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RIBOSOMAL PROTEIN S6 KINASE C1; RPS6KC1

RIBOSOMAL PROTEIN S6 KINASE C1; RPS6KC1

Alternative titles; symbolsRIBOSOMAL PROTEIN S6 KINASE-LIKE PROTEIN WITH 2 PSK DOMAINS, 118-KD; RPK118HGNC Approved Gene Symbol: RPS6KC1Cytogenetic location: 1q3...

Alternative titles; symbols

  • RIBOSOMAL PROTEIN S6 KINASE-LIKE PROTEIN WITH 2 PSK DOMAINS, 118-KD; RPK118

HGNC Approved Gene Symbol: RPS6KC1

Cytogenetic location: 1q32.3 Genomic coordinates (GRCh38): 1:213,051,240-213,378,752 (from NCBI)

▼ Description
RPS6KC1 is a sphingosine kinase-1 (SPHK1; 603730)-binding protein implicated in sphingosine-1-phosphate (SPP)-mediated signaling (Hayashi et al., 2002).

▼ Cloning and Expression
By screening a skeletal muscle cDNA library with p90(rsk) (RPS6KA1; 601684) and p70(rsk) (RPS6KB1; 608938) as probes, followed by PCR of human cDNA libraries, Zhang et al. (1999) obtained a partial cDNA encoding RPS6KC1. The deduced protein sequence contains a putative ser/thr kinase catalytic domain. Northern blot analysis of 16 human tissues revealed ubiquitous expression of a 4.4-kb transcript, with highest expression in testis, skeletal muscle, brain, and pancreas.

By yeast 2-hybrid analysis of a rat brain cDNA library using mouse Sphk1 as bait, followed by screening and 5-prime RACE of a human fetal brain cDNA library, Hayashi et al. (2002) obtained a full-length human cDNA encoding RPS6KC1, which they called RPK118. The deduced 1,066-amino acid protein has a calculated molecular mass of 118 kD and contains an N-terminal phox homology (PX) domain, followed by ESP, pseudokinase-1 (PSK1), and PSK2 domains. Database analysis revealed RPK118 orthologs in fly and worm. Northern blot analysis of human tissues confirmed ubiquitous expression of RPK118, with highest levels in skeletal muscle, brain, heart, placenta, kidney, and liver. Confocal microscopy demonstrated colocalization of RPK118 with SPHK1 and EEA1 (605070) in early endosomes of transfected COS-7 cells.

▼ Gene Function
Using coimmunoprecipitation analysis, Hayashi et al. (2002) confirmed that the PSK2 domain of human RPK118 interacted with SPHK1. In vitro protein kinase assays showed that RPK118 lacked kinase activity. A dot-blot overlay assay revealed that RPK118 bound phosphatidylinositol 3-phosphate, and this binding required the PX domain of RPK118. Hayashi et al. (2002) concluded that RPK118 is an SPHK1-binding protein that may be involved in transmitting SPP-mediated signaling into the cell.

By yeast 2-hybrid, pull-down, and coimmunoprecipitation analyses, Liu et al. (2005) found that PRDX3 (604769) interacted with the PSK domains of RPK118. Confocal microscopy showed that RPK118 and PRDX3 colocalized on early endosomes in transfected COS-7 cells. Liu et al. (2005) proposed that RPK118 may be involved in transporting PRDX3 from cytoplasm, where it is synthesized, to mitochondria, where it functions, or to other membrane structures.

▼ Mapping
Using FISH and radiation hybrid analysis, Zhang et al. (1999) mapped the RPS6KC1 gene to chromosome 12q12-q13.1. However, Gross (2017) mapped the RPS6KC1 gene to chromosome 1q32.3 based on an alignment of the RPS6KC1 sequence (GenBank BC104769) with the genomic sequence (GRCh38).

Tags: 1q32.3