RNA recognition motif 2 (RRM2) found in the c-myc gene single-strand binding proteins (MSSP) family; This subfamily corresponds to the RRM2 of c-myc gene single-strand binding proteins (MSSP) family, including single-stranded DNA-binding protein MSSP-1 (also termed RBMS1 or SCR2) and MSSP-2 (also termed RBMS2 or SCR3). All MSSP family members contain two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), both of which are responsible for the specific DNA binding activity. Both, MSSP-1 and -2, have been identified as protein factors binding to a putative DNA replication origin/transcriptional enhancer sequence present upstream from the human c-myc gene in both single- and double-stranded forms. Thus they have been implied in regulating DNA replication, transcription, apoptosis induction, and cell-cycle movement, via the interaction with C-MYC, the product of protooncogene c-myc. Moreover, they family includes a new member termed RNA-binding motif, single-stranded-interacting protein 3 (RBMS3), which is not a transcriptional regulator. RBMS3 binds with high affinity to A/U-rich stretches of RNA, and to A/T-rich DNA sequences, and functions as a regulator of cytoplasmic activity. In addition, a putative meiosis-specific RNA-binding protein termed sporulation-specific protein 5 (SPO5, or meiotic RNA-binding protein 1, or meiotically up-regulated gene 12 protein), encoded by Schizosaccharomyces pombe Spo5/Mug12 gene, is also included in this family. SPO5 is a novel meiosis I regulator that may function in the vicinity of the Mei2 dot.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19112839 384 TNLYISNLPLHWNESDISTLFKP-SKIISNRVLRDSKEQSRGVGFARMQDRKTAEDIINKFNNFVLDP---ALPPLQIRF 459
Cdd:cd12244   1 TNLYISNLPLDMDEQDLENMLKPfGQVISTRILRDSKGQSRGVGFARMESREKCEDVISKFNGKVLKTpsaSGEPLLVKF 80

                ..
gi 19112839 460 AD 461
Cdd:cd12244  81 AD 82

RNA recognition motif 2 (RRM2) found in the c-myc gene single-strand binding proteins (MSSP) family; This subfamily corresponds to the RRM2 of c-myc gene single-strand binding proteins (MSSP) family, including single-stranded DNA-binding protein MSSP-1 (also termed RBMS1 or SCR2) and MSSP-2 (also termed RBMS2 or SCR3). All MSSP family members contain two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), both of which are responsible for the specific DNA binding activity. Both, MSSP-1 and -2, have been identified as protein factors binding to a putative DNA replication origin/transcriptional enhancer sequence present upstream from the human c-myc gene in both single- and double-stranded forms. Thus they have been implied in regulating DNA replication, transcription, apoptosis induction, and cell-cycle movement, via the interaction with C-MYC, the product of protooncogene c-myc. Moreover, they family includes a new member termed RNA-binding motif, single-stranded-interacting protein 3 (RBMS3), which is not a transcriptional regulator. RBMS3 binds with high affinity to A/U-rich stretches of RNA, and to A/T-rich DNA sequences, and functions as a regulator of cytoplasmic activity. In addition, a putative meiosis-specific RNA-binding protein termed sporulation-specific protein 5 (SPO5, or meiotic RNA-binding protein 1, or meiotically up-regulated gene 12 protein), encoded by Schizosaccharomyces pombe Spo5/Mug12 gene, is also included in this family. SPO5 is a novel meiosis I regulator that may function in the vicinity of the Mei2 dot.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19112839 384 TNLYISNLPLHWNESDISTLFKP-SKIISNRVLRDSKEQSRGVGFARMQDRKTAEDIINKFNNFVLDP---ALPPLQIRF 459
Cdd:cd12244   1 TNLYISNLPLDMDEQDLENMLKPfGQVISTRILRDSKGQSRGVGFARMESREKCEDVISKFNGKVLKTpsaSGEPLLVKF 80

                ..
gi 19112839 460 AD 461
Cdd:cd12244  81 AD 82

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 19112839   293 SRTrNVYIRGLPPNTSDENLLLYTNRFGKVSSSKAIIDMETNLCKGYGFACFEEEKSALICISAMTLCGYQCSFAKESFs 372
Cdd:TIGR01661   2 SKT-NLIVNYLPQTMTQEEIRSLFTSIGEIESCKLVRDKVTGQSLGYGFVNYVRPEDAEKAVNSLNGLRLQNKTIKVSY- 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19112839   373 ARLQSLQdTESTNLYISNLPLHWNESDISTLFKP-SKIISNRVLRDS-KEQSRGVGFARMQDRKTAEDIINKFNNFVLDP 450
Cdd:TIGR01661  80 ARPSSDS-IKGANLYVSGLPKTMTQHELESIFSPfGQIITSRILSDNvTGLSKGVGFIRFDKRDEADRAIKTLNGTTPSG 158

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 19112839   451 ALPPLQIRFADSTDQKKFKG------QTQKRRLWRAREYSVLTKGMTA 492
Cdd:TIGR01661 159 CTEPITVKFANNPSSSNSKGllsqleAVQNPQTTRVPLSTILTAAGIG 206

RNA recognition motif;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 19112839    385 NLYISNLPLHWNESDISTLFKP-SKIISNRVLRDSK-EQSRGVGFARMQDRKTAEDIINKFNNFVLD 449
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSKfGKVESVRLVRDKEtGKSKGFAFVEFESEEDAEKALEALNGKELD 67

RNA recognition motif. (a.k.a. RRM, RBD, or RNP domain); The RRM motif is probably diagnostic of an RNA binding protein. RRMs are found in a variety of RNA binding proteins, including various hnRNP proteins, proteins implicated in regulation of alternative splicing, and protein components of snRNPs. The motif also appears in a few single stranded DNA binding proteins. The RRM structure consists of four strands and two helices arranged in an alpha/beta sandwich, with a third helix present during RNA binding in some cases The C-terminal beta strand (4th strand) and final helix are hard to align and have been omitted in the SEED alignment The LA proteins have an N terminal rrm which is included in the seed. There is a second region towards the C terminus that has some features characteriztic of a rrm but does not appear to have the important structural core of a rrm. The LA proteins are one of the main autoantigens in Systemic lupus erythematosus (SLE), an autoimmune disease.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 19112839   386 LYISNLPLHWNESDISTLFKP-SKIISNRVLRDSKEQSRGVGFARMQDRKTAEDIINKFNNFVLD 449
Cdd:pfam00076   1 LFVGNLPPDTTEEDLKDLFSKfGPIKSIRLVRDETGRSKGFAFVEFEDEEDAEKAIEALNGKELG 65

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19112839 383 STNLYISNLPLHWNESDISTLFKPS-KIISNRVLRDsKE--QSRGVGFARMQDRKTAEDIINKFNNFVLD 449
Cdd:COG0724   1 SMKIYVGNLPYSVTEEDLRELFSEYgEVTSVKLITD-REtgRSRGFGFVEMPDDEEAQAAIEALNGAELM 69

glycine-rich RNA-binding protein 4; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 19112839  298 VYIRGLPPNTSDENLLLYTNRFGKVSSSKAIIDMETNLCKGYGFACFEEEKSALICISAM 357
Cdd:PLN03134  37 LFIGGLSWGTDDASLRDAFAHFGDVVDAKVIVDRETGRSRGFGFVNFNDEGAATAAISEM 96

RNA recognition motif 2 (RRM2) found in the c-myc gene single-strand binding proteins (MSSP) family; This subfamily corresponds to the RRM2 of c-myc gene single-strand binding proteins (MSSP) family, including single-stranded DNA-binding protein MSSP-1 (also termed RBMS1 or SCR2) and MSSP-2 (also termed RBMS2 or SCR3). All MSSP family members contain two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), both of which are responsible for the specific DNA binding activity. Both, MSSP-1 and -2, have been identified as protein factors binding to a putative DNA replication origin/transcriptional enhancer sequence present upstream from the human c-myc gene in both single- and double-stranded forms. Thus they have been implied in regulating DNA replication, transcription, apoptosis induction, and cell-cycle movement, via the interaction with C-MYC, the product of protooncogene c-myc. Moreover, they family includes a new member termed RNA-binding motif, single-stranded-interacting protein 3 (RBMS3), which is not a transcriptional regulator. RBMS3 binds with high affinity to A/U-rich stretches of RNA, and to A/T-rich DNA sequences, and functions as a regulator of cytoplasmic activity. In addition, a putative meiosis-specific RNA-binding protein termed sporulation-specific protein 5 (SPO5, or meiotic RNA-binding protein 1, or meiotically up-regulated gene 12 protein), encoded by Schizosaccharomyces pombe Spo5/Mug12 gene, is also included in this family. SPO5 is a novel meiosis I regulator that may function in the vicinity of the Mei2 dot.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19112839 384 TNLYISNLPLHWNESDISTLFKP-SKIISNRVLRDSKEQSRGVGFARMQDRKTAEDIINKFNNFVLDP---ALPPLQIRF 459
Cdd:cd12244   1 TNLYISNLPLDMDEQDLENMLKPfGQVISTRILRDSKGQSRGVGFARMESREKCEDVISKFNGKVLKTpsaSGEPLLVKF 80

                ..
gi 19112839 460 AD 461
Cdd:cd12244  81 AD 82

RNA recognition motif 2 (RRM2) found in vertebrate single-stranded DNA-binding protein MSSP-1; This subgroup corresponds to the RRM2 of MSSP-1, also termed RNA-binding motif, single-stranded-interacting protein 1 (RBMS1), or suppressor of CDC2 with RNA-binding motif 2 (SCR2). MSSP-1 is a double- and single-stranded DNA binding protein that belongs to the c-myc single-strand binding proteins (MSSP) family. It specifically recognizes the sequence CT(A/T)(A/T)T, and stimulates DNA replication in the system using SV40 DNA. MSSP-1 is identical with Scr2, a human protein which complements the defect of cdc2 kinase in Schizosaccharomyces pombe. MSSP-1 has been implied in regulating DNA replication, transcription, apoptosis induction, and cell-cycle movement, via the interaction with c-MYC, the product of protooncogene c-myc. MSSP-1 contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), both of which are responsible for the specific DNA binding activity as well as induction of apoptosis.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19112839 384 TNLYISNLPLHWNESDISTLFKP-SKIISNRVLRDSKEQSRGVGFARMQDRKTAEDIINKFN-NFVLDPA-----LPPLQ 456
Cdd:cd12473   1 TNLYISNLPLSMDEQELENMLKPfGQVISTRILRDSSGTSRGVGFARMESTEKCEAVISHFNgKFIKTPPgvsapAEPLL 80

                ....*
gi 19112839 457 IRFAD 461
Cdd:cd12473  81 CKFAD 85

RNA recognition motif 1 (RRM1) found in vertebrate single-stranded DNA-binding protein MSSP-1; This subgroup corresponds to the RRM1 of MSSP-1, also termed RNA-binding motif, single-stranded-interacting protein 1 (RBMS1), or suppressor of CDC2 with RNA-binding motif 2 (SCR2), a double- and single-stranded DNA binding protein that belongs to the c-myc single-strand binding proteins (MSSP) family. It specifically recognizes the sequence CT(A/T)(A/T)T, and stimulates DNA replication in the system using SV40 DNA. MSSP-1 is identical with Scr2, a human protein which complements the defect of cdc2 kinase in Schizosaccharomyces pombe. MSSP-1 has been implied in regulating DNA replication, transcription, apoptosis induction, and cell-cycle movement, via the interaction with C-MYC, the product of protooncogene c-myc. MSSP-1 contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), both of which are responsible for the specific DNA binding activity as well as induction of apoptosis.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19112839 290 ESTSRTrNVYIRGLPPNTSDENLLLYTNRFGKVSSSKAIIDMETNLCKGYGFACFEEEKSALICISAMTLCGYQCSFAKE 369
Cdd:cd12470   3 DQLSKT-NLYIRGLPPNTTDQDLVKLCQPYGKIVSTKAILDKTTNKCKGYGFVDFDSPAAAQKAVSALKASGVQAQMAKQ 81

RNA recognition motif 2 (RRM2) found in the Hu proteins family; This subfamily corresponds to the RRM2 of Hu proteins family which represents a group of RNA-binding proteins involved in diverse biological processes. Since the Hu proteins share high homology with the Drosophila embryonic lethal abnormal vision (ELAV) protein, the Hu family is sometimes referred to as the ELAV family. Drosophila ELAV is exclusively expressed in neurons and is required for the correct differentiation and survival of neurons in flies. The neuronal members of the Hu family include Hu-antigen B (HuB or ELAV-2 or Hel-N1), Hu-antigen C (HuC or ELAV-3 or PLE21), and Hu-antigen D (HuD or ELAV-4), which play important roles in neuronal differentiation, plasticity and memory. HuB is also expressed in gonads. Hu-antigen R (HuR or ELAV-1 or HuA) is the ubiquitously expressed Hu family member. It has a variety of biological functions mostly related to the regulation of cellular response to DNA damage and other types of stress. Moreover, HuR has an anti-apoptotic function during early cell stress response. It binds to mRNAs and enhances the expression of several anti-apoptotic proteins, such as p21waf1, p53, and prothymosin alpha. HuR also has pro-apoptotic function by promoting apoptosis when cell death is unavoidable. Furthermore, HuR may be important in muscle differentiation, adipogenesis, suppression of inflammatory response and modulation of gene expression in response to chronic ethanol exposure and amino acid starvation. Hu proteins perform their cytoplasmic and nuclear molecular functions by coordinately regulating functionally related mRNAs. In the cytoplasm, Hu proteins recognize and bind to AU-rich RNA elements (AREs) in the 3' untranslated regions (UTRs) of certain target mRNAs, such as GAP-43, vascular epithelial growth factor (VEGF), the glucose transporter GLUT1, eotaxin and c-fos, and stabilize those ARE-containing mRNAs. They also bind and regulate the translation of some target mRNAs, such as neurofilament M, GLUT1, and p27. In the nucleus, Hu proteins function as regulators of polyadenylation and alternative splicing. Each Hu protein contains three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). RRM1 and RRM2 may cooperate in binding to an ARE. RRM3 may help to maintain the stability of the RNA-protein complex, and might also bind to poly(A) tails or be involved in protein-protein interactions.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 19112839 385 NLYISNLPLHWNESDISTLFKP-SKIISNRVLRDSK-EQSRGVGFARMQDRKTAEDIINKFNNFVLDPALPPLQIRFA 460
Cdd:cd12652   2 NLYVSGLPKTMTQKELEQLFSQfGRIITSRILCDNVtGLSRGVGFIRFDKRVEAERAIKALNGTIPPGATEPITVKFA 79

RNA recognition motif 1 (RRM1) found in vertebrate RNA-binding motif, single-stranded-interacting protein 3 (RBMS3); This subgroup corresponds to the RRM1 of RBMS3, a new member of the c-myc gene single-strand binding proteins (MSSP) family of DNA regulators. Unlike other MSSP proteins, RBMS3 is not a transcriptional regulator. It binds with high affinity to A/U-rich stretches of RNA, and to A/T-rich DNA sequences, and functions as a regulator of cytoplasmic activity. RBMS3 contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and its C-terminal region is acidic and enriched in prolines, glutamines and threonines.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 19112839 297 NVYIRGLPPNTSDENLLLYTNRFGKVSSSKAIIDMETNLCKGYGFACFEEEKSALICISAMTLCGYQCSFAKE 369
Cdd:cd12472   6 NLYIRGLPPGTTDQDLIKLCQPYGKIVSTKAILDKNTNQCKGYGFVDFDSPAAAQKAVASLKASGVQAQMAKQ 78

polyadenylate binding protein, human types 1, 2, 3, 4 family; These eukaryotic proteins recognize the poly-A of mRNA and consists of four tandem RNA recognition domains at the N-terminus (rrm: pfam00076) followed by a PABP-specific domain (pfam00658) at the C-terminus. The protein is involved in the transport of mRNA's from the nucleus to the cytoplasm. There are four paralogs in Homo sapiens which are expressed in testis, platelets, broadly expressed and of unknown tissue range.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19112839   285 KKSNMESTSRTR--NVYIRGLPPNTSDENLLLYTNRFGKVSSSKAIIDmETNLCKGYGFACFEEEKSALICISAMT---- 358
Cdd:TIGR01628 166 KKHEREAAPLKKftNLYVKNLDPSVNEDKLRELFAKFGEITSAAVMKD-GSGRSRGFAFVNFEKHEDAAKAVEEMNgkki 244

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19112839   359 ------LCGYQCSFAKESFSARL----------QSLQDTESTNLYISNLPLHWNESDISTLFKP-SKIISNRVLRDSKEQ 421
Cdd:TIGR01628 245 glakegKKLYVGRAQKRAEREAElrrkfeelqqERKMKAQGVNLYVKNLDDTVTDEKLRELFSEcGEITSAKVMLDEKGV 324

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 19112839   422 SRGVGFARMQDRKTAEDIINKFNNFVLDPAlpPLQIRFADSTDQKKFKGQTQ 473
Cdd:TIGR01628 325 SRGFGFVCFSNPEEANRAVTEMHGRMLGGK--PLYVALAQRKEQRRAHLQDQ 374

RNA recognition motif;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 19112839    297 NVYIRGLPPNTSDENLLLYTNRFGKVSSSKAIIDMETNLCKGYGFACFEEEKSALICISAM 357
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSKFGKVESVRLVRDKETGKSKGFAFVEFESEEDAEKALEAL 61

RNA recognition motif 2 (RRM2) found in the Hu proteins family, Drosophila sex-lethal (SXL), and similar proteins; This subfamily corresponds to the RRM2 of Hu proteins and SXL. The Hu proteins family represents a group of RNA-binding proteins involved in diverse biological processes. Since the Hu proteins share high homology with the Drosophila embryonic lethal abnormal vision (ELAV) protein, the Hu family is sometimes referred to as the ELAV family. Drosophila ELAV is exclusively expressed in neurons and is required for the correct differentiation and survival of neurons in flies. The neuronal members of the Hu family include Hu-antigen B (HuB or ELAV-2 or Hel-N1), Hu-antigen C (HuC or ELAV-3 or PLE21), and Hu-antigen D (HuD or ELAV-4), which play important roles in neuronal differentiation, plasticity and memory. HuB is also expressed in gonads. Hu-antigen R (HuR or ELAV-1 or HuA) is the ubiquitously expressed Hu family member. It has a variety of biological functions mostly related to the regulation of cellular response to DNA damage and other types of stress. Hu proteins perform their cytoplasmic and nuclear molecular functions by coordinately regulating functionally related mRNAs. In the cytoplasm, Hu proteins recognize and bind to AU-rich RNA elements (AREs) in the 3' untranslated regions (UTRs) of certain target mRNAs, such as GAP-43, vascular epithelial growth factor (VEGF), the glucose transporter GLUT1, eotaxin and c-fos, and stabilize those ARE-containing mRNAs. They also bind and regulate the translation of some target mRNAs, such as neurofilament M, GLUT1, and p27. In the nucleus, Hu proteins function as regulators of polyadenylation and alternative splicing. Each Hu protein contains three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). RRM1 and RRM2 may cooperate in binding to an ARE. RRM3 may help to maintain the stability of the RNA-protein complex, and might also bind to poly(A) tails or be involved in protein-protein interactions. Also included in this subfamily is the sex-lethal protein (SXL) from Drosophila melanogaster. SXL governs sexual differentiation and X chromosome dosage compensation in flies. It induces female-specific alternative splicing of the transformer (tra) pre-mRNA by binding to the tra uridine-rich polypyrimidine tract at the non-sex-specific 3' splice site during the sex-determination process. SXL binds also to its own pre-mRNA and promotes female-specific alternative splicing. SXL contains an N-terminal Gly/Asn-rich domain that may be responsible for the protein-protein interaction, and tandem RRMs that show high preference to bind single-stranded, uridine-rich target RNA transcripts.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 19112839 384 TNLYISNLPLHWNESDISTLF-KPSKIISNRVLRDSKE-QSRGVGFARMQDRKTAEDIINKFNNFVLDPALPPLQIRFA 460
Cdd:cd12376   1 ANLYVSGLPKTMTQKELEQLFsQYGRIITSRILRDQLTgVSRGVGFIRFDKRIEAEEAIKGLNGQKPEGASEPITVKFA 79

RNA recognition motif 2 (RRM2) found in vertebrate Hu-antigen R (HuR); This subgroup corresponds to the RRM2 of HuR, also termed ELAV-like protein 1 (ELAV-1), the ubiquitously expressed Hu family member. It has a variety of biological functions mostly related to the regulation of cellular response to DNA damage and other types of stress. HuR has an anti-apoptotic function during early cell stress response. It binds to mRNAs and enhances the expression of several anti-apoptotic proteins, such as p21waf1, p53, and prothymosin alpha. HuR also has pro-apoptotic function by promoting apoptosis when cell death is unavoidable. Furthermore, HuR may be important in muscle differentiation, adipogenesis, suppression of inflammatory response and modulation of gene expression in response to chronic ethanol exposure and amino acid starvation. Like other Hu proteins, HuR contains three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). RRM1 and RRM2 may cooperate in binding to an AU-rich RNA element (ARE). RRM3 may help to maintain the stability of the RNA-protein complex, and might also bind to poly(A) tails or be involved in protein-protein interactions.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19112839 385 NLYISNLPLHWNESDISTLFKP-SKIISNRVLRDSKE-QSRGVGFARMQDRKTAEDIINKFNNFVLDPALPPLQIRFADS 462
Cdd:cd12773   2 NLYISGLPRTMTQKDVEDMFSRfGRIINSRVLVDQATgLSRGVAFIRFDKRSEAEEAITNFNGHKPPGSSEPITVKFAAN 81

                ...
gi 19112839 463 TDQ 465
Cdd:cd12773  82 PNQ 84

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 19112839 386 LYISNLPLHWNESDISTLFKP-SKIISNRVLRDSKEQSRGVGFARMQDRKTAEDIINKFNNFVLD 449
Cdd:cd00590   1 LFVGNLPPDTTEEDLRELFSKfGEVVSVRIVRDRDGKSKGFAFVEFESPEDAEKALEALNGTELG 65

RNA recognition motif 2 (RRM2) found in vertebrate Hu-antigen C (HuC); This subgroup corresponds to the RRM2 of HuC, also termed ELAV-like protein 3 (ELAV-3), or paraneoplastic cerebellar degeneration-associated antigen, or paraneoplastic limbic encephalitis antigen 21 (PLE21), one of the neuronal members of the Hu family. The neuronal Hu proteins play important roles in neuronal differentiation, plasticity and memory. Like other Hu proteins, HuC contains three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). RRM1 and RRM2 may cooperate in binding to an AU-rich RNA element (ARE). The AU-rich element binding of HuC can be inhibited by flavonoids. RRM3 may help to maintain the stability of the RNA-protein complex, and might also bind to poly(A) tails or be involved in protein-protein interactions.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 19112839 385 NLYISNLPLHWNESDISTLFKP-SKIISNRVLRDSKEQ-SRGVGFARMQDRKTAEDIINKFNNFVLDPALPPLQIRFAD 461
Cdd:cd12776   3 NLYVSGLPKTMSQKEMEQLFSQyGRIITSRILVDQVTGvSRGVGFIRFDKRIEAEEAIKGLNGQKPLGAAEPITVKFAN 81

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
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 19112839 298 VYIRGLPPNTSDENLLLYTNRFGKVSSSKaIIDMETNLCKGYGFACFEEEKSALICISAM 357
Cdd:cd00590   1 LFVGNLPPDTTEEDLRELFSKFGEVVSVR-IVRDRDGKSKGFAFVEFESPEDAEKALEAL 59

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 19112839 297 NVYIRGLPPNTSDENLLLYTNRFGKVSSSKAIIDMETNLCKGYGFACFEEEKSALICISAM 357
Cdd:cd21608   1 KLYVGNLSWDTTEDDLRDLFSEFGEVESAKVITDRETGRSRGFGFVTFSTAEAAEAAIDAL 61

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

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19112839 383 STNLYISNLPLHWNESDISTLFKPS-KIISNRVLRDsKE--QSRGVGFARMQDRKTAEDIINKFNNFVLD 449
Cdd:COG0724   1 SMKIYVGNLPYSVTEEDLRELFSEYgEVTSVKLITD-REtgRSRGFGFVEMPDDEEAQAAIEALNGAELM 69

RNA recognition motif 2 (RRM2) found in vertebrate Hu-antigen B (HuB); This subgroup corresponds to the RRM2 of HuB, also termed ELAV-like protein 2 (ELAV-2), or ELAV-like neuronal protein 1, or nervous system-specific RNA-binding protein Hel-N1 (Hel-N1), one of the neuronal members of the Hu family. The neuronal Hu proteins play important roles in neuronal differentiation, plasticity and memory. HuB is also expressed in gonads. It is up-regulated during neuronal differentiation of embryonic carcinoma P19 cells. Like other Hu proteins, HuB contains three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). RRM1 and RRM2 may cooperate in binding to an AU-rich RNA element (ARE). RRM3 may help to maintain the stability of the RNA-protein complex, and might also bind to poly(A) tails or be involved in protein-protein interactions.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 19112839 385 NLYISNLPLHWNESDISTLFKP-SKIISNRVLRDSKEQ-SRGVGFARMQDRKTAEDIINKFNNFVLDPALPPLQIRFA 460
Cdd:cd12775   7 NLYVSGLPKTMTQKELEQLFSQyGRIITSRILVDQVTGvSRGVGFIRFDKRIEAEEAIKGLNGQKPPGATEPITVKFA 84

RNA recognition motif 2 (RRM2) found in Deleted in azoospermia-associated protein 1 (DAZAP1) and similar proteins; This subfamily corresponds to the RRM2 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 is predominantly nuclear and the nonacetylated form is in cytoplasm. DAZAP1 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
                ....*....|....*....|....*....|....*....|....*....|..
gi 19112839 298 VYIRGLPPNTSDENLLLYTNRFGKVSSSKAIIDMETNLCKGYGFACFEEEKS 349
Cdd:cd12327   5 VFVGGIPHNCGETELRDYFKRYGVVTEVVMMYDAEKQRSRGFGFITFEDEQS 56

RNA recognition motif 3 (RRM3) found in CELF/Bruno-like family of RNA binding proteins CELF1, CELF2, CELF3, CELF4, CELF5, CELF6 and similar proteins; This subgroup corresponds to the RRM3 of the CUGBP1 and ETR-3-like factors (CELF) or BRUNOL (Bruno-like) proteins, a family of structurally related RNA-binding proteins involved in the regulation of pre-mRNA splicing in the nucleus and in the control of mRNA translation and deadenylation in the cytoplasm. The family contains six members: CELF-1 (also termed BRUNOL-2, or CUG-BP1, or NAPOR, or EDEN-BP), CELF-2 (also termed BRUNOL-3, or ETR-3, or CUG-BP2, or NAPOR-2), CELF-3 (also termed BRUNOL-1, or TNRC4, or ETR-1, or CAGH4, or ER DA4), CELF-4 (also termed BRUNOL-4), CELF-5 (also termed BRUNOL-5), CELF-6 (also termed BRUNOL-6). They all contain three highly conserved RNA recognition motifs (RRMs), also known as RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains): two consecutive RRMs (RRM1 and RRM2) situated in the N-terminal region followed by a linker region and the third RRM (RRM3) close to the C-terminus of the protein. The low sequence conservation of the linker region is highly suggestive of a large variety in the co-factors that associate with the various CELF family members. Based on both sequence similarity and function, the CELF family can be divided into two subfamilies, the first containing CELFs 1 and 2, and the second containing CELFs 3, 4, 5, and 6. The different CELF proteins may act through different sites on at least some substrates. Furthermore, CELF proteins may interact with each other in varying combinations to influence alternative splicing in different contexts.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 19112839 298 VYIRGLPPNTSDENLLLYTNRFGKVSSSKAIIDMETNLCKGYGFACFEEEKSALICISAMTlcGYQ 363
Cdd:cd12362   1 LFVYHLPNEFTDQDLYQLFAPFGNVVSAKVFVDKNTGRSKGFGFVSYDNPLSAQAAIKAMN--GFQ 64

RNA recognition motif 3 (RRM3) found in yeast nucleolar protein 4 (Nop4p) and similar proteins; This subgroup corresponds to the RRM3 of Nop4p (also known as Nop77p), encoded by YPL043W from Saccharomyces cerevisiae. It is an essential nucleolar protein involved in processing and maturation of 27S pre-rRNA and biogenesis of 60S ribosomal subunits. Nop4p has four RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 19112839 296 RNVYIRGLPPNTSDENLLLYTNRFGKVSSSKAIIDMETNLCKGYGFACFEEEKSALICISA 356
Cdd:cd12676   2 RTLFVRNLPFDATEDELYSHFSQFGPLKYARVVKDPATGRSKGTAFVKFKNKEDADNCLSA 62

RNA recognition motif 1 (RRM1) and 2 (RRM2) found in CELF/Bruno-like family of RNA binding proteins and plant flowering time control protein FCA; This subfamily corresponds to the RRM1 and RRM2 domains of the CUGBP1 and ETR-3-like factors (CELF) as well as plant flowering time control protein FCA. CELF, also termed BRUNOL (Bruno-like) proteins, is a family of structurally related RNA-binding proteins involved in regulation of pre-mRNA splicing in the nucleus, and control of mRNA translation and deadenylation in the cytoplasm. The family contains six members: CELF-1 (also known as BRUNOL-2, CUG-BP1, NAPOR, EDEN-BP), CELF-2 (also known as BRUNOL-3, ETR-3, CUG-BP2, NAPOR-2), CELF-3 (also known as BRUNOL-1, TNRC4, ETR-1, CAGH4, ER DA4), CELF-4 (BRUNOL-4), CELF-5 (BRUNOL-5) and CELF-6 (BRUNOL-6). They all contain three highly conserved RNA recognition motifs (RRMs), also known as RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains): two consecutive RRMs (RRM1 and RRM2) situated in the N-terminal region followed by a linker region and the third RRM (RRM3) close to the C-terminus of the protein. The low sequence conservation of the linker region is highly suggestive of a large variety in the co-factors that associate with the various CELF family members. Based on both, sequence similarity and function, the CELF family can be divided into two subfamilies, the first containing CELFs 1 and 2, and the second containing CELFs 3, 4, 5, and 6. The different CELF proteins may act through different sites on at least some substrates. Furthermore, CELF proteins may interact with each other in varying combinations to influence alternative splicing in different contexts. This subfamily also includes plant flowering time control protein FCA that functions in the posttranscriptional regulation of transcripts involved in the flowering process. FCA contains two RRMs, and a WW protein interaction domain.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 19112839 386 LYISNLPLHWNESDISTLFKP-SKIISNRVLRDSKE-QSRGVGFARMQDRKTAEDIINKFNN-FVLDPALPPLQIR 458
Cdd:cd12361   2 LFVGMIPKTASEEDVRPLFEQfGNIEEVQILRDKQTgQSKGCAFVTFSTREEALRAIEALHNkKTMPGCSSPLQVK 77

RNA recognition motif 2 (RRM2) 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.

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                ....*....|....*....|....*....|....*....|....*....|....*....
gi 19112839 298 VYIRGLPPNTSDENLLLYTNRFGKVSSSKAIIDMETNLCKGYGFACFEEEKSALICISA 356
Cdd:cd12330   2 IFVGGLAPDVTEEEFKEYFEQFGTVVDAVVMLDHDTGRSRGFGFVTFDSESAVEKVLSK 60

polyadenylate binding protein, human types 1, 2, 3, 4 family; These eukaryotic proteins recognize the poly-A of mRNA and consists of four tandem RNA recognition domains at the N-terminus (rrm: pfam00076) followed by a PABP-specific domain (pfam00658) at the C-terminus. The protein is involved in the transport of mRNA's from the nucleus to the cytoplasm. There are four paralogs in Homo sapiens which are expressed in testis, platelets, broadly expressed and of unknown tissue range.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 19112839   283 DNKKSNMESTSRTRNVYIRGLPPNTSDENLLLYTNRFGKVSSSKAIIDmETNLCKGYGFACFEEEKSALICISAM 357
Cdd:TIGR01628 273 EELQQERKMKAQGVNLYVKNLDDTVTDEKLRELFSECGEITSAKVMLD-EKGVSRGFGFVCFSNPEEANRAVTEM 346

RNA recognition motif 2 (RRM2) found in granule-associated RNA binding proteins p40-TIA-1 and TIAR; This subfamily corresponds to the RRM2 of nucleolysin TIA-1 isoform p40 (p40-TIA-1 or TIA-1) and nucleolysin TIA-1-related protein (TIAR), both of which are granule-associated RNA binding proteins involved in inducing apoptosis in cytotoxic lymphocyte (CTL) target cells. TIA-1 and TIAR share high sequence similarity. They 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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 19112839 298 VYIRGLPPNTSDENLLLYTNRFGKVSSSKAIIDMETNLCKGYGFACFEEEKSALICISAM 357
Cdd:cd12353   2 IFVGDLSPEIETEDLKEAFAPFGEISDARVVKDTQTGKSKGYGFVSFVKKEDAENAIQGM 61

RNA recognition motif 2 (RRM2) found in (U)-binding-splicing factor PUF60 and similar proteins; This subfamily corresponds to the RRM2 of PUF60, also termed FUSE-binding protein-interacting repressor (FBP-interacting repressor or FIR), or Ro-binding protein 1 (RoBP1), or Siah-binding protein 1 (Siah-BP1). PUF60 is an essential splicing factor that functions as a poly-U RNA-binding protein required to reconstitute splicing in depleted nuclear extracts. Its function is enhanced through interaction with U2 auxiliary factor U2AF65. PUF60 also controls human c-myc gene expression by binding and inhibiting the transcription factor far upstream sequence element (FUSE)-binding-protein (FBP), an activator of c-myc promoters. PUF60 contains two central RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a C-terminal U2AF (U2 auxiliary factor) homology motifs (UHM) that harbors another RRM and binds to tryptophan-containing linear peptide motifs (UHM ligand motifs, ULMs) in several nuclear proteins. Research indicates that PUF60 binds FUSE as a dimer, and only the first two RRM domains participate in the single-stranded DNA recognition.

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                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 19112839 298 VYIRGLPPNTSDENLLLYTNRFGKVSSSKAIIDMETNLCKGYGFACFEEEKSALICISAMTL 359
Cdd:cd12371   3 IYVASVHPDLSEDDIKSVFEAFGKIKSCSLAPDPETGKHKGYGFIEYENPQSAQDAIASMNL 64

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.

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                ....*....|....*....|....*....|....*....|....*....|...
gi 19112839 298 VYIRGLPPNTSDENLLLYTNRFGKVSSSKAIIDMETNLCKGYGFACFEEEKSA 350
Cdd:cd12323   2 IFVGGLSANTTEDDVKKYFSQFGKVEDAMLMFDKQTNRHRGFGFVTFESEDVV 54

RNA recognition motif 2 (RRM2) found in CUGBP Elav-like family member CELF-3, CELF-4, CELF-5, CELF-6 and similar proteins; This subgroup corresponds to the RRM3 of CELF-3, CELF-4, CELF-5, and CELF-6, all of which belong to the CUGBP1 and ETR-3-like factors (CELF) or BRUNOL (Bruno-like) family of RNA-binding proteins that display dual nuclear and cytoplasmic localizations and have been implicated in the regulation of pre-mRNA splicing and in the control of mRNA translation and deadenylation. CELF-3, expressed in brain and testis only, is also known as bruno-like protein 1 (BRUNOL-1), or CAG repeat protein 4, or CUG-BP- and ETR-3-like factor 3, or embryonic lethal abnormal vision (ELAV)-type RNA-binding protein 1 (ETR-1), or expanded repeat domain protein CAG/CTG 4, or trinucleotide repeat-containing gene 4 protein (TNRC4). It plays an important role in the pathogenesis of tauopathies. CELF-3 contains three highly conserved RNA recognition motifs (RRMs), also known as RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains): two consecutive RRMs (RRM1 and RRM2) situated in the N-terminal region followed by a linker region and the third RRM (RRM3) close to the C-terminus of the protein.The effect of CELF-3 on tau splicing is mediated mainly by the RNA-binding activity of RRM2. The divergent linker region might mediate the interaction of CELF-3 with other proteins regulating its activity or involved in target recognition. CELF-4, highly expressed throughout the brain and in glandular tissues, moderately expressed in heart, skeletal muscle, and liver, is also known as bruno-like protein 4 (BRUNOL-4), or CUG-BP- and ETR-3-like factor 4. Like CELF-3, CELF-4 also contains three highly conserved RRMs. The splicing activation or repression activity of CELF-4 on some specific substrates is mediated by its RRM1/RRM2. Both, RRM1 and RRM2 of CELF-4, can activate cardiac troponin T (cTNT) exon 5 inclusion. CELF-5, expressed in brain, is also known as bruno-like protein 5 (BRUNOL-5), or CUG-BP- and ETR-3-like factor 5. Although its biological role remains unclear, CELF-5 shares same domain architecture with CELF-3. CELF-6, strongly expressed in kidney, brain, and testis, is also known as bruno-like protein 6 (BRUNOL-6), or CUG-BP- and ETR-3-like factor 6. It activates exon inclusion of a cardiac troponin T minigene in transient transfection assays in an muscle-specific splicing enhancer (MSE)-dependent manner and can activate inclusion via multiple copies of a single element, MSE2. CELF-6 also promotes skipping of exon 11 of insulin receptor, a known target of CELF activity that is expressed in kidney. In addition to three highly conserved RRMs, CELF-6 also possesses numerous potential phosphorylation sites, a potential nuclear localization signal (NLS) at the C terminus, and an alanine-rich region within the divergent linker region.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 19112839 297 NVYIRGLPPNTSDENLLLYTNRFGKVSSSKAIIDMETNLCKGYGFACFEEEKSALICISAMTlcGYQ 363
Cdd:cd12639   6 NLFIYHLPQEFGDAELMQMFLPFGNVISAKVFVDRATNQSKCFGFVSFDNPASAQAAIQAMN--GFQ 70

glycine-rich RNA-binding protein 4; Provisional

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                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 19112839  298 VYIRGLPPNTSDENLLLYTNRFGKVSSSKAIIDMETNLCKGYGFACFEEEKSALICISAM 357
Cdd:PLN03134  37 LFIGGLSWGTDDASLRDAFAHFGDVVDAKVIVDRETGRSRGFGFVNFNDEGAATAAISEM 96

RNA recognition motif (RRM) found in cleavage stimulation factor subunit 2 (CSTF2), cleavage stimulation factor subunit 2 tau variant (CSTF2T) and similar proteins; This subgroup corresponds to the RRM domain of CSTF2, its tau variant and eukaryotic homologs. CSTF2, also termed cleavage stimulation factor 64 kDa subunit (CstF64), is the vertebrate conterpart of yeast mRNA 3'-end-processing protein RNA15. It is expressed in all somatic tissues and is one of three cleavage stimulatory factor (CstF) subunits required for polyadenylation. CstF64 contains an N-terminal RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a CstF77-binding domain, a repeated MEARA helical region and a conserved C-terminal domain reported to bind the transcription factor PC-4. During polyadenylation, CstF interacts with the pre-mRNA through the RRM of CstF64 at U- or GU-rich sequences within 10 to 30 nucleotides downstream of the cleavage site. CSTF2T, also termed tauCstF64, is a paralog of the X-linked cleavage stimulation factor CstF64 protein that supports polyadenylation in most somatic cells. It is expressed during meiosis and subsequent haploid differentiation in a more limited set of tissues and cell types, largely in meiotic and postmeiotic male germ cells, and to a lesser extent in brain. The loss of CSTF2T will cause male infertility, as it is necessary for spermatogenesis and fertilization. Moreover, CSTF2T is required for expression of genes involved in morphological differentiation of spermatids, as well as for genes having products that function during interaction of motile spermatozoa with eggs. It promotes germ cell-specific patterns of polyadenylation by using its RRM to bind to different sequence elements downstream of polyadenylation sites than does CstF64.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 19112839 296 RNVYIRGLPPNTSDENLLLYTNRFGKVSSSKAIIDMETNLCKGYGFACFEEEKSALiciSAM-TLCGYQ 363
Cdd:cd12671   7 RSVFVGNIPYEATEEQLKDIFSEVGPVVSFRLVYDRETGKPKGYGFCEYQDQETAL---SAMrNLNGYE 72

RNA recognition motif 2 (RRM2) found in RNA-binding protein Musashi homolog 1 (Musashi-1) and similar proteins; This subgroup corresponds to the RRM2 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) and 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. 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.

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                ....*....|....*....|....*....|....*....|....*....|
gi 19112839 298 VYIRGLPPNTSDENLLLYTNRFGKVSSSKAIIDMETNLCKGYGFACFEEE 347
Cdd:cd12572   2 IFVGGLSVNTTVEDVKQYFEQFGKVDDAMLMFDKTTNRHRGFGFVTFESE 51

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 19112839 384 TNLYISNLPLHWNESDISTLFKP-SKIISNRVLRDSKEQSRGVGFARMQDRKTAEDIINKFNN 445
Cdd:cd12380   2 TNVYVKNFGEDVDDDELKELFEKyGKITSAKVMKDDSGKSKGFGFVNFENHEAAQKAVEELNG 64