CTLH/CRA C-terminal to LisH motif domain; RanBPM is a scaffolding protein and is important in regulating cellular function in both the immune system and the nervous system. This domain is at the C-terminus of the proteins and is the binding domain for the CRA motif (for CT11-RanBPM), which is comprised of approximately 100 amino acids at the C terminal of RanBPM. It was found to be important for the interaction of RanBPM with fragile X mental retardation protein (FMRP), but its functional significance has yet to be determined. This region contains CTLH and CRA domains annotated by SMART; however, these may be a single domain, and it is refereed to as a C-terminal to LisH motif.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1246417729 153 PFVELNRILEALKVRVLRPALEWAVSNREMLIAQNSSLEFKLHRLYFISLLMGGttNQREALQYAK-NFQPFALNHQKDI 231
Cdd:pfam10607   1 VFKERNRILEAILNGDITEAIEWCNENKPELLKINSNLEFELRLQQFIELIRSG--KILEALEYAReNLAPFNEEHLKEL 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1246417729 232 QVLMGSLVYLRQGiENSPYVHLLDANQWADICDIFTRDACALLGLSVESPLSVSFSAGCVALPALI 297
Cdd:pfam10607  79 EKLMGLLAFPDPT-DSSPYKSLLSPSRWEKLASEFNRAILKLLGLSSESPLEILLKAGLSALKTLS 143

CTLH/CRA C-terminal to LisH motif domain; RanBPM is a scaffolding protein and is important in regulating cellular function in both the immune system and the nervous system. This domain is at the C-terminus of the proteins and is the binding domain for the CRA motif (for CT11-RanBPM), which is comprised of approximately 100 amino acids at the C terminal of RanBPM. It was found to be important for the interaction of RanBPM with fragile X mental retardation protein (FMRP), but its functional significance has yet to be determined. This region contains CTLH and CRA domains annotated by SMART; however, these may be a single domain, and it is refereed to as a C-terminal to LisH motif.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1246417729 153 PFVELNRILEALKVRVLRPALEWAVSNREMLIAQNSSLEFKLHRLYFISLLMGGttNQREALQYAK-NFQPFALNHQKDI 231
Cdd:pfam10607   1 VFKERNRILEAILNGDITEAIEWCNENKPELLKINSNLEFELRLQQFIELIRSG--KILEALEYAReNLAPFNEEHLKEL 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1246417729 232 QVLMGSLVYLRQGiENSPYVHLLDANQWADICDIFTRDACALLGLSVESPLSVSFSAGCVALPALI 297
Cdd:pfam10607  79 EKLMGLLAFPDPT-DSSPYKSLLSPSRWEKLASEFNRAILKLLGLSSESPLEILLKAGLSALKTLS 143

Degenerated RING finger found in protein RMD5 homolog A (RMD5A); RMD5A is one of the vertebrate homologs of yeast Rmd5p. The biological function of RMD5A remains unclear. RMD5A contains a Lissencephaly type-1-like homology motif (LisH), a C-terminal to LisH motif (CTLH) domain, and a degenerated RING finger that is characterized by lacking the second, fifth, and sixth Zn2+ ion-coordinating residues compared with the classic C3H2C3-/C3HC4-type RING fingers.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1246417729 332 SIFACPILRQQTTDNNPPMKLVCGHIISRDALNKMFNGSKLKCPYCPMEQSPGDAKQIFF 391
Cdd:cd16794     1 SIFACPILRQQTTENNPPMKLVCGHIISRDALNKMFNGSKLKCPYCPMEQSPGDAKQIFF 60

Lissencephaly type-1-like homology motif; Alpha-helical motif present in Lis1, treacle, Nopp140, some katanin p60 subunits, muskelin, tonneau, LEUNIG and numerous WD40 repeat-containing proteins. It is suggested that LisH motifs contribute to the regulation of microtubule dynamics, either by mediating dimerisation, or else by binding cytoplasmic dynein heavy chain or microtubules directly.

                           10        20        30
                   ....*....|....*....|....*....|...
gi 1246417729  114 SQRLLNEVMVEHFFRQGMLDVAEELCQESGLSV 146
Cdd:smart00667   2 SRSELNRLILEYLLRNGYEETAETLQKESGLSL 34

CTLH/CRA C-terminal to LisH motif domain; RanBPM is a scaffolding protein and is important in regulating cellular function in both the immune system and the nervous system. This domain is at the C-terminus of the proteins and is the binding domain for the CRA motif (for CT11-RanBPM), which is comprised of approximately 100 amino acids at the C terminal of RanBPM. It was found to be important for the interaction of RanBPM with fragile X mental retardation protein (FMRP), but its functional significance has yet to be determined. This region contains CTLH and CRA domains annotated by SMART; however, these may be a single domain, and it is refereed to as a C-terminal to LisH motif.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1246417729 153 PFVELNRILEALKVRVLRPALEWAVSNREMLIAQNSSLEFKLHRLYFISLLMGGttNQREALQYAK-NFQPFALNHQKDI 231
Cdd:pfam10607   1 VFKERNRILEAILNGDITEAIEWCNENKPELLKINSNLEFELRLQQFIELIRSG--KILEALEYAReNLAPFNEEHLKEL 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1246417729 232 QVLMGSLVYLRQGiENSPYVHLLDANQWADICDIFTRDACALLGLSVESPLSVSFSAGCVALPALI 297
Cdd:pfam10607  79 EKLMGLLAFPDPT-DSSPYKSLLSPSRWEKLASEFNRAILKLLGLSSESPLEILLKAGLSALKTLS 143

Degenerated RING finger found in protein RMD5 homolog A (RMD5A); RMD5A is one of the vertebrate homologs of yeast Rmd5p. The biological function of RMD5A remains unclear. RMD5A contains a Lissencephaly type-1-like homology motif (LisH), a C-terminal to LisH motif (CTLH) domain, and a degenerated RING finger that is characterized by lacking the second, fifth, and sixth Zn2+ ion-coordinating residues compared with the classic C3H2C3-/C3HC4-type RING fingers.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1246417729 332 SIFACPILRQQTTDNNPPMKLVCGHIISRDALNKMFNGSKLKCPYCPMEQSPGDAKQIFF 391
Cdd:cd16794     1 SIFACPILRQQTTENNPPMKLVCGHIISRDALNKMFNGSKLKCPYCPMEQSPGDAKQIFF 60

Degenerated RING (dRING) finger found in Saccharomyces cerevisiae required for meiotic nuclear division protein 5 (Rmd5p) and similar proteins; Rmd5p, also known as glucose-induced degradation protein 2 (Gid2) or sporulation protein RMD5, is an E3 ubiquitin ligase containing a Lissencephaly type-1-like homology motif (LisH), a C-terminal to LisH motif (CTLH) domain, and a degenerated RING finger that is characterized by lacking the second, fifth, and sixth Zn2+ ion-coordinating residues compared with the classic C3H2C3-/C3HC4-type RING fingers. It forms the heterodimeric E3 ligase unit of the glucose induced degradation deficient (GID) complex with Gid9 (also known as Fyv10), which has a degenerated RING finger as well. The GID complex triggers polyubiquitylation and subsequent proteasomal degradation of the gluconeogenic enzymes fructose-1, 6-bisphosphate by fructose-1, 6-bisphosphatase (FBPase), phosphoenolpyruvate carboxykinase (PEPCK), and cytoplasmic malate dehydrogenase (c-MDH). Moreover, Rmd5p can form the GID complex with the other six Gid proteins, including Gid1/Vid30, Gid4/Vid24, Gid5/Vid28, Gid7, Gid8, and Gid9/Fyv10. The GID complex in which the seven Gid proteins reside functions as a novel ubiquitin ligase (E3) involved in the regulation of carbohydrate metabolism.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1246417729 334 FACPILRQQTTDNNPPMKLVCGHIISRDALNKMF--NGSKLKCPYCPME 380
Cdd:cd16652     1 FACPVSREQSTEENPPMRLPCGHVISKDSLKKLSknNGNKFKCPYCPVE 49

RING finger (Really Interesting New Gene) domain and U-box domain superfamily; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers: some have different Cys/His patterns while some lack a single Cys or His residue at typical Zn ligand positions (the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can indeed chelate Zn in a RING finger as well). C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type RING fingers are closely related to RING-HC fingers. In contrast, C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type RING fingers are more closely related to RING-H2 fingers. However, not all RING finger-containing proteins display regular RING finger features, and the RING finger family has turned out to be multifarious. The degenerate RING fingers of the Siz/PIAS RING (SP-RING) family proteins and sporulation protein RMD5, are characterized by lacking the second, fifth, and sixth Zn2+ ion-coordinating residues. They bind only one Zn2+ ion. On the other hand, the RING fingers of the human APC11 and RBX1 proteins can bind a third Zn atom since they harbor four additional Zn ligands. U-box is a modified form of the RING finger domain that lacks metal chelating Cys and His residues. It resembles the cross-brace RING structure consisting of three beta-sheets and a single alpha-helix, which would be stabilized by salt bridges instead of chelated metal ions. U-box proteins are widely distributed among eukaryotic organisms and show a higher prevalence in plants than in other organisms. RING finger/U-box-containing proteins are a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serve as scaffolds for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enable efficient transfer of ubiquitin from E2 to the substrates.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1246417729 336 CPILRQQTTDNNPPMKLVCGHIISRDALNKMFNGSKLKCPYC 377
Cdd:cd00162     1 CPICREEMNDRRPVVLLSCGHTFSRSAIARWLEGSKQKCPFC 42

U-box domain, a modified RING finger, found in erythroblast macrophage protein (Emp) and similar proteins; Emp, also known as cell proliferation-inducing gene 5 protein or macrophage erythroblast attacher (MAEA), is a key protein which functions in normal differentiation of erythroid cells and macrophages. It is a potential biomarker for hematopoietic evaluation of Hematopoietic stem cell transplantation (HSCT) patients. Emp was initially identified as a heparin-binding protein involved in the association of erythroblasts with macrophages. It promotes erythroid proliferation and maturation. It also plays an important role in erythroblastic island formation. Absence of Emp leads to failure of erythroblast nuclear extrusion. It is required in definitive erythropoiesis and plays a cell intrinsic role in the erythroid lineage. Emp contains a Lissencephaly type-1-like homology (LisH) motif, a C-terminal to LisH (CTLH) domain, and a RING-like U-box domain at the C-terminus.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1246417729 332 SIFACPILRQQTTDNNPPMKLVCGHIISRDALNKM--FNGSKLKCPY 376
Cdd:cd16659     1 SRLVCRITGEVMNEHNPPLALPNGYVYSEKALEEMaeKNDGKVVCPR 47

SPL-RING finger found in E3 SUMO-protein ligase NSE2 and similar proteins; NSE2, also known as MMS21 homolog (MMS21) or non-structural maintenance of chromosomes element 2 homolog (Non-SMC element 2 homolog, NSMCE2), is an autosumoylating small ubiquitin-like modifier (SUMO) ligase required for the response to DNA damage. It regulates sumoylation and nuclear-to-cytoplasmic translocation of skeletal and heart muscle-specific variant of the alpha subunit of nascent polypeptide associated complex (skNAC)-Smyd1 in myogenesis. It is also required for resisting extrinsically induced genotoxic stress. Moreover, NSE2 together with its partner proteins SMC6 and SMC5 form a tight subcomplex of the structural maintenance of chromosomes SMC5-6 complex, which includes another two subcomplexes, NSE1-NSE3-NSE4 and NSE5-NSE6. SMC6 and NSE3 are sumoylated in an NSE2-dependent manner, but SMC5 and NSE1 are not. NSE2-dependent E3 SUMO ligase activity is required for efficient DNA repair, but not for SMC5-6 complex stability. NSE2 contains a RING variant known as a Siz/PIAS (protein inhibitor of activated signal transducer and activator of transcription)-like RING (SPL-RING) finger that is likely shared by the SP-RING type SUMO E3 ligases, such as PIAS family proteins. The SPL-RING finger is a variant of the RING finger, which lacks the second, fifth, and sixth zinc-binding residues of the consensus C3H2C3-/C3HC4-type RING fingers. It harbors only one Zn binding site and is required for the sumoylating activity.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1246417729 336 CPILRQQTTDnnpPMKL-VCGHIISRDALNKMFNGSKLKCPyCPM 379
Cdd:cd16651     3 CPITQQLMVD---PVRNkKCGHTYEKAAILQYLQSRKKKAK-CPV 43