RNA recognition motif (RRM) found in eukaryotic RNA-binding protein 25 and similar proteins; This subfamily corresponds to the RRM of RBM25, also termed Arg/Glu/Asp-rich protein of 120 kDa (RED120), or protein S164, or RNA-binding region-containing protein 7, an evolutionary-conserved splicing coactivator SRm160 (SR-related nuclear matrix protein of 160 kDa, )-interacting protein. RBM25 belongs to a family of RNA-binding proteins containing a well conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), at the N-terminus, a RE/RD-rich (ER) central region, and a C-terminal proline-tryptophan-isoleucine (PWI) motif. It localizes to the nuclear speckles and associates with multiple splicing components, including splicing cofactors SRm160/300, U snRNAs, assembled splicing complexes, and spliced mRNAs. It may play an important role in pre-mRNA processing by coupling splicing with mRNA 3'-end formation. Additional research indicates that RBM25 is one of the RNA-binding regulators that direct the alternative splicing of apoptotic factors. It can activate proapoptotic Bcl-xS 5'ss by binding to the exonic splicing enhancer, CGGGCA, and stabilize the pre-mRNA-U1 snRNP through interaction with hLuc7A, a U1 snRNP-associated factor.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 684400095  142 TTVFVGNISDRAPDQLIKTLLMRCGNILSWKRVQGASGKLQAFGFCEYEDPESTMRCVRLLNGLAVGDKKLLVKVDPKTE 221
Cdd:cd12446     1 TTVFVGNIPDDVSDDFIRQLLEKCGKVLSWKRVQDPSGKLKAFGFCEFEDPEGALRALRLLNGLELGGKKLLVKVDAKTK 80

                  ...
gi 684400095  222 DLL 224
Cdd:cd12446    81 KFL 83

Exonuclease-Endonuclease-Phosphatase (EEP) domain superfamily; This large superfamily includes the catalytic domain (exonuclease/endonuclease/phosphatase or EEP domain) of a diverse set of proteins including the ExoIII family of apurinic/apyrimidinic (AP) endonucleases, inositol polyphosphate 5-phosphatases (INPP5), neutral sphingomyelinases (nSMases), deadenylases (such as the vertebrate circadian-clock regulated nocturnin), bacterial cytolethal distending toxin B (CdtB), deoxyribonuclease 1 (DNase1), the endonuclease domain of the non-LTR retrotransposon LINE-1, and related domains. These diverse enzymes share a common catalytic mechanism of cleaving phosphodiester bonds; their substrates range from nucleic acids to phospholipids and perhaps proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 684400095  512 EAQRLKEFFEDYDDevedpkyyryVLAKIT--DIVILAGDLNAQVGRLSSLESHLGgrfgvdaRRTDNGDRLL-QLCADH 588
Cdd:cd09076   112 DEEEKEEFYDQLQD----------VLDKVPrhDTLIIGGDFNAVLGPKDDGRKGLD-------KRNENGERALsALIEEH 174

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 684400095  589 ELF-LASTNfqHKRSHRVTWRPPTTNQpWTQLDHVAISHRWRATIQDCRSFWGTplDSDHAVVRARL 654
Cdd:cd09076   175 DLVdVWREN--NPKTREYTWRSPDHGS-RSRIDRILVSKRLRVKVKKTKITPGA--GSDHRLVTLKL 236

Domain of unknown function (DUF4200); This family is found in eukaryotes. It is a coiled-coil domain of unknwon function.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 684400095   450 EKRRIVDEEEEAIRKKlERKLREKEESYQKRLKQWE---TRERKKANEYEHEREHEQKRQRELQIEAQRLKEFFEDYDDE 526
Cdd:pfam13863   24 RLEELLKQREEELEKK-EQELKEDLIKFDKFLKENDakrRRALKKAEEETKLKKEKEKEIKKLTAQIEELKSEISKLEEK 102

                           90
                   ....*....|....*..
gi 684400095   527 VEDPKYYRYVLAKITDI 543
Cdd:pfam13863  103 LEEYKPYEDFLEKVVPK 119

RNA recognition motif (RRM) found in eukaryotic RNA-binding protein 25 and similar proteins; This subfamily corresponds to the RRM of RBM25, also termed Arg/Glu/Asp-rich protein of 120 kDa (RED120), or protein S164, or RNA-binding region-containing protein 7, an evolutionary-conserved splicing coactivator SRm160 (SR-related nuclear matrix protein of 160 kDa, )-interacting protein. RBM25 belongs to a family of RNA-binding proteins containing a well conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), at the N-terminus, a RE/RD-rich (ER) central region, and a C-terminal proline-tryptophan-isoleucine (PWI) motif. It localizes to the nuclear speckles and associates with multiple splicing components, including splicing cofactors SRm160/300, U snRNAs, assembled splicing complexes, and spliced mRNAs. It may play an important role in pre-mRNA processing by coupling splicing with mRNA 3'-end formation. Additional research indicates that RBM25 is one of the RNA-binding regulators that direct the alternative splicing of apoptotic factors. It can activate proapoptotic Bcl-xS 5'ss by binding to the exonic splicing enhancer, CGGGCA, and stabilize the pre-mRNA-U1 snRNP through interaction with hLuc7A, a U1 snRNP-associated factor.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 684400095  142 TTVFVGNISDRAPDQLIKTLLMRCGNILSWKRVQGASGKLQAFGFCEYEDPESTMRCVRLLNGLAVGDKKLLVKVDPKTE 221
Cdd:cd12446     1 TTVFVGNIPDDVSDDFIRQLLEKCGKVLSWKRVQDPSGKLKAFGFCEFEDPEGALRALRLLNGLELGGKKLLVKVDAKTK 80

                  ...
gi 684400095  222 DLL 224
Cdd:cd12446    81 KFL 83

Endonuclease domain (L1-EN) of the non-LTR retrotransposon LINE-1 (L1), and related domains; This family contains the endonuclease domain (L1-EN) of the non-LTR retrotransposon LINE-1 (L1), and related domains, including the endonuclease of Xenopus laevis Tx1. These retrotranspons belong to the subtype 2, L1-clade. LINES can be classified into two subtypes. Subtype 2 has two ORFs: the second (ORF2) encodes a modular protein consisting of an N-terminal apurine/apyrimidine endonuclease domain (EN), a central reverse transcriptase, and a zinc-finger-like domain at the C-terminus. LINE-1/L1 elements (full length and truncated) comprise about 17% of the human genome. This endonuclease nicks the genomic DNA at the consensus target sequence 5'TTTT-AA3' producing a ribose 3'-hydroxyl end as a primer for reverse transcription of associated template RNA. This subgroup also includes the endonuclease of Xenopus laevis Tx1, another member of the L1-clade. This family belongs to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 684400095  512 EAQRLKEFFEDYDDevedpkyyryVLAKIT--DIVILAGDLNAQVGRLSSLESHLGgrfgvdaRRTDNGDRLL-QLCADH 588
Cdd:cd09076   112 DEEEKEEFYDQLQD----------VLDKVPrhDTLIIGGDFNAVLGPKDDGRKGLD-------KRNENGERALsALIEEH 174

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 684400095  589 ELF-LASTNfqHKRSHRVTWRPPTTNQpWTQLDHVAISHRWRATIQDCRSFWGTplDSDHAVVRARL 654
Cdd:cd09076   175 DLVdVWREN--NPKTREYTWRSPDHGS-RSRIDRILVSKRLRVKVKKTKITPGA--GSDHRLVTLKL 236

RNA recognition motif;

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 684400095    143 TVFVGNISDRAPDQLIKTLLMRCGNILSWK-RVQGASGKLQAFGFCEYEDPESTMRCVRLLNGLAVGDKKLLV 214
Cdd:smart00360    1 TLFVGNLPPDTTEEELRELFSKFGKVESVRlVRDKETGKSKGFAFVEFESEEDAEKALEALNGKELDGRPLKV 73

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 684400095   144 VFVGNISDRAPDQLIKTLLMRCGNILSWKRVQGASGKLQAFGFCEYEDPESTMRCVRLLNGLAVGDKKLL 213
Cdd:pfam00076    1 LFVGNLPPDTTEEDLKDLFSKFGPIKSIRLVRDETGRSKGFAFVEFEDEEDAEKAIEALNGKELGGRELK 70

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 684400095    90 PHYYgfvgIPPPQlvtvpqVIPTPVTVAaPALAVTTQSETPVVQYVREKPpvTTVFVGNISDRAPDQLIKTLLMRCGNIL 169
Cdd:TIGR01642  257 PHDY----IPVPQ------ITPEVSQKN-PDDNAKNVEKLVNSTTVLDSK--DRIYIGNLPLYLGEDQIKELLESFGDLK 323

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 684400095   170 SWKRVQG-ASGKLQAFGFCEYEDPESTMRCVRLLNGLAVGDKKLLVK 215
Cdd:TIGR01642  324 AFNLIKDiATGLSKGYAFCEYKDPSVTDVAIAALNGKDTGDNKLHVQ 370

Guanylate-binding protein, C-terminal domain; Guanylate-binding protein (GBP), C-terminal domain. Guanylate-binding proteins (GBPs) are synthesized after activation of the cell by interferons. The biochemical properties of GBPs are clearly different from those of Ras-like and heterotrimeric GTP-binding proteins. They bind guanine nucleotides with low affinity (micromolar range), are stable in their absence, and have a high turnover GTPase. In addition to binding GDP/GTP, they have the unique ability to bind GMP with equal affinity and hydrolyze GTP not only to GDP, but also to GMP. This C-terminal domain has been shown to mediate inhibition of endothelial cell proliferation by inflammatory cytokines.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 684400095  457 EEEEAIRKKLERKLREKEESYQKRLKQWE---TRERKK-ANEYEHEREHEQKRQRELQIE-----AQRLKEFFED 522
Cdd:cd16269   215 KLLEEQQRELEQKLEDQERSYEEHLRQLKekmEEERENlLKEQERALESKLKEQEALLEEgfkeqAELLQEEIRS 289

Septin family protein [Cell cycle control, cell division, chromosome partitioning, Cytoskeleton];

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 684400095  456 DEEEEAIRKKLERKLREKEesyqKRLKQWETRERKKANEYEHEREHEQKRQRELQIEAQRLK 517
Cdd:COG5019   312 NEEERELKKKFTEKIREKE----KRLEELEQNLIEERKELNSKLEEIQKKLEDLEKRLEKLK 369

Outer membrane protein (OmpH-like); This family includes outer membrane proteins such as OmpH among others. Skp (OmpH) has been characterized as a molecular chaperone that interacts with unfolded proteins as they emerge in the periplasm from the Sec translocation machinery.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 684400095    463 RKKLERKLREKEESYQKRLKQWETRERKKANEYEHER-----EHEQKRQRELQIEAQRLKEFFEDYDDEVEdpKYYRYVL 537
Cdd:smart00935   16 GKAAQKQLEKEFKKRQAELEKLEKELQKLKEKLQKDAatlseAAREKKEKELQKKVQEFQRKQQKLQQDLQ--KRQQEEL 93

                            90
                    ....*....|
gi 684400095    538 AKITDIVILA 547
Cdd:smart00935   94 QKILDKINKA 103

RNA recognition motif (RRM) found in eukaryotic RNA-binding protein 25 and similar proteins; This subfamily corresponds to the RRM of RBM25, also termed Arg/Glu/Asp-rich protein of 120 kDa (RED120), or protein S164, or RNA-binding region-containing protein 7, an evolutionary-conserved splicing coactivator SRm160 (SR-related nuclear matrix protein of 160 kDa, )-interacting protein. RBM25 belongs to a family of RNA-binding proteins containing a well conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), at the N-terminus, a RE/RD-rich (ER) central region, and a C-terminal proline-tryptophan-isoleucine (PWI) motif. It localizes to the nuclear speckles and associates with multiple splicing components, including splicing cofactors SRm160/300, U snRNAs, assembled splicing complexes, and spliced mRNAs. It may play an important role in pre-mRNA processing by coupling splicing with mRNA 3'-end formation. Additional research indicates that RBM25 is one of the RNA-binding regulators that direct the alternative splicing of apoptotic factors. It can activate proapoptotic Bcl-xS 5'ss by binding to the exonic splicing enhancer, CGGGCA, and stabilize the pre-mRNA-U1 snRNP through interaction with hLuc7A, a U1 snRNP-associated factor.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 684400095  142 TTVFVGNISDRAPDQLIKTLLMRCGNILSWKRVQGASGKLQAFGFCEYEDPESTMRCVRLLNGLAVGDKKLLVKVDPKTE 221
Cdd:cd12446     1 TTVFVGNIPDDVSDDFIRQLLEKCGKVLSWKRVQDPSGKLKAFGFCEFEDPEGALRALRLLNGLELGGKKLLVKVDAKTK 80

                  ...
gi 684400095  222 DLL 224
Cdd:cd12446    81 KFL 83

Dipeptidyl aminopeptidase/acylaminoacyl peptidase [Amino acid transport and metabolism];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 684400095 1442 PDGKPmpmITGYLLLqddPSVRPTSPTVLILHGNAGNI-GHRLPFCRLLADHvQCNILIVDYRGYGRSSGKPTEpGLYAD 1520
Cdd:COG1506     5 ADGTT---LPGWLYL---PADGKKYPVVVYVHGGPGSRdDSFLPLAQALASR-GYAVLAPDYRGYGESAGDWGG-DEVDD 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 684400095 1521 AKASLEFLLDRTDIAKDKLFLFGRSIGGAVAIWLTAHlRSAILRGVIIENSFTSLpeaaqhifsKSFGSFARHLLPKALF 1600
Cdd:COG1506    77 VLAAIDYLAARPYVDPDRIGIYGHSYGGYMALLAAAR-HPDRFKAAVALAGVSDL---------RSYYGTTREYTERLMG 146

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 684400095 1601 INKYPALDLMR----EFVcrSSVRPRFLFISGSADDLIPPRMMQELA 1643
Cdd:COG1506   147 GPWEDPEAYAArsplAYA--DKLKTPLLLIHGEADDRVPPEQAERLY 191

Endonuclease domain (L1-EN) of the non-LTR retrotransposon LINE-1 (L1), and related domains; This family contains the endonuclease domain (L1-EN) of the non-LTR retrotransposon LINE-1 (L1), and related domains, including the endonuclease of Xenopus laevis Tx1. These retrotranspons belong to the subtype 2, L1-clade. LINES can be classified into two subtypes. Subtype 2 has two ORFs: the second (ORF2) encodes a modular protein consisting of an N-terminal apurine/apyrimidine endonuclease domain (EN), a central reverse transcriptase, and a zinc-finger-like domain at the C-terminus. LINE-1/L1 elements (full length and truncated) comprise about 17% of the human genome. This endonuclease nicks the genomic DNA at the consensus target sequence 5'TTTT-AA3' producing a ribose 3'-hydroxyl end as a primer for reverse transcription of associated template RNA. This subgroup also includes the endonuclease of Xenopus laevis Tx1, another member of the L1-clade. This family belongs to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 684400095  512 EAQRLKEFFEDYDDevedpkyyryVLAKIT--DIVILAGDLNAQVGRLSSLESHLGgrfgvdaRRTDNGDRLL-QLCADH 588
Cdd:cd09076   112 DEEEKEEFYDQLQD----------VLDKVPrhDTLIIGGDFNAVLGPKDDGRKGLD-------KRNENGERALsALIEEH 174

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 684400095  589 ELF-LASTNfqHKRSHRVTWRPPTTNQpWTQLDHVAISHRWRATIQDCRSFWGTplDSDHAVVRARL 654
Cdd:cd09076   175 DLVdVWREN--NPKTREYTWRSPDHGS-RSRIDRILVSKRLRVKVKKTKITPGA--GSDHRLVTLKL 236

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 684400095  144 VFVGNISDRAPDQLIKTLLMRCGNILSWKRVQGASGKLQAFGFCEYEDPESTMRCVRLLNGLAVGDKKLLVK 215
Cdd:cd00590     1 LFVGNLPPDTTEEDLRELFSKFGEVVSVRIVRDRDGKSKGFAFVEFESPEDAEKALEALNGTELGGRPLKVS 72

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 684400095  143 TVFVGNISDRAPDQLIKTLLMRCGNILSWKRVQGA-SGKLQAFGFCEYEDPESTMRCVRLLNGLAVGDKKLlvKVD 217
Cdd:cd12398     2 SVFVGNIPYDATEEQLKEIFSEVGPVVSFRLVTDReTGKPKGYGFCEFRDAETALSAVRNLNGYELNGRPL--RVD 75

RNA recognition motif 2 (RRM2) found in U2 large nuclear ribonucleoprotein auxiliary factor U2AF 65 kDa subunit (U2AF65) and similar proteins; This subfamily corresponds to the RRM2 of U2AF65 and dU2AF50. U2AF65, also termed U2AF2, is the large subunit of U2 small nuclear ribonucleoprotein (snRNP) auxiliary factor (U2AF), which has been implicated in the recruitment of U2 snRNP to pre-mRNAs and is a highly conserved heterodimer composed of large and small subunits. U2AF65 specifically recognizes the intron polypyrimidine tract upstream of the 3' splice site and promotes binding of U2 snRNP to the pre-mRNA branchpoint. U2AF65 also plays an important role in the nuclear export of mRNA. It facilitates the formation of a messenger ribonucleoprotein export complex, containing both the NXF1 receptor and the RNA substrate. Moreover, U2AF65 interacts directly and specifically with expanded CAG RNA, and serves as an adaptor to link expanded CAG RNA to NXF1 for RNA export. U2AF65 contains an N-terminal RS domain rich in arginine and serine, followed by a proline-rich segment and three C-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The N-terminal RS domain stabilizes the interaction of U2 snRNP with the branch point (BP) by contacting the branch region, and further promotes base pair interactions between U2 snRNA and the BP. The proline-rich segment mediates protein-protein interactions with the RRM domain of the small U2AF subunit (U2AF35 or U2AF1). The RRM1 and RRM2 are sufficient for specific RNA binding, while RRM3 is responsible for protein-protein interactions. The family also includes Splicing factor U2AF 50 kDa subunit (dU2AF50), the Drosophila ortholog of U2AF65. dU2AF50 functions as an essential pre-mRNA splicing factor in flies. It associates with intronless mRNAs and plays a significant and unexpected role in the nuclear export of a large number of intronless mRNAs.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 684400095  144 VFVGNISDRAPDQLIKTLLMRCGNILSWKRVQ-GASGKLQAFGFCEYEDPESTMRCVRLLNGLAVGDKKLLVK 215
Cdd:cd12231     3 LFIGGLPNYLNEDQVKELLQSFGKLKAFNLVKdSATGLSKGYAFCEYVDDNVTDQAIAGLNGMQLGDKKLLVQ 75

RNA recognition motif 3 (RRM3) found found in type I polyadenylate-binding proteins; This subfamily corresponds to the RRM3 of type I poly(A)-binding proteins (PABPs), highly conserved proteins that bind to the poly(A) tail present at the 3' ends of most eukaryotic mRNAs. They have been implicated in the regulation of poly(A) tail length during the polyadenylation reaction, translation initiation, mRNA stabilization by influencing the rate of deadenylation and inhibition of mRNA decapping. The family represents type I polyadenylate-binding proteins (PABPs), including polyadenylate-binding protein 1 (PABP-1 or PABPC1), polyadenylate-binding protein 3 (PABP-3 or PABPC3), polyadenylate-binding protein 4 (PABP-4 or APP-1 or iPABP), polyadenylate-binding protein 5 (PABP-5 or PABPC5), polyadenylate-binding protein 1-like (PABP-1-like or PABPC1L), polyadenylate-binding protein 1-like 2 (PABPC1L2 or RBM32), polyadenylate-binding protein 4-like (PABP-4-like or PABPC4L), yeast polyadenylate-binding protein, cytoplasmic and nuclear (PABP or ACBP-67), and similar proteins. PABP-1 is an ubiquitously expressed multifunctional protein that may play a role in 3' end formation of mRNA, translation initiation, mRNA stabilization, protection of poly(A) from nuclease activity, mRNA deadenylation, inhibition of mRNA decapping, and mRNP maturation. Although PABP-1 is thought to be a cytoplasmic protein, it is also found in the nucleus. PABP-1 may be involved in nucleocytoplasmic trafficking and utilization of mRNP particles. PABP-1 contains four copies of RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), a less well conserved linker region, and a proline-rich C-terminal conserved domain (CTD). PABP-3 is a testis-specific poly(A)-binding protein specifically expressed in round spermatids. It is mainly found in mammalian and may play an important role in the testis-specific regulation of mRNA homeostasis. PABP-3 shows significant sequence similarity to PABP-1. However, it binds to poly(A) with a lower affinity than PABP-1. PABP-1 possesses an A-rich sequence in its 5'-UTR and allows binding of PABP and blockage of translation of its own mRNA. In contrast, PABP-3 lacks the A-rich sequence in its 5'-UTR. PABP-4 is an inducible poly(A)-binding protein (iPABP) that is primarily localized to the cytoplasm. It shows significant sequence similarity to PABP-1 as well. The RNA binding properties of PABP-1 and PABP-4 appear to be identical. PABP-5 is encoded by PABPC5 gene within the X-specific subinterval, and expressed in fetal brain and in a range of adult tissues in mammalian, such as ovary and testis. It may play an important role in germ cell development. Moreover, unlike other PABPs, PABP-5 contains only four RRMs, but lacks both the linker region and the CTD. PABP-1-like and PABP-1-like 2 are the orthologs of PABP-1. PABP-4-like is the ortholog of PABP-5. Their cellular functions remain unclear. The family also includes the yeast PABP, a conserved poly(A) binding protein containing poly(A) tails that can be attached to the 3'-ends of mRNAs. The yeast PABP and its homologs may play important roles in the initiation of translation and in mRNA decay. Like vertebrate PABP-1, the yeast PABP contains four RRMs, a linker region, and a proline-rich CTD as well. The first two RRMs are mainly responsible for specific binding to poly(A). The proline-rich region may be involved in protein-protein interactions.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 684400095  142 TTVFVGNISDRAPDQLIKTLLMRCGNILSWKRVQGASGKLQAFGFCEYEDPESTMRCVRLLNGLAVGDKKLLV 214
Cdd:cd12380     2 TNVYVKNFGEDVDDDELKELFEKYGKITSAKVMKDDSGKSKGFGFVNFENHEAAQKAVEELNGKELNGKKLYV 74

Dienelactone hydrolase [Secondary metabolites biosynthesis, transport and catabolism];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 684400095 1442 PDGKPMPmitGYLLLqddPSVRPTSPTVLILHGNAGNIGHRLPFCRLLADH---VqcniLIVDYRGYGRSSGKPTE---- 1514
Cdd:COG0412    11 PDGVTLP---GYLAR---PAGGGPRPGVVVLHEIFGLNPHIRDVARRLAAAgyvV----LAPDLYGRGGPGDDPDEaral 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 684400095 1515 ------PGLYADAKASLEFLLDRTDIAKDKLFLFGRSIGGAVAIWLTAHLrsAILRGVIienSFtslpeaaqhifsksfg 1588
Cdd:COG0412    81 mgaldpELLAADLRAALDWLKAQPEVDAGRVGVVGFCFGGGLALLAAARG--PDLAAAV---SF---------------- 139

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 684400095 1589 sfarhllpkalfinkYPALDLMREFVCRSSVRPRFLFISGSADDLIPPRMMQELAHVYRFSGSD 1652
Cdd:COG0412   140 ---------------YGGLPADDLLDLAARIKAPVLLLYGEKDPLVPPEQVAALEAALAAAGVD 188

Acetyl esterase/lipase [Lipid transport and metabolism];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 684400095 1463 RPTSPTVLILHG---NAGNIGHRLPFCRLLADHVQCNILIVDYrgygRSSGKPTEPGLYADAKASLEFLLDRTD---IAK 1536
Cdd:COG0657    10 KGPLPVVVYFHGggwVSGSKDTHDPLARRLAARAGAAVVSVDY----RLAPEHPFPAALEDAYAALRWLRANAAelgIDP 85

                          90       100
                  ....*....|....*....|...
gi 684400095 1537 DKLFLFGRSIGGAVAIWLTAHLR 1559
Cdd:COG0657    86 DRIAVAGDSAGGHLAAALALRAR 108

Serine aminopeptidase, S33; This domain is found in bacteria and eukaryotes and is approximately 110 amino acids in length. It is found in association with pfam00561. The majority of the members in this family carry the exopeptidase active-site residues of Ser-122, Asp-239 and His-269 as in UniProtKB:Q7ZWC2.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 684400095  1468 TVLILHGNAGNIGHRLPFCRLLAdhvQCNI--LIVDYRGYGRSSGKPTEPG----LYADAKASLEFLLDRTdiAKDKLFL 1541
Cdd:pfam12146    6 VVVLVHGLGEHSGRYAHLADALA---AQGFavYAYDHRGHGRSDGKRGHVPsfddYVDDLDTFVDKIREEH--PGLPLFL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 684400095  1542 FGRSIGGAVAIwLTAHLRSAILRGVIIENSFTSLPEAAQHIFSKSFGSFARHLLPKALFINKYPALDLMR--EFV----- 1614
Cdd:pfam12146   81 LGHSMGGLIAA-LYALRYPDKVDGLILSAPALKIKPYLAPPILKLLAKLLGKLFPRLRVPNNLLPDSLSRdpEVVaayaa 159

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 684400095  1615 ---CRSSVRPRF----------------------LFISGSADDLIPPRMMQELA 1643
Cdd:pfam12146  160 dplVHGGISARTlyelldagerllrraaaitvplLLLHGGADRVVDPAGSREFY 213

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 684400095    90 PHYYgfvgIPPPQlvtvpqVIPTPVTVAaPALAVTTQSETPVVQYVREKPpvTTVFVGNISDRAPDQLIKTLLMRCGNIL 169
Cdd:TIGR01642  257 PHDY----IPVPQ------ITPEVSQKN-PDDNAKNVEKLVNSTTVLDSK--DRIYIGNLPLYLGEDQIKELLESFGDLK 323

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 684400095   170 SWKRVQG-ASGKLQAFGFCEYEDPESTMRCVRLLNGLAVGDKKLLVK 215
Cdd:TIGR01642  324 AFNLIKDiATGLSKGYAFCEYKDPSVTDVAIAALNGKDTGDNKLHVQ 370

DDRGK domain; This is a family of proteins of approximately 300 residues, found in plants and vertebrates. They contain a highly conserved DDRGK motif.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 684400095   450 EKRRIVDEEEEAIRKKLERKLREKEESYQKRLKQWETRERKKANEYEHER-EHEQKRQRELqieaQRLKEFF--EDYDDE 526
Cdd:pfam09756   15 EAKRQQREAEEEEREEREKLEEKREEEYKEREEREEEAEKEKEEEERKQEeEQERKEQEEY----EKLKSQFvvEEEGTD 90

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 684400095   527 VEDPKYYRYVLAKITDIVILAgdlnaqvgRLSSLEsHLGGRFGVDArrTDNGDRLLQLCADHELF 591
Cdd:pfam09756   91 KLSAEDESQLLEDFINYIKLK--------KVVLLE-ELAAEFGLKT--QDVIDRIQDLEEQGSLT 144

Ezrin/radixin/moesin, alpha-helical domain; The ERM family consists of three closely-related proteins, ezrin, radixin and moesin. Ezrin was first identified as a constituent of microvilli, radixin as a barbed, end-capping actin-modulating protein from isolated junctional fractions, and moesin as a heparin binding protein. A tumour suppressor molecule responsible for neurofibromatosis type 2 (NF2) is highly similar to ERM proteins and has been designated merlin (moesin-ezrin-radixin-like protein). ERM molecules contain 3 domains, an N-terminal globular domain, an extended alpha-helical domain and a charged C-terminal domain (pfam00769). Ezrin, radixin and merlin also contain a polyproline linker region between the helical and C-terminal domains. The N-terminal domain is highly conserved and is also found in merlin, band 4.1 proteins and members of the band 4.1 superfamily, designated the FERM domain. ERM proteins crosslink actin filaments with plasma membranes. They co-localize with CD44 at actin filament plasma membrane interaction sites, associating with CD44 via their N-terminal domains and with actin filaments via their C-terminal domains. This is the alpha-helical domain, which is involved in intramolecular masking of protein-protein interaction sites, regulating the activity of this proteins.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 684400095   459 EEAIRKK--LERKLREKEESYQKR----LKQWETRER--KKANEYEHEREHEQKRQRELQIEAQRLKEFFEDYDDEVE 528
Cdd:pfam20492    2 EEAEREKqeLEERLKQYEEETKKAqeelEESEETAEEleEERRQAEEEAERLEQKRQEAEEEKERLEESAEMEAEEKE 79

Guanylate-binding protein, C-terminal domain; Guanylate-binding protein (GBP), C-terminal domain. Guanylate-binding proteins (GBPs) are synthesized after activation of the cell by interferons. The biochemical properties of GBPs are clearly different from those of Ras-like and heterotrimeric GTP-binding proteins. They bind guanine nucleotides with low affinity (micromolar range), are stable in their absence, and have a high turnover GTPase. In addition to binding GDP/GTP, they have the unique ability to bind GMP with equal affinity and hydrolyze GTP not only to GDP, but also to GMP. This C-terminal domain has been shown to mediate inhibition of endothelial cell proliferation by inflammatory cytokines.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 684400095  457 EEEEAIRKKLERKLREKEESYQKRLKQWE---TRERKK-ANEYEHEREHEQKRQRELQIE-----AQRLKEFFED 522
Cdd:cd16269   215 KLLEEQQRELEQKLEDQERSYEEHLRQLKekmEEERENlLKEQERALESKLKEQEALLEEgfkeqAELLQEEIRS 289

Family of unknown function (DUF5401); This is a family of unknown function found in Chromadorea.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 684400095   446 SRSPEKRRIVDEEEEAIRKKLERKLREKEEsyQKRLKQWETRERKKANEYEHEREHEQKRQRELQIEAQRLKEF 519
Cdd:pfam17380  309 AREVERRRKLEEAEKARQAEMDRQAAIYAE--QERMAMERERELERIRQEERKRELERIRQEEIAMEISRMREL 380

MAP7 (E-MAP-115) family; The organization of microtubules varies with the cell type and is presumably controlled by tissue-specific microtubule-associated proteins (MAPs). The 115-kDa epithelial MAP (E-MAP-115/MAP7) has been identified as a microtubule-stabilising protein predominantly expressed in cell lines of epithelial origin. The binding of this microtubule associated protein is nucleotide independent.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 684400095   440 KPGVGSSRSPEKRRIVDEeeeaiRKKLERKLREKEEsyQKRLKQwETRERKKANEYEHEREHE-QKRqrelQIEAQRLKE 518
Cdd:pfam05672    1 KPSAGTTDAEEAARILAE-----KRRQAREQREREE--QERLEK-EEEERLRKEELRRRAEEErARR----EEEARRLEE 68

MAP7 (E-MAP-115) family; The organization of microtubules varies with the cell type and is presumably controlled by tissue-specific microtubule-associated proteins (MAPs). The 115-kDa epithelial MAP (E-MAP-115/MAP7) has been identified as a microtubule-stabilising protein predominantly expressed in cell lines of epithelial origin. The binding of this microtubule associated protein is nucleotide independent.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 684400095   450 EKRRIVDEE------EEAIRKKLERKLREKEESY---QKRLKQWETRERKKaneyEHEREHEQKRQRELQIEAQRLKE 518
Cdd:pfam05672   31 EQERLEKEEeerlrkEELRRRAEEERARREEEARrleEERRREEEERQRKA----EEEAEEREQREQEEQERLQKQKE 104

RNA recognition motif 1 (RRM1) found in splicing factor 3B subunit 4 (SF3B4) and similar proteins; This subfamily corresponds to the RRM1 of SF3B4, also termed pre-mRNA-splicing factor SF3b 49 kDa (SF3b50), or spliceosome-associated protein 49 (SAP 49). SF3B4 a component of the multiprotein complex splicing factor 3b (SF3B), an integral part of the U2 small nuclear ribonucleoprotein (snRNP) and the U11/U12 di-snRNP. SF3B is essential for the accurate excision of introns from pre-messenger RNA, and is involved in the recognition of the pre-mRNA's branch site within the major and minor spliceosomes. SF3B4 functions to tether U2 snRNP with pre-mRNA at the branch site during spliceosome assembly. It is an evolutionarily highly conserved protein with orthologs across diverse species. SF3B4 contains two closely adjacent N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). It binds directly to pre-mRNA and also interacts directly and highly specifically with another SF3B subunit called SAP 145.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 684400095  144 VFVGNISDRAPDQLIKTLLMRCGNILSWK----RVqgaSGKLQAFGFCEYEDPESTMRCVRLLNGLAVGDKKLLVK 215
Cdd:cd12334     1 VYVGNLDEKVTEELLWELFIQAGPVVNVHmpkdRV---TQQHQGYGFVEFLSEEDADYAIKIMNMIKLYGKPIRVN 73

RNA recognition motif 2 in fungal pre-messenger RNA splicing protein 24 (Prp24) and similar proteins; This subfamily corresponds to the RRM2 of Prp24, also termed U4/U6 snRNA-associated-splicing factor PRP24 (U4/U6 snRNP), an RNA-binding protein with four well conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). It facilitates U6 RNA base-pairing with U4 RNA during spliceosome assembly. Prp24 specifically binds free U6 RNA primarily with RRMs 1 and 2 and facilitates pairing of U6 RNA bases with U4 RNA bases. Additionally, it may also be involved in dissociation of the U4/U6 complex during spliceosome activation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 684400095  142 TTVFVGNISDRAPDQLIKTLLMRCGNILSwkrVQGASGKLQA---FGFCEYEDPESTMRCVRLLNGLAVGDKKLLVKV-D 217
Cdd:cd12297     1 CTLWVTNFPPSYDERSIRDLFGDYGVILS---VRLPSLRYNTsrrFCYIDFTSPESARAAVELLNGLLEEGYTLVVKIsD 77