5M2X

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

External Resource: Annotation

Domain Annotation: ECOD Classification
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification

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	e5m2xA1	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	e5m2xA2	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	e5m2xA3	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	e5m2xB3	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	e5m2xB2	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	e5m2xB1	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	e5m2xC1	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	e5m2xC2	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	e5m2xC3	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	e5m2xD1	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	e5m2xD2	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	e5m2xD3	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	e5m2xE1	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	e5m2xE3	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	e5m2xE2	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	e5m2xF1	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	e5m2xF3	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	e5m2xF2	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: S-adenosyl-L-methionine-dependent methyltransferases	F: FtsJ	ECOD (1.6)

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 adenyl ribonucleotide 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 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 small molecule binding pyrophosphatase activity ribonucleoside triphosphate phosphatase activity hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides hydrolase activity, acting on acid anhydrides 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 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 biological process involved in interspecies interaction between organisms symbiont entry into host cell symbiont entry into host biological process involved in interaction with host biological process involved in symbiotic interaction symbiont-mediated perturbation of host defense response symbiont-mediated perturbation of host process modulation by virus of host process virus-mediated perturbation of host defense response modulation of process of another organism modulation by virus of host cellular process response to host defenses response to stimulus response to other organism symbiont-mediated perturbation of host immune response symbiont-mediated perturbation of host defenses response to defenses of other organism response to external stimulus response to biotic stimulus 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 external biotic stimulus symbiont-mediated suppression of host signal transduction pathway symbiont-mediated perturbation of host cellular process symbiont-mediated suppression of host interferon-mediated signaling pathway symbiont-mediated suppression of host type I interferon-mediated signaling pathway symbiont-mediated perturbation of host signal transduction 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 symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT activity virion attachment to host cell adhesion of symbiont to host cell adhesion of symbiont to host 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 viral capsid virion component virion membrane extracellular region host cell nucleus

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

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.

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5M2X

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

External Resource: Annotation

Domain Annotation: ECOD Classification ECOD Database Homepage

Protein Family Annotation Pfam Database Homepage

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

InterPro: Protein Family Classification InterPro Database Homepage