Q8VE98 (CD276_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
CD276 antigen

Alternative name(s):
B7 homolog 3
Short name=B7-H3
Costimulatory molecule
CD_antigen=CD276

Gene names

Name:	Cd276
Synonyms:	B7h3

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	316 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Modulates T-cell-mediated immune responses and the development of acute and chronic transplant rejection. Plays a positive regulatory role in bone formation and has a dual role in the bone-immune interface. Induces antitumor immunity as it activates both acquired and innate immunity leading to natural killer cell and CD8 T-cell dependent killing of tumor cells. Ref.1 Ref.2 Ref.6 Ref.7 Ref.8
Subunit structure	Interacts with TREML2 and this interaction enhances T-cell activation By similarity.
Subcellular location	Membrane; Single-pass type I membrane protein Probable.
Tissue specificity	Ubiquitous. Ref.1
Developmental stage	Highly expressed in developing bones during embryogenesis and expression increases as osteoblast precursor cells differentiate into mature osteoblasts. Ref.2
Induction	Up-regulated in cells mediating rejection of mouse transplant. Ref.8
Disruption phenotype	Mice display a lower bone mineral density in cortical bones with femurs more susceptible to bone fracture, but do not exhibit any important skeletal abnormalities. Calvarial cells reveal normal number of osteoblast precursor cells with adequate proliferative capacity, but have impaired osteogenic differentiation. Furthermore, following cardiac transplantation, they display permanent survival under rapamycin regimen and cardiac transplants also show markedly decreased production of key cytokine and chemokine. The incidence of chronic transplant rejection is also inhibited. Mice also develop more severe airway inflammation and experimental autoimmune encephalomyelitis earlier than wild-type littermates as well as accumulate higher concentrations of autoantibodies to DNA. Ref.2
Miscellaneous	Gene transfer of B7-H3 leads to complete regression of 50 per cent tumors, or significantly slows tumor growth. In primates, B7-H3 locus underwent genomic duplication leading to tandemly repeated immunoglobulin-like V and C domains (VC domains). The dominantly expressed human B7-H3 isoform contains tandemly duplicated VC domains. In contrast, mouse B7-H3 transcript contains only one single VC domain form due to an exon structure corresponding to V domain-(pseudoexon C)-(pseudoexon V)-C domain. This duplication appearing in primates is suggested to be very recent supporting a model of multiple independent emergence of tandem VC repeats within human and monkey species.
Sequence similarities	Belongs to the immunoglobulin superfamily. BTN/MOG family. Contains 1 Ig-like C2-type (immunoglobulin-like) domain. Contains 1 Ig-like V-type (immunoglobulin-like) domain.

Ontologies

Keywords
Cellular component	Membrane
Domain	Immunoglobulin domain Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	T cell activation Inferred from electronic annotation. Source: Compara negative regulation of T cell proliferation Inferred from direct assay Ref.2. Source: MGI negative regulation of inflammatory response Inferred from mutant phenotype Ref.2. Source: MGI negative regulation of interferon-gamma biosynthetic process Inferred from direct assay Ref.2. Source: MGI negative regulation of interleukin-2 biosynthetic process Inferred from direct assay Ref.2. Source: MGI positive regulation of T cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of bone mineralization Inferred from mutant phenotype PubMed 15317945. Source: MGI positive regulation of interferon-gamma biosynthetic process Inferred from electronic annotation. Source: Compara positive regulation of osteoblast differentiation Inferred from mutant phenotype PubMed 15317945. Source: MGI regulation of immune response Inferred from mutant phenotype Ref.2. Source: MGI
Cellular_component	external side of plasma membrane Inferred from direct assay Ref.2PubMed 15317945. Source: MGI integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	receptor binding Inferred from direct assay Ref.1. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 28

28

Potential

Chain

29 – 316

288

CD276 antigen

PRO_0000045802

Regions

Topological domain

29 – 248

220

Extracellular Potential

Transmembrane

249 – 269

21

Helical; Potential

Topological domain

270 – 316

47

Cytoplasmic Potential

Domain

29 – 139

111

Ig-like V-type

Domain

145 – 238

94

Ig-like C2-type

Amino acid modifications

Glycosylation

104

1

N-linked (GlcNAc...) Ref.9 Ref.10

Glycosylation

189

1

N-linked (GlcNAc...) Ref.9 Ref.10

Glycosylation

197

1

N-linked (GlcNAc...) Ref.9

Glycosylation

215

1

N-linked (GlcNAc...) Ref.10

Disulfide bond

165 ↔ 220

By similarity

Secondary structure

1

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316

Helix Strand Turn

Details...

Beta strand

46 – 48

3

Turn

60 – 62

3

Beta strand

63 – 69

7

Turn

70 – 72

3

Beta strand

75 – 80

6

Beta strand

83 – 89

7

Turn

97 – 99

3

Helix

100 – 102

3

Beta strand

107 – 109

3

Helix

114 – 116

3

Beta strand

120 – 126

7

Beta strand

146 – 148

3

Beta strand

159 – 172

14

Beta strand

175 – 179

5

Beta strand

188 – 196

9

Beta strand

202 – 211

10

Beta strand

217 – 224

8

Turn

225 – 228

4

Beta strand

229 – 236

8

Sequences

	Sequence		Length	Mass (Da)
	Q8VE98 [UniParc]. Last modified March 1, 2002. Version 1. Checksum: 7BA30B1E67F55827	FASTA	316	34,001
	10 20 30 40 50 60 MLRGWGGPSV GVCVRTALGV LCLCLTGAVE VQVSEDPVVA LVDTDATLRC SFSPEPGFSL 70 80 90 100 110 120 AQLNLIWQLT DTKQLVHSFT EGRDQGSAYS NRTALFPDLL VQGNASLRLQ RVRVTDEGSY 130 140 150 160 170 180 TCFVSIQDFD SAAVSLQVAA PYSKPSMTLE PNKDLRPGNM VTITCSSYQG YPEAEVFWKD 190 200 210 220 230 240 GQGVPLTGNV TTSQMANERG LFDVHSVLRV VLGANGTYSC LVRNPVLQQD AHGSVTITGQ 250 260 270 280 290 300 PLTFPPEALW VTVGLSVCLV VLLVALAFVC WRKIKQSCEE ENAGAEDQDG DGEGSKTALR 310 PLKPSENKED DGQEIA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of mouse and human B7-H3 genes." Sun M., Richards S., Prasad D.V., Mai X.M., Rudensky A., Dong C. J. Immunol. 168:6294-6297(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY.
[2]	"The B7 family member B7-H3 preferentially down-regulates T helper type 1-mediated immune responses." Suh W.-K., Gajewska B.U., Okada H., Gronski M.A., Bertram E.M., Dawicki W., Duncan G.S., Bukczynski J., Plyte S., Elia A., Wakeham A., Itie A., Chung S., Da Costa J., Arya S., Horan T., Campbell P., Gaida K. , Ohashi P.S., Watts T.H., Yoshinaga S.K., Bray M.R., Jordana M., Mak T.W. Nat. Immunol. 4:899-906(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE. Strain: C57BL/6.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: NOD.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: FVB/N. Tissue: Colon and Mammary tumor.
[5]	"Duplication of primate and rodent B7-H3 immunoglobulin V- and C-like domains: divergent history of functional redundancy and exon loss." Ling V., Wu P.W., Spaulding V., Kieleczawa J., Luxenberg D., Carreno B.M., Collins M. Genomics 82:365-377(2003) [PubMed] [Europe PMC] [Abstract] Cited for: GENOMIC DOMAIN DUPLICATION.
[6]	"Mouse B7-H3 induces antitumor immunity." Sun X., Vale M., Leung E., Kanwar J.R., Gupta R., Krissansen G.W. Gene Ther. 10:1728-1734(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, GENE TRANSFER.
[7]	"Murine B7-H3 is a negative regulator of T cells." Prasad D.V., Nguyen T., Li Z., Yang Y., Duong J., Wang Y., Dong C. J. Immunol. 173:2500-2506(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"B7-H3 promotes acute and chronic allograft rejection." Wang L., Fraser C.C., Kikly K., Wells A.D., Han R., Coyle A.J., Chen L., Hancock W.W. Eur. J. Immunol. 35:428-438(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INDUCTION.
[9]	"The mouse C2C12 myoblast cell surface N-linked glycoproteome: identification, glycosite occupancy, and membrane orientation." Gundry R.L., Raginski K., Tarasova Y., Tchernyshyov I., Bausch-Fluck D., Elliott S.T., Boheler K.R., Van Eyk J.E., Wollscheid B. Mol. Cell. Proteomics 8:2555-2569(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-104; ASN-189 AND ASN-197, MASS SPECTROMETRY. Tissue: Myoblast.
[10]	"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins." Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D. Nat. Biotechnol. 27:378-386(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-104; ASN-189 AND ASN-215, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AY190318 mRNA. Translation: AAP04007.1.
AK155114 mRNA. Translation: BAE33058.1.
BC019436 mRNA. Translation: AAH19436.1.
BC056608 mRNA. Translation: AAH56608.1.

IPI

IPI00124078.

RefSeq

NP_598744.1. NM_133983.4.

UniGene

Mm.5356.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4I0K	X-ray	2.97	A	34-247	[»]

ProteinModelPortal

Q8VE98.

SMR

Q8VE98. Positions 35-239.

ModBase

Search...

PTM databases

PhosphoSite

Q8VE98.

Proteomic databases

PRIDE

Q8VE98.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000039788; ENSMUSP00000042681; ENSMUSG00000035914.
ENSMUST00000165365; ENSMUSP00000129418; ENSMUSG00000035914.

GeneID

102657.

KEGG

mmu:102657.

Organism-specific databases

CTD

80381.

MGI

MGI:2183926. Cd276.

Phylogenomic databases

eggNOG

NOG85729.

GeneTree

ENSGT00700000104325.

HOGENOM

HOG000293131.

HOVERGEN

HBG079786.

InParanoid

Q8VE98.

KO

K06746.

OMA

ETHASVT.

OrthoDB

EOG4PC9T7.

Gene expression databases

ArrayExpress

Q8VE98.

Bgee

Q8VE98.

CleanEx

MM_CD276.

Genevestigator

Q8VE98.

GermOnline

ENSMUSG00000035914. Mus musculus.

Family and domain databases

Gene3D

2.60.40.10. 2 hits.

InterPro

IPR013162. CD80_C2-set.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
[Graphical view]

Pfam

PF08205. C2-set_2. 1 hit.
PF07686. V-set. 1 hit.
[Graphical view]

SMART

SM00409. IG. 1 hit.
[Graphical view]

PROSITE

PS50835. IG_LIKE. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

NextBio

355600.

SOURCE

Search...

Entry information

Entry name

CD276_MOUSE

Accession

Primary (citable) accession number: Q8VE98

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 24, 2006
Last sequence update:	March 1, 2002
Last modified:	May 1, 2013
This is version 98 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program