Full text data of VCAM1
VCAM1
(L1CAM)
[Confidence: high (a blood group or CD marker)]
Vascular cell adhesion protein 1; V-CAM 1; VCAM-1 (INCAM-100; CD106; Flags: Precursor)
Vascular cell adhesion protein 1; V-CAM 1; VCAM-1 (INCAM-100; CD106; Flags: Precursor)
UniProt
P19320
ID VCAM1_HUMAN Reviewed; 739 AA.
AC P19320; A8K6R7; B4DKS4; E9PDD1; Q6NUP8;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1990, sequence version 1.
DT 22-JAN-2014, entry version 180.
DE RecName: Full=Vascular cell adhesion protein 1;
DE Short=V-CAM 1;
DE Short=VCAM-1;
DE AltName: Full=INCAM-100;
DE AltName: CD_antigen=CD106;
DE Flags: Precursor;
GN Name=VCAM1; Synonyms=L1CAM;
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] (ISOFORM 2).
RX PubMed=2688898; DOI=10.1016/0092-8674(89)90775-7;
RA Osborn L., Hession C., Tizard R., Vassallo C., Luhowskyj S.,
RA Chi-Rosso G., Lobb R.;
RT "Direct expression cloning of vascular cell adhesion molecule 1, a
RT cytokine-induced endothelial protein that binds to lymphocytes.";
RL Cell 59:1203-1211(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Umbilical vein;
RX PubMed=1699207; DOI=10.1093/nar/18.19.5901;
RA Polte T., Newman W., Gopal T.V.;
RT "Full length vascular cell adhesion molecule 1 (VCAM-1).";
RL Nucleic Acids Res. 18:5901-5901(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1707873;
RA Hession C., Tizard R., Vassallo C., Schiffer S.B., Goff D., Moy P.,
RA Chi-Rosso G., Luhowskyj S., Lobb R., Osborn L.;
RT "Cloning of an alternate form of vascular cell adhesion molecule-1
RT (VCAM1).";
RL J. Biol. Chem. 266:6682-6685(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND ALTERNATIVE
RP SPLICING.
RX PubMed=1715583; DOI=10.1073/pnas.88.17.7859;
RA Cybulsky M.I., Fries J.W.U., Williams A.J., Sultan P., Eddy R.,
RA Byers M., Shows T., Gimbrone M.A. Jr., Collins T.;
RT "Gene structure, chromosomal location, and basis for alternative mRNA
RT splicing of the human VCAM1 gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:7859-7863(1991).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS PHE-318; ALA-384;
RP ALA-413 AND LEU-716.
RG SeattleSNPs variation discovery resource;
RL Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Placenta, and Tongue;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [8]
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Retinal pigment epithelium;
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 [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-21.
RX PubMed=1379595;
RA Iademarco M.F., McQuillan J.J., Rosen G.D., Dean D.C.;
RT "Characterization of the promoter for vascular cell adhesion molecule-
RT 1 (VCAM-1).";
RL J. Biol. Chem. 267:16323-16329(1992).
RN [11]
RP NUCLEOTIDE SEQUENCE OF 25-686 (ISOFORMS 1 AND 2).
RC TISSUE=Umbilical vein endothelial cell;
RX PubMed=1707234;
RA Cybulsky M.I., Fries J.W., Williams A.J., Sultan P., Davis V.M.,
RA Gimbrone M.A. Jr., Collins T.;
RT "Alternative splicing of human VCAM-1 in activated vascular
RT endothelium.";
RL Am. J. Pathol. 138:815-820(1991).
RN [12]
RP NUCLEOTIDE SEQUENCE OF 25-402 (ISOFORMS 1 AND 2), AND CELL ADHESION
RP DOMAIN.
RC TISSUE=Endothelial cell;
RX PubMed=1377228; DOI=10.1084/jem.176.1.99;
RA Osborn L., Vassallo C., Benjamin C.D.;
RT "Activated endothelium binds lymphocytes through a novel binding site
RT in the alternately spliced domain of vascular cell adhesion molecule-
RT 1.";
RL J. Exp. Med. 176:99-107(1992).
RN [13]
RP PROTEIN SEQUENCE OF 25-39.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally
RT verified cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [14]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-561, AND MASS
RP SPECTROMETRY.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E.,
RA Moore R.J., Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 25-226.
RX PubMed=7531291; DOI=10.1038/373539a0;
RA Jones E.Y., Harlos K., Bottomley M.J., Robinson R.C., Driscoll P.C.,
RA Edwards R.M., Clements J.M., Dudgeon T.J., Stuart D.I.;
RT "Crystal structure of an integrin-binding fragment of vascular cell
RT adhesion molecule-1 at 1.8-A resolution.";
RL Nature 373:539-544(1995).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 25-220.
RX PubMed=7539925; DOI=10.1073/pnas.92.12.5714;
RA Wang J.-H., Pepinsky R.B., Stehle T., Liu J.-H., Karpusas M.,
RA Browning B., Osborn L.;
RT "The crystal structure of an N-terminal two-domain fragment of
RT vascular cell adhesion molecule 1 (VCAM-1): a cyclic peptide based on
RT the domain 1 C-D loop can inhibit VCAM-1-alpha 4 integrin
RT interaction.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:5714-5718(1995).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 25-220.
RX PubMed=15299708; DOI=10.1107/S0907444995012352;
RA Wang J.-H., Stehle T., Pepinsky R.B., Liu J.-H., Karpusas M.,
RA Osborn L.;
RT "Structure of a functional fragment of VCAM-1 refined at 1.9-A
RT resolution.";
RL Acta Crystallogr. D 52:369-379(1996).
CC -!- FUNCTION: Important in cell-cell recognition. Appears to function
CC in leukocyte-endothelial cell adhesion. Interacts with integrin
CC alpha-4/beta-1 (ITGA4/ITGB1) on leukocytes, and mediates both
CC adhesion and signal transduction. The VCAM1/ITGA4/ITGB1
CC interaction may play a pathophysiologic role both in immune
CC responses and in leukocyte emigration to sites of inflammation.
CC -!- SUBUNIT: Binds to ECMV-D capsid proteins and acts as a receptor
CC for this virus (By similarity).
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane
CC protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Additional isoforms seem to exist;
CC Name=1; Synonyms=Long, VCAM-7D;
CC IsoId=P19320-1; Sequence=Displayed;
CC Note=Major isoform;
CC Name=2; Synonyms=Short, VCAM-6D;
CC IsoId=P19320-2; Sequence=VSP_002580;
CC Name=3;
CC IsoId=P19320-3; Sequence=VSP_044636;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed on inflammed vascular endothelium,
CC as well as on macrophage-like and dendritic cell types in both
CC normal and inflammed tissue.
CC -!- INDUCTION: By cytokines (e.g. IL-1, TNF-alpha).
CC -!- DOMAIN: Either the first or the fourth Ig-like C2-type domain is
CC required for VLA4-dependent cell adhesion.
CC -!- PTM: Sialoglycoprotein.
CC -!- SIMILARITY: Contains 7 Ig-like C2-type (immunoglobulin-like)
CC domains.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=VCAM1 entry;
CC URL="http://en.wikipedia.org/wiki/VCAM1";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/vcam1/";
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - Glycan Binding;
CC Note=VCAM-1;
CC URL="http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType;=view&cbpId;=cbp_hum_Itlect_266";
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; M30257; AAA51917.1; -; mRNA.
DR EMBL; X53051; CAA37218.1; -; mRNA.
DR EMBL; M60335; AAA61269.1; -; mRNA.
DR EMBL; M73255; AAA61270.1; -; Genomic_DNA.
DR EMBL; AF536818; AAM96190.1; -; Genomic_DNA.
DR EMBL; AK291732; BAF84421.1; -; mRNA.
DR EMBL; AK296692; BAG59286.1; -; mRNA.
DR EMBL; AC093428; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471097; EAW72950.1; -; Genomic_DNA.
DR EMBL; BC017276; AAH17276.3; -; mRNA.
DR EMBL; BC068490; AAH68490.2; -; mRNA.
DR EMBL; BC085003; AAH85003.1; -; mRNA.
DR EMBL; M92431; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; A41288; A41288.
DR PIR; B41288; B41288.
DR RefSeq; NP_001069.1; NM_001078.3.
DR RefSeq; NP_001186763.1; NM_001199834.1.
DR RefSeq; NP_542413.1; NM_080682.2.
DR UniGene; Hs.109225; -.
DR PDB; 1IJ9; X-ray; 3.00 A; A=25-220.
DR PDB; 1VCA; X-ray; 1.80 A; A/B=25-226.
DR PDB; 1VSC; X-ray; 1.90 A; A/B=25-219.
DR PDBsum; 1IJ9; -.
DR PDBsum; 1VCA; -.
DR PDBsum; 1VSC; -.
DR ProteinModelPortal; P19320; -.
DR SMR; P19320; 25-712.
DR IntAct; P19320; 630.
DR STRING; 9606.ENSP00000294728; -.
DR BindingDB; P19320; -.
DR ChEMBL; CHEMBL3735; -.
DR DrugBank; DB01136; Carvedilol.
DR PhosphoSite; P19320; -.
DR DMDM; 137560; -.
DR PaxDb; P19320; -.
DR PRIDE; P19320; -.
DR DNASU; 7412; -.
DR Ensembl; ENST00000294728; ENSP00000294728; ENSG00000162692.
DR Ensembl; ENST00000347652; ENSP00000304611; ENSG00000162692.
DR Ensembl; ENST00000370119; ENSP00000359137; ENSG00000162692.
DR GeneID; 7412; -.
DR KEGG; hsa:7412; -.
DR UCSC; uc001dti.3; human.
DR CTD; 7412; -.
DR GeneCards; GC01P101185; -.
DR HGNC; HGNC:12663; VCAM1.
DR HPA; CAB005426; -.
DR MIM; 192225; gene.
DR neXtProt; NX_P19320; -.
DR PharmGKB; PA37286; -.
DR eggNOG; NOG148090; -.
DR HOGENOM; HOG000004820; -.
DR HOVERGEN; HBG053965; -.
DR InParanoid; P19320; -.
DR KO; K06527; -.
DR OMA; ENEHSYL; -.
DR OrthoDB; EOG7JMGD2; -.
DR Reactome; REACT_118779; Extracellular matrix organization.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; VCAM1; human.
DR EvolutionaryTrace; P19320; -.
DR GeneWiki; VCAM-1; -.
DR GenomeRNAi; 7412; -.
DR NextBio; 29020; -.
DR PMAP-CutDB; P19320; -.
DR PRO; PR:P19320; -.
DR ArrayExpress; P19320; -.
DR Bgee; P19320; -.
DR CleanEx; HS_L1CAM; -.
DR CleanEx; HS_VCAM1; -.
DR Genevestigator; P19320; -.
DR GO; GO:0071065; C:alpha9-beta1 integrin-vascular cell adhesion molecule-1 complex; IDA:BHF-UCL.
DR GO; GO:0045177; C:apical part of cell; IDA:BHF-UCL.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:BHF-UCL.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0030175; C:filopodium; IDA:BHF-UCL.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0005902; C:microvillus; IDA:BHF-UCL.
DR GO; GO:0002102; C:podosome; IDA:BHF-UCL.
DR GO; GO:0042383; C:sarcolemma; IEA:Ensembl.
DR GO; GO:0050839; F:cell adhesion molecule binding; IDA:BHF-UCL.
DR GO; GO:0005178; F:integrin binding; IDA:BHF-UCL.
DR GO; GO:0008131; F:primary amine oxidase activity; IDA:UniProtKB.
DR GO; GO:0002526; P:acute inflammatory response; IEA:Ensembl.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0009308; P:amine metabolic process; IDA:UniProtKB.
DR GO; GO:0030183; P:B cell differentiation; IC:BHF-UCL.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IEA:Ensembl.
DR GO; GO:0060710; P:chorio-allantoic fusion; IEA:Ensembl.
DR GO; GO:0002544; P:chronic inflammatory response; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0007157; P:heterophilic cell-cell adhesion; IDA:BHF-UCL.
DR GO; GO:0060333; P:interferon-gamma-mediated signaling pathway; TAS:Reactome.
DR GO; GO:0050901; P:leukocyte tethering or rolling; IEP:BHF-UCL.
DR GO; GO:0022614; P:membrane to membrane docking; IEP:BHF-UCL.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; IDA:BHF-UCL.
DR GO; GO:0050776; P:regulation of immune response; TAS:Reactome.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0010212; P:response to ionizing radiation; IEA:Ensembl.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR Gene3D; 2.60.40.10; -; 7.
DR InterPro; IPR003987; ICAM_VCAM_N.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR008424; Ig_C2-set.
DR InterPro; IPR013098; Ig_I-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR013151; Immunoglobulin.
DR InterPro; IPR003989; VCAM-1.
DR Pfam; PF05790; C2-set; 2.
DR Pfam; PF07679; I-set; 3.
DR Pfam; PF00047; ig; 1.
DR PRINTS; PR01472; ICAMVCAM1.
DR PRINTS; PR01474; VCAM1.
DR SMART; SM00409; IG; 2.
DR SMART; SM00408; IGc2; 3.
DR PROSITE; PS50835; IG_LIKE; 5.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell adhesion; Complete proteome;
KW Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Host-virus interaction; Immunoglobulin domain; Membrane; Polymorphism;
KW Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1 24
FT CHAIN 25 739 Vascular cell adhesion protein 1.
FT /FTId=PRO_0000014997.
FT TOPO_DOM 25 698 Extracellular (Potential).
FT TRANSMEM 699 720 Helical; (Potential).
FT TOPO_DOM 721 739 Cytoplasmic (Potential).
FT DOMAIN 25 105 Ig-like C2-type 1.
FT DOMAIN 109 212 Ig-like C2-type 2.
FT DOMAIN 223 309 Ig-like C2-type 3.
FT DOMAIN 312 399 Ig-like C2-type 4.
FT DOMAIN 408 506 Ig-like C2-type 5.
FT DOMAIN 511 595 Ig-like C2-type 6.
FT DOMAIN 600 684 Ig-like C2-type 7.
FT CARBOHYD 273 273 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 365 365 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 417 417 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 463 463 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 531 531 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 561 561 N-linked (GlcNAc...).
FT DISULFID 47 95
FT DISULFID 52 99
FT DISULFID 137 195
FT DISULFID 246 291 By similarity.
FT DISULFID 335 383 By similarity.
FT DISULFID 534 579 By similarity.
FT VAR_SEQ 52 113 Missing (in isoform 3).
FT /FTId=VSP_044636.
FT VAR_SEQ 310 402 EKPFTVEISPGPRIAAQIGDSVMLTCSVMGCESPSFSWRTQ
FT IDSPLSGKVRSEGTNSTLTLSPVSFENEHSYLCTVTCGHKK
FT LEKGIQVELYS -> A (in isoform 2).
FT /FTId=VSP_002580.
FT VARIANT 18 18 M -> I (in dbSNP:rs34228330).
FT /FTId=VAR_049951.
FT VARIANT 318 318 S -> F (in dbSNP:rs3783611).
FT /FTId=VAR_014309.
FT VARIANT 384 384 T -> A (in dbSNP:rs3783612).
FT /FTId=VAR_014310.
FT VARIANT 413 413 G -> A (in dbSNP:rs3783613).
FT /FTId=VAR_014311.
FT VARIANT 421 421 V -> I (in dbSNP:rs34100871).
FT /FTId=VAR_049952.
FT VARIANT 488 488 H -> R (in dbSNP:rs34199378).
FT /FTId=VAR_049953.
FT VARIANT 716 716 I -> L (in dbSNP:rs3783615).
FT /FTId=VAR_014312.
FT CONFLICT 182 182 F -> G (in Ref. 12).
FT CONFLICT 402 402 S -> T (in Ref. 11).
FT CONFLICT 728 728 S -> P (in Ref. 6; BAG59286).
FT STRAND 26 38
FT STRAND 43 51
FT STRAND 56 61
FT STRAND 68 74
FT STRAND 77 84
FT HELIX 87 89
FT STRAND 91 99
FT STRAND 102 114
FT STRAND 120 125
FT STRAND 133 144
FT HELIX 145 147
FT STRAND 148 154
FT STRAND 157 163
FT STRAND 169 171
FT STRAND 174 182
FT HELIX 186 188
FT STRAND 192 199
FT STRAND 209 216
SQ SEQUENCE 739 AA; 81276 MW; 050E2EBD39AC2FF4 CRC64;
MPGKMVVILG ASNILWIMFA ASQAFKIETT PESRYLAQIG DSVSLTCSTT GCESPFFSWR
TQIDSPLNGK VTNEGTTSTL TMNPVSFGNE HSYLCTATCE SRKLEKGIQV EIYSFPKDPE
IHLSGPLEAG KPITVKCSVA DVYPFDRLEI DLLKGDHLMK SQEFLEDADR KSLETKSLEV
TFTPVIEDIG KVLVCRAKLH IDEMDSVPTV RQAVKELQVY ISPKNTVISV NPSTKLQEGG
SVTMTCSSEG LPAPEIFWSK KLDNGNLQHL SGNATLTLIA MRMEDSGIYV CEGVNLIGKN
RKEVELIVQE KPFTVEISPG PRIAAQIGDS VMLTCSVMGC ESPSFSWRTQ IDSPLSGKVR
SEGTNSTLTL SPVSFENEHS YLCTVTCGHK KLEKGIQVEL YSFPRDPEIE MSGGLVNGSS
VTVSCKVPSV YPLDRLEIEL LKGETILENI EFLEDTDMKS LENKSLEMTF IPTIEDTGKA
LVCQAKLHID DMEFEPKQRQ STQTLYVNVA PRDTTVLVSP SSILEEGSSV NMTCLSQGFP
APKILWSRQL PNGELQPLSE NATLTLISTK MEDSGVYLCE GINQAGRSRK EVELIIQVTP
KDIKLTAFPS ESVKEGDTVI ISCTCGNVPE TWIILKKKAE TGDTVLKSID GAYTIRKAQL
KDAGVYECES KNKVGSQLRS LTLDVQGREN NKDYFSPELL VLYFASSLII PAIGMIIYFA
RKANMKGSYS LVEAQKSKV
//
ID VCAM1_HUMAN Reviewed; 739 AA.
AC P19320; A8K6R7; B4DKS4; E9PDD1; Q6NUP8;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1990, sequence version 1.
DT 22-JAN-2014, entry version 180.
DE RecName: Full=Vascular cell adhesion protein 1;
DE Short=V-CAM 1;
DE Short=VCAM-1;
DE AltName: Full=INCAM-100;
DE AltName: CD_antigen=CD106;
DE Flags: Precursor;
GN Name=VCAM1; Synonyms=L1CAM;
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] (ISOFORM 2).
RX PubMed=2688898; DOI=10.1016/0092-8674(89)90775-7;
RA Osborn L., Hession C., Tizard R., Vassallo C., Luhowskyj S.,
RA Chi-Rosso G., Lobb R.;
RT "Direct expression cloning of vascular cell adhesion molecule 1, a
RT cytokine-induced endothelial protein that binds to lymphocytes.";
RL Cell 59:1203-1211(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Umbilical vein;
RX PubMed=1699207; DOI=10.1093/nar/18.19.5901;
RA Polte T., Newman W., Gopal T.V.;
RT "Full length vascular cell adhesion molecule 1 (VCAM-1).";
RL Nucleic Acids Res. 18:5901-5901(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1707873;
RA Hession C., Tizard R., Vassallo C., Schiffer S.B., Goff D., Moy P.,
RA Chi-Rosso G., Luhowskyj S., Lobb R., Osborn L.;
RT "Cloning of an alternate form of vascular cell adhesion molecule-1
RT (VCAM1).";
RL J. Biol. Chem. 266:6682-6685(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND ALTERNATIVE
RP SPLICING.
RX PubMed=1715583; DOI=10.1073/pnas.88.17.7859;
RA Cybulsky M.I., Fries J.W.U., Williams A.J., Sultan P., Eddy R.,
RA Byers M., Shows T., Gimbrone M.A. Jr., Collins T.;
RT "Gene structure, chromosomal location, and basis for alternative mRNA
RT splicing of the human VCAM1 gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:7859-7863(1991).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS PHE-318; ALA-384;
RP ALA-413 AND LEU-716.
RG SeattleSNPs variation discovery resource;
RL Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Placenta, and Tongue;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [8]
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Retinal pigment epithelium;
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 [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-21.
RX PubMed=1379595;
RA Iademarco M.F., McQuillan J.J., Rosen G.D., Dean D.C.;
RT "Characterization of the promoter for vascular cell adhesion molecule-
RT 1 (VCAM-1).";
RL J. Biol. Chem. 267:16323-16329(1992).
RN [11]
RP NUCLEOTIDE SEQUENCE OF 25-686 (ISOFORMS 1 AND 2).
RC TISSUE=Umbilical vein endothelial cell;
RX PubMed=1707234;
RA Cybulsky M.I., Fries J.W., Williams A.J., Sultan P., Davis V.M.,
RA Gimbrone M.A. Jr., Collins T.;
RT "Alternative splicing of human VCAM-1 in activated vascular
RT endothelium.";
RL Am. J. Pathol. 138:815-820(1991).
RN [12]
RP NUCLEOTIDE SEQUENCE OF 25-402 (ISOFORMS 1 AND 2), AND CELL ADHESION
RP DOMAIN.
RC TISSUE=Endothelial cell;
RX PubMed=1377228; DOI=10.1084/jem.176.1.99;
RA Osborn L., Vassallo C., Benjamin C.D.;
RT "Activated endothelium binds lymphocytes through a novel binding site
RT in the alternately spliced domain of vascular cell adhesion molecule-
RT 1.";
RL J. Exp. Med. 176:99-107(1992).
RN [13]
RP PROTEIN SEQUENCE OF 25-39.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally
RT verified cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [14]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-561, AND MASS
RP SPECTROMETRY.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E.,
RA Moore R.J., Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 25-226.
RX PubMed=7531291; DOI=10.1038/373539a0;
RA Jones E.Y., Harlos K., Bottomley M.J., Robinson R.C., Driscoll P.C.,
RA Edwards R.M., Clements J.M., Dudgeon T.J., Stuart D.I.;
RT "Crystal structure of an integrin-binding fragment of vascular cell
RT adhesion molecule-1 at 1.8-A resolution.";
RL Nature 373:539-544(1995).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 25-220.
RX PubMed=7539925; DOI=10.1073/pnas.92.12.5714;
RA Wang J.-H., Pepinsky R.B., Stehle T., Liu J.-H., Karpusas M.,
RA Browning B., Osborn L.;
RT "The crystal structure of an N-terminal two-domain fragment of
RT vascular cell adhesion molecule 1 (VCAM-1): a cyclic peptide based on
RT the domain 1 C-D loop can inhibit VCAM-1-alpha 4 integrin
RT interaction.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:5714-5718(1995).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 25-220.
RX PubMed=15299708; DOI=10.1107/S0907444995012352;
RA Wang J.-H., Stehle T., Pepinsky R.B., Liu J.-H., Karpusas M.,
RA Osborn L.;
RT "Structure of a functional fragment of VCAM-1 refined at 1.9-A
RT resolution.";
RL Acta Crystallogr. D 52:369-379(1996).
CC -!- FUNCTION: Important in cell-cell recognition. Appears to function
CC in leukocyte-endothelial cell adhesion. Interacts with integrin
CC alpha-4/beta-1 (ITGA4/ITGB1) on leukocytes, and mediates both
CC adhesion and signal transduction. The VCAM1/ITGA4/ITGB1
CC interaction may play a pathophysiologic role both in immune
CC responses and in leukocyte emigration to sites of inflammation.
CC -!- SUBUNIT: Binds to ECMV-D capsid proteins and acts as a receptor
CC for this virus (By similarity).
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane
CC protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Additional isoforms seem to exist;
CC Name=1; Synonyms=Long, VCAM-7D;
CC IsoId=P19320-1; Sequence=Displayed;
CC Note=Major isoform;
CC Name=2; Synonyms=Short, VCAM-6D;
CC IsoId=P19320-2; Sequence=VSP_002580;
CC Name=3;
CC IsoId=P19320-3; Sequence=VSP_044636;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed on inflammed vascular endothelium,
CC as well as on macrophage-like and dendritic cell types in both
CC normal and inflammed tissue.
CC -!- INDUCTION: By cytokines (e.g. IL-1, TNF-alpha).
CC -!- DOMAIN: Either the first or the fourth Ig-like C2-type domain is
CC required for VLA4-dependent cell adhesion.
CC -!- PTM: Sialoglycoprotein.
CC -!- SIMILARITY: Contains 7 Ig-like C2-type (immunoglobulin-like)
CC domains.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=VCAM1 entry;
CC URL="http://en.wikipedia.org/wiki/VCAM1";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/vcam1/";
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - Glycan Binding;
CC Note=VCAM-1;
CC URL="http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType;=view&cbpId;=cbp_hum_Itlect_266";
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; M30257; AAA51917.1; -; mRNA.
DR EMBL; X53051; CAA37218.1; -; mRNA.
DR EMBL; M60335; AAA61269.1; -; mRNA.
DR EMBL; M73255; AAA61270.1; -; Genomic_DNA.
DR EMBL; AF536818; AAM96190.1; -; Genomic_DNA.
DR EMBL; AK291732; BAF84421.1; -; mRNA.
DR EMBL; AK296692; BAG59286.1; -; mRNA.
DR EMBL; AC093428; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471097; EAW72950.1; -; Genomic_DNA.
DR EMBL; BC017276; AAH17276.3; -; mRNA.
DR EMBL; BC068490; AAH68490.2; -; mRNA.
DR EMBL; BC085003; AAH85003.1; -; mRNA.
DR EMBL; M92431; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; A41288; A41288.
DR PIR; B41288; B41288.
DR RefSeq; NP_001069.1; NM_001078.3.
DR RefSeq; NP_001186763.1; NM_001199834.1.
DR RefSeq; NP_542413.1; NM_080682.2.
DR UniGene; Hs.109225; -.
DR PDB; 1IJ9; X-ray; 3.00 A; A=25-220.
DR PDB; 1VCA; X-ray; 1.80 A; A/B=25-226.
DR PDB; 1VSC; X-ray; 1.90 A; A/B=25-219.
DR PDBsum; 1IJ9; -.
DR PDBsum; 1VCA; -.
DR PDBsum; 1VSC; -.
DR ProteinModelPortal; P19320; -.
DR SMR; P19320; 25-712.
DR IntAct; P19320; 630.
DR STRING; 9606.ENSP00000294728; -.
DR BindingDB; P19320; -.
DR ChEMBL; CHEMBL3735; -.
DR DrugBank; DB01136; Carvedilol.
DR PhosphoSite; P19320; -.
DR DMDM; 137560; -.
DR PaxDb; P19320; -.
DR PRIDE; P19320; -.
DR DNASU; 7412; -.
DR Ensembl; ENST00000294728; ENSP00000294728; ENSG00000162692.
DR Ensembl; ENST00000347652; ENSP00000304611; ENSG00000162692.
DR Ensembl; ENST00000370119; ENSP00000359137; ENSG00000162692.
DR GeneID; 7412; -.
DR KEGG; hsa:7412; -.
DR UCSC; uc001dti.3; human.
DR CTD; 7412; -.
DR GeneCards; GC01P101185; -.
DR HGNC; HGNC:12663; VCAM1.
DR HPA; CAB005426; -.
DR MIM; 192225; gene.
DR neXtProt; NX_P19320; -.
DR PharmGKB; PA37286; -.
DR eggNOG; NOG148090; -.
DR HOGENOM; HOG000004820; -.
DR HOVERGEN; HBG053965; -.
DR InParanoid; P19320; -.
DR KO; K06527; -.
DR OMA; ENEHSYL; -.
DR OrthoDB; EOG7JMGD2; -.
DR Reactome; REACT_118779; Extracellular matrix organization.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; VCAM1; human.
DR EvolutionaryTrace; P19320; -.
DR GeneWiki; VCAM-1; -.
DR GenomeRNAi; 7412; -.
DR NextBio; 29020; -.
DR PMAP-CutDB; P19320; -.
DR PRO; PR:P19320; -.
DR ArrayExpress; P19320; -.
DR Bgee; P19320; -.
DR CleanEx; HS_L1CAM; -.
DR CleanEx; HS_VCAM1; -.
DR Genevestigator; P19320; -.
DR GO; GO:0071065; C:alpha9-beta1 integrin-vascular cell adhesion molecule-1 complex; IDA:BHF-UCL.
DR GO; GO:0045177; C:apical part of cell; IDA:BHF-UCL.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:BHF-UCL.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0030175; C:filopodium; IDA:BHF-UCL.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0005902; C:microvillus; IDA:BHF-UCL.
DR GO; GO:0002102; C:podosome; IDA:BHF-UCL.
DR GO; GO:0042383; C:sarcolemma; IEA:Ensembl.
DR GO; GO:0050839; F:cell adhesion molecule binding; IDA:BHF-UCL.
DR GO; GO:0005178; F:integrin binding; IDA:BHF-UCL.
DR GO; GO:0008131; F:primary amine oxidase activity; IDA:UniProtKB.
DR GO; GO:0002526; P:acute inflammatory response; IEA:Ensembl.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0009308; P:amine metabolic process; IDA:UniProtKB.
DR GO; GO:0030183; P:B cell differentiation; IC:BHF-UCL.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IEA:Ensembl.
DR GO; GO:0060710; P:chorio-allantoic fusion; IEA:Ensembl.
DR GO; GO:0002544; P:chronic inflammatory response; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0007157; P:heterophilic cell-cell adhesion; IDA:BHF-UCL.
DR GO; GO:0060333; P:interferon-gamma-mediated signaling pathway; TAS:Reactome.
DR GO; GO:0050901; P:leukocyte tethering or rolling; IEP:BHF-UCL.
DR GO; GO:0022614; P:membrane to membrane docking; IEP:BHF-UCL.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; IDA:BHF-UCL.
DR GO; GO:0050776; P:regulation of immune response; TAS:Reactome.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0010212; P:response to ionizing radiation; IEA:Ensembl.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR Gene3D; 2.60.40.10; -; 7.
DR InterPro; IPR003987; ICAM_VCAM_N.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR008424; Ig_C2-set.
DR InterPro; IPR013098; Ig_I-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR013151; Immunoglobulin.
DR InterPro; IPR003989; VCAM-1.
DR Pfam; PF05790; C2-set; 2.
DR Pfam; PF07679; I-set; 3.
DR Pfam; PF00047; ig; 1.
DR PRINTS; PR01472; ICAMVCAM1.
DR PRINTS; PR01474; VCAM1.
DR SMART; SM00409; IG; 2.
DR SMART; SM00408; IGc2; 3.
DR PROSITE; PS50835; IG_LIKE; 5.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell adhesion; Complete proteome;
KW Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Host-virus interaction; Immunoglobulin domain; Membrane; Polymorphism;
KW Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1 24
FT CHAIN 25 739 Vascular cell adhesion protein 1.
FT /FTId=PRO_0000014997.
FT TOPO_DOM 25 698 Extracellular (Potential).
FT TRANSMEM 699 720 Helical; (Potential).
FT TOPO_DOM 721 739 Cytoplasmic (Potential).
FT DOMAIN 25 105 Ig-like C2-type 1.
FT DOMAIN 109 212 Ig-like C2-type 2.
FT DOMAIN 223 309 Ig-like C2-type 3.
FT DOMAIN 312 399 Ig-like C2-type 4.
FT DOMAIN 408 506 Ig-like C2-type 5.
FT DOMAIN 511 595 Ig-like C2-type 6.
FT DOMAIN 600 684 Ig-like C2-type 7.
FT CARBOHYD 273 273 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 365 365 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 417 417 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 463 463 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 531 531 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 561 561 N-linked (GlcNAc...).
FT DISULFID 47 95
FT DISULFID 52 99
FT DISULFID 137 195
FT DISULFID 246 291 By similarity.
FT DISULFID 335 383 By similarity.
FT DISULFID 534 579 By similarity.
FT VAR_SEQ 52 113 Missing (in isoform 3).
FT /FTId=VSP_044636.
FT VAR_SEQ 310 402 EKPFTVEISPGPRIAAQIGDSVMLTCSVMGCESPSFSWRTQ
FT IDSPLSGKVRSEGTNSTLTLSPVSFENEHSYLCTVTCGHKK
FT LEKGIQVELYS -> A (in isoform 2).
FT /FTId=VSP_002580.
FT VARIANT 18 18 M -> I (in dbSNP:rs34228330).
FT /FTId=VAR_049951.
FT VARIANT 318 318 S -> F (in dbSNP:rs3783611).
FT /FTId=VAR_014309.
FT VARIANT 384 384 T -> A (in dbSNP:rs3783612).
FT /FTId=VAR_014310.
FT VARIANT 413 413 G -> A (in dbSNP:rs3783613).
FT /FTId=VAR_014311.
FT VARIANT 421 421 V -> I (in dbSNP:rs34100871).
FT /FTId=VAR_049952.
FT VARIANT 488 488 H -> R (in dbSNP:rs34199378).
FT /FTId=VAR_049953.
FT VARIANT 716 716 I -> L (in dbSNP:rs3783615).
FT /FTId=VAR_014312.
FT CONFLICT 182 182 F -> G (in Ref. 12).
FT CONFLICT 402 402 S -> T (in Ref. 11).
FT CONFLICT 728 728 S -> P (in Ref. 6; BAG59286).
FT STRAND 26 38
FT STRAND 43 51
FT STRAND 56 61
FT STRAND 68 74
FT STRAND 77 84
FT HELIX 87 89
FT STRAND 91 99
FT STRAND 102 114
FT STRAND 120 125
FT STRAND 133 144
FT HELIX 145 147
FT STRAND 148 154
FT STRAND 157 163
FT STRAND 169 171
FT STRAND 174 182
FT HELIX 186 188
FT STRAND 192 199
FT STRAND 209 216
SQ SEQUENCE 739 AA; 81276 MW; 050E2EBD39AC2FF4 CRC64;
MPGKMVVILG ASNILWIMFA ASQAFKIETT PESRYLAQIG DSVSLTCSTT GCESPFFSWR
TQIDSPLNGK VTNEGTTSTL TMNPVSFGNE HSYLCTATCE SRKLEKGIQV EIYSFPKDPE
IHLSGPLEAG KPITVKCSVA DVYPFDRLEI DLLKGDHLMK SQEFLEDADR KSLETKSLEV
TFTPVIEDIG KVLVCRAKLH IDEMDSVPTV RQAVKELQVY ISPKNTVISV NPSTKLQEGG
SVTMTCSSEG LPAPEIFWSK KLDNGNLQHL SGNATLTLIA MRMEDSGIYV CEGVNLIGKN
RKEVELIVQE KPFTVEISPG PRIAAQIGDS VMLTCSVMGC ESPSFSWRTQ IDSPLSGKVR
SEGTNSTLTL SPVSFENEHS YLCTVTCGHK KLEKGIQVEL YSFPRDPEIE MSGGLVNGSS
VTVSCKVPSV YPLDRLEIEL LKGETILENI EFLEDTDMKS LENKSLEMTF IPTIEDTGKA
LVCQAKLHID DMEFEPKQRQ STQTLYVNVA PRDTTVLVSP SSILEEGSSV NMTCLSQGFP
APKILWSRQL PNGELQPLSE NATLTLISTK MEDSGVYLCE GINQAGRSRK EVELIIQVTP
KDIKLTAFPS ESVKEGDTVI ISCTCGNVPE TWIILKKKAE TGDTVLKSID GAYTIRKAQL
KDAGVYECES KNKVGSQLRS LTLDVQGREN NKDYFSPELL VLYFASSLII PAIGMIIYFA
RKANMKGSYS LVEAQKSKV
//
MIM
192225
*RECORD*
*FIELD* NO
192225
*FIELD* TI
*192225 VASCULAR CELL ADHESION MOLECULE 1; VCAM1
*FIELD* TX
DESCRIPTION
Vascular cell adhesion molecule-1, a cell surface glycoprotein expressed
read moreby cytokine-activated endothelium, mediates the adhesion of monocytes
and lymphocytes (Cybulsky et al., 1991). In inflammatory conditions and
in cardiac allografts undergoing rejection, VCAM1 is upregulated in
endothelium of postcapillary venules. Arterial expression of VCAM1 is
also found in experimental models of atherosclerosis in the rabbit.
GENE STRUCTURE
Cybulsky et al. (1991) demonstrated that VCAM1 is present in single copy
in the human genome and contains 9 exons spanning about 25 kb of DNA. At
least 2 different VCAM1 precursors can be generated from the human gene
as a result of alternative mRNA splicing events, which include or
exclude exon 5.
MAPPING
Cybulsky et al. (1991) mapped the VCAM1 gene to chromosome 1 by Southern
analysis of somatic cell hybrids. A study of 2 hybrid lines carrying
translocations involving chromosome 1 permitted regionalization to
1p34-p21. Fluorescence in situ hybridization to metaphase chromosomes
further narrowed the localization to 1p32-p31. (Another endothelial
leukocyte adhesion molecule, ELAM1 (131210), is located on chromosome 1,
but on the long arm.)
Kumar et al. (1994) mapped the murine Vcam1 gene to chromosome 3 near
Amy1.
GENE FUNCTION
In a review of molecular pathways controlling heart development, Olson
and Srivastava (1996) cited studies indicating that deficiencies of the
cell adhesion molecules VCAM and alpha-4 integrin (192975) result in
epicardial dissolution and subsequent myocardial thinning.
Lu and Cyster (2002) studied the mechanisms that control localization of
marginal zone B cells. They demonstrated that marginal zone B cells
express elevated levels of the integrins LFA1 (see 153370/600065) and
alpha-4 (192975)-beta-1 (135630), and that the marginal zone B cells
bind to the ligands ICAM1 (147840) and VCAM1. These ligands are
expressed within the marginal zone in a lymphotoxin-dependent manner.
Combined inhibition of LFA1 and alpha-4-beta-1 causes a rapid and
selective release of B cells from the marginal zone. Furthermore,
lipopolysaccharide-triggered marginal zone B cell relocalization
involves downregulation of integrin-mediated adhesion. Lu and Cyster
(2002) concluded that their studies identified key requirements for
marginal zone B cell localization and established a role for integrins
in peripheral lymphoid tissue compartmentalization.
Garmy-Susini et al. (2005) demonstrated that integrin alpha-4-beta-1 and
VCAM1 are expressed by proliferating but not quiescent endothelial cells
and mural cells, respectively. Antagonists of this integrin-ligand pair
blocked the adhesion of mural cells to proliferating endothelia in vitro
and in vivo, thereby inducing apoptosis of endothelial cells and
pericytes and inhibiting neovascularization. Garmy-Susini et al. (2005)
concluded that integrin alpha-4-beta-1 and VCAM1 facilitate a critical
cell-cell adhesion event required for survival of endothelial and mural
cells during vascularization.
Garrison et al. (2005) described cotransin, a small molecule that
inhibits protein translocation into the endoplasmic reticulum. Cotransin
acts in a signal-sequence-discriminatory manner to prevent the stable
insertion of select nascent chains (specifically VCAM1, and P-selectin,
173610) into the Sec61 translocation channel. Garrison et al. (2005)
concluded that the range of substrates accommodated by the channel can
be specifically and reversibly modulated by a cell-permeable small
molecule that alters the interaction between signal sequences and the
Sec61 complex. This has various implications for drug development.
Besemer et al. (2005) developed a very similar VCAM1 depressing agent,
which they called CAM741. CAM741 works similar to cotransin in that it
represses the biosynthesis of VCAM1 cells by blocking the process of
cotranslational translocation, which is dependent on the signal peptide
of VCAM1. CAM741 does not inhibit targeting of the VCAM1 nascent chains
to the translocon channel but prevents translocation to the luminal side
of the endoplasmic reticulum through a process that involves the
translocon component Sec61-beta (609214). Consequently, the VCAM1
precursor protein is synthesized towards the cytosolic compartment of
the cells, where it is degraded.
By in vivo selection, transcriptomic analysis, functional verification,
and clinical validation, Minn et al. (2005) identified a set of genes
that marks and mediates breast cancer metastasis to the lungs. Some of
these genes serve dual functions, providing growth advantages both in
the primary tumor and in the lung microenvironment. Others contribute to
aggressive growth selectivity in the lung. Among the lung metastasis
signature genes identified, several, including VCAM1, were functionally
validated. Those subjects expressing the lung metastasis signature had a
significantly poorer lung metastasis-free survival, but not bone
metastasis-free survival, compared to subjects without the signature.
Campbell et al. (2006) found that increased serum levels of soluble
VCAM1 predicted recurrent ischemic stroke (601367) in a study of 252
patients. A smaller but similar trend was noted for serum levels of
N-terminal pro-B-type natriuretic peptide (NPPB; 600295). Patients in
the highest quarters for both sVCAM1 and NT-proBNP levels had 3.6 times
the risk of recurrent ischemic stroke compared to patients in the lowest
quarters for both biologic markers.
By database analysis, Harris et al. (2008) identified a potential target
sequence for miR126 (MIRN126; 611767), a microRNA selectively expressed
in endothelial cells, in the 3-prime UTR of VCAM1. Transfection of human
endothelial cells with antisense miR126 permitted an increase in
TNF-alpha (TNF; 191160)-stimulated VCAM1 expression. Conversely,
overexpression of the miR126 precursor increased miR126 levels and
decreased VCAM1 expression. Decreasing endogenous miR126 levels
increased leukocyte adherence to endothelial cells. Harris et al. (2008)
concluded that miR126 inhibits VCAM1 expression.
MOLECULAR GENETICS
Taylor et al. (2002) identified 33 SNPs in the VCAM1 locus. They then
analyzed a subset of these SNPs in 51 cases of stroke in sickle cell
disease (603903) patients derived from a single institution in Jamaica
and in 51 matched controls. They found that the C variant allele of the
nonsynonymous SNP 1238G-C, which results in a gly413-to-ala amino acid
change (G413A), may be associated with protection from stroke (odds
ratio = 0.35). Dover (2002) stated that sickle cell disease is not a
single gene disorder and emphasized the need for further studies of the
relationship of VCAM1 to strokes in this disorder.
Idelman et al. (2007) stated that VCAM1 transcription induction is
highly dependent on cell and organ type and mode of stimulation by
various transcription factors. The authors identified 8 VCAM1 promoter
haplotypes comprising 13 SNPs previously identified by Taylor et al.
(2002) in African Americans. Functional cellular expression studies in T
cells stimulated by T-cell mitogens assessed the inducibility of
expression of the different haplotypes. A -540A-G SNP (dbSNP rs3783605)
was found to gain an ETS2 (164740)-binding site, which was postulated by
Idelman et al. (2007) to have functional importance.
*FIELD* RF
1. Besemer, J.; Harant, H.; Wang, S.; Oberhauser, B.; Marquardt, K.;
Foster, C. A.; Schreiner, E. P.; de Vries, J. E.; Dascher-Nadel, C.;
Lindley, I. J. D.: Selective inhibition of cotranslational translocation
of vascular cell adhesion molecule 1. (Letter) Nature 436: 290-293,
2005.
2. Campbell, D. J.; Woodward, M.; Chalmers, J. P.; Colman, S. A.;
Jenkins, A. J.; Kemp, B. E.; Neal, B. C.; Patel, A.; MacMahon, S.
W.: Soluble vascular cell adhesion molecule 1 and N-terminal pro-B-type
natriuretic peptide in predicting ischemic stroke in patients with
cerebrovascular disease. Arch. Neurol. 63: 60-65, 2006.
3. Cybulsky, M.; Fries, J. W.; Williams, A. J.; Sultan, P.; Eddy,
R. L.; Byers, M. G.; Shows, T. B.; Gimbrone, M. A., Jr.; Collins,
T.: The human VCAM1 gene is assigned to chromosome 1p31-p32. (Abstract) Cytogenet.
Cell Genet. 58: 1852, 1991.
4. Cybulsky, M. I.; Fries, J. W. U.; Williams, A. J.; Sultan, P.;
Eddy, R.; Byers, M.; Shows, T.; Gimbrone, M. A., Jr.; Collins, T.
: Gene structure, chromosomal location, and basis for alternative
mRNA splicing of the human VCAM1 gene. Proc. Nat. Acad. Sci. 88:
7859-7863, 1991.
5. Dover, G. J.: SS disease is not a single gene disorder. (Letter) Blood 100:
4255 only, 2002.
6. Garmy-Susini, B.; Jin, H.; Zhu, Y.; Sung, R.-J.; Hwang, R.; Varner,
J.: Integrin alpha-4-beta-1--VCAM-1--mediated adhesion between endothelial
and mural cells is required for blood vessel maturation. J. Clin.
Invest. 115: 1542-1551, 2005.
7. Garrison, J. L.; Kunkel, E. J.; Hedge, R. S.; Taunton, J.: A substrate-specific
inhibitor of protein translocation into the endoplasmic reticulum.
(Letter) Nature 436: 285-289, 2005.
8. Harris, T. A.; Yamakuchi, M.; Ferlito, M.; Mendell, J. T.; Lowenstein,
C. J.: MicroRNA-126 regulates endothelial expression of vascular
cell adhesion molecule 1. Proc. Nat. Acad. Sci. 105: 1516-1521,
2008.
9. Idelman, G.; Taylor, J. G.; Tongbai, R.; Chen, R. A.; Haggerty,
C. M.; Bilke, S.; Chanock, S. J.; Gardner, K.: Functional profiling
of uncommon VCAM1 promoter polymorphisms prevalent in African American
populations. Hum. Mutat. 28: 824-829, 2007.
10. Kumar, A. G.; Dai, X. Y.; Kozak, C. A.; Mims, M. P.; Gotto, A.
M.; Ballantyne, C. M.: Murine VCAM-1: molecular cloning, mapping,
and analysis of a truncated form. J. Immun. 153: 4088-4098, 1994.
11. Lu, T. T.; Cyster, J. G.: Integrin-mediated long-term B cell
retention in the splenic marginal zone. Science 297: 409-412, 2002.
12. Minn, A. J.; Gupta, G. P.; Siegel, P. M.; Bos, P. D.; Shu, W.;
Giri, D. D.; Viale, A.; Olshen, A. B.; Gerald, W. L.; Massague, J.
: Genes that mediate breast cancer metastasis to lung. Nature 436:
518-524, 2005.
13. Olson, E.; Srivastava, D.: Molecular pathways controlling heart
development. Science 272: 671-676, 1996.
14. Taylor, J. G., VI; Tang, D. C.; Savage, S. A.; Leitman, S. F.;
Heller, S. I.; Serjeant, G. R.; Rodgers, G. P.; Chanock, S. J.: Variants
in the VCAM1 gene and risk for symptomatic stroke in sickle cell disease. Blood 100:
4303-4309, 2002.
*FIELD* CN
Patricia A. Hartz - updated: 04/15/2008
Cassandra L. Kniffin - updated: 10/10/2007
Cassandra L. Kniffin - updated: 7/14/2006
Ada Hamosh - updated: 8/17/2005
Ada Hamosh - updated: 8/15/2005
Marla J. F. O'Neill - updated: 7/8/2005
Victor A. McKusick - updated: 2/12/2003
Ada Hamosh - updated: 9/11/2002
Moyra Smith - Updated: 5/18/1996
*FIELD* CD
Victor A. McKusick: 8/8/1991
*FIELD* ED
mgross: 04/15/2008
wwang: 10/18/2007
ckniffin: 10/10/2007
carol: 5/16/2007
carol: 7/19/2006
ckniffin: 7/14/2006
alopez: 8/23/2005
alopez: 8/18/2005
terry: 8/17/2005
terry: 8/15/2005
wwang: 7/19/2005
wwang: 7/13/2005
terry: 7/8/2005
carol: 2/27/2003
tkritzer: 2/24/2003
terry: 2/12/2003
alopez: 9/11/2002
tkritzer: 9/11/2002
dkim: 7/17/1998
carol: 5/18/1996
carol: 1/27/1995
supermim: 3/16/1992
carol: 2/23/1992
carol: 9/27/1991
carol: 8/30/1991
carol: 8/8/1991
*RECORD*
*FIELD* NO
192225
*FIELD* TI
*192225 VASCULAR CELL ADHESION MOLECULE 1; VCAM1
*FIELD* TX
DESCRIPTION
Vascular cell adhesion molecule-1, a cell surface glycoprotein expressed
read moreby cytokine-activated endothelium, mediates the adhesion of monocytes
and lymphocytes (Cybulsky et al., 1991). In inflammatory conditions and
in cardiac allografts undergoing rejection, VCAM1 is upregulated in
endothelium of postcapillary venules. Arterial expression of VCAM1 is
also found in experimental models of atherosclerosis in the rabbit.
GENE STRUCTURE
Cybulsky et al. (1991) demonstrated that VCAM1 is present in single copy
in the human genome and contains 9 exons spanning about 25 kb of DNA. At
least 2 different VCAM1 precursors can be generated from the human gene
as a result of alternative mRNA splicing events, which include or
exclude exon 5.
MAPPING
Cybulsky et al. (1991) mapped the VCAM1 gene to chromosome 1 by Southern
analysis of somatic cell hybrids. A study of 2 hybrid lines carrying
translocations involving chromosome 1 permitted regionalization to
1p34-p21. Fluorescence in situ hybridization to metaphase chromosomes
further narrowed the localization to 1p32-p31. (Another endothelial
leukocyte adhesion molecule, ELAM1 (131210), is located on chromosome 1,
but on the long arm.)
Kumar et al. (1994) mapped the murine Vcam1 gene to chromosome 3 near
Amy1.
GENE FUNCTION
In a review of molecular pathways controlling heart development, Olson
and Srivastava (1996) cited studies indicating that deficiencies of the
cell adhesion molecules VCAM and alpha-4 integrin (192975) result in
epicardial dissolution and subsequent myocardial thinning.
Lu and Cyster (2002) studied the mechanisms that control localization of
marginal zone B cells. They demonstrated that marginal zone B cells
express elevated levels of the integrins LFA1 (see 153370/600065) and
alpha-4 (192975)-beta-1 (135630), and that the marginal zone B cells
bind to the ligands ICAM1 (147840) and VCAM1. These ligands are
expressed within the marginal zone in a lymphotoxin-dependent manner.
Combined inhibition of LFA1 and alpha-4-beta-1 causes a rapid and
selective release of B cells from the marginal zone. Furthermore,
lipopolysaccharide-triggered marginal zone B cell relocalization
involves downregulation of integrin-mediated adhesion. Lu and Cyster
(2002) concluded that their studies identified key requirements for
marginal zone B cell localization and established a role for integrins
in peripheral lymphoid tissue compartmentalization.
Garmy-Susini et al. (2005) demonstrated that integrin alpha-4-beta-1 and
VCAM1 are expressed by proliferating but not quiescent endothelial cells
and mural cells, respectively. Antagonists of this integrin-ligand pair
blocked the adhesion of mural cells to proliferating endothelia in vitro
and in vivo, thereby inducing apoptosis of endothelial cells and
pericytes and inhibiting neovascularization. Garmy-Susini et al. (2005)
concluded that integrin alpha-4-beta-1 and VCAM1 facilitate a critical
cell-cell adhesion event required for survival of endothelial and mural
cells during vascularization.
Garrison et al. (2005) described cotransin, a small molecule that
inhibits protein translocation into the endoplasmic reticulum. Cotransin
acts in a signal-sequence-discriminatory manner to prevent the stable
insertion of select nascent chains (specifically VCAM1, and P-selectin,
173610) into the Sec61 translocation channel. Garrison et al. (2005)
concluded that the range of substrates accommodated by the channel can
be specifically and reversibly modulated by a cell-permeable small
molecule that alters the interaction between signal sequences and the
Sec61 complex. This has various implications for drug development.
Besemer et al. (2005) developed a very similar VCAM1 depressing agent,
which they called CAM741. CAM741 works similar to cotransin in that it
represses the biosynthesis of VCAM1 cells by blocking the process of
cotranslational translocation, which is dependent on the signal peptide
of VCAM1. CAM741 does not inhibit targeting of the VCAM1 nascent chains
to the translocon channel but prevents translocation to the luminal side
of the endoplasmic reticulum through a process that involves the
translocon component Sec61-beta (609214). Consequently, the VCAM1
precursor protein is synthesized towards the cytosolic compartment of
the cells, where it is degraded.
By in vivo selection, transcriptomic analysis, functional verification,
and clinical validation, Minn et al. (2005) identified a set of genes
that marks and mediates breast cancer metastasis to the lungs. Some of
these genes serve dual functions, providing growth advantages both in
the primary tumor and in the lung microenvironment. Others contribute to
aggressive growth selectivity in the lung. Among the lung metastasis
signature genes identified, several, including VCAM1, were functionally
validated. Those subjects expressing the lung metastasis signature had a
significantly poorer lung metastasis-free survival, but not bone
metastasis-free survival, compared to subjects without the signature.
Campbell et al. (2006) found that increased serum levels of soluble
VCAM1 predicted recurrent ischemic stroke (601367) in a study of 252
patients. A smaller but similar trend was noted for serum levels of
N-terminal pro-B-type natriuretic peptide (NPPB; 600295). Patients in
the highest quarters for both sVCAM1 and NT-proBNP levels had 3.6 times
the risk of recurrent ischemic stroke compared to patients in the lowest
quarters for both biologic markers.
By database analysis, Harris et al. (2008) identified a potential target
sequence for miR126 (MIRN126; 611767), a microRNA selectively expressed
in endothelial cells, in the 3-prime UTR of VCAM1. Transfection of human
endothelial cells with antisense miR126 permitted an increase in
TNF-alpha (TNF; 191160)-stimulated VCAM1 expression. Conversely,
overexpression of the miR126 precursor increased miR126 levels and
decreased VCAM1 expression. Decreasing endogenous miR126 levels
increased leukocyte adherence to endothelial cells. Harris et al. (2008)
concluded that miR126 inhibits VCAM1 expression.
MOLECULAR GENETICS
Taylor et al. (2002) identified 33 SNPs in the VCAM1 locus. They then
analyzed a subset of these SNPs in 51 cases of stroke in sickle cell
disease (603903) patients derived from a single institution in Jamaica
and in 51 matched controls. They found that the C variant allele of the
nonsynonymous SNP 1238G-C, which results in a gly413-to-ala amino acid
change (G413A), may be associated with protection from stroke (odds
ratio = 0.35). Dover (2002) stated that sickle cell disease is not a
single gene disorder and emphasized the need for further studies of the
relationship of VCAM1 to strokes in this disorder.
Idelman et al. (2007) stated that VCAM1 transcription induction is
highly dependent on cell and organ type and mode of stimulation by
various transcription factors. The authors identified 8 VCAM1 promoter
haplotypes comprising 13 SNPs previously identified by Taylor et al.
(2002) in African Americans. Functional cellular expression studies in T
cells stimulated by T-cell mitogens assessed the inducibility of
expression of the different haplotypes. A -540A-G SNP (dbSNP rs3783605)
was found to gain an ETS2 (164740)-binding site, which was postulated by
Idelman et al. (2007) to have functional importance.
*FIELD* RF
1. Besemer, J.; Harant, H.; Wang, S.; Oberhauser, B.; Marquardt, K.;
Foster, C. A.; Schreiner, E. P.; de Vries, J. E.; Dascher-Nadel, C.;
Lindley, I. J. D.: Selective inhibition of cotranslational translocation
of vascular cell adhesion molecule 1. (Letter) Nature 436: 290-293,
2005.
2. Campbell, D. J.; Woodward, M.; Chalmers, J. P.; Colman, S. A.;
Jenkins, A. J.; Kemp, B. E.; Neal, B. C.; Patel, A.; MacMahon, S.
W.: Soluble vascular cell adhesion molecule 1 and N-terminal pro-B-type
natriuretic peptide in predicting ischemic stroke in patients with
cerebrovascular disease. Arch. Neurol. 63: 60-65, 2006.
3. Cybulsky, M.; Fries, J. W.; Williams, A. J.; Sultan, P.; Eddy,
R. L.; Byers, M. G.; Shows, T. B.; Gimbrone, M. A., Jr.; Collins,
T.: The human VCAM1 gene is assigned to chromosome 1p31-p32. (Abstract) Cytogenet.
Cell Genet. 58: 1852, 1991.
4. Cybulsky, M. I.; Fries, J. W. U.; Williams, A. J.; Sultan, P.;
Eddy, R.; Byers, M.; Shows, T.; Gimbrone, M. A., Jr.; Collins, T.
: Gene structure, chromosomal location, and basis for alternative
mRNA splicing of the human VCAM1 gene. Proc. Nat. Acad. Sci. 88:
7859-7863, 1991.
5. Dover, G. J.: SS disease is not a single gene disorder. (Letter) Blood 100:
4255 only, 2002.
6. Garmy-Susini, B.; Jin, H.; Zhu, Y.; Sung, R.-J.; Hwang, R.; Varner,
J.: Integrin alpha-4-beta-1--VCAM-1--mediated adhesion between endothelial
and mural cells is required for blood vessel maturation. J. Clin.
Invest. 115: 1542-1551, 2005.
7. Garrison, J. L.; Kunkel, E. J.; Hedge, R. S.; Taunton, J.: A substrate-specific
inhibitor of protein translocation into the endoplasmic reticulum.
(Letter) Nature 436: 285-289, 2005.
8. Harris, T. A.; Yamakuchi, M.; Ferlito, M.; Mendell, J. T.; Lowenstein,
C. J.: MicroRNA-126 regulates endothelial expression of vascular
cell adhesion molecule 1. Proc. Nat. Acad. Sci. 105: 1516-1521,
2008.
9. Idelman, G.; Taylor, J. G.; Tongbai, R.; Chen, R. A.; Haggerty,
C. M.; Bilke, S.; Chanock, S. J.; Gardner, K.: Functional profiling
of uncommon VCAM1 promoter polymorphisms prevalent in African American
populations. Hum. Mutat. 28: 824-829, 2007.
10. Kumar, A. G.; Dai, X. Y.; Kozak, C. A.; Mims, M. P.; Gotto, A.
M.; Ballantyne, C. M.: Murine VCAM-1: molecular cloning, mapping,
and analysis of a truncated form. J. Immun. 153: 4088-4098, 1994.
11. Lu, T. T.; Cyster, J. G.: Integrin-mediated long-term B cell
retention in the splenic marginal zone. Science 297: 409-412, 2002.
12. Minn, A. J.; Gupta, G. P.; Siegel, P. M.; Bos, P. D.; Shu, W.;
Giri, D. D.; Viale, A.; Olshen, A. B.; Gerald, W. L.; Massague, J.
: Genes that mediate breast cancer metastasis to lung. Nature 436:
518-524, 2005.
13. Olson, E.; Srivastava, D.: Molecular pathways controlling heart
development. Science 272: 671-676, 1996.
14. Taylor, J. G., VI; Tang, D. C.; Savage, S. A.; Leitman, S. F.;
Heller, S. I.; Serjeant, G. R.; Rodgers, G. P.; Chanock, S. J.: Variants
in the VCAM1 gene and risk for symptomatic stroke in sickle cell disease. Blood 100:
4303-4309, 2002.
*FIELD* CN
Patricia A. Hartz - updated: 04/15/2008
Cassandra L. Kniffin - updated: 10/10/2007
Cassandra L. Kniffin - updated: 7/14/2006
Ada Hamosh - updated: 8/17/2005
Ada Hamosh - updated: 8/15/2005
Marla J. F. O'Neill - updated: 7/8/2005
Victor A. McKusick - updated: 2/12/2003
Ada Hamosh - updated: 9/11/2002
Moyra Smith - Updated: 5/18/1996
*FIELD* CD
Victor A. McKusick: 8/8/1991
*FIELD* ED
mgross: 04/15/2008
wwang: 10/18/2007
ckniffin: 10/10/2007
carol: 5/16/2007
carol: 7/19/2006
ckniffin: 7/14/2006
alopez: 8/23/2005
alopez: 8/18/2005
terry: 8/17/2005
terry: 8/15/2005
wwang: 7/19/2005
wwang: 7/13/2005
terry: 7/8/2005
carol: 2/27/2003
tkritzer: 2/24/2003
terry: 2/12/2003
alopez: 9/11/2002
tkritzer: 9/11/2002
dkim: 7/17/1998
carol: 5/18/1996
carol: 1/27/1995
supermim: 3/16/1992
carol: 2/23/1992
carol: 9/27/1991
carol: 8/30/1991
carol: 8/8/1991