RNA recognition motif 3 (RRM3) found found in vertebrate ribonucleoprotein PTB-binding 2 (raver-2); This subgroup corresponds to the RRM3 of raver-2, a novel member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family. It is present in vertebrates and shows high sequence homology to raver-1, a ubiquitously expressed co-repressor of the nucleoplasmic splicing repressor polypyrimidine tract-binding protein (PTB)-directed splicing of select mRNAs. In contrast, raver-2 exerts a distinct spatio-temporal expression pattern during embryogenesis and is mainly limited to differentiated neurons and glia cells. Although it displays nucleo-cytoplasmic shuttling in heterokaryons, raver2 localizes to the nucleus in glia cells and neurons. Raver-2 can interact with PTB and may participate in PTB-mediated RNA-processing. However, there is no evidence indicating that raver-2 can bind to cytoplasmic proteins. Raver-2 contains three N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two putative nuclear localization signals (NLS) at the N- and C-termini, a central leucine-rich region, and a C-terminal region harboring two [SG][IL]LGxxP motifs. Raver-2 binds to PTB through the SLLGEPP motif only, and binds to RNA through its RRMs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1929828186 204 HSKCLCVDKFQKDYADSKELIQAFSLKYKPVFCQFAQDEDSCIGDFAVVEYETAEQAEKVHEVTDGMTIKGKRIQVSYCA 283
Cdd:cd12668     1 HSKCLCVDKLPKDYSDSEELTQLFSRPYKPVFCQLAQDEGSCIGGFAVVEYETAEQAEEVQRAMDGMTIGGSRVQVSFCA 80

                          90
                  ....*....|....*...
gi 1929828186 284 PGAPGRSTLAALIAAQRM 301
Cdd:cd12668    81 PGSPGRSTLAALIAAQGM 98

RNA recognition motif 1 (RRM1) found in vertebrate ribonucleoprotein PTB-binding 2 (raver-2); This subgroup corresponds to the RRM1 of raver-2, a novel member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family. It is present in vertebrates and shows high sequence homology to raver-1, a ubiquitously expressed co-repressor of the nucleoplasmic splicing repressor polypyrimidine tract-binding protein (PTB)-directed splicing of select mRNAs. In contrast, raver-2 exerts a distinct spatio-temporal expression pattern during embryogenesis and is mainly limited to differentiated neurons and glia cells. Although it displays nucleo-cytoplasmic shuttling in heterokaryons, raver2 localizes to the nucleus in glia cells and neurons. Raver-2 can interact with PTB and may participate in PTB-mediated RNA-processing. However, there is no evidence indicating that raver-2 can bind to cytoplasmic proteins. Raver-2 contains three N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two putative nuclear localization signals (NLS) at the N- and C-termini, a central leucine-rich region, and a C-terminal region harboring two [SG][IL]LGxxP motifs. Raver-2 binds to PTB through the SLLGEPP motif only, and binds to RNA through its RRMs.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1929828186  45 KILLRNLPAESSSQEIHDLFKDYEIKYCYVDRNKRTAFVTLLNGEQAQNAIQKFHQYSLRGKEISVQLQP 114
Cdd:cd12664     1 KILIKNLPQDSTSQEVHDLLKDYELKYCYVDRNKRTAFVTLLNGEQAQDAIRTFHQHSLRGRDISVQLQP 70

RNA recognition motif 3 (RRM3) found found in vertebrate ribonucleoprotein PTB-binding 2 (raver-2); This subgroup corresponds to the RRM3 of raver-2, a novel member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family. It is present in vertebrates and shows high sequence homology to raver-1, a ubiquitously expressed co-repressor of the nucleoplasmic splicing repressor polypyrimidine tract-binding protein (PTB)-directed splicing of select mRNAs. In contrast, raver-2 exerts a distinct spatio-temporal expression pattern during embryogenesis and is mainly limited to differentiated neurons and glia cells. Although it displays nucleo-cytoplasmic shuttling in heterokaryons, raver2 localizes to the nucleus in glia cells and neurons. Raver-2 can interact with PTB and may participate in PTB-mediated RNA-processing. However, there is no evidence indicating that raver-2 can bind to cytoplasmic proteins. Raver-2 contains three N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two putative nuclear localization signals (NLS) at the N- and C-termini, a central leucine-rich region, and a C-terminal region harboring two [SG][IL]LGxxP motifs. Raver-2 binds to PTB through the SLLGEPP motif only, and binds to RNA through its RRMs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1929828186 204 HSKCLCVDKFQKDYADSKELIQAFSLKYKPVFCQFAQDEDSCIGDFAVVEYETAEQAEKVHEVTDGMTIKGKRIQVSYCA 283
Cdd:cd12668     1 HSKCLCVDKLPKDYSDSEELTQLFSRPYKPVFCQLAQDEGSCIGGFAVVEYETAEQAEEVQRAMDGMTIGGSRVQVSFCA 80

                          90
                  ....*....|....*...
gi 1929828186 284 PGAPGRSTLAALIAAQRM 301
Cdd:cd12668    81 PGSPGRSTLAALIAAQGM 98

RNA recognition motif 1 (RRM1) found in vertebrate ribonucleoprotein PTB-binding 2 (raver-2); This subgroup corresponds to the RRM1 of raver-2, a novel member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family. It is present in vertebrates and shows high sequence homology to raver-1, a ubiquitously expressed co-repressor of the nucleoplasmic splicing repressor polypyrimidine tract-binding protein (PTB)-directed splicing of select mRNAs. In contrast, raver-2 exerts a distinct spatio-temporal expression pattern during embryogenesis and is mainly limited to differentiated neurons and glia cells. Although it displays nucleo-cytoplasmic shuttling in heterokaryons, raver2 localizes to the nucleus in glia cells and neurons. Raver-2 can interact with PTB and may participate in PTB-mediated RNA-processing. However, there is no evidence indicating that raver-2 can bind to cytoplasmic proteins. Raver-2 contains three N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two putative nuclear localization signals (NLS) at the N- and C-termini, a central leucine-rich region, and a C-terminal region harboring two [SG][IL]LGxxP motifs. Raver-2 binds to PTB through the SLLGEPP motif only, and binds to RNA through its RRMs.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1929828186  45 KILLRNLPAESSSQEIHDLFKDYEIKYCYVDRNKRTAFVTLLNGEQAQNAIQKFHQYSLRGKEISVQLQP 114
Cdd:cd12664     1 KILIKNLPQDSTSQEVHDLLKDYELKYCYVDRNKRTAFVTLLNGEQAQDAIRTFHQHSLRGRDISVQLQP 70

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 1929828186 121 ITNLPISFTLEEFEELVRAYGNVERCFLVYNEvTGHSKGYGFVEYMKKDSAAKARLELLGKQLDESTL 188
Cdd:pfam00076   3 VGNLPPDTTEEDLKDLFSKFGPIKSIRLVRDE-TGRSKGFAFVEFEDEEDAEKAIEALNGKELGGREL 69

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 1929828186  43 RRKILLRNLPAESSSQEIHDLFKDY-EIKYCYVDRNKRTA------FVTLLNGEQAQNAIQKFHQYSLRGKEISVQL-QP 114
Cdd:TIGR01661   3 KTNLIVNYLPQTMTQEEIRSLFTSIgEIESCKLVRDKVTGqslgygFVNYVRPEDAEKAVNSLNGLRLQNKTIKVSYaRP 82

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1929828186 115 T-----DALLCITNLPISFTLEEFEELVRAYGNVERCFLVYNEVTGHSKGYGFVEYMKKDSAAKARLELLG 180
Cdd:TIGR01661  83 SsdsikGANLYVSGLPKTMTQHELESIFSPFGQIITSRILSDNVTGLSKGVGFIRFDKRDEADRAIKTLNG 153

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 1929828186  32 RLASTRRE-LGNrrkILLRNLPAESSSQEIHDLFKDY-EIKYCYV--DRNKRT---AFVTLLNGEQAQNAIQKFHQYSLR 104
Cdd:TIGR01628  79 RDPSLRRSgVGN---IFVKNLDKSVDNKALFDTFSKFgNILSCKVatDENGKSrgyGFVHFEKEESAKAAIQKVNGMLLN 155

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1929828186 105 GKEISVQL---------QPTDAL--LCITNLPISFTLEEFEELVRAYGNVERCfLVYNEVTGHSKGYGFVEYMKKDSAAK 173
Cdd:TIGR01628 156 DKEVYVGRfikkhereaAPLKKFtnLYVKNLDPSVNEDKLRELFAKFGEITSA-AVMKDGSGRSRGFAFVNFEKHEDAAK 234

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1929828186 174 ARLELLGKQLDESTlfaqwmdvnllttnliHSKCLCVDKFQKDYADSKELIQAF-------------------------- 227
Cdd:TIGR01628 235 AVEEMNGKKIGLAK----------------EGKKLYVGRAQKRAEREAELRRKFeelqqerkmkaqgvnlyvknlddtvt 298

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1929828186 228 SLKYKPVFCQFAQ--------DEDSCIGDFAVVEYETAEQAEKVHEVTDGMTIKGKRIQVSYCAPGAPGRSTLAALIA-A 298
Cdd:TIGR01628 299 DEKLRELFSECGEitsakvmlDEKGVSRGFGFVCFSNPEEANRAVTEMHGRMLGGKPLYVALAQRKEQRRAHLQDQFMqL 378

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1929828186 299 QRMMRNNRKG----------LLPEPNPVQIMKS--FNNPAMlQMLLQPQLRGHAVKPVlgasaGLPHliNSAVG-PPFLQ 365
Cdd:TIGR01628 379 QPRMRQLPMGspmggamgqpPYYGQGPQQQFNGqpLGWPRM-SMMPTPMGPGGPLRPN-----GLAP--MNAVRaPSRNA 450

                         410       420       430       440       450       460
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1929828186 366 LNKVHQSS---ILGSTSNLLLQSPAHLPLPQQQLMKIENIKANSKPgLLGEPPTMLLQtVLG 424
Cdd:TIGR01628 451 QNAAQKPPmqpVMYPPNYQSLPLSQDLPQPQSTASQGGQNKKLAQV-LASATPQMQKQ-VLG 510

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1929828186 119 LCITNLPISFTLEEFEELVRAYGNVERCFLVYNEVTGHSKGYGFVEYMKKDSAAKARLELLGKQLDESTL 188
Cdd:TIGR01661   6 LIVNYLPQTMTQEEIRSLFTSIGEIESCKLVRDKVTGQSLGYGFVNYVRPEDAEKAVNSLNGLRLQNKTI 75

Trafficking protein particle complex subunit 4; Trafficking protein particle complex subunit 4 (TRAPPC4), also known as synbindin or TRS23, has been identified as a component of the transport protein particle (TRAPP), required for tethering endoplasmic reticulum (ER)-derived vesicles to Golgi membranes and for Golgi traffic.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1929828186 536 PKEIRLSTNPYLNLASVLPGIClpAIASKASSPPQQTGL 574
Cdd:cd14856    20 DALAKLSSNDYLRLASTFHGLH--AIAAQLSPVPGSSGI 56

RNA recognition motif 3 (RRM3) found found in vertebrate ribonucleoprotein PTB-binding 2 (raver-2); This subgroup corresponds to the RRM3 of raver-2, a novel member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family. It is present in vertebrates and shows high sequence homology to raver-1, a ubiquitously expressed co-repressor of the nucleoplasmic splicing repressor polypyrimidine tract-binding protein (PTB)-directed splicing of select mRNAs. In contrast, raver-2 exerts a distinct spatio-temporal expression pattern during embryogenesis and is mainly limited to differentiated neurons and glia cells. Although it displays nucleo-cytoplasmic shuttling in heterokaryons, raver2 localizes to the nucleus in glia cells and neurons. Raver-2 can interact with PTB and may participate in PTB-mediated RNA-processing. However, there is no evidence indicating that raver-2 can bind to cytoplasmic proteins. Raver-2 contains three N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two putative nuclear localization signals (NLS) at the N- and C-termini, a central leucine-rich region, and a C-terminal region harboring two [SG][IL]LGxxP motifs. Raver-2 binds to PTB through the SLLGEPP motif only, and binds to RNA through its RRMs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1929828186 204 HSKCLCVDKFQKDYADSKELIQAFSLKYKPVFCQFAQDEDSCIGDFAVVEYETAEQAEKVHEVTDGMTIKGKRIQVSYCA 283
Cdd:cd12668     1 HSKCLCVDKLPKDYSDSEELTQLFSRPYKPVFCQLAQDEGSCIGGFAVVEYETAEQAEEVQRAMDGMTIGGSRVQVSFCA 80

                          90
                  ....*....|....*...
gi 1929828186 284 PGAPGRSTLAALIAAQRM 301
Cdd:cd12668    81 PGSPGRSTLAALIAAQGM 98

RNA recognition motif 1 (RRM1) found in vertebrate ribonucleoprotein PTB-binding 2 (raver-2); This subgroup corresponds to the RRM1 of raver-2, a novel member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family. It is present in vertebrates and shows high sequence homology to raver-1, a ubiquitously expressed co-repressor of the nucleoplasmic splicing repressor polypyrimidine tract-binding protein (PTB)-directed splicing of select mRNAs. In contrast, raver-2 exerts a distinct spatio-temporal expression pattern during embryogenesis and is mainly limited to differentiated neurons and glia cells. Although it displays nucleo-cytoplasmic shuttling in heterokaryons, raver2 localizes to the nucleus in glia cells and neurons. Raver-2 can interact with PTB and may participate in PTB-mediated RNA-processing. However, there is no evidence indicating that raver-2 can bind to cytoplasmic proteins. Raver-2 contains three N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two putative nuclear localization signals (NLS) at the N- and C-termini, a central leucine-rich region, and a C-terminal region harboring two [SG][IL]LGxxP motifs. Raver-2 binds to PTB through the SLLGEPP motif only, and binds to RNA through its RRMs.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1929828186  45 KILLRNLPAESSSQEIHDLFKDYEIKYCYVDRNKRTAFVTLLNGEQAQNAIQKFHQYSLRGKEISVQLQP 114
Cdd:cd12664     1 KILIKNLPQDSTSQEVHDLLKDYELKYCYVDRNKRTAFVTLLNGEQAQDAIRTFHQHSLRGRDISVQLQP 70

RNA recognition motif 2 (RRM2) found found in vertebrate ribonucleoprotein PTB-binding 1 (raver-1); This subgroup corresponds to the RRM2 of raver-1, a ubiquitously expressed heterogeneous nuclear ribonucleoprotein (hnRNP) that serves as a co-repressor of the nucleoplasmic splicing repressor polypyrimidine tract-binding protein (PTB)-directed splicing of select mRNAs. It shuttles between the cytoplasm and the nucleus and can accumulate in the perinucleolar compartment, a dynamic nuclear substructure that harbors PTB. Raver-1 also modulates focal adhesion assembly by binding to the cytoskeletal proteins, including alpha-actinin, vinculin, and metavinculin (an alternatively spliced isoform of vinculin) at adhesion complexes, particularly in differentiated muscle tissue. Raver-1 contains three N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two putative nuclear localization signals (NLS) at the N- and C-termini, a central leucine-rich region, and a C-terminal region harboring two PTB-binding [SG][IL]LGxxP motifs. Raver1 binds to PTB through the PTB-binding motifs at its C-terminal half, and binds to other partners, such as RNA having the sequence UCAUGCAGUCUG, through its N-terminal RRMs. Interestingly, the 12-nucleotide RNA having the sequence UCAUGCAGUCUG with micromolar affinity is found in vinculin mRNA. Additional research indicates that the RRM1 of raver-1 directs its interaction with the tail domain of activated vinculin. Then the raver1/vinculin tail (Vt) complex binds to vinculin mRNA, which is permissive for vinculin binding to F-actin.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1929828186 118 LLCITNLPISFTLEEFEELVRAYGNVERCFLVYNEVTGHSKGYGFVEYMKKDSAAKARLELLGKQLDESTLFAQWMD 194
Cdd:cd12665     1 LLCIANLPPSYTQQQFEELVRPFGNLERCFLVYSETTGHSKGYGFVEYMKKDSAARAKSDLLGKQLGTRTLYVHWTD 77

RNA recognition motif 1 (RRM1) found in vertebrate ribonucleoprotein PTB-binding 1 (raver-1); This subgroup corresponds to the RRM1 of raver-1, a ubiquitously expressed heterogeneous nuclear ribonucleoprotein (hnRNP) that serves as a co-repressor of the nucleoplasmic splicing repressor polypyrimidine tract-binding protein (PTB)-directed splicing of select mRNAs. It shuttles between the cytoplasm and the nucleus and can accumulate in the perinucleolar compartment, a dynamic nuclear substructure that harbors PTB. Raver-1 also modulates focal adhesion assembly by binding to the cytoskeletal proteins, including alpha-actinin, vinculin, and metavinculin (an alternatively spliced isoform of vinculin) at adhesion complexes, particularly in differentiated muscle tissue. Raver-1 contains three N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two putative nuclear localization signals (NLS) at the N- and C-termini, a central leucine-rich region, and a C-terminal region harboring two PTB-binding [SG][IL]LGxxP motifs. Raver1 binds to PTB through the PTB-binding motifs at its C-terminal half, and binds to other partners, such as RNA having the sequence UCAUGCAGUCUG, through its N-terminal RRMs. Interestingly, the 12-nucleotide RNA having the sequence UCAUGCAGUCUG with micromolar affinity is found in vinculin mRNA. Additional research indicates that the RRM1 of raver-1 directs its interaction with the tail domain of activated vinculin. Then the raver1/vinculin tail (Vt) complex binds to vinculin mRNA, which is permissive for vinculin binding to F-actin.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1929828186  44 RKILLRNLPAESSSQEIHDLFKDYEIKYCYVDRNKRTAFVTLLNGEQAQNAIQKFHQYSLRGKEISVQLQP 114
Cdd:cd12663     1 RKILIRGLPGDVTNQEVHDLLSDYELKYCFVDKYKGTAFVTLLNGEQAEAAINAFHQSRLRERELSVQLQP 71

RNA recognition motif 3 (RRM3) found in ribonucleoprotein PTB-binding raver-1, raver-2 and similar proteins; This subfamily corresponds to the RRM3 of raver-1 and raver-2. Raver-1 is a ubiquitously expressed heterogeneous nuclear ribonucleoprotein (hnRNP) that serves as a co-repressor of the nucleoplasmic splicing repressor polypyrimidine tract-binding protein (PTB)-directed splicing of select mRNAs. It shuttles between the cytoplasm and the nucleus and can accumulate in the perinucleolar compartment, a dynamic nuclear substructure that harbors PTB. Raver-1 also modulates focal adhesion assembly by binding to the cytoskeletal proteins, including alpha-actinin, vinculin, and metavinculin (an alternatively spliced isoform of vinculin) at adhesion complexes, particularly in differentiated muscle tissue. Raver-2 is a novel member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family. It shows high sequence homology to raver-1. Raver-2 exerts a spatio-temporal expression pattern during embryogenesis and is mainly limited to differentiated neurons and glia cells. Although it displays nucleo-cytoplasmic shuttling in heterokaryons, raver2 localizes to the nucleus in glia cells and neurons. Raver-2 can interact with PTB and may participate in PTB-mediated RNA-processing. However, there is no evidence indicating that raver-2 can bind to cytoplasmic proteins. Both, raver-1 and raver-2, contain three N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two putative nuclear localization signals (NLS) at the N- and C-termini, a central leucine-rich region, and a C-terminal region harboring two [SG][IL]LGxxP motifs. They binds to RNA through the RRMs. In addition, the two [SG][IL]LGxxP motifs serve as the PTB-binding motifs in raver1. However, raver-2 interacts with PTB through the SLLGEPP motif only.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1929828186 204 HSKCLCVDKFQKDYADSKELIQAFSLKYKPVFCQFAQDEdSCIGDFAVVEYETAEQAEKVHEVTDGMTIKGKRIQVSYCA 283
Cdd:cd12390     1 HSKCLFVDRLPKDFRDGSELRKLFSQVGKPTFCQLAMGN-GVPRGFAFVEFASAEDAEEAQQLLNGHDLQGSPIRVSFGN 79

                          90
                  ....*....|..
gi 1929828186 284 PGAPGRSTLAAL 295
Cdd:cd12390    80 PGRPGASLLRRL 91

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 1929828186 119 LCITNLPISFTLEEFEELVRAYGNVERCFLVYNEvTGHSKGYGFVEYMKKDSAAKARLELLGKQLDESTL 188
Cdd:cd00590     1 LFVGNLPPDTTEEDLRELFSKFGEVVSVRIVRDR-DGKSKGFAFVEFESPEDAEKALEALNGTELGGRPL 69

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1929828186 119 LCITNLPISFTLEEFEELVRAYGNVERCFLVYNEVTGHSKGYGFVEYMKKDSAAKARLELLGKQLDESTL 188
Cdd:COG0724     4 IYVGNLPYSVTEEDLRELFSEYGEVTSVKLITDRETGRSRGFGFVEMPDDEEAQAAIEALNGAELMGRTL 73

RNA recognition motif 1 (RRM1) found in the Hu proteins family, Drosophila sex-lethal (SXL), and similar proteins; This subfamily corresponds to the RRM1 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 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. This family also includes 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 to its own pre-mRNA and promotes female-specific alternative splicing. It 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 1929828186 119 LCITNLPISFTLEEFEELVRAYGNVERCFLVYNEVTGHSKGYGFVEYMKKDSAAKARLELLGKQLDESTL 188
Cdd:cd12375     2 LIVNYLPQSMTQEELRSLFGAIGPIESCKLVRDKITGQSLGYGFVNYRDPNDARKAINTLNGLDLENKRL 71

RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1929828186   45 KILLRNLPAESSSQEIHDLFKDY-EIKYCYVDRNKRT------AFVTLLNGEQAQNAIQKFHQYSLRGKEISV 110
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSKFgKVESVRLVRDKETgkskgfAFVEFESEEDAEKALEALNGKELDGRPLKV 73

RNA recognition motif 3 (RRM3) found in RNA-binding protein 28 (RBM28) and similar proteins; This subfamily corresponds to the RRM3 of RBM28 and Nop4p. RBM28 is a specific nucleolar component of the spliceosomal small nuclear ribonucleoproteins (snRNPs), possibly coordinating their transition through the nucleolus. It specifically associates with U1, U2, U4, U5, and U6 small nuclear RNAs (snRNAs), and may play a role in the maturation of both small nuclear and ribosomal RNAs. RBM28 has four RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and an extremely acidic region between RRM2 and RRM3. The family also includes nucleolar protein 4 (Nop4p or 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 also contains four RRMs.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1929828186 121 ITNLPISFTLEEFEELVRAYGNVERCFLVYNEVTGHSKGYGFVEYMKKDSAAKA 174
Cdd:cd12415     5 IRNLSFDTTEEDLKEFFSKFGEVKYARIVLDKDTGHSKGTAFVQFKTKESADKC 58

RNA recognition motif (RRM) found in eukaryotic translation initiation factor 3 subunit G (eIF-3G) and similar proteins; This subfamily corresponds to the RRM of eIF-3G and similar proteins. eIF-3G, also termed eIF-3 subunit 4, or eIF-3-delta, or eIF3-p42, or eIF3-p44, is the RNA-binding subunit of eIF3, a large multisubunit complex that plays a central role in the initiation of translation by binding to the 40 S ribosomal subunit and promoting the binding of methionyl-tRNAi and mRNA. eIF-3G binds 18 S rRNA and beta-globin mRNA, and therefore appears to be a nonspecific RNA-binding protein. eIF-3G is one of the cytosolic targets and interacts with mature apoptosis-inducing factor (AIF). eIF-3G contains one RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). This family also includes yeast eIF3-p33, a homolog of vertebrate eIF-3G, plays an important role in the initiation phase of protein synthesis in yeast. It binds both, mRNA and rRNA, fragments due to an RRM near its C-terminus.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1929828186 121 ITNLPISFTLEEFEELVRAYGNVERCFLVYNEVTGHSKGYGFVEYMKKDSAAKARLELLGKQLDESTLFAQW 192
Cdd:cd12408     4 VTNLSEDATEEDLRELFRPFGPISRVYLAKDKETGQSKGFAFVTFETREDAERAIEKLNGFGYDNLILSVEW 75

RNA recognition motif 3 (RRM3) found in RNA-binding protein 19 (RBM19) and RNA recognition motif 2 found in multiple RNA-binding domain-containing protein 1 (MRD1); This subfamily corresponds to the RRM3 of RBM19 and RRM2 of MRD1. RBM19, also termed RNA-binding domain-1 (RBD-1), is a nucleolar protein conserved in eukaryotes involved in ribosome biogenesis by processing rRNA and is essential for preimplantation development. It has a unique domain organization containing 6 conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). MRD1 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 RRMs, which may play an important structural role in organizing specific rRNA processing events.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1929828186 119 LCITNLPISFTLEEFEELVRAYGNVERCFLVYNEVTGHSKGYGFVEYMKKDSAAKARLELLGK 181
Cdd:cd12316     2 LFVRNLPFTATEDELRELFEAFGKISEVHIPLDKQTKRSKGFAFVLFVIPEDAVKAYQELDGS 64

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1929828186  45 KILLRNLPAESSSQEIHDLFKDY-EIKYCYVDRNKRT------AFVTLLNGEQAQNAIQKFHQYSLRGKEISV 110
Cdd:COG0724     3 KIYVGNLPYSVTEEDLRELFSEYgEVTSVKLITDRETgrsrgfGFVEMPDDEEAQAAIEALNGAELMGRTLKV 75

RNA recognition motif 1 (RRM1) found in vertebrate Hu-antigen D (HuD); This subgroup corresponds to the RRM1 of HuD, also termed ELAV-like protein 4 (ELAV-4), or paraneoplastic encephalomyelitis antigen HuD, one of the neuronal members of the Hu family. The neuronal Hu proteins play important roles in neuronal differentiation, plasticity and memory. HuD has been implicated in various aspects of neuronal function, such as the commitment and differentiation of neuronal precursors as well as synaptic remodeling in mature neurons. HuD also functions as an important regulator of mRNA expression in neurons by interacting with AU-rich RNA element (ARE) and stabilizing multiple transcripts. Moreover, HuD regulates the nuclear processing/stability of N-myc pre-mRNA in neuroblastoma cells, as well as the neurite elongation and morphological differentiation. HuD specifically binds poly(A) RNA. Like other Hu proteins, HuD 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 1929828186 119 LCITNLPISFTLEEFEELVRAYGNVERCFLVYNEVTGHSKGYGFVEYMKKDSAAKARLELLGKQLDESTL 188
Cdd:cd12770     4 LIVNYLPQNMTQEEFRSLFGSIGEIESCKLVRDKITGQSLGYGFVNYIDPKDAEKAINTLNGLRLQTKTI 73

RNA recognition motif 1 (RRM1) found in vertebrate Hu-antigen C (HuC); This subgroup corresponds to the RRM1 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 1929828186 119 LCITNLPISFTLEEFEELVRAYGNVERCFLVYNEVTGHSKGYGFVEYMKKDSAAKARLELLGKQLDESTL 188
Cdd:cd12772     7 LIVNYLPQNMTQEEFKSLFGSIGDIESCKLVRDKITGQSLGYGFVNYVDPNDADKAINTLNGLKLQTKTI 76

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 1929828186 117 ALLCITNLPISFTLEEFEELVRAYGNVERCFLVYNEVTGHSKGYGFVEYMKKDSAAKARLELLGKQLDEST 187
Cdd:cd12652     1 ANLYVSGLPKTMTQKELEQLFSQFGRIITSRILCDNVTGLSRGVGFIRFDKRVEAERAIKALNGTIPPGAT 71

RNA recognition motif 1 (RRM1) found in vertebrate Hu-antigen B (HuB); This subgroup corresponds to the RRM1 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 and 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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1929828186 119 LCITNLPISFTLEEFEELVRAYGNVERCFLVYNEVTGHSKGYGFVEYMKKDSAAKARLELLGKQLDESTL 188
Cdd:cd12771     7 LIVNYLPQNMTQEELKSLFGSIGEIESCKLVRDKITGQSLGYGFVNYIEPKDAEKAINTLNGLRLQTKTI 76

RNA recognition motif 1 (RRM1) found in yeast nucleolar protein 4 (Nop4p) and similar proteins; This subgroup corresponds to the RRM1 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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1929828186 119 LCITNLPISFTLEEFEELVRAYGNVERCFLVYNEVTGHSKGYGFVEYMKKDSAAKARLELLGKQLDESTLFAQW 192
Cdd:cd12674     3 LFVRNLPFDVTLESLTDFFSDIGPVKHAVVVTDPETKKSRGYGFVSFSTHDDAEEALAKLKNRKLSGHILKLDF 76

RNA recognition motif 2 (RRM2) found in squamous cell carcinoma antigen recognized by T-cells 3 (SART3) and similar proteins; This subfamily corresponds to the RRM2 of SART3, also termed Tat-interacting protein of 110 kDa (Tip110), is an RNA-binding protein expressed in the nucleus of the majority of proliferating cells, including normal cells and malignant cells, but not in normal tissues except for the testes and fetal liver. It is involved in the regulation of mRNA splicing probably via its complex formation with RNA-binding protein with a serine-rich domain (RNPS1), a pre-mRNA-splicing factor. SART3 has also been identified as a nuclear Tat-interacting protein that regulates Tat transactivation activity through direct interaction and functions as an important cellular factor for HIV-1 gene expression and viral replication. In addition, SART3 is required for U6 snRNP targeting to Cajal bodies. It binds specifically and directly to the U6 snRNA, interacts transiently with the U6 and U4/U6 snRNPs, and promotes the reassembly of U4/U6 snRNPs after splicing in vitro. SART3 contains an N-terminal half-a-tetratricopeptide repeat (HAT)-rich domain, a nuclearlocalization signal (NLS) domain, and two C-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1929828186 119 LCITNLPISFTLEEFEELVRAYGNVERCFLVYNEvTGHSKGYGFVEYMKKDSAAKARLELLGKQLDESTL 188
Cdd:cd12392     5 LFVKGLPFSCTKEELEELFKQHGTVKDVRLVTYR-NGKPKGLAYVEYENEADASQAVLKTDGTEIKDHTI 73

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 1929828186  29 VARRLASTRRELGNRRK---ILLRNLPAESSSQEIHDLFKDY-EIKYCYV--DRNKRT---AFVTLLNGEQAQNAIQKFH 99
Cdd:TIGR01628 161 VGRFIKKHEREAAPLKKftnLYVKNLDPSVNEDKLRELFAKFgEITSAAVmkDGSGRSrgfAFVNFEKHEDAAKAVEEMN 240

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1929828186 100 QYSL----RGKEISVQ-LQPTD-----------------------ALLCITNLPISFTLEEFEELVRAYGNVERCFLVYN 151
Cdd:TIGR01628 241 GKKIglakEGKKLYVGrAQKRAereaelrrkfeelqqerkmkaqgVNLYVKNLDDTVTDEKLRELFSECGEITSAKVMLD 320

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1929828186 152 EvTGHSKGYGFVEYMKKDSAAKARLELLGKqldestlfaqwmdvnllttnLIHSKCLCVDKFQKDYADSKELIQAFSlKY 231
Cdd:TIGR01628 321 E-KGVSRGFGFVCFSNPEEANRAVTEMHGR--------------------MLGGKPLYVALAQRKEQRRAHLQDQFM-QL 378

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1929828186 232 KPVFCQFAQdEDSCIGDFAVVEYETAEQAEKVHEVTDGMTIKGKRIQVSYcaPGAPGRSTLAALIAAQRMMRNNRKGLLP 311
Cdd:TIGR01628 379 QPRMRQLPM-GSPMGGAMGQPPYYGQGPQQQFNGQPLGWPRMSMMPTPMG--PGGPLRPNGLAPMNAVRAPSRNAQNAAQ 455

                         330       340
                  ....*....|....*....|....*.
gi 1929828186 312 EP--NPVQIMKSFNNPAMLQMLLQPQ 335
Cdd:TIGR01628 456 KPpmQPVMYPPNYQSLPLSQDLPQPQ 481

RNA recognition motif 2 (RRM2) found in RNA-binding protein 45 (RBM45) and similar proteins; This subfamily corresponds to the RRM2 of RBM45, also termed developmentally-regulated RNA-binding protein 1 (DRB1), a new member of RNA recognition motif (RRM)-type neural RNA-binding proteins, which expresses under spatiotemporal control. It is encoded by gene drb1 that is expressed in neurons, not in glial cells. RBM45 predominantly localizes in cytoplasm of cultured cells and specifically binds to poly(C) RNA. It could play an important role during neurogenesis. RBM45 carries four RRMs, also known as RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1929828186 125 PISFTLEEFEELVRAYGNVERCFLVYNEVTGHSKGYGFVEYMKKDSAAKA 174
Cdd:cd12367     9 PKSYTEEDLREKFKEFGDIEYCSIVKDKNTGESKGFGYVKFLKPSQAALA 58

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 1929828186  46 ILLRNLPAESSSQEIHDLFKDY-EIKYCYV-----DRNKRTAFVTLLNGEQAQNAIQKFHQYSLRGKEI 108
Cdd:pfam00076   1 LFVGNLPPDTTEEDLKDLFSKFgPIKSIRLvrdetGRSKGFAFVEFEDEEDAEKAIEALNGKELGGREL 69

RNA recognition motif 1 (RRM1) found in vertebrate Hu-antigen R (HuR); This subgroup corresponds to the RRM1 of HuR, also termed ELAV-like protein 1 (ELAV-1), a 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. Meanwhile, 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1929828186 119 LCITNLPISFTLEEFEELVRAYGNVERCFLVYNEVTGHSKGYGFVEYMKKDSAAKARLELLGKQLDESTL 188
Cdd:cd12769     5 LIVNYLPQNMTQDELRSLFSSIGEVESAKLIRDKVAGHSLGYGFVNYVTAKDAERAINTLNGLRLQSKTI 74

RNA recognition motif (RRM) found in heterogeneous nuclear ribonucleoprotein (hnRNP) H protein family, epithelial splicing regulatory proteins (ESRPs), Drosophila RNA-binding protein Fusilli, RNA-binding protein 12 (RBM12) and similar proteins; The family includes RRM domains in the hnRNP H protein family, G-rich sequence factor 1 (GRSF-1), ESRPs (also termed RBM35), Drosophila Fusilli, RBM12 (also termed SWAN), RBM12B, RBM19 (also termed RBD-1) and similar proteins. The hnRNP H protein family includes hnRNP H (also termed mcs94-1), hnRNP H2 (also termed FTP-3 or hnRNP H'), hnRNP F and hnRNP H3 (also termed hnRNP 2H9), which represent a group of nuclear RNA binding proteins that are involved in pre-mRNA processing. GRSF-1 is a cytoplasmic poly(A)+ mRNA binding protein which interacts with RNA in a G-rich element-dependent manner. It may function in RNA packaging, stabilization of RNA secondary structure, or other macromolecular interactions. ESRP1 (also termed RBM35A) and ESRP2 (also termed RBM35B) are epithelial-specific RNA binding proteins that promote splicing of the epithelial variant of fibroblast growth factor receptor 2 (FGFR2), ENAH (also termed hMena), CD44 and CTNND1 (also termed p120-Catenin) transcripts. Fusilli shows high sequence homology to ESRPs. It can regulate endogenous FGFR2 splicing and functions as a splicing factor. The biological roles of both, RBM12 and RBM12B, remain unclear. RBM19 is a nucleolar protein conserved in eukaryotes. It is involved in ribosome biogenesis by processing rRNA. In addition, it is essential for preimplantation development. Members in this family contain 2~6 conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1929828186  46 ILLRNLPAESSSQEIHDLFKDYE-----IKYCYVDRNKRT--AFVTLLNGEQAQNAIQKfHQYSLRGKEISV 110
Cdd:cd12254     2 VRLRGLPFSATEEDIRDFFSGLDippdgIHIVYDDDGRPTgeAYVEFASEEDAQRALRR-HKGKMGGRYIEV 72

RNA recognition motif (RRM) found in cold inducible RNA binding protein (CIRBP), RNA binding motif protein 3 (RBM3) and similar proteins; This subfamily corresponds to the RRM domain of two structurally related heterogenous nuclear ribonucleoproteins, CIRBP (also termed CIRP or A18 hnRNP) and RBM3 (also termed RNPL), both of which belong to a highly conserved cold shock proteins family. The cold shock proteins can be induced after exposure to a moderate cold-shock and other cellular stresses such as UV radiation and hypoxia. CIRBP and RBM3 may function in posttranscriptional regulation of gene expression by binding to different transcripts, thus allowing the cell to response rapidly to environmental signals. However, the kinetics and degree of cold induction are different between CIRBP and RBM3. Tissue distribution of their expression is different. CIRBP and RBM3 may be differentially regulated under physiological and stress conditions and may play distinct roles in cold responses of cells. CIRBP, also termed glycine-rich RNA-binding protein CIRP, is localized in the nucleus and mediates the cold-induced suppression of cell cycle progression. CIRBP also binds DNA and possibly serves as a chaperone that assists in the folding/unfolding, assembly/disassembly and transport of various proteins. RBM3 may enhance global protein synthesis and the formation of active polysomes while reducing the levels of ribonucleoprotein complexes containing microRNAs. RBM3 may also serve to prevent the loss of muscle mass by its ability to decrease cell death. Furthermore, RBM3 may be essential for cell proliferation and mitosis. Both, CIRBP and RBM3, contain an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), that is involved in RNA binding, and C-terminal glycine-rich domain (RGG motif) that probably enhances RNA-binding via protein-protein and/or protein-RNA interactions. Like CIRBP, RBM3 can also bind to both RNA and DNA via its RRM domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1929828186 126 ISFTLEE--FEELVRAYGNVERCFLVYNEVTGHSKGYGFVEYMKKDSAAKARLELLGKQLDESTLF 189
Cdd:cd12449     8 LSFDTNEqsLEEVFSKYGQISEVVVVKDRETQRSRGFGFVTFENPDDAKDAMMAMNGKSLDGRQIR 73