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   24-JAN-2024, entry version 199.
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/";
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) 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   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   GlyCosmos; Q14773; 4 sites, No reported glycans.
DR   GlyGen; Q14773; 5 sites, 1 O-linked glycan (1 site).
DR   BioMuta; ICAM4; -.
DR   DMDM; 2497309; -.
DR   MassIVE; Q14773; -.
DR   PaxDb; 9606-ENSP00000342114; -.
DR   PeptideAtlas; Q14773; -.
DR   ProteomicsDB; 60165; -. [Q14773-1]
DR   ProteomicsDB; 60166; -. [Q14773-2]
DR   Pumba; Q14773; -.
DR   TopDownProteomics; Q14773-1; -. [Q14773-1]
DR   Antibodypedia; 25271; 315 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   AGR; HGNC:5347; -.
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; QPVICHT; -.
DR   OrthoDB; 4634025at2759; -.
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; 15 hits in 1156 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 male germ line stem cell (sensu Vertebrata) in testis and 103 other cell types or tissues.
DR   ExpressionAtlas; Q14773; baseline and differential.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; TAS:ProtInc.
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; Immunoglobulins; 2.
DR   InterPro; IPR013768; ICAM_N.
DR   InterPro; IPR047012; ICAM_VCAM.
DR   InterPro; IPR003987; ICAM_VCAM_N.
DR   InterPro; IPR036179; Ig-like_dom_sf.
DR   InterPro; IPR013783; Ig-like_fold.
DR   PANTHER; PTHR13771; INTERCELLULAR ADHESION MOLECULE; 1.
DR   PANTHER; PTHR13771:SF8; INTERCELLULAR ADHESION MOLECULE 4; 1.
DR   Pfam; PF03921; ICAM_N; 1.
DR   PRINTS; PR01472; ICAMVCAM1.
DR   SUPFAM; SSF48726; Immunoglobulin; 2.
DR   Genevisible; Q14773; HS.
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
//