UniProt functional annotation for Q12904



	UniProt functional annotation for Q12904

UniProt code: Q12904.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Non-catalytic component of the multisynthase complex. Stimulates the catalytic activity of cytoplasmic arginyl-tRNA synthase (PubMed:10358004). Binds tRNA. Possesses inflammatory cytokine activity (PubMed:11306575). Negatively regulates TGF-beta signaling through stabilization of SMURF2 by binding to SMURF2 and inhibiting its SMAD7- mediated degradation (By similarity). Involved in glucose homeostasis through induction of glucagon secretion at low glucose levels (By similarity). Promotes dermal fibroblast proliferation and wound repair (PubMed:16472771). Regulates KDELR1-mediated retention of HSP90B1/gp96 in the endoplasmic reticulum (By similarity). Plays a role in angiogenesis by inducing endothelial cell migration at low concentrations and endothelian cell apoptosis at high concentrations (PubMed:12237313). Induces maturation of dendritic cells and monocyte cell adhesion (PubMed:11818442). Modulates endothelial cell responses by degrading HIF-1A through interaction with PSMA7 (PubMed:19362550). {ECO:0000250|UniProtKB:P31230, ECO:0000269|PubMed:10358004, ECO:0000269|PubMed:11157763, ECO:0000269|PubMed:11306575, ECO:0000269|PubMed:11818442, ECO:0000269|PubMed:12237313, ECO:0000269|PubMed:19362550}.

Subunit: Homodimer. Part of the multisynthetase complex (MSC), a multisubunit complex that groups tRNA ligases for Arg (RARS1), Asp (DARS1), Gln (QARS1), Ile (IARS1), Leu (LARS1), Lys (KARS1), Met (MARS1) the bifunctional ligase for Glu and Pro (EPRS1) and the auxiliary subunits AIMP1/p43, AIMP2/p38 and EEF1E1/p18 (PubMed:24312579, PubMed:19131329, PubMed:19289464). Interacts (via N- terminus) with RARS1 (via N-terminus) (PubMed:10358004, PubMed:17443684). Part of a complex composed of RARS1, QARS1 and AIMP1 (PubMed:25288775). Interacts (via C-terminus) with SMURF2. Interacts (via N-terminus) with HSP90B1/gp96 (via C-terminus) (By similarity). Interacts with PSMA7 (PubMed:19362550). Interacts with TARS3 (PubMed:24312579). {ECO:0000250|UniProtKB:P31230, ECO:0000269|PubMed:10358004, ECO:0000269|PubMed:11306575, ECO:0000269|PubMed:17443684, ECO:0000269|PubMed:19131329, ECO:0000269|PubMed:19289464, ECO:0000269|PubMed:19362550, ECO:0000269|PubMed:24312579, ECO:0000269|PubMed:25288775}.

Subcellular location: Nucleus {ECO:0000269|PubMed:14500886}. Cytoplasm, cytosol {ECO:0000269|PubMed:19289464}. Secreted {ECO:0000269|PubMed:10850427}. Endoplasmic reticulum {ECO:0000250|UniProtKB:P31230}. Golgi apparatus {ECO:0000250|UniProtKB:P31230}. Note=Enriched in secretory vesicles of pancreatic alpha cells and secreted from the pancreas in response to low glucose levels (By similarity). Secreted in response to hypoxia (PubMed:10850427). Also secreted in response to both apoptotic and necrotic cell death. {ECO:0000250|UniProtKB:P31230, ECO:0000269|PubMed:10850427}.

Ptm: Cleaved by caspase-7 in response to apoptosis to produce EMAP-II. {ECO:0000269|PubMed:10850427, ECO:0000269|PubMed:11306575}.

Disease: Leukodystrophy, hypomyelinating, 3 (HLD3) [MIM:260600]: A severe autosomal recessive hypomyelinating leukodystrophy characterized by early infantile onset of global developmental delay, lack of development, lack of speech acquisition, and peripheral spasticity associated with decreased myelination in the central nervous system. {ECO:0000269|PubMed:21092922}. Note=The disease is caused by variants affecting the gene represented in this entry.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Non-catalytic component of the multisynthase complex. Stimulates the catalytic activity of cytoplasmic arginyl-tRNA synthase (PubMed:10358004). Binds tRNA. Possesses inflammatory cytokine activity (PubMed:11306575). Negatively regulates TGF-beta signaling through stabilization of SMURF2 by binding to SMURF2 and inhibiting its SMAD7- mediated degradation (By similarity). Involved in glucose homeostasis through induction of glucagon secretion at low glucose levels (By similarity). Promotes dermal fibroblast proliferation and wound repair (PubMed:16472771). Regulates KDELR1-mediated retention of HSP90B1/gp96 in the endoplasmic reticulum (By similarity). Plays a role in angiogenesis by inducing endothelial cell migration at low concentrations and endothelian cell apoptosis at high concentrations (PubMed:12237313). Induces maturation of dendritic cells and monocyte cell adhesion (PubMed:11818442). Modulates endothelial cell responses by degrading HIF-1A through interaction with PSMA7 (PubMed:19362550). {ECO:0000250\|UniProtKB:P31230, ECO:0000269\|PubMed:10358004, ECO:0000269\|PubMed:11157763, ECO:0000269\|PubMed:11306575, ECO:0000269\|PubMed:11818442, ECO:0000269\|PubMed:12237313, ECO:0000269\|PubMed:19362550}.


Subunit:		Homodimer. Part of the multisynthetase complex (MSC), a multisubunit complex that groups tRNA ligases for Arg (RARS1), Asp (DARS1), Gln (QARS1), Ile (IARS1), Leu (LARS1), Lys (KARS1), Met (MARS1) the bifunctional ligase for Glu and Pro (EPRS1) and the auxiliary subunits AIMP1/p43, AIMP2/p38 and EEF1E1/p18 (PubMed:24312579, PubMed:19131329, PubMed:19289464). Interacts (via N- terminus) with RARS1 (via N-terminus) (PubMed:10358004, PubMed:17443684). Part of a complex composed of RARS1, QARS1 and AIMP1 (PubMed:25288775). Interacts (via C-terminus) with SMURF2. Interacts (via N-terminus) with HSP90B1/gp96 (via C-terminus) (By similarity). Interacts with PSMA7 (PubMed:19362550). Interacts with TARS3 (PubMed:24312579). {ECO:0000250\|UniProtKB:P31230, ECO:0000269\|PubMed:10358004, ECO:0000269\|PubMed:11306575, ECO:0000269\|PubMed:17443684, ECO:0000269\|PubMed:19131329, ECO:0000269\|PubMed:19289464, ECO:0000269\|PubMed:19362550, ECO:0000269\|PubMed:24312579, ECO:0000269\|PubMed:25288775}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:14500886}. Cytoplasm, cytosol {ECO:0000269\|PubMed:19289464}. Secreted {ECO:0000269\|PubMed:10850427}. Endoplasmic reticulum {ECO:0000250\|UniProtKB:P31230}. Golgi apparatus {ECO:0000250\|UniProtKB:P31230}. Note=Enriched in secretory vesicles of pancreatic alpha cells and secreted from the pancreas in response to low glucose levels (By similarity). Secreted in response to hypoxia (PubMed:10850427). Also secreted in response to both apoptotic and necrotic cell death. {ECO:0000250\|UniProtKB:P31230, ECO:0000269\|PubMed:10850427}.
Ptm:		Cleaved by caspase-7 in response to apoptosis to produce EMAP-II. {ECO:0000269\|PubMed:10850427, ECO:0000269\|PubMed:11306575}.
Disease:		Leukodystrophy, hypomyelinating, 3 (HLD3) [MIM:260600]: A severe autosomal recessive hypomyelinating leukodystrophy characterized by early infantile onset of global developmental delay, lack of development, lack of speech acquisition, and peripheral spasticity associated with decreased myelination in the central nervous system. {ECO:0000269\|PubMed:21092922}. Note=The disease is caused by variants affecting the gene represented in this entry.