InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: CUBN

Summary

InnateDB Protein

IDBP-58022.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

CUBN

Protein Name

cubilin (intrinsic factor-cobalamin receptor)

Synonyms

gp280; IFCR; MGA1;

Species

Homo sapiens

Ensembl Protein

ENSP00000367064

InnateDB Gene

IDBG-58020 (CUBN)

Protein Structure

UniProt Annotation

Function

Cotransporter which plays a role in lipoprotein, vitamin and iron metabolism, by facilitating their uptake. Binds to ALB, MB, Kappa and lambda-light chains, TF, hemoglobin, GC, SCGB1A1, APOA1, high density lipoprotein, and the GIF-cobalamin complex. The binding of all ligands requires calcium. Serves as important transporter in several absorptive epithelia, including intestine, renal proximal tubules and embryonic yolk sac. Interaction with LRP2 mediates its trafficking throughout vesicles and facilitates the uptake of specific ligands like GC, hemoglobin, ALB, TF and SCGB1A1. Interaction with AMN controls its trafficking to the plasma membrane and facilitates endocytosis of ligands. May play an important role in the development of the peri-implantation embryo through internalization of APOA1 and cholesterol. Binds to LGALS3 at the maternal-fetal interface. {ECO:0000269PubMed:10371504, ECO:0000269PubMed:11606717, ECO:0000269PubMed:11717447, ECO:0000269PubMed:14576052, ECO:0000269PubMed:9572993}.

Subcellular Localization

Endosome membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Lysosome membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Note=Colocalizes with AMN and LRP2 in the endocytotic apparatus of epithelial cells. {ECO:0000250}.

Disease Associations

Recessive hereditary megaloblastic anemia 1 (RH-MGA1) [MIM:261100]: Due to selective malabsorption of vitamin B12. Defects in vitamin B12 absorption lead to impaired function of thymidine synthase. As a consequence DNA synthesis is interrupted. Rapidly dividing cells involved in erythropoiesis are particularly affected. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Expressed in kidney proximal tubule cells, placenta, visceral yolk-sac cells and in absorptive intestinal cells. Expressed in the epithelium of intestine and kidney.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 11 experimentally validated interaction(s) in this database.
They are also associated with 2 interaction(s) predicted by orthology.

Experimentally validated
Total	11 [view]
Protein-Protein	11 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	2 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004872	receptor activity
GO:0005215	transporter activity
GO:0005509	calcium ion binding
GO:0005515	protein binding
GO:0031419	cobalamin binding
GO:0042803	protein homodimerization activity

Biological Process

GO:0001894	tissue homeostasis
GO:0006766	vitamin metabolic process
GO:0006767	water-soluble vitamin metabolic process
GO:0006898	receptor-mediated endocytosis
GO:0008202	steroid metabolic process
GO:0008203	cholesterol metabolic process
GO:0009235	cobalamin metabolic process
GO:0015889	cobalamin transport
GO:0042157	lipoprotein metabolic process
GO:0042359	vitamin D metabolic process
GO:0042953	lipoprotein transport
GO:0044281	small molecule metabolic process

Cellular Component

GO:0005737	cytoplasm
GO:0005765	lysosomal membrane
GO:0005768	endosome
GO:0005783	endoplasmic reticulum
GO:0005794	Golgi apparatus
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0005903	brush border
GO:0005905	coated pit
GO:0010008	endosome membrane
GO:0016020	membrane
GO:0016324	apical plasma membrane
GO:0030139	endocytic vesicle
GO:0031232	extrinsic component of external side of plasma membrane
GO:0031526	brush border membrane
GO:0043202	lysosomal lumen
GO:0045177	apical part of cell
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

InterPro

IPR000742 Epidermal growth factor-like domain
IPR000859 CUB domain
IPR001881 EGF-like calcium-binding domain
IPR009030 Insulin-like growth factor binding protein, N-terminal

PFAM

PF00008
PF00431
PF07645

PRINTS

PIRSF

SMART

SM00181
SM00042
SM00179

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

O60494