.
DR Reactome; R-HSA-379716; Cytosolic tRNA aminoacylation.
DR SignaLink; Q13155; -.
DR BioGRID-ORCS; 7965; 16 hits in 1084 CRISPR screens.
DR ChiTaRS; AIMP2; human.
DR GeneWiki; Multisynthetase_complex_auxiliary_component_p38; -.
DR GenomeRNAi; 7965; -.
DR Pharos; Q13155; Tchem.
DR PRO; PR:Q13155; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q13155; protein.
DR Bgee; ENSG00000106305; Expressed in oocyte and 217 other tissues.
DR ExpressionAtlas; Q13155; baseline and differential.
DR Genevisible; Q13155; HS.
DR GO; GO:0017101; C:aminoacyl-tRNA synthetase multienzyme complex; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0060090; F:molecular adaptor activity; IEA:Ensembl.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:1903632; P:positive regulation of aminoacyl-tRNA ligase activity; IBA:GO_Central.
DR GO; GO:1901216; P:positive regulation of neuron death; IEA:Ensembl.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IEA:Ensembl.
DR GO; GO:0016567; P:protein ubiquitination; IEA:Ensembl.
DR GO; GO:0065003; P:protein-containing complex assembly; IEA:Ensembl.
DR GO; GO:0006412; P:translation; IEA:UniProtKB-KW.
DR GO; GO:0060510; P:type II pneumocyte differentiation; IEA:Ensembl.
DR InterPro; IPR042360; AIMP2.
DR InterPro; IPR031889; AIMP2_LysRS-bd.
DR InterPro; IPR041503; AIMP2_thioredoxin.
DR InterPro; IPR036282; Glutathione-S-Trfase_C_sf.
DR InterPro; IPR004046; GST_C.
DR PANTHER; PTHR13438; PTHR13438; 1.
DR Pfam; PF16780; AIMP2_LysRS_bd; 1.
DR Pfam; PF14497; GST_C_3; 1.
DR Pfam; PF18569; Thioredoxin_16; 1.
DR SUPFAM; SSF47616; SSF47616; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; Cytoplasm;
KW Developmental protein; Differentiation; Direct protein sequencing;
KW Disease variant; Leukodystrophy; Nucleus; Phosphoprotein;
KW Protein biosynthesis; Reference proteome; Ubl conjugation.
FT CHAIN 1..320
FT /note="Aminoacyl tRNA synthase complex-interacting
FT multifunctional protein 2"
FT /id="PRO_0000221129"
FT DOMAIN 220..317
FT /note="GST C-terminal"
FT REGION 82..162
FT /note="Interaction with PRKN"
FT /evidence="ECO:0000269|PubMed:16135753"
FT REGION 162..225
FT /note="Interaction with TP53"
FT /evidence="ECO:0000269|PubMed:18695251"
FT VAR_SEQ 46..114
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000269|PubMed:24312579"
FT /id="VSP_059914"
FT VARIANT 35..320
FT /note="Missing (in HLD17)"
FT /evidence="ECO:0000269|PubMed:29215095"
FT /id="VAR_081108"
FT VARIANT 92
FT /note="I -> V (in a lung cancer cell line; reduced
FT interaction with TP53, loss of TP53 activation and loss of
FT proapoptotic activity)"
FT /evidence="ECO:0000269|PubMed:18695251"
FT /id="VAR_058392"
FT VARIANT 97..99
FT /note="EPT -> DLS (in a lung cancer cell line; no effect on
FT proapoptotic activity)"
FT /id="VAR_058393"
FT VARIANT 129
FT /note="A -> G (in dbSNP:rs17855441)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_025521"
FT VARIANT 166
FT /note="L -> I (in dbSNP:rs34525431)"
FT /id="VAR_050125"
FT VARIANT 209
FT /note="G -> S (in a lung cancer cell line; no effect on
FT proapoptotic activity; dbSNP:rs982080297)"
FT /evidence="ECO:0000269|PubMed:18695251"
FT /id="VAR_058394"
FT MUTAGEN 163..164
FT /note="EN->AA: Reduced interaction with TP53, loss of TP53
FT activation and loss of proapoptotic activity."
FT /evidence="ECO:0000269|PubMed:18695251"
FT MUTAGEN 172..173
FT /note="QN->AA: Reduced interaction with TP53, loss of TP53
FT activation and loss of proapoptotic activity."
FT /evidence="ECO:0000269|PubMed:18695251"
FT MUTAGEN 215
FT /note="R->A: Nearly abolishes interaction with EPRS1."
FT /evidence="ECO:0000269|PubMed:26472928"
FT MUTAGEN 238
FT /note="D->R: Nearly abolishes interaction with EPRS1."
FT /evidence="ECO:0000269|PubMed:26472928"
FT STRAND 12..14
FT /evidence="ECO:0007829|PDB:6ILD"
FT HELIX 108..112
FT /evidence="ECO:0007829|PDB:5A1N"
FT HELIX 113..115
FT /evidence="ECO:0007829|PDB:5A1N"
FT HELIX 116..119
FT /evidence="ECO:0007829|PDB:5A1N"
FT STRAND 120..126
FT /evidence="ECO:0007829|PDB:5A1N"
FT STRAND 128..130
FT /evidence="ECO:0007829|PDB:5A34"
FT HELIX 133..143
FT /evidence="ECO:0007829|PDB:5A1N"
FT STRAND 148..154
FT /evidence="ECO:0007829|PDB:5A1N"
FT HELIX 163..166
FT /evidence="ECO:0007829|PDB:5A1N"
FT TURN 167..169
FT /evidence="ECO:0007829|PDB:5A5H"
FT STRAND 182..189
FT /evidence="ECO:0007829|PDB:5A1N"
FT STRAND 196..198
FT /evidence="ECO:0007829|PDB:5A1N"
FT STRAND 202..204
FT /evidence="ECO:0007829|PDB:5A5H"
FT STRAND 207..209
FT /evidence="ECO:0007829|PDB:5A5H"
FT HELIX 210..219
FT /evidence="ECO:0007829|PDB:5A1N"
FT HELIX 227..242
FT /evidence="ECO:0007829|PDB:5A1N"
FT TURN 243..246
FT /evidence="ECO:0007829|PDB:5A1N"
FT HELIX 249..262
FT /evidence="ECO:0007829|PDB:5A1N"
FT TURN 263..265
FT /evidence="ECO:0007829|PDB:5A1N"
FT STRAND 266..268
FT /evidence="ECO:0007829|PDB:5A1N"
FT STRAND 271..273
FT /evidence="ECO:0007829|PDB:5A1N"
FT HELIX 276..286
FT /evidence="ECO:0007829|PDB:5A1N"
FT STRAND 291..293
FT /evidence="ECO:0007829|PDB:5Y6L"
FT HELIX 297..307
FT /evidence="ECO:0007829|PDB:5A1N"
FT HELIX 310..318
FT /evidence="ECO:0007829|PDB:5A1N"
SQ SEQUENCE 320 AA; 35349 MW; F253726B63C12BAB CRC64;
MPMYQVKPYH GGGAPLRVEL PTCMYRLPNV HGRSYGPAPG AGHVQEESNL SLQALESRQD
DILKRLYELK AAVDGLSKMI QTPDADLDVT NIIQADEPTT LTTNALDLNS VLGKDYGALK
DIVINANPAS PPLSLLVLHR LLCEHFRVLS TVHTHSSVKS VPENLLKCFG EQNKKQPRQD
YQLGFTLIWK NVPKTQMKFS IQTMCPIEGE GNIARFLFSL FGQKHNAVNA TLIDSWVDIA
IFQLKEGSSK EKAAVFRSMN SALGKSPWLA GNELTVADVV LWSVLQQIGG CSVTVPANVQ
RWMRSCENLA PFNTALKLLK
