"While HuRI displays highly significant overlap with known functional relationships, the cellular function of most individual PPIs remains to be elucidated."

"that leucine-rich repeats and guanylate kinase-domain containing isoform 1 (LRGUK-1) is required for multiple aspects of sperm assembly, including acrosome attachment, sperm head shaping and the initiation of the axoneme growth to form the core of the sperm tail. Specifically, LRGUK-1 is required for basal body attachment to the plasma membrane, the appropriate formation of the sub-distal appendages, the extension of axoneme microtubules and for microtubule movement and organisation within the manchette."

"As maturation proceeded and nuclear elongation initiated, LRGUK moved distally to ultimately reside on the microtubules of the manchette (Fig. 3D and S2 Fig.). LRGUK was also evident in the sperm basal body and the sperm tail (Fig. 3E)."

"Specific transfection of the full length HOOK2 with LRGUK-1 in a separate yeast two hybid assay confirmed this interaction and the introduction of the R528Stop mutation into the Lrguk-1 sequence completely abolished binding to HOOK2 (Fig. 6A). An interaction between LRGUK-1 and endogenous HOOK2 was confirmed by co-immunoprecipitation, wherein full-length mouse Lrguk-1-GFP was transfected into HEK293T cells then the complex co-precipitated (Fig. 6B)."

"Lrguk is predicted to encode 3 splice variants, Lrguk transcript 1 (Lrguk-1), -2 (Lrguk-2) and -3 (Lrguk-3). Lrguk-1 is the longest transcript and the only isoform affected by the mutation (Fig. 1A)."

"The data indicate that LRGUK1 likely achieves its function in partnership with members of the HOOK family of proteins (HOOK-1-3), Rab3-interacting molecule binding protein (RIMBP)-3 and kinesin light chain (KLC)-3, all of which are associated with intracellular protein transport as cargo adaptor proteins and are localized to the manchette."

"In the present study, we showed that the GUK-like domain is essential for binding to HOOK2 and RIMBP3, and the LRR domain is essential for binding to KLC3."

"These findings establish LRGUK1 as a key component of a multiprotein complex with an essential role in microtubule dynamics within haploid male germ cells."

"In contrast to the much larger human ortholog (94 kDa), Tetrahymena Cfap246 protein lacks the guanylate kinase domain within its C-terminal region (Fig. S1)."

"We conclude that Cfap69, Cfap246, Adgb, Cfap174, and Tt170 are positioned near Spef2A, and thus, most likely are subunits of the C1b/C1f projections."

"only minor alterations in ciliary motility."

"It remains to be determined if LRGUK is indeed a C1b/C1f component in mammals."

"Here, we identify a homozygous truncating variant in LRGUK (c.1063C>T; p.Arg355Ter) in an infertile man presenting with a typical MMAF phenotype. The variant, identified by whole-exome sequencing in a cohort of 168 MMAF patients and confirmed by Sanger sequencing, is predicted to result in loss of the C-terminal guanylate kinase-like domain."

"Immunofluorescence showed absence of LRGUK protein in patient spermatozoa, supporting a loss-of-function effect. Semen analysis revealed impaired motility and complete teratozoospermia. Morphological and ultrastructural analyzes demonstrated severe defects affecting both sperm head and flagellum, including disorganized axonemal architecture and central pair abnormalities."

"Immunostaining further indicated alterations of central apparatus-associated proteins, supporting a role for LRGUK in C1b projection organization."