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

Summary

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

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_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The Molecular Mechanisms of Complement Receptor 1-It Is Complicated.
Title: The Molecular Mechanisms of Complement Receptor 1-It Is Complicated.
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.
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.
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.
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).
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.
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.
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.
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.
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	Compare labs
Malaria, susceptibility to MedGen: C1970028 OMIM: 611162 GeneReviews: Not available	Compare labs

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 EBI GWAS CatalogPubMed
Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Complement receptor 1 gene variants are associated with erythrocyte sedimentation rate. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-35372 (e-PCR)
- UniSTS:70660

D1S2538 (e-PCR)
- UniSTS:41503

RH11128 (e-PCR)
- UniSTS:53552

SHGC-35375 (e-PCR)
- UniSTS:3635

D8S2279 (e-PCR)
- UniSTS:473907

AL034227 (e-PCR)
- UniSTS:94045

SHGC-33387 (e-PCR)
- UniSTS:30072

D1S2796 (e-PCR), detects polymorphism
- UniSTS:71296

L17971 (e-PCR)
- UniSTS:43966

D1S2782 (e-PCR), detects polymorphism
- UniSTS:49643

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 more info	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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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

NG_007481.1 RefSeqGene

Range

5030..150638

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_814

mRNA and Protein(s)

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)
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)
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