2FCW

Structure of a Complex Between the Pair of the LDL Receptor Ligand-Binding Modules 3-4 and the Receptor Associated Protein (RAP).

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
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)
A	d2fcwa1	All alpha proteins	RAP domain-like	RAP domain-like	RAP domain	alpha-2-Macroglobulin receptor associated protein (RAP)	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d2fcwb1	Small proteins	LDL receptor-like module	LDL receptor-like module	LDL receptor-like module	Ligand-binding domain of low-density lipoprotein receptor	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)
A	SCOP2 Family	RAP domain	8028398	4000754	SCOP2 (2022-06-29)
A	SCOP2 Superfamily	RAP domain-like	8040777	3001254	SCOP2 (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	PF06401	e2fcwA1	A: alpha bundles	X: immunoglobulin/albumin-binding domain-like	H: alpha-2-Macroglobulin receptor associated protein (RAP) domain 1 (From Topology)	T: alpha-2-Macroglobulin receptor associated protein (RAP) domain 1	F: PF06401	ECOD (1.6)
B	PF00057	e2fcwB1	A: few secondary structure elements	X: EGF-like	H: LDL receptor-like module (From Topology)	T: LDL receptor-like module	F: PF00057	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	1.20.81.10	Mainly Alpha	Up-down Bundle	Receptor-associated Protein	RAP domain	CATH (4.3.0)
B	4.10.400.10	Few Secondary Structures	Irregular	Low-density Lipoprotein Receptor	Low-density Lipoprotein Receptor	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF06401	Alpha-2-macroglobulin RAP, C-terminal domain (Alpha-2-MRAP_C)	Alpha-2-macroglobulin RAP, C-terminal domain	The alpha-2-macroglobulin receptor-associated protein (RAP) is a intracellular glycoprotein that binds to the 2-macroglobulin receptor and other members of the low density lipoprotein receptor family. The protein inhibits binding of all currently ...	The alpha-2-macroglobulin receptor-associated protein (RAP) is a intracellular glycoprotein that binds to the 2-macroglobulin receptor and other members of the low density lipoprotein receptor family. The protein inhibits binding of all currently known ligands of these receptors [1]. Two different studies have provided conflicted domain boundaries [2,3].	Domain
B	PF00057	Low-density lipoprotein receptor domain class A (Ldl_recept_a)	Low-density lipoprotein receptor domain class A	-	Repeat

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	Alpha-2-macroglobulin receptor-associated protein	protein binding binding signaling receptor binding amide binding amyloid-beta binding peptide binding molecular function activator activity molecular function regulator activity signaling receptor regulator activity receptor ligand activity signaling receptor activator activity molecular function inhibitor activity signaling receptor inhibitor activity receptor antagonist activity protein binding binding signaling receptor binding amide binding amyloid-beta binding peptide binding molecular function activator activity molecular function regulator activity signaling receptor regulator activity receptor ligand activity signaling receptor activator activity molecular function inhibitor activity signaling receptor inhibitor activity receptor antagonist activity enzyme binding lipase binding low-density lipoprotein particle receptor binding lipoprotein particle receptor binding very-low-density lipoprotein particle receptor binding heparin binding glycosaminoglycan binding carbohydrate derivative binding sulfur compound binding	regulation of protein binding regulation of molecular function negative regulation of protein binding negative regulation of binding regulation of binding biological regulation negative regulation of molecular function multicellular organismal process regulation of biological process positive regulation of biological process positive regulation of amyloid-beta clearance positive regulation of multicellular organismal process regulation of multicellular organismal process amyloid-beta clearance regulation of protein binding regulation of molecular function negative regulation of protein binding negative regulation of binding regulation of binding biological regulation negative regulation of molecular function multicellular organismal process regulation of biological process positive regulation of biological process positive regulation of amyloid-beta clearance positive regulation of multicellular organismal process regulation of multicellular organismal process amyloid-beta clearance regulation of amyloid-beta clearance regulation of localization import into cell regulation of cellular process regulation of cellular component organization receptor internalization transport negative regulation of biological process negative regulation of transport negative regulation of endocytosis regulation of receptor internalization vesicle-mediated transport cellular component organization localization negative regulation of cellular process cellular component organization or biogenesis regulation of endocytosis negative regulation of cellular component organization regulation of transport negative regulation of receptor-mediated endocytosis regulation of receptor-mediated endocytosis regulation of vesicle-mediated transport establishment of localization cellular process endocytosis receptor-mediated endocytosis negative regulation of receptor internalization cellular response to stimulus response to stimulus signaling signal transduction cell communication regulation of signaling negative regulation of signaling negative regulation of response to stimulus regulation of signal transduction negative regulation of signal transduction negative regulation of cell communication extracellular negative regulation of signal transduction regulation of response to stimulus regulation of cell communication extracellular regulation of signal transduction very-low-density lipoprotein particle clearance regulation of plasma lipoprotein particle levels plasma lipoprotein particle clearance negative regulation of very-low-density lipoprotein particle clearance negative regulation of lipoprotein particle clearance regulation of lipoprotein particle clearance regulation of very-low-density lipoprotein particle clearance negative regulation of multicellular organismal process amyloid-beta clearance by transcytosis transcytosis negative regulation of amyloid-beta clearance	cellular anatomical entity endomembrane system membrane-bounded organelle intracellular organelle intracellular anatomical structure Golgi apparatus cis-Golgi network organelle intracellular membrane-bounded organelle cytoplasm cell surface cell periphery plasma membrane membrane cellular anatomical entity endomembrane system membrane-bounded organelle intracellular organelle intracellular anatomical structure Golgi apparatus cis-Golgi network organelle intracellular membrane-bounded organelle cytoplasm cell surface cell periphery plasma membrane membrane membrane-enclosed lumen intracellular organelle lumen endoplasmic reticulum lumen rough endoplasmic reticulum rough endoplasmic reticulum lumen organelle lumen endoplasmic reticulum Golgi lumen endosome intracellular vesicle cytoplasmic vesicle vesicle extracellular region endoplasmic reticulum-Golgi intermediate compartment endosome lumen
B	Low-density lipoprotein receptor	amide binding amyloid-beta binding binding peptide binding molecular adaptor activity identical protein binding protein binding virus receptor activity exogenous protein binding cation binding ion binding calcium ion binding metal ion binding small molecule binding amide binding amyloid-beta binding binding peptide binding molecular adaptor activity identical protein binding protein binding virus receptor activity exogenous protein binding cation binding ion binding calcium ion binding metal ion binding small molecule binding lipoprotein particle receptor activity cargo receptor activity very-low-density lipoprotein particle receptor activity enzyme binding protease binding clathrin heavy chain binding clathrin binding low-density lipoprotein particle receptor activity lipoprotein particle binding protein-containing complex binding protein-lipid complex binding low-density lipoprotein particle binding	cellular catabolic process multicellular organismal process catabolic process amyloid-beta clearance by cellular catabolic process cellular metabolic process metabolic process cellular process amyloid-beta clearance regulation of defense response regulation of biological process response to stimulus regulation of response to external stimulus defense response biological regulation cellular catabolic process multicellular organismal process catabolic process amyloid-beta clearance by cellular catabolic process cellular metabolic process metabolic process cellular process amyloid-beta clearance regulation of defense response regulation of biological process response to stimulus regulation of response to external stimulus defense response biological regulation positive regulation of biological process response to external stimulus regulation of inflammatory response positive regulation of response to stimulus positive regulation of response to external stimulus positive regulation of inflammatory response regulation of response to stimulus regulation of response to stress response to stress positive regulation of defense response inflammatory response localization import into cell transport phagocytosis endocytosis establishment of localization vesicle-mediated transport regulation of cellular process cellular biosynthetic process positive regulation of cellular metabolic process positive regulation of macromolecule biosynthetic process positive regulation of metabolic process organic substance metabolic process positive regulation of biosynthetic process organic substance biosynthetic process positive regulation of macromolecule metabolic process positive regulation of cellular process regulation of biosynthetic process regulation of cellular metabolic process regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process regulation of cellular biosynthetic process regulation of gene expression biosynthetic process positive regulation of gene expression regulation of macromolecule biosynthetic process macromolecule metabolic process regulation of metabolic process positive regulation of cellular biosynthetic process macromolecule localization organic substance transport phospholipid transport lipid localization lipid transport organophosphate ester transport cholesterol transport sterol transport organic hydroxy compound transport plasma lipoprotein particle clearance regulation of plasma lipoprotein particle levels developmental process blood vessel morphogenesis tube development artery development vasculature development circulatory system development multicellular organism development anatomical structure morphogenesis tube morphogenesis anatomical structure development artery morphogenesis blood vessel development system development regulation of cholesterol metabolic process organic hydroxy compound metabolic process sterol metabolic process steroid metabolic process regulation of steroid metabolic process regulation of lipid metabolic process cholesterol metabolic process alcohol metabolic process primary metabolic process regulation of primary metabolic process organic cyclic compound metabolic process secondary alcohol metabolic process regulation of small molecule metabolic process small molecule metabolic process lipid metabolic process response to nutrient levels response to caloric restriction organonitrogen compound metabolic process regulation of protein metabolic process negative regulation of metabolic process negative regulation of biological process protein metabolic process negative regulation of protein metabolic process negative regulation of macromolecule metabolic process regulation of low-density lipoprotein particle clearance negative regulation of low-density lipoprotein particle clearance negative regulation of lipoprotein particle clearance regulation of lipoprotein particle clearance regulation of multicellular organismal process low-density lipoprotein particle clearance negative regulation of multicellular organismal process intestinal lipid absorption digestion system process intestinal absorption digestive system process intestinal cholesterol absorption lipid digestion cellular response to stimulus response to organic substance response to endogenous stimulus response to organonitrogen compound response to lipoprotein particle response to nitrogen compound cellular response to low-density lipoprotein particle stimulus response to chemical cellular response to lipoprotein particle stimulus cellular localization intracellular lipid transport intracellular cholesterol transport intracellular transport intracellular sterol transport establishment of localization in cell receptor-mediated endocytosis involved in cholesterol transport receptor-mediated endocytosis cholesterol import astrocyte differentiation negative regulation of astrocyte activation regulation of cell activation regulation of cell differentiation regulation of neurogenesis astrocyte activation glial cell development regulation of astrocyte differentiation regulation of cell development gliogenesis cell differentiation nervous system development negative regulation of gliogenesis negative regulation of glial cell differentiation central nervous system development negative regulation of response to external stimulus negative regulation of defense response glial cell activation neuroinflammatory response cellular developmental process regulation of developmental process negative regulation of inflammatory response cell development regulation of gliogenesis regulation of nervous system development neurogenesis negative regulation of neurogenesis astrocyte development regulation of neuroinflammatory response negative regulation of cellular process negative regulation of nervous system development negative regulation of cell differentiation regulation of multicellular organismal development negative regulation of response to stimulus negative regulation of developmental process cell activation regulation of glial cell differentiation negative regulation of astrocyte differentiation negative regulation of cell activation negative regulation of cell development glial cell differentiation regulation of astrocyte activation negative regulation of neuroinflammatory response regulation of macrophage activation regulation of leukocyte activation myeloid leukocyte activation leukocyte activation macrophage activation leukocyte activation involved in inflammatory response regulation of immune system process negative regulation of microglial cell activation negative regulation of immune system process immune system process microglial cell activation regulation of microglial cell activation negative regulation of leukocyte activation negative regulation of macrophage activation sterol homeostasis chemical homeostasis homeostatic process cholesterol homeostasis lipid homeostasis neutral lipid metabolic process neutral lipid biosynthetic process regulation of triglyceride metabolic process positive regulation of triglyceride metabolic process lipid biosynthetic process acylglycerol biosynthetic process triglyceride metabolic process triglyceride biosynthetic process positive regulation of lipid metabolic process regulation of triglyceride biosynthetic process positive regulation of triglyceride biosynthetic process glycerolipid biosynthetic process positive regulation of lipid biosynthetic process cellular lipid metabolic process glycerolipid metabolic process regulation of lipid biosynthetic process acylglycerol metabolic process behavior learning or memory long-term memory nervous system process cognition memory high-density lipoprotein particle clearance regulation of protein catabolic process in the vacuole positive regulation of protein metabolic process lysosomal protein catabolic process macromolecule catabolic process positive regulation of lysosomal protein catabolic process organonitrogen compound catabolic process protein catabolic process in the vacuole protein catabolic process regulation of catabolic process positive regulation of protein catabolic process positive regulation of catabolic process regulation of lysosomal protein catabolic process positive regulation of protein catabolic process in the vacuole organic substance catabolic process regulation of protein catabolic process regulation of signaling negative regulation of signaling signaling regulation of receptor recycling negative regulation of receptor recycling receptor recycling receptor metabolic process response to lipid response to fatty acid response to oxygen-containing compound cellular response to oxygen-containing compound cellular response to fatty acid cellular response to chemical stimulus cellular response to lipid cellular response to organic substance lipoprotein metabolic process lipoprotein catabolic process negative regulation of cellular metabolic process negative regulation of cellular biosynthetic process negative regulation of gene expression negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process regulation of cellular component organization negative regulation of amyloid fibril formation regulation of amyloid fibril formation amyloid fibril formation cellular component organization cellular component organization or biogenesis negative regulation of supramolecular fiber organization negative regulation of cellular component organization regulation of supramolecular fiber organization supramolecular fiber organization phospholipid catabolic process glycerophospholipid metabolic process glycerolipid catabolic process organophosphate catabolic process cellular lipid catabolic process phospholipid metabolic process regulation of phosphate metabolic process phosphate-containing compound metabolic process phosphatidylcholine metabolic process phosphorus metabolic process regulation of phospholipid catabolic process lipid catabolic process regulation of phosphatidylcholine metabolic process regulation of phospholipid metabolic process regulation of lipid catabolic process phosphatidylcholine catabolic process organophosphate metabolic process regulation of phosphatidylcholine catabolic process regulation of cellular catabolic process regulation of phosphorus metabolic process glycerophospholipid catabolic process	cell periphery cell surface membrane plasma membrane cellular anatomical entity external side of plasma membrane side of membrane clathrin-coated pit endomembrane system apical part of cell membrane-bounded organelle intracellular anatomical structure intracellular vesicle intracellular organelle cell periphery cell surface membrane plasma membrane cellular anatomical entity external side of plasma membrane side of membrane clathrin-coated pit endomembrane system apical part of cell 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 basal part of cell basal plasma membrane plasma membrane region basolateral plasma membrane protein-containing complex receptor complex Golgi apparatus endosome membrane endosome sorting endosome somatodendritic compartment endolysosome membrane lytic vacuole endolysosome lysosome vacuolar membrane vacuole lytic vacuole membrane lysosomal membrane early endosome PCSK9-LDLR complex low-density lipoprotein particle extracellular region plasma lipoprotein particle extracellular space lipoprotein particle protein-lipid complex late endosome

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR036744	RAP domain superfamily	Homologous Superfamily
A	IPR038003	Alpha-2-macroglobulin receptor-associated protein	Family
A	IPR010483	Alpha-2-macroglobulin RAP, C-terminal	Domain
A	IPR037999	Alpha-2-macroglobulin RAP, domain 3	Domain
A	IPR009066	Alpha-2-macroglobulin receptor-associated protein, domain 1	Domain
A	IPR038001	Alpha-2-macroglobulin RAP, domain 2	Domain
B	IPR018097	EGF-like calcium-binding, conserved site	Conserved Site
B	IPR036055	LDL receptor-like superfamily	Homologous Superfamily
B	IPR000033	LDLR class B repeat	Repeat
B	IPR001881	EGF-like calcium-binding domain	Domain
B	IPR023415	Low-density lipoprotein (LDL) receptor class A, conserved site	Conserved Site
B	IPR011042	Six-bladed beta-propeller, TolB-like	Homologous Superfamily
B	IPR002172	Low-density lipoprotein (LDL) receptor class A repeat	Repeat
B	IPR000742	EGF-like domain	Domain
B	IPR009030	Growth factor receptor cysteine-rich domain superfamily	Homologous Superfamily
B	IPR000152	EGF-type aspartate/asparagine hydroxylation site	PTM

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: P30533	myopia myopia 23, autosomal recessive atypical teratoid rhabdoid tumor heart disease medulloblastoma ovarian cancer plasma cell myeloma dermatomyositis large cell medulloblastoma Pick disease primitive neuroectodermal tumor glioblastoma malignant glioma pilocytic astrocytoma psoriasis
B	Pharos: P01130	familial hypercholesterolemia Dyslipidemias abdominal aortic aneurysm coronary artery disease non-alcoholic fatty liver disease obesity disorder Q fever amyotrophic lateral sclerosis type 1 hyperplasia atherosclerosis ovarian cancer psoriasis sinusitis glioblastoma invasive ductal breast carcinoma familial hypercholesterolemia Dyslipidemias abdominal aortic aneurysm coronary artery disease non-alcoholic fatty liver disease obesity disorder Q fever amyotrophic lateral sclerosis type 1 hyperplasia atherosclerosis ovarian cancer psoriasis sinusitis glioblastoma invasive ductal breast carcinoma arteriosclerosis disorder lung adenocarcinoma atypical teratoid rhabdoid tumor malignant pancreatic neoplasm cystic fibrosis pancreatic ductal adenocarcinoma fatty liver disease Sjogren syndrome heart disease type 2 diabetes mellitus breast cancer lung cancer congestive heart failure medulloblastoma non-small cell lung carcinoma ductal breast carcinoma in situ osteosarcoma exocrine pancreatic carcinoma peripheral arterial disease familial hyperlipidemia sarcoidosis Gaucher disease spina bifida hydrolethalus syndrome ulcerative colitis hyperlipidemia alcohol abuse carotid artery disease lung carcinoma myocardial infarction

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.