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    CR1 complement C3b/C4b receptor 1 (Knops blood group) [ Homo sapiens (human) ]

    Gene ID: 1378, updated on 2-Nov-2024

    Summary

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    Official Symbol
    CR1provided by HGNC
    Official Full Name
    complement C3b/C4b receptor 1 (Knops blood group)provided by HGNC
    Primary source
    HGNC:HGNC:2334
    See related
    Ensembl:ENSG00000203710 MIM:120620; AllianceGenome:HGNC:2334
    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
    KN; C3BR; C4BR; CD35
    Summary
    This gene is a member of the receptors of complement activation (RCA) family and is located in the 'cluster RCA' region of chromosome 1. The genome is polymorphic at this locus with allele-specific splice variants encoding different isoforms, based on the presence/absence of long homologous repeats (LHRs). The gene encodes a monomeric single-pass type I membrane glycoprotein found on erythrocytes, leukocytes, glomerular podocytes, and splenic follicular dendritic cells. The Knops blood group system is a system of antigens located on this protein. The protein mediates cellular binding to particles and immune complexes that have activated complement. Decreases in expression of this protein and/or mutations in this gene have been associated with gallbladder carcinomas, mesangiocapillary glomerulonephritis, systemic lupus erythematosus, sarcoidosis and Alzheimer's disease. Mutations in this gene have also been associated with a reduction in Plasmodium falciparum rosetting, conferring protection against severe malaria. [provided by RefSeq, May 2020]
    Expression
    Biased expression in appendix (RPKM 18.3), spleen (RPKM 14.7) and 10 other tissues See more
    Orthologs
    all
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    Genomic context

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    See CR1 in Genome Data Viewer
    Location:
    1q32.2
    Exon count:
    47
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (207496157..207641765)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (206761475..206888507)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (207669502..207815110)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105372880 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2446 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1771 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1772 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr1:207642622-207643821 Neighboring gene complement C3d receptor 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2447 Neighboring gene NANOG hESC enhancer GRCh37_chr1:207773753-207774311 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr1:207806821-207807492 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:207808163-207808834 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:207808835-207809506 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1773 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2448 Neighboring gene CD46 molecule pseudogene 1 Neighboring gene complement C3b/C4b receptor 1 like Neighboring gene cell division cycle associated 4 pseudogene 3

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues 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

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    Related articles in PubMed

    1. CR1 is associated with amyloid plaque burden and age-related cognitive decline. Chibnik LB, et al. Ann Neurol, 2011 Mar. PMID 21391232, Free PMC Article
    2. Complement receptor type 1 (CD35) mediates inhibitory signals in human B lymphocytes. Józsi M, et al. J Immunol, 2002 Mar 15. PMID 11884446
    3. CR1 genotype is associated with entorhinal cortex volume in young healthy adults. Bralten J, et al. Neurobiol Aging, 2011 Nov. PMID 21726919
    4. Expansion of the Knops blood group system and subdivision of Sl(a). Moulds JM, et al. Transfusion, 2002 Feb. PMID 11896343
    5. Layer-by-layer co-immobilization of soluble complement receptor 1 and heparin on islets. Luan NM, et al. Biomaterials, 2011 Sep. PMID 21663961

    See all (244) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The Molecular Mechanisms of Complement Receptor 1-It Is Complicated.
      Title: The Molecular Mechanisms of Complement Receptor 1-It Is Complicated.
    2. Complement receptor type 1 and 2 (CR1 and CR2) gene polymorphisms and plasma protein levels are associated with the Dengue disease severity.
      Title: Complement receptor type 1 and 2 (CR1 and CR2) gene polymorphisms and plasma protein levels are associated with the Dengue disease severity.
    3. Genetic variant in complement receptor 1 (CR1, CD35) is associated with a cluster of severe fatal COVID-19 in a family.
      Title: Genetic variant in complement receptor 1 (CR1, CD35) is associated with a cluster of severe fatal COVID-19 in a family.
    4. Elucidation of the low-expressing erythroid CR1 phenotype by bioinformatic mining of the GATA1-driven blood-group regulome.
      Title: Elucidation of the low-expressing erythroid CR1 phenotype by bioinformatic mining of the GATA1-driven blood-group regulome.
    5. Erythrocyte complement receptor 1 (ECR1) and erythrocyte-bound C4d (EC4d) in the prediction of poor pregnancy outcomes in systemic lupus erythematosus (SLE).
      Title: Erythrocyte complement receptor 1 (ECR1) and erythrocyte-bound C4d (EC4d) in the prediction of poor pregnancy outcomes in systemic lupus erythematosus (SLE).
    6. Population-specific positive selection on low CR1 expression in malaria-endemic regions.
      Title: Population-specific positive selection on low CR1 expression in malaria-endemic regions.
    7. Complement C3b contributes to Escherichia coli-induced platelet aggregation in human whole blood.
      Title: Complement C3b contributes to Escherichia coli-induced platelet aggregation in human whole blood.
    8. CASP5 and CR1 as potential biomarkers for Kawasaki disease: an Integrated Bioinformatics-Experimental Study.
      Title: CASP5 and CR1 as potential biomarkers for Kawasaki disease: an Integrated Bioinformatics-Experimental Study.
    9. Explore the role of CR1 genetic variants in late-onset Alzheimer's disease susceptibility.
      Title: Explore the role of CR1 genetic variants in late-onset Alzheimer's disease susceptibility.
    10. Immunoregulatory complement receptor-1 and leukocyte-associated Ig-like receptor-1 expression on leukocytes in Psoriasis vulgaris.
      Title: Immunoregulatory complement receptor-1 and leukocyte-associated Ig-like receptor-1 expression on leukocytes in Psoriasis vulgaris.
    Submit: New GeneRIF Correction See all GeneRIFs (165)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    KNOPS BLOOD GROUP SYSTEM
    MedGen: C1292327 OMIM: 607486 GeneReviews: Not available
    		not available
    Malaria, susceptibility to
    MedGen: C1970028 OMIM: 611162 GeneReviews: Not available
    		not available

    EBI GWAS Catalog

    Description
    A genome-wide association scan on the levels of markers of inflammation in Sardinians reveals associations that underpin its complex regulation.
    EBI GWAS Catalog
    Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease.
    EBI GWAS Catalog
    Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease.
    EBI GWAS Catalog
    Complement receptor 1 gene variants are associated with erythrocyte sedimentation rate.
    EBI GWAS Catalog
    Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease.
    EBI GWAS Catalog
    Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease.
    EBI GWAS Catalog

    Variation

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    See Variation Viewer (GRCh37.p13)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env HIV-1 gp120 downregulates the expression of complement component receptor 1 (CR1) in human B cells PubMed
    Tat tat HIV-1 Tat downregulates the expression of complement component (3b/4b) receptor 1 (CR1; CD35) in human primary T cells PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables complement component C3b binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables complement component C3b receptor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables complement component C4b binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables complement component C4b receptor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables virus receptor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    acts_upstream_of_or_within ATP export IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in T cell mediated immunity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in complement activation, alternative pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in complement activation, classical pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in complement receptor mediated signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in immune complex clearance by erythrocytes IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of T cell proliferation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of negative regulation of activation of membrane attack complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of complement activation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of complement activation, alternative pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of complement activation, classical pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of complement activation, classical pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of complement-dependent cytotoxicity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of negative regulation of immunoglobulin production IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_or_within negative regulation of interleukin-2 production IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of negative regulation of plasma cell differentiation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of serine-type endopeptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_or_within negative regulation of type II interferon production IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in plasma membrane organization IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of activation of membrane attack complex IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of cell population proliferation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of regulatory T cell differentiation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of serine-type endopeptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in symbiont entry into host cell IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in cell surface IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytoskeleton IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in extracellular exosome HDA PubMed 
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in ficolin-1-rich granule membrane TAS
    Traceable Author Statement
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in plasma membrane raft IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in secretory granule membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    complement receptor type 1
    Names
    C3-binding protein
    C3b/C4b receptor
    CD35 antigen
    Knops blood group antigen
    complement component (3b/4b) receptor 1 (Knops blood group)
    complement receptor 1

    NCBI Reference Sequences (RefSeq)

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    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_007481.1 RefSeqGene

      Range
      5030..150638
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_814

    mRNA and Protein(s)

    1. NM_000573.4 → NP_000564.2  complement receptor type 1 isoform F precursor

      See identical proteins and their annotated locations for NP_000564.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (F, also referred to as A) is the most common allele. This allele is not represented in the reference genome. It lacks eight alternate exons, compared to variant S, but maintains the reading frame. The resulting protein (F, also referred to as isoform CR1-A or CR1*1) is shorter than isoform S. Isoforms F and 3 are the same length but differ in their protein sequence.
      Source sequence(s)
      AL137789, AL691452, BF900429, BX113709, BX643705, Y00816
      UniProtKB/Swiss-Prot
      P17927, Q16744, Q16745, Q5SR43, Q5SR45, Q9UQV2
      UniProtKB/TrEMBL
      Q5SR44
      Conserved Domains (4) summary
      cd00033
      Location:1197 → 1253
      CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system
      smart00032
      Location:43 → 99
      CCP; Domain abundant in complement control proteins; SUSHI repeat; short complement-like repeat (SCR)
      PHA02927
      Location:52 → 295
      PHA02927; secreted complement-binding protein; Provisional
      pfam00084
      Location:1591 → 1646
      Sushi; Sushi repeat (SCR repeat)

    2. NM_000651.6 → NP_000642.3  complement receptor type 1 isoform S precursor

      See identical proteins and their annotated locations for NP_000642.3

      Status: REVIEWED

      Source sequence(s)
      AL137789, AL691452
      Consensus CDS
      CCDS44308.1
      UniProtKB/TrEMBL
      E9PDY4, Q5SR44
      Related
      ENSP00000356016.4, ENST00000367049.9
      Conserved Domains (4) summary
      cd00033
      Location:1647 → 1703
      CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system
      smart00032
      Location:43 → 99
      CCP; Domain abundant in complement control proteins; SUSHI repeat; short complement-like repeat (SCR)
      PHA02927
      Location:52 → 295
      PHA02927; secreted complement-binding protein; Provisional
      pfam00084
      Location:2041 → 2096
      Sushi; Sushi repeat (SCR repeat)

    3. NM_001381851.1 → NP_001368780.1  complement receptor type 1 isoform 3 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks 8 alternate exons compared to variant S, but maintains the reading frame. This allele is not represented in the reference genome. The resulting protein (isoform 3) is shorter than isoform S. Isoforms 3 and F are the same length but differ in their protein sequence.
      Source sequence(s)
      AL137789, AL691452
      UniProtKB/Swiss-Prot
      P17927, Q16744, Q16745, Q5SR43, Q5SR45, Q9UQV2
      UniProtKB/TrEMBL
      Q5SR44

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      207496157..207641765
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      206761475..206888507
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P17927.3 GenPept UniProtKB/Swiss-Prot:P17927

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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