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Domain

The CUB domains 5 to 8 mediate binding to CBLIF and ALB. CUB domains 1 and 2 mediate interaction with LRP2.

The cubam complex is composed of a 400 Angstrom long stem and a globular crown region. The stem region is probably formed by AMN and the CUBN N-terminal region, including the EGF-like domains. The crown is probably formed by the CUBN CUB domains.

Function

Endocytic receptor which plays a role in lipoprotein, vitamin and iron metabolism by facilitating their uptake (PubMed:10371504, PubMed:11606717, PubMed:11717447, PubMed:14576052, PubMed:9572993). Acts together with LRP2 to mediate endocytosis of high-density lipoproteins, GC, hemoglobin, ALB, TF and SCGB1A1. Acts together with AMN to mediate endocytosis of the CBLIF-cobalamin complex (PubMed:14576052, PubMed:9572993). Binds to ALB, MB, Kappa and lambda-light chains, TF, hemoglobin, GC, SCGB1A1, APOA1, high density lipoprotein, and the CBLIF-cobalamin complex. Ligand binding requires calcium (PubMed:9572993). Serves as important transporter in several absorptive epithelia, including intestine, renal proximal tubules and embryonic yolk sac. 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.

Involvement in disease

Imerslund-Grasbeck syndrome 1

IGS1

A form of Imerslund-Grasbeck syndrome, a rare autosomal recessive disorder characterized by vitamin B12 deficiency commonly resulting in megaloblastic anemia, which is responsive to parenteral vitamin B12 therapy and appears in infancy or early childhood. Clinical manifestations include failure to thrive, infections and neurological damage. Mild proteinuria, with no signs of kidney disease, is present in about half of the patients.

None

The disease is caused by variants affecting the gene represented in this entry.

Proteinuria, chronic benign

PROCHOB

An autosomal recessive condition characterized by isolated, non-progressive proteinuria in absence of renal disease and hypertension. Onset of proteinuria is in the first decade of life.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

The precursor is cleaved by a trans-Golgi proteinase furin, removing a propeptide.

N-glycosylated.

Tissue specificity

Detected in kidney cortex (at protein level) (PubMed:9572993). Expressed in kidney proximal tubule cells, placenta, visceral yolk-sac cells and in absorptive intestinal cells. Expressed in the epithelium of intestine and kidney.

Cellular localization

  • Apical cell membrane
  • Peripheral membrane protein
  • Cell membrane
  • Peripheral membrane protein
  • Membrane
  • Coated pit
  • Endosome
  • Lysosome membrane
  • Peripheral membrane protein
  • Lacks a transmembrane domain and depends on interaction with AMN for location at the plasma membrane (PubMed:29402915, PubMed:30523278). Colocalizes with AMN and LRP2 in the endocytotic apparatus of epithelial cells (By similarity).

Alternative names

IFCR, CUBN, Cubilin, 460 kDa receptor, Intestinal intrinsic factor receptor, Intrinsic factor-cobalamin receptor, Intrinsic factor-vitamin B12 receptor

Target type

Proteins

Primary research area

Metabolism

Molecular weight

398736Da

We found 6 products in 1 category

Primary Antibodies

Target

Application

Reactive species