ICAM4_HUMAN
ID ICAM4_HUMAN Reviewed; 271 AA.
AC Q14773; A0M8X2; Q14771; Q14772; Q16375; Q9BWR0;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 191.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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 adhesion
RT 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 protein in
RT 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 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., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., 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., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., 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 project:
RT 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) ARG-100.
RX PubMed=7632968;
RA Hermand P., Gane P., Mattei M.-G., Sistonen P., Cartron J.-P., Bailly P.;
RT "Molecular basis and expression of the LWa/LWb blood group 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 protein
CC LFA-1 (integrin alpha-L/beta-2). ICAM4 is also a ligand for alpha-
CC 4/beta-1 and alpha-V integrins. {ECO:0000269|PubMed:11435317}.
CC -!- INTERACTION:
CC Q14773-3; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-10233928, EBI-3867333;
CC Q14773-3; Q15323: KRT31; NbExp=6; IntAct=EBI-10233928, EBI-948001;
CC Q14773-3; O76011: KRT34; NbExp=3; IntAct=EBI-10233928, EBI-1047093;
CC Q14773-3; Q5JR59-3: MTUS2; NbExp=3; IntAct=EBI-10233928, EBI-11522433;
CC Q14773-3; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-10233928, EBI-945833;
CC Q14773-3; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-10233928, EBI-22310682;
CC -!- SUBCELLULAR LOCATION: [Isoform Long]: Cell membrane; Single-pass type I
CC membrane protein.
CC -!- SUBCELLULAR LOCATION: [Isoform Short]: Secreted {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9ERM2};
CC Single-pass type I membrane protein {ECO:0000255}.
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 system
CC [MIM:111250]. The molecular basis of the LW(A)=LW5/LW(B)=LW7 blood
CC group antigens is a single variation in position 100; Gln-100
CC corresponds to LW(A) and Arg-100 to LW(B).
CC {ECO:0000269|PubMed:7632968}.
CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. ICAM family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=dbRBC/BGMUT; Note=Blood group antigen gene mutation
CC database;
CC URL="https://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/";
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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 CCDS; CCDS12232.1; -. [Q14773-1]
DR CCDS; CCDS32904.1; -. [Q14773-3]
DR PIR; I52612; I52612.
DR PIR; I59300; I59300.
DR PIR; I80159; I80159.
DR RefSeq; NP_001034221.1; NM_001039132.2. [Q14773-3]
DR RefSeq; NP_001535.1; NM_001544.4. [Q14773-1]
DR AlphaFoldDB; Q14773; -.
DR SMR; Q14773; -.
DR BioGRID; 109613; 45.
DR CORUM; Q14773; -.
DR IntAct; Q14773; 11.
DR MINT; Q14773; -.
DR STRING; 9606.ENSP00000342114; -.
DR GlyGen; Q14773; 4 sites.
DR BioMuta; ICAM4; -.
DR DMDM; 2497309; -.
DR MassIVE; Q14773; -.
DR PaxDb; Q14773; -.
DR PeptideAtlas; Q14773; -.
DR PRIDE; Q14773; -.
DR ProteomicsDB; 60165; -. [Q14773-1]
DR ProteomicsDB; 60166; -. [Q14773-2]
DR TopDownProteomics; Q14773-1; -. [Q14773-1]
DR Antibodypedia; 25271; 276 antibodies from 30 providers.
DR DNASU; 3386; -.
DR Ensembl; ENST00000340992.4; ENSP00000342114.3; ENSG00000105371.10. [Q14773-3]
DR Ensembl; ENST00000380770.5; ENSP00000370147.2; ENSG00000105371.10. [Q14773-1]
DR Ensembl; ENST00000393717.2; ENSP00000377320.1; ENSG00000105371.10. [Q14773-2]
DR GeneID; 3386; -.
DR KEGG; hsa:3386; -.
DR MANE-Select; ENST00000380770.5; ENSP00000370147.2; NM_001544.5; NP_001535.1.
DR UCSC; uc002mns.3; human. [Q14773-1]
DR CTD; 3386; -.
DR DisGeNET; 3386; -.
DR GeneCards; ICAM4; -.
DR HGNC; HGNC:5347; ICAM4.
DR HPA; ENSG00000105371; Group enriched (bone marrow, lung).
DR MalaCards; ICAM4; -.
DR MIM; 111250; phenotype.
DR MIM; 614088; gene.
DR neXtProt; NX_Q14773; -.
DR OpenTargets; ENSG00000105371; -.
DR PharmGKB; PA29595; -.
DR VEuPathDB; HostDB:ENSG00000105371; -.
DR eggNOG; ENOG502TF7X; Eukaryota.
DR GeneTree; ENSGT00940000162431; -.
DR HOGENOM; CLU_1165526_0_0_1; -.
DR InParanoid; Q14773; -.
DR OMA; APFWVRI; -.
DR PhylomeDB; Q14773; -.
DR PathwayCommons; Q14773; -.
DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR Reactome; R-HSA-216083; Integrin cell surface interactions.
DR SignaLink; Q14773; -.
DR SIGNOR; Q14773; -.
DR BioGRID-ORCS; 3386; 14 hits in 1078 CRISPR screens.
DR GenomeRNAi; 3386; -.
DR Pharos; Q14773; Tbio.
DR PRO; PR:Q14773; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q14773; protein.
DR Bgee; ENSG00000105371; Expressed in monocyte and 103 other tissues.
DR ExpressionAtlas; Q14773; baseline and differential.
DR Genevisible; Q14773; HS.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005178; F:integrin binding; IBA:GO_Central.
DR GO; GO:0007155; P:cell adhesion; IBA:GO_Central.
DR GO; GO:0098609; P:cell-cell adhesion; IEA:InterPro.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR013768; ICAM_N.
DR InterPro; IPR003987; ICAM_VCAM_N.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR Pfam; PF03921; ICAM_N; 1.
DR PRINTS; PR01472; ICAMVCAM1.
DR SUPFAM; SSF48726; SSF48726; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Blood group antigen; Cell adhesion; Cell membrane;
KW Disulfide bond; Glycoprotein; Immunoglobulin domain; Membrane;
KW Reference proteome; Repeat; Secreted; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..271
FT /note="Intercellular adhesion molecule 4"
FT /id="PRO_0000014796"
FT TOPO_DOM 23..240
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 241..261
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 262..271
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 62..124
FT /note="Ig-like C2-type 1"
FT DOMAIN 146..217
FT /note="Ig-like C2-type 2"
FT CARBOHYD 68
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 78
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 190
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 223
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 69..117
FT /evidence="ECO:0000250"
FT DISULFID 69..113
FT /evidence="ECO:0000250|UniProtKB:P32942,
FT ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 73..117
FT /evidence="ECO:0000250|UniProtKB:P32942"
FT DISULFID 153..210
FT /evidence="ECO:0000250"
FT VAR_SEQ 132..271
FT /note="KPPHSVILEPPVLKGRKYTLRCHVTQVFPVGYLVVTLRHGSRVIYSESLERF
FT TGLDLANVTLTYEFAAGPRDFWQPVICHARLNLDGLVVRNSSAPITLMLAWSPAPTALA
FT SGSIAALVGILLTVGAAYLCKCLAMKSQA -> SVPGGLLGGDPEAWKPGHLFRKPGAL
FT HRPGSGQRDLDLRVCCWTPRLLAARDLPRAPQSRRPGGPQQLGTHYTDARLEPRAHSFG
FT LRFHRCPCRDPPHCGRCVPMQVPSYEVPGVKGDVLCRLSEKKRNMKQSGEMAIHGG
FT (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.3"
FT /id="VSP_043229"
FT VAR_SEQ 233..271
FT /note="AWSPAPTALASGSIAALVGILLTVGAAYLCKCLAMKSQA -> GEAPL (in
FT isoform Short)"
FT /evidence="ECO:0000303|PubMed:8202485"
FT /id="VSP_002519"
FT VARIANT 100
FT /note="Q -> R (in LW(B); dbSNP:rs77493670)"
FT /evidence="ECO:0000269|PubMed:7632968"
FT /id="VAR_003912"
FT VARIANT 208
FT /note="V -> L (in dbSNP:rs36023325)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_038721"
FT CONFLICT 14..29
FT /note="AAAYPGVGSALGRRTK -> RPPTRELGARWDAGL (in Ref. 1;
FT AAA59538/AAA59537)"
FT /evidence="ECO:0000305"
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
