AIMP1, also called p43 or proEMAPII, is a tRNA-binding auxiliary component of the mammalian aminoacyl-tRNA synthetase multienzyme complex. Its N-terminal interaction region helps organize the RARS1βQARS1 subcomplex and connect it to AIMP2, while cooperation between its N- and C-terminal regions supports high-affinity tRNA binding and stimulation of arginyl-tRNA aminoacylation. AIMP1 is predominantly cytosolic, with a nuclear complex-associated pool and additional ER/Golgi-associated populations. Full-length AIMP1 and its processed C-terminal EMAP-II domain also have extracellular cytokine activities. These include leukocyte recruitment and context-dependent endothelial responses; recombinant full-length p43 stimulates endothelial migration at lower concentrations and apoptosis at higher concentrations. Caspase-7 cleavage can release EMAP-II from the complex and greatly reduce the high-affinity RNA-binding capacity of intact p43. AIMP1 also participates in gp96 retention and retrieval at the ERβGolgi interface. Biallelic pathogenic variants cause a severe neurodevelopmental disorder with hypomyelination.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0007165 signal transduction | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Extracellular AIMP1/EMAP-II can signal to recipient cells. Reason: EMAP-II binding to recipient-cell surfaces and inhibition of endothelial growth in PMID:11741979 support the logical mapping from cytokine activity to signal transduction. These are extracellular ligand effects, retained as a contextual function alongside AIMP1's intracellular RNA-binding and complex-assembly work. The paper's statement about intact-p43 secretion is background, not a release experiment performed in that study. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: GO_REF:0000108 SUPPORTS TRANSFER The logical inference from cytokine activity is supported by extracellular p43/EMAP-II responses; it does not imply a particular intracellular signaling enzyme. Supporting Evidence: PMID:11741979 EMAP II inhibited the growth of endothelial cells, and this effect was relieved by soluble alpha-ATP synthase. PMID:11741979 The binding of EMAP II to the surface of serum-starved cells was inhibited in the presence of soluble alpha-ATP synthase. |
| GO:0000049 tRNA binding | IEA GO_REF:0000120 | ACCEPT | Summary: AIMP1 binds tRNA through cooperating N- and C-terminal regions. Reason: The combined domain/keyword inference is directly corroborated by purified p43 binding experiments in PMID:11306575. Intact protein binds tested tRNAs much more strongly than either separated domain. The EMAPII-like fold supports this activity, but the source does not establish a specific bacterial Trbp111-style terminal-base recognition mechanism for human AIMP1. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR002547 SUPPORTS TRANSFER The EMAPII-like domain mapping agrees with direct p43 tRNA binding; high-affinity binding depends on the intact protein rather than the domain alone. UniProtKB-KW:KW-0820 SUPPORTS TRANSFER The tRNA-binding keyword agrees with direct intact-p43 binding experiments. Supporting Evidence: PMID:11306575 p43/proEMAPII has a strong tRNA binding capacity (K(D) = 0.2 microm) |
| GO:0001525 angiogenesis | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: Extracellular p43 has concentration-dependent angiogenic effects. Reason: Full-length recombinant p43 promoted endothelial migration at lower concentrations and endothelial apoptosis at higher concentrations in PMID:12237313, with angiogenesis tested in chick chorioallantoic membrane and mouse Matrigel assays. These positive effects support the broad keyword mapping in an extracellular context. They do not establish a constitutive intracellular role in vessel formation or justify dismissing the response as nonphysiological solely on the basis of dose. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-KW:KW-0037 SUPPORTS TRANSFER The angiogenesis keyword captures experimentally observed, dose-dependent extracellular p43 activity. Supporting Evidence: PMID:12237313 It promoted the migration of endothelial cells at low dose but induced their apoptosis at high dose. |
| GO:0003723 RNA binding | IEA GO_REF:0000043 | ACCEPT | Summary: RNA binding is a valid broader description of AIMP1βs tRNA-binding activity. Reason: PMID:11306575 directly measured strong tRNA binding by intact p43, providing positive support for the broader RNA-binding keyword annotation. The separately retained tRNA-binding rows supply substrate specificity; the keyword mapping itself is correct. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-KW:KW-0694 SUPPORTS TRANSFER Direct tRNA binding supports this broader RNA-binding assertion. Supporting Evidence: PMID:11306575 p43/proEMAPII has a strong tRNA binding capacity (K(D) = 0.2 microm) |
| GO:0005125 cytokine activity | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: Both full-length p43 and processed EMAP-II have extracellular cytokine activity. Reason: PMID:11741979 directly assays the C-terminal EMAP-II ligand's endothelial effects; PMID:11306575 tests phagocyte migration by complex-derived EMAP-II. Recombinant full-length p43 also produces dose-dependent endothelial responses in PMID:12237313. Retain cytokine activity with these molecular-form and extracellular boundaries. Its non-core status reflects dependence on extracellular availability, the intact or processed molecular form, and responding-cell context. The integrated core describes intracellular substrate recruitment and complex assembly; this distinction does not deny the positive cytokine assays or require proteolytic processing for every extracellular effect. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-KW:KW-0202 SUPPORTS TRANSFER The keyword is supported by full-length recombinant p43 and processed EMAP-II effector assays; the distinct protein forms and conditions are retained. Supporting Evidence: PMID:11741979 EMAP II inhibited the growth of endothelial cells, and this effect was relieved by soluble alpha-ATP synthase. PMID:11306575 is able to induce migration of human mononuclear phagocytes. PMID:12237313 It promoted the migration of endothelial cells at low dose but induced their apoptosis at high dose. |
| GO:0005576 extracellular region | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: AIMP1-derived cytokine activity occurs extracellularly. Reason: PMID:10850427 directly detects stress-associated extracellular release of the 34-kDa precursor and smaller EMAP-II forms from human prostate-cancer cells. This supports an extracellular population without establishing constitutive secretion or a single release mechanism. The predominant intracellular synthetase-complex pool is independently supported. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-SubCell:SL-0243 SUPPORTS TRANSFER Human precursor/processed-form release in PMID:10850427 supports the extracellular mapping; it does not place all cellular AIMP1 outside the cell. Supporting Evidence: PMID:10850427 Hypoxia, but not heat shock, is a potent inducer of release and processing of biologically active EMAP-II |
| GO:0005615 extracellular space | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: AIMP1-derived cytokine activity occurs extracellularly. Reason: PMID:10850427 directly detects stress-associated extracellular release of the 34-kDa precursor and smaller EMAP-II forms from human prostate-cancer cells. This supports an extracellular population without establishing constitutive secretion or a single release mechanism. The predominant intracellular synthetase-complex pool is independently supported. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-KW:KW-0202 SUPPORTS TRANSFER Human precursor/processed-form release in PMID:10850427 supports the extracellular mapping; it does not place all cellular AIMP1 outside the cell. Supporting Evidence: PMID:10850427 Hypoxia, but not heat shock, is a potent inducer of release and processing of biologically active EMAP-II |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: A nuclear pool of complex-associated p43 is experimentally supported. Reason: PMID:14500886 isolated human nuclear and cytosolic synthetase complexes, and its full Results describe p43 immunoblots of gel-filtered extracts from both compartments. This supports the broad nucleus mapping alongside cytosolic localization. It does not transfer the distinct nucleolar MARS1 function from PMID:10791971 to AIMP1. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0191 SUPPORTS TRANSFER Human nuclear complex purification and p43 fractionation support nuclear localization; no narrower nucleolar function is inferred. Supporting Evidence: PMID:14500886 has been isolated from the nuclear and cytosolic compartments of human cells and purified to near homogeneity. PMID:14500886 a major biological role for the cytokine precursor p43 is as an integral part of the multisynthetase complex. |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: An ER-associated AIMP1 population supports gp96 trafficking. Reason: PMID:17525271 Figure 2 reports endogenous AIMP1 in HeLa microsomal fractions and colocalization with calnexin and GM130; most signal follows the ER marker and a smaller pool follows the Golgi marker. The study links AIMP1 to gp96βKDELR1 association and retention/retrieval. Retain the broad ER location without claiming a transmembrane topology or assigning all AIMP1 to the organelle lumen. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-SubCell:SL-0095 SUPPORTS TRANSFER The broad ER mapping has direct fractionation and imaging support in the gp96-trafficking study; suborganelle topology is not resolved here. Supporting Evidence: PMID:17525271 AIMP1 enhances gp96 dimerization and the interaction between gp96 and KDEL receptor-1 (KDELR-1) |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: A Golgi-associated AIMP1 population supports gp96 trafficking. Reason: PMID:17525271 Figure 2 reports endogenous AIMP1 in HeLa microsomal fractions and colocalization with calnexin and GM130; most signal follows the ER marker and a smaller pool follows the Golgi marker. The study links AIMP1 to gp96βKDELR1 association and retention/retrieval. Retain the broad Golgi location without claiming a transmembrane topology or assigning all AIMP1 to the organelle lumen. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-SubCell:SL-0132 SUPPORTS TRANSFER The broad Golgi mapping has direct fractionation and imaging support in the gp96-trafficking study; suborganelle topology is not resolved here. Supporting Evidence: PMID:17525271 AIMP1 enhances gp96 dimerization and the interaction between gp96 and KDEL receptor-1 (KDELR-1) |
| GO:0005829 cytosol | IEA GO_REF:0000044 | ACCEPT | Summary: Cytosol is a principal location of AIMP1βs synthetase-complex activity. Reason: Human complex purification, p43 imaging/fractionation and cross-linking studies consistently support the cytosolic population. The broad subcellular-location mapping is appropriate without excluding nuclear or secretory-pathway-associated pools. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0091 SUPPORTS TRANSFER Human p43 and synthetase-complex experiments independently corroborate cytosolic localization. Supporting Evidence: PMID:19289464 The sequestration of its components within the cytoplasm rests on the presence of the eukaryotic-specific polypeptide extensions PMID:14500886 a major biological role for the cytokine precursor p43 is as an integral part of the multisynthetase complex. |
| GO:0006412 translation | IEA GO_REF:0000043 | ACCEPT | Summary: AIMP1 contributes RNA-binding and structural work to the translation apparatus. Reason: AIMP1 binds tRNA and organizes a functional synthetase subcomplex. The human RARS interaction lowers the apparent tRNA Km without changing kcat in PMID:10358004. These are direct contributions to charging tRNAs for translation, so the broad translation keyword is appropriate even though AIMP1 itself does not catalyze aminoacyl transfer. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-KW:KW-0648 SUPPORTS TRANSFER AIMP1βs tRNA-binding and complex-assembly contributions support participation in translation. Supporting Evidence: PMID:11306575 p43/proEMAPII has a strong tRNA binding capacity (K(D) = 0.2 microm) PMID:10358004 Pro-EMAPII reduced the apparent Km of RRS to tRNA, whereas the kcat value remained unchanged. |
| GO:0006915 apoptotic process | IEA GO_REF:0000043 | MODIFY | Summary: Extracellular p43 can positively regulate endothelial apoptosis. Reason: PMID:12237313 directly assayed apoptosis induced by higher concentrations of recombinant full-length p43 in bovine aortic endothelial cells, including DNA fragmentation and caspase activation. This positive effector evidence is distinct from AIMP1 merely being cleaved during apoptosis. Refine the broad apoptosis keyword to positive regulation of endothelial cell apoptotic process, with the recombinant-ligand, endothelial-cell and dose boundaries explicit. The same study reports migration at lower doses, so the replacement describes the high-dose apoptotic arm rather than a uniform response to p43. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB-KW:KW-0053 SUPPORTS TRANSFER The keyword combines apoptosis-associated processing and extracellular effector activity; the latter supports a more precise regulatory process. Proposed replacements: positive regulation of endothelial cell apoptotic process Supporting Evidence: PMID:12237313 It promoted the migration of endothelial cells at low dose but induced their apoptosis at high dose. |
| GO:0006954 inflammatory response | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: AIMP1/EMAP-II can promote inflammatory cell responses. Reason: Complex-derived EMAP-II attracts human mononuclear phagocytes in PMID:11306575, providing positive effector participation in an inflammatory response. Human stress-associated release is directly detected in PMID:10850427. Its externally read Figures 5 and 6 test TNF-dependent potentiation of endothelial coagulation by conditioned medium and recombinant precursor/mature EMAP-II; hypoxic conditioned medium alone did not significantly increase coagulation. This bounded effector context supports the retained non-core function, without assigning intrinsic coagulation chemistry to AIMP1 or treating an introductory statement in PMID:11741979 as a release experiment. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-KW:KW-0395 SUPPORTS TRANSFER The mapping is consistent with proinflammatory signaling and phagocyte recruitment by p43-derived cytokine activity. Supporting Evidence: PMID:11306575 is able to induce migration of human mononuclear phagocytes. file:human/AIMP1/AIMP1-notes.md Potentiation of TNF-induced endothelial coagulation |
| GO:0005515 protein binding | IPI PMID:22190034 Global landscape of HIV-human protein complexes. | REMOVE | Summary: Generic protein binding does not specify AIMP1βs molecular work. Reason: This IPI annotation derives from HIVβhuman affinity-purification mass spectrometry in HEK293 and Jurkat cells. The interaction evidence is retained as provenance, but GO:0005515 alone provides no functional discrimination. Remove the uninformative term without claiming the reported association is false or assigning an adaptor, enzyme-regulator or viral-defense activity from association alone. Supporting Evidence: PMID:22190034 the physical interactions of all 18 HIV-1 proteins and polyproteins with host proteins in two different human cell lines (HEK293 and Jurkat). |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Generic protein binding does not specify AIMP1βs molecular work. Reason: This IPI annotation derives from a systematic human binary-interaction screen. The interaction evidence is retained as provenance, but GO:0005515 alone provides no functional discrimination. Remove the uninformative term without claiming the reported association is false or assigning an adaptor, enzyme-regulator or viral-defense activity from association alone. Supporting Evidence: PMID:25416956 Here, we describe a systematic map of ?14,000 high-quality human binary protein-protein interactions. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Generic protein binding does not specify AIMP1βs molecular work. Reason: This IPI annotation derives from the BioPlex 2.0 affinity-purification mass-spectrometry network. The interaction evidence is retained as provenance, but GO:0005515 alone provides no functional discrimination. Remove the uninformative term without claiming the reported association is false or assigning an adaptor, enzyme-regulator or viral-defense activity from association alone. Supporting Evidence: PMID:28514442 BioPlex 2.0 contains more than 29,000 previously unknown co-associations |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Generic protein binding does not specify AIMP1βs molecular work. Reason: This IPI annotation derives from BioPlex affinity-purification networks from 293T and HCT116 cells. The interaction evidence is retained as provenance, but GO:0005515 alone provides no functional discrimination. Remove the uninformative term without claiming the reported association is false or assigning an adaptor, enzyme-regulator or viral-defense activity from association alone. Supporting Evidence: PMID:33961781 Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks. |
| GO:0048514 blood vessel morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Extracellular p43 contributes to blood-vessel responses in experimental models. Reason: The Ensembl transfer names rat Aimp1 sources Q4G079 and ENSRNOP00000077517. The exact donor experiment was not recovered, but independent p43 experiments in PMID:12237313 demonstrate migration/apoptosis effects and angiogenesis in chick and mouse assays. Retain the broad vessel-morphogenesis role as contextual biology while leaving the precise donor-to-annotation chain unresolved. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q4G079 UNRESOLVED Rat Aimp1 identity is established; the original donor experiment was not recovered. Independent p43 angiogenesis evidence supports the target judgment, not a reconstructed donor chain. Ensembl:ENSRNOP00000077517 UNRESOLVED This is the additional Ensembl source in the seeded transfer; its exact source annotation/experiment was not recovered. Supporting Evidence: PMID:12237313 It promoted the migration of endothelial cells at low dose but induced their apoptosis at high dose. |
| GO:0051607 defense response to virus | IEA GO_REF:0000107 | UNDECIDED | Summary: The exact rat-to-human antiviral-defense transfer remains unresolved. Reason: The seeded Ensembl transfer cites rat Aimp1, but its original experiment was not recovered. PMID:29379495 supports Aimp1-dependent antiviral immunity in knockout mice challenged with influenza, with dendritic-cell and TH1 response mechanisms considered. That is relevant corroboration but does not identify the rat donor assertion or establish the precise conserved human activity behind this transfer. Retain uncertainty without treating incomplete access as evidence that AIMP1 lacks antiviral function. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q4G079 UNRESOLVED Rat donor identity is verified, but its virus-defense experiment remains untraced; the inspected mouse knockout study is a different source. Ensembl:ENSRNOP00000077517 UNRESOLVED The seeded Ensembl source is preserved; exact experimental grounding of its antiviral annotation was not recovered. Supporting Evidence: PMID:29379495 A sub-lethal dose of 7.50 TCID50 per mouse still caused 60% mortality among AIMp1β/β mice versus 0% among WT animals (Figure 5A). |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: The curated immunofluorescence assignment agrees with direct human p43 localization. Reason: Retain the cytosolic IDA from GO_REF:0000052. Independently, PMID:19289464 examines full-length human p43 in HeLa cells and its retention in the cytoplasm within the synthetase complex. This supports the same broad compartment without inventing details of the original antibody image. Supporting Evidence: PMID:19289464 The sequestration of its components within the cytoplasm rests on the presence of the eukaryotic-specific polypeptide extensions |
| GO:0005737 cytoplasm | NAS PMID:32644155 3-Dimensional architecture of the human multi-tRNA synthetas... | ACCEPT | Summary: Human AIMP1 is part of the cytoplasmic synthetase complex. Reason: PMID:32644155 purified and cross-linked the human complex from HEK293T cells and placed its components in a compact structural model. The broad cytoplasm annotation is directly compatible with this complexβs location and with p43-specific localization studies; a narrower cytosol row does not invalidate it. Supporting Evidence: PMID:32644155 inter-protein cross-links spanning all MSC constituents were observed PMID:19289464 The sequestration of its components within the cytoplasm rests on the presence of the eukaryotic-specific polypeptide extensions |
| GO:0006418 tRNA aminoacylation for protein translation | NAS PMID:32644155 3-Dimensional architecture of the human multi-tRNA synthetas... | ACCEPT | Summary: AIMP1 contributes tRNA binding and assembly to the aminoacylation complex. Reason: The cited structural study maps AIMP1 within the human multi-tRNA synthetase complex. Its positive functional contribution is independently established by tRNA binding, RARS stimulation and the AIMP1-dependent RARSβQARS/AIMP2 assembly. It therefore does some of the work supporting tRNA aminoacylation, while the cognate synthetases perform the catalytic transfer. Supporting Evidence: PMID:32644155 inter-protein cross-links spanning all MSC constituents were observed PMID:11306575 p43/proEMAPII has a strong tRNA binding capacity (K(D) = 0.2 microm) PMID:10358004 Pro-EMAPII reduced the apparent Km of RRS to tRNA, whereas the kcat value remained unchanged. |
| GO:0005515 protein binding | IPI PMID:24312579 Reinvestigation of aminoacyl-tRNA synthetase core complex by... | MODIFY | Summary: AIMP1βs complex interactions have a demonstrated scaffold function. Reason: The source AP-MS study used AIMP1 as bait and recovered the multi-synthetase complex. Human structural and mutational experiments in PMID:25288775 show how AIMP1βs N-terminal helix organizes the RARSβQARS subcomplex and connects it to AIMP2; PMID:19131329 independently supports the structural role of the auxiliary proteins. Refine the generic interaction term to protein complex scaffold activity. This judgment uses experimentally resolved assembly work, not association alone. Proposed replacements: protein complex scaffold activity Supporting Evidence: PMID:24312579 we conducted affinity purification-mass spectrometry (AP-MS) using each of AIMP1, AIMP2 and KARS as a bait protein. PMID:25288775 This ternary complex was further anchored to AIMP2/p38 through interaction with AIMP1. PMID:19131329 The data are consistent with a structural role of the three nonsynthetase components of MARS |
| GO:0070094 positive regulation of glucagon secretion | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The mouse-derived glucagon-secretion role is a bounded extracellular activity. Reason: The donor is mouse Aimp1 (P31230). PMID:17001013 reports secretion during glucose starvation and stimulation of glucagon release from mouse alphaTC1 cells; rodent in vivo experiments corroborate a hormonal response. Retain the curatorβs ortholog transfer as a secondary ligand activity. The study does not establish these release/endocrine responses in normal human physiology. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P31230 SUPPORTS TRANSFER Mouse Aimp1 secretion and glucagon-release experiments support this curator transfer, with the species and endocrine-context limits retained. Supporting Evidence: PMID:17001013 AIMP1 is secreted from the pancreas upon glucose starvation. |
| GO:0005615 extracellular space | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mouse secretion evidence supports an extracellular AIMP1 population. Reason: The mouse P31230 donor study, PMID:17001013, documents pancreatic Aimp1 secretion during glucose starvation. Independent human PMID:10850427 demonstrates stress-associated precursor/processed-form release. Together these support the broad extracellular-space location; they do not establish the mouse endocrine circuit or glucose-responsive secretion in humans. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P31230 SUPPORTS TRANSFER Mouse secretion experiments support the donor location; human stress-associated release independently corroborates extracellular localization, with physiological triggers kept separate. Supporting Evidence: PMID:17001013 AIMP1 is secreted from the pancreas upon glucose starvation. PMID:10850427 Hypoxia, but not heat shock, is a potent inducer of release and processing of biologically active EMAP-II |
| GO:0005829 cytosol | IDA PMID:19289464 Dynamic Organization of Aminoacyl-tRNA Synthetase Complexes ... | ACCEPT | Summary: Full-length human p43 is retained in the cytoplasm as part of the complex. Reason: The externally inspected full Results of PMID:19289464 compare full-length GFP-p43 with an N-terminally truncated derivative in HeLa cells and examine mobility and complex/polysome association. These experiments support the cytosolic localization of intact AIMP1; distributions of truncated proteins are not used to redefine the intact proteinβs location. Supporting Evidence: PMID:19289464 The sequestration of its components within the cytoplasm rests on the presence of the eukaryotic-specific polypeptide extensions |
| GO:0017101 aminoacyl-tRNA synthetase multienzyme complex | IDA PMID:19131329 Dissection of the structural organization of the aminoacyl-t... | ACCEPT | Summary: Human p43 is a structural auxiliary component of the synthetase complex. Reason: PMID:19131329 purified human complexes after stable silencing of individual auxiliary components, including p43. The residual assemblies support a structural role for these proteins. Retain experimentally established MSC membership without attributing p38/AIMP2-specific bridging details to p43. Supporting Evidence: PMID:19131329 The data are consistent with a structural role of the three nonsynthetase components of MARS |
| GO:0017101 aminoacyl-tRNA synthetase multienzyme complex | IDA PMID:10791971 Nucleolar localization of human methionyl-tRNA synthetase an... | ACCEPT | Summary: The MARS1 study directly detects p43 in the high-molecular-weight synthetase complex. Reason: The cached full text of PMID:10791971 includes p43 immunoblot detection in gel-filtration fractions containing the synthetase complex. This is direct support for AIMP1 complex membership even though the paperβs main topic is MARS1 nucleolar function. The MARS1-specific rRNA and nucleolar results are not transferred to AIMP1. Supporting Evidence: PMID:10791971 MRS and two other complex-components, EPRS (Fett and Knippers 1991) and p43 (Quevillon et al. 1997), were detected by immunoblotting with their respective antibodies. The majority of the three proteins were coeluted in the void volume as expected. |
| GO:0051020 GTPase binding | IPI PMID:24337748 Guanylate binding protein 1-mediated interaction of T cell a... | KEEP AS NON CORE | Summary: AIMP1/p43 was recovered in GBP1-associated protein preparations. Reason: The full primary PMID:24337748 explicitly names p43 among GBP1-associated proteins. Figure 3D reports positive control-subtracted signals in four independent tagged-GBP1 Jurkat-cell MS runs. Retain the curated IPI as a non-core interaction with a defined GTPase partner, deferring to its experimental interpretation. GO:0051020 identifies an enzyme class and does not require GAP/GEF activity; it is more informative than generic GO:0005515. The generic removals are an information-content policy, not rejection of AP-MS evidence. Direct binary contact remains unresolved, and no AIMP1 signaling mechanism is inferred. Supporting Evidence: file:human/AIMP1/AIMP1-notes.md identiο¬ed by us by mass spectrometry (multisynthetase complex auxiliary component p43 |
| GO:0005515 protein binding | IPI PMID:11741979 Interaction of the C-terminal domain of p43 and the alpha su... | REMOVE | Summary: The EMAP-IIβATP-synthase interaction is real but generic protein binding is uninformative. Reason: PMID:11741979 supports binding of the EMAP-II domain to the ATP-synthase alpha subunit and links that interaction to endothelial growth inhibition. Remove the generic term on functional-information grounds, preserving the interaction evidence. The inspected source does not justify replacing it with ATPase-inhibitor activity, and proposing GO:0005515 again would not be a refinement. Supporting Evidence: PMID:11741979 The interaction of EMAP II and alpha-ATP synthase was confirmed by enzyme-linked immunosorbent assay and in vitro pull down assays PMID:11741979 EMAP II inhibited the growth of endothelial cells, and this effect was relieved by soluble alpha-ATP synthase. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | UNDECIDED | Summary: The AIMP1-specific membrane-proteomics assignment could not be independently resolved. Reason: PMID:19946888 describes YTS-cell membrane isolation and mass spectrometry, including proteins that can associate transiently with membranes. The cached abstract and accessible publisher record do not expose the AIMP1 identification/peptide entry needed to adjudicate this HDA row. Keep the annotation unresolved; a soluble MSC role does not exclude membrane association or establish contamination. Supporting Evidence: PMID:19946888 Mass spectrometric analysis identified 1843 proteins with high confidence scores. |
| GO:0009986 cell surface | IDA PMID:11741979 Interaction of the C-terminal domain of p43 and the alpha su... | KEEP AS NON CORE | Summary: The extracellular EMAP-II domain binds recipient-cell surfaces. Reason: PMID:11741979 assayed EMAP-II binding to serum-starved CEM cells and identified an interacting surface ATP-synthase alpha subunit. The location is retained for the surface-bound ligand population. This does not imply AIMP1 is an integral membrane protein or that its intracellular synthetase-complex pool resides on the cell surface. Supporting Evidence: PMID:11741979 The binding of EMAP II to the surface of serum-starved cells was inhibited in the presence of soluble alpha-ATP synthase. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-379861 | ACCEPT | Summary: The glutamate-charging event places AIMP1 in the cytosolic synthetase complex. Reason: The cached Reactome:R-HSA-379861 event describes the cognate EPRS1 reaction within the cytosolic multi-synthetase complex. AIMP1 is a structural/RNA-binding component of that complex, so the location assertion is supported. The eventβs aminoacyl-tRNA ligase chemistry belongs to EPRS1, not AIMP1. Supporting Evidence: Reactome:R-HSA-379861 PMID:14500886 a major biological role for the cytokine precursor p43 is as an integral part of the multisynthetase complex. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-379865 | ACCEPT | Summary: The proline-charging event places AIMP1 in the cytosolic synthetase complex. Reason: The cached Reactome:R-HSA-379865 event describes the cognate EPRS1 reaction within the cytosolic multi-synthetase complex. AIMP1 is a structural/RNA-binding component of that complex, so the location assertion is supported. The eventβs aminoacyl-tRNA ligase chemistry belongs to EPRS1, not AIMP1. Supporting Evidence: Reactome:R-HSA-379865 PMID:14500886 a major biological role for the cytokine precursor p43 is as an integral part of the multisynthetase complex. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-379867 | ACCEPT | Summary: The aspartate-charging event places AIMP1 in the cytosolic synthetase complex. Reason: The cached Reactome:R-HSA-379867 event describes the cognate DARS1 reaction within the cytosolic multi-synthetase complex. AIMP1 is a structural/RNA-binding component of that complex, so the location assertion is supported. The eventβs aminoacyl-tRNA ligase chemistry belongs to DARS1, not AIMP1. Supporting Evidence: Reactome:R-HSA-379867 PMID:14500886 a major biological role for the cytokine precursor p43 is as an integral part of the multisynthetase complex. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-379893 | ACCEPT | Summary: The isoleucine-charging event places AIMP1 in the cytosolic synthetase complex. Reason: The cached Reactome:R-HSA-379893 event describes the cognate IARS1 reaction within the cytosolic multi-synthetase complex. AIMP1 is a structural/RNA-binding component of that complex, so the location assertion is supported. The eventβs aminoacyl-tRNA ligase chemistry belongs to IARS1, not AIMP1. Supporting Evidence: Reactome:R-HSA-379893 PMID:14500886 a major biological role for the cytokine precursor p43 is as an integral part of the multisynthetase complex. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-379974 | ACCEPT | Summary: The leucine-charging event places AIMP1 in the cytosolic synthetase complex. Reason: The cached Reactome:R-HSA-379974 event describes the cognate LARS1 reaction within the cytosolic multi-synthetase complex. AIMP1 is a structural/RNA-binding component of that complex, so the location assertion is supported. The eventβs aminoacyl-tRNA ligase chemistry belongs to LARS1, not AIMP1. Supporting Evidence: Reactome:R-HSA-379974 PMID:14500886 a major biological role for the cytokine precursor p43 is as an integral part of the multisynthetase complex. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-379982 | ACCEPT | Summary: The glutamine-charging event places AIMP1 in the cytosolic synthetase complex. Reason: The cached Reactome:R-HSA-379982 event describes the cognate QARS1 reaction within the cytosolic multi-synthetase complex. AIMP1 is a structural/RNA-binding component of that complex, so the location assertion is supported. The eventβs aminoacyl-tRNA ligase chemistry belongs to QARS1, not AIMP1. Supporting Evidence: Reactome:R-HSA-379982 PMID:14500886 a major biological role for the cytokine precursor p43 is as an integral part of the multisynthetase complex. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-379993 | ACCEPT | Summary: The arginine-charging event places AIMP1 in the cytosolic synthetase complex. Reason: The cached Reactome:R-HSA-379993 event describes the cognate RARS1 reaction within the cytosolic multi-synthetase complex. AIMP1 is a structural/RNA-binding component of that complex, so the location assertion is supported. The eventβs aminoacyl-tRNA ligase chemistry belongs to RARS1, not AIMP1. Supporting Evidence: Reactome:R-HSA-379993 PMID:14500886 a major biological role for the cytokine precursor p43 is as an integral part of the multisynthetase complex. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-379994 | ACCEPT | Summary: The methionine-charging event places AIMP1 in the cytosolic synthetase complex. Reason: The cached Reactome:R-HSA-379994 event describes the cognate MARS1 reaction within the cytosolic multi-synthetase complex. AIMP1 is a structural/RNA-binding component of that complex, so the location assertion is supported. The eventβs aminoacyl-tRNA ligase chemistry belongs to MARS1, not AIMP1. Supporting Evidence: Reactome:R-HSA-379994 PMID:14500886 a major biological role for the cytokine precursor p43 is as an integral part of the multisynthetase complex. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380008 | ACCEPT | Summary: The lysine-charging event places AIMP1 in the cytosolic synthetase complex. Reason: The cached Reactome:R-HSA-380008 event describes the cognate KARS1 reaction within the cytosolic multi-synthetase complex. AIMP1 is a structural/RNA-binding component of that complex, so the location assertion is supported. The eventβs aminoacyl-tRNA ligase chemistry belongs to KARS1, not AIMP1. Supporting Evidence: Reactome:R-HSA-380008 PMID:14500886 a major biological role for the cytokine precursor p43 is as an integral part of the multisynthetase complex. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9825759 | ACCEPT | Summary: The KARS phosphorylation event includes the cytosolic AIMP1-containing complex. Reason: The cached Reactome event concerns MAPK-dependent phosphorylation and release of KARS from the multi-synthetase complex. The seeded assertion is cytosolic localization of AIMP1, which is compatible with its complex membership. It does not assign MAPK kinase activity, KARS catalysis or downstream Ap4A signaling to AIMP1. Supporting Evidence: Reactome:R-HSA-9825759 PMID:14500886 a major biological role for the cytokine precursor p43 is as an integral part of the multisynthetase complex. |
| GO:0000049 tRNA binding | IDA PMID:11306575 The EMAPII cytokine is released from the mammalian multisynt... | ACCEPT | Summary: Intact p43 has directly measured high-affinity tRNA binding. Reason: PMID:11306575 reports a Kd of approximately 0.2 micromolar for intact p43, compared with 7.5 and 40 micromolar for its isolated N- and C-terminal regions. The full human-protein binding experiments therefore support this IDA. Cleavage greatly weakens the cooperative high-affinity activity; it does not show that each isolated domain loses all RNA binding. Supporting Evidence: PMID:11306575 p43/proEMAPII has a strong tRNA binding capacity (K(D) = 0.2 microm) |
| GO:0001937 negative regulation of endothelial cell proliferation | IDA PMID:11741979 Interaction of the C-terminal domain of p43 and the alpha su... | KEEP AS NON CORE | Summary: EMAP-II inhibits endothelial cell proliferation in the cited assay. Reason: PMID:11741979 reports endothelial growth inhibition by the C-terminal EMAP-II domain and relief of that inhibition by soluble ATP-synthase alpha subunit. This is positive extracellular effector evidence for the existing regulatory process, retained separately from AIMP1βs intracellular role. Supporting Evidence: PMID:11741979 EMAP II inhibited the growth of endothelial cells, and this effect was relieved by soluble alpha-ATP synthase. |
| GO:0005125 cytokine activity | ISS PMID:11306575 The EMAPII cytokine is released from the mammalian multisynt... | KEEP AS NON CORE | Summary: Mouse-derived EMAP-II cytokine activity is supported and conserved in the human evidence. Reason: The source study releases EMAP-II from a murine synthetase complex with caspase 7 and tests migration of human mononuclear phagocytes. Human EMAP-II endothelial assays in PMID:11741979 independently support the cytokine function. Retain the P31230 transfer with its molecular-form, donor-preparation and responding-cell boundaries; do not use the latter paper's background sentence as a primary intact-p43 release experiment. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P31230 SUPPORTS TRANSFER Murine complex-derived EMAP-II acts on human phagocytes in the source study; independent human p43/EMAP-II evidence corroborates the cytokine function. Supporting Evidence: PMID:11306575 is able to induce migration of human mononuclear phagocytes. PMID:11741979 EMAP II inhibited the growth of endothelial cells, and this effect was relieved by soluble alpha-ATP synthase. |
| GO:0007267 cell-cell signaling | IDA PMID:11741979 Interaction of the C-terminal domain of p43 and the alpha su... | KEEP AS NON CORE | Summary: EMAP-II acts as an extracellular signal between cells. Reason: The cited source directly links EMAP-II binding to recipient-cell surfaces with inhibition of endothelial proliferation. This supports cell-cell signaling by an extracellular ligand. Its introductory statement about secreted intact p43 is background; it is not required to establish the measured EMAP-II response. Supporting Evidence: PMID:11741979 EMAP II inhibited the growth of endothelial cells, and this effect was relieved by soluble alpha-ATP synthase. |
| GO:0017101 aminoacyl-tRNA synthetase multienzyme complex | IDA PMID:14500886 Isolation and characterization of human nuclear and cytosoli... | ACCEPT | Summary: Human p43 is an integral component of nuclear and cytosolic synthetase complexes. Reason: PMID:14500886 isolated the complexes from human cells and used gel filtration plus p43 immunoblotting to establish membership. The full Results report high-molecular-weight p43 in nuclear and cytosolic extracts, rather than a prominent free monomeric or dimeric pool in those extracts. Supporting Evidence: PMID:14500886 a major biological role for the cytokine precursor p43 is as an integral part of the multisynthetase complex. PMID:14500886 has been isolated from the nuclear and cytosolic compartments of human cells and purified to near homogeneity. |
| GO:0042803 protein homodimerization activity | IDA PMID:11306575 The EMAPII cytokine is released from the mammalian multisynt... | ACCEPT | Summary: Purified full-length human p43 forms a homodimer. Reason: The externally inspected PMID:11306575 Results/Figure 6 measures purified human full-length p43 as a solution dimer and isolated C-terminal EMAP-II as a monomer. UniProt's Homodimer statement is additional database corroboration. The AIMP1-AIMP2 leucine-zipper assembly in PMID:39542129 concerns a different complex-associated state; it does not negate purified p43 self-association or establish one universal native MSC stoichiometry. Supporting Evidence: file:human/AIMP1/AIMP1-notes.md we concluded that p43 is a dimer in solution. file:human/AIMP1/AIMP1-uniprot.txt CC -!- SUBUNIT: Homodimer. |
| GO:0050900 leukocyte migration | IDA PMID:11306575 The EMAPII cytokine is released from the mammalian multisynt... | KEEP AS NON CORE | Summary: Released EMAP-II directly promotes mononuclear phagocyte migration. Reason: The source study digested a murine synthetase complex with caspase 7 and assayed the released EMAP-II preparation on human mononuclear phagocytes. This supports the curated leukocyte-migration process as an extracellular cytokine effect, with the donor preparation and responding-cell species explicit. Supporting Evidence: PMID:11306575 is able to induce migration of human mononuclear phagocytes. |
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Download this section (compressed HTML)Q: Which endogenous human conditions release full-length AIMP1 versus processed EMAP-II, and how do their local concentrations determine endothelial migration, survival and apoptosis?
Q: What topology and trafficking route place AIMP1 in the gp96/KDELR1-associated ER/Golgi pool while most protein is retained in the cytosolic synthetase complex?
Q: Which rat experiment underlies the current Ensembl antiviral-defense transfer, and what conserved human AIMP1 activity does it establish?
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