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 749764901 712 CLKIRHMFDPEIETEDDWETKVQDAILEKCGESVKILHIRVDIASREGCVYMKCLSQEDAGKAYRALHGCWFDGNLVTVK 791
Cdd:cd12286    1 CLKIRNMFDPEMEIGEDWHVRIQEAILEKCSDNGGIVHIAVDKNSREGCVYIKCASPEDAGKAFKALHGCWFDGRLVTVK 80

                         90
                 ....*....|..
gi 749764901 792 YLRLERYHERFP 803
Cdd:cd12286   81 YLRLERYHSRFP 92

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 749764901    3 VDTLTDSELRTKLMEYGYPVGPVTQTTRKILAKKLKNLI 41
Cdd:pfam03020   2 VDQLSDEELREQLKEYGVSPGPITATTRKLYEKKLKKLL 40

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 749764901 712 CLKIRHMFDPEIETEDDWETKVQDAILEKCGESVKILHIRVDIASREGCVYMKCLSQEDAGKAYRALHGCWFDGNLVTVK 791
Cdd:cd12286    1 CLKIRNMFDPEMEIGEDWHVRIQEAILEKCSDNGGIVHIAVDKNSREGCVYIKCASPEDAGKAFKALHGCWFDGRLVTVK 80

                         90
                 ....*....|..
gi 749764901 792 YLRLERYHERFP 803
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 749764901  534 PELPMQCLVKNKLF-TIFSSLLIVAFGVLAVIGIQKLGLWYVKYKKsTEREVFKLVSEIL----NIVETHHQNASVQPgt 608
Cdd:pfam09402 197 AYLPLKCRLRRSVRdTLARYRLILLGLLLLLLAILYLRSRYRRRRA-EKARVEELVQEVLerlkNQKALHAEDPSLYP-- 273

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 749764901  609 qDSFLAINHVRDnLIL-----PKDRKRmsgLWEKAVKFLDENESrIRKEVQQVAGEEFCVWRW 666
Cdd:pfam09402 274 -DPYLSSVQLRD-DILrdehsLKRRNR---LWKRVVKVVEGNSN-VRTSLREVHGEIMRVWEW 330

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 749764901   6 LTDSELRTKLMEYGYPVGPVTQTTRKILAKKLKNLIE 42
Cdd:cd12934    1 LSDDELRRELKELGEPPGPITDTTRKVYLKKLAKLLK 37

linker between RRM2 and RRM3 domains in RBM39 protein; A conserved linker between the second and the third RRM domain in human RBM39 (CAPER) protein, also present in other RNA binding proteins, especially those involved in RNA splicing. This linker was implicated in interactions with ESR1 and ESR2. Preliminary results from JCSG suggest that this is a structured domain with a well defined fold.

                          10        20
                  ....*....|....*....|.
gi 749764901  709 PTPCLKIRHMFDPEIETEDDW 729
Cdd:pfam15519  61 ASRCVLLKNMFDPAEETEPDW 81

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 749764901 712 CLKIRHMFDPEIETEDDWETKVQDAILEKCGESVKILHIRVDIASREGCVYMKCLSQEDAGKAYRALHGCWFDGNLVTVK 791
Cdd:cd12286    1 CLKIRNMFDPEMEIGEDWHVRIQEAILEKCSDNGGIVHIAVDKNSREGCVYIKCASPEDAGKAFKALHGCWFDGRLVTVK 80

                         90
                 ....*....|..
gi 749764901 792 YLRLERYHERFP 803
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 749764901  701 SVNSLTCSPTPCLKIRHMFDPEIETEDDWETKVQDAILEKCGESVKILHIRVDIASREGCVYMKCLSQEDAGKAYRALHG 780
Cdd:TIGR01622 390 FVPVNVNLASRCLVLSNMFDPATEEEPNWDKEIEDDVREECSKYGGVVHIYVDDKNSAGDIYLKFDSVQAAEAAIKALNG 469

                          90       100
                  ....*....|....*....|....
gi 749764901  781 CWFDGNLVTVKYLRLERYHERFPD 804
Cdd:TIGR01622 470 RYFGGKMITAAFVVDAVYSKSRLP 493

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 749764901    3 VDTLTDSELRTKLMEYGYPVGPVTQTTRKILAKKLKNLI 41
Cdd:pfam03020   2 VDQLSDEELREQLKEYGVSPGPITATTRKLYEKKLKKLL 40

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 749764901     1 MSVDTLTDSELRTKLMEYGYPVGPVTQTTRKILAKKLKNLIETR 44
Cdd:smart00540   1 DDVDRLSDAELRAELKQYGLPPGPITDTTRKLYEKKLRKLRRGG 44

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 749764901 710 TPCLKIRHMFDPEiETEDDWETK-VQDAILEKCGESVKILHIRVDIASRE-------GCVYMKCLSQEDAGKAYRALHGC 781
Cdd:cd12232    1 SRVLCLLNMVTPE-ELEDDEEYEeILEDVKEECSKYGKVLSVVIPRPEAEgvdvpgvGKVFVEFEDVEDAQKAQKALAGR 79

                 ....*..
gi 749764901 782 WFDGNLV 788
Cdd:cd12232   80 KFDGRTV 86

LEM (Lap2/Emerin/Man1) domain found in LEM domain-containing protein 2 (LEM2); This CD corresponds to the LEM domain that is responsible for the interaction with chromatin protein barrier-to-autointegration factor (BAF). 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. It also binds to lamin C and plays an important role in the organization of lamin A/C complexes. LEM2 contains an N-terminal LEM domain, two putative transmembrane domains and a MAN1-Src1p C-terminal (MSC) domain, but lacks the Man1-specific C-terminal RNA recognition motif (RRM).

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 749764901   6 LTDSELRTKLMEYGYPVGPVTQTTRKILAKKLKNL 40
Cdd:cd12941    1 LTDAELRRELLALGFRPGPITETTRKVYIKKLSCL 35

linker between RRM2 and RRM3 domains in RBM39 protein; A conserved linker between the second and the third RRM domain in human RBM39 (CAPER) protein, also present in other RNA binding proteins, especially those involved in RNA splicing. This linker was implicated in interactions with ESR1 and ESR2. Preliminary results from JCSG suggest that this is a structured domain with a well defined fold.

                          10        20
                  ....*....|....*....|.
gi 749764901  709 PTPCLKIRHMFDPEIETEDDW 729
Cdd:pfam15519  61 ASRCVLLKNMFDPAEETEPDW 81

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
                 ....*....|....*....|....*....|....*....
gi 749764901   6 LTDSELRTKLMEYGYPVGPVTQTTRKILAKKLKNLIETR 44
Cdd:cd12939    4 LSDDELIKVLRKYGIKHGPVVGSTRKLYEKKLREAERES 42

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
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 749764901 737 ILEKCGESVKILHIRVDIASREGCVYMKCLSQEDAGKAYRALHGCWFDGNLVTVK 791
Cdd:cd00590   18 LFSKFGEVVSVRIVRDRDGKSKGFAFVEFESPEDAEKALEALNGTELGGRPLKVS 72