5EDV

Structure of the HOIP-RBR/UbcH5B~ubiquitin transfer 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	RING/U-box like	8039274	3000160	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	RING/U-box like	8039274	3000160	SCOP2B (2022-06-29)
E	SCOP2B Superfamily	Ubiquitin-like	8101457	3000157	SCOP2B (2022-06-29)
F	SCOP2B Superfamily	Ubiquitin-like	8101457	3000157	SCOP2B (2022-06-29)
G	SCOP2B Superfamily	Ubiquitin-like	8101457	3000157	SCOP2B (2022-06-29)
H	SCOP2B Superfamily	Ubiquitin-like	8101457	3000157	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	UBC-like	8040137	3000570	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	UBC-like	8040137	3000570	SCOP2B (2022-06-29)
I	SCOP2B Superfamily	UBC-like	8040137	3000570	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	F_UNCLASSIFIED	e5edvA1	A: few secondary structure elements	X: RING/U-box-like	H: RING/U-box-like	T: RING/U-box	F: F_UNCLASSIFIED	ECOD (1.6)
A	PF22191	e5edvA2	A: few secondary structure elements	X: RING/U-box-like	H: RING/U-box-like	T: IBR domain	F: PF22191	ECOD (1.6)
B	F_UNCLASSIFIED	e5edvB1	A: few secondary structure elements	X: RING/U-box-like	H: RING/U-box-like	T: RING/U-box	F: F_UNCLASSIFIED	ECOD (1.6)
B	PF22191	e5edvB2	A: few secondary structure elements	X: RING/U-box-like	H: RING/U-box-like	T: IBR domain	F: PF22191	ECOD (1.6)
B	PF18091	e5edvB4	A: few secondary structure elements	X: E3 ligase HOIP C-terminal domain (From Topology)	H: E3 ligase HOIP C-terminal domain (From Topology)	T: E3 ligase HOIP C-terminal domain	F: PF18091	ECOD (1.6)
E	PF00240	e5edvE1	A: a+b two layers	X: beta-Grasp	H: Ubiquitin-related	T: Ubiquitin-like	F: PF00240	ECOD (1.6)
F	PF00240	e5edvF1	A: a+b two layers	X: beta-Grasp	H: Ubiquitin-related	T: Ubiquitin-like	F: PF00240	ECOD (1.6)
G	PF00240	e5edvG1	A: a+b two layers	X: beta-Grasp	H: Ubiquitin-related	T: Ubiquitin-like	F: PF00240	ECOD (1.6)
H	PF00240	e5edvH1	A: a+b two layers	X: beta-Grasp	H: Ubiquitin-related	T: Ubiquitin-like	F: PF00240	ECOD (1.6)
C	PF00179	e5edvC1	A: a+b two layers	X: UBC-like	H: UBC-like (From Topology)	T: UBC-like	F: PF00179	ECOD (1.6)
D	PF00179	e5edvD1	A: a+b two layers	X: UBC-like	H: UBC-like (From Topology)	T: UBC-like	F: PF00179	ECOD (1.6)
I	PF00179	e5edvI1	A: a+b two layers	X: UBC-like	H: UBC-like (From Topology)	T: UBC-like	F: PF00179	ECOD (1.6)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B	PF18091	E3 Ubiquitin Ligase RBR C-terminal domain (E3_UbLigase_RBR)	E3 Ubiquitin Ligase RBR C-terminal domain	This is the C-terminal domain of HOIP present in Homo sapiens. HOIP synthesize the linear ubiquitin chains that help control innate immunity and inflammation. This region has an RBR domain which catalyzes the transfer of ubiquitin onto a substrate [1 ...	This is the C-terminal domain of HOIP present in Homo sapiens. HOIP synthesize the linear ubiquitin chains that help control innate immunity and inflammation. This region has an RBR domain which catalyzes the transfer of ubiquitin onto a substrate [1].	Domain
A, B	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
E, F, G, H	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
C, D, I	PF00179	Ubiquitin-conjugating enzyme (UQ_con)	Ubiquitin-conjugating enzyme	Proteins destined for proteasome-mediated degradation may be ubiquitinated. Ubiquitination follows conjugation of ubiquitin to a conserved cysteine residue of UBC homologues. TSG101 is one of several UBC homologues that lacks this active site cystein ...	Proteins destined for proteasome-mediated degradation may be ubiquitinated. Ubiquitination follows conjugation of ubiquitin to a conserved cysteine residue of UBC homologues. TSG101 is one of several UBC homologues that lacks this active site cysteine [4, 5].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B	E3 ubiquitin-protein ligase RNF31	polyubiquitin modification-dependent protein binding protein binding binding K48-linked polyubiquitin modification-dependent protein binding modification-dependent protein binding ubiquitin binding ubiquitin-like protein binding linear polyubiquitin binding K63-linked polyubiquitin modification-dependent protein binding aminoacyltransferase activity ubiquitin-like protein transferase activity catalytic activity, acting on a protein acyltransferase activity ubiquitin-like protein ligase activity polyubiquitin modification-dependent protein binding protein binding binding K48-linked polyubiquitin modification-dependent protein binding modification-dependent protein binding ubiquitin binding ubiquitin-like protein binding linear polyubiquitin binding K63-linked polyubiquitin modification-dependent protein 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 protein ligase binding ubiquitin-like protein ligase binding enzyme binding cation binding transition metal ion binding zinc ion binding ion binding metal ion binding small molecule binding identical protein binding	organonitrogen compound metabolic process protein polyubiquitination 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 linear polyubiquitination protein modification by small protein conjugation or removal organonitrogen compound metabolic process protein polyubiquitination 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 linear polyubiquitination protein modification by small protein conjugation or removal cellular response to stimulus positive regulation of cell communication regulation of cellular process positive regulation of signal transduction positive regulation of canonical NF-kappaB signal transduction response to stimulus signaling positive regulation of biological process regulation of signal transduction intracellular signal transduction cell communication positive regulation of response to stimulus regulation of intracellular signal transduction intracellular signaling cassette signal transduction positive regulation of cellular process regulation of biological process regulation of signaling biological regulation positive regulation of intracellular signal transduction canonical NF-kappaB signal transduction regulation of response to stimulus regulation of cell communication regulation of canonical NF-kappaB signal transduction cellular process positive regulation of signaling immune response-regulating cell surface receptor signaling pathway immune response-activating signaling pathway immune response-regulating signaling pathway positive regulation of immune response regulation of immune system process positive regulation of immune system process cell surface receptor signaling pathway immune response-activating cell surface receptor signaling pathway immune response T cell receptor signaling pathway immune system process regulation of immune response antigen receptor-mediated signaling pathway activation of immune response biological process involved in interspecies interaction between organisms response to other organism defense response response to external stimulus response to biotic stimulus defense response to bacterium defense response to other organism response to stress response to bacterium response to external biotic stimulus protein localization regulation of localization establishment of protein localization cellular localization regulation of protein localization protein targeting regulation of protein targeting to mitochondrion positive regulation of establishment of protein localization localization cellular macromolecule localization positive regulation of protein targeting to mitochondrion regulation of establishment of protein localization establishment of localization regulation of establishment of protein localization to mitochondrion establishment of protein localization to organelle regulation of protein targeting regulation of cellular localization macromolecule localization protein localization to organelle protein localization to mitochondrion positive regulation of protein localization protein targeting to mitochondrion establishment of protein localization to mitochondrion positive regulation of establishment of protein localization to mitochondrion regulation of defense response regulation of response to biotic stimulus catabolic process regulation of response to external stimulus macroautophagy positive regulation of xenophagy autophagy positive regulation of cellular metabolic process xenophagy regulation of autophagy cellular catabolic process positive regulation of metabolic process positive regulation of response to external stimulus regulation of response to stress positive regulation of macroautophagy process utilizing autophagic mechanism positive regulation of autophagy regulation of xenophagy cellular metabolic process regulation of cellular metabolic process regulation of catabolic process positive regulation of catabolic process regulation of macroautophagy regulation of cellular catabolic process positive regulation of defense response positive regulation of cellular catabolic process regulation of metabolic process CD40 signaling pathway necroptotic process negative regulation of programmed cell death negative regulation of necroptotic process negative regulation of biological process programmed necrotic cell death regulation of programmed cell death cell death regulation of necroptotic process negative regulation of programmed necrotic cell death negative regulation of cellular process regulation of programmed necrotic cell death programmed cell death positive regulation of DNA-binding transcription factor activity cellular biosynthetic process positive regulation of NF-kappaB transcription factor activity RNA metabolic process regulation of primary metabolic process nucleobase-containing compound metabolic process RNA biosynthetic process positive regulation of molecular function nucleic acid biosynthetic process DNA-templated transcription regulation of RNA metabolic process organic substance biosynthetic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process regulation of biosynthetic 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 regulation of molecular function organic cyclic compound metabolic process regulation of gene expression biosynthetic process regulation of DNA-binding transcription factor activity organic cyclic compound biosynthetic process regulation of macromolecule biosynthetic process regulation of DNA-templated transcription	cell periphery protein-containing complex plasma membrane protein complex membrane plasma membrane plasma membrane signaling receptor complex membrane protein complex CD40 receptor complex cellular anatomical entity receptor complex intracellular anatomical structure cytoplasm cytosol LUBAC complex cell periphery protein-containing complex plasma membrane protein complex membrane plasma membrane plasma membrane signaling receptor complex membrane protein complex CD40 receptor complex cellular anatomical entity receptor complex intracellular anatomical structure cytoplasm cytosol LUBAC complex ubiquitin ligase complex catalytic complex transferase complex intracellular protein-containing complex cytoplasmic side of plasma membrane cytoplasmic side of membrane side of membrane
E, F, G, H	Polyubiquitin-B	protein tag activity molecular tag activity ubiquitin protein ligase binding protein binding binding ubiquitin-like protein ligase binding enzyme binding	developmental process multicellular organismal process reproductive system development gonad development tube development reproductive process sex differentiation animal organ development developmental process involved in reproduction male gonad development male sex differentiation multicellular organism development development of primary male sexual characteristics development of primary sexual characteristics seminiferous tubule development developmental process multicellular organismal process reproductive system development gonad development tube development reproductive process sex differentiation animal organ development developmental process involved in reproduction male gonad development male sex differentiation multicellular organism development development of primary male sexual characteristics development of primary sexual characteristics seminiferous tubule development anatomical structure development reproductive structure development system development regulation of mitochondrial membrane potential biological regulation regulation of biological quality regulation of membrane potential organonitrogen compound catabolic process organonitrogen compound metabolic process catabolic process proteolysis involved in protein catabolic process primary metabolic process protein catabolic process macromolecule catabolic process organic substance metabolic process modification-dependent macromolecule catabolic process modification-dependent protein catabolic process proteolysis metabolic process protein metabolic process macromolecule metabolic process organic substance catabolic process regulation of biological process neuron apoptotic process regulation of cellular process regulation of apoptotic process regulation of programmed cell death cell death cellular process apoptotic process programmed cell death regulation of neuron apoptotic process multicellular organismal-level homeostasis homeostatic process energy homeostasis regulation of protein modification process positive regulation of protein metabolic process positive regulation of biological process regulation of protein ubiquitination positive regulation of post-translational protein modification regulation of primary metabolic process positive regulation of metabolic process positive regulation of protein modification process protein ubiquitination positive regulation of macromolecule metabolic process regulation of protein modification by small protein conjugation or removal protein modification process positive regulation of protein modification by small protein conjugation or removal positive regulation of protein ubiquitination regulation of post-translational protein modification regulation of protein metabolic process regulation of macromolecule metabolic process macromolecule modification 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 positive regulation of cell communication positive regulation of signal transduction response to stimulus signaling positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator regulation of signal transduction regulation of intrinsic apoptotic signaling pathway intracellular signal transduction cell communication positive regulation of apoptotic signaling pathway positive regulation of response to stimulus regulation of intracellular signal transduction regulation of signal transduction by p53 class mediator positive regulation of signal transduction by p53 class mediator signal transduction intrinsic apoptotic signaling pathway positive regulation of cellular process regulation of signaling positive regulation of programmed cell death positive regulation of intracellular signal transduction signal transduction by p53 class mediator positive regulation of apoptotic process apoptotic signaling pathway regulation of response to stimulus regulation of cell communication intrinsic apoptotic signaling pathway by p53 class mediator positive regulation of intrinsic apoptotic signaling pathway regulation of intrinsic apoptotic signaling pathway by p53 class mediator regulation of apoptotic signaling pathway positive regulation of signaling cellular developmental process cell projection organization plasma membrane bounded cell projection morphogenesis cell development neuron projection development cell morphogenesis cellular component organization neurogenesis cell projection morphogenesis neuron differentiation neuron projection morphogenesis cell differentiation cellular component organization or biogenesis plasma membrane bounded cell projection organization nervous system development generation of neurons anatomical structure morphogenesis neuron development hypothalamus development forebrain development central nervous system neuron development central nervous system neuron differentiation hypothalamus cell differentiation hypothalamus gonadotrophin-releasing hormone neuron development limbic system development head development forebrain generation of neurons hypothalamus gonadotrophin-releasing hormone neuron differentiation brain development diencephalon development forebrain neuron development central nervous system development forebrain neuron differentiation sexual reproduction organelle fission meiotic cell cycle multicellular organismal reproductive process female gamete generation meiotic cell cycle process gamete generation nuclear division organelle organization meiosis I meiosis I cell cycle process female meiosis I female meiotic nuclear division meiotic nuclear division cell cycle cell cycle process positive regulation of protein monoubiquitination protein monoubiquitination regulation of protein monoubiquitination regulation of proteolysis involved in protein catabolic process regulation of proteolysis proteasomal protein catabolic process regulation of catabolic process regulation of proteasomal protein catabolic process regulation of protein catabolic process male meiosis I male meiotic nuclear division male gamete generation connective tissue development adipose tissue development fat pad development tissue development female gonad development female sex differentiation development of primary female sexual characteristics establishment of organelle localization cellular localization organelle transport along microtubule transport establishment of mitochondrion localization intracellular transport establishment of localization localization mitochondrion localization establishment of mitochondrion localization, microtubule-mediated mitochondrion transport along microtubule organelle localization establishment of localization in cell microtubule-based transport transport along microtubule cytoskeleton-dependent intracellular transport microtubule-based movement microtubule-based process	membrane-bounded organelle intracellular organelle intracellular anatomical structure mitochondrion organelle cytoplasm cellular anatomical entity intracellular membrane-bounded organelle vesicle extracellular exosome extracellular vesicle extracellular organelle extracellular region extracellular space membrane-bounded organelle intracellular organelle intracellular anatomical structure mitochondrion organelle cytoplasm cellular anatomical entity intracellular membrane-bounded organelle vesicle extracellular exosome extracellular vesicle extracellular organelle extracellular region extracellular space extracellular membrane-bounded organelle cytosol cell periphery plasma membrane membrane nucleus membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen organelle subcompartment endomembrane system endoplasmic reticulum subcompartment nuclear outer membrane-endoplasmic reticulum membrane network endoplasmic reticulum organelle membrane endoplasmic reticulum membrane cell projection neuron projection plasma membrane bounded cell projection intracellular vesicle cytoplasmic vesicle membrane bounding membrane of organelle cytoplasmic vesicle vesicle membrane endocytic vesicle membrane endocytic vesicle endosome membrane endosome mitochondrial membrane organelle outer membrane organelle envelope mitochondrial envelope mitochondrial outer membrane outer membrane somatodendritic compartment cell body neuronal cell body
C, D, I	Ubiquitin-conjugating enzyme E2 D2	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 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 ubiquitin conjugating enzyme activity aminoacyltransferase activity ubiquitin-like protein transferase activity catalytic activity, acting on a protein acyltransferase activity ubiquitin-like protein conjugating enzyme activity transferase activity catalytic activity ubiquitin-protein transferase activity ubiquitin protein ligase binding protein binding ubiquitin-like protein ligase binding enzyme binding ubiquitin-like protein ligase activity ubiquitin protein ligase activity	organonitrogen compound catabolic process organonitrogen compound metabolic process catabolic process proteolysis involved in protein catabolic process primary metabolic process protein catabolic process macromolecule catabolic process organic substance metabolic process modification-dependent macromolecule catabolic process modification-dependent protein catabolic process proteolysis ubiquitin-dependent protein catabolic process metabolic process protein metabolic process organonitrogen compound catabolic process organonitrogen compound metabolic process catabolic process proteolysis involved in protein catabolic process primary metabolic process protein catabolic process macromolecule catabolic process organic substance metabolic process modification-dependent macromolecule catabolic process modification-dependent protein catabolic process proteolysis ubiquitin-dependent protein catabolic process metabolic process protein metabolic process macromolecule metabolic process organic substance catabolic process protein polyubiquitination 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 K48-linked ubiquitination protein autoubiquitination	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 cytosol nucleus 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 cytosol nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen intracellular organelle nucleoplasm organelle lumen nuclear lumen 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, B	IPR002867	IBR domain	Domain
A, B	IPR044066	TRIAD supradomain	Domain
A, B	IPR036339	PUB-like domain superfamily	Homologous Superfamily
A, B	IPR026254	E3 ubiquitin-protein ligase RNF31-like	Family
A, B	IPR047541	E3 ubiquitin-protein ligase RNF31-like, modified RING finger, HC subclass	Domain
A, B	IPR032065	E3 ubiquitin-protein ligase RNF31, UBA-like domain	Domain
A, B	IPR047539	E3 ubiquitin-protein ligase RNF31, UBA domain	Domain
A, B	IPR015940	Ubiquitin-associated domain	Domain
A, B	IPR036443	Zinc finger, RanBP2-type superfamily	Homologous Superfamily
A, B	IPR017907	Zinc finger, RING-type, conserved site	Conserved Site
A, B	IPR018997	PUB domain	Domain
A, B	IPR047542	E3 ubiquitin-protein ligase RNF31-like, Rcat domain	Domain
A, B	IPR013083	Zinc finger, RING/FYVE/PHD-type	Homologous Superfamily
A, B	IPR047543	E3 ubiquitin-protein ligase RNF31-like, Bbox1 zinc finger	Domain
A, B	IPR040641	E3 ubiquitin-protein ligase RNF31, PUB domain	Domain
A, B	IPR047540	E3 ubiquitin-protein ligase RNF31-like, BRcat domain	Domain
A, B	IPR001876	Zinc finger, RanBP2-type	Domain
A, B	IPR041031	RNF31, C-terminal	Domain
E, F, G, H	IPR019954	Ubiquitin conserved site	Conserved Site
E, F, G, H	IPR000626	Ubiquitin-like domain	Domain
E, F, G, H	IPR019956	Ubiquitin domain	Domain
E, F, G, H	IPR029071	Ubiquitin-like domain superfamily	Homologous Superfamily
C, D, I	IPR000608	Ubiquitin-conjugating enzyme E2	Domain
C, D, I	IPR016135	Ubiquitin-conjugating enzyme/RWD-like	Homologous Superfamily
C, D, I	IPR023313	Ubiquitin-conjugating enzyme, active site	Active Site

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B	Pharos: Q96EP0	prostate cancer Prostatic Neoplasms
E, F, G, H	Pharos: P0CG47	astrocytic tumor cleft soft palate lung cancer Cleft of hard palate ovarian cancer isolated cleft palate
C, D, I	Pharos: P62837	astrocytic tumor esophageal squamous cell carcinoma malignant ependymoma osteosarcoma atypical teratoid rhabdoid tumor glioblastoma malignant glioma ovarian cancer breast cancer large cell medulloblastoma malignant mesothelioma plasma cell myeloma