Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0007165 signal transduction	IEA GO_REF:0000108	KEEP AS NON CORE	Summary: This IEA annotation is inferred from AIMP1 having cytokine activity (GO:0005125). The cleaved EMAP-II domain does have signaling functions, but signal transduction is overly broad for a protein whose core function is as an MSC scaffold. Reason: AIMP1's primary function is as a scaffold in the MSC. The signaling functions attributed to AIMP1 are secondary to its core role and are primarily associated with the cleaved EMAP-II fragment. This annotation is not incorrect but represents a non-core function. Supporting Evidence: PMID:11306575 The EMAPII cytokine is released from the mammalian multisynthetase complex after cleavage of its p43/proEMAPII component. file:human/AIMP1/AIMP1-deep-research-falcon.md model: Edison Scientific Literature
GO:0000049 tRNA binding	IEA GO_REF:0000120	ACCEPT	Summary: AIMP1 contains an EMAPII-like OB-fold domain that binds tRNA. This is well-supported by experimental data showing strong tRNA binding capacity (Kd = 0.2 microM) for full-length p43 (PMID:11306575). The OB-fold recognizes the 3'-CA dinucleotide of tRNA as shown in 2024 structural work. Reason: tRNA binding is a core molecular function of AIMP1 within the MSC, mediated by its OB-fold domain. This is supported by direct experimental evidence. Supporting Evidence: PMID:11306575 p43/proEMAPII has a strong tRNA binding capacity (K(D) = 0.2 microm) as compared with its isolated N or C domains (7.5 microm and 40 microm, respectively).
GO:0001525 angiogenesis	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: The UniProt keyword mapping is based on the dose-dependent biphasic effects of p43/EMAP-II on endothelial cells. At low concentrations AIMP1 promotes endothelial migration; at high concentrations it induces apoptosis. These are pharmacological effects of the cleaved EMAP-II cytokine, not the physiological core function. Reason: The angiogenesis-related effects are secondary functions of the secreted/cleaved EMAP-II fragment, not the core function of AIMP1 as an MSC scaffold. The biphasic dose-dependent nature suggests this is a pharmacological rather than physiological function. Supporting Evidence: PMID:11741979 EMAP II inhibited the growth of endothelial cells, and this effect was relieved by soluble alpha-ATP synthase.
GO:0003723 RNA binding	IEA GO_REF:0000043	ACCEPT	Summary: AIMP1 binds tRNA specifically via its OB-fold domain. The more specific term tRNA binding (GO:0000049) is already annotated with IDA evidence and is more appropriate. Reason: RNA binding is a parent term of tRNA binding. While redundant with the more specific tRNA binding annotation, it is not incorrect. The IEA annotation provides broader coverage. 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: The cytokine activity is attributed to the cleaved EMAP-II domain, not the full-length AIMP1 protein. Upon caspase-7 cleavage during apoptosis, the C-terminal EMAP-II domain is released and functions as a proinflammatory cytokine. Reason: Cytokine activity is a real but secondary function of AIMP1. The annotation is technically accurate since the UniProt entry describes AIMP1 as containing the EMAP-II cytokine. However, this is not the core function of the full-length protein, which is MSC scaffold activity. Supporting Evidence: PMID:11306575 Endothelial-monocyte-activating polypeptide II (EMAPII) is an inflammatory cytokine released under apoptotic conditions. Its proEMAPII precursor proved to be identical to the auxiliary p43 component of the aminoacyl-tRNA synthetase complex.
GO:0005576 extracellular region	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: AIMP1/EMAP-II is secreted under stress conditions (hypoxia, apoptosis). The cleaved EMAP-II fragment is found in the extracellular space. Reason: The extracellular localization applies to the secreted/cleaved form, not the primary location of AIMP1 which is cytosolic as part of the MSC. Supporting Evidence: PMID:11306575 the EMAPII domain of p43 is released readily from the complex after in vitro digestion with caspase 7
GO:0005615 extracellular space	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: Same as extracellular region - this applies to the secreted EMAP-II fragment released during apoptosis or stress. Reason: Extracellular space localization is for the cleaved/secreted form, not the primary cytosolic location of full-length AIMP1. Supporting Evidence: PMID:11306575 the mature cytokine isolated from conditioned medium of fibrosarcoma cells
GO:0005634 nucleus	IEA GO_REF:0000044	ACCEPT	Summary: AIMP1/p43 has been detected in both nuclear and cytosolic fractions. Nuclear localization was confirmed experimentally (PMID:14500886). Reason: Nuclear localization is documented for AIMP1. The protein can be found in both nuclear and cytoplasmic compartments. Supporting Evidence: PMID:14500886 In this study, the human multienzyme aminoacyl-tRNA synthetase "core" complex has been isolated from the nuclear and cytosolic compartments of human cells and purified to near homogeneity.
GO:0005783 endoplasmic reticulum	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: AIMP1 interacts with gp96 (HSP90B1) and regulates KDELR1-mediated ER retention. This is based on similarity evidence from mouse studies. Reason: The ER localization relates to AIMP1's role in regulating gp96/KDELR trafficking, which is a secondary function. The primary location is cytosol as part of the MSC.
GO:0005794 Golgi apparatus	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Golgi localization is inferred from subcellular location annotation, likely related to the secretory pathway for AIMP1/EMAP-II secretion. Reason: This may relate to the secretory pathway for the EMAP-II cytokine but is not the primary location for AIMP1's core function.
GO:0005829 cytosol	IEA GO_REF:0000044	ACCEPT	Summary: The cytosol is the primary location of AIMP1 where it functions as part of the multi-aminoacyl tRNA synthetase complex (MSC). Reason: Cytosolic localization is the core cellular location for AIMP1 as a scaffold component of the MSC. This is well-supported by multiple experimental studies. Supporting Evidence: PMID:19289464 The sequestration of its components within the cytoplasm rests on the presence of the eukaryotic-specific polypeptide extensions
GO:0006412 translation	IEA GO_REF:0000043	ACCEPT	Summary: AIMP1 is part of the MSC which contains aminoacyl-tRNA synthetases essential for translation. AIMP1 stimulates arginyl-tRNA synthetase activity. While AIMP1 does not directly catalyze aminoacylation, it supports translation machinery. Reason: As a scaffold component of the MSC that enhances aminoacyl-tRNA synthetase activity, AIMP1 participates in translation. This is a core function. Supporting Evidence: PMID:19131329 The data are consistent with a structural role of the three nonsynthetase components of MARS
GO:0006915 apoptotic process	IEA GO_REF:0000043	MARK AS OVER ANNOTATED	Summary: AIMP1 is CLEAVED BY caspase-7 during apoptosis, releasing the EMAP-II cytokine. Being a caspase substrate makes AIMP1 a TARGET of the apoptotic process, not a participant IN the apoptotic process. This is a classic example of over-annotation. Reason: The UniProt keyword "Apoptosis" was applied because AIMP1 is cleaved during apoptosis. However, this does not mean AIMP1 is involved in executing the apoptotic process. Being a substrate of caspase-7 makes AIMP1 a target/consequence of apoptosis, not an active participant. The GO annotation guidelines distinguish between genes that regulate/execute apoptosis vs. genes that are affected by it. Supporting Evidence: PMID:11306575 Endothelial-monocyte-activating polypeptide II (EMAPII) is an inflammatory cytokine released under apoptotic conditions... the EMAPII domain of p43 is released readily from the complex after in vitro digestion with caspase 7
GO:0006954 inflammatory response	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: The EMAP-II cytokine released from AIMP1 has proinflammatory activity. It induces migration of mononuclear phagocytes and activates inflammatory pathways. Reason: The inflammatory response is a function of the cleaved EMAP-II fragment, not the core function of full-length AIMP1. This is a secondary function that occurs after proteolytic processing. Supporting Evidence: PMID:11306575 the EMAPII domain of p43... is able to induce migration of human mononuclear phagocytes
GO:0005515 protein binding	IPI PMID:22190034 Global landscape of HIV-human protein complexes.	REMOVE	Summary: This annotation is from a large-scale HIV-human protein interaction study. The with/from column shows interaction with HIV gag protein. While technically correct, "protein binding" is uninformative for understanding AIMP1's function. Reason: Protein binding is an uninformative GO term that tells us nothing specific about AIMP1's molecular function. AIMP1 has more informative functional annotations (tRNA binding, homodimerization). The interaction with HIV proteins in a large-scale screen is not relevant to AIMP1's physiological function. Supporting Evidence: PMID:22190034 Global landscape of HIV-human protein complexes.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	REMOVE	Summary: Large-scale interactome study showing AIMP1 interacts with AIMP2 and TSNAX. The AIMP1-AIMP2 interaction is functionally meaningful (both are MSC scaffold components), but "protein binding" is too generic. Reason: The AIMP1-AIMP2 interaction within the MSC is biologically relevant, but the generic "protein binding" term does not capture this specificity. More informative annotations for MSC complex membership already exist. Supporting Evidence: PMID:25416956 A proteome-scale map of the human interactome network.
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	REMOVE	Summary: Another large-scale interactome study showing AIMP1-AIMP2 interaction. Same issue as above - protein binding is uninformative. Reason: Generic protein binding annotation from interactome study. The specific interaction is already captured by MSC complex membership annotations. Supporting Evidence: PMID:28514442 Architecture of the human interactome defines protein communities and disease networks.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	REMOVE	Summary: Large-scale proteomics study. AIMP1-AIMP2 interaction again. Reason: Redundant with other protein binding annotations and uninformative. Supporting Evidence: PMID:33961781 2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
GO:0048514 blood vessel morphogenesis	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: This annotation is transferred from rat ortholog based on Ensembl Compara. The EMAP-II cytokine has documented effects on endothelial cells, but this represents pharmacological/pathological effects rather than physiological function. Reason: Effects on blood vessel morphogenesis are attributed to the secreted EMAP-II cytokine at varying concentrations. This is not the core function of AIMP1 as an MSC scaffold. Supporting Evidence: PMID:11741979 EMAP II inhibited the growth of endothelial cells
GO:0051607 defense response to virus	IEA GO_REF:0000107	UNDECIDED	Summary: Transferred from rat ortholog. The basis for this annotation is unclear from the available literature on AIMP1's core functions. Reason: Cannot verify the basis for this annotation. AIMP1's role in antiviral defense is not well-characterized in the literature I have access to.
GO:0005829 cytosol	IDA GO_REF:0000052	ACCEPT	Summary: IDA evidence from HPA immunofluorescence data confirming cytosolic localization. Reason: Direct experimental evidence for cytosolic localization, consistent with AIMP1's role as an MSC component.
GO:0005737 cytoplasm	NAS PMID:32644155 3-Dimensional architecture of the human multi-tRNA synthetas...	ACCEPT	Summary: This publication describes the 3D architecture of the human multi-tRNA synthetase complex. Cytoplasmic localization is consistent with AIMP1's role in the MSC. Reason: Well-supported localization annotation for AIMP1 as part of the cytoplasmic MSC. Supporting Evidence: PMID:32644155 3-Dimensional architecture of the human multi-tRNA synthetase complex
GO:0006418 tRNA aminoacylation for protein translation	NAS PMID:32644155 3-Dimensional architecture of the human multi-tRNA synthetas...	ACCEPT	Summary: AIMP1 is a scaffold component of the MSC containing multiple aminoacyl-tRNA synthetases. While AIMP1 itself does not catalyze aminoacylation, it supports this process by organizing the complex and binding tRNA. Reason: AIMP1 participates in tRNA aminoacylation as a scaffold that stimulates arginyl-tRNA synthetase activity and binds tRNA for presentation to synthetases. Supporting Evidence: PMID:19131329 The data are consistent with a structural role of the three nonsynthetase components of MARS PMID:32644155 3-Dimensional architecture of the human multi-tRNA synthetase complex.
GO:0005515 protein binding	IPI PMID:24312579 Reinvestigation of aminoacyl-tRNA synthetase core complex by...	REMOVE	Summary: This study identified TARSL2 as a potential MSC member and confirmed AIMP1 interactions with MSC components including TARS3. The interaction is meaningful but "protein binding" is uninformative. Reason: Generic protein binding annotation. The specific interactions within the MSC are better captured by complex membership annotations. Supporting Evidence: PMID:24312579 eCollection 2013. Reinvestigation of aminoacyl-tRNA synthetase core complex by affinity purification-mass spectrometry reveals TARSL2 as a potential member of the complex.
GO:0070094 positive regulation of glucagon secretion	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: This annotation is based on sequence similarity to mouse AIMP1 (P31230), which has been shown to be involved in glucose homeostasis through glucagon secretion. UniProt states AIMP1 is "enriched in secretory vesicles of pancreatic alpha cells". Reason: This is a secondary function of AIMP1 not related to its core MSC scaffold role. The annotation is based on mouse ortholog data and represents a tissue-specific signaling function.
GO:0005615 extracellular space	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Based on similarity to mouse ortholog. AIMP1 can be secreted under various conditions. Reason: Extracellular localization is for the secreted form, secondary to cytosolic MSC function.
GO:0005829 cytosol	IDA PMID:19289464 Dynamic Organization of Aminoacyl-tRNA Synthetase Complexes ...	ACCEPT	Summary: Direct experimental evidence showing AIMP1 is part of cytosolic MSC complexes in human cells. This study examined subcellular localization of the MSC. Reason: Strong experimental support for cytosolic localization as part of the MSC. 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: This study dissected the structural organization of the MSC (called MARS in the paper) and showed AIMP1 (p43) is a core scaffold component. This is the primary cellular location and functional context for AIMP1. Reason: This is the core cellular component annotation for AIMP1. Direct experimental evidence shows AIMP1 is an integral scaffold component of the MSC. Supporting Evidence: PMID:19131329 This complex contains nine aminoacyl-tRNA synthetases and three auxiliary proteins... The data are consistent with a structural role of the three nonsynthetase components of MARS, with p38 connecting two subcomplexes
GO:0017101 aminoacyl-tRNA synthetase multienzyme complex	IDA PMID:10791971 Nucleolar localization of human methionyl-tRNA synthetase an...	ACCEPT	Summary: This paper primarily focuses on methionyl-tRNA synthetase (MRS) nucleolar localization, but also confirms that AIMP1 (p43) is part of the MSC through gel filtration studies. Reason: Provides additional experimental support for AIMP1 as an MSC component. Supporting Evidence: PMID:10791971 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...	UNDECIDED	Summary: This study identified GBP-1 (guanylate binding protein 1) binding partners by mass spectrometry. AIMP1 was identified as an interactor of GBP-1 (P32455). The functional significance of this interaction is unclear. Reason: The interaction with GBP-1 was identified in a mass spectrometry screen. The biological relevance of AIMP1 binding to this GTPase is not established. This may be an indirect or non-physiological interaction. Supporting Evidence: PMID:24337748 Mass spectrometry analyses showed that regulatory cytoskeletal proteins... are binding partners of GBP-1
GO:0005515 protein binding	IPI PMID:11741979 Interaction of the C-terminal domain of p43 and the alpha su...	MODIFY	Summary: This study showed EMAP-II (the C-terminal domain of AIMP1) binds to the alpha subunit of ATP synthase on the cell surface. This is a specific, functionally characterized interaction related to endothelial cell effects. Reason: This is a meaningful interaction but "protein binding" is too generic. The specific interaction with ATP5A1 on the cell surface mediates EMAP-II's effects on endothelial cells. However, this is the cleaved EMAP-II fragment, not full-length AIMP1. Proposed replacements: protein binding Supporting Evidence: PMID:11741979 The isolated protein was determined to be the alpha subunit of ATP synthase. The interaction of EMAP II and alpha-ATP synthase was confirmed by enzyme-linked immunosorbent assay and in vitro pull down assays
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	KEEP AS NON CORE	Summary: This study defined the membrane proteome of NK cells and detected AIMP1 in membrane fractions. This may relate to secreted/surface AIMP1/EMAP-II. Reason: Membrane association may relate to the secretory pathway or EMAP-II surface binding functions, not the core cytosolic MSC function. Supporting Evidence: PMID:19946888 Defining the membrane proteome of NK cells.
GO:0009986 cell surface	IDA PMID:11741979 Interaction of the C-terminal domain of p43 and the alpha su...	KEEP AS NON CORE	Summary: This study showed EMAP-II binds to alpha-ATP synthase on the cell surface. The cell surface localization refers to EMAP-II binding to its receptor, not AIMP1 being a cell surface protein. Reason: The study shows EMAP-II (the cleaved C-terminal fragment) binds to cell surface ATP synthase. This is a secondary function of the cytokine fragment. 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: Reactome annotation for cytosolic tRNA aminoacylation reaction (glutamate). AIMP1 is part of the MSC that performs this reaction. Reason: Consistent with AIMP1's role as an MSC scaffold component in the cytosol.
GO:0005829 cytosol	TAS Reactome:R-HSA-379865	ACCEPT	Summary: Reactome annotation for cytosolic proline tRNA aminoacylation. Reason: Consistent with AIMP1's role as an MSC scaffold component in the cytosol.
GO:0005829 cytosol	TAS Reactome:R-HSA-379867	ACCEPT	Summary: Reactome annotation for cytosolic aspartate tRNA aminoacylation. Reason: Consistent with AIMP1's role as an MSC scaffold component in the cytosol.
GO:0005829 cytosol	TAS Reactome:R-HSA-379893	ACCEPT	Summary: Reactome annotation for cytosolic isoleucine tRNA aminoacylation. Reason: Consistent with AIMP1's role as an MSC scaffold component in the cytosol.
GO:0005829 cytosol	TAS Reactome:R-HSA-379974	ACCEPT	Summary: Reactome annotation for cytosolic leucine tRNA aminoacylation. Reason: Consistent with AIMP1's role as an MSC scaffold component in the cytosol.
GO:0005829 cytosol	TAS Reactome:R-HSA-379982	ACCEPT	Summary: Reactome annotation for cytosolic glutamine tRNA aminoacylation. Reason: Consistent with AIMP1's role as an MSC scaffold component in the cytosol.
GO:0005829 cytosol	TAS Reactome:R-HSA-379993	ACCEPT	Summary: Reactome annotation for cytosolic arginine tRNA aminoacylation. Reason: Consistent with AIMP1's role as an MSC scaffold component in the cytosol.
GO:0005829 cytosol	TAS Reactome:R-HSA-379994	ACCEPT	Summary: Reactome annotation for cytosolic methionine tRNA aminoacylation. Reason: Consistent with AIMP1's role as an MSC scaffold component in the cytosol.
GO:0005829 cytosol	TAS Reactome:R-HSA-380008	ACCEPT	Summary: Reactome annotation for cytosolic lysine tRNA aminoacylation. Reason: Consistent with AIMP1's role as an MSC scaffold component in the cytosol.
GO:0005829 cytosol	TAS Reactome:R-HSA-9825759	ACCEPT	Summary: Reactome annotation for MAPK-dependent phosphorylation of KARS. AIMP1 is part of the MSC containing KARS. Reason: Consistent with AIMP1's role as an MSC scaffold component in the cytosol.
GO:0000049 tRNA binding	IDA PMID:11306575 The EMAPII cytokine is released from the mammalian multisynt...	ACCEPT	Summary: Direct experimental evidence showing p43/AIMP1 has strong tRNA binding capacity (Kd = 0.2 microM). The tRNA binding is mediated by both N and C terminal domains working together. Reason: Strong experimental evidence for tRNA binding as a core molecular function of AIMP1. This is essential for its role in the MSC. Supporting Evidence: PMID:11306575 p43/proEMAPII has a strong tRNA binding capacity (K(D) = 0.2 microm) as compared with its isolated N or C domains (7.5 microm and 40 microm, respectively)
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: This study showed EMAP-II inhibits endothelial cell growth by binding to cell surface ATP synthase. This is a function of the cleaved EMAP-II cytokine fragment. Reason: The anti-proliferative effect on endothelial cells is a function of the secreted EMAP-II fragment, not the core MSC scaffold function of full-length AIMP1. 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: Based on similarity to mouse ortholog. The EMAP-II domain has documented cytokine activity inducing phagocyte migration. Reason: Cytokine activity is a secondary function of the cleaved EMAP-II fragment. Supporting Evidence: PMID:11306575 the EMAPII domain of p43 is released readily from the complex after in vitro digestion with caspase 7 and is able to induce migration of human mononuclear phagocytes
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: This study showed EMAP-II/p43 can act as a signaling molecule affecting endothelial cells through interaction with cell surface ATP synthase. Reason: Cell-cell signaling is a function of the secreted EMAP-II cytokine, not the core MSC scaffold function. Supporting Evidence: PMID:11741979 p43 is also secreted to induce proinflammatory genes
GO:0017101 aminoacyl-tRNA synthetase multienzyme complex	IDA PMID:14500886 Isolation and characterization of human nuclear and cytosoli...	ACCEPT	Summary: This study isolated and characterized the MSC from human cells and demonstrated that p43/AIMP1 is an integral component. Reason: Direct experimental evidence confirming AIMP1 is part of the MSC. This is the core cellular context for AIMP1 function. Supporting Evidence: PMID:14500886 gel filtration and immunoblot analysis demonstrate that a major biological role for the cytokine precursor p43 is as an integral part of the multisynthetase complex
GO:0042803 protein homodimerization activity	IDA PMID:11306575 The EMAPII cytokine is released from the mammalian multisynt...	ACCEPT	Summary: The EMAP-II domain structure shows it exists as a homodimer. Crystal structures confirm this dimeric arrangement. Reason: Homodimerization is a documented property of AIMP1, particularly the EMAP-II domain. This may be relevant for its function in the MSC. Supporting Evidence: PMID:11306575 Its proEMAPII precursor proved to be identical to the auxiliary p43 component of the aminoacyl-tRNA synthetase complex.
GO:0050900 leukocyte migration	IDA PMID:11306575 The EMAPII cytokine is released from the mammalian multisynt...	KEEP AS NON CORE	Summary: The EMAP-II cytokine released from AIMP1 induces migration of mononuclear phagocytes. This is a chemotactic activity of the cytokine. Reason: Leukocyte migration is induced by the cleaved EMAP-II cytokine fragment. This is a secondary function, not the core MSC scaffold role. Supporting Evidence: PMID:11306575 the EMAPII domain of p43... is able to induce migration of human mononuclear phagocytes

Core Functions

AIMP1 is a non-catalytic scaffold component of the MSC (multi-aminoacyl tRNA synthetase complex). Multiple studies confirm it is an integral part of this complex along with AIMP2 and AIMP3 (PMID:19131329, PMID:14500886). The complex contains nine aminoacyl-tRNA synthetases.

Molecular Function:

tRNA binding

Directly Involved In:

tRNA aminoacylation for protein translation

Cellular Locations:

cytosol

In Complex:

aminoacyl-tRNA synthetase multienzyme complex

References

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000052

Gene Ontology annotation based on curation of immunofluorescence data

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000108

Automatic assignment of GO terms using logical inference, based on on inter-ontology links

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:10791971

Nucleolar localization of human methionyl-tRNA synthetase and its role in ribosomal RNA synthesis.

AIMP1 (p43) co-elutes with MSC components in gel filtration

PMID:11306575

The EMAPII cytokine is released from the mammalian multisynthetase complex after cleavage of its p43/proEMAPII component.

p43/AIMP1 has strong tRNA binding (Kd = 0.2 microM)
EMAP-II is released by caspase-7 cleavage during apoptosis
EMAP-II induces mononuclear phagocyte migration
tRNA binding is lost upon EMAP-II release

PMID:11741979

Interaction of the C-terminal domain of p43 and the alpha subunit of ATP synthase. Its functional implication in endothelial cell proliferation.

EMAP-II binds cell surface alpha-ATP synthase
EMAP-II inhibits endothelial cell proliferation

PMID:14500886

Isolation and characterization of human nuclear and cytosolic multisynthetase complexes and the intracellular distribution of p43/EMAPII.

p43/AIMP1 is an integral part of the MSC
MSC isolated from both nuclear and cytosolic compartments

PMID:19131329

Dissection of the structural organization of the aminoacyl-tRNA synthetase complex.

AIMP1 (p43) is one of three auxiliary scaffold proteins in MSC
Structural role confirmed by siRNA knockdown studies

PMID:19289464

Dynamic Organization of Aminoacyl-tRNA Synthetase Complexes in the Cytoplasm of Human Cells.

AIMP1 is sequestered in cytoplasm as part of MSC
MSC components interact with ribosomes and actin cytoskeleton

PMID:19946888

Defining the membrane proteome of NK cells.

PMID:22190034

Global landscape of HIV-human protein complexes.

PMID:24312579

Reinvestigation of aminoacyl-tRNA synthetase core complex by affinity purification-mass spectrometry reveals TARSL2 as a potential member of the complex.

Confirmed AIMP1 as MSC component
Identified interaction with TARS3

PMID:24337748

Guanylate binding protein 1-mediated interaction of T cell antigen receptor signaling with the cytoskeleton.

AIMP1 identified as GBP-1 interactor by mass spectrometry

PMID:25416956

A proteome-scale map of the human interactome network.

PMID:28514442

Architecture of the human interactome defines protein communities and disease networks.

PMID:32644155

3-Dimensional architecture of the human multi-tRNA synthetase complex.

PMID:33961781

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

Reactome:R-HSA-379861

glutamate + tRNA(Glu) + ATP => Glu-tRNA(Glu) + AMP + pyrophosphate

Reactome:R-HSA-379865

proline + tRNA(Pro) + ATP => Pro-tRNA(Pro) + AMP + pyrophosphate

Reactome:R-HSA-379867

aspartate + tRNA(Asp) + ATP => Asp-tRNA(Asp) + AMP + pyrophosphate

Reactome:R-HSA-379893

isoleucine + tRNA(Ile) + ATP => Ile-tRNA(Ile) + AMP + pyrophosphate

Reactome:R-HSA-379974

leucine + tRNA(Leu) + ATP => Leu-tRNA(Leu) + AMP + pyrophosphate

Reactome:R-HSA-379982

glutamine + tRNA(Gln) + ATP => Gln-tRNA(Gln) + AMP + pyrophosphate

Reactome:R-HSA-379993

arginine + tRNA(Arg) + ATP => Arg-tRNA(Arg) + AMP + pyrophosphate

Reactome:R-HSA-379994

methionine + tRNA(Met) + ATP => Met-tRNA(Met) + AMP + pyrophosphate

Reactome:R-HSA-380008

lysine + tRNA(Lys) + ATP => Lys-tRNA(Lys) + AMP + pyrophosphate

Reactome:R-HSA-9825759

MAPK-dependent phosphorylation of KARS

file:human/AIMP1/AIMP1-deep-research-falcon.md

Deep research report on AIMP1

📚 Additional Documentation

Deep Research Falcon

(AIMP1-deep-research-falcon.md)

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organism: human
gene_id: AIMP1
gene_symbol: AIMP1
uniprot_accession: Q12904
protein_description: 'RecName: Full=Aminoacyl tRNA synthase complex-interacting
multifunctional protein 1; AltName: Full=Multisynthase complex auxiliary component
p43; Contains: RecName: Full=Endothelial monocyte-activating polypeptide 2; Short=EMAP-2;
AltName: Full=Endothelial monocyte-activating polypeptide II; Short=EMAP-II; AltName:
Full=Small inducible cytokine subfamily E member 1;'
gene_info: Name=AIMP1; Synonyms=EMAP2, SCYE1;
organism_full: Homo sapiens (Human).
protein_family: Not specified in UniProt
protein_domains: NA-bd_OB-fold. (IPR012340); tRNA-bd_dom. (IPR002547); Tyrosine-tRNA_ligase_regulator.
(IPR051270); tRNA_bind (PF01588)
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Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: Q12904
Protein Description: RecName: Full=Aminoacyl tRNA synthase complex-interacting multifunctional protein 1; AltName: Full=Multisynthase complex auxiliary component p43; Contains: RecName: Full=Endothelial monocyte-activating polypeptide 2; Short=EMAP-2; AltName: Full=Endothelial monocyte-activating polypeptide II; Short=EMAP-II; AltName: Full=Small inducible cytokine subfamily E member 1;
Gene Information: Name=AIMP1; Synonyms=EMAP2, SCYE1;
Organism (full): Homo sapiens (Human).
Protein Family: Not specified in UniProt
Key Domains: NA-bd_OB-fold. (IPR012340); tRNA-bd_dom. (IPR002547); Tyrosine-tRNA_ligase_regulator. (IPR051270); tRNA_bind (PF01588)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "AIMP1" matches the protein description above
Verify the organism is correct: Homo sapiens (Human).
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'AIMP1' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

Research Target:

Please provide a comprehensive research report on the gene AIMP1 (gene ID: AIMP1, UniProt: Q12904) in human.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Output

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: Q12904
Protein Description: RecName: Full=Aminoacyl tRNA synthase complex-interacting multifunctional protein 1; AltName: Full=Multisynthase complex auxiliary component p43; Contains: RecName: Full=Endothelial monocyte-activating polypeptide 2; Short=EMAP-2; AltName: Full=Endothelial monocyte-activating polypeptide II; Short=EMAP-II; AltName: Full=Small inducible cytokine subfamily E member 1;
Gene Information: Name=AIMP1; Synonyms=EMAP2, SCYE1;
Organism (full): Homo sapiens (Human).
Protein Family: Not specified in UniProt
Key Domains: NA-bd_OB-fold. (IPR012340); tRNA-bd_dom. (IPR002547); Tyrosine-tRNA_ligase_regulator. (IPR051270); tRNA_bind (PF01588)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "AIMP1" matches the protein description above
Verify the organism is correct: Homo sapiens (Human).
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Please provide a comprehensive research report on the gene AIMP1 (gene ID: AIMP1, UniProt: Q12904) in human.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Research plan status: Verified identity and domains of human AIMP1 (UniProt Q12904) and gathered 2023–2024 evidence on structure, intracellular roles in the multi-aminoacyl tRNA synthetase complex (MSC), extracellular processing/signaling, and emerging applications (hair growth peptide TN41). Below is a comprehensive, citation-based report prioritized to recent, authoritative sources.

Comprehensive research report: AIMP1 (Q12904) — structure, function, localization, and recent developments

1) Key concepts and definitions
- Identity and synonyms: AIMP1 (also known as p43; gene aliases EMAP2, SCYE1) is a human subunit of the multi-aminoacyl tRNA synthetase complex (MSC). AIMP1 contains an EMAP-II-like OB-fold tRNA-binding module and functions as an organizational scaffold in the MSC (Nature Communications, 2024-07; https://doi.org/10.1038/s41467-024-50730-1) (juru2024structuralbasisof pages 1-2). AIMP1 can be proteolytically processed to release the cytokine EMAP-II, historically linked to proinflammatory and anti-/pro-angiogenic effects depending on context (Nature Communications, 2024-07; https://doi.org/10.1038/s41467-024-50730-1; Int J Biol Sci, 2024-10-21; https://doi.org/10.7150/ijbs.101127) (juru2024structuralbasisof pages 1-2, kim2024aimp1derivedpeptidesecreted pages 15-15).
- Domains: AIMP1 harbors an EMAPII-like OB-fold that engages tRNA, and additional basic regions that contribute to multivalent tRNA contacts in the MSC. The OB-fold region is the part proteolytically released as EMAP-II during apoptosis (Nature Communications, 2024-07; https://doi.org/10.1038/s41467-024-50730-1) (juru2024structuralbasisof pages 1-2).
- Primary role: In the cytosol, AIMP1 is a non-enzymatic scaffolding/organizing subunit of the MSC, aiding assembly and potentially tRNA recruitment via its OB-fold, rather than catalyzing aminoacylation (Nature Communications, 2024-07; https://doi.org/10.1038/s41467-024-50730-1) (juru2024structuralbasisof pages 1-2).

2) Structure and molecular mechanism (with 2023–2024 updates)
- OB-fold recognition of tRNA 3′ ends: A 2024 co-crystal structure of an EMAPII-like OB-fold protein (Trbp111) bound to tRNAIle at 2.6 Å revealed that EMAPII-like OB folds recognize the single-stranded tRNA 3′ end, with precise readout of the conserved 3′-CA dinucleotide. The study places AIMP1’s OB-fold in this structural paradigm and explains its tRNA-binding function in the MSC (Nature Communications, 2024-07; https://doi.org/10.1038/s41467-024-50730-1) (juru2024structuralbasisof pages 1-2).
- Supplementary contacts: In Arc1p/AIMP1, additional basic regions outside the OB-fold enhance affinity via contacts to the tRNA body, consistent with a multivalent tRNA-recruitment role in the MSC (Nature Communications, 2024-07; https://doi.org/10.1038/s41467-024-50730-1) (juru2024structuralbasisof pages 1-2).
- Proteolysis and EMAP-II generation: The OB-fold region of AIMP1 is cleaved during apoptosis (caspase-7 is implicated), releasing EMAP-II and eliminating tRNA-binding capacity, thereby transitioning AIMP1 from intracellular scaffold to extracellular cytokine (Nature Communications, 2024-07; https://doi.org/10.1038/s41467-024-50730-1) (juru2024structuralbasisof pages 1-2).

3) Intracellular role in the MSC and binding partners
- MSC scaffold: Human AIMP1 acts with AIMP2/AIMP3 as an organizational scaffold for MSC aminoacyl-tRNA synthetases and can directly complex with specific synthetases (e.g., ArgRS/GlnRS), consistent with structural analyses of MSC subcomplexes in prior work and summarized in recent literature (Int J Biol Sci, 2024-10-21; https://doi.org/10.7150/ijbs.101127) (kim2024aimp1derivedpeptidesecreted pages 15-15).
- Immunoregulatory interactions and trafficking: AIMP1 interacts with the ER chaperone gp96 and COPI/KDELR machinery; loss of AIMP1 misroutes gp96 to the plasma membrane. Mechanistically, AIMP1 also binds and stabilizes Smurf2, promoting TGF-β receptor ubiquitination and degradation, thereby antagonizing TGF-β signaling. Region mapping indicates AIMP1 residues 193–312 bind Smurf2 WW domains, while an N-terminal region associates with gp96/KDELR (Frontiers in Immunology, 2024-06; https://doi.org/10.3389/fimmu.2024.1423510) (amanya2024themarscomplex pages 9-10).

4) Extracellular biology: EMAP-II and AIMP1-derived peptides
- EMAP-II release and function: C-terminal cleavage of AIMP1 yields EMAP-II, a proinflammatory cytokine associated with macrophage recruitment, inflammation, and angiogenesis control. EMAP-II generation coincides with apoptosis-associated caspase activation (Nature Communications, 2024-07; https://doi.org/10.1038/s41467-024-50730-1) (juru2024structuralbasisof pages 1-2). Reviews summarize EMAP-II as elevated in microglia and contributing to proinflammatory programs (Frontiers in Immunology, 2024-06; https://doi.org/10.3389/fimmu.2024.1423510) (amanya2024themarscomplex pages 8-9).
- N-terminal AIMP1 fragment and hair growth (2024): AIMP1 also yields a secreted N-terminal peptide under Wnt stimulation in hair follicle stem cells. MMP1 cleaves AIMP1 to generate an N-terminal fragment (active core TN41, aa 6–46), which is secreted and activates dermal papilla cells (DPCs), triggering Akt and ERK signaling and increasing β-catenin, thereby promoting hair shaft elongation and hair regrowth (Int J Biol Sci, 2024-10-21; https://doi.org/10.7150/ijbs.101127) (kim2024aimp1derivedpeptidesecreted pages 1-2, kim2024aimp1derivedpeptidesecreted pages 3-5).

5) Localization
- Cytosolic and MSC-associated: AIMP1 is primarily cytosolic as part of the MSC; the OB-fold-mediated tRNA interaction is consistent with cytosolic tRNA handling (Nature Communications, 2024-07; https://doi.org/10.1038/s41467-024-50730-1) (juru2024structuralbasisof pages 1-2).
- Dynamic subcellular shifts in disease: In chondrocytes, AIMP1 is reported to shift from nuclear localization in healthy cells to cytoplasmic in osteoarthritis; reduction of AIMP1 reinstates TGF-β signaling and cartilage markers in models (Frontiers in Immunology, 2024-06; https://doi.org/10.3389/fimmu.2024.1423510) (amanya2024themarscomplex pages 10-11).
- Secreted extracellular fragments: Under Wnt stimulation, HFSCs secrete an N-terminal AIMP1 fragment processed by MMP1; this was verified by fragment-specific antibodies and protease inhibitor studies (Int J Biol Sci, 2024-10-21; https://doi.org/10.7150/ijbs.101127) (kim2024aimp1derivedpeptidesecreted pages 3-5, kim2024aimp1derivedpeptidesecreted pages 1-2).

6) Pathways and signaling roles
- TGF-β pathway negative regulation: AIMP1 physically supports Smurf2-mediated ubiquitination and degradation of TGF-β receptors, thereby suppressing TGF-β signaling; loss of AIMP1 enhances TGF-β-driven gene expression. This mechanism links AIMP1 to fibrosis and cartilage biology (Frontiers in Immunology, 2024-06; https://doi.org/10.3389/fimmu.2024.1423510) (amanya2024themarscomplex pages 9-10, amanya2024themarscomplex pages 10-11).
- Immune activation and NF-κB/MAPK axes: AIMP1 (full-length or EMAP-II) engages dendritic cells, B cells, and microglia, elevating IL-6, IL-1β, TNF and activation markers through JNK/p38/NF-κB signaling; overactivity is implicated in autoimmunity and multiple myeloma osteoclastogenesis (Frontiers in Immunology, 2024-06; https://doi.org/10.3389/fimmu.2024.1423510) (amanya2024themarscomplex pages 8-9).
- Angiogenesis and apoptosis: The AIMP1/EMAP-II axis is linked to macrophage recruitment, inflammation, and angiogenesis control in the context of OB-fold cleavage; EMAP-II has classically been linked to endothelial responses and apoptosis, as summarized in 2024 structural work (Nature Communications, 2024-07; https://doi.org/10.1038/s41467-024-50730-1) (juru2024structuralbasisof pages 1-2) and in overview of p43 extracellular activities (Int J Biol Sci, 2024-10-21; https://doi.org/10.7150/ijbs.101127) (kim2024aimp1derivedpeptidesecreted pages 15-15).
- Hair follicle signaling: The AIMP1-derived TN41 fragment activates Akt/ERK and stabilizes β-catenin in DPCs, promoting hair growth (Int J Biol Sci, 2024-10-21; https://doi.org/10.7150/ijbs.101127) (kim2024aimp1derivedpeptidesecreted pages 1-2).

7) Recent developments (2023–2024 priority) and expert perspectives
- Structural advance: 2024 elucidation of EMAPII-like OB-fold recognition of the universal tRNA 3′-CA explains how AIMP1’s OB-fold engages tRNA in the MSC, and how cleavage would repurpose this domain as a cytokine (Nature Communications, 2024-07; https://doi.org/10.1038/s41467-024-50730-1) (juru2024structuralbasisof pages 1-2).
- Immune regulation by the mARS complex: A 2024 immunology synthesis details AIMP1’s roles in immune cell activation, ER chaperone trafficking (gp96), suppression of TGF-β signaling via Smurf2, and disease links, highlighting therapeutic exploration (Frontiers in Immunology, 2024-06; https://doi.org/10.3389/fimmu.2024.1423510) (amanya2024themarscomplex pages 9-10, amanya2024themarscomplex pages 8-9, amanya2024themarscomplex pages 10-11).
- Application/hair biology: A 2024 study identifies a defined N-terminal peptide (TN41, aa 6–46) generated by MMP1 that enhances human hair follicle shaft growth ex vivo and accelerates hair regrowth in mice through DPC activation, nominating AIMP1-derived peptides as potential therapeutics in alopecia (Int J Biol Sci, 2024-10-21; https://doi.org/10.7150/ijbs.101127) (kim2024aimp1derivedpeptidesecreted pages 1-2, kim2024aimp1derivedpeptidesecreted pages 3-5).

8) Current applications and real-world implementations
- Preclinical therapeutic concepts: Anti-AIMP1 monoclonal antibody approaches (e.g., reported as reducing lupus nephritis severity and inflammatory cytokines while increasing IL-10+ Tregs) and exosomal siAIMP1 are discussed in 2024 immunology synthesis, suggesting avenues for autoimmune disease and myeloma-associated bone disease; clinical translation status is preclinical in the cited review (Frontiers in Immunology, 2024-06; https://doi.org/10.3389/fimmu.2024.1423510) (amanya2024themarscomplex pages 8-9, amanya2024themarscomplex pages 9-10).
- Regenerative dermatology: The TN41 peptide improved hair shaft elongation in cultured human hair follicles and hair regrowth in mouse models, supporting development of peptide-based hair growth agents (Int J Biol Sci, 2024-10-21; https://doi.org/10.7150/ijbs.101127) (kim2024aimp1derivedpeptidesecreted pages 1-2).

9) Relevant statistics and concrete data points
- Hair follicle biology (2024): AIMP1 protein intensity was approximately three-fold higher in healthy versus sparse-hair regions; inducible AIMP1 mice achieved >80% back-hair regrowth versus controls; MMP1 cleaved AIMP1 within 2 h and completely by 4 h in vitro; siRNA against AIMP1 reduced the secreted N-terminal fragment by ~50% (Int J Biol Sci, 2024-10-21; https://doi.org/10.7150/ijbs.101127) (kim2024aimp1derivedpeptidesecreted pages 3-5, kim2024aimp1derivedpeptidesecreted pages 1-2).
- Mechanistic mapping (immunoregulation): AIMP1 residues 193–312 bind Smurf2 WW domains; AIMP1–gp96/KDELR interactions influence gp96 surface display; anti-AIMP1 reduced IFN-γ, IL-17A, IL-6 and increased IL-10+ Tregs in lupus nephritis models (Frontiers in Immunology, 2024-06; https://doi.org/10.3389/fimmu.2024.1423510) (amanya2024themarscomplex pages 9-10).

10) Expert analysis and open questions
- Receptor identity for EMAP-II and AIMP1-derived fragments: 2024 sources emphasize functional outcomes (inflammation, macrophage recruitment, angiogenesis) but do not definitively establish a single human receptor in these new data; receptor usage may be cell- and context-dependent and remains an important area for clarification (Nature Communications, 2024-07; https://doi.org/10.1038/s41467-024-50730-1; Frontiers in Immunology, 2024-06; https://doi.org/10.3389/fimmu.2024.1423510) (juru2024structuralbasisof pages 1-2, amanya2024themarscomplex pages 8-9, amanya2024themarscomplex pages 9-10).
- Post-translational regulation and trafficking: The precise signals and PTMs controlling AIMP1 dissociation from the MSC, cleavage (beyond caspases in apoptosis and MMP1 in HFSCs), and secretory routes require further definition (Frontiers in Immunology, 2024-06; https://doi.org/10.3389/fimmu.2024.1423510; Int J Biol Sci, 2024-10-21; https://doi.org/10.7150/ijbs.101127) (amanya2024themarscomplex pages 10-11, kim2024aimp1derivedpeptidesecreted pages 1-2).

11) Mandatory verification checklist
- Gene symbol and description match UniProt: AIMP1 (p43) with EMAP-II contained region — verified and consistent with human (Homo sapiens) protein Q12904 (Nature Communications, 2024-07; Int J Biol Sci, 2024-10-21) (juru2024structuralbasisof pages 1-2, kim2024aimp1derivedpeptidesecreted pages 15-15).
- Organism: All cited primary 2024 structural/immunology sources explicitly discuss human AIMP1 or place AIMP1 within metazoan MSC biology; the hair study uses human hair follicles and mouse models (juru2024structuralbasisof pages 1-2, kim2024aimp1derivedpeptidesecreted pages 1-2).
- Domains/family: EMAPII-like OB-fold and tRNA-binding confirmed (juru2024structuralbasisof pages 1-2). No conflicting gene symbol usage detected.

References (URLs and publication dates)
- Juru AU, Ghirlando R, Zhang J. Structural basis of tRNA recognition by the widespread OB fold. Nature Communications. 2024-07. https://doi.org/10.1038/s41467-024-50730-1 (juru2024structuralbasisof pages 1-2).
- Amanya SB, Oyewole-Said D, Ernste KJ, et al. The mARS complex: a critical mediator of immune regulation and homeostasis. Frontiers in Immunology. 2024-06. https://doi.org/10.3389/fimmu.2024.1423510 (amanya2024themarscomplex pages 10-11, amanya2024themarscomplex pages 8-9, amanya2024themarscomplex pages 9-10).
- Kim Y, Kim SB, Lee H, et al. AIMP1-Derived Peptide Secreted from Hair Follicle Stem Cells Promotes Hair Growth by Activating Dermal Papilla Cells. International Journal of Biological Sciences. 2024-10-21. https://doi.org/10.7150/ijbs.101127 (kim2024aimp1derivedpeptidesecreted pages 1-2, kim2024aimp1derivedpeptidesecreted pages 3-5, kim2024aimp1derivedpeptidesecreted pages 15-15).

Notes on evidence limits
- Historically reported EMAP-II receptors (e.g., CXCR3 variants) and anti-/pro-angiogenic biphasic activities are part of the legacy literature; however, explicit receptor validation and dose-dependence parameters were not directly available in the 2023–2024 sources cited here. Where receptor identity or precise angiogenic polarity could not be confirmed from 2024 literature, claims have been framed cautiously (juru2024structuralbasisof pages 1-2, amanya2024themarscomplex pages 8-9, amanya2024themarscomplex pages 9-10).

References

(juru2024structuralbasisof pages 1-2): Aline Umuhire Juru, Rodolfo Ghirlando, and Jinwei Zhang. Structural basis of trna recognition by the widespread ob fold. Nature Communications, Jul 2024. URL: https://doi.org/10.1038/s41467-024-50730-1, doi:10.1038/s41467-024-50730-1. This article has 7 citations and is from a highest quality peer-reviewed journal.
(kim2024aimp1derivedpeptidesecreted pages 15-15): YounHa Kim, Sang Bum Kim, Ho Lee, Doyeun Kim, Soon Sun Bak, Ina Yoon, Seongmin Cho, Seung Jae Jeong, Yoon Jeon, Jina Kim, Ji-hee Kim, Soohwan Oh, Khas-Erdene Battogtokh, Min Chul Park, Young Kwan Sung, and Sunghoon Kim. Aimp1-derived peptide secreted from hair follicle stem cells promotes hair growth by activating dermal papilla cells. International Journal of Biological Sciences, 20:5764-5778, Oct 2024. URL: https://doi.org/10.7150/ijbs.101127, doi:10.7150/ijbs.101127. This article has 5 citations and is from a peer-reviewed journal.
(amanya2024themarscomplex pages 9-10): Sharon Bright Amanya, Damilola Oyewole-Said, Keenan J. Ernste, Nalini Bisht, Arnav Murthy, Jonathan Vazquez-Perez, Vanaja Konduri, and William K. Decker. The mars complex: a critical mediator of immune regulation and homeostasis. Frontiers in Immunology, Jun 2024. URL: https://doi.org/10.3389/fimmu.2024.1423510, doi:10.3389/fimmu.2024.1423510. This article has 0 citations and is from a peer-reviewed journal.
(amanya2024themarscomplex pages 8-9): Sharon Bright Amanya, Damilola Oyewole-Said, Keenan J. Ernste, Nalini Bisht, Arnav Murthy, Jonathan Vazquez-Perez, Vanaja Konduri, and William K. Decker. The mars complex: a critical mediator of immune regulation and homeostasis. Frontiers in Immunology, Jun 2024. URL: https://doi.org/10.3389/fimmu.2024.1423510, doi:10.3389/fimmu.2024.1423510. This article has 0 citations and is from a peer-reviewed journal.
(kim2024aimp1derivedpeptidesecreted pages 1-2): YounHa Kim, Sang Bum Kim, Ho Lee, Doyeun Kim, Soon Sun Bak, Ina Yoon, Seongmin Cho, Seung Jae Jeong, Yoon Jeon, Jina Kim, Ji-hee Kim, Soohwan Oh, Khas-Erdene Battogtokh, Min Chul Park, Young Kwan Sung, and Sunghoon Kim. Aimp1-derived peptide secreted from hair follicle stem cells promotes hair growth by activating dermal papilla cells. International Journal of Biological Sciences, 20:5764-5778, Oct 2024. URL: https://doi.org/10.7150/ijbs.101127, doi:10.7150/ijbs.101127. This article has 5 citations and is from a peer-reviewed journal.
(kim2024aimp1derivedpeptidesecreted pages 3-5): YounHa Kim, Sang Bum Kim, Ho Lee, Doyeun Kim, Soon Sun Bak, Ina Yoon, Seongmin Cho, Seung Jae Jeong, Yoon Jeon, Jina Kim, Ji-hee Kim, Soohwan Oh, Khas-Erdene Battogtokh, Min Chul Park, Young Kwan Sung, and Sunghoon Kim. Aimp1-derived peptide secreted from hair follicle stem cells promotes hair growth by activating dermal papilla cells. International Journal of Biological Sciences, 20:5764-5778, Oct 2024. URL: https://doi.org/10.7150/ijbs.101127, doi:10.7150/ijbs.101127. This article has 5 citations and is from a peer-reviewed journal.
(amanya2024themarscomplex pages 10-11): Sharon Bright Amanya, Damilola Oyewole-Said, Keenan J. Ernste, Nalini Bisht, Arnav Murthy, Jonathan Vazquez-Perez, Vanaja Konduri, and William K. Decker. The mars complex: a critical mediator of immune regulation and homeostasis. Frontiers in Immunology, Jun 2024. URL: https://doi.org/10.3389/fimmu.2024.1423510, doi:10.3389/fimmu.2024.1423510. This article has 0 citations and is from a peer-reviewed journal.

Citations

juru2024structuralbasisof pages 1-2
amanya2024themarscomplex pages 9-10
amanya2024themarscomplex pages 8-9
amanya2024themarscomplex pages 10-11
https://doi.org/10.1038/s41467-024-50730-1
https://doi.org/10.1038/s41467-024-50730-1;
https://doi.org/10.7150/ijbs.101127
https://doi.org/10.3389/fimmu.2024.1423510
https://doi.org/10.3389/fimmu.2024.1423510;
https://doi.org/10.1038/s41467-024-50730-1,
https://doi.org/10.7150/ijbs.101127,
https://doi.org/10.3389/fimmu.2024.1423510,

📄 View Raw YAML

id: Q12904
gene_symbol: AIMP1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  AIMP1 (also known as p43) is a non-catalytic scaffold component of the multi-aminoacyl
  tRNA synthetase complex (MSC) in mammals. It contains an EMAPII-like OB-fold domain
  that binds tRNA and contributes to tRNA recruitment for the MSC. AIMP1 interacts
  with RARS1 (arginyl-tRNA synthetase) and QARS1 (glutaminyl-tRNA synthetase) within
  the complex and stimulates arginyl-tRNA synthetase catalytic activity. The protein
  is primarily cytosolic where it functions as part of the MSC. Upon apoptosis, AIMP1
  is cleaved by caspase-7 at its C-terminus to release the EMAP-II cytokine domain,
  which has proinflammatory and anti-angiogenic activities. This cleavage eliminates
  tRNA-binding capacity and represents a transition from intracellular scaffold to
  extracellular cytokine. AIMP1 also has additional signaling functions including
  negative regulation of TGF-beta signaling through Smurf2 stabilization, and regulation
  of ER chaperone trafficking (gp96/KDELR1). Mutations in AIMP1 cause hypomyelinating
  leukodystrophy type 3 (HLD3).
existing_annotations:
  - term:
      id: GO:0007165
      label: signal transduction
    evidence_type: IEA
    original_reference_id: GO_REF:0000108
    review:
      summary: >-
        This IEA annotation is inferred from AIMP1 having cytokine activity (GO:0005125).
        The cleaved EMAP-II domain does have signaling functions, but signal transduction
        is overly broad for a protein whose core function is as an MSC scaffold.
      action: KEEP_AS_NON_CORE
      reason: >-
        AIMP1's primary function is as a scaffold in the MSC. The signaling functions
        attributed to AIMP1 are secondary to its core role and are primarily associated
        with the cleaved EMAP-II fragment. This annotation is not incorrect but represents
        a non-core function.
      supported_by:
        - reference_id: PMID:11306575
          supporting_text: "The EMAPII cytokine is released from the mammalian multisynthetase
            complex after cleavage of its p43/proEMAPII component."
        - reference_id: file:human/AIMP1/AIMP1-deep-research-falcon.md
          supporting_text: 'model: Edison Scientific Literature'
  - term:
      id: GO:0000049
      label: tRNA binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: >-
        AIMP1 contains an EMAPII-like OB-fold domain that binds tRNA. This is well-supported
        by experimental data showing strong tRNA binding capacity (Kd = 0.2 microM)
        for
        full-length p43 (PMID:11306575). The OB-fold recognizes the 3'-CA dinucleotide
        of tRNA as shown in 2024 structural work.
      action: ACCEPT
      reason: >-
        tRNA binding is a core molecular function of AIMP1 within the MSC, mediated
        by
        its OB-fold domain. This is supported by direct experimental evidence.
      supported_by:
        - reference_id: PMID:11306575
          supporting_text: "p43/proEMAPII has a strong tRNA binding capacity (K(D)
            = 0.2 microm) as compared with its isolated N or C domains (7.5 microm
            and 40 microm, respectively)."
  - term:
      id: GO:0001525
      label: angiogenesis
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: >-
        The UniProt keyword mapping is based on the dose-dependent biphasic effects
        of
        p43/EMAP-II on endothelial cells. At low concentrations AIMP1 promotes endothelial
        migration; at high concentrations it induces apoptosis. These are pharmacological
        effects of the cleaved EMAP-II cytokine, not the physiological core function.
      action: KEEP_AS_NON_CORE
      reason: >-
        The angiogenesis-related effects are secondary functions of the secreted/cleaved
        EMAP-II fragment, not the core function of AIMP1 as an MSC scaffold. The biphasic
        dose-dependent nature suggests this is a pharmacological rather than physiological
        function.
      supported_by:
        - reference_id: PMID:11741979
          supporting_text: "EMAP II inhibited the growth of endothelial cells, and
            this effect was relieved by soluble alpha-ATP synthase."
  - term:
      id: GO:0003723
      label: RNA binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: >-
        AIMP1 binds tRNA specifically via its OB-fold domain. The more specific term
        tRNA binding (GO:0000049) is already annotated with IDA evidence and is more
        appropriate.
      action: ACCEPT
      reason: >-
        RNA binding is a parent term of tRNA binding. While redundant with the more
        specific
        tRNA binding annotation, it is not incorrect. The IEA annotation provides
        broader
        coverage.
      supported_by:
        - reference_id: PMID:11306575
          supporting_text: "p43/proEMAPII has a strong tRNA binding capacity (K(D)
            = 0.2 microm)"
  - term:
      id: GO:0005125
      label: cytokine activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: >-
        The cytokine activity is attributed to the cleaved EMAP-II domain, not the
        full-length
        AIMP1 protein. Upon caspase-7 cleavage during apoptosis, the C-terminal EMAP-II
        domain is released and functions as a proinflammatory cytokine.
      action: KEEP_AS_NON_CORE
      reason: >-
        Cytokine activity is a real but secondary function of AIMP1. The annotation
        is
        technically accurate since the UniProt entry describes AIMP1 as containing
        the
        EMAP-II cytokine. However, this is not the core function of the full-length
        protein,
        which is MSC scaffold activity.
      supported_by:
        - reference_id: PMID:11306575
          supporting_text: "Endothelial-monocyte-activating polypeptide II (EMAPII)
            is an inflammatory cytokine released under apoptotic conditions. Its proEMAPII
            precursor proved to be identical to the auxiliary p43 component of the
            aminoacyl-tRNA synthetase complex."
  - term:
      id: GO:0005576
      label: extracellular region
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: >-
        AIMP1/EMAP-II is secreted under stress conditions (hypoxia, apoptosis). The
        cleaved EMAP-II fragment is found in the extracellular space.
      action: KEEP_AS_NON_CORE
      reason: >-
        The extracellular localization applies to the secreted/cleaved form, not the
        primary location of AIMP1 which is cytosolic as part of the MSC.
      supported_by:
        - reference_id: PMID:11306575
          supporting_text: "the EMAPII domain of p43 is released readily from the
            complex after in vitro digestion with caspase 7"
  - term:
      id: GO:0005615
      label: extracellular space
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: >-
        Same as extracellular region - this applies to the secreted EMAP-II fragment
        released during apoptosis or stress.
      action: KEEP_AS_NON_CORE
      reason: >-
        Extracellular space localization is for the cleaved/secreted form, not the
        primary cytosolic location of full-length AIMP1.
      supported_by:
        - reference_id: PMID:11306575
          supporting_text: "the mature cytokine isolated from conditioned medium of
            fibrosarcoma cells"
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: >-
        AIMP1/p43 has been detected in both nuclear and cytosolic fractions. Nuclear
        localization was confirmed experimentally (PMID:14500886).
      action: ACCEPT
      reason: >-
        Nuclear localization is documented for AIMP1. The protein can be found in
        both
        nuclear and cytoplasmic compartments.
      supported_by:
        - reference_id: PMID:14500886
          supporting_text: "In this study, the human multienzyme aminoacyl-tRNA synthetase
            \"core\" complex has been isolated from the nuclear and cytosolic compartments
            of human cells and purified to near homogeneity."
  - term:
      id: GO:0005783
      label: endoplasmic reticulum
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: >-
        AIMP1 interacts with gp96 (HSP90B1) and regulates KDELR1-mediated ER retention.
        This is based on similarity evidence from mouse studies.
      action: KEEP_AS_NON_CORE
      reason: >-
        The ER localization relates to AIMP1's role in regulating gp96/KDELR trafficking,
        which is a secondary function. The primary location is cytosol as part of
        the MSC.
      supported_by: []
  - term:
      id: GO:0005794
      label: Golgi apparatus
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: >-
        Golgi localization is inferred from subcellular location annotation, likely
        related
        to the secretory pathway for AIMP1/EMAP-II secretion.
      action: KEEP_AS_NON_CORE
      reason: >-
        This may relate to the secretory pathway for the EMAP-II cytokine but is not
        the primary location for AIMP1's core function.
      supported_by: []
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: >-
        The cytosol is the primary location of AIMP1 where it functions as part of
        the
        multi-aminoacyl tRNA synthetase complex (MSC).
      action: ACCEPT
      reason: >-
        Cytosolic localization is the core cellular location for AIMP1 as a scaffold
        component of the MSC. This is well-supported by multiple experimental studies.
      supported_by:
        - reference_id: PMID:19289464
          supporting_text: "The sequestration of its components within the cytoplasm
            rests on the presence of the eukaryotic-specific polypeptide extensions"
  - term:
      id: GO:0006412
      label: translation
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: >-
        AIMP1 is part of the MSC which contains aminoacyl-tRNA synthetases essential
        for translation. AIMP1 stimulates arginyl-tRNA synthetase activity. While
        AIMP1
        does not directly catalyze aminoacylation, it supports translation machinery.
      action: ACCEPT
      reason: >-
        As a scaffold component of the MSC that enhances aminoacyl-tRNA synthetase
        activity, AIMP1 participates in translation. This is a core function.
      supported_by:
        - reference_id: PMID:19131329
          supporting_text: "The data are consistent with a structural role of the
            three nonsynthetase components of MARS"
  - term:
      id: GO:0006915
      label: apoptotic process
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: >-
        AIMP1 is CLEAVED BY caspase-7 during apoptosis, releasing the EMAP-II cytokine.
        Being a caspase substrate makes AIMP1 a TARGET of the apoptotic process, not
        a
        participant IN the apoptotic process. This is a classic example of over-annotation.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        The UniProt keyword "Apoptosis" was applied because AIMP1 is cleaved during
        apoptosis. However, this does not mean AIMP1 is involved in executing the
        apoptotic
        process. Being a substrate of caspase-7 makes AIMP1 a target/consequence of
        apoptosis, not an active participant. The GO annotation guidelines distinguish
        between genes that regulate/execute apoptosis vs. genes that are affected
        by it.
      supported_by:
        - reference_id: PMID:11306575
          supporting_text: "Endothelial-monocyte-activating polypeptide II (EMAPII)
            is an inflammatory cytokine released under apoptotic conditions... the
            EMAPII domain of p43 is released readily from the complex after in vitro
            digestion with caspase 7"
  - term:
      id: GO:0006954
      label: inflammatory response
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: >-
        The EMAP-II cytokine released from AIMP1 has proinflammatory activity. It
        induces
        migration of mononuclear phagocytes and activates inflammatory pathways.
      action: KEEP_AS_NON_CORE
      reason: >-
        The inflammatory response is a function of the cleaved EMAP-II fragment, not
        the core function of full-length AIMP1. This is a secondary function that
        occurs
        after proteolytic processing.
      supported_by:
        - reference_id: PMID:11306575
          supporting_text: "the EMAPII domain of p43... is able to induce migration
            of human mononuclear phagocytes"
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:22190034
    review:
      summary: >-
        This annotation is from a large-scale HIV-human protein interaction study.
        The
        with/from column shows interaction with HIV gag protein. While technically
        correct,
        "protein binding" is uninformative for understanding AIMP1's function.
      action: REMOVE
      reason: >-
        Protein binding is an uninformative GO term that tells us nothing specific
        about
        AIMP1's molecular function. AIMP1 has more informative functional annotations
        (tRNA binding, homodimerization). The interaction with HIV proteins in a large-scale
        screen is not relevant to AIMP1's physiological function.
      supported_by:
        - reference_id: PMID:22190034
          supporting_text: Global landscape of HIV-human protein complexes.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:25416956
    review:
      summary: >-
        Large-scale interactome study showing AIMP1 interacts with AIMP2 and TSNAX.
        The AIMP1-AIMP2 interaction is functionally meaningful (both are MSC scaffold
        components), but "protein binding" is too generic.
      action: REMOVE
      reason: >-
        The AIMP1-AIMP2 interaction within the MSC is biologically relevant, but the
        generic "protein binding" term does not capture this specificity. More informative
        annotations for MSC complex membership already exist.
      supported_by:
        - reference_id: PMID:25416956
          supporting_text: A proteome-scale map of the human interactome 
            network.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:28514442
    review:
      summary: >-
        Another large-scale interactome study showing AIMP1-AIMP2 interaction. Same
        issue as above - protein binding is uninformative.
      action: REMOVE
      reason: >-
        Generic protein binding annotation from interactome study. The specific interaction
        is already captured by MSC complex membership annotations.
      supported_by:
        - reference_id: PMID:28514442
          supporting_text: Architecture of the human interactome defines protein
            communities and disease networks.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:33961781
    review:
      summary: >-
        Large-scale proteomics study. AIMP1-AIMP2 interaction again.
      action: REMOVE
      reason: >-
        Redundant with other protein binding annotations and uninformative.
      supported_by:
        - reference_id: PMID:33961781
          supporting_text: 2021 May 6. Dual proteome-scale networks reveal 
            cell-specific remodeling of the human interactome.
  - term:
      id: GO:0048514
      label: blood vessel morphogenesis
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        This annotation is transferred from rat ortholog based on Ensembl Compara.
        The EMAP-II cytokine has documented effects on endothelial cells, but this
        represents pharmacological/pathological effects rather than physiological
        function.
      action: KEEP_AS_NON_CORE
      reason: >-
        Effects on blood vessel morphogenesis are attributed to the secreted EMAP-II
        cytokine at varying concentrations. This is not the core function of AIMP1
        as
        an MSC scaffold.
      supported_by:
        - reference_id: PMID:11741979
          supporting_text: "EMAP II inhibited the growth of endothelial cells"
  - term:
      id: GO:0051607
      label: defense response to virus
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        Transferred from rat ortholog. The basis for this annotation is unclear from
        the available literature on AIMP1's core functions.
      action: UNDECIDED
      reason: >-
        Cannot verify the basis for this annotation. AIMP1's role in antiviral defense
        is not well-characterized in the literature I have access to.
      supported_by: []
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: IDA
    original_reference_id: GO_REF:0000052
    review:
      summary: >-
        IDA evidence from HPA immunofluorescence data confirming cytosolic localization.
      action: ACCEPT
      reason: >-
        Direct experimental evidence for cytosolic localization, consistent with AIMP1's
        role as an MSC component.
      supported_by: []
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: NAS
    original_reference_id: PMID:32644155
    review:
      summary: >-
        This publication describes the 3D architecture of the human multi-tRNA synthetase
        complex. Cytoplasmic localization is consistent with AIMP1's role in the MSC.
      action: ACCEPT
      reason: >-
        Well-supported localization annotation for AIMP1 as part of the cytoplasmic
        MSC.
      supported_by:
        - reference_id: PMID:32644155
          supporting_text: "3-Dimensional architecture of the human multi-tRNA synthetase
            complex"
  - term:
      id: GO:0006418
      label: tRNA aminoacylation for protein translation
    evidence_type: NAS
    original_reference_id: PMID:32644155
    review:
      summary: >-
        AIMP1 is a scaffold component of the MSC containing multiple aminoacyl-tRNA
        synthetases. While AIMP1 itself does not catalyze aminoacylation, it supports
        this process by organizing the complex and binding tRNA.
      action: ACCEPT
      reason: >-
        AIMP1 participates in tRNA aminoacylation as a scaffold that stimulates
        arginyl-tRNA synthetase activity and binds tRNA for presentation to synthetases.
      supported_by:
        - reference_id: PMID:19131329
          supporting_text: "The data are consistent with a structural role of the
            three nonsynthetase components of MARS"
        - reference_id: PMID:32644155
          supporting_text: 3-Dimensional architecture of the human multi-tRNA 
            synthetase complex.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:24312579
    review:
      summary: >-
        This study identified TARSL2 as a potential MSC member and confirmed AIMP1
        interactions with MSC components including TARS3. The interaction is meaningful
        but "protein binding" is uninformative.
      action: REMOVE
      reason: >-
        Generic protein binding annotation. The specific interactions within the MSC
        are better captured by complex membership annotations.
      supported_by:
        - reference_id: PMID:24312579
          supporting_text: eCollection 2013. Reinvestigation of aminoacyl-tRNA 
            synthetase core complex by affinity purification-mass spectrometry 
            reveals TARSL2 as a potential member of the complex.
  - term:
      id: GO:0070094
      label: positive regulation of glucagon secretion
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        This annotation is based on sequence similarity to mouse AIMP1 (P31230), which
        has been shown to be involved in glucose homeostasis through glucagon secretion.
        UniProt states AIMP1 is "enriched in secretory vesicles of pancreatic alpha
        cells".
      action: KEEP_AS_NON_CORE
      reason: >-
        This is a secondary function of AIMP1 not related to its core MSC scaffold
        role.
        The annotation is based on mouse ortholog data and represents a tissue-specific
        signaling function.
      supported_by: []
  - term:
      id: GO:0005615
      label: extracellular space
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        Based on similarity to mouse ortholog. AIMP1 can be secreted under various
        conditions.
      action: KEEP_AS_NON_CORE
      reason: >-
        Extracellular localization is for the secreted form, secondary to cytosolic
        MSC function.
      supported_by: []
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: IDA
    original_reference_id: PMID:19289464
    review:
      summary: >-
        Direct experimental evidence showing AIMP1 is part of cytosolic MSC complexes
        in human cells. This study examined subcellular localization of the MSC.
      action: ACCEPT
      reason: >-
        Strong experimental support for cytosolic localization as part of the MSC.
      supported_by:
        - reference_id: PMID:19289464
          supporting_text: "The sequestration of its components within the cytoplasm
            rests on the presence of the eukaryotic-specific polypeptide extensions"
  - term:
      id: GO:0017101
      label: aminoacyl-tRNA synthetase multienzyme complex
    evidence_type: IDA
    original_reference_id: PMID:19131329
    review:
      summary: >-
        This study dissected the structural organization of the MSC (called MARS in
        the paper) and showed AIMP1 (p43) is a core scaffold component. This is the
        primary cellular location and functional context for AIMP1.
      action: ACCEPT
      reason: >-
        This is the core cellular component annotation for AIMP1. Direct experimental
        evidence shows AIMP1 is an integral scaffold component of the MSC.
      supported_by:
        - reference_id: PMID:19131329
          supporting_text: "This complex contains nine aminoacyl-tRNA synthetases
            and three auxiliary proteins... The data are consistent with a structural
            role of the three nonsynthetase components of MARS, with p38 connecting
            two subcomplexes"
  - term:
      id: GO:0017101
      label: aminoacyl-tRNA synthetase multienzyme complex
    evidence_type: IDA
    original_reference_id: PMID:10791971
    review:
      summary: >-
        This paper primarily focuses on methionyl-tRNA synthetase (MRS) nucleolar
        localization,
        but also confirms that AIMP1 (p43) is part of the MSC through gel filtration
        studies.
      action: ACCEPT
      reason: >-
        Provides additional experimental support for AIMP1 as an MSC component.
      supported_by:
        - reference_id: PMID:10791971
          supporting_text: "The majority of the three proteins were coeluted in the
            void volume as expected."
  - term:
      id: GO:0051020
      label: GTPase binding
    evidence_type: IPI
    original_reference_id: PMID:24337748
    review:
      summary: >-
        This study identified GBP-1 (guanylate binding protein 1) binding partners
        by
        mass spectrometry. AIMP1 was identified as an interactor of GBP-1 (P32455).
        The functional significance of this interaction is unclear.
      action: UNDECIDED
      reason: >-
        The interaction with GBP-1 was identified in a mass spectrometry screen. The
        biological relevance of AIMP1 binding to this GTPase is not established. This
        may be an indirect or non-physiological interaction.
      supported_by:
        - reference_id: PMID:24337748
          supporting_text: "Mass spectrometry analyses showed that regulatory cytoskeletal
            proteins... are binding partners of GBP-1"
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:11741979
    review:
      summary: >-
        This study showed EMAP-II (the C-terminal domain of AIMP1) binds to the alpha
        subunit of ATP synthase on the cell surface. This is a specific, functionally
        characterized interaction related to endothelial cell effects.
      action: MODIFY
      reason: >-
        This is a meaningful interaction but "protein binding" is too generic. The
        specific interaction with ATP5A1 on the cell surface mediates EMAP-II's effects
        on endothelial cells. However, this is the cleaved EMAP-II fragment, not full-length
        AIMP1.
      proposed_replacement_terms:
        - id: GO:0005515
          label: protein binding
      additional_reference_ids:
        - PMID:11741979
      supported_by:
        - reference_id: PMID:11741979
          supporting_text: "The isolated protein was determined to be the alpha subunit
            of ATP synthase. The interaction of EMAP II and alpha-ATP synthase was
            confirmed by enzyme-linked immunosorbent assay and in vitro pull down
            assays"
  - term:
      id: GO:0016020
      label: membrane
    evidence_type: HDA
    original_reference_id: PMID:19946888
    review:
      summary: >-
        This study defined the membrane proteome of NK cells and detected AIMP1 in
        membrane fractions. This may relate to secreted/surface AIMP1/EMAP-II.
      action: KEEP_AS_NON_CORE
      reason: >-
        Membrane association may relate to the secretory pathway or EMAP-II surface
        binding functions, not the core cytosolic MSC function.
      supported_by:
        - reference_id: PMID:19946888
          supporting_text: Defining the membrane proteome of NK cells.
  - term:
      id: GO:0009986
      label: cell surface
    evidence_type: IDA
    original_reference_id: PMID:11741979
    review:
      summary: >-
        This study showed EMAP-II binds to alpha-ATP synthase on the cell surface.
        The cell surface localization refers to EMAP-II binding to its receptor, not
        AIMP1 being a cell surface protein.
      action: KEEP_AS_NON_CORE
      reason: >-
        The study shows EMAP-II (the cleaved C-terminal fragment) binds to cell surface
        ATP synthase. This is a secondary function of the cytokine fragment.
      supported_by:
        - reference_id: PMID:11741979
          supporting_text: "The binding of EMAP II to the surface of serum-starved
            cells was inhibited in the presence of soluble alpha-ATP synthase"
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-379861
    review:
      summary: >-
        Reactome annotation for cytosolic tRNA aminoacylation reaction (glutamate).
        AIMP1 is part of the MSC that performs this reaction.
      action: ACCEPT
      reason: >-
        Consistent with AIMP1's role as an MSC scaffold component in the cytosol.
      supported_by: []
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-379865
    review:
      summary: >-
        Reactome annotation for cytosolic proline tRNA aminoacylation.
      action: ACCEPT
      reason: >-
        Consistent with AIMP1's role as an MSC scaffold component in the cytosol.
      supported_by: []
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-379867
    review:
      summary: >-
        Reactome annotation for cytosolic aspartate tRNA aminoacylation.
      action: ACCEPT
      reason: >-
        Consistent with AIMP1's role as an MSC scaffold component in the cytosol.
      supported_by: []
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-379893
    review:
      summary: >-
        Reactome annotation for cytosolic isoleucine tRNA aminoacylation.
      action: ACCEPT
      reason: >-
        Consistent with AIMP1's role as an MSC scaffold component in the cytosol.
      supported_by: []
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-379974
    review:
      summary: >-
        Reactome annotation for cytosolic leucine tRNA aminoacylation.
      action: ACCEPT
      reason: >-
        Consistent with AIMP1's role as an MSC scaffold component in the cytosol.
      supported_by: []
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-379982
    review:
      summary: >-
        Reactome annotation for cytosolic glutamine tRNA aminoacylation.
      action: ACCEPT
      reason: >-
        Consistent with AIMP1's role as an MSC scaffold component in the cytosol.
      supported_by: []
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-379993
    review:
      summary: >-
        Reactome annotation for cytosolic arginine tRNA aminoacylation.
      action: ACCEPT
      reason: >-
        Consistent with AIMP1's role as an MSC scaffold component in the cytosol.
      supported_by: []
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-379994
    review:
      summary: >-
        Reactome annotation for cytosolic methionine tRNA aminoacylation.
      action: ACCEPT
      reason: >-
        Consistent with AIMP1's role as an MSC scaffold component in the cytosol.
      supported_by: []
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-380008
    review:
      summary: >-
        Reactome annotation for cytosolic lysine tRNA aminoacylation.
      action: ACCEPT
      reason: >-
        Consistent with AIMP1's role as an MSC scaffold component in the cytosol.
      supported_by: []
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9825759
    review:
      summary: >-
        Reactome annotation for MAPK-dependent phosphorylation of KARS. AIMP1 is part
        of the MSC containing KARS.
      action: ACCEPT
      reason: >-
        Consistent with AIMP1's role as an MSC scaffold component in the cytosol.
      supported_by: []
  - term:
      id: GO:0000049
      label: tRNA binding
    evidence_type: IDA
    original_reference_id: PMID:11306575
    review:
      summary: >-
        Direct experimental evidence showing p43/AIMP1 has strong tRNA binding capacity
        (Kd = 0.2 microM). The tRNA binding is mediated by both N and C terminal domains
        working together.
      action: ACCEPT
      reason: >-
        Strong experimental evidence for tRNA binding as a core molecular function
        of
        AIMP1. This is essential for its role in the MSC.
      supported_by:
        - reference_id: PMID:11306575
          supporting_text: "p43/proEMAPII has a strong tRNA binding capacity (K(D)
            = 0.2 microm) as compared with its isolated N or C domains (7.5 microm
            and 40 microm, respectively)"
  - term:
      id: GO:0001937
      label: negative regulation of endothelial cell proliferation
    evidence_type: IDA
    original_reference_id: PMID:11741979
    review:
      summary: >-
        This study showed EMAP-II inhibits endothelial cell growth by binding to cell
        surface ATP synthase. This is a function of the cleaved EMAP-II cytokine fragment.
      action: KEEP_AS_NON_CORE
      reason: >-
        The anti-proliferative effect on endothelial cells is a function of the secreted
        EMAP-II fragment, not the core MSC scaffold function of full-length AIMP1.
      supported_by:
        - reference_id: PMID:11741979
          supporting_text: "EMAP II inhibited the growth of endothelial cells, and
            this effect was relieved by soluble alpha-ATP synthase"
  - term:
      id: GO:0005125
      label: cytokine activity
    evidence_type: ISS
    original_reference_id: PMID:11306575
    review:
      summary: >-
        Based on similarity to mouse ortholog. The EMAP-II domain has documented cytokine
        activity inducing phagocyte migration.
      action: KEEP_AS_NON_CORE
      reason: >-
        Cytokine activity is a secondary function of the cleaved EMAP-II fragment.
      supported_by:
        - reference_id: PMID:11306575
          supporting_text: "the EMAPII domain of p43 is released readily from the
            complex after in vitro digestion with caspase 7 and is able to induce
            migration of human mononuclear phagocytes"
  - term:
      id: GO:0007267
      label: cell-cell signaling
    evidence_type: IDA
    original_reference_id: PMID:11741979
    review:
      summary: >-
        This study showed EMAP-II/p43 can act as a signaling molecule affecting endothelial
        cells through interaction with cell surface ATP synthase.
      action: KEEP_AS_NON_CORE
      reason: >-
        Cell-cell signaling is a function of the secreted EMAP-II cytokine, not the
        core MSC scaffold function.
      supported_by:
        - reference_id: PMID:11741979
          supporting_text: "p43 is also secreted to induce proinflammatory genes"
  - term:
      id: GO:0017101
      label: aminoacyl-tRNA synthetase multienzyme complex
    evidence_type: IDA
    original_reference_id: PMID:14500886
    review:
      summary: >-
        This study isolated and characterized the MSC from human cells and demonstrated
        that p43/AIMP1 is an integral component.
      action: ACCEPT
      reason: >-
        Direct experimental evidence confirming AIMP1 is part of the MSC. This is
        the
        core cellular context for AIMP1 function.
      supported_by:
        - reference_id: PMID:14500886
          supporting_text: "gel filtration and immunoblot analysis demonstrate that
            a major biological role for the cytokine precursor p43 is as an integral
            part of the multisynthetase complex"
  - term:
      id: GO:0042803
      label: protein homodimerization activity
    evidence_type: IDA
    original_reference_id: PMID:11306575
    review:
      summary: >-
        The EMAP-II domain structure shows it exists as a homodimer. Crystal structures
        confirm this dimeric arrangement.
      action: ACCEPT
      reason: >-
        Homodimerization is a documented property of AIMP1, particularly the EMAP-II
        domain. This may be relevant for its function in the MSC.
      supported_by:
        - reference_id: PMID:11306575
          supporting_text: "Its proEMAPII precursor proved to be identical to the
            auxiliary p43 component of the aminoacyl-tRNA synthetase complex."
  - term:
      id: GO:0050900
      label: leukocyte migration
    evidence_type: IDA
    original_reference_id: PMID:11306575
    review:
      summary: >-
        The EMAP-II cytokine released from AIMP1 induces migration of mononuclear
        phagocytes. This is a chemotactic activity of the cytokine.
      action: KEEP_AS_NON_CORE
      reason: >-
        Leukocyte migration is induced by the cleaved EMAP-II cytokine fragment. This
        is a secondary function, not the core MSC scaffold role.
      supported_by:
        - reference_id: PMID:11306575
          supporting_text: "the EMAPII domain of p43... is able to induce migration
            of human mononuclear phagocytes"
references:
  - id: GO_REF:0000024
    title: Manual transfer of experimentally-verified manual GO annotation data 
      to orthologs by curator judgment of sequence similarity
    findings: []
  - id: GO_REF:0000043
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword 
      mapping
    findings: []
  - id: GO_REF:0000044
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular 
      Location vocabulary mapping, accompanied by conservative changes to GO 
      terms applied by UniProt
    findings: []
  - id: GO_REF:0000052
    title: Gene Ontology annotation based on curation of immunofluorescence data
    findings: []
  - id: GO_REF:0000107
    title: Automatic transfer of experimentally verified manual GO annotation 
      data to orthologs using Ensembl Compara
    findings: []
  - id: GO_REF:0000108
    title: Automatic assignment of GO terms using logical inference, based on on
      inter-ontology links
    findings: []
  - id: GO_REF:0000120
    title: Combined Automated Annotation using Multiple IEA Methods
    findings: []
  - id: PMID:10791971
    title: Nucleolar localization of human methionyl-tRNA synthetase and its 
      role in ribosomal RNA synthesis.
    findings:
      - statement: AIMP1 (p43) co-elutes with MSC components in gel filtration
  - id: PMID:11306575
    title: The EMAPII cytokine is released from the mammalian multisynthetase 
      complex after cleavage of its p43/proEMAPII component.
    findings:
      - statement: p43/AIMP1 has strong tRNA binding (Kd = 0.2 microM)
      - statement: EMAP-II is released by caspase-7 cleavage during apoptosis
      - statement: EMAP-II induces mononuclear phagocyte migration
      - statement: tRNA binding is lost upon EMAP-II release
  - id: PMID:11741979
    title: Interaction of the C-terminal domain of p43 and the alpha subunit of 
      ATP synthase. Its functional implication in endothelial cell 
      proliferation.
    findings:
      - statement: EMAP-II binds cell surface alpha-ATP synthase
      - statement: EMAP-II inhibits endothelial cell proliferation
  - id: PMID:14500886
    title: Isolation and characterization of human nuclear and cytosolic 
      multisynthetase complexes and the intracellular distribution of 
      p43/EMAPII.
    findings:
      - statement: p43/AIMP1 is an integral part of the MSC
      - statement: MSC isolated from both nuclear and cytosolic compartments
  - id: PMID:19131329
    title: Dissection of the structural organization of the aminoacyl-tRNA 
      synthetase complex.
    findings:
      - statement: AIMP1 (p43) is one of three auxiliary scaffold proteins in 
          MSC
      - statement: Structural role confirmed by siRNA knockdown studies
  - id: PMID:19289464
    title: Dynamic Organization of Aminoacyl-tRNA Synthetase Complexes in the 
      Cytoplasm of Human Cells.
    findings:
      - statement: AIMP1 is sequestered in cytoplasm as part of MSC
      - statement: MSC components interact with ribosomes and actin cytoskeleton
  - id: PMID:19946888
    title: Defining the membrane proteome of NK cells.
    findings: []
  - id: PMID:22190034
    title: Global landscape of HIV-human protein complexes.
    findings: []
  - id: PMID:24312579
    title: Reinvestigation of aminoacyl-tRNA synthetase core complex by affinity
      purification-mass spectrometry reveals TARSL2 as a potential member of the
      complex.
    findings:
      - statement: Confirmed AIMP1 as MSC component
      - statement: Identified interaction with TARS3
  - id: PMID:24337748
    title: Guanylate binding protein 1-mediated interaction of T cell antigen 
      receptor signaling with the cytoskeleton.
    findings:
      - statement: AIMP1 identified as GBP-1 interactor by mass spectrometry
  - id: PMID:25416956
    title: A proteome-scale map of the human interactome network.
    findings: []
  - id: PMID:28514442
    title: Architecture of the human interactome defines protein communities and
      disease networks.
    findings: []
  - id: PMID:32644155
    title: 3-Dimensional architecture of the human multi-tRNA synthetase 
      complex.
    findings: []
  - id: PMID:33961781
    title: Dual proteome-scale networks reveal cell-specific remodeling of the 
      human interactome.
    findings: []
  - id: Reactome:R-HSA-379861
    title: glutamate + tRNA(Glu) + ATP => Glu-tRNA(Glu) + AMP + pyrophosphate
    findings: []
  - id: Reactome:R-HSA-379865
    title: proline + tRNA(Pro) + ATP => Pro-tRNA(Pro) + AMP + pyrophosphate
    findings: []
  - id: Reactome:R-HSA-379867
    title: aspartate + tRNA(Asp) + ATP => Asp-tRNA(Asp) + AMP + pyrophosphate
    findings: []
  - id: Reactome:R-HSA-379893
    title: isoleucine + tRNA(Ile) + ATP => Ile-tRNA(Ile) + AMP + pyrophosphate
    findings: []
  - id: Reactome:R-HSA-379974
    title: leucine + tRNA(Leu) + ATP => Leu-tRNA(Leu) + AMP + pyrophosphate
    findings: []
  - id: Reactome:R-HSA-379982
    title: glutamine + tRNA(Gln) + ATP => Gln-tRNA(Gln) + AMP + pyrophosphate
    findings: []
  - id: Reactome:R-HSA-379993
    title: arginine + tRNA(Arg) + ATP => Arg-tRNA(Arg) + AMP + pyrophosphate
    findings: []
  - id: Reactome:R-HSA-379994
    title: methionine + tRNA(Met) + ATP => Met-tRNA(Met) + AMP + pyrophosphate
    findings: []
  - id: Reactome:R-HSA-380008
    title: lysine + tRNA(Lys) + ATP => Lys-tRNA(Lys) + AMP + pyrophosphate
    findings: []
  - id: Reactome:R-HSA-9825759
    title: MAPK-dependent phosphorylation of KARS
    findings: []
  - id: file:human/AIMP1/AIMP1-deep-research-falcon.md
    title: Deep research report on AIMP1
    findings: []
core_functions:
  - description: >-
      AIMP1 is a non-catalytic scaffold component of the MSC (multi-aminoacyl tRNA
      synthetase complex). Multiple studies confirm it is an integral part of this
      complex along with AIMP2 and AIMP3 (PMID:19131329, PMID:14500886). The complex
      contains nine aminoacyl-tRNA synthetases.
    molecular_function:
      id: GO:0000049
      label: tRNA binding
    directly_involved_in:
      - id: GO:0006418
        label: tRNA aminoacylation for protein translation
    locations:
      - id: GO:0005829
        label: cytosol
    in_complex:
      id: GO:0017101
      label: aminoacyl-tRNA synthetase multienzyme complex

AIMP1

Gene Description

Existing Annotations Review

Core Functions

AIMP1 is a non-catalytic scaffold component of the MSC (multi-aminoacyl tRNA synthetase complex). Multiple studies confirm it is an integral part of this complex along with AIMP2 and AIMP3 (PMID:19131329, PMID:14500886). The complex contains nine aminoacyl-tRNA synthetases.

References

📚 Additional Documentation

Deep Research Falcon

Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

Target Gene/Protein Identity (from UniProt):

MANDATORY VERIFICATION STEPS:

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Output

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

Target Gene/Protein Identity (from UniProt):

MANDATORY VERIFICATION STEPS:

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Citations

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