cubilin (intrinsic factor-cobalamin receptor, intrinsic factor-vitamin B12 receptor, 460 kD receptor, intestinal intrinsic factor receptor, CUBN, IFCR)

Function

• cotransporter
• faciltates uptake of lipoprotein, vitamin & iron
• binds to ALB, MB, Kappa & lambda-light chains, TF, hemoglobin, GC, SCGB1A1, APOA1, high density lipoprotein, & the intrinsic factor-cobalamin complex (Ca+2-dependent)
• transporter in several absorptive epithelia
  • intestine, renal proximal tubules, embryonic yolk sac
• interaction with LRP2 mediates trafficking throughout vesicles & facilitates uptake of ligands
  • GC, hemoglobin, ALB, TF, SCGB1A1
• interaction with AMN controls trafficking to the plasma membrane & facilitates endocytosis of ligands
• development of the peri-implantation embryo through internalization of APOA1 & cholesterol
• binds to LGALS3 at the maternal-fetal interface
• interacts with LRP2 in a dual-receptor complex (Ca+2- dependent)
• component of the cubam complex
• 27 CUB domains
  • CUB domains 5 to 8 mediate binding to GIF & ALB
  • CUB domains 1 & 2 mediate interaction with LRP2
• 7 EGF domains
• precursor is cleaved by a trans-Golgi proteinase furin

Structure

N-glycosylated

Compartment

• endosomal membrane,
• peripheral membrane
• lysosomal membrane
• colocalizes with AMN & LRP2 in the endocytotic apparatus of epithelial cells

Expression

• expressed in kidney proximal tubule cells, placenta, visceral yolk-sac cells & in absorptive intestinal cells
• expressed in the epithelium of intestine & kidney

Pathology

• defects in CUBN result in recessive hereditary megaloblastic anemia 1

More general terms

• membrane protein
• glycoprotein

Additional terms

• intrinsic factor; gastric intrinsic factor; IF; INF (GIF, IFMH)
• vitamin B12; cobalamin

Component of

• cubam complex

Database

• OMIM: https://mirror.omim.org/entry/261100
• OMIM: https://mirror.omim.org/entry/602997
• UniProt: http://www.uniprot.org/uniprot/O60494.html