ID   AIMP1_MOUSE             Reviewed;         310 AA.
AC   P31230; Q60659;
DT   01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT   18-OCT-2001, sequence version 2.
DT   27-MAR-2024, entry version 163.
DE   RecName: Full=Aminoacyl tRNA synthase complex-interacting multifunctional protein 1;
DE   AltName: Full=Multisynthase complex auxiliary component p43;
DE   Contains:
DE     RecName: Full=Endothelial monocyte-activating polypeptide 2;
DE              Short=EMAP-2;
DE     AltName: Full=Endothelial monocyte-activating polypeptide II {ECO:0000303|PubMed:7929199};
DE              Short=EMAP-II;
DE     AltName: Full=Small inducible cytokine subfamily E member 1;
GN   Name=Aimp1; Synonyms=Emap2, Scye1;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=7929199; DOI=10.1016/s0021-9258(17)31505-3;
RA   Kao J., Houck K., Fan Y., Haehnel I., Libutti S.K., Kayton M.L.,
RA   Grikscheit T., Chabot J., Nowygrod R., Greenberg S., Kuang W.J.,
RA   Leung D.W., Hayward J.R., Kisiel W., Heath M., Brett J., Stern D.M.;
RT   "Characterization of a novel tumor-derived cytokine. Endothelial-monocyte
RT   activating polypeptide II.";
RL   J. Biol. Chem. 269:25106-25119(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   [3]
RP   PROTEIN SEQUENCE OF 145-164, AND FUNCTION.
RX   PubMed=1400342; DOI=10.1016/s0021-9258(19)88692-1;
RA   Kao J., Ryan J., Brett G., Chen J., Shen H., Fan Y.-G., Godman G.,
RA   Familletti P.C., Wang F., Pan Y.-C.E., Stern D., Clauss M.;
RT   "Endothelial monocyte-activating polypeptide II. A novel tumor-derived
RT   polypeptide that activates host-response mechanisms.";
RL   J. Biol. Chem. 267:20239-20247(1992).
RN   [4]
RP   FUNCTION.
RX   PubMed=7545917; DOI=10.1016/s0021-9258(17)36950-8;
RA   Kao J., Fan Y., Haehnel I., Brett J., Greenberg S., Clauss M., Kayton M.,
RA   Houck K., Kisiel W., Seljelid R., Burnier J., Stern D.;
RT   "A peptide derived from the amino terminus of endothelial-monocyte-
RT   activating polypeptide II modulates mononuclear and polymorphonuclear
RT   leukocyte functions, defines an apparently novel cellular interaction site,
RT   and induces an acute inflammatory response.";
RL   J. Biol. Chem. 269:9774-9782(1994).
RN   [5]
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=9770485; DOI=10.1073/pnas.95.21.12322;
RA   Knies U.E., Behrensdorf H.A., Mitchell C.A., Deutsch U., Risau W.,
RA   Drexler H.C.A., Clauss M.;
RT   "Regulation of endothelial monocyte-activating polypeptide II release by
RT   apoptosis.";
RL   Proc. Natl. Acad. Sci. U.S.A. 95:12322-12327(1998).
RN   [6]
RP   CLEAVAGE.
RX   PubMed=11306575; DOI=10.1074/jbc.m100489200;
RA   Shalak V., Kaminska M., Mitnacht-Kraus R., Vandenabeele P., Clauss M.,
RA   Mirande M.;
RT   "The EMAPII cytokine is released from the mammalian multisynthetase complex
RT   after cleavage of its p43/proEMAPII component.";
RL   J. Biol. Chem. 276:23769-23776(2001).
RN   [7]
RP   SUBUNIT, AND FUNCTION.
RX   PubMed=12060739; DOI=10.1073/pnas.122110199;
RA   Kim J.Y., Kang Y.-S., Lee J.-W., Kim H.J., Ahn Y.H., Park H., Ko Y.-G.,
RA   Kim S.;
RT   "p38 is essential for the assembly and stability of macromolecular tRNA
RT   synthetase complex: implications for its physiological significance.";
RL   Proc. Natl. Acad. Sci. U.S.A. 99:7912-7916(2002).
RN   [8]
RP   FUNCTION.
RX   PubMed=15681823; DOI=10.1016/s0002-9440(10)62262-6;
RA   Park S.G., Shin H., Shin Y.K., Lee Y., Choi E.-C., Park B.-J., Kim S.;
RT   "The novel cytokine p43 stimulates dermal fibroblast proliferation and
RT   wound repair.";
RL   Am. J. Pathol. 166:387-398(2005).
RN   [9]
RP   FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP   PHENOTYPE.
RX   PubMed=17001013; DOI=10.1073/pnas.0602045103;
RA   Park S.G., Kang Y.S., Kim J.Y., Lee C.S., Ko Y.G., Lee W.J., Lee K.-U.,
RA   Yeom Y.I., Kim S.;
RT   "Hormonal activity of AIMP1/p43 for glucose homeostasis.";
RL   Proc. Natl. Acad. Sci. U.S.A. 103:14913-14918(2006).
RN   [10]
RP   FUNCTION, INTERACTION WITH HSP90B1, SUBCELLULAR LOCATION, AND DISRUPTION
RP   PHENOTYPE.
RX   PubMed=17525271; DOI=10.2353/ajpath.2007.061266;
RA   Han J.M., Park S.G., Liu B., Park B.-J., Kim J.Y., Jin C.H., Song Y.W.,
RA   Li Z., Kim S.;
RT   "Aminoacyl-tRNA synthetase-interacting multifunctional protein 1/p43
RT   controls endoplasmic reticulum retention of heat shock protein gp96: its
RT   pathological implications in lupus-like autoimmune diseases.";
RL   Am. J. Pathol. 170:2042-2054(2007).
RN   [11]
RP   FUNCTION, INTERACTION WITH SMURF2, AND INDUCTION.
RX   PubMed=18448069; DOI=10.1016/j.bbrc.2008.04.099;
RA   Lee Y.S., Han J.M., Son S.H., Choi J.W., Jeon E.J., Bae S.-C., Park Y.I.,
RA   Kim S.;
RT   "AIMP1/p43 downregulates TGF-beta signaling via stabilization of smurf2.";
RL   Biochem. Biophys. Res. Commun. 371:395-400(2008).
RN   [12]
RP   FUNCTION.
RX   PubMed=18292511; DOI=10.4049/jimmunol.180.5.2894;
RA   Kim E., Kim S.H., Kim S., Cho D., Kim T.S.;
RT   "AIMP1/p43 protein induces the maturation of bone marrow-derived dendritic
RT   cells with T helper type 1-polarizing ability.";
RL   J. Immunol. 180:2894-2902(2008).
RN   [13]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung,
RC   Pancreas, Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [14]
RP   SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-267, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA   Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA   Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT   "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT   pathways.";
RL   Mol. Cell 50:919-930(2013).
CC   -!- FUNCTION: Non-catalytic component of the multisynthase complex
CC       (PubMed:12060739). Stimulates the catalytic activity of cytoplasmic
CC       arginyl-tRNA synthase (By similarity). Binds tRNA. Possesses
CC       inflammatory cytokine activity (PubMed:1400342, PubMed:7545917).
CC       Negatively regulates TGF-beta signaling through stabilization of SMURF2
CC       by binding to SMURF2 and inhibiting its SMAD7-mediated degradation
CC       (PubMed:18448069). Involved in glucose homeostasis through induction of
CC       glucagon secretion at low glucose levels (PubMed:17001013). Promotes
CC       dermal fibroblast proliferation and wound repair (PubMed:15681823).
CC       Regulates KDELR1-mediated retention of HSP90B1/gp96 in the endoplasmic
CC       reticulum (PubMed:17525271). Plays a role in angiogenesis by inducing
CC       endothelial cell migration at low concentrations and endothelian cell
CC       apoptosis at high concentrations (By similarity). Induces maturation of
CC       dendritic cells and monocyte cell adhesion (PubMed:18292511). Modulates
CC       endothelial cell responses by degrading HIF-1A through interaction with
CC       PSMA7 (By similarity). {ECO:0000250|UniProtKB:Q12904,
CC       ECO:0000269|PubMed:12060739, ECO:0000269|PubMed:1400342,
CC       ECO:0000269|PubMed:15681823, ECO:0000269|PubMed:17001013,
CC       ECO:0000269|PubMed:17525271, ECO:0000269|PubMed:18292511,
CC       ECO:0000269|PubMed:18448069, ECO:0000269|PubMed:7545917}.
CC   -!- SUBUNIT: Homodimer. Part of the multisynthetase complex (MSC), a
CC       multisubunit complex that groups tRNA ligases for Arg (RARS1), Asp
CC       (DARS1), Gln (QARS1), Ile (IARS1), Leu (LARS1), Lys (KARS1), Met
CC       (MARS1) the bifunctional ligase for Glu and Pro (EPRS1) and the
CC       auxiliary subunits AIMP1/p43, AIMP2/p38 and EEF1E1/p18
CC       (PubMed:12060739). Interacts (via N-terminus) with RARS1 (via N-
CC       terminus). Part of a complex composed of RARS1, QARS1 and AIMP1.
CC       Interacts (via C-terminus) with SMURF2 (PubMed:18448069). Interacts
CC       (via N-terminus) with HSP90B1/gp96 (via C-terminus) (PubMed:17525271).
CC       Interacts with PSMA7 (By similarity). Interacts with TARS3.
CC       {ECO:0000250|UniProtKB:Q12904, ECO:0000269|PubMed:12060739,
CC       ECO:0000269|PubMed:17525271, ECO:0000269|PubMed:18448069}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q12904}.
CC       Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q12904}. Secreted
CC       {ECO:0000269|PubMed:17001013, ECO:0000269|PubMed:9770485}. Endoplasmic
CC       reticulum {ECO:0000269|PubMed:17525271}. Golgi apparatus
CC       {ECO:0000269|PubMed:17525271}. Note=Enriched in secretory vesicles of
CC       pancreatic alpha cells and secreted from the pancreas in response to
CC       low glucose levels (PubMed:17001013). Secreted in response to hypoxia
CC       (By similarity). Also secreted in response to both apoptotic and
CC       necrotic cell death. {ECO:0000250|UniProtKB:Q12904,
CC       ECO:0000269|PubMed:17001013}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in salivary glands and pancreatic
CC       alpha cells in the adult (at protein level) (PubMed:17001013). In the
CC       embryo, expressed primarily at sites of tissue remodeling such as
CC       ganglia, developing bones and teeth (PubMed:9770485).
CC       {ECO:0000269|PubMed:17001013, ECO:0000269|PubMed:9770485}.
CC   -!- INDUCTION: By wounding. {ECO:0000269|PubMed:18448069}.
CC   -!- PTM: Cleaved by caspase-7 in response to apoptosis to produce EMAP-II.
CC       {ECO:0000269|PubMed:11306575}.
CC   -!- DISRUPTION PHENOTYPE: Increased Hsp90b1 surface expression, dendritic
CC       cell hyperactivation and development of lupus-like autoimmune
CC       phenotypes (PubMed:17525271). Retarded growth after birth, reduced food
CC       intake, reduced plasma levels of glucose, free fatty acid, glucagon and
CC       insulin, increased glycogen content in the liver, and rapid decrease in
CC       blood glucose concentration upon fasting (PubMed:17001013).
CC       {ECO:0000269|PubMed:17001013, ECO:0000269|PubMed:17525271}.
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DR   EMBL; U10118; AAA62203.1; -; mRNA.
DR   EMBL; BC002054; AAH02054.1; -; mRNA.
DR   CCDS; CCDS89689.1; -.
DR   PIR; A55053; A55053.
DR   AlphaFoldDB; P31230; -.
DR   SMR; P31230; -.
DR   IntAct; P31230; 2.
DR   STRING; 10090.ENSMUSP00000029663; -.
DR   MoonProt; P31230; -.
DR   GlyGen; P31230; 7 sites, 1 O-linked glycan (7 sites).
DR   iPTMnet; P31230; -.
DR   PhosphoSitePlus; P31230; -.
DR   SwissPalm; P31230; -.
DR   CPTAC; non-CPTAC-3361; -.
DR   EPD; P31230; -.
DR   jPOST; P31230; -.
DR   MaxQB; P31230; -.
DR   PaxDb; 10090-ENSMUSP00000029663; -.
DR   PeptideAtlas; P31230; -.
DR   ProteomicsDB; 285787; -.
DR   Pumba; P31230; -.
DR   Antibodypedia; 4317; 678 antibodies from 46 providers.
DR   Ensembl; ENSMUST00000198513.6; ENSMUSP00000142513.3; ENSMUSG00000028029.12.
DR   AGR; MGI:102774; -.
DR   MGI; MGI:102774; Aimp1.
DR   VEuPathDB; HostDB:ENSMUSG00000028029; -.
DR   eggNOG; KOG2241; Eukaryota.
DR   GeneTree; ENSGT00940000154950; -.
DR   InParanoid; P31230; -.
DR   PhylomeDB; P31230; -.
DR   ChiTaRS; Aimp1; mouse.
DR   PRO; PR:P31230; -.
DR   Proteomes; UP000000589; Chromosome 3.
DR   RNAct; P31230; Protein.
DR   Bgee; ENSMUSG00000028029; Expressed in urogenital fold and 295 other cell types or tissues.
DR   ExpressionAtlas; P31230; baseline and differential.
DR   GO; GO:0017101; C:aminoacyl-tRNA synthetase multienzyme complex; IDA:CAFA.
DR   GO; GO:0009986; C:cell surface; ISS:HGNC.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR   GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR   GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0005125; F:cytokine activity; IDA:HGNC-UCL.
DR   GO; GO:0051020; F:GTPase binding; ISO:MGI.
DR   GO; GO:0042803; F:protein homodimerization activity; ISS:HGNC-UCL.
DR   GO; GO:0000049; F:tRNA binding; ISS:HGNC-UCL.
DR   GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR   GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR   GO; GO:0007267; P:cell-cell signaling; ISO:MGI.
DR   GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR   GO; GO:0050900; P:leukocyte migration; IDA:HGNC-UCL.
DR   GO; GO:0001937; P:negative regulation of endothelial cell proliferation; ISS:HGNC-UCL.
DR   GO; GO:0070094; P:positive regulation of glucagon secretion; IDA:UniProtKB.
DR   GO; GO:0006412; P:translation; IEA:UniProtKB-KW.
DR   CDD; cd02799; tRNA_bind_EMAP-II_like; 1.
DR   Gene3D; 2.40.50.140; Nucleic acid-binding proteins; 1.
DR   InterPro; IPR012340; NA-bd_OB-fold.
DR   InterPro; IPR002547; tRNA-bd_dom.
DR   PANTHER; PTHR11586:SF46; AMINOACYL TRNA SYNTHASE COMPLEX-INTERACTING MULTIFUNCTIONAL PROTEIN 1; 1.
DR   PANTHER; PTHR11586; TRNA-AMINOACYLATION COFACTOR ARC1 FAMILY MEMBER; 1.
DR   Pfam; PF01588; tRNA_bind; 1.
DR   SUPFAM; SSF50249; Nucleic acid-binding proteins; 1.
DR   PROSITE; PS50886; TRBD; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Angiogenesis; Apoptosis; Cytokine; Cytoplasm;
KW   Direct protein sequencing; Endoplasmic reticulum; Golgi apparatus;
KW   Inflammatory response; Nucleus; Phosphoprotein; Protein biosynthesis;
KW   Reference proteome; RNA-binding; Secreted; tRNA-binding.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250|UniProtKB:Q12904"
FT   CHAIN           2..310
FT                   /note="Aminoacyl tRNA synthase complex-interacting
FT                   multifunctional protein 1"
FT                   /id="PRO_0000223395"
FT   CHAIN           145..310
FT                   /note="Endothelial monocyte-activating polypeptide 2"
FT                   /id="PRO_0000019244"
FT   DOMAIN          149..250
FT                   /note="tRNA-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00209"
FT   REGION          6..46
FT                   /note="Required for fibroblast proliferation"
FT                   /evidence="ECO:0000250"
FT   REGION          54..192
FT                   /note="Interaction with HSP90B1"
FT                   /evidence="ECO:0000269|PubMed:17525271"
FT   REGION          92..147
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          101..115
FT                   /note="Required for endothelial cell death"
FT                   /evidence="ECO:0000250"
FT   REGION          115..190
FT                   /note="Required for endothelial cell migration"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        92..111
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        113..139
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         2
FT                   /note="N-acetylalanine"
FT                   /evidence="ECO:0000250|UniProtKB:Q12904"
FT   MOD_RES         138
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q12904"
FT   MOD_RES         267
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
SQ   SEQUENCE   310 AA;  33997 MW;  A2F8FF52A33D03A0 CRC64;
     MATNDAVLKR LEQKGAEADQ IIEYLKQQVA LLKEKAILQA TMREEKKLRV ENAKLKKEIE
     ELKQELILAE IHNGVEQVRV RLSTPLQTNC TASESVVQSP SVATTASPAT KEQIKAGEEK
     KVKEKTEKKG EKKEKQQSAA ASTDSKPIDA SRLDLRIGCI VTAKKHPDAD SLYVEEVDVG
     EAAPRTVVSG LVNHVPLEQM QNRMVVLLCN LKPAKMRGVL SQAMVMCASS PEKVEILAPP
     NGSVPGDRIT FDAFPGEPDK ELNPKKKIWE QIQPDLHTNA ECVATYKGAP FEVKGKGVCR
     AQTMANSGIK
//