Sequence analysis predicted that the 316-amino acid type I transmembrane protein contains an N-terminal signal peptide; extracellular V- and C-like Ig domains with 4 conserved cysteine residues; a transmembrane region; and a 45-amino acid cytoplasmic tail.

The extracellular receptor-binding domain of B7H3 shares 27% and 25% identity with those of B7H1 and B7H2, respectively. Northern blot analysis detected highest expression of a 4.1-kb transcript in heart, liver, placenta, prostate, testis, uterus, pancreas, small intestine, colon, and lymphoid organs, with lower expression in brain, skeletal muscle, kidney, and lung, and no expression in peripheral blood leukocytes. B7H3 expression was detected in most tumor cell lines tested.