6UML

Structural Basis for Thalidomide Teratogenicity Revealed by the Cereblon-DDB1-SALL4-Pomalidomide Complex

External Resource: Annotation

Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
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	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)
A	SCOP2B Superfamily	WD40 repeat-like	8052531	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)
C [auth E]	PF00096	e6umlE1	A: few secondary structure elements	X: beta-beta-alpha zinc fingers	H: beta-beta-alpha zinc fingers (From Topology)	T: beta-beta-alpha zinc fingers	F: PF00096	ECOD (1.6)
A	PF03178,PF10433	e6umlA3	A: beta duplicates or obligate multimers	X: beta-propeller-like	H: beta-propeller	T: 7-bladed	F: PF03178,PF10433	ECOD (1.6)
A	PF10433	e6umlA1	A: beta duplicates or obligate multimers	X: beta-propeller-like	H: beta-propeller	T: 7-bladed	F: PF10433	ECOD (1.6)
A	PF03178	e6umlA2	A: alpha arrays	X: HTH	H: HTH	T: tri-helical	F: PF03178	ECOD (1.6)
B [auth C]	PF02190	e6umlC1	A: beta barrels	X: cradle loop barrel	H: RIFT-related	T: PUA domain	F: PF02190	ECOD (1.6)
B [auth C]	PF03226	e6umlC2	A: beta complex topology	X: ETN0001 domain-like (From Homology)	H: ETN0001 domain-like	T: Mss4-like	F: PF03226	ECOD (1.6)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
C [auth E]	PF00096	Zinc finger, C2H2 type (zf-C2H2)	Zinc finger, C2H2 type	The C2H2 zinc finger is the classical zinc finger domain. The two conserved cysteines and histidines co-ordinate a zinc ion. The following pattern describes the zinc finger. #-X-C-X(1-5)-C-X3-#-X5-#-X2-H-X(3-6)-[H/C] Where X can be any amino acid, an ...	The C2H2 zinc finger is the classical zinc finger domain. The two conserved cysteines and histidines co-ordinate a zinc ion. The following pattern describes the zinc finger. #-X-C-X(1-5)-C-X3-#-X5-#-X2-H-X(3-6)-[H/C] Where X can be any amino acid, and numbers in brackets indicate the number of residues. The positions marked # are those that are important for the stable fold of the zinc finger. The final position can be either his or cys. The C2H2 zinc finger is composed of two short beta strands followed by an alpha helix. The amino terminal part of the helix binds the major groove in DNA binding zinc fingers. The accepted consensus binding sequence for Sp1 is usually defined by the asymmetric hexanucleotide core GGGCGG but this sequence does not include, among others, the GAG (=CTC) repeat that constitutes a high-affinity site for Sp1 binding to the wt1 promoter [2].	Domain
A	PF10433	Mono-functional DNA-alkylating methyl methanesulfonate N-term (MMS1_N)	Mono-functional DNA-alkylating methyl methanesulfonate N-term	-	Repeat
A	PF03178	CPSF A subunit region (CPSF_A)	CPSF A subunit region	-	Repeat
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

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
C [auth E]	Sal-like protein 4	DNA-binding transcription factor activity, RNA polymerase II-specific transcription regulator activity DNA-binding transcription factor activity DNA binding sequence-specific DNA binding binding double-stranded DNA binding nucleic acid binding RNA polymerase II transcription regulatory region sequence-specific DNA binding cis-regulatory region sequence-specific DNA binding sequence-specific double-stranded DNA binding transcription cis-regulatory region binding organic cyclic compound binding transcription regulatory region nucleic acid binding DNA-binding transcription factor activity, RNA polymerase II-specific transcription regulator activity DNA-binding transcription factor activity DNA binding sequence-specific DNA binding binding double-stranded DNA binding nucleic acid binding RNA polymerase II transcription regulatory region sequence-specific DNA binding cis-regulatory region sequence-specific DNA binding sequence-specific double-stranded DNA binding transcription cis-regulatory region binding organic cyclic compound binding transcription regulatory region nucleic acid binding RNA polymerase II cis-regulatory region sequence-specific DNA binding cation binding ion binding metal ion binding small molecule binding	multicellular organismal process embryonic epithelial tube formation chordate embryonic development tube formation embryo development multicellular organism development epithelial tube formation tube morphogenesis primary neural tube formation embryo development ending in birth or egg hatching anatomical structure development epithelial tube morphogenesis system development developmental process multicellular organismal process embryonic epithelial tube formation chordate embryonic development tube formation embryo development multicellular organism development epithelial tube formation tube morphogenesis primary neural tube formation embryo development ending in birth or egg hatching anatomical structure development epithelial tube morphogenesis system development developmental process morphogenesis of embryonic epithelium epithelium development neural tube development tube development embryonic morphogenesis morphogenesis of an epithelium nervous system development tissue development anatomical structure morphogenesis tissue morphogenesis neural tube closure neural tube formation anatomical structure formation involved in morphogenesis tube closure heart development animal organ development ventricular septum development circulatory system development cardiac septum development cardiac chamber development cardiac ventricle development somatic stem cell population maintenance maintenance of cell number stem cell population maintenance regulation of cellular process cellular biosynthetic process RNA metabolic process regulation of primary metabolic process RNA biosynthetic process nucleobase-containing compound metabolic process DNA-templated transcription nucleic acid biosynthetic process regulation of RNA metabolic process transcription by RNA polymerase II organic substance metabolic process organic substance biosynthetic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process regulation of transcription by RNA polymerase II regulation of biosynthetic process regulation of biological process cellular metabolic process biological regulation primary metabolic process regulation of cellular metabolic process regulation of macromolecule metabolic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process nucleic acid metabolic process regulation of cellular biosynthetic process organic cyclic compound metabolic process regulation of gene expression biosynthetic process organic cyclic compound biosynthetic process metabolic process cellular process regulation of macromolecule biosynthetic process macromolecule metabolic process regulation of DNA-templated transcription regulation of metabolic process negative regulation of biological process negative regulation of cellular metabolic process negative regulation of RNA biosynthetic process negative regulation of nucleobase-containing compound metabolic process negative regulation of DNA-templated transcription negative regulation of transcription by RNA polymerase II negative regulation of metabolic process negative regulation of cellular biosynthetic process negative regulation of macromolecule biosynthetic process negative regulation of RNA metabolic process negative regulation of cellular process negative regulation of macromolecule metabolic process negative regulation of biosynthetic process positive regulation of macromolecule biosynthetic process positive regulation of metabolic process positive regulation of macromolecule metabolic process positive regulation of nucleobase-containing compound metabolic process positive regulation of transcription by RNA polymerase II positive regulation of RNA metabolic process positive regulation of DNA-templated transcription positive regulation of biological process positive regulation of cellular metabolic process positive regulation of biosynthetic process positive regulation of cellular process positive regulation of RNA biosynthetic process positive regulation of cellular biosynthetic process limb development appendage development embryonic limb morphogenesis embryonic appendage morphogenesis appendage morphogenesis limb morphogenesis inner cell mass cell proliferation cell population proliferation developmental growth growth in utero embryonic development blastocyst growth blastocyst development	protein-containing complex intracellular anatomical structure protein-DNA complex chromatin chromosome cellular anatomical entity heterochromatin intracellular organelle organelle intracellular non-membrane-bounded organelle non-membrane-bounded organelle membrane-bounded organelle intracellular membrane-bounded organelle cytoplasm protein-containing complex intracellular anatomical structure protein-DNA complex chromatin chromosome cellular anatomical entity heterochromatin intracellular organelle organelle intracellular non-membrane-bounded organelle non-membrane-bounded organelle membrane-bounded organelle intracellular membrane-bounded organelle cytoplasm nucleus membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen
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 organonitrogen compound catabolic process organonitrogen compound metabolic process catabolic process proteolysis involved in protein catabolic process proteasomal protein catabolic process primary metabolic process protein catabolic process macromolecule catabolic process cellular response to stimulus cellular response to stress response to stimulus DNA damage response response to stress cellular process organonitrogen compound catabolic process organonitrogen compound metabolic process catabolic process proteolysis involved in protein catabolic process proteasomal protein catabolic process primary metabolic process protein catabolic process macromolecule catabolic process organic substance metabolic process proteolysis metabolic process protein metabolic process macromolecule metabolic process organic substance catabolic 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 cellular process epigenetic programming in the zygotic pronuclei cellular biosynthetic process protein-DNA complex organization cellular component organization chromatin organization organic substance biosynthetic process chromatin remodeling cellular component organization or biogenesis regulation of biosynthetic process epigenetic programming of gene expression protein-containing complex organization epigenetic regulation of gene expression cellular metabolic process regulation of cellular metabolic process regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process regulation of cellular biosynthetic process regulation of gene expression biosynthetic process regulation of macromolecule biosynthetic process 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 organic cyclic 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 positive regulation of cellular 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 positive regulation of cellular biosynthetic 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 non-membrane-bounded organelle assembly microtubule cytoskeleton organization 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 extracellular organelle extracellular region organelle extracellular space cellular anatomical entity vesicle extracellular membrane-bounded organelle intracellular anatomical structure cytoplasm intracellular organelle intracellular non-membrane-bounded organelle extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space cellular anatomical entity vesicle extracellular membrane-bounded organelle intracellular anatomical structure cytoplasm intracellular organelle intracellular non-membrane-bounded organelle chromosome chromosome, telomeric region chromosomal region non-membrane-bounded organelle 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
B [auth C]	Protein cereblon	protein binding binding transmembrane transporter binding cation binding ion binding metal ion binding small molecule binding	regulation of localization regulation of biological process regulation of cellular process transport regulation of transport negative regulation of monoatomic ion transport regulation of monoatomic ion transport monoatomic ion transmembrane transport biological regulation negative regulation of biological process negative regulation of transport regulation of monoatomic ion transmembrane transport establishment of localization negative regulation of transmembrane transport transmembrane transport regulation of localization regulation of biological process regulation of cellular process transport regulation of transport negative regulation of monoatomic ion transport regulation of monoatomic ion transport monoatomic ion transmembrane transport biological regulation negative regulation of biological process negative regulation of transport regulation of monoatomic ion transmembrane transport establishment of localization negative regulation of transmembrane transport transmembrane transport localization regulation of transmembrane transport negative regulation of monoatomic ion transmembrane transport negative regulation of cellular process monoatomic ion transport cellular process cellular response to stimulus positive regulation of cell communication 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 signaling cell surface receptor signaling pathway regulation of Wnt signaling pathway regulation of response to stimulus regulation of cell communication 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 organonitrogen compound metabolic process primary metabolic process organic substance 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 organonitrogen compound catabolic process 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 organic substance catabolic process behavior multicellular organismal process locomotory behavior exploration behavior locomotory exploration behavior	membrane cellular anatomical entity 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 cellular anatomical entity 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

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
C [auth E]	IPR013087	Zinc finger C2H2-type	Domain
C [auth E]	IPR036236	Zinc finger C2H2 superfamily	Homologous Superfamily
A	IPR018846	Cleavage/polyadenylation specificity factor, A subunit, N-terminal	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
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

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
C [auth E]	Pharos: Q9UJQ4	Duane-radial ray syndrome IVIC syndrome Duane retraction syndrome Craniofacial Abnormalities osteosarcoma breast carcinoma coloboma intellectual disability lung adenocarcinoma ovarian cancer atypical teratoid rhabdoid tumor cancer esophageal squamous cell carcinoma polydactyly ventricular septal defect Duane-radial ray syndrome IVIC syndrome Duane retraction syndrome Craniofacial Abnormalities osteosarcoma breast carcinoma coloboma intellectual disability lung adenocarcinoma ovarian cancer atypical teratoid rhabdoid tumor cancer esophageal squamous cell carcinoma polydactyly ventricular septal defect breast cancer choanal atresia Holt-Oram syndrome
A	Pharos: Q16531	Disease Exacerbation gastric cancer lung cancer xeroderma pigmentosum gastric neoplasm drug-induced liver injury hereditary diffuse gastric adenocarcinoma psoriasis
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

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.