Full text data of PVRL1
PVRL1
(HVEC, PRR1)
[Confidence: high (a blood group or CD marker)]
Poliovirus receptor-related protein 1 (Herpes virus entry mediator C; Herpesvirus entry mediator C; HveC; Herpesvirus Ig-like receptor; HIgR; Nectin-1; CD111; Flags: Precursor)
Poliovirus receptor-related protein 1 (Herpes virus entry mediator C; Herpesvirus entry mediator C; HveC; Herpesvirus Ig-like receptor; HIgR; Nectin-1; CD111; Flags: Precursor)
UniProt
Q15223
ID PVRL1_HUMAN Reviewed; 517 AA.
AC Q15223; O75465; Q2M3D3; Q9HBE6; Q9HBW2;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 26-SEP-2001, sequence version 3.
DT 22-JAN-2014, entry version 133.
DE RecName: Full=Poliovirus receptor-related protein 1;
DE AltName: Full=Herpes virus entry mediator C;
DE Short=Herpesvirus entry mediator C;
DE Short=HveC;
DE AltName: Full=Herpesvirus Ig-like receptor;
DE Short=HIgR;
DE AltName: Full=Nectin-1;
DE AltName: CD_antigen=CD111;
DE Flags: Precursor;
GN Name=PVRL1; Synonyms=HVEC, PRR1;
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 DELTA), AND FUNCTION AS A RECEPTOR
RP FOR HHV-1; HHV-2 AND PRV.
RX PubMed=7721102; DOI=10.1016/0378-1119(94)00842-G;
RA Lopez M., Eberle F., Mattei M.-G., Gabert J., Bardin F., Maroc C.,
RA Dubreuil P.;
RT "cDNA characterization and chromosomal localization of a gene related
RT to the poliovirus receptor gene.";
RL Gene 155:261-265(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM DELTA).
RX PubMed=9616127; DOI=10.1126/science.280.5369.1618;
RA Geraghty R.J., Krummenacher C., Cohen G.H., Eisenberg R.J.,
RA Spear P.G.;
RT "Entry of alphaherpesviruses mediated by poliovirus receptor-related
RT protein 1 and poliovirus receptor.";
RL Science 280:1618-1620(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM GAMMA).
RX PubMed=11356977; DOI=10.1128/JVI.75.12.5684-5691.2001;
RA Lopez M., Cocchi F., Avitabile E., Leclerc A., Adelaide J.,
RA Campadelli-Fjume G., Dubreuil P.;
RT "Novel, soluble isoform of the herpes simplex virus (HSV) receptor
RT nectin1 (or prr1-HIgR-Hvec) modulates positively and negatively
RT susceptibility to hsv infection.";
RL J. Virol. 75:5684-5691(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM DELTA).
RC TISSUE=Brain;
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 [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 28-517 (ISOFORMS ALPHA AND
RP DELTA), AND DISEASE.
RX PubMed=10932188; DOI=10.1038/78119;
RA Suzuki K., Hu D., Bustos T., Zlotogora J., Richieri-Costa A.,
RA Helms J.A., Spritz R.A.;
RT "Mutations of PVRL1, encoding a cell-cell adhesion
RT molecule/herpesvirus receptor, in cleft lip/palate-ectodermal
RT dysplasia.";
RL Nat. Genet. 25:427-430(2000).
RN [6]
RP INTERACTION WITH HHV-1 AND HHV-2 GLYCOPROTEIN D.
RX PubMed=9696799;
RA Krummenacher C., Nicola A.V., Whitbeck J.C., Lou H., Hou W.,
RA Lambris J.D., Geraghty R.J., Spear P.G., Cohen G.H., Eisenberg R.J.;
RT "Herpes simplex virus glycoprotein D can bind to poliovirus receptor-
RT related protein 1 or herpesvirus entry mediator, two structurally
RT unrelated mediators of virus entry.";
RL J. Virol. 72:7064-7074(1998).
RN [7]
RP INTERACTION WITH AFADIN.
RX PubMed=10225955; DOI=10.1083/jcb.145.3.539;
RA Takahashi K., Nakanishi H., Miyahara M., Mandai K., Satoh K.,
RA Satoh A., Nishioka H., Aoki J., Nomoto A., Mizoguchi A., Takai Y.;
RT "Nectin/PRR: an immunoglobulin-like cell adhesion molecule recruited
RT to cadherin-based adherens junctions through interaction with Afadin,
RT a PDZ domain-containing protein.";
RL J. Cell Biol. 145:539-549(1999).
RN [8]
RP INTERACTION WITH PVRL3 AND PVRL4.
RX PubMed=11544254; DOI=10.1074/jbc.M103810200;
RA Reymond N., Fabre S., Lecocq E., Adelaide J., Dubreuil P., Lopez M.;
RT "Nectin4/PRR4, a new afadin-associated member of the nectin family
RT that trans-interacts with nectin1/PRR1 through V domain interaction.";
RL J. Biol. Chem. 276:43205-43215(2001).
RN [9]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-202, 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 [10]
RP INTERACTION WITH INTEGRIN ITGAV/ITGB3.
RX PubMed=16679515; DOI=10.1074/jbc.M600301200;
RA Sakamoto Y., Ogita H., Hirota T., Kawakatsu T., Fukuyama T.,
RA Yasumi M., Kanzaki N., Ozaki M., Takai Y.;
RT "Interaction of integrin alpha(v)beta3 with nectin. Implication in
RT cross-talk between cell-matrix and cell-cell junctions.";
RL J. Biol. Chem. 281:19631-19644(2006).
RN [11]
RP GLYCOSYLATION AT ASN-202.
RX PubMed=19139490; DOI=10.1074/mcp.M800504-MCP200;
RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F.,
RA Zheng Z.B., Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y.,
RA Zhang Y.K., Deng Y.L., Ying W.T., He S.M., Qian X.H.;
RT "A strategy for precise and large scale identification of core
RT fucosylated glycoproteins.";
RL Mol. Cell. Proteomics 8:913-923(2009).
RN [12]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-332, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-
RT linked cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-422 AND SER-434, AND
RP MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 30-335 IN COMPLEX WITH HERPES
RP SIMPLEX VIRUS GLYCOPROTEIN D, SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=22146396; DOI=10.1038/ncomms1571;
RA Zhang N., Yan J., Lu G., Guo Z., Fan Z., Wang J., Shi Y., Qi J.,
RA Gao G.F.;
RT "Binding of herpes simplex virus glycoprotein D to nectin-1 exploits
RT host cell adhesion.";
RL Nat. Commun. 2:577-577(2011).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (4.0 ANGSTROMS) OF 31-345 IN COMPLEX WITH HERPES
RP SIMPLEX VIRUS GLYCOPROTEIN D, FUNCTION, SUBUNIT, MUTAGENESIS OF
RP ASN-82; SER-84 AND PHE-129, DISULFIDE BONDS, AND GLYCOSYLATION AT
RP ASN-72; ASN-139 AND ASN-202.
RX PubMed=21980294; DOI=10.1371/journal.ppat.1002277;
RA Di Giovine P., Settembre E.C., Bhargava A.K., Luftig M.A., Lou H.,
RA Cohen G.H., Eisenberg R.J., Krummenacher C., Carfi A.;
RT "Structure of herpes simplex virus glycoprotein D bound to the human
RT receptor nectin-1.";
RL PLoS Pathog. 7:E1002277-E1002277(2011).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 31-337, SUBUNIT, MASS
RP SPECTROMETRY, GLYCOSYLATION AT ASN-202, AND DISULFIDE BONDS.
RX PubMed=22902367; DOI=10.1038/nsmb.2366;
RA Harrison O.J., Vendome J., Brasch J., Jin X., Hong S., Katsamba P.S.,
RA Ahlsen G., Troyanovsky R.B., Troyanovsky S.M., Honig B., Shapiro L.;
RT "Nectin ectodomain structures reveal a canonical adhesive interface.";
RL Nat. Struct. Mol. Biol. 19:906-915(2012).
CC -!- FUNCTION: Promotes cell-cell contacts by forming homophilic or
CC heterophilic trans-dimers. Heterophilic interactions have been
CC detected between PVRL1/nectin-1 and PVRL3/nectin-3 and between
CC PVRL1/nectin-1 and PVRL4/nectin-4. Functions as an entry receptor
CC for herpes simplex virus and pseudorabies virus.
CC -!- SUBUNIT: Can form trans-heterodimers with PVRL3/nectin-3 and with
CC PVRL4/nectin-4. Interacts (via C-terminus) with afadin (via PDZ
CC domain); this interaction recruits PVRL1 to cadherin-based
CC adherens junctions. Interacts with integrin alphaV/beta3.
CC Interacts with herpes simplex virus 1 (HHV-1), herpes simplex
CC virus 2 (HHV-2), and pseudorabies virus (PRV) envelope
CC glycoprotein D; functions as an entry receptor for these viruses.
CC -!- INTERACTION:
CC Q9NQS3:PVRL3; NbExp=2; IntAct=EBI-1771314, EBI-2826725;
CC Q96NY8:PVRL4; NbExp=2; IntAct=EBI-1771314, EBI-4314784;
CC -!- SUBCELLULAR LOCATION: Isoform Alpha: Cell membrane; Single-pass
CC type I membrane protein.
CC -!- SUBCELLULAR LOCATION: Isoform Delta: Cell membrane; Single-pass
CC type I membrane protein.
CC -!- SUBCELLULAR LOCATION: Isoform Gamma: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=Delta;
CC IsoId=Q15223-1; Sequence=Displayed;
CC Name=Alpha;
CC IsoId=Q15223-2; Sequence=VSP_002626, VSP_002627;
CC Name=Gamma;
CC IsoId=Q15223-3; Sequence=VSP_002624, VSP_002625;
CC -!- DISEASE: Ectodermal dysplasia, Margarita Island type (EDMI)
CC [MIM:225060]: An autosomal recessive form of ectodermal dysplasia,
CC a heterogeneous group of disorders due to abnormal development of
CC two or more ectodermal structures. It is a syndrome characterized
CC by the association of cleft lip/palate, ectodermal dysplasia
CC (sparse short and dry scalp hair, sparse eyebrows and eyelashes),
CC and partial syndactyly of the fingers and/or toes. Two thirds of
CC the patients do not manifest oral cleft but present with abnormal
CC teeth and nails. Note=The disease is caused by mutations affecting
CC the gene represented in this entry.
CC -!- DISEASE: Non-syndromic orofacial cleft 7 (OFC7) [MIM:225060]: A
CC birth defect consisting of cleft lips with or without cleft
CC palate. Cleft lips are associated with cleft palate in two-third
CC of cases. A cleft lip can occur on one or both sides and range in
CC severity from a simple notch in the upper lip to a complete
CC opening in the lip extending into the floor of the nostril and
CC involving the upper gum. Note=The disease is caused by mutations
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the nectin family.
CC -!- SIMILARITY: Contains 2 Ig-like C2-type (immunoglobulin-like)
CC domains.
CC -!- SIMILARITY: Contains 1 Ig-like V-type (immunoglobulin-like)
CC domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA53980.2; Type=Erroneous initiation;
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DR EMBL; X76400; CAA53980.2; ALT_INIT; mRNA.
DR EMBL; AF060231; AAC23798.1; -; mRNA.
DR EMBL; AY029539; AAK33124.1; -; mRNA.
DR EMBL; BC104948; AAI04949.1; -; mRNA.
DR EMBL; BC113471; AAI13472.1; -; mRNA.
DR EMBL; AF252867; AAG16648.1; -; Genomic_DNA.
DR EMBL; AF196768; AAG16648.1; JOINED; Genomic_DNA.
DR EMBL; AF196769; AAG16648.1; JOINED; Genomic_DNA.
DR EMBL; AF196770; AAG16648.1; JOINED; Genomic_DNA.
DR EMBL; AF196771; AAG16648.1; JOINED; Genomic_DNA.
DR EMBL; AF196774; AAG16649.1; -; Genomic_DNA.
DR EMBL; AF196768; AAG16649.1; JOINED; Genomic_DNA.
DR EMBL; AF196769; AAG16649.1; JOINED; Genomic_DNA.
DR EMBL; AF196770; AAG16649.1; JOINED; Genomic_DNA.
DR EMBL; AF196771; AAG16649.1; JOINED; Genomic_DNA.
DR EMBL; AF196772; AAG16649.1; JOINED; Genomic_DNA.
DR EMBL; AF196773; AAG16649.1; JOINED; Genomic_DNA.
DR PIR; JC4024; JC4024.
DR RefSeq; NP_002846.3; NM_002855.4.
DR RefSeq; NP_976030.1; NM_203285.1.
DR RefSeq; NP_976031.1; NM_203286.1.
DR UniGene; Hs.334846; -.
DR PDB; 3ALP; X-ray; 2.80 A; A/B=30-335.
DR PDB; 3SKU; X-ray; 4.00 A; D/E/F=31-345.
DR PDB; 3U82; X-ray; 3.16 A; B=30-335.
DR PDB; 3U83; X-ray; 2.50 A; A=30-335.
DR PDB; 4FMF; X-ray; 3.20 A; A/B/C/D=31-337.
DR PDBsum; 3ALP; -.
DR PDBsum; 3SKU; -.
DR PDBsum; 3U82; -.
DR PDBsum; 3U83; -.
DR PDBsum; 4FMF; -.
DR ProteinModelPortal; Q15223; -.
DR SMR; Q15223; 33-335.
DR DIP; DIP-40302N; -.
DR IntAct; Q15223; 4.
DR MINT; MINT-90873; -.
DR STRING; 9606.ENSP00000264025; -.
DR MEROPS; I43.001; -.
DR PhosphoSite; Q15223; -.
DR DMDM; 18202503; -.
DR PaxDb; Q15223; -.
DR PeptideAtlas; Q15223; -.
DR PRIDE; Q15223; -.
DR DNASU; 5818; -.
DR Ensembl; ENST00000264025; ENSP00000264025; ENSG00000110400.
DR Ensembl; ENST00000340882; ENSP00000345289; ENSG00000110400.
DR Ensembl; ENST00000341398; ENSP00000344974; ENSG00000110400.
DR GeneID; 5818; -.
DR KEGG; hsa:5818; -.
DR UCSC; uc001pwv.3; human.
DR CTD; 5818; -.
DR GeneCards; GC11M119542; -.
DR HGNC; HGNC:9706; PVRL1.
DR HPA; CAB016135; -.
DR HPA; HPA026846; -.
DR MIM; 225060; phenotype.
DR MIM; 600644; gene.
DR neXtProt; NX_Q15223; -.
DR Orphanet; 1991; Cleft lip with or without cleft palate.
DR Orphanet; 3253; Zlotogora-Ogur syndrome.
DR PharmGKB; PA34051; -.
DR eggNOG; NOG147558; -.
DR HOGENOM; HOG000115804; -.
DR HOVERGEN; HBG100542; -.
DR InParanoid; Q15223; -.
DR KO; K06081; -.
DR OMA; MARMGHA; -.
DR OrthoDB; EOG73RBB5; -.
DR PhylomeDB; Q15223; -.
DR Reactome; REACT_111155; Cell-Cell communication.
DR ChiTaRS; PVRL1; human.
DR EvolutionaryTrace; Q15223; -.
DR GeneWiki; PVRL1; -.
DR GenomeRNAi; 5818; -.
DR NextBio; 22658; -.
DR PMAP-CutDB; Q15223; -.
DR PRO; PR:Q15223; -.
DR ArrayExpress; Q15223; -.
DR Bgee; Q15223; -.
DR CleanEx; HS_PVRL1; -.
DR Genevestigator; Q15223; -.
DR GO; GO:0005913; C:cell-cell adherens junction; IDA:BHF-UCL.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral to membrane; NAS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0015026; F:coreceptor activity; TAS:ProtInc.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:HGNC.
DR GO; GO:0001618; F:virus receptor activity; IEA:UniProtKB-KW.
DR GO; GO:0034332; P:adherens junction organization; TAS:Reactome.
DR GO; GO:0034329; P:cell junction assembly; TAS:Reactome.
DR GO; GO:0002934; P:desmosome organization; IEA:Ensembl.
DR GO; GO:0070166; P:enamel mineralization; IEA:Ensembl.
DR GO; GO:0007157; P:heterophilic cell-cell adhesion; ISS:HGNC.
DR GO; GO:0007156; P:homophilic cell adhesion; ISS:HGNC.
DR GO; GO:0006955; P:immune response; NAS:UniProtKB.
DR GO; GO:0006826; P:iron ion transport; IEA:Ensembl.
DR GO; GO:0002089; P:lens morphogenesis in camera-type eye; IEA:Ensembl.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0009615; P:response to virus; IEA:GOC.
DR GO; GO:0060041; P:retina development in camera-type eye; IEA:Ensembl.
DR GO; GO:0046718; P:viral entry into host cell; NAS:UniProtKB.
DR Gene3D; 2.60.40.10; -; 3.
DR InterPro; IPR013162; CD80_C2-set.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR013106; Ig_V-set.
DR InterPro; IPR003596; Ig_V-set_subgr.
DR Pfam; PF08205; C2-set_2; 1.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00409; IG; 1.
DR SMART; SM00406; IGv; 1.
DR PROSITE; PS50835; IG_LIKE; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell adhesion; Cell membrane;
KW Complete proteome; Disulfide bond; Ectodermal dysplasia; Glycoprotein;
KW Host cell receptor for virus entry; Host-virus interaction;
KW Immunoglobulin domain; Membrane; Phosphoprotein; Receptor;
KW Reference proteome; Repeat; Secreted; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1 30 Potential.
FT CHAIN 31 517 Poliovirus receptor-related protein 1.
FT /FTId=PRO_0000015133.
FT TOPO_DOM 31 355 Extracellular (Potential).
FT TRANSMEM 356 376 Helical; (Potential).
FT TOPO_DOM 377 517 Cytoplasmic (Potential).
FT DOMAIN 31 141 Ig-like V-type.
FT DOMAIN 149 238 Ig-like C2-type 1.
FT DOMAIN 247 334 Ig-like C2-type 2.
FT COMPBIAS 437 444 Poly-Glu.
FT COMPBIAS 445 449 Poly-Gly.
FT MOD_RES 422 422 Phosphoserine.
FT MOD_RES 434 434 Phosphoserine.
FT MOD_RES 435 435 Phosphoserine (By similarity).
FT CARBOHYD 36 36 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 72 72 N-linked (GlcNAc...).
FT CARBOHYD 139 139 N-linked (GlcNAc...).
FT CARBOHYD 202 202 N-linked (GlcNAc...) (complex).
FT CARBOHYD 286 286 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 297 297 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 307 307 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 332 332 N-linked (GlcNAc...).
FT DISULFID 51 124
FT DISULFID 172 226
FT DISULFID 269 316
FT VAR_SEQ 335 352 EFPYTPSPPEHGRRAGPV -> AFCQLIYPGKGRTRARMF
FT (in isoform Gamma).
FT /FTId=VSP_002624.
FT VAR_SEQ 336 458 FPYTPSPPEHGRRAGPVPTAIIGGVAGSILLVLIVVGGIVV
FT ALRRRRHTFKGDYSTKKHVYGNGYSKAGIPQHHPPMAQNLQ
FT YPDDSDDEKKAGPLGGSSYEEEEEEEEGGGGGERKVGGPHP
FT -> KPRPQRGLGSAARLLAGTVAVFLILVAVLTVFFLYNRQ
FT QKSPPETDGAGTDQPLSQKPEPSPSRQSSLVPEDIQVVHLD
FT PGRQQQQEEEDLQKLSLQPPYYDLGVSPSYHPSVRTTEPRG
FT ECP (in isoform Alpha).
FT /FTId=VSP_002626.
FT VAR_SEQ 353 517 Missing (in isoform Gamma).
FT /FTId=VSP_002625.
FT VAR_SEQ 459 517 Missing (in isoform Alpha).
FT /FTId=VSP_002627.
FT MUTAGEN 82 82 N->Y: Impairs interaction with herpes
FT simplex glycoprotein D. Decreases
FT susceptibility to infection by herpes
FT simplex virus.
FT MUTAGEN 84 84 S->Y: Impairs interaction with herpes
FT simplex glycoprotein D. Decreases
FT susceptibility to infection by herpes
FT simplex virus.
FT MUTAGEN 129 129 F->A,S: Impairs interaction with herpes
FT simplex glycoprotein D. Decreases
FT susceptibility to infection by herpes
FT simplex virus.
FT STRAND 37 42
FT STRAND 47 49
FT STRAND 61 71
FT STRAND 74 82
FT TURN 83 85
FT STRAND 86 89
FT TURN 94 96
FT STRAND 97 101
FT STRAND 103 106
FT STRAND 109 111
FT HELIX 116 118
FT STRAND 120 129
FT STRAND 132 144
FT STRAND 147 152
FT STRAND 157 159
FT STRAND 167 179
FT STRAND 182 189
FT STRAND 192 199
FT STRAND 205 213
FT HELIX 217 219
FT STRAND 223 230
FT STRAND 233 240
FT STRAND 243 252
FT STRAND 265 275
FT STRAND 279 284
FT STRAND 293 296
FT STRAND 299 302
FT HELIX 308 310
FT STRAND 312 320
FT STRAND 323 331
SQ SEQUENCE 517 AA; 57158 MW; DF34C8AEC893EE6D CRC64;
MARMGLAGAA GRWWGLALGL TAFFLPGVHS QVVQVNDSMY GFIGTDVVLH CSFANPLPSV
KITQVTWQKS TNGSKQNVAI YNPSMGVSVL APYRERVEFL RPSFTDGTIR LSRLELEDEG
VYICEFATFP TGNRESQLNL TVMAKPTNWI EGTQAVLRAK KGQDDKVLVA TCTSANGKPP
SVVSWETRLK GEAEYQEIRN PNGTVTVISR YRLVPSREAH QQSLACIVNY HMDRFKESLT
LNVQYEPEVT IEGFDGNWYL QRMDVKLTCK ADANPPATEY HWTTLNGSLP KGVEAQNRTL
FFKGPINYSL AGTYICEATN PIGTRSGQVE VNITEFPYTP SPPEHGRRAG PVPTAIIGGV
AGSILLVLIV VGGIVVALRR RRHTFKGDYS TKKHVYGNGY SKAGIPQHHP PMAQNLQYPD
DSDDEKKAGP LGGSSYEEEE EEEEGGGGGE RKVGGPHPKY DEDAKRPYFT VDEAEARQDG
YGDRTLGYQY DPEQLDLAEN MVSQNDGSFI SKKEWYV
//
ID PVRL1_HUMAN Reviewed; 517 AA.
AC Q15223; O75465; Q2M3D3; Q9HBE6; Q9HBW2;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 26-SEP-2001, sequence version 3.
DT 22-JAN-2014, entry version 133.
DE RecName: Full=Poliovirus receptor-related protein 1;
DE AltName: Full=Herpes virus entry mediator C;
DE Short=Herpesvirus entry mediator C;
DE Short=HveC;
DE AltName: Full=Herpesvirus Ig-like receptor;
DE Short=HIgR;
DE AltName: Full=Nectin-1;
DE AltName: CD_antigen=CD111;
DE Flags: Precursor;
GN Name=PVRL1; Synonyms=HVEC, PRR1;
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 DELTA), AND FUNCTION AS A RECEPTOR
RP FOR HHV-1; HHV-2 AND PRV.
RX PubMed=7721102; DOI=10.1016/0378-1119(94)00842-G;
RA Lopez M., Eberle F., Mattei M.-G., Gabert J., Bardin F., Maroc C.,
RA Dubreuil P.;
RT "cDNA characterization and chromosomal localization of a gene related
RT to the poliovirus receptor gene.";
RL Gene 155:261-265(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM DELTA).
RX PubMed=9616127; DOI=10.1126/science.280.5369.1618;
RA Geraghty R.J., Krummenacher C., Cohen G.H., Eisenberg R.J.,
RA Spear P.G.;
RT "Entry of alphaherpesviruses mediated by poliovirus receptor-related
RT protein 1 and poliovirus receptor.";
RL Science 280:1618-1620(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM GAMMA).
RX PubMed=11356977; DOI=10.1128/JVI.75.12.5684-5691.2001;
RA Lopez M., Cocchi F., Avitabile E., Leclerc A., Adelaide J.,
RA Campadelli-Fjume G., Dubreuil P.;
RT "Novel, soluble isoform of the herpes simplex virus (HSV) receptor
RT nectin1 (or prr1-HIgR-Hvec) modulates positively and negatively
RT susceptibility to hsv infection.";
RL J. Virol. 75:5684-5691(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM DELTA).
RC TISSUE=Brain;
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 [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 28-517 (ISOFORMS ALPHA AND
RP DELTA), AND DISEASE.
RX PubMed=10932188; DOI=10.1038/78119;
RA Suzuki K., Hu D., Bustos T., Zlotogora J., Richieri-Costa A.,
RA Helms J.A., Spritz R.A.;
RT "Mutations of PVRL1, encoding a cell-cell adhesion
RT molecule/herpesvirus receptor, in cleft lip/palate-ectodermal
RT dysplasia.";
RL Nat. Genet. 25:427-430(2000).
RN [6]
RP INTERACTION WITH HHV-1 AND HHV-2 GLYCOPROTEIN D.
RX PubMed=9696799;
RA Krummenacher C., Nicola A.V., Whitbeck J.C., Lou H., Hou W.,
RA Lambris J.D., Geraghty R.J., Spear P.G., Cohen G.H., Eisenberg R.J.;
RT "Herpes simplex virus glycoprotein D can bind to poliovirus receptor-
RT related protein 1 or herpesvirus entry mediator, two structurally
RT unrelated mediators of virus entry.";
RL J. Virol. 72:7064-7074(1998).
RN [7]
RP INTERACTION WITH AFADIN.
RX PubMed=10225955; DOI=10.1083/jcb.145.3.539;
RA Takahashi K., Nakanishi H., Miyahara M., Mandai K., Satoh K.,
RA Satoh A., Nishioka H., Aoki J., Nomoto A., Mizoguchi A., Takai Y.;
RT "Nectin/PRR: an immunoglobulin-like cell adhesion molecule recruited
RT to cadherin-based adherens junctions through interaction with Afadin,
RT a PDZ domain-containing protein.";
RL J. Cell Biol. 145:539-549(1999).
RN [8]
RP INTERACTION WITH PVRL3 AND PVRL4.
RX PubMed=11544254; DOI=10.1074/jbc.M103810200;
RA Reymond N., Fabre S., Lecocq E., Adelaide J., Dubreuil P., Lopez M.;
RT "Nectin4/PRR4, a new afadin-associated member of the nectin family
RT that trans-interacts with nectin1/PRR1 through V domain interaction.";
RL J. Biol. Chem. 276:43205-43215(2001).
RN [9]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-202, 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 [10]
RP INTERACTION WITH INTEGRIN ITGAV/ITGB3.
RX PubMed=16679515; DOI=10.1074/jbc.M600301200;
RA Sakamoto Y., Ogita H., Hirota T., Kawakatsu T., Fukuyama T.,
RA Yasumi M., Kanzaki N., Ozaki M., Takai Y.;
RT "Interaction of integrin alpha(v)beta3 with nectin. Implication in
RT cross-talk between cell-matrix and cell-cell junctions.";
RL J. Biol. Chem. 281:19631-19644(2006).
RN [11]
RP GLYCOSYLATION AT ASN-202.
RX PubMed=19139490; DOI=10.1074/mcp.M800504-MCP200;
RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F.,
RA Zheng Z.B., Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y.,
RA Zhang Y.K., Deng Y.L., Ying W.T., He S.M., Qian X.H.;
RT "A strategy for precise and large scale identification of core
RT fucosylated glycoproteins.";
RL Mol. Cell. Proteomics 8:913-923(2009).
RN [12]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-332, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-
RT linked cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-422 AND SER-434, AND
RP MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 30-335 IN COMPLEX WITH HERPES
RP SIMPLEX VIRUS GLYCOPROTEIN D, SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=22146396; DOI=10.1038/ncomms1571;
RA Zhang N., Yan J., Lu G., Guo Z., Fan Z., Wang J., Shi Y., Qi J.,
RA Gao G.F.;
RT "Binding of herpes simplex virus glycoprotein D to nectin-1 exploits
RT host cell adhesion.";
RL Nat. Commun. 2:577-577(2011).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (4.0 ANGSTROMS) OF 31-345 IN COMPLEX WITH HERPES
RP SIMPLEX VIRUS GLYCOPROTEIN D, FUNCTION, SUBUNIT, MUTAGENESIS OF
RP ASN-82; SER-84 AND PHE-129, DISULFIDE BONDS, AND GLYCOSYLATION AT
RP ASN-72; ASN-139 AND ASN-202.
RX PubMed=21980294; DOI=10.1371/journal.ppat.1002277;
RA Di Giovine P., Settembre E.C., Bhargava A.K., Luftig M.A., Lou H.,
RA Cohen G.H., Eisenberg R.J., Krummenacher C., Carfi A.;
RT "Structure of herpes simplex virus glycoprotein D bound to the human
RT receptor nectin-1.";
RL PLoS Pathog. 7:E1002277-E1002277(2011).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 31-337, SUBUNIT, MASS
RP SPECTROMETRY, GLYCOSYLATION AT ASN-202, AND DISULFIDE BONDS.
RX PubMed=22902367; DOI=10.1038/nsmb.2366;
RA Harrison O.J., Vendome J., Brasch J., Jin X., Hong S., Katsamba P.S.,
RA Ahlsen G., Troyanovsky R.B., Troyanovsky S.M., Honig B., Shapiro L.;
RT "Nectin ectodomain structures reveal a canonical adhesive interface.";
RL Nat. Struct. Mol. Biol. 19:906-915(2012).
CC -!- FUNCTION: Promotes cell-cell contacts by forming homophilic or
CC heterophilic trans-dimers. Heterophilic interactions have been
CC detected between PVRL1/nectin-1 and PVRL3/nectin-3 and between
CC PVRL1/nectin-1 and PVRL4/nectin-4. Functions as an entry receptor
CC for herpes simplex virus and pseudorabies virus.
CC -!- SUBUNIT: Can form trans-heterodimers with PVRL3/nectin-3 and with
CC PVRL4/nectin-4. Interacts (via C-terminus) with afadin (via PDZ
CC domain); this interaction recruits PVRL1 to cadherin-based
CC adherens junctions. Interacts with integrin alphaV/beta3.
CC Interacts with herpes simplex virus 1 (HHV-1), herpes simplex
CC virus 2 (HHV-2), and pseudorabies virus (PRV) envelope
CC glycoprotein D; functions as an entry receptor for these viruses.
CC -!- INTERACTION:
CC Q9NQS3:PVRL3; NbExp=2; IntAct=EBI-1771314, EBI-2826725;
CC Q96NY8:PVRL4; NbExp=2; IntAct=EBI-1771314, EBI-4314784;
CC -!- SUBCELLULAR LOCATION: Isoform Alpha: Cell membrane; Single-pass
CC type I membrane protein.
CC -!- SUBCELLULAR LOCATION: Isoform Delta: Cell membrane; Single-pass
CC type I membrane protein.
CC -!- SUBCELLULAR LOCATION: Isoform Gamma: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=Delta;
CC IsoId=Q15223-1; Sequence=Displayed;
CC Name=Alpha;
CC IsoId=Q15223-2; Sequence=VSP_002626, VSP_002627;
CC Name=Gamma;
CC IsoId=Q15223-3; Sequence=VSP_002624, VSP_002625;
CC -!- DISEASE: Ectodermal dysplasia, Margarita Island type (EDMI)
CC [MIM:225060]: An autosomal recessive form of ectodermal dysplasia,
CC a heterogeneous group of disorders due to abnormal development of
CC two or more ectodermal structures. It is a syndrome characterized
CC by the association of cleft lip/palate, ectodermal dysplasia
CC (sparse short and dry scalp hair, sparse eyebrows and eyelashes),
CC and partial syndactyly of the fingers and/or toes. Two thirds of
CC the patients do not manifest oral cleft but present with abnormal
CC teeth and nails. Note=The disease is caused by mutations affecting
CC the gene represented in this entry.
CC -!- DISEASE: Non-syndromic orofacial cleft 7 (OFC7) [MIM:225060]: A
CC birth defect consisting of cleft lips with or without cleft
CC palate. Cleft lips are associated with cleft palate in two-third
CC of cases. A cleft lip can occur on one or both sides and range in
CC severity from a simple notch in the upper lip to a complete
CC opening in the lip extending into the floor of the nostril and
CC involving the upper gum. Note=The disease is caused by mutations
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the nectin family.
CC -!- SIMILARITY: Contains 2 Ig-like C2-type (immunoglobulin-like)
CC domains.
CC -!- SIMILARITY: Contains 1 Ig-like V-type (immunoglobulin-like)
CC domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA53980.2; Type=Erroneous initiation;
CC -----------------------------------------------------------------------
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DR EMBL; X76400; CAA53980.2; ALT_INIT; mRNA.
DR EMBL; AF060231; AAC23798.1; -; mRNA.
DR EMBL; AY029539; AAK33124.1; -; mRNA.
DR EMBL; BC104948; AAI04949.1; -; mRNA.
DR EMBL; BC113471; AAI13472.1; -; mRNA.
DR EMBL; AF252867; AAG16648.1; -; Genomic_DNA.
DR EMBL; AF196768; AAG16648.1; JOINED; Genomic_DNA.
DR EMBL; AF196769; AAG16648.1; JOINED; Genomic_DNA.
DR EMBL; AF196770; AAG16648.1; JOINED; Genomic_DNA.
DR EMBL; AF196771; AAG16648.1; JOINED; Genomic_DNA.
DR EMBL; AF196774; AAG16649.1; -; Genomic_DNA.
DR EMBL; AF196768; AAG16649.1; JOINED; Genomic_DNA.
DR EMBL; AF196769; AAG16649.1; JOINED; Genomic_DNA.
DR EMBL; AF196770; AAG16649.1; JOINED; Genomic_DNA.
DR EMBL; AF196771; AAG16649.1; JOINED; Genomic_DNA.
DR EMBL; AF196772; AAG16649.1; JOINED; Genomic_DNA.
DR EMBL; AF196773; AAG16649.1; JOINED; Genomic_DNA.
DR PIR; JC4024; JC4024.
DR RefSeq; NP_002846.3; NM_002855.4.
DR RefSeq; NP_976030.1; NM_203285.1.
DR RefSeq; NP_976031.1; NM_203286.1.
DR UniGene; Hs.334846; -.
DR PDB; 3ALP; X-ray; 2.80 A; A/B=30-335.
DR PDB; 3SKU; X-ray; 4.00 A; D/E/F=31-345.
DR PDB; 3U82; X-ray; 3.16 A; B=30-335.
DR PDB; 3U83; X-ray; 2.50 A; A=30-335.
DR PDB; 4FMF; X-ray; 3.20 A; A/B/C/D=31-337.
DR PDBsum; 3ALP; -.
DR PDBsum; 3SKU; -.
DR PDBsum; 3U82; -.
DR PDBsum; 3U83; -.
DR PDBsum; 4FMF; -.
DR ProteinModelPortal; Q15223; -.
DR SMR; Q15223; 33-335.
DR DIP; DIP-40302N; -.
DR IntAct; Q15223; 4.
DR MINT; MINT-90873; -.
DR STRING; 9606.ENSP00000264025; -.
DR MEROPS; I43.001; -.
DR PhosphoSite; Q15223; -.
DR DMDM; 18202503; -.
DR PaxDb; Q15223; -.
DR PeptideAtlas; Q15223; -.
DR PRIDE; Q15223; -.
DR DNASU; 5818; -.
DR Ensembl; ENST00000264025; ENSP00000264025; ENSG00000110400.
DR Ensembl; ENST00000340882; ENSP00000345289; ENSG00000110400.
DR Ensembl; ENST00000341398; ENSP00000344974; ENSG00000110400.
DR GeneID; 5818; -.
DR KEGG; hsa:5818; -.
DR UCSC; uc001pwv.3; human.
DR CTD; 5818; -.
DR GeneCards; GC11M119542; -.
DR HGNC; HGNC:9706; PVRL1.
DR HPA; CAB016135; -.
DR HPA; HPA026846; -.
DR MIM; 225060; phenotype.
DR MIM; 600644; gene.
DR neXtProt; NX_Q15223; -.
DR Orphanet; 1991; Cleft lip with or without cleft palate.
DR Orphanet; 3253; Zlotogora-Ogur syndrome.
DR PharmGKB; PA34051; -.
DR eggNOG; NOG147558; -.
DR HOGENOM; HOG000115804; -.
DR HOVERGEN; HBG100542; -.
DR InParanoid; Q15223; -.
DR KO; K06081; -.
DR OMA; MARMGHA; -.
DR OrthoDB; EOG73RBB5; -.
DR PhylomeDB; Q15223; -.
DR Reactome; REACT_111155; Cell-Cell communication.
DR ChiTaRS; PVRL1; human.
DR EvolutionaryTrace; Q15223; -.
DR GeneWiki; PVRL1; -.
DR GenomeRNAi; 5818; -.
DR NextBio; 22658; -.
DR PMAP-CutDB; Q15223; -.
DR PRO; PR:Q15223; -.
DR ArrayExpress; Q15223; -.
DR Bgee; Q15223; -.
DR CleanEx; HS_PVRL1; -.
DR Genevestigator; Q15223; -.
DR GO; GO:0005913; C:cell-cell adherens junction; IDA:BHF-UCL.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral to membrane; NAS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0015026; F:coreceptor activity; TAS:ProtInc.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:HGNC.
DR GO; GO:0001618; F:virus receptor activity; IEA:UniProtKB-KW.
DR GO; GO:0034332; P:adherens junction organization; TAS:Reactome.
DR GO; GO:0034329; P:cell junction assembly; TAS:Reactome.
DR GO; GO:0002934; P:desmosome organization; IEA:Ensembl.
DR GO; GO:0070166; P:enamel mineralization; IEA:Ensembl.
DR GO; GO:0007157; P:heterophilic cell-cell adhesion; ISS:HGNC.
DR GO; GO:0007156; P:homophilic cell adhesion; ISS:HGNC.
DR GO; GO:0006955; P:immune response; NAS:UniProtKB.
DR GO; GO:0006826; P:iron ion transport; IEA:Ensembl.
DR GO; GO:0002089; P:lens morphogenesis in camera-type eye; IEA:Ensembl.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0009615; P:response to virus; IEA:GOC.
DR GO; GO:0060041; P:retina development in camera-type eye; IEA:Ensembl.
DR GO; GO:0046718; P:viral entry into host cell; NAS:UniProtKB.
DR Gene3D; 2.60.40.10; -; 3.
DR InterPro; IPR013162; CD80_C2-set.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR013106; Ig_V-set.
DR InterPro; IPR003596; Ig_V-set_subgr.
DR Pfam; PF08205; C2-set_2; 1.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00409; IG; 1.
DR SMART; SM00406; IGv; 1.
DR PROSITE; PS50835; IG_LIKE; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell adhesion; Cell membrane;
KW Complete proteome; Disulfide bond; Ectodermal dysplasia; Glycoprotein;
KW Host cell receptor for virus entry; Host-virus interaction;
KW Immunoglobulin domain; Membrane; Phosphoprotein; Receptor;
KW Reference proteome; Repeat; Secreted; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1 30 Potential.
FT CHAIN 31 517 Poliovirus receptor-related protein 1.
FT /FTId=PRO_0000015133.
FT TOPO_DOM 31 355 Extracellular (Potential).
FT TRANSMEM 356 376 Helical; (Potential).
FT TOPO_DOM 377 517 Cytoplasmic (Potential).
FT DOMAIN 31 141 Ig-like V-type.
FT DOMAIN 149 238 Ig-like C2-type 1.
FT DOMAIN 247 334 Ig-like C2-type 2.
FT COMPBIAS 437 444 Poly-Glu.
FT COMPBIAS 445 449 Poly-Gly.
FT MOD_RES 422 422 Phosphoserine.
FT MOD_RES 434 434 Phosphoserine.
FT MOD_RES 435 435 Phosphoserine (By similarity).
FT CARBOHYD 36 36 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 72 72 N-linked (GlcNAc...).
FT CARBOHYD 139 139 N-linked (GlcNAc...).
FT CARBOHYD 202 202 N-linked (GlcNAc...) (complex).
FT CARBOHYD 286 286 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 297 297 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 307 307 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 332 332 N-linked (GlcNAc...).
FT DISULFID 51 124
FT DISULFID 172 226
FT DISULFID 269 316
FT VAR_SEQ 335 352 EFPYTPSPPEHGRRAGPV -> AFCQLIYPGKGRTRARMF
FT (in isoform Gamma).
FT /FTId=VSP_002624.
FT VAR_SEQ 336 458 FPYTPSPPEHGRRAGPVPTAIIGGVAGSILLVLIVVGGIVV
FT ALRRRRHTFKGDYSTKKHVYGNGYSKAGIPQHHPPMAQNLQ
FT YPDDSDDEKKAGPLGGSSYEEEEEEEEGGGGGERKVGGPHP
FT -> KPRPQRGLGSAARLLAGTVAVFLILVAVLTVFFLYNRQ
FT QKSPPETDGAGTDQPLSQKPEPSPSRQSSLVPEDIQVVHLD
FT PGRQQQQEEEDLQKLSLQPPYYDLGVSPSYHPSVRTTEPRG
FT ECP (in isoform Alpha).
FT /FTId=VSP_002626.
FT VAR_SEQ 353 517 Missing (in isoform Gamma).
FT /FTId=VSP_002625.
FT VAR_SEQ 459 517 Missing (in isoform Alpha).
FT /FTId=VSP_002627.
FT MUTAGEN 82 82 N->Y: Impairs interaction with herpes
FT simplex glycoprotein D. Decreases
FT susceptibility to infection by herpes
FT simplex virus.
FT MUTAGEN 84 84 S->Y: Impairs interaction with herpes
FT simplex glycoprotein D. Decreases
FT susceptibility to infection by herpes
FT simplex virus.
FT MUTAGEN 129 129 F->A,S: Impairs interaction with herpes
FT simplex glycoprotein D. Decreases
FT susceptibility to infection by herpes
FT simplex virus.
FT STRAND 37 42
FT STRAND 47 49
FT STRAND 61 71
FT STRAND 74 82
FT TURN 83 85
FT STRAND 86 89
FT TURN 94 96
FT STRAND 97 101
FT STRAND 103 106
FT STRAND 109 111
FT HELIX 116 118
FT STRAND 120 129
FT STRAND 132 144
FT STRAND 147 152
FT STRAND 157 159
FT STRAND 167 179
FT STRAND 182 189
FT STRAND 192 199
FT STRAND 205 213
FT HELIX 217 219
FT STRAND 223 230
FT STRAND 233 240
FT STRAND 243 252
FT STRAND 265 275
FT STRAND 279 284
FT STRAND 293 296
FT STRAND 299 302
FT HELIX 308 310
FT STRAND 312 320
FT STRAND 323 331
SQ SEQUENCE 517 AA; 57158 MW; DF34C8AEC893EE6D CRC64;
MARMGLAGAA GRWWGLALGL TAFFLPGVHS QVVQVNDSMY GFIGTDVVLH CSFANPLPSV
KITQVTWQKS TNGSKQNVAI YNPSMGVSVL APYRERVEFL RPSFTDGTIR LSRLELEDEG
VYICEFATFP TGNRESQLNL TVMAKPTNWI EGTQAVLRAK KGQDDKVLVA TCTSANGKPP
SVVSWETRLK GEAEYQEIRN PNGTVTVISR YRLVPSREAH QQSLACIVNY HMDRFKESLT
LNVQYEPEVT IEGFDGNWYL QRMDVKLTCK ADANPPATEY HWTTLNGSLP KGVEAQNRTL
FFKGPINYSL AGTYICEATN PIGTRSGQVE VNITEFPYTP SPPEHGRRAG PVPTAIIGGV
AGSILLVLIV VGGIVVALRR RRHTFKGDYS TKKHVYGNGY SKAGIPQHHP PMAQNLQYPD
DSDDEKKAGP LGGSSYEEEE EEEEGGGGGE RKVGGPHPKY DEDAKRPYFT VDEAEARQDG
YGDRTLGYQY DPEQLDLAEN MVSQNDGSFI SKKEWYV
//
MIM
225060
*RECORD*
*FIELD* NO
225060
*FIELD* TI
#225060 CLEFT LIP/PALATE-ECTODERMAL DYSPLASIA SYNDROME; CLPED1
;;ZLOTOGORA-OGUR SYNDROME;;
read moreECTODERMAL DYSPLASIA, MARGARITA ISLAND TYPE;;
ECTODERMAL DYSPLASIA, TYPE 4; ED4;;
ECTODERMAL DYSPLASIA, CLEFT LIP AND PALATE, MENTAL RETARDATION, AND
SYNDACTYLY
OROFACIAL CLEFT 7, INCLUDED; OFC7, INCLUDED;;
CLEFT LIP WITH OR WITHOUT CLEFT PALATE, NONSYNDROMIC, 7, INCLUDED
*FIELD* TX
A number sign (#) is used with this entry because of evidence that the
phenotype of syndactyly, ectodermal dysplasia, and cleft lip/palate is
due to mutations in the gene encoding the cell-cell adhesion
molecule/herpesvirus receptor, PVRL1 (600644). Mutation in the PVRL1
gene has also been found in a form of orofacial cleft (OFC7).
CLINICAL FEATURES
Zlotogora et al. (1987) reported 2 sibs with a syndrome including cleft
lip and palate, sparse scalp hair, malformed protruding ears, and
partial syndactyly of the fingers and toes. An older sib also had mental
retardation and pili torti. The parents were consanguineous. In 2
Turkish sibs, products of a second-cousin marriage, Ogur and Yuksel
(1988) found the combination of tetramelic syndactyly, ectodermal
dysplasia, cleft lip and palate, renal anomalies, and mental
retardation. In 3 Brazilian brothers and a half brother, all born of
first-cousin matings in a Brazilian kindred, Rodini and Richieri-Costa
(1990) described a syndrome which they proposed to call the
Zlotogora-Ogur syndrome on the basis of the reports by Zlotogora et al.
(1987) and Ogur and Yuksel (1988). The features were ectodermal
dysplasia, bilateral cleft lip/palate, mental retardation, and
syndactyly of fingers 2 and 3.
In the Caribbean island of Margarita off the coast of northeastern
Venezuela (Nueva Esparta State), Bustos et al. (1991) identified a form
of ectodermal dysplasia in 15 females and 12 males in 7 families, each
with considerable consanguinity. It was considered likely that the 7
families were related to each other. The patients had scanty eyebrows
and eyelashes, sparse, short and dry scalp hair, and striking changes in
the teeth, which showed hypodontia mainly of the upper lateral incisors
and changes in size and shape. Cleft lip/palate (in 7), syndactyly of
fingers and toes (in 13), and onychodysplasia were often also observed.
Males and females were affected to an equal degree, although in general
severity was variable. Notably, sweating was normal in all.
Zlotogora (1994) gave a review of the syndrome of syndactyly, ectodermal
dysplasia, and cleft lip/palate in which he proposed that the disorder
called Zlotogora-Ogur syndrome (Zlotogora and Ogur, 1988) is the same as
that reported by Bustos et al. (1991) and referred to here as the
Margarita form of ectodermal dysplasia. Mental retardation was present
in those families described as having Zlotogora-Ogur syndrome but absent
in the Margarita families. Zlotogora (1994) noted that mental
development may differ from family to family. Zlotogora (1994) and
Rodini and Richieri-Costa (1990) considered this to be a separate
disorder from that described by Rosselli and Gulienetti (1961) (see
225000) and from other clefting-ectodermal dysplasia syndromes with limb
involvement.
Suzuki et al. (1998) pointed out that Columbus discovered Isla de
Margarita, a group of 3 islands in the south-central Caribbean, in 1498
and that one of the earliest Spanish colonies in the New World was
established there. They also commented that the philtrum is strikingly
broad and flat in many Margarita Island ectodermal dysplasia (ED)
obligate heterozygotes, who would be expected to number perhaps 1 in 22
among the indigenous population of the island. The incidence of
nonsyndromic cleft lip/cleft palate is quite high on Margarita Island,
approximately 5.4 per 1,000. Although this high incidence might result
from environmental factors, such as lack of dietary folate, it is also
possible that heterozygosity for ED4 constitutes a significant genetic
risk factor for nonsyndromic cleft lip/cleft palate on the island.
MAPPING
Suzuki et al. (1998) described linkage disequilibrium mapping of the
gene for ED4, using an affected-only DNA-pooling strategy. Haplotype
analysis of 4 complex Margarita Island ED4 families localized the ED4
gene to an approximately 1- to 2-Mb interval on 11q23 spanned by just 2
YACS. Suzuki et al. (1998) pointed out that 'rough fur' (ruf) in the
mouse is located in the region of chromosome 9 with conserved synteny to
11q24. The ruf locus gives rise to autosomal recessive rough fur and
hyperkeratosis, features reminiscent of Margarita Island ED.
MOLECULAR GENETICS
In patients with the Margarita type of ectodermal dysplasia, Suzuki et
al. (2000) identified a nonsense mutation in the poliovirus
receptor-like-1 gene (PVRL1; 600644.0001). The authors suggested that
the high frequency of the disorder on Margarita Island may have resulted
from resistance of heterozygotes to infection by alpha-herpesviruses. In
2 families from Israel and Brazil described as having Zlotogora-Ogur
syndrome, Suzuki et al. (2000) also found mutations in the PVRL1 gene
(600644.0002-600644.0003).
Sozen et al. (2001) demonstrated a highly significant association
between heterozygosity for the W185X mutation in the PVRL1 gene
(600644.0001) and sporadic, nonsyndromic cleft lip with or without cleft
palate in northern Venezuela.
*FIELD* RF
1. Bustos, T.; Simosa, V.; Pinto-Cisternas, J.; Abramovits, W.; Jolay,
L.; Rodriguez, L.; Fernandez, L.; Ramela, M.: Autosomal recessive
ectodermal dysplasia. I. An undescribed dysplasia/malformation syndrome. Am.
J. Med. Genet. 41: 398-404, 1991.
2. Ogur, G.; Yuksel, M.: Association of syndactyly, ectodermal dysplasia,
and cleft lip and palate: report of two sibs from Turkey. J. Med.
Genet. 25: 37-40, 1988.
3. Rodini, E. S. O.; Richieri-Costa, A.: Autosomal recessive ectodermal
dysplasia, cleft lip/palate, mental retardation, and syndactyly: the
Zlotogora-Ogur syndrome. Am. J. Med. Genet. 36: 473-476, 1990.
4. Rosselli, D.; Gulienetti, R.: Ectodermal dysplasia. Brit. J.
Plast. Surg. 14: 190-204, 1961.
5. Sozen, M. A.; Suzuki, K.; Tolarova, M. M.; Bustos, T.; Fernandez
Iglesias, J. E.; Spritz, R. A.: Mutation of PVRL1 is associated with
sporadic, non-syndromic cleft lip/palate in northern Venezuela. Nature
Genet. 29: 141-142, 2001.
6. Suzuki, K.; Bustos, T.; Spritz, R. A.: Linkage disequilibrium
mapping of the gene for Margarita Island ectodermal dysplasia (ED4)
to 11q23. Am. J. Hum. Genet. 63: 1102-1107, 1998.
7. Suzuki, K.; Hu, D.; Bustos, T.; Zlotogora, J.; Richieri-Costa,
A.; Helms, J. A.; Spritz, R. A.: Mutations of PVRL1, encoding a cell-cell
adhesion molecule/herpesvirus receptor, in cleft lip/palate-ectodermal
dysplasia. Nature Genet. 25: 427-430, 2000.
8. Zlotogora, J.: Syndactyly, ectodermal dysplasia, and cleft lip/palate. J.
Med. Genet. 31: 957-959, 1994.
9. Zlotogora, J.; Ogur, G.: Syndactyly, ectodermal dysplasia, and
cleft lip and palate. (Letter) J. Med. Genet. 25: 503 only, 1988.
10. Zlotogora, J.; Zilberman, Y.; Tenenbaum, A.; Wexler, M. R.: Cleft
lip and palate, pili torti, malformed ears, partial syndactyly of
fingers and toes, and mental retardation: a new syndrome? J. Med.
Genet. 24: 291-293, 1987.
*FIELD* CS
INHERITANCE:
Autosomal recessive
HEAD AND NECK:
[Face];
Triangular face;
Malar hypoplasia;
[Ears];
Anteverted pinnae;
[Eyes];
Sparse eyelashes;
Sparse eyebrows;
[Nose];
Abnormal philtrum;
[Mouth];
Cleft lip;
Cleft palate;
[Teeth];
Hypodontia;
Anodontia;
Microdontia
SKELETAL:
[Hands];
Syndactyly, cutaneous;
[Feet];
Syndactyly, cutaneous
SKIN, NAILS, HAIR:
[Skin];
Palmoplantar hyperkeratosis;
Normal sweating capacity;
[Nails];
Onychodysplasia;
[Hair];
Hypotrichosis, progressive;
Short, brittle hair;
Sparse eyelashes;
Sparse eyebrows
MISCELLANEOUS:
Allelic disorder to the Zlotogora-Ogur syndrome (225000)
MOLECULAR BASIS:
Caused by mutation in the poliovirus receptor-like 1 gene (PVRL1,
600644.0001)
*FIELD* CN
Cassandra L. Kniffin - revised: 9/11/2003
*FIELD* CD
John F. Jackson: 6/15/1995
*FIELD* ED
joanna: 12/05/2008
joanna: 9/17/2003
ckniffin: 9/11/2003
*FIELD* CN
Cassandra L. Kniffin - reorganized: 9/15/2003
Victor A. McKusick - updated: 7/31/2000
Victor A. McKusick - updated: 10/20/1998
*FIELD* CD
Victor A. McKusick: 1/9/1992
*FIELD* ED
carol: 06/30/2006
carol: 6/30/2006
alopez: 5/10/2006
carol: 9/15/2003
ckniffin: 9/11/2003
alopez: 7/31/2000
terry: 7/31/2000
carol: 10/26/1998
terry: 10/20/1998
alopez: 6/8/1998
carol: 2/13/1995
mimadm: 2/19/1994
supermim: 3/16/1992
carol: 1/9/1992
*RECORD*
*FIELD* NO
225060
*FIELD* TI
#225060 CLEFT LIP/PALATE-ECTODERMAL DYSPLASIA SYNDROME; CLPED1
;;ZLOTOGORA-OGUR SYNDROME;;
read moreECTODERMAL DYSPLASIA, MARGARITA ISLAND TYPE;;
ECTODERMAL DYSPLASIA, TYPE 4; ED4;;
ECTODERMAL DYSPLASIA, CLEFT LIP AND PALATE, MENTAL RETARDATION, AND
SYNDACTYLY
OROFACIAL CLEFT 7, INCLUDED; OFC7, INCLUDED;;
CLEFT LIP WITH OR WITHOUT CLEFT PALATE, NONSYNDROMIC, 7, INCLUDED
*FIELD* TX
A number sign (#) is used with this entry because of evidence that the
phenotype of syndactyly, ectodermal dysplasia, and cleft lip/palate is
due to mutations in the gene encoding the cell-cell adhesion
molecule/herpesvirus receptor, PVRL1 (600644). Mutation in the PVRL1
gene has also been found in a form of orofacial cleft (OFC7).
CLINICAL FEATURES
Zlotogora et al. (1987) reported 2 sibs with a syndrome including cleft
lip and palate, sparse scalp hair, malformed protruding ears, and
partial syndactyly of the fingers and toes. An older sib also had mental
retardation and pili torti. The parents were consanguineous. In 2
Turkish sibs, products of a second-cousin marriage, Ogur and Yuksel
(1988) found the combination of tetramelic syndactyly, ectodermal
dysplasia, cleft lip and palate, renal anomalies, and mental
retardation. In 3 Brazilian brothers and a half brother, all born of
first-cousin matings in a Brazilian kindred, Rodini and Richieri-Costa
(1990) described a syndrome which they proposed to call the
Zlotogora-Ogur syndrome on the basis of the reports by Zlotogora et al.
(1987) and Ogur and Yuksel (1988). The features were ectodermal
dysplasia, bilateral cleft lip/palate, mental retardation, and
syndactyly of fingers 2 and 3.
In the Caribbean island of Margarita off the coast of northeastern
Venezuela (Nueva Esparta State), Bustos et al. (1991) identified a form
of ectodermal dysplasia in 15 females and 12 males in 7 families, each
with considerable consanguinity. It was considered likely that the 7
families were related to each other. The patients had scanty eyebrows
and eyelashes, sparse, short and dry scalp hair, and striking changes in
the teeth, which showed hypodontia mainly of the upper lateral incisors
and changes in size and shape. Cleft lip/palate (in 7), syndactyly of
fingers and toes (in 13), and onychodysplasia were often also observed.
Males and females were affected to an equal degree, although in general
severity was variable. Notably, sweating was normal in all.
Zlotogora (1994) gave a review of the syndrome of syndactyly, ectodermal
dysplasia, and cleft lip/palate in which he proposed that the disorder
called Zlotogora-Ogur syndrome (Zlotogora and Ogur, 1988) is the same as
that reported by Bustos et al. (1991) and referred to here as the
Margarita form of ectodermal dysplasia. Mental retardation was present
in those families described as having Zlotogora-Ogur syndrome but absent
in the Margarita families. Zlotogora (1994) noted that mental
development may differ from family to family. Zlotogora (1994) and
Rodini and Richieri-Costa (1990) considered this to be a separate
disorder from that described by Rosselli and Gulienetti (1961) (see
225000) and from other clefting-ectodermal dysplasia syndromes with limb
involvement.
Suzuki et al. (1998) pointed out that Columbus discovered Isla de
Margarita, a group of 3 islands in the south-central Caribbean, in 1498
and that one of the earliest Spanish colonies in the New World was
established there. They also commented that the philtrum is strikingly
broad and flat in many Margarita Island ectodermal dysplasia (ED)
obligate heterozygotes, who would be expected to number perhaps 1 in 22
among the indigenous population of the island. The incidence of
nonsyndromic cleft lip/cleft palate is quite high on Margarita Island,
approximately 5.4 per 1,000. Although this high incidence might result
from environmental factors, such as lack of dietary folate, it is also
possible that heterozygosity for ED4 constitutes a significant genetic
risk factor for nonsyndromic cleft lip/cleft palate on the island.
MAPPING
Suzuki et al. (1998) described linkage disequilibrium mapping of the
gene for ED4, using an affected-only DNA-pooling strategy. Haplotype
analysis of 4 complex Margarita Island ED4 families localized the ED4
gene to an approximately 1- to 2-Mb interval on 11q23 spanned by just 2
YACS. Suzuki et al. (1998) pointed out that 'rough fur' (ruf) in the
mouse is located in the region of chromosome 9 with conserved synteny to
11q24. The ruf locus gives rise to autosomal recessive rough fur and
hyperkeratosis, features reminiscent of Margarita Island ED.
MOLECULAR GENETICS
In patients with the Margarita type of ectodermal dysplasia, Suzuki et
al. (2000) identified a nonsense mutation in the poliovirus
receptor-like-1 gene (PVRL1; 600644.0001). The authors suggested that
the high frequency of the disorder on Margarita Island may have resulted
from resistance of heterozygotes to infection by alpha-herpesviruses. In
2 families from Israel and Brazil described as having Zlotogora-Ogur
syndrome, Suzuki et al. (2000) also found mutations in the PVRL1 gene
(600644.0002-600644.0003).
Sozen et al. (2001) demonstrated a highly significant association
between heterozygosity for the W185X mutation in the PVRL1 gene
(600644.0001) and sporadic, nonsyndromic cleft lip with or without cleft
palate in northern Venezuela.
*FIELD* RF
1. Bustos, T.; Simosa, V.; Pinto-Cisternas, J.; Abramovits, W.; Jolay,
L.; Rodriguez, L.; Fernandez, L.; Ramela, M.: Autosomal recessive
ectodermal dysplasia. I. An undescribed dysplasia/malformation syndrome. Am.
J. Med. Genet. 41: 398-404, 1991.
2. Ogur, G.; Yuksel, M.: Association of syndactyly, ectodermal dysplasia,
and cleft lip and palate: report of two sibs from Turkey. J. Med.
Genet. 25: 37-40, 1988.
3. Rodini, E. S. O.; Richieri-Costa, A.: Autosomal recessive ectodermal
dysplasia, cleft lip/palate, mental retardation, and syndactyly: the
Zlotogora-Ogur syndrome. Am. J. Med. Genet. 36: 473-476, 1990.
4. Rosselli, D.; Gulienetti, R.: Ectodermal dysplasia. Brit. J.
Plast. Surg. 14: 190-204, 1961.
5. Sozen, M. A.; Suzuki, K.; Tolarova, M. M.; Bustos, T.; Fernandez
Iglesias, J. E.; Spritz, R. A.: Mutation of PVRL1 is associated with
sporadic, non-syndromic cleft lip/palate in northern Venezuela. Nature
Genet. 29: 141-142, 2001.
6. Suzuki, K.; Bustos, T.; Spritz, R. A.: Linkage disequilibrium
mapping of the gene for Margarita Island ectodermal dysplasia (ED4)
to 11q23. Am. J. Hum. Genet. 63: 1102-1107, 1998.
7. Suzuki, K.; Hu, D.; Bustos, T.; Zlotogora, J.; Richieri-Costa,
A.; Helms, J. A.; Spritz, R. A.: Mutations of PVRL1, encoding a cell-cell
adhesion molecule/herpesvirus receptor, in cleft lip/palate-ectodermal
dysplasia. Nature Genet. 25: 427-430, 2000.
8. Zlotogora, J.: Syndactyly, ectodermal dysplasia, and cleft lip/palate. J.
Med. Genet. 31: 957-959, 1994.
9. Zlotogora, J.; Ogur, G.: Syndactyly, ectodermal dysplasia, and
cleft lip and palate. (Letter) J. Med. Genet. 25: 503 only, 1988.
10. Zlotogora, J.; Zilberman, Y.; Tenenbaum, A.; Wexler, M. R.: Cleft
lip and palate, pili torti, malformed ears, partial syndactyly of
fingers and toes, and mental retardation: a new syndrome? J. Med.
Genet. 24: 291-293, 1987.
*FIELD* CS
INHERITANCE:
Autosomal recessive
HEAD AND NECK:
[Face];
Triangular face;
Malar hypoplasia;
[Ears];
Anteverted pinnae;
[Eyes];
Sparse eyelashes;
Sparse eyebrows;
[Nose];
Abnormal philtrum;
[Mouth];
Cleft lip;
Cleft palate;
[Teeth];
Hypodontia;
Anodontia;
Microdontia
SKELETAL:
[Hands];
Syndactyly, cutaneous;
[Feet];
Syndactyly, cutaneous
SKIN, NAILS, HAIR:
[Skin];
Palmoplantar hyperkeratosis;
Normal sweating capacity;
[Nails];
Onychodysplasia;
[Hair];
Hypotrichosis, progressive;
Short, brittle hair;
Sparse eyelashes;
Sparse eyebrows
MISCELLANEOUS:
Allelic disorder to the Zlotogora-Ogur syndrome (225000)
MOLECULAR BASIS:
Caused by mutation in the poliovirus receptor-like 1 gene (PVRL1,
600644.0001)
*FIELD* CN
Cassandra L. Kniffin - revised: 9/11/2003
*FIELD* CD
John F. Jackson: 6/15/1995
*FIELD* ED
joanna: 12/05/2008
joanna: 9/17/2003
ckniffin: 9/11/2003
*FIELD* CN
Cassandra L. Kniffin - reorganized: 9/15/2003
Victor A. McKusick - updated: 7/31/2000
Victor A. McKusick - updated: 10/20/1998
*FIELD* CD
Victor A. McKusick: 1/9/1992
*FIELD* ED
carol: 06/30/2006
carol: 6/30/2006
alopez: 5/10/2006
carol: 9/15/2003
ckniffin: 9/11/2003
alopez: 7/31/2000
terry: 7/31/2000
carol: 10/26/1998
terry: 10/20/1998
alopez: 6/8/1998
carol: 2/13/1995
mimadm: 2/19/1994
supermim: 3/16/1992
carol: 1/9/1992
MIM
600644
*RECORD*
*FIELD* NO
600644
*FIELD* TI
*600644 POLIOVIRUS RECEPTOR-LIKE 1; PVRL1
;;HERPESVIRUS ENTRY MEDIATOR C; HVEC;;
POLIOVIRUS RECEPTOR-RELATED 1; PVRR1;;
read morePVRR; PRR;;
NECTIN 1
*FIELD* TX
DESCRIPTION
PVRL1, or nectin-1, belongs to the nectin subfamily of
immunoglobulin-like adhesion molecules that participate in
Ca(2+)-independent cell-cell adhesion. Nectins bind to the actin
cytoskeleton through the adaptor protein afadin (MLLT4; 159559) and are
key components of adherens junctions (summary by Barron et al. (2008)).
CLONING
Members of the immunoglobin (Ig) superfamily have been shown to serve as
receptors for various viruses. The human poliovirus receptor (PVR;
173850) is an integral membrane protein with one V-like extracellular Ig
domain, 2 C-like extracellular Ig domains, a transmembrane region, and
an intracytoplasmic region. Lopez et al. (1995) isolated a cDNA for a
poliovirus receptor related gene, which they symbolized PRR. The
predicted protein is 518 amino acids long and has a domain structure
similar to PVR. In the extracellular domain, PRR is nearly 52% identical
to PVR and 54% identical to the murine homolog of PVR. Northern blots
showed a major 5.9-kb mRNA in all tissues tested.
GENE FUNCTION
Using the Don Chinese hamster line, Carritt and Goldfarb (1976) found
that susceptibility to herpesvirus is determined by a gene on chromosome
3. Francke and Francke (1979) used a V79 line and concluded that human
chromosome 11 is responsible for susceptibility; Don and V79 did not
complement.
Geraghty et al. (1998) showed that poliovirus receptor-related protein-1
mediated entry of several alphaherpesviruses, including herpes simplex
viruses (HSV) 1 and 2, porcine pseudorabies virus (PRV), and bovine
herpesvirus 1 (BHV-1) into cells. The poliovirus receptor itself
mediated entry of PRV and BHV-1, but not of the HSV strains tested by
Geraghty et al. (1998). They found that PVRR1 was expressed in human
cells of epithelial and neuronal origin and concluded that it is a prime
candidate for the coreceptor that allows both HSV-1 and HSV-2 to infect
epithelial cells on mucosal surfaces and spread to cells of the nervous
system.
Using immunolocalization of adult mouse hippocampal sections Mizoguchi
et al. (2002) found that the nectin-afadin system colocalizes with the
cadherin (see 192090)-catenin (see 116805) system at synapses between
mossy fiber terminals and dendrites of pyramidal cells in the CA3 area.
Nectins-1 and -3 (PVRL3; 607147) asymmetrically localize at the pre- and
postsynaptic sides of puncta adherentia junctions, respectively. During
development, nectins-1 and -3 asymmetrically localize not only at puncta
adherentia junctions but also at synaptic junctions. Using rat
hippocampal neurons in culture, Mizoguchi et al. (2002) observed that
inhibition of the nectin-based adhesion results in a decrease in synapse
size and a concomitant increase in synapse number.
Togashi et al. (2011) found that mouse hair cells and supporting cells
express the immunoglobulin-like adhesion molecules nectin-1 and -3,
respectively, and that their interaction mediates the heterotypic
adhesion between these 2 cell types. Genetic removal of nectin-1 or -3
disrupted the checkerboard-like pattern, inducing aberrant attachment
between hair cells. When cells expressing either nectin-1 or -3 were
cocultured, they arranged themselves into a mosaic pattern. Thus,
Togashi et al. (2011) concluded that nectin-1 and nectin-3 promote the
formation of the checkerboard-like pattern of the auditory epithelia.
MAPPING
Lopez et al. (1995) mapped the PVRR gene to 11q23-q24 by in situ
hybridization.
MOLECULAR GENETICS
The cleft lip/palate-ectodermal dysplasia syndrome (CLPED1; 225060),
which has been called both Zlotogora-Ogur syndrome and Margarita Island
ectodermal dysplasia, is characterized clinically by cleft lip/palate,
hidrotic ectodermal dysplasia, developmental defects of the hands, and,
in some cases, mental retardation. Although generally rare, CLPED1
occurs with a frequency of approximately 1 per 2,000 among the
indigenous population of Margarita Island, in whom Suzuki et al. (1998)
assigned the CLPED1 locus to 11q23 by linkage mapping. Suzuki et al.
(2000) genotyped markers spanning the CLPED1 interval in an inbred
Israeli family with a diagnosis of Zlotogora-Ogur syndrome. The proband
was homozygous and the first-cousin parents heterozygous for all markers
tested, but with a different disease-associated haplotype than in
Margarita Island families, consistent with allelism between Margarita
Island and Israeli CLPED1. Suzuki et al. (2000) followed a positional
cloning approach to identify the CLPED1 gene as PVRL1, encoding
nectin-1, an immunoglobulin-related transmembrane cell-cell adhesion
molecule that is part of the NAP cell adhesion system. Nectin-1 is also
the principal cell surface receptor for alpha-herpesviruses (Geraghty et
al., 1998). Suzuki et al. (2000) speculated that the high frequency of
CLPED1 on Margarita Island in the Caribbean Sea might have resulted from
resistance of heterozygotes to infection by these viruses.
In Margarita Island CLPED1 patients, Suzuki et al. (2000) identified a
nonsense mutation (W185X; 600644.0001) in the PVRL1 gene.
Sozen et al. (2001) demonstrated a highly significant association
between heterozygosity for the W185X mutation and sporadic, nonsyndromic
cleft lip with or without cleft palate (see 225060) in northern
Venezuela.
ANIMAL MODEL
Barron et al. (2008) found that nectin-1 -/- mice were viable and
fertile, but manifested microphthalmia and defective amelogenesis of
their incisor teeth. Nectin-1 -/- incisors lacked the normal iron
pigmentation characteristic of rodent enamel and were prone to wear and
breakage. Immunohistochemical analysis of wildtype mice showed nectin-1
staining at the interface between the maturation-stage ameloblasts and
the underlying cells of the stratum intermedium. In the absence of
nectin-1, these cell layers were separated. Numerous large desmosomes
were present at this interface in wildtype mice; however, where adhesion
persisted in nectin-1 -/- mice, the desmosomes were smaller and less
numerous. Barron et al. (2008) concluded that nectin-1 participates in
desmosome assembly.
*FIELD* AV
.0001
CLEFT LIP/PALATE-ECTODERMAL DYSPLASIA SYNDROME
OROFACIAL CLEFT 7, INCLUDED
PVRL1, TRP185TER
In Margarita Island CLPED1 patients (225060), Suzuki et al. (2000)
identified a nonsense mutation of codon trp185 (TGG to TAG) in the PVRL1
gene.
Sozen et al. (2001) demonstrated a highly significant association
between heterozygosity for the W185X mutation and nonsyndromic, sporadic
cleft lip with or without cleft palate (see 119530) in northern
Venezuela. In the Cumana region of northern Venezuela, 14 (5.8%) of 243
individuals with cleft lip with or without cleft palate carried this
mutation, versus 1 of 245 controls (0.4%) (p = 0.00039).
.0002
CLEFT LIP/PALATE-ECTODERMAL DYSPLASIA SYNDROME
PVRL1, 1-BP DEL
In an Israeli family with cleft lip/palate-ectodermal dysplasia (225060)
reported by Zlotogora et al. (1987), Suzuki et al. (2000) identified
deletion of 1 guanine from codon 185 (trp) of the PVRL1 gene, converting
TGG to T-G and resulting in a frameshift. Notably this involved the same
codon as was involved in a nonsense mutation in the Margarita Island
CLEPD1 patients (600644.0001).
.0003
CLEFT LIP/PALATE-ECTODERMAL DYSPLASIA SYNDROME
PVRL1, 1-BP DUP
In a Brazilian family with CLEPD1 (225060), Suzuki et al. (2000)
identified a single-base duplication in codon gly323 of the PVRL1 gene
(GGT to GGTT), resulting in frameshift.
*FIELD* RF
1. Barron, M. J.; Brookes, S. J.; Draper, C. E.; Garrod, D.; Kirkham,
J.; Shore, R. C.; Dixon, M. J.: The cell adhesion molecule nectin-1
is critical for normal enamel formation in mice. Hum. Molec. Genet. 17:
3509-3520, 2008.
2. Carritt, B.; Goldfarb, P.: Human chromosomal determinant for susceptibility
to HSV. Nature 264: 556-558, 1976.
3. Francke, U.; Francke, B. R.: Assignment of gene(s) required for
Herpes simplex virus type 1 (HV1S) replication to human chromosome
11. (Abstract) Cytogenet. Cell Genet. 25: 155 only, 1979.
4. Geraghty, R. J.; Krummenacher, C.; Cohen, G. H.; Eisenberg, R.
J.; Spear, P. G.: Entry of alphaherpesviruses mediated by poliovirus
receptor-related protein 1 and poliovirus receptor. Science 280:
1618-1620, 1998.
5. Lopez, M.; Eberle, F.; Mattei, M. G.; Gabert, J.; Birg, F.; Bardin,
F.; Maroc, C.; Dubreuil, P.: Complementary DNA characterization and
chromosomal localization of a human gene related to the poliovirus
receptor-encoding gene. Gene 155: 261-265, 1995.
6. Mizoguchi, A.; Nakanishi, H.; Kimura, K.; Matsubara, K.; Ozaki-Kuroda,
K.; Katata, T.; Honda, T.; Kiyohara, Y.; Heo, K.; Higashi, M.; Tsutsumi,
T.; Sonoda, S.; Ide, C.; Takai, Y.: Nectin: an adhesion molecule
involved in formation of synapses. J. Cell Biol. 156: 555-565, 2002.
7. Sozen, M. A.; Suzuki, K.; Tolarova, M. M.; Bustos, T.; Fernandez
Iglesias, J. E.; Spritz, R. A.: Mutation of PVRL1 is associated with
sporadic, non-syndromic cleft lip/palate in northern Venezuela. Nature
Genet. 29: 141-142, 2001.
8. Suzuki, K.; Bustos, T.; Spritz, R. A.: Linkage disequilibrium
mapping of the gene for Margarita Island ectodermal dysplasia (ED4)
to 11q23. Am. J. Hum. Genet. 63: 1102-1107, 1998.
9. Suzuki, K.; Hu, D.; Bustos, T.; Zlotogora, J.; Richieri-Costa,
A.; Helms, J. A.; Spritz, R. A.: Mutations of PVRL1, encoding a cell-cell
adhesion molecule/herpesvirus receptor, in cleft lip/palate-ectodermal
dysplasia. Nature Genet. 25: 427-430, 2000.
10. Togashi, H.; Kominami, K.; Waseda, M.; Komura, H.; Miyoshi, J.;
Takeichi, M.; Takai, Y.: Nectins establish a checkerboard-like cellular
pattern in the auditory epithelium. Science 333: 1144-1147, 2011.
11. Zlotogora, J.; Zilberman, Y.; Tenenbaum, A.; Wexler, M. R.: Cleft
lip and palate, pili torti, malformed ears, partial syndactyly of
fingers and toes and mental retardation: a new syndrome? J. Med.
Genet. 24: 291-293, 1987.
*FIELD* CN
Ada Hamosh - updated: 9/21/2011
Patricia A. Hartz - updated: 11/3/2009
Patricia A. Hartz - updated: 8/14/2002
Ada Hamosh - updated: 9/21/2001
Victor A. McKusick - updated: 7/31/2000
Victor A. McKusick - updated: 6/8/1998
*FIELD* CD
Alan F. Scott: 7/10/1995
*FIELD* ED
alopez: 09/23/2011
terry: 9/21/2011
carol: 1/12/2011
joanna: 7/27/2010
alopez: 7/13/2010
mgross: 11/9/2009
terry: 11/3/2009
mgross: 9/3/2009
carol: 7/11/2006
carol: 6/30/2006
alopez: 5/10/2006
ckniffin: 9/11/2003
mgross: 8/14/2002
alopez: 10/15/2001
alopez: 9/21/2001
terry: 9/21/2001
joanna: 9/10/2001
alopez: 7/31/2000
terry: 7/31/2000
carol: 11/10/1999
carol: 8/12/1998
alopez: 6/8/1998
dholmes: 6/8/1998
joanna: 3/20/1997
mark: 9/27/1995
mark: 7/10/1995
*RECORD*
*FIELD* NO
600644
*FIELD* TI
*600644 POLIOVIRUS RECEPTOR-LIKE 1; PVRL1
;;HERPESVIRUS ENTRY MEDIATOR C; HVEC;;
POLIOVIRUS RECEPTOR-RELATED 1; PVRR1;;
read morePVRR; PRR;;
NECTIN 1
*FIELD* TX
DESCRIPTION
PVRL1, or nectin-1, belongs to the nectin subfamily of
immunoglobulin-like adhesion molecules that participate in
Ca(2+)-independent cell-cell adhesion. Nectins bind to the actin
cytoskeleton through the adaptor protein afadin (MLLT4; 159559) and are
key components of adherens junctions (summary by Barron et al. (2008)).
CLONING
Members of the immunoglobin (Ig) superfamily have been shown to serve as
receptors for various viruses. The human poliovirus receptor (PVR;
173850) is an integral membrane protein with one V-like extracellular Ig
domain, 2 C-like extracellular Ig domains, a transmembrane region, and
an intracytoplasmic region. Lopez et al. (1995) isolated a cDNA for a
poliovirus receptor related gene, which they symbolized PRR. The
predicted protein is 518 amino acids long and has a domain structure
similar to PVR. In the extracellular domain, PRR is nearly 52% identical
to PVR and 54% identical to the murine homolog of PVR. Northern blots
showed a major 5.9-kb mRNA in all tissues tested.
GENE FUNCTION
Using the Don Chinese hamster line, Carritt and Goldfarb (1976) found
that susceptibility to herpesvirus is determined by a gene on chromosome
3. Francke and Francke (1979) used a V79 line and concluded that human
chromosome 11 is responsible for susceptibility; Don and V79 did not
complement.
Geraghty et al. (1998) showed that poliovirus receptor-related protein-1
mediated entry of several alphaherpesviruses, including herpes simplex
viruses (HSV) 1 and 2, porcine pseudorabies virus (PRV), and bovine
herpesvirus 1 (BHV-1) into cells. The poliovirus receptor itself
mediated entry of PRV and BHV-1, but not of the HSV strains tested by
Geraghty et al. (1998). They found that PVRR1 was expressed in human
cells of epithelial and neuronal origin and concluded that it is a prime
candidate for the coreceptor that allows both HSV-1 and HSV-2 to infect
epithelial cells on mucosal surfaces and spread to cells of the nervous
system.
Using immunolocalization of adult mouse hippocampal sections Mizoguchi
et al. (2002) found that the nectin-afadin system colocalizes with the
cadherin (see 192090)-catenin (see 116805) system at synapses between
mossy fiber terminals and dendrites of pyramidal cells in the CA3 area.
Nectins-1 and -3 (PVRL3; 607147) asymmetrically localize at the pre- and
postsynaptic sides of puncta adherentia junctions, respectively. During
development, nectins-1 and -3 asymmetrically localize not only at puncta
adherentia junctions but also at synaptic junctions. Using rat
hippocampal neurons in culture, Mizoguchi et al. (2002) observed that
inhibition of the nectin-based adhesion results in a decrease in synapse
size and a concomitant increase in synapse number.
Togashi et al. (2011) found that mouse hair cells and supporting cells
express the immunoglobulin-like adhesion molecules nectin-1 and -3,
respectively, and that their interaction mediates the heterotypic
adhesion between these 2 cell types. Genetic removal of nectin-1 or -3
disrupted the checkerboard-like pattern, inducing aberrant attachment
between hair cells. When cells expressing either nectin-1 or -3 were
cocultured, they arranged themselves into a mosaic pattern. Thus,
Togashi et al. (2011) concluded that nectin-1 and nectin-3 promote the
formation of the checkerboard-like pattern of the auditory epithelia.
MAPPING
Lopez et al. (1995) mapped the PVRR gene to 11q23-q24 by in situ
hybridization.
MOLECULAR GENETICS
The cleft lip/palate-ectodermal dysplasia syndrome (CLPED1; 225060),
which has been called both Zlotogora-Ogur syndrome and Margarita Island
ectodermal dysplasia, is characterized clinically by cleft lip/palate,
hidrotic ectodermal dysplasia, developmental defects of the hands, and,
in some cases, mental retardation. Although generally rare, CLPED1
occurs with a frequency of approximately 1 per 2,000 among the
indigenous population of Margarita Island, in whom Suzuki et al. (1998)
assigned the CLPED1 locus to 11q23 by linkage mapping. Suzuki et al.
(2000) genotyped markers spanning the CLPED1 interval in an inbred
Israeli family with a diagnosis of Zlotogora-Ogur syndrome. The proband
was homozygous and the first-cousin parents heterozygous for all markers
tested, but with a different disease-associated haplotype than in
Margarita Island families, consistent with allelism between Margarita
Island and Israeli CLPED1. Suzuki et al. (2000) followed a positional
cloning approach to identify the CLPED1 gene as PVRL1, encoding
nectin-1, an immunoglobulin-related transmembrane cell-cell adhesion
molecule that is part of the NAP cell adhesion system. Nectin-1 is also
the principal cell surface receptor for alpha-herpesviruses (Geraghty et
al., 1998). Suzuki et al. (2000) speculated that the high frequency of
CLPED1 on Margarita Island in the Caribbean Sea might have resulted from
resistance of heterozygotes to infection by these viruses.
In Margarita Island CLPED1 patients, Suzuki et al. (2000) identified a
nonsense mutation (W185X; 600644.0001) in the PVRL1 gene.
Sozen et al. (2001) demonstrated a highly significant association
between heterozygosity for the W185X mutation and sporadic, nonsyndromic
cleft lip with or without cleft palate (see 225060) in northern
Venezuela.
ANIMAL MODEL
Barron et al. (2008) found that nectin-1 -/- mice were viable and
fertile, but manifested microphthalmia and defective amelogenesis of
their incisor teeth. Nectin-1 -/- incisors lacked the normal iron
pigmentation characteristic of rodent enamel and were prone to wear and
breakage. Immunohistochemical analysis of wildtype mice showed nectin-1
staining at the interface between the maturation-stage ameloblasts and
the underlying cells of the stratum intermedium. In the absence of
nectin-1, these cell layers were separated. Numerous large desmosomes
were present at this interface in wildtype mice; however, where adhesion
persisted in nectin-1 -/- mice, the desmosomes were smaller and less
numerous. Barron et al. (2008) concluded that nectin-1 participates in
desmosome assembly.
*FIELD* AV
.0001
CLEFT LIP/PALATE-ECTODERMAL DYSPLASIA SYNDROME
OROFACIAL CLEFT 7, INCLUDED
PVRL1, TRP185TER
In Margarita Island CLPED1 patients (225060), Suzuki et al. (2000)
identified a nonsense mutation of codon trp185 (TGG to TAG) in the PVRL1
gene.
Sozen et al. (2001) demonstrated a highly significant association
between heterozygosity for the W185X mutation and nonsyndromic, sporadic
cleft lip with or without cleft palate (see 119530) in northern
Venezuela. In the Cumana region of northern Venezuela, 14 (5.8%) of 243
individuals with cleft lip with or without cleft palate carried this
mutation, versus 1 of 245 controls (0.4%) (p = 0.00039).
.0002
CLEFT LIP/PALATE-ECTODERMAL DYSPLASIA SYNDROME
PVRL1, 1-BP DEL
In an Israeli family with cleft lip/palate-ectodermal dysplasia (225060)
reported by Zlotogora et al. (1987), Suzuki et al. (2000) identified
deletion of 1 guanine from codon 185 (trp) of the PVRL1 gene, converting
TGG to T-G and resulting in a frameshift. Notably this involved the same
codon as was involved in a nonsense mutation in the Margarita Island
CLEPD1 patients (600644.0001).
.0003
CLEFT LIP/PALATE-ECTODERMAL DYSPLASIA SYNDROME
PVRL1, 1-BP DUP
In a Brazilian family with CLEPD1 (225060), Suzuki et al. (2000)
identified a single-base duplication in codon gly323 of the PVRL1 gene
(GGT to GGTT), resulting in frameshift.
*FIELD* RF
1. Barron, M. J.; Brookes, S. J.; Draper, C. E.; Garrod, D.; Kirkham,
J.; Shore, R. C.; Dixon, M. J.: The cell adhesion molecule nectin-1
is critical for normal enamel formation in mice. Hum. Molec. Genet. 17:
3509-3520, 2008.
2. Carritt, B.; Goldfarb, P.: Human chromosomal determinant for susceptibility
to HSV. Nature 264: 556-558, 1976.
3. Francke, U.; Francke, B. R.: Assignment of gene(s) required for
Herpes simplex virus type 1 (HV1S) replication to human chromosome
11. (Abstract) Cytogenet. Cell Genet. 25: 155 only, 1979.
4. Geraghty, R. J.; Krummenacher, C.; Cohen, G. H.; Eisenberg, R.
J.; Spear, P. G.: Entry of alphaherpesviruses mediated by poliovirus
receptor-related protein 1 and poliovirus receptor. Science 280:
1618-1620, 1998.
5. Lopez, M.; Eberle, F.; Mattei, M. G.; Gabert, J.; Birg, F.; Bardin,
F.; Maroc, C.; Dubreuil, P.: Complementary DNA characterization and
chromosomal localization of a human gene related to the poliovirus
receptor-encoding gene. Gene 155: 261-265, 1995.
6. Mizoguchi, A.; Nakanishi, H.; Kimura, K.; Matsubara, K.; Ozaki-Kuroda,
K.; Katata, T.; Honda, T.; Kiyohara, Y.; Heo, K.; Higashi, M.; Tsutsumi,
T.; Sonoda, S.; Ide, C.; Takai, Y.: Nectin: an adhesion molecule
involved in formation of synapses. J. Cell Biol. 156: 555-565, 2002.
7. Sozen, M. A.; Suzuki, K.; Tolarova, M. M.; Bustos, T.; Fernandez
Iglesias, J. E.; Spritz, R. A.: Mutation of PVRL1 is associated with
sporadic, non-syndromic cleft lip/palate in northern Venezuela. Nature
Genet. 29: 141-142, 2001.
8. Suzuki, K.; Bustos, T.; Spritz, R. A.: Linkage disequilibrium
mapping of the gene for Margarita Island ectodermal dysplasia (ED4)
to 11q23. Am. J. Hum. Genet. 63: 1102-1107, 1998.
9. Suzuki, K.; Hu, D.; Bustos, T.; Zlotogora, J.; Richieri-Costa,
A.; Helms, J. A.; Spritz, R. A.: Mutations of PVRL1, encoding a cell-cell
adhesion molecule/herpesvirus receptor, in cleft lip/palate-ectodermal
dysplasia. Nature Genet. 25: 427-430, 2000.
10. Togashi, H.; Kominami, K.; Waseda, M.; Komura, H.; Miyoshi, J.;
Takeichi, M.; Takai, Y.: Nectins establish a checkerboard-like cellular
pattern in the auditory epithelium. Science 333: 1144-1147, 2011.
11. Zlotogora, J.; Zilberman, Y.; Tenenbaum, A.; Wexler, M. R.: Cleft
lip and palate, pili torti, malformed ears, partial syndactyly of
fingers and toes and mental retardation: a new syndrome? J. Med.
Genet. 24: 291-293, 1987.
*FIELD* CN
Ada Hamosh - updated: 9/21/2011
Patricia A. Hartz - updated: 11/3/2009
Patricia A. Hartz - updated: 8/14/2002
Ada Hamosh - updated: 9/21/2001
Victor A. McKusick - updated: 7/31/2000
Victor A. McKusick - updated: 6/8/1998
*FIELD* CD
Alan F. Scott: 7/10/1995
*FIELD* ED
alopez: 09/23/2011
terry: 9/21/2011
carol: 1/12/2011
joanna: 7/27/2010
alopez: 7/13/2010
mgross: 11/9/2009
terry: 11/3/2009
mgross: 9/3/2009
carol: 7/11/2006
carol: 6/30/2006
alopez: 5/10/2006
ckniffin: 9/11/2003
mgross: 8/14/2002
alopez: 10/15/2001
alopez: 9/21/2001
terry: 9/21/2001
joanna: 9/10/2001
alopez: 7/31/2000
terry: 7/31/2000
carol: 11/10/1999
carol: 8/12/1998
alopez: 6/8/1998
dholmes: 6/8/1998
joanna: 3/20/1997
mark: 9/27/1995
mark: 7/10/1995