RNA recognition motif (RRM) found in yeast cell wall integrity protein scw1 and similar proteins; This subfamily corresponds to the RRM of the family including yeast cell wall integrity protein scw1, yeast Whi3 protein, yeast Whi4 protein and similar proteins. The strong cell wall protein 1, scw1, is a nonessential cytoplasmic RNA-binding protein that regulates septation and cell-wall structure in fission yeast. It may function as an inhibitor of septum formation, such that its loss of function allows weak SIN signaling to promote septum formation. It's RRM domain shows high homology to two budding yeast proteins, Whi3 and Whi4. Whi3 is a dose-dependent modulator of cell size and has been implicated in cell cycle control in the yeast Saccharomyces cerevisiae. It functions as a negative regulator of ceroid-lipofuscinosis, neuronal 3 (Cln3), a G1 cyclin that promotes transcription of many genes to trigger the G1/S transition in budding yeast. It specifically binds the CLN3 mRNA and localizes it into discrete cytoplasmic loci that may locally restrict Cln3 synthesis to modulate cell cycle progression. Moreover, Whi3 plays a key role in cell fate determination in budding yeast. The RRM domain is essential for Whi3 function. Whi4 is a partially redundant homolog of Whi3, also containing one RRM. Some uncharacterized family members of this subfamily contain two RRMs; their RRM1 shows high sequence homology to the RRM of RNA-binding protein with multiple splicing (RBP-MS)-like proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767227475 536 PCNTLYVGNLPSDATEQELRQLFSGQEGFRRLSFRNKNttsnghsHGPMCFVEFDDVSFATRALAELYGRQLPrstVSSK 615
Cdd:cd12245    1 PCNTLFVANLGPNVSEQELRQLFSRQPGFRRLRMHNKG-------GGPVCFVEFEDVPFATQALNHLQGAILS---SSDR 70

                 ....*....
gi 767227475 616 GGIRLSFSK 624
Cdd:cd12245   71 GGIRIEYAK 79

RNA recognition motif (RRM) found in yeast cell wall integrity protein scw1 and similar proteins; This subfamily corresponds to the RRM of the family including yeast cell wall integrity protein scw1, yeast Whi3 protein, yeast Whi4 protein and similar proteins. The strong cell wall protein 1, scw1, is a nonessential cytoplasmic RNA-binding protein that regulates septation and cell-wall structure in fission yeast. It may function as an inhibitor of septum formation, such that its loss of function allows weak SIN signaling to promote septum formation. It's RRM domain shows high homology to two budding yeast proteins, Whi3 and Whi4. Whi3 is a dose-dependent modulator of cell size and has been implicated in cell cycle control in the yeast Saccharomyces cerevisiae. It functions as a negative regulator of ceroid-lipofuscinosis, neuronal 3 (Cln3), a G1 cyclin that promotes transcription of many genes to trigger the G1/S transition in budding yeast. It specifically binds the CLN3 mRNA and localizes it into discrete cytoplasmic loci that may locally restrict Cln3 synthesis to modulate cell cycle progression. Moreover, Whi3 plays a key role in cell fate determination in budding yeast. The RRM domain is essential for Whi3 function. Whi4 is a partially redundant homolog of Whi3, also containing one RRM. Some uncharacterized family members of this subfamily contain two RRMs; their RRM1 shows high sequence homology to the RRM of RNA-binding protein with multiple splicing (RBP-MS)-like proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767227475 536 PCNTLYVGNLPSDATEQELRQLFSGQEGFRRLSFRNKNttsnghsHGPMCFVEFDDVSFATRALAELYGRQLPrstVSSK 615
Cdd:cd12245    1 PCNTLFVANLGPNVSEQELRQLFSRQPGFRRLRMHNKG-------GGPVCFVEFEDVPFATQALNHLQGAILS---SSDR 70

                 ....*....
gi 767227475 616 GGIRLSFSK 624
Cdd:cd12245   71 GGIRIEYAK 79

RNA recognition motif;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767227475   539 TLYVGNLPSDATEQELRQLFSGQEGFRRLSFRNKNTTsnGHSHGpMCFVEFDDVSFATRALAELYGRQL 607
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSKFGKVESVRLVRDKET--GKSKG-FAFVEFESEEDAEKALEALNGKEL 66

hnRNP-L/PTB/hephaestus splicing factor family; Included in this family of heterogeneous ribonucleoproteins are PTB (polypyrimidine tract binding protein) and hnRNP-L. These proteins contain four RNA recognition motifs (rrm: pfam00067).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767227475  509 GSASISQADLSLLARIPPPANPADQN--PPCNTLYVGNLPSDATEQELRQLFSGQEGFRRLSFRNKNTTSNGHShgpMCF 586
Cdd:TIGR01649 364 GLTSYKDYSSSRNHRFKKPGSANKNNiqPPSATLHLSNIPLSVSEEDLKELFAENGVHKVKKFKFFPKDNERSK---MGL 440

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 767227475  587 VEFDDVSFATRALAELYGRQLPRSTVSSKGGIRLSFSK 624
Cdd:TIGR01649 441 LEWESVEDAVEALIALNHHQLNEPNGSAPYHLKVSFST 478

RNA recognition motif (RRM) found in yeast cell wall integrity protein scw1 and similar proteins; This subfamily corresponds to the RRM of the family including yeast cell wall integrity protein scw1, yeast Whi3 protein, yeast Whi4 protein and similar proteins. The strong cell wall protein 1, scw1, is a nonessential cytoplasmic RNA-binding protein that regulates septation and cell-wall structure in fission yeast. It may function as an inhibitor of septum formation, such that its loss of function allows weak SIN signaling to promote septum formation. It's RRM domain shows high homology to two budding yeast proteins, Whi3 and Whi4. Whi3 is a dose-dependent modulator of cell size and has been implicated in cell cycle control in the yeast Saccharomyces cerevisiae. It functions as a negative regulator of ceroid-lipofuscinosis, neuronal 3 (Cln3), a G1 cyclin that promotes transcription of many genes to trigger the G1/S transition in budding yeast. It specifically binds the CLN3 mRNA and localizes it into discrete cytoplasmic loci that may locally restrict Cln3 synthesis to modulate cell cycle progression. Moreover, Whi3 plays a key role in cell fate determination in budding yeast. The RRM domain is essential for Whi3 function. Whi4 is a partially redundant homolog of Whi3, also containing one RRM. Some uncharacterized family members of this subfamily contain two RRMs; their RRM1 shows high sequence homology to the RRM of RNA-binding protein with multiple splicing (RBP-MS)-like proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767227475 536 PCNTLYVGNLPSDATEQELRQLFSGQEGFRRLSFRNKNttsnghsHGPMCFVEFDDVSFATRALAELYGRQLPrstVSSK 615
Cdd:cd12245    1 PCNTLFVANLGPNVSEQELRQLFSRQPGFRRLRMHNKG-------GGPVCFVEFEDVPFATQALNHLQGAILS---SSDR 70

                 ....*....
gi 767227475 616 GGIRLSFSK 624
Cdd:cd12245   71 GGIRIEYAK 79

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 767227475  540 LYVGNLPSDATEQELRQLFSGQEGFRRLSFRNKNTtsnGHSHGpMCFVEFDDVSFATRALAELYGRQLPRSTV 612
Cdd:pfam00076   1 LFVGNLPPDTTEEDLKDLFSKFGPIKSIRLVRDET---GRSKG-FAFVEFEDEEDAEKAIEALNGKELGGREL 69

RNA recognition motif (RRM) superfamily; RRM, also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), is a highly abundant domain in eukaryotes found in proteins involved in post-transcriptional gene expression processes including mRNA and rRNA processing, RNA export, and RNA stability. This domain is 90 amino acids in length and consists of a four-stranded beta-sheet packed against two alpha-helices. RRM usually interacts with ssRNA, but is also known to interact with ssDNA as well as proteins. RRM binds a variable number of nucleotides, ranging from two to eight. The active site includes three aromatic side-chains located within the conserved RNP1 and RNP2 motifs of the domain. The RRM domain is found in a variety heterogeneous nuclear ribonucleoproteins (hnRNPs), proteins implicated in regulation of alternative splicing, and protein components of small nuclear ribonucleoproteins (snRNPs).

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767227475 540 LYVGNLPSDATEQELRQLFSGQEGFRRLSF-RNKNTTSNGHshgpmCFVEFDDVSFATRALAELYGRQL 607
Cdd:cd00590    1 LFVGNLPPDTTEEDLRELFSKFGEVVSVRIvRDRDGKSKGF-----AFVEFESPEDAEKALEALNGTEL 64

RNA recognition motif 1 (RRM1) found in granule-associated RNA binding proteins p40-TIA-1 and TIAR; This subfamily corresponds to the RRM1 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767227475 540 LYVGNLPSDATEQELRQLFsGQEGfrrlSFRNKNTTSNGHSHGPMCFVEFDDVSFATRALAELYGRQL 607
Cdd:cd12352    1 LYVGNLDRQVTEDLILQLF-SQIG----PCKSCKMITEHGGNDPYCFVEFYEHNHAAAALQAMNGRKI 63

RNA recognition motif 2 (RRM2) found in the U1A/U2B"/SNF protein family; This subfamily corresponds to the RRM2 of U1A/U2B"/SNF protein family, containing Drosophila sex determination protein SNF and its two mammalian counterparts, U1 small nuclear ribonucleoprotein A (U1 snRNP A or U1-A or U1A) and U2 small nuclear ribonucleoprotein B" (U2 snRNP B" or U2B"), all of which consist of two RNA recognition motifs (RRMs) connected by a variable, flexible linker. SNF is an RNA-binding protein found in the U1 and U2 snRNPs of Drosophila where it is essential in sex determination and possesses a novel dual RNA binding specificity. SNF binds with high affinity to both Drosophila U1 snRNA stem-loop II (SLII) and U2 snRNA stem-loop IV (SLIV). It can also bind to poly(U) RNA tracts flanking the alternatively spliced Sex-lethal (Sxl) exon, as does Drosophila Sex-lethal protein (SXL). U1A is an RNA-binding protein associated with the U1 snRNP, a small RNA-protein complex involved in pre-mRNA splicing. U1A binds with high affinity and specificity to stem-loop II (SLII) of U1 snRNA. It is predominantly a nuclear protein that shuttles between the nucleus and the cytoplasm independently of interactions with U1 snRNA. Moreover, U1A may be involved in RNA 3'-end processing, specifically cleavage, splicing and polyadenylation, through interacting with a large number of non-snRNP proteins. U2B", initially identified to bind to stem-loop IV (SLIV) at the 3' end of U2 snRNA, is a unique protein that comprises of the U2 snRNP. Additional research indicates U2B" binds to U1 snRNA stem-loop II (SLII) as well and shows no preference for SLIV or SLII on the basis of binding affinity. U2B" does not require an auxiliary protein for binding to RNA and its nuclear transport is independent on U2 snRNA binding.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767227475 536 PCNTLYVGNLPSDATEQELRQLFSGQEGF---RRLSFRNknttsnghshgpMCFVEFDDVSFATRALAELYG 604
Cdd:cd12247    1 PNKILFLQNLPEETTKEMLEMLFNQFPGFkevRLVPRRG------------IAFVEFETEEQATVALQALQG 60

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 767227475 538 NTLYVGNLPSDATEQELRQLFSgQEGfRRLSFRNKNTTSNGHSHGpMCFVEFDDVSFATRAL-----AELYGRQL 607
Cdd:cd12398    1 RSVFVGNIPYDATEEQLKEIFS-EVG-PVVSFRLVTDRETGKPKG-YGFCEFRDAETALSAVrnlngYELNGRPL 72

RNA recognition motif (RRM) found in RNA-binding protein with multiple splicing (RBP-MS)-like proteins; This subfamily corresponds to the RRM of RNA-binding proteins with multiple splicing (RBP-MS)-like proteins, including protein products of RBPMS genes (RBP-MS and its paralogue RBP-MS2), the Drosophila couch potato (cpo), and Caenorhabditis elegans Mec-8 genes. RBP-MS may be involved in regulation of mRNA translation and localization during Xenopus laevis development. It has also been shown to physically interact with Smad2, Smad3 and Smad4, and stimulates Smad-mediated transactivation. Cpo may play an important role in regulating normal function of the nervous system, whereas mutations in Mec-8 affect mechanosensory and chemosensory neuronal function. All members contain a well conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). Some uncharacterized family members contain two RRMs; this subfamily includes their RRM1. Their RRM2 shows high sequence homology to the RRM of yeast proteins scw1, Whi3, and Whi4.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767227475 539 TLYVGNLPSDATEQELRQLFSGQEGFR--RLSFRNKNTTsnghshgPMCFVEFDDVSFATRALAELYG 604
Cdd:cd12420    2 TLFVSGLPLDVKERELYNLFRPLPGYEasQLKFTGKNTQ-------PVGFVTFESRAAAEAAKDALQG 62

RNA recognition motif (RRM) found in eukaryotic RNA-binding protein 18 and similar proteins; This subfamily corresponds to the RRM of RBM18, a putative RNA-binding protein containing a well-conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). The biological role of RBM18 remains unclear.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767227475 540 LYVGNLPSDATEQELRQLFSGQEGFRRLSFR-NKNTTSNGHSHGpMCFVEFDDVSFATRALAELYGRQL 607
Cdd:cd12355    2 LWIGNLDPRLTEYHLLKLLSKYGKIKKFDFLfHKTGPLKGQPRG-YCFVTFETKEEAEKAIECLNGKLA 69

RNA recognition motif 1 (RRM1) found in squamous cell carcinoma antigen recognized by T-cells 3 (SART3) and similar proteins; This subfamily corresponds to the RRM1 of SART3, also termed Tat-interacting protein of 110 kDa (Tip110), an RNA-binding protein expressed in the nucleus of the majority of proliferating cells, including normal cells and malignant cells, but not in normal tissues except for the testes and fetal liver. It is involved in the regulation of mRNA splicing probably via its complex formation with RNA-binding protein with a serine-rich domain (RNPS1), a pre-mRNA-splicing factor. SART3 has also been identified as a nuclear Tat-interacting protein that regulates Tat transactivation activity through direct interaction and functions as an important cellular factor for HIV-1 gene expression and viral replication. In addition, SART3 is required for U6 snRNP targeting to Cajal bodies. It binds specifically and directly to the U6 snRNA, interacts transiently with the U6 and U4/U6 snRNPs, and promotes the reassembly of U4/U6 snRNPs after splicing in vitro. SART3 contains an N-terminal half-a-tetratricopeptide repeat (HAT)-rich domain, a nuclearlocalization signal (NLS) domain, and two C-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767227475 539 TLYVGNLPSDATEQELRQLFS--GQEGFRRLSFRNKnttsnGHSHGpMCFVEFDDVSFATRALA 600
Cdd:cd12391    1 TVFVSNLDYSVPEDKIREIFSgcGEITDVRLVKNYK-----GKSKG-YCYVEFKDEESAQKALK 58

RNA recognition motif 1 (RRM1) found in nucleolysin TIA-1 isoform p40 (p40-TIA-1) and similar proteins; This subgroup corresponds to the RRM1 of TIA-1, the 40-kDa isoform of T-cell-restricted intracellular antigen-1 (TIA-1) and a cytotoxic granule-associated RNA-binding protein mainly found in the granules of cytotoxic lymphocytes. TIA-1 can be phosphorylated by a serine/threonine kinase that is activated during Fas-mediated apoptosis, and functions as the granule component responsible for inducing apoptosis in cytolytic lymphocyte (CTL) targets. It is 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 interacts with RNAs containing short stretches of uridylates and its RRM2 can mediate the specific binding to uridylate-rich RNAs.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767227475 539 TLYVGNLPSDATEQELRQLFSgQEGfrrlSFRNKNTTSNGHSHGPMCFVEFDDVSFATRALAELYGRQL 607
Cdd:cd12615    1 TLYVGNLSRDVTEALILQLFS-QIG----PCKNCKMIMDTAGNDPYCFVEFHEHRHAAAALAAMNGRKI 64

RNA recognition motif 6 (RRM6) found in RNA-binding protein 19 (RBM19 or RBD-1) and RNA recognition motif 5 (RRM5) found in multiple RNA-binding domain-containing protein 1 (MRD1); This subfamily corresponds to the RRM6 of RBM19 and RRM5 of MRD1. RBM19, also termed RNA-binding domain-1 (RBD-1), is a nucleolar protein conserved in eukaryotes. It is involved in ribosome biogenesis by processing rRNA and is essential for preimplantation development. It has a unique domain organization containing 6 conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). MRD1 is encoded by a novel yeast gene MRD1 (multiple RNA-binding domain). It is well-conserved in yeast and its homologs exist in all eukaryotes. MRD1 is present in the nucleolus and the nucleoplasm. It interacts with the 35 S precursor rRNA (pre-rRNA) and U3 small nucleolar RNAs (snoRNAs). It is essential for the initial processing at the A0-A2 cleavage sites in the 35 S pre-rRNA. MRD1 contains 5 conserved RRMs, which may play an important structural role in organizing specific rRNA processing events.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767227475 538 NTLYVGNLPSDATEQELRQLFSGQEGFRRLSFRNKNTTsnghSHGPMCFVEF---DDVSFATRALA--ELYGRQL 607
Cdd:cd12320    1 TKLIVKNVPFEATRKEIRELFSPFGQLKSVRLPKKFDG----SHRGFAFVEFvtkQEAQNAMEALKstHLYGRHL 71

RNA recognition motif 1 (RRM1) found in Saccharomyces cerevisiae protein HRB1, G-strand-binding protein 2 (GBP2) and similar proteins; The family includes Saccharomyces cerevisiae protein HRB1 (also called protein TOM34) and GBP2, both of which are SR-like mRNA-binding proteins which shuttle from the nucleus to the cytoplasm when bound to the mature mRNA molecules. They act as quality control factors for spliced mRNAs. GBP2, also called RAP1 localization factor 6, is a single-strand telomeric DNA-binding protein that binds single-stranded telomeric sequences of the type (TG[1-3])n in vitro. It also binds to RNA. GBP2 influences the localization of RAP1 in the nuclei and plays a role in modulating telomere length. Members in this family contain three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The model corresponds to the first RRM motif.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767227475 538 NTLYVGNLPSDATEQELRQLFSgqeGFRRLsFRNKNTTSNGHSHGpMCFVEFDDVSFATRALAEL 602
Cdd:cd21605    2 NSIFVGNLPFDCTWEDLKDHFS---QVGEV-IRADIVTSRGRHRG-MGTVEFTNKEDVDRAISKF 61

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767227475 540 LYVGNLPSDATEQELRQLFSgQEGfRRLSFRNKNTTSNGHSHGpMCFVEFDDVSFATRALAELYGRQLPRSTV 612
Cdd:cd12652    3 LYVSGLPKTMTQKELEQLFS-QFG-RIITSRILCDNVTGLSRG-VGFIRFDKRVEAERAIKALNGTIPPGATE 72

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 767227475 539 TLYVGNLPSDATEQELRQLFSGQEGFRRLSFRnknttsNGHSHGPMCFVEFDDVSFATRAlaeLYGR 605
Cdd:cd12338    1 RIYVGNLPGDIRERDIEDLFYKYGPILAIDLK------NRRRGPPFAFVEFEDPRDAEDA---IRGR 58

RNA recognition motif 1 (RRM1) found in nucleolysin TIAR and similar proteins; This subgroup corresponds to the RRM1 of nucleolysin TIAR, also termed TIA-1-related protein, and a cytotoxic granule-associated RNA-binding protein that shows high sequence similarity with 40-kDa isoform of T-cell-restricted intracellular antigen-1 (p40-TIA-1). 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. TIAR possesses nucleolytic activity against cytolytic lymphocyte (CTL) target cells. It can trigger DNA fragmentation in permeabilized thymocytes, and thus may function as an effector responsible for inducing apoptosis. TIAR is 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. It interacts with RNAs containing short stretches of uridylates and its RRM2 can mediate the specific binding to uridylate-rich RNAs.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767227475 539 TLYVGNLPSDATEQELRQLFSGQEGFRRLSFRNKNTTSNghshgPMCFVEFDDVSFATRALAELYGRQL 607
Cdd:cd12616    1 TLYVGNLSRDVTEVLILQLFSQIGPCKSCKMITEHTSND-----PYCFVEFYEHRDAAAALAAMNGRKI 64

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767227475 539 TLYVGNLPSDATEQELRQLFSgqEGFRRLSFRNKNTTSNGHSHGpMCFVEFDDVSFATRALAELYGRQL 607
Cdd:cd12671    8 SVFVGNIPYEATEEQLKDIFS--EVGPVVSFRLVYDRETGKPKG-YGFCEYQDQETALSAMRNLNGYEL 73

RNA recognition motif 1 (RRM1) found in serine/arginine-rich splicing factor 4 (SRSF4) and similar proteins; This subfamily corresponds to the RRM1 in three serine/arginine (SR) proteins: serine/arginine-rich splicing factor 4 (SRSF4 or SRp75 or SFRS4), serine/arginine-rich splicing factor 5 (SRSF5 or SRp40 or SFRS5 or HRS), serine/arginine-rich splicing factor 6 (SRSF6 or SRp55). SRSF4 plays an important role in both, constitutive and alternative, splicing of many pre-mRNAs. It can shuttle between the nucleus and cytoplasm. SRSF5 regulates both alternative splicing and basal splicing. It is the only SR protein efficiently selected from nuclear extracts (NE) by the splicing enhancer (ESE) and essential for enhancer activation. SRSF6 preferentially interacts with a number of purine-rich splicing enhancers (ESEs) to activate splicing of the ESE-containing exon. It is the only protein from HeLa nuclear extract or purified SR proteins that specifically binds B element RNA after UV irradiation. SRSF6 may also recognize different types of RNA sites. Members in this family contain two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a C-terminal RS domains rich in serine-arginine dipeptides.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767227475 540 LYVGNLPSDATEQELRQLFSGQEGFRRLSFRNknttsnghSHGpmcFVEFDDVSFATRALAELYGRQL 607
Cdd:cd12337    2 VYIGRLPYRARERDVERFFRGYGRIRDINLKN--------GFG---FVEFEDPRDADDAVYELNGKEL 58

RNA recognition motif in type II polyadenylate-binding proteins; This subfamily corresponds to the RRM of type II polyadenylate-binding proteins (PABPs), including polyadenylate-binding protein 2 (PABP-2 or PABPN1), embryonic polyadenylate-binding protein 2 (ePABP-2 or PABPN1L) and similar proteins. PABPs are 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. ePABP-2 is predominantly located in the cytoplasm and PABP-2 is located in the nucleus. In contrast to the type I PABPs containing four copies of RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), the type II PABPs contains a single highly-conserved RRM. This subfamily also includes Saccharomyces cerevisiae RBP29 (SGN1, YIR001C) gene encoding cytoplasmic mRNA-binding protein Rbp29 that binds preferentially to poly(A). Although not essential for cell viability, Rbp29 plays a role in modulating the expression of cytoplasmic mRNA. Like other type II PABPs, Rbp29 contains one RRM only.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767227475 541 YVGNLPSDATEQELRQLFSGQEGFRRLSFR-NKNTtsnGHSHGpMCFVEFDDVSFATRALA----ELYGRQL 607
Cdd:cd12306    3 YVGNVDYGTTPEELQAHFKSCGTINRVTILcDKFT---GQPKG-FAYIEFVDKSSVENALLlnesEFRGRQI 70

RNA recognition motif 5 (RRM5) found in RNA-binding protein 19 (RBM19 or RBD-1) and similar proteins; This subfamily corresponds to the RRM5 of RBM19 and RRM4 of MRD1. RBM19, also termed RNA-binding domain-1 (RBD-1), is a nucleolar protein conserved in eukaryotes involved in ribosome biogenesis by processing rRNA and is essential for preimplantation development. It has a unique domain organization containing 6 conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767227475 538 NTLYVGNLPSDATEQELRQLFSGQEGFRRLSF-RNKNTTSNGHSHGpMCFVEFDDVSFATRALAELYGRQL 607
Cdd:cd12318    1 TTLFVKNLNFKTTEEALKKHFEKCGPIRSVTIaKKKDPKGPLLSMG-YGFVEFKSPEAAQKALKQLQGTVL 70

RNA recognition motif 1 (RRM1) and 2 (RRM2) found in RNA-binding protein 5 (RBM5) and similar proteins; This subfamily includes the RRM1 and RRM2 of RNA-binding protein 5 (RBM5 or LUCA15 or H37) and RNA-binding protein 10 (RBM10 or S1-1), and the RRM2 of RNA-binding protein 6 (RBM6 or NY-LU-12 or g16 or DEF-3). These RBMs share high sequence homology and may play an important role in regulating apoptosis. RBM5 is a known modulator of apoptosis. It may also act as a tumor suppressor or an RNA splicing factor. RBM6 has been predicted to be a nuclear factor based on its nuclear localization signal. Both, RBM6 and RBM5, specifically bind poly(G) RNA. RBM10 is a paralog of RBM5. It may play an important role in mRNA generation, processing and degradation in several cell types. The rat homolog of human RBM10 is protein S1-1, a hypothetical RNA binding protein with poly(G) and poly(U) binding capabilities. All family members contain two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two C2H2-type zinc fingers, and a G-patch/D111 domain.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767227475 536 PCNTLYVGNLPSDATEQELRQLFSGQEGFR----RLSfRNKNTtsnGHSHGpMCFVEFDDVSFATRALAELYG 604
Cdd:cd12313    1 PTNVLILRGLDVLTTEEDILSALQAHADLPikdvRLI-RDKLT---GTSRG-FAFVEFSSLEDATQVMDALQN 68

RNA recognition motif 6 (RRM6) found in RNA-binding protein 19 (RBM19) and similar proteins; This subgroup corresponds to the RRM6 of RBM19, also termed RNA-binding domain-1 (RBD-1), which is a nucleolar protein conserved in eukaryotes. It is involved in ribosome biogenesis by processing rRNA. In addition, it is essential for preimplantation development. RBM19 has a unique domain organization containing 6 conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767227475 540 LYVGNLPSDATEQELRQLFS--GQEGFRRLSfrnKNTTSNGhSHGPMCFVEF---DDVSFATRALAE---LYGRQL 607
Cdd:cd12571    3 ILVRNIPFQATVKEVRELFStfGELKTVRLP---KKMGGTG-QHRGFGFVDFitkQDAKRAFDALCHsthLYGRRL 74

RNA recognition motif 1 (RRM1) found in vertebrate RRM-containing coactivator activator/modulator (CoAA); This subgroup corresponds to the RRM1 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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767227475 540 LYVGNLPSDATEQELRQLFSGQEGFRRLSFRNKnttsnghshgpMCFVEFDDVSFATRALAELYGRQLP 608
Cdd:cd12608    3 IFVGNVDEDTSQEELSALFEPYGAVLSCAVMKQ-----------FAFVHMRGEAAADRAIRELNGRELH 60

RNA recognition motif in nucleolar protein interacting with the FHA domain of pKI-67 (NIFK) and similar proteins; This subgroup corresponds to the RRM of NIFK and Nop15p. NIFK, also termed MKI67 FHA domain-interacting nucleolar phosphoprotein, or nucleolar phosphoprotein Nopp34, is a putative RNA-binding protein interacting with the forkhead associated (FHA) domain of pKi-67 antigen in a mitosis-specific and phosphorylation-dependent manner. It is nucleolar in interphase but associates with condensed mitotic chromosomes. This family also includes Saccharomyces cerevisiae YNL110C gene encoding ribosome biogenesis protein 15 (Nop15p), also termed nucleolar protein 15. Both, NIFK and Nop15p, contain an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain).

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 767227475 539 TLYVGNLPSDATEQELRQLFS--GQEGFRRLSfRNKNTtsnGHSHGpMCFVEFDD 591
Cdd:cd12307    1 VVYIGHLPHGFYEPELRKYFSqfGTVTRLRLS-RSKKT---GKSKG-YAFVEFED 50

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
                 ....*....|....*....
gi 767227475 540 LYVGNLPSDATEQELRQLF 558
Cdd:cd12343    2 IFVGNLPDAATSEELRALF 20

RNA recognition motif 2 (RRM2) found in vertebrate U1 small nuclear ribonucleoprotein A (U1 snRNP A or U1-A or U1A); This subgroup corresponds to the RRM2 of U1A (also termed U1 snRNP A or U1-A), an RNA-binding protein associated with the U1 snRNP, a small RNA-protein complex involved in pre-mRNA splicing. U1A binds with high affinity and specificity to stem-loop II (SLII) of U1 snRNA. It is predominantly a nuclear protein that shuttles between the nucleus and the cytoplasm independently of interactions with U1 snRNA. U1A may be involved in RNA 3'-end processing, specifically cleavage, splicing and polyadenylation, through interacting with a large number of non-snRNP proteins, including polypyrimidine tract binding protein (PTB), polypyrimidine-tract binding protein-associated factor (PSF), and non-POU-domain-containing, octamer-binding (NONO), DEAD (Asp-Glu-Ala-Asp) box polypeptide 5 (DDX5). U1A also binds to a flavivirus NS5 protein and plays an important role in virus replication. It contains two RNA recognition motifs (RRMs); the N-terminal RRM (RRM1) binds tightly and specifically to the U1 snRNA SLII and its own 3'-UTR, while in contrast, the C-terminal RRM (RRM2) does not appear to associate with any RNA and it may be free for binding other proteins. U1A also contains a proline-rich region, and a nuclear localization signal (NLS) in the central domain that is responsible for its nuclear import.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767227475 527 PANPADQNPPCNTLYVGNLPSDATEQELRQLFSGQEGFRRLSFrnkntTSNGHShgpMCFVEFDDVSFATRALAELYGRQ 606
Cdd:cd12480    1 PPQPVSENPPNHILFLTNLPEETNELMLSMLFNQFPGFKEVRL-----VPGRHD---IAFVEFDNEVQAGAAREALQGFK 72

                         90
                 ....*....|....*...
gi 767227475 607 LPRSTvsskgGIRLSFSK 624
Cdd:cd12480   73 ITQSN-----AMKISFAK 85

RNA recognition motif 2 (RRM2) found in RNA-binding protein 40 (RBM40) and similar proteins; This subfamily corresponds to the RRM2 of RBM40 and the RRM of RBM41. RBM40, also known as RNA-binding region-containing protein 3 (RNPC3) or U11/U12 small nuclear ribonucleoprotein 65 kDa protein (U11/U12-65K protein). It serves as a bridging factor between the U11 and U12 snRNPs. It contains two RNA recognition motifs (RRMs), also known as RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), connected by a linker that includes a proline-rich region. It binds to the U11-associated 59K protein via its RRM1 and employs the RRM2 to bind hairpin III of the U12 small nuclear RNA (snRNA). The proline-rich region might be involved in protein-protein interactions. RBM41 contains only one RRM. Its biological function remains unclear.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767227475 537 CNTLYVGNLPSDATEQELRQLFSgqegfrrlSFRNKNTTSNG------HSHGPM---CFVEFDDVSFATRALAELYG 604
Cdd:cd12239    1 SNRLYVKNLSKRVSEKDLKYIFG--------RFVDSSSEEKNmfdirlMTEGRMkgqAFITFPSEELAEKALNLTNG 69

RNA recognition motif 4 (RRM4) found in type I polyadenylate-binding proteins; This subfamily corresponds to the RRM4 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 theThe CD corresponds to the RRM. 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. Moreover, 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767227475 540 LYVGNLPSDATEQELRQLFSgqeGFRRLSFRNKNTTSNGHSHGpMCFVEFDDVSFATRALAELYGR 605
Cdd:cd12381    4 LYVKNLDDTIDDEKLREEFS---PFGTITSAKVMTDEGGRSKG-FGFVCFSSPEEATKAVTEMNGR 65

RNA recognition motif 1 (RRM1) found in plant flowering time control protein FCA and similar proteins; This subgroup corresponds to the RRM1 of FCA, a gene controlling flowering time in Arabidopsis, encoding a flowering time control protein that functions in the posttranscriptional regulation of transcripts involved in the flowering process. 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        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767227475 540 LYVGNLPSDATEQELRQLFSGQEGFRRLSF-RNKNTtsnGHSHGpMCFVEFDDVSFATRALAELYG-RQLP 608
Cdd:cd12633    2 LFVGSVPRTITEQEVRPMFEEHGNVLEVAIiKDKRT---GHQQG-CCFVKYSTRDEADRAIRALHNqRTLP 68

RNA recognition motif 2 (RRM2) found in yeast protein gar2 and similar proteins; This subfamily corresponds to the RRM2 of yeast protein gar2, a novel nucleolar protein required for 18S rRNA and 40S ribosomal subunit accumulation. It shares similar domain architecture with nucleolin from vertebrates and NSR1 from Saccharomyces cerevisiae. The highly phosphorylated N-terminal domain of gar2 is made up of highly acidic regions separated from each other by basic sequences, and contains multiple phosphorylation sites. The central domain of gar2 contains two closely adjacent N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The C-terminal RGG (or GAR) domain of gar2 is rich in glycine, arginine and phenylalanine residues.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767227475 540 LYVGNLPSDATEQELRQLFSGQEGFRRLSFRNKNTTSNGHSHGpmcFVEFDDVSFATRALA-----ELYGRQL 607
Cdd:cd12448    1 LFVGNLPFSATQDALYEAFSQHGSIVSVRLPTDRETGQPKGFG---YVDFSTIDSAEAAIDalggeYIDGRPI 70

RNA recognition motif (RRM) found in eukaryotic translation initiation factor 4H (eIF-4H) and similar proteins; This subfamily corresponds to the RRM of eIF-4H, also termed Williams-Beuren syndrome chromosomal region 1 protein, which, together with elf-4B/eIF-4G, serves as the accessory protein of RNA helicase eIF-4A. eIF-4H contains a well conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). It stimulates protein synthesis by enhancing the helicase activity of eIF-4A in the initiation step of mRNA translation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767227475 535 PPCnTLYVGNLPSDATEQELRQLFSGQEgFR--RLsFRNKNTTS-NGhshgpMCFVEFDDVSFATRAL----AELYGRQL 607
Cdd:cd12401    4 PPF-TAYVGNLPFNTVQGDLDAIFKDLK-VRsvRL-VRDRETDKfKG-----FCYVEFEDLESLKEALeydgALFEDRPL 75

RNA recognition motif 1 (RRM1) found in vertebrate 54 kDa nuclear RNA- and DNA-binding protein (p54nrb); This subgroup corresponds to the RRM1 of p54nrb, also termed non-POU domain-containing octamer-binding protein (NonO), or 55 kDa nuclear protein (NMT55), or DNA-binding p52/p100 complex 52 kDa subunit. p54nrb is a multifunctional protein involved in numerous nuclear processes including transcriptional regulation, splicing, DNA unwinding, nuclear retention of hyperedited double-stranded RNA, viral RNA processing, control of cell proliferation, and circadian rhythm maintenance. It is ubiquitously expressed and highly conserved in vertebrates. p54nrb binds both, single- and double-stranded RNA and DNA, and also possesses inherent carbonic anhydrase activity. It forms a heterodimer with paraspeckle component 1 (PSPC1 or PSP1), localizing to paraspeckles in an RNA-dependent manneras well as with polypyrimidine tract-binding protein-associated-splicing factor (PSF). p54nrb contains two conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), at the N-terminus.

                         10        20
                 ....*....|....*....|
gi 767227475 540 LYVGNLPSDATEQELRQLFS 559
Cdd:cd12588    4 LFVGNLPPDITEEEMRKLFE 23

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 767227475 538 NTLYVGNLPSDATEQELRQLFsgqEGFRRL-SFRNKNTTSNGHSHGpMCFVEFDDVSFATRALAELYGRQL 607
Cdd:cd12231    1 NKLFIGGLPNYLNEDQVKELL---QSFGKLkAFNLVKDSATGLSKG-YAFCEYVDDNVTDQAIAGLNGMQL 67

RNA recognition motif 1 (RRM1) found in plant Mei2-like proteins; This subgroup corresponds to the RRM1 of Mei2-like proteins that represent an ancient eukaryotic RNA-binding proteins family. Their corresponding Mei2-like genes appear to have arisen early in eukaryote evolution, been lost from some lineages such as Saccharomyces cerevisiae and metazoans, and diversified in the plant lineage. The plant Mei2-like genes may function in cell fate specification during development, rather than as stimulators of meiosis. Members in this family contain three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The C-terminal RRM (RRM3) is unique to Mei2-like proteins and it is highly conserved between plants and fungi. Up to date, the intracellular localization, RNA target(s), cellular interactions and phosphorylation states of Mei2-like proteins in plants remain unclear.

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gi 767227475 539 TLYVGNLPSDATEQELRQLFSGQEGFRRLSFRNKNttsnghsHGpMCFVEFDDVSFATRALAELYGRQLPRSTVSskggI 618
Cdd:cd12524    3 TLFVRNINSSVEDEELRALFEQFGEIRTLYTACKH-------RG-FIMVSYYDIRAAQSAKRALQGTELGGRKLD----I 70

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gi 767227475 619 RLSFSK 624
Cdd:cd12524   71 HFSIPK 76

RNA recognition motif 2 (RRM2) found in the Spen (split end) protein family; This subfamily corresponds to the RRM2 domain in the Spen (split end) protein family which includes RNA binding motif protein 15 (RBM15), putative RNA binding motif protein 15B (RBM15B), and similar proteins found in Metazoa. RBM15, also termed one-twenty two protein 1 (OTT1), conserved in eukaryotes, is a novel mRNA export factor and component of the NXF1 pathway. It binds to NXF1 and serves as receptor for the RNA export element RTE. It also possess mRNA export activity and can facilitate the access of DEAD-box protein DBP5 to mRNA at the nuclear pore complex (NPC). RNA-binding protein 15B (RBM15B), also termed one twenty-two 3 (OTT3), is a paralog of RBM15 and therefore has post-transcriptional regulatory activity. It is a nuclear protein sharing with RBM15 the association with the splicing factor compartment and the nuclear envelope as well as the binding to mRNA export factors NXF1 and Aly/REF. Members in this family belong to the Spen (split end) protein family, which share a domain architecture comprising of three N-terminal RNA recognition motifs (RRMs), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal SPOC (Spen paralog and ortholog C-terminal) domain.

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gi 767227475 539 TLYVGNLPSDATEQELRQLFsGQEGFRRLSFRNKNTTSNGHSHGpmcFVEFDDVSFATRALAELYGRQLPR 609
Cdd:cd12309    4 TLFVGNLEITITEEELRRAF-ERYGVVEDVDIKRPPRGQGNAYA---FVKFLNLDMAHRAKVAMSGQYIGR 70

RNA recognition motif (RRM) found in the cell surface Ecto-NOX disulfide-thiol exchanger (ECTO-NOX or ENOX) proteins; This subgroup corresponds to the conserved RNA recognition motif (RRM) in ECTO-NOX proteins (also termed ENOX), comprising a family of plant and animal NAD(P)H oxidases exhibiting both, oxidative and protein disulfide isomerase-like, activities. They are growth-related and drive cell enlargement, and may play roles in aging and neurodegenerative diseases. ENOX proteins function as terminal oxidases of plasma membrane electron transport (PMET) through catalyzing electron transport from plasma membrane quinones to extracellular oxygen, forming water as a product. They are also hydroquinone oxidases that oxidize externally supplied NADH, hence NOX. ENOX proteins harbor a di-copper center that lack flavin. ENOX proteins display protein disulfide interchange activity that is also possessed by protein disulfide isomerase. In contrast to the classic protein disulfide isomerases, ENOX proteins lack the double CXXC motif. This family includes two ENOX proteins, ENOX1 and ENOX2. ENOX1, also termed candidate growth-related and time keeping constitutive hydroquinone [NADH] oxidase (cCNOX), or cell proliferation-inducing gene 38 protein, or Constitutive Ecto-NOX (cNOX), is the constitutively expressed cell surface NADH (ubiquinone) oxidase that is ubiquitous and refractory to drugs. ENOX2, also termed APK1 antigen, or cytosolic ovarian carcinoma antigen 1, or tumor-associated hydroquinone oxidase (tNOX), is a cancer-specific variant of ENOX1 and plays a key role in cell proliferation and tumor progression. In contrast to ENOX1, ENOX2 is drug-responsive and harbors a drug binding site to which the cancer-specific S-peptide tagged pan-ENOX2 recombinant (scFv) is directed. Moreover, ENOX2 is specifically inhibited by a variety of quinone site inhibitors that have anticancer activity and is unique to the surface of cancer cells. ENOX proteins contain many functional motifs.

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gi 767227475 535 PPCNTLYVGNLPSDATEQELRQLFS--GQEGFRRLSFRNknttsnghshgpMCFVEFDDVSFATRALA 600
Cdd:cd12228    4 PGCKTVFVGGLPENATEEIIREVFEqcGEIIAIRMSKKN------------FCHIRFAEEFAVDKAIY 59