cyclophilin_ABH_like: Cyclophilin A, B and H-like cyclophilin-type peptidylprolyl cis- trans isomerase (PPIase) domain. This family represents the archetypal cystolic cyclophilin similar to human cyclophilins A, B and H. PPIase is an enzyme which accelerates protein folding by catalyzing the cis-trans isomerization of the peptide bonds preceding proline residues. These enzymes have been implicated in protein folding processes which depend on catalytic /chaperone-like activities. As cyclophilins, Human hCyP-A, human cyclophilin-B (hCyP-19), S. cerevisiae Cpr1 and C. elegans Cyp-3, are inhibited by the immunosuppressive drug cyclopsporin A (CsA). CsA binds to the PPIase active site. Cyp-3. S. cerevisiae Cpr1 interacts with the Rpd3 - Sin3 complex and in addition is a component of the Set3 complex. S. cerevisiae Cpr1 has also been shown to have a role in Zpr1p nuclear transport. Human cyclophilin H associates with the [U4/U6.U5] tri-snRNP particles of the splicesome.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647301 139 PQVFFDIRIGGNDAGRIVMLLRADVVPKTAENFRQLCTHEQG-----YGYKGCSFHRVIPEFMCQGGDFTNNNGTGGKSI 213
Cdd:cd01926   1 PKVFFDITIGGEPAGRIVMELFADVVPKTAENFRALCTGEKGkggkpFGYKGSTFHRVIPDFMIQGGDFTRGNGTGGKSI 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647301 214 YGKKFNDENFNLKHNSFGTLSMANSGANTNGSQFFICTTKTDWLDNKHVVFGHVISGAEVVRKMERCGSKSGTPSQKIVI 293
Cdd:cd01926  81 YGEKFPDENFKLKHTGPGLLSMANAGPNTNGSQFFITTVKTPWLDGKHVVFGKVVEGMDVVKKIENVGSGNGKPKKKVVI 160

                ....
gi 17647301 294 YSCG 297
Cdd:cd01926 161 ADCG 164

cyclophilin_ABH_like: Cyclophilin A, B and H-like cyclophilin-type peptidylprolyl cis- trans isomerase (PPIase) domain. This family represents the archetypal cystolic cyclophilin similar to human cyclophilins A, B and H. PPIase is an enzyme which accelerates protein folding by catalyzing the cis-trans isomerization of the peptide bonds preceding proline residues. These enzymes have been implicated in protein folding processes which depend on catalytic /chaperone-like activities. As cyclophilins, Human hCyP-A, human cyclophilin-B (hCyP-19), S. cerevisiae Cpr1 and C. elegans Cyp-3, are inhibited by the immunosuppressive drug cyclopsporin A (CsA). CsA binds to the PPIase active site. Cyp-3. S. cerevisiae Cpr1 interacts with the Rpd3 - Sin3 complex and in addition is a component of the Set3 complex. S. cerevisiae Cpr1 has also been shown to have a role in Zpr1p nuclear transport. Human cyclophilin H associates with the [U4/U6.U5] tri-snRNP particles of the splicesome.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647301 139 PQVFFDIRIGGNDAGRIVMLLRADVVPKTAENFRQLCTHEQG-----YGYKGCSFHRVIPEFMCQGGDFTNNNGTGGKSI 213
Cdd:cd01926   1 PKVFFDITIGGEPAGRIVMELFADVVPKTAENFRALCTGEKGkggkpFGYKGSTFHRVIPDFMIQGGDFTRGNGTGGKSI 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647301 214 YGKKFNDENFNLKHNSFGTLSMANSGANTNGSQFFICTTKTDWLDNKHVVFGHVISGAEVVRKMERCGSKSGTPSQKIVI 293
Cdd:cd01926  81 YGEKFPDENFKLKHTGPGLLSMANAGPNTNGSQFFITTVKTPWLDGKHVVFGKVVEGMDVVKKIENVGSGNGKPKKKVVI 160

                ....
gi 17647301 294 YSCG 297
Cdd:cd01926 161 ADCG 164

Cyclophilin type peptidyl-prolyl cis-trans isomerase/CLD; The peptidyl-prolyl cis-trans isomerases, also known as cyclophilins, share this domain of about 109 amino acids. Cyclophilins have been found in all organizms studied so far and catalyze peptidyl-prolyl isomerization during which the peptide bond preceding proline (the peptidyl-prolyl bond) is stabilized in the cis conformation. Mammalian cyclophilin A (CypA) is a major cellular target for the immunosuppressive drug cyclosporin A (CsA). Other roles for cyclophilins may include chaperone and cell signalling function.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647301   150 NDAGRIVMLLRADVVPKTAENFRQLCTheQGYgYKGCSFHRVIPEFMCQGGDFTnnnGTGGKSIYGKKFNDENFNLK-HN 228
Cdd:pfam00160   4 NGLGRIVIELFGDKAPKTVENFLQLCK--KGF-YDGTTFHRVIPGFMVQGGDPT---GTGGGGKSIFPIPDEIFPLLlKH 77

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 17647301   229 SFGTLSMANSGA--NTNGSQFFICTTKTDWLDNKHVVFGHVISGAEVVRKMERCGSKSGTPSQKIVIYSCGE 298
Cdd:pfam00160  78 KRGALSMANTGPapNSNGSQFFITLGPAPHLDGKYTVFGKVVEGMDVLEKIEKVPTDGDRPVKPVKILSCGV 149

RNA recognition motif (RRM) found in cyclophilin-33 (Cyp33) and similar proteins; This subfamily corresponds to the RRM of Cyp33, also termed peptidyl-prolyl cis-trans isomerase E (PPIase E), or cyclophilin E, or rotamase E. Cyp33 is a nuclear RNA-binding cyclophilin with an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal PPIase domain. Cyp33 possesses RNA-binding activity and preferentially binds to polyribonucleotide polyA and polyU, but hardly to polyG and polyC. It binds specifically to mRNA, which can stimulate its PPIase activity. Moreover, Cyp33 interacts with the third plant homeodomain (PHD3) zinc finger cassette of the mixed lineage leukemia (MLL) proto-oncoprotein and a poly-A RNA sequence through its RRM domain. It further mediates downregulation of the expression of MLL target genes HOXC8, HOXA9, CDKN1B, and C-MYC, in a proline isomerase-dependent manner. Cyp33 also possesses a PPIase activity that catalyzes cis-trans isomerization of the peptide bond preceding a proline, which has been implicated in the stimulation of folding and conformational changes in folded and unfolded proteins. The PPIase activity can be inhibited by the immunosuppressive drug cyclosporin A.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 17647301   8 IYVGGLADEVTERLLNNAFIPFGDIADIQMPADYESQRHRGFAFIEYEQSEDAAAAIDNMNDSELCGRTIRVNLA 82
Cdd:cd12347   1 LYVGGLAEEVDEKVLHAAFIPFGDIVDIQIPLDYETEKHRGFAFVEFEEAEDAAAAIDNMNESELFGRTIRVNLA 75

RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 17647301      7 TIYVGGLADEVTERLLNNAFIPFGDIADIQMPADYESQRHRGFAFIEYEQSEDAAAAIDNMNDSELCGRTIRV 79
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSKFGKVESVRLVRDKETGKSKGFAFVEFESEEDAEKALEALNGKELDGRPLKV 73

splicing factor, CC1-like family; This model represents a subfamily of RNA splicing factors including the Pad-1 protein (N. crassa), CAPER (M. musculus) and CC1.3 (H.sapiens). These proteins are characterized by an N-terminal arginine-rich, low complexity domain followed by three (or in the case of 4 H. sapiens paralogs, two) RNA recognition domains (rrm: pfam00706). These splicing factors are closely related to the U2AF splicing factor family (TIGR01642). A homologous gene from Plasmodium falciparum was identified in the course of the analysis of that genome at TIGR and was included in the seed.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647301     2 SNDKRTIYVGGLADEVTERLLNNAFIPFGDIADIQMPADYESQRHRGFAFIEYEQSEDAAAAIDNMNDSELCGRTIRVNL 81
Cdd:TIGR01622 211 SIPFHRLYVGNLHFNITEQDLRQIFEPFGEIEFVQLQKDPETGRSKGYGFIQFRDAEQAKEALEKMNGFELAGRPIKVGL 290

                          90
                  ....*....|
gi 17647301    82 AKPVRVKEDS 91
Cdd:TIGR01622 291 GNDFTPESDA 300

cyclophilin_ABH_like: Cyclophilin A, B and H-like cyclophilin-type peptidylprolyl cis- trans isomerase (PPIase) domain. This family represents the archetypal cystolic cyclophilin similar to human cyclophilins A, B and H. PPIase is an enzyme which accelerates protein folding by catalyzing the cis-trans isomerization of the peptide bonds preceding proline residues. These enzymes have been implicated in protein folding processes which depend on catalytic /chaperone-like activities. As cyclophilins, Human hCyP-A, human cyclophilin-B (hCyP-19), S. cerevisiae Cpr1 and C. elegans Cyp-3, are inhibited by the immunosuppressive drug cyclopsporin A (CsA). CsA binds to the PPIase active site. Cyp-3. S. cerevisiae Cpr1 interacts with the Rpd3 - Sin3 complex and in addition is a component of the Set3 complex. S. cerevisiae Cpr1 has also been shown to have a role in Zpr1p nuclear transport. Human cyclophilin H associates with the [U4/U6.U5] tri-snRNP particles of the splicesome.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647301 139 PQVFFDIRIGGNDAGRIVMLLRADVVPKTAENFRQLCTHEQG-----YGYKGCSFHRVIPEFMCQGGDFTNNNGTGGKSI 213
Cdd:cd01926   1 PKVFFDITIGGEPAGRIVMELFADVVPKTAENFRALCTGEKGkggkpFGYKGSTFHRVIPDFMIQGGDFTRGNGTGGKSI 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647301 214 YGKKFNDENFNLKHNSFGTLSMANSGANTNGSQFFICTTKTDWLDNKHVVFGHVISGAEVVRKMERCGSKSGTPSQKIVI 293
Cdd:cd01926  81 YGEKFPDENFKLKHTGPGLLSMANAGPNTNGSQFFITTVKTPWLDGKHVVFGKVVEGMDVVKKIENVGSGNGKPKKKVVI 160

                ....
gi 17647301 294 YSCG 297
Cdd:cd01926 161 ADCG 164

peptidyl-prolyl isomerase H (cyclophilin H); Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647301  137 RNPQVFFDIRIGGNDAGRIVMLLRADVVPKTAENFRQLCTHE---QGY--GYKGCSFHRVIPEFMCQGGDFTNNNGTGGK 211
Cdd:PLN03149  17 KNPVVFFDVTIGGIPAGRIKMELFADIAPKTAENFRQFCTGEfrkAGLpqGYKGCQFHRVIKDFMIQGGDFLKGDGTGCV 96

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647301  212 SIYGKKFNDENFNLKHNSFGTLSMANSGANTNGSQFFICTTKTDWLDNKHVVFGHVI-SGAEVVRKMERCGSKSGT-PSQ 289
Cdd:PLN03149  97 SIYGSKFEDENFIAKHTGPGLLSMANSGPNTNGCQFFITCAKCDWLDNKHVVFGRVLgDGLLVVRKIENVATGPNNrPKL 176

                        170
                 ....*....|
gi 17647301  290 KIVIYSCGEL 299
Cdd:PLN03149 177 ACVISECGEM 186

Cyclophilin type peptidyl-prolyl cis-trans isomerase/CLD; The peptidyl-prolyl cis-trans isomerases, also known as cyclophilins, share this domain of about 109 amino acids. Cyclophilins have been found in all organizms studied so far and catalyze peptidyl-prolyl isomerization during which the peptide bond preceding proline (the peptidyl-prolyl bond) is stabilized in the cis conformation. Mammalian cyclophilin A (CypA) is a major cellular target for the immunosuppressive drug cyclosporin A (CsA). Other roles for cyclophilins may include chaperone and cell signalling function.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647301   150 NDAGRIVMLLRADVVPKTAENFRQLCTheQGYgYKGCSFHRVIPEFMCQGGDFTnnnGTGGKSIYGKKFNDENFNLK-HN 228
Cdd:pfam00160   4 NGLGRIVIELFGDKAPKTVENFLQLCK--KGF-YDGTTFHRVIPGFMVQGGDPT---GTGGGGKSIFPIPDEIFPLLlKH 77

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 17647301   229 SFGTLSMANSGA--NTNGSQFFICTTKTDWLDNKHVVFGHVISGAEVVRKMERCGSKSGTPSQKIVIYSCGE 298
Cdd:pfam00160  78 KRGALSMANTGPapNSNGSQFFITLGPAPHLDGKYTVFGKVVEGMDVLEKIEKVPTDGDRPVKPVKILSCGV 149

RNA recognition motif (RRM) found in cyclophilin-33 (Cyp33) and similar proteins; This subfamily corresponds to the RRM of Cyp33, also termed peptidyl-prolyl cis-trans isomerase E (PPIase E), or cyclophilin E, or rotamase E. Cyp33 is a nuclear RNA-binding cyclophilin with an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal PPIase domain. Cyp33 possesses RNA-binding activity and preferentially binds to polyribonucleotide polyA and polyU, but hardly to polyG and polyC. It binds specifically to mRNA, which can stimulate its PPIase activity. Moreover, Cyp33 interacts with the third plant homeodomain (PHD3) zinc finger cassette of the mixed lineage leukemia (MLL) proto-oncoprotein and a poly-A RNA sequence through its RRM domain. It further mediates downregulation of the expression of MLL target genes HOXC8, HOXA9, CDKN1B, and C-MYC, in a proline isomerase-dependent manner. Cyp33 also possesses a PPIase activity that catalyzes cis-trans isomerization of the peptide bond preceding a proline, which has been implicated in the stimulation of folding and conformational changes in folded and unfolded proteins. The PPIase activity can be inhibited by the immunosuppressive drug cyclosporin A.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 17647301   8 IYVGGLADEVTERLLNNAFIPFGDIADIQMPADYESQRHRGFAFIEYEQSEDAAAAIDNMNDSELCGRTIRVNLA 82
Cdd:cd12347   1 LYVGGLAEEVDEKVLHAAFIPFGDIVDIQIPLDYETEKHRGFAFVEFEEAEDAAAAIDNMNESELFGRTIRVNLA 75

cyclophilin_RING: cyclophilin-type peptidylprolyl cis- trans isomerases (cyclophilins) having a modified RING finger domain. This group includes the nuclear proteins, Human hCyP-60 and Caenorhabditis elegans MOG-6 which, compared to the archetypal cyclophilin Human cyclophilin A exhibit reduced peptidylprolyl cis- trans isomerase activity and lack a residue important for cyclophilin binding. Human hCyP-60 has been shown to physically interact with the proteinase inhibitor peptide eglin c and; C. elegans MOG-6 to physically interact with MEP-1, a nuclear zinc finger protein. MOG-6 has been shown to function in germline sex determination.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647301 153 GRIVMLLRADVVPKTAENFRQLCthEQGYgYKGCSFHRVIPEFMCQGGDFTNNnGTGGKSIYGKKFNDE-NFNLKHNSFG 231
Cdd:cd01923   9 GDLNLELHCDKAPKACENFIKLC--KKGY-YDGTIFHRSIRNFMIQGGDPTGT-GRGGESIWGKPFKDEfKPNLSHDGRG 84

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 17647301 232 TLSMANSGANTNGSQFFICTTKTDWLDNKHVVFGHVISGAEVVRKMERCGS-KSGTPSQKIVI 293
Cdd:cd01923  85 VLSMANSGPNTNGSQFFITYRSCKHLDGKHTVFGRVVGGLETLEAMENVPDpGTDRPKEEIKI 147

Cyclophilin_PPIL3_like. Proteins similar to Human cyclophilin-like peptidylprolyl cis- trans isomerase (PPIL3). Members of this family lack a key residue important for cyclosporin binding: the tryptophan residue corresponding to W121 in human hCyP-18a; most members have a histidine at this position. The exact function of the protein is not known.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647301 151 DAGRIVMLLRADVVPKTAENFRQLCTheQGYgYKGCSFHRVIPEFMCQGGDFTNNnGTGGKSIYGKKFNDENFN-LKHNS 229
Cdd:cd01928   8 NLGDIKIELFCDDCPKACENFLALCA--SGY-YNGCIFHRNIKGFMVQTGDPTGT-GKGGESIWGKKFEDEFREtLKHDS 83

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 17647301 230 FGTLSMANSGANTNGSQFFICTTKTDWLDNKHVVFGHVISGAEVVRKMERC-GSKSGTPSQKIVI 293
Cdd:cd01928  84 RGVVSMANNGPNTNGSQFFITYAKQPHLDGKYTVFGKVIDGFETLDTLEKLpVDKKYRPLEEIRI 148

cyclophilin_RRM: cyclophilin-type peptidylprolyl cis- trans isomerase domain occuring with a C-terminal RNA recognition motif domain (RRM). This subfamily of the cyclophilin domain family contains a number of eukaryotic cyclophilins having the RRM domain including the nuclear proteins: human hCyP-57, Arabidopsis thaliana AtCYP59, Caenorhabditis elegans CeCyP-44 and Paramecium tetrurelia Kin241. The Kin241 protein has been shown to have a role in cell morphogenesis.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647301 153 GRIVMLLRADVVPKTAENFRQLCthEQGYgYKGCSFHRVIPEFMCQGGDfTNNNGTGGKSIYGKK-------FNDE-NFN 224
Cdd:cd01921   7 GDLVIDLFTDECPLACLNFLKLC--KLKY-YNFCLFYNVQKDFIAQTGD-PTGTGAGGESIYSQLygrqarfFEPEiLPL 82

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 17647301 225 LKHNSFGTLSMANSGANTNGSQFFICTTK-TDWLDNKHVVFGHVISGAEVVRKM-ERCGSKSGTPSQKIVI 293
Cdd:cd01921  83 LKHSKKGTVSMVNAGDNLNGSQFYITLGEnLDYLDGKHTVFGQVVEGFDVLEKInDAIVDDDGRPLKDIRI 153

RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 17647301      7 TIYVGGLADEVTERLLNNAFIPFGDIADIQMPADYESQRHRGFAFIEYEQSEDAAAAIDNMNDSELCGRTIRV 79
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSKFGKVESVRLVRDKETGKSKGFAFVEFESEEDAEKALEALNGKELDGRPLKV 73

cyclophilin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647301  133 KAEKRNPQVFFDIRIGGNDAGRIVMLLRADVVPKTAENFRQLCTHEQG--------YGYKGCSFHRVipefmcqggDFTN 204
Cdd:PTZ00221  47 KEEQNSCRAFLDISIGDVLAGRLVFELFEDVVPETVENFRALITGSCGidtntgvkLDYLYTPVHHV---------DRNN 117

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17647301  205 NNGTGGK------SIYGKKFNDENFNLKHNSFGTLSMANSGANTNGSQFFICTTKTDWLDNKHVVFGHVISGAEVVRKME 278
Cdd:PTZ00221 118 NIIVLGEldsfnvSSTGTPIADEGYRHRHTERGLLTMISEGPHTSGSVFGITLGPSPSLDFKQVVFGKAVDDLSLLEKLE 197

                        170       180
                 ....*....|....*....|..
gi 17647301  279 RCG-SKSGTPSQKIVIYSCGEL 299
Cdd:PTZ00221 198 SLPlDDVGRPLLPVTVSFCGAL 219

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 17647301   8 IYVGGLADEVTERLLNNAFIPFGDIADIQMPADyESQRHRGFAFIEYEQSEDAAAAIDNMNDSELCGRTIRVN 80
Cdd:cd00590   1 LFVGNLPPDTTEEDLRELFSKFGEVVSVRIVRD-RDGKSKGFAFVEFESPEDAEKALEALNGTELGGRPLKVS 72

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 17647301     8 IYVGGLADEVTERLLNNAFIPFGDIADIQMPADyESQRHRGFAFIEYEQSEDAAAAIDNMNDSELCGRTIR 78
Cdd:pfam00076   1 LFVGNLPPDTTEEDLKDLFSKFGPIKSIRLVRD-ETGRSKGFAFVEFEDEEDAEKAIEALNGKELGGRELK 70

RNA recognition motif 1 (RRM1) found in (U)-binding-splicing factor PUF60 and similar proteins; This subfamily corresponds to the RRM1 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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 17647301   8 IYVGGLADEVTERLLNNAFIPFGDIADIQMPADYESQRHRGFAFIEYEQSEDAAAAIDNMNDSELCGRTIRVN 80
Cdd:cd12370   3 VYVGSIYFELGEDTIRQAFAPFGPIKSIDMSWDPVTMKHKGFAFVEYEVPEAAQLALEQMNGVMLGGRNIKVG 75

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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 17647301   8 IYVGGLADEVTERLLNNAFIPFGDIADIQMPADYESQRHRGFAFIEYEQSEDAAAAIDNMNDSELCGRTIRVN 80
Cdd:cd12353   2 IFVGDLSPEIETEDLKEAFAPFGEISDARVVKDTQTGKSKGYGFVSFVKKEDAENAIQGMNGQWLGGRNIRTN 74

RNA recognition motif (RRM) found in ist3 family; This subfamily corresponds to the RRM of the ist3 family that includes fungal U2 small nuclear ribonucleoprotein (snRNP) component increased sodium tolerance protein 3 (ist3), X-linked 2 RNA-binding motif proteins (RBMX2) found in Metazoa and plants, and similar proteins. Gene IST3 encoding ist3, also termed U2 snRNP protein SNU17 (Snu17p), is a novel yeast Saccharomyces cerevisiae protein required for the first catalytic step of splicing and for progression of spliceosome assembly. It binds specifically to the U2 snRNP and is an intrinsic component of prespliceosomes and spliceosomes. Yeast ist3 contains an atypical RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). In the yeast pre-mRNA retention and splicing complex, the atypical RRM of ist3 functions as a scaffold that organizes the other two constituents, Bud13p (bud site selection 13) and Pml1p (pre-mRNA leakage 1). Fission yeast Schizosaccharomyces pombe gene cwf29 encoding ist3, also termed cell cycle control protein cwf29, is an RNA-binding protein complexed with cdc5 protein 29. It also contains one RRM. The biological function of RBMX2 remains unclear. It shows high sequence similarity to yeast ist3 protein and harbors one RRM as well.

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gi 17647301   8 IYVGGLADEVTERLLNNAFIPFGDIADIQMPADYESQRHRGFAFIEYEQSEDAAAAIDNMNDSELCGRTIRV 79
Cdd:cd12411  12 IYIGGLPYELTEGDILCVFSQYGEIVDINLVRDKKTGKSKGFAFLAYEDQRSTILAVDNLNGIKLLGRTIRV 83

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.

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gi 17647301   8 IYVGGLADEVTERLLNNAFIPFGDIADIQMPADYESQRHRGFAFIEYEQSEDAAAAIDNMNDSELCGRTIRVNLAK 83
Cdd:cd12449   3 LFVGGLSFDTNEQSLEEVFSKYGQISEVVVVKDRETQRSRGFGFVTFENPDDAKDAMMAMNGKSLDGRQIRVDQAG 78

RNA recognition motif (RRM) found in cleavage stimulation factor subunit 2 (CSTF2), yeast ortholog mRNA 3'-end-processing protein RNA15 and similar proteins; This subfamily 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. The family also includes yeast ortholog mRNA 3'-end-processing protein RNA15 and similar proteins. RNA15 is a core subunit of cleavage factor IA (CFIA), an essential transcriptional 3'-end processing factor from Saccharomyces cerevisiae. RNA recognition by CFIA is mediated by an N-terminal RRM, which is contained in the RNA15 subunit of the complex. The RRM of RNA15 has a strong preference for GU-rich RNAs, mediated by a binding pocket that is entirely conserved in both yeast and vertebrate RNA15 orthologs.

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gi 17647301   6 RTIYVGGLADEVTERLLNNAFIPFGDIADIQMPADYESQRHRGFAFIEYEQSEDAAAAIDNMNDSELCGRTIRVNLA 82
Cdd:cd12398   1 RSVFVGNIPYDATEEQLKEIFSEVGPVVSFRLVTDRETGKPKGYGFCEFRDAETALSAVRNLNGYELNGRPLRVDFA 77

RNA recognition motif (RRM) found in heterogeneous nuclear ribonucleoprotein G (hnRNP G), Y chromosome RNA recognition motif 1 (hRBMY), testis-specific heterogeneous nuclear ribonucleoprotein G-T (hnRNP G-T) and similar proteins; This subfamily corresponds to the RRM domain of hnRNP G, also termed glycoprotein p43 or RBMX, an RNA-binding motif protein located on the X chromosome. It is expressed ubiquitously and has been implicated in the splicing control of several pre-mRNAs. Moreover, hnRNP G may function as a regulator of transcription for SREBP-1c and GnRH1. Research has shown that hnRNP G may also act as a tumor-suppressor since it upregulates the Txnip gene and promotes the fidelity of DNA end-joining activity. In addition, hnRNP G appears to play a critical role in proper neural development of zebrafish and frog embryos. The family also includes several paralogs of hnRNP G, such as hRBMY and hnRNP G-T (also termed RNA-binding motif protein, X-linked-like-2). Both, hRBMY and hnRNP G-T, are exclusively expressed in testis and critical for male fertility. Like hnRNP G, hRBMY and hnRNP G-T interact with factors implicated in the regulation of pre-mRNA splicing, such as hTra2-beta1 and T-STAR. Although members in this family share a high conserved N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), they appear to recognize different RNA targets. For instance, hRBMY interacts specifically with a stem-loop structure in which the loop is formed by the sequence CA/UCAA. In contrast, hnRNP G associates with single stranded RNA sequences containing a CCA/C motif. In addition to the RRM, hnRNP G contains a nascent transcripts targeting domain (NTD) in the middle region and a novel auxiliary RNA-binding domain (RBD) in its C-terminal region. The C-terminal RBD exhibits distinct RNA binding specificity, and would play a critical role in the regulation of alternative splicing by hnRNP G.

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gi 17647301   8 IYVGGLADEVTERLLNNAFIPFGDIADIQMPADYESQRHRGFAFIEYEQSEDAAAAIDNMNDSELCGRTIRVNLAK 83
Cdd:cd12382   4 LFIGGLNTETNEKALEAVFGKYGRIVEVLLMKDRETNKSRGFAFVTFESPADAKDAARDMNGKELDGKAIKVEQAT 79

RNA recognition motif (RRM) found in transformer-2 protein homolog TRA2-alpha, TRA2-beta and similar proteins; This subfamily corresponds to the RRM of two mammalian homologs of Drosophila transformer-2 (Tra2), TRA2-alpha, TRA2-beta (also termed SFRS10), and similar proteins found in eukaryotes. TRA2-alpha is a 40-kDa serine/arginine-rich (SR) protein that specifically binds to gonadotropin-releasing hormone (GnRH) exonic splicing enhancer on exon 4 (ESE4) and is necessary for enhanced GnRH pre-mRNA splicing. It strongly stimulates GnRH intron A excision in a dose-dependent manner. In addition, TRA2-alpha can interact with either 9G8 or SRp30c, which may also be crucial for ESE-dependent GnRH pre-mRNA splicing. TRA2-beta is a serine/arginine-rich (SR) protein that controls the pre-mRNA alternative splicing of the calcitonin/calcitonin gene-related peptide (CGRP), the survival motor neuron 1 (SMN1) protein and the tau protein. Both, TRA2-alpha and TRA2-beta, contains a well conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), flanked by the N- and C-terminal arginine/serine (RS)-rich regions.

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gi 17647301   6 RTIYVGGLADEVTERLLNNAFIPFGDIADIQMPADYESQRHRGFAFIEYEQSEDAAAAIDNMNDSELCGRTIRV 79
Cdd:cd12363   2 RCLGVFGLSLYTTERDLREVFSRYGPIEKVQVVYDQQTGRSRGFGFVYFESVEDAKEAKERLNGQEIDGRRIRV 75

RNA recognition motif (RRM) found in RNA-binding protein with serine-rich domain 1 (RNPS1) and similar proteins; This subfamily corresponds to the RRM of RNPS1 and its eukaryotic homologs. RNPS1, also termed RNA-binding protein prevalent during the S phase, or SR-related protein LDC2, was originally characterized as a general pre-mRNA splicing activator, which activates both constitutive and alternative splicing of pre-mRNA in vitro.It has been identified as a protein component of the splicing-dependent mRNP complex, or exon-exon junction complex (EJC), and is directly involved in mRNA surveillance. Furthermore, RNPS1 is a splicing regulator whose activator function is controlled in part by CK2 (casein kinase II) protein kinase phosphorylation. It can also function as a squamous-cell carcinoma antigen recognized by T cells-3 (SART3)-binding protein, and is involved in the regulation of mRNA splicing. RNPS1 contains an N-terminal serine-rich (S) domain, a central RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and the C-terminal arginine/serine/proline-rich (RS/P) domain.

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gi 17647301   8 IYVGGLADEVTERLLNNAFIPFGDIADIQMPADYESQRHRGFAFIEYEQSEDAAAAIDNMNDSELCGRTIRV 79
Cdd:cd12365   1 LHVGKLTRNVTKDHLKEIFSVYGTVKNVDLPIDREPNLPRGYAYVEFESPEDAEKAIKHMDGGQIDGQEVTV 72

RNA recognition motif (RRM) found in serine/arginine-rich splicing factor 10 (SRSF10) and similar proteins; This subgroup corresponds to the RRM of SRSF10, also termed 40 kDa SR-repressor protein (SRrp40), or FUS-interacting serine-arginine-rich protein 1 (FUSIP1), or splicing factor SRp38, or splicing factor, arginine/serine-rich 13A (SFRS13A), or TLS-associated protein with Ser-Arg repeats (TASR). SRSF10 is a serine-arginine (SR) protein that acts as a potent and general splicing repressor when dephosphorylated. It mediates global inhibition of splicing both in M phase of the cell cycle and in response to heat shock. SRSF10 emerges as a modulator of cholesterol homeostasis through the regulation of low-density lipoprotein receptor (LDLR) splicing efficiency. It also regulates cardiac-specific alternative splicing of triadin pre-mRNA and is required for proper Ca2+ handling during embryonic heart development. In contrast, the phosphorylated SRSF10 functions as a sequence-specific splicing activator in the presence of a nuclear cofactor. It activates distal alternative 5' splice site of adenovirus E1A pre-mRNA in vivo. Moreover, SRSF10 strengthens pre-mRNA recognition by U1 and U2 snRNPs. SRSF10 localizes to the nuclear speckles and can shuttle between nucleus and cytoplasm. It contains a single N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), followed by a C-terminal RS domain rich in serine-arginine dipeptides.

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gi 17647301   7 TIYVGGLADEVTERLLNNAFIPFGDIADIQMPADYESQRHRGFAFIEYEQSEDAAAAIDNMNDSELCGRTIRVNLAKPVR 86
Cdd:cd12559   7 SLFVRNVADDTRSEDLRREFGRYGPIVDVYVPLDFYTRRPRGFAYVQFEDVRDAEDALHNLDRKWICGRQIEIQFAQGDR 86

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 17647301   8 IYVGGLADEVTERLLNNAFIPFGDIADIQMPADYESQRHRGFAFIEYEQSEDAAAAIDNMNDSELCGRTIRVNLA 82
Cdd:cd12371   3 IYVASVHPDLSEDDIKSVFEAFGKIKSCSLAPDPETGKHKGYGFIEYENPQSAQDAIASMNLFDLGGQYLRVGRA 77

RNA recognition motif 3 (RRM3) found in heterogeneous nuclear ribonucleoprotein R (hnRNP R) and similar proteins; This subfamily corresponds to the RRM3 in hnRNP R, hnRNP Q, and APOBEC-1 complementation factor (ACF). hnRNP R is a ubiquitously expressed nuclear RNA-binding protein that specifically bind mRNAs with a preference for poly(U) stretches and has been implicated in mRNA processing and mRNA transport, and also acts as a regulator to modify binding to ribosomes and RNA translation. hnRNP Q is also a ubiquitously expressed nuclear RNA-binding protein. It has been identified as a component of the spliceosome complex, as well as a component of the apobec-1 editosome, and has been implicated in the regulation of specific mRNA transport. ACF is an RNA-binding subunit of a core complex that interacts with apoB mRNA to facilitate C to U RNA editing. It may also act as an apoB mRNA recognition factor and chaperone and play a key role in cell growth and differentiation. This family also includes two functionally unknown RNA-binding proteins, RBM46 and RBM47. All members contain three conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

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gi 17647301   6 RTIYVGGLADEVTERLLNNAFIPFGDIADIQMPADYesqrhrgfAFIEYEQSEDAAAAIDNMNDSELCGRTIRVNLAKP 84
Cdd:cd12251   2 KVLYVRNLMLSTTEEKLRELFSEYGKVERVKKIKDY--------AFVHFEERDDAVKAMEEMNGKELEGSEIEVSLAKP 72