NCBI logo
  
 dbRBC  Logged in as: Guest  

  Blood Group Antigen Gene Mutation Database
   Home  |  Systems  |  Resources  |  Administration  |  About        30-Aug-2014

Knops Blood Group System

KN
Gene locus - CR1 (CD35)
Alleles

Introduction

The protein carrying the Knops blood group antigens is complement receptor 1 (CR1), the product of the complement receptor 1 (CR1) gene. It is a type 1 integral membrane glycoprotein whose extracellular domain contains 29-32 complement control modules (CCPs) or short consensus repeats (SCRs), that are further arranged into four long homologous regions (LHRs). The CR1 gene exists in four forms giving rise to four different molecular weight protein isoforms, that differ by approximately 30kD. These range from the smallest form of 190 kD (CR1*3) to the largest form of 280kD (CR*4). The basis for this molecular weight polymorphism is the deletion or duplication, by unequal crossover events, of sequences encoding the SCRs. The most common structural allele , i.e., CR1*1, contains 39 exons (total gene size 133kb), of which the leader sequence encodes either 41 or 46 amino acids, depending on the translation initiation site. The major functions of CR1 are the binding of C4b/C3b opsonized complexes as well as complement regulation.

Function of proteins

Binding and removal of circulating immune complexes; decay acceleration of C3, C5 and C3bBb convertases; cofactor for Factor I cleavage of C3b; rosetting receptor for Plasmodium falciparum erythrocyte membrane protein one (PfEMP-1).

Tissue distribution

Erythrocytes, B cells, polymorphonuclear leukocytes, monocytes, some T cells, follicular dendritic cells, glomelular podocytes, peripheral nerve fibers.

Disease association

No individual completely defficient in CR1 has been reported to date, although 1-2% of Caucasians may have low level of erythrocyte CR1 (E-CR1). Acquired low levels of E-CR1 are observed in patients with systemic lupus erythromatosis, AIDS, glomerulonephritis, autoimmune hemolytic anemia and other syndromes featuring immune complexes. The serological null (Helgeson phenotype) may also be due to low E-CR1 but is not associated with a disease state.The presence of McCb and Sl2 alleles in African populations is correlated with resistance to Myobacterium Tuberculosis infection (Noumsi et al. Trannsfusion 2011 51 2462-2469).

Historical aspects

During the 1960s and 70s, a number of weak antiglobulin (AHG) antibodies were studied that appeared to have unusual but similar characteristics. Consequently, serologists began to refer to this group as"high-titered, low avidity" (HTLA) antibodies. Members of this new group included: Chido, Rogers, Knops, McCoy, Swain-Langley, Cost, York, JMH, Holley, Gregory and, sometimes, Cartwright. The Knops blood group system began to take form when anti-KNa was described in a transfused Caucasian female (Hegelson et al., Transfusion, 10:737, 1970). Subsequently, several high incidence antigens related to KN were identified, namely York (Yka - Molthan and Giles), McCa (Molthan and Moulds), Sla (also known as McCc) and Vil (Lacey et al., Transfusion, 20:632, 1980). In 1991, CR1 was identified as the protein carrying the KNa, McCa, Sla and Yka blood group antigens (Moulds et al.; Rao et al., J.Immunol. 146, 3501, 1991; Petty et al., Transfusion Med. 7:55, 1997). The Hegelson phenotype, i.e., serological null,appears to be due to low CR1 copy number on erythrocytes (E-CR1).

About the alleles

The CR1 gene exhibits three kinds of polymorphisms: 1) DNA variation reflected in amino acid polymorphisms. A number of those changes is associated with the Knops blood group system. Some of the Knops alleles differ significantly among populations. The most common blood group phenotypes among Asians and Caucasians is Kn(a+b-), McC(a+b-), Sl(a+)Vil-; in Blacks, the Sl(a-)Vil+ type predominates. Nucleotide changes corresponding to serological phenotypes give rise to defined haplotypes. For example, haplotypes, for three Brazilian populations, are documented in Cavos et al. Transfusion 2007 47 147-153 (acc. nos. provided)) 2) structural polymorphism as reflected by molecular weight polymorphism of the CR1 protein, based on deletion or duplication, by unequal crossover events, of sequences encoding the SCRs (Hourcadeet al.; Vik and Wong).The most common size allele in all populations studied is CR1*1, whereas the smallest size, i.e., CR1*3 is found most frequently in those of African descent. 3) level of expression on the erythrocyte surface: the H (high expression) and L (low expression) alleles are associated with the HindIII restriction fragment length polymorphism in Caucasians and Asians but not in Blacks (Xianget al., Herrera et al.). In the list of alleles, sequence acc. no. Y00816 is taken as reference (coding sequence starts at nt. 28); the cDNA and translation changes are numbered from the codon for the initiator Met.

When searching for a particular allele, use "name" if DNA alteration is known or, if you wish to search by phenotype or the designation used by author, use "alias" (see "Details").

Other database IDs and links

NCBI genes Uniprot ID Genbank proteins
NP_000642 for variant S which is 450 aa longer
Gene nomenclature database ID Genbank nucleic acids
NM_000651 for variant S
NCBI homologenes for homologs and orthologs NCBI dbSNP for single nucleotide polymorphisms OMIM ID - at Online Mendelian Inheritance in Man
120620 for CR1
607486 for Knops

Literature

New PubMed entries with the terms Knops and blood from the last 30 days.
NCBI Book Sections with the terms Knops and blood.

Contributors

Joann M. Moulds, PhD, Research Associate Professor, Dept. of Microbiology and Immunology, MCP Hahnemann Univ. School of Medicine, 2900 Gueen Lane, Room G44, Philadelphia, PA 19129; Tel.: 215 991-8379; Fax: 215 848-2271; email: jmm56@drexel.edu

Contributors for specific alleles are listed with the alleles.

Links


Updated 2011-11-14 16:24:17.587
 
spacer | Disclaimer | Privacy statement | Accessibility |