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C4A complement component 4A (Rodgers blood group) [ Homo sapiens (human) ]

Gene ID: 720, updated on 26-May-2016
Official Symbol
C4Aprovided by HGNC
Official Full Name
complement component 4A (Rodgers blood group)provided by HGNC
Primary source
HGNC:HGNC:1323
See related
Ensembl:ENSG00000244731 HPRD:00401; MIM:120810; Vega:OTTHUMG00000031186
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]
Orthologs
Location:
6p21.3
Exon count:
41
Annotation release Status Assembly Chr Location
107 current GRCh38.p2 (GCF_000001405.28) 6 NC_000006.12 (31982057..32002680)
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 negative elongation factor complex member E Neighboring gene Ski2 like RNA helicase Neighboring gene serine/threonine kinase 19 Neighboring gene decapping exoribonuclease Neighboring gene cytochrome P450 family 21 subfamily A member 1, pseudogene Neighboring gene tenascin XA (pseudogene) Neighboring gene serine/threonine kinase 19B (pseudogene)

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Associated conditions

Description Tests
Blood group, Chido/Rodgers system
MedGen: CN119410 OMIM: 614374 GeneReviews: Not available
Compare labs
Complement component 4a deficiency
MedGen: C1852692 OMIM: 614380 GeneReviews: Not available
Compare labs

NHGRI GWAS Catalog

Description
Genome-wide association study for serum complement C3 and C4 levels in healthy Chinese subjects.
NHGRI GWA Catalog
Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array.
NHGRI GWA Catalog
  • Activation of C3 and C5, organism-specific biosystem (from REACTOME)
    Activation of C3 and C5, organism-specific biosystemThe 3 pathways of complement activation converge on the cleavage of C3 by C3 convertases. C3 convertase cleaves C3 into C3a and C3b - a central step of complement activation. C3a remains in the flu...
  • Allograft Rejection, organism-specific biosystem (from WikiPathways)
    Allograft Rejection, organism-specific biosystemThis pathway illustrates molecular interactions involved in the fundamental adaptive immune response for allograft destruction. This pathway was adapted in large part from the KEGG pathway http://www...
  • Complement Activation, Classical Pathway, organism-specific biosystem (from WikiPathways)
    Complement Activation, Classical Pathway, organism-specific biosystemThe complement system is a biochemical cascade that helps, or ???complements???, the ability of antibodies to clear pathogens from an organism. It is part of the immune system called the innate immun...
  • Complement and coagulation cascades, organism-specific biosystem (from KEGG)
    Complement and coagulation cascades, organism-specific biosystemThe complement system is a proteolytic cascade in blood plasma and a mediator of innate immunity, a nonspecific defense mechanism against pathogens. There are three pathways of complement activation:...
  • Complement and coagulation cascades, conserved biosystem (from KEGG)
    Complement and coagulation cascades, conserved biosystemThe complement system is a proteolytic cascade in blood plasma and a mediator of innate immunity, a nonspecific defense mechanism against pathogens. There are three pathways of complement activation:...
  • Complement cascade, organism-specific biosystem (from REACTOME)
    Complement cascade, organism-specific biosystemIn the complement cascade, a panel of soluble molecules rapidly and effectively senses a danger or damage and triggers reactions to provide a response that discriminates among foreign intruders, cell...
  • Immune System, organism-specific biosystem (from REACTOME)
    Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
  • Initial triggering of complement, organism-specific biosystem (from REACTOME)
    Initial triggering of complement, organism-specific biosystemComplement activation is due to a cascade of proteolytic steps, performed by serine protease domains in some of the components. Three different pathways of activation are distinguished triggered by t...
  • Innate Immune System, organism-specific biosystem (from REACTOME)
    Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
  • Pertussis, organism-specific biosystem (from KEGG)
    Pertussis, organism-specific biosystemPertussis, also known as whooping cough, is an acute respiratory infectious disease caused by a bacteria called Bordetella Pertussis. The characteristic symptoms are paroxysmal cough, inspiratory whe...
  • Pertussis, conserved biosystem (from KEGG)
    Pertussis, conserved biosystemPertussis, also known as whooping cough, is an acute respiratory infectious disease caused by a bacteria called Bordetella Pertussis. The characteristic symptoms are paroxysmal cough, inspiratory whe...
  • Regulation of Complement cascade, organism-specific biosystem (from REACTOME)
    Regulation of Complement cascade, organism-specific biosystemTwo inherent features of complement activation make its regulation very important: 1. There is an inherent positive feedback loop because the product of C3 activation forms part of an enzyme that cau...
  • SIDS Susceptibility Pathways, organism-specific biosystem (from WikiPathways)
    SIDS Susceptibility Pathways, organism-specific biosystemIn this model, we provide an integrated view of Sudden Infant Death Syndrome (SIDS) at the level of implicated tissues, signaling networks and genetics. The purpose of this model is to serve as an ov...
  • Staphylococcus aureus infection, organism-specific biosystem (from KEGG)
    Staphylococcus aureus infection, organism-specific biosystemStaphylococcus aureus can cause multiple forms of infections ranging from superficial skin infections to food poisoning and life-threatening infections. The organism has several ways to divert the ef...
  • Staphylococcus aureus infection, conserved biosystem (from KEGG)
    Staphylococcus aureus infection, conserved biosystemStaphylococcus aureus can cause multiple forms of infections ranging from superficial skin infections to food poisoning and life-threatening infections. The organism has several ways to divert the ef...
  • Systemic lupus erythematosus, organism-specific biosystem (from KEGG)
    Systemic lupus erythematosus, organism-specific biosystemSystemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterised by the production of IgG autoantibodies that are specific for self-antigens, such as DNA, nuclear proteins and cert...
  • Systemic lupus erythematosus, conserved biosystem (from KEGG)
    Systemic lupus erythematosus, conserved biosystemSystemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterised by the production of IgG autoantibodies that are specific for self-antigens, such as DNA, nuclear proteins and cert...
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Clone Names

  • FLJ60561, MGC164979

Gene Ontology Provided by GOA

Function Evidence Code Pubs
complement component C1q binding IDA
Inferred from Direct Assay
more info
PubMed 
endopeptidase inhibitor activity IEA
Inferred from Electronic Annotation
more info
 
serine-type endopeptidase activity TAS
Traceable Author Statement
more info
 
Process Evidence Code Pubs
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 
proteolysis IEA
Inferred from Electronic Annotation
more info
 
regulation of complement activation TAS
Traceable Author Statement
more info
 
Component Evidence Code Pubs
blood microparticle IDA
Inferred from Direct Assay
more info
PubMed 
extracellular exosome IDA
Inferred from Direct Assay
more info
PubMed 
extracellular region TAS
Traceable Author Statement
more info
 
extracellular space IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 
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

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_001252204.1NP_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, OTTHUMP00000216221, ENST00000498271, OTTHUMT00000356896
    Conserved Domains (9) 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:140233
    A2M_N; MG2 domain
    pfam07677
    Location:14571524
    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
    pfam11974
    Location:1090
    MG1; Alpha-2-macroglobulin MG1 domain
  2. NM_007293.2NP_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, BC146673, DA304049, K02403
    Consensus CDS
    CCDS47404.1
    UniProtKB/Swiss-Prot
    P0C0L4
    Related
    ENSP00000396688, OTTHUMP00000029266, ENST00000428956, OTTHUMT00000076364
    Conserved Domains (9) 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:140233
    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
    pfam11974
    Location:1090
    MG1; Alpha-2-macroglobulin MG1 domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 107 details...

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

Reference GRCh38.p2 Primary Assembly

Genomic

  1. NC_000006.12 Reference GRCh38.p2 Primary Assembly

    Range
    31982057..32002680
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p2 ALT_REF_LOCI_3

Genomic

  1. NT_167245.2 Reference GRCh38.p2 ALT_REF_LOCI_3

    Range
    3229830..3250454
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p2 ALT_REF_LOCI_5

Genomic

  1. NT_167247.2 Reference GRCh38.p2 ALT_REF_LOCI_5

    Range
    3356831..3377455
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011548125.1XP_011546427.1  

Reference GRCh38.p2 ALT_REF_LOCI_6

Genomic

  1. NT_167248.2 Reference GRCh38.p2 ALT_REF_LOCI_6

    Range
    3238028..3258652
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018917.2 Alternate CHM1_1.1

    Range
    31951915..31972655
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)