BAG domains, present in regulator of Hsp70 proteins; BAG domains, present in Bcl-2-associated athanogene 1 and silencer of death domains

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1154885290  175 QLEELNKELTGIQqGFLPKDLQAEALCKLDRRVKATIEQFMKILEEIDTLIlPENFKDSRLKRKGLVKKVQAFLAECDTV 254
Cdd:smart00264   1 SIKKINEVLDEVQ-KKIEKEVQVADGKKDDKEYLRLSEELMKLLLKLDSVD-VEGCEDIREARKRLVRLIQNLLNALDSK 78

                   .
gi 1154885290  255 E 255
Cdd:smart00264  79 K 79

BAG domains, present in regulator of Hsp70 proteins; BAG domains, present in Bcl-2-associated athanogene 1 and silencer of death domains

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1154885290  175 QLEELNKELTGIQqGFLPKDLQAEALCKLDRRVKATIEQFMKILEEIDTLIlPENFKDSRLKRKGLVKKVQAFLAECDTV 254
Cdd:smart00264   1 SIKKINEVLDEVQ-KKIEKEVQVADGKKDDKEYLRLSEELMKLLLKLDSVD-VEGCEDIREARKRLVRLIQNLLNALDSK 78

                   .
gi 1154885290  255 E 255
Cdd:smart00264  79 K 79

Ubiquitin family; This family contains a number of ubiquitin-like proteins: SUMO (smt3 homolog), Nedd8, Elongin B, Rub1, and Parkin. A number of them are thought to carry a distinctive five-residue motif termed the proteasome-interacting motif (PIM), which may have a biologically significant role in protein delivery to proteasomes and recruitment of proteasomes to transcription sites.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1154885290  86 LHVTSQQGSSEPV-------VQDLAQVVEEVIGVPQSFQKLIFKGKSLKEmETPLSALGIQDGCRVMLIGKK 150
Cdd:pfam00240   1 ITVKTLDGKKITLevdptdtVLELKEKIAEKEGVPPEQQRLIYSGKVLED-DQTLGEYGIEDGSTIHLVLRQ 71

BAG domains, present in regulator of Hsp70 proteins; BAG domains, present in Bcl-2-associated athanogene 1 and silencer of death domains

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1154885290  175 QLEELNKELTGIQqGFLPKDLQAEALCKLDRRVKATIEQFMKILEEIDTLIlPENFKDSRLKRKGLVKKVQAFLAECDTV 254
Cdd:smart00264   1 SIKKINEVLDEVQ-KKIEKEVQVADGKKDDKEYLRLSEELMKLLLKLDSVD-VEGCEDIREARKRLVRLIQNLLNALDSK 78

                   .
gi 1154885290  255 E 255
Cdd:smart00264  79 K 79

Ubiquitin homologues; Ubiquitin-mediated proteolysis is involved in the regulated turnover of proteins required for controlling cell cycle progression

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1154885290   85 DLHVTSQQGSSEPV-------VQDLAQVVEEVIGVPQSFQKLIFKGKSLKEmETPLSALGIQDGCRVMLIGK 149
Cdd:smart00213   2 ELTVKTLDGKTITLevkpsdtVSELKEKIAELTGIPPEQQRLIYKGKVLED-DRTLADYGIQDGSTIHLVLR 72

ubiquitin-like (Ubl) domain found in Saccharomyces cerevisiae proteasome interacting protein Dsk2p and similar proteins; The family contains several fungal multiubiquitin receptors, including Saccharomyces cerevisiae Dsk2p and Schizosaccharomyces pombe Dph1p, both of which have been characterized as shuttle proteins transporting ubiquitinated substrates destined for degradation from the E3 ligase to the 26S proteasome. They interact with the proteasome through their N-terminal ubiquitin-like domain (Ubl) and with ubiquitin (Ub) through their C-terminal Ub-associated domain (UBA). S. cerevisiae Dsk2p is a nuclear-enriched protein that may involve in the ubiquitin-proteasome proteolytic pathway through interacting with K48-linked polyubiquitin and the proteasome. Moreover, it has been implicated in spindle pole duplication through assisting in Cdc31 assembly into the new spindle pole body (SPB). S. pombe Dph1p is an ubiquitin (Ub0 receptor working in concert with the class V myosin, Myo52, to target the degradation of the S. pombe CLIP-170 homolog, Tip1. It also can protect Ub chains against disassembly by deubiquitinating enzymes.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1154885290  73 LTVTVTHSN-EKHDLHVtsqqgSSEPVVQDLAQVVEEVIGVPQSFQKLIFKGKSLKEMETpLSALGIQDGCRVMLI 147
Cdd:cd16106     1 IKVTVKCSNgKKFTVEV-----EPDATVLELKELIAEKSDIPAEQQRLIYKGKILKDEET-LSSYKIQDGHTVHLV 70

ubiquitin-like (Ubl) domain found in ubiquitin carboxyl-terminal hydrolase 14 (USP14) and similar proteins; USP14 (EC 3.4.19.12), also termed deubiquitinating enzyme 14, or ubiquitin thioesterase 14, or ubiquitin-specific-processing protease 14, or ubiquitin carboxyl-terminal hydrolase 14, is a component of proteasome regulatory subunit 19S that regulates deubiquitinated proteins entering inside the proteasome core 20S, which plays an inhibitory role in protein degradation. USP14 is also associated with various signal transduction pathways and tumorigenesis, and thus plays an essential role in the development of various types of cancer. Moreover, USP14 mediates the development of cardiac hypertrophy by promoting GSK-3beta phosphorylation, suggesting a role in cardiac hypertrophy treatment. USP14 contains an N-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, and a C-terminal ubiquitin-specific protease (USP) domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1154885290  73 LTVTVTHSNEKHDLHVTsqqGSSEPVVQDLAQVvEEVIGVPQSFQKLIFKGKSLKEmETPLSALGIQDGCRVMLIG 148
Cdd:cd16104     2 YKVNVKWGKEKFDDVEL---DTDEPPLVFKAQL-FALTGVPPERQKIMVKGGVLKD-DDDLSKLKLKDGQTLMLMG 72

MAEBL; Provisional

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1154885290    2 KKKTRRRSTRSEELTRSEELTLSEEATWSEEATQSEEATQGEEMNRSQEVTRDEESTRSEEVTREE 67
Cdd:PTZ00121  1496 KKKADEAKKAAEAKKKADEAKKAEEAKKADEAKKAEEAKKADEAKKAEEKKKADELKKAEELKKAE 1561

ubiquitin-like (Ubl) domain found in the eukaryotic Ddi1 family; The eukaryotic Ddi1 family, including yeast aspartyl protease DNA-damage inducible 1 (Ddi1) and Ddi1-like proteins from vertebrates and other eukaryotes, has been characterized by containing an N-terminal ubiquitin-like (Ubl) domain and a conserved retroviral aspartyl-protease-like domain (RVP) that is important in cell-cycle control. Yeast Ddi1 and many family members also contain a C-terminal ubiquitin-association (UBA) domain, however, Ddi1-like proteins from all vertebrates lack the UBA domain. Ddi1, also termed v-SNARE-master 1 (Vsm1), is an ubiquitin receptor involved in the cell cycle and late secretory pathway in Saccharomyces cerevisiae. It functions as an UBA-Ubl shuttle protein that is required for the proteasome to enable ubiquitin-dependent degradation of its ligands. For instance, Ddi1 plays an essential role in the final stages of proteasomal degradation of Ho endonuclease and of its cognate FBP, Ufo1. Moreover, Ddi1 and its associated protein Rad23p play a cooperative role as negative regulators in yeast PHO pathway. This family also includes mammalian regulatory solute carrier protein family 1 member 1 (RSC1A1), also termed transporter regulator RS1 (RS1), which mediates transcriptional and post-transcriptional regulation of Na(+)-D-glucose cotransporter SGLT1. Ddi1-like proteins play a significant role in cell cycle control, growth control, and trafficking in yeast and may play a crucial role in embryogenesis in higher eukaryotes.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1154885290  73 LTVTVTHSNekhdlHVTSQQGSSEPVVQDLAQVVEEVIGVPQSFQKLIFKGKSLKEMETPLSALGIQDGCRVMLI 147
Cdd:cd01796     3 LTVTTEDDD-----RLFSLEVSPDMTLEDLKALCEAETGIPAAEQVLLHNGQPLTDDKKTLEALGLKDGDLLLLR 72

MAEBL; Provisional

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1154885290   11 RSEELTRSEELTLSEEATWSEEATQSEEATQGEEMNRSQEVTRDEESTRSEEVTREEMAA 70
Cdd:PTZ00121  1183 KAEEVRKAEELRKAEDARKAEAARKAEEERKAEEARKAEDAKKAEAVKKAEEAKKDAEEA 1242

ubiquitin-like (Ubl) domain found in ubiquitin-specific-processing protease 48 (USP48) and similar proteins; USP48, also termed USP31, or deubiquitinating enzyme 48, or ubiquitin thioesterase 48, or ubiquitin carboxyl-terminal hydrolase 48, belongs to the ubiquitin specific protease (USP) family that is one of at least seven deubiquitylating enzyme (DUB) families capable of deconjugating ubiquitin (Ub)and ubiquitin-like (Ubl) adducts. While the USP proteins have a conserved catalytic core domain, USP48 differs in its domain architecture. It contains an N-terminal USP domain, three DUSP (domain present in ubiquitin-specific protease) domains, and a C-terminal Ubl domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions. USP48 is a deubiquitinating enzyme that interacts with TNF receptor-associated factor 2 (TRAF2) and has been implicated in activation of nuclear factor-kappaB (NF-kappaB). Moreover, as a nuclear deubiquitinase regulated by casein kinase 2 (CK2), USP48 controls the ubiquitin/proteasome-system (UPS)-dependent turnover of activated NF-kappaB/RelA in the nucleus together with the COP9 signalosome, suggesting a role of USP48 in a timely control of immune responses.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1154885290  81 NEKHDLHVTSQQgssepVVQDLAQVVEEVIGVPQSFQKLIFKGKSLKEMETPLSALGIQDGCRVML 146
Cdd:cd01795     5 GERKSLTVSSTT-----TLKELKLQIMEKFSVAPFDQHLYFNGRELTDDSATLADLGILPGDVLYL 65

MAEBL; Provisional

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1154885290   11 RSEELTRSEELTLSEEATWSEEATQSEEATQGEEMNRSQEVTRDEESTRSEEVTREEMA 69
Cdd:PTZ00121  1147 KAEDAKRVEIARKAEDARKAEEARKAEDAKKAEAARKAEEVRKAEELRKAEDARKAEAA 1205

ubiquitin-like (Ubl) domain found in NEDD8 ultimate buster 1 (NUB1) and similar proteins; NUB1, also termed negative regulator of ubiquitin-like proteins 1, or renal carcinoma antigen NY-REN-18, or protein BS4, is a NEDD8-interacting protein that can be induced by interferon. It functions as a strong post-transcriptional down-regulator of the NEDD8 expression and plays critical roles in regulating many biological events, such as cell growth, NF-kappaB signaling, and biological responses to hypoxia. NUB1 can also interact with aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1), which may function in the regulation of cell cycle progression. NUB1 contains a conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, three ubiquitin-associated domains (UBA), a bipartite nuclear localization signal (NLS) and a PEST motif.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1154885290  86 LHVTSQQGSSEPV---------VQDLAQVVEEVIGVPQSFQKLIFKGKSLKeMETPLSALGIQDGCRVMLI 147
Cdd:cd17062     7 VRLPGQGSKKKKItletslditGSELREKIAEELGVPEDRIKLISNGKVLK-DEKTLAEQGVKNNSQVMVL 76

ubiquitin-like (Ubl) domain 2 found in leukocyte antigen F (HLA-F) adjacent transcript 10 (FAT10) and similar proteins; FAT10, also termed ubiquitin D (UBD), or diubiquitin, is a cytokine-inducible ubiquitin-like (Ubl) modifer that is highly expressed in the thymus, and targets substrates covalently for 26S proteasomal degradation. It is also associated with cancer development, antigen processing and antimicrobial defense, chromosomal stability and cell cycle regulation. FAT10 is presented on immune cells and under the inflammatory conditions, is synergistically induced by interferon gamma (IFNgamma) and tumor necrosis factor (TNFalpha) in the non-immune (liver parenchymal) cells. FAT10 contains two Ubl domains. The family corresponds to the second Ubl domain of FAT10. Some family members contain only one Ubl domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1154885290  76 TVTHSNEKHDLHVTSQQGSSepVVQDLAQVVEEVIGVPQSFQKLIFKGKSLKEMETPLSALGIQDGCRVMLI 147
Cdd:cd17053     2 TVNSKLLTGTVHTLQVSRST--TVAQVKAMIEDQSGVPPNEQILVYNGKRLEDGDKTLGEYGIKTGDTLYLL 71

ubiquitin-like (Ubl) domain found in ubiquitin-like proteins UBL4A and similar proteins; UBL4A, also termed GdX, is a ubiquitously expressed ubiquitin-like (Ubl) protein that forms a complex with partner proteins and participates in the protein processing through endoplasmic reticulum (ER), acting as a chaperone. As a key component of the BCL2-associated athanogene 6 (BAG6) chaperone complex, UBL4A plays a role in mediating DNA damage signaling and cell death. UBL4A also regulates insulin-induced Akt plasma membrane translocation through promotion of Arp2/3-dependent actin branching. Moreover, UBL4A specifically stabilizes the TC45/STAT3 association and promotes dephosphorylation of STAT3 to repress tumorigenesis. UBL4B is testis-specific, and encoded by an X-derived retrogene Ubl4b, which is specifically expressed in post-meiotic germ cells in mammals. As a germ cell-specific cytoplasmic protein, UBL4B is not present in somatic cells. Moreover, UBL4B is present in elongated spermatids, but not in spermatocytes and round spermatids, suggesting its function is restricted to late spermiogenesis. The function of UBL4A may be compensated by either UBL4B or other Ubl proteins in normal conditions. Both UBL4A and UBL4B contain a conserved Ubl domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1154885290  92 QGSSEPVVQDLAQVVEEVIGVPQSFQKLIFKGKSLKEmETPLSALGIQDGCRVMLIGK 149
Cdd:cd01807    16 EVSPTESVLTVKQLVAEQLNVPVSQQRLVFKGKTLAD-EHSLSDYSIGPGSKIHLVVK 72

MAEBL; Provisional

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1154885290    9 STRSEELTRSEELTLSEEATWSEEATQSEEATQGEEMNRSQEVTRDEESTRSEEVTREE 67
Cdd:PTZ00121  1169 ARKAEDAKKAEAARKAEEVRKAEELRKAEDARKAEAARKAEEERKAEEARKAEDAKKAE 1227