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 31044432   4 LSDLELRRELQALGFQPGPITDTTRDVYRNKLRRLRGE 41
Cdd:cd12941   1 LTDAELRRELLALGFRPGPITETTRKVYIKKLSCLRAE 38

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 31044432   4 LSDLELRRELQALGFQPGPITDTTRDVYRNKLRRLRGE 41
Cdd:cd12941   1 LTDAELRRELLALGFRPGPITETTRKVYIKKLSCLRAE 38

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 31044432     1 MAGLSDLELRRELQALGFQPGPITDTTRDVYRNKLRRLR 39
Cdd:pfam03020   2 VDQLSDEELREQLKEYGVSPGPITATTRKLYEKKLKKLL 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 31044432   4 LSDLELRRELQALGFQPGPITDTTRDVYRNKLRRLRGE 41
Cdd:cd12941   1 LTDAELRRELLALGFRPGPITETTRKVYIKKLSCLRAE 38

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 31044432   4 LSDLELRRELQALGFQPGPITDTTRDVYRNKLRRLRG 40
Cdd:cd12934   1 LSDDELRRELKELGEPPGPITDTTRKVYLKKLAKLLK 37

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 31044432   278 NFLAIQAGNFECGNPENLKSKCIPVMEAQEyIANVTSSSSAKfeaaltWILSSNKDVgIW------LKGEDqsELVTTVD 351
Cdd:pfam09402 109 ELLREKNAKVECGEGKDDLGALESGISEEE-LKDILSEKKSP------SLSDEEFEE-LWaaalgeLKKRP--EIVWRQD 178

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31044432   352 KVVCLE---------SAHPRMGVGCRLSRALLTAVTNVLIFFWCLAFLWGLLILLKYRWRKLEEEEQAMYEMVKKIIDVV 422
Cdd:pfam09402 179 SVGNSDgestrllrsTSLAYLPLKCRLRRSVRDTLARYRLILLGLLLLLLAILYLRSRYRRRRAEKARVEELVQEVLERL 258

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 31044432   423 QDHYVDWEQDMERYP--YVGILHVRDSLIP--PQSRRRMkRVWDRAVEFLASNESrIQTESHRVAGEDMLVWRWT 493
Cdd:pfam09402 259 KNQKALHAEDPSLYPdpYLSSVQLRDDILRdeHSLKRRN-RLWKRVVKVVEGNSN-VRTSLREVHGEIMRVWEWI 331

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 31044432   2 AGLSDLELRRELQALGFQPGPITDTTRDVYRNKLRRLRGEAR 43
Cdd:cd12942   3 AQLTDEELFSELKRLGFSPGPVTESTRPVYLKKLKKLREEER 44

LEM (Lap2/Emerin/Man1) domain found in ankyrin repeat and LEM domain-containing protein 1 (ANKL1); The family includes ANKL1, also termed ankyrin repeat domain-containing protein 41 (ANKRD41), or LEM-domain containing protein 3 (LEM3), and similar proteins. Although their biological roles remain unclear, the family members contain an N-terminal ankyrin repeat region, LEM domain and C-terminal GIY-YIG nuclease domain. The ankyrin repeats are unique motifs mediating protein-protein interactions. The LEM domain, mainly found in inner nuclear membrane proteins, may be involved in protein- or DNA-binding.

                        10        20        30
                ....*....|....*....|....*....|....*.
gi 31044432   4 LSDLELRRELQALGFQPGPITDTTRDVYRNKLRRLR 39
Cdd:cd12943   1 LSDLDLLRGLRALGESPGPITPFTRRVYLRRLEELQ 36