ID   CD276_MOUSE             Reviewed;         316 AA.
AC   Q8VE98;
DT   24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2002, sequence version 1.
DT   27-MAR-2024, entry version 167.
DE   RecName: Full=CD276 antigen;
DE   AltName: Full=B7 homolog 3;
DE            Short=B7-H3;
DE   AltName: Full=Costimulatory molecule;
DE   AltName: CD_antigen=CD276;
DE   Flags: Precursor;
GN   Name=Cd276; Synonyms=B7h3;
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], FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=12055244; DOI=10.4049/jimmunol.168.12.6294;
RA   Sun M., Richards S., Prasad D.V., Mai X.M., Rudensky A., Dong C.;
RT   "Characterization of mouse and human B7-H3 genes.";
RL   J. Immunol. 168:6294-6297(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION
RP   PHENOTYPE.
RC   STRAIN=C57BL/6J;
RX   PubMed=12925852; DOI=10.1038/ni967;
RA   Suh W.-K., Gajewska B.U., Okada H., Gronski M.A., Bertram E.M., Dawicki W.,
RA   Duncan G.S., Bukczynski J., Plyte S., Elia A., Wakeham A., Itie A.,
RA   Chung S., Da Costa J., Arya S., Horan T., Campbell P., Gaida K.,
RA   Ohashi P.S., Watts T.H., Yoshinaga S.K., Bray M.R., Jordana M., Mak T.W.;
RT   "The B7 family member B7-H3 preferentially down-regulates T helper type 1-
RT   mediated immune responses.";
RL   Nat. Immunol. 4:899-906(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=NOD;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Colon, and Mammary tumor;
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   [5]
RP   GENOMIC DOMAIN DUPLICATION.
RX   PubMed=12906861; DOI=10.1016/s0888-7543(03)00126-5;
RA   Ling V., Wu P.W., Spaulding V., Kieleczawa J., Luxenberg D., Carreno B.M.,
RA   Collins M.;
RT   "Duplication of primate and rodent B7-H3 immunoglobulin V- and C-like
RT   domains: divergent history of functional redundancy and exon loss.";
RL   Genomics 82:365-377(2003).
RN   [6]
RP   FUNCTION, AND GENE TRANSFER.
RX   PubMed=12939639; DOI=10.1038/sj.gt.3302070;
RA   Sun X., Vale M., Leung E., Kanwar J.R., Gupta R., Krissansen G.W.;
RT   "Mouse B7-H3 induces antitumor immunity.";
RL   Gene Ther. 10:1728-1734(2003).
RN   [7]
RP   FUNCTION.
RX   PubMed=15294965; DOI=10.4049/jimmunol.173.4.2500;
RA   Prasad D.V., Nguyen T., Li Z., Yang Y., Duong J., Wang Y., Dong C.;
RT   "Murine B7-H3 is a negative regulator of T cells.";
RL   J. Immunol. 173:2500-2506(2004).
RN   [8]
RP   FUNCTION, AND INDUCTION.
RX   PubMed=15682454; DOI=10.1002/eji.200425518;
RA   Wang L., Fraser C.C., Kikly K., Wells A.D., Han R., Coyle A.J., Chen L.,
RA   Hancock W.W.;
RT   "B7-H3 promotes acute and chronic allograft rejection.";
RL   Eur. J. Immunol. 35:428-438(2005).
RN   [9]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-104 AND ASN-189.
RC   TISSUE=Myoblast;
RX   PubMed=19656770; DOI=10.1074/mcp.m900195-mcp200;
RA   Gundry R.L., Raginski K., Tarasova Y., Tchernyshyov I., Bausch-Fluck D.,
RA   Elliott S.T., Boheler K.R., Van Eyk J.E., Wollscheid B.;
RT   "The mouse C2C12 myoblast cell surface N-linked glycoproteome:
RT   identification, glycosite occupancy, and membrane orientation.";
RL   Mol. Cell. Proteomics 8:2555-2569(2009).
RN   [10]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-104; ASN-189 AND ASN-215.
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).
CC   -!- FUNCTION: Modulates T-cell-mediated immune responses and the
CC       development of acute and chronic transplant rejection. Plays a positive
CC       regulatory role in bone formation and has a dual role in the bone-
CC       immune interface. Induces antitumor immunity as it activates both
CC       acquired and innate immunity leading to natural killer cell and CD8 T-
CC       cell dependent killing of tumor cells. {ECO:0000269|PubMed:12055244,
CC       ECO:0000269|PubMed:12925852, ECO:0000269|PubMed:12939639,
CC       ECO:0000269|PubMed:15294965, ECO:0000269|PubMed:15682454}.
CC   -!- SUBUNIT: Interacts with TREML2 and this interaction enhances T-cell
CC       activation. {ECO:0000250}.
CC   -!- INTERACTION:
CC       Q8VE98; Q8VE98: Cd276; NbExp=2; IntAct=EBI-16044767, EBI-16044767;
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC       membrane protein {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:12055244}.
CC   -!- DEVELOPMENTAL STAGE: Highly expressed in developing bones during
CC       embryogenesis and expression increases as osteoblast precursor cells
CC       differentiate into mature osteoblasts. {ECO:0000269|PubMed:12925852}.
CC   -!- INDUCTION: Up-regulated in cells mediating rejection of mouse
CC       transplant. {ECO:0000269|PubMed:15682454}.
CC   -!- DISRUPTION PHENOTYPE: Mice display a lower bone mineral density in
CC       cortical bones with femurs more susceptible to bone fracture, but do
CC       not exhibit any important skeletal abnormalities. Calvarial cells
CC       reveal normal number of osteoblast precursor cells with adequate
CC       proliferative capacity, but have impaired osteogenic differentiation.
CC       Furthermore, following cardiac transplantation, they display permanent
CC       survival under rapamycin regimen and cardiac transplants also show
CC       markedly decreased production of key cytokine and chemokine. The
CC       incidence of chronic transplant rejection is also inhibited. Mice also
CC       develop more severe airway inflammation and experimental autoimmune
CC       encephalomyelitis earlier than wild-type littermates as well as
CC       accumulate higher concentrations of autoantibodies to DNA.
CC       {ECO:0000269|PubMed:12925852}.
CC   -!- MISCELLANEOUS: Gene transfer of B7-H3 leads to complete regression of
CC       50 per cent tumors, or significantly slows tumor growth.
CC   -!- MISCELLANEOUS: In primates, B7-H3 locus underwent genomic duplication
CC       leading to tandemly repeated immunoglobulin-like V and C domains (VC
CC       domains). The dominantly expressed human B7-H3 isoform contains
CC       tandemly duplicated VC domains. In contrast, mouse B7-H3 transcript
CC       contains only one single VC domain form due to an exon structure
CC       corresponding to V domain-(pseudoexon C)-(pseudoexon V)-C domain. This
CC       duplication appearing in primates is suggested to be very recent
CC       supporting a model of multiple independent emergence of tandem VC
CC       repeats within human and monkey species.
CC   -!- SIMILARITY: Belongs to the immunoglobulin superfamily. BTN/MOG family.
CC       {ECO:0000305}.
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DR   EMBL; AY190318; AAP04007.1; -; mRNA.
DR   EMBL; AK155114; BAE33058.1; -; mRNA.
DR   EMBL; BC019436; AAH19436.1; -; mRNA.
DR   EMBL; BC056608; AAH56608.1; -; mRNA.
DR   CCDS; CCDS23244.1; -.
DR   RefSeq; NP_598744.1; NM_133983.4.
DR   PDB; 4I0K; X-ray; 2.97 A; A=34-247.
DR   PDBsum; 4I0K; -.
DR   AlphaFoldDB; Q8VE98; -.
DR   SMR; Q8VE98; -.
DR   BioGRID; 221924; 1.
DR   DIP; DIP-60156N; -.
DR   STRING; 10090.ENSMUSP00000129418; -.
DR   GlyCosmos; Q8VE98; 3 sites, No reported glycans.
DR   GlyGen; Q8VE98; 3 sites.
DR   iPTMnet; Q8VE98; -.
DR   PhosphoSitePlus; Q8VE98; -.
DR   SwissPalm; Q8VE98; -.
DR   MaxQB; Q8VE98; -.
DR   PaxDb; 10090-ENSMUSP00000129418; -.
DR   PeptideAtlas; Q8VE98; -.
DR   ProteomicsDB; 265622; -.
DR   Pumba; Q8VE98; -.
DR   Antibodypedia; 2288; 1092 antibodies from 46 providers.
DR   Ensembl; ENSMUST00000039788.11; ENSMUSP00000042681.5; ENSMUSG00000035914.12.
DR   Ensembl; ENSMUST00000165365.3; ENSMUSP00000129418.2; ENSMUSG00000035914.12.
DR   GeneID; 102657; -.
DR   KEGG; mmu:102657; -.
DR   UCSC; uc009pxb.1; mouse.
DR   AGR; MGI:2183926; -.
DR   CTD; 80381; -.
DR   MGI; MGI:2183926; Cd276.
DR   VEuPathDB; HostDB:ENSMUSG00000035914; -.
DR   eggNOG; ENOG502QU94; Eukaryota.
DR   GeneTree; ENSGT00940000154641; -.
DR   HOGENOM; CLU_013137_8_1_1; -.
DR   InParanoid; Q8VE98; -.
DR   OMA; VLWQDSQ; -.
DR   OrthoDB; 5354085at2759; -.
DR   PhylomeDB; Q8VE98; -.
DR   TreeFam; TF331083; -.
DR   BioGRID-ORCS; 102657; 7 hits in 82 CRISPR screens.
DR   ChiTaRS; Cd276; mouse.
DR   PRO; PR:Q8VE98; -.
DR   Proteomes; UP000000589; Chromosome 9.
DR   RNAct; Q8VE98; Protein.
DR   Bgee; ENSMUSG00000035914; Expressed in embryonic post-anal tail and 193 other cell types or tissues.
DR   ExpressionAtlas; Q8VE98; baseline and differential.
DR   GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0005102; F:signaling receptor binding; IDA:MGI.
DR   GO; GO:0050728; P:negative regulation of inflammatory response; IMP:MGI.
DR   GO; GO:0032703; P:negative regulation of interleukin-2 production; IDA:MGI.
DR   GO; GO:0042130; P:negative regulation of T cell proliferation; IDA:MGI.
DR   GO; GO:0032689; P:negative regulation of type II interferon production; IDA:MGI.
DR   GO; GO:0030501; P:positive regulation of bone mineralization; IMP:MGI.
DR   GO; GO:0032743; P:positive regulation of interleukin-2 production; IMP:MGI.
DR   GO; GO:0045669; P:positive regulation of osteoblast differentiation; IMP:MGI.
DR   GO; GO:0042102; P:positive regulation of T cell proliferation; IMP:MGI.
DR   GO; GO:0032729; P:positive regulation of type II interferon production; ISO:MGI.
DR   GO; GO:0001817; P:regulation of cytokine production; IBA:GO_Central.
DR   GO; GO:0050776; P:regulation of immune response; IMP:MGI.
DR   GO; GO:0042110; P:T cell activation; ISO:MGI.
DR   GO; GO:0042098; P:T cell proliferation; IDA:MGI.
DR   GO; GO:0050852; P:T cell receptor signaling pathway; IBA:GO_Central.
DR   CDD; cd00096; Ig; 1.
DR   CDD; cd20934; IgV_B7-H3; 1.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 2.
DR   InterPro; IPR047318; CD276_IgV.
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; IPR003598; Ig_sub2.
DR   InterPro; IPR013106; Ig_V-set.
DR   PANTHER; PTHR24100; BUTYROPHILIN; 1.
DR   PANTHER; PTHR24100:SF147; CD276 ANTIGEN; 1.
DR   Pfam; PF13927; Ig_3; 1.
DR   Pfam; PF07686; V-set; 1.
DR   SMART; SM00409; IG; 2.
DR   SMART; SM00408; IGc2; 2.
DR   SMART; SM00406; IGv; 1.
DR   SUPFAM; SSF48726; Immunoglobulin; 2.
DR   PROSITE; PS50835; IG_LIKE; 2.
DR   Genevisible; Q8VE98; MM.
PE   1: Evidence at protein level;
KW   3D-structure; Disulfide bond; Glycoprotein; Immunoglobulin domain;
KW   Membrane; Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT   SIGNAL          1..28
FT                   /evidence="ECO:0000255"
FT   CHAIN           29..316
FT                   /note="CD276 antigen"
FT                   /id="PRO_0000045802"
FT   TOPO_DOM        29..248
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        249..269
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        270..316
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          29..139
FT                   /note="Ig-like V-type"
FT   DOMAIN          145..238
FT                   /note="Ig-like C2-type"
FT   REGION          280..316
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        289..316
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        104
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:19349973,
FT                   ECO:0000269|PubMed:19656770"
FT   CARBOHYD        189
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:19349973,
FT                   ECO:0000269|PubMed:19656770"
FT   CARBOHYD        215
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:19349973"
FT   DISULFID        165..220
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   STRAND          46..48
FT                   /evidence="ECO:0007829|PDB:4I0K"
FT   TURN            60..62
FT                   /evidence="ECO:0007829|PDB:4I0K"
FT   STRAND          63..69
FT                   /evidence="ECO:0007829|PDB:4I0K"
FT   TURN            70..72
FT                   /evidence="ECO:0007829|PDB:4I0K"
FT   STRAND          75..80
FT                   /evidence="ECO:0007829|PDB:4I0K"
FT   STRAND          83..89
FT                   /evidence="ECO:0007829|PDB:4I0K"
FT   TURN            97..99
FT                   /evidence="ECO:0007829|PDB:4I0K"
FT   HELIX           100..102
FT                   /evidence="ECO:0007829|PDB:4I0K"
FT   STRAND          107..109
FT                   /evidence="ECO:0007829|PDB:4I0K"
FT   HELIX           114..116
FT                   /evidence="ECO:0007829|PDB:4I0K"
FT   STRAND          120..126
FT                   /evidence="ECO:0007829|PDB:4I0K"
FT   STRAND          146..148
FT                   /evidence="ECO:0007829|PDB:4I0K"
FT   STRAND          159..172
FT                   /evidence="ECO:0007829|PDB:4I0K"
FT   STRAND          175..179
FT                   /evidence="ECO:0007829|PDB:4I0K"
FT   STRAND          188..196
FT                   /evidence="ECO:0007829|PDB:4I0K"
FT   STRAND          202..211
FT                   /evidence="ECO:0007829|PDB:4I0K"
FT   STRAND          217..224
FT                   /evidence="ECO:0007829|PDB:4I0K"
FT   TURN            225..228
FT                   /evidence="ECO:0007829|PDB:4I0K"
FT   STRAND          229..236
FT                   /evidence="ECO:0007829|PDB:4I0K"
SQ   SEQUENCE   316 AA;  34001 MW;  7BA30B1E67F55827 CRC64;
     MLRGWGGPSV GVCVRTALGV LCLCLTGAVE VQVSEDPVVA LVDTDATLRC SFSPEPGFSL
     AQLNLIWQLT DTKQLVHSFT EGRDQGSAYS NRTALFPDLL VQGNASLRLQ RVRVTDEGSY
     TCFVSIQDFD SAAVSLQVAA PYSKPSMTLE PNKDLRPGNM VTITCSSYQG YPEAEVFWKD
     GQGVPLTGNV TTSQMANERG LFDVHSVLRV VLGANGTYSC LVRNPVLQQD AHGSVTITGQ
     PLTFPPEALW VTVGLSVCLV VLLVALAFVC WRKIKQSCEE ENAGAEDQDG DGEGSKTALR
     PLKPSENKED DGQEIA
//