4CL1

The crystal structure of NS5A domain 1 from genotype 1a reveals new clues to the mechanism of action for dimeric HCV inhibitors

External Resource: Annotation

Domain Annotation: ECOD Classification
Domain Annotation: CATH
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	HCV_NS5a_1a	e4cl1A1	A: few secondary structure elements	X: HCV NS5A domain I subdomains (From Topology)	H: HCV NS5A domain I subdomains (From Topology)	T: HCV NS5A domain I subdomains	F: HCV_NS5a_1a	ECOD (1.6)
A	HCV_NS5a_1b	e4cl1A2	A: few secondary structure elements	X: HCV NS5A domain I subdomains (From Topology)	H: HCV NS5A domain I subdomains (From Topology)	T: HCV NS5A domain I subdomains	F: HCV_NS5a_1b	ECOD (1.6)
B	HCV_NS5a_1a	e4cl1B1	A: few secondary structure elements	X: HCV NS5A domain I subdomains (From Topology)	H: HCV NS5A domain I subdomains (From Topology)	T: HCV NS5A domain I subdomains	F: HCV_NS5a_1a	ECOD (1.6)
B	HCV_NS5a_1b	e4cl1B2	A: few secondary structure elements	X: HCV NS5A domain I subdomains (From Topology)	H: HCV NS5A domain I subdomains (From Topology)	T: HCV NS5A domain I subdomains	F: HCV_NS5a_1b	ECOD (1.6)
C	HCV_NS5a_1a	e4cl1C1	A: few secondary structure elements	X: HCV NS5A domain I subdomains (From Topology)	H: HCV NS5A domain I subdomains (From Topology)	T: HCV NS5A domain I subdomains	F: HCV_NS5a_1a	ECOD (1.6)
C	HCV_NS5a_1b	e4cl1C2	A: few secondary structure elements	X: HCV NS5A domain I subdomains (From Topology)	H: HCV NS5A domain I subdomains (From Topology)	T: HCV NS5A domain I subdomains	F: HCV_NS5a_1b	ECOD (1.6)
D	HCV_NS5a_1a	e4cl1D1	A: few secondary structure elements	X: HCV NS5A domain I subdomains (From Topology)	H: HCV NS5A domain I subdomains (From Topology)	T: HCV NS5A domain I subdomains	F: HCV_NS5a_1a	ECOD (1.6)
D	HCV_NS5a_1b	e4cl1D2	A: few secondary structure elements	X: HCV NS5A domain I subdomains (From Topology)	H: HCV NS5A domain I subdomains (From Topology)	T: HCV NS5A domain I subdomains	F: HCV_NS5a_1b	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	2.20.25.210	Mainly Beta	Single Sheet	N-terminal domain of TfIIb	Hepatitis C NS5A, domain 1B	CATH (4.3.0)
A	2.20.25.220	Mainly Beta	Single Sheet	N-terminal domain of TfIIb	Hepatitis C virus NS5A, 1B domain	CATH (4.3.0)
B	2.20.25.210	Mainly Beta	Single Sheet	N-terminal domain of TfIIb	Hepatitis C NS5A, domain 1B	CATH (4.3.0)
B	2.20.25.220	Mainly Beta	Single Sheet	N-terminal domain of TfIIb	Hepatitis C virus NS5A, 1B domain	CATH (4.3.0)
C	2.20.25.210	Mainly Beta	Single Sheet	N-terminal domain of TfIIb	Hepatitis C NS5A, domain 1B	CATH (4.3.0)
C	2.20.25.220	Mainly Beta	Single Sheet	N-terminal domain of TfIIb	Hepatitis C virus NS5A, 1B domain	CATH (4.3.0)
D	2.20.25.210	Mainly Beta	Single Sheet	N-terminal domain of TfIIb	Hepatitis C NS5A, domain 1B	CATH (4.3.0)
D	2.20.25.220	Mainly Beta	Single Sheet	N-terminal domain of TfIIb	Hepatitis C virus NS5A, 1B domain	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, C, D	PF08300	Hepatitis C virus non-structural 5a zinc finger domain (HCV_NS5a_1a)	Hepatitis C virus non-structural 5a zinc finger domain	The molecular function of the non-structural 5a protein is uncertain. The NS5a protein is phosphorylated when expressed in mammalian cells. It is thought to interact with the ds RNA dependent (interferon inducible) kinase PKR, Swiss:P19525 [1,2]. T ...	The molecular function of the non-structural 5a protein is uncertain. The NS5a protein is phosphorylated when expressed in mammalian cells. It is thought to interact with the ds RNA dependent (interferon inducible) kinase PKR, Swiss:P19525 [1,2]. This domain corresponds to the N-terminal zinc binding domain [3].	Domain
A, B, C, D	PF08301	Hepatitis C virus non-structural 5a domain 1b (HCV_NS5a_1b)	Hepatitis C virus non-structural 5a domain 1b	The molecular function of the non-structural 5a protein is uncertain. The NS5a protein is phosphorylated when expressed in mammalian cells. It is thought to interact with the ds RNA dependent (interferon inducible) kinase PKR, Swiss:P19525 [1,2]. T ...	The molecular function of the non-structural 5a protein is uncertain. The NS5a protein is phosphorylated when expressed in mammalian cells. It is thought to interact with the ds RNA dependent (interferon inducible) kinase PKR, Swiss:P19525 [1,2]. This region corresponds to the 1b domain [3].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C, D	NON-STRUCTURAL PROTEIN 5A	passive transmembrane transporter activity monoatomic ion channel activity channel activity monoatomic ion transmembrane transporter activity transporter activity transmembrane transporter activity 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 passive transmembrane transporter activity monoatomic ion channel activity channel activity monoatomic ion transmembrane transporter activity transporter activity transmembrane transporter activity 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 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 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 5'-3' RNA polymerase activity RNA polymerase activity transferase activity RNA-dependent RNA polymerase activity nucleotidyltransferase activity transferase activity, transferring phosphorus-containing groups cysteine-type peptidase activity cysteine-type endopeptidase activity RNA binding nucleic acid binding structural molecule activity cation binding transition metal ion binding zinc ion binding metal ion binding	cellular component organization cellular component biogenesis cellular component assembly protein-containing complex organization protein complex oligomerization protein-containing complex assembly cellular process cellular component organization or biogenesis cellular biosynthetic process cellular metabolic process RNA metabolic process viral life cycle primary metabolic process nucleobase-containing compound biosynthetic process cellular component organization cellular component biogenesis cellular component assembly protein-containing complex organization protein complex oligomerization protein-containing complex assembly cellular process cellular component organization or biogenesis cellular biosynthetic process cellular 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 organic cyclic compound metabolic process nucleic acid biosynthetic process organic substance metabolic process viral genome replication biosynthetic process viral RNA genome replication organic cyclic compound biosynthetic process viral process organic substance biosynthetic process metabolic 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 suppression of host JAK-STAT cascade via inhibition of STAT1 activity modulation by symbiont of host process symbiont-mediated perturbation of host signal transduction pathway modulation of process of another organism symbiont-mediated perturbation of host cell cycle progression symbiont-mediated perturbation of host cell cycle G1/S transition checkpoint symbiont-mediated suppression of host TRAF-mediated signal transduction catabolic process regulation of cellular process autophagy positive regulation of biological process modulation by virus of host process positive regulation of cellular metabolic process regulation of autophagy cellular catabolic process positive regulation of metabolic process induction by virus of host autophagy process utilizing autophagic mechanism positive regulation of cellular process modulation by virus of host cellular process positive regulation of autophagy regulation of biological process modulation by virus of host autophagy biological regulation regulation of cellular metabolic process regulation of catabolic process symbiont-mediated perturbation of host autophagy positive regulation of catabolic process regulation of cellular catabolic process positive regulation of cellular catabolic process regulation of metabolic process symbiont-mediated suppression of host type I interferon-mediated signaling pathway symbiont-mediated suppression of host interferon-mediated signaling pathway symbiont entry into host cell symbiont entry into host fusion of virus membrane with host endosome membrane membrane fusion involved in viral entry into host cell symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity response to stimulus symbiont-mediated suppression of host pathogen-associated molecular pattern receptor signaling pathway response to biotic stimulus symbiont-mediated suppression of host immune response symbiont-mediated suppression of host innate immune response response to host 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 perturbation of host defense response response to host defenses response to other organism symbiont-mediated perturbation of host immune response response to defenses of other organism symbiont-mediated perturbation of host defenses response to external stimulus symbiont-mediated suppression of cytoplasmic pattern recognition receptor signaling pathway virion attachment to host cell adhesion of symbiont to host cell adhesion of symbiont to host transformation of host cell by virus organonitrogen compound metabolic process proteolysis protein metabolic process	host cellular component host intracellular part host cell cytoplasm host cell part host cell lipid droplet host intracellular region cellular anatomical entity host cell cytoplasm part intracellular anatomical structure cytoplasm host intracellular membrane-bounded organelle host cell mitochondrion host intracellular organelle host cell endoplasmic reticulum host cellular component host intracellular part host cell cytoplasm host cell part host cell lipid droplet host intracellular region cellular anatomical entity host cell cytoplasm part intracellular anatomical structure cytoplasm host intracellular membrane-bounded organelle host cell mitochondrion host intracellular organelle host cell endoplasmic reticulum host cell membrane host cell endomembrane system host cell endoplasmic reticulum membrane viral nucleocapsid viral capsid virion component cell periphery plasma membrane membrane host cell plasma membrane host cell perinuclear region of cytoplasm virion membrane lipid droplet intracellular organelle organelle intracellular non-membrane-bounded organelle non-membrane-bounded organelle viral membrane viral envelope protein-containing complex ribonucleoprotein complex

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C, D	IPR002522	Hepatitis C virus, Core protein, N-terminal	Domain
A, B, C, D	IPR043128	Reverse transcriptase/Diguanylate cyclase domain	Homologous Superfamily
A, B, C, D	IPR038568	Hepatitis C virus NS5A, 1B domain superfamily	Homologous Superfamily
A, B, C, D	IPR027417	P-loop containing nucleoside triphosphate hydrolase	Homologous Superfamily
A, B, C, D	IPR009003	Peptidase S1, PA clan	Homologous Superfamily
A, B, C, D	IPR001650	Helicase, C-terminal domain-like	Domain
A, B, C, D	IPR014001	Helicase superfamily 1/2, ATP-binding domain	Domain
A, B, C, D	IPR002868	Hepatitis C virus, Non-structural 5a protein	Domain
A, B, C, D	IPR038170	NS5A domain 1a superfamily	Homologous Superfamily
A, B, C, D	IPR002518	Hepatitis C virus, Non-structural protein NS2	Domain
A, B, C, D	IPR013192	Hepatitis C virus, Non-structural 5a protein, domain 1a	Domain
A, B, C, D	IPR002521	Hepatitis C virus, Core protein, C-terminal	Domain
A, B, C, D	IPR042209	Hepatitis C virus non-structural protein NS2, N-terminal domain	Homologous Superfamily
A, B, C, D	IPR000745	Hepatitis C virus, Non-structural protein NS4a	Domain
A, B, C, D	IPR011492	Non-structural protein NS3-like, DEAD box helicase, flavivirus	Domain
A, B, C, D	IPR042205	Hepatitis C virus non-structural protein NS2, C-terminal domain	Homologous Superfamily
A, B, C, D	IPR002166	RNA dependent RNA polymerase, hepatitis C virus	Family
A, B, C, D	IPR002519	Hepatitis C virus, Envelope glycoprotein E1	Domain
A, B, C, D	IPR043502	DNA/RNA polymerase superfamily	Homologous Superfamily
A, B, C, D	IPR044896	Hepatitis C virus core protein, chain A superfamily	Homologous Superfamily
A, B, C, D	IPR024350	Hepatitus C virus, Non-structural 5a protein, C-terminal	Domain
A, B, C, D	IPR013193	Hepatitis C virus non-structural 5a, 1B domain	Domain
A, B, C, D	IPR004109	Hepatitis C virus, NS3 protease	Domain
A, B, C, D	IPR002531	Hepatitis C virus, Non-structural protein E2/NS1	Domain
A, B, C, D	IPR043504	Peptidase S1, PA clan, chymotrypsin-like fold	Homologous Superfamily
A, B, C, D	IPR007094	RNA-directed RNA polymerase, catalytic domain	Domain
A, B, C, D	IPR001490	Hepatitis C virus, Non-structural protein NS4b	Domain