large tegument protein UL36; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622967120  603 GPVPVDPGFVDLASTSSELVEPLPAgPVLINPVlADSAAVDPAVVPISdNLPPVDAVPSGPAPVDLAlVDPVPNDLTAVD 682
Cdd:PHA03247  2550 DPPPPLPPAAPPAAPDRSVPPPRPA-PRPSEPA-VTSRARRPDAPPQS-ARPRAPVDDRGDPRGPAP-PSPLPPDTHAPD 2625

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622967120  683 PvlvksRPTDPRRAAVSSALGGPAPQLLLESESLDPPktiIPEVKEVVDSLKIESGTSATTHEARPRPlslseyrrrrqq 762
Cdd:PHA03247  2626 P-----PPPSPSPAANEPDPHPPPTVPPPERPRDDPA---PGRVSRPRRARRLGRAAQASSPPQRPRR------------ 2685

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622967120  763 rqaeteeRSPQPPTGkwpslpeTPTGLADIPCLVIPPAPAKKTALQRSPEAP-PETCLVPVGPSPASPGPEPPVSKSVAS 841
Cdd:PHA03247  2686 -------RAARPTVG-------SLTSLADPPPPPPTPEPAPHALVSATPLPPgPAAARQASPALPAAPAPPAVPAGPATP 2751

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622967120  842 ALTEQVPSQemPLLARPSSPVQSVSPVVPTPPAMPTALSFPAgglgippslpppplqppSLPVSMGPVLPDPFTHYApmp 921
Cdd:PHA03247  2752 GGPARPARP--PTTAGPPAPAPPAAPAAGPPRRLTRPAVASL-----------------SESRESLPSPWDPADPPA--- 2809

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622967120  922 pwpcyppvspsgypCLPPPPTVPLVSGTPGAYAMPPTCNVPWAPPPAPVSPYSSTCTYGSLGWG-----PGPQHAPFWST 996
Cdd:PHA03247  2810 --------------AVLAPAAALPPAASPAGPLPPPTSAQPTAPPPPPGPPPPSLPLGGSVAPGgdvrrRPPSRSPAAKP 2875

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622967120  997 VPPPPLPPASVGRAVPQAKMESRGTPAGPPENV-LPVSMTPPLSGLPGHGAPQIEPTkvevKPVLASPHPKHKVSALVQS 1075
Cdd:PHA03247  2876 AAPARPPVRRLARPAVSRSTESFALPPDQPERPpQPQAPPPPQPQPQPPPPPQPQPP----PPPPPRPQPPLAPTTDPAG 2951

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622967120 1076 PRLKAPAAPVCVSAEGVTVEEPASEGLKPETQETRPREKPPLPATKAVPTPRQSTVSKLPAVH------PARLrKLSFLP 1149
Cdd:PHA03247  2952 AGEPSGAVPQPWLGALVPGRVAVPRFRVPQPAPSREAPASSTPPLTGHSLSRVSSWASSLALHeetdppPVSL-KQTLWP 3030

                          570       580       590       600       610
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1622967120 1150 TPHTQGSEDVVQAFISEIGIEASDLSSLLEQFEKSEAKKECPPPAPADSLAV 1201
Cdd:PHA03247  3031 PDDTEDSDADSLFDSDSERSDLEALDPLPPEPHDPFAHEPDPATPEAGARES 3082

RNA recognition motif;

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1622967120  1282 VVFIGKIPGRMTRSELKQRFSVFGEIEECTIHF---RVQGDNYGFVTYRYAEEAFAAIES-------GHKLR 1343
Cdd:smart00360    1 TLFVGNLPPDTTEEELRELFSKFGKVESVRLVRdkeTGKSKGFAFVEFESEEDAEKALEAlngkeldGRPLK 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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1622967120 1283 VFIGKIPGRMTRSELKQRFSVFGEIEECTIHFRVQGDN--YGFVTYRYAEEAFAAIES--GHKLRQ 1344
Cdd:pfam00076    1 LFVGNLPPDTTEEDLKDLFSKFGPIKSIRLVRDETGRSkgFAFVEFEDEEDAEKAIEAlnGKELGG 66

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622967120 1284 FIGKIPGRMTRSELKQRFSVFGEIEECTI---HF--RVQGdnYGFVTYRYAEEAFAAIEsghKLRQADeqpfdlcFGGRR 1358
Cdd:COG0724      5 YVGNLPYSVTEEDLRELFSEYGEVTSVKLitdREtgRSRG--FGFVEMPDDEEAQAAIE---ALNGAE-------LMGRT 72

RNA recognition motif (RRM) found in the peroxisome proliferator-activated receptor gamma coactivator 1A (PGC-1alpha) family of regulated coactivators; This subfamily corresponds to the RRM of PGC-1alpha, PGC-1beta, and PGC-1-related coactivator (PRC), which serve as mediators between environmental or endogenous signals and the transcriptional machinery governing mitochondrial biogenesis. They play an important integrative role in the control of respiratory gene expression through interacting with a number of transcription factors, such as NRF-1, NRF-2, ERR, CREB and YY1. All family members are multi-domain proteins containing the N-terminal activation domain, an LXXLL coactivator signature, a tetrapeptide motif (DHDY) responsible for HCF binding, and an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). In contrast to PGC-1alpha and PRC, PGC-1beta possesses two glutamic/aspartic acid-rich acidic domains, but lacks most of the arginine/serine (SR)-rich domain that is responsible for the regulation of RNA processing.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622967120 1279 ERRVVFIGKIPGRMTRSELKQRFSVFGEIEECTIHFRVQGDNYGFVTYRYAEEAFAAIESGHKLRQADEQPFDLCFGGRR 1358
Cdd:cd12357      1 ERRVVYVGKLEQDTTRSELRRRFEVFGEIEECTVHFRERGDKYGFVTYRYSEDAFLALENGHDLRKRNEPMFDLSFGGRR 80

                           90
                   ....*....|.
gi 1622967120 1359 QFCKRSYSDLD 1369
Cdd:cd12357     81 AFCKSSYADLD 91

RNA recognition motif (RRM) found in peroxisome proliferator-activated receptor gamma coactivator 1-beta (PGC-1-beta) and similar proteins; This subfamily corresponds to the RRM of PGC-1beta, also termed PPAR-gamma coactivator 1-beta, or PPARGC-1-beta, or PGC-1-related estrogen receptor alpha coactivator, which is one of the members of PGC-1 transcriptional coactivators family, including PGC-1alpha and PGC-1-related coactivator (PRC). PGC-1beta plays a nonredundant role in controlling mitochondrial oxidative energy metabolism and affects both, insulin sensitivity and mitochondrial biogenesis, and functions in a number of oxidative tissues. It is involved in maintaining baseline mitochondrial function and cardiac contractile function following pressure overload hypertrophy by preserving glucose metabolism and preventing oxidative stress. PGC-1beta induces hypertriglyceridemia in response to dietary fats through activating hepatic lipogenesis and lipoprotein secretion. It can stimulate apolipoprotein C3 (APOC3) expression, further mediating hypolipidemic effect of nicotinic acid. PGC-1beta also drives nuclear respiratory factor 1 (NRF-1) target gene expression and NRF-1 and estrogen related receptor alpha (ERRalpha)-dependent mitochondrial biogenesis. The modulation of the expression of PGC-1beta can trigger ERRalpha-induced adipogenesis. PGC-1beta is also a potent regulator inducing angiogenesis in skeletal muscle. The transcriptional activity of PGC-1beta can be increased through binding to host cell factor (HCF), a cellular protein involved in herpes simplex virus (HSV) infection and cell cycle regulation. PGC-1beta is a multi-domain protein containing an N-terminal activation domain, an LXXLL coactivator signature, a tetrapeptide motif (DHDY) responsible for HCF binding, two glutamic/aspartic acid-rich acidic domains, and an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). In contrast to PGC-1alpha, PGC-1beta lacks most of the arginine/serine (SR)-rich domain that is responsible for the regulation of RNA processing.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622967120 1274 ERAIEERRVVFIGKIPGRMTRSELKQRFSVFGEIEECTIHFRV-QGDNYGFVTYRYAEEAFAAIESGHKLRQADEQPFDL 1352
Cdd:cd12356      1 EKAIGEGRVVYIRNLSSSMSSNELKRRFEVFGEITECCVLSRSnRGEKYGFITYRDSEHAALSLQKGASLRKRNEPSFQL 80

                           90
                   ....*....|....*..
gi 1622967120 1353 CFGGRRQFCKRSYSDLD 1369
Cdd:cd12356     81 SYGGLRHFFWTRYTDLD 97

RNA recognition motif;

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1622967120  1282 VVFIGKIPGRMTRSELKQRFSVFGEIEECTIHF---RVQGDNYGFVTYRYAEEAFAAIES-------GHKLR 1343
Cdd:smart00360    1 TLFVGNLPPDTTEEELRELFSKFGKVESVRLVRdkeTGKSKGFAFVEFESEEDAEKALEAlngkeldGRPLK 72

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1622967120 1284 FIGKIPGRMTRSELKQRFSVFGEIEECTIhfrVQGDNYG------FVTYRYAEEAFAAIESGH 1340
Cdd:cd12361      3 FVGMIPKTASEEDVRPLFEQFGNIEEVQI---LRDKQTGqskgcaFVTFSTREEALRAIEALH 62

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 1622967120 1283 VFIGKIPGRMTRSELKQRFSVFGEIEECTIHFRVQGDN--YGFVTYRYAEEAFAAIES--GHKLRQ 1344
Cdd:pfam00076    1 LFVGNLPPDTTEEDLKDLFSKFGPIKSIRLVRDETGRSkgFAFVEFEDEEDAEKAIEAlnGKELGG 66

RNA recognition motif 2 (RRM2) found in plant flowering time control protein FCA and similar proteins; This subgroup corresponds to the RRM2 of FCA, a gene controlling flowering time in Arabidopsis, which encodes a flowering time control protein that functions in the posttranscriptional regulation of transcripts involved in the flowering process. The flowering time control protein FCA contains two RNA recognition motifs (RRMs), also known as RBDs (RNA binding domains) or RNP (ribonucleoprotein domains), and a WW protein interaction domain.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1622967120 1284 FIGKIPGRMTRSELKQRFSVFGEIEECTI---HFRVQGDNYGFVTYRYAEEAFAAIES 1338
Cdd:cd12637      3 FVGSLPKTATEQEVRDLFEAYGEVEEVYLmkdPVTQQGTGCAFVKFAYKEEALAAIRS 60

RNA recognition motif 2 (RRM2) found in yeast meiotic activator RIM4 and similar proteins; This subfamily corresponds to the RRM2 of RIM4, also termed regulator of IME2 protein 4, a putative RNA binding protein that is expressed at elevated levels early in meiosis. It functions as a meiotic activator required for both the IME1- and IME2-dependent pathways of meiotic gene expression, as well as early events of meiosis, such as meiotic division and recombination, in Saccharomyces cerevisiae. RIM4 contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The family also includes a putative RNA-binding protein termed multicopy suppressor of sporulation protein Msa1. It is a putative RNA-binding protein encoded by a novel gene, msa1, from the fission yeast Schizosaccharomyces pombe. Msa1 may be involved in the inhibition of sexual differentiation by controlling the expression of Ste11-regulated genes, possibly through the pheromone-signaling pathway. Like RIM4, Msa1 also contains two RRMs, both of which are essential for the function of Msa1.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1622967120 1279 ERRVVFIGKIPGRMTRSELKQRFSVFGEIEECTIHFRVQGDN-YGFVTYRYAEEAFAAIES 1338
Cdd:cd12454      2 DKLSIFVGQLDPKTTDSELFRRFSKYGKIVDCKLIKRPEPVNaFAFLRFESEEAAEAAVEE 62

RNA recognition motif 1 (RRM1) found in the Hu proteins family; This subfamily corresponds to the RRM1 of the 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. 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
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1622967120 1288 IPGRMTRSELKQRFSVFGEIEECT-IHFRVQGDN--YGFVTYRYAEEAFAAIESGHKLR 1343
Cdd:cd12650      8 LPQNMTQDEIRSLFSSIGEIESCKlIRDKVTGQSlgYGFVNYVDPSDAEKAINTLNGLR 66

RNA recognition motif 1 (RRM1) found in heterogeneous nuclear ribonucleoprotein hnRNP A and hnRNP D subfamilies and similar proteins; This subfamily corresponds to the RRM1 in the hnRNP A subfamily which includes hnRNP A0, hnRNP A1, hnRNP A2/B1, hnRNP A3 and similar proteins. hnRNP A0 is a low abundance hnRNP protein that has been implicated in mRNA stability in mammalian cells. hnRNP A1 is an abundant eukaryotic nuclear RNA-binding protein that may modulate splice site selection in pre-mRNA splicing. hnRNP A2/B1 is an RNA trafficking response element-binding protein that interacts with the hnRNP A2 response element (A2RE). hnRNP A3 is also a RNA trafficking response element-binding protein that participates in the trafficking of A2RE-containing RNA. The hnRNP A subfamily is characterized by two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a long glycine-rich region at the C-terminus. The hnRNP D subfamily includes hnRNP D0, hnRNP A/B, hnRNP DL and similar proteins. hnRNP D0 is a UUAG-specific nuclear RNA binding protein that may be involved in pre-mRNA splicing and telomere elongation. hnRNP A/B is an RNA unwinding protein with a high affinity for G- followed by U-rich regions. hnRNP A/B has also been identified as an APOBEC1-binding protein that interacts with apolipoprotein B (apoB) mRNA transcripts around the editing site and thus, plays an important role in apoB mRNA editing. hnRNP DL (or hnRNP D-like) is a dual functional protein that possesses DNA- and RNA-binding properties. It has been implicated in mRNA biogenesis at the transcriptional and post-transcriptional levels. All members in this subfamily contain two putative RRMs and a glycine- and tyrosine-rich C-terminus. The family also contains DAZAP1 (Deleted in azoospermia-associated protein 1), RNA-binding protein Musashi homolog Musashi-1, Musashi-2 and similar proteins. They all harbor two RRMs.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1622967120 1283 VFIGKIPGRMTRSELKQRFSVFGEIEECTIHF-----RVQGdnYGFVTYRYAEEAFAAIESG-HKL--RQAD 1346
Cdd:cd12325      1 LFVGGLSWETTEESLREYFSKYGEVVDCVVMKdpatgRSRG--FGFVTFKDPSSVDAVLAARpHTLdgRTID 70

RNA recognition motif 1 (RRM1) and 2 (RRM2) found in RRM-containing coactivator activator/modulator (CoAA) and similar proteins; This subfamily corresponds to the RRM in CoAA (also known as RBM14 or PSP2) and RNA-binding protein 4 (RBM4). CoAA is a heterogeneous nuclear ribonucleoprotein (hnRNP)-like protein identified as a nuclear receptor coactivator. It mediates transcriptional coactivation and RNA splicing effects in a promoter-preferential manner, and is enhanced by thyroid hormone receptor-binding protein (TRBP). CoAA contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a TRBP-interacting domain. RBM4 is a ubiquitously expressed splicing factor with two isoforms, RBM4A (also known as Lark homolog) and RBM4B (also known as RBM30), which are very similar in structure and sequence. RBM4 may also function as a translational regulator of stress-associated mRNAs as well as play a role in micro-RNA-mediated gene regulation. RBM4 contains two N-terminal RRMs, a CCHC-type zinc finger, and three alanine-rich regions within their C-terminal regions. This family also includes Drosophila RNA-binding protein lark (Dlark), a homolog of human RBM4. It plays an important role in embryonic development and in the circadian regulation of adult eclosion. Dlark shares high sequence similarity with RBM4 at the N-terminal region. However, Dlark has three proline-rich segments instead of three alanine-rich segments within the C-terminal region.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1622967120 1283 VFIGKIPGRMTRSELKQRFSVFGEIEECTIhfrVQgdNYGFVTYRYAEEAFAAIESGHK 1341
Cdd:cd12343      2 IFVGNLPDAATSEELRALFEKYGKVTECDI---VK--NYAFVHMEKEEDAEDAIKALNG 55

RNA recognition motif 3 (RRM3) found in yeast nuclear and cytoplasmic polyadenylated RNA-binding protein PUB1 and similar proteins; This subfamily corresponds to the RRM3 of yeast protein PUB1, also termed ARS consensus-binding protein ACBP-60, or poly uridylate-binding protein, or poly(U)-binding protein. PUB1 has been identified as both, a heterogeneous nuclear RNA-binding protein (hnRNP) and a cytoplasmic mRNA-binding protein (mRNP), which may be stably bound to a translationally inactive subpopulation of mRNAs within the cytoplasm. PUB1 is distributed in both, the nucleus and the cytoplasm, and binds to poly(A)+ RNA (mRNA or pre-mRNA). Although it is one of the major cellular proteins cross-linked by UV light to polyadenylated RNAs in vivo, PUB1 is nonessential for cell growth in yeast. PUB1 also binds to T-rich single stranded DNA (ssDNA); however, there is no strong evidence implicating PUB1 in the mechanism of DNA replication. PUB1 contains three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a GAR motif (glycine and arginine rich stretch) that is located between RRM2 and RRM3.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1622967120 1283 VFIGKIPGRMTRSELKQRFSVFGEIEEctihFRVQGDN-YGFVTYRYAEEAFAAIESG 1339
Cdd:cd12622      3 VYVGNLPPEVTQADLIPLFQNFGVIEE----VRVQRDKgFGFVKYDTHEEAALAIQQL 56

RNA recognition motif 2 (RRM2) found in vertebrate RNA-binding protein RBM23, RBM39 and similar proteins; This subfamily corresponds to the RRM2 of RBM39 (also termed HCC1), a nuclear autoantigen that contains an N-terminal arginine/serine rich (RS) motif and three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). An octapeptide sequence called the RS-ERK motif is repeated six times in the RS region of RBM39. Although the cellular function of RBM23 remains unclear, it shows high sequence homology to RBM39 and contains two RRMs. It may possibly function as a pre-mRNA splicing factor.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1622967120 1284 FIGKIPGRMTRSELKQRFSVFGEIEECTIHF-----RVQGdnYGFVTYRYAEEAFAAIE 1337
Cdd:cd12284      2 YVGSLHFNITEDMLRGIFEPFGKIEFVQLQKdpetgRSKG--YGFIQFRDAEDAKKALE 58

RNA recognition motif 2 (RRM2) found in TAR DNA-binding protein 43 (TDP-43) and similar proteins; This subfamily corresponds to the RRM2 of TDP-43 (also termed TARDBP), a ubiquitously expressed pathogenic protein whose normal function and abnormal aggregation are directly linked to the genetic disease cystic fibrosis, and two neurodegenerative disorders: frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). TDP-43 binds both DNA and RNA, and has been implicated in transcriptional repression, pre-mRNA splicing and translational regulation. TDP-43 is a dimeric protein with two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a C-terminal glycine-rich domain. The RRMs are responsible for DNA and RNA binding; they bind to TAR DNA and RNA sequences with UG-repeats. The glycine-rich domain can interact with the hnRNP family proteins to form the hnRNP-rich complex involved in splicing inhibition. It is also essential for the cystic fibrosis transmembrane conductance regulator (CFTR) exon 9-skipping activity.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1622967120 1281 RVVFIGKIPGRMTRSELKQRFSVFGEIEECTI--HFRvqgdNYGFVTYRYAEEAFAAIESGHKLR 1343
Cdd:cd12322      1 RKVFVGRCTEDMTEDDLRQYFSQFGEVTDVFIpkPFR----AFAFVTFADDEVAQSLCGEDHIIK 61

RNA recognition motif 1 (RRM1) found in yeast nucleolar protein 3 (Npl3p) and similar proteins; This subfamily corresponds to the RRM1 of Npl3p, also termed mitochondrial targeting suppressor 1 protein, or nuclear polyadenylated RNA-binding protein 1. Npl3p is a major yeast RNA-binding protein that competes with 3'-end processing factors, such as Rna15, for binding to the nascent RNA, protecting the transcript from premature termination and coordinating transcription termination and the packaging of the fully processed transcript for export. It specifically recognizes a class of G/U-rich RNAs. Npl3p is a multi-domain protein containing two central RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), separated by a short linker and a C-terminal domain rich in glycine, arginine and serine residues.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1622967120 1284 FIGKIPGRMTRSELKQRFSVFGEIEECTIhfrVQGDNYGFVTYRYAEEAFAAIESGH 1340
Cdd:cd12340      3 FVRPFPPDTSESAIREIFSPYGPVKEVKM---LSDSNFAFVEFEELEDAIRAKDSVH 56

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).

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                   ....*....|....*....|....*....|....*....|....*....|...
gi 1622967120 1288 IPGRMTRSELKQRFSVFGEIEECTI-HFRVQGDN--YGFVTYRYAEEAFAAIE 1337
Cdd:cd12367      8 IPKSYTEEDLREKFKEFGDIEYCSIvKDKNTGESkgFGYVKFLKPSQAALAIE 60

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

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622967120 1284 FIGKIPGRMTRSELKQRFSVFGEIEECTI---HF--RVQGdnYGFVTYRYAEEAFAAIEsghKLRQADeqpfdlcFGGRR 1358
Cdd:COG0724      5 YVGNLPYSVTEEDLRELFSEYGEVTSVKLitdREtgRSRG--FGFVEMPDDEEAQAAIE---ALNGAE-------LMGRT 72

RNA recognition motif 1 (RRM1) found in heterogeneous nuclear ribonucleoprotein A0 (hnRNP A0) and similar proteins; This subfamily corresponds to the RRM1 of hnRNP A0 which is a low abundance hnRNP protein that has been implicated in mRNA stability in mammalian cells. It has been identified as the substrate for MAPKAP-K2 and may be involved in the lipopolysaccharide (LPS)-induced post-transcriptional regulation of tumor necrosis factor-alpha (TNF-alpha), cyclooxygenase 2 (COX-2) and macrophage inflammatory protein 2 (MIP-2). hnRNP A0 contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a long glycine-rich region at the C-terminus.

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                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1622967120 1283 VFIGKIPGRMTRSELKQRFSVFGEIEECTIHFRVQGDN---YGFVTYRYAEEAFAAIES 1338
Cdd:cd12326      5 LFIGGLNVQTTEEGLRAHFEAYGQLTDCVVVVNPQTKRsrcFGFVTYSSAEEADAAMAA 63

RNA recognition motif 1 (RRM1) found in vertebrate RNA-binding protein 46 (RBM46); This subgroup corresponds to the RRM1 of RBM46, also termed cancer/testis antigen 68 (CT68), a putative RNA-binding protein that shows high sequence homology with heterogeneous nuclear ribonucleoprotein R (hnRNP R) and heterogeneous nuclear ribonucleoprotein Q (hnRNP Q). Its biological function remains unclear. Like hnRNP R and hnRNP Q, RBM46 contains two well-defined and one degenerated RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

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                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1622967120 1283 VFIGKIPGRMTRSELKQRFSVFGEIEECTIHFRVQGDN--YGFVTYRYAEEAFAAIE 1337
Cdd:cd12484      4 VFVGKIPRDMYEDELVPVFERAGKIYEFRLMMEFSGENrgYAFVMYTTKEEAQLAIK 60

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.

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                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1622967120 1285 IGKIPGRMTRSELKQRFSVFGEIEECTIHF-RVQGDN--YGFVTYRYAEEAFAAIESGHKLR 1343
Cdd:cd12375      4 VNYLPQSMTQEELRSLFGAIGPIESCKLVRdKITGQSlgYGFVNYRDPNDARKAINTLNGLD 65

RNA recognition motif 1 (RRM1) found in serine/arginine-rich splicing factor 1 (SRSF1) and similar proteins; This subgroup corresponds to the RRM1 in three serine/arginine (SR) proteins: serine/arginine-rich splicing factor 1 (SRSF1 or ASF-1), serine/arginine-rich splicing factor 9 (SRSF9 or SRp30C), and plant pre-mRNA-splicing factor SF2 (SR1). SRSF1 is a shuttling SR protein involved in constitutive and alternative splicing, nonsense-mediated mRNA decay (NMD), mRNA export and translation. It also functions as a splicing-factor oncoprotein that regulates apoptosis and proliferation to promote mammary epithelial cell transformation. SRSF9 has been implicated in the activity of many elements that control splice site selection, the alternative splicing of the glucocorticoid receptor beta in neutrophils and in the gonadotropin-releasing hormone pre-mRNA. It can also interact with other proteins implicated in alternative splicing, including YB-1, rSLM-1, rSLM-2, E4-ORF4, Nop30, and p32. Both, SRSF1 and SRSF9, contain two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a C-terminal RS domains rich in serine-arginine dipeptides. In contrast, SF2 contains two N-terminal RRMs and a C-terminal PSK domain rich in proline, serine and lysine residues.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1622967120 1283 VFIGKIPGRMTRSELKQRFSVFGEIEECTIHFRVQGDNYGFVTYRYAEEAFAAIES-------GHKLR 1343
Cdd:cd12338      2 IYVGNLPGDIRERDIEDLFYKYGPILAIDLKNRRRGPPFAFVEFEDPRDAEDAIRGrdgydfdGYRLR 69

RNA recognition motif 1 (RRM1) found in RNA-binding protein 34 (RBM34) and similar proteins; This subfamily corresponds to the RRM1 of RBM34, a putative RNA-binding protein containing two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). Although the function of RBM34 remains unclear currently, its RRM domains may participate in mRNA processing. RBM34 may act as an mRNA processing-related protein.

                           10        20        30
                   ....*....|....*....|....*....|....*
gi 1622967120 1281 RVVFIGKIPGRMTRSELKQRFSVFGEIEecTIHFR 1315
Cdd:cd12394      1 RTVFVGNLPVTVKKKALKKLFKEFGKIE--SVRFR 33

RNA recognition motif 2 (RRM2) found in CUGBP Elav-like family member CELF-1, CELF-2 and similar proteins; This subgroup corresponds to the RRM2 of CELF-1 (also termed BRUNOL-2, or CUG-BP1, or EDEN-BP), CELF-2 (also termed BRUNOL-3, or ETR-3, or CUG-BP2, or NAPOR), both of which belong to the CUGBP1 and ETR-3-like factors (CELF) or BRUNOL (Bruno-like) family of RNA-binding proteins that have been implicated in the regulation of pre-mRNA splicing and in the control of mRNA translation and deadenylation. CELF-1 is strongly expressed in all adult and fetal tissues tested. Human CELF-1 is a nuclear and cytoplasmic RNA-binding protein that regulates multiple aspects of nuclear and cytoplasmic mRNA processing, with implications for onset of type 1 myotonic dystrophy (DM1), a neuromuscular disease associated with an unstable CUG triplet expansion in the 3'-UTR (3'-untranslated region) of the DMPK (myotonic dystrophy protein kinase) gene; it preferentially targets UGU-rich mRNA elements. It has been shown to bind to a Bruno response element, a cis-element involved in translational control of oskar mRNA in Drosophila, and share sequence similarity to Bruno, the Drosophila protein that mediates this process. The Xenopus homolog embryo deadenylation element-binding protein (EDEN-BP) mediates sequence-specific deadenylation of Eg5 mRNA. It binds specifically to the EDEN motif in the 3'-untranslated regions of maternal mRNAs and targets these mRNAs for deadenylation and translational repression. CELF-1 contains three highly conserved RNA recognition motifs (RRMs), also known as RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains): two consecutive RRMs (RRM1 and RRM2) situated in the N-terminal region followed by a linker region and the third RRM (RRM3) close to the C-terminus of the protein. The two N-terminal RRMs of EDEN-BP are necessary for the interaction with EDEN as well as a part of the linker region (between RRM2 and RRM3). Oligomerization of EDEN-BP is required for specific mRNA deadenylation and binding. CELF-2 is expressed in all tissues at some level, but highest in brain, heart, and thymus. It has been implicated in the regulation of nuclear and cytoplasmic RNA processing events, including alternative splicing, RNA editing, stability and translation. CELF-2 shares high sequence identity with CELF-1, but shows different binding specificity; it preferentially binds to sequences with UG repeats and UGUU motifs. It has been shown to bind to a Bruno response element, a cis-element involved in translational control of oskar mRNA in Drosophila, and share sequence similarity to Bruno, the Drosophila protein that mediates this process. It also binds to the 3'-UTR of cyclooxygenase-2 messages, affecting both translation and mRNA stability, and binds to apoB mRNA, regulating its C to U editing. CELF-2 also contains three highly conserved RRMs. It binds to RNA via the first two RRMs, which are also important for localization in the cytoplasm. The splicing activation or repression activity of CELF-2 on some specific substrates is mediated by RRM1/RRM2. Both, RRM1 and RRM2 of CELF-2, can activate cardiac troponin T (cTNT) exon 5 inclusion. In addition, CELF-2 possesses a typical arginine and lysine-rich nuclear localization signal (NLS) in the C-terminus, within RRM3.

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                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1622967120 1281 RVVFIGKIPGRMTRSELKQRFSVFGEIEECTIHFRVQGDNYG--FVTYRYAEEAFAAIESGHK 1341
Cdd:cd12634      2 RKLFIGMVSKKCNENDIRVMFSPFGQIEECRILRGPDGLSRGcaFVTFSTRAMAQNAIKAMHQ 64

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.

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1622967120 1283 VFIGKIPGRMTRSELKQRFSVFGEIEECT-IHFRVQGDN--YGFVTYRYAEEAFAAIESGHKLR 1343
Cdd:cd12769      5 LIVNYLPQNMTQDELRSLFSSIGEVESAKlIRDKVAGHSlgYGFVNYVTAKDAERAINTLNGLR 68

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

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1622967120 1283 VFIGKIPGRMTRSELKQRFSVFGEIeectIHFRVQGDN-------YGFVTYRYAEEAFAAIESGH 1340
Cdd:cd12362      1 LFVYHLPNEFTDQDLYQLFAPFGNV----VSAKVFVDKntgrskgFGFVSYDNPLSAQAAIKAMN 61

RNA recognition motif 2 (RRM2) found in vertebrate RRM-containing coactivator activator/modulator (CoAA); This subgroup corresponds to the RRM2 of CoAA, also termed RNA-binding protein 14 (RBM14), or paraspeckle protein 2 (PSP2), or synaptotagmin-interacting protein (SYT-interacting protein), a heterogeneous nuclear ribonucleoprotein (hnRNP)-like protein identified as a nuclear receptor coactivator. It mediates transcriptional coactivation and RNA splicing effects in a promoter-preferential manner and is enhanced by thyroid hormone receptor-binding protein (TRBP). CoAA contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a TRBP-interacting domain. It stimulates transcription through its interactions with coactivators, such as TRBP and CREB-binding protein CBP/p300, via the TRBP-interacting domain and interaction with an RNA-containing complex, such as DNA-dependent protein kinase-poly(ADP-ribose) polymerase complexes, via the RRMs.

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                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1622967120 1283 VFIGKIPGRMTRSELKQRFSVFGEIEECTIhfrVQGdnYGFVTYRYAEEAFAAIES 1338
Cdd:cd12609      3 IFVGNVSATCTSDELRGLFEEFGRVVECDK---VKD--YAFVHMEREEEALAAIEA 53

RNA recognition motif (RRM) found in fission yeast pre-mRNA-splicing factor Srp1p, Arabidopsis thaliana arginine/serine-rich-splicing factor RSp31 and similar proteins; This subfamily corresponds to the RRM of Srp1p and RRM2 of plant SR splicing factors. Srp1p is encoded by gene srp1 from fission yeast Schizosaccharomyces pombe. It plays a role in the pre-mRNA splicing process, but is not essential for growth. Srp1p is closely related to the SR protein family found in Metazoa. It contains an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a glycine hinge and a RS domain in the middle, and a C-terminal domain. The family also includes a novel group of arginine/serine (RS) or serine/arginine (SR) splicing factors existing in plants, such as A. thaliana RSp31, RSp35, RSp41 and similar proteins. Like vertebrate RS splicing factors, these proteins function as plant splicing factors and play crucial roles in constitutive and alternative splicing in plants. They all contain two RRMs at their N-terminus and an RS domain at their C-terminus.

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                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1622967120 1289 PGRMTRSELKQRFSVFGEIEECTIHfrvqgDNYGFVTYRYAEEAFAAIESGHKLR 1343
Cdd:cd12233      9 PGTTREEDIEKLFEPFGPLVRCDIR-----KTFAFVEFEDSEDATKALEALHGSR 58

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 1622967120 1281 RVVFIGKIPGRMTRSELKQRFSVFGEIeectIHFRVQGDN-------YGFVTYRYAEEAFAAI 1336
Cdd:cd12398      1 RSVFVGNIPYDATEEQLKEIFSEVGPV----VSFRLVTDRetgkpkgYGFCEFRDAETALSAV 59

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
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1622967120 1283 VFIGKIPGRMTRSELKQRFSVFGEIEECTIHFRVQGD---NYGFVTYRYAEEAFAAIE 1337
Cdd:cd12347      1 LYVGGLAEEVDEKVLHAAFIPFGDIVDIQIPLDYETEkhrGFAFVEFEEAEDAAAAID 58