6WRV

Crystal structure of computationally designed protein 3DS18 in complex with the human Transferrin receptor ectodomain

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)
B	SCOP2B Superfamily	PA domain	8043922	3000955	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Transferrin receptor-like dimerisation domain	8037591	3000375	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Zn-dependent exopeptidases	8032205	3000662	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Zn-dependent exopeptidases	8032205	3000662	SCOP2B (2022-06-29)
C [auth E]	SCOP2B Superfamily	Zn-dependent exopeptidases	8032205	3000662	SCOP2B (2022-06-29)
C [auth E]	SCOP2B Superfamily	PA domain	8043922	3000955	SCOP2B (2022-06-29)
C [auth E]	SCOP2B Superfamily	Transferrin receptor-like dimerisation domain	8037591	3000375	SCOP2B (2022-06-29)
C [auth E]	SCOP2B Superfamily	Zn-dependent exopeptidases	8032205	3000662	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	Zn-dependent exopeptidases	8032205	3000662	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	Transferrin receptor-like dimerisation domain	8037591	3000375	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	PA domain	8043922	3000955	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	Zn-dependent exopeptidases	8032205	3000662	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	TFR_dimer	e6wrvB2	A: alpha bundles	X: N-cbl like	H: Transferrin receptor ectodomain, C-terminal domain (From Topology)	T: Transferrin receptor ectodomain, C-terminal domain	F: TFR_dimer	ECOD (1.6)
B	Peptidase_M28	e6wrvB1	A: a/b three-layered sandwiches	X: Phosphorylase/hydrolase-like	H: Zn-dependent exopeptidases (From Topology)	T: Zn-dependent exopeptidases	F: Peptidase_M28	ECOD (1.6)
B	PA	e6wrvB3	A: a/b three-layered sandwiches	X: The swivelling beta/beta/alpha domains	H: The swivelling beta/beta/alpha domain (From Topology)	T: The swivelling beta/beta/alpha domain	F: PA	ECOD (1.6)
C [auth E]	TFR_dimer	e6wrvE1	A: alpha bundles	X: N-cbl like	H: Transferrin receptor ectodomain, C-terminal domain (From Topology)	T: Transferrin receptor ectodomain, C-terminal domain	F: TFR_dimer	ECOD (1.6)
C [auth E]	Peptidase_M28	e6wrvE3	A: a/b three-layered sandwiches	X: Phosphorylase/hydrolase-like	H: Zn-dependent exopeptidases (From Topology)	T: Zn-dependent exopeptidases	F: Peptidase_M28	ECOD (1.6)
C [auth E]	PA	e6wrvE2	A: a/b three-layered sandwiches	X: The swivelling beta/beta/alpha domains	H: The swivelling beta/beta/alpha domain (From Topology)	T: The swivelling beta/beta/alpha domain	F: PA	ECOD (1.6)
A	TFR_dimer	e6wrvA3	A: alpha bundles	X: N-cbl like	H: Transferrin receptor ectodomain, C-terminal domain (From Topology)	T: Transferrin receptor ectodomain, C-terminal domain	F: TFR_dimer	ECOD (1.6)
A	Peptidase_M28	e6wrvA1	A: a/b three-layered sandwiches	X: Phosphorylase/hydrolase-like	H: Zn-dependent exopeptidases (From Topology)	T: Zn-dependent exopeptidases	F: Peptidase_M28	ECOD (1.6)
A	PA	e6wrvA2	A: a/b three-layered sandwiches	X: The swivelling beta/beta/alpha domains	H: The swivelling beta/beta/alpha domain (From Topology)	T: The swivelling beta/beta/alpha domain	F: PA	ECOD (1.6)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, C [auth E]	PF04253	Transferrin receptor-like dimerisation domain (TFR_dimer)	Transferrin receptor-like dimerisation domain	This domain is involved in dimerisation of the transferrin receptor as shown in its crystal structure.	Domain
A, B, C [auth E]	PF04389	Peptidase family M28 (Peptidase_M28)	Peptidase family M28	-	Family
A, B, C [auth E]	PF02225	PA domain (PA)	PA domain	-	Family

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C [auth E]	Transferrin receptor protein 1	RNA binding double-stranded RNA binding binding organic cyclic compound binding nucleic acid binding transferrin receptor activity cargo receptor activity protein-containing complex binding identical protein binding protein binding virus receptor activity exogenous protein binding Hsp70 protein binding protein-folding chaperone binding RNA binding double-stranded RNA binding binding organic cyclic compound binding nucleic acid binding transferrin receptor activity cargo receptor activity protein-containing complex binding identical protein binding protein binding virus receptor activity exogenous protein binding Hsp70 protein binding protein-folding chaperone binding heat shock protein binding protein homodimerization activity protein dimerization activity kinase binding enzyme binding protein kinase binding	intracellular iron ion homeostasis inorganic ion homeostasis cellular homeostasis chemical homeostasis homeostatic process intracellular monoatomic cation homeostasis monoatomic ion homeostasis intracellular chemical homeostasis monoatomic cation homeostasis intracellular monoatomic ion homeostasis adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains response to stimulus regulation of leukocyte activation regulation of cell activation intracellular iron ion homeostasis inorganic ion homeostasis cellular homeostasis chemical homeostasis homeostatic process intracellular monoatomic cation homeostasis monoatomic ion homeostasis intracellular chemical homeostasis monoatomic cation homeostasis intracellular monoatomic ion homeostasis adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains response to stimulus regulation of leukocyte activation regulation of cell activation B cell activation involved in immune response positive regulation of macromolecule biosynthetic process regulation of primary metabolic process multicellular organism development positive regulation of immune response regulation of immune system process positive regulation of macromolecule metabolic process system development positive regulation of DNA recombination positive regulation of immunoglobulin mediated immune response immune response DNA recombination primary metabolic process DNA metabolic process immune effector process regulation of gene expression biosynthetic process positive regulation of DNA metabolic process regulation of response to stimulus B cell mediated immunity positive regulation of production of molecular mediator of immune response regulation of macromolecule biosynthetic process metabolic process regulation of DNA metabolic process immunoglobulin production regulation of developmental process positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains somatic cell DNA recombination positive regulation of lymphocyte activation somatic diversification of immunoglobulins involved in immune response somatic recombination of immunoglobulin gene segments positive regulation of biosynthetic process regulation of immunoglobulin mediated immune response positive regulation of isotype switching regulation of B cell activation leukocyte activation involved in immune response positive regulation of immune effector process positive regulation of cellular process positive regulation of immunoglobulin production production of molecular mediator of immune response regulation of isotype switching cell activation regulation of macromolecule metabolic process macromolecule biosynthetic process nucleic acid metabolic process positive regulation of gene expression immune system process somatic diversification of immune receptors via germline recombination within a single locus cellular process regulation of lymphocyte activation multicellular organismal process regulation of immune effector process lymphocyte mediated immunity regulation of DNA recombination positive regulation of leukocyte mediated immunity regulation of cellular process cell activation involved in immune response positive regulation of developmental process nucleobase-containing compound metabolic process positive regulation of cell activation positive regulation of metabolic process positive regulation of leukocyte activation anatomical structure development leukocyte mediated immunity somatic diversification of immune receptors regulation of nucleobase-containing compound metabolic process positive regulation of adaptive immune response positive regulation of immune system process somatic recombination of immunoglobulin genes involved in immune response developmental process regulation of biological process positive regulation of nucleobase-containing compound metabolic process regulation of adaptive immune response regulation of B cell mediated immunity somatic diversification of immunoglobulins regulation of leukocyte mediated immunity positive regulation of multicellular organismal process regulation of immune response regulation of production of molecular mediator of immune response macromolecule metabolic process regulation of metabolic process isotype switching immune system development immunoglobulin production involved in immunoglobulin-mediated immune response positive regulation of lymphocyte mediated immunity positive regulation of biological process lymphocyte activation positive regulation of B cell mediated immunity leukocyte activation positive regulation of response to stimulus regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains regulation of multicellular organismal process lymphocyte activation involved in immune response regulation of biosynthetic process B cell activation biological regulation gene expression positive regulation of B cell activation adaptive immune response immunoglobulin mediated immune response regulation of immunoglobulin production regulation of lymphocyte mediated immunity regulation of postsynaptic membrane neurotransmitter receptor levels regulation of biological quality localization import into cell receptor internalization transport receptor-mediated endocytosis endocytosis establishment of localization vesicle-mediated transport regulation of cellular component organization negative regulation of mitochondrial fusion negative regulation of biological process cellular component organization negative regulation of cellular process regulation of mitochondrial fusion cellular component organization or biogenesis mitochondrial fusion regulation of anatomical structure morphogenesis mitochondrion organization negative regulation of cellular component organization negative regulation of developmental process regulation of organelle organization organelle fusion anatomical structure morphogenesis organelle organization negative regulation of organelle organization regulation of mitochondrion organization positive regulation of cellular component organization protein-containing complex organization positive regulation of cellular component biogenesis regulation of cellular component biogenesis cellular component biogenesis positive regulation of protein-containing complex assembly regulation of protein-containing complex assembly cellular component assembly protein-containing complex assembly multicellular organismal-level iron ion homeostasis multicellular organismal-level homeostasis multicellular organismal-level chemical homeostasis positive regulation of phosphorylation regulation of protein modification process regulation of protein phosphorylation positive regulation of protein metabolic process regulation of peptidyl-serine phosphorylation positive regulation of phosphate metabolic process peptidyl-serine modification positive regulation of protein modification process peptidyl-serine phosphorylation regulation of phosphate metabolic process phosphate-containing compound metabolic process peptidyl-amino acid modification protein metabolic process positive regulation of protein phosphorylation phosphorus metabolic process protein modification process protein phosphorylation positive regulation of phosphorus metabolic process phosphorylation regulation of protein metabolic process positive regulation of peptidyl-serine phosphorylation macromolecule modification regulation of phosphorus metabolic process regulation of phosphorylation response to metal ion response to iron ion response to chemical positive regulation of DNA-binding transcription factor activity positive regulation of NF-kappaB transcription factor activity RNA metabolic process RNA biosynthetic process positive regulation of molecular function nucleic acid biosynthetic process DNA-templated transcription regulation of RNA metabolic process regulation of RNA biosynthetic process nucleobase-containing compound biosynthetic process regulation of molecular function regulation of DNA-binding transcription factor activity regulation of DNA-templated transcription acute-phase response defense response response to stress inflammatory response acute inflammatory response response to decreased oxygen levels response to hypoxia response to oxygen levels response to abiotic stimulus regulation of bone remodeling tissue homeostasis regulation of tissue remodeling regulation of bone resorption bone resorption tissue remodeling bone remodeling anatomical structure homeostasis positive regulation of bone resorption cellular response to stimulus cellular response to chemical stimulus cellular response to xenobiotic stimulus response to xenobiotic stimulus positive regulation of cell population proliferation positive regulation of B cell proliferation leukocyte proliferation regulation of B cell proliferation lymphocyte proliferation positive regulation of mononuclear cell proliferation regulation of lymphocyte proliferation regulation of leukocyte proliferation cell population proliferation positive regulation of lymphocyte proliferation B cell proliferation regulation of cell population proliferation mononuclear cell proliferation positive regulation of leukocyte proliferation regulation of mononuclear cell proliferation system process circulatory system process vascular process in circulatory system vascular transport transport across blood-brain barrier T cell activation positive regulation of T cell activation positive regulation of T cell proliferation regulation of leukocyte cell-cell adhesion positive regulation of leukocyte cell-cell adhesion leukocyte cell-cell adhesion positive regulation of cell-cell adhesion cell adhesion cell-cell adhesion regulation of cell-cell adhesion T cell proliferation positive regulation of cell adhesion regulation of cell adhesion regulation of T cell activation regulation of T cell proliferation protein localization establishment of protein localization cellular localization nitrogen compound transport iron ion transport metal ion transport protein transport cellular macromolecule localization macromolecule localization transferrin transport transition metal ion transport monoatomic ion transport monoatomic cation transport positive regulation of cell communication positive regulation of signal transduction positive regulation of canonical NF-kappaB signal transduction signaling regulation of signal transduction intracellular signal transduction cell communication regulation of intracellular signal transduction intracellular signaling cassette signal transduction regulation of signaling positive regulation of intracellular signal transduction canonical NF-kappaB signal transduction regulation of cell communication regulation of canonical NF-kappaB signal transduction positive regulation of signaling regulation of localization regulation of protein localization positive regulation of protein localization to nucleus regulation of protein localization to nucleus protein localization to nucleus regulation of cellular localization protein localization to organelle positive regulation of protein localization response to copper ion response to manganese ion negative regulation of programmed cell death regulation of apoptotic process regulation of programmed cell death cell death negative regulation of apoptotic process apoptotic process programmed cell death response to retinoic acid response to lipid response to oxygen-containing compound myeloid leukocyte differentiation cellular developmental process hemopoiesis cell development myeloid cell differentiation cell differentiation osteoclast differentiation leukocyte differentiation response to nutrient levels response to nutrient response to peptide response to cytokine response to leukemia inhibitory factor cellular response to cytokine stimulus cellular response to leukemia inhibitory factor	cell periphery cellular anatomical structure cell surface membrane plasma membrane external side of plasma membrane side of membrane clathrin-coated pit endomembrane system membrane-bounded organelle intracellular anatomical structure intracellular vesicle intracellular organelle bounding membrane of organelle cell periphery cellular anatomical structure cell surface membrane plasma membrane external side of plasma membrane side of membrane clathrin-coated pit endomembrane system membrane-bounded organelle intracellular anatomical structure intracellular vesicle intracellular organelle bounding membrane of organelle cytoplasmic vesicle vesicle membrane clathrin-coated vesicle endocytic vesicle membrane coated vesicle vesicle endocytic vesicle clathrin-coated vesicle membrane clathrin-coated endocytic vesicle membrane intracellular membrane-bounded organelle clathrin-coated endocytic vesicle cytoplasmic vesicle membrane coated vesicle membrane organelle cytoplasm organelle membrane extracellular exosome extracellular vesicle extracellular organelle extracellular region extracellular space extracellular membrane-bounded organelle protein-containing complex plasma membrane protein complex plasma membrane signaling receptor complex membrane protein complex HFE-transferrin receptor complex receptor complex basal part of cell basal plasma membrane plasma membrane region basolateral plasma membrane synapse cell junction glutamatergic synapse endosome recycling endosome endosome membrane postsynaptic recycling endosome postsynaptic endosome postsynapse postsynaptic recycling endosome membrane postsynaptic endosome membrane perinuclear region of cytoplasm pigment granule melanosome early endosome blood microparticle recycling endosome membrane
D, E [auth C], F	Computationally designed protein 3DS18	-	-	-

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C [auth E]	IPR036757	Transferrin receptor-like, dimerisation domain superfamily	Homologous Superfamily
A, B, C [auth E]	IPR039373	Transferrin receptor protein 1/Glutamate carboxypeptidase 2-like	Family
A, B, C [auth E]	IPR003137	PA domain	Domain
A, B, C [auth E]	IPR046450	PA domain superfamily	Homologous Superfamily
A, B, C [auth E]	IPR007365	Transferrin receptor-like, dimerisation domain	Domain
A, B, C [auth E]	IPR037324	Transferrin receptor protein 1/2, PA domain	Domain
A, B, C [auth E]	IPR007484	Peptidase M28	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, C [auth E]	Pharos: P02786	B-cell chronic lymphocytic leukemia malignant glioma iron deficiency anemia TFRC-related combined immunodeficiency polycystic ovary syndrome beta thalassemia severe combined immunodeficiency breast cancer urinary bladder cancer mixed glioma Myocardial Reperfusion Injury obesity disorder breast carcinoma colorectal cancer iron metabolism disease B-cell chronic lymphocytic leukemia malignant glioma iron deficiency anemia TFRC-related combined immunodeficiency polycystic ovary syndrome beta thalassemia severe combined immunodeficiency breast cancer urinary bladder cancer mixed glioma Myocardial Reperfusion Injury obesity disorder breast carcinoma colorectal cancer iron metabolism disease ulcerative colitis MHC class II deficiency Duchenne muscular dystrophy myocardial ischemia gastric carcinoma nasopharyngeal carcinoma Helicobacter pylori infectious disease non-small cell lung carcinoma ovarian cancer anemia invasive ductal breast carcinoma pilocytic astrocytoma asthma large cell medulloblastoma progressive supranuclear palsy lung carcinoma reticulum cell sarcoma thalassemia minor coronary artery disease ductal breast carcinoma in situ glioma hereditary hemochromatosis pancreatic intraductal papillary-mucinous neoplasm plasma cell myeloma astrocytic tumor psoriasis lymphoplasmacytic lymphoma type 2 diabetes mellitus congestive heart failure urinary bladder neoplasm mucopolysaccharidosis type 2 esophageal adenocarcinoma myopathy non-Hodgkin lymphoma hereditary persistence of fetal hemoglobin Omenn syndrome Alzheimer disease Pick disease Arenaviridae infectious disease atypical teratoid rhabdoid tumor lung benign neoplasm cancer lymphosarcoma colorectal carcinoma

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.