Full text data of PVRL3
PVRL3
(PRR3)
[Confidence: high (a blood group or CD marker)]
Poliovirus receptor-related protein 3 (CDw113; Nectin-3; CD113; Flags: Precursor)
Poliovirus receptor-related protein 3 (CDw113; Nectin-3; CD113; Flags: Precursor)
UniProt
Q9NQS3
ID PVRL3_HUMAN Reviewed; 549 AA.
AC Q9NQS3; E9PFR0; Q6NVZ3; Q8NC05; Q8WVU4; Q9BVA9; Q9Y412;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-2000, sequence version 1.
DT 22-JAN-2014, entry version 99.
DE RecName: Full=Poliovirus receptor-related protein 3;
DE AltName: Full=CDw113;
DE AltName: Full=Nectin-3;
DE AltName: CD_antigen=CD113;
DE Flags: Precursor;
GN Name=PVRL3; Synonyms=PRR3;
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 1), TISSUE SPECIFICITY, AND
RP INTERACTION WITH MLLT4.
RX PubMed=11024295; DOI=10.1016/S0378-1119(00)00316-4;
RA Reymond N., Borg J.-P., Lecocq E., Adelaide J., Campadelli-Fiume G.,
RA Dubreuil P., Lopez M.;
RT "Human nectin3/PRR3: a novel member of the PVR/PRR/nectin family that
RT interacts with afadin.";
RL Gene 255:347-355(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Placenta;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 246-549 (ISOFORM 1).
RC TISSUE=Brain, Cervix, and Kidney;
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 [LARGE SCALE MRNA] OF 143-549 (ISOFORM 1).
RC TISSUE=Fetal kidney;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP INTERACTION WITH PVR.
RX PubMed=12759359; DOI=10.1074/jbc.M304166200;
RA Mueller S., Wimmer E.;
RT "Recruitment of nectin-3 to cell-cell junctions through trans-
RT heterophilic interaction with CD155, a vitronectin and poliovirus
RT receptor that localizes to alpha(v)beta3 integrin-containing membrane
RT microdomains.";
RL J. Biol. Chem. 278:31251-31260(2003).
RN [7]
RP FUNCTION, AND INTERACTION WITH PVR.
RX PubMed=16216929; DOI=10.1083/jcb.200501090;
RA Fujito T., Ikeda W., Kakunaga S., Minami Y., Kajita M., Sakamoto Y.,
RA Monden M., Takai Y.;
RT "Inhibition of cell movement and proliferation by cell-cell contact-
RT induced interaction of Necl-5 with nectin-3.";
RL J. Cell Biol. 171:165-173(2005).
RN [8]
RP INTERACTION WITH TIGIT.
RX PubMed=19011627; DOI=10.1038/ni.1674;
RA Yu X., Harden K., Gonzalez L.C., Francesco M., Chiang E., Irving B.,
RA Tom I., Ivelja S., Refino C.J., Clark H., Eaton D., Grogan J.L.;
RT "The surface protein TIGIT suppresses T cell activation by promoting
RT the generation of mature immunoregulatory dendritic cells.";
RL Nat. Immunol. 10:48-57(2009).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (3.93 ANGSTROMS) OF 58-359, SUBUNIT,
RP GLYCOSYLATION AT ASN-73; ASN-125; ASN-186; ASN-222 AND ASN-331, AND
RP MASS SPECTROMETRY.
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: Plays a role in cell-cell adhesion through heterophilic
CC trans-interactions with nectin-like proteins or nectins, such as
CC trans-interaction with PVRL2/nectin-2 at Sertoli-spermatid
CC junctions. Trans-interaction with PVR induces activation of CDC42
CC and RAC small G proteins through common signaling molecules such
CC as SRC and RAP1. Also involved in the formation of cell-cell
CC junctions, including adherens junctions and synapses. Induces
CC endocytosis-mediated down-regulation of PVR from the cell surface,
CC resulting in reduction of cell movement and proliferation. Plays a
CC role in the morphology of the ciliary body.
CC -!- SUBUNIT: Cis- and trans-homodimer. Can form trans-heterodimers
CC with PVRL1/nectin-1, PVRL2/nectin-2, PVR, IGSF4B/Necl-1 and with
CC IGSF4. Interacts with MLLT4/afadin. Binds with low affinity to
CC TIGIT.
CC -!- INTERACTION:
CC Q15223:PVRL1; NbExp=2; IntAct=EBI-2826725, EBI-1771314;
CC Q92692:PVRL2; NbExp=2; IntAct=EBI-2826725, EBI-718419;
CC Q495A1:TIGIT; NbExp=2; IntAct=EBI-2826725, EBI-4314807;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass membrane protein
CC (Potential).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9NQS3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NQS3-2; Sequence=VSP_017435, VSP_017436;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=Q9NQS3-3; Sequence=VSP_046893, VSP_046894;
CC Note=Ref.2 (BAC11404) sequence differs from that shown at
CC position 268 due to erroneous termination (Translated as Cys);
CC -!- TISSUE SPECIFICITY: Predominantly expressed in testis and placenta
CC as well as in many cell lines, including epithelial cell lines.
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=AAH17572.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
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DR EMBL; AF282874; AAF97597.1; -; mRNA.
DR EMBL; AK075105; BAC11404.1; ALT_TERM; mRNA.
DR EMBL; AC133436; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC133477; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC137833; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001336; AAH01336.1; -; mRNA.
DR EMBL; BC017572; AAH17572.1; ALT_INIT; mRNA.
DR EMBL; BC067808; AAH67808.1; -; mRNA.
DR EMBL; AL050071; CAB43256.1; -; mRNA.
DR PIR; T08732; T08732.
DR RefSeq; NP_001230215.1; NM_001243286.1.
DR RefSeq; NP_001230217.1; NM_001243288.1.
DR RefSeq; NP_056295.1; NM_015480.2.
DR UniGene; Hs.293917; -.
DR PDB; 4FOM; X-ray; 3.93 A; A=58-359.
DR PDBsum; 4FOM; -.
DR ProteinModelPortal; Q9NQS3; -.
DR SMR; Q9NQS3; 58-359.
DR DIP; DIP-41491N; -.
DR IntAct; Q9NQS3; 7.
DR MINT; MINT-147327; -.
DR STRING; 9606.ENSP00000418070; -.
DR MEROPS; I43.001; -.
DR PhosphoSite; Q9NQS3; -.
DR DMDM; 74762752; -.
DR PaxDb; Q9NQS3; -.
DR PRIDE; Q9NQS3; -.
DR DNASU; 25945; -.
DR Ensembl; ENST00000319792; ENSP00000321514; ENSG00000177707.
DR Ensembl; ENST00000485303; ENSP00000418070; ENSG00000177707.
DR Ensembl; ENST00000493615; ENSP00000420579; ENSG00000177707.
DR GeneID; 25945; -.
DR KEGG; hsa:25945; -.
DR UCSC; uc003dxu.2; human.
DR CTD; 25945; -.
DR GeneCards; GC03P110788; -.
DR HGNC; HGNC:17664; PVRL3.
DR HPA; CAB009869; -.
DR HPA; HPA011038; -.
DR MIM; 607147; gene.
DR neXtProt; NX_Q9NQS3; -.
DR PharmGKB; PA134969621; -.
DR eggNOG; NOG47602; -.
DR HOGENOM; HOG000115805; -.
DR HOVERGEN; HBG082234; -.
DR InParanoid; Q9NQS3; -.
DR KO; K06592; -.
DR OMA; DVPFKQT; -.
DR OrthoDB; EOG73RBB5; -.
DR PhylomeDB; Q9NQS3; -.
DR Reactome; REACT_111155; Cell-Cell communication.
DR ChiTaRS; PVRL3; human.
DR GeneWiki; PVRL3; -.
DR GenomeRNAi; 25945; -.
DR NextBio; 47534; -.
DR PRO; PR:Q9NQS3; -.
DR ArrayExpress; Q9NQS3; -.
DR Bgee; Q9NQS3; -.
DR CleanEx; HS_PRR3; -.
DR CleanEx; HS_PVRL3; -.
DR Genevestigator; Q9NQS3; -.
DR GO; GO:0043296; C:apical junction complex; IEA:Ensembl.
DR GO; GO:0005913; C:cell-cell adherens junction; IEA:Ensembl.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISS:HGNC.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:HGNC.
DR GO; GO:0034332; P:adherens junction organization; TAS:Reactome.
DR GO; GO:0034329; P:cell junction assembly; TAS:Reactome.
DR GO; GO:0009566; P:fertilization; IEA:Ensembl.
DR GO; GO:0007156; P:homophilic cell adhesion; ISS:HGNC.
DR GO; GO:0002089; P:lens morphogenesis in camera-type eye; IEA:Ensembl.
DR GO; GO:0060042; P:retina morphogenesis in camera-type eye; IEA:Ensembl.
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 Pfam; PF08205; C2-set_2; 1.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00409; IG; 1.
DR PROSITE; PS50835; IG_LIKE; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell adhesion; Cell membrane;
KW Complete proteome; Disulfide bond; Glycoprotein;
KW Immunoglobulin domain; Membrane; Polymorphism; Reference proteome;
KW Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1 57 Potential.
FT CHAIN 58 549 Poliovirus receptor-related protein 3.
FT /FTId=PRO_0000226372.
FT TOPO_DOM 58 404 Extracellular (Potential).
FT TRANSMEM 405 425 Helical; (Potential).
FT TOPO_DOM 426 549 Cytoplasmic (Potential).
FT DOMAIN 59 165 Ig-like V-type.
FT DOMAIN 170 258 Ig-like C2-type 1.
FT DOMAIN 269 354 Ig-like C2-type 2.
FT CARBOHYD 73 73 N-linked (GlcNAc...).
FT CARBOHYD 83 83 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 125 125 N-linked (GlcNAc...).
FT CARBOHYD 186 186 N-linked (GlcNAc...).
FT CARBOHYD 222 222 N-linked (GlcNAc...).
FT CARBOHYD 331 331 N-linked (GlcNAc...).
FT DISULFID 78 148 By similarity.
FT DISULFID 193 246 By similarity.
FT DISULFID 291 338 By similarity.
FT VAR_SEQ 1 54 MARTLRPSPLCPGGGKAQLSSASLLGAGLLLQPPTPPPLLL
FT LLFPLLLFSRLCG -> MAEGWRWCFVRRTPGLLRGPLLPR
FT SFSGNPR (in isoform 3).
FT /FTId=VSP_046893.
FT VAR_SEQ 357 549 DPPTTTTLQPTIQWHPSTADIEDLATEPKKLPFPLSTLATI
FT KDDTIATIIASVVGGALFIVLVSVLAGIFCYRRRRTFRGDY
FT FAKNYIPPSDMQKESQIDVLQQDELDSYPDSVKKENKNPVN
FT NLIRKDYLEEPEKTQWNNVENLNRFERPMDYYEDLKMGMKF
FT VSDEHYDENEDDLVSHVDGSVISRREWYV -> DVPFKQTS
FT SIAVAGAVIGAVLALFIIAIFVTVLLTPRKKRPSYLDKVID
FT LPPTHKPPPLYEERSPPLPQKDLFQPEHLPLQTQFKEREVG
FT NLQHSNGLNSRSFDYEDENPVGEDGIQQMYPLYNQMCYQDR
FT SPGKHHQNNDPKRVYIDPREHYV (in isoform 3).
FT /FTId=VSP_046894.
FT VAR_SEQ 357 366 DPPTTTTLQP -> AYNSVASLNC (in isoform 2).
FT /FTId=VSP_017435.
FT VAR_SEQ 367 549 Missing (in isoform 2).
FT /FTId=VSP_017436.
FT VARIANT 432 432 R -> L (in dbSNP:rs15611).
FT /FTId=VAR_049995.
FT CONFLICT 251 251 P -> Q (in Ref. 4; AAH67808).
FT CONFLICT 284 284 R -> G (in Ref. 2; BAC11404).
FT CONFLICT 386 386 K -> E (in Ref. 4; AAH17572).
FT CONFLICT 465 465 S -> P (in Ref. 5; CAB43256).
FT CONFLICT 519 519 K -> R (in Ref. 5; CAB43256).
FT CONFLICT 548 548 Y -> C (in Ref. 5; CAB43256).
SQ SEQUENCE 549 AA; 61002 MW; 6D1104CCB4A9D731 CRC64;
MARTLRPSPL CPGGGKAQLS SASLLGAGLL LQPPTPPPLL LLLFPLLLFS RLCGALAGPI
IVEPHVTAVW GKNVSLKCLI EVNETITQIS WEKIHGKSSQ TVAVHHPQYG FSVQGEYQGR
VLFKNYSLND ATITLHNIGF SDSGKYICKA VTFPLGNAQS STTVTVLVEP TVSLIKGPDS
LIDGGNETVA AICIAATGKP VAHIDWEGDL GEMESTTTSF PNETATIISQ YKLFPTRFAR
GRRITCVVKH PALEKDIRYS FILDIQYAPE VSVTGYDGNW FVGRKGVNLK CNADANPPPF
KSVWSRLDGQ WPDGLLASDN TLHFVHPLTF NYSGVYICKV TNSLGQRSDQ KVIYISDPPT
TTTLQPTIQW HPSTADIEDL ATEPKKLPFP LSTLATIKDD TIATIIASVV GGALFIVLVS
VLAGIFCYRR RRTFRGDYFA KNYIPPSDMQ KESQIDVLQQ DELDSYPDSV KKENKNPVNN
LIRKDYLEEP EKTQWNNVEN LNRFERPMDY YEDLKMGMKF VSDEHYDENE DDLVSHVDGS
VISRREWYV
//
ID PVRL3_HUMAN Reviewed; 549 AA.
AC Q9NQS3; E9PFR0; Q6NVZ3; Q8NC05; Q8WVU4; Q9BVA9; Q9Y412;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-2000, sequence version 1.
DT 22-JAN-2014, entry version 99.
DE RecName: Full=Poliovirus receptor-related protein 3;
DE AltName: Full=CDw113;
DE AltName: Full=Nectin-3;
DE AltName: CD_antigen=CD113;
DE Flags: Precursor;
GN Name=PVRL3; Synonyms=PRR3;
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 1), TISSUE SPECIFICITY, AND
RP INTERACTION WITH MLLT4.
RX PubMed=11024295; DOI=10.1016/S0378-1119(00)00316-4;
RA Reymond N., Borg J.-P., Lecocq E., Adelaide J., Campadelli-Fiume G.,
RA Dubreuil P., Lopez M.;
RT "Human nectin3/PRR3: a novel member of the PVR/PRR/nectin family that
RT interacts with afadin.";
RL Gene 255:347-355(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Placenta;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 246-549 (ISOFORM 1).
RC TISSUE=Brain, Cervix, and Kidney;
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 [LARGE SCALE MRNA] OF 143-549 (ISOFORM 1).
RC TISSUE=Fetal kidney;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP INTERACTION WITH PVR.
RX PubMed=12759359; DOI=10.1074/jbc.M304166200;
RA Mueller S., Wimmer E.;
RT "Recruitment of nectin-3 to cell-cell junctions through trans-
RT heterophilic interaction with CD155, a vitronectin and poliovirus
RT receptor that localizes to alpha(v)beta3 integrin-containing membrane
RT microdomains.";
RL J. Biol. Chem. 278:31251-31260(2003).
RN [7]
RP FUNCTION, AND INTERACTION WITH PVR.
RX PubMed=16216929; DOI=10.1083/jcb.200501090;
RA Fujito T., Ikeda W., Kakunaga S., Minami Y., Kajita M., Sakamoto Y.,
RA Monden M., Takai Y.;
RT "Inhibition of cell movement and proliferation by cell-cell contact-
RT induced interaction of Necl-5 with nectin-3.";
RL J. Cell Biol. 171:165-173(2005).
RN [8]
RP INTERACTION WITH TIGIT.
RX PubMed=19011627; DOI=10.1038/ni.1674;
RA Yu X., Harden K., Gonzalez L.C., Francesco M., Chiang E., Irving B.,
RA Tom I., Ivelja S., Refino C.J., Clark H., Eaton D., Grogan J.L.;
RT "The surface protein TIGIT suppresses T cell activation by promoting
RT the generation of mature immunoregulatory dendritic cells.";
RL Nat. Immunol. 10:48-57(2009).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (3.93 ANGSTROMS) OF 58-359, SUBUNIT,
RP GLYCOSYLATION AT ASN-73; ASN-125; ASN-186; ASN-222 AND ASN-331, AND
RP MASS SPECTROMETRY.
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: Plays a role in cell-cell adhesion through heterophilic
CC trans-interactions with nectin-like proteins or nectins, such as
CC trans-interaction with PVRL2/nectin-2 at Sertoli-spermatid
CC junctions. Trans-interaction with PVR induces activation of CDC42
CC and RAC small G proteins through common signaling molecules such
CC as SRC and RAP1. Also involved in the formation of cell-cell
CC junctions, including adherens junctions and synapses. Induces
CC endocytosis-mediated down-regulation of PVR from the cell surface,
CC resulting in reduction of cell movement and proliferation. Plays a
CC role in the morphology of the ciliary body.
CC -!- SUBUNIT: Cis- and trans-homodimer. Can form trans-heterodimers
CC with PVRL1/nectin-1, PVRL2/nectin-2, PVR, IGSF4B/Necl-1 and with
CC IGSF4. Interacts with MLLT4/afadin. Binds with low affinity to
CC TIGIT.
CC -!- INTERACTION:
CC Q15223:PVRL1; NbExp=2; IntAct=EBI-2826725, EBI-1771314;
CC Q92692:PVRL2; NbExp=2; IntAct=EBI-2826725, EBI-718419;
CC Q495A1:TIGIT; NbExp=2; IntAct=EBI-2826725, EBI-4314807;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass membrane protein
CC (Potential).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9NQS3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NQS3-2; Sequence=VSP_017435, VSP_017436;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=Q9NQS3-3; Sequence=VSP_046893, VSP_046894;
CC Note=Ref.2 (BAC11404) sequence differs from that shown at
CC position 268 due to erroneous termination (Translated as Cys);
CC -!- TISSUE SPECIFICITY: Predominantly expressed in testis and placenta
CC as well as in many cell lines, including epithelial cell lines.
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=AAH17572.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC -----------------------------------------------------------------------
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DR EMBL; AF282874; AAF97597.1; -; mRNA.
DR EMBL; AK075105; BAC11404.1; ALT_TERM; mRNA.
DR EMBL; AC133436; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC133477; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC137833; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001336; AAH01336.1; -; mRNA.
DR EMBL; BC017572; AAH17572.1; ALT_INIT; mRNA.
DR EMBL; BC067808; AAH67808.1; -; mRNA.
DR EMBL; AL050071; CAB43256.1; -; mRNA.
DR PIR; T08732; T08732.
DR RefSeq; NP_001230215.1; NM_001243286.1.
DR RefSeq; NP_001230217.1; NM_001243288.1.
DR RefSeq; NP_056295.1; NM_015480.2.
DR UniGene; Hs.293917; -.
DR PDB; 4FOM; X-ray; 3.93 A; A=58-359.
DR PDBsum; 4FOM; -.
DR ProteinModelPortal; Q9NQS3; -.
DR SMR; Q9NQS3; 58-359.
DR DIP; DIP-41491N; -.
DR IntAct; Q9NQS3; 7.
DR MINT; MINT-147327; -.
DR STRING; 9606.ENSP00000418070; -.
DR MEROPS; I43.001; -.
DR PhosphoSite; Q9NQS3; -.
DR DMDM; 74762752; -.
DR PaxDb; Q9NQS3; -.
DR PRIDE; Q9NQS3; -.
DR DNASU; 25945; -.
DR Ensembl; ENST00000319792; ENSP00000321514; ENSG00000177707.
DR Ensembl; ENST00000485303; ENSP00000418070; ENSG00000177707.
DR Ensembl; ENST00000493615; ENSP00000420579; ENSG00000177707.
DR GeneID; 25945; -.
DR KEGG; hsa:25945; -.
DR UCSC; uc003dxu.2; human.
DR CTD; 25945; -.
DR GeneCards; GC03P110788; -.
DR HGNC; HGNC:17664; PVRL3.
DR HPA; CAB009869; -.
DR HPA; HPA011038; -.
DR MIM; 607147; gene.
DR neXtProt; NX_Q9NQS3; -.
DR PharmGKB; PA134969621; -.
DR eggNOG; NOG47602; -.
DR HOGENOM; HOG000115805; -.
DR HOVERGEN; HBG082234; -.
DR InParanoid; Q9NQS3; -.
DR KO; K06592; -.
DR OMA; DVPFKQT; -.
DR OrthoDB; EOG73RBB5; -.
DR PhylomeDB; Q9NQS3; -.
DR Reactome; REACT_111155; Cell-Cell communication.
DR ChiTaRS; PVRL3; human.
DR GeneWiki; PVRL3; -.
DR GenomeRNAi; 25945; -.
DR NextBio; 47534; -.
DR PRO; PR:Q9NQS3; -.
DR ArrayExpress; Q9NQS3; -.
DR Bgee; Q9NQS3; -.
DR CleanEx; HS_PRR3; -.
DR CleanEx; HS_PVRL3; -.
DR Genevestigator; Q9NQS3; -.
DR GO; GO:0043296; C:apical junction complex; IEA:Ensembl.
DR GO; GO:0005913; C:cell-cell adherens junction; IEA:Ensembl.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISS:HGNC.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:HGNC.
DR GO; GO:0034332; P:adherens junction organization; TAS:Reactome.
DR GO; GO:0034329; P:cell junction assembly; TAS:Reactome.
DR GO; GO:0009566; P:fertilization; IEA:Ensembl.
DR GO; GO:0007156; P:homophilic cell adhesion; ISS:HGNC.
DR GO; GO:0002089; P:lens morphogenesis in camera-type eye; IEA:Ensembl.
DR GO; GO:0060042; P:retina morphogenesis in camera-type eye; IEA:Ensembl.
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 Pfam; PF08205; C2-set_2; 1.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00409; IG; 1.
DR PROSITE; PS50835; IG_LIKE; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell adhesion; Cell membrane;
KW Complete proteome; Disulfide bond; Glycoprotein;
KW Immunoglobulin domain; Membrane; Polymorphism; Reference proteome;
KW Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1 57 Potential.
FT CHAIN 58 549 Poliovirus receptor-related protein 3.
FT /FTId=PRO_0000226372.
FT TOPO_DOM 58 404 Extracellular (Potential).
FT TRANSMEM 405 425 Helical; (Potential).
FT TOPO_DOM 426 549 Cytoplasmic (Potential).
FT DOMAIN 59 165 Ig-like V-type.
FT DOMAIN 170 258 Ig-like C2-type 1.
FT DOMAIN 269 354 Ig-like C2-type 2.
FT CARBOHYD 73 73 N-linked (GlcNAc...).
FT CARBOHYD 83 83 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 125 125 N-linked (GlcNAc...).
FT CARBOHYD 186 186 N-linked (GlcNAc...).
FT CARBOHYD 222 222 N-linked (GlcNAc...).
FT CARBOHYD 331 331 N-linked (GlcNAc...).
FT DISULFID 78 148 By similarity.
FT DISULFID 193 246 By similarity.
FT DISULFID 291 338 By similarity.
FT VAR_SEQ 1 54 MARTLRPSPLCPGGGKAQLSSASLLGAGLLLQPPTPPPLLL
FT LLFPLLLFSRLCG -> MAEGWRWCFVRRTPGLLRGPLLPR
FT SFSGNPR (in isoform 3).
FT /FTId=VSP_046893.
FT VAR_SEQ 357 549 DPPTTTTLQPTIQWHPSTADIEDLATEPKKLPFPLSTLATI
FT KDDTIATIIASVVGGALFIVLVSVLAGIFCYRRRRTFRGDY
FT FAKNYIPPSDMQKESQIDVLQQDELDSYPDSVKKENKNPVN
FT NLIRKDYLEEPEKTQWNNVENLNRFERPMDYYEDLKMGMKF
FT VSDEHYDENEDDLVSHVDGSVISRREWYV -> DVPFKQTS
FT SIAVAGAVIGAVLALFIIAIFVTVLLTPRKKRPSYLDKVID
FT LPPTHKPPPLYEERSPPLPQKDLFQPEHLPLQTQFKEREVG
FT NLQHSNGLNSRSFDYEDENPVGEDGIQQMYPLYNQMCYQDR
FT SPGKHHQNNDPKRVYIDPREHYV (in isoform 3).
FT /FTId=VSP_046894.
FT VAR_SEQ 357 366 DPPTTTTLQP -> AYNSVASLNC (in isoform 2).
FT /FTId=VSP_017435.
FT VAR_SEQ 367 549 Missing (in isoform 2).
FT /FTId=VSP_017436.
FT VARIANT 432 432 R -> L (in dbSNP:rs15611).
FT /FTId=VAR_049995.
FT CONFLICT 251 251 P -> Q (in Ref. 4; AAH67808).
FT CONFLICT 284 284 R -> G (in Ref. 2; BAC11404).
FT CONFLICT 386 386 K -> E (in Ref. 4; AAH17572).
FT CONFLICT 465 465 S -> P (in Ref. 5; CAB43256).
FT CONFLICT 519 519 K -> R (in Ref. 5; CAB43256).
FT CONFLICT 548 548 Y -> C (in Ref. 5; CAB43256).
SQ SEQUENCE 549 AA; 61002 MW; 6D1104CCB4A9D731 CRC64;
MARTLRPSPL CPGGGKAQLS SASLLGAGLL LQPPTPPPLL LLLFPLLLFS RLCGALAGPI
IVEPHVTAVW GKNVSLKCLI EVNETITQIS WEKIHGKSSQ TVAVHHPQYG FSVQGEYQGR
VLFKNYSLND ATITLHNIGF SDSGKYICKA VTFPLGNAQS STTVTVLVEP TVSLIKGPDS
LIDGGNETVA AICIAATGKP VAHIDWEGDL GEMESTTTSF PNETATIISQ YKLFPTRFAR
GRRITCVVKH PALEKDIRYS FILDIQYAPE VSVTGYDGNW FVGRKGVNLK CNADANPPPF
KSVWSRLDGQ WPDGLLASDN TLHFVHPLTF NYSGVYICKV TNSLGQRSDQ KVIYISDPPT
TTTLQPTIQW HPSTADIEDL ATEPKKLPFP LSTLATIKDD TIATIIASVV GGALFIVLVS
VLAGIFCYRR RRTFRGDYFA KNYIPPSDMQ KESQIDVLQQ DELDSYPDSV KKENKNPVNN
LIRKDYLEEP EKTQWNNVEN LNRFERPMDY YEDLKMGMKF VSDEHYDENE DDLVSHVDGS
VISRREWYV
//
MIM
607147
*RECORD*
*FIELD* NO
607147
*FIELD* TI
*607147 POLIOVIRUS RECEPTOR-LIKE 3; PVRL3
;;POLIOVIRUS RECEPTOR-RELATED 3; PVRR3; PRR3;;
read moreNECTIN 3
*FIELD* TX
DESCRIPTION
Nectins (e.g., PVRL1, 600644) are immunoglobulin-like adhesion molecules
that interact with afadin (AF6; 159559). Afadin is an actin
filament-binding protein that connects nectins to the actin
cytoskeleton. The nectin-afadin system organizes adherens junctions
cooperatively with the cadherin (see 192090)-catenin (see 116805) system
in epithelial cells.
CLONING
By searching an EST database using PRR1, PRR2 (PVRL2; 600798), and PVR
(173850) as queries, followed by RT-PCR of placenta mRNA, Reymond et al.
(2000) cloned a full-length cDNA encoding PRR3. The deduced 550-amino
acid PRR3 protein has a calculated molecular mass of 55.4 kD and
contains an N-terminal hydrophobic leader sequence; an ectodomain
containing a V-type Ig domain and 2 C-type Ig domains bracketed by 6
cysteine residues; a hydrophobic transmembrane region; and a long
cytoplasmic sequence. PRR3 also has 6 potential N-glycosylation sites.
Northern blot analysis revealed PRR3 expression predominantly in
placenta and testis, with faint or no expression in other tissues. A
major transcript of 2.8 kb and minor transcripts of 9.5, 6.0, and 4.7 kb
were detected in placenta. PRR3 was also expressed in mammalian
epithelial cell lines. Flow cytometry showed expression of PRR3 at the
surface of transfected COS-1 cells.
GENE FUNCTION
Using coimmunoprecipitation experiments, Reymond et al. (2000) found
that PRR3 interacts with both the L- and S-afadin isoforms in a similar
ratio.
Using immunolocalization of adult mouse hippocampal sections Mizoguchi
et al. (2002) found that the nectin-afadin system colocalizes with the
cadherin-catenin system at synapses between mossy fiber terminals and
dendrites of pyramidal cells in the CA3 area. Nectins-1 and -3
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 (600644) 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.
ANIMAL MODEL
Inagaki et al. (2006) found that male, but not female, nectin-3 -/- mice
were infertile. Phase contrast microscopy revealed that spermatozoa of
mutant mice showed severe malformation of the head and midpiece.
Nectin-3 knockout resulted in defects in the later steps of sperm
morphogenesis, including distorted nuclei and abnormal distribution of
mitochondria, as well as loss of nectin-2 (PVRL2; 600798) at
Sertoli-spermatid junctions. The localization of nectin-2 at
Sertoli-Sertoli junctions was unaffected.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the PVRL3
gene to chromosome 3 (TMAP stSG2552).
MOLECULAR GENETICS
For discussion of a possible role of variation in the PVRL3 gene in
Tourette syndrome/chronic tic disorder, see 137580.
*FIELD* RF
1. Inagaki, M.; Irie, K.; Ishizaki, H.; Tanaka-Okamoto, M.; Miyoshi,
J.; Takai, Y.: Role of cell adhesion molecule nectin-3 in spermatid
development. Genes Cells 11: 1125-1132, 2006.
2. 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.
3. Reymond, N.; Borg, J.-P.; Lecocq, E.; Adelaide, J.; Campadelli-Fiume,
G.; Dubreuil, P.; Lopez, M.: Human nectin3/PRR3: a novel member of
the PVR/PRR/nectin family that interacts with afadin. Gene 255:
347-355, 2000.
4. 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.
*FIELD* CN
Cassandra L. Kniffin - updated: 3/27/2012
Ada Hamosh - updated: 9/21/2011
Patricia A. Hartz - updated: 12/11/2006
*FIELD* CD
Patricia A. Hartz: 8/14/2002
*FIELD* ED
carol: 03/27/2012
ckniffin: 3/8/2012
alopez: 9/23/2011
terry: 9/21/2011
wwang: 12/12/2006
terry: 12/11/2006
terry: 7/20/2004
mgross: 8/14/2002
*RECORD*
*FIELD* NO
607147
*FIELD* TI
*607147 POLIOVIRUS RECEPTOR-LIKE 3; PVRL3
;;POLIOVIRUS RECEPTOR-RELATED 3; PVRR3; PRR3;;
read moreNECTIN 3
*FIELD* TX
DESCRIPTION
Nectins (e.g., PVRL1, 600644) are immunoglobulin-like adhesion molecules
that interact with afadin (AF6; 159559). Afadin is an actin
filament-binding protein that connects nectins to the actin
cytoskeleton. The nectin-afadin system organizes adherens junctions
cooperatively with the cadherin (see 192090)-catenin (see 116805) system
in epithelial cells.
CLONING
By searching an EST database using PRR1, PRR2 (PVRL2; 600798), and PVR
(173850) as queries, followed by RT-PCR of placenta mRNA, Reymond et al.
(2000) cloned a full-length cDNA encoding PRR3. The deduced 550-amino
acid PRR3 protein has a calculated molecular mass of 55.4 kD and
contains an N-terminal hydrophobic leader sequence; an ectodomain
containing a V-type Ig domain and 2 C-type Ig domains bracketed by 6
cysteine residues; a hydrophobic transmembrane region; and a long
cytoplasmic sequence. PRR3 also has 6 potential N-glycosylation sites.
Northern blot analysis revealed PRR3 expression predominantly in
placenta and testis, with faint or no expression in other tissues. A
major transcript of 2.8 kb and minor transcripts of 9.5, 6.0, and 4.7 kb
were detected in placenta. PRR3 was also expressed in mammalian
epithelial cell lines. Flow cytometry showed expression of PRR3 at the
surface of transfected COS-1 cells.
GENE FUNCTION
Using coimmunoprecipitation experiments, Reymond et al. (2000) found
that PRR3 interacts with both the L- and S-afadin isoforms in a similar
ratio.
Using immunolocalization of adult mouse hippocampal sections Mizoguchi
et al. (2002) found that the nectin-afadin system colocalizes with the
cadherin-catenin system at synapses between mossy fiber terminals and
dendrites of pyramidal cells in the CA3 area. Nectins-1 and -3
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 (600644) 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.
ANIMAL MODEL
Inagaki et al. (2006) found that male, but not female, nectin-3 -/- mice
were infertile. Phase contrast microscopy revealed that spermatozoa of
mutant mice showed severe malformation of the head and midpiece.
Nectin-3 knockout resulted in defects in the later steps of sperm
morphogenesis, including distorted nuclei and abnormal distribution of
mitochondria, as well as loss of nectin-2 (PVRL2; 600798) at
Sertoli-spermatid junctions. The localization of nectin-2 at
Sertoli-Sertoli junctions was unaffected.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the PVRL3
gene to chromosome 3 (TMAP stSG2552).
MOLECULAR GENETICS
For discussion of a possible role of variation in the PVRL3 gene in
Tourette syndrome/chronic tic disorder, see 137580.
*FIELD* RF
1. Inagaki, M.; Irie, K.; Ishizaki, H.; Tanaka-Okamoto, M.; Miyoshi,
J.; Takai, Y.: Role of cell adhesion molecule nectin-3 in spermatid
development. Genes Cells 11: 1125-1132, 2006.
2. 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.
3. Reymond, N.; Borg, J.-P.; Lecocq, E.; Adelaide, J.; Campadelli-Fiume,
G.; Dubreuil, P.; Lopez, M.: Human nectin3/PRR3: a novel member of
the PVR/PRR/nectin family that interacts with afadin. Gene 255:
347-355, 2000.
4. 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.
*FIELD* CN
Cassandra L. Kniffin - updated: 3/27/2012
Ada Hamosh - updated: 9/21/2011
Patricia A. Hartz - updated: 12/11/2006
*FIELD* CD
Patricia A. Hartz: 8/14/2002
*FIELD* ED
carol: 03/27/2012
ckniffin: 3/8/2012
alopez: 9/23/2011
terry: 9/21/2011
wwang: 12/12/2006
terry: 12/11/2006
terry: 7/20/2004
mgross: 8/14/2002