4KC9

Structure of HHARI, a RING-IBR-RING ubiquitin ligase: autoinhibition of an Ariadne-family E3 and insights into ligation mechanism

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
Pharos: Disease Associations

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	RING/U-box like	8041693	3000160	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	PF21235	e4kc9A4	A: alpha arrays	X: RuvA-C	H: RuvA-C, UBA, CRAL/TRIO-N, HBS1 (From Topology)	T: RuvA-C, UBA, CRAL/TRIO-N, HBS1	F: PF21235	ECOD (1.6)
A	PF19422	e4kc9A1	A: alpha bundles	X: N-cbl like	H: C-terminal domain of E3 ubiquitin-protein ligase ARIH1 (From Topology)	T: C-terminal domain of E3 ubiquitin-protein ligase ARIH1	F: PF19422	ECOD (1.6)
A	PF13923	e4kc9A3	A: few secondary structure elements	X: RING/U-box-like	H: RING/U-box-like	T: RING/U-box	F: PF13923	ECOD (1.6)
A	PF01485	e4kc9A5	A: few secondary structure elements	X: RING/U-box-like	H: RING/U-box-like	T: IBR domain	F: PF01485	ECOD (1.6)
A	PF22191	e4kc9A2	A: few secondary structure elements	X: RING/U-box-like	H: RING/U-box-like	T: IBR domain	F: PF22191	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	1.20.120.1750	Mainly Alpha	Up-down Bundle	Four Helix Bundle (Hemerythrin (Met), subunit A)		CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF21235	E3 ubiquitin-protein ligase ARIH1, UBA-like domain (ARI1_UBAl)	E3 ubiquitin-protein ligase ARIH1, UBA-like domain	This entry represents the UBA-like (UBL) domain from the Human Homologue of Ariadne (HHARI) and its homologues, which are Ariadne subfamily E3 ubiquitin ligase proteins [1-4]. This domain binds to Ubiquitin and NEDD8 [3,4].	Domain
A	PF00097	Zinc finger, C3HC4 type (RING finger) (zf-C3HC4)	Zinc finger, C3HC4 type (RING finger)	The C3HC4 type zinc-finger (RING finger) is a cysteine-rich domain of 40 to 60 residues that coordinates two zinc ions, and has the consensus sequence: C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C where X is any amino acid [1]. Many protein ...	The C3HC4 type zinc-finger (RING finger) is a cysteine-rich domain of 40 to 60 residues that coordinates two zinc ions, and has the consensus sequence: C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C where X is any amino acid [1]. Many proteins containing a RING finger play a key role in the ubiquitination pathway [2].	Domain
A	PF01485	IBR domain, a half RING-finger domain (IBR)	IBR domain, a half RING-finger domain	The IBR (In Between Ring fingers) domain is often found to occur between pairs of ring fingers (Pfam:PF00097). This domain has also been called the C6HC domain and DRIL (for double RING finger linked) domain [2]. Proteins that contain two Ring fing ...	The IBR (In Between Ring fingers) domain is often found to occur between pairs of ring fingers (Pfam:PF00097). This domain has also been called the C6HC domain and DRIL (for double RING finger linked) domain [2]. Proteins that contain two Ring fingers and an IBR domain (these proteins are also termed RBR family proteins) are thought to exist in all eukaryotic organisms. RBR family members play roles in protein quality control and can indirectly regulate transcription [3]. Evidence suggests that RBR proteins are often parts of cullin-containing ubiquitin ligase complexes. The ubiquitin ligase Parkin is an RBR family protein whose mutations are involved in forms of familial Parkinson's disease [3][4].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	E3 ubiquitin-protein ligase ARIH1	aminoacyltransferase activity ubiquitin-like protein transferase activity catalytic activity, acting on a protein acyltransferase activity ubiquitin-like protein ligase activity ubiquitin protein ligase activity transferase activity catalytic activity ubiquitin-protein transferase activity ubiquitin-like protein conjugating enzyme binding protein binding binding enzyme binding ubiquitin conjugating enzyme binding aminoacyltransferase activity ubiquitin-like protein transferase activity catalytic activity, acting on a protein acyltransferase activity ubiquitin-like protein ligase activity ubiquitin protein ligase activity transferase activity catalytic activity ubiquitin-protein transferase activity ubiquitin-like protein conjugating enzyme binding protein binding binding enzyme binding ubiquitin conjugating enzyme binding ubiquitin protein ligase binding ubiquitin-like protein ligase binding cation binding transition metal ion binding zinc ion binding ion binding metal ion binding small molecule binding	positive regulation of proteasomal protein catabolic process catabolic process positive regulation of protein metabolic process proteolysis involved in protein catabolic process positive regulation of biological process proteasome-mediated ubiquitin-dependent protein catabolic process macromolecule catabolic process regulation of ubiquitin-dependent protein catabolic process regulation of primary metabolic process positive regulation of metabolic process organic substance metabolic process positive regulation of ubiquitin-dependent protein catabolic process regulation of proteolysis regulation of proteolysis involved in protein catabolic process modification-dependent macromolecule catabolic process positive regulation of proteasomal protein catabolic process catabolic process positive regulation of protein metabolic process proteolysis involved in protein catabolic process positive regulation of biological process proteasome-mediated ubiquitin-dependent protein catabolic process macromolecule catabolic process regulation of ubiquitin-dependent protein catabolic process regulation of primary metabolic process positive regulation of metabolic process organic substance metabolic process positive regulation of ubiquitin-dependent protein catabolic process regulation of proteolysis regulation of proteolysis involved in protein catabolic process modification-dependent macromolecule catabolic process proteolysis positive regulation of macromolecule metabolic process protein metabolic process organonitrogen compound catabolic process regulation of biological process organonitrogen compound metabolic process regulation of protein metabolic process biological regulation primary metabolic process proteasomal protein catabolic process regulation of macromolecule metabolic process protein catabolic process regulation of catabolic process positive regulation of protein catabolic process positive regulation of proteolysis involved in protein catabolic process positive regulation of catabolic process regulation of proteasomal ubiquitin-dependent protein catabolic process modification-dependent protein catabolic process positive regulation of proteolysis regulation of proteasomal protein catabolic process positive regulation of proteasomal ubiquitin-dependent protein catabolic process metabolic process ubiquitin-dependent protein catabolic process macromolecule metabolic process regulation of metabolic process organic substance catabolic process regulation of protein catabolic process protein ubiquitination macromolecule modification post-translational protein modification protein modification process protein modification by small protein conjugation protein modification by small protein conjugation or removal protein polyubiquitination cellular response to stimulus regulation of cellular process response to stimulus signaling PKR/eIFalpha signaling integrated stress response signaling intracellular signal transduction cell communication cellular response to stress response to stress intracellular signaling cassette cellular process signal transduction	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 Cajal body nuclear body inclusion body Lewy body protein-containing complex ubiquitin ligase complex catalytic complex transferase complex intracellular protein-containing complex

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR002867	IBR domain	Domain
A	IPR044066	TRIAD supradomain	Domain
A	IPR048962	E3 ubiquitin-protein ligase ARIH1-like, UBA-like domain	Domain
A	IPR018957	Zinc finger, C3HC4 RING-type	Domain
A	IPR045840	Ariadne domain	Domain
A	IPR013083	Zinc finger, RING/FYVE/PHD-type	Homologous Superfamily
A	IPR031127	E3 ubiquitin ligase RBR family	Family
A	IPR001841	Zinc finger, RING-type	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: Q9Y4X5	atypical teratoid rhabdoid tumor malignant glioma Pick disease psoriasis glioblastoma osteosarcoma pilocytic astrocytoma spina bifida intellectual disability ovarian cancer plasma cell myeloma subependymal giant cell astrocytoma

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 R01GM133198.