Transactive response DNA-binding protein N-terminal domain; This domain can be found at the N-terminal region of transactive response DNA-binding protein 43 kDa (TDP-43), an RNA transporting and processing protein whose aberrant aggregates are implicated in neurodegenerative diseases. TDP-43 N-terminal domain has been shown to play an important role in the aggregation of TDP-43 monomers and its loss of function affects the RNA metabolic levels. Secondary structure of the N-terminal domain consists of six beta-strands and it resembles axin 1.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1529015658  24 YVLVGESEDGEKLELPTNPpDKSLGFSTLTHAFPGAQGLKFKNPVTKASRALLMDssGTKFLPPADGWKDKTFIVIY 100
Cdd:pfam18694   1 YVQVSEDEGDEPIEIPLED-DGTLLLSTLQAQFPGACGLKYRNPETGCKRGVRLD--DGKLHPPAGGWGNKVYYVVF 74

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 1529015658 238 SRIFVGRLPEKFTVEDLRNFFNEEAAkidpeacVTDVFIPRPFRSFAFVNFSSSLVARTIIKlGDVVLDGCSLAVSAA 315
Cdd:cd12322     1 RKVFVGRCTEDMTEDDLRQYFSQFGE-------VTDVFIPKPFRAFAFVTFADDEVAQSLCG-EDHIIKGVSVHISNA 70

Transactive response DNA-binding protein N-terminal domain; This domain can be found at the N-terminal region of transactive response DNA-binding protein 43 kDa (TDP-43), an RNA transporting and processing protein whose aberrant aggregates are implicated in neurodegenerative diseases. TDP-43 N-terminal domain has been shown to play an important role in the aggregation of TDP-43 monomers and its loss of function affects the RNA metabolic levels. Secondary structure of the N-terminal domain consists of six beta-strands and it resembles axin 1.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1529015658  24 YVLVGESEDGEKLELPTNPpDKSLGFSTLTHAFPGAQGLKFKNPVTKASRALLMDssGTKFLPPADGWKDKTFIVIY 100
Cdd:pfam18694   1 YVQVSEDEGDEPIEIPLED-DGTLLLSTLQAQFPGACGLKYRNPETGCKRGVRLD--DGKLHPPAGGWGNKVYYVVF 74

N-terminal domain of transactive response DNA-binding protein 43; Transactive response DNA-binding protein of 43 kDa (TDP-43) is a nuclear DNA/RNA-binding protein involved in gene transcription and mRNA processing, transport, and translational regulation. It is vital to pre-mRNA and microRNA processing and regulates stress granule activity through the differential regulation of G3BP and TIA-1. It also forms aggregates implicated in amyotrophic lateral sclerosis. The N-terminal domain of TDP-43 is required for its physiological functions and pathological aggregation.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1529015658  24 YVLVGESEDGEKLELPTNPpDKSLGFSTLTHAFPGAQGLKFKNPVTKasRALLMDSSGTKFLPPADGWKDKTFIVIY 100
Cdd:cd19609     1 YVRVAEDEGDEPIEVPLEE-DGTLLLSTLQAQFPGATGLKYRNPETG--RARGVRLVDGKLYPPEGGWGDRVYYVVF 74

RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1529015658  154 LIVLGIPYTTSSETCKAYFELFGDVVMFDLKKD-ASGNSKGFGFVRMADYNAQIRVLAK-QTHEIDGRRCQV 223
Cdd:smart00360   2 LFVGNLPPDTTEEELRELFSKFGKVESVRLVRDkETGKSKGFAFVEFESEEDAEKALEAlNGKELDGRPLKV 73

RNA recognition motif (RRM) domain [Translation, ribosomal structure and biogenesis];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1529015658 239 RIFVGRLPEKFTVEDLRNFFNE----EAAKIdpeacVTDVFIPRPfRSFAFVNFSSSLVARTII-KLGDVVLDGCSLAVS 313
Cdd:COG0724     3 KIYVGNLPYSVTEEDLRELFSEygevTSVKL-----ITDRETGRS-RGFGFVEMPDDEEAQAAIeALNGAELMGRTLKVN 76

                  ....*.
gi 1529015658 314 AAAPRE 319
Cdd:COG0724    77 EARPRE 82

RNA recognition motif;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1529015658  239 RIFVGRLPEKFTVEDLRNFFNEEAAkidpeacVTDVFIPRP-----FRSFAFVNFSSSLVARTIIK-LGDVVLDGCSLAV 312
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSKFGK-------VESVRLVRDketgkSKGFAFVEFESEEDAEKALEaLNGKELDGRPLKV 73

heterogeneous nuclear ribonucleoprotein R, Q family; Sequences in this subfamily include the human heterogeneous nuclear ribonucleoproteins (hnRNP) R, Q, and APOBEC-1 complementation factor (aka APOBEC-1 stimulating protein). These proteins contain three RNA recognition domains (rrm: pfam00076) and a somewhat variable C-terminal domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1529015658 172 FELFGDVVMFDLKKDASGNSKGFGFVRMAD-YNAQIRVLAKQTHEI-DGRRCQVKIPLSKgesaqatvSRIFVGRLPEKF 249
Cdd:TIGR01648  79 FEKAGPIYELRLMMDFSGQNRGYAFVTFCGkEEAKEAVKLLNNYEIrPGRLLGVCISVDN--------CRLFVGGIPKNK 150

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1529015658 250 TVEDLRnffnEEAAKIDpEACVTDVFIPRPF-----RSFAFVNFSS---SLVARTIIKLGDVVLDGCSLAVSAAAPREAP 321
Cdd:TIGR01648 151 KREEIL----EEFSKVT-EGVVDVIVYHSAAdkkknRGFAFVEYEShraAAMARRKLMPGRIQLWGHVIAVDWAEPEEEV 225

                  .
gi 1529015658 322 D 322
Cdd:TIGR01648 226 D 226

U2 snRNP auxilliary factor, large subunit, splicing factor; These splicing factors consist of an N-terminal arginine-rich low complexity domain followed by three tandem RNA recognition motifs (pfam00076). The well-characterized members of this family are auxilliary components of the U2 small nuclear ribonuclearprotein splicing factor (U2AF). These proteins are closely related to the CC1-like subfamily of splicing factors (TIGR01622). Members of this subfamily are found in plants, metazoa and fungi.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1529015658 154 LIVLGIPYTTSSETCKAYFELFGDVVMFDLKKD-ASGNSKGFGFVRMADYN 203
Cdd:TIGR01642 298 IYIGNLPLYLGEDQIKELLESFGDLKAFNLIKDiATGLSKGYAFCEYKDPS 348

Transactive response DNA-binding protein N-terminal domain; This domain can be found at the N-terminal region of transactive response DNA-binding protein 43 kDa (TDP-43), an RNA transporting and processing protein whose aberrant aggregates are implicated in neurodegenerative diseases. TDP-43 N-terminal domain has been shown to play an important role in the aggregation of TDP-43 monomers and its loss of function affects the RNA metabolic levels. Secondary structure of the N-terminal domain consists of six beta-strands and it resembles axin 1.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1529015658  24 YVLVGESEDGEKLELPTNPpDKSLGFSTLTHAFPGAQGLKFKNPVTKASRALLMDssGTKFLPPADGWKDKTFIVIY 100
Cdd:pfam18694   1 YVQVSEDEGDEPIEIPLED-DGTLLLSTLQAQFPGACGLKYRNPETGCKRGVRLD--DGKLHPPAGGWGNKVYYVVF 74

N-terminal domain of transactive response DNA-binding protein 43; Transactive response DNA-binding protein of 43 kDa (TDP-43) is a nuclear DNA/RNA-binding protein involved in gene transcription and mRNA processing, transport, and translational regulation. It is vital to pre-mRNA and microRNA processing and regulates stress granule activity through the differential regulation of G3BP and TIA-1. It also forms aggregates implicated in amyotrophic lateral sclerosis. The N-terminal domain of TDP-43 is required for its physiological functions and pathological aggregation.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1529015658  24 YVLVGESEDGEKLELPTNPpDKSLGFSTLTHAFPGAQGLKFKNPVTKasRALLMDSSGTKFLPPADGWKDKTFIVIY 100
Cdd:cd19609     1 YVRVAEDEGDEPIEVPLEE-DGTLLLSTLQAQFPGATGLKYRNPETG--RARGVRLVDGKLYPPEGGWGDRVYYVVF 74

RNA recognition motif (RRM) found in eukaryotic RNA-binding protein RBM24, RBM38 and similar proteins; This subfamily corresponds to the RRM of RBM24 and RBM38 from vertebrate, SUPpressor family member SUP-12 from Caenorhabditis elegans and similar proteins. Both, RBM24 and RBM38, are preferentially expressed in cardiac and skeletal muscle tissues. They regulate myogenic differentiation by controlling the cell cycle in a p21-dependent or -independent manner. RBM24, also termed RNA-binding region-containing protein 6, interacts with the 3'-untranslated region (UTR) of myogenin mRNA and regulates its stability in C2C12 cells. RBM38, also termed CLL-associated antigen KW-5, or HSRNASEB, or RNA-binding region-containing protein 1(RNPC1), or ssDNA-binding protein SEB4, is a direct target of the p53 family. It is required for maintaining the stability of the basal and stress-induced p21 mRNA by binding to their 3'-UTRs. It also binds the AU-/U-rich elements in p63 3'-UTR and regulates p63 mRNA stability and activity. SUP-12 is a novel tissue-specific splicing factor that controls muscle-specific splicing of the ADF/cofilin pre-mRNA in C. elegans. All family members contain a conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1529015658 152 TDLIVLGIPYTTSSETCKAYFELFGD----VVMFDlkkDASGNSKGFGFVRMADYNAQIRVLAKQTHEIDGRRCQV 223
Cdd:cd12384     1 TKIFVGGLPYHTTDDSLREYFEQFGEieeaVVITD---RQTGKSRGYGFVTMADREAAERACKDPNPIIDGRKANV 73

RNA recognition motif 1 (RRM1) found in heterogeneous nuclear ribonucleoprotein hnRNP A and hnRNP D subfamilies and similar proteins; This subfamily corresponds to the RRM1 in the hnRNP A subfamily which includes hnRNP A0, hnRNP A1, hnRNP A2/B1, hnRNP A3 and similar proteins. hnRNP A0 is a low abundance hnRNP protein that has been implicated in mRNA stability in mammalian cells. hnRNP A1 is an abundant eukaryotic nuclear RNA-binding protein that may modulate splice site selection in pre-mRNA splicing. hnRNP A2/B1 is an RNA trafficking response element-binding protein that interacts with the hnRNP A2 response element (A2RE). hnRNP A3 is also a RNA trafficking response element-binding protein that participates in the trafficking of A2RE-containing RNA. The hnRNP A subfamily is characterized by two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a long glycine-rich region at the C-terminus. The hnRNP D subfamily includes hnRNP D0, hnRNP A/B, hnRNP DL and similar proteins. hnRNP D0 is 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. hnRNP A/B 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 members in this subfamily contain two putative RRMs and a glycine- and tyrosine-rich C-terminus. The family also contains DAZAP1 (Deleted in azoospermia-associated protein 1), RNA-binding protein Musashi homolog Musashi-1, Musashi-2 and similar proteins. They all harbor two RRMs.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1529015658 154 LIVLGIPYTTSSETCKAYFELFGDVVMFDLKKD-ASGNSKGFGFVRMADYNAQIRVLAKQTHEIDGRRCQVK 224
Cdd:cd12325     1 LFVGGLSWETTEESLREYFSKYGEVVDCVVMKDpATGRSRGFGFVTFKDPSSVDAVLAARPHTLDGRTIDPK 72

RNA recognition motif 1 (RRM1) found in Deleted in azoospermia-associated protein 1 (DAZAP1) and similar proteins; This subfamily corresponds to the RRM1 of DAZAP1 or DAZ-associated protein 1, also termed proline-rich RNA binding protein (Prrp), a multi-functional ubiquitous RNA-binding protein expressed most abundantly in the testis and essential for normal cell growth, development, and spermatogenesis. DAZAP1 is a shuttling protein whose acetylated form is predominantly nuclear and the nonacetylated form is in cytoplasm. It also functions as a translational regulator that activates translation in an mRNA-specific manner. DAZAP1 was initially identified as a binding partner of Deleted in Azoospermia (DAZ). It also interacts with numerous hnRNPs, including hnRNP U, hnRNP U like-1, hnRNPA1, hnRNPA/B, and hnRNP D, suggesting DAZAP1 might associate and cooperate with hnRNP particles to regulate adenylate-uridylate-rich elements (AU-rich element or ARE)-containing mRNAs. DAZAP1 contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a C-terminal proline-rich domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1529015658 154 LIVLGIPYTTSSETCKAYFELFGDVVMFDLKKDASGN-SKGFGFVRMADYNAQIRVLAKQTHEIDGR 219
Cdd:cd12574     2 LFVGGLDWSTTQETLRSYFSQYGEVVDCVIMKDKTTNqSRGFGFVKFKDPNCVGTVLASRPHNLDGR 68

RNA recognition motif 1 (RRM1) found in RNA-binding protein Musashi homolog Musashi-1, Musashi-2 and similar proteins; This subfamily corresponds to the RRM1 in Musashi-1 and Musashi-2. Musashi-1 (also termed Msi1) is a neural RNA-binding protein putatively expressed in central nervous system (CNS) stem cells and neural progenitor cells, and associated with asymmetric divisions in neural progenitor cells. It is evolutionarily conserved from invertebrates to vertebrates. Musashi-1 is a homolog of Drosophila Musashi and Xenopus laevis nervous system-specific RNP protein-1 (Nrp-1). It has been implicated in the maintenance of the stem-cell state, differentiation, and tumorigenesis. It translationally regulates the expression of a mammalian numb gene by binding to the 3'-untranslated region of mRNA of Numb, encoding a membrane-associated inhibitor of Notch signaling, and further influences neural development. Moreover, Musashi-1 represses translation by interacting with the poly(A)-binding protein and competes for binding of the eukaryotic initiation factor-4G (eIF-4G). Musashi-2 (also termed Msi2) has been identified as a regulator of the hematopoietic stem cell (HSC) compartment and of leukemic stem cells after transplantation of cells with loss and gain of function of the gene. It influences proliferation and differentiation of HSCs and myeloid progenitors, and further modulates normal hematopoiesis and promotes aggressive myeloid leukemia. Both, Musashi-1 and Musashi-2, contain two conserved N-terminal tandem RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), along with other domains of unknown function.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1529015658 158 GIPYTTSSETCKAYFELFGDV----VMFDlkkDASGNSKGFGFVRMADYNAQIRVLAKQTHEIDGRRCQVKI 225
Cdd:cd12576     6 GLSWQTTPEGLREYFSKFGEItecmVMRD---PTTKRSRGFGFVTFSDPASVDKVLAQGPHELDGKKIDPKV 74

RNA recognition motif 1 (RRM1) found in heterogeneous nuclear ribonucleoprotein A/B (hnRNP A/B) and similar proteins; This subgroup corresponds to the RRM1 of hnRNP A/B, also termed APOBEC1-binding protein 1 (ABBP-1), which is an RNA unwinding protein with a high affinity for G- followed by U-rich regions. hnRNP A/B 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 A/B contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a long C-terminal glycine-rich domain that contains a potential ATP/GTP binding loop.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1529015658 148 EKNCTDLIVLGIPYTTSSETCKAYFELFGDVVMFDLKKDA-SGNSKGFGFVRMADYNAQIRVLAKQTHEIDGR 219
Cdd:cd12757     1 EEDAGKMFVGGLSWDTSKKDLKDYFTKFGEVVDCTIKMDPnTGRSRGFGFILFKDAASVDKVLEQKEHRLDGR 73

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein A3 (hnRNP A3) and similar proteins; This subgroup corresponds to the RRM2 of hnRNP A3, a novel RNA trafficking response element-binding protein that interacts with the hnRNP A2 response element (A2RE) independently of hnRNP A2 and participates in the trafficking of A2RE-containing RNA. hnRNP A3 can shuttle between the nucleus and the cytoplasm. It contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a long glycine-rich region at the C-terminus.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1529015658 154 LIVLGIPYTTSSETCKAYFELFGDVVMFDLKKD-ASGNSKGFGFVRMADYNAQIRVLAKQTHEIDGRRCQVKIPLSK 229
Cdd:cd12582     3 IFVGGIKEDTEEYHLRDYFEKYGKIETIEVMEDrQSGKKRGFAFVTFDDHDTVDKIVVQKYHTINGHNCEVKKALSK 79

RNA recognition motif 2 (RRM2) found in Saccharomyces cerevisiae protein HRB1, G-strand-binding protein 2 (GBP2) and similar proteins; The family includes Saccharomyces cerevisiae protein HRB1 (also called protein TOM34) and GBP2, both of which are SR-like mRNA-binding proteins which shuttle from the nucleus to the cytoplasm when bound to the mature mRNA molecules. They act as quality control factors for spliced mRNAs. GBP2, also called RAP1 localization factor 6, is a single-strand telomeric DNA-binding protein that binds single-stranded telomeric sequences of the type (TG[1-3])n in vitro. It also binds to RNA. GBP2 influences the localization of RAP1 in the nuclei and plays a role in modulating telomere length. Members in this family contain three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The model corresponds to the second RRM motif.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1529015658 153 DLIVLGIPYTTSSETCKAYFELFGDVVMFDLKKDASGNSKGFGFVRMADYNAQIRVLAKQT-HEIDGRRCQVK 224
Cdd:cd21606     3 EVFIANLPYSINWQALKDMFKECGDVLRADVELDYNGRSRGFGTVIYATEEEMHRAIDTFNgYELEGRVLEVK 75

RNA recognition motif (RRM) domain [Translation, ribosomal structure and biogenesis];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1529015658 239 RIFVGRLPEKFTVEDLRNFFNE----EAAKIdpeacVTDVFIPRPfRSFAFVNFSSSLVARTII-KLGDVVLDGCSLAVS 313
Cdd:COG0724     3 KIYVGNLPYSVTEEDLRELFSEygevTSVKL-----ITDRETGRS-RGFGFVEMPDDEEAQAAIeALNGAELMGRTLKVN 76

                  ....*.
gi 1529015658 314 AAAPRE 319
Cdd:COG0724    77 EARPRE 82

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein A/B (hnRNP A/B) and similar proteins; This subgroup corresponds to the RRM2 of hnRNP A/B, also termed APOBEC1-binding protein 1 (ABBP-1), an RNA unwinding protein with a high affinity for G- followed by U-rich regions. hnRNP A/B 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 A/B contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a long C-terminal glycine-rich domain that contains a potential ATP/GTP binding loop.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1529015658 144 EDPSEKnctdLIVLGIPYTTSSETCKAYFELFGDVVMFDLKKDASGNSK-GFGFVRMADYNAQIRVLAKQTHEIDGRRCQ 222
Cdd:cd12584     1 KDPVKK----IFVGGLNPETTEEKIREYFGEFGEIEAIELPMDPKTNKRrGFVFITFKEEDPVKKILEKKFHNVSGSKCE 76

                  ...
gi 1529015658 223 VKI 225
Cdd:cd12584    77 IKI 79

RNA recognition motif;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1529015658  239 RIFVGRLPEKFTVEDLRNFFNEEAAkidpeacVTDVFIPRP-----FRSFAFVNFSSSLVARTIIK-LGDVVLDGCSLAV 312
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSKFGK-------VESVRLVRDketgkSKGFAFVEFESEEDAEKALEaLNGKELDGRPLKV 73

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) and similar proteins; This subgroup corresponds to the RRM2 of hnRNP A1, also termed helix-destabilizing protein, or single-strand RNA-binding protein, or hnRNP core protein A1, an abundant eukaryotic nuclear RNA-binding protein that may modulate splice site selection in pre-mRNA splicing. hnRNP A1 has been characterized as a splicing silencer, often acting in opposition to an activating hnRNP H. It silences exons when bound to exonic elements in the alternatively spliced transcripts of c-src, HIV, GRIN1, and beta-tropomyosin. hnRNP A1 can shuttle between the nucleus and the cytoplasm. Thus, it may be involved in transport of cellular RNAs, including the packaging of pre-mRNA into hnRNP particles and transport of poly A+ mRNA from the nucleus to the cytoplasm. The cytoplasmic hnRNP A1 has high affinity with AU-rich elements, whereas the nuclear hnRNP A1 has high affinity with a polypyrimidine stretch bordered by AG at the 3' ends of introns. hnRNP A1 is also involved in the replication of an RNA virus, such as mouse hepatitis virus (MHV), through an interaction with the transcription-regulatory region of viral RNA. Moreover, hnRNP A1, together with the scaffold protein septin 6, serves as host proteins to form a complex with NS5b and viral RNA, and further play important roles in the replication of Hepatitis C virus (HCV). hnRNP A1 contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a long glycine-rich region at the C-terminus. The RRMs of hnRNP A1 play an important role in silencing the exon and the glycine-rich domain is responsible for protein-protein interactions.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1529015658 154 LIVLGIPYTTSSETCKAYFELFGDVVMFDLKKD-ASGNSKGFGFVRMADYNAQIRVLAKQTHEIDGRRCQVKIPL 227
Cdd:cd12580     3 IFVGGIKEDTEEHHLRDYFEQYGKIEVIEIMTDrGSGKKRGFAFVTFDDHDSVDKIVIQKYHTVNGHNCEVRKAL 77

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1529015658 156 VLGIPYTTSSETCKAYFELFGDVVMFDLKKDASGNSKGFGFVRMADYNAQIRVLAKQTH-EIDGRRCQVKIPLSK 229
Cdd:cd12412     7 VGGIDWDTTEEELREFFSKFGKVKDVKIIKDRAGVSKGYGFVTFETQEDAEKIQKWGANlVFKGKKLNVGPAIRK 81

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1529015658 154 LIVLGIPYTTSSETCKAYFELFGDVVMFDLKKDASGNS-KGFGFVRMADYNAQIRVLAKQTHEIDGRRCQVK 224
Cdd:cd12329     2 IFVGGLSPETTEEKIREYFGKFGNIVEIELPMDKKTNKrRGFCFITFDSEEPVKKILETQFHVIGGKKVEVK 73

RNA recognition motif 2 (RRM2) found in Nicotiana sylvestris chloroplastic 33 kDa ribonucleoprotein (NsCP33) and similar proteins; The family includes NsCP33, Arabidopsis thaliana chloroplastic 31 kDa ribonucleoprotein (CP31A) and mitochondrial glycine-rich RNA-binding protein 2 (AtGR-RBP2). NsCP33 may be involved in splicing and/or processing of chloroplast RNA's. AtCP31A, also called RNA-binding protein 1/2/3 (AtRBP33), or RNA-binding protein CP31A, or RNA-binding protein RNP-T, or RNA-binding protein cp31, is required for specific RNA editing events in chloroplasts and stabilizes specific chloroplast mRNAs, as well as for normal chloroplast development under cold stress conditions by stabilizing transcripts of numerous mRNAs under these conditions. CP31A may modulate telomere replication through RNA binding domains. AtGR-RBP2, also called AtRBG2, or glycine-rich protein 2 (AtGRP2), or mitochondrial RNA-binding protein 1a (At-mRBP1a), plays a role in RNA transcription or processing during stress. It binds RNAs and DNAs sequence with a preference to single-stranded nucleic acids. AtGR-RBP2 displays strong affinity to poly(U) sequence. It exerts cold and freezing tolerance, probably by exhibiting an RNA chaperone activity during the cold and freezing adaptation process. Some members in this family contain two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The model corresponds to the second RRM motif.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1529015658 154 LIVLGIPYTTSSETCKAYFELFGDV----VMFDlkkDASGNSKGFGFVRMADYN-AQIRVLAKQTHEIDGRRCQVKI 225
Cdd:cd21608     2 LYVGNLSWDTTEDDLRDLFSEFGEVesakVITD---RETGRSRGFGFVTFSTAEaAEAAIDALNGKELDGRSIVVNE 75

RNA recognition motif 2 (RRM2) found in RNA-binding protein Musashi homologs Musashi-1, Musashi-2 and similar proteins; This subfamily corresponds to the RRM2.in Musashi-1 (also termed Msi1), a neural RNA-binding protein putatively expressed in central nervous system (CNS) stem cells and neural progenitor cells, and associated with asymmetric divisions in neural progenitor cells. It is evolutionarily conserved from invertebrates to vertebrates. Musashi-1 is a homolog of Drosophila Musashi and Xenopus laevis nervous system-specific RNP protein-1 (Nrp-1). It has been implicated in the maintenance of the stem-cell state, differentiation, and tumorigenesis. It translationally regulates the expression of a mammalian numb gene by binding to the 3'-untranslated region of mRNA of Numb, encoding a membrane-associated inhibitor of Notch signaling, and further influences neural development. Moreover, Musashi-1 represses translation by interacting with the poly(A)-binding protein and competes for binding of the eukaryotic initiation factor-4G (eIF-4G). Musashi-2 (also termed Msi2) has been identified as a regulator of the hematopoietic stem cell (HSC) compartment and of leukemic stem cells after transplantation of cells with loss and gain of function of the gene. It influences proliferation and differentiation of HSCs and myeloid progenitors, and further modulates normal hematopoiesis and promotes aggressive myeloid leukemia. Both, Musashi-1 and Musashi-2, contain two conserved N-terminal tandem RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), along with other domains of unknown function.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1529015658 156 VLGIPYTTSSETCKAYFELFGDV----VMFDlkkDASGNSKGFGFVRMADYNAQIRVLAKQTHEIDGRRCQVK 224
Cdd:cd12323     4 VGGLSANTTEDDVKKYFSQFGKVedamLMFD---KQTNRHRGFGFVTFESEDVVDKVCEIHFHEINNKMVECK 73

RNA recognition motif 1 (RRM1) found in yeast nuclear polyadenylated RNA-binding protein 4 (Hrp1p or Nab4p) and similar proteins; This subfamily corresponds to the RRM1 of Hrp1p and similar proteins. Hrp1p or Nab4p, also termed cleavage factor IB (CFIB), is a sequence-specific trans-acting factor that is essential for mRNA 3'-end formation in yeast Saccharomyces cerevisiae. It can be UV cross-linked to RNA and specifically recognizes the (UA)6 RNA element required for both, the cleavage and poly(A) addition, steps. Moreover, Hrp1p can shuttle between the nucleus and the cytoplasm, and play an additional role in the export of mRNAs to the cytoplasm. Hrp1p also interacts with Rna15p and Rna14p, two components of CF1A. In addition, Hrp1p functions as a factor directly involved in modulating the activity of the nonsense-mediated mRNA decay (NMD) pathway. It binds specifically to a downstream sequence element (DSE)-containing RNA and interacts with Upf1p, a component of the surveillance complex, further triggering the NMD pathway. Hrp1p contains two central RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and an arginine-glycine-rich region harboring repeats of the sequence RGGF/Y.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1529015658 158 GIPYTTSSETCKAYFELFGDVV-MFDLKKDASGNSKGFGFVRMADYNAQIRVLAKQtHEIDGR 219
Cdd:cd12577     5 GLNWDTTEEGLRDYFSQFGTVVdCTIMKDSATGRSRGFGFLTFEDPSSVNEVMKKE-HVLDGK 66

RNA recognition motif 1 (RRM1) found in RNA-binding protein Musashi homolog 1 (Musashi-1) and similar proteins; This subgroup corresponds to the RRM1 of Musashi-1. The mammalian MSI1 gene encoding Musashi-1 (also termed Msi1) is a neural RNA-binding protein putatively expressed in central nervous system (CNS) stem cells and neural progenitor cells and associated with asymmetric divisions in neural progenitor cells. Musashi-1 is evolutionarily conserved from invertebrates to vertebrates. It is a homolog of Drosophila Musashi and Xenopus laevis nervous system-specific RNP protein-1 (Nrp-1). Musashi-1 has been implicated in the maintenance of the stem-cell state, differentiation, and tumorigenesis. It translationally regulates the expression of a mammalian numb gene by binding to the 3'-untranslated region of mRNA of Numb, encoding a membrane-associated inhibitor of Notch signaling, and further influences neural development. Moreover, it represses translation by interacting with the poly(A)-binding protein and competes for binding of the eukaryotic initiation factor-4G (eIF-4G). Musashi-1 contains two conserved N-terminal tandem RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), along with other domains of unknown function.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1529015658 154 LIVLGIPYTTSSETCKAYFELFGDVVMFDLKKD-ASGNSKGFGFVRMADYNAQIRVLAKQTHEIDGRRCQVKI 225
Cdd:cd12759     3 MFIGGLSWQTTQEGLREYFGQFGEVKECLVMRDpLTKRSRGFGFVTFMDQAGVDKVLAQSRHELDSKTIDPKV 75

RNA recognition motif 1 (RRM1) found in RNA-binding protein Musashi homolog 2 (Musashi-2 ) and similar proteins; This subgroup corresponds to the RRM2 of Musashi-2 (also termed Msi2) which has been identified as a regulator of the hematopoietic stem cell (HSC) compartment and of leukemic stem cells after transplantation of cells with loss and gain of function of the gene. It influences proliferation and differentiation of HSCs and myeloid progenitors, and further modulates normal hematopoiesis and promotes aggressive myeloid leukemia. Musashi-2 contains two conserved N-terminal tandem RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), along with other domains of unknown function.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1529015658 148 EKNCTDLIVLGIPYTTSSETCKAYFELFGDVVMFDLKKD-ASGNSKGFGFVRMADYNAQIRVLAKQTHEIDGRRCQVKIP 226
Cdd:cd12760     1 QHDPGKMFIGGLSWQTSPDSLRDYFSKFGEIRECMVMRDpTTKRSRGFGFVTFADPASVDKVLAQPHHELDSKTIDPKVA 80

                  ...
gi 1529015658 227 LSK 229
Cdd:cd12760    81 FPR 83

RNA recognition motif 1 (RRM1) found in heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) and similar proteins; This subgroup corresponds to the RRM1 of hnRNP A2/B1 which is an RNA trafficking response element-binding protein that interacts with the hnRNP A2 response element (A2RE). Many mRNAs, such as myelin basic protein (MBP), myelin-associated oligodendrocytic basic protein (MOBP), carboxyanhydrase II (CAII), microtubule-associated protein tau, and amyloid precursor protein (APP) are trafficked by hnRNP A2/B1. hnRNP A2/B1 also functions as a splicing factor that regulates alternative splicing of the tumor suppressors, such as BIN1, WWOX, the antiapoptotic proteins c-FLIP and caspase-9B, the insulin receptor (IR), and the RON proto-oncogene among others. Moreover, the overexpression of hnRNP A2/B1 has been described in many cancers. It functions as a nuclear matrix protein involving in RNA synthesis and the regulation of cellular migration through alternatively splicing pre-mRNA. It may play a role in tumor cell differentiation. hnRNP A2/B1 contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a long glycine-rich region at the C-terminus.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1529015658 154 LIVLGIPYTTSSETCKAYFELFGD----VVMFDlkkDASGNSKGFGFVRMADYNAQIRVLAKQTHEIDGRRCQVK 224
Cdd:cd12762     5 LFIGGLSFETTEESLRNYYEQWGKltdcVVMRD---PASKRSRGFGFVTFSSMAEVDAAMAARPHSIDGRVVEPK 76

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein D-like (hnRNP DL) and similar proteins; This subgroup corresponds to the RRM2 of hnRNP DL (or hnRNP D-like), also termed AU-rich element RNA-binding factor, or JKT41-binding protein (protein laAUF1 or JKTBP), 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. hnRNP DL binds single-stranded DNA (ssDNA) or double-stranded DNA (dsDNA) in a non-sequencespecific manner, and interacts with poly(G) and poly(A) tenaciously. It contains two putative two 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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1529015658 154 LIVLGIPYTTSSETCKAYFELFGDVVMFDLKKDASGNSK-GFGFVRMADYNAQIRVLAKQTHEIDGRRCQVKI 225
Cdd:cd12585     2 VFVGGLSPDTSEEQIKEYFGAFGEIENIELPMDTKTNERrGFCFITYTDEEPVQKLLESRYHQIGSGKCEIKV 74

RNA recognition motif 1 (RRM1) found in chloroplastic plastid-specific 30S ribosomal protein 2 (PSRP-2) and similar proteins; PSRP-2, also called chloroplastic 30S ribosomal protein 2, or chloroplastic small ribosomal subunit protein cS22, is a component of the chloroplast ribosome (chloro-ribosome), a dedicated translation machinery responsible for the synthesis of chloroplast genome-encoded proteins, including proteins of the transcription and translation machinery and components of the photosynthetic apparatus. It binds single strand DNA (ssDNA) and RNA in vitro. It exhibits RNA chaperone activity and regulates negatively resistance responses to abiotic stresses during seed germination (e.g. salt, dehydration, and low temperature) and seedling growth (e.g. salt). The family also includes Nicotiana sylvestris chloroplastic 33 kDa ribonucleoprotein (NsCP33) and Arabidopsis thaliana chloroplastic 31 kDa ribonucleoprotein (AtCP31A). NsCP33 may be involved in splicing and/or processing of chloroplast RNA's. AtCP31A, also called RNA-binding protein 1/2/3 (AtRBP33), or RNA-binding protein CP31A, or RNA-binding protein RNP-T, or RNA-binding protein cp31, is required for specific RNA editing events in chloroplasts and stabilizes specific chloroplast mRNAs, as well as for normal chloroplast development under cold stress conditions by stabilizing transcripts of numerous mRNAs under these conditions. CP31A may modulate telomere replication through RNA binding domains. Members in this family contain two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The model corresponds to the first RRM motif.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1529015658 154 LIVLGIPYTTSSETCKAYFELFGDV----VMFDlkkDASGNSKGFGFVRMADYN-AQIRVLAKQTHEIDGRRCQVKIP 226
Cdd:cd21609     2 LYVGNIPRNVTSEELAKIFEEAGTVeiaeVMYD---RYTGRSRGFGFVTMGSVEdAKAAIEKLNGTEVGGREIKVNIT 76

RNA recognition motif 2 (RRM2) found in yeast multiple RNA-binding domain-containing protein 1 (MRD1) and similar proteins; This subgroup corresponds to the RRM2 of MRD1 which is encoded by a novel yeast gene MRD1 (multiple RNA-binding domain). It is well-conserved in yeast and its homologs exist in all eukaryotes. MRD1 is present in the nucleolus and the nucleoplasm. It interacts with the 35 S precursor rRNA (pre-rRNA) and U3 small nucleolar RNAs (snoRNAs). It is essential for the initial processing at the A0-A2 cleavage sites in the 35 S pre-rRNA. MRD1 contains 5 conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), which may play an important structural role in organizing specific rRNA processing events.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1529015658 154 LIVLGIPYTTSSETCKAYFELFGDV----VMFDLKkdaSGNSKGFGFVRMADYNAQIRVLAkqthEIDGRRCQ 222
Cdd:cd12566     5 LFLRNLPYSTKEDDLQKLFSKFGEVsevhVPIDKK---TKKSKGFAYVLFLDPEDAVQAYN----ELDGKVFQ 70

ELAV/HuD family splicing factor; This model describes the ELAV/HuD subfamily of splicing factors found in metazoa. HuD stands for the human paraneoplastic encephalomyelitis antigen D of which there are 4 variants in human. ELAV stnds for the Drosophila Embryonic lethal abnormal visual protein. ELAV-like splicing factors are also known in human as HuB (ELAV-like protein 2), HuC (ELAV-like protein 3, Paraneoplastic cerebellar degeneration-associated antigen) and HuR (ELAV-like protein 1). These genes are most closely related to the sex-lethal subfamily of splicing factors found in Dipteran insects (TIGR01659). These proteins contain 3 RNA-recognition motifs (rrm: pfam00076).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1529015658 152 TDLIVLGIPYTTSSETCKAYFELFGDVVMFDLKKDAS-GNSKGFGFV---RMADYNAQIRVLakqtheiDGRRCQ---VK 224
Cdd:TIGR01661   4 TNLIVNYLPQTMTQEEIRSLFTSIGEIESCKLVRDKVtGQSLGYGFVnyvRPEDAEKAVNSL-------NGLRLQnktIK 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1529015658 225 IPLSKGESAQATVSRIFVGRLPEKFTVEDLRNFFNEEAAKIDPEAC---VTDVfiprpFRSFAFVNFSSSLVA-RTIIKL 300
Cdd:TIGR01661  77 VSYARPSSDSIKGANLYVSGLPKTMTQHELESIFSPFGQIITSRILsdnVTGL-----SKGVGFIRFDKRDEAdRAIKTL 151

                  ....*....
gi 1529015658 301 GDVVLDGCS 309
Cdd:TIGR01661 152 NGTTPSGCT 160

RNA recognition motif 1 (RRM1) found in Arabidopsis thaliana phragmoplastin interacting protein 1 (PHIP1) and similar proteins; This subfamily corresponds to the RRM1 of PHIP1. A. thaliana PHIP1 and its homologs represent a novel class of plant-specific RNA-binding proteins that may play a unique role in the polarized mRNA transport to the vicinity of the cell plate. The family members consist of multiple functional domains, including a lysine-rich domain (KRD domain) that contains three nuclear localization motifs (KKKR/NK), two RNA recognition motifs (RRMs), and three CCHC-type zinc fingers. PHIP1 is a peripheral membrane protein and is localized at the cell plate during cytokinesis in plants. In addition to phragmoplastin, PHIP1 interacts with two Arabidopsis small GTP-binding proteins, Rop1 and Ran2. However, PHIP1 interacted only with the GTP-bound form of Rop1 but not the GDP-bound form. It also binds specifically to Ran2 mRNA.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1529015658 156 VLGIPYTTSSETCKAYFELFGDVVMFDLKK-DASGNSKGFGFVRMADYNAQIRVLAKQTHEIDGRRCQVK 224
Cdd:cd12271     3 VGGIPYYSTEAEIRSYFSSCGEVRSVDLMRfPDSGNFRGIAFITFKTEEAAKRALALDGEMLGNRFLKVE 72

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        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1529015658 169 KAYFELFGDVVMFDLKKDASGNSKGFGFVRMADYN-AQIRVLAKQTHEIDGR 219
Cdd:cd12380    19 KELFEKYGKITSAKVMKDDSGKSKGFGFVNFENHEaAQKAVEELNGKELNGK 70