6FFA

FMDV Leader protease bound to substrate ISG15

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	d6ffaa_	Alpha and beta proteins (a+b)	Cysteine proteinases	Cysteine proteinases	FMDV leader protease	automated matches	(Foot-and-mouth disease virus ) [TaxId: 12110 ],	SCOPe (2.08)
B	d6ffab_	Alpha and beta proteins (a+b)	beta-Grasp (ubiquitin-like)	Ubiquitin-like	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	Cysteine proteinases	8034060	3001808	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Ubiquitin-like	8035116	3000157	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	Peptidase_C28	e6ffaA1	A: a+b complex topology	X: Cysteine proteinases-like	H: Cysteine proteinases (From Topology)	T: Cysteine proteinases	F: Peptidase_C28	ECOD (1.6)
B	ubiquitin_2	e6ffaB1	A: a+b two layers	X: beta-Grasp	H: Ubiquitin-related	T: Ubiquitin-like	F: ubiquitin_2	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.90.70.10	Alpha Beta	Alpha-Beta Complex	Cathepsin B	Chain A	CATH (4.3.0)
B	3.10.20.90	Alpha Beta	Roll	Ubiquitin-like (UB roll)	Phosphatidylinositol 3-kinase Catalytic Subunit	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF05408	Foot-and-mouth virus L-proteinase (Peptidase_C28)	Foot-and-mouth virus L-proteinase	-	Family
B	PF00240	Ubiquitin family (ubiquitin)	Ubiquitin family	This family contains a number of ubiquitin-like proteins: SUMO (smt3 homologue) (see Swiss:Q02724), Nedd8 (see Swiss:P29595), Elongin B (see Swiss:Q15370), Rub1 (see Swiss:Q9SHE7), and Parkin (see Swiss:O60260). A number of them are thought to carry ...	This family contains a number of ubiquitin-like proteins: SUMO (smt3 homologue) (see Swiss:Q02724), Nedd8 (see Swiss:P29595), Elongin B (see Swiss:Q15370), Rub1 (see Swiss:Q9SHE7), and Parkin (see Swiss:O60260). A number of them are thought to carry a distinctive five-residue motif termed the proteasome-interacting motif (PIM), which may have a biologically significant role in protein delivery to proteasomes and recruitment of proteasomes to transcription sites [5].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	Lbpro	5'-3' RNA polymerase activity catalytic activity, acting on RNA catalytic activity, acting on a nucleic acid RNA polymerase activity transferase activity RNA-dependent RNA polymerase activity nucleotidyltransferase activity catalytic activity transferase activity, transferring phosphorus-containing groups cysteine-type peptidase activity peptidase activity catalytic activity, acting on a protein cysteine-type endopeptidase activity hydrolase activity 5'-3' RNA polymerase activity catalytic activity, acting on RNA catalytic activity, acting on a nucleic acid RNA polymerase activity transferase activity RNA-dependent RNA polymerase activity nucleotidyltransferase activity catalytic activity transferase activity, transferring phosphorus-containing groups cysteine-type peptidase activity peptidase activity catalytic activity, acting on a protein cysteine-type endopeptidase activity hydrolase activity endopeptidase activity RNA binding binding organic cyclic compound binding nucleic acid 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 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 passive transmembrane transporter activity channel activity transporter activity transmembrane transporter activity molecular adaptor activity helicase activity RNA helicase activity ATP-dependent activity, acting on RNA ATP-dependent activity structural molecule activity	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 nucleic acid biosynthetic process viral genome replication biosynthetic process viral RNA genome replication viral process 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 nucleic acid biosynthetic process viral genome replication biosynthetic process viral RNA genome replication viral process metabolic process cellular process macromolecule metabolic process import into cell receptor-mediated endocytosis of virus by host cell biological process involved in interspecies interaction between organisms transport establishment of localization vesicle-mediated transport biological process involved in interaction with host biological process involved in symbiotic interaction 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 multicellular organismal process regulation of cellular process response to stimulus negative regulation of biological process modulation by virus of host process negative regulation of cellular metabolic process response to biotic stimulus symbiont-mediated suppression of host immune response symbiont-mediated suppression of host innate immune response cytokine production symbiont-mediated perturbation of host innate immune response symbiont-mediated perturbation of host defense response regulation of biological process response to host defenses response to other organism type I interferon production symbiont-mediated perturbation of host immune response negative regulation of metabolic process symbiont-mediated perturbation of host defenses regulation of cellular metabolic process response to external stimulus negative regulation of cellular biosynthetic process regulation of gene expression negative regulation of gene expression negative regulation of macromolecule biosynthetic process regulation of macromolecule biosynthetic process negative regulation of multicellular organismal process regulation of metabolic process virus-mediated perturbation of host defense response perturbation by virus of host immune response suppression by virus of host type I interferon production negative regulation of type I interferon production symbiont-mediated perturbation of host process response to host immune response symbiont-mediated suppression of host defenses negative regulation of cellular process regulation of cytokine production regulation of multicellular organismal process response to host response to external biotic stimulus modulation of process of another organism negative regulation of macromolecule metabolic process modulation by virus of host cellular process regulation of biosynthetic process suppression by virus of host cytokine production response to defenses of other organism biological regulation negative regulation of cytokine production regulation of macromolecule metabolic process gene expression regulation of cellular biosynthetic process negative regulation of biosynthetic process modulation by virus of host cytokine production symbiont-mediated suppression of host cytokine production regulation of type I interferon production transmembrane transport monoatomic ion transmembrane transport monoatomic ion transport regulation of primary metabolic process post-transcriptional regulation of gene expression protein metabolic process regulation of protein metabolic process translation regulation of translation viral gene expression viral protein processing DNA-templated transcription modulation by virus of host chromatin organization cellular component organization chromatin organization cellular component organization or biogenesis virion attachment to host cell adhesion of symbiont to host cell adhesion of symbiont to host symbiont-mediated perturbation of host cellular process catabolic process autophagy positive regulation of biological 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 positive regulation of autophagy modulation by virus of host autophagy regulation of catabolic process positive regulation of catabolic process regulation of cellular catabolic process positive regulation of cellular catabolic process proteolysis	membrane cellular anatomical entity host intracellular membrane-bounded organelle host cellular component host intracellular part host cell membrane host cell cytoplasmic vesicle membrane host cell cytoplasm part host intracellular organelle host cell cytoplasmic vesicle host cell cytoplasm host cell part host intracellular region viral capsid membrane cellular anatomical entity host intracellular membrane-bounded organelle host cellular component host intracellular part host cell membrane host cell cytoplasmic vesicle membrane host cell cytoplasm part host intracellular organelle host cell cytoplasmic vesicle host cell cytoplasm host cell part host intracellular region viral capsid icosahedral viral capsid virion component T=pseudo3 icosahedral viral capsid host cell endoplasmic reticulum host cell endomembrane system host cell endoplasmic reticulum membrane host cell nucleus
B	Ubiquitin-like protein ISG15	cell adhesion molecule binding protein-containing complex binding protein binding binding integrin binding signaling receptor binding protein tag activity molecular tag activity ubiquitin protein ligase binding ubiquitin-like protein ligase binding enzyme binding	negative regulation of post-translational protein modification regulation of protein modification process negative regulation of biological process regulation of protein ubiquitination regulation of primary metabolic process protein ubiquitination negative regulation of protein modification process protein metabolic process negative regulation of protein ubiquitination regulation of protein modification by small protein conjugation or removal protein modification process negative regulation of protein metabolic process negative regulation of macromolecule metabolic process regulation of biological process negative regulation of post-translational protein modification regulation of protein modification process negative regulation of biological process regulation of protein ubiquitination regulation of primary metabolic process protein ubiquitination negative regulation of protein modification process protein metabolic process negative regulation of protein ubiquitination regulation of protein modification by small protein conjugation or removal protein modification process negative regulation of protein metabolic process negative regulation of macromolecule metabolic process regulation of biological process negative regulation of protein modification by small protein conjugation or removal regulation of post-translational protein modification regulation of protein metabolic process negative regulation of metabolic process biological regulation primary metabolic process regulation of macromolecule metabolic process macromolecule modification metabolic process macromolecule metabolic process post-translational protein modification regulation of metabolic process protein modification by small protein conjugation protein modification by small protein conjugation or removal cellular response to stimulus regulation of cellular process response to stimulus regulation of type I interferon-mediated signaling pathway response to cytokine regulation of signal transduction response to biotic stimulus cell communication interferon-mediated signaling pathway cellular response to type I interferon cellular response to cytokine stimulus regulation of immune system process signal transduction immune response response to other organism regulation of innate immune response negative regulation of immune response response to external stimulus regulation of response to cytokine stimulus negative regulation of response to cytokine stimulus regulation of response to stimulus response to chemical defense response to other organism negative regulation of response to external stimulus negative regulation of defense response regulation of immune response response to type I interferon regulation of defense response regulation of response to biotic stimulus biological process involved in interspecies interaction between organisms regulation of response to external stimulus negative regulation of response to biotic stimulus negative regulation of signaling signaling negative regulation of cell communication cytokine-mediated signaling pathway response to stress regulation of response to stress negative regulation of cellular process innate immune response response to external biotic stimulus regulation of signaling cell surface receptor signaling pathway negative regulation of response to stimulus defense response regulation of cytokine-mediated signaling pathway defense response to symbiont negative regulation of signal transduction response to peptide negative regulation of immune system process negative regulation of cytokine-mediated signaling pathway immune system process type I interferon-mediated signaling pathway regulation of cell communication cellular process negative regulation of type I interferon-mediated signaling pathway negative regulation of innate immune response catabolic process proteolysis involved in protein catabolic process protein catabolic process macromolecule catabolic process modification-dependent macromolecule catabolic process modification-dependent protein catabolic process proteolysis integrin-mediated signaling pathway multicellular organismal process regulation of type II interferon production type II interferon production cellular biosynthetic process cytokine production regulation of cytokine production regulation of multicellular organismal process regulation of biosynthetic process cellular metabolic process regulation of cellular metabolic process gene expression macromolecule biosynthetic process regulation of cellular biosynthetic process regulation of gene expression biosynthetic process regulation of macromolecule biosynthetic process ISG15-protein conjugation regulation of developmental process positive regulation of biological process regulation of biomineral tissue development regulation of bone mineralization positive regulation of ossification positive regulation of developmental process multicellular organism development positive regulation of biomineral tissue development ossification anatomical structure development biomineral tissue development developmental process regulation of multicellular organismal development bone mineralization animal organ development tissue development positive regulation of bone mineralization positive regulation of multicellular organismal process regulation of ossification defense response to bacterium response to bacterium positive regulation of cellular metabolic process positive regulation of macromolecule biosynthetic process positive regulation of metabolic process positive regulation of biosynthetic process positive regulation of macromolecule metabolic process regulation of interferon-beta production interferon-beta production positive regulation of cellular process positive regulation of type I interferon production type I interferon production positive regulation of gene expression positive regulation of interferon-beta production positive regulation of cytokine production positive regulation of cellular biosynthetic process regulation of type I interferon production regulation of cellular component organization positive regulation of cellular component organization protein-containing complex organization positive regulation of cellular component biogenesis regulation of protein oligomerization regulation of cellular component biogenesis cellular component biogenesis cellular component organization regulation of protein-containing complex assembly positive regulation of protein-containing complex assembly cellular component assembly positive regulation of protein oligomerization protein complex oligomerization protein-containing complex assembly cellular component organization or biogenesis cellular developmental process homeostatic process cell development regulation of cell differentiation regulation of cell development positive regulation of cell differentiation cell differentiation myeloid cell homeostasis erythrocyte homeostasis hemopoiesis regulation of myeloid cell differentiation erythrocyte differentiation regulation of erythrocyte differentiation positive regulation of erythrocyte differentiation multicellular organismal-level homeostasis myeloid cell differentiation positive regulation of myeloid cell differentiation regulation of hemopoiesis homeostasis of number of cells interleukin-10 production regulation of interleukin-10 production positive regulation of interleukin-10 production protein localization localization cellular localization protein localization to organelle cellular macromolecule localization macromolecule localization protein localization to mitochondrion negative regulation of viral genome replication viral life cycle negative regulation of viral process regulation of viral process regulation of viral life cycle viral genome replication viral process regulation of viral genome replication response to virus defense response to virus positive regulation of type II interferon production	intracellular anatomical structure cytoplasm cellular anatomical entity cytosol membrane-bounded organelle nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen intracellular organelle nucleoplasm organelle lumen organelle nuclear lumen intracellular anatomical structure cytoplasm cellular anatomical entity cytosol membrane-bounded organelle nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen intracellular organelle nucleoplasm organelle lumen organelle nuclear lumen extracellular region

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR015031	Capsid protein VP4, Picornavirus	Domain
A	IPR001205	RNA-directed RNA polymerase, C-terminal domain	Domain
A	IPR043128	Reverse transcriptase/Diguanylate cyclase domain	Homologous Superfamily
A	IPR038765	Papain-like cysteine peptidase superfamily	Homologous Superfamily
A	IPR008739	Peptidase C28, foot-and-mouth virus L-proteinase	Domain
A	IPR000199	Peptidase C3A/C3B, picornaviral	Domain
A	IPR001676	Picornavirus capsid	Domain
A	IPR014759	Helicase, superfamily 3, single-stranded RNA virus	Domain
A	IPR027417	P-loop containing nucleoside triphosphate hydrolase	Homologous Superfamily
A	IPR029053	Viral coat protein subunit	Homologous Superfamily
A	IPR004080	Foot-and-mouth disease virus VP1 coat	Domain
A	IPR009003	Peptidase S1, PA clan	Homologous Superfamily
A	IPR004004	Helicase/polymerase/peptidase polyprotein, Calicivirus-type	Family
A	IPR043502	DNA/RNA polymerase superfamily	Homologous Superfamily
A	IPR044067	Picornavirales 3C/3C-like protease domain	Domain
A	IPR033703	Picornavirus/Calicivirus coat protein	Domain
A	IPR043504	Peptidase S1, PA clan, chymotrypsin-like fold	Homologous Superfamily
A	IPR007094	RNA-directed RNA polymerase, catalytic domain	Domain
A	IPR000605	Helicase, superfamily 3, single-stranded DNA/RNA virus	Domain
A	IPR037080	Capsid protein VP4 superfamily, Picornavirus	Homologous Superfamily
B	IPR000626	Ubiquitin-like domain	Domain
B	IPR015496	Ubiquilin	Family
B	IPR019956	Ubiquitin domain	Domain
B	IPR029071	Ubiquitin-like domain superfamily	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
B	Pharos: P05161	mendelian susceptibility to mycobacterial diseases due to complete ISG15 deficiency influenza malignant mesothelioma ovarian cancer pilocytic astrocytoma atopic eczema Sjogren syndrome tuberculosis breast carcinoma cystic fibrosis exocrine pancreatic carcinoma juvenile dermatomyositis lung adenocarcinoma malignant pancreatic neoplasm microphthalmia with limb anomalies mendelian susceptibility to mycobacterial diseases due to complete ISG15 deficiency influenza malignant mesothelioma ovarian cancer pilocytic astrocytoma atopic eczema Sjogren syndrome tuberculosis breast carcinoma cystic fibrosis exocrine pancreatic carcinoma juvenile dermatomyositis lung adenocarcinoma malignant pancreatic neoplasm microphthalmia with limb anomalies pancreatic ductal adenocarcinoma plasma cell myeloma Barrett esophagus subependymal giant cell astrocytoma ulcerative colitis Crohn disease dermatomyositis glioblastoma interstitial cystitis large cell medulloblastoma malignant ependymoma medulloblastoma multiple sclerosis pancreatic intraductal papillary-mucinous neoplasm psoriasis systemic lupus erythematosus breast cancer cutaneous lupus erythematosus esophageal adenocarcinoma hepatocellular carcinoma invasive ductal breast carcinoma Liver carcinoma