NECT2_HUMAN
ID NECT2_HUMAN Reviewed; 538 AA.
AC Q92692; A8K5L5; O75455; Q6IBI6; Q96J29;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 213.
DE RecName: Full=Nectin-2;
DE AltName: Full=Herpes virus entry mediator B;
DE Short=Herpesvirus entry mediator B;
DE Short=HveB;
DE AltName: Full=Nectin cell adhesion molecule 2 {ECO:0000312|HGNC:HGNC:9707};
DE AltName: Full=Poliovirus receptor-related protein 2;
DE AltName: CD_antigen=CD112;
DE Flags: Precursor;
GN Name=NECTIN2 {ECO:0000312|HGNC:HGNC:9707}; Synonyms=HVEB, PRR2, PVRL2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM DELTA).
RX PubMed=7622062; DOI=10.1016/0378-1119(95)00180-e;
RA Eberle F., Dubreuil P., Mattei M.-G., Devilard E., Lopez M.;
RT "The human PRR2 gene, related to the human poliovirus receptor gene (PVR),
RT is the true homolog of the murine MPH gene.";
RL Gene 159:267-272(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA), FUNCTION (MICROBIAL INFECTION),
RP AND INTERACTION WITH HUMAN HERPESVIRUS 1/HHV-1; HUMAN HERPESVIRUS 2/HHV-2
RP ABD PSEUDORABIES VIRUS GLYCOPROTEIN D.
RX PubMed=9657005; DOI=10.1006/viro.1998.9218;
RA Warner M.S., Geraghty R.J., Martinez W.M., Montgomery R.I., Whitbeck J.C.,
RA Xu R., Eisenberg R.J., Cohen G.H., Spear P.G.;
RT "A cell surface protein with herpesvirus entry activity (HveB) confers
RT susceptibility to infection by mutants of herpes simplex virus type 1,
RT herpes simplex virus type 2, and pseudorabies virus.";
RL Virology 246:179-189(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA).
RC TISSUE=Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA).
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 31-538.
RA Yoshiura K., Murray J.C.;
RT "A transcriptional map in the region of 19q13 derived using direct
RT sequencing and exon trapping.";
RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 449-538.
RX PubMed=10520737; DOI=10.3109/10425179809086433;
RA Freitas E.M., Zhang W.J., Lalonde J.P., Tay G.K., Gaudieri S.,
RA Ashworth L.K., Van Bockxmeer F.M., Dawkins R.L.;
RT "Sequencing of 42kb of the APO E-C2 gene cluster reveals a new gene:
RT PEREC1.";
RL DNA Seq. 9:89-100(1998).
RN [9]
RP FUNCTION (MICROBIAL INFECTION), INTERACTION WITH HHV-1 MUTANT RID1; HHV-2
RP AND PRV GLYCOPROTEIN D, AND MUTAGENESIS OF MET-89.
RX PubMed=11602758; DOI=10.1128/jvi.75.22.11185-11195.2001;
RA Martinez W.M., Spear P.G.;
RT "Structural features of nectin-2 (HveB) required for herpes simplex virus
RT entry.";
RL J. Virol. 75:11185-11195(2001).
RN [10]
RP INTERACTION WITH CD226.
RX PubMed=15607800; DOI=10.1016/j.molimm.2004.07.028;
RA Pende D., Bottino C., Castriconi R., Cantoni C., Marcenaro S., Rivera P.,
RA Spaggiari G.M., Dondero A., Carnemolla B., Reymond N., Mingari M.C.,
RA Lopez M., Moretta L., Moretta A.;
RT "PVR (CD155) and Nectin-2 (CD112) as ligands of the human DNAM-1 (CD226)
RT activating receptor: involvement in tumor cell lysis.";
RL Mol. Immunol. 42:463-469(2005).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-433, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [13]
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 the
RT generation of mature immunoregulatory dendritic cells.";
RL Nat. Immunol. 10:48-57(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-433, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-433, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-410, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-465 AND SER-470 (ISOFORM ALPHA), AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [17]
RP FUNCTION AS PVRIG LIGAND.
RX PubMed=26755705; DOI=10.1084/jem.20150785;
RA Zhu Y., Paniccia A., Schulick A.C., Chen W., Koenig M.R., Byers J.T.,
RA Yao S., Bevers S., Edil B.H.;
RT "Identification of CD112R as a novel checkpoint for human T cells.";
RL J. Exp. Med. 213:167-176(2016).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) OF 32-158, SUBUNIT, DISULFIDE BOND,
RP AND MUTAGENESIS OF ASN-81.
RX PubMed=22927415; DOI=10.1073/pnas.1212912109;
RA Samanta D., Ramagopal U.A., Rubinstein R., Vigdorovich V., Nathenson S.G.,
RA Almo S.C.;
RT "Structure of Nectin-2 reveals determinants of homophilic and heterophilic
RT interactions that control cell-cell adhesion.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:14836-14840(2012).
CC -!- FUNCTION: Modulator of T-cell signaling. Can be either a costimulator
CC of T-cell function, or a coinhibitor, depending on the receptor it
CC binds to. Upon binding to CD226, stimulates T-cell proliferation and
CC cytokine production, including that of IL2, IL5, IL10, IL13, and IFNG.
CC Upon interaction with PVRIG, inhibits T-cell proliferation. These
CC interactions are competitive (PubMed:26755705). Probable cell adhesion
CC protein (PubMed:9657005). {ECO:0000269|PubMed:26755705,
CC ECO:0000269|PubMed:9657005}.
CC -!- FUNCTION: (Microbial infection) Acts as a receptor for herpes simplex
CC virus 1 (HHV-1) mutant Rid1, herpes simplex virus 1 (HHV-2) and
CC pseudorabies virus (PRV). {ECO:0000269|PubMed:11602758,
CC ECO:0000269|PubMed:9657005}.
CC -!- SUBUNIT: Can form trans-heterodimers with NECTIN3 (By similarity).
CC Interacts with CD226 or with PVRIG; these interactions are competitive
CC and have a differential functional outcome on T-cell activation, either
CC positive or negative, respectively. Binds with low affinity to TIGIT.
CC {ECO:0000250, ECO:0000269|PubMed:15607800, ECO:0000269|PubMed:19011627,
CC ECO:0000269|PubMed:22927415}.
CC -!- SUBUNIT: (Microbial infection) Interacts with herpes simplex virus 1
CC (HHV-1) mutant Rid1, herpes simplex virus 1 (HHV-2) and pseudorabies
CC virus (PRV) envelope glycoprotein D (PubMed:11602758, PubMed:9657005).
CC {ECO:0000269|PubMed:11602758, ECO:0000269|PubMed:9657005}.
CC -!- INTERACTION:
CC Q92692; P55196: AFDN; NbExp=2; IntAct=EBI-718419, EBI-365875;
CC Q92692; Q15762: CD226; NbExp=2; IntAct=EBI-718419, EBI-4314442;
CC Q92692; P60370: KRTAP10-5; NbExp=3; IntAct=EBI-718419, EBI-10172150;
CC Q92692; P60409: KRTAP10-7; NbExp=3; IntAct=EBI-718419, EBI-10172290;
CC Q92692; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-718419, EBI-3958099;
CC Q92692; Q99750: MDFI; NbExp=4; IntAct=EBI-718419, EBI-724076;
CC Q92692; Q92692: NECTIN2; NbExp=8; IntAct=EBI-718419, EBI-718419;
CC Q92692; Q9NQS3: NECTIN3; NbExp=3; IntAct=EBI-718419, EBI-2826725;
CC Q92692; Q9NQS3-1: NECTIN3; NbExp=2; IntAct=EBI-718419, EBI-16007706;
CC Q92692; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-718419, EBI-945833;
CC Q92692; Q8IUQ4: SIAH1; NbExp=3; IntAct=EBI-718419, EBI-747107;
CC Q92692; Q495A1: TIGIT; NbExp=6; IntAct=EBI-718419, EBI-4314807;
CC Q92692-2; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-6979889, EBI-3867333;
CC Q92692-2; P49639: HOXA1; NbExp=3; IntAct=EBI-6979889, EBI-740785;
CC Q92692-2; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-6979889, EBI-11959885;
CC Q92692-2; Q8IUG1: KRTAP1-3; NbExp=3; IntAct=EBI-6979889, EBI-11749135;
CC Q92692-2; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-6979889, EBI-10171774;
CC Q92692-2; P59991: KRTAP12-2; NbExp=3; IntAct=EBI-6979889, EBI-10176379;
CC Q92692-2; Q5T751: LCE1C; NbExp=3; IntAct=EBI-6979889, EBI-12224199;
CC Q92692-2; O14633: LCE2B; NbExp=3; IntAct=EBI-6979889, EBI-11478468;
CC Q92692-2; Q5TA81: LCE2C; NbExp=3; IntAct=EBI-6979889, EBI-11973993;
CC Q92692-2; Q5TCM9: LCE5A; NbExp=3; IntAct=EBI-6979889, EBI-11955689;
CC Q92692-2; Q99750: MDFI; NbExp=3; IntAct=EBI-6979889, EBI-724076;
CC Q92692-2; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-6979889, EBI-16439278;
CC Q92692-2; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-6979889, EBI-22310682;
CC Q92692-2; Q92570: NR4A3; NbExp=3; IntAct=EBI-6979889, EBI-13644623;
CC Q92692-2; P07237: P4HB; NbExp=3; IntAct=EBI-6979889, EBI-395883;
CC Q92692-2; O76081-6: RGS20; NbExp=3; IntAct=EBI-6979889, EBI-10178530;
CC Q92692-2; P15884-3: TCF4; NbExp=3; IntAct=EBI-6979889, EBI-13636688;
CC Q92692-2; P22735: TGM1; NbExp=3; IntAct=EBI-6979889, EBI-2562368;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Delta;
CC IsoId=Q92692-1; Sequence=Displayed;
CC Name=Alpha;
CC IsoId=Q92692-2; Sequence=VSP_002628, VSP_002629;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- SIMILARITY: Belongs to the nectin family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X80038; CAA56342.1; -; mRNA.
DR EMBL; AF058448; AAC23797.1; -; mRNA.
DR EMBL; AK291330; BAF84019.1; -; mRNA.
DR EMBL; CR456818; CAG33099.1; -; mRNA.
DR EMBL; CH471126; EAW57298.1; -; Genomic_DNA.
DR EMBL; BC003091; AAH03091.1; -; mRNA.
DR EMBL; AF044968; AAC82348.1; -; Genomic_DNA.
DR EMBL; AF044962; AAC82348.1; JOINED; Genomic_DNA.
DR EMBL; AF044963; AAC82348.1; JOINED; Genomic_DNA.
DR EMBL; AF044964; AAC82348.1; JOINED; Genomic_DNA.
DR EMBL; AF044966; AAC82348.1; JOINED; Genomic_DNA.
DR EMBL; AF044967; AAC82348.1; JOINED; Genomic_DNA.
DR EMBL; AF050154; AAD02503.1; -; Genomic_DNA.
DR CCDS; CCDS12645.1; -. [Q92692-2]
DR CCDS; CCDS42576.1; -. [Q92692-1]
DR PIR; I68093; I68093.
DR RefSeq; NP_001036189.1; NM_001042724.1. [Q92692-1]
DR RefSeq; NP_002847.1; NM_002856.2. [Q92692-2]
DR PDB; 3R0N; X-ray; 1.30 A; A=32-158.
DR PDB; 4DFH; X-ray; 1.85 A; A/B=32-158.
DR PDB; 4DFI; X-ray; 1.80 A; A=32-158.
DR PDB; 4HZA; X-ray; 1.70 A; A/B=32-158.
DR PDB; 5V52; X-ray; 3.10 A; C/D=32-158.
DR PDBsum; 3R0N; -.
DR PDBsum; 4DFH; -.
DR PDBsum; 4DFI; -.
DR PDBsum; 4HZA; -.
DR PDBsum; 5V52; -.
DR AlphaFoldDB; Q92692; -.
DR SMR; Q92692; -.
DR BioGRID; 111777; 145.
DR DIP; DIP-41043N; -.
DR IntAct; Q92692; 63.
DR MINT; Q92692; -.
DR STRING; 9606.ENSP00000252483; -.
DR GlyConnect; 1537; 2 N-Linked glycans (1 site).
DR GlyGen; Q92692; 2 sites, 2 N-linked glycans (1 site).
DR iPTMnet; Q92692; -.
DR PhosphoSitePlus; Q92692; -.
DR SwissPalm; Q92692; -.
DR BioMuta; NECTIN2; -.
DR DMDM; 12643789; -.
DR EPD; Q92692; -.
DR jPOST; Q92692; -.
DR MassIVE; Q92692; -.
DR MaxQB; Q92692; -.
DR PaxDb; Q92692; -.
DR PeptideAtlas; Q92692; -.
DR PRIDE; Q92692; -.
DR ProteomicsDB; 75411; -. [Q92692-1]
DR ProteomicsDB; 75412; -. [Q92692-2]
DR ABCD; Q92692; 12 sequenced antibodies.
DR Antibodypedia; 2425; 589 antibodies from 40 providers.
DR DNASU; 5819; -.
DR Ensembl; ENST00000252483.10; ENSP00000252483.4; ENSG00000130202.10. [Q92692-1]
DR Ensembl; ENST00000252485.8; ENSP00000252485.3; ENSG00000130202.10. [Q92692-2]
DR GeneID; 5819; -.
DR KEGG; hsa:5819; -.
DR MANE-Select; ENST00000252483.10; ENSP00000252483.4; NM_001042724.2; NP_001036189.1.
DR UCSC; uc002ozv.4; human. [Q92692-1]
DR CTD; 5819; -.
DR DisGeNET; 5819; -.
DR GeneCards; NECTIN2; -.
DR HGNC; HGNC:9707; NECTIN2.
DR HPA; ENSG00000130202; Low tissue specificity.
DR MIM; 600798; gene.
DR neXtProt; NX_Q92692; -.
DR OpenTargets; ENSG00000130202; -.
DR PharmGKB; PA34052; -.
DR VEuPathDB; HostDB:ENSG00000130202; -.
DR eggNOG; ENOG502QWSY; Eukaryota.
DR GeneTree; ENSGT00940000161167; -.
DR HOGENOM; CLU_029618_0_1_1; -.
DR InParanoid; Q92692; -.
DR OMA; AVVKGPQ; -.
DR OrthoDB; 1087343at2759; -.
DR PhylomeDB; Q92692; -.
DR TreeFam; TF331051; -.
DR PathwayCommons; Q92692; -.
DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR Reactome; R-HSA-418990; Adherens junctions interactions.
DR Reactome; R-HSA-420597; Nectin/Necl trans heterodimerization.
DR SignaLink; Q92692; -.
DR SIGNOR; Q92692; -.
DR BioGRID-ORCS; 5819; 17 hits in 1067 CRISPR screens.
DR ChiTaRS; NECTIN2; human.
DR EvolutionaryTrace; Q92692; -.
DR GeneWiki; PVRL2; -.
DR GenomeRNAi; 5819; -.
DR Pharos; Q92692; Tbio.
DR PRO; PR:Q92692; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q92692; protein.
DR Bgee; ENSG00000130202; Expressed in lower esophagus mucosa and 180 other tissues.
DR ExpressionAtlas; Q92692; baseline and differential.
DR Genevisible; Q92692; HS.
DR GO; GO:0043296; C:apical junction complex; IBA:GO_Central.
DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL.
DR GO; GO:0044291; C:cell-cell contact zone; IEA:Ensembl.
DR GO; GO:0005911; C:cell-cell junction; IDA:BHF-UCL.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005915; C:zonula adherens; ISS:BHF-UCL.
DR GO; GO:0050839; F:cell adhesion molecule binding; IPI:BHF-UCL.
DR GO; GO:0015026; F:coreceptor activity; TAS:ProtInc.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL.
DR GO; GO:0001618; F:virus receptor activity; IEA:UniProtKB-KW.
DR GO; GO:0001675; P:acrosome assembly; IBA:GO_Central.
DR GO; GO:0044406; P:adhesion of symbiont to host; IDA:BHF-UCL.
DR GO; GO:0032990; P:cell part morphogenesis; IEA:Ensembl.
DR GO; GO:0044782; P:cilium organization; IEA:Ensembl.
DR GO; GO:0046814; P:coreceptor-mediated virion attachment to host cell; IDA:BHF-UCL.
DR GO; GO:0007010; P:cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl.
DR GO; GO:0051654; P:establishment of mitochondrion localization; IBA:GO_Central.
DR GO; GO:0009566; P:fertilization; IEA:Ensembl.
DR GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IDA:BHF-UCL.
DR GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; IDA:BHF-UCL.
DR GO; GO:0002891; P:positive regulation of immunoglobulin mediated immune response; IMP:BHF-UCL.
DR GO; GO:0033005; P:positive regulation of mast cell activation; IMP:BHF-UCL.
DR GO; GO:0045954; P:positive regulation of natural killer cell mediated cytotoxicity; IMP:BHF-UCL.
DR GO; GO:0002860; P:positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target; IMP:BHF-UCL.
DR GO; GO:0050862; P:positive regulation of T cell receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0046596; P:regulation of viral entry into host cell; IDA:CACAO.
DR GO; GO:0030382; P:sperm mitochondrion organization; IEA:Ensembl.
DR GO; GO:0007286; P:spermatid development; ISS:BHF-UCL.
DR GO; GO:0007289; P:spermatid nucleus differentiation; IEA:Ensembl.
DR GO; GO:0042271; P:susceptibility to natural killer cell mediated cytotoxicity; IMP:BHF-UCL.
DR GO; GO:0060370; P:susceptibility to T cell mediated cytotoxicity; IDA:BHF-UCL.
DR Gene3D; 2.60.40.10; -; 3.
DR InterPro; IPR013162; CD80_C2-set.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR013106; Ig_V-set.
DR InterPro; IPR033318; Nectin-2.
DR PANTHER; PTHR47387:SF1; PTHR47387:SF1; 1.
DR Pfam; PF08205; C2-set_2; 1.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00409; IG; 2.
DR SMART; SM00406; IGv; 1.
DR SUPFAM; SSF48726; SSF48726; 3.
DR PROSITE; PS50835; IG_LIKE; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell adhesion; Cell membrane;
KW Disulfide bond; Glycoprotein; Host cell receptor for virus entry;
KW Host-virus interaction; Immunoglobulin domain; Membrane; Phosphoprotein;
KW Receptor; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..31
FT /evidence="ECO:0000255"
FT CHAIN 32..538
FT /note="Nectin-2"
FT /id="PRO_0000015136"
FT TOPO_DOM 32..360
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 361..381
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 382..538
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 32..156
FT /note="Ig-like V-type"
FT DOMAIN 162..256
FT /note="Ig-like C2-type 1"
FT DOMAIN 261..345
FT /note="Ig-like C2-type 2"
FT REGION 390..414
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 462..489
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 410
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 433
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT CARBOHYD 137
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 324
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 54..140
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:22927415"
FT DISULFID 183..238
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 283..329
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 351..479
FT /note="NTAGAGATGGIIGGIIAAIIATAVAATGILICRQQRKEQTLQGAEEDEDLEG
FT PPSYKPPTPKAKLEAQEMPSQLFTLGASEHSPLKTPYFDAGASCTEQEMPRYHELPTLE
FT ERSGPLHPGATSLGSPIP -> RASPRDVGPLVWGAVGGTLLVLLLLAGGSLAFILLRV
FT RRRRKSPGGAGGGASGDGGFYDPKAQVLGNGDPVFWTPVVPGPMEPDGKDEEEEEEEEK
FT AEKGLMLPPPPALEDDMESQLDGSLISRRAVYV (in isoform Alpha)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:9657005,
FT ECO:0000303|Ref.4"
FT /id="VSP_002628"
FT VAR_SEQ 480..538
FT /note="Missing (in isoform Alpha)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:9657005,
FT ECO:0000303|Ref.4"
FT /id="VSP_002629"
FT MUTAGEN 81
FT /note="N->A: Abolishes homodimerization."
FT /evidence="ECO:0000269|PubMed:22927415"
FT MUTAGEN 89
FT /note="M->F: Loss of entry of HHV-1/Rid1 and HSV-2. No
FT effect on PRV entry."
FT /evidence="ECO:0000269|PubMed:11602758"
FT MUTAGEN 89
FT /note="M->I: Increased entry of HHV-1/Rid1 and HSV-2."
FT /evidence="ECO:0000269|PubMed:11602758"
FT STRAND 35..37
FT /evidence="ECO:0007829|PDB:3R0N"
FT STRAND 40..43
FT /evidence="ECO:0007829|PDB:3R0N"
FT STRAND 50..52
FT /evidence="ECO:0007829|PDB:3R0N"
FT STRAND 55..58
FT /evidence="ECO:0007829|PDB:3R0N"
FT STRAND 64..71
FT /evidence="ECO:0007829|PDB:3R0N"
FT STRAND 73..75
FT /evidence="ECO:0007829|PDB:5V52"
FT HELIX 77..79
FT /evidence="ECO:0007829|PDB:3R0N"
FT STRAND 81..86
FT /evidence="ECO:0007829|PDB:3R0N"
FT TURN 87..89
FT /evidence="ECO:0007829|PDB:3R0N"
FT STRAND 90..92
FT /evidence="ECO:0007829|PDB:3R0N"
FT STRAND 95..98
FT /evidence="ECO:0007829|PDB:3R0N"
FT HELIX 100..102
FT /evidence="ECO:0007829|PDB:3R0N"
FT STRAND 103..107
FT /evidence="ECO:0007829|PDB:3R0N"
FT TURN 113..115
FT /evidence="ECO:0007829|PDB:4DFH"
FT STRAND 125..127
FT /evidence="ECO:0007829|PDB:3R0N"
FT HELIX 132..134
FT /evidence="ECO:0007829|PDB:3R0N"
FT STRAND 136..145
FT /evidence="ECO:0007829|PDB:3R0N"
FT STRAND 148..157
FT /evidence="ECO:0007829|PDB:3R0N"
FT MOD_RES Q92692-2:465
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES Q92692-2:470
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT CONFLICT Q92692-2:410
FT /note="P -> L (in Ref. 3; BAF84019)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 538 AA; 57742 MW; 3AE4F83E92F6F624 CRC64;
MARAAALLPS RSPPTPLLWP LLLLLLLETG AQDVRVQVLP EVRGQLGGTV ELPCHLLPPV
PGLYISLVTW QRPDAPANHQ NVAAFHPKMG PSFPSPKPGS ERLSFVSAKQ STGQDTEAEL
QDATLALHGL TVEDEGNYTC EFATFPKGSV RGMTWLRVIA KPKNQAEAQK VTFSQDPTTV
ALCISKEGRP PARISWLSSL DWEAKETQVS GTLAGTVTVT SRFTLVPSGR ADGVTVTCKV
EHESFEEPAL IPVTLSVRYP PEVSISGYDD NWYLGRTDAT LSCDVRSNPE PTGYDWSTTS
GTFPTSAVAQ GSQLVIHAVD SLFNTTFVCT VTNAVGMGRA EQVIFVRETP NTAGAGATGG
IIGGIIAAII ATAVAATGIL ICRQQRKEQT LQGAEEDEDL EGPPSYKPPT PKAKLEAQEM
PSQLFTLGAS EHSPLKTPYF DAGASCTEQE MPRYHELPTL EERSGPLHPG ATSLGSPIPV
PPGPPAVEDV SLDLEDEEGE EEEEYLDKIN PIYDALSYSS PSDSYQGKGF VMSRAMYV
