5FOA

Crystal Structure of Human Complement C3b in complex with DAF (CCP2-4)

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	Terpenoid cyclases/Protein prenyltransferases	8038414	3001024	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	Terpenoid cyclases/Protein prenyltransferases	8038414	3001024	SCOP2B (2022-06-29)
E	SCOP2B Superfamily	Sushi/CCP/SCR domain	8044483	3000902	SCOP2B (2022-06-29)
E	SCOP2B Superfamily	Sushi/CCP/SCR domain	8044485	3000902	SCOP2B (2022-06-29)
F	SCOP2B Superfamily	Sushi/CCP/SCR domain	8044485	3000902	SCOP2B (2022-06-29)
F	SCOP2B Superfamily	Sushi/CCP/SCR domain	8044483	3000902	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	A2M_N_1	e5foaA6	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: A2M_N_1	ECOD (1.6)
A	KOG1366_2nd_1	e5foaA1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: KOG1366_2nd_1	ECOD (1.6)
A	MG4	e5foaA2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: MG4	ECOD (1.6)
A	KOG1366_1st	e5foaA5	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: KOG1366_1st	ECOD (1.6)
A	ANATO	e5foaA4	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: ANATO	ECOD (1.6)
A	A2M_N_2	e5foaA3	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: A2M_N_2	ECOD (1.6)
C	A2M_N_1	e5foaC4	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: A2M_N_1	ECOD (1.6)
C	KOG1366_2nd_1	e5foaC2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: KOG1366_2nd_1	ECOD (1.6)
C	MG4	e5foaC1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: MG4	ECOD (1.6)
C	KOG1366_1st	e5foaC6	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: KOG1366_1st	ECOD (1.6)
C	ANATO	e5foaC5	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: ANATO	ECOD (1.6)
C	A2M_N_2	e5foaC3	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: A2M_N_2	ECOD (1.6)
B	NTR	e5foaB5	A: beta barrels	X: OB-fold	H: TIMP-like (From Topology)	T: TIMP-like	F: NTR	ECOD (1.6)
B	EUF07663	e5foaB2	A: beta sandwiches	X: jelly-roll	H: Spermadhesin, CUB domain (From Topology)	T: Spermadhesin, CUB domain	F: EUF07663	ECOD (1.6)
B	A2M_C	e5foaB4	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: A2M_C	ECOD (1.6)
B	A2M_N	e5foaB1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: A2M_N	ECOD (1.6)
B	A2M_recep	e5foaB6	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Common fold of diphtheria toxin/transcription factors/cytochrome f	F: A2M_recep	ECOD (1.6)
B	A2M_comp_2	e5foaB3	A: alpha superhelices	X: Repetitive alpha hairpins	H: alpha/alpha toroid (From Topology)	T: alpha/alpha toroid	F: A2M_comp_2	ECOD (1.6)
D	NTR	e5foaD6	A: beta barrels	X: OB-fold	H: TIMP-like (From Topology)	T: TIMP-like	F: NTR	ECOD (1.6)
D	EUF07663	e5foaD1	A: beta sandwiches	X: jelly-roll	H: Spermadhesin, CUB domain (From Topology)	T: Spermadhesin, CUB domain	F: EUF07663	ECOD (1.6)
D	A2M_C	e5foaD5	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: A2M_C	ECOD (1.6)
D	A2M_N	e5foaD4	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: A2M_N	ECOD (1.6)
D	A2M_recep	e5foaD2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Common fold of diphtheria toxin/transcription factors/cytochrome f	F: A2M_recep	ECOD (1.6)
D	A2M_comp_2	e5foaD3	A: alpha superhelices	X: Repetitive alpha hairpins	H: alpha/alpha toroid (From Topology)	T: alpha/alpha toroid	F: A2M_comp_2	ECOD (1.6)
E	Sushi_4	e5foaE3	A: few secondary structure elements	X: EGF-like	H: EGF-related	T: Complement control module/SCR domain	F: Sushi_4	ECOD (1.6)
E	Sushi_3	e5foaE2	A: few secondary structure elements	X: EGF-like	H: EGF-related	T: Complement control module/SCR domain	F: Sushi_3	ECOD (1.6)
E	Sushi_1	e5foaE1	A: few secondary structure elements	X: EGF-like	H: EGF-related	T: Complement control module/SCR domain	F: Sushi_1	ECOD (1.6)
F	Sushi_4	e5foaF3	A: few secondary structure elements	X: EGF-like	H: EGF-related	T: Complement control module/SCR domain	F: Sushi_4	ECOD (1.6)
F	Sushi_3	e5foaF1	A: few secondary structure elements	X: EGF-like	H: EGF-related	T: Complement control module/SCR domain	F: Sushi_3	ECOD (1.6)
F	Sushi_1	e5foaF2	A: few secondary structure elements	X: EGF-like	H: EGF-related	T: Complement control module/SCR domain	F: Sushi_1	ECOD (1.6)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, C	PF17790	Macroglobulin domain MG1 (MG1)	Macroglobulin domain MG1	This entry represents the N-terminal macroglobulin domain found in complement proteins C3, C4 and C5.	Domain
A, C	PF17791	Macroglobulin domain MG3 (MG3)	Macroglobulin domain MG3	This entry corresponds to the MG3 domain found in complement components C3, C4 and C5.	Domain
A, C	PF01835	MG2 domain (MG2)	MG2 domain	This is the MG2 (macroglobulin) domain of alpha-2-macroglobulin in eukaryotes [1]. Alpha-2-macroglobulins (A2Ms) are plasma proteins that trap and inhibit a broad range of proteases and are major components of the eukaryotic innate immune system. How ...	This is the MG2 (macroglobulin) domain of alpha-2-macroglobulin in eukaryotes [1]. Alpha-2-macroglobulins (A2Ms) are plasma proteins that trap and inhibit a broad range of proteases and are major components of the eukaryotic innate immune system. However, A2M-like proteins were identified in pathogenically invasive bacteria and species that colonize higher eukaryotes. This domain is found in eukaryotic and bacterial proteins. In human A2Ms, this domain is termed macroglobulin-like (MG) domain 2 and in Salmonella enterica ser A2Ms, this is domain 4 [2] [3].	Domain
A, C	PF07703	Alpha-2-macroglobulin bait region domain (A2M_BRD)	Alpha-2-macroglobulin bait region domain	Alpha-2-macroglobulins (A2Ms) are plasma proteins that trap and inhibit a broad range of proteases and are major components of the eukaryotic innate immune system. However, A2M-like proteins were identified in pathogenically invasive bacteria and spe ...	Alpha-2-macroglobulins (A2Ms) are plasma proteins that trap and inhibit a broad range of proteases and are major components of the eukaryotic innate immune system. However, A2M-like proteins were identified in pathogenically invasive bacteria and species that colonize higher eukaryotes. This domain is found in eukaryotic and bacterial proteins. In human A2Ms, this domain encompasses macroglobulin-like domain MG5 and 6 including bait region. In Salmonella enterica ser A2Ms, this domain encompasses MG7 and MG8 including the bait region [1] [2]. The Bait region is cleaved by proteases, followed by a large conformational change that blocks the target protease within a cage-like complex. This model of protease entrapment is recognised as the Venus flytrap mechanism [1].	Domain
A, C	PF17789	Macroglobulin domain MG4 (MG4)	Macroglobulin domain MG4	This domain is MG4 found in complement C3 and C5 proteins.	Domain
B, D	PF00207	Alpha-2-macroglobulin family (A2M)	Alpha-2-macroglobulin family	-	Family
B, D	PF01759	UNC-6/NTR/C345C module (NTR)	UNC-6/NTR/C345C module	Sequence similarity between netrin UNC-6 and C345C complement protein family members, and hence the existence of the UNC-6 module, was first reported in [1]. Subsequently, many additional members of the family were identified on the basis of sequence ...	Sequence similarity between netrin UNC-6 and C345C complement protein family members, and hence the existence of the UNC-6 module, was first reported in [1]. Subsequently, many additional members of the family were identified on the basis of sequence similarity between the C-terminal domains of netrins, complement proteins C3, C4, C5, secreted frizzled-related proteins, and type I pro-collagen C-proteinase enhancer proteins (PCOLCEs), which are homologous with the N-terminal domains of tissue inhibitors of metalloproteinases (TIMPs). The TIMPs are classified as a separate family in Pfam (Pfam:PF00965) [2]. This expanded domain family has been named as the NTR module [2].	Domain
B, D	PF21406	Complement component 3, CUB domain, first segment (C3_CUB1)	Complement component 3, CUB domain, first segment	This entry represents the first segment of the CUB domain from complement component C3, which is completed but a second segment represented in Pfam:PF21308. The CUB domain is interrupted by the TE domain. The CUB domain forms a massive, tightly packe ...	This entry represents the first segment of the CUB domain from complement component C3, which is completed but a second segment represented in Pfam:PF21308. The CUB domain is interrupted by the TE domain. The CUB domain forms a massive, tightly packed super domain with the TE and MG8 domains [1-5]. These entry also includes venom factors, also known as Complement C3 homologues. These are complement-activating proteins with structural and functional similarities to complement component C3b, the activated form of C3 [6].	Domain
B, D	PF07678	A-macroglobulin TED domain (TED_complement)	A-macroglobulin TED domain	-	Repeat
B, D	PF07677	A-macroglobulin receptor binding domain (A2M_recep)	A-macroglobulin receptor binding domain	This family includes the receptor binding domain region of the alpha-2-macroglobulin family.	Domain
B, D	PF21308	Complement component 3, CUB domain, second segment (C3_CUB2)	Complement component 3, CUB domain, second segment	Complement C3 is major component in the both the classical and alternative complement activation pathways. C3 is cleaved into two chains (alpha and beta) by C3 convertases. This entry represents the second segment of the CUB domain, which is complete ...	Complement C3 is major component in the both the classical and alternative complement activation pathways. C3 is cleaved into two chains (alpha and beta) by C3 convertases. This entry represents the second segment of the CUB domain, which is completed by Pfam:PF21406 [2]. The CUB domain is interrupted by the TE domain. The CUB, TE and MG8 domains form a massive, tightly packed super domain. This entry also includes venom factors, also known as Complement C3 homologues. These are complement-activating proteins with structural and functional similarities to complement component C3b, the activated form of C3 [6].	Domain
E, F	PF00084	Sushi repeat (SCR repeat) (Sushi)	Sushi repeat (SCR repeat)	-	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, C	COMPLEMENT C3 BETA CHAIN	enzyme regulator activity molecular function inhibitor activity peptidase regulator activity molecular function regulator activity enzyme inhibitor activity peptidase inhibitor activity endopeptidase regulator activity endopeptidase inhibitor activity C5L2 anaphylatoxin chemotactic receptor binding protein binding binding signaling receptor binding G protein-coupled receptor binding C5a anaphylatoxin chemotactic receptor binding enzyme regulator activity molecular function inhibitor activity peptidase regulator activity molecular function regulator activity enzyme inhibitor activity peptidase inhibitor activity endopeptidase regulator activity endopeptidase inhibitor activity C5L2 anaphylatoxin chemotactic receptor binding protein binding binding signaling receptor binding G protein-coupled receptor binding C5a anaphylatoxin chemotactic receptor binding molecular function activator activity signaling receptor regulator activity receptor ligand activity signaling receptor activator activity	cellular response to stimulus positive regulation of cell communication regulation of biological process regulation of signaling regulation of cellular process positive regulation of signal transduction response to stimulus signaling biological regulation positive regulation of biological process regulation of signal transduction positive regulation of G protein-coupled receptor signaling pathway cell communication positive regulation of response to stimulus regulation of response to stimulus cellular response to stimulus positive regulation of cell communication regulation of biological process regulation of signaling regulation of cellular process positive regulation of signal transduction response to stimulus signaling biological regulation positive regulation of biological process regulation of signal transduction positive regulation of G protein-coupled receptor signaling pathway cell communication positive regulation of response to stimulus regulation of response to stimulus regulation of cell communication G protein-coupled receptor signaling pathway cellular process signal transduction regulation of G protein-coupled receptor signaling pathway positive regulation of cellular process positive regulation of signaling neutral lipid metabolic process neutral lipid biosynthetic process regulation of triglyceride metabolic process cellular biosynthetic process regulation of lipid metabolic process lipid biosynthetic process regulation of primary metabolic process acylglycerol biosynthetic process triglyceride metabolic process triglyceride biosynthetic process regulation of biosynthetic process cellular metabolic process regulation of triglyceride biosynthetic process primary metabolic process regulation of cellular metabolic process regulation of cellular biosynthetic process biosynthetic process glycerolipid biosynthetic process cellular lipid metabolic process metabolic process glycerolipid metabolic process regulation of lipid biosynthetic process acylglycerol metabolic process regulation of metabolic process lipid metabolic process adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains lymphocyte mediated immunity humoral immune response complement activation humoral immune response mediated by circulating immunoglobulin positive regulation of immune response leukocyte mediated immunity regulation of immune system process positive regulation of immune system process complement activation, classical pathway immune response immunoglobulin mediated immune response adaptive immune response immune effector process immune system process B cell mediated immunity regulation of immune response activation of immune response developmental process multicellular organismal process cellular developmental process cell development developmental maturation nervous system development generation of neurons neurogenesis multicellular organism development neuron differentiation neuron remodeling anatomical structure maturation cell differentiation neuron development anatomical structure development neuron maturation cell maturation system development B cell activation cell activation lymphocyte activation leukocyte activation regulation of humoral immune response regulation of immune effector process positive regulation of humoral immune response positive regulation of complement activation positive regulation of immune effector process activation of membrane attack complex positive regulation of activation of membrane attack complex regulation of activation of membrane attack complex regulation of complement activation visual system development pattern specification process regionalization central nervous system development sensory system development vertebrate eye-specific patterning regulation of localization hexose transmembrane transport regulation of transport transport carbohydrate transport establishment of localization positive regulation of D-glucose transmembrane transport transmembrane transport localization regulation of transmembrane transport positive regulation of transport D-glucose transmembrane transport positive regulation of transmembrane transport regulation of D-glucose transmembrane transport monosaccharide transmembrane transport carbohydrate transmembrane transport import into cell positive regulation of cellular component organization regulation of cellular component organization vesicle-mediated transport cellular component organization positive regulation of endocytosis cellular component organization or biogenesis positive regulation of receptor-mediated endocytosis regulation of endocytosis regulation of receptor-mediated endocytosis regulation of vesicle-mediated transport endocytosis receptor-mediated endocytosis biological process involved in interspecies interaction between organisms complement activation, alternative pathway response to biotic stimulus response to stress innate immune response response to external biotic stimulus response to other organism defense response defense response to symbiont response to external stimulus defense response to other organism epithelium development oviduct development reproductive system development oviduct epithelium development tube development reproductive process developmental process involved in reproduction tissue development reproductive structure development positive regulation of cellular metabolic process positive regulation of macromolecule biosynthetic process positive regulation of metabolic process positive regulation of biosynthetic process regulation of cytokine production cytokine production regulation of multicellular organismal process positive regulation of macromolecule metabolic process regulation of vascular endothelial growth factor production regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process regulation of gene expression vascular endothelial growth factor production positive regulation of gene expression positive regulation of multicellular organismal process positive regulation of vascular endothelial growth factor production regulation of macromolecule biosynthetic process macromolecule metabolic process positive regulation of cytokine production positive regulation of cellular biosynthetic process positive regulation of membrane invagination regulation of phagocytosis, engulfment membrane invagination phagocytosis plasma membrane invagination membrane organization regulation of phagocytosis phagocytosis, engulfment positive regulation of phagocytosis positive regulation of phagocytosis, engulfment regulation of membrane invagination cellular component disassembly complement-mediated synapse pruning cell junction organization cell junction disassembly synapse pruning synapse organization immune response-regulating cell surface receptor signaling pathway complement receptor mediated signaling pathway immune response-activating signaling pathway immune response-regulating signaling pathway cell surface receptor signaling pathway immune response-activating cell surface receptor signaling pathway amyloid-beta clearance lipid storage lipid localization positive regulation of lipid localization maintenance of location regulation of lipid storage regulation of lipid localization macromolecule localization positive regulation of lipid storage fatty acid metabolic process oxoacid metabolic process carboxylic acid metabolic process organic acid metabolic process small molecule metabolic process monocarboxylic acid metabolic process positive regulation of acute inflammatory response to antigenic stimulus regulation of myeloid leukocyte mediated immunity regulation of acute inflammatory response to antigenic stimulus positive regulation of leukocyte mediated immunity regulation of type IIa hypersensitivity myeloid leukocyte mediated immunity inflammatory response to antigenic stimulus positive regulation of hypersensitivity positive regulation of inflammatory response positive regulation of adaptive immune response regulation of type II hypersensitivity positive regulation of immunoglobulin mediated immune response hypersensitivity regulation of adaptive immune response regulation of inflammatory response regulation of B cell mediated immunity regulation of leukocyte mediated immunity type II hypersensitivity positive regulation of myeloid leukocyte mediated immunity type IIa hypersensitivity positive regulation of defense response regulation of acute inflammatory response inflammatory response regulation of defense response regulation of response to external stimulus positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains positive regulation of lymphocyte mediated immunity positive regulation of acute inflammatory response positive regulation of B cell mediated immunity regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains positive regulation of response to external stimulus regulation of immunoglobulin mediated immune response regulation of response to stress acute inflammatory response regulation of hypersensitivity regulation of inflammatory response to antigenic stimulus acute inflammatory response to antigenic stimulus positive regulation of inflammatory response to antigenic stimulus positive regulation of type IIa hypersensitivity regulation of lymphocyte mediated immunity positive regulation of type II hypersensitivity regulation of developmental process angiogenesis regulation of vasculature development positive regulation of developmental process tube morphogenesis regulation of anatomical structure morphogenesis blood vessel development regulation of multicellular organismal development blood vessel morphogenesis positive regulation of angiogenesis vasculature development circulatory system development anatomical structure morphogenesis positive regulation of vasculature development regulation of angiogenesis anatomical structure formation involved in morphogenesis response to bacterium complement-dependent cytotoxicity cell killing positive regulation of phosphorylation regulation of protein modification process regulation of protein phosphorylation positive regulation of protein metabolic process positive regulation of phosphate metabolic process positive regulation of protein modification process regulation of phosphate metabolic process phosphate-containing compound metabolic process 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 macromolecule modification regulation of phosphorus metabolic process regulation of phosphorylation positive regulation of apoptotic cell clearance apoptotic cell clearance regulation of apoptotic cell clearance	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 membrane-enclosed lumen intracellular membrane-bounded organelle endomembrane system 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 membrane-enclosed lumen intracellular membrane-bounded organelle endomembrane system intracellular organelle lumen endoplasmic reticulum lumen intracellular organelle organelle lumen endoplasmic reticulum cytoplasm cell surface cell periphery plasma membrane membrane lytic vacuole intracellular vesicle cytoplasmic vesicle lumen vacuolar lumen cytoplasmic vesicle lysosome vesicle lumen azurophil granule vacuole secretory granule lumen azurophil granule lumen secretory granule primary lysosome secretory vesicle protein-containing complex blood microparticle
B, D	COMPLEMENT C3B ALPHA CHAIN	enzyme regulator activity molecular function inhibitor activity peptidase regulator activity molecular function regulator activity enzyme inhibitor activity peptidase inhibitor activity endopeptidase regulator activity endopeptidase inhibitor activity C5L2 anaphylatoxin chemotactic receptor binding protein binding binding signaling receptor binding G protein-coupled receptor binding C5a anaphylatoxin chemotactic receptor binding enzyme regulator activity molecular function inhibitor activity peptidase regulator activity molecular function regulator activity enzyme inhibitor activity peptidase inhibitor activity endopeptidase regulator activity endopeptidase inhibitor activity C5L2 anaphylatoxin chemotactic receptor binding protein binding binding signaling receptor binding G protein-coupled receptor binding C5a anaphylatoxin chemotactic receptor binding molecular function activator activity signaling receptor regulator activity receptor ligand activity signaling receptor activator activity	cellular response to stimulus positive regulation of cell communication regulation of biological process regulation of signaling regulation of cellular process positive regulation of signal transduction response to stimulus signaling biological regulation positive regulation of biological process regulation of signal transduction positive regulation of G protein-coupled receptor signaling pathway cell communication positive regulation of response to stimulus regulation of response to stimulus cellular response to stimulus positive regulation of cell communication regulation of biological process regulation of signaling regulation of cellular process positive regulation of signal transduction response to stimulus signaling biological regulation positive regulation of biological process regulation of signal transduction positive regulation of G protein-coupled receptor signaling pathway cell communication positive regulation of response to stimulus regulation of response to stimulus regulation of cell communication G protein-coupled receptor signaling pathway cellular process signal transduction regulation of G protein-coupled receptor signaling pathway positive regulation of cellular process positive regulation of signaling neutral lipid metabolic process neutral lipid biosynthetic process regulation of triglyceride metabolic process cellular biosynthetic process regulation of lipid metabolic process lipid biosynthetic process regulation of primary metabolic process acylglycerol biosynthetic process triglyceride metabolic process triglyceride biosynthetic process regulation of biosynthetic process cellular metabolic process regulation of triglyceride biosynthetic process primary metabolic process regulation of cellular metabolic process regulation of cellular biosynthetic process biosynthetic process glycerolipid biosynthetic process cellular lipid metabolic process metabolic process glycerolipid metabolic process regulation of lipid biosynthetic process acylglycerol metabolic process regulation of metabolic process lipid metabolic process adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains lymphocyte mediated immunity humoral immune response complement activation humoral immune response mediated by circulating immunoglobulin positive regulation of immune response leukocyte mediated immunity regulation of immune system process positive regulation of immune system process complement activation, classical pathway immune response immunoglobulin mediated immune response adaptive immune response immune effector process immune system process B cell mediated immunity regulation of immune response activation of immune response developmental process multicellular organismal process cellular developmental process cell development developmental maturation nervous system development generation of neurons neurogenesis multicellular organism development neuron differentiation neuron remodeling anatomical structure maturation cell differentiation neuron development anatomical structure development neuron maturation cell maturation system development B cell activation cell activation lymphocyte activation leukocyte activation regulation of humoral immune response regulation of immune effector process positive regulation of humoral immune response positive regulation of complement activation positive regulation of immune effector process activation of membrane attack complex positive regulation of activation of membrane attack complex regulation of activation of membrane attack complex regulation of complement activation visual system development pattern specification process regionalization central nervous system development sensory system development vertebrate eye-specific patterning regulation of localization hexose transmembrane transport regulation of transport transport carbohydrate transport establishment of localization positive regulation of D-glucose transmembrane transport transmembrane transport localization regulation of transmembrane transport positive regulation of transport D-glucose transmembrane transport positive regulation of transmembrane transport regulation of D-glucose transmembrane transport monosaccharide transmembrane transport carbohydrate transmembrane transport import into cell positive regulation of cellular component organization regulation of cellular component organization vesicle-mediated transport cellular component organization positive regulation of endocytosis cellular component organization or biogenesis positive regulation of receptor-mediated endocytosis regulation of endocytosis regulation of receptor-mediated endocytosis regulation of vesicle-mediated transport endocytosis receptor-mediated endocytosis biological process involved in interspecies interaction between organisms complement activation, alternative pathway response to biotic stimulus response to stress innate immune response response to external biotic stimulus response to other organism defense response defense response to symbiont response to external stimulus defense response to other organism epithelium development oviduct development reproductive system development oviduct epithelium development tube development reproductive process developmental process involved in reproduction tissue development reproductive structure development positive regulation of cellular metabolic process positive regulation of macromolecule biosynthetic process positive regulation of metabolic process positive regulation of biosynthetic process regulation of cytokine production cytokine production regulation of multicellular organismal process positive regulation of macromolecule metabolic process regulation of vascular endothelial growth factor production regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process regulation of gene expression vascular endothelial growth factor production positive regulation of gene expression positive regulation of multicellular organismal process positive regulation of vascular endothelial growth factor production regulation of macromolecule biosynthetic process macromolecule metabolic process positive regulation of cytokine production positive regulation of cellular biosynthetic process positive regulation of membrane invagination regulation of phagocytosis, engulfment membrane invagination phagocytosis plasma membrane invagination membrane organization regulation of phagocytosis phagocytosis, engulfment positive regulation of phagocytosis positive regulation of phagocytosis, engulfment regulation of membrane invagination cellular component disassembly complement-mediated synapse pruning cell junction organization cell junction disassembly synapse pruning synapse organization immune response-regulating cell surface receptor signaling pathway complement receptor mediated signaling pathway immune response-activating signaling pathway immune response-regulating signaling pathway cell surface receptor signaling pathway immune response-activating cell surface receptor signaling pathway amyloid-beta clearance lipid storage lipid localization positive regulation of lipid localization maintenance of location regulation of lipid storage regulation of lipid localization macromolecule localization positive regulation of lipid storage fatty acid metabolic process oxoacid metabolic process carboxylic acid metabolic process organic acid metabolic process small molecule metabolic process monocarboxylic acid metabolic process positive regulation of acute inflammatory response to antigenic stimulus regulation of myeloid leukocyte mediated immunity regulation of acute inflammatory response to antigenic stimulus positive regulation of leukocyte mediated immunity regulation of type IIa hypersensitivity myeloid leukocyte mediated immunity inflammatory response to antigenic stimulus positive regulation of hypersensitivity positive regulation of inflammatory response positive regulation of adaptive immune response regulation of type II hypersensitivity positive regulation of immunoglobulin mediated immune response hypersensitivity regulation of adaptive immune response regulation of inflammatory response regulation of B cell mediated immunity regulation of leukocyte mediated immunity type II hypersensitivity positive regulation of myeloid leukocyte mediated immunity type IIa hypersensitivity positive regulation of defense response regulation of acute inflammatory response inflammatory response regulation of defense response regulation of response to external stimulus positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains positive regulation of lymphocyte mediated immunity positive regulation of acute inflammatory response positive regulation of B cell mediated immunity regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains positive regulation of response to external stimulus regulation of immunoglobulin mediated immune response regulation of response to stress acute inflammatory response regulation of hypersensitivity regulation of inflammatory response to antigenic stimulus acute inflammatory response to antigenic stimulus positive regulation of inflammatory response to antigenic stimulus positive regulation of type IIa hypersensitivity regulation of lymphocyte mediated immunity positive regulation of type II hypersensitivity regulation of developmental process angiogenesis regulation of vasculature development positive regulation of developmental process tube morphogenesis regulation of anatomical structure morphogenesis blood vessel development regulation of multicellular organismal development blood vessel morphogenesis positive regulation of angiogenesis vasculature development circulatory system development anatomical structure morphogenesis positive regulation of vasculature development regulation of angiogenesis anatomical structure formation involved in morphogenesis response to bacterium complement-dependent cytotoxicity cell killing positive regulation of phosphorylation regulation of protein modification process regulation of protein phosphorylation positive regulation of protein metabolic process positive regulation of phosphate metabolic process positive regulation of protein modification process regulation of phosphate metabolic process phosphate-containing compound metabolic process 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 macromolecule modification regulation of phosphorus metabolic process regulation of phosphorylation positive regulation of apoptotic cell clearance apoptotic cell clearance regulation of apoptotic cell clearance	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 membrane-enclosed lumen intracellular membrane-bounded organelle endomembrane system 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 membrane-enclosed lumen intracellular membrane-bounded organelle endomembrane system intracellular organelle lumen endoplasmic reticulum lumen intracellular organelle organelle lumen endoplasmic reticulum cytoplasm cell surface cell periphery plasma membrane membrane lytic vacuole intracellular vesicle cytoplasmic vesicle lumen vacuolar lumen cytoplasmic vesicle lysosome vesicle lumen azurophil granule vacuole secretory granule lumen azurophil granule lumen secretory granule primary lysosome secretory vesicle protein-containing complex blood microparticle
E, F	DECAY ACCELERATING FACTOR, CD55	protein binding binding virus receptor activity exogenous protein binding lipid binding	multicellular organismal process regulation of cellular process regulation of alpha-beta T cell activation regulation of leukocyte activation positive regulation of biological process regulation of cell activation positive regulation of leukocyte cell-cell adhesion lymphocyte activation leukocyte cell-cell adhesion leukocyte activation positive regulation of cell-cell adhesion positive regulation of CD4-positive, alpha-beta T cell activation positive regulation of lymphocyte activation positive regulation of cell activation cell adhesion multicellular organismal process regulation of cellular process regulation of alpha-beta T cell activation regulation of leukocyte activation positive regulation of biological process regulation of cell activation positive regulation of leukocyte cell-cell adhesion lymphocyte activation leukocyte cell-cell adhesion leukocyte activation positive regulation of cell-cell adhesion positive regulation of CD4-positive, alpha-beta T cell activation positive regulation of lymphocyte activation positive regulation of cell activation cell adhesion cell-cell adhesion T cell activation CD4-positive, alpha-beta T cell activation positive regulation of leukocyte activation alpha-beta T cell activation regulation of multicellular organismal process regulation of immune system process regulation of cell-cell adhesion positive regulation of immune system process positive regulation of cellular process regulation of biological process positive regulation of T cell activation positive regulation of cell adhesion regulation of cell adhesion cell activation biological regulation regulation of T cell activation positive regulation of alpha-beta T cell activation regulation of CD4-positive, alpha-beta T cell activation immune system process regulation of leukocyte cell-cell adhesion positive regulation of multicellular organismal process cellular process regulation of lymphocyte activation positive regulation of cytosolic calcium ion concentration regulation of biological quality adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains regulation of immune effector process lymphocyte mediated immunity T cell mediated immunity positive regulation of leukocyte mediated immunity response to stimulus T cell cytokine production positive regulation of macromolecule biosynthetic process positive regulation of metabolic process positive regulation of immune response cytokine production leukocyte mediated immunity positive regulation of macromolecule metabolic process positive regulation of adaptive immune response positive regulation of T cell cytokine production regulation of T cell mediated immunity regulation of cytokine production involved in immune response immune response regulation of adaptive immune response cellular metabolic process regulation of cellular metabolic process immune effector process regulation of gene expression regulation of leukocyte mediated immunity biosynthetic process regulation of response to stimulus positive regulation of production of molecular mediator of immune response regulation of immune response metabolic process regulation of macromolecule biosynthetic process macromolecule metabolic process regulation of production of molecular mediator of immune response positive regulation of cytokine production regulation of metabolic process positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains positive regulation of lymphocyte mediated immunity cellular biosynthetic process positive regulation of cellular metabolic process positive regulation of response to stimulus regulation of T cell cytokine production regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains positive regulation of biosynthetic process regulation of cytokine production positive regulation of immune effector process cytokine production involved in immune response production of molecular mediator of immune response regulation of biosynthetic process regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process adaptive immune response regulation of cellular biosynthetic process regulation of lymphocyte mediated immunity positive regulation of gene expression positive regulation of T cell mediated immunity positive regulation of cytokine production involved in immune response positive regulation of cellular biosynthetic process humoral immune response complement activation humoral immune response mediated by circulating immunoglobulin complement activation, classical pathway immunoglobulin mediated immune response B cell mediated immunity activation of immune response regulation of humoral immune response negative regulation of biological process negative regulation of complement activation negative regulation of response to stimulus negative regulation of immune response negative regulation of immune effector process negative regulation of humoral immune response negative regulation of immune system process regulation of complement activation biological process involved in interspecies interaction between organisms response to other organism defense response defense response to symbiont response to external stimulus response to biotic stimulus defense response to other organism response to stress innate immune response response to external biotic stimulus regulation of lipopolysaccharide-mediated signaling pathway cellular response to stimulus regulation of response to biotic stimulus response to lipid regulation of response to external stimulus signaling cellular response to lipopolysaccharide regulation of signal transduction cell communication lipopolysaccharide-mediated signaling pathway cellular response to biotic stimulus response to bacterium signal transduction regulation of signaling cell surface receptor signaling pathway response to oxygen-containing compound cellular response to molecule of bacterial origin response to lipopolysaccharide cellular response to oxygen-containing compound cellular response to chemical stimulus response to chemical cellular response to lipid regulation of cell communication response to molecule of bacterial origin regulation of complement-dependent cytotoxicity regulation of cell killing complement-dependent cytotoxicity cell killing positive regulation of cell population proliferation positive regulation of alpha-beta T cell proliferation positive regulation of CD4-positive, alpha-beta T cell proliferation alpha-beta T cell proliferation lymphocyte proliferation regulation of leukocyte proliferation cell population proliferation regulation of CD4-positive, alpha-beta T cell proliferation positive regulation of lymphocyte proliferation positive regulation of T cell proliferation regulation of cell population proliferation mononuclear cell proliferation positive regulation of leukocyte proliferation leukocyte proliferation regulation of alpha-beta T cell proliferation positive regulation of mononuclear cell proliferation T cell proliferation regulation of lymphocyte proliferation CD4-positive, alpha-beta T cell proliferation regulation of T cell proliferation regulation of mononuclear cell proliferation respiratory burst	extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space cellular anatomical entity vesicle extracellular membrane-bounded organelle cell surface cell periphery plasma membrane membrane extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space cellular anatomical entity vesicle extracellular membrane-bounded organelle cell surface cell periphery plasma membrane membrane membrane microdomain membrane raft intracellular anatomical structure transport vesicle intracellular vesicle intracellular membrane-bounded organelle endomembrane system intracellular organelle cytoplasmic vesicle cytoplasm side of membrane cytoplasmic vesicle membrane bounding membrane of organelle vesicle membrane secretory granule secretory vesicle organelle membrane secretory granule membrane Golgi membrane Golgi apparatus endoplasmic reticulum-Golgi intermediate compartment membrane endoplasmic reticulum-Golgi intermediate compartment ficolin-1-rich granule membrane ficolin-1-rich granule tertiary granule

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, C	IPR019742	Alpha-2-macroglobulin, conserved site	Conserved Site
A, C	IPR009048	Alpha-macroglobulin, receptor-binding	Domain
A, C	IPR049466	Complement component 3, CUB domain, first segment	Domain
A, C	IPR001599	Alpha-2-macroglobulin	Domain
A, C	IPR001134	Netrin domain	Domain
A, C	IPR011626	Alpha-macroglobulin-like, TED domain	Domain
A, C	IPR002890	Macroglobulin domain	Domain
A, C	IPR013783	Immunoglobulin-like fold	Homologous Superfamily
A, C	IPR008930	Terpenoid cyclases/protein prenyltransferase alpha-alpha toroid	Homologous Superfamily
A, C	IPR041555	Macroglobulin domain MG3	Domain
A, C	IPR047565	Alpha-macroglobulin-like, thiol-ester bond-forming region	Conserved Site
A, C	IPR048848	Complement component 3, CUB domain, second segment	Domain
A, C	IPR018081	Anaphylatoxin, complement system	Homologous Superfamily
A, C	IPR035815	Complement C3-like, NTR domain	Domain
A, C	IPR018933	Netrin module, non-TIMP type	Domain
A, C	IPR001840	Anaphylatoxin, complement system domain	Domain
A, C	IPR041425	Complement C3/4/5, macroglobulin domain MG1	Domain
A, C	IPR011625	Alpha-2-macroglobulin, bait region domain	Domain
A, C	IPR008993	Tissue inhibitor of metalloproteinases-like, OB-fold	Homologous Superfamily
A, C	IPR000020	Anaphylatoxin/fibulin	Domain
A, C	IPR036595	Alpha-macroglobulin, receptor-binding domain superfamily	Homologous Superfamily
A, C	IPR050473	Alpha-2-macroglobulin/Complement system	Family
A, C	IPR040839	Macroglobulin domain MG4	Domain
B, D	IPR019742	Alpha-2-macroglobulin, conserved site	Conserved Site
B, D	IPR009048	Alpha-macroglobulin, receptor-binding	Domain
B, D	IPR049466	Complement component 3, CUB domain, first segment	Domain
B, D	IPR001599	Alpha-2-macroglobulin	Domain
B, D	IPR001134	Netrin domain	Domain
B, D	IPR011626	Alpha-macroglobulin-like, TED domain	Domain
B, D	IPR002890	Macroglobulin domain	Domain
B, D	IPR013783	Immunoglobulin-like fold	Homologous Superfamily
B, D	IPR008930	Terpenoid cyclases/protein prenyltransferase alpha-alpha toroid	Homologous Superfamily
B, D	IPR041555	Macroglobulin domain MG3	Domain
B, D	IPR047565	Alpha-macroglobulin-like, thiol-ester bond-forming region	Conserved Site
B, D	IPR048848	Complement component 3, CUB domain, second segment	Domain
B, D	IPR018081	Anaphylatoxin, complement system	Homologous Superfamily
B, D	IPR035815	Complement C3-like, NTR domain	Domain
B, D	IPR018933	Netrin module, non-TIMP type	Domain
B, D	IPR001840	Anaphylatoxin, complement system domain	Domain
B, D	IPR041425	Complement C3/4/5, macroglobulin domain MG1	Domain
B, D	IPR011625	Alpha-2-macroglobulin, bait region domain	Domain
B, D	IPR008993	Tissue inhibitor of metalloproteinases-like, OB-fold	Homologous Superfamily
B, D	IPR000020	Anaphylatoxin/fibulin	Domain
B, D	IPR036595	Alpha-macroglobulin, receptor-binding domain superfamily	Homologous Superfamily
B, D	IPR050473	Alpha-2-macroglobulin/Complement system	Family
B, D	IPR040839	Macroglobulin domain MG4	Domain
E, F	IPR000436	Sushi/SCR/CCP domain	Domain
E, F	IPR035976	Sushi/SCR/CCP superfamily	Homologous Superfamily
E, F	IPR050350	Complement & Cell Adhesion Regulators	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, C	Pharos: P01024	complement component 3 deficiency age-related macular degeneration Henoch-Schoenlein purpura atypical hemolytic-uremic syndrome pemphigus age related macular degeneration 9 membranous glomerulonephritis Insulin Resistance pemphigus vulgaris transient ischemic attack atypical hemolytic-uremic syndrome with C3 anomaly primary immunodeficiency disease middle cerebral artery infarction type 2 diabetes mellitus hemolytic-uremic syndrome complement component 3 deficiency age-related macular degeneration Henoch-Schoenlein purpura atypical hemolytic-uremic syndrome pemphigus age related macular degeneration 9 membranous glomerulonephritis Insulin Resistance pemphigus vulgaris transient ischemic attack atypical hemolytic-uremic syndrome with C3 anomaly primary immunodeficiency disease middle cerebral artery infarction type 2 diabetes mellitus hemolytic-uremic syndrome paratuberculosis chronic kidney disease juvenile dermatomyositis congestive heart failure large cell medulloblastoma cystic fibrosis lung cancer malignant colon neoplasm acquired paroxysmal nocturnal hemoglobinuria subependymal giant cell astrocytoma maturity-onset diabetes of the young tuberculosis Emery-Dreifuss muscular dystrophy Gaucher disease hemolytic anemia non-small cell lung carcinoma pancreatic intraductal papillary-mucinous carcinoma Becker muscular dystrophy periodontitis chronic obstructive pulmonary disease kidney disease dermatomyositis lung carcinoma Down syndrome malignant ependymoma acute kidney failure medulloblastoma adenoma Duchenne muscular dystrophy Finnish type amyloidosis astrocytic tumor wet macular degeneration glioblastoma ovarian cancer atypical teratoid rhabdoid tumor pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia idiopathic membranous glomerulonephritis pemphigus foliaceus invasive ductal breast carcinoma pilocytic astrocytoma psoriasis Creutzfeldt Jacob disease limb-girdle muscular dystrophy retinal degeneration diabetes mellitus macular degeneration Sjogren syndrome malignant mesothelioma drug-induced liver injury adrenal cortex carcinoma ulcerative colitis gastric carcinoma myopathy head and neck cancer pancreatic ductal adenocarcinoma autoimmune disease
B, D	Pharos: P01024	complement component 3 deficiency age-related macular degeneration Henoch-Schoenlein purpura atypical hemolytic-uremic syndrome pemphigus age related macular degeneration 9 membranous glomerulonephritis Insulin Resistance pemphigus vulgaris transient ischemic attack atypical hemolytic-uremic syndrome with C3 anomaly primary immunodeficiency disease middle cerebral artery infarction type 2 diabetes mellitus hemolytic-uremic syndrome complement component 3 deficiency age-related macular degeneration Henoch-Schoenlein purpura atypical hemolytic-uremic syndrome pemphigus age related macular degeneration 9 membranous glomerulonephritis Insulin Resistance pemphigus vulgaris transient ischemic attack atypical hemolytic-uremic syndrome with C3 anomaly primary immunodeficiency disease middle cerebral artery infarction type 2 diabetes mellitus hemolytic-uremic syndrome paratuberculosis chronic kidney disease juvenile dermatomyositis congestive heart failure large cell medulloblastoma cystic fibrosis lung cancer malignant colon neoplasm acquired paroxysmal nocturnal hemoglobinuria subependymal giant cell astrocytoma maturity-onset diabetes of the young tuberculosis Emery-Dreifuss muscular dystrophy Gaucher disease hemolytic anemia non-small cell lung carcinoma pancreatic intraductal papillary-mucinous carcinoma Becker muscular dystrophy periodontitis chronic obstructive pulmonary disease kidney disease dermatomyositis lung carcinoma Down syndrome malignant ependymoma acute kidney failure medulloblastoma adenoma Duchenne muscular dystrophy Finnish type amyloidosis astrocytic tumor wet macular degeneration glioblastoma ovarian cancer atypical teratoid rhabdoid tumor pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia idiopathic membranous glomerulonephritis pemphigus foliaceus invasive ductal breast carcinoma pilocytic astrocytoma psoriasis Creutzfeldt Jacob disease limb-girdle muscular dystrophy retinal degeneration diabetes mellitus macular degeneration Sjogren syndrome malignant mesothelioma drug-induced liver injury adrenal cortex carcinoma ulcerative colitis gastric carcinoma myopathy head and neck cancer pancreatic ductal adenocarcinoma autoimmune disease
E, F	Pharos: P08174	protein-losing enteropathy endometriosis amphetamine abuse lung cancer malignant mesothelioma myopathy oligodendroglioma adrenal cortex carcinoma pancreatic intraductal papillary-mucinous carcinoma Amphetamine-Related Disorders Barrett esophagus tuberculosis gastric carcinoma interstitial lung disease lung carcinoma protein-losing enteropathy endometriosis amphetamine abuse lung cancer malignant mesothelioma myopathy oligodendroglioma adrenal cortex carcinoma pancreatic intraductal papillary-mucinous carcinoma Amphetamine-Related Disorders Barrett esophagus tuberculosis gastric carcinoma interstitial lung disease lung carcinoma malignant pancreatic neoplasm nasopharyngeal carcinoma ovarian cancer pancreatic intraductal papillary-mucinous neoplasm astrocytic tumor proteinuria breast cancer ulcerative colitis dermatomyositis lung adenocarcinoma malignant glioma medulloblastoma non-small cell lung carcinoma pancreatic ductal adenocarcinoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia atopic eczema spina bifida common variable immunodeficiency Down syndrome esophageal adenocarcinoma interstitial cystitis