RNA recognition motif (RRM) found in nucleolar protein 8 (NOL8) and similar proteins; This model corresponds to the RRM of NOL8 (also termed Nop132) encoded by a novel NOL8 gene that is up-regulated in the majority of diffuse-type, but not intestinal-type, gastric cancers. Thus, NOL8 may be a good molecular target for treatment of diffuse-type gastric cancer. Also, NOL8 is a phosphorylated protein that contains an N-terminal RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), suggesting NOL8 is likely to function as a novel RNA-binding protein. It may be involved in regulation of gene expression at the post-transcriptional level or in ribosome biogenesis in cancer cells.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568982568   27 RLFVGGLGQGISETDLQNQFGRFGEVSDVEIITRKDDQGNSqkvFAYVNIQITEADLKKCMSILNKTKWKGGTLQIQLAK 106
Cdd:cd12226     1 RLFVGGLSPSITEDDLERRFSRFGTVSDVEIIRKKDAPDRG---FAYIDLRTSEAALQKCLSTLNGVKWKGSRLKIQLAK 77

RNA recognition motif (RRM) found in nucleolar protein 8 (NOL8) and similar proteins; This model corresponds to the RRM of NOL8 (also termed Nop132) encoded by a novel NOL8 gene that is up-regulated in the majority of diffuse-type, but not intestinal-type, gastric cancers. Thus, NOL8 may be a good molecular target for treatment of diffuse-type gastric cancer. Also, NOL8 is a phosphorylated protein that contains an N-terminal RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), suggesting NOL8 is likely to function as a novel RNA-binding protein. It may be involved in regulation of gene expression at the post-transcriptional level or in ribosome biogenesis in cancer cells.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568982568   27 RLFVGGLGQGISETDLQNQFGRFGEVSDVEIITRKDDQGNSqkvFAYVNIQITEADLKKCMSILNKTKWKGGTLQIQLAK 106
Cdd:cd12226     1 RLFVGGLSPSITEDDLERRFSRFGTVSDVEIIRKKDAPDRG---FAYIDLRTSEAALQKCLSTLNGVKWKGSRLKIQLAK 77

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568982568   25 MKRLFVGGLGQGISETDLQNQFGRFGEVSDVEIITRKDDqGNSqKVFAYVNIQiTEADLKKCMSILNKTKWKGGTLQIQL 104
Cdd:COG0724     1 SMKIYVGNLPYSVTEEDLRELFSEYGEVTSVKLITDRET-GRS-RGFGFVEMP-DDEEAQAAIEALNGAELMGRTLKVNE 77

                  ...
gi 568982568  105 AKE 107
Cdd:COG0724    78 ARP 80

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 568982568    28 LFVGGLGQGISETDLQNQFGRFGEVSDVEIItrKDDQGNSqKVFAYVNIQiTEADLKKCMSILNKTKWKGGTL 100
Cdd:pfam00076    1 LFVGNLPPDTTEEDLKDLFSKFGPIKSIRLV--RDETGRS-KGFAFVEFE-DEEDAEKAIEALNGKELGGREL 69

RNA recognition motif (RRM) found in nucleolar protein 8 (NOL8) and similar proteins; This model corresponds to the RRM of NOL8 (also termed Nop132) encoded by a novel NOL8 gene that is up-regulated in the majority of diffuse-type, but not intestinal-type, gastric cancers. Thus, NOL8 may be a good molecular target for treatment of diffuse-type gastric cancer. Also, NOL8 is a phosphorylated protein that contains an N-terminal RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), suggesting NOL8 is likely to function as a novel RNA-binding protein. It may be involved in regulation of gene expression at the post-transcriptional level or in ribosome biogenesis in cancer cells.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568982568   27 RLFVGGLGQGISETDLQNQFGRFGEVSDVEIITRKDDQGNSqkvFAYVNIQITEADLKKCMSILNKTKWKGGTLQIQLAK 106
Cdd:cd12226     1 RLFVGGLSPSITEDDLERRFSRFGTVSDVEIIRKKDAPDRG---FAYIDLRTSEAALQKCLSTLNGVKWKGSRLKIQLAK 77

RNA recognition motif;

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568982568     27 RLFVGGLGQGISETDLQNQFGRFGEVSDVEIItrKDDQGNSQKVFAYVNIQiTEADLKKCMSILNKTKWKGGTLQI 102
Cdd:smart00360    1 TLFVGNLPPDTTEEELRELFSKFGKVESVRLV--RDKETGKSKGFAFVEFE-SEEDAEKALEALNGKELDGRPLKV 73

RNA recognition motif 2 (RRM2) found in Nicotiana sylvestris chloroplastic 33 kDa ribonucleoprotein (NsCP33) and similar proteins; The family includes NsCP33, Arabidopsis thaliana chloroplastic 31 kDa ribonucleoprotein (CP31A) and mitochondrial glycine-rich RNA-binding protein 2 (AtGR-RBP2). NsCP33 may be involved in splicing and/or processing of chloroplast RNA's. AtCP31A, also called RNA-binding protein 1/2/3 (AtRBP33), or RNA-binding protein CP31A, or RNA-binding protein RNP-T, or RNA-binding protein cp31, is required for specific RNA editing events in chloroplasts and stabilizes specific chloroplast mRNAs, as well as for normal chloroplast development under cold stress conditions by stabilizing transcripts of numerous mRNAs under these conditions. CP31A may modulate telomere replication through RNA binding domains. AtGR-RBP2, also called AtRBG2, or glycine-rich protein 2 (AtGRP2), or mitochondrial RNA-binding protein 1a (At-mRBP1a), plays a role in RNA transcription or processing during stress. It binds RNAs and DNAs sequence with a preference to single-stranded nucleic acids. AtGR-RBP2 displays strong affinity to poly(U) sequence. It exerts cold and freezing tolerance, probably by exhibiting an RNA chaperone activity during the cold and freezing adaptation process. Some members in this family contain two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The model corresponds to the second RRM motif.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568982568   27 RLFVGGLGQGISETDLQNQFGRFGEVSDVEIITRKdDQGNSqKVFAYVNIQiTEADLKKCMSILNKTKWKGGTLQIQLA 105
Cdd:cd21608     1 KLYVGNLSWDTTEDDLRDLFSEFGEVESAKVITDR-ETGRS-RGFGFVTFS-TAEAAEAAIDALNGKELDGRSIVVNEA 76

RNA recognition motif (RRM) found in Pre-mRNA-splicing factor RBM22 and similar proteins; This subgroup corresponds to the RRM of RBM22 (also known as RNA-binding motif protein 22, or Zinc finger CCCH domain-containing protein 16), a newly discovered RNA-binding motif protein which belongs to the SLT11 gene family. SLT11 gene encoding protein (Slt11p) is a splicing factor in yeast, which is required for spliceosome assembly. Slt11p has two distinct biochemical properties: RNA-annealing and RNA-binding activities. RBM22 is the homolog of SLT11 in vertebrate. It has been reported to be involved in pre-splicesome assembly and to interact with the Ca2+-signaling protein ALG-2. It also plays an important role in embryogenesis. RBM22 contains a conserved RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a zinc finger of the unusual type C-x8-C-x5-C-x3-H, and a C-terminus that is unusually rich in the amino acids Gly and Pro, including sequences of tetraprolines.

                          10        20        30
                  ....*....|....*....|....*....|....
gi 568982568   28 LFVGGLGQGISETDLQNQFGRFGEVSDVEIITRK 61
Cdd:cd12224     4 LYVGGLGDKITEKDLRDHFYQFGEIRSITVVARQ 37

glycine-rich RNA-binding protein 4; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568982568    6 ENVSSNLDRCPTSMQGN-REMK-RLFVGGLGQGISETDLQNQFGRFGEVSDVEIITrkDDQGNSQKVFAYVNIQiTEADL 83
Cdd:PLN03134   13 QNISSNGNVPVTSMLGSlRLMStKLFIGGLSWGTDDASLRDAFAHFGDVVDAKVIV--DRETGRSRGFGFVNFN-DEGAA 89

                          90       100
                  ....*....|....*....|....
gi 568982568   84 KKCMSILNKTKWKGGTLQIQLAKE 107
Cdd:PLN03134   90 TAAISEMDGKELNGRHIRVNPAND 113

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 568982568    28 LFVGGLGQGISETDLQNQFGRFGEVSDVEIItrKDDQGNSqKVFAYVNIQiTEADLKKCMSILNKTKWKGGTL 100
Cdd:pfam00076    1 LFVGNLPPDTTEEDLKDLFSKFGPIKSIRLV--RDETGRS-KGFAFVEFE-DEEDAEKAIEALNGKELGGREL 69

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein A subfamily; This subfamily corresponds to the RRM2 of 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. 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 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). Many mRNAs, such as myelin basic protein (MBP), myelin-associated oligodendrocytic basic protein (MOBP), carboxyanhydrase II (CAII), microtubule-associated protein tau, and amyloid precursor protein (APP) are trafficked by hnRNP A2/B1. 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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568982568   27 RLFVGGLGQGISETDLQNQFGRFGEVSDVEIITrkDDQGNSQKVFAYVN 75
Cdd:cd12328     1 KLFVGGLKEDVEEEDLREYFSQFGKVESVEIVT--DKETGKKRGFAFVT 47

RNA recognition motif 1 (RRM1) found in the p54nrb/PSF/PSP1 family; This subfamily corresponds to the RRM1 of the p54nrb/PSF/PSP1 family, including 54 kDa nuclear RNA- and DNA-binding protein (p54nrb or NonO or NMT55), polypyrimidine tract-binding protein (PTB)-associated-splicing factor (PSF or POMp100), paraspeckle protein 1 (PSP1 or PSPC1), which are ubiquitously expressed and are conserved in vertebrates. p54nrb is a multi-functional 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. PSF is also a multi-functional protein that binds RNA, single-stranded DNA (ssDNA), double-stranded DNA (dsDNA) and many factors, and mediates diverse activities in the cell. PSP1 is a novel nucleolar factor that accumulates within a new nucleoplasmic compartment, termed paraspeckles, and diffusely distributes in the nucleoplasm. The cellular function of PSP1 remains unknown currently. This subfamily also includes some p54nrb/PSF/PSP1 homologs from invertebrate species, such as the Drosophila melanogaster gene no-ontransient A (nonA) encoding puff-specific protein Bj6 (also termed NONA) and Chironomus tentans hrp65 gene encoding protein Hrp65. D. melanogaster NONA is involved in eye development and behavior, and may play a role in circadian rhythm maintenance, similar to vertebrate p54nrb. C. tentans Hrp65 is a component of nuclear fibers associated with ribonucleoprotein particles in transit from the gene to the nuclear pore. All family members contain a DBHS domain (for Drosophila behavior, human splicing), which comprises two conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a charged protein-protein interaction module. PSF has an additional large N-terminal domain that differentiates it from other family members.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568982568   27 RLFVGGLGQGISETDLQNQFGRFGEVSDVEIitrkddqgNSQKVFAYVNIQiTEADLKKCMSILNKTKWKGGTLQI 102
Cdd:cd12332     3 RLFVGNLPNDITEEEFKELFQKYGEVSEVFL--------NKGKGFGFIRLD-TRANAEAAKAELDGTPRKGRQLRV 69

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein hnRNP D0, hnRNP A/B, hnRNP DL and similar proteins; This subfamily corresponds to the RRM2 of hnRNP D0, hnRNP A/B, hnRNP DL and similar proteins. hnRNP D0, 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. It 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 memembers in this family contain two putative RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a glycine- and tyrosine-rich C-terminus.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568982568   27 RLFVGGLGQGISETDLQNQFGRFGEVSDVEIITrkDDQGNSQKVFAYV 74
Cdd:cd12329     1 KIFVGGLSPETTEEKIREYFGKFGNIVEIELPM--DKKTNKRRGFCFI 46

RNA recognition motif (RRM) found in vertebrate RNA binding protein fox-1 homologs and similar proteins; This subfamily corresponds to the RRM of several tissue-specific alternative splicing isoforms of vertebrate RNA binding protein Fox-1 homologs, which show high sequence similarity to the Caenorhabditis elegans feminizing locus on X (Fox-1) gene encoding Fox-1 protein. RNA binding protein Fox-1 homolog 1 (RBFOX1), also termed ataxin-2-binding protein 1 (A2BP1), or Fox-1 homolog A, or hexaribonucleotide-binding protein 1 (HRNBP1), is predominantly expressed in neurons, skeletal muscle and heart. It regulates alternative splicing of tissue-specific exons by binding to UGCAUG elements. Moreover, RBFOX1 binds to the C-terminus of ataxin-2 and forms an ataxin-2/A2BP1 complex involved in RNA processing. RNA binding protein fox-1 homolog 2 (RBFOX2), also termed Fox-1 homolog B, or hexaribonucleotide-binding protein 2 (HRNBP2), or RNA-binding motif protein 9 (RBM9), or repressor of tamoxifen transcriptional activity, is expressed in ovary, whole embryo, and human embryonic cell lines in addition to neurons and muscle. RBFOX2 activates splicing of neuron-specific exons through binding to downstream UGCAUG elements. RBFOX2 also functions as a repressor of tamoxifen activation of the estrogen receptor. RNA binding protein Fox-1 homolog 3 (RBFOX3 or NeuN or HRNBP3), also termed Fox-1 homolog C, is a nuclear RNA-binding protein that regulates alternative splicing of the RBFOX2 pre-mRNA, producing a message encoding a dominant negative form of the RBFOX2 protein. Its message is detected exclusively in post-mitotic regions of embryonic brain. Like RBFOX1, both RBFOX2 and RBFOX3 bind to the hexanucleotide UGCAUG elements and modulate brain and muscle-specific splicing of exon EIIIB of fibronectin, exon N1 of c-src, and calcitonin/CGRP. Members in this family also harbor one RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568982568   26 KRLFVGGLGQGISETDLQNQFGRFGEVSDVEIITrkDDQGNsqKVFAYVNIQiTEADLKKCMSILNKTKWKGGTLQIQLA 105
Cdd:cd12407     1 KRLHVSNIPFRFRDPDLRQMFGQFGTILDVEIIF--NERGS--KGFGFVTFA-NSADADRAREKLNGTVVEGRKIEVNNA 75

RNA recognition motif (RRM) found in Saccharomyces cerevisiae U1 small nuclear ribonucleoprotein SNP1 and similar proteins; SNP1, also called U1 snRNP protein SNP1, or U1 small nuclear ribonucleoprotein 70 kDa homolog, or U1 70K, or U1 snRNP 70 kDa homolog, interacts with mRNA and is involved in nuclear mRNA splicing. It is a component of the spliceosome, where it is associated with snRNP U1 by binding stem loop I of U1 snRNA. Members in this family contain an N-terminal U1snRNP70 domain and an RNA recognition motif (RRM), also called RBD (RNA binding domain) or RNP (ribonucleoprotein domain).

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568982568   26 KRLFVGGLGQGISETDLQNQFGRFGEVSDVEIItrKDDQGNSQKVFAYVnIQITEADLKKCMSILNKTK 94
Cdd:cd21615    19 KTLFVGRLDYSLTELELQKKFSKFGEIEKIRIV--RDKETGKSRGYAFI-VFKSESDAKNAFKEGNGLR 84

RNA recognition motif (RRM) found in Scaffold attachment factor (SAF)-like transcription modulator (SLTM) and similar proteins; This subgroup corresponds to the RRM domain of SLTM, also termed modulator of estrogen-induced transcription, which shares high sequence similarity with scaffold attachment factor B1 (SAFB1). It contains a scaffold attachment factor-box (SAF-box, also known as SAP domain) DNA-binding motif, an RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a region rich in glutamine and arginine residues. To a large extent, SLTM co-localizes with SAFB1 in the nucleus, which suggests that they share similar functions, such as the inhibition of an oestrogen reporter gene. However, rather than mediating a specific inhibitory effect on oestrogen action, SLTM is shown to exert a generalized inhibitory effect on gene expression associated with induction of apoptosis in a wide range of cell lines.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568982568   28 LFVGGLGQGISETDLQNQFGRFGEVSDVEIITRKDDQGnsQKVFAYVNIQiTEADLKKCMSILNKTKWKGGTLQIQ 103
Cdd:cd12678     2 LWVSGLSSNTKAADLKNLFGKYGKVLSAKVVTNARSPG--AKCYGIVTMS-SSTEVARCISHLHRTELHGQQISVE 74

RNA recognition motif 1 (RRM1) found in yeast multiple RNA-binding domain-containing protein 1 (MRD1) and similar proteins; This subgroup corresponds to the RRM1 of MRD1 which 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). MRD1 is essential for the initial processing at the A0-A2 cleavage sites in the 35 S pre-rRNA. It contains 5 conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), which may play an important structural role in organizing specific rRNA processing events.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568982568   27 RLFVGGLGQGISETDLQNQFGRFGEVSDVEIITRKDdqGNSQKvFAYVNIQiTEADLKKCMSILNKTKWKGGTLQIQLA 105
Cdd:cd12565     2 RIIVKNLPKYVTEKRLKEHFSKKGEITDVKVMRTKD--GKSRR-FGFIGFK-SEEEAQKAVKYFNKTFIDTSKISVEFA 76

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568982568   27 RLFVGGLGQGISETDLQNQFGRFGEVSDVEIItrKDDQGNSQKVFAYVNIQITEaDLKKCMSILNKTKWKGGTLQIQLAK 106
Cdd:cd12449     2 KLFVGGLSFDTNEQSLEEVFSKYGQISEVVVV--KDRETQRSRGFGFVTFENPD-DAKDAMMAMNGKSLDGRQIRVDQAG 78

                  ..
gi 568982568  107 ES 108
Cdd:cd12449    79 KS 80

RNA recognition motif (RRM) found in U2-associated protein SR140 and similar proteins; This subgroup corresponds to the RRM of SR140 (also termed U2 snRNP-associated SURP motif-containing protein orU2SURP, or 140 kDa Ser/Arg-rich domain protein) which is a putative splicing factor mainly found in higher eukaryotes. Although it is initially identified as one of the 17S U2 snRNP-associated proteins, the molecular and physiological function of SR140 remains unclear. SR140 contains an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a SWAP/SURP domain that is found in a number of pre-mRNA splicing factors in the middle region, and a C-terminal arginine/serine-rich domain (RS domain).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568982568   28 LFVGGLGQGISETDLQNQFGRFGEVSDVEII-TRKDDQGNSQKVFAYVNIqITEADLKKCMSILNKTKWKGGTLQIQLAK 106
Cdd:cd12223     4 LYVGNLPPSVTEEVLLREFGRFGPLASVKIMwPRTEEERRRNRNCGFVAF-MSRADAERAMRELNGKDVMGYELKLGWGK 82

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568982568    27 RLFVGGLGQGISETDLQNQFGRFGEVSDVEIitRKDDQGNSQKVFAYvnIQITEAD-LKKCMSILNKTKWKGGTLQIQLA 105
Cdd:TIGR01622  216 RLYVGNLHFNITEQDLRQIFEPFGEIEFVQL--QKDPETGRSKGYGF--IQFRDAEqAKEALEKMNGFELAGRPIKVGLG 291

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 568982568   106 KE-------SFLHRLAQEREDAKAKKEKSTTGNPTLLEKMGAVDfhMKAVPGTEVPG 155
Cdd:TIGR01622  292 NDftpesdaNLAQRFQDQDGSAFSGAGLNTPARSQLMRKLARDN--EKGTGGLAIPG 346

RNA recognition motif (RRM) found in serine/arginine-rich splicing factor 3 (SRSF3) and similar proteins; This subfamily corresponds to the RRM of two serine/arginine (SR) proteins, serine/arginine-rich splicing factor 3 (SRSF3) and serine/arginine-rich splicing factor 7 (SRSF7). SRSF3, also termed pre-mRNA-splicing factor SRp20, modulates alternative splicing by interacting with RNA cis-elements in a concentration- and cell differentiation-dependent manner. It is also involved in termination of transcription, alternative RNA polyadenylation, RNA export, and protein translation. SRSF3 is critical for cell proliferation, and tumor induction and maintenance. It can shuttle between the nucleus and cytoplasm. SRSF7, also termed splicing factor 9G8, plays a crucial role in both constitutive splicing and alternative splicing of many pre-mRNAs. Its localization and functions are tightly regulated by phosphorylation. SRSF7 is predominantly present in the nuclear and can shuttle between nucleus and cytoplasm. It cooperates with the export protein, Tap/NXF1, helps mRNA export to the cytoplasm, and enhances the expression of unspliced mRNA. Moreover, SRSF7 inhibits tau E10 inclusion through directly interacting with the proximal downstream intron of E10, a clustering region for frontotemporal dementia with Parkinsonism (FTDP) mutations. Both SRSF3 and SRSF7 contain a single N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal RS domain rich in serine-arginine dipeptides. The RRM domain is involved in RNA binding, and the RS domain has been implicated in protein shuttling and protein-protein interactions.

                          10        20
                  ....*....|....*....|....*....
gi 568982568   27 RLFVGGLGQGISETDLQNQFGRFGEVSDV 55
Cdd:cd12373     1 KVYVGNLGPRVTKRELEDAFEKYGPLRNV 29

RNA recognition motif 2 (RRM2) found in RNA-binding protein Musashi homologs Musashi-1, Musashi-2 and similar proteins; This subfamily corresponds to the RRM2.in Musashi-1 (also termed Msi1), a neural RNA-binding protein putatively expressed in central nervous system (CNS) stem cells and neural progenitor cells, and associated with asymmetric divisions in neural progenitor cells. It is evolutionarily conserved from invertebrates to vertebrates. Musashi-1 is a homolog of Drosophila Musashi and Xenopus laevis nervous system-specific RNP protein-1 (Nrp-1). It has been implicated in the maintenance of the stem-cell state, differentiation, and tumorigenesis. It translationally regulates the expression of a mammalian numb gene by binding to the 3'-untranslated region of mRNA of Numb, encoding a membrane-associated inhibitor of Notch signaling, and further influences neural development. Moreover, Musashi-1 represses translation by interacting with the poly(A)-binding protein and competes for binding of the eukaryotic initiation factor-4G (eIF-4G). Musashi-2 (also termed Msi2) has been identified as a regulator of the hematopoietic stem cell (HSC) compartment and of leukemic stem cells after transplantation of cells with loss and gain of function of the gene. It influences proliferation and differentiation of HSCs and myeloid progenitors, and further modulates normal hematopoiesis and promotes aggressive myeloid leukemia. Both, Musashi-1 and Musashi-2, contain two conserved N-terminal tandem RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), along with other domains of unknown function.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568982568   27 RLFVGGLGQGISETDLQNQFGRFGEVSDVEIITrkDDQGNSQKVFAYVNIQITEADLKKC 86
Cdd:cd12323     1 KIFVGGLSANTTEDDVKKYFSQFGKVEDAMLMF--DKQTNRHRGFGFVTFESEDVVDKVC 58

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein D-like (hnRNP DL) and similar proteins; This subgroup corresponds to the RRM2 of hnRNP DL (or hnRNP D-like), also termed AU-rich element RNA-binding factor, or JKT41-binding protein (protein laAUF1 or JKTBP), 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. hnRNP DL binds single-stranded DNA (ssDNA) or double-stranded DNA (dsDNA) in a non-sequencespecific manner, and interacts with poly(G) and poly(A) tenaciously. It contains two putative two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a glycine- and tyrosine-rich C-terminus.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568982568   27 RLFVGGLGQGISETDLQNQFGRFGEVSDVEIITrkDDQGNSQKVFAYVNIQITE 80
Cdd:cd12585     1 KVFVGGLSPDTSEEQIKEYFGAFGEIENIELPM--DTKTNERRGFCFITYTDEE 52

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) and similar proteins; This subgroup corresponds to the RRM2 of hnRNP A2/B1, an RNA trafficking response element-binding protein that interacts with the hnRNP A2 response element (A2RE). Many mRNAs, such as myelin basic protein (MBP), myelin-associated oligodendrocytic basic protein (MOBP), carboxyanhydrase II (CAII), microtubule-associated protein tau, and amyloid precursor protein (APP) are trafficked by hnRNP A2/B1. hnRNP A2/B1 also functions as a splicing factor that regulates alternative splicing of the tumor suppressors, such as BIN1, WWOX, the antiapoptotic proteins c-FLIP and caspase-9B, the insulin receptor (IR), and the RON proto-oncogene among others. Overexpression of hnRNP A2/B1 has been described in many cancers. It functions as a nuclear matrix protein involving in RNA synthesis and the regulation of cellular migration through alternatively splicing pre-mRNA. It may play a role in tumor cell differentiation. hnRNP A2/B1 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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568982568   26 KRLFVGGLGQGISETDLQNQFGRFGEVSDVEIITrkDDQGNSQKVFAYV 74
Cdd:cd12581     1 KKLFVGGIKEDTEEHHLRDYFEEYGKIDTIEIIT--DRQSGKKRGFGFV 47

RNA recognition motif 2 (RRM2) found in Deleted in azoospermia-associated protein 1 (DAZAP1) and similar proteins; This subfamily corresponds to the RRM2 of DAZAP1 or DAZ-associated protein 1, also termed proline-rich RNA binding protein (Prrp), a multi-functional ubiquitous RNA-binding protein expressed most abundantly in the testis and essential for normal cell growth, development, and spermatogenesis. DAZAP1 is a shuttling protein whose acetylated is predominantly nuclear and the nonacetylated form is in cytoplasm. DAZAP1 also functions as a translational regulator that activates translation in an mRNA-specific manner. DAZAP1 was initially identified as a binding partner of Deleted in Azoospermia (DAZ). It also interacts with numerous hnRNPs, including hnRNP U, hnRNP U like-1, hnRNPA1, hnRNPA/B, and hnRNP D, suggesting DAZAP1 might associate and cooperate with hnRNP particles to regulate adenylate-uridylate-rich elements (AU-rich element or ARE)-containing mRNAs. DAZAP1 contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a C-terminal proline-rich domain.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 568982568   26 KRLFVGGLGQGISETDLQNQFGRFGEVSDVEIITRKDDQ 64
Cdd:cd12327     3 KKVFVGGIPHNCGETELRDYFKRYGVVTEVVMMYDAEKQ 41

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
                  ....*....|....*....|....*....|..
gi 568982568   26 KRLFVGGLGQGISETDLQNQFGRFGEVSDVEI 57
Cdd:cd12322     1 RKVFVGRCTEDMTEDDLRQYFSQFGEVTDVFI 32

RNA recognition motif (RRM) found in Helicobacter pylori HP0827 protein and similar proteins; This subfamily corresponds to the RRM of H. pylori HP0827, a putative ssDNA-binding protein 12rnp2 precursor, containing one RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). The ssDNA binding may be important in activation of HP0827.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568982568   28 LFVGGLGQGISETDLQNQFGRFGEVSDVEIITrkdDQGNSQ-KVFAYVNIQITEAdLKKCMSILNKTKWKGGTLQIQLA 105
Cdd:cd12399     1 LYVGNLPYSASEEQLKSLFGQFGAVFDVKLPM---DRETKRpRGFGFVELQEEES-AEKAIAKLDGTDFMGRTIRVNEA 75

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568982568   28 LFVGGLGQGISETDLQNQFGRFGEVSDVEIItrKDDQGNSQKVFAYVNIQITEaDLKKCMSILNKTKWKG 97
Cdd:cd12363     4 LGVFGLSLYTTERDLREVFSRYGPIEKVQVV--YDQQTGRSRGFGFVYFESVE-DAKEAKERLNGQEIDG 70

RNA recognition motif 3 (RRM3) found in RNA-binding protein 19 (RBM19) and RNA recognition motif 2 found in multiple RNA-binding domain-containing protein 1 (MRD1); This subfamily corresponds to the RRM3 of RBM19 and RRM2 of MRD1. RBM19, also termed RNA-binding domain-1 (RBD-1), is a nucleolar protein conserved in eukaryotes involved in ribosome biogenesis by processing rRNA and is essential for preimplantation development. It has a unique domain organization containing 6 conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). MRD1 is encoded by a novel yeast gene MRD1 (multiple RNA-binding domain). It is well conserved in yeast and its homologs exist in all eukaryotes. MRD1 is present in the nucleolus and the nucleoplasm. It interacts with the 35 S precursor rRNA (pre-rRNA) and U3 small nucleolar RNAs (snoRNAs). It is essential for the initial processing at the A0-A2 cleavage sites in the 35 S pre-rRNA. MRD1 contains 5 conserved RRMs, which may play an important structural role in organizing specific rRNA processing events.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568982568   27 RLFVGGLGQGISETDLQNQFGRFGEVSDVEIITrkDDQGNSQKVFAYVNIQITEaDLKKCMSILNKTKWKGGTLQI 102
Cdd:cd12316     1 RLFVRNLPFTATEDELRELFEAFGKISEVHIPL--DKQTKRSKGFAFVLFVIPE-DAVKAYQELDGSIFQGRLLHV 73

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568982568   24 EMKRLFVGGLGQGISETDLQNQFGRFGEVSDVEIITRKDdqgNSQKVFAYVNIQiTEADLKKCMSILNKTKWKGGTLQIQ 103
Cdd:cd12392     1 EKNKLFVKGLPFSCTKEELEELFKQHGTVKDVRLVTYRN---GKPKGLAYVEYE-NEADASQAVLKTDGTEIKDHTISVA 76

                  .
gi 568982568  104 L 104
Cdd:cd12392    77 I 77

RNA recognition motif (RRM) found in Saccharomyces cerevisiae nucleolar protein 6 (Nop6) and similar proteins; This subfamily corresponds to the RRM of Nop6, also known as Ydl213c, a component of 90S pre-ribosomal particles in yeast S. cerevisiae. It is enriched in the nucleolus and is required for 40S ribosomal subunit biogenesis. Nop6 is a non-essential putative RNA-binding protein with two N-terminal putative nuclear localisation sequences (NLS-1 and NLS-2) and an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). It binds to the pre-rRNA early during transcription and plays an essential role in pre-rRNA processing.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568982568   28 LFVGGLGQGISETDLQNQFGRFGEVSDVEIITRKDdqGNSQKVFAYVNIQITEAdLKKCMS 88
Cdd:cd12400     3 LFVGNLPYDTTAEDLKEHFKKAGEPPSVRLLTDKK--TGKSKGCAFVEFDNQKA-LQKALK 60

RNA recognition motif 2 (RRM2) found in vertebrate RNA binding motif protein 15 (RBM15); This subgroup corresponds to the RRM2 of RBM15, also termed one-twenty two protein 1 (OTT1), conserved in eukaryotes, 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 possesses mRNA export activity and can facilitate the access of DEAD-box protein DBP5 to mRNA at the nuclear pore complex (NPC). RBM15 belongs to the Spen (split end) protein family, which contain 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. This family also includes a RBM15-MKL1 (OTT-MAL) fusion protein that RBM15 is N-terminally fused to megakaryoblastic leukemia 1 protein (MKL1) at the C-terminus in a translocation involving chromosome 1 and 22, resulting in acute megakaryoblastic leukemia. The fusion protein could interact with the mRNA export machinery. Although it maintains the specific transactivator function of MKL1, the fusion protein cannot activate RTE-mediated mRNA expression and has lost the post-transcriptional activator function of RBM15. However, it has transdominant suppressor function contributing to its oncogenic properties.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568982568   23 REMKRLFVGGLGQGISETDLQNQFGRFGEVSDVEIITRKDDQGNSQKVFAYVNIQI 78
Cdd:cd12555     5 RANRTLFLGNLDITVTENDLRRAFDRFGVITEVDIKRPGRGQTSTYGFLKFENLDM 60

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568982568   28 LFVGGLGQGISETDLQNQFGRFGEVSDVEIitRKDDQGNSQKVFAYVNIQITEaDLKKCMSILNKTKWKGGTLQIQLA 105
Cdd:cd12347     1 LYVGGLAEEVDEKVLHAAFIPFGDIVDIQI--PLDYETEKHRGFAFVEFEEAE-DAAAAIDNMNESELFGRTIRVNLA 75