Tbio COL4A3 Collagen alpha-3(IV) chain

Protein Summary

Description

Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen. Tumstatin, a cleavage fragment corresponding to the collagen alpha 3(IV) NC1 domain, possesses both anti-angiogenic and anti-tumor cell activity; these two anti-tumor properties may be regulated via RGD-independent ITGB3-mediated mechanisms. Type IV collagen, the major structural component of basement membranes, is a multimeric protein composed of 3 alpha subunits. These subunits are encoded by 6 different genes, alpha 1 through alpha 6, each of which can form a triple helix structure with 2 other subunits to form type IV collagen. This gene encodes alpha 3. In the Goodpasture syndrome, autoantibodies bind to the collagen molecules in the basement membranes of alveoli and glomeruli. The epitopes that elicit these autoantibodies are localized largely to the non-collagenous C-terminal domain of the protein. A specific kinase phosphorylates amino acids in this same C-terminal region and the expression of this kinase is upregulated during pathogenesis. This gene is also linked to an autosomal recessive form of Alport syndrome. The mutations contributing to this syndrome are also located within the exons that encode this C-terminal region. Like the other members of the type IV collagen gene family, this gene is organized in a head-to-head conformation with another type IV collagen gene so that each gene pair shares a common promoter. [provided by RefSeq, Jun 2010]

Uniprot Accession IDs

• Q01955
• Q53QQ1
• Q53R14
• Q53RW8
• Q9BQT2
• Q9NYC4
• Q9UDJ9
• Q9UDK9
• Q9UDL0
• Q9UDL1

Gene Name

• COL4A3

Ensembl ID

• ENST00000396578
• ENSP00000379823
• ENSG00000169031

Symbol

• ATS2
• ATS3

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
gene perturbation	0.92
biological process	0.81
kinase perturbation	0.76
transcription factor perturbation	0.74
molecular function	0.7

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GENEVA

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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: 350.88   (req: < 5)

Gene RIFs: 79   (req: <= 3)

Antibodies: 274   (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: 350.88   (req: >= 5)

Gene RIFs: 79   (req: > 3)

Antibodies: 274   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 18

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

GWAS Traits (11)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
central corneal thickness	EFO_0005213	3	3	0	2.4	86.3
type I diabetes mellitus	EFO_0001359	4	1	0	1.3	78.8
intraocular pressure measurement	EFO_0004695	2	2	2		77.6
type 1 diabetes nephropathy	EFO_0004996	3	1	0	1.3	76.2
albuminuria	EFO_0004285	2	1	0	1.2	61.7

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
central corneal thickness	EFO_0005213	0	2.4	86.3
type I diabetes mellitus	EFO_0001359	0	1.3	78.8
intraocular pressure measurement	EFO_0004695	2		77.6
type 1 diabetes nephropathy	EFO_0004996	0	1.3	76.2
albuminuria	EFO_0004285	0	1.2	61.7

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Orthologs (7)

1 – 5 of 7

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Macaque	collagen type IV alpha 3 chain		712444
Mouse	collagen, type IV, alpha 3	MGI:104688	12828
Rat	collagen type IV alpha 3 chain	RGD:71085	363265
Dog	collagen type IV alpha 3 chain		403842
Horse	collagen type IV alpha 3 chain		100037402

Species	Name	OMA	EggNOG	Inparanoid
Macaque	collagen type IV alpha 3 chain
Mouse	collagen, type IV, alpha 3
Rat	collagen type IV alpha 3 chain
Dog	collagen type IV alpha 3 chain
Horse	collagen type IV alpha 3 chain

Protein Data Bank (1)

1 – 1 of 1

PDB Structure Id	Ligand	Method	Resolution (Å)	M.W. (kDa)	Pub Year	Title

PDB Structure Id	M.W.	Resolution	Pub Year

Pathways (33)

Reactome (13)

KEGG (10)

PathwayCommons (6)

WikiPathways (4)

Assembly of collagen fibrils and other multimeric structures (R-HSA-2022090)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Assembly of collagen fibrils and other multimeric structures	57 targets	R-HSA-2022090
Reactome	Axon guidance	533 targets	R-HSA-422475
Reactome	Collagen biosynthesis and modifying enzymes	67 targets	R-HSA-1650814
Reactome	Collagen chain trimerization	44 targets	R-HSA-8948216
Reactome	Collagen formation	90 targets	R-HSA-1474290

Name	Explore in Pharos	Explore in Source
Assembly of collagen fibrils and other multimeric structures	57 targets	R-HSA-2022090
Axon guidance	533 targets	R-HSA-422475
Collagen biosynthesis and modifying enzymes	67 targets	R-HSA-1650814
Collagen chain trimerization	44 targets	R-HSA-8948216
Collagen formation	90 targets	R-HSA-1474290

Gene Ontology Terms (27)

Functions (5)

Components (9)

Processes (13)

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GO Term	Evidence	Assigned by
integrin binding	Inferred from Direct Assay (IDA)	UniProtKB
extracellular matrix structural constituent conferring tensile strength	Inferred from High Throughput Direct Assay (HDA)	BHF-UCL
extracellular matrix structural constituent	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
metalloendopeptidase inhibitor activity	Non-traceable Author Statement (NAS)	UniProtKB
structural molecule activity	Non-traceable Author Statement (NAS)	ProtInc

Protein-Protein Interactions (146)

Explore Interacting Targets

1 – 10 of 146

• See Interactions on String-DB

COL4A4

Tbio

Novelty: 0.00833684

Score: 0.949

Data Source: Reactome,STRINGDB

COL18A1

Tbio

Novelty: 0.00074602

Score: 0.932

Data Source: STRINGDB

COL26A1

Tbio

Novelty: 0.07322658

Score: 0.928

Data Source: STRINGDB

COL8A2

Tbio

Novelty: 0.01672103

Score: 0.926

Data Source: STRINGDB

COL1A1

Tbio

Novelty: 0.00063584

Score: 0.926

Data Source: STRINGDB

COL3A1

Tbio

Novelty: 0.00197327

Score: 0.924

Data Source: STRINGDB

COL15A1

Tbio

Novelty: 0.04078006

Score: 0.924

Data Source: STRINGDB

ITGA3

Tchem

Novelty: 0.00505981

Score: 0.923

Data Source: STRINGDB

ITGA2

Tbio

Novelty: 0.0013482

Score: 0.923

Data Source: STRINGDB

COL1A2

Tbio

Novelty: 0.00048334

Score: 0.923

Data Source: STRINGDB

Publication Statistics

PubMed Score  350.88

PubMed score by year

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PubTator Score  154.13

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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UniProt Keyword Find Similar Targets

3D-structure
Alport syndrome
Alternative splicing
Basement membrane
Cell adhesion
Collagen
Complete proteome
Deafness
Direct protein sequencing
Disease mutation

GWAS Trait Find Similar Targets

age-related macular degeneration
albuminuria
atrophic macular degeneration
central corneal thickness
corneal topography
hematocrit
intraocular pressure measurement
refractive error measurement
type 1 diabetes nephropathy
type I diabetes mellitus

MGI Phenotype Find Similar Targets

behavior/neurological phenotype
cardiovascular system phenotype
cellular phenotype
growth/size/body region phenotype
hearing/vestibular/ear phenotype
homeostasis/metabolism phenotype
immune system phenotype
mortality/aging
renal/urinary system phenotype
vision/eye phenotype