6I7P

Crystal structure of the full-length Zika virus NS5 protein (Human isolate Z1106033)

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

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	S-adenosyl-L-methionine-dependent methyltransferases	8077179	3000118	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	S-adenosyl-L-methionine-dependent methyltransferases	8077179	3000118	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	S-adenosyl-L-methionine-dependent methyltransferases	8077179	3000118	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	S-adenosyl-L-methionine-dependent methyltransferases	8077179	3000118	SCOP2B (2022-06-29)
E	SCOP2B Superfamily	S-adenosyl-L-methionine-dependent methyltransferases	8077179	3000118	SCOP2B (2022-06-29)
F	SCOP2B Superfamily	S-adenosyl-L-methionine-dependent methyltransferases	8077179	3000118	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	Flavi_NS5_2nd	e6i7pA2	A: alpha bundles	X: helical bundle domain in reverse transcriptase-like polymerases (From Topology)	H: helical bundle domain in reverse transcriptase-like polymerases (From Topology)	T: helical bundle domain in reverse transcriptase-like polymerases	F: Flavi_NS5_2nd	ECOD (1.6)
A	Flavi_NS5_1st	e6i7pA3	A: a+b two layers	X: Alpha-beta plaits	H: Adenylyl and guanylyl cyclase catalytic domain-like	T: Adenylyl and guanylyl cyclase catalytic domain-like	F: Flavi_NS5_1st	ECOD (1.6)
A	FtsJ	e6i7pA1	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: S-adenosyl-L-methionine-dependent methyltransferases	F: FtsJ	ECOD (1.6)
B	Flavi_NS5_2nd	e6i7pB3	A: alpha bundles	X: helical bundle domain in reverse transcriptase-like polymerases (From Topology)	H: helical bundle domain in reverse transcriptase-like polymerases (From Topology)	T: helical bundle domain in reverse transcriptase-like polymerases	F: Flavi_NS5_2nd	ECOD (1.6)
B	Flavi_NS5_1st	e6i7pB2	A: a+b two layers	X: Alpha-beta plaits	H: Adenylyl and guanylyl cyclase catalytic domain-like	T: Adenylyl and guanylyl cyclase catalytic domain-like	F: Flavi_NS5_1st	ECOD (1.6)
B	FtsJ	e6i7pB1	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: S-adenosyl-L-methionine-dependent methyltransferases	F: FtsJ	ECOD (1.6)
C	Flavi_NS5_2nd	e6i7pC1	A: alpha bundles	X: helical bundle domain in reverse transcriptase-like polymerases (From Topology)	H: helical bundle domain in reverse transcriptase-like polymerases (From Topology)	T: helical bundle domain in reverse transcriptase-like polymerases	F: Flavi_NS5_2nd	ECOD (1.6)
C	Flavi_NS5_1st	e6i7pC2	A: a+b two layers	X: Alpha-beta plaits	H: Adenylyl and guanylyl cyclase catalytic domain-like	T: Adenylyl and guanylyl cyclase catalytic domain-like	F: Flavi_NS5_1st	ECOD (1.6)
C	FtsJ	e6i7pC3	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: S-adenosyl-L-methionine-dependent methyltransferases	F: FtsJ	ECOD (1.6)
D	Flavi_NS5_2nd	e6i7pD2	A: alpha bundles	X: helical bundle domain in reverse transcriptase-like polymerases (From Topology)	H: helical bundle domain in reverse transcriptase-like polymerases (From Topology)	T: helical bundle domain in reverse transcriptase-like polymerases	F: Flavi_NS5_2nd	ECOD (1.6)
D	Flavi_NS5_1st	e6i7pD1	A: a+b two layers	X: Alpha-beta plaits	H: Adenylyl and guanylyl cyclase catalytic domain-like	T: Adenylyl and guanylyl cyclase catalytic domain-like	F: Flavi_NS5_1st	ECOD (1.6)
D	FtsJ	e6i7pD3	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: S-adenosyl-L-methionine-dependent methyltransferases	F: FtsJ	ECOD (1.6)
E	Flavi_NS5_2nd	e6i7pE2	A: alpha bundles	X: helical bundle domain in reverse transcriptase-like polymerases (From Topology)	H: helical bundle domain in reverse transcriptase-like polymerases (From Topology)	T: helical bundle domain in reverse transcriptase-like polymerases	F: Flavi_NS5_2nd	ECOD (1.6)
E	Flavi_NS5_1st	e6i7pE3	A: a+b two layers	X: Alpha-beta plaits	H: Adenylyl and guanylyl cyclase catalytic domain-like	T: Adenylyl and guanylyl cyclase catalytic domain-like	F: Flavi_NS5_1st	ECOD (1.6)
E	FtsJ	e6i7pE1	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: S-adenosyl-L-methionine-dependent methyltransferases	F: FtsJ	ECOD (1.6)
F	Flavi_NS5_2nd	e6i7pF2	A: alpha bundles	X: helical bundle domain in reverse transcriptase-like polymerases (From Topology)	H: helical bundle domain in reverse transcriptase-like polymerases (From Topology)	T: helical bundle domain in reverse transcriptase-like polymerases	F: Flavi_NS5_2nd	ECOD (1.6)
F	Flavi_NS5_1st	e6i7pF1	A: a+b two layers	X: Alpha-beta plaits	H: Adenylyl and guanylyl cyclase catalytic domain-like	T: Adenylyl and guanylyl cyclase catalytic domain-like	F: Flavi_NS5_1st	ECOD (1.6)
F	FtsJ	e6i7pF3	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: S-adenosyl-L-methionine-dependent methyltransferases	F: FtsJ	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.40.50.150	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	Vaccinia Virus protein VP39	CATH (utative)
B	3.40.50.150	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	Vaccinia Virus protein VP39	CATH (utative)
C	3.40.50.150	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	Vaccinia Virus protein VP39	CATH (utative)
D	3.40.50.150	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	Vaccinia Virus protein VP39	CATH (utative)
E	3.40.50.150	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	Vaccinia Virus protein VP39	CATH (utative)
F	3.40.50.150	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	Vaccinia Virus protein VP39	CATH (utative)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, C, D, E A, B, C, D, E, F	PF20483	Flavivirus RNA-directed RNA polymerase, thumb domain (Flavi_NS5_thumb)	Flavivirus RNA-directed RNA polymerase, thumb domain	Flaviviruses produce a large polyprotein from the ssRNA genome, encoding structural proteins required for virus assembly and non-structural (NS1-5) proteins involved in replication of the viral genome [1,2,3]. This polyprotein is cleaved by viral and ...	Flaviviruses produce a large polyprotein from the ssRNA genome, encoding structural proteins required for virus assembly and non-structural (NS1-5) proteins involved in replication of the viral genome [1,2,3]. This polyprotein is cleaved by viral and cellular proteases to produce mature viral proteins. NS5 is the largest mature viral protein and contains a N-terminal methyltransferase (MTase) domain separated by a short linker from the C-terminal RNA-directed RNA polymerase domain (RdRp) that adopts a characteristic right-handed fingers-palm-thumb fold and possesses a number of short regions and motifs homologous to other RNA-directed RNA polymerases [2,3]. This entry represents the thumb domain of NS5 RdRp. NS5 binds to a the stem loop A (SLA) at the 5' extremity of Flavivirus genome and regulates translation of the viral genome [3].	Domain
A, B, C, D, E A, B, C, D, E, F	PF01728	FtsJ-like methyltransferase (FtsJ)	FtsJ-like methyltransferase	-	Family
A, B, C, D, E A, B, C, D, E, F	PF00972	Flavivirus RNA-directed RNA polymerase, fingers and palm domains (Flavi_NS5)	Flavivirus RNA-directed RNA polymerase, fingers and palm domains	Flaviviruses produce a large polyprotein from the ssRNA genome, encoding structural proteins required for virus assembly and non-structural (NS1-5) proteins involved in replication of the viral genome [1-6]. This polyprotein is cleaved by viral and c ...	Flaviviruses produce a large polyprotein from the ssRNA genome, encoding structural proteins required for virus assembly and non-structural (NS1-5) proteins involved in replication of the viral genome [1-6]. This polyprotein is cleaved by viral and cellular proteases to produce mature viral proteins. NS5 is the largest mature viral protein and contains a N-terminal methyltransferase (MTase) domain separated by a short linker from the C-terminal RNA-directed RNA polymerase domain (RdRp) that adopts a characteristic right-handed fingers-palm-thumb fold and possesses a number of short regions and motifs homologous to other RNA-directed RNA polymerases [2,5,6]. This entry covers the fingers and palm domains of RNA-directed RNA polymerase (RdRp) from Flavivirus NS5. NS5 binds to a the stem loop A (SLA) at the 5' extremity of Flavivirus genome and regulates translation of the viral genome [5,6].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C, D, E A, B, C, D, E, F	NS5	RNA binding double-stranded RNA binding binding organic cyclic compound binding nucleic acid binding peptidase activity catalytic activity, acting on a protein serine hydrolase activity serine-type peptidase activity hydrolase activity serine-type endopeptidase activity catalytic activity endopeptidase activity iron-sulfur cluster binding RNA binding double-stranded RNA binding binding organic cyclic compound binding nucleic acid binding peptidase activity catalytic activity, acting on a protein serine hydrolase activity serine-type peptidase activity hydrolase activity serine-type endopeptidase activity catalytic activity endopeptidase activity iron-sulfur cluster binding 4 iron, 4 sulfur cluster binding metal cluster binding small molecule binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding purine nucleotide binding anion binding adenyl nucleotide binding ATP binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding molecular adaptor activity catalytic activity, acting on RNA catalytic activity, acting on a nucleic acid helicase activity RNA helicase activity ATP-dependent activity, acting on RNA ATP-dependent activity protein binding protein dimerization activity cation binding metal ion binding RNA methyltransferase activity O-methyltransferase activity transferase activity, transferring one-carbon groups mRNA (nucleoside-2'-O-)-methyltransferase activity transferase activity S-adenosylmethionine-dependent methyltransferase activity methyltransferase activity mRNA methyltransferase activity 5'-3' RNA polymerase activity RNA polymerase activity RNA-dependent RNA polymerase activity nucleotidyltransferase activity transferase activity, transferring phosphorus-containing groups mRNA 5'-cap (guanine-N7-)-methyltransferase activity N-methyltransferase activity guanyl nucleotide binding GTP binding guanyl ribonucleotide binding lipid binding pyrophosphatase activity ATP hydrolysis activity ribonucleoside triphosphate phosphatase activity hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides hydrolase activity, acting on acid anhydrides structural molecule activity	RNA metabolic process viral life cycle primary metabolic process nucleobase-containing compound biosynthetic process macromolecule biosynthetic process nucleic acid metabolic process RNA biosynthetic process nucleobase-containing compound metabolic process nucleic acid biosynthetic process viral genome replication biosynthetic process viral RNA genome replication viral process metabolic process RNA metabolic process viral life cycle primary metabolic process nucleobase-containing compound biosynthetic process macromolecule biosynthetic process nucleic acid metabolic process RNA biosynthetic process nucleobase-containing compound metabolic process nucleic acid biosynthetic process viral genome replication biosynthetic process viral RNA genome replication viral process metabolic process cellular process macromolecule metabolic process symbiont-mediated perturbation of host cellular process biological process involved in interspecies interaction between organisms symbiont-mediated suppression of host JAK-STAT cascade biological process involved in interaction with host biological process involved in symbiotic interaction symbiont-mediated suppression of host signal transduction pathway symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT activity symbiont-mediated perturbation of host process symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity symbiont-mediated perturbation of host signal transduction pathway modulation of process of another organism symbiont-mediated perturbation of host defense response modulation by virus of host process virus-mediated perturbation of host defense response modulation by virus of host cellular process catabolic process regulation of cellular process autophagy positive regulation of biological process regulation of autophagy positive regulation of metabolic process induction by virus of host autophagy process utilizing autophagic mechanism positive regulation of cellular process positive regulation of autophagy regulation of biological process modulation by virus of host autophagy biological regulation regulation of catabolic process positive regulation of catabolic process regulation of metabolic process symbiont-mediated suppression of host interferon-mediated signaling pathway symbiont-mediated suppression of host type I interferon-mediated signaling pathway fusion of virus membrane with host endosome membrane membrane fusion involved in viral entry into host cell symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity import into cell receptor-mediated endocytosis of virus by host cell transport establishment of localization vesicle-mediated transport localization symbiont entry into host cell clathrin-dependent endocytosis symbiont entry into host clathrin-dependent endocytosis of virus by host cell receptor-mediated endocytosis endocytosis endocytosis involved in viral entry into host cell transport of virus regulation of defense response regulation of response to biotic stimulus negative regulation of response to biotic stimulus response to stimulus regulation of response to external stimulus negative regulation of biological process response to biotic stimulus response to stress regulation of response to stress innate immune response regulation of immune system process response to external biotic stimulus negative regulation of response to stimulus immune response response to other organism defense response regulation of innate immune response negative regulation of immune response defense response to symbiont response to external stimulus regulation of response to stimulus negative regulation of immune system process immune system process defense response to other organism negative regulation of response to external stimulus negative regulation of defense response regulation of immune response negative regulation of innate immune response virion attachment to host cell adhesion of symbiont to host cell adhesion of symbiont to host symbiont-mediated suppression of host immune response symbiont-mediated suppression of host innate immune response symbiont-mediated suppression of host defenses symbiont-mediated perturbation of host innate immune response response to host response to host defenses symbiont-mediated perturbation of host immune response symbiont-mediated perturbation of host defenses response to defenses of other organism symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity proteolysis protein metabolic process	cellular anatomical structure membrane host intracellular membrane-bounded organelle host cellular component host intracellular part host cell endoplasmic reticulum host cell membrane host cell cytoplasm part host intracellular organelle host cell cytoplasm host cell part host cell endomembrane system host intracellular region host cell endoplasmic reticulum membrane cellular anatomical structure membrane host intracellular membrane-bounded organelle host cellular component host intracellular part host cell endoplasmic reticulum host cell membrane host cell cytoplasm part host intracellular organelle host cell cytoplasm host cell part host cell endomembrane system host intracellular region host cell endoplasmic reticulum membrane intracellular organelle centrosome microtubule organizing center intracellular anatomical structure cytoskeleton organelle membraneless organelle intracellular membraneless organelle microtubule cytoskeleton viral capsid virion component host cell perinuclear region of cytoplasm virion membrane extracellular region host cell nucleus viral membrane viral envelope

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C, D, E A, B, C, D, E, F	IPR000208	RNA-directed RNA polymerase, fingers/palm subdomains, flavivirus	Domain
A, B, C, D, E A, B, C, D, E, F	IPR014756	Immunoglobulin E-set	Homologous Superfamily
A, B, C, D, E A, B, C, D, E, F	IPR001122	Capsid protein C, flavivirus	Domain
A, B, C, D, E A, B, C, D, E, F	IPR027287	Glycoprotein E, immunoglobulin-like domain, flavivirus	Domain
A, B, C, D, E A, B, C, D, E, F	IPR014412	Genome polyprotein, Flavivirus	Family
A, B, C, D, E A, B, C, D, E, F	IPR036253	Flavivirus glycoprotein, central and dimerisation domain superfamily	Homologous Superfamily
A, B, C, D, E A, B, C, D, E, F	IPR027417	P-loop containing nucleoside triphosphate hydrolase	Homologous Superfamily
A, B, C, D, E A, B, C, D, E, F	IPR026490	mRNA cap 0/1 methyltransferase	Domain
A, B, C, D, E A, B, C, D, E, F	IPR009003	Peptidase S1, PA clan	Homologous Superfamily
A, B, C, D, E A, B, C, D, E, F	IPR001650	Helicase, C-terminal domain-like	Domain
A, B, C, D, E A, B, C, D, E, F	IPR014001	Helicase superfamily 1/2, ATP-binding domain	Domain
A, B, C, D, E A, B, C, D, E, F	IPR013755	Flaviviral glycoprotein E, central domain, subdomain 1	Homologous Superfamily
A, B, C, D, E A, B, C, D, E, F	IPR000752	Flavivirus non-structural protein NS2A	Domain
A, B, C, D, E A, B, C, D, E, F	IPR047530	RNA-dependent RNA polymerase, flavivirus	Domain
A, B, C, D, E A, B, C, D, E, F	IPR049486	Flavivridae NS3 helicase, C-terminal helical domain	Domain
A, B, C, D, E A, B, C, D, E, F	IPR046811	RNA-directed RNA polymerase, thumb subdomain, flavivirus	Domain
A, B, C, D, E A, B, C, D, E, F	IPR038055	Flaviviral glycoprotein E, dimerisation domain	Homologous Superfamily
A, B, C, D, E A, B, C, D, E, F	IPR002877	Ribosomal RNA methyltransferase, FtsJ domain	Domain
A, B, C, D, E A, B, C, D, E, F	IPR038302	Envelope glycoprotein M superfamily, flavivirus	Homologous Superfamily
A, B, C, D, E A, B, C, D, E, F	IPR000069	Envelope glycoprotein M, flavivirus	Domain
A, B, C, D, E A, B, C, D, E, F	IPR011492	Non-structural protein NS3-like, DEAD box helicase, flavivirus	Domain
A, B, C, D, E A, B, C, D, E, F	IPR038345	Flavivirus envelope glycoprotein E, Stem/Anchor domain superfamily	Homologous Superfamily
A, B, C, D, E A, B, C, D, E, F	IPR038688	Flavivirus polyprotein propeptide superfamily	Homologous Superfamily
A, B, C, D, E A, B, C, D, E, F	IPR029063	S-adenosyl-L-methionine-dependent methyltransferase superfamily	Homologous Superfamily
A, B, C, D, E A, B, C, D, E, F	IPR026470	Flavivirus envelope glycoprotein E, Stem/Anchor domain	Domain
A, B, C, D, E A, B, C, D, E, F	IPR011998	Envelope glycoprotein E, central and dimerisation domain, flavivirus	Domain
A, B, C, D, E A, B, C, D, E, F	IPR043502	DNA/RNA polymerase superfamily	Homologous Superfamily
A, B, C, D, E A, B, C, D, E, F	IPR037172	Flavivirus capsid protein C superfamily	Homologous Superfamily
A, B, C, D, E A, B, C, D, E, F	IPR000404	Flavivirus non-structural protein NS4A	Domain
A, B, C, D, E A, B, C, D, E, F	IPR000487	Non-structural protein NS2B, flavivirus	Domain
A, B, C, D, E A, B, C, D, E, F	IPR001528	Flavivirus non-structural protein NS4B	Domain
A, B, C, D, E A, B, C, D, E, F	IPR001157	Non-structural protein NS1, flavivirus	Domain
A, B, C, D, E A, B, C, D, E, F	IPR013756	Flaviviral glycoprotein E, central domain, subdomain 2	Homologous Superfamily
A, B, C, D, E A, B, C, D, E, F	IPR001850	Non-structural protein NS3, peptidase S7, flavivirus	Domain
A, B, C, D, E A, B, C, D, E, F	IPR000336	Flavivirus/Alphavirus glycoprotein, immunoglobulin-like domain superfamily	Homologous Superfamily
A, B, C, D, E A, B, C, D, E, F	IPR002535	Flavivirus polyprotein propeptide	Domain
A, B, C, D, E A, B, C, D, E, F	IPR007094	RNA-directed RNA polymerase, catalytic domain	Domain