RNA recognition motif (RRM) found in vertebrate regulator of calcineurin 3 (RCAN3); This subgroup corresponds to the RRM of RCAN3, also termed calcipressin-3, or Down syndrome candidate region 1-like protein 2 (DSCR1L2), or myocyte-enriched calcineurin-interacting protein 3 (MCIP3), encoded by a ubiquitously expressed DSCR1L2 gene. Overexpressed RCAN3 binds and inhibits the Ca2+/calmodulin-dependent phosphatase calcineurin (also termed PP2B or PP3C), and further down-regulates nuclear factor of activated T cells (NFAT)-dependent cytokine gene expression in activated human Jurkat T cells. Moreover, RCAN3 interacts with cardiac troponin I (TNNI3), a heart-specific inhibitory subunit of the troponin complex, and may play a role in cardiac contraction. RCAN3 consists of an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a highly conserved SP repeat domain containing the phosphorylation site by GSK-3, a well-known PxIxIT motif responsible for docking many substrates to calcineurin, and an unrecognized C-terminal TxxP motif of unknown function.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 354548848  47 TSLFACSVHEAVFEAREQKERFEALFTIYDDQVTFQLFKSFRRVRINFSKPEAAARARIELHETDFNGQKLKLYFAQ 123
Cdd:cd12710    1 TALFACSVHEAVFEDQEQRERFEALFRIYDNQVTFQLFKSFRRVRINFSNPEAAARARIELHESDFNGKKLKLYFAQ 77

RNA recognition motif (RRM) found in vertebrate regulator of calcineurin 3 (RCAN3); This subgroup corresponds to the RRM of RCAN3, also termed calcipressin-3, or Down syndrome candidate region 1-like protein 2 (DSCR1L2), or myocyte-enriched calcineurin-interacting protein 3 (MCIP3), encoded by a ubiquitously expressed DSCR1L2 gene. Overexpressed RCAN3 binds and inhibits the Ca2+/calmodulin-dependent phosphatase calcineurin (also termed PP2B or PP3C), and further down-regulates nuclear factor of activated T cells (NFAT)-dependent cytokine gene expression in activated human Jurkat T cells. Moreover, RCAN3 interacts with cardiac troponin I (TNNI3), a heart-specific inhibitory subunit of the troponin complex, and may play a role in cardiac contraction. RCAN3 consists of an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a highly conserved SP repeat domain containing the phosphorylation site by GSK-3, a well-known PxIxIT motif responsible for docking many substrates to calcineurin, and an unrecognized C-terminal TxxP motif of unknown function.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 354548848  47 TSLFACSVHEAVFEAREQKERFEALFTIYDDQVTFQLFKSFRRVRINFSKPEAAARARIELHETDFNGQKLKLYFAQ 123
Cdd:cd12710    1 TALFACSVHEAVFEDQEQRERFEALFRIYDNQVTFQLFKSFRRVRINFSNPEAAARARIELHESDFNGKKLKLYFAQ 77

RNA recognition motif (RRM) found in vertebrate regulator of calcineurin 1 (RCAN1); This subgroup corresponds to the RRM of RCAN1, also termed calcipressin-1, or Adapt78, or Down syndrome critical region protein 1, or myocyte-enriched calcineurin-interacting protein 1 (MCIP1), encoded by the Down syndrome critical region 1 (DSCR1) gene that is abundantly expressed in human brain, heart and muscles. Overexpressed RCAN1 functions as an inhibitor of the Ca2+/calmodulin-dependent phosphatase calcineurin (also termed PP2B or PP3C), and is associated with Alzheimer's disease (AD) and Down syndrome (DS). RCAN1 can be phosphorylated by several kinases such as big MAP kinase 1 (BMK1), glycogen synthase kinase-3 (GSK-3), NF-kappaB inducing kinase (NIK), and protein kinase A (PKA). The phosphorylation of RCAN1 can positively or negatively regulate calcineurin-mediated gene transcription, and also affect its protein stability in the ubiquitin-proteasome pathway. RCAN1 consists of an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a highly conserved SP repeat domain containing the phosphorylation site by GSK-3, a well-known PxIxIT motif responsible for docking many substrates to calcineurin, and an unrecognized C-terminal TxxP motif of unknown function.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 354548848  48 SLFACSVHEAVFEAREQKERFEALFTIYDDQVTFQLFKSFRRVRINFSKPEAAARARIELHETDFNGQKLKLYFAQVQMS 127
Cdd:cd12708    2 SLVACVADTDVFTDSETRAKFESLFRAYDKDATFQFFKSFKRVRINFSNPISAAEARIRLHKTEFNGKEIKLYFAQTLHI 81

                         90
                 ....*....|....*.
gi 354548848 128 GEvrdkSYLLPPQPVK 143
Cdd:cd12708   82 GS----PHLAPPNPDK 93

RNA recognition motif 3 (RRM3) found found in type I polyadenylate-binding proteins; This subfamily corresponds to the RRM3 of type I poly(A)-binding proteins (PABPs), highly conserved proteins that bind to the poly(A) tail present at the 3' ends of most eukaryotic mRNAs. They have been implicated in the regulation of poly(A) tail length during the polyadenylation reaction, translation initiation, mRNA stabilization by influencing the rate of deadenylation and inhibition of mRNA decapping. The family represents type I polyadenylate-binding proteins (PABPs), including polyadenylate-binding protein 1 (PABP-1 or PABPC1), polyadenylate-binding protein 3 (PABP-3 or PABPC3), polyadenylate-binding protein 4 (PABP-4 or APP-1 or iPABP), polyadenylate-binding protein 5 (PABP-5 or PABPC5), polyadenylate-binding protein 1-like (PABP-1-like or PABPC1L), polyadenylate-binding protein 1-like 2 (PABPC1L2 or RBM32), polyadenylate-binding protein 4-like (PABP-4-like or PABPC4L), yeast polyadenylate-binding protein, cytoplasmic and nuclear (PABP or ACBP-67), and similar proteins. PABP-1 is an ubiquitously expressed multifunctional protein that may play a role in 3' end formation of mRNA, translation initiation, mRNA stabilization, protection of poly(A) from nuclease activity, mRNA deadenylation, inhibition of mRNA decapping, and mRNP maturation. Although PABP-1 is thought to be a cytoplasmic protein, it is also found in the nucleus. PABP-1 may be involved in nucleocytoplasmic trafficking and utilization of mRNP particles. PABP-1 contains four copies of RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), a less well conserved linker region, and a proline-rich C-terminal conserved domain (CTD). PABP-3 is a testis-specific poly(A)-binding protein specifically expressed in round spermatids. It is mainly found in mammalian and may play an important role in the testis-specific regulation of mRNA homeostasis. PABP-3 shows significant sequence similarity to PABP-1. However, it binds to poly(A) with a lower affinity than PABP-1. PABP-1 possesses an A-rich sequence in its 5'-UTR and allows binding of PABP and blockage of translation of its own mRNA. In contrast, PABP-3 lacks the A-rich sequence in its 5'-UTR. PABP-4 is an inducible poly(A)-binding protein (iPABP) that is primarily localized to the cytoplasm. It shows significant sequence similarity to PABP-1 as well. The RNA binding properties of PABP-1 and PABP-4 appear to be identical. PABP-5 is encoded by PABPC5 gene within the X-specific subinterval, and expressed in fetal brain and in a range of adult tissues in mammalian, such as ovary and testis. It may play an important role in germ cell development. Moreover, unlike other PABPs, PABP-5 contains only four RRMs, but lacks both the linker region and the CTD. PABP-1-like and PABP-1-like 2 are the orthologs of PABP-1. PABP-4-like is the ortholog of PABP-5. Their cellular functions remain unclear. The family also includes the yeast PABP, a conserved poly(A) binding protein containing poly(A) tails that can be attached to the 3'-ends of mRNAs. The yeast PABP and its homologs may play important roles in the initiation of translation and in mRNA decay. Like vertebrate PABP-1, the yeast PABP contains four RRMs, a linker region, and a proline-rich CTD as well. The first two RRMs are mainly responsible for specific binding to poly(A). The proline-rich region may be involved in protein-protein interactions.

                         10        20
                 ....*....|....*....|....*.
gi 354548848  92 INFSKPEAAARARIELHETDFNGQKL 117
Cdd:cd12380   47 VNFENHEAAQKAVEELNGKELNGKKL 72