CD276
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4I0K
Identifiers
Aliases	CD276, 4Ig-B7-H3, B7-H3, B7H3, B7RP-2, CD276 molecule
External IDs	OMIM: 605715 MGI: 2183926 HomoloGene: 11892 GeneCards: CD276
Gene location (Human) Chr. Chromosome 15 (human)[1] Band 15q24.1 Start 73,683,966 bp[1] End 73,714,514 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9|9 B Start 58,431,581 bp[2] End 58,462,720 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in stromal cell of endometrium ganglionic eminence gallbladder canal of the cervix left adrenal gland islet of Langerhans right coronary artery smooth muscle tissue ascending aorta subcutaneous adipose tissue Top expressed in external carotid artery internal carotid artery calvaria molar body of femur hand ganglionic eminence fossa condyle corneal stroma More reference expression data BioGPS n/a
Gene ontology Molecular function protein binding signaling receptor binding Cellular component membrane integral component of membrane external side of plasma membrane Biological process cell population proliferation T cell activation immune response positive regulation of T cell proliferation regulation of immune response T cell receptor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 80381 102657 Ensembl ENSG00000103855 ENSMUSG00000035914 UniProt Q5ZPR3 Q8VE98 RefSeq (mRNA) NM_001024736 NM_025240 NM_001329628 NM_001329629 NM_133983 RefSeq (protein) NP_001019907 NP_001316557 NP_001316558 NP_079516 NP_598744 Location (UCSC) Chr 15: 73.68 – 73.71 Mb Chr 9: 58.43 – 58.46 Mb PubMed search [3] [4]
Wikidata
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Cluster of Differentiation 276 (CD276) or B7 Homolog 3 (B7-H3) is a human protein encoded by the CD276 gene.^[5]

Structure

B7-H3 is a 316 amino acid-long type I transmembrane protein, existing in two isoforms determined by its extracellular domain. In mice, the extracellular domain consists of a single pair of immunoglobulin variable (IgV)-like and immunoglobulin constant (IgC)-like domains, whereas in humans it consists of one pair (2Ig-B7-H3) or two identical pairs (4Ig-B7-H3) due to exon duplication. B7-H3 mRNA is expressed in most normal tissues. In contrast, B7-H3 protein has a very limited expression on normal tissues because of its post-transcriptional regulation by microRNAs. However, B7-H3 protein is expressed at high frequency on many different cancer types (60% of all cancers). ^[6] The 4Ig-B7-H3 isoform is predominant in cancer.^[7]

Function

In non-malignant tissues, B7-H3 has a predominantly inhibitory role in adaptive immunity, suppressing T cell activation and proliferation.

In malignant tissues, B7-H3 is an immune checkpoint molecule that inhibits tumor antigen-specific immune responses. B7-H3 also possesses non-immunological pro-tumorigenic functions such as promoting migration, invasion, angiogenesis, chemoresistance, epithelial-to-mesenchymal transition, and affecting tumor cell metabolism.^[6]

As a possible drug target

Due to its selective expression on solid tumors, B7-H3 has been the target of several anticancer agents such as enoblituzumab (MGA271),^[8] omburtamab, MGD009, MGC018, DS-7300a, and CAR T cells.^[6][7] Nanobodies targeting the IgV and IgC domains of B7-H3 have been developed in the laboratory of Mitchell Ho at the NCI, NIH (Bethesda, US). The nanobody-based CAR T cells are active in preclinical models of pancreatic cancer and neuroblastoma and show efficacy against large tumors in mice.^[7]