4TZ4

Crystal Structure of Human Cereblon in Complex with DDB1 and Lenalidomide

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	WD40 repeat-like	8052531	3001694	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	WD40 repeat-like	8051194	3001694	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	WD40 repeat-like	8052530	3001694	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	WD40 repeat-like	8052530	3001694	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)
B [auth C]	LON_substr_bdg	e4tz4C1	A: beta barrels	X: cradle loop barrel	H: RIFT-related	T: PUA domain	F: LON_substr_bdg	ECOD (1.6)
B [auth C]	Yippee-Mis18_1	e4tz4C2	A: beta complex topology	X: ETN0001 domain-like (From Homology)	H: ETN0001 domain-like	T: Mss4-like	F: Yippee-Mis18_1	ECOD (1.6)
A	CPSF_A_N	e4tz4A3	A: beta duplicates or obligate multimers	X: beta-propeller-like	H: beta-propeller	T: 7-bladed	F: CPSF_A_N	ECOD (1.6)
A	MMS1_N_C	e4tz4A2	A: beta duplicates or obligate multimers	X: beta-propeller-like	H: beta-propeller	T: 7-bladed	F: MMS1_N_C	ECOD (1.6)
A	MMS1_N_N	e4tz4A1	A: beta duplicates or obligate multimers	X: beta-propeller-like	H: beta-propeller	T: 7-bladed	F: MMS1_N_N	ECOD (1.6)
A	CPSF_A_C	e4tz4A4	A: alpha arrays	X: HTH	H: HTH	T: tri-helical	F: CPSF_A_C	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
B [auth C]	2.170.150.20	Mainly Beta	Beta Complex	Metal Binding Protein, Guanine Nucleotide Exchange Factor	Chain A	CATH (4.3.0)
B [auth C]	2.30.130.40	Mainly Beta	Roll	Archaeosine Trna-guanine Transglycosylase	Chain: A, domain 4	CATH (4.3.0)
B [auth C]	1.20.58.1480	Mainly Alpha	Up-down Bundle	Methane Monooxygenase Hydroxylase	Chain G, domain 1	CATH (4.3.0)
A	2.130.10.10	Mainly Beta	7 Propeller	Methylamine Dehydrogenase	Chain H	CATH (4.3.0)
A	1.10.150.910	Mainly Alpha	Orthogonal Bundle	DNA polymerase	domain 1	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
B [auth C]	PF02190	ATP-dependent protease La (LON) substrate-binding domain (LON_substr_bdg)	ATP-dependent protease La (LON) substrate-binding domain	-	Family
B [auth C]	PF03226	Yippee zinc-binding/DNA-binding /Mis18, centromere assembly (Yippee-Mis18)	Yippee zinc-binding/DNA-binding /Mis18, centromere assembly	This family includes both Yippee-type proteins and Mis18 kinetochore proteins. Yippee are putative zinc-binding/DNA-binding proteins. Mis18 are proteins involved in the priming of centromeres for recruiting CENP-A. Mis18-alpha and beta form part of ...	This family includes both Yippee-type proteins and Mis18 kinetochore proteins. Yippee are putative zinc-binding/DNA-binding proteins. Mis18 are proteins involved in the priming of centromeres for recruiting CENP-A. Mis18-alpha and beta form part of a small complex with Mis18-binding protein. Mis18-alpha is found to interact with DNA de-methylases through a Leu-rich region located at its carboxyl terminus [5]. This entry also includes the CULT domain proteins such as Cereblon [6].	Domain
A	PF10433	RSE1/DDB1/CPSF1 first beta-propeller (Beta-prop_RSE1_1st)	Mono-functional DNA-alkylating methyl methanesulfonate N-term	-	Repeat
A	PF03178	CPSF A subunit region (CPSF_A)	CPSF A subunit region	-	Repeat

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
B [auth C]	Protein cereblon	protein binding binding transmembrane transporter binding cation binding ion binding metal ion binding small molecule binding	cellular response to stimulus positive regulation of cell communication regulation of cellular process positive regulation of signal transduction response to stimulus signaling positive regulation of biological process regulation of signal transduction cell communication positive regulation of response to stimulus positive regulation of Wnt signaling pathway signal transduction Wnt signaling pathway positive regulation of cellular process cellular response to stimulus positive regulation of cell communication regulation of cellular process positive regulation of signal transduction response to stimulus signaling positive regulation of biological process regulation of signal transduction cell communication positive regulation of response to stimulus positive regulation of Wnt signaling pathway signal transduction Wnt signaling pathway positive regulation of cellular process regulation of biological process regulation of signaling cell surface receptor signaling pathway regulation of Wnt signaling pathway biological regulation regulation of response to stimulus regulation of cell communication cellular process positive regulation of signaling positive regulation of cellular component organization regulation of cellular component organization protein-containing complex organization positive regulation of cellular component biogenesis regulation of cellular component biogenesis cellular component organization cellular component biogenesis positive regulation of protein-containing complex assembly regulation of protein-containing complex assembly cellular component assembly protein-containing complex assembly cellular component organization or biogenesis regulation of localization negative regulation of ion transmembrane transporter activity negative regulation of potassium ion transmembrane transporter activity negative regulation of biological process negative regulation of transport localization regulation of large conductance calcium-activated potassium channel activity negative regulation of cation transmembrane transport monoatomic cation transport regulation of potassium ion transmembrane transporter activity regulation of monoatomic ion transport inorganic ion transmembrane transport regulation of potassium ion transmembrane transport establishment of localization regulation of cation channel activity inorganic cation transmembrane transport transmembrane transport regulation of molecular function regulation of transmembrane transport potassium ion transport regulation of potassium ion transport transport negative regulation of cation channel activity monoatomic ion transmembrane transport negative regulation of monoatomic ion transport potassium ion transmembrane transport regulation of transmembrane transporter activity regulation of monoatomic ion transmembrane transport metal ion transport negative regulation of transmembrane transport regulation of transporter activity monoatomic cation transmembrane transport negative regulation of monoatomic ion transmembrane transport negative regulation of cellular process monoatomic ion transport regulation of metal ion transport negative regulation of potassium ion transport regulation of monoatomic ion transmembrane transporter activity negative regulation of large conductance calcium-activated potassium channel activity regulation of transport negative regulation of transporter activity negative regulation of molecular function negative regulation of potassium ion transmembrane transport regulation of monoatomic cation transmembrane transport primary metabolic process protein ubiquitination macromolecule modification metabolic process protein metabolic process macromolecule metabolic process post-translational protein modification protein modification process protein modification by small protein conjugation protein modification by small protein conjugation or removal negative regulation of cellular component organization negative regulation of protein-containing complex assembly catabolic process proteolysis involved in protein catabolic process proteasomal protein catabolic process protein catabolic process proteasome-mediated ubiquitin-dependent protein catabolic process macromolecule catabolic process modification-dependent macromolecule catabolic process modification-dependent protein catabolic process proteolysis ubiquitin-dependent protein catabolic process behavior multicellular organismal process locomotory behavior exploration behavior locomotory exploration behavior	cellular anatomical structure membrane intracellular anatomical structure cytoplasm cytosol perinuclear region of cytoplasm cullin-RING ubiquitin ligase complex protein-containing complex ubiquitin ligase complex catalytic complex Cul4-RING E3 ubiquitin ligase complex transferase complex intracellular protein-containing complex Cul4A-RING E3 ubiquitin ligase complex cellular anatomical structure membrane intracellular anatomical structure cytoplasm cytosol perinuclear region of cytoplasm cullin-RING ubiquitin ligase complex protein-containing complex ubiquitin ligase complex catalytic complex Cul4-RING E3 ubiquitin ligase complex transferase complex intracellular protein-containing complex Cul4A-RING E3 ubiquitin ligase complex membrane-bounded organelle intracellular organelle organelle nucleus intracellular membrane-bounded organelle
A	DNA damage-binding protein 1	ubiquitin ligase complex scaffold activity protein-macromolecule adaptor activity molecular adaptor activity DNA binding binding organic cyclic compound binding nucleic acid binding protein-containing complex binding protein binding cullin family protein binding damaged DNA binding WD40-repeat domain binding protein domain specific binding	cellular response to stimulus cellular response to stress response to stimulus DNA damage response response to stress cellular process catabolic process proteolysis involved in protein catabolic process proteasomal protein catabolic process primary metabolic process protein catabolic process macromolecule catabolic process proteolysis metabolic process cellular response to stimulus cellular response to stress response to stimulus DNA damage response response to stress cellular process catabolic process proteolysis involved in protein catabolic process proteasomal protein catabolic process primary metabolic process protein catabolic process macromolecule catabolic process proteolysis metabolic process protein metabolic process macromolecule metabolic process apoptotic process cell death programmed cell death 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 regulation of biological process negative regulation of reproductive process regulation of reproductive process reproductive process biological regulation negative regulation of biological process modification-dependent macromolecule catabolic process modification-dependent protein catabolic process ubiquitin-dependent protein catabolic process regulation of biosynthetic process epigenetic programming of gene expression regulation of cellular process epigenetic programming in the zygotic pronuclei epigenetic regulation of gene expression regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process cellular component organization regulation of gene expression biosynthetic process chromatin organization chromatin remodeling regulation of macromolecule biosynthetic process cellular component organization or biogenesis regulation of metabolic process regulation of cell cycle phase transition regulation of cell cycle process cell cycle phase transition mitotic cell cycle regulation of mitotic cell cycle phase transition regulation of mitotic cell cycle mitotic cell cycle process cell cycle regulation of cell cycle mitotic cell cycle phase transition cell cycle process DNA metabolic process nucleic acid metabolic process nucleobase-containing compound metabolic process DNA repair positive regulation of viral genome replication positive regulation of viral process positive regulation of biological process viral life cycle regulation of viral process regulation of viral life cycle viral genome replication viral process regulation of viral genome replication developmental process cellular developmental process cell development developmental process involved in reproduction programmed cell death involved in cell development cell differentiation anatomical structure development ectopic germ cell programmed cell death nucleotide-excision repair response to light stimulus cellular response to environmental stimulus cellular response to light stimulus cellular response to radiation response to UV UV-damage excision repair response to radiation response to abiotic stimulus cellular response to abiotic stimulus cellular response to UV monosaccharide metabolic process gluconeogenesis regulation of primary metabolic process positive regulation of metabolic process regulation of small molecule metabolic process positive regulation of biosynthetic process small molecule metabolic process regulation of carbohydrate metabolic process regulation of glucose metabolic process positive regulation of cellular process positive regulation of gluconeogenesis carbohydrate metabolic process small molecule biosynthetic process carbohydrate biosynthetic process hexose metabolic process monosaccharide biosynthetic process hexose biosynthetic process positive regulation of glucose metabolic process regulation of gluconeogenesis positive regulation of carbohydrate metabolic process regulation of carbohydrate biosynthetic process positive regulation of small molecule metabolic process glucose metabolic process rhythmic process circadian rhythm regulation of circadian rhythm negative regulation of programmed cell death regulation of apoptotic process regulation of programmed cell death negative regulation of apoptotic process negative regulation of cellular process positive regulation of protein metabolic process positive regulation of macromolecule metabolic process regulation of protein metabolic process regulation of catabolic process positive regulation of protein catabolic process positive regulation of catabolic process regulation of protein catabolic process biological process involved in interspecies interaction between organisms biological process involved in interaction with symbiont biological process involved in symbiotic interaction regulation by virus of viral protein levels in host cell positive regulation by virus of viral protein levels in host cell regulation of biological quality proteasome-mediated ubiquitin-dependent protein catabolic process regulation of developmental process negative regulation of developmental process exit from host cell viral release from host cell biological process involved in interaction with host meiotic chromosome segregation sexual reproduction microtubule cytoskeleton organization membraneless organelle assembly female gamete generation meiotic cell cycle process gamete generation cellular component biogenesis cellular component assembly female meiotic nuclear division meiotic nuclear division chromosome segregation spindle organization organelle assembly organelle fission meiotic cell cycle multicellular organismal reproductive process meiotic spindle organization meiotic spindle assembly spindle assembly nuclear division organelle organization nuclear chromosome segregation microtubule-based process cytoskeleton organization spindle assembly involved in female meiosis cell surface receptor signaling pathway signaling cell communication signal transduction Wnt signaling pathway	extracellular exosome membrane-bounded organelle extracellular vesicle cellular anatomical structure extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle intracellular anatomical structure cytoplasm intracellular organelle membraneless organelle extracellular exosome membrane-bounded organelle extracellular vesicle cellular anatomical structure extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle intracellular anatomical structure cytoplasm intracellular organelle membraneless organelle intracellular membraneless organelle chromosome chromosome, telomeric region chromosomal region nucleus membrane-enclosed lumen intracellular membrane-bounded organelle nucleolus intracellular organelle lumen organelle lumen nuclear lumen cullin-RING ubiquitin ligase complex protein-containing complex ubiquitin ligase complex catalytic complex Cul4-RING E3 ubiquitin ligase complex transferase complex intracellular protein-containing complex Cul4A-RING E3 ubiquitin ligase complex nucleoplasm site of double-strand break site of DNA damage Cul4B-RING E3 ubiquitin ligase complex

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
B [auth C]	IPR015947	PUA-like superfamily	Homologous Superfamily
B [auth C]	IPR046336	Lon protease, N-terminal domain superfamily	Homologous Superfamily
B [auth C]	IPR004910	Yippee/Mis18/Cereblon	Domain
B [auth C]	IPR003111	Lon protease, N-terminal domain	Domain
B [auth C]	IPR034750	CULT domain	Domain
A	IPR018846	RSE1/DDB1/CPSF1, first beta-propeller domain	Domain
A	IPR036322	WD40-repeat-containing domain superfamily	Homologous Superfamily
A	IPR015943	WD40/YVTN repeat-like-containing domain superfamily	Homologous Superfamily
A	IPR004871	Cleavage/polyadenylation specificity factor, A subunit, C-terminal	Domain
A	IPR050358	RSE1/DDB1/CFT1/CPSF1	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
B [auth C]	Pharos: Q96SW2	intellectual disability, autosomal recessive 2 plasma cell myeloma 3p- syndrome intellectual disability toxic or drug-related embryofetopathy central nervous system malformation Erythema nodosum leprosum mantle cell lymphoma non-small cell lung carcinoma follicular lymphoma large cell medulloblastoma marginal zone lymphoma osteosarcoma POEMS syndrome attention deficit hyperactivity disorder, inattentive type intellectual disability, autosomal recessive 2 plasma cell myeloma 3p- syndrome intellectual disability toxic or drug-related embryofetopathy central nervous system malformation Erythema nodosum leprosum mantle cell lymphoma non-small cell lung carcinoma follicular lymphoma large cell medulloblastoma marginal zone lymphoma osteosarcoma POEMS syndrome attention deficit hyperactivity disorder, inattentive type lung adenocarcinoma myelodysplastic syndrome ovarian cancer
A	Pharos: Q16531	Disease Exacerbation gastric cancer lung cancer xeroderma pigmentosum gastric neoplasm drug-induced liver injury hereditary diffuse gastric adenocarcinoma psoriasis

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.