Thymopoietin protein; Short protein of 49 amino acid isolated from bovine spleen cells. Thymopoietins (TMPOs) are a group of ubiquitously expressed nuclear proteins. They are suggested to play an important role in nuclear envelope organization and cell cycle control.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 66472550     2 AQFHEDPALLTKEKLKSELMANNVALPSADSKKDVYVQLYLKNLTVLN 49
Cdd:pfam08198   1 PEFLEDPSVLTKDRLKSELVAHNVALPPGEQRKDVYVQLYLKHLTARN 48

Thymopoietin protein; Short protein of 49 amino acid isolated from bovine spleen cells. Thymopoietins (TMPOs) are a group of ubiquitously expressed nuclear proteins. They are suggested to play an important role in nuclear envelope organization and cell cycle control.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 66472550     2 AQFHEDPALLTKEKLKSELMANNVALPSADSKKDVYVQLYLKNLTVLN 49
Cdd:pfam08198   1 PEFLEDPSVLTKDRLKSELVAHNVALPPGEQRKDVYVQLYLKHLTARN 48

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        40
                  ....*....|....*....|....*....|....*....|
gi 66472550    95 DVSGLTGEELKVQLQKFGIHSGPIVASTRKVYEKKLQQVL 134
Cdd:pfam03020   1 DVDQLSDEELREQLKEYGVSPGPITATTRKLYEKKLKKLL 40

LEM-like domain of lamina-associated polypeptide 2 (LAP2) 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 postmitotic reassembly. Some of the LAP2 isoforms are inner nuclear membrane proteins that can bind to nuclear lamins and chromatin, while others are nonmembrane nuclear polypeptides. All LAP2 isoforms contain an N-terminal lamina-associated polypeptide-Emerin-MAN1 (LEM)-domain that is connected to a highly divergent LEM-like domain by an unstructured linker. Both LEM and LEM-like domains share the same structural fold, mainly composed of two large parallel alpha helices. However, their biochemical nature of the solvent-accessible residues is completely different, which indicates the two domains may target different protein surfaces. The LEM domain is responsible for the interaction with the nonspecific DNA binding protein barrier-to-autointegration factor (BAF), and the LEM-like domain is involved in chromosome binding. The family also includes the yeast helix-extension-helix domain-containing proteins, Heh1p (formerly called Src1p) and Heh2p, and their uncharacterized homologs found mainly in fungi and several in bacteria. Heh1p and Heh2p are inner nuclear membrane proteins that might interact with nuclear pore complexes (NPCs). Heh1p is involved in mitosis. It functions at the interface between subtelomeric gene expression and transcription export (TREX)-dependent messenger RNA export through NPCs. The function of Heh2p remains ill-defined. Both Heh1p and Heh2p contain a LEM-like domain (also termed HeH domain), but lack a LEM domain.

                        10        20        30
                ....*....|....*....|....*....|....*..
gi 66472550   8 PALLTKEKLKSELMANNVALPSaDSKKDVYVQLYLKN 44
Cdd:cd12935   1 PSSLTVAELRSILTEHGVEYPS-NAKKAELVKLFNKH 36

Thymopoietin protein; Short protein of 49 amino acid isolated from bovine spleen cells. Thymopoietins (TMPOs) are a group of ubiquitously expressed nuclear proteins. They are suggested to play an important role in nuclear envelope organization and cell cycle control.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 66472550     2 AQFHEDPALLTKEKLKSELMANNVALPSADSKKDVYVQLYLKNLTVLN 49
Cdd:pfam08198   1 PEFLEDPSVLTKDRLKSELVAHNVALPPGEQRKDVYVQLYLKHLTARN 48

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        40
                  ....*....|....*....|....*....|....*....|
gi 66472550    95 DVSGLTGEELKVQLQKFGIHSGPIVASTRKVYEKKLQQVL 134
Cdd:pfam03020   1 DVDQLSDEELREQLKEYGVSPGPITATTRKLYEKKLKKLL 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 66472550  99 LTGEELKVQLQKFGIHSGPIVASTRKVYEKKLQQVL 134
Cdd:cd12934   1 LSDDELRRELKELGEPPGPITDTTRKVYLKKLAKLL 36

LEM-like domain of lamina-associated polypeptide 2 (LAP2) 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 postmitotic reassembly. Some of the LAP2 isoforms are inner nuclear membrane proteins that can bind to nuclear lamins and chromatin, while others are nonmembrane nuclear polypeptides. All LAP2 isoforms contain an N-terminal lamina-associated polypeptide-Emerin-MAN1 (LEM)-domain that is connected to a highly divergent LEM-like domain by an unstructured linker. Both LEM and LEM-like domains share the same structural fold, mainly composed of two large parallel alpha helices. However, their biochemical nature of the solvent-accessible residues is completely different, which indicates the two domains may target different protein surfaces. The LEM domain is responsible for the interaction with the nonspecific DNA binding protein barrier-to-autointegration factor (BAF), and the LEM-like domain is involved in chromosome binding. The family also includes the yeast helix-extension-helix domain-containing proteins, Heh1p (formerly called Src1p) and Heh2p, and their uncharacterized homologs found mainly in fungi and several in bacteria. Heh1p and Heh2p are inner nuclear membrane proteins that might interact with nuclear pore complexes (NPCs). Heh1p is involved in mitosis. It functions at the interface between subtelomeric gene expression and transcription export (TREX)-dependent messenger RNA export through NPCs. The function of Heh2p remains ill-defined. Both Heh1p and Heh2p contain a LEM-like domain (also termed HeH domain), but lack a LEM domain.

                        10        20        30
                ....*....|....*....|....*....|....*..
gi 66472550   8 PALLTKEKLKSELMANNVALPSaDSKKDVYVQLYLKN 44
Cdd:cd12935   1 PSSLTVAELRSILTEHGVEYPS-NAKKAELVKLFNKH 36

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 66472550  99 LTGEELKVQLQKFGIHSGPIVASTRKVYEKKLQQVLDQPP 138
Cdd:cd12942   5 LTDEELFSELKRLGFSPGPVTESTRPVYLKKLKKLREEER 44