Until recently, the microtubule-associated protein, EMAP, was identified only in echinoderms such as sea urchin, starfish and sand dollar. Sea urchin EMAP localizes to the mitotic apparatus in vivo and modifies the assembly dynamics of microtubules in vitro. To identify domains important for EMAP function, we cloned and sequenced cDNAs for an EMAP-related protein in human. The nucleotide sequence of a human EMAP-related protein-2 (HuEMAP-2) encodes a protein of 649 amino acids in length. The translated polypeptide sequence and domain structure of sea urchin EMAP and HuEMAP-2 are highly conserved, with greater than 57% identity and 77% similarity at the translated amino acid level. Southern blot analysis is consistent with the presence of a single HuEMAP-2 gene in the human genome. Moreover, HuEMAP-2 is a member of a larger protein family with at least four HuEMAP sequences in the NCBI databases. One of these, HuEMAP-1, is identified as the candidate gene for the Usher syndrome 1 a locus (Genomics 43:104-106, 1997). Northern blot analysis indicates that HuEMAP-1, and HuEMAP-2 are expressed in different human tissues. In addition, these RNA blots indicate that HuEMAP-2 transcripts may be differentially spliced in neuronal tissues.