This contrasts with the fact that the B42 gene product was previously labelled as a ��processed transcript�� in Ensembl and as ��retired�� in more recent releases. The experimentally measured secondary structure content of the B42 protein is in agreement with that calculated for our chemokine-like model of B42 and the one reported for vMIP-I and other chemokines. Furthermore, mass spectrometry experiments corroborate the existence of three disulfide bonds, which our model predicts to be determining the folding of the IL8-like WZ4002 EGFR/HER2 inhibitor chemokine architecture and that could be indicative of a putative chemokine function for B42. All in all, our experimental results further support our prediction of B42 adopting an IL8-like chemokine fold, and they SCH727965 abmole bioscience substantiate our structure-based functional hypothesis, which proposes B42 as a putative novel human chemokine. Conclusions We have developed a new computational approach for automatic proteome-wide identification of novel chemokines based on three-dimensional properties of this protein family. In this 3D profile-based methodology, we combine fold recognition methods with automatic scaffold-based disulfide mapping to detect structural and functional patterns in 3D space indicative of a preference for a functional IL8-like chemokine fold. We apply our methodology to several thousands of so far uncharacterized human proteins to identify potential remote homologs of the chemokine protein family that may have not yet been discovered due to their low or inexistent sequence similarity to already characterized family members, and possibly also due to their noncanonical cysteine patterns in sequence and in 3D. We describe the discovery of two new proteins, B42 and N73, which we predict with high confidence to resemble the IL8-like chemokine fold of vMIP-I and vMIP-II, despite their respective low sequence similarities to known members of the chemokine protein family. Based on our computational results and in the obtained experimental supporting evidence, we propose the B42 protein to be a new structural member of the IL8-like chemokine fold family and possibly a new human chemokine. Based on the observation that B42 and N73 are primate specific proteins and because of their structural resemblances towards known anti-HIV chemokines, we postulate the possibility that both proteins might have an HIV inhibitory function. Furthermore, based on the sequence features observed for N73, we hypothesize that N73 might be able to promote tumor necrosis in cancer, like known angiostatic chemokines. Further experimental analyses will be necessary to support these hypotheses. Our findings are relevant for the signature of the chemokine family, as it gets enriched with the discovery of each new family member, and it may then help to identify new members. Each of these discoveries may shed light on the molecular mechanisms of the functions of the chemokine protein family, an understanding essential for the development of treatments for pathological processes where these proteins are involved.