RBCC Red Blood Cell Collection

ICAM4 (LW) [Confidence: high (a blood group or CD marker)]
Intercellular adhesion molecule 4; ICAM-4 (Landsteiner-Wiener blood group glycoprotein; LW blood group protein; CD242; Flags: Precursor)

hRBCD IPI00000118
IPI00000118 Splice isoform Long of Q14773 Intercellular adhesion molecule-4 precursor Splice isoform Long of Q14773 Intercellular adhesion molecule-4 precursor membrane n/a 1 2 3 3 n/a 3 1 7 n/a 1 1 3 2 n/a 1 4 n/a 1 1 integral membrane protein splice isoform Long and Short expected molecular weight found in band between 43-49 kDa

BGMUT lw
516 lw ICAM4 ICAM4 299G LW B; LW 299G (LW 7) 299A>G Q100R LW(a-b+) or LW(a+b+) Generally rare; Latvians and Lithuanians ~12% (gene frequency 0.06); Estonians 8%; Finns 6%; Poles 4%; other Europeans <1% (Sistonen et al. Hum Hered. 1999 49:154) 7632968 not available Hermand et al. Blood 1995 86 1590-1594 this allele shows the same sequence as the reference allele used here except it specifies the LW b phenotype. The numbering of sites of nucleotde and amino acid changes are according to the reference sequence and that shown in publication shown above PMID 7632968 Blumenfeld OO,curator 2012-07-21 14:22:38.333 NA

Comments
Isoform Q14773-2 was detected.

UniProt Q14773
ID ICAM4_HUMAN Reviewed; 271 AA.
AC Q14773; A0M8X2; Q14771; Q14772; Q16375; Q9BWR0;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1997, sequence version 1.
DT 22-JAN-2014, entry version 127.
DE RecName: Full=Intercellular adhesion molecule 4;
DE Short=ICAM-4;
DE AltName: Full=Landsteiner-Wiener blood group glycoprotein;
DE Short=LW blood group protein;
DE AltName: CD_antigen=CD242;
DE Flags: Precursor;
GN Name=ICAM4; Synonyms=LW;
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] (ISOFORMS LONG AND SHORT).
RX PubMed=8202485; DOI=10.1073/pnas.91.12.5306;
RA Bailly P., Hermand P., Callebaut I., Sonneborn H.H., Khamlichi S.,
RA Mornon J.-P., Cartron J.-P.;
RT "The LW blood group glycoprotein is homologous to intercellular
RT adhesion molecules.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:5306-5310(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM LONG).
RX PubMed=8639917;
RA Hermand P., le Pennec P.Y., Rouger P., Cartron J.-P., Bailly P.;
RT "Characterization of the gene encoding the human LW blood group
RT protein in LW+ and LW- phenotypes.";
RL Blood 87:2962-2967(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LEU-208.
RG SeattleSNPs variation discovery resource;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J.,
RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS LONG AND 3).
RC TISSUE=Lung, and Placenta;
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 [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-130, AND VARIANT BLOOD GROUP LW(B)
RP ARG-100.
RX PubMed=7632968;
RA Hermand P., Gane P., Mattei M.-G., Sistonen P., Cartron J.-P.,
RA Bailly P.;
RT "Molecular basis and expression of the LWa/LWb blood group
RT polymorphism.";
RL Blood 86:1590-1594(1995).
RN [9]
RP FUNCTION.
RX PubMed=11435317; DOI=10.1182/blood.V98.2.458;
RA Spring F.A., Parsons S.F., Ortlepp S., Olsson M.L., Sessions R.,
RA Brady R.L., Anstee D.J.;
RT "Intercellular adhesion molecule-4 binds alpha(4)beta(1) and alpha(V)-
RT family integrins through novel integrin-binding mechanisms.";
RL Blood 98:458-466(2001).
CC -!- FUNCTION: ICAM proteins are ligands for the leukocyte adhesion
CC protein LFA-1 (integrin alpha-L/beta-2). ICAM4 is also a ligand
CC for alpha-4/beta-1 and alpha-V integrins.
CC -!- SUBCELLULAR LOCATION: Isoform Long: Cell membrane; Single-pass
CC type I membrane protein.
CC -!- SUBCELLULAR LOCATION: Isoform Short: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=Long;
CC IsoId=Q14773-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=Q14773-2; Sequence=VSP_002519;
CC Name=3;
CC IsoId=Q14773-3; Sequence=VSP_043229;
CC -!- TISSUE SPECIFICITY: Erythrocytes.
CC -!- PTM: N- and O-glycosylated.
CC -!- POLYMORPHISM: Responsible for the Landsteiner-Wiener blood group
CC system [MIM:111250]. The molecular basis of the
CC LW(A)=LW5/LW(B)=LW7 blood group antigens is a single variation in
CC position 100; Gln-100 corresponds to LW(A) and Arg-100 to LW(B).
CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. ICAM
CC family.
CC -!- SIMILARITY: Contains 2 Ig-like C2-type (immunoglobulin-like)
CC domains.
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;=lw";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/icam4/";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; L27671; AAA59538.1; -; mRNA.
DR EMBL; L27670; AAA59537.1; -; mRNA.
DR EMBL; X93093; CAA63646.1; -; Genomic_DNA.
DR EMBL; BT009816; AAP88818.1; -; mRNA.
DR EMBL; DQ011692; AAY16986.1; -; Genomic_DNA.
DR EMBL; AC011511; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471106; EAW84089.1; -; Genomic_DNA.
DR EMBL; BC000046; AAH00046.1; -; mRNA.
DR EMBL; BC029364; AAH29364.1; -; mRNA.
DR EMBL; S78852; AAB35046.1; -; mRNA.
DR PIR; I52612; I52612.
DR PIR; I59300; I59300.
DR PIR; I80159; I80159.
DR RefSeq; NP_001034221.1; NM_001039132.2.
DR RefSeq; NP_001535.1; NM_001544.4.
DR RefSeq; NP_071772.1; NM_022377.3.
DR UniGene; Hs.706750; -.
DR ProteinModelPortal; Q14773; -.
DR SMR; Q14773; 47-227.
DR IntAct; Q14773; 2.
DR STRING; 9606.ENSP00000342114; -.
DR DMDM; 2497309; -.
DR PaxDb; Q14773; -.
DR PRIDE; Q14773; -.
DR DNASU; 3386; -.
DR Ensembl; ENST00000340992; ENSP00000342114; ENSG00000105371.
DR Ensembl; ENST00000380770; ENSP00000370147; ENSG00000105371.
DR Ensembl; ENST00000393717; ENSP00000377320; ENSG00000105371.
DR GeneID; 3386; -.
DR KEGG; hsa:3386; -.
DR UCSC; uc002mns.2; human.
DR CTD; 3386; -.
DR GeneCards; GC19P010397; -.
DR HGNC; HGNC:5347; ICAM4.
DR MIM; 111250; phenotype.
DR MIM; 614088; gene.
DR neXtProt; NX_Q14773; -.
DR PharmGKB; PA29595; -.
DR eggNOG; NOG47696; -.
DR HOGENOM; HOG000112993; -.
DR HOVERGEN; HBG052076; -.
DR KO; K06581; -.
DR OMA; TLRCHVT; -.
DR OrthoDB; EOG7B31NV; -.
DR PhylomeDB; Q14773; -.
DR Reactome; REACT_118779; Extracellular matrix organization.
DR Reactome; REACT_6900; Immune System.
DR GenomeRNAi; 3386; -.
DR NextBio; 13396; -.
DR PRO; PR:Q14773; -.
DR Bgee; Q14773; -.
DR CleanEx; HS_ICAM4; -.
DR Genevestigator; Q14773; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral to membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005178; F:integrin binding; TAS:ProtInc.
DR GO; GO:0016337; P:cell-cell adhesion; IEA:InterPro.
DR GO; GO:0050776; P:regulation of immune response; TAS:Reactome.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR013768; ICAM_N.
DR InterPro; IPR003987; ICAM_VCAM_N.
DR InterPro; IPR013783; Ig-like_fold.
DR Pfam; PF03921; ICAM_N; 1.
DR PRINTS; PR01472; ICAMVCAM1.
DR PROSITE; PS50835; IG_LIKE; FALSE_NEG.
PE 2: Evidence at transcript level;
KW Alternative splicing; Blood group antigen; Cell adhesion;
KW Cell membrane; Complete proteome; Disulfide bond; Glycoprotein;
KW Immunoglobulin domain; Membrane; Polymorphism; Reference proteome;
KW Repeat; Secreted; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1 22 Potential.
FT CHAIN 23 271 Intercellular adhesion molecule 4.
FT /FTId=PRO_0000014796.
FT TOPO_DOM 23 240 Extracellular (Potential).
FT TRANSMEM 241 261 Helical; (Potential).
FT TOPO_DOM 262 271 Cytoplasmic (Potential).
FT DOMAIN 62 124 Ig-like C2-type 1.
FT DOMAIN 146 217 Ig-like C2-type 2.
FT CARBOHYD 68 68 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 78 78 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 190 190 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 223 223 N-linked (GlcNAc...) (Potential).
FT DISULFID 69 117 By similarity.
FT DISULFID 153 210 By similarity.
FT VAR_SEQ 132 271 KPPHSVILEPPVLKGRKYTLRCHVTQVFPVGYLVVTLRHGS
FT RVIYSESLERFTGLDLANVTLTYEFAAGPRDFWQPVICHAR
FT LNLDGLVVRNSSAPITLMLAWSPAPTALASGSIAALVGILL
FT TVGAAYLCKCLAMKSQA -> SVPGGLLGGDPEAWKPGHLF
FT RKPGALHRPGSGQRDLDLRVCCWTPRLLAARDLPRAPQSRR
FT PGGPQQLGTHYTDARLEPRAHSFGLRFHRCPCRDPPHCGRC
FT VPMQVPSYEVPGVKGDVLCRLSEKKRNMKQSGEMAIHGG
FT (in isoform 3).
FT /FTId=VSP_043229.
FT VAR_SEQ 233 271 AWSPAPTALASGSIAALVGILLTVGAAYLCKCLAMKSQA
FT -> GEAPL (in isoform Short).
FT /FTId=VSP_002519.
FT VARIANT 100 100 Q -> R (in LW(B); dbSNP:rs77493670).
FT /FTId=VAR_003912.
FT VARIANT 208 208 V -> L (in dbSNP:rs36023325).
FT /FTId=VAR_038721.
FT CONFLICT 14 29 AAAYPGVGSALGRRTK -> RPPTRELGARWDAGL (in
FT Ref. 1; AAA59538/AAA59537).
SQ SEQUENCE 271 AA; 29265 MW; 2F6BC8BABD79E615 CRC64;
MGSLFPLSLL FFLAAAYPGV GSALGRRTKR AQSPKGSPLA PSGTSVPFWV RMSPEFVAVQ
PGKSVQLNCS NSCPQPQNSS LRTPLRQGKT LRGPGWVSYQ LLDVRAWSSL AHCLVTCAGK
TRWATSRITA YKPPHSVILE PPVLKGRKYT LRCHVTQVFP VGYLVVTLRH GSRVIYSESL
ERFTGLDLAN VTLTYEFAAG PRDFWQPVIC HARLNLDGLV VRNSSAPITL MLAWSPAPTA
LASGSIAALV GILLTVGAAY LCKCLAMKSQ A
//

MIM 111250
*RECORD*
*FIELD* NO
111250
*FIELD* TI
#111250 BLOOD GROUP SYSTEM, LANDSTEINER-WIENER; LW
;;LANDSTEINER-WIENER BLOOD GROUP SYSTEM
read more*FIELD* TX
A number sign (#) is used with this entry because LW blood group
antigens reside on a protein encoded by the ICAM4 gene (614088) on
chromosome 19p13.3.

DESCRIPTION

The LW blood group antigens reside on a 42-kD red cell intercellular
adhesion molecule designated ICAM4 (Bailly et al., 1994; Bailly et al.,
1995).

MAPPING

Sistonen (1984) showed that the LW locus is closely linked to C3
(120700) and Lutheran (111200) on chromosome 19. The maximum lod score
was 3.61 at theta = 0.00 for LW:C3 and 3.67 at theta = 0.05 for LW:Lu.
The data suggested that the Lewis blood group locus is situated outside
the C3-LW region.

Using a C3 DNA probe, Lewis et al. (1987) found no recombinants between
LW and C3 (maximum lod score = 4.216 at theta = 0.00). No recombinants
were found in 16 female meioses. Combined with the data of Sistonen
(1984), the recombination fraction between LW and C3 was estimated to be
0.09 in females (maximum lod score = 3.773).

Lewis et al. (1988) established close linkage between LW and LDLR
(606945); maximum lod = 8.43 at theta = 0.00. They concluded that LDLR,
C3, and LW constitute a tightly linked gene cluster. Their findings
supported a 19p13.2-cen position for LW.

The LW locus was assigned to 19p13.3 by isotopic in situ hybridization
(Hermand et al., 1995).

MOLECULAR GENETICS

- LW(a)/LW(b) Polymorphism

Hermand et al. (1995) demonstrated that the molecular basis for the
LW(a)/LW(b) polymorphism is a single-basepair change (308A-G) in the
ICAM4 gene that correlates with a PvuII restriction site and results in
a gln70-to-arg (Q70R) amino acid substitution (614088.0001). COS-7 cells
transfected with LW(a) or LW(b) cDNAs reacted with human anti-LW(a) and
anti-LW(b) sera, respectively, as well as with a murine monoclonal
anti-LW(ab) antibody, as shown by flow cytometry analysis. Study by
Southern blot analysis indicated that the LW locus is composed of a
single gene that is not grossly rearranged in the rare LW(a-b-)
individuals or in Rh-null individuals deficient for LW antigens. RFLP
analysis using PvuII indicated that these variants were homozygous for a
phenotypically silent LW(a) allele in all cases.

- LW(a-b-) Phenotype

Individuals with the rare LW(a-b-) phenotype lack LW antigens and LW
protein expression on red blood cells. Some of these individuals express
normal Rh antigens, but others also lack Rh and Rh-associated antigens
and proteins. Using Southern blot analysis, Hermand et al. (1995) showed
that the ICAM4 gene was not grossly rearranged in an individual with the
LW(a-b-) phenotype or in individuals with the Rh-null phenotype, who
also lack LW antigens. RFLP analysis using PvuII indicated that the
LW(a-b-) individual and 3 Rh-null individuals were homozygous for a
phenotypically silent LW(a) allele.

In an individual with the LW(a-b-) phenotype who carried a normal Rh
phenotype, Hermand et al. (1996) identified a 10-bp deletion in exon 1
of the ICAM4 gene (614088.0002) that generated a premature stop codon,
resulting in a truncated protein without the transmembrane and
cytoplasmic domains. Heterogeneity was indicated by the fact that no
detectable abnormality of the LW gene or transcript could be detected in
another LW(a-b-) individual.

HISTORY

LW stands for Landsteiner and Wiener, the researchers who first
discovered the LW blood group with antibody raised in guinea pigs
injected with the cells of rhesus monkeys. It was originally thought to
be identical to the anti-D first described in a woman with an
erythroblastotic infant studied by Levine and Stetson (1939). Hence, the
name of the Rh system. It was later found to be distinct; LW is the true
Rhesus blood group, but this designation had been preempted. Levine
suggested the designation LW.

*FIELD* SA
Race and Sanger (1975); Sistonen and Virtaranta-Knowles (1985)
*FIELD* RF
1. Bailly, P.; Hermand, P.; Callebaut, I.; Sonneborn, H. H.; Khamlichi,
S.; Mornon, J.-P.; Cartron, J.-P.: The LW blood group glycoprotein
in homologous to intercellular adhesion molecules. Proc. Nat. Acad.
Sci. 91: 5306-5310, 1994.

2. Bailly, P.; Tontti, E.; Hermand, P.; Cartron, J.-P.; Gahmberg,
C. G.: The red cell LW blood group protein is an intercellular adhesion
molecule which binds to CD11/CD18 leukocyte integrins. Europ. J.
Immun. 25: 3316-3320, 1995.

3. Hermand, P.; Gane, P.; Mattei, M. G.; Sistonen, P.; Cartron, J.-P.;
Bailly, P.: Molecular basis and expression of the LW(a)/LW(b) blood
group polymorphism. Blood 86: 1590-1594, 1995.

4. Hermand, P.; Le Pennec, P. Y.; Rouger, P.; Cartron, J.-P.; Bailly,
P.: Characterization of the gene encoding the human LW blood group
protein in LW(+) and LW(-) phenotypes. Blood 87: 2962-2967, 1996.

5. Levine, P.; Stetson, R. E.: An unusual case of intragroup agglutination. JAMA 113:
126-127, 1939.

6. Lewis, M.; Kaita, H.; Coghlan, G.; Philipps, S.; Belcher, E.; McAlpine,
P. J.; Coopland, G. R.; Woods, R. A.: The chromosome 19 linkage group
LDLR, C3, LW, APOC2, LU, SE in man. Ann. Hum. Genet. 52: 137-144,
1988.

7. Lewis, M.; Kaita, H.; Philipps, S.; Coghlan, G.; McAlpine, P. J.;
Coopland, G. R.; Woods, R. A.: The LW:C3 recombination fraction in
female meioses. Ann. Hum. Genet. 51: 201-203, 1987.

8. Race, R. R.; Sanger, R.: Blood Groups in Man. Oxford: Blackwell
(pub.) (6th ed.): 1975. Pp. 228-232.

9. Sistonen, P.: Linkage of the LW blood group locus with the complement
C3 and Lutheran blood group loci. Ann. Hum. Genet. 48: 239-242,
1984.

10. Sistonen, P.; Virtaranta-Knowles, K.: Evidence for linkage of
LW blood group locus with the complement C3, and Le, Lu and Se loci
with assignment to chromosome 19. (Abstract) Cytogenet. Cell Genet. 40:
747, 1985.

*FIELD* CN
Matthew B. Gross - updated: 7/14/2011

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

*FIELD* ED
mgross: 07/14/2011
mgross: 7/14/2011
carol: 7/14/2011
terry: 6/3/2009
carol: 5/16/2007
carol: 5/15/2007
alopez: 3/18/2004
ckniffin: 6/5/2002
mark: 5/10/1996
terry: 5/10/1996
terry: 5/2/1996
mark: 2/13/1996
mark: 10/16/1995
davew: 8/18/1994
jason: 6/22/1994
supermim: 3/16/1992
carol: 2/26/1992
supermim: 3/20/1990

MIM 614088
*RECORD*
*FIELD* NO
614088
*FIELD* TI
*614088 INTRACELLULAR ADHESION MOLECULE 4; ICAM4
;;CD242 ANTIGEN; CD242;;
LW GENE; LW
read more*FIELD* TX

DESCRIPTION

Intracellular adhesion molecule-4 (ICAM4) is a member of the
immunoglobulin (Ig) gene superfamily and encodes the Landsteiner-Wiener
(LW) blood group antigens (111250) (Bailly et al., 1994; Bailly et al.,
1995).

CLONING

Bailly et al. (1994) cloned ICAM4 cDNAs from a human bone marrow cDNA
library. One form encodes a single-spanning transmembrane protein of 270
amino acids, including a 29-amino acid signal peptide. A second form
encodes a shortened protein of 236 residues without transmembrane and
cytoplasm domains. The predicted protein shares approximately 30%
identity with intercellular adhesion molecules ICAM1 (147840), ICAM2
(146630), and ICAM3 (146631), which are the counterreceptors for the
lymphocyte function-associated antigen LFA1 (see 153370 and 600065). The
extracellular domain of ICAM4 consists, like that of ICAM2, of 2 Ig-like
domains, and the critical residues involved in binding of LFA1 to ICAMs
are partially conserved in ICAM4.

Using RT-PCR, Hermand et al. (1995) cloned ICAM4 from whole blood RNA.
The sequence was identical to that of the full-length cDNA reported by
Bailly et al. (1994) except for differences in the region encoding the
signal sequence. The corrected ICAM4 sequence reported by Hermand et al.
(1995) encodes a 271-amino acid protein with a 30-amino acid signal
peptide.

GENE STRUCTURE

Hermand et al. (1996) characterized the ICAM4 gene, which contains 3
exons spanning approximately 2.65 kb.

MAPPING

ICAM4 maps to chromosome 19p13.2, based on the previous mapping of the
LW locus to this location (Hermand et al., 1995).

GENE FUNCTION

Bailly et al. (1995) purified the ICAM4 (LW) protein from red cells and
found that the protein bound to the leukocyte CD11a/CD18 and CD11b/CD18
integrins (see 600065). They speculated that ICAM4 may be involved in
regulation of red cell turnover.

MOLECULAR GENETICS

- LW Blood Group System: LW(a)/LW(b) Polymorphism

Hermand et al. (1995) determined that the LW(a)/LW(b) polymorphism of
the LW blood group system (111250) is determined by a single-basepair
substitution in the ICAM4 gene (614088.0001).

- LW Blood Group System: LW(a-b-) Phenotype

Using Southern blot analysis, Hermand et al. (1995) showed that the
ICAM4 gene was not grossly rearranged in an individual with the LW(a-b-)
phenotype of the LW blood group system (111250) or in individuals with
the Rh-null phenotype, who also lack LW antigens. RFLP analysis using
PvuII indicated that the LW(a-b-) individual and 3 Rh-null individuals
were homozygous for a phenotypically silent LW(a) allele.

In an individual with the LW(a-b-) phenotype who carried a normal Rh
phenotype, Hermand et al. (1996) found a 10-bp deletion in the ICAM4
gene (614088.0002) that generated a premature stop codon and encoded a
truncated protein without the transmembrane and cytoplasmic domains.
Heterogeneity was indicated by the fact that no detectable abnormality
of the LW gene or transcript could be detected in another LW(a-b-)
individual.

*FIELD* AV
.0001
LW BLOOD GROUP SYSTEM, LW(a)/LW(b) POLYMORPHISM
ICAM4, GLN100ARG

Hermand et al. (1995) demonstrated that the molecular basis for the
LW(a)/LW(b) polymorphism of the LW blood group system (111250) is an
A-to-G change at nucleotide 299 (relative to the translation initiation
site) of the ICAM4 gene that correlates with a PvuII restriction site
and results in a gln100-to-arg (Q100R) amino acid substitution. COS-7
cells transfected with LW(a) or LW(b) cDNAs reacted with human
anti-LW(a) and anti-LW(b) sera, respectively, as well as with a murine
monoclonal anti-LW(ab) antibody, as shown by flow cytometry analysis.
Hermand et al. (1995) referred to this polymorphism as an A-to-G change
at nucleotide 308 (relative to the transcription initiation site),
resulting in a GLN70ARG (Q70R) substitution (numbering using the mature
ICAM4 protein sequence, after removal of the signal peptide).

.0002
LW BLOOD GROUP SYSTEM, LW(a-b-) PHENOTYPE
ICAM4, 10-BP DEL, NT346

In an individual with the rare LW(a-b-) phenotype of the LW blood group
system (111250) who carried a normal Rh phenotype, Hermand et al. (1996)
identified a 10-bp deletion (ACCTGCGCAG) at nucleotide 346 (relative to
the translation initiation site) in exon 1 of the ICAM4 gene. The
deletion generated a premature stop codon, resulting in a truncated
protein without the transmembrane and cytoplasmic domains. Heterogeneity
was indicated by the fact that no detectable abnormality of the ICAM4
gene or transcript could be detected in another LW(a-b-) individual.
Hermand et al. (1996) referred to this mutation as a 10-bp deletion at
nucleotide 355 (relative to the transcription initiation site).

*FIELD* RF
1. Bailly, P.; Hermand, P.; Callebaut, I.; Sonneborn, H. H.; Khamlichi,
S.; Mornon, J.-P.; Cartron, J.-P.: The LW blood group glycoprotein
in homologous to intercellular adhesion molecules. Proc. Nat. Acad.
Sci. 91: 5306-5310, 1994.

2. Bailly, P.; Tontti, E.; Hermand, P.; Cartron, J.-P.; Gahmberg,
C. G.: The red cell LW blood group protein is an intercellular adhesion
molecule which binds to CD11/CD18 leukocyte integrins. Europ. J.
Immun. 25: 3316-3320, 1995.

3. Hermand, P.; Gane, P.; Mattei, M. G.; Sistonen, P.; Cartron, J.-P.;
Bailly, P.: Molecular basis and expression of the LW(a)/LW(b) blood
group polymorphism. Blood 86: 1590-1594, 1995.

4. Hermand, P.; Le Pennec, P. Y.; Rouger, P.; Cartron, J.-P.; Bailly,
P.: Characterization of the gene encoding the human LW blood group
protein in LW(+) and LW(-) phenotypes. Blood 87: 2962-2967, 1996.

*FIELD* CN
Matthew B. Gross - updated: 7/14/2011

*FIELD* CD
Carol A. Bocchini: 7/13/2011

*FIELD* ED
terry: 07/21/2011
mgross: 7/14/2011
carol: 7/14/2011