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 300253233  12 PQQLSDEELFSQLRRYGLSPGPVTESTRPVYLKKLKKLR 50
Cdd:cd12942    2 AAQLTDEELFSELKRLGFSPGPVTESTRPVYLKKLKKLR 40

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300253233  143 ESDVEASPREQAGGGgarrDRAALQYRGLKAPPAPPVAGEAtsgnSAERRKPHSWWGARRPVGPePQLPSGSDGA----A 218
Cdd:PHA03247  251 DIAAPAPPPVVGEGA----DRAPETARGATGPPPPPEAAAP----NGAAAPPDGVWGAALAGAP-LALPAPPDPPppapA 321

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300253233  219 EDVDEEvaDGEDRDPEAEEPLWGSRAvNGSRLLPYSCREHYSDSEEEDdggDVASARQVLKDDSLSRhRPRRSHSKPFSA 298
Cdd:PHA03247  322 GDAEEE--DDEDGAMEVVSPLPRPRQ-HYPLGFPKRRRPTWTPPSSLE---DLSAGRHHPKRASLPT-RKRRSARHAATP 394

                         170
                  ....*....|...
gi 300253233  299 LTAKSGGSRQETS 311
Cdd:PHA03247  395 FARGPGGDDQTRP 407

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
                 ....*....|....*....|....*....|....*....
gi 300253233  12 PQQLSDEELFSQLRRYGLSPGPVTESTRPVYLKKLKKLR 50
Cdd:cd12942    2 AAQLTDEELFSELKRLGFSPGPVTESTRPVYLKKLKKLR 40

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 300253233   13 QQLSDEELFSQLRRYGLSPGPVTESTRPVYLKKLKKLR 50
Cdd:pfam03020   3 DQLSDEELREQLKEYGVSPGPITATTRKLYEKKLKKLL 40

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 300253233  534 LYKLHDRLAQIagdhECGRSS----QRMLSVQEAAayLKDL----------GPEYEDVFNTSLLWIfKNGKDVGIRcvgY 599
Cdd:pfam09402 108 LELLREKNAKV----ECGEGKddlgALESGISEEE--LKDIlsekkspslsDEEFEELWAAALGEL-KKRPEIVWR---Q 177

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300253233  600 GPEEDLTNITDVQFLQSTRPQMPFWCRFRRAFITVTHRLLLLCLGVVLVCAVLRYMRYRWTKEEEETRQMYDMVVKIIDV 679
Cdd:pfam09402 178 DSVGNSDGESTRLLRSTSLAYLPLKCRLRRSVRDTLARYRLILLGLLLLLLAILYLRSRYRRRRAEKARVEELVQEVLER 257

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 300253233  680 LRSHNEACQETKDL--QPYMPIPHVRDSLIQPQDRKKMK-KVWERAVDFLAANESrVRTETRRVGGADFVVWRWV 751
Cdd:pfam09402 258 LKNQKALHAEDPSLypDPYLSSVQLRDDILRDEHSLKRRnRLWKRVVKVVEGNSN-VRTSLREVHGEIMRVWEWI 331

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 300253233  781 PPNSLTPCLKIRNMFDPVMEIGDHW 805
Cdd:pfam15519  57 AVPIASRCVLLKNMFDPAEETEPDW 81

RNA recognition motif 3 (RRM3) found in vertebrate RNA-binding protein 39 (RBM39) and similar proteins; This subfamily corresponds to the RRM3 of RBM39, also termed hepatocellular carcinoma protein 1, or RNA-binding region-containing protein 2, or splicing factor HCC1, ia nuclear autoantigen that contains an N-terminal arginine/serine rich (RS) motif and three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). An octapeptide sequence called the RS-ERK motif is repeated six times in the RS region of RBM39. Based on the specific domain composition, RBM39 has been classified into a family of non-snRNP (small nuclear ribonucleoprotein) splicing factors that are usually not complexed to snRNAs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300253233 786 TPCLKIRNMFDPVMEIGDHWHLAIQEAILEKCSDNDGIVHIAVDRNSREGCVYVKCLSPGHAGKAFKALHGSWFDGKLVT 865
Cdd:cd12285    1 SRCVILKNMFDPAEETEDNWDDEIKEDVIEECSKYGPVLHIYVDKNSPQGNVYVKFKTIEAAQKCVQAMNGRWFDGRQIT 80

                 ....
gi 300253233 866 VKYL 869
Cdd:cd12285   81 AAYV 84

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 300253233  779 NSPPNSLTPCLKIRNMFDPVMEIGDHWHLAIQEAILEKCSDNDGIVHIAVDRNSREGCVYVKCLSPGHAGKAFKALHGSW 858
Cdd:TIGR01622 392 PVNVNLASRCLVLSNMFDPATEEEPNWDKEIEDDVREECSKYGGVVHIYVDDKNSAGDIYLKFDSVQAAEAAIKALNGRY 471

                          90       100
                  ....*....|....*....|.
gi 300253233  859 FDGKLVTVKYLRLDRYHHRFP 879
Cdd:TIGR01622 472 FGGKMITAAFVVDAVYSKSRL 492

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 300253233  15 LSDEELFSQLRRYGLSPGPVTESTRPVYLKKLKKLR 50
Cdd:cd12934    1 LSDDELRRELKELGEPPGPITDTTRKVYLKKLAKLL 36

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
                 ....*....|....*....|....*....|....*....
gi 300253233  12 PQQLSDEELFSQLRRYGLSPGPVTESTRPVYLKKLKKLR 50
Cdd:cd12940    2 VTELSDEELKAQLLKYGVKPGPITASTRKLYEKKLQKLL 40

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 300253233  15 LSDEELFSQLRRYGLSPGPVTESTRPVYLKKLKKLR 50
Cdd:cd12941    1 LTDAELRRELLALGFRPGPITETTRKVYIKKLSCLR 36

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 300253233  12 PQQLSDEELFSQLRRYGLSPGPVTESTRPVYLKKLKK 48
Cdd:cd12939    1 YKDLSDDELIKVLRKYGIKHGPVVGSTRKLYEKKLRE 37

RNA recognition motif (RRM) found in UHM domain of 45 kDa-splicing factor (SPF45) and similar proteins; This subfamily corresponds to the RRM found in UHM domain of 45 kDa-splicing factor (SPF45 or RBM17), poly(U)-binding-splicing factor PUF60 (FIR or Hfp or RoBP1 or Siah-BP1), and similar proteins. SPF45 is an RNA-binding protein consisting of an unstructured N-terminal region, followed by a G-patch motif and a C-terminal U2AF (U2 auxiliary factor) homology motifs (UHM) that harbors a RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain) and an Arg-Xaa-Phe sequence motif. SPF45 regulates alternative splicing of the apoptosis regulatory gene FAS (also known as CD95). It induces exon 6 skipping in FAS pre-mRNA through the UHM domain that binds to tryptophan-containing linear peptide motifs (UHM ligand motifs, ULMs) present in the 3' splice site-recognizing factors U2AF65, SF1 and SF3b155. PUF60 is an essential splicing factor that functions as a poly-U RNA-binding protein required to reconstitute splicing in depleted nuclear extracts. Its function is enhanced through interaction with U2 auxiliary factor U2AF65. PUF60 also controls human c-myc gene expression by binding and inhibiting the transcription factor far upstream sequence element (FUSE)-binding-protein (FBP), an activator of c-myc promoters. PUF60 contains two central RRMs and a C-terminal UHM domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300253233 786 TPCLKIRNMFDPvMEIGDHwhlaIQEAILEKCSDNDGI--VHIAVDRNS---REGCVYVKCLSPGHAGKAFKALHGSWFD 860
Cdd:cd12374    1 TKILVLRNMVGP-GEIDED----LKDEIKEECSKYGKVlnVIIHEVASSeadDAVRVFVEFEDADEAIKAFRALNGRFFG 75

                 ....*...
gi 300253233 861 GKLVTVKY 868
Cdd:cd12374   76 GRKVKARF 83

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 300253233 810 QEAILEKCSDNDGIVHIAVDRNSRE---GCVYVKCLSPGHAGKAFKALHGSWFDGKLVTVK 867
Cdd:cd00590   12 EEDLRELFSKFGEVVSVRIVRDRDGkskGFAFVEFESPEDAEKALEALNGTELGGRPLKVS 72

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        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300253233 789 LKIRNMFD-PVMEIGDHwHLAIQEAILEKcSDND--------------------GIVHIAVDRNSRE---GCVYVKCLSP 844
Cdd:cd12540    2 LLIPNMFNtFGLEQCKR-DDYDTDAGLEY-SEEDlysdflefyedvlpefkkfgKVVQFKVCCNSEPhlrGNVYVQYQSE 79

                         90       100
                 ....*....|....*....|....
gi 300253233 845 GHAGKAFKALHGSWFDGKLVTVKY 868
Cdd:cd12540   80 EEALKAFTSFNGRWYAGKQLQCEF 103

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300253233  143 ESDVEASPREQAGGGgarrDRAALQYRGLKAPPAPPVAGEAtsgnSAERRKPHSWWGARRPVGPePQLPSGSDGA----A 218
Cdd:PHA03247  251 DIAAPAPPPVVGEGA----DRAPETARGATGPPPPPEAAAP----NGAAAPPDGVWGAALAGAP-LALPAPPDPPppapA 321

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300253233  219 EDVDEEvaDGEDRDPEAEEPLWGSRAvNGSRLLPYSCREHYSDSEEEDdggDVASARQVLKDDSLSRhRPRRSHSKPFSA 298
Cdd:PHA03247  322 GDAEEE--DDEDGAMEVVSPLPRPRQ-HYPLGFPKRRRPTWTPPSSLE---DLSAGRHHPKRASLPT-RKRRSARHAATP 394

                         170
                  ....*....|...
gi 300253233  299 LTAKSGGSRQETS 311
Cdd:PHA03247  395 FARGPGGDDQTRP 407

RNA recognition motif (RRM) found in RNA-binding protein with serine-rich domain 1 (RNPS1) and similar proteins; This subfamily corresponds to the RRM of RNPS1 and its eukaryotic homologs. RNPS1, also termed RNA-binding protein prevalent during the S phase, or SR-related protein LDC2, was originally characterized as a general pre-mRNA splicing activator, which activates both constitutive and alternative splicing of pre-mRNA in vitro.It has been identified as a protein component of the splicing-dependent mRNP complex, or exon-exon junction complex (EJC), and is directly involved in mRNA surveillance. Furthermore, RNPS1 is a splicing regulator whose activator function is controlled in part by CK2 (casein kinase II) protein kinase phosphorylation. It can also function as a squamous-cell carcinoma antigen recognized by T cells-3 (SART3)-binding protein, and is involved in the regulation of mRNA splicing. RNPS1 contains an N-terminal serine-rich (S) domain, a central RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and the C-terminal arginine/serine/proline-rich (RS/P) domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 300253233 824 VHIAVDR--NSREGCVYVKCLSPGHAGKAFKALHGSWFDGKLVTV 866
Cdd:cd12365   28 VDLPIDRepNLPRGYAYVEFESPEDAEKAIKHMDGGQIDGQEVTV 72