Human Gene COL3A1 (uc002uqj.1) Description and Page Index
  Description: Homo sapiens collagen, type III, alpha 1 (COL3A1), mRNA.
RefSeq Summary (NM_000090): This gene encodes the pro-alpha1 chains of type III collagen, a fibrillar collagen that is found in extensible connective tissues such as skin, lung, uterus, intestine and the vascular system, frequently in association with type I collagen. Mutations in this gene are associated with Ehlers-Danlos syndrome types IV, and with aortic and arterial aneurysms. Two transcripts, resulting from the use of alternate polyadenylation signals, have been identified for this gene. [provided by R. Dalgleish, Feb 2008]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: X14420.1, SRR1660809.108164.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA1965299, SAMEA1966682 [ECO:0000348] ##Evidence-Data-END## ##RefSeq-Attributes-START## RefSeq Select criteria :: based on single protein-coding transcript ##RefSeq-Attributes-END##
Transcript (Including UTRs)
   Position: hg19 chr2:189,839,099-189,877,472 Size: 38,374 Total Exon Count: 51 Strand: +
Coding Region
   Position: hg19 chr2:189,839,216-189,876,500 Size: 37,285 Coding Exon Count: 51 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviewsModel Information
Methods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr2:189,839,099-189,877,472)mRNA (may differ from genome)Protein (1466 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMGI
neXtProtOMIMPubMedReactomeStanford SOURCETreefam
UniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: CO3A1_HUMAN
DESCRIPTION: RecName: Full=Collagen alpha-1(III) chain; Flags: Precursor;
FUNCTION: Collagen type III occurs in most soft connective tissues along with type I collagen.
SUBUNIT: Trimers of identical alpha 1(III) chains. The chains are linked to each other by interchain disulfide bonds. Trimers are also cross-linked via hydroxylysines.
SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix (By similarity).
DOMAIN: The C-terminal propeptide, also known as COLFI domain, have crucial roles in tissue growth and repair by controlling both the intracellular assembly of procollagen molecules and the extracellular assembly of collagen fibrils. It binds a calcium ion which is essential for its function.
PTM: Proline residues at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.
PTM: O-linked glycan consists of a Glc-Gal disaccharide bound to the oxygen atom of a post-translationally added hydroxyl group.
DISEASE: Defects in COL3A1 are a cause of Ehlers-Danlos syndrome type 3 (EDS3) [MIM:130020]; also known as benign hypermobility syndrome. EDS is a connective tissue disorder characterized by hyperextensible skin, atrophic cutaneous scars due to tissue fragility and joint hyperlaxity. EDS3 is a form of Ehlers-Danlos syndrome characterized by marked joint hyperextensibility without skeletal deformity.
DISEASE: Defects in COL3A1 are the cause of Ehlers-Danlos syndrome type 4 (EDS4) [MIM:130050]. EDS is a connective tissue disorder characterized by hyperextensible skin, atrophic cutaneous scars due to tissue fragility and joint hyperlaxity. EDS4 is the most severe form of the disease. It is characterized by the joint and dermal manifestations as in other forms of the syndrome, characteristic facial features (acrogeria) in most patients, and by proneness to spontaneous rupture of bowel and large arteries. The vascular complications may affect all anatomical areas.
DISEASE: Defects in COL3A1 are a cause of susceptibility to aortic aneurysm abdominal (AAA) [MIM:100070]. AAA is a common multifactorial disorder characterized by permanent dilation of the abdominal aorta, usually due to degenerative changes in the aortic wall. Histologically, AAA is characterized by signs of chronic inflammation, destructive remodeling of the extracellular matrix, and depletion of vascular smooth muscle cells.
SIMILARITY: Belongs to the fibrillar collagen family.
SIMILARITY: Contains 1 fibrillar collagen NC1 domain.
SIMILARITY: Contains 1 VWFC domain.
WEB RESOURCE: Name=COL3A1; Note=Collagen type III alpha-1 chain mutations; URL="http://www.le.ac.uk/genetics/collagen/col3a1.html";
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/COL3A1";
WEB RESOURCE: Name=Wikipedia; Note=Type-III collagen entry; URL="http://en.wikipedia.org/wiki/Type-III_collagen";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): COL3A1
CDC HuGE Published Literature: COL3A1
Positive Disease Associations: coronary artery disease , Ehlers-Danlos syndrome type IV , mild Ehlers-Danlos syndrome type IV , mitral valve prolapse
Related Studies:
  1. coronary artery disease
    Muckian, C. et al. 2002, Genetic variability in the extracellular matrix as a determinant of cardiovascular risk: associationof type III collagen COL3A1 polymorphisms with coronary artery disease, Blood. 2002 Aug;100(4):1220-3. [PubMed 12149201]
    We conclude that variants in the COL3A1 gene, the product of which is a vessel-wall protein and platelet ligand, modulate the risk of coronary artery disease and could also modulate the response to antithrombotic therapy. This is the first reported association between polymorphisms of extracellular matrix components and cardiovascular risk.
  2. Ehlers-Danlos syndrome type IV
    Lee B et al. 1991, Characterization of a large deletion associated with a polymorphic block of repeated dinucleotides in the type III procollagen gene (COL3A1) of a patient with Ehlers-Danlos syndrome type IV., American journal of human genetics. 1991 Mar;48(3):511-7. [PubMed 1998337]
  3. mild Ehlers-Danlos syndrome type IV
    Vissing H et al. 1991, Multiexon deletion in the procollagen III gene is associated with mild Ehlers-Danlos syndrome type IV., The Journal of biological chemistry. 1991 Mar;266(8):5244-8. [PubMed 2002056]
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: COL3A1
Diseases sorted by gene-association score: ehlers-danlos syndrome, type iv* (1693), acrogeria, gottron type* (368), ehlers-danlos syndrome, hypermobility type* (134), thoracic aortic aneurysms and aortic dissections* (115), ehlers-danlos syndrome (89), familial abdominal aortic aneurysm* (25), intracranial aneurysm (17), ehlers-danlos syndrome, classic type (15), familial cerebral saccular aneurysm* (14), hypermobility syndrome (13), hiatus hernia (13), larsen-like syndrome (9), hemopneumothorax (8), connective tissue disease (8), collagen disease (7), lipoblastoma (6), char syndrome (6), loeys-dietz syndrome (5), aortic aneurysm, familial thoracic 1 (4), sed congenita (4)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 743.89 RPKM in Cells - Transformed fibroblasts
Total median expression: 4870.75 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -28.00117-0.239 Picture PostScript Text
3' UTR -188.39972-0.194 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR008160 - Collagen
IPR000885 - Fib_collagen_C
IPR001007 - VWF_C

Pfam Domains:
PF00093 - von Willebrand factor type C domain
PF01391 - Collagen triple helix repeat (20 copies)
PF01410 - Fibrillar collagen C-terminal domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help

2V53
- X-ray MuPIT

3DMW
- X-ray

4AE2
- X-ray MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
4AEJ - X-ray MuPIT 4AK3 - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P02461
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGD    
 Protein Sequence    
 Alignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0002020 protease binding
GO:0005178 integrin binding
GO:0005201 extracellular matrix structural constituent
GO:0005515 protein binding
GO:0046332 SMAD binding
GO:0046872 metal ion binding
GO:0048407 platelet-derived growth factor binding

Biological Process:
GO:0001501 skeletal system development
GO:0001568 blood vessel development
GO:0007160 cell-matrix adhesion
GO:0007179 transforming growth factor beta receptor signaling pathway
GO:0007229 integrin-mediated signaling pathway
GO:0007507 heart development
GO:0007568 aging
GO:0009314 response to radiation
GO:0009612 response to mechanical stimulus
GO:0018149 peptide cross-linking
GO:0021987 cerebral cortex development
GO:0030168 platelet activation
GO:0030198 extracellular matrix organization
GO:0030199 collagen fibril organization
GO:0034097 response to cytokine
GO:0035025 positive regulation of Rho protein signal transduction
GO:0042060 wound healing
GO:0043588 skin development
GO:0048565 digestive tract development
GO:0050776 regulation of immune response
GO:0050777 negative regulation of immune response
GO:0060414 aorta smooth muscle tissue morphogenesis
GO:0071230 cellular response to amino acid stimulus
GO:0097435 supramolecular fiber organization
GO:2001223 negative regulation of neuron migration

Cellular Component:
GO:0005576 extracellular region
GO:0005581 collagen trimer
GO:0005586 collagen type III trimer
GO:0005615 extracellular space
GO:0005788 endoplasmic reticulum lumen
GO:0031012 extracellular matrix


-  Descriptions from all associated GenBank mRNAs
  LF205196 - JP 2014500723-A/12699: Polycomb-Associated Non-Coding RNAs.
AK308010 - Homo sapiens cDNA, FLJ97958.
BC028178 - Homo sapiens collagen, type III, alpha 1, mRNA (cDNA clone MGC:39848 IMAGE:5405119), complete cds.
E10600 - cDNA encoding human type 3 collagen alpha 1.
X14420 - Human mRNA for pro-alpha-1 type 3 collagen.
BX649097 - Homo sapiens mRNA; cDNA DKFZp686M0856 (from clone DKFZp686M0856).
AB384877 - Synthetic construct DNA, clone: pF1KB3954, Homo sapiens COL3A1 gene for collagen alpha-1(III) chain precursor, complete cds, without stop codon, in Flexi system.
X07240 - Human mRNA for prepro alpha1(III) collagen (N-term.).
LF317593 - JP 2014500723-A/125096: Polycomb-Associated Non-Coding RNAs.
LF317597 - JP 2014500723-A/125100: Polycomb-Associated Non-Coding RNAs.
LF317598 - JP 2014500723-A/125101: Polycomb-Associated Non-Coding RNAs.
X15332 - Human COL3A1 mRNA for pro alpha-1 (III) collagen.
JA187668 - Sequence 32 from Patent WO2011019793.
JA187669 - Sequence 33 from Patent WO2011019793.
LF317599 - JP 2014500723-A/125102: Polycomb-Associated Non-Coding RNAs.
S79877 - COL3A1=type III collagen alpha 1(III) chain {alternatively spliced, exon-17-skipping} [human, type IV Ehlers-Danlos syndrome patient, fibroblast culture, mRNA Mutant, 268 nt].
LF317600 - JP 2014500723-A/125103: Polycomb-Associated Non-Coding RNAs.
LF317601 - JP 2014500723-A/125104: Polycomb-Associated Non-Coding RNAs.
LF317602 - JP 2014500723-A/125105: Polycomb-Associated Non-Coding RNAs.
LF317603 - JP 2014500723-A/125106: Polycomb-Associated Non-Coding RNAs.
LF317604 - JP 2014500723-A/125107: Polycomb-Associated Non-Coding RNAs.
LF317605 - JP 2014500723-A/125108: Polycomb-Associated Non-Coding RNAs.
LF317606 - JP 2014500723-A/125109: Polycomb-Associated Non-Coding RNAs.
LF317607 - JP 2014500723-A/125110: Polycomb-Associated Non-Coding RNAs.
M59227 - Human alpha-1 collagen type III (COL3A1) mRNA, partial cds.
X06700 - Human mRNA 3' region for pro-alpha1(III) collagen.
LF317608 - JP 2014500723-A/125111: Polycomb-Associated Non-Coding RNAs.
LF317609 - JP 2014500723-A/125112: Polycomb-Associated Non-Coding RNAs.
LF317610 - JP 2014500723-A/125113: Polycomb-Associated Non-Coding RNAs.
X01655 - Human mRNA for alpha 1 (III) collagen fragment (aa 892-1023).
LF317611 - JP 2014500723-A/125114: Polycomb-Associated Non-Coding RNAs.
LF317612 - JP 2014500723-A/125115: Polycomb-Associated Non-Coding RNAs.
M13146 - Human alpha-1 type III collagen mRNA, partial cds.
M11134 - Human procollagen type III alpha-1 chain, mRNA.
AK091853 - Homo sapiens cDNA FLJ34534 fis, clone HLUNG2008333, highly similar to Alpha1 (III) collagen.
AX747222 - Sequence 747 from Patent EP1308459.
LF317613 - JP 2014500723-A/125116: Polycomb-Associated Non-Coding RNAs.
X01742 - Human mRNA for pro alpha 1 (III) collagen C-terminal propeptide.
LF317614 - JP 2014500723-A/125117: Polycomb-Associated Non-Coding RNAs.
AK021490 - Homo sapiens cDNA FLJ11428 fis, clone HEMBA1001071, highly similar to PROCOLLAGEN ALPHA 1(III) CHAIN PRECURSOR.
LF317615 - JP 2014500723-A/125118: Polycomb-Associated Non-Coding RNAs.
LF317616 - JP 2014500723-A/125119: Polycomb-Associated Non-Coding RNAs.
LF317617 - JP 2014500723-A/125120: Polycomb-Associated Non-Coding RNAs.
LF317618 - JP 2014500723-A/125121: Polycomb-Associated Non-Coding RNAs.
LF317619 - JP 2014500723-A/125122: Polycomb-Associated Non-Coding RNAs.
LF317620 - JP 2014500723-A/125123: Polycomb-Associated Non-Coding RNAs.
JD244239 - Sequence 225263 from Patent EP1572962.
LF317621 - JP 2014500723-A/125124: Polycomb-Associated Non-Coding RNAs.
MA265475 - JP 2017503859-A/17: Materials and methods for modulation of tendon healing.
JD360313 - Sequence 341337 from Patent EP1572962.
JD019790 - Sequence 814 from Patent EP1572962.
JD028340 - Sequence 9364 from Patent EP1572962.
JD145845 - Sequence 126869 from Patent EP1572962.
LF317622 - JP 2014500723-A/125125: Polycomb-Associated Non-Coding RNAs.
JD263216 - Sequence 244240 from Patent EP1572962.
JD048302 - Sequence 29326 from Patent EP1572962.
LF317623 - JP 2014500723-A/125126: Polycomb-Associated Non-Coding RNAs.
JD318367 - Sequence 299391 from Patent EP1572962.
JD343482 - Sequence 324506 from Patent EP1572962.
MA440773 - JP 2018138019-A/12699: Polycomb-Associated Non-Coding RNAs.
MA553170 - JP 2018138019-A/125096: Polycomb-Associated Non-Coding RNAs.
MA553174 - JP 2018138019-A/125100: Polycomb-Associated Non-Coding RNAs.
MA553175 - JP 2018138019-A/125101: Polycomb-Associated Non-Coding RNAs.
MA553176 - JP 2018138019-A/125102: Polycomb-Associated Non-Coding RNAs.
MA553177 - JP 2018138019-A/125103: Polycomb-Associated Non-Coding RNAs.
MA553178 - JP 2018138019-A/125104: Polycomb-Associated Non-Coding RNAs.
MA553179 - JP 2018138019-A/125105: Polycomb-Associated Non-Coding RNAs.
MA553180 - JP 2018138019-A/125106: Polycomb-Associated Non-Coding RNAs.
MA553181 - JP 2018138019-A/125107: Polycomb-Associated Non-Coding RNAs.
MA553182 - JP 2018138019-A/125108: Polycomb-Associated Non-Coding RNAs.
MA553183 - JP 2018138019-A/125109: Polycomb-Associated Non-Coding RNAs.
MA553184 - JP 2018138019-A/125110: Polycomb-Associated Non-Coding RNAs.
MA553185 - JP 2018138019-A/125111: Polycomb-Associated Non-Coding RNAs.
MA553186 - JP 2018138019-A/125112: Polycomb-Associated Non-Coding RNAs.
MA553187 - JP 2018138019-A/125113: Polycomb-Associated Non-Coding RNAs.
MA553188 - JP 2018138019-A/125114: Polycomb-Associated Non-Coding RNAs.
MA553189 - JP 2018138019-A/125115: Polycomb-Associated Non-Coding RNAs.
MA553190 - JP 2018138019-A/125116: Polycomb-Associated Non-Coding RNAs.
MA553191 - JP 2018138019-A/125117: Polycomb-Associated Non-Coding RNAs.
MA553192 - JP 2018138019-A/125118: Polycomb-Associated Non-Coding RNAs.
MA553193 - JP 2018138019-A/125119: Polycomb-Associated Non-Coding RNAs.
MA553194 - JP 2018138019-A/125120: Polycomb-Associated Non-Coding RNAs.
MA553195 - JP 2018138019-A/125121: Polycomb-Associated Non-Coding RNAs.
MA553196 - JP 2018138019-A/125122: Polycomb-Associated Non-Coding RNAs.
MA553197 - JP 2018138019-A/125123: Polycomb-Associated Non-Coding RNAs.
MA553198 - JP 2018138019-A/125124: Polycomb-Associated Non-Coding RNAs.
MA553199 - JP 2018138019-A/125125: Polycomb-Associated Non-Coding RNAs.
MA553200 - JP 2018138019-A/125126: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04510 - Focal adhesion
hsa04512 - ECM-receptor interaction

Reactome (by CSHL, EBI, and GO)

Protein P02461 (Reactome details) participates in the following event(s):

R-HSA-2002460 P4HB binds Collagen chains
R-HSA-8944240 Association of procollagen type III
R-HSA-8948230 P3HB binds 4-Hyp-collagen propeptides
R-HSA-1650808 Prolyl 4-hydroxylase converts collagen prolines to 4-hydroxyprolines
R-HSA-1980233 Collagen prolyl 3-hydroxylase converts 4-Hyp collagen to 3,4-Hyp collagen
R-HSA-8948219 PLOD3 binds Lysyl hydroxylated collagen propeptides
R-HSA-8948228 COLGALT1,COLGALT2 bind Lysyl hydroxylated collagen propeptides
R-HSA-2002440 Removal of fibrillar collagen C-propeptides
R-HSA-3221843 MSR1 (SCARA1) binds collagen
R-HSA-2022073 Procollagen triple helix formation
R-HSA-1981104 Procollagen lysyl hydroxylases convert collagen lysines to 5-hydroxylysines
R-HSA-1981120 Galactosylation of collagen propeptide hydroxylysines by procollagen galactosyltransferases 1, 2.
R-HSA-1981128 Galactosylation of collagen propeptide hydroxylysines by PLOD3
R-HSA-1981157 Glucosylation of collagen propeptide hydroxylysines
R-HSA-2002428 Removal of fibrillar collagen N-propeptides
R-HSA-1650814 Collagen biosynthesis and modifying enzymes
R-HSA-8948216 Collagen chain trimerization
R-HSA-1474290 Collagen formation
R-HSA-2022090 Assembly of collagen fibrils and other multimeric structures
R-HSA-3000480 Scavenging by Class A Receptors
R-HSA-1474244 Extracellular matrix organization
R-HSA-2173782 Binding and Uptake of Ligands by Scavenger Receptors
R-HSA-5653656 Vesicle-mediated transport

-  Other Names for This Gene
  Alternate Gene Symbols: CO3A1_HUMAN, D3DPH4, NM_000090, NP_000081, P02461, P78429, Q15112, Q16403, Q53S91, Q541P8, Q6LDB3, Q6LDJ2, Q6LDJ3, Q7KZ56, Q8N6U4, Q9UC88, Q9UC89, Q9UC90, Q9UC91
UCSC ID: uc002uqj.1
RefSeq Accession: NM_000090
Protein: P02461 (aka CO3A1_HUMAN or CA13_HUMAN)
CCDS: CCDS2297.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene COL3A1:
cdh-ov (Congenital Diaphragmatic Hernia Overview)
eds4 (Vascular Ehlers-Danlos Syndrome)
taa (Heritable Thoracic Aortic Disease Overview)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_000090.3
exon count: 51CDS single in 3' UTR: no RNA size: 5490
ORF size: 4401CDS single in intron: no Alignment % ID: 99.98
txCdsPredict score: 8941.50frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.