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

    Gene ID: 720, updated on 19-May-2024

    Summary

    Official Symbol
    C4Aprovided by HGNC
    Official Full Name
    complement C4A (Chido/Rodgers blood group)provided by HGNC
    Primary source
    HGNC:HGNC:1323
    See related
    Ensembl:ENSG00000244731 MIM:120810; AllianceGenome:HGNC:1323
    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
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See C4A in Genome Data Viewer
    Location:
    6p21.33
    Exon count:
    41
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (31982057..32002681)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (31835263..31855887)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (31949834..31970458)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr6:31929542-31930741 Neighboring gene SKI2 subunit of superkiller complex Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:31939702-31940412 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) Neighboring gene serine/threonine kinase 19B (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: C3280642 OMIM: 614380 GeneReviews: Not available
    Compare labs

    EBI GWAS Catalog

    Description
    Genome-wide association study for serum complement C3 and C4 levels in healthy Chinese subjects.
    EBI GWAS Catalog
    Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array.
    EBI GWAS Catalog

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Clone Names

    • FLJ60561, MGC164979

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables complement component C1q complex binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables endopeptidase inhibitor activity IEA
    Inferred from Electronic Annotation
    more info
     
    Process Evidence Code Pubs
    involved_in complement activation IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in complement activation IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    involved_in complement activation, classical pathway IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in inflammatory response IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in innate immune response IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of apoptotic cell clearance IGI
    Inferred from Genetic Interaction
    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 C4A (Rodgers blood group)
    complement component 4A (Rodgers blood group)

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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/TrEMBL
      A0A140TA32, A0A140TA44
      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
      A6H8M8, A6NHJ5, A7E2V2, B0QZR6, B0V2C8, B2RUT6, B7ZVZ6, P01028, P0C0L4, P78445, Q13160, Q13906, Q14033, Q14835, Q4LE82, Q5JNX2, Q5JQM8, Q6P4R1, Q6U2E5, Q6U2E8, Q6U2F0, Q6U2F3, Q6U2F4, Q6U2F6, Q6U2F8, Q6U2G0, Q96EG2, Q96SA8, Q9NPK5, Q9UIP5
      UniProtKB/TrEMBL
      A0A0G2JPR0
      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: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

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

    Reference GRCh38.p14 ALT_REF_LOCI_3

    Genomic

    1. NT_167245.2 Reference GRCh38.p14 ALT_REF_LOCI_3

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

    Reference GRCh38.p14 ALT_REF_LOCI_6

    Genomic

    1. NT_167248.2 Reference GRCh38.p14 ALT_REF_LOCI_6

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

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      31835263..31855887
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)