NECT2_MOUSE
ID NECT2_MOUSE Reviewed; 530 AA.
AC P32507; Q62096;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2001, sequence version 2.
DT 03-AUG-2022, entry version 186.
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=Murine herpes virus entry protein B;
DE Short=mHveB;
DE AltName: Full=Nectin cell adhesion molecule 2 {ECO:0000250|UniProtKB:Q92692};
DE AltName: Full=Poliovirus receptor homolog;
DE AltName: Full=Poliovirus receptor-related protein 2;
DE AltName: CD_antigen=CD112;
DE Flags: Precursor;
GN Name=Nectin2 {ECO:0000250|UniProtKB:Q92692}; Synonyms=Mph, Pvr, Pvrl2, Pvs;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA).
RX PubMed=1560525; DOI=10.1128/jvi.66.5.2807-2813.1992;
RA Morrison M.E., Racaniello V.R.;
RT "Molecular cloning and expression of a murine homolog of the human
RT poliovirus receptor gene.";
RL J. Virol. 66:2807-2813(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA).
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=8132569; DOI=10.1016/s0021-9258(17)37212-5;
RA Aoki J., Koike S., Ise I., Sato-Yoshida Y., Nomoto A.;
RT "Amino acid residues on human poliovirus receptor involved in interaction
RT with poliovirus.";
RL J. Biol. Chem. 269:8431-8438(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BETA).
RC STRAIN=FVB/N; TISSUE=Colon;
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 [4]
RP CHARACTERIZATION.
RX PubMed=10196354; DOI=10.1128/jvi.73.5.4493-4497.1999;
RA Shukla D., Rowe C.L., Dong Y., Racaniello V.R., Spear P.G.;
RT "The murine homolog (Mph) of human herpesvirus entry protein B (HveB)
RT mediates entry of pseudorabies virus but not herpes simplex virus types 1
RT and 2.";
RL J. Virol. 73:4493-4497(1999).
RN [5]
RP INTERACTION WITH NECTIN3.
RX PubMed=10744716; DOI=10.1074/jbc.275.14.10291;
RA Satoh-Horikawa K., Nakanishi H., Takahashi K., Miyahara M., Nishimura M.,
RA Tachibana K., Mizoguchi A., Takai Y.;
RT "Nectin-3: a new member of immunoglobulin-like cell adhesion molecules that
RT shows homophilic and heterophilic cell-cell adhesion activities.";
RL J. Biol. Chem. 275:10291-10299(2000).
RN [6]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-128; ASN-138 AND ASN-315.
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-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-401 AND SER-424, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.56 ANGSTROMS) OF 32-250, SUBUNIT, DISULFIDE BONDS,
RP GLYCOSYLATION AT ASN-128 AND ASN-138, AND IDENTIFICATION BY MASS
RP 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: 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. Probable cell adhesion protein.
CC {ECO:0000250|UniProtKB:Q92692}.
CC -!- SUBUNIT: Can form trans-heterodimers with NECTIN3 (PubMed:10744716,
CC PubMed:22902367). Interacts with CD226 or with PVRIG; these
CC interactions are competitive and have a differential functional outcome
CC on T-cell activation, either positive or negative, respectively. Binds
CC with low affinity to TIGIT (By similarity).
CC {ECO:0000250|UniProtKB:Q92692, ECO:0000269|PubMed:10744716,
CC ECO:0000269|PubMed:22902367}.
CC -!- INTERACTION:
CC P32507-2; P32507-2: Nectin2; NbExp=3; IntAct=EBI-8844104, EBI-8844104;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q92692};
CC Single-pass type I membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Beta;
CC IsoId=P32507-1; Sequence=Displayed;
CC Name=Alpha;
CC IsoId=P32507-2; Sequence=VSP_002630, VSP_002631;
CC -!- TISSUE SPECIFICITY: Brain, spinal cord, spleen, kidney, heart and
CC liver.
CC -!- SIMILARITY: Belongs to the nectin family. {ECO:0000305}.
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DR EMBL; M80206; AAA39734.1; -; mRNA.
DR EMBL; D26107; BAA05103.1; -; mRNA.
DR EMBL; BC059941; AAH59941.1; -; mRNA.
DR CCDS; CCDS20913.1; -. [P32507-1]
DR CCDS; CCDS52063.1; -. [P32507-2]
DR PIR; A38211; HLMSP3.
DR PIR; A53437; A53437.
DR RefSeq; NP_001153196.1; NM_001159724.1. [P32507-2]
DR RefSeq; NP_033016.3; NM_008990.3. [P32507-1]
DR PDB; 4FMK; X-ray; 2.56 A; A=32-250.
DR PDB; 4FN0; X-ray; 3.35 A; A/B/C=32-250.
DR PDB; 4FS0; X-ray; 3.25 A; A=32-250.
DR PDBsum; 4FMK; -.
DR PDBsum; 4FN0; -.
DR PDBsum; 4FS0; -.
DR AlphaFoldDB; P32507; -.
DR SMR; P32507; -.
DR BioGRID; 202518; 2.
DR DIP; DIP-59964N; -.
DR IntAct; P32507; 3.
DR STRING; 10090.ENSMUSP00000074898; -.
DR GlyGen; P32507; 3 sites.
DR iPTMnet; P32507; -.
DR PhosphoSitePlus; P32507; -.
DR SwissPalm; P32507; -.
DR jPOST; P32507; -.
DR MaxQB; P32507; -.
DR PaxDb; P32507; -.
DR PeptideAtlas; P32507; -.
DR PRIDE; P32507; -.
DR ProteomicsDB; 286172; -. [P32507-1]
DR ProteomicsDB; 286173; -. [P32507-2]
DR ABCD; P32507; 11 sequenced antibodies.
DR Antibodypedia; 2425; 589 antibodies from 40 providers.
DR DNASU; 19294; -.
DR Ensembl; ENSMUST00000075447; ENSMUSP00000074898; ENSMUSG00000062300. [P32507-1]
DR Ensembl; ENSMUST00000108450; ENSMUSP00000104089; ENSMUSG00000062300. [P32507-2]
DR GeneID; 19294; -.
DR KEGG; mmu:19294; -.
DR UCSC; uc009fnd.2; mouse. [P32507-1]
DR UCSC; uc009fne.3; mouse. [P32507-2]
DR CTD; 5819; -.
DR MGI; MGI:97822; Nectin2.
DR VEuPathDB; HostDB:ENSMUSG00000062300; -.
DR eggNOG; ENOG502QWSY; Eukaryota.
DR GeneTree; ENSGT00940000161167; -.
DR HOGENOM; CLU_029618_0_1_1; -.
DR InParanoid; P32507; -.
DR OMA; AVVKGPQ; -.
DR PhylomeDB; P32507; -.
DR TreeFam; TF331051; -.
DR Reactome; R-MMU-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR Reactome; R-MMU-418990; Adherens junctions interactions.
DR Reactome; R-MMU-420597; Nectin/Necl trans heterodimerization.
DR BioGRID-ORCS; 19294; 0 hits in 73 CRISPR screens.
DR ChiTaRS; Nectin2; mouse.
DR PRO; PR:P32507; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P32507; protein.
DR Bgee; ENSMUSG00000062300; Expressed in placenta labyrinth and 211 other tissues.
DR Genevisible; P32507; MM.
DR GO; GO:0043296; C:apical junction complex; IDA:MGI.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0044291; C:cell-cell contact zone; IDA:MGI.
DR GO; GO:0005911; C:cell-cell junction; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:HGNC-UCL.
DR GO; GO:0005915; C:zonula adherens; IDA:BHF-UCL.
DR GO; GO:0050839; F:cell adhesion molecule binding; IPI:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:HGNC-UCL.
DR GO; GO:0001675; P:acrosome assembly; IMP:MGI.
DR GO; GO:0044406; P:adhesion of symbiont to host; ISO:MGI.
DR GO; GO:0032990; P:cell part morphogenesis; IMP:MGI.
DR GO; GO:0044782; P:cilium organization; IMP:MGI.
DR GO; GO:0046814; P:coreceptor-mediated virion attachment to host cell; ISO:MGI.
DR GO; GO:0007010; P:cytoskeleton organization; IMP:MGI.
DR GO; GO:0051649; P:establishment of localization in cell; IMP:MGI.
DR GO; GO:0051654; P:establishment of mitochondrion localization; IMP:MGI.
DR GO; GO:0009566; P:fertilization; IMP:MGI.
DR GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; ISO:MGI.
DR GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; IDA:HGNC-UCL.
DR GO; GO:0002891; P:positive regulation of immunoglobulin mediated immune response; ISO:MGI.
DR GO; GO:0033005; P:positive regulation of mast cell activation; ISO:MGI.
DR GO; GO:0045954; P:positive regulation of natural killer cell mediated cytotoxicity; ISO:MGI.
DR GO; GO:0002860; P:positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target; ISO:MGI.
DR GO; GO:0050862; P:positive regulation of T cell receptor signaling pathway; ISO:MGI.
DR GO; GO:0046596; P:regulation of viral entry into host cell; ISO:MGI.
DR GO; GO:0030382; P:sperm mitochondrion organization; IMP:MGI.
DR GO; GO:0007286; P:spermatid development; IMP:BHF-UCL.
DR GO; GO:0007289; P:spermatid nucleus differentiation; IMP:MGI.
DR GO; GO:0042271; P:susceptibility to natural killer cell mediated cytotoxicity; ISO:MGI.
DR GO; GO:0060370; P:susceptibility to T cell mediated cytotoxicity; ISO:MGI.
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; 3.
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; Immunoglobulin domain; Membrane;
KW Phosphoprotein; Receptor; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..31
FT /evidence="ECO:0000255"
FT CHAIN 32..530
FT /note="Nectin-2"
FT /id="PRO_0000015137"
FT TOPO_DOM 32..351
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 352..372
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 373..530
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 32..147
FT /note="Ig-like V-type"
FT DOMAIN 153..247
FT /note="Ig-like C2-type 1"
FT DOMAIN 252..337
FT /note="Ig-like C2-type 2"
FT REGION 382..407
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 401
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 424
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CARBOHYD 128
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973,
FT ECO:0000269|PubMed:22902367"
FT CARBOHYD 138
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973,
FT ECO:0000269|PubMed:22902367"
FT CARBOHYD 315
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT DISULFID 54..131
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:22902367"
FT DISULFID 174..229
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:22902367"
FT DISULFID 274..320
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 339..467
FT /note="ESPSTAGAGATGGIIGGIIAAIIATAVAGTGILICRQQRKEQRLQAADEEEE
FT LEGPPSYKPPTPKAKLEEPEMPSQLFTLGASEHSPVKTPYFDAGVSCADQEMPRYHELP
FT TLEERSGPLLLGATGLGP -> DTPQASRDVGPLVWGAVGGTLLVLLLAGGFLALILLR
FT GRRRRKSPGGGGNDGDRGSYDPKTQVFGNGGPVFWRSASPEPMRPDGREEDEEEEEEMK
FT AEEGLMLPPHESPKDDMESHLDGSLISRRAVYV (in isoform Alpha)"
FT /evidence="ECO:0000303|PubMed:1560525"
FT /id="VSP_002630"
FT VAR_SEQ 468..530
FT /note="Missing (in isoform Alpha)"
FT /evidence="ECO:0000303|PubMed:1560525"
FT /id="VSP_002631"
FT STRAND 35..37
FT /evidence="ECO:0007829|PDB:4FMK"
FT STRAND 40..45
FT /evidence="ECO:0007829|PDB:4FMK"
FT STRAND 50..52
FT /evidence="ECO:0007829|PDB:4FMK"
FT STRAND 54..56
FT /evidence="ECO:0007829|PDB:4FN0"
FT STRAND 63..70
FT /evidence="ECO:0007829|PDB:4FMK"
FT STRAND 76..81
FT /evidence="ECO:0007829|PDB:4FMK"
FT TURN 82..84
FT /evidence="ECO:0007829|PDB:4FMK"
FT STRAND 85..87
FT /evidence="ECO:0007829|PDB:4FMK"
FT TURN 95..97
FT /evidence="ECO:0007829|PDB:4FMK"
FT STRAND 98..100
FT /evidence="ECO:0007829|PDB:4FMK"
FT STRAND 104..106
FT /evidence="ECO:0007829|PDB:4FN0"
FT HELIX 108..111
FT /evidence="ECO:0007829|PDB:4FS0"
FT STRAND 116..118
FT /evidence="ECO:0007829|PDB:4FMK"
FT HELIX 123..125
FT /evidence="ECO:0007829|PDB:4FMK"
FT STRAND 127..136
FT /evidence="ECO:0007829|PDB:4FMK"
FT STRAND 139..151
FT /evidence="ECO:0007829|PDB:4FMK"
FT STRAND 154..159
FT /evidence="ECO:0007829|PDB:4FMK"
FT STRAND 165..167
FT /evidence="ECO:0007829|PDB:4FMK"
FT STRAND 169..181
FT /evidence="ECO:0007829|PDB:4FMK"
FT STRAND 184..188
FT /evidence="ECO:0007829|PDB:4FMK"
FT STRAND 194..201
FT /evidence="ECO:0007829|PDB:4FMK"
FT STRAND 208..216
FT /evidence="ECO:0007829|PDB:4FMK"
FT HELIX 220..222
FT /evidence="ECO:0007829|PDB:4FMK"
FT STRAND 226..232
FT /evidence="ECO:0007829|PDB:4FMK"
FT STRAND 236..238
FT /evidence="ECO:0007829|PDB:4FS0"
FT STRAND 240..245
FT /evidence="ECO:0007829|PDB:4FMK"
SQ SEQUENCE 530 AA; 57318 MW; 0ED71BFA2B231BBE CRC64;
MARAAVLPPS RLSPTLPLLP LLLLLLQETG AQDVRVRVLP EVRGRLGGTV ELPCHLLPPT
TERVSQVTWQ RLDGTVVAAF HPSFGVDFPN SQFSKDRLSF VRARPETNAD LRDATLAFRG
LRVEDEGNYT CEFATFPNGT RRGVTWLRVI AQPENHAEAQ EVTIGPQSVA VARCVSTGGR
PPARITWISS LGGEAKDTQE PGIQAGTVTI ISRYSLVPVG RADGVKVTCR VEHESFEEPI
LLPVTLSVRY PPEVSISGYD DNWYLGRSEA ILTCDVRSNP EPTDYDWSTT SGVFPASAVA
QGSQLLVHSV DRMVNTTFIC TATNAVGTGR AEQVILVRES PSTAGAGATG GIIGGIIAAI
IATAVAGTGI LICRQQRKEQ RLQAADEEEE LEGPPSYKPP TPKAKLEEPE MPSQLFTLGA
SEHSPVKTPY FDAGVSCADQ EMPRYHELPT LEERSGPLLL GATGLGPSLL VPPGPNVVEG
VSLSLEDEEE DDEEEDFLDK INPIYDALSY PSPSDSYQSK DFFVSRAMYV
