Tbio CUBN Cubilin

Protein Summary

Description

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. 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]

Uniprot Accession IDs

• O60494
• B0YIZ4
• Q5VTA6
• Q96RU9

Gene Name

• CUBN

Ensembl ID

• ENST00000377833
• ENSP00000367064
• ENSG00000107611

Symbol

• IFCR
• IFCR
• MGA1
• gp280

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
trait	1
protein domain	0.99
gene perturbation	0.93
disease	0.77
cellular component	0.74

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 227.67   (req: < 5)

Gene RIFs: 44   (req: <= 3)

Antibodies: 139   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 227.67   (req: >= 5)

Gene RIFs: 44   (req: > 3)

Antibodies: 139   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 29

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

Show Full Sequence

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Related Tools

Target Illumination GWAS Analytics (TIGA)

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GENEVA

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Protein-Protein Interactions (62)

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1 – 10 of 62

• See Interactions on String-DB

LRP2

Tbio

Novelty:  0.00143258

Score:  0.997

Data Source:  STRINGDB

GIF

Tbio

Novelty:  0.00508343

Score:  0.997

Data Source:  Reactome,STRINGDB

AMN

Tbio

Novelty:  0.030358

Score:  0.993

Data Source:  Reactome,STRINGDB

GC

Tchem

Novelty:  0.00065382

Score:  0.978

Data Source:  Reactome,STRINGDB

APOA1

Tbio

Novelty:  0.0001216

Score:  0.943

Data Source:  Reactome,STRINGDB

LGMN

Tchem

Family:  Enzyme

Novelty:  0.00296582

Score:  0.914

Data Source:  STRINGDB

ALB

Tchem

Novelty:  0.00000616

Score:  0.771

Data Source:  STRINGDB

CLCN5

Tbio

Family:  IC

Novelty:  0.00419772

Score:  0.684

Data Source:  STRINGDB

TCN1

Tbio

Novelty:  0.00305315

Score:  0.677

Data Source:  STRINGDB

TCN2

Tbio

Novelty:  0.00213334

Score:  0.671

Data Source:  STRINGDB

Pathways (20)

Reactome (17)

KEGG (1)

WikiPathways (2)

Cobalamin (Cbl, vitamin B12) transport and metabolism (R-HSA-196741)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Cobalamin (Cbl, vitamin B12) transport and metabolism	19 targets	R-HSA-196741
Reactome	Defective AMN causes hereditary megaloblastic anemia 1	2 targets	R-HSA-3359462
Reactome	Defective CUBN causes hereditary megaloblastic anemia 1	2 targets	R-HSA-3359463
Reactome	Defects in cobalamin (B12) metabolism	12 targets	R-HSA-3296469
Reactome	Defects in vitamin and cofactor metabolism	20 targets	R-HSA-3296482

Name	Explore in Pharos	Explore in Source
Cobalamin (Cbl, vitamin B12) transport and metabolism	19 targets	R-HSA-196741
Defective AMN causes hereditary megaloblastic anemia 1	2 targets	R-HSA-3359462
Defective CUBN causes hereditary megaloblastic anemia 1	2 targets	R-HSA-3359463
Defects in cobalamin (B12) metabolism	12 targets	R-HSA-3296469
Defects in vitamin and cofactor metabolism	20 targets	R-HSA-3296482

Gene Ontology Terms (49)

Functions (9)

Components (20)

Processes (20)

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1 – 9 of 9

GO Term	Evidence	Assigned by
protein homodimerization activity	Inferred from Direct Assay (IDA)	UniProtKB
cargo receptor activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
channel regulator activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
hemoglobin binding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
signaling receptor activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
drug binding	Inferred from Sequence or structural Similarity (ISS)	UniProtKB
transporter activity	Traceable Author Statement (TAS)	ProtInc
calcium ion binding	Inferred from Electronic Annotation (IEA)	InterPro
cobalamin binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

GWAS Traits (17)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
urinary albumin to creatinine ratio	EFO_0007778	7	9	15		99.4
albuminuria	EFO_0004285	3	5	8		98.8
Moderate albuminuria	HP_0012594	2	2	1	1.8	94.7
urinary microalbumin measurement	EFO_0010967	1	4	4		93.1
total cholesterol measurement	EFO_0004574	3	2	3		78.7

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
urinary albumin to creatinine ratio	EFO_0007778	15		99.4
albuminuria	EFO_0004285	8		98.8
Moderate albuminuria	HP_0012594	1	1.8	94.7
urinary microalbumin measurement	EFO_0010967	4		93.1
total cholesterol measurement	EFO_0004574	3		78.7

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Calcium
Cell membrane
Cholesterol metabolism
Cleavage on pair of basic residues
Coated pit
Cobalamin
Cobalt
Complete proteome
Direct protein sequencing

GWAS Trait Find Similar Targets

No Header	No Header
albuminuria
aspartate aminotransferase measurement
gut microbiome measurement
high density lipoprotein cholesterol measurement
homocysteine measurement
low density lipoprotein cholesterol measurement
Moderate albuminuria
platelet count
platelet crit
Proteinuria

MGI Phenotype Find Similar Targets

No Header	No Header
cardiovascular system phenotype
embryo phenotype
growth/size/body region phenotype
homeostasis/metabolism phenotype
limbs/digits/tail phenotype
mortality/aging
renal/urinary system phenotype
skeleton phenotype

Orthologs (12)

1 – 5 of 12

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	cubilin	VGNC:5385	450327
Macaque	cubilin [Source:HGNC Symbol;Acc:HGNC:2548]
Mouse	cubilin (intrinsic factor-cobalamin receptor)	MGI:1931256	65969
Rat	cubilin	RGD:68355	80848
Dog	cubilin	VGNC:39725	403767

Species	Name	OMA	EggNOG	Inparanoid
Chimp	cubilin
Macaque	cubilin [Source:HGNC Symbol;Acc:HGNC:2548]
Mouse	cubilin (intrinsic factor-cobalamin receptor)
Rat	cubilin
Dog	cubilin

Publication Statistics

PubMed Score 227.67

PubMed score by year

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PubTator Score 109.67

PubTator score by year

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