AIMP1_MOUSE
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 03-AUG-2022, entry version 154.
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, Pancreas,
RC 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 iPTMnet; P31230; -.
DR PhosphoSitePlus; P31230; -.
DR SwissPalm; P31230; -.
DR CPTAC; non-CPTAC-3361; -.
DR EPD; P31230; -.
DR jPOST; P31230; -.
DR MaxQB; P31230; -.
DR PaxDb; P31230; -.
DR PeptideAtlas; P31230; -.
DR PRIDE; P31230; -.
DR ProteomicsDB; 285787; -.
DR Antibodypedia; 4317; 610 antibodies from 46 providers.
DR Ensembl; ENSMUST00000198513; ENSMUSP00000142513; ENSMUSG00000028029.
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 291 other 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 Gene3D; 2.40.50.140; -; 1.
DR InterPro; IPR012340; NA-bd_OB-fold.
DR InterPro; IPR002547; tRNA-bd_dom.
DR Pfam; PF01588; tRNA_bind; 1.
DR SUPFAM; SSF50249; SSF50249; 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
