RBCC

Full text data of KEL

KEL [Confidence: high (a blood group or CD marker)]
Kell blood group glycoprotein; 3.4.24.- (CD238)

hRBCD IPI00220459
IPI00220459 Kell blood group glycoprotein Kell blood group glycoprotein membrane n/a 3 12 13 15 2 15 5 n/a n/a 1 9 5 11 4 6 5 9 6 6 integral membrane protein n/a found at its expected molecular weight found at molecular weight

BGMUT kell
421 kell KEL KEL 1042T Ko (Portugal) 1042C>T Q348X Ko; Kell null very rare; identified in a single family (Portugal) 11375401 Lee et al. No Kell protein on erythrocytes. Mutation in exon 9. Blumenfeld OO, curator 2009-01-16 22:02:03.377 NA

UniProt P23276
ID KELL_HUMAN Reviewed; 732 AA.
AC P23276; B2RBV4; Q96RS8; Q99885;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1996, sequence version 2.
DT 22-JAN-2014, entry version 143.
DE RecName: Full=Kell blood group glycoprotein;
DE EC=3.4.24.-;
DE AltName: CD_antigen=CD238;
GN Name=KEL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=1712490; DOI=10.1073/pnas.88.14.6353;
RA Lee S., Zambas E.D., Marsh W.L., Redman C.M.;
RT "Molecular cloning and primary structure of Kell blood group
RT protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:6353-6357(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7858266;
RA Lee S., Zambas E., Green E.D., Redman C.M.;
RT "Organization of the gene encoding the human Kell blood group
RT protein.";
RL Blood 85:1364-1370(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-163; MET-193;
RP TRP-281; PRO-597 AND ALA-726.
RG SeattleSNPs variation discovery resource;
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 225-308.
RA Denomme G.A., Matheson K.A.;
RT "PCR amplification and sequencing of the human KEL gene.";
RL Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 569-647, AND VARIANT BLOOD GROUP
RP KEL6/KEL7.
RX PubMed=7570911; DOI=10.1046/j.1537-2995.1995.351096026362.x;
RA Lee S., Wu X., Reid M.E., Redman C.M.;
RT "Molecular basis of the K:6,-7 [Js(a+b-)] phenotype in the Kell blood
RT group system.";
RL Transfusion 35:822-825(1995).
RN [9]
RP INTERACTION WITH XK, DISULFIDE BOND, AND MUTAGENESIS OF CYS-72 AND
RP CYS-319.
RX PubMed=9593744; DOI=10.1074/jbc.273.22.13950;
RA Russo D., Redman C., Lee S.;
RT "Association of XK and Kell blood group proteins.";
RL J. Biol. Chem. 273:13950-13956(1998).
RN [10]
RP FUNCTION, AND MUTAGENESIS OF GLU-582.
RX PubMed=10438732;
RA Lee S., Lin M., Mele A., Cao Y., Farmar J., Russo D., Redman C.;
RT "Proteolytic processing of big endothelin-3 by the kell blood group
RT protein.";
RL Blood 94:1440-1450(1999).
RN [11]
RP TISSUE SPECIFICITY, AND INTERACTION WITH XK.
RX PubMed=10891471;
RA Russo D., Wu X., Redman C.M., Lee S.;
RT "Expression of Kell blood group protein in nonerythroid tissues.";
RL Blood 96:340-346(2000).
RN [12]
RP TISSUE SPECIFICITY, AND GLYCOSYLATION.
RX PubMed=11336649; DOI=10.1042/0264-6021:3560171;
RA Camara-Clayette V., Rahuel C., Lopez C., Hattab C., Verkarre V.,
RA Bertrand O., Cartron J.P.;
RT "Transcriptional regulation of the KEL gene and Kell protein
RT expression in erythroid and non-erythroid cells.";
RL Biochem. J. 356:171-180(2001).
RN [13]
RP VARIANT BLOOD GROUP KEL1/KEL2 MET-193.
RX PubMed=7849312;
RA Lee S., Wu X., Reid M.E., Zelinski T., Redman C.M.;
RT "Molecular basis of the Kell (K1) phenotype.";
RL Blood 85:912-916(1995).
RN [14]
RP VARIANTS BLOOD GROUP KEL3/KEL4/KEL21; KEL11/17 AND KEL10.
RX PubMed=8669078; DOI=10.1046/j.1537-2995.1996.36696269505.x;
RA Lee S., Wu X., Son S., Naime D., Reid M.E., Okubo Y., Sistonen P.,
RA Redman C.M.;
RT "Point mutations characterize KEL10, the KEL3, KEL4, and KEL21
RT alleles, and the KEL17 and KEL11 alleles.";
RL Transfusion 36:490-494(1996).
CC -!- FUNCTION: Zinc endopeptidase with endothelin-3-converting enzyme
CC activity. Cleaves EDN1, EDN2 and EDN3, with a marked preference
CC for EDN3.
CC -!- COFACTOR: Binds 1 zinc ion per subunit (By similarity).
CC -!- SUBUNIT: Heterodimer with XK; disulfide-linked.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type II membrane
CC protein. Note=Spans the erythrocyte membrane, and is attached to
CC the underlying cytoskeleton.
CC -!- TISSUE SPECIFICITY: Expressed at high levels in erythrocytes and
CC testis (in Sertoli cells), and, at lower levels, in skeletal
CC muscle, tonsils (in follicular dendritic cells), lymph node,
CC spleen and appendix (at protein level). Also expressed in many
CC adult and fetal nonerythroid tissues, including brain, spleen,
CC lymph nodes and bone marrow.
CC -!- PTM: N-glycosylated.
CC -!- POLYMORPHISM: KEL is responsible for the Kell blood group system.
CC The molecular basis of the K=KEL1/k=KEL2 blood group antigens is a
CC single variation in position 193; Thr-193 corresponds to KEL2 and
CC Met-193 to KEL1. The molecular basis of the
CC Kpa=KEL3/Kpb=KEL4/Kpc=KEL21 blood group antigens is a single
CC variation in position 281; Arg-281 corresponds to KEL4, Trp-281 to
CC KEL3 and Gln-281 to KEL21. The molecular basis of the
CC Jsa=KEL6/Jsb=KEL7 blood group antigens is a single variation in
CC position 597; Leu-597 corresponds to KEL7 and Pro-597 to KEL6. The
CC molecular basis of the KEL11/KEL17 blood group antigens is a
CC single variation in position 302; Val-302 corresponds to KEL11 and
CC Ala-302 to KEL17. The molecular basis of the KEL14/KEL24 blood
CC group antigens is a single variation in position 180; Arg-180
CC corresponds to KEL14 and Pro-180 to KEL24.
CC -!- SIMILARITY: Belongs to the peptidase M13 family.
CC -!- WEB RESOURCE: Name=dbRBC/BGMUT; Note=Blood group antigen gene
CC mutation database;
CC URL="http://www.ncbi.nlm.nih.gov/gv/mhc/xslcgi.cgi?cmd=bgmut/systems_info&system;=kell";
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/KEL";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/kel/";
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DR EMBL; M64934; AAA03192.1; -; mRNA.
DR EMBL; AF172627; AAB33459.1; -; Genomic_DNA.
DR EMBL; AF172609; AAB33459.1; JOINED; Genomic_DNA.
DR EMBL; AF172610; AAB33459.1; JOINED; Genomic_DNA.
DR EMBL; AF172611; AAB33459.1; JOINED; Genomic_DNA.
DR EMBL; AF172612; AAB33459.1; JOINED; Genomic_DNA.
DR EMBL; AF172613; AAB33459.1; JOINED; Genomic_DNA.
DR EMBL; AF172614; AAB33459.1; JOINED; Genomic_DNA.
DR EMBL; AF172615; AAB33459.1; JOINED; Genomic_DNA.
DR EMBL; AF172616; AAB33459.1; JOINED; Genomic_DNA.
DR EMBL; AF172617; AAB33459.1; JOINED; Genomic_DNA.
DR EMBL; AF172618; AAB33459.1; JOINED; Genomic_DNA.
DR EMBL; AF172619; AAB33459.1; JOINED; Genomic_DNA.
DR EMBL; AF172620; AAB33459.1; JOINED; Genomic_DNA.
DR EMBL; AF172621; AAB33459.1; JOINED; Genomic_DNA.
DR EMBL; AF172622; AAB33459.1; JOINED; Genomic_DNA.
DR EMBL; AF172623; AAB33459.1; JOINED; Genomic_DNA.
DR EMBL; AF172624; AAB33459.1; JOINED; Genomic_DNA.
DR EMBL; AF172625; AAB33459.1; JOINED; Genomic_DNA.
DR EMBL; AF172626; AAB33459.1; JOINED; Genomic_DNA.
DR EMBL; AY228336; AAO38053.1; -; Genomic_DNA.
DR EMBL; AK314831; BAG37351.1; -; mRNA.
DR EMBL; CH471198; EAW51891.1; -; Genomic_DNA.
DR EMBL; BC003135; AAH03135.1; -; mRNA.
DR EMBL; BC050639; AAH50639.1; -; mRNA.
DR EMBL; AF279657; AAK69488.1; -; Genomic_DNA.
DR EMBL; S80081; AAB47018.1; -; Genomic_DNA.
DR RefSeq; NP_000411.1; NM_000420.2.
DR UniGene; Hs.368588; -.
DR ProteinModelPortal; P23276; -.
DR SMR; P23276; 313-732.
DR IntAct; P23276; 2.
DR MINT; MINT-1464824; -.
DR STRING; 9606.ENSP00000347409; -.
DR MEROPS; M13.090; -.
DR PhosphoSite; P23276; -.
DR DMDM; 1346376; -.
DR PaxDb; P23276; -.
DR PRIDE; P23276; -.
DR DNASU; 3792; -.
DR Ensembl; ENST00000355265; ENSP00000347409; ENSG00000197993.
DR Ensembl; ENST00000561891; ENSP00000457677; ENSG00000260040.
DR GeneID; 3792; -.
DR KEGG; hsa:3792; -.
DR UCSC; uc003wcb.3; human.
DR CTD; 3792; -.
DR GeneCards; GC07M142638; -.
DR HGNC; HGNC:6308; KEL.
DR HPA; HPA042391; -.
DR MIM; 110900; phenotype.
DR MIM; 613883; gene.
DR neXtProt; NX_P23276; -.
DR Orphanet; 157938; Joker disease.
DR PharmGKB; PA30087; -.
DR eggNOG; COG3590; -.
DR HOGENOM; HOG000245574; -.
DR HOVERGEN; HBG002194; -.
DR InParanoid; P23276; -.
DR KO; K06577; -.
DR OMA; SYAQVMC; -.
DR PhylomeDB; P23276; -.
DR GenomeRNAi; 3792; -.
DR NextBio; 14891; -.
DR PRO; PR:P23276; -.
DR ArrayExpress; P23276; -.
DR Bgee; P23276; -.
DR CleanEx; HS_KEL; -.
DR Genevestigator; P23276; -.
DR GO; GO:0016021; C:integral to membrane; TAS:HGNC.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IDA:HGNC.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0042310; P:vasoconstriction; TAS:HGNC.
DR InterPro; IPR000718; Peptidase_M13.
DR InterPro; IPR018497; Peptidase_M13_C.
DR InterPro; IPR008753; Peptidase_M13_N.
DR PANTHER; PTHR11733; PTHR11733; 1.
DR Pfam; PF01431; Peptidase_M13; 1.
DR Pfam; PF05649; Peptidase_M13_N; 1.
DR PRINTS; PR00786; NEPRILYSIN.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Blood group antigen; Cell membrane; Complete proteome;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Hydrolase;
KW Membrane; Metal-binding; Metalloprotease; Polymorphism; Protease;
KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix;
KW Zinc.
FT CHAIN 1 732 Kell blood group glycoprotein.
FT /FTId=PRO_0000078227.
FT TOPO_DOM 1 47 Cytoplasmic (Potential).
FT TRANSMEM 48 67 Helical; Signal-anchor for type II
FT membrane protein; (Potential).
FT TOPO_DOM 68 732 Extracellular (Potential).
FT ACT_SITE 582 582
FT ACT_SITE 638 638 Proton donor (By similarity).
FT METAL 581 581 Zinc; catalytic (By similarity).
FT METAL 585 585 Zinc; catalytic (By similarity).
FT METAL 634 634 Zinc; catalytic (By similarity).
FT CARBOHYD 94 94 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 115 115 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 191 191 N-linked (GlcNAc...); in KEL2 antigen.
FT CARBOHYD 345 345 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 627 627 N-linked (GlcNAc...) (Potential).
FT DISULFID 72 72 Interchain (with C-347 in XK).
FT VARIANT 163 163 A -> T (in dbSNP:rs8175974).
FT /FTId=VAR_016265.
FT VARIANT 180 180 R -> P (in KEL24 antigen).
FT /FTId=VAR_006731.
FT VARIANT 193 193 T -> M (in KEL1/K antigen;
FT dbSNP:rs8176058).
FT /FTId=VAR_006732.
FT VARIANT 248 248 R -> Q (in KEL25 antigen).
FT /FTId=VAR_015120.
FT VARIANT 249 249 E -> K (in KEL27 antigen).
FT /FTId=VAR_015121.
FT VARIANT 281 281 R -> Q (in KEL21/Kp(c) antigen).
FT /FTId=VAR_006734.
FT VARIANT 281 281 R -> W (in KEL3/Kp(a) antigen;
FT dbSNP:rs8176059).
FT /FTId=VAR_006733.
FT VARIANT 302 302 V -> A (in KEL17 antigen;
FT dbSNP:rs61729034).
FT /FTId=VAR_006735.
FT VARIANT 322 322 A -> V (in KEL22 antigen).
FT /FTId=VAR_015122.
FT VARIANT 382 382 Q -> R (in KEL23 antigen).
FT /FTId=VAR_015123.
FT VARIANT 406 406 R -> Q (in KEL26 antigen).
FT /FTId=VAR_015124.
FT VARIANT 492 492 R -> Q (in KEL19 antigen;
FT dbSNP:rs61729035).
FT /FTId=VAR_015125.
FT VARIANT 494 494 E -> V (in KEL10/Ul(a) antigen;
FT dbSNP:rs61729032).
FT /FTId=VAR_006736.
FT VARIANT 548 548 H -> R (in KEL12 antigen).
FT /FTId=VAR_015126.
FT VARIANT 597 597 L -> P (in KEL6/Js(a) antigen;
FT dbSNP:rs8176038).
FT /FTId=VAR_006737.
FT VARIANT 726 726 S -> A (in dbSNP:rs8176048).
FT /FTId=VAR_016266.
FT MUTAGEN 72 72 C->S: Loss of Kell-XK complex.
FT MUTAGEN 319 319 C->S: No loss of Kell-XK complex.
FT MUTAGEN 582 582 E->G: Loss of catalytic activity.
SQ SEQUENCE 732 AA; 82824 MW; 604A168AD300EDB4 CRC64;
MEGGDQSEEE PRERSQAGGM GTLWSQESTP EERLPVEGSR PWAVARRVLT AILILGLLLC
FSVLLFYNFQ NCGPRPCETS VCLDLRDHYL ASGNTSVAPC TDFFSFACGR AKETNNSFQE
LATKNKNRLR RILEVQNSWH PGSGEEKAFQ FYNSCMDTLA IEAAGTGPLR QVIEELGGWR
ISGKWTSLNF NRTLRLLMSQ YGHFPFFRAY LGPHPASPHT PVIQIDQPEF DVPLKQDQEQ
KIYAQIFREY LTYLNQLGTL LGGDPSKVQE HSSLSISITS RLFQFLRPLE QRRAQGKLFQ
MVTIDQLKEM APAIDWLSCL QATFTPMSLS PSQSLVVHDV EYLKNMSQLV EEMLLKQRDF
LQSHMILGLV VTLSPALDSQ FQEARRKLSQ KLRELTEQPP MPARPRWMKC VEETGTFFEP
TLAALFVREA FGPSTRSAAM KLFTAIRDAL ITRLRNLPWM NEETQNMAQD KVAQLQVEMG
ASEWALKPEL ARQEYNDIQL GSSFLQSVLS CVRSLRARIV QSFLQPHPQH RWKVSPWDVN
AYYSVSDHVV VFPAGLLQPP FFHPGYPRAV NFGAAGSIMA HELLHIFYQL LLPGGCLACD
NHALQEAHLC LKRHYAAFPL PSRTSFNDSL TFLENAADVG GLAIALQAYS KRLLRHHGET
VLPSLDLSPQ QIFFRSYAQV MCRKPSPQDS HDTHSPPHLR VHGPLSSTPA FARYFRCARG
ALLNPSSRCQ LW
//

MIM 110900
*RECORD*
*FIELD* NO
110900
*FIELD* TI
#110900 BLOOD GROUP--KELL SYSTEM; KEL
;;BLOOD GROUP--KELL-CELLANO SYSTEM
KELL-NULL, INCLUDED;;
read moreK(0), INCLUDED;;
Ko, INCLUDED
*FIELD* TX
A number sign (#) is used with this entry because more than 25 antigens
of the Kell blood group system are determined by variation in the KEL
gene on chromosome 7q33 (KEL; 613883). A single antigen, Kx, is carried
by the XK gene (314850) on chromosome Xp21.

DESCRIPTION

The Kell blood group system is formed by 2 disulfide-linked proteins,
Kell and XK. The Kell protein is a type II membrane glycoprotein sharing
sequence homology with members of the M13 family of zinc-dependent
metalloproteases and possessing enzymatic activity characteristic of
that group (summary by Claperon et al., 2007).

The Kell blood group system is highly polymorphic, expressing over 25
antigens that have been classified in to 5 antithetical sets of high and
low prevalence antigens with the others being independently expressed or
having unknown antithetical partners. The different phenotypes are due
to single-nucleotide mutations that result in an amino acid substitution
(summary by Sha et al., 2006). See, for example, Kell (designated K or
K1)/Cellano (k, K2) (T193M; 613883.0001).

Yu et al. (2001) noted that the Kell antigens are the most potent
immunogens aside from the A and B antigens of the ABO system (110300)
and the D antigen (111680) of the Rh system (see 111700).

CLINICAL FEATURES

K1 is a strong immunogen; its antibodies can cause severe reactions if
incompatible blood is transfused and may cause hemolytic disease of the
newborn of sensitized mothers (summary by Lee et al., 1995). Newborns
with hemolytic anemia caused by anti-Kell antibodies present signs of
suppressed erythropoiesis, suggesting that anti-Kell antibodies suppress
erythropoiesis at the progenitor level (summary by Camara-Clayette et
al., 2001). Consequently, neither maternal antibody titers nor amniotic
bilirubin levels are good predictors of the severity of the disease
(summary by Westhoff and Reid, 2004).

The lack of Kell antigens, K(0), can be caused by several different gene
defects. K-null individuals do not have any obvious defect (summary by
Westhoff and Reid, 2004).

Weakened Kell antigens and absence of the Kx antigen at the surface of
red blood cells define the McLeod phenotype (300842). Although this
phenotype is related to Kell, it is the Kx antigen which is either
deleted or mutated and no longer able to bind Kell (summary by Claperon
et al., 2007). While K-null red cells have no detectable Kell surface
antigens, an enhanced level of Kx antigens differentiates the K-null
from the McLeod phenotype (summary by Westhoff and Reid, 2004). The
McLeod phenotype also includes acanthocytosis and neurologic
abnormalities.

POPULATION GENETICS

Kell antigens show population variations. K has an incidence of 9% in
Caucasians but is much less common in other ethnic backgrounds (summary
by Westhoff and Reid, 2004). The KEL6 antigen (see 613883.0003) has an
incidence of 20% in persons of African heritage but occurs in only about
1% of Caucasians (summary by Lee et al., 2003). Although it is very
rare, the K-null phenotype is widely distributed and has been identified
in Europeans, Japanese, Africans, and Indians (summary by Yu et al.,
2001).

MAPPING

Conneally et al. (1974, 1976) found Kell and PTC (171200) to be closely
linked: total lod = 10.78 at theta = 0.045. Keats et al. (1978) raised
the question of linkage of Kell and PTC to Jk-Km-Co, then thought to be
on chromosome 7. Spence et al. (1984) analyzed 2 new datasets regarding
PTC/Kell linkage and found a maximum likelihood estimate for theta (both
sexes) of 0.28. All published data including these gave a combined
maximum likelihood estimate of 0.14 (lod = 8.94) but there was
statistically significant evidence of heterogeneity among the published
studies.

HISTORY

The Kell and Cellano blood groups are symbolized K and k, respectively.
The Kell-Cellano system illustrates nicely the manner in which the
understanding of several of the blood group systems has developed.
Sutter is part of the Kell system (VAM).

Linkage data, suggestive but not conclusive, on Kell and pepsinogen
(169700) were reported by Weitkamp et al. (1975).

Westhoff and Reid (2004) summarized the history of the Kell/Kx blood
group system. The Kell blood group system was discovered in 1946, just a
few weeks after the introduction of the antiglobulin test. The red blood
cells of a newborn baby, thought to be suffering from hemolytic disease
of the newborn (HDN), gave a positive reaction in the direct
antiglobulin test (DAT). The serum of the mother reacted with red blood
cells from her husband and her older child and was later shown to react
with 9% of random donors. The system was named from Kelleher, her
surname, and the antigen is referred to as K (Kell, K1). Three years
later, the antithetical antigen, k (Cellano, K2), which is of high
incidence in all populations, was identified by typing large numbers of
red blood cell samples with an antibody that had also caused mild HDN
(Levine et al., 1949).

*FIELD* SA
Morton et al. (1965); Stroup et al. (1965); Zelinski et al. (1991)
*FIELD* RF
1. Camara-Clayette, V.; Rahuel, C.; Lopez, C.; Hattab, C.; Verkarre,
V.; Bertrand, O.; Cartron, J.-P.: Transcriptional regulation of the
KEL gene and Kell protein expression in erythroid and non-erythroid
cells. Biochem. J. 356: 171-180, 2001.

2. Claperon, A.; Hattab, C.; Armand, V.; Trottier, S.; Bertrand, O.;
Ouimet, T.: The Kell and XK proteins of the Kell blood group are
not co-expressed in the central nervous system. Brain Res. 1147:
12-24, 2007.

3. Conneally, P. M.; Dumont-Driscoll, M.; Huntzinger, R. S.; Nance,
W. E.; Jackson, C. E.: Linkage relations of the loci for Kell and
phenylthiocarbamide (PTC) taste sensitivity. Hum. Hered. 26: 267-271,
1976.

4. Conneally, P. M.; Nance, W. E.; Huntzinger, R. S.: Linkage analysis
of Kell-Sutter and PTC loci. (Abstract) Am. J. Hum. Genet. 26: 22A
only, 1974.

5. Keats, B. J. B.; Morton, N. E.; Rao, D. C.: Possible linkages
(lod score over 1.5) and a tentative map of the Jk-Km linkage group. Cytogenet.
Cell Genet. 22: 304-308, 1978.

6. Lee, S.; Debnath, A. K.; Redman, C. M.: Active amino acids of
the Kell blood group protein and model of the ectodomain based on
the structure of neutral endopeptidase 24.11. Blood 102: 3028-3034,
2003.

7. Lee, S.; Wu, X.; Reid, M. E.; Zelinski, T.; Redman, C. M.: Molecular
basis of the Kell (K1) phenotype. Blood 85: 912-916, 1995.

8. Levine, P.; Backer, M.; Wigod, M.; Ponder, R.: A new human hereditary
blood property (Cellano) present in 99.8% of all bloods. Science 109:
464-466, 1949.

9. Morton, N. E.; Krieger, H.; Steinberg, A. G.; Rosenfield, R. E.
: Genetic evidence confirming the localization of Sutter in the Kell
blood-group system. Vox Sang. 10: 608-613, 1965.

10. Sha, Q.; Redman, C. M.; Lee, S.: Endothelin-3-converting enzyme
activity of the KEL1 and KEL6 phenotypes of the Kell blood group system. J.
Biol. Chem. 281: 7180-7192, 2006.

11. Spence, M. A.; Falk, C. T.; Neiswanger, K.; Field, L. L.; Marazita,
M. L.; Allen, F. H., Jr.; Siervogel, R. M.; Roche, A. F.; Crandall,
B. F.; Sparkes, R. S.: Estimating the recombination frequency for
the PTC-Kell linkage. Hum. Genet. 67: 183-186, 1984.

12. Stroup, M.; MacIlroy, M.; Walker, R.; Aydelotte, J. V.: Evidence
that Sutter belongs to the Kell blood group system. Transfusion 5:
309-314, 1965.

13. Weitkamp, L. R.; Townes, P. L.; Johnston, E.: Linkage data on
urinary pepsinogen and the Kell blood group. Birth Defects Orig.
Art. Ser. 11(3): 281-282, 1975. Note: Alternate: Cytogenet. Cell
Genet. 14: 451-452, 1975.

14. Westhoff, C. M.; Reid, M. E.: Review: the Kell, Duffy, and Kidd
blood group systems. Immunohematology 20: 37-49, 2004.

15. Yu, L.-C.; Twu, Y.-C.; Chang, C.-Y.; Lin, M.: Molecular basis
of the Kell-null phenotype: a mutation at the splice site of human
KEL gene abolishes the expression of Kell blood group antigens. J.
Biol. Chem. 276: 10247-10252, 2001.

16. Zelinski, T. A.; Coghlan, G. E.; Myal, Y.; White, L. J.; Philipps,
S. E.: Assignment of the Kell blood group locus to chromosome 7q.
(Abstract) Cytogenet. Cell Genet. 58: 1927 only, 1991.

*FIELD* CN
Cassandra L. Kniffin - updated: 11/13/2007
Paul J. Converse - updated: 4/6/2001
Victor A. McKusick - updated: 11/29/2000
Victor A. McKusick - updated: 10/13/1999

*FIELD* CD
Victor A. McKusick: 6/4/1986

*FIELD* ED
alopez: 05/02/2011
alopez: 4/18/2011
alopez: 11/10/2010
wwang: 11/20/2007
ckniffin: 11/13/2007
carol: 9/1/2005
joanna: 3/17/2004
terry: 8/13/2003
terry: 3/21/2002
cwells: 5/3/2001
mgross: 4/6/2001
terry: 3/21/2001
mcapotos: 12/18/2000
terry: 11/29/2000
mcapotos: 9/8/2000
mcapotos: 9/6/2000
mgross: 10/13/1999
carol: 3/28/1998
mark: 8/20/1996
davew: 6/9/1994
terry: 5/13/1994
mimadm: 4/13/1994
warfield: 4/6/1994
pfoster: 3/25/1994
carol: 9/14/1993

MIM 613883
*RECORD*
*FIELD* NO
613883
*FIELD* TI
*613883 KELL BLOOD GROUP METALLOENDOPEPTIDASE; KEL
;;KELL BLOOD GROUP GLYCOPROTEIN;;
read moreKELL BLOOD GROUP ANTIGEN
*FIELD* TX

DESCRIPTION

The KEL gene encodes the Kell blood group protein, a
metalloendopeptidase that preferentially cleaves big endothelin-3
(131242) to produce bioactive endothelin-3. Kell is a polymorphic
protein; the more than 25 antigens of the Kell blood group (110900)
result from point mutations resulting in single amino acid substitutions
(summary by Sha et al., 2006).

CLONING

KEL antigens reside on a 93-kD membrane glycoprotein that is surface
exposed and associated with the underlying cytoskeleton. Lee et al.
(1991) isolated tryptic peptides of this glycoprotein and, based on the
amino acid sequence of one of the peptides and by using PCR, prepared a
specific oligonucleotide to screen a lambda-gt10 human bone marrow cDNA
library. One clone contained cDNA with an open reading frame for a
predicted 83-kD protein. All known KEL amino acid sequences were present
in the deduced sequence; moreover, rabbit antibody to a 30-amino acid
peptide prepared from this sequence reacted on an immunoblot with
authentic KEL protein. The KEL cDNA sequence predicted a 732-amino acid
protein. A computer-based search showed that KEL has structural and
sequence homology to a family of zinc metalloglycoproteins with neutral
endopeptidase activity.

Marsh (1992) reviewed the cloning of the KEL gene and its
characterization. By Northern blot analysis of RNA from multiple
tissues, Lee et al. (1993) demonstrated that the KEL gene is expressed
only in erythroid tissues. Wagner et al. (2000) presented data
indicating that KEL is expressed not only on erythroid blood cells but
also on myeloid progenitor cells. By dot-blot analysis, Camara-Clayette
et al. (2001) detected high levels of Kell expression in brain tissues,
spleen, lymph node, bone marrow, and testis. Most tissues analyzed
exhibited low levels of Kell transcripts. All fetal tissues showed Kell
expression.

GENE STRUCTURE

Lee et al. (1995) determined that the KEL gene comprises 19 exons and
spans 21.5 kb. The single membrane spanning region of the Kell protein
is encoded in exon 3 and the putative zinc endopeptidase active site is
in exon 16.

MAPPING

Despite its high level of polymorphism with a series of serologically
distinct antigens (KEL1 to KEL24), the gene controlling KEL antigen
expression (KEL) eluded chromosomal assignment until the mapping work of
Zelinski et al. (1991). They succeeded in showing linkage with
prolactin-inducible protein (PIP; 176720), which had been assigned to
7q32-q36. No evidence of recombination was found; maximum lod = 10.36 at
theta = 0.00. The mapping of the Kell blood group to chromosome 7 means
that PTC tasting (171200), the YT blood group (112100), and
hyperreflexia (145290) are also located there. Purohit et al. (1992)
demonstrated close linkage to cystic fibrosis (see CFTR; 602421);
sex-specific estimates of recombination fractions were 0.013 in males
and 0.219 in females, with a joint maximum lod score of 4.58.

Lee et al. (1993) used genomic clones as probes to confirm the
assignment of the gene to chromosome 7 by Southern analysis of
human/hamster somatic cell hybrids; by in situ hybridization, they
localized the KEL gene to 7q33. Using a biotinylated 1.1-kb DNA fragment
containing the 3-prime half of the KEL cDNA for in situ hybridization,
Murphy et al. (1993) likewise assigned the KEL gene to 7q33-q35. They
suggested that since the in situ assignment agrees with the genetic
localization using antigenic variation as the marker, KEL antigenic
determinants are part of the polypeptide chain rather than the
associated sugar molecules.

GENE FUNCTION

The Kell blood group protein shares a consensus sequence with a large
family of zinc-dependent endopeptidases. Kell has homology with
endothelin-converting enzyme-1 (ECE1; 600423) and the PHEX gene product
(300550) which, as a group, comprise the M13 subfamily of mammalian
neutral endopeptidases. Lee et al. (1999) expressed a secreted form of
wildtype protein, devoid of the intracellular and transmembrane domains,
in Sf9 cells. As a negative control, an inactive mutant Kell protein,
E582G, was expressed. As determined by N-terminal amino acid sequencing
and mass spectrometry of the cleaved products, wildtype secreted Kell,
but not the control mutant protein, specifically cleaved big
endothelin-3 (ET3; 131242) at trp21/ile22, yielding ET3. Red blood cells
of common Kell phenotype also preferentially processed big ET3, in
contrast to Kell-null cells, which did not. These data demonstrated that
the Kell blood group protein is a proteolytic enzyme that processes big
ET3, generating ET3, a potent bioactive peptide with multiple biologic
roles.

On red cells, Kell protein is linked by a single disulfide bond to XK
(314850), a protein that traverses the membrane 10 times and whose
absence, as occurs in the McLeod phenotype, is associated with a set of
clinical symptoms that include nerve and muscle disorders and red cell
acanthocytosis (109270). Russo et al. (2000) confirmed that, whereas XK
has a wider tissue distribution, Kell is expressed primarily in the
erythroid tissues, and in a near-equal amount in testis, with weaker
expression in a large number of other tissues. In skeletal muscle,
isolation of XK with a specific antibody coisolated Kell protein.

The Kell and XK proteins exist as a disulfide-bonded complex on the
human red cell membrane. Russo et al. (1998) determined that Kell is
covalently linked through the nonconserved cys72 to cys347 of XK
protein. The covalent linkage of Kell and XK is not necessary for cell
surface expression of Kell antigens, since Kell antigens are expressed
in a recombinant system that synthesizes only Kell protein and not XK
and Kell antigens can be detected in McLeod red cells that lack XK.
There was no evidence that Kell and XK are part of a larger membrane
complex.

MOLECULAR GENETICS

Westhoff and Reid (2004) listed the molecular basis of many antigens of
the Kell blood group system. The lack of Kell antigens, K(0), is caused
by several different gene defects, including nucleotide deletion,
defective splicing, premature stop codons, and amino acid substitutions;
see e.g., 613883.0002 and Lee et al. (2001).

Data on gene frequencies of allelic variants were tabulated by
Roychoudhury and Nei (1988).

Chiaroni et al. (2005) analyzed allelic variations at pocket P4 of the
HLA-DRB1 complex (142857) in 54 French patients with Kell blood group
immunization. All patients had anti-K antibodies and K-negative
phenotype. The frequency of HLA-DRB1*11 was significantly higher in
patients (57%) compared to controls (28%), whereas HLA-DRB1*07 was less
frequent in patients (4%) compared to controls (27%). Further analysis
showed that the frequency of the epitope formed by residues S13, D70,
and A74, common to both DRB1*11 and DRB1*13, was significantly higher in
patients (83%) compared to controls (52%), yielding an odds ratio of
4.5. Chiaroni et al. (2005) concluded that the development of K
immunization after exposure to K-positive blood, which occurs
approximately 9% of the time, is due in part to genetic variation at the
HLA-DRB1 locus, which is involved in K peptide presentation.

*FIELD* AV
.0001
KELL K/k BLOOD GROUP POLYMORPHISM
KEL, THR193MET

The importance of the Kell blood group system to transfusion medicine is
indicated by the fact that the Kell antigen (K1) is probably secondary
in importance to Rh D as an immunogen in alloimmunized pregnancies that
cause hemolytic disease of the newborn. The K/k (K1/K2) blood group
polymorphism, otherwise known as the Kell/Cellano polymorphism, was
shown by Lee et al. (1995) to represent a point mutation resulting in a
thr193(k) to met193(K) amino acid substitution in the Kell glycoprotein.
The C-to-T substitution in exon 6 creates a BsmI restriction site that
was exploited by Lee et al. (1995) to form the basis of a simple PCR
assay to determine the Kell type of an individual. Avent and Martin
(1996) described a simple allele-specific PCR assay for the
determination of K1/K2 status of an individual. The assay was
successfully applied to the determination of the Kell status of fetal
material and was found suitable for use in the clinical management of
pregnancies in which the fetus is at risk for hemolytic disease of the
newborn (HDN) due to anti-K.

.0002
KELL-NULL PHENOTYPE
KEL, IVS3DS, G-C

Different Kell phenotypes result from point mutations leading to amino
acid changes in the Kell glycoprotein. Chown et al. (1957) first
described the Kell null phenotype as the complete lack of all known Kell
antigens on red cells. Kell null is found at a very low frequency in all
population groups. In a Chinese individual with the Kell null phenotype,
Yu et al. (2001) identified a homozygous G-to-C transversion at the
5-prime splice donor site of intron 3 of the KEL gene. RT-PCR analysis
revealed the absence of the complete 909-bp KEL mRNA and its replacement
by a 767-bp product lacking the 142-bp exon 3 region. Exon 3 encodes the
transmembrane region of the Kell glycoprotein.

.0003
KEL6 ANTIGEN
KEL, LEU597PRO

Lee et al. (1995) demonstrated that the KEL6 antigen, present in
approximately 20% of persons of African heritage, is determined by a
T-to-C transition at nucleotide 1910 in exon 17 of the KEL gene,
resulting in a leu597-to-pro (L597P) amino acid substitution. Lee et al.
(2003) noted that the L597P substitution occurs between 2 closely spaced
nonconserved cysteine residues, and in a linear sequence is located
close to the zinc binding site beginning at codon 581.

*FIELD* RF
1. Avent, N. D.; Martin, P. G.: Kell typing by allele-specific PCR
(ASP). Brit. J. Haemat. 93: 728-730, 1996.

2. Camara-Clayette, V.; Rahuel, C.; Lopez, C.; Hattab, C.; Verkarre,
V.; Bertrand, O.; Cartron, J.-P.: Transcriptional regulation of the
KEL gene and Kell protein expression in erythroid and non-erythroid
cells. Biochem. J. 356: 171-180, 2001.

3. Chiaroni, J.; Dettori, I.; Ferrera, V.; Legrand, D.; Touinssi,
M.; Mercier, P.; de Micco, P.; Reviron, D.: HLA-DRB1 polymorphism
is associated with Kell immunisation. Brit. J. Haemat. 132: 374-378,
2005.

4. Chown, B.; Lewis, M.; Kaita, K.: A 'new' Kell blood-group phenotype. Nature
180: 711 only, 1957.

5. Lee, S.; Debnath, A. K.; Redman, C. M.: Active amino acids of
the Kell blood group protein and model of the ectodomain based on
the structure of neutral endopeptidase 24.11. Blood 102: 3028-3034,
2003.

6. Lee, S.; Lin, M.; Mele, A.; Cao, Y.; Farmar, J.; Russo, D.; Redman,
C.: Proteolytic processing of big endothelin-3 by the Kell blood
group protein. Blood 94: 1440-1450, 1999.

7. Lee, S.; Russo, D. C. W.; Reiner, A. P.; Lee, J. H.; Sy, M. Y.;
Telen, M. J.; Judd, W. J.; Simon, P.; Rodrigues, M. J.; Chabert,
T.; Poole, J.; Jovanovic-Srzentic, S.; Levene, C.; Yahalom, V.; Redman,
C. M.: Molecular defects underlying the Kell null phenotype. J.
Biol. Chem. 276: 27281-27289, 2001.

8. Lee, S.; Wu, X.; Reid, M.; Redman, C.: Molecular basis of the
K:6,-7 [Js(a+b-)] phenotype in the Kell blood group system. Transfusion 35:
822-825, 1995.

9. Lee, S.; Wu, X.; Reid, M. E.; Zelinski, T.; Redman, C. M.: Molecular
basis of the Kell (K1) phenotype. Blood 85: 912-916, 1995.

10. Lee, S.; Zambas, E.; Green, E. D.; Redman, C.: Organization of
the gene encoding the human Kell blood group protein. Blood 85:
1364-1370, 1995. Note: Erratum: Blood 87: 4922 only, 1996.

11. Lee, S.; Zambas, E. D.; Marsh, W. L.; Redman, C. M.: Molecular
cloning and primary structure of Kell blood group protein. Proc.
Nat. Acad. Sci. 88: 6353-6357, 1991.

12. Lee, S.; Zambas, E. D.; Marsh, W. L.; Redman, C. M.: The human
Kell blood group gene maps to chromosome 7q33 and its expression is
restricted to erythroid cells. Blood 81: 2804-2809, 1993.

13. Marsh, W. L.: Molecular biology of blood groups: cloning of the
Kell gene. Transfusion 32: 98-101, 1992.

14. Murphy, M. T.; Morrison, N.; Miles, J. S.; Fraser, R. H.; Spurr,
N. K.; Boyd, E.: Regional chromosomal assignment of the Kell blood
group locus (KEL) to chromosome 7q33-q35 by fluorescence in situ hybridization:
evidence for the polypeptide nature of antigenic variation. Hum.
Genet. 91: 585-588, 1993.

15. Purohit, K. R.; Weber, J. L.; Ward, L. J.; Keats, B. J. B.: The
Kell blood group locus is close to the cystic fibrosis locus on chromosome
7. Hum. Genet. 89: 457-458, 1992.

16. Roychoudhury, A. K.; Nei, M.: Human Polymorphic Genes: World
Distribution. New York: Oxford Univ. Press (pub.) 1988.

17. Russo, D.; Redman, C.; Lee, S.: Association of XK and Kell blood
group proteins. J. Biol. Chem. 273: 13950-13956, 1998.

18. Russo, D.; Wu, X.; Redman, C. M.; Lee, S.: Expression of Kell
blood group protein in nonerythroid tissues Blood 96: 340-346, 2000.

19. Sha, Q.; Redman, C. M.; Lee, S.: Endothelin-3-converting enzyme
activity of the KEL1 and KEL6 phenotypes of the Kell blood group system. J.
Biol. Chem. 281: 7180-7192, 2006.

20. Wagner, T.; Berer, A.; Lanzer, G.; Geissler, K.: Kell is not
restricted to the erythropoietic lineage but is also expressed on
myeloid progenitor cells. Brit. J. Haemat. 110: 409-411, 2000.

21. Westhoff, C. M.; Reid, M. E.: Review: the Kell, Duffy, and Kidd
blood group systems. Immunohematology 20: 37-49, 2004.

22. Yu, L.-C.; Twu, Y.-C.; Chang, C.-Y.; Lin, M.: Molecular basis
of the Kell-null phenotype: a mutation at the splice site of human
KEL gene abolishes the expression of Kell blood group antigens. J.
Biol. Chem. 276: 10247-10252, 2001.

23. Zelinski, T.; Coghlan, G.; Myal, Y.; Shiu, R. P. C.; Philipps,
S.; White, L.; Lewis, M.: Genetic linkage between the Kell blood
group system and prolactin-inducible protein loci: provisional assignment
of KEL to chromosome 7. Ann. Hum. Genet. 55: 137-140, 1991.

*FIELD* CD
Anne M. Stumpf: 4/8/2011

*FIELD* ED
terry: 03/15/2013
terry: 3/15/2013
terry: 5/24/2011
terry: 5/4/2011
alopez: 4/18/2011

RBCC Red Blood Cell Collection

Full text data of KEL