RNA recognition motif (RRM) found in inner nuclear membrane protein Man1 (Man1) and similar proteins; This subfamily corresponds to the RRM of Man1, also termed LEM domain-containing protein 3 (LEMD3), an integral protein of the inner nuclear membrane that binds to nuclear lamins and emerin, thus playing a role in nuclear organization. It is part of a protein complex essential for chromatin organization and cell division. It also functions as an important negative regulator for the transforming growth factor (TGF) beta/activin/Nodal signaling pathway by directly interacting with chromatin-associated proteins and transcriptional regulators, including the R-Smads, Smad1, Smad2, and Smad3. Moreover, Man1 is a unique type of left-right (LR) signaling regulator that acts on the inner nuclear membrane. Man1 plays a crucial role in angiogenesis. The vascular remodeling can be regulated at the inner nuclear membrane through the interaction between Man1 and Smads. Man1 contains an N-terminal LEM domain, two putative transmembrane domains, a MAN1-Src1p C-terminal (MSC) domain, and a C-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). The LEM domain interacts with the DNA and chromatin-binding protein Barrier-to-Autointegration Factor, and is also necessary for efficient localization of MAN1 in the inner nuclear membrane. Research has indicated that C-terminal nucleoplasmic region of Man1 exhibits a DNA binding winged helix domain and is responsible for both DNA- and Smad-binding.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706607  785 CLKIRNMFDPVMEIGDQWHLAIQEAILEKCSDNDGIVHIAVDKNSREGCVYVKCLSPEYAGKAFKALHGSWFDGKLVTVK 864
Cdd:cd12286   1 CLKIRNMFDPEMEIGEDWHVRIQEAILEKCSDNGGIVHIAVDKNSREGCVYIKCASPEDAGKAFKALHGCWFDGRLVTVK 80

                        90
                ....*....|..
gi 7706607  865 YLRLDRYHHRFP 876
Cdd:cd12286  81 YLRLERYHSRFP 92

Man1-Src1p-C-terminal domain; MAN1 is an integral protein of the inner nuclear membrane which binds to chromatin associated proteins and plays a role in nuclear organization. The C terminal nucleoplasmic region forms a DNA binding winged helix and binds to Smad. This C-terminal tail is also found in S. cerevisiae and is thought to consist of three conserved helices followed by two downstream strands.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706607    538 LAQLAGDHECGSSSQRT------LSVQEaaayLKDL----------GPEYEGIFNTSLQwILENGKDVGIRCVGFGPEEE 601
Cdd:pfam09402 111 LREKNAKVECGEGKDDLgalesgISEEE----LKDIlsekkspslsDEEFEELWAAALG-ELKKRPEIVWRQDSVGNSDG 185

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706607    602 LTNITdvqFLQSTRPLMSFWCRFRRAFVTVTHRLLLLCLGVVMVCVVLRYMKYRWTKEEEETRQMYDMVVKIIDVLRSHN 681
Cdd:pfam09402 186 ESTRL---LRSTSLAYLPLKCRLRRSVRDTLARYRLILLGLLLLLLAILYLRSRYRRRRAEKARVEELVQEVLERLKNQK 262

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706607    682 EACQENKDL--QPYMPIPHVRDSLIQP-HDRKKMKKVWDRAVDFLAANESrVRTETRRIGGADFLVWRWI 748
Cdd:pfam09402 263 ALHAEDPSLypDPYLSSVQLRDDILRDeHSLKRRNRLWKRVVKVVEGNSN-VRTSLREVHGEIMRVWEWI 331

RNA recognition motif (RRM) found in inner nuclear membrane protein Man1 (Man1) and similar proteins; This subfamily corresponds to the RRM of Man1, also termed LEM domain-containing protein 3 (LEMD3), an integral protein of the inner nuclear membrane that binds to nuclear lamins and emerin, thus playing a role in nuclear organization. It is part of a protein complex essential for chromatin organization and cell division. It also functions as an important negative regulator for the transforming growth factor (TGF) beta/activin/Nodal signaling pathway by directly interacting with chromatin-associated proteins and transcriptional regulators, including the R-Smads, Smad1, Smad2, and Smad3. Moreover, Man1 is a unique type of left-right (LR) signaling regulator that acts on the inner nuclear membrane. Man1 plays a crucial role in angiogenesis. The vascular remodeling can be regulated at the inner nuclear membrane through the interaction between Man1 and Smads. Man1 contains an N-terminal LEM domain, two putative transmembrane domains, a MAN1-Src1p C-terminal (MSC) domain, and a C-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). The LEM domain interacts with the DNA and chromatin-binding protein Barrier-to-Autointegration Factor, and is also necessary for efficient localization of MAN1 in the inner nuclear membrane. Research has indicated that C-terminal nucleoplasmic region of Man1 exhibits a DNA binding winged helix domain and is responsible for both DNA- and Smad-binding.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706607  785 CLKIRNMFDPVMEIGDQWHLAIQEAILEKCSDNDGIVHIAVDKNSREGCVYVKCLSPEYAGKAFKALHGSWFDGKLVTVK 864
Cdd:cd12286   1 CLKIRNMFDPEMEIGEDWHVRIQEAILEKCSDNGGIVHIAVDKNSREGCVYIKCASPEDAGKAFKALHGCWFDGRLVTVK 80

                        90
                ....*....|..
gi 7706607  865 YLRLDRYHHRFP 876
Cdd:cd12286  81 YLRLERYHSRFP 92

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 7706607    776 NSPPNSLTPCLKIRNMFDPVMEIGDQWHLAIQEAILEKCSDNDGIVHIAVDKNSREGCVYVKCLSPEYAGKAFKALHGSW 855
Cdd:TIGR01622 392 PVNVNLASRCLVLSNMFDPATEEEPNWDKEIEDDVREECSKYGGVVHIYVDDKNSAGDIYLKFDSVQAAEAAIKALNGRY 471

                          90       100
                  ....*....|....*....|.
gi 7706607    856 FDGKLVTVKYLRLDRYHHRFP 876
Cdd:TIGR01622 472 FGGKMITAAFVVDAVYSKSRL 492

in nuclear membrane-associated proteins; LEM, domain in nuclear membrane-associated proteins, including lamino-associated polypeptide 2 and emerin.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 7706607       9 PQQLSDEELFSQLRRYGLSPGPVTESTRPVYLKKLKKLREEE 50
Cdd:smart00540   3 VDRLSDAELRAELKQYGLPPGPITDTTRKLYEKKLRKLRRGG 44

RNA recognition motif (RRM) found in inner nuclear membrane protein Man1 (Man1) and similar proteins; This subfamily corresponds to the RRM of Man1, also termed LEM domain-containing protein 3 (LEMD3), an integral protein of the inner nuclear membrane that binds to nuclear lamins and emerin, thus playing a role in nuclear organization. It is part of a protein complex essential for chromatin organization and cell division. It also functions as an important negative regulator for the transforming growth factor (TGF) beta/activin/Nodal signaling pathway by directly interacting with chromatin-associated proteins and transcriptional regulators, including the R-Smads, Smad1, Smad2, and Smad3. Moreover, Man1 is a unique type of left-right (LR) signaling regulator that acts on the inner nuclear membrane. Man1 plays a crucial role in angiogenesis. The vascular remodeling can be regulated at the inner nuclear membrane through the interaction between Man1 and Smads. Man1 contains an N-terminal LEM domain, two putative transmembrane domains, a MAN1-Src1p C-terminal (MSC) domain, and a C-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). The LEM domain interacts with the DNA and chromatin-binding protein Barrier-to-Autointegration Factor, and is also necessary for efficient localization of MAN1 in the inner nuclear membrane. Research has indicated that C-terminal nucleoplasmic region of Man1 exhibits a DNA binding winged helix domain and is responsible for both DNA- and Smad-binding.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706607  785 CLKIRNMFDPVMEIGDQWHLAIQEAILEKCSDNDGIVHIAVDKNSREGCVYVKCLSPEYAGKAFKALHGSWFDGKLVTVK 864
Cdd:cd12286   1 CLKIRNMFDPEMEIGEDWHVRIQEAILEKCSDNGGIVHIAVDKNSREGCVYIKCASPEDAGKAFKALHGCWFDGRLVTVK 80

                        90
                ....*....|..
gi 7706607  865 YLRLDRYHHRFP 876
Cdd:cd12286  81 YLRLERYHSRFP 92

LEM (Lap2/Emerin/Man1) domain found in inner nuclear membrane protein Man1; This CD corresponds to the LEM domain of Man1 and similar proteins. Man1, also termed LEM domain-containing protein 3 (LEMD3), is an integral protein of the inner nuclear membrane that binds to nuclear lamins and emerin, thus playing a role in nuclear organization. It is part of a protein complex essential for chromatin organization and cell division. It also functions as an important negative regulator for the transforming growth factor beta (TGF-beta) /activin/Nodal signaling pathway and bone morphogenetic protein (BMP) signaling pathway by directly interacting with chromatin-associated proteins and transcriptional regulators, including the R-Smads, Smad1, Smad2, and Smad3. Man1 is a unique type of left/right (LR) signaling regulator that acts on the inner nuclear membrane. Furthermore, Man1 plays a crucial role in angiogenesis. The vascular remodeling can be regulated at the inner nuclear membrane through interactions between Man1 and Smads. Man1 contains an N-terminal LEM domain, two putative transmembrane domains, a Man1-Src1p C-terminal (MSC) domain, and a C-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). The LEM domain interacts with DNA and chromatin-binding protein Barrier-to-Autointegration Factor, and is also necessary for efficient localization of Man1 in the inner nuclear membrane. It has been shown that the C-terminal nucleoplasmic region of Man1 exhibits a DNA binding winged helix domain and is responsible for both, DNA- and Smad-binding.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 7706607    9 PQQLSDEELFSQLRRYGLSPGPVTESTRPVYLKKLKKLREEEQ 51
Cdd:cd12942   2 AAQLTDEELFSELKRLGFSPGPVTESTRPVYLKKLKKLREEER 44

LEM domain; The LEM domain is 50 residues long and is composed of two parallel alpha helices. This domain is found in inner nuclear membrane proteins. It is called the LEM domain after LAP2, Emerin and Man1.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 7706607     10 QQLSDEELFSQLRRYGLSPGPVTESTRPVYLKKLKKLR 47
Cdd:pfam03020   3 DQLSDEELREQLKEYGVSPGPITATTRKLYEKKLKKLL 40

LEM (Lap2/Emerin/Man1) domain found in emerin, lamina-associated polypeptide 2 (LAP2), inner nuclear membrane protein Man1 and similar proteins; The family corresponds to a group of inner nuclear membrane proteins containing LEM domain. Emerin occurs in four phosphorylated forms and plays a role in cell cycle-dependent events. It is absent from the inner nuclear membrane in most patients with X-linked muscular dystrophy. Emerin interacts with A-type and B-type lamins. Man1, also termed LEM domain-containing protein 3 (LEMD3) is an integral protein of the inner nuclear membrane that binds to nuclear lamins and emerin, thus playing a role in nuclear organization. LAP2, also termed thymopoietin (TP), or thymopoietin-related peptide (TPRP), is composed of isoform alpha and isoforms beta/gamma and may be involved in chromatin organization and post-mitotic reassembly. Some LAP2 isoforms are inner nuclear membrane proteins that can bind to nuclear lamins and chromatin, while others are non-membrane nuclear polypeptides. This family also contains LEM domain-containing protein LEMP-1 and LEM2. LEMP-1, also termed cancer/testis antigen 50 (CT50), is encoded by LEMD1, a novel testis-specific gene expressed in colorectal cancers. LEMP-1 may function as a cancer-testis antigen for immunotherapy of colorectal carcinoma (CRC). LEM2, also termed LEMD2, is a novel Man1-related ubiquitously expressed inner nuclear membrane protein required for normal nuclear envelope morphology. Association with lamin A is required for its proper nuclear envelope localization while its binding to lamin C plays an important role in the organization of lamin A/C complexes. Some uncharacterized LEM domain-containing proteins are also included in this family. Unlike other family members, these harbor an ankyrin repeat region that may mediate protein-protein interactions.

                        10        20        30
                ....*....|....*....|....*....|....*..
gi 7706607   12 LSDEELFSQLRRYGLSPGPVTESTRPVYLKKLKKLRE 48
Cdd:cd12934   1 LSDDELRRELKELGEPPGPITDTTRKVYLKKLAKLLK 37

LEM (Lap2/Emerin/Man1) domain found in lamina-associated polypeptide 2 (LAP2), LEM domain-containing protein 1 (LEMP-1) and similar proteins; This CD corresponds to the LEM domain of LAP2, LEMP-1 and similar proteins. LAP2, also termed thymopoietin (TP), or thymopoietin-related peptide (TPRP), is composed of isoform alpha and isoforms beta/gamma and may be involved in chromatin organization and post-mitotic reassembly. Some of LAP2 isoforms are inner nuclear membrane proteins that can bind to nuclear lamins and chromatin, while others are non-membrane nuclear polypeptides. All LAP2 isoforms contain an N-terminal LEM domain that is connected to a highly divergent LEM-like domain by an unstructured linker. Although LEM and LEM-like domains share the same structural fold composed of two large parallel alpha helices, the biochemical nature of the solvent-accessible residues is completely different, indicating that the two domains may target different protein surfaces. The LEM domain interacts with the nonspecific DNA binding protein barrier-to-autointegration factor (BAF) while the LEM-like domain is involved in chromosome binding. LEMP-1, also termed cancer/testis antigen 50 (CT50), is encoded by LEMD1, a novel testis-specific gene expressed in colorectal cancers. It may function as a cancer-testis antigen for immunotherapy of colorectal carcinoma (CRC). LEMP-1 contains an N-terminal LEM domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 7706607    9 PQQLSDEELFSQLRRYGLSPGPVTESTRPVYLKKLKKLREE 49
Cdd:cd12940   2 VTELSDEELKAQLLKYGVKPGPITASTRKLYEKKLQKLLDQ 42

LEM (Lap2/Emerin/Man1) domain found in emerin; This CD corresponds to the LEM domain that is critical for binding to lamin A/C and is also involved in interaction with the DNA binding protein barrier-to-autointegration factor (BAF). Emerin is an inner nuclear membrane protein that occurs in four differently phosphorylated forms and plays a role in cell cycle-dependent events. It is absent from the inner nuclear membrane in most patients with X-linked muscular dystrophy. Emerin interacts with A-type and B-type lamins. It contains an N-terminal LEM domain followed by a poly-serine segment, a region rich in hydrophobic amino acids comprising the nuclear localization signal (NLS) followed by another poly-serine segment, and a C-terminal transmembrane region.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 7706607    9 PQQLSDEELFSQLRRYGLSPGPVTESTRPVYLKKLKKLREEEQ 51
Cdd:cd12939   1 YKDLSDDELIKVLRKYGIKHGPVVGSTRKLYEKKLREAERESK 43

RNA recognition motif 2 (RRM2) found in HIV Tat-specific factor 1 (Tat-SF1) and similar proteins; This subfamily corresponds to the RRM2 of Tat-SF1 and CUS2. Tat-SF1 is the cofactor for stimulation of transcriptional elongation by human immunodeficiency virus-type 1 (HIV-1) Tat. It is a substrate of an associated cellular kinase. Tat-SF1 contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a highly acidic carboxyl-terminal half. The family also includes CUS2, a yeast homolog of human Tat-SF1. CUS2 interacts with U2 RNA in splicing extracts and functions as a splicing factor that aids assembly of the splicing-competent U2 snRNP in vivo. CUS2 also associates with PRP11 that is a subunit of the conserved splicing factor SF3a. Like Tat-SF1, CUS2 contains two RRMs as well.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706607  788 IRNMFDP-VMEIGDQWHLAIQEAILEKCSDNdGIVH--IAVDKNSrEGCVYVKCLSPEYAGKAFKALHGSWFDGKLVTVK 864
Cdd:cd12282   6 LKNMFHPkEFEEDPELINEIKEDLREECEKF-GQVKkvVVFDRHP-DGVASVKFKEPEEADKCIQALNGRWFAGRKLEAE 83

                .
gi 7706607  865 Y 865
Cdd:cd12282  84 T 84

RNA recognition motif 3 (RRM3) found in U2 large nuclear ribonucleoprotein auxiliary factor U2AF 65 kDa subunit (U2AF65) and similar proteins; This subfamily corresponds to the RRM3 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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706607  783 TPCLKIRNMFDPVMEIGDQWHLAIQEAILEKCSDNDGIVHIAVDKNSRE-------GCVYVKCLSPEYAGKAFKALHGSW 855
Cdd:cd12232   1 SRVLCLLNMVTPEELEDDEEYEEILEDVKEECSKYGKVLSVVIPRPEAEgvdvpgvGKVFVEFEDVEDAQKAQKALAGRK 80

                ....*.
gi 7706607  856 FDGKLV 861
Cdd:cd12232  81 FDGRTV 86

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
                ....*....|....*....|....*....|....*....|....*
gi 7706607  821 VHIAVDKNS--REGCVYVKCLSPEYAGKAFKALHGSWFDGKLVTV 863
Cdd:cd12316  29 VHIPLDKQTkrSKGFAFVLFVIPEDAVKAYQELDGSIFQGRLLHV 73

RNA recognition motif (RRM) found in U2 small nuclear ribonucleoprotein auxiliary factor 35 kDa subunit-related protein 1 (U2AFBPL) and similar proteins; This subgroup corresponds to the RRM of U2AFBPL, a human homolog of the imprinted mouse gene U2afbp-rs, which encodes a U2 small nuclear ribonucleoprotein auxiliary factor 35 kDa subunit-related protein 1 (U2AFBPL), also termed CCCH type zinc finger, RNA-binding motif and serine/arginine rich protein 1 (U2AF1RS1), or U2 small nuclear RNA auxiliary factor 1-like 1 (U2AF1L1). Although the biological role of U2AFBPL remains unclear, it shows high sequence homology to splicing factor U2AF 35 kDa subunit (U2AF35 or U2AF1) that directly binds to the 3' splice site of the conserved AG dinucleotide and performs multiple functions in the splicing process in a substrate-specific manner. Like U2AF35, U2AFBPL contains two N-terminal zinc fingers, a central RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal arginine/serine (SR)-rich domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 7706607  820 IVHIAVDKNSRE---GCVYVKCLSPEYAGKAFKALHGSWFDGKLVTVKY 865
Cdd:cd12540  55 VVQFKVCCNSEPhlrGNVYVQYQSEEEALKAFTSFNGRWYAGKQLQCEF 103