Conserved Protein Domain Family

cd12445: RRM2_CPEBs 
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RNA recognition motif 2 (RRM2) found in cytoplasmic polyadenylation element-binding protein CPEB-1, CPEB-2, CPEB-3, CPEB-4 and similar protiens
This subfamily corresponds to the RRM2 of CPEB family of proteins that bind to defined groups of mRNAs and act as either translational repressors or activators to regulate their translation. CPEB proteins are well conserved in both, vertebrates and invertebrates. Based on sequence similarity, RNA-binding specificity, and functional regulation of translation, the CPEB proteins has been classified into two subfamilies. The first subfamily includes CPEB-1 and related proteins. CPEB-1 is an RNA-binding protein that interacts with the cytoplasmic polyadenylation element (CPE), a short U-rich motif in the 3' untranslated regions (UTRs) of certain mRNAs. It functions as a translational regulator that plays a major role in the control of maternal CPE-containing mRNA in oocytes, as well as of subsynaptic CPE-containing mRNA in neurons. Once phosphorylated and recruiting the polyadenylation complex, CPEB-1 may function as a translational activator stimulating polyadenylation and translation. Otherwise, it may function as a translational inhibitor when dephosphorylated and bound to a protein such as maskin or neuroguidin, which blocks translation initiation through interfering with the assembly of eIF-4E and eIF-4G. Although CPEB-1 is mainly located in cytoplasm, it can shuttle between nucleus and cytoplasm. The second subfamily includes CPEB-2, CPEB-3, CPEB-4, and related protiens. Due to the high sequence similarity, members in this subfamily may share similar expression patterns and functions. CPEB-2 is an RNA-binding protein that is abundantly expressed in testis and localized in cytoplasm in transfected HeLa cells. It preferentially binds to poly(U) RNA oligomers and may regulate the translation of stored mRNAs during spermiogenesis. Moreover, CPEB-2 impedes target RNA translation at elongation. It directly interacts with the elongation factor, eEF2, to reduce eEF2/ribosome-activated GTP hydrolysis in vitro and inhibit peptide elongation of CPEB2-bound RNA in vivo. CPEB-3 is a sequence-specific translational regulatory protein that regulates translation in a polyadenylation-independent manner. It functions as a translational repressor that governs the synthesis of the AMPA receptor GluR2 through binding GluR2 mRNA. It also represses translation of a reporter RNA in transfected neurons and stimulates translation in response to NMDA. CPEB-4 is an RNA-binding protein that mediates meiotic mRNA cytoplasmic polyadenylation and translation. It is essential for neuron survival and present on the endoplasmic reticulum (ER). It is accumulated in the nucleus upon ischemia or the depletion of ER calcium. CPEB-4 is overexpressed in a large variety of tumors and is associated with many mRNAs in cancer cells. All CPEB proteins are nucleus-cytoplasm shuttling proteins. They contain an N-terminal unstructured region, followed by two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a Zn-finger motif. CPEB-2, -3, and -4 have conserved nuclear export signals that are not present in CPEB-1.
PSSM-Id: 409879
Aligned: 7 rows
Threshold Bit Score: 119.002
Created: 1-Jun-2012
Updated: 25-Oct-2021
Aligned Rows:
PubMed ReferencesClick to see Conserved Features Help

Sequence Alignment
Format: Row Display: Color Bits: Type Selection:
XP_003381763 133 HCVMLSNLPlgltAPMLAKLVdekyPGVAYLAIQTDevynyptGSARVFFDnkqSFEKCSQEGSTIFnfi-rgpKKIDIR 211 Trichinella spi...
XP_003382200  17 LSVLVSKTPfnakAAQLAEAVekifPGVACVKILTDemydyptGYARVFFTnenSYEKCISEQYVSLefn-dkkRRVKFI 95  Trichinella spi...
XP_003377921 316 MTVVCTNLPlpckAAELSAALerryLGIGAVRLDLDefe-yptGCARLTFKdvvSYRKILDEVHLKLampstnnHIIRIA 394 Trichinella spi...
2MKI_A       200 PY 201 human
ADY44221     234 PY 235 pig roundworm
ADY47313     213 PF 214 pig roundworm
XP_003381763 212 VY 213 Trichinella spiralis
XP_003382200  96 PF 97  Trichinella spiralis
XP_003377921 395 PY 396 Trichinella spiralis
2MKH_A       211 PY 212 human
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