6IY6

Crystal structure of human cytosolic aspartyl-tRNA synthetase (DRS) in complex with glutathion-S transferase (GST) domains from Aminoacyl tRNA synthase complex-interacting multifunctional protein 2 (AIMP2) and glutamyl-prolyl-tRNA synthetase (EPRS)

External Resource: Annotation

Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	PF01336	e6iy6A1	A: beta barrels	X: OB-fold	H: Nucleic acid-binding proteins (From Topology)	T: Nucleic acid-binding proteins	F: PF01336	ECOD (1.6)
A	PF00152	e6iy6A2	A: a+b three layers	X: Class II aaRS and biotin synthetases (From Topology)	H: Class II aaRS and biotin synthetases (From Topology)	T: Class II aaRS and biotin synthetases	F: PF00152	ECOD (1.6)
B	PF01336	e6iy6B1	A: beta barrels	X: OB-fold	H: Nucleic acid-binding proteins (From Topology)	T: Nucleic acid-binding proteins	F: PF01336	ECOD (1.6)
B	PF00152	e6iy6B2	A: a+b three layers	X: Class II aaRS and biotin synthetases (From Topology)	H: Class II aaRS and biotin synthetases (From Topology)	T: Class II aaRS and biotin synthetases	F: PF00152	ECOD (1.6)
G	PF01336	e6iy6G2	A: beta barrels	X: OB-fold	H: Nucleic acid-binding proteins (From Topology)	T: Nucleic acid-binding proteins	F: PF01336	ECOD (1.6)
G	PF00152	e6iy6G1	A: a+b three layers	X: Class II aaRS and biotin synthetases (From Topology)	H: Class II aaRS and biotin synthetases (From Topology)	T: Class II aaRS and biotin synthetases	F: PF00152	ECOD (1.6)
H	PF01336	e6iy6H2	A: beta barrels	X: OB-fold	H: Nucleic acid-binding proteins (From Topology)	T: Nucleic acid-binding proteins	F: PF01336	ECOD (1.6)
H	PF00152	e6iy6H1	A: a+b three layers	X: Class II aaRS and biotin synthetases (From Topology)	H: Class II aaRS and biotin synthetases (From Topology)	T: Class II aaRS and biotin synthetases	F: PF00152	ECOD (1.6)
C	PF13410	e6iy6C2	A: alpha superhelices	X: Repetitive alpha hairpins	H: Glutathione S-transferase (GST)-C (From Topology)	T: Glutathione S-transferase (GST)-C	F: PF13410	ECOD (1.6)
C	PF18569	e6iy6C1	A: a+b three layers	X: Thioredoxin-like	H: Thioredoxin-like (From Topology)	T: Thioredoxin-like	F: PF18569	ECOD (1.6)
D	PF13410	e6iy6D1	A: alpha superhelices	X: Repetitive alpha hairpins	H: Glutathione S-transferase (GST)-C (From Topology)	T: Glutathione S-transferase (GST)-C	F: PF13410	ECOD (1.6)
D	PF18569	e6iy6D2	A: a+b three layers	X: Thioredoxin-like	H: Thioredoxin-like (From Topology)	T: Thioredoxin-like	F: PF18569	ECOD (1.6)
I	PF13410	e6iy6I2	A: alpha superhelices	X: Repetitive alpha hairpins	H: Glutathione S-transferase (GST)-C (From Topology)	T: Glutathione S-transferase (GST)-C	F: PF13410	ECOD (1.6)
I	PF18569	e6iy6I1	A: a+b three layers	X: Thioredoxin-like	H: Thioredoxin-like (From Topology)	T: Thioredoxin-like	F: PF18569	ECOD (1.6)
J	PF13410	e6iy6J2	A: alpha superhelices	X: Repetitive alpha hairpins	H: Glutathione S-transferase (GST)-C (From Topology)	T: Glutathione S-transferase (GST)-C	F: PF13410	ECOD (1.6)
J	PF18569	e6iy6J1	A: a+b three layers	X: Thioredoxin-like	H: Thioredoxin-like (From Topology)	T: Thioredoxin-like	F: PF18569	ECOD (1.6)
E	PF21972	e6iy6E1	A: alpha superhelices	X: Repetitive alpha hairpins	H: Glutathione S-transferase (GST)-C (From Topology)	T: Glutathione S-transferase (GST)-C	F: PF21972	ECOD (1.6)
F	PF21972	e6iy6F1	A: alpha superhelices	X: Repetitive alpha hairpins	H: Glutathione S-transferase (GST)-C (From Topology)	T: Glutathione S-transferase (GST)-C	F: PF21972	ECOD (1.6)
K	PF21972	e6iy6K1	A: alpha superhelices	X: Repetitive alpha hairpins	H: Glutathione S-transferase (GST)-C (From Topology)	T: Glutathione S-transferase (GST)-C	F: PF21972	ECOD (1.6)
L	PF21972	e6iy6L1	A: alpha superhelices	X: Repetitive alpha hairpins	H: Glutathione S-transferase (GST)-C (From Topology)	T: Glutathione S-transferase (GST)-C	F: PF21972	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
C	1.20.1050.130	Mainly Alpha	Up-down Bundle	Glutathione S-transferase Yfyf (Class Pi)	Chain A, domain 2	CATH (utative)
D	1.20.1050.130	Mainly Alpha	Up-down Bundle	Glutathione S-transferase Yfyf (Class Pi)	Chain A, domain 2	CATH (utative)
I	1.20.1050.130	Mainly Alpha	Up-down Bundle	Glutathione S-transferase Yfyf (Class Pi)	Chain A, domain 2	CATH (utative)
J	1.20.1050.130	Mainly Alpha	Up-down Bundle	Glutathione S-transferase Yfyf (Class Pi)	Chain A, domain 2	CATH (utative)
E	1.20.1050.130	Mainly Alpha	Up-down Bundle	Glutathione S-transferase Yfyf (Class Pi)	Chain A, domain 2	CATH (utative)
F	1.20.1050.130	Mainly Alpha	Up-down Bundle	Glutathione S-transferase Yfyf (Class Pi)	Chain A, domain 2	CATH (utative)
K	1.20.1050.130	Mainly Alpha	Up-down Bundle	Glutathione S-transferase Yfyf (Class Pi)	Chain A, domain 2	CATH (utative)
L	1.20.1050.130	Mainly Alpha	Up-down Bundle	Glutathione S-transferase Yfyf (Class Pi)	Chain A, domain 2	CATH (utative)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, G, H	PF01336	OB-fold nucleic acid binding domain (tRNA_anti-codon)	OB-fold nucleic acid binding domain	This family contains OB-fold domains that bind to nucleic acids [4]. The family includes the anti-codon binding domain of lysyl, aspartyl, and asparaginyl -tRNA synthetases (See Pfam:PF00152). Aminoacyl-tRNA synthetases catalyse the addition of an a ...	This family contains OB-fold domains that bind to nucleic acids [4]. The family includes the anti-codon binding domain of lysyl, aspartyl, and asparaginyl -tRNA synthetases (See Pfam:PF00152). Aminoacyl-tRNA synthetases catalyse the addition of an amino acid to the appropriate tRNA molecule EC:6.1.1.-. This family also includes part of RecG helicase involved in DNA repair. Replication factor A is a hetero-trimeric complex, that contains a subunit in this family [2,3]. This domain is also found at the C-terminus of bacterial DNA polymerase III alpha chain.	Domain
C, D, I, J	PF00043	Glutathione S-transferase, C-terminal domain (GST_C)	Glutathione S-transferase, C-terminal domain	GST conjugates reduced glutathione to a variety of targets including S-crystallin from squid, the eukaryotic elongation factor 1-gamma, the HSP26 family of stress-related proteins and auxin-regulated proteins in plants. Stringent starvation proteins ...	GST conjugates reduced glutathione to a variety of targets including S-crystallin from squid, the eukaryotic elongation factor 1-gamma, the HSP26 family of stress-related proteins and auxin-regulated proteins in plants. Stringent starvation proteins in E. coli are also included in the alignment but are not known to have GST activity. The glutathione molecule binds in a cleft between N and C-terminal domains. The catalytically important residues are proposed to reside in the N-terminal domain [1]. In plants, GSTs are encoded by a large gene family (48 GST genes in Arabidopsis) and can be divided into the phi, tau, theta, zeta, and lambda classes [2].	Domain
C, D, I, J	PF18569	Thioredoxin-like domain (Thioredoxin_16)	Thioredoxin-like domain	This is a thioredoxin like domain found in AIMP2 proteins (Aminoacyl tRNA synthetase complex interacting multifunctional protein 2). Aimp2 is a component of human multi-tRNA synthetase complex (MSC). MSC is a macromolecular protein complex consisting ...	This is a thioredoxin like domain found in AIMP2 proteins (Aminoacyl tRNA synthetase complex interacting multifunctional protein 2). Aimp2 is a component of human multi-tRNA synthetase complex (MSC). MSC is a macromolecular protein complex consisting of nine different ARSs and three ARS-interacting multifunctional proteins (AIMPs) [1].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, G, H	Aspartate--tRNA ligase, cytoplasmic	binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding adenyl nucleotide binding ATP binding heterocyclic compound binding carbohydrate derivative binding binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding adenyl nucleotide binding ATP binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding aminoacylase activity hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides hydrolase activity catalytic activity hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds RNA binding nucleic acid binding ligase activity, forming carbon-oxygen bonds aminoacyl-tRNA ligase activity catalytic activity, acting on RNA catalytic activity, acting on a nucleic acid catalytic activity, acting on a tRNA aspartate-tRNA ligase activity ligase activity	cellular component organization cellular component biogenesis cellular component assembly protein-containing complex organization protein-containing complex assembly cellular process cellular component organization or biogenesis amino acid activation tRNA aminoacylation cellular biosynthetic process organonitrogen compound biosynthetic process RNA metabolic process amino acid metabolic process nucleobase-containing compound metabolic process cellular component organization cellular component biogenesis cellular component assembly protein-containing complex organization protein-containing complex assembly cellular process cellular component organization or biogenesis amino acid activation tRNA aminoacylation cellular biosynthetic process organonitrogen compound biosynthetic process RNA metabolic process amino acid metabolic process nucleobase-containing compound metabolic process organic substance metabolic process organic substance biosynthetic process protein metabolic process organonitrogen compound metabolic process aspartyl-tRNA aminoacylation cellular metabolic process primary metabolic process translation gene expression tRNA aminoacylation for protein translation macromolecule biosynthetic process nucleic acid metabolic process tRNA metabolic process organic cyclic compound metabolic process biosynthetic process ncRNA metabolic process metabolic process macromolecule metabolic process	membrane cellular anatomical entity extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle protein-containing complex catalytic complex aminoacyl-tRNA synthetase multienzyme complex membrane cellular anatomical entity extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle protein-containing complex catalytic complex aminoacyl-tRNA synthetase multienzyme complex intracellular protein-containing complex synapse cell junction intracellular anatomical structure cytoplasm cytosol
C, D, I, J	Aminoacyl tRNA synthase complex-interacting multifunctional protein 2	molecular adaptor activity	cellular component organization cellular component biogenesis cellular component assembly protein-containing complex organization protein-containing complex assembly cellular process cellular component organization or biogenesis developmental process multicellular organismal process epithelium development cellular developmental process tube development animal organ development respiratory tube development cellular component organization cellular component biogenesis cellular component assembly protein-containing complex organization protein-containing complex assembly cellular process cellular component organization or biogenesis developmental process multicellular organismal process epithelium development cellular developmental process tube development animal organ development respiratory tube development lung epithelium development tissue development type II pneumocyte differentiation epithelial cell differentiation lung secretory cell differentiation lung epithelial cell differentiation multicellular organism development lung cell differentiation cell differentiation anatomical structure development lung development respiratory system development system development negative regulation of cell population proliferation regulation of biological process cell population proliferation regulation of cellular process regulation of cell population proliferation negative regulation of cellular process biological regulation negative regulation of biological process apoptotic process cell death programmed cell death regulation of protein modification process positive regulation of protein metabolic process positive regulation of biological process regulation of protein ubiquitination positive regulation of post-translational protein modification regulation of primary metabolic process positive regulation of metabolic process positive regulation of protein modification process organic substance metabolic process protein ubiquitination positive regulation of macromolecule metabolic process protein metabolic process regulation of protein modification by small protein conjugation or removal protein modification process positive regulation of protein modification by small protein conjugation or removal positive regulation of protein ubiquitination organonitrogen compound metabolic process regulation of post-translational protein modification regulation of protein metabolic process primary metabolic process regulation of macromolecule metabolic process macromolecule modification metabolic process macromolecule metabolic process post-translational protein modification regulation of metabolic process protein modification by small protein conjugation protein modification by small protein conjugation or removal cellular biosynthetic process cellular metabolic process organonitrogen compound biosynthetic process translation gene expression macromolecule biosynthetic process biosynthetic process organic substance biosynthetic process	membrane cellular anatomical entity protein-containing complex catalytic complex aminoacyl-tRNA synthetase multienzyme complex intracellular protein-containing complex intracellular anatomical structure cytoplasm cytosol membrane-bounded organelle intracellular organelle organelle nucleus intracellular membrane-bounded organelle
E, F, K, L	Bifunctional glutamate/proline--tRNA ligase	glutamate-tRNA ligase activity ligase activity, forming carbon-oxygen bonds aminoacyl-tRNA ligase activity catalytic activity, acting on RNA catalytic activity, acting on a nucleic acid catalytic activity, acting on a tRNA catalytic activity ligase activity protein binding binding enzyme binding GTPase binding adenyl ribonucleotide binding nucleotide binding glutamate-tRNA ligase activity ligase activity, forming carbon-oxygen bonds aminoacyl-tRNA ligase activity catalytic activity, acting on RNA catalytic activity, acting on a nucleic acid catalytic activity, acting on a tRNA catalytic activity ligase activity protein binding binding enzyme binding GTPase binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding adenyl nucleotide binding ATP binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding identical protein binding protein homodimerization activity protein dimerization activity RNA binding RNA stem-loop binding nucleic acid binding proline-tRNA ligase activity cation binding transition metal ion binding zinc ion binding metal ion binding	regulation of cellular process cellular biosynthetic process organonitrogen compound biosynthetic process negative regulation of biological process negative regulation of cellular metabolic process regulation of primary metabolic process post-transcriptional regulation of gene expression negative regulation of translation organic substance metabolic process organic substance biosynthetic process negative regulation of cellular process protein metabolic process negative regulation of protein metabolic process negative regulation of macromolecule metabolic process regulation of cellular process cellular biosynthetic process organonitrogen compound biosynthetic process negative regulation of biological process negative regulation of cellular metabolic process regulation of primary metabolic process post-transcriptional regulation of gene expression negative regulation of translation organic substance metabolic process organic substance biosynthetic process negative regulation of cellular process protein metabolic process negative regulation of protein metabolic process negative regulation of macromolecule metabolic process regulation of biosynthetic process regulation of biological process organonitrogen compound metabolic process cellular metabolic process regulation of protein metabolic process negative regulation of metabolic process biological regulation regulation of cellular metabolic process primary metabolic process regulation of macromolecule metabolic process gene expression translation macromolecule biosynthetic process negative regulation of cellular biosynthetic process regulation of cellular biosynthetic process regulation of gene expression negative regulation of gene expression biosynthetic process negative regulation of biosynthetic process regulation of translation negative regulation of macromolecule biosynthetic process regulation of macromolecule biosynthetic process metabolic process cellular process macromolecule metabolic process regulation of metabolic process import into cell regulation of localization transport regulation of lipid transport localization monocarboxylic acid transport fatty acid transport lipid import into cell long-chain fatty acid import into cell long-chain fatty acid transport organic anion transport carboxylic acid transport regulation of transport organic substance transport regulation of long-chain fatty acid import into cell lipid localization lipid transport establishment of localization regulation of fatty acid transport organic acid transport regulation of lipid localization macromolecule localization regulation of organic acid transport amino acid activation tRNA aminoacylation RNA metabolic process amino acid metabolic process nucleobase-containing compound metabolic process tRNA aminoacylation for protein translation nucleic acid metabolic process tRNA metabolic process organic cyclic compound metabolic process ncRNA metabolic process cellular response to stimulus response to organic substance biological process involved in interspecies interaction between organisms response to stimulus response to type II interferon response to cytokine cellular response to type II interferon response to biotic stimulus response to stress innate immune response cellular response to cytokine stimulus response to external biotic stimulus cellular response to organic substance immune response response to other organism defense response defense response to symbiont response to external stimulus cellular response to chemical stimulus response to chemical immune system process defense response to other organism glutamyl-tRNA aminoacylation prolyl-tRNA aminoacylation cellular response to nitrogen compound response to endogenous stimulus response to organonitrogen compound response to peptide hormone response to oxygen-containing compound cellular response to peptide hormone stimulus response to nitrogen compound cellular response to oxygen-containing compound cellular response to endogenous stimulus cellular response to organonitrogen compound response to hormone response to insulin cellular response to insulin stimulus cellular response to hormone stimulus	membrane cellular anatomical entity intracellular anatomical structure cytoplasm cytosol protein-containing complex GAIT complex cell periphery plasma membrane catalytic complex aminoacyl-tRNA synthetase multienzyme complex intracellular protein-containing complex ribonucleoprotein complex

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, G, H	IPR045864	Class II Aminoacyl-tRNA synthetase/Biotinyl protein ligase (BPL) and lipoyl protein ligase (LPL)	Homologous Superfamily
A, B, G, H	IPR002312	Aspartyl/Asparaginyl-tRNA synthetase, class IIb	Family
A, B, G, H	IPR004523	Aspartate-tRNA synthetase, type 2	Family
A, B, G, H	IPR004365	OB-fold nucleic acid binding domain, AA-tRNA synthetase-type	Domain
A, B, G, H	IPR006195	Aminoacyl-tRNA synthetase, class II	Domain
A, B, G, H	IPR012340	Nucleic acid-binding, OB-fold	Homologous Superfamily
A, B, G, H	IPR004364	Aminoacyl-tRNA synthetase, class II (D/K/N)	Domain
C, D, I, J	IPR031889	AIMP2, lysyl-tRNA synthetase binding domain	Domain
C, D, I, J	IPR004046	Glutathione S-transferase, C-terminal	Domain
C, D, I, J	IPR042360	Aminoacyl tRNA synthase complex-interacting multifunctional protein 2	Family
C, D, I, J	IPR041503	AIMP2, thioredoxin-like domain	Domain
C, D, I, J	IPR036282	Glutathione S-transferase, C-terminal domain superfamily	Homologous Superfamily
E, F, K, L	IPR045864	Class II Aminoacyl-tRNA synthetase/Biotinyl protein ligase (BPL) and lipoyl protein ligase (LPL)	Homologous Superfamily
E, F, K, L	IPR009068	uS15/NS1, RNA-binding domain superfamily	Homologous Superfamily
E, F, K, L	IPR001412	Aminoacyl-tRNA synthetase, class I, conserved site	Conserved Site
E, F, K, L	IPR004154	Anticodon-binding	Domain
E, F, K, L	IPR014729	Rossmann-like alpha/beta/alpha sandwich fold	Homologous Superfamily
E, F, K, L	IPR006195	Aminoacyl-tRNA synthetase, class II	Domain
E, F, K, L	IPR002314	Aminoacyl-tRNA synthetase, class II (G/ P/ S/T)	Domain
E, F, K, L	IPR036621	Anticodon-binding domain superfamily	Homologous Superfamily
E, F, K, L	IPR004499	Proline-tRNA ligase, class IIa, archaeal-type	Family
E, F, K, L	IPR000738	WHEP-TRS domain	Domain
E, F, K, L	IPR004526	Glutamyl-tRNA synthetase, archaeal/eukaryotic cytosolic	Family
E, F, K, L	IPR000924	Glutamyl/glutaminyl-tRNA synthetase	Family
E, F, K, L	IPR020058	Glutamyl/glutaminyl-tRNA synthetase, class Ib, catalytic domain	Domain
E, F, K, L	IPR017449	Prolyl-tRNA synthetase, class II	Homologous Superfamily
E, F, K, L	IPR020056	Large ribosomal subunit protein bL25/Gln-tRNA synthetase, N-terminal	Homologous Superfamily
E, F, K, L	IPR049437	tRNA synthetases class I (E and Q), anti-codon binding domain	Domain
E, F, K, L	IPR020059	Glutamyl/glutaminyl-tRNA synthetase, class Ib, anti-codon binding domain	Domain
E, F, K, L	IPR011035	Large ribosomal subunit protein bL25/Gln-tRNA synthetase, anti-codon-binding domain superfamily	Homologous Superfamily
E, F, K, L	IPR033721	Prolyl-tRNA synthetase, catalytic domain	Domain
E, F, K, L	IPR036282	Glutathione S-transferase, C-terminal domain superfamily	Homologous Superfamily
E, F, K, L	IPR016061	Proline-tRNA ligase, class II, C-terminal	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, G, H	Pharos: P14868	hypomyelination with brain stem and spinal cord involvement and leg spasticity astrocytic tumor malignant glioma ovarian cancer breast cancer lung cancer medulloblastoma plasma cell myeloma glioblastoma malignant ependymoma myopathy
C, D, I, J	Pharos: Q13155	astrocytic tumor leukodystrophy lung cancer ovarian cancer glioblastoma leukodystrophy, hypomyelinating, 17 malignant glioma Sjogren syndrome large cell medulloblastoma lung adenocarcinoma medulloblastoma
E, F, K, L	Pharos: P07814	pancreatic intraductal papillary-mucinous carcinoma primitive neuroectodermal tumor astrocytic tumor Gaucher disease large cell medulloblastoma lung adenocarcinoma malignant glioma neurodegenerative disease osteosarcoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia psoriasis atypical teratoid rhabdoid tumor glioblastoma leukodystrophy lung cancer pancreatic intraductal papillary-mucinous carcinoma primitive neuroectodermal tumor astrocytic tumor Gaucher disease large cell medulloblastoma lung adenocarcinoma malignant glioma neurodegenerative disease osteosarcoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia psoriasis atypical teratoid rhabdoid tumor glioblastoma leukodystrophy lung cancer malignant pancreatic neoplasm non-small cell lung carcinoma ovarian cancer plasma cell myeloma breast cancer invasive ductal breast carcinoma leukodystrophy, hypomyelinating, 15 malignant ependymoma medulloblastoma oligodendroglioma