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C4A complement C4A (Rodgers blood group) [ Homo sapiens (human) ]

Gene ID: 720, updated on 24-Nov-2020

Summary

Official Symbol
C4Aprovided by HGNC
Official Full Name
complement C4A (Rodgers blood group)provided by HGNC
Primary source
HGNC:HGNC:1323
See related
Ensembl:ENSG00000244731 MIM:120810
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
C4; RG; C4S; CO4; C4A2; C4A3; C4A4; C4A6; C4AD; CPAMD2
Summary
This gene encodes the acidic form of complement factor 4, part of the classical activation pathway. The protein is expressed as a single chain precursor which is proteolytically cleaved into a trimer of alpha, beta, and gamma chains prior to secretion. The trimer provides a surface for interaction between the antigen-antibody complex and other complement components. The alpha chain is cleaved to release C4 anaphylatoxin, an antimicrobial peptide and a mediator of local inflammation. Deficiency of this protein is associated with systemic lupus erythematosus and type I diabetes mellitus. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. Varying haplotypes of this gene cluster exist, such that individuals may have 1, 2, or 3 copies of this gene. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2014]
Expression
Biased expression in liver (RPKM 487.9), adrenal (RPKM 99.6) and 7 other tissues See more
Orthologs

Genomic context

See C4A in Genome Data Viewer
Location:
6p21.33
Exon count:
41
Annotation release Status Assembly Chr Location
109.20201120 current GRCh38.p13 (GCF_000001405.39) 6 NC_000006.12 (31982057..32002681)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (31949834..31970457)

Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene Ski2 like RNA helicase Neighboring gene serine/threonine kinase 19 Neighboring gene decapping exoribonuclease Neighboring gene CYP21A1P recombination region Neighboring gene cytochrome P450 family 21 subfamily A member 1, pseudogene Neighboring gene tenascin XA (pseudogene) recombination region Neighboring gene tenascin XA (pseudogene)

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Blood group, Chido/Rodgers system
MedGen: C1292315 OMIM: 614374 GeneReviews: Not available
Compare labs
Complement component 4a deficiency
MedGen: C1852692 OMIM: 614380 GeneReviews: Not available
Compare labs
Genome-wide association study for serum complement C3 and C4 levels in healthy Chinese subjects.
GeneReviews: Not available
Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array.
GeneReviews: Not available

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • FLJ60561, MGC164979

Gene Ontology Provided by GOA

Function Evidence Code Pubs
complement component C1q complex binding IDA
Inferred from Direct Assay
more info
PubMed 
endopeptidase inhibitor activity IEA
Inferred from Electronic Annotation
more info
 
Process Evidence Code Pubs
cellular protein metabolic process TAS
Traceable Author Statement
more info
 
complement activation IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
complement activation IGI
Inferred from Genetic Interaction
more info
PubMed 
complement activation TAS
Traceable Author Statement
more info
 
complement activation, classical pathway IEA
Inferred from Electronic Annotation
more info
 
inflammatory response IEA
Inferred from Electronic Annotation
more info
 
innate immune response IEA
Inferred from Electronic Annotation
more info
 
negative regulation of endopeptidase activity IEA
Inferred from Electronic Annotation
more info
 
positive regulation of apoptotic cell clearance IGI
Inferred from Genetic Interaction
more info
PubMed 
post-translational protein modification TAS
Traceable Author Statement
more info
 
regulation of complement activation TAS
Traceable Author Statement
more info
 
Component Evidence Code Pubs
axon IDA
Inferred from Direct Assay
more info
PubMed 
blood microparticle HDA PubMed 
dendrite IDA
Inferred from Direct Assay
more info
PubMed 
endoplasmic reticulum lumen TAS
Traceable Author Statement
more info
 
extracellular exosome HDA PubMed 
extracellular region TAS
Traceable Author Statement
more info
 
extracellular space HDA PubMed 
extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
extracellular space IDA
Inferred from Direct Assay
more info
PubMed 
neuronal cell body IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 
synapse IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

Preferred Names
complement C4-A
Names
C3 and PZP-like alpha-2-macroglobulin domain-containing protein 2
C4A anaphylatoxin
MHC class III region complement
Rodgers form of C4
acidic C4
acidic complement C4
complement component 4A (Rodgers blood group)

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

  1. NG_011638.1 RefSeqGene

    Range
    5001..25624
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_137

mRNA and Protein(s)

  1. NM_001252204.2NP_001239133.1  complement C4-A isoform 2 preproprotein

    See identical proteins and their annotated locations for NP_001239133.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame segment compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.
    Source sequence(s)
    AL645922, BC146673, DA304049, K02403
    Consensus CDS
    CCDS59005.1
    UniProtKB/Swiss-Prot
    P0C0L4
    Related
    ENSP00000420212.1, ENST00000498271.1
    Conserved Domains (8) summary
    cd00017
    Location:686750
    ANATO; Anaphylatoxin homologous domain; C3a, C4a and C5a anaphylatoxins are protein fragments generated enzymatically in serum during activation of complement molecules C3, C4, and C5. They induce smooth muscle contraction. These fragments are homologous to ...
    cd02896
    Location:9961315
    complement_C3_C4_C5; Proteins similar to C3, C4 and C5 of vertebrate complement. The vertebrate complement system, comprised of a large number of distinct plasma proteins, is an effector of both the acquired and innate immune systems. The point of convergence of the ...
    cd03584
    Location:15421696
    NTR_complement_C4; NTR/C345C domain, complement C4 subfamily; The NTR domain found in complement C4 is also known as the C345C domain because it occurs at the C-terminus of complement C3, C4 and C5. Complement C4 is a key player in the activation of the component classical ...
    pfam00207
    Location:782869
    A2M; Alpha-2-macroglobulin family
    pfam01835
    Location:141233
    A2M_N; MG2 domain
    pfam07677
    Location:14621524
    A2M_recep; A-macroglobulin receptor
    pfam07678
    Location:10511317
    A2M_comp; A-macroglobulin complement component
    pfam07703
    Location:478610
    A2M_N_2; Alpha-2-macroglobulin family N-terminal region
  2. NM_007293.3NP_009224.2  complement C4-A isoform 1 preproprotein

    See identical proteins and their annotated locations for NP_009224.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AL645922, BC016933, BC146673, DA304049, K02403
    Consensus CDS
    CCDS47404.1
    UniProtKB/Swiss-Prot
    P0C0L4
    Related
    ENSP00000396688.2, ENST00000428956.7
    Conserved Domains (8) summary
    cd00017
    Location:686750
    ANATO; Anaphylatoxin homologous domain; C3a, C4a and C5a anaphylatoxins are protein fragments generated enzymatically in serum during activation of complement molecules C3, C4, and C5. They induce smooth muscle contraction. These fragments are homologous to ...
    cd02896
    Location:9961315
    complement_C3_C4_C5; Proteins similar to C3, C4 and C5 of vertebrate complement. The vertebrate complement system, comprised of a large number of distinct plasma proteins, is an effector of both the acquired and innate immune systems. The point of convergence of the ...
    cd03584
    Location:15881742
    NTR_complement_C4; NTR/C345C domain, complement C4 subfamily; The NTR domain found in complement C4 is also known as the C345C domain because it occurs at the C-terminus of complement C3, C4 and C5. Complement C4 is a key player in the activation of the component classical ...
    pfam00207
    Location:782869
    A2M; Alpha-2-macroglobulin family
    pfam01835
    Location:141233
    A2M_N; MG2 domain
    pfam07677
    Location:14811570
    A2M_recep; A-macroglobulin receptor
    pfam07678
    Location:10511317
    A2M_comp; A-macroglobulin complement component
    pfam07703
    Location:478610
    A2M_N_2; Alpha-2-macroglobulin family N-terminal region

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20201120

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000006.12 Reference GRCh38.p13 Primary Assembly

    Range
    31982057..32002681
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p13 ALT_REF_LOCI_3

Genomic

  1. NT_167245.2 Reference GRCh38.p13 ALT_REF_LOCI_3

    Range
    3229830..3250455
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p13 ALT_REF_LOCI_6

Genomic

  1. NT_167248.2 Reference GRCh38.p13 ALT_REF_LOCI_6

    Range
    3238028..3258653
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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