CR1

Protein identityUniProt · HPA

UniProt accession

P17927

Gene

CR1

Ensembl

ENSG00000203710

Chromosome

1

Canonical length

2039 aa

Protein class

Blood group antigen proteins, CD markers, Plasma proteins, Predicted membrane proteins

Subcellular location

Plasma membrane

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

2039 residues, UniProt reviewed canonical sequence.

>P17927|CR1
     1  MGASSPRSPE PVGPPAPGLP FCCGGSLLAV VVLLALPVAW GQCNAPEWLP FARPTNLTDE
    61  FEFPIGTYLN YECRPGYSGR PFSIICLKNS VWTGAKDRCR RKSCRNPPDP VNGMVHVIKG
   121  IQFGSQIKYS CTKGYRLIGS SSATCIISGD TVIWDNETPI CDRIPCGLPP TITNGDFIST
   181  NRENFHYGSV VTYRCNPGSG GRKVFELVGE PSIYCTSNDD QVGIWSGPAP QCIIPNKCTP
   241  PNVENGILVS DNRSLFSLNE VVEFRCQPGF VMKGPRRVKC QALNKWEPEL PSCSRVCQPP
   301  PDVLHAERTQ RDKDNFSPGQ EVFYSCEPGY DLRGAASMRC TPQGDWSPAA PTCEVKSCDD
   361  FMGQLLNGRV LFPVNLQLGA KVDFVCDEGF QLKGSSASYC VLAGMESLWN SSVPVCEQIF
   421  CPSPPVIPNG RHTGKPLEVF PFGKTVNYTC DPHPDRGTSF DLIGESTIRC TSDPQGNGVW
   481  SSPAPRCGIL GHCQAPDHFL FAKLKTQTNA SDFPIGTSLK YECRPEYYGR PFSITCLDNL
   541  VWSSPKDVCK RKSCKTPPDP VNGMVHVITD IQVGSRINYS CTTGHRLIGH SSAECILSGN
   601  AAHWSTKPPI CQRIPCGLPP TIANGDFIST NRENFHYGSV VTYRCNPGSG GRKVFELVGE
   661  PSIYCTSNDD QVGIWSGPAP QCIIPNKCTP PNVENGILVS DNRSLFSLNE VVEFRCQPGF
   721  VMKGPRRVKC QALNKWEPEL PSCSRVCQPP PDVLHAERTQ RDKDNFSPGQ EVFYSCEPGY
   781  DLRGAASMRC TPQGDWSPAA PTCEVKSCDD FMGQLLNGRV LFPVNLQLGA KVDFVCDEGF
   841  QLKGSSASYC VLAGMESLWN SSVPVCEQIF CPSPPVIPNG RHTGKPLEVF PFGKAVNYTC
   901  DPHPDRGTSF DLIGESTIRC TSDPQGNGVW SSPAPRCGIL GHCQAPDHFL FAKLKTQTNA
   961  SDFPIGTSLK YECRPEYYGR PFSITCLDNL VWSSPKDVCK RKSCKTPPDP VNGMVHVITD
  1021  IQVGSRINYS CTTGHRLIGH SSAECILSGN TAHWSTKPPI CQRIPCGLPP TIANGDFIST
  1081  NRENFHYGSV VTYRCNLGSR GRKVFELVGE PSIYCTSNDD QVGIWSGPAP QCIIPNKCTP
  1141  PNVENGILVS DNRSLFSLNE VVEFRCQPGF VMKGPRRVKC QALNKWEPEL PSCSRVCQPP
  1201  PEILHGEHTP SHQDNFSPGQ EVFYSCEPGY DLRGAASLHC TPQGDWSPEA PRCAVKSCDD
  1261  FLGQLPHGRV LFPLNLQLGA KVSFVCDEGF RLKGSSVSHC VLVGMRSLWN NSVPVCEHIF
  1321  CPNPPAILNG RHTGTPSGDI PYGKEISYTC DPHPDRGMTF NLIGESTIRC TSDPHGNGVW
  1381  SSPAPRCELS VRAGHCKTPE QFPFASPTIP INDFEFPVGT SLNYECRPGY FGKMFSISCL
  1441  ENLVWSSVED NCRRKSCGPP PEPFNGMVHI NTDTQFGSTV NYSCNEGFRL IGSPSTTCLV
  1501  SGNNVTWDKK APICEIISCE PPPTISNGDF YSNNRTSFHN GTVVTYQCHT GPDGEQLFEL
  1561  VGERSIYCTS KDDQVGVWSS PPPRCISTNK CTAPEVENAI RVPGNRSFFS LTEIIRFRCQ
  1621  PGFVMVGSHT VQCQTNGRWG PKLPHCSRVC QPPPEILHGE HTLSHQDNFS PGQEVFYSCE
  1681  PSYDLRGAAS LHCTPQGDWS PEAPRCTVKS CDDFLGQLPH GRVLLPLNLQ LGAKVSFVCD
  1741  EGFRLKGRSA SHCVLAGMKA LWNSSVPVCE QIFCPNPPAI LNGRHTGTPF GDIPYGKEIS
  1801  YACDTHPDRG MTFNLIGESS IRCTSDPQGN GVWSSPAPRC ELSVPAACPH PPKIQNGHYI
  1861  GGHVSLYLPG MTISYICDPG YLLVGKGFIF CTDQGIWSQL DHYCKEVNCS FPLFMNGISK
  1921  ELEMKKVYHY GDYVTLKCED GYTLEGSPWS QCQADDRWDP PLAKCTSRTH DALIVGTLSG
  1981  TIFFILLIIF LSWIILKHRK GNNAHENPKE VAIHLHSQGG SSVHPRTLQT NEENSRVLP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CR1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.37

Highest tissue expression

26 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CR1.

Disease | AutoantibodyPubMed

Conditions in which antibodies against CR1 are reported. Each links to that disease's full target list.

• Lupus Erythematosus, Systemic 7

ReferencesPubMed · IEDB

Publications for CR1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.96

gnomAD pLI

0

gnomAD missense Z

-0.47

DepMap mean gene effect

0.14

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• ATP export
• complement activation
• complement activation, alternative pathway
• complement activation, classical pathway
• complement receptor mediated signaling pathway
• glomerulus development
• immune complex clearance
• negative regulation of activation of membrane attack complex
• negative regulation of complement activation
• negative regulation of complement activation, alternative pathway
• negative regulation of complement activation, classical pathway
• negative regulation of complement-dependent cytotoxicity
• negative regulation of immunoglobulin production
• negative regulation of interleukin-2 production
• negative regulation of plasma cell differentiation
• negative regulation of T cell proliferation
• negative regulation of type II interferon production
• organ or tissue specific immune response
• plasma membrane organization
• positive regulation of activation of membrane attack complex
• positive regulation of cell population proliferation
• positive regulation of regulatory T cell differentiation
• positive regulation of serine-type endopeptidase activity
• T cell mediated immunity
• immune complex clearance by erythrocytes
• negative regulation of serine-type endopeptidase activity

Molecular functions

• complement component C3b binding
• complement component C4b binding
• virus receptor activity
• complement component C3b receptor activity
• complement component C4b receptor activity

Cellular components

• cell surface
• cytoskeleton
• extracellular exosome
• extracellular space
• ficolin-1-rich granule membrane
• plasma membrane
• plasma membrane raft
• secretory granule membrane

Protein domainsUniProt · Pfam · InterPro

• Sushi/SCR/CCP domain
• Sushi/SCR/CCP superfamily
• SEZ6/CSMD/C4BPB Neuronal & Immune Regulators
• Sushi repeat (SCR repeat)

KeywordsUniProt

• Blood group antigen
• Complement pathway
• Disulfide bond
• Glycoprotein
• Host cell receptor for virus entry
• Host-virus interaction
• Immunity
• Innate immunity
• Membrane
• Pyrrolidone carboxylic acid
• Receptor
• Repeat
• Signal
• Sushi
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of CR1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CR2
• FCN2
• C3
• C1QA
• C4B
• MBL2