3EJL

Replacement of Val3 in Human Thymidylate Synthase Affects Its Kinetic Properties and Intracellular Stability

External Resource: Annotation

Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	Thymidylate synthase/dCMP hydroxymethylase	8036156	3000544	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Thymidylate synthase/dCMP hydroxymethylase	8036156	3000544	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	Thymidylate synthase/dCMP hydroxymethylase	8036156	3000544	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	Thymidylate synthase/dCMP hydroxymethylase	8036156	3000544	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	Thymidylat_synt	e3ejlA1	A: a+b two layers	X: Thymidylate synthase/dCMP hydroxymethylase (From Topology)	H: Thymidylate synthase/dCMP hydroxymethylase (From Topology)	T: Thymidylate synthase/dCMP hydroxymethylase	F: Thymidylat_synt	ECOD (1.6)
B	Thymidylat_synt	e3ejlB1	A: a+b two layers	X: Thymidylate synthase/dCMP hydroxymethylase (From Topology)	H: Thymidylate synthase/dCMP hydroxymethylase (From Topology)	T: Thymidylate synthase/dCMP hydroxymethylase	F: Thymidylat_synt	ECOD (1.6)
C	Thymidylat_synt	e3ejlC1	A: a+b two layers	X: Thymidylate synthase/dCMP hydroxymethylase (From Topology)	H: Thymidylate synthase/dCMP hydroxymethylase (From Topology)	T: Thymidylate synthase/dCMP hydroxymethylase	F: Thymidylat_synt	ECOD (1.6)
D	Thymidylat_synt	e3ejlD1	A: a+b two layers	X: Thymidylate synthase/dCMP hydroxymethylase (From Topology)	H: Thymidylate synthase/dCMP hydroxymethylase (From Topology)	T: Thymidylate synthase/dCMP hydroxymethylase	F: Thymidylat_synt	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.30.572.10	Alpha Beta	2-Layer Sandwich	Thymidylate Synthase	Chain A	CATH (4.3.0)
B	3.30.572.10	Alpha Beta	2-Layer Sandwich	Thymidylate Synthase	Chain A	CATH (4.3.0)
C	3.30.572.10	Alpha Beta	2-Layer Sandwich	Thymidylate Synthase	Chain A	CATH (4.3.0)
D	3.30.572.10	Alpha Beta	2-Layer Sandwich	Thymidylate Synthase	Chain A	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, C, D	PF00303	Thymidylate synthase (Thymidylat_synt)	Thymidylate synthase	This is a family of proteins that are flavin-dependent thymidylate synthases.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C, D	Thymidylate synthase	translation regulator activity binding mRNA regulatory element binding translation repressor activity organic cyclic compound binding translation regulator activity, nucleic acid binding nucleic acid binding translation repressor activity RNA binding sequence-specific mRNA binding mRNA binding transferase activity, transferring one-carbon groups transferase activity methyltransferase activity thymidylate synthase activity translation regulator activity binding mRNA regulatory element binding translation repressor activity organic cyclic compound binding translation regulator activity, nucleic acid binding nucleic acid binding translation repressor activity RNA binding sequence-specific mRNA binding mRNA binding transferase activity, transferring one-carbon groups transferase activity methyltransferase activity thymidylate synthase activity 5,10-methylenetetrahydrofolate-dependent methyltransferase activity catalytic activity identical protein binding protein binding protein homodimerization activity protein dimerization activity amide binding organic acid binding modified amino acid binding vitamin binding ion binding folic acid binding anion binding carboxylic acid binding heterocyclic compound binding small molecule binding	developmental process multicellular organism development multicellular organismal process skeletal system development connective tissue development anatomical structure development animal organ development tissue development cartilage development system development response to stimulus response to chemical response to xenobiotic stimulus rhythmic process developmental process multicellular organism development multicellular organismal process skeletal system development connective tissue development anatomical structure development animal organ development tissue development cartilage development system development response to stimulus response to chemical response to xenobiotic stimulus rhythmic process circadian rhythm regulation of cellular process cellular 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 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 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 pyrimidine deoxyribonucleotide metabolic process deoxyribose phosphate biosynthetic process nucleotide biosynthetic process carbohydrate derivative metabolic process pyrimidine nucleotide metabolic process pyrimidine deoxyribonucleoside monophosphate metabolic process nucleobase-containing compound metabolic process deoxyribonucleotide biosynthetic process deoxyribonucleotide metabolic process pyrimidine deoxyribonucleotide biosynthetic process nucleobase-containing small molecule metabolic process dTMP metabolic process phosphate-containing compound metabolic process deoxyribonucleoside monophosphate biosynthetic process dTMP biosynthetic process small molecule metabolic process pyrimidine deoxyribonucleoside monophosphate biosynthetic process pyrimidine-containing compound biosynthetic process nucleoside monophosphate metabolic process phosphorus metabolic process nucleoside phosphate metabolic process carbohydrate derivative biosynthetic process pyrimidine nucleoside monophosphate metabolic process pyrimidine-containing compound metabolic process 2'-deoxyribonucleotide metabolic process 2'-deoxyribonucleotide biosynthetic process nucleotide metabolic process deoxyribose phosphate metabolic process nucleobase-containing compound biosynthetic process deoxyribonucleoside monophosphate metabolic process nucleoside monophosphate biosynthetic process organophosphate metabolic process organophosphate biosynthetic process nucleoside phosphate biosynthetic process pyrimidine nucleoside monophosphate biosynthetic process pyrimidine nucleotide biosynthetic process response to ketone response to lipid response to hormone response to steroid hormone response to endogenous stimulus response to progesterone response to oxygen-containing compound response to organic cyclic compound cellular developmental process cell development epithelial cell differentiation intestinal epithelial cell maturation columnar/cuboidal epithelial cell development cell differentiation cell maturation epithelium development digestive system development intestinal epithelial cell differentiation tube development intestinal epithelial cell development developmental maturation digestive tract development epithelial cell development anatomical structure maturation columnar/cuboidal epithelial cell differentiation epithelial cell maturation columnar/cuboidal epithelial cell maturation methylation pyrimidine nucleobase metabolic process uracil metabolic process nucleobase metabolic process folic acid-containing compound metabolic process tetrahydrofolate interconversion tetrahydrofolate metabolic process pteridine-containing compound metabolic process cellular modified amino acid metabolic process one-carbon metabolic process response to nutrient levels response to nutrient response to vitamin A response to vitamin gland development animal organ regeneration liver development regeneration hepaticobiliary system development liver regeneration response to toxic substance developmental growth growth pyrimidine deoxyribonucleoside triphosphate biosynthetic process dTTP biosynthetic process pyrimidine deoxyribonucleoside triphosphate metabolic process pyrimidine nucleoside triphosphate biosynthetic process pyrimidine nucleoside triphosphate metabolic process dTTP metabolic process nucleoside triphosphate biosynthetic process nucleoside triphosphate metabolic process response to peptide response to cytokine response to corticosteroid response to glucocorticoid response to alcohol response to ethanol DNA metabolic process nucleic acid metabolic process nucleic acid biosynthetic process DNA biosynthetic process response to organophosphorus response to folic acid response to nitrogen compound	membrane-bounded organelle intracellular organelle intracellular anatomical structure mitochondrion organelle cytoplasm cellular anatomical entity intracellular membrane-bounded organelle mitochondrial membrane organelle inner membrane membrane mitochondrial inner membrane organelle envelope mitochondrial envelope membrane-bounded organelle intracellular organelle intracellular anatomical structure mitochondrion organelle cytoplasm cellular anatomical entity intracellular membrane-bounded organelle mitochondrial membrane organelle inner membrane membrane mitochondrial inner membrane organelle envelope mitochondrial envelope organelle membrane cytosol membrane-enclosed lumen mitochondrial matrix intracellular organelle lumen organelle lumen nucleus

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C, D	IPR036926	Thymidylate synthase/dCMP hydroxymethylase superfamily	Homologous Superfamily
A, B, C, D	IPR000398	Thymidylate synthase	Family
A, B, C, D	IPR020940	Thymidylate synthase, active site	Active Site
A, B, C, D	IPR023451	Thymidylate synthase/dCMP hydroxymethylase domain	Domain
A, B, C, D	IPR045097	Thymidylate synthase/dCMP hydroxymethylase	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, C, D	Pharos: P04818	malignant colon neoplasm breast carcinoma cleft palate squamous cell carcinoma follicular lymphoma colorectal cancer lung adenocarcinoma nervous system disorder non-small cell lung carcinoma gastric cancer head and neck cancer breast cancer Hyperammonemia malignant pancreatic neoplasm neuroendocrine neoplasm malignant colon neoplasm breast carcinoma cleft palate squamous cell carcinoma follicular lymphoma colorectal cancer lung adenocarcinoma nervous system disorder non-small cell lung carcinoma gastric cancer head and neck cancer breast cancer Hyperammonemia malignant pancreatic neoplasm neuroendocrine neoplasm ovarian cancer anemia rectal neoplasm brain disease prostate cancer medulloblastoma Sjogren syndrome nasopharyngeal carcinoma cystic fibrosis superficial multifocal basal cell carcinoma digestive system disease Down syndrome actinic keratosis pancreatic adenocarcinoma ductal breast carcinoma in situ pancreatic neoplasm atypical teratoid rhabdoid tumor pituitary cancer primitive neuroectodermal tumor hepatocellular carcinoma cancer cleft lip rectal carcinoma invasive ductal breast carcinoma reticulum cell sarcoma colorectal carcinoma small intestine cancer lung benign neoplasm neoplasm of neck testicular germ cell tumor Tourette syndrome pancreatic intraductal papillary-mucinous carcinoma endometriosis lymphoplasmacytic lymphoma Pick disease gastric neoplasm malignant ependymoma benign colon neoplasm head and neck neoplasm progressive supranuclear palsy hereditary diffuse gastric adenocarcinoma psoriasis IgA glomerulonephritis malignant pleural mesothelioma large cell medulloblastoma colonic neoplasm sinusitis lung cancer digestive system cancer tongue cancer non-Hodgkin lymphoma tuberculosis ovarian neoplasm adrenal cortex carcinoma pancreatic intraductal papillary-mucinous neoplasm lymphosarcoma atopic eczema pilocytic astrocytoma glioblastoma malignant glioma breast fibroadenoma rectal cancer interstitial cystitis malignant tumor of neck liver cancer

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM157729.