2WK5

Structural features of native human thymidine phosphorylase and in complex with 5-iodouracil

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
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: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d2wk5a1	All alpha proteins	Methionine synthase domain-like	Nucleoside phosphorylase/phosphoribosyltransferase N-terminal domain	automated matches	automated matches	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d2wk5a2	Alpha and beta proteins (a/b)	Nucleoside phosphorylase/phosphoribosyltransferase catalytic domain	Nucleoside phosphorylase/phosphoribosyltransferase catalytic domain	Nucleoside phosphorylase/phosphoribosyltransferase catalytic domain	automated matches	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d2wk5a3	Alpha and beta proteins (a+b)	alpha/beta-Hammerhead	Pyrimidine nucleoside phosphorylase C-terminal domain	automated matches	automated matches	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d2wk5b1	All alpha proteins	Methionine synthase domain-like	Nucleoside phosphorylase/phosphoribosyltransferase N-terminal domain	automated matches	automated matches	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d2wk5b2	Alpha and beta proteins (a/b)	Nucleoside phosphorylase/phosphoribosyltransferase catalytic domain	Nucleoside phosphorylase/phosphoribosyltransferase catalytic domain	Nucleoside phosphorylase/phosphoribosyltransferase catalytic domain	automated matches	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d2wk5b3	Alpha and beta proteins (a+b)	alpha/beta-Hammerhead	Pyrimidine nucleoside phosphorylase C-terminal domain	automated matches	automated matches	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d2wk5c1	All alpha proteins	Methionine synthase domain-like	Nucleoside phosphorylase/phosphoribosyltransferase N-terminal domain	automated matches	automated matches	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d2wk5c2	Alpha and beta proteins (a/b)	Nucleoside phosphorylase/phosphoribosyltransferase catalytic domain	Nucleoside phosphorylase/phosphoribosyltransferase catalytic domain	Nucleoside phosphorylase/phosphoribosyltransferase catalytic domain	automated matches	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d2wk5c3	Alpha and beta proteins (a+b)	alpha/beta-Hammerhead	Pyrimidine nucleoside phosphorylase C-terminal domain	automated matches	automated matches	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d2wk5d1	All alpha proteins	Methionine synthase domain-like	Nucleoside phosphorylase/phosphoribosyltransferase N-terminal domain	automated matches	automated matches	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d2wk5d2	Alpha and beta proteins (a/b)	Nucleoside phosphorylase/phosphoribosyltransferase catalytic domain	Nucleoside phosphorylase/phosphoribosyltransferase catalytic domain	Nucleoside phosphorylase/phosphoribosyltransferase catalytic domain	automated matches	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d2wk5d3	Alpha and beta proteins (a+b)	alpha/beta-Hammerhead	Pyrimidine nucleoside phosphorylase C-terminal domain	automated matches	automated matches	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	Nucleoside phosphorylase/phosphoribosyltransferase catalytic domain	8041939	3001630	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	Nucleoside phosphorylase/phosphoribosyltransferase N-terminal domain	8041938	3000348	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	Pyrimidine nucleoside phosphorylase C-terminal domain	8041940	3000876	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Nucleoside phosphorylase/phosphoribosyltransferase catalytic domain	8041939	3001630	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Pyrimidine nucleoside phosphorylase C-terminal domain	8041940	3000876	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Nucleoside phosphorylase/phosphoribosyltransferase N-terminal domain	8041938	3000348	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	Nucleoside phosphorylase/phosphoribosyltransferase N-terminal domain	8041938	3000348	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	Pyrimidine nucleoside phosphorylase C-terminal domain	8041940	3000876	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	Nucleoside phosphorylase/phosphoribosyltransferase catalytic domain	8041939	3001630	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	Pyrimidine nucleoside phosphorylase C-terminal domain	8041940	3000876	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	Nucleoside phosphorylase/phosphoribosyltransferase catalytic domain	8041939	3001630	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	Nucleoside phosphorylase/phosphoribosyltransferase N-terminal domain	8041938	3000348	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	PF02885	e2wk5A1	A: alpha arrays	X: Nucleoside phosphorylase/phosphoribosyltransferase-N (From Topology)	H: Nucleoside phosphorylase/phosphoribosyltransferase-N (From Topology)	T: Nucleoside phosphorylase/phosphoribosyltransferase-N	F: PF02885	ECOD (1.6)
A	PF07831	e2wk5A2	A: a+b complex topology	X: alpha/beta-Hammerhead/Barrel-sandwich hybrid	H: alpha/beta-Hammerhead/Barrel-sandwich hybrid	T: Pyrimidine nucleoside phosphorylase C-terminal domain	F: PF07831	ECOD (1.6)
A	PF00591	e2wk5A3	A: a/b three-layered sandwiches	X: Nucleoside phosphorylase/phosphoribosyltransferase catalytic domain (From Topology)	H: Nucleoside phosphorylase/phosphoribosyltransferase catalytic domain (From Topology)	T: Nucleoside phosphorylase/phosphoribosyltransferase catalytic domain	F: PF00591	ECOD (1.6)
B	PF02885	e2wk5B1	A: alpha arrays	X: Nucleoside phosphorylase/phosphoribosyltransferase-N (From Topology)	H: Nucleoside phosphorylase/phosphoribosyltransferase-N (From Topology)	T: Nucleoside phosphorylase/phosphoribosyltransferase-N	F: PF02885	ECOD (1.6)
B	PF07831	e2wk5B2	A: a+b complex topology	X: alpha/beta-Hammerhead/Barrel-sandwich hybrid	H: alpha/beta-Hammerhead/Barrel-sandwich hybrid	T: Pyrimidine nucleoside phosphorylase C-terminal domain	F: PF07831	ECOD (1.6)
B	PF00591	e2wk5B3	A: a/b three-layered sandwiches	X: Nucleoside phosphorylase/phosphoribosyltransferase catalytic domain (From Topology)	H: Nucleoside phosphorylase/phosphoribosyltransferase catalytic domain (From Topology)	T: Nucleoside phosphorylase/phosphoribosyltransferase catalytic domain	F: PF00591	ECOD (1.6)
C	PF02885	e2wk5C1	A: alpha arrays	X: Nucleoside phosphorylase/phosphoribosyltransferase-N (From Topology)	H: Nucleoside phosphorylase/phosphoribosyltransferase-N (From Topology)	T: Nucleoside phosphorylase/phosphoribosyltransferase-N	F: PF02885	ECOD (1.6)
C	PF07831	e2wk5C2	A: a+b complex topology	X: alpha/beta-Hammerhead/Barrel-sandwich hybrid	H: alpha/beta-Hammerhead/Barrel-sandwich hybrid	T: Pyrimidine nucleoside phosphorylase C-terminal domain	F: PF07831	ECOD (1.6)
C	PF00591	e2wk5C3	A: a/b three-layered sandwiches	X: Nucleoside phosphorylase/phosphoribosyltransferase catalytic domain (From Topology)	H: Nucleoside phosphorylase/phosphoribosyltransferase catalytic domain (From Topology)	T: Nucleoside phosphorylase/phosphoribosyltransferase catalytic domain	F: PF00591	ECOD (1.6)
D	PF02885	e2wk5D1	A: alpha arrays	X: Nucleoside phosphorylase/phosphoribosyltransferase-N (From Topology)	H: Nucleoside phosphorylase/phosphoribosyltransferase-N (From Topology)	T: Nucleoside phosphorylase/phosphoribosyltransferase-N	F: PF02885	ECOD (1.6)
D	PF07831	e2wk5D2	A: a+b complex topology	X: alpha/beta-Hammerhead/Barrel-sandwich hybrid	H: alpha/beta-Hammerhead/Barrel-sandwich hybrid	T: Pyrimidine nucleoside phosphorylase C-terminal domain	F: PF07831	ECOD (1.6)
D	PF00591	e2wk5D3	A: a/b three-layered sandwiches	X: Nucleoside phosphorylase/phosphoribosyltransferase catalytic domain (From Topology)	H: Nucleoside phosphorylase/phosphoribosyltransferase catalytic domain (From Topology)	T: Nucleoside phosphorylase/phosphoribosyltransferase catalytic domain	F: PF00591	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	1.20.970.10	Mainly Alpha	Up-down Bundle	Transferase, Pyrimidine Nucleoside Phosphorylase	Chain A, domain 3	CATH (4.3.0)
A	3.40.1030.10	Alpha Beta	3-Layer(aba) Sandwich	Pyrimidine Nucleoside Phosphorylase	Chain A, domain 2	CATH (4.3.0)
A	3.90.1170.30	Alpha Beta	Alpha-Beta Complex	Aldehyde Oxidoreductase	domain 3	CATH (4.3.0)
B	1.20.970.10	Mainly Alpha	Up-down Bundle	Transferase, Pyrimidine Nucleoside Phosphorylase	Chain A, domain 3	CATH (4.3.0)
B	3.40.1030.10	Alpha Beta	3-Layer(aba) Sandwich	Pyrimidine Nucleoside Phosphorylase	Chain A, domain 2	CATH (4.3.0)
B	3.90.1170.30	Alpha Beta	Alpha-Beta Complex	Aldehyde Oxidoreductase	domain 3	CATH (4.3.0)
C	1.20.970.10	Mainly Alpha	Up-down Bundle	Transferase, Pyrimidine Nucleoside Phosphorylase	Chain A, domain 3	CATH (4.3.0)
C	3.40.1030.10	Alpha Beta	3-Layer(aba) Sandwich	Pyrimidine Nucleoside Phosphorylase	Chain A, domain 2	CATH (4.3.0)
C	3.90.1170.30	Alpha Beta	Alpha-Beta Complex	Aldehyde Oxidoreductase	domain 3	CATH (4.3.0)
D	1.20.970.10	Mainly Alpha	Up-down Bundle	Transferase, Pyrimidine Nucleoside Phosphorylase	Chain A, domain 3	CATH (4.3.0)
D	3.40.1030.10	Alpha Beta	3-Layer(aba) Sandwich	Pyrimidine Nucleoside Phosphorylase	Chain A, domain 2	CATH (4.3.0)
D	3.90.1170.30	Alpha Beta	Alpha-Beta Complex	Aldehyde Oxidoreductase	domain 3	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, C, D	PF00591	Glycosyl transferase family, a/b domain (Glycos_transf_3)	Glycosyl transferase family, a/b domain	-	Family
A, B, C, D	PF02885	Glycosyl transferase family, helical bundle domain (Glycos_trans_3N)	Glycosyl transferase family, helical bundle domain	This family includes anthranilate phosphoribosyltransferase (TrpD), thymidine phosphorylase. All these proteins can transfer a phosphorylated ribose substrate.	Domain
A, B, C, D	PF07831	Pyrimidine nucleoside phosphorylase C-terminal domain (PYNP_C)	Pyrimidine nucleoside phosphorylase C-terminal domain	This domain is found at the C-terminal end of the large alpha/beta domain making up various pyrimidine nucleoside phosphorylases [1,2]. It has slightly different conformations in different members of this family. For example, in pyrimidine nucleoside ...	This domain is found at the C-terminal end of the large alpha/beta domain making up various pyrimidine nucleoside phosphorylases [1,2]. It has slightly different conformations in different members of this family. For example, in pyrimidine nucleoside phosphorylase (PYNP, Swiss:P77826) there is an added three-stranded anti-parallel beta sheet as compared to other members of the family, such as E. coli thymidine phosphorylase (TP, Swiss:P07650) [1]. The domain contains an alpha/ beta hammerhead fold and residues in this domain seem to be important in formation of the homodimer [1].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C, D	THYMIDINE PHOSPHORYLASE	protein binding binding molecular function activator activity signaling receptor binding molecular function regulator activity signaling receptor regulator activity growth factor activity receptor ligand activity signaling receptor activator activity pentosyltransferase activity glycosyltransferase activity transferase activity catalytic activity pyrimidine-nucleoside phosphorylase activity protein binding binding molecular function activator activity signaling receptor binding molecular function regulator activity signaling receptor regulator activity growth factor activity receptor ligand activity signaling receptor activator activity pentosyltransferase activity glycosyltransferase activity transferase activity catalytic activity pyrimidine-nucleoside phosphorylase activity 1,4-alpha-oligoglucan phosphorylase activity hexosyltransferase activity identical protein binding protein homodimerization activity protein dimerization activity thymidine phosphorylase activity	multicellular organismal process system process regulation of biological process digestive system process regulation of system process regulation of gastric motility biological regulation regulation of digestive system process digestion gastric motility regulation of multicellular organismal process developmental process cellular developmental process cell differentiation multicellular organismal process system process regulation of biological process digestive system process regulation of system process regulation of gastric motility biological regulation regulation of digestive system process digestion gastric motility regulation of multicellular organismal process developmental process cellular developmental process cell differentiation cellular process regulation of multicellular organismal development regulation of cellular process regulation of developmental process regulation of myelination nervous system development regulation of nervous system development myelination multicellular organism development axon ensheathment ensheathment of neurons anatomical structure development system development blood vessel morphogenesis tube development angiogenesis vasculature development circulatory system development anatomical structure morphogenesis tube morphogenesis anatomical structure formation involved in morphogenesis blood vessel development chemotaxis response to stimulus taxis response to chemical response to external stimulus locomotion cellular component organization organelle organization mitochondrial genome maintenance cellular component organization or biogenesis mitochondrion organization pyrimidine deoxyribonucleotide catabolic process pyrimidine deoxyribonucleoside monophosphate catabolic process catabolic process deoxyribonucleoside monophosphate catabolic process deoxyribonucleotide catabolic process pyrimidine deoxyribonucleotide metabolic process pyrimidine-containing compound catabolic process carbohydrate derivative metabolic process organophosphate catabolic process nucleoside phosphate catabolic process deoxyribose phosphate catabolic process pyrimidine nucleotide metabolic process dTMP catabolic process pyrimidine deoxyribonucleoside monophosphate metabolic process nucleobase-containing compound metabolic process pyrimidine nucleotide catabolic process organic substance metabolic process deoxyribonucleotide metabolic process nucleobase-containing small molecule metabolic process dTMP metabolic process phosphate-containing compound metabolic process small molecule metabolic process nucleoside monophosphate metabolic process phosphorus metabolic process nucleotide catabolic process pyrimidine nucleoside monophosphate catabolic process nucleoside phosphate metabolic process organonitrogen compound catabolic process pyrimidine nucleoside monophosphate metabolic process carbohydrate derivative catabolic process pyrimidine-containing compound metabolic process organonitrogen compound metabolic process nucleoside monophosphate catabolic process cellular metabolic process 2'-deoxyribonucleotide metabolic process primary metabolic process nucleotide metabolic process deoxyribose phosphate metabolic process deoxyribonucleoside monophosphate metabolic process organic cyclic compound catabolic process nucleobase-containing compound catabolic process organic cyclic compound metabolic process organophosphate metabolic process metabolic process organic substance catabolic process pyrimidine nucleobase metabolic process nucleobase metabolic process glycosyl compound metabolic process pyrimidine nucleoside metabolic process nucleoside metabolic process nervous system process transmission of nerve impulse cell communication regulation of nervous system process regulation of transmission of nerve impulse regulation of cell communication	intracellular anatomical structure cytoplasm cellular anatomical entity cytosol

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C, D	IPR000312	Glycosyl transferase, family 3	Domain
A, B, C, D	IPR013102	Pyrimidine nucleoside phosphorylase, C-terminal	Domain
A, B, C, D	IPR018090	Pyrimidine-nucleoside phosphorylase, bacterial/eukaryotic	Family
A, B, C, D	IPR000053	Thymidine/pyrimidine-nucleoside phosphorylase	Family
A, B, C, D	IPR035902	Nucleoside phosphorylase/phosphoribosyltransferase catalytic domain superfamily	Homologous Superfamily
A, B, C, D	IPR036320	Glycosyl transferase family 3, N-terminal domain superfamily	Homologous Superfamily
A, B, C, D	IPR036566	Pyrimidine nucleoside phosphorylase-like, C-terminal domain superfamily	Homologous Superfamily
A, B, C, D	IPR017872	Pyrimidine-nucleoside phosphorylase, conserved site	Conserved Site
A, B, C, D	IPR017459	Glycosyl transferase family 3, N-terminal domain	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, C, D	Pharos: P19971	mitochondrial DNA depletion syndrome 1 esophageal squamous cell carcinoma malignant colon neoplasm gastric cancer malignant pancreatic neoplasm Neoplasm Metastasis progressive external ophthalmoplegia sarcomatoid carcinoma urinary bladder cancer carcinoma colorectal cancer leukodystrophy malignant ependymoma mitochondrial DNA depletion syndrome 4b benign colon neoplasm mitochondrial DNA depletion syndrome 1 esophageal squamous cell carcinoma malignant colon neoplasm gastric cancer malignant pancreatic neoplasm Neoplasm Metastasis progressive external ophthalmoplegia sarcomatoid carcinoma urinary bladder cancer carcinoma colorectal cancer leukodystrophy malignant ependymoma mitochondrial DNA depletion syndrome 4b benign colon neoplasm muscle tissue disease Charcot-Marie-Tooth disease colorectal carcinoma diffuse large B-cell lymphoma gastric neoplasm juvenile dermatomyositis lung cancer mitochondrial DNA depletion syndrome 8a atopic eczema muscular disease pancreatic neoplasm colonic neoplasm psoriasis ulcerative colitis urinary bladder neoplasm hereditary diffuse gastric adenocarcinoma large cell medulloblastoma mitochondrial neurogastrointestinal encephalomyopathy B-cell chronic lymphocytic leukemia myopathy peripheral neuropathy rhabdomyolysis cutaneous lupus erythematosus undifferentiated carcinoma X-linked mixed deafness with perilymphatic gusher interstitial cystitis

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), 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 R01GM133198.