{"uniprot":"Q6ZRH7","gene":"CATSPERG","name":"Cation channel sperm-associated protein subunit gamma","organism":"Homo sapiens (Human)","status":"dark","length":1159,"sequence":"MCGPAMFPAGPPWPRVRVVQVLWALLAVLLASWRLWAIKDFQECTWQVVLNEFKRVGESGVSDSFFEQEPVDTVSSLFHMLVDSPIDPSEKYLGFPYYLKINYSCEEKPSEDLVRMGHLTGLKPLVLVTFQSPVNFYRWKIEQLQIQMEAAPFRSKEPCMAEEVCSMSWYTPMPIKKGSVVMRVDISSNGLGTFIPDKRFQMNINGFLKRDRDNNIQFTVGEELFNLMPQYFVGVSSRPLWHTVDQSPVLILGGIPNEKYVLMTDTSFKDFSLVELSIDSCWVGSFYCPHSGFTATIYDTIATESTLFIRQNQLVYYFTGTYTTLYERNRGSGSWIRVLASECIKKLCPVYFHSNGSEYIMALTTGKHEGYVHFGTIRDGQVSFEMLPRQWSVCEQIGVTTCSIIWSEYIAGEYTLLLLVESGYGNASKRFQVVSYNTASDDLELLYHIPEFIPEARGLEFLMILGTESYTSTAMAPKGIFCNPYNNLIFIWGNFLLQSSNKENFIYLADFPKELSIKYMARSFRGAVAIVTETEEIWYLLEGSYRVYQLFPSKGWQVHISLKLMQQSSLYASNETMLTLFYEDSKLYQLVYLMNNQKGQLVKRLVPVEQLLMYQQHTSHYDLERKGGYLMLSFIDFCPFSVMRLRSLPSPQRYTRQERYRARPPRVLERSGFHNENSLAIYQGLVYYLLWLHSVYDKPYADPVHDPTWRWWANNKQDQDYYFFLASNWRSAGGVSIEMDSYEKIYNLESAYELPERIFLDKGTEYSFAIFLSAQGHSFRTQSELGTAFQLHSQVDVGVVLADPGCIEASVKQEVLINRNSVLFSITLKDKKLCYDQGISGHHLMETSMTVNVVGSSGLCFQETHLGPHMQGNLMVPVFIGCPPGKRLAFDITYTLEYSRLKNKHYFDCVNVNPEMPCFLFRDIFYPFFLIQDLVTGDSGSFQGSYVLLVVGGGPTLDSLKDYSEDEIYRFNSPLDKTNSLIWTTRTTRTTKDSAFHIMSHESPGIEWLCLENAPCYDNVPQGIFAPEFFFKVLVSNRGVDTSTYCNYQLTFLLHIHGLPLSPKRALFIIMVSASVFVGLVIFYIAFCLLWPLVVKGCTMIRWKINNLIASESYYTYASISGISSMPSLRHSRMGSMFSSRMTEDRAEPKEAVERQLMT","function_summary":"An auxiliary membrane subunit that organizes and stabilizes a sperm flagellar calcium-channel assembly. Its large extracellular region forms a multivalent binding scaffold that positions and maintains the channel array at the flagellar membrane, while its cytosolic tail anchors intracellular adaptors. By coupling adhesion-like and scaffolding functions to a single-pass membrane anchor, it supports calcium-dependent hyperactivation and the acrosome reaction in sperm and extends to broader roles in junctional organization and morphogenesis.","plain_language":"CATSPERG has barely been studied. The model's best guess: An auxiliary membrane subunit that organizes and stabilizes a sperm flagellar calcium-channel assembly. Its large extracellular region forms a multivalent binding scaffold that positions and maintains the channel array at the flagellar membrane, while its cytosolic tail anchors intracellular adaptors.","uniprot_summary":"Auxiliary component of the CatSper complex, a complex involved in sperm cell hyperactivation.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0045216","label":"cell-cell junction organization"},{"id":"GO:0001947","label":"heart looping"}],"cellular_component":[{"id":"GO:0005886","label":"plasma membrane"}]},"interpro":[{"id":"IPR053872","name":"CATSPERG, N-terminal domain","type":"domain","start":44,"end":203},{"id":"IPR053871","name":"CATSPERG, beta-propeller domain","type":"domain","start":207,"end":649},{"id":"IPR053874","name":"CATSPERG, Ig-like domain","type":"domain","start":753,"end":879},{"id":"IPR053873","name":"CATSPERG, C-terminal domain","type":"domain","start":905,"end":1106},{"id":"IPR028246","name":"Cation channel sperm-associated auxiliary subunit gamma","type":"family","start":14,"end":1147}],"reasoning":"I begin with the InterPro architecture. The polypeptide starts with IPR053872 (CATSPERG, N-terminal domain, residues 44–203), followed by a large IPR053871 (CATSPERG, beta-propeller domain, residues 207–649), then an IPR053874 (CATSPERG, Ig-like domain, residues 753–879), and ends with IPR053873 (CATSPERG, C-terminal domain, residues 905–1106). The entire sequence is encompassed by IPR028246 (Cation channel sperm-associated auxiliary subunit gamma family, residues 14–1147). This ordered luminal ectodomain—N-terminal module, central beta-propeller, and Ig-like fold—preceding a single C-terminal domain strongly implies a type I single-pass membrane protein whose large extracellular region mediates adhesion-like and scaffolding interactions rather than catalysis. The presence of a beta-propeller and Ig-like domain creates multivalent binding surfaces that stabilize supramolecular assemblies and mediate extracellular contacts, which causally supports a non-enzymatic role centered on GO:0005515 protein binding.\n\nFrom this binding-centric ectodomain, I infer the molecular function as protein binding (GO:0005515). The auxiliary-subunit family signature (IPR028246) ties this binding activity specifically to the CatSper calcium channel apparatus in sperm flagella. The N-terminal and beta-propeller modules likely nucleate assembly of the CatSper complex, while the Ig-like domain confers rigidity and spacing that tune the extracellular architecture of the flagellar membrane domain. The C-terminal cytosolic tail (IPR053873) would anchor intracellular partners and cytoskeletal adaptors, completing a bidirectional coupling that stabilizes the channel array.\n\nThis binding-driven architecture explains higher-order biology. By scaffolding and stabilizing the CatSper complex, the protein enables Ca2+-dependent hyperactivation and the acrosome reaction in sperm, processes that require tightly regulated membrane-channel assemblies. The same adhesive and organizational logic extends to epithelial and developmental contexts: Ig-like and beta-propeller modules commonly regulate junctional integrity and morphogenetic signaling. This provides a mechanistic route to GO:0045216 cell-cell junction organization and to morphogenetic programs such as GO:0001947 heart looping, where coordinated cell adhesion and signaling are essential.\n\nCellular location follows directly from the architecture and function. A single-pass topology with a large luminal ectodomain and cytosolic tail is characteristic of membrane-tethered scaffolds, placing the protein at the GO:0005886 plasma membrane. In sperm, this membrane residency is specialized to the flagellar principal piece, where CatSper arrays reside and where Ca2+ fluxes drive motility.\n\nMechanistically, I hypothesize that the N-terminal and beta-propeller domains assemble an extracellular lattice that positions and stabilizes CatSper channel subunits within the flagellar membrane, while the Ig-like domain enforces spacing and mechanical resilience. The C-terminal domain recruits intracellular adaptors and cytoskeletal regulators, coupling the channel complex to local signaling hubs. Likely partners include core CatSper pore-forming and auxiliary subunits, flagellar cytoskeletal elements, and junctional/cortical scaffolds that together coordinate Ca2+ entry with motility and exocytosis.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q6ZRH7.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q6ZRH7"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q6ZRH7/entry","atlas":"/p/Q6ZRH7"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}