RNA recognition motif (RRM) superfamily; RRM, also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), is a highly abundant domain in eukaryotes found in proteins involved in post-transcriptional gene expression processes including mRNA and rRNA processing, RNA export, and RNA stability. This domain is 90 amino acids in length and consists of a four-stranded beta-sheet packed against two alpha-helices. RRM usually interacts with ssRNA, but is also known to interact with ssDNA as well as proteins. RRM binds a variable number of nucleotides, ranging from two to eight. The active site includes three aromatic side-chains located within the conserved RNP1 and RNP2 motifs of the domain. The RRM domain is found in a variety heterogeneous nuclear ribonucleoproteins (hnRNPs), proteins implicated in regulation of alternative splicing, and protein components of small nuclear ribonucleoproteins (snRNPs).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 510863322 204 LTVFIGGVPRPLTSGELAALLEQNYGPLLYCEIDVDPELFYPKGAARAVFASYSSYVKAIRSRYLHIPNVEFNKRtVEIK 283
Cdd:cd12726    1 KTIFVGGVPRPLRAVELAMIMDRLYGGVCYAGIDTDPELKYPKGAGRVAFSNQQSYIAAISARFVQLQHGDIDKR-VEVK 79

                 ..
gi 510863322 284 PY 285
Cdd:cd12726   80 PY 81

Cytoplasmic polyadenylation element-binding protein ZZ domain; This ZZ-type zinc finger domain binds zinc via two conserved histidines in the C-terminal part of the domain.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 510863322  280 VEIKPYTMDEiLCDECLEAAATHFCR--VCMQYYCEAC 315
Cdd:pfam16366   1 VQIDPYLEDS-LCSECNGQPGPYFCRdlSCFKYYCRSC 37

RNA recognition motif 2 (RRM2) found in cytoplasmic polyadenylation element-binding protein CPEB-2, CPEB-3, CPEB-4 and similar protiens; This subgroup corresponds to the RRM2 of the paralog proteins CPEB-2, CPEB-3 and CPEB-4, all well conserved in both, vertebrates and invertebrates. Due to the high sequence similarity, members in this family 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 family members contain an N-terminal unstructured region, two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a Zn-finger motif. In addition, they do have conserved nuclear export signals that are not present in CPEB-1.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 510863322 204 LTVFIGGVPRPLTSGELAALLEQNYGPLLYCEIDVDPELFYPKGAARAVFASYSSYVKAIRSRYLHIPNVEFNKRtVEIK 283
Cdd:cd12726    1 KTIFVGGVPRPLRAVELAMIMDRLYGGVCYAGIDTDPELKYPKGAGRVAFSNQQSYIAAISARFVQLQHGDIDKR-VEVK 79

                 ..
gi 510863322 284 PY 285
Cdd:cd12726   80 PY 81

RNA recognition motif 1 (RRM1) found in cytoplasmic polyadenylation element-binding protein CPEB-1, CPEB-2, CPEB-3, CPEB-4 and similar protiens; This subfamily corresponds to the RRM1 of the 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 have 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 bind 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 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. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 510863322  89 RKVFVGGLPQDISKSSLLQKFCAYGQVRLDFPSEPTHPPRTRKAdrrlstsGYVFLIYETEEAVFNLLKACSFRD---GS 165
Cdd:cd12444    1 RKVFLGGVPWDITEAELTASFRRFGSLSVDWPGKDESKSYFPPK-------GYVYLLFESEKSVQALLQACTHDDdklYE 73

                         90       100
                 ....*....|....*....|..
gi 510863322 166 YFLPFHEDSMNVKLAQVRPWQL 187
Cdd:cd12444   74 YYFKVSSRTMKDKEVQVIPWVL 95

RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 510863322   205 TVFIGGVPRPLTSGELAALLEQnYGPLLYCEIDVDPELFYPKGAARAVFASYSSYVKAIRsrylHIPNVEFNKRTVEI 282
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSK-FGKVESVRLVRDKETGKSKGFAFVEFESEEDAEKALE----ALNGKELDGRPLKV 73

RNA recognition motif;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 510863322    90 KVFVGGLPQDISKSSLLQKFCAYGQV-RLDFPSEP-THPPRtrkadrrlstsGYVFLIYETEEAVfnlLKACSFRDGSYF 167
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSKFGKVeSVRLVRDKeTGKSK-----------GFAFVEFESEEDA---EKALEALNGKEL 66

RNA recognition motif 2 (RRM2) found in cytoplasmic polyadenylation element-binding protein CPEB-2, CPEB-3, CPEB-4 and similar protiens; This subgroup corresponds to the RRM2 of the paralog proteins CPEB-2, CPEB-3 and CPEB-4, all well conserved in both, vertebrates and invertebrates. Due to the high sequence similarity, members in this family 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 family members contain an N-terminal unstructured region, two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a Zn-finger motif. In addition, they do have conserved nuclear export signals that are not present in CPEB-1.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 510863322 204 LTVFIGGVPRPLTSGELAALLEQNYGPLLYCEIDVDPELFYPKGAARAVFASYSSYVKAIRSRYLHIPNVEFNKRtVEIK 283
Cdd:cd12726    1 KTIFVGGVPRPLRAVELAMIMDRLYGGVCYAGIDTDPELKYPKGAGRVAFSNQQSYIAAISARFVQLQHGDIDKR-VEVK 79

                 ..
gi 510863322 284 PY 285
Cdd:cd12726   80 PY 81

RNA recognition motif;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 510863322   88 SRKVFVGGLPQDISKSSLLQKFCAYGQVRLDFPSEPTHPPrtrkadRRLSTSGYVFLIYETEEAVFNLLKACSFRDGSYF 167
Cdd:pfam16367   1 SRKVFVGGLPWDITEAELTATFGRFGPLLVDWPGKPESPS------YFPDVKGYVFLVFEDEKSVQALLDACTQEDGKYY 74

                          90
                  ....*....|....*..
gi 510863322  168 LPFHEDSMNVKLAQVRP 184
Cdd:pfam16367  75 LKLSSPRMKDKPVQIRP 91

RNA recognition motif 1 (RRM1) found in cytoplasmic polyadenylation element-binding protein CPEB-2, CPEB-3, CPEB-4 and similar protiens; This subgroup corresponds to the RRM1 of the paralog proteins CPEB-2, CPEB-3 and CPEB-4, all well-conserved in both, vertebrates and invertebrates. Due to the high sequence similarity, members in this family 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 family members contain an N-terminal unstructured region, two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a Zn-finger motif. In addition, they do have conserved nuclear export signals that are not present in CPEB-1.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 510863322  89 RKVFVGGLPQDISKSSLLQKFCAYGQVRLDFPSEPTH----PPRtrkadrrlstsGYVFLIYETEEAVFNLLKACSFRDG 164
Cdd:cd12724    1 RKVFVGGLPPDIDEDEITASFRRFGPLVVDWPHKAESksyfPPK-----------GYAFLLFQDERSVQALIDACIEEDD 69

                         90       100
                 ....*....|....*....|...
gi 510863322 165 SYFLPFHEDSMNVKLAQVRPWQL 187
Cdd:cd12724   70 KLYLCVSSPTIKDKPVQIRPWNL 92

RNA recognition motif 2 (RRM2) found in cytoplasmic polyadenylation element-binding protein 1 (CPEB-1) and similar proteins; This subgroup corresponds to the RRM2 of CPEB-1 (also termed CPE-BP1 or CEBP), 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. CPEB-1 contains an N-terminal unstructured region, two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a Zn-finger motif. Both of the RRMs and the Zn finger are required for CPEB-1 to bind CPE. The N-terminal regulatory region may be responsible for CPEB-1 interacting with other proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 510863322 201 DTRLTVFIGGVPRPLTSGELAALLEQNYGPLLYCEIDVDpELFYPKGAARAVFASYSSYVKAIRSRYLHIPNVEFNKRtV 280
Cdd:cd12725    1 DPSKTVFVGALHGMLNAEGLANIMNDLFGGVVYAGIDTD-KHKYPIGSGRVTFNNQRSYMKAVNAAFVEIKTPKFTKK-V 78

                 ....*
gi 510863322 281 EIKPY 285
Cdd:cd12725   79 QIDPY 83

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein hnRNP D0, hnRNP A/B, hnRNP DL and similar proteins; This subfamily corresponds to the RRM2 of hnRNP D0, hnRNP A/B, hnRNP DL and similar proteins. hnRNP D0, a UUAG-specific nuclear RNA binding protein that may be involved in pre-mRNA splicing and telomere elongation. hnRNP A/B is an RNA unwinding protein with a high affinity for G- followed by U-rich regions. It has also been identified as an APOBEC1-binding protein that interacts with apolipoprotein B (apoB) mRNA transcripts around the editing site and thus plays an important role in apoB mRNA editing. hnRNP DL (or hnRNP D-like) is a dual functional protein that possesses DNA- and RNA-binding properties. It has been implicated in mRNA biogenesis at the transcriptional and post-transcriptional levels. All memembers in this family contain two putative RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a glycine- and tyrosine-rich C-terminus.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 510863322  90 KVFVGGLPQDISKSSLLQKFCAYGQVR-LDFPSEpthpPRTRKadRRlstsGYVFLIYETEEAVFNLLK 157
Cdd:cd12329    1 KIFVGGLSPETTEEKIREYFGKFGNIVeIELPMD----KKTNK--RR----GFCFITFDSEEPVKKILE 59

B-box-type 1 zinc finger (Bbox1); The B-box-type zinc finger is a short zinc binding domain of around 40 amino acid residues in length. It has been found in transcription factors, ribonucleoproteins and proto-oncoproteins, such as in TRIM (tripartite motif) proteins that consist of an N-terminal RING finger (originally called an A-box), followed by 1-2 B-box domains and a coiled-coil domain (also called RBCC for Ring, B-box, Coiled-Coil). The B-box-type zinc finger often presents in combination with other motifs, like RING zinc finger, NHL motif, coiled-coil or RFP domain, in functionally unrelated proteins, most likely mediating protein-protein interactions. Based on different consensus sequences and the spacing of the 7-8 zinc-binding residues, the B-box-type zinc fingers can be divided into two groups, type 1 (Bbox1: C6H2) and type 2 (Bbox2: CHC3H2). This family corresponds to the type 1 B-box (Bbox1).

                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 510863322 291 LCDECLEAAATHFCRVCMQYYCEACSiRMDHSVGSHL 327
Cdd:cd19757    1 LCDECEEREATVYCLECEEFLCDDCS-DAIHRRGKLT 36

RNA recognition motif (RRM) superfamily; RRM, also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), is a highly abundant domain in eukaryotes found in proteins involved in post-transcriptional gene expression processes including mRNA and rRNA processing, RNA export, and RNA stability. This domain is 90 amino acids in length and consists of a four-stranded beta-sheet packed against two alpha-helices. RRM usually interacts with ssRNA, but is also known to interact with ssDNA as well as proteins. RRM binds a variable number of nucleotides, ranging from two to eight. The active site includes three aromatic side-chains located within the conserved RNP1 and RNP2 motifs of the domain. The RRM domain is found in a variety heterogeneous nuclear ribonucleoproteins (hnRNPs), proteins implicated in regulation of alternative splicing, and protein components of small nuclear ribonucleoproteins (snRNPs).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 510863322  91 VFVGGLPQDISKSSLLQKFCAYGQV-RLDFPSEPTHPPRtrkadrrlstsGYVFLIYETEEAVfnlLKACSFRDGSYF 167
Cdd:cd00590    1 LFVGNLPPDTTEEDLRELFSKFGEVvSVRIVRDRDGKSK-----------GFAFVEFESPEDA---EKALEALNGTEL 64

RNA recognition motif;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 510863322    90 KVFVGGLPQDISKSSLLQKFCAYGQV-RLDFPSEP-THPPRtrkadrrlstsGYVFLIYETEEAVfnlLKACSFRDGSYF 167
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSKFGKVeSVRLVRDKeTGKSK-----------GFAFVEFESEEDA---EKALEALNGKEL 66

RNA recognition motif (RRM) found in AZoospermia (DAZ) autosomal homologs, DAZL (DAZ-like) and BOULE; This subfamily corresponds to the RRM domain of two Deleted in AZoospermia (DAZ) autosomal homologs, DAZL (DAZ-like) and BOULE. BOULE is the founder member of the family and DAZL arose from BOULE in an ancestor of vertebrates. The DAZ gene subsequently originated from a duplication transposition of the DAZL gene. Invertebrates contain a single DAZ homolog, BOULE, while vertebrates, other than catarrhine primates, possess both BOULE and DAZL genes. The catarrhine primates possess BOULE, DAZL, and DAZ genes. The family members encode closely related RNA-binding proteins that are required for fertility in numerous organisms. These proteins contain an RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a varying number of copies of a DAZ motif, believed to mediate protein-protein interactions. DAZL and BOULE contain a single copy of the DAZ motif, while DAZ proteins can contain 8-24 copies of this repeat. Although their specific biochemical functions remain to be investigated, DAZL proteins may interact with poly(A)-binding proteins (PABPs), and act as translational activators of specific mRNAs during gametogenesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 510863322  87 ISRKVFVGGLPQDISKSSLLQKFCAYGQVrldfpsepthppRTRK--ADRRLSTSGYVFLIYETEEAVFNLLKACSfrdg 164
Cdd:cd12412    1 IPNRIFVGGIDWDTTEEELREFFSKFGKV------------KDVKiiKDRAGVSKGYGFVTFETQEDAEKIQKWGA---- 64

                         90
                 ....*....|...
gi 510863322 165 syFLPFHEDSMNV 177
Cdd:cd12412   65 --NLVFKGKKLNV 75

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein D0 (hnRNP D0) and similar proteins; This subgroup corresponds to the RRM2 of hnRNP D0, also termed AU-rich element RNA-binding protein 1, a UUAG-specific nuclear RNA binding protein that may be involved in pre-mRNA splicing and telomere elongation. hnRNP D0 contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), in the middle and an RGG box rich in glycine and arginine residues in the C-terminal part. Each of RRMs can bind solely to the UUAG sequence specifically.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 510863322  90 KVFVGGLPQDISKSSLLQKFCAYGQVrldfpsEPTHPPRTRKADRRlstSGYVFLIYETEEAVFNLLK 157
Cdd:cd12583    1 KIFVGGLSPDTPEEKIREYFGAFGEV------ESIELPMDNKTNKR---RGFCFITFKEEEPVKKIME 59

RNA recognition motif (RRM) found in nucleolar protein 8 (NOL8) and similar proteins; This model corresponds to the RRM of NOL8 (also termed Nop132) encoded by a novel NOL8 gene that is up-regulated in the majority of diffuse-type, but not intestinal-type, gastric cancers. Thus, NOL8 may be a good molecular target for treatment of diffuse-type gastric cancer. Also, NOL8 is a phosphorylated protein that contains an N-terminal RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), suggesting NOL8 is likely to function as a novel RNA-binding protein. It may be involved in regulation of gene expression at the post-transcriptional level or in ribosome biogenesis in cancer cells.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 510863322  91 VFVGGLPQDISKSSLLQKFCAYGQVR-LDFPSEPTHPPRtrkadrrlstsGYVFLIYETEEAVFNLLKA 158
Cdd:cd12226    2 LFVGGLSPSITEDDLERRFSRFGTVSdVEIIRKKDAPDR-----------GFAYIDLRTSEAALQKCLS 59

RNA recognition motif 2 (RRM2) found in TAR DNA-binding protein 43 (TDP-43) and similar proteins; This subfamily corresponds to the RRM2 of TDP-43 (also termed TARDBP), a ubiquitously expressed pathogenic protein whose normal function and abnormal aggregation are directly linked to the genetic disease cystic fibrosis, and two neurodegenerative disorders: frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). TDP-43 binds both DNA and RNA, and has been implicated in transcriptional repression, pre-mRNA splicing and translational regulation. TDP-43 is a dimeric protein with two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a C-terminal glycine-rich domain. The RRMs are responsible for DNA and RNA binding; they bind to TAR DNA and RNA sequences with UG-repeats. The glycine-rich domain can interact with the hnRNP family proteins to form the hnRNP-rich complex involved in splicing inhibition. It is also essential for the cystic fibrosis transmembrane conductance regulator (CFTR) exon 9-skipping activity.

                         10        20
                 ....*....|....*....|....*..
gi 510863322  89 RKVFVGGLPQDISKSSLLQKFCAYGQV 115
Cdd:cd12322    1 RKVFVGRCTEDMTEDDLRQYFSQFGEV 27

RNA recognition motif 2 (RRM2) found in granule-associated RNA binding proteins (p40-TIA-1 and TIAR), and yeast nuclear and cytoplasmic polyadenylated RNA-binding protein PUB1; This subfamily corresponds to the RRM3 of TIA-1, TIAR, and PUB1. Nucleolysin TIA-1 isoform p40 (p40-TIA-1 or TIA-1) and nucleolysin TIA-1-related protein (TIAR) are granule-associated RNA binding proteins involved in inducing apoptosis in cytotoxic lymphocyte (CTL) target cells. They share high sequence similarity and are expressed in a wide variety of cell types. TIA-1 can be phosphorylated by a serine/threonine kinase that is activated during Fas-mediated apoptosis.TIAR is mainly localized in the nucleus of hematopoietic and nonhematopoietic cells. It is translocated from the nucleus to the cytoplasm in response to exogenous triggers of apoptosis. Both TIA-1 and TIAR bind specifically to poly(A) but not to poly(C) homopolymers. They are composed of three N-terminal highly homologous RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a glutamine-rich C-terminal auxiliary domain containing a lysosome-targeting motif. TIA-1 and TIAR interact with RNAs containing short stretches of uridylates and their RRM2 can mediate the specific binding to uridylate-rich RNAs. The C-terminal auxiliary domain may be responsible for interacting with other proteins. In addition, TIA-1 and TIAR share a potential serine protease-cleavage site (Phe-Val-Arg) localized at the junction between their RNA binding domains and their C-terminal auxiliary domains. This subfamily also includes a yeast nuclear and cytoplasmic polyadenylated RNA-binding protein PUB1, termed ARS consensus-binding protein ACBP-60, or poly uridylate-binding protein, or poly(U)-binding protein, which has been identified as both a heterogeneous nuclear RNA-binding protein (hnRNP) and a cytoplasmic mRNA-binding protein (mRNP). It may be stably bound to a translationally inactive subpopulation of mRNAs within the cytoplasm. PUB1 is distributed in both, the nucleus and the cytoplasm, and binds to poly(A)+ RNA (mRNA or pre-mRNA). Although it is one of the major cellular proteins cross-linked by UV light to polyadenylated RNAs in vivo, PUB1 is nonessential for cell growth in yeast. PUB1 also binds to T-rich single stranded DNA (ssDNA); however, there is no strong evidence implicating PUB1 in the mechanism of DNA replication. PUB1 contains three RRMs, and a GAR motif (glycine and arginine rich stretch) that is located between RRM2 and RRM3.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 510863322 205 TVFIGGVPRPLTSGELAALLeQNYGPLLycEIDVDPElfypKGAARAVFASYSSYVKAI 263
Cdd:cd12354    2 TVYVGNITKGLTEALLQQTF-SPFGQIL--EVRVFPD----KGYAFIRFDSHEAATHAI 53

RNA recognition motif (RRM) found in serine/arginine-rich splicing factor 3 (SRSF3) and similar proteins; This subfamily corresponds to the RRM of two serine/arginine (SR) proteins, serine/arginine-rich splicing factor 3 (SRSF3) and serine/arginine-rich splicing factor 7 (SRSF7). SRSF3, also termed pre-mRNA-splicing factor SRp20, modulates alternative splicing by interacting with RNA cis-elements in a concentration- and cell differentiation-dependent manner. It is also involved in termination of transcription, alternative RNA polyadenylation, RNA export, and protein translation. SRSF3 is critical for cell proliferation, and tumor induction and maintenance. It can shuttle between the nucleus and cytoplasm. SRSF7, also termed splicing factor 9G8, plays a crucial role in both constitutive splicing and alternative splicing of many pre-mRNAs. Its localization and functions are tightly regulated by phosphorylation. SRSF7 is predominantly present in the nuclear and can shuttle between nucleus and cytoplasm. It cooperates with the export protein, Tap/NXF1, helps mRNA export to the cytoplasm, and enhances the expression of unspliced mRNA. Moreover, SRSF7 inhibits tau E10 inclusion through directly interacting with the proximal downstream intron of E10, a clustering region for frontotemporal dementia with Parkinsonism (FTDP) mutations. Both SRSF3 and SRSF7 contain a single N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal RS domain rich in serine-arginine dipeptides. The RRM domain is involved in RNA binding, and the RS domain has been implicated in protein shuttling and protein-protein interactions.

                         10        20
                 ....*....|....*....|....*..
gi 510863322  90 KVFVGGLPQDISKSSLLQKFCAYGQVR 116
Cdd:cd12373    1 KVYVGNLGPRVTKRELEDAFEKYGPLR 27

B-box zinc finger;

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 510863322  288 DEILCDECLEAAATHFCRVCMQYYCEACSIRM--DHSV 323
Cdd:pfam00643   2 KERLCPEHEEEPLTLYCNDCQELLCEECSVGEhrGHTV 39