Human Gene C2 (ENST00000442278.6) from GENCODE V44
  Description: Homo sapiens complement C2 (C2), transcript variant 2, mRNA. (from RefSeq NM_001145903)
RefSeq Summary (NM_001145903): Component C2 is a serum glycoprotein that functions as part of the classical pathway of the complement system. Activated C1 cleaves C2 into C2a and C2b. The serine proteinase C2a then combines with complement factor 4b to create the C3 or C5 convertase. Deficiency of C2 has been reported to associated with certain autoimmune diseases and SNPs in this gene have been associated with altered susceptibility to age-related macular degeneration. This gene localizes within the class III region of the MHC on the short arm of chromosome 6. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants have been described in publications but their full-length sequence has not been determined.[provided by RefSeq, Mar 2009].
Gencode Transcript: ENST00000442278.6
Gencode Gene: ENSG00000166278.16
Transcript (Including UTRs)
   Position: hg38 chr6:31,927,496-31,945,671 Size: 18,176 Total Exon Count: 16 Strand: +
Coding Region
   Position: hg38 chr6:31,927,753-31,945,357 Size: 17,605 Coding Exon Count: 16 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr6:31,927,496-31,945,671)mRNA (may differ from genome)Protein (620 aa)
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OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: CO2_HUMAN
DESCRIPTION: RecName: Full=Complement C2; EC=3.4.21.43; AltName: Full=C3/C5 convertase; Contains: RecName: Full=Complement C2b fragment; Contains: RecName: Full=Complement C2a fragment; Flags: Precursor;
FUNCTION: Component C2 which is part of the classical pathway of the complement system is cleaved by activated factor C1 into two fragments: C2b and C2a. C2a, a serine protease, then combines with complement factor 4b to generate the C3 or C5 convertase.
CATALYTIC ACTIVITY: Selective cleavage of Arg-|-Ser bond in complement component C3 alpha-chain to form C3a and C3b, and Arg-|-Xaa bond in complement component C5 alpha-chain to form C5a and C5b.
SUBUNIT: C2a interacts with Schistosoma haematobium TOR (via N- terminal extracellular domain). This results in inhibition of the classical and lectin pathway of complement activation, probably due to interference with binding of C2a to C4b such that C3 convertase cannot be formed. This infers resistance to complement- mediated cell lysis, allowing parasite survival and infection.
SUBCELLULAR LOCATION: Secreted.
POLYMORPHISM: The variant Asp-318 is associated with a reduced risk of age-related macular degeneration (ARMD) [MIM:603075]. ARMD is a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world.
DISEASE: Defects in C2 are the cause of complement component 2 deficiency (C2D) [MIM:217000]. A deficiency of the complement classical pathway associated with the development of autoimmune disorders, mainly systemic lupus erythematosus. Skin and joint manifestations are common and renal disease is relatively rare. Patients with complement component 2 deficiency are also reported to have recurrent or invasive infections.
MISCELLANEOUS: C2 is a major histocompatibility complex class-III protein.
SIMILARITY: Belongs to the peptidase S1 family.
SIMILARITY: Contains 1 peptidase S1 domain.
SIMILARITY: Contains 3 Sushi (CCP/SCR) domains.
SIMILARITY: Contains 1 VWFA domain.
WEB RESOURCE: Name=C2base; Note=C2 mutation db; URL="http://bioinf.uta.fi/C2base/";
WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/c2/";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: C2
Diseases sorted by gene-association score: c2 deficiency* (828), macular degeneration, age-related, 14, reduced risk of* (575), immunodeficiency due to a classical component pathway complement deficiency* (350), complement component c2 deficiency* (100), macular degeneration, age-related, 1* (29), tympanic membrane disease (11), complement deficiency (8), arachnoiditis (7), retinal drusen (7), eye disease (7), lupus erythematosus (6), meningocele (5), systemic lupus erythematosus (5)
* = Manually curated disease association

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

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 48.04 RPKM in Liver
Total median expression: 120.51 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 -72.20257-0.281 Picture PostScript Text
3' UTR -78.20314-0.249 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
IPR011360 - Compl_C2_B
IPR016060 - Complement_control_module
IPR009003 - Pept_cys/ser_Trypsin-like
IPR018114 - Peptidase_S1/S6_AS
IPR001254 - Peptidase_S1_S6
IPR001314 - Peptidase_S1A
IPR000436 - Sushi_SCR_CCP
IPR002035 - VWF_A

Pfam Domains:
PF00084 - Sushi repeat (SCR repeat)
PF00089 - Trypsin
PF00092 - von Willebrand factor type A domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
2I6Q - X-ray MuPIT 2I6S - X-ray MuPIT 2ODP - X-ray MuPIT 2ODQ - X-ray MuPIT 3ERB - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P06681
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-  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
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004252 serine-type endopeptidase activity
GO:0005515 protein binding
GO:0008233 peptidase activity
GO:0008236 serine-type peptidase activity
GO:0016787 hydrolase activity
GO:0046872 metal ion binding

Biological Process:
GO:0002376 immune system process
GO:0006508 proteolysis
GO:0006956 complement activation
GO:0006958 complement activation, classical pathway
GO:0007584 response to nutrient
GO:0030449 regulation of complement activation
GO:0045087 innate immune response
GO:2000427 positive regulation of apoptotic cell clearance

Cellular Component:
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  AK298808 - Homo sapiens cDNA FLJ54376 complete cds, highly similar to Complement C2 precursor (EC 3.4.21.43).
AK096258 - Homo sapiens cDNA FLJ38939 fis, clone NT2NE2015747, highly similar to COMPLEMENT C2 PRECURSOR (EC 3.4.21.43).
AK298311 - Homo sapiens cDNA FLJ59728 complete cds, highly similar to Complement C2 precursor (EC 3.4.21.43).
M26301 - Huma complement component C2 mRNA, 5' end.
AK312581 - Homo sapiens cDNA, FLJ92956, Homo sapiens complement component 2 (C2), mRNA.
AK304045 - Homo sapiens cDNA FLJ55673 complete cds, highly similar to Complement factor B precursor (EC 3.4.21.47).
BC029781 - Homo sapiens complement component 2, mRNA (cDNA clone IMAGE:5183067), complete cds.
AK300892 - Homo sapiens cDNA FLJ54076 complete cds, highly similar to Complement C2 precursor (EC 3.4.21.43).
X04481 - Human mRNA for complement component C2.
AK307930 - Homo sapiens cDNA, FLJ97878.
AK222537 - Homo sapiens mRNA for complement component 2 precursor variant, clone: adSE01995.
AK300930 - Homo sapiens cDNA FLJ55526 complete cds, highly similar to Complement C2 precursor (EC 3.4.21.43).
BC043484 - Homo sapiens complement component 2, mRNA (cDNA clone MGC:49826 IMAGE:5763774), complete cds.
KJ890790 - Synthetic construct Homo sapiens clone ccsbBroadEn_00184 C2 gene, encodes complete protein.
KR712045 - Synthetic construct Homo sapiens clone CCSBHm_00035064 C2 (C2) mRNA, encodes complete protein.
KR712046 - Synthetic construct Homo sapiens clone CCSBHm_00035065 C2 (C2) mRNA, encodes complete protein.
KR712047 - Synthetic construct Homo sapiens clone CCSBHm_00035066 C2 (C2) mRNA, encodes complete protein.
KR712048 - Synthetic construct Homo sapiens clone CCSBHm_00035067 C2 (C2) mRNA, encodes complete protein.
KR712211 - Synthetic construct Homo sapiens clone CCSBHm_00900164 C2 (C2) mRNA, encodes complete protein.
AK222783 - Homo sapiens mRNA for complement component 2 precursor variant, clone: HEP01788.
BX537504 - Homo sapiens mRNA; cDNA DKFZp779M0311 (from clone DKFZp779M0311).
JD367443 - Sequence 348467 from Patent EP1572962.
JD192522 - Sequence 173546 from Patent EP1572962.
JD102926 - Sequence 83950 from Patent EP1572962.
JD390474 - Sequence 371498 from Patent EP1572962.
JD116055 - Sequence 97079 from Patent EP1572962.
JD488212 - Sequence 469236 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04610 - Complement and coagulation cascades
hsa05322 - Systemic lupus erythematosus

BioCarta from NCI Cancer Genome Anatomy Project
h_compPathway - Complement Pathway
h_classicPathway - Classical Complement Pathway
h_lectinPathway - Lectin Induced Complement Pathway

Reactome (by CSHL, EBI, and GO)

Protein P06681 (Reactome details) participates in the following event(s):

R-HSA-166792 Conversion of C2 into C2a and C2b
R-HSA-166795 Formation of Classical C3 convertase (C4b:C2a complex)
R-HSA-977619 CD55 (DAF) promotes C3bBb/C4bC2a dissociation
R-HSA-977629 Displacement of C2a/Bb by CR1
R-HSA-981621 C3 convertases spontaneously dissociate
R-HSA-173636 Formation of classic pathway C5 convertase
R-HSA-977375 CR1 binds C3bBb/C4bC2a
R-HSA-981535 CD55 (DAF) binds C3bBb, C4bC2a
R-HSA-166817 Cleavage of C3 by C3 convertases
R-HSA-173680 Activation of C5
R-HSA-166663 Initial triggering of complement
R-HSA-977606 Regulation of Complement cascade
R-HSA-166658 Complement cascade
R-HSA-174577 Activation of C3 and C5
R-HSA-168249 Innate Immune System
R-HSA-168256 Immune System

-  Other Names for This Gene
  Alternate Gene Symbols: B4DPF3, CO2_HUMAN, ENST00000442278.1, ENST00000442278.2, ENST00000442278.3, ENST00000442278.4, ENST00000442278.5, NM_001145903, O19694, P06681, Q13904, uc010jtk.1, uc010jtk.2, uc010jtk.3, uc010jtk.4, uc010jtk.5
UCSC ID: ENST00000442278.6
RefSeq Accession: NM_001145903
Protein: P06681 (aka CO2_HUMAN)
CCDS: CCDS54991.1

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