CUBN cubilin (intrinsic factor-cobalamin receptor) [Homo sapiens] - Gene

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Summary

Official Symbol: CUBNprovided by HGNC
Official Full Name: cubilin (intrinsic factor-cobalamin receptor)provided by HGNC
Primary source: HGNC:2548
Locus tag: RP11-416D8.1
See related: Ensembl:ENSG00000107611; HPRD:04296; MIM:602997; Vega:OTTHUMG00000017741
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: IFCR; MGA1; gp280; FLJ90055; FLJ90747
Summary: Cubilin (CUBN) acts as a receptor for intrinsic factor-vitamin B12 complexes. The role of receptor is supported by the presence of 27 CUB domains. Cubulin is located within the epithelium of intestine and kidney. Mutations in CUBN may play a role in autosomal recessive megaloblastic anemia. [provided by RefSeq, Jul 2008]

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Genomic context

Location :: 10p12.31

Sequence :: Chromosome: 10; NC_000010.10 (16865965..17171816, complement)

See CUBN in Epigenomics, MapViewer

Chromosome 10 - NC_000010.10 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

amnionless is essential for the correct luminal expression of cubilin in humans.
Title: Luminal expression of cubilin is impaired in Imerslund-Grasbeck syndrome with compound AMN mutations in intron 3 and exon 7.
A novel 1-bp homozygous deletion of the cubilin was found to be the cause of proteinuria with nephrotic syndrome.
Title: Exome sequencing reveals cubilin mutation as a single-gene cause of proteinuria.
megalin and cubilin are involved in the metabolism of vitamin D by reabsorbing vitamin D binding protein; dysfunction of these receptors is likely to be associated with the development of vitamin D deficiency in patients with chronic kidney disease
Title: Role of megalin and cubilin in the metabolism of vitamin D(3).
There is a missense CUBN variant that associates with levels of albuminuria in both the general population and in individuals with diabetes.
Title: CUBN is a gene locus for albuminuria.
cubilin gene polymorphisms have an influence on 25(OH)D3 and 1,25(OH)2D3 plasma levels in type 1 diabetes patients
Title: The role of cubilin gene polymorphisms and their influence on 25(OH)D3 and 1,25(OH)2D3 plasma levels in type 1 diabetes patients.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: A candidate gene study of folate-associated one carbon metabolism genes and colorectal cancer risk.
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
crystal structure of the complex between IF-Cbl and the cubilin IF-Cbl-binding-region (CUB(5-8)) determined at 3.3 A resolution
Title: Structural basis for receptor recognition of vitamin-B(12)-intrinsic factor complexes.
Aberrant shedding of megalin and cubilin may contribute to albuminuria in diabetes and to deficiency states of important vitamins and hormones.
Title: Microalbuminuria in type 1 diabetes is associated with enhanced excretion of the endocytic multiligand receptors megalin and cubilin.

Submit: New GeneRIF Correction See all (22)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

CUBN is a gene locus for albuminuria.

Genome-wide association studies in an isolated founder population from the Pacific Island of Kosrae.

Genome-wide association study of vitamin B6, vitamin B12, folate, and homocysteine blood concentrations.

Genome-wide association with MRI atrophy measures as a quantitative trait locus for Alzheimer's disease.

Megaloblastic anemia-1, Finnish type

MIM: 261100

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_001072.1	NP_001054.1	TF	BIND	PubMed	Transferrin interacts with Cubilin.
O60494	P02768	ALB	HPRD	PubMed
O60494	P02774	GC	HPRD	PubMed
O60494	P27352	GIF	HPRD	PubMed
O60494	P17931	LGALS3	HPRD	PubMed
O60494	P98164	LRP2	HPRD	PubMed
O60494	P11684	SCGB1A1	HPRD	PubMed
O60494	P02787	TF	HPRD	PubMed
BioGRID:113724	BioGRID:108908	GC	BioGRID	PubMed	Affinity Capture-Western
BioGRID:113724	BioGRID:108961	GIF	BioGRID	PubMed	Reconstituted Complex
BioGRID:113724	BioGRID:116708	RRP1B	BioGRID	PubMed	Affinity Capture-MS
BioGRID:113724	BioGRID:215383	Rrp1b	BioGRID	PubMed	Affinity Capture-MS
BioGRID:113724	BioGRID:113203	SCGB1A1	BioGRID	PubMed	Reconstituted Complex

Function	Evidence Code	Pubs
calcium ion binding	IEA Inferred from Electronic Annotation more info
cobalamin binding	IEA Inferred from Electronic Annotation more info
hemoglobin binding	IEA Inferred from Electronic Annotation more info
protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
receptor activity	IEA Inferred from Electronic Annotation more info
transporter activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
cholesterol metabolic process	IEA Inferred from Electronic Annotation more info
cobalamin transport	TAS Traceable Author Statement more info	PubMed
hemoglobin import	IEA Inferred from Electronic Annotation more info
in utero embryonic development	IEA Inferred from Electronic Annotation more info
lipid metabolic process	TAS Traceable Author Statement more info
lipoprotein metabolic process	TAS Traceable Author Statement more info
lipoprotein transport	IEA Inferred from Electronic Annotation more info
protein homotrimerization	IEA Inferred from Electronic Annotation more info
receptor-mediated endocytosis	NAS Non-traceable Author Statement more info	PubMed
response to nutrient	IEA Inferred from Electronic Annotation more info
small molecule metabolic process	TAS Traceable Author Statement more info
steroid metabolic process	TAS Traceable Author Statement more info
tissue homeostasis	NAS Non-traceable Author Statement more info	PubMed
vitamin D metabolic process	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
Golgi apparatus	IEA Inferred from Electronic Annotation more info
apical plasma membrane	IEA Inferred from Electronic Annotation more info
brush border membrane	NAS Non-traceable Author Statement more info	PubMed
coated pit	IEA Inferred from Electronic Annotation more info
cytoplasm	IEA Inferred from Electronic Annotation more info
cytosol	TAS Traceable Author Statement more info
endocytic vesicle membrane	IEA Inferred from Electronic Annotation more info
endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
endosome	IEA Inferred from Electronic Annotation more info
endosome membrane	IEA Inferred from Electronic Annotation more info
extrinsic to external side of plasma membrane	NAS Non-traceable Author Statement more info	PubMed
lysosomal lumen	TAS Traceable Author Statement more info
lysosomal membrane	IEA Inferred from Electronic Annotation more info
membrane	TAS Traceable Author Statement more info	PubMed
membrane fraction	IEA Inferred from Electronic Annotation more info
plasma membrane	TAS Traceable Author Statement more info
protein complex	IEA Inferred from Electronic Annotation more info

General protein information

Preferred Names: cubilin

Names: cubilin; 460 kDa receptor; cubilin precursor variant 1; cubilin precursor variant 2; intrinsic factor B12-receptor; intrinsic factor-cobalamin receptor; intestinal intrinsic factor receptor; intrinsic factor-vitamin B12 receptor

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008967.1 RefSeqGene

Range

5001..310852

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001081.3 → NP_001072.2 cubilin precursor

Status: REVIEWED

Source sequence(s)

AC067747, AF034611, AL365215, AL731551, BP270790, BP271329

Consensus CDS

CCDS7113.1

UniProtKB/Swiss-Prot

O60494

Related

ENSP00000367064, OTTHUMP00000019220, ENST00000377833, OTTHUMT00000047009

Conserved Domains (3) summary

cd00041
Location:1620 – 1733
Blast Score: 318

CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.

cd00054
Location:170 – 210
Blast Score: 123

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

cl09941
Location:309 – 347
Blast Score: 116

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000010.10 Reference GRCh37.p5 Primary Assembly

Range

16865965..17171816, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000142.1 Alternate HuRef

Range

16779758..17084998, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC067747.7 (43613..145279)	None
genomic	AF243082.1	AAK61829.1
genomic	AL365215.23	CAH73630.1
genomic	AL596445.2	CAH72450.1
genomic	AL731551.9	CAI40246.1
		CAI40247.1
genomic	CH471072.2	EAW86221.1
genomic	EF444970.1	ACA05973.1
		ACA05974.1
mRNA	AB209880.1	BAD93117.1
mRNA	AF034611.1	AAC82612.1
mRNA	AF086456.1	None
mRNA	AK074536.1	BAG51968.1
mRNA	AK075228.1	BAG52089.1
mRNA	AK308290.1	None
mRNA	AK309623.1	None
mRNA	AK310404.1	None
mRNA	BP270790.1	None
mRNA	BP271329.1	None

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
O60494.5	GenPept	UniProtKB/Swiss-Prot:O60494
Q59ED1	GenPept	UniProtKB/TrEMBL:Q59ED1
Q5JQ33	GenPept	UniProtKB/TrEMBL:Q5JQ33
Q7LC53	GenPept	UniProtKB/TrEMBL:Q7LC53
Q96RV0	GenPept	UniProtKB/TrEMBL:Q96RV0