Reviewed,
UniProtKB/Swiss-Prot P78310 (CXAR_HUMAN)
Last modified
November 25, 2008.
Version 90.
History...
Clusters with 100%,
90%,
50% identity |
Documents (4) |
Third-party data |
Customize display | text xml rdf/xml gff fasta |
Names and origin
| Protein names | Recommended name: Coxsackievirus and adenovirus receptor Alternative name(s): Coxsackievirus B-adenovirus receptor HCVADR Short name=hCAR CVB3-binding protein | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 365 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Component of the epithelial apical junction complex that is essential for the tight junction integrity. Proposed to function as a homophilic cell adhesion molecule. Recruits MPDZ to intercellular contact sites. Probably involved in transepithelial migration of polymorphonuclear leukocytes (PMN) through adhesive interactions with AMICA1/JAML located in the plasma membrane of PMN. Receptor for group B coxsackieviruses and subgroup C of adenoviruses (AD2 and AD5), susceptibility to infection is correlated to its level of expression and availability at the plasma membrane of cells. |
| Subunit structure | Monomer. Probably homodimer formed by 2 molecules on adjacent cells. Interacts with LNX, MPDZ, BAIAP1, DLG4, PRKCABP, TJP1 and CTNNB1. Secreted isoform 3, isoform 4 and isoform 5 can interact with the extracellular domain of the receptor. Binds adenovirus 12 fiber protein. Isoform 5 but not isoform 3 binds to coxsackievirus. |
| Subcellular location | Isoform 1: Cell membrane; Single-pass type I membrane protein. Cell junction › tight junction. Cell junction › adherens junction. Basolateral cell membrane; Single-pass type I membrane protein. Note= In epithelial cells localizes to the apical junction complex composced of tight and adherens junctions. In airway epithelial cells localized to basolateral membrane but not to apical surface. Isoform 2: Cell membrane; Single-pass type I membrane protein. Cell junction › tight junction. Cell junction › adherens junction. Basolateral cell membrane; Single-pass membrane protein. Note= In epithelial cells localizes to the apical junction complex composced of tight and adherens junctions. In airway epithelial cells localized to basolateral membrane but not to apical surface. Isoform 3: Secreted. Isoform 4: Secreted. Isoform 5: Secreted. |
| Tissue specificity | Expressed in pancreas, brain, heart, small intestine, testis, prostate and at a lower level in liver and lung. Isoform 5 is ubiquitoulsy expressed while isoform 3 is expressed in heart, lung and pancreas. In skeletal muscle, isoform 1 is found at the neuromuscular junction and isoform 2 is found in blood vessels. In cardiac muscle, isoform 1 and isoform 2 are found at intercalated disks. In heart expressed in subendothelial layers of the vessel wall but not in the luminal endothelial surface. Expression is elevated in hearts with dilated cardiomyopathy. |
| Domain | The Ig-like C2-type 1 domain probably mediates homodimerization and interaction with JAML. The PDZ-binding motif mediates interaction with MPDZ and BAIAP1. |
| Post-translational modification | N-glycosylated By similarity. Palmitoylated on Cys-259 and/or Cys-260; required for proper localization to the plasma membrane. |
| Sequence similarities | Contains 2 Ig-like C2-type (immunoglobulin-like) domains. |
Ontologies
Alternative products
| This entry describes 5 isoforms produced by alternative splicing. [Align] [Select] | ||||||||
| Isoform 1 (identifier: P78310-1) Also known as: SIV; This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||||
| Notes: In epithelial cells localizes to the apical junction complex composced of tight and adherens junctions. In airway epithelial cells localized to basolateral membrane but not to apical surface. | ||||||||
| Isoform 2 (identifier: P78310-2) Also known as: CAR2; HCAR2; TVV; The sequence of this isoform differs from the canonical sequence as follows: 340-345: VAAPNL → FKYPY 346-365: Missing. | ||||||||
| Notes: In epithelial cells localizes to the apical junction complex composced of tight and adherens junctions. In airway epithelial cells localized to basolateral membrane but not to apical surface. | ||||||||
Sequence annotation (Features) | ||||||||
|---|---|---|---|---|---|---|---|---|
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | |||
| Sequence conflict | 343 | 1 | P → A in AAD31772. Ref.10 | |||||
| Isoform 3 (identifier: P78310-3) Also known as: CAR2/7; Gamma; The sequence of this isoform differs from the canonical sequence as follows: 71-89: IILYSGDKIYDDYYPDLKG → GRCATSKEPYVHCQKLHRQ 90-365: Missing. | ||||||||
| Isoform 4 (identifier: P78310-4) Also known as: CAR3/7; The sequence of this isoform differs from the canonical sequence as follows: 139-139: V → GKMCHLQRAVRPLPEATSAVIIHPWGPCLLPTWKDIPRLSITKYQVKTLNALLRVRLSHLLR 140-365: Missing. | ||||||||
| Isoform 5 (identifier: P78310-5) Also known as: CAR4/7; Beta; The sequence of this isoform differs from the canonical sequence as follows: 191-191: E → GKMCHLQRAVRPLPEATSAVIIHPWGPCLLPTWKDIPRLSITKYQVKTLNALLRVRLSHLLR 192-365: Missing. | ||||||||
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | |||||||||||||||||||||||||||||||||||||||||||||
Molecule processing | ||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Signal peptide | 1 – 19 | 19 | Potential | |||||||||||||||||||||||||||||||||||||||||||||||
| Chain | 20 – 365 | 346 | Coxsackievirus and adenovirus receptor | PRO_0000014739 | ||||||||||||||||||||||||||||||||||||||||||||||
Regions | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Topological domain | 20 – 237 | 218 | Extracellular Potential | |||||||||||||||||||||||||||||||||||||||||||||||
| Transmembrane | 238 – 258 | 21 | Potential | |||||||||||||||||||||||||||||||||||||||||||||||
| Topological domain | 259 – 365 | 107 | Cytoplasmic Potential | |||||||||||||||||||||||||||||||||||||||||||||||
| Domain | 20 – 134 | 115 | Ig-like C2-type 1 | |||||||||||||||||||||||||||||||||||||||||||||||
| Domain | 141 – 228 | 88 | Ig-like C2-type 2 | |||||||||||||||||||||||||||||||||||||||||||||||
| Motif | 360 – 365 | 6 | PDZ-binding | |||||||||||||||||||||||||||||||||||||||||||||||
Amino acid modifications | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 293 | 1 | Phosphoserine By similarity | |||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 300 | 1 | Phosphoserine By similarity | |||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 306 | 1 | Phosphoserine | |||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 323 | 1 | Phosphoserine By similarity | |||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 332 | 1 | Phosphoserine | |||||||||||||||||||||||||||||||||||||||||||||||
| Lipidation | 259 | 1 | S-palmitoyl cysteine Probable | |||||||||||||||||||||||||||||||||||||||||||||||
| Lipidation | 260 | 1 | S-palmitoyl cysteine Probable | |||||||||||||||||||||||||||||||||||||||||||||||
| Glycosylation | 106 | 1 | N-linked (GlcNAc...) Potential | |||||||||||||||||||||||||||||||||||||||||||||||
| Glycosylation | 201 | 1 | N-linked (GlcNAc...) Potential | |||||||||||||||||||||||||||||||||||||||||||||||
| Disulfide bond | 41 ↔ 120 | |||||||||||||||||||||||||||||||||||||||||||||||||
| Disulfide bond | 162 ↔ 212 | By similarity | ||||||||||||||||||||||||||||||||||||||||||||||||
Natural variations | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Alternative sequence | 71 – 89 | 19 | IILYS…PDLKG → GRCATSKEPYVHCQKLHRQ in isoform 3. | VSP_014819 | ||||||||||||||||||||||||||||||||||||||||||||||
| Alternative sequence | 90 – 365 | 276 | Missing in isoform 3. | VSP_014820 | ||||||||||||||||||||||||||||||||||||||||||||||
| Alternative sequence | 139 | 1 | V → GKMCHLQRAVRPLPEATSAV IIHPWGPCLLPTWKDIPRLS ITKYQVKTLNALLRVRLSHL LR in isoform 4. | VSP_014821 | ||||||||||||||||||||||||||||||||||||||||||||||
| Alternative sequence | 140 – 365 | 226 | Missing in isoform 4. | VSP_014822 | ||||||||||||||||||||||||||||||||||||||||||||||
| Alternative sequence | 191 | 1 | E → GKMCHLQRAVRPLPEATSAV IIHPWGPCLLPTWKDIPRLS ITKYQVKTLNALLRVRLSHL LR in isoform 5. | VSP_014823 | ||||||||||||||||||||||||||||||||||||||||||||||
| Alternative sequence | 192 – 365 | 174 | Missing in isoform 5. | VSP_014824 | ||||||||||||||||||||||||||||||||||||||||||||||
| Alternative sequence | 340 – 345 | 6 | VAAPNL → FKYPY in isoform 2. | VSP_014825 | ||||||||||||||||||||||||||||||||||||||||||||||
| Alternative sequence | 346 – 365 | 20 | Missing in isoform 2. | VSP_014826 | ||||||||||||||||||||||||||||||||||||||||||||||
Experimental info | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Mutagenesis | 70 – 72 | 3 | VII → AID: Abolishes binding to adenovirus type 5 | |||||||||||||||||||||||||||||||||||||||||||||||
| Mutagenesis | 259 – 260 | 2 | CC → AA: Loss of palmitoylation and altered localization | |||||||||||||||||||||||||||||||||||||||||||||||
| Mutagenesis | 318 | 1 | Y → A: Affects basolateral localization in airway epithelial cells | |||||||||||||||||||||||||||||||||||||||||||||||
| Mutagenesis | 345 – 348 | 4 | LSRM → AAAA: Affects basolateral localization in airway epithelial cells | |||||||||||||||||||||||||||||||||||||||||||||||
Secondary structure | ||||||||||||||||||||||||||||||||||||||||||||||||||
Helix Strand Turn | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 21 – 32 | 12 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 37 – 39 | 3 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 42 – 44 | 3 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 53 – 61 | 9 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 68 – 75 | 8 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 78 – 80 | 3 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Turn | 86 – 90 | 5 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 91 – 93 | 3 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 98 – 100 | 3 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 105 – 107 | 3 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 112 – 114 | 3 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 116 – 124 | 9 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 127 – 138 | 12 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 145 – 148 | 4 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 156 – 163 | 8 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 166 – 168 | 3 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 171 – 178 | 8 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 185 – 192 | 8 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 195 – 201 | 7 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 208 – 215 | 8 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 221 – 227 | 7 | ||||||||||||||||||||||||||||||||||||||||||||||||
Sequences
| ||||||||||||||||||||||||||||||||||||||||||
References
| « Hide 'large scale' references | |
| [1] | "HCAR and MCAR: the human and mouse cellular receptors for subgroup C adenoviruses and group B coxsackieviruses." Tomko R.P., Xu R., Philipson L. Proc. Natl. Acad. Sci. U.S.A. 94:3352-3356(1997) [PubMed: 9096397] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION AS A VIRUS RECEPTOR, TISSUE SPECIFICITY. |
| [2] | "Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5." Bergelson J.M., Cunningham J.A., Droguett G., Kurt-Jones E., Krithivas A., Hong J.S., Horwitz M.S., Crowell R.L., Finberg R.W. Science 275:1320-1323(1997) [PubMed: 9036860] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). |
| [3] | "Genomic organization and chromosomal localization of the human Coxsackievirus B-adenovirus receptor gene." Bowles K.R., Gibson J., Wu J., Shaffer L.G., Towbin J.A., Bowles N.E. Hum. Genet. 105:354-359(1999) [PubMed: 10543405] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [4] | "Interaction of coxsackievirus B3 with the full length coxsackievirus-adenovirus receptor." He Y., Chipman P.R., Howitt J., Bator C.M., Whitt M.A., Baker T.S., Kuhn R.J., Anderson C.W., Freimuth P., Rossmann M.G. Nat. Struct. Biol. 8:874-878(2001) [PubMed: 11573093] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [5] | "Alternatively spliced soluble coxsackie-adenovirus receptors inhibit coxsackievirus infection." Doerner A., Xiong D., Couch K., Yajima T., Knowlton K.U. J. Biol. Chem. 279:18497-18503(2004) [PubMed: 14978041] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3; 4 AND 5), INTERACTION WITH COXSACKIEVIRUS TYPE B3, SUBCELLULAR LOCATION. |
| [6] | "Putative regulatory domains in the human and mouse CAR genes." Andersson B., Tomko R.P., Andersson K., Darban H., Oncu D., Mizra M., Sollerbrant K., Sonnhammer E., Philipson L. Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [7] | "Full-length cDNA libraries and normalization." Li W.B., Gruber C., Jessee J., Polayes D. Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Cervix. |
| [8] | "Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). |
| [9] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Cervix. |
| [10] | "Expression of Coxsackie-adenovirus-receptor and alpha v-integrin does not correlate with adenovector targeting in vivo indicating anatomical vector barriers." Fechner H., Haack A., Wang H., Wang X., Eizema K., Pauschinger M., Schoemaker R.G., van Veghel R., Houtsmuller A.B., Schultheiss H.-P., Lamers J.M.J., Poller W. Gene Ther. 6:1520-1535(1999) [ |

Clusters with