Transmembrane protein 89

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TMEM89 (transmembrane protein 89) is a small human protein encoded by the TMEM89 gene. It is a membrane protein about 159 amino acids long, with a molecular mass of roughly 17.5 kDa and a basic isoelectric point around 10. The protein spans the membrane once and has two main regions outside and inside the cell ( extracellular and cytoplasmic domains).

Gene location and structure
TMEM89 sits on chromosome 3 at the 3p21.31 region, on the minus strand. The gene is about 1,011 nucleotides long and contains two exons, with no strong evidence of alternative splicing.

Expression in humans
TMEM89 is most highly expressed in the testis. It is also found at lower levels in other tissues, including the stomach, kidneys, heart, ovaries, thyroid, colon, bone marrow, and adrenal glands. In fetal tissues, TMEM89 is present in heart, stomach, kidney, and intestine. Immunohistochemistry shows TMEM89 in cell membranes of the colon, kidney, and testis. In mice, TMEM89 is detected at low levels in the cerebellum.

Protein features and structure
The human TMEM89 protein is predicted to have two topological domains (extracellular and cytoplasmic) with a single transmembrane helix. It is rich in histidine, leucine, and tryptophan, and contains a predicted N-myristoylation site (amino acids 47–52), an SH3-binding motif (106–111), and a phosphorylation site at serine 117. Structural models suggest alpha-helical and strand elements throughout the protein. Predicted three-dimensional models from AlphaFold and other tools illustrate its membrane-spanning nature.

Localization and interactions
TMEM89 is located in cell membranes. It interacts with several other proteins, including C4A, RBM15B, GOLGA6A, PFKFB4, DOCK3, MAPKAPK3, ZNF557, and ZBTB47, indicating potential roles in signaling and cellular organization.

Evolution and related notes
Orthologs of TMEM89 are found in mammals, with monotremes lacking a TMEM89 ortholog. The most conserved portions are within the cytoplasmic and extracellular domains, suggesting these regions are important for function.

Possible roles and research context
Some data link TMEM89 to higher expression in certain cancers (notably upper tract urothelial carcinomas) and to potential biomarker roles. It has also been discussed as a possible modifier in autism spectrum disorder studies and as part of models predicting relapse risk in some testicular germ cell tumors. Overall, TMEM89 appears to be a small membrane protein with tissue-specific expression and several predicted functional motifs, but its exact biological function requires further investigation.