4D9R

Inhibiting Alternative Pathway Complement Activation by Targeting the Exosite on Factor D

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
IMGT Antibody Annotation
SAbDab Antibody Annotation
Thera-SAbDab Antibody Annotation
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
D [auth B]	d4d9rb_	All beta proteins	Trypsin-like serine proteases	Trypsin-like serine proteases	Eukaryotic proteases	Factor D	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d4d9ra_	All beta proteins	Trypsin-like serine proteases	Trypsin-like serine proteases	Eukaryotic proteases	Factor D	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B [auth L]	d4d9rl2	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	C1 set domains (antibody constant domain-like)	Immunoglobulin light chain kappa constant domain, CL-kappa	human (Homo sapiens ) [TaxId: 9606 ], human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B [auth L]	d4d9rl1	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	automated matches	automated matches	human (Homo sapiens ) [TaxId: 9606 ], human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
F [auth D]	d4d9rd2	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	C1 set domains (antibody constant domain-like)	Immunoglobulin light chain kappa constant domain, CL-kappa	human (Homo sapiens ) [TaxId: 9606 ], human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
F [auth D]	d4d9rd1	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	automated matches	automated matches	human (Homo sapiens ) [TaxId: 9606 ], human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C [auth H]	d4d9rh_	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	automated matches	automated matches	human (Homo sapiens ) [TaxId: 9606 ], human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
E	d4d9re_	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	automated matches	automated matches	human (Homo sapiens ) [TaxId: 9606 ], human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
D [auth B]	SCOP2B Superfamily	Trypsin-like serine proteases	8042234	3000114	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	Trypsin-like serine proteases	8042234	3000114	SCOP2B (2022-06-29)
B [auth L]	SCOP2B Superfamily	Immunoglobulin (Ig) domain-like	8091527	3000071	SCOP2B (2022-06-29)
F [auth D]	SCOP2B Superfamily	Immunoglobulin (Ig) domain-like	8091527	3000071	SCOP2B (2022-06-29)
C [auth H]	SCOP2B Superfamily	Immunoglobulin (Ig) domain-like	8091519	3000071	SCOP2B (2022-06-29)
E	SCOP2B Superfamily	Immunoglobulin (Ig) domain-like	8091519	3000071	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)
D [auth B]	Trypsin_1	e4d9rB1	A: beta barrels	X: cradle loop barrel	H: RIFT-related	T: FMN-binding split barrel 2	F: Trypsin_1	ECOD (1.6)
A	Trypsin_1	e4d9rA1	A: beta barrels	X: cradle loop barrel	H: RIFT-related	T: FMN-binding split barrel 2	F: Trypsin_1	ECOD (1.6)
B [auth L]	C1-set_4	e4d9rL2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: C1-set_4	ECOD (1.6)
B [auth L]	V-set	e4d9rL1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: V-set	ECOD (1.6)
F [auth D]	C1-set_4	e4d9rD2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: C1-set_4	ECOD (1.6)
F [auth D]	V-set	e4d9rD1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: V-set	ECOD (1.6)
C [auth H]	V-set_8	e4d9rH1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: V-set_8	ECOD (1.6)
C [auth H]	C1-set_1	e4d9rH2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: C1-set_1	ECOD (1.6)
E	V-set_8	e4d9rE1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: V-set_8	ECOD (1.6)
E	C1-set_1	e4d9rE2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: C1-set_1	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
D [auth B]	2.40.10.10	Mainly Beta	Beta Barrel	Thrombin, subunit H	Trypsin-like serine proteases	CATH (4.3.0)
A	2.40.10.10	Mainly Beta	Beta Barrel	Thrombin, subunit H	Trypsin-like serine proteases	CATH (4.3.0)
B [auth L]	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (4.3.0)
F [auth D]	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (4.3.0)
C [auth H]	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (4.3.0)
E	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (4.3.0)

IMGT Antibody Annotation IMGT Database Homepage

Chain	Protein Name	Description	Organism Name	Gene Allele Name(s)	Domain Name(s)	Receptor Type	Receptor Description	Provenance Source
B [auth L], F [auth D]	Antibody Fab Fragment	L-KAPPA	Homo sapiens (human)	IGKV1-2701, IGKV1-3301, IGKV1D-3301, IGKV1-3901, IGKV1D-3901, IGKJ101, IGKJ201, IGKC01	V-DOMAIN V-KAPPA, C-DOMAIN C-KAPPA	IG	FAB-GAMMA-1_KAPPA	IMGT (202452-0)
C [auth H], E	Antibody Fab Fragment	VH-CH1	Homo sapiens (human)	IGHV7-4-102, IGHJ401, IGHJ502, IGHJ402, IGHJ403, IGHG101, IGHG102, IGHG104	V-DOMAIN VH, C-DOMAIN CH1	IG	FAB-GAMMA-1_KAPPA	IMGT (202452-0)

SAbDab Antibody Annotation SAbDab Database Homepage

Chain	Chain Class	Chain Subclass	Chain Type	Antigen Name(s)	Provenance Source
B [auth L], F [auth D]	Light Chain	IGKV1	Kappa	complement factor d	SAbDab (2025-01-03)
C [auth H], E	Heavy Chain	IGHV7	-	complement factor d	SAbDab (2025-01-03)

Thera-SAbDab Antibody Annotation Thera-SAbDab Database Homepage

Chain	Name	Target	Provenance Source
B [auth L], F [auth D]	Lampalizumab	CFD	Therapeutic SAbDab (2025-01-03)
C [auth H], E	Lampalizumab	CFD	Therapeutic SAbDab (2025-01-03)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, D [auth B]	PF00089	Trypsin (Trypsin)	Trypsin	-	Domain
B [auth L], F [auth D]	PF07654	Immunoglobulin C1-set domain (C1-set)	Immunoglobulin C1-set domain	-	Domain
C [auth H], E	PF07654	Immunoglobulin C1-set domain (C1-set)	Immunoglobulin C1-set domain	-	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, D [auth B]	Complement factor D	peptidase activity catalytic activity, acting on a protein serine hydrolase activity serine-type peptidase activity hydrolase activity serine-type endopeptidase activity catalytic activity endopeptidase activity	biological process involved in interspecies interaction between organisms response to stimulus response to other organism response to bacterium response to external stimulus response to external biotic stimulus response to biotic stimulus humoral immune response positive regulation of biological process complement activation, alternative pathway positive regulation of response to stimulus complement activation positive regulation of immune response response to stress biological process involved in interspecies interaction between organisms response to stimulus response to other organism response to bacterium response to external stimulus response to external biotic stimulus response to biotic stimulus humoral immune response positive regulation of biological process complement activation, alternative pathway positive regulation of response to stimulus complement activation positive regulation of immune response response to stress innate immune response regulation of immune system process positive regulation of immune system process regulation of biological process immune response defense response biological regulation defense response to symbiont immune effector process regulation of response to stimulus immune system process defense response to other organism regulation of immune response activation of immune response proteolysis metabolic process cellular process primary metabolic process protein metabolic process macromolecule metabolic process	cellular anatomical structure extracellular region extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle organelle extracellular space vesicle extracellular membrane-bounded organelle vesicle lumen intracellular anatomical structure intracellular vesicle membrane-enclosed lumen cellular anatomical structure extracellular region extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle organelle extracellular space vesicle extracellular membrane-bounded organelle vesicle lumen intracellular anatomical structure intracellular vesicle membrane-enclosed lumen cytoplasmic vesicle lumen secretory granule lumen intracellular membrane-bounded organelle endomembrane system intracellular organelle lumen intracellular organelle cytoplasmic vesicle organelle lumen secretory granule secretory vesicle cytoplasm platelet alpha granule platelet alpha granule lumen ficolin-1-rich granule ficolin-1-rich granule lumen
B [auth L], F [auth D]	Fab light chain	binding antigen binding	adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains lymphocyte mediated immunity response to stimulus immune response immune system process B cell mediated immunity leukocyte mediated immunity immunoglobulin mediated immune response adaptive immune response immune effector process cellular response to stimulus immune response-regulating cell surface receptor signaling pathway regulation of cellular process signaling adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains lymphocyte mediated immunity response to stimulus immune response immune system process B cell mediated immunity leukocyte mediated immunity immunoglobulin mediated immune response adaptive immune response immune effector process cellular response to stimulus immune response-regulating cell surface receptor signaling pathway regulation of cellular process signaling positive regulation of biological process cell communication positive regulation of response to stimulus immune response-activating signaling pathway immune response-regulating signaling pathway positive regulation of immune response regulation of immune system process signal transduction positive regulation of immune system process regulation of biological process cell surface receptor signaling pathway immune response-activating cell surface receptor signaling pathway B cell receptor signaling pathway biological regulation regulation of response to stimulus regulation of immune response cellular process antigen receptor-mediated signaling pathway activation of immune response	protein-containing complex IgA immunoglobulin complex immunoglobulin complex cellular anatomical structure extracellular region extracellular space blood microparticle IgM immunoglobulin complex IgE immunoglobulin complex IgD immunoglobulin complex extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle protein-containing complex IgA immunoglobulin complex immunoglobulin complex cellular anatomical structure extracellular region extracellular space blood microparticle IgM immunoglobulin complex IgE immunoglobulin complex IgD immunoglobulin complex extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle organelle vesicle extracellular membrane-bounded organelle cell periphery plasma membrane membrane IgG immunoglobulin complex
C [auth H], E	Fab heavy chain	protein-containing complex binding protein binding binding signaling receptor binding immunoglobulin receptor binding Fc-gamma receptor I complex binding antigen binding	adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains lymphocyte mediated immunity response to stimulus myeloid leukocyte mediated immunity inflammatory response to antigenic stimulus response to stress leukocyte mediated immunity antibody-dependent cellular cytotoxicity acute inflammatory response hypersensitivity defense response immune response leukocyte mediated cytotoxicity acute inflammatory response to antigenic stimulus adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains lymphocyte mediated immunity response to stimulus myeloid leukocyte mediated immunity inflammatory response to antigenic stimulus response to stress leukocyte mediated immunity antibody-dependent cellular cytotoxicity acute inflammatory response hypersensitivity defense response immune response leukocyte mediated cytotoxicity acute inflammatory response to antigenic stimulus immunoglobulin mediated immune response adaptive immune response immune effector process type II hypersensitivity immune system process type IIa hypersensitivity B cell mediated immunity cellular process inflammatory response cell killing cellular response to stimulus immune response-regulating cell surface receptor signaling pathway regulation of cellular process signaling positive regulation of biological process cell communication positive regulation of response to stimulus immune response-activating signaling pathway immune response-regulating signaling pathway positive regulation of immune response regulation of immune system process signal transduction positive regulation of immune system process regulation of biological process cell surface receptor signaling pathway immune response-activating cell surface receptor signaling pathway B cell receptor signaling pathway biological regulation regulation of response to stimulus regulation of immune response antigen receptor-mediated signaling pathway activation of immune response humoral immune response complement activation humoral immune response mediated by circulating immunoglobulin complement activation, classical pathway complement-dependent cytotoxicity biological process involved in interspecies interaction between organisms response to other organism antibacterial humoral response defense response to symbiont response to external stimulus antimicrobial humoral response response to biotic stimulus defense response to bacterium defense response to other organism response to bacterium response to external biotic stimulus	cellular anatomical structure extracellular region extracellular space blood microparticle protein-containing complex immunoglobulin complex, circulating immunoglobulin complex extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle organelle vesicle extracellular membrane-bounded organelle cellular anatomical structure extracellular region extracellular space blood microparticle protein-containing complex immunoglobulin complex, circulating immunoglobulin complex extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle organelle vesicle extracellular membrane-bounded organelle cell periphery plasma membrane membrane IgG immunoglobulin complex

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, D [auth B]	IPR009003	Peptidase S1, PA clan	Homologous Superfamily
A, D [auth B]	IPR001314	Peptidase S1A, chymotrypsin family	Family
A, D [auth B]	IPR033116	Serine proteases, trypsin family, serine active site	Active Site
A, D [auth B]	IPR001254	Serine proteases, trypsin domain	Domain
A, D [auth B]	IPR043504	Peptidase S1, PA clan, chymotrypsin-like fold	Homologous Superfamily
A, D [auth B]	IPR018114	Serine proteases, trypsin family, histidine active site	Active Site
B [auth L], F [auth D]	IPR036179	Immunoglobulin-like domain superfamily	Homologous Superfamily
B [auth L], F [auth D]	IPR050160	Major Histocompatibility Complex/Immunoglobulin	Family
B [auth L], F [auth D]	IPR003597	Immunoglobulin C1-set	Domain
B [auth L], F [auth D]	IPR013783	Immunoglobulin-like fold	Homologous Superfamily
B [auth L], F [auth D]	IPR007110	Immunoglobulin-like domain	Domain
B [auth L], F [auth D]	IPR003006	Immunoglobulin/major histocompatibility complex, conserved site	Conserved Site
C [auth H], E	IPR036179	Immunoglobulin-like domain superfamily	Homologous Superfamily
C [auth H], E	IPR050380	Immune Recognition and Response Modulators	Family
C [auth H], E	IPR003597	Immunoglobulin C1-set	Domain
C [auth H], E	IPR013783	Immunoglobulin-like fold	Homologous Superfamily
C [auth H], E	IPR007110	Immunoglobulin-like domain	Domain
C [auth H], E	IPR003006	Immunoglobulin/major histocompatibility complex, conserved site	Conserved Site

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, D [auth B]	Pharos: P00746	recurrent Neisseria infections due to factor D deficiency glomerulonephritis meningococcal infection endometriosis Neisseriaceae Infections congestive heart failure pulmonary fibrosis asbestosis primary immunodeficiency disease idiopathic interstitial pneumonia limb-girdle muscular dystrophy lung cancer malignant mesothelioma adrenal cortex carcinoma atopic eczema recurrent Neisseria infections due to factor D deficiency glomerulonephritis meningococcal infection endometriosis Neisseriaceae Infections congestive heart failure pulmonary fibrosis asbestosis primary immunodeficiency disease idiopathic interstitial pneumonia limb-girdle muscular dystrophy lung cancer malignant mesothelioma adrenal cortex carcinoma atopic eczema ovarian cyst breast carcinoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia psoriasis ductal breast carcinoma in situ heart failure invasive ductal breast carcinoma lung carcinoma non-small cell lung carcinoma B-cell chronic lymphocytic leukemia breast fibroadenoma primary biliary cholangitis corpus luteum cyst Sjogren syndrome lung adenocarcinoma malignant colon neoplasm ovarian cancer breast cancer pancreatic intraductal papillary-mucinous carcinoma Duchenne muscular dystrophy tuberculosis
B [auth L], F [auth D]	Pharos: P01834	recurrent infections associated with rare immunoglobulin isotypes deficiency myositis dysgammaglobulinemia Hepatomegaly acquired idiopathic inflammatory myopathy selective IgG immunodeficiency
C [auth H], E	Pharos: P01857	B-cell chronic lymphocytic leukemia myositis polycystic ovary syndrome plasma cell myeloma plasma cell neoplasm Sclerocystic Ovaries acquired idiopathic inflammatory myopathy lung adenocarcinoma ovarian cancer peripheral neuropathy Sjogren syndrome amyloidosis breast cancer medulloblastoma nasopharyngeal carcinoma B-cell chronic lymphocytic leukemia myositis polycystic ovary syndrome plasma cell myeloma plasma cell neoplasm Sclerocystic Ovaries acquired idiopathic inflammatory myopathy lung adenocarcinoma ovarian cancer peripheral neuropathy Sjogren syndrome amyloidosis breast cancer medulloblastoma nasopharyngeal carcinoma periodontitis interstitial cystitis myeloid neoplasm osteosarcoma peripheral nervous system disease

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.