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cubilin (intrinsic factor-cobalamin receptor, intrinsic factor-vitamin B12 receptor, 460 kD receptor, intestinal intrinsic factor receptor, CUBN, IFCR)
Function:
1) cotransporter
2) faciltates uptake of lipoprotein, vitamin & iron
3) binds to ALB, MB, Kappa & lambda-light chains, TF, hemoglobin, GC, SCGB1A1, APOA1, high density lipoprotein, & the intrinsic factor-cobalamin complex (Ca+2-dependent)
4) transporter in several absorptive epithelia
- intestine, renal proximal tubules, embryonic yolk sac
5) interaction with LRP2 mediates trafficking throughout vesicles & facilitates uptake of ligands
- GC, hemoglobin, ALB, TF, SCGB1A1
6) interaction with AMN controls trafficking to the plasma membrane & facilitates endocytosis of ligands
7) development of the peri-implantation embryo through internalization of APOA1 & cholesterol
8) binds to LGALS3 at the maternal-fetal interface
9) interacts with LRP2 in a dual-receptor complex (Ca+2- dependent)
10) component of the cubam complex
11) 27 CUB domains
a) CUB domains 5 to 8 mediate binding to GIF & ALB
b) CUB domains 1 & 2 mediate interaction with LRP2
12) 7 EGF domains
13) 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
Related
intrinsic factor; gastric intrinsic factor; IF; INF (GIF, IFMH)
vitamin B12; cobalamin
General
glycoprotein
membrane protein
Properties
SIZE: MW = 399 kD
entity length = 3623 aa
COMPARTMENT: lysosome
endosome
MOTIF: signal sequence {1-23}
MOTIF: N-glycosylation site {N3}
proteolytic site {35-36}
N-glycosylation site {N105}
EGF domain {132-168} (7)
MOTIF: cysteine residue {C136}
MODIFICATION: cysteine residue {C147}
cysteine residue {C141}
MODIFICATION: cysteine residue {C156}
cysteine residue {C147}
MODIFICATION: cysteine residue {C136}
cysteine residue {C156}
MODIFICATION: cysteine residue {C141}
cysteine residue {C158}
MODIFICATION: cysteine residue {C167}
cysteine residue {C167}
MODIFICATION: cysteine residue {C158}
CUB domain {474-586} (27)
MOTIF: cysteine residue {C474}
MODIFICATION: cysteine residue {C500}
N-glycosylation site {N482}
cysteine residue {C500}
MODIFICATION: cysteine residue {C474}
cysteine residue {C527}
MODIFICATION: cysteine residue {C549}
cysteine residue {C549}
MODIFICATION: cysteine residue {C527}
Database Correlations
OMIM correlations
MORBIDMAP 602997
UniProt O60494
PFAM correlations
References
- UniProt :accession O60494
- GeneReviews
https://www.genecards.org/cgi-bin/carddisp.pl?gene=CUBN
Component-of
cubam complex