RING finger-like zinc-binding domain 0 of parkin; Parkin, also called Parkinson juvenile disease protein 2, is a RBR (RING1-BRcat-Rcat)-type E3 ubiquitin-protein ligase that is associated with recessive early onset Parkinson's disease (PD), and exerts a protective effect against dopamine-induced alpha-synuclein-dependent cell toxicity. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Parkin functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. It is involved in regulating mitochondrial quality control. Its activation is a key regulatory event in the pathway to the clearance of depolarized or damaged mitochondria. Parkin contains an N-terminal ubiquitin-like domain, an acid linker, a RING finger-like domain 0 (RING0), and a C-terminal RBR domain that was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. This model represents RING0 of parkin.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10179811 146 FFIYCKGPCHKVQPGKLRVQCGTCKQATLTLAQGPSCWDDVLIPNRMSGECQSPDCPGTRAEFFFKCGAHPTSDKDTSVA 225
Cdd:cd21382   1 FYVYCKGPCKKVQPGKLRVRCATCKQGAFTLDRGPSCWDDVLIPNRISGVCQSPDCPGTRAEFYFKCASHPTSDKDTSVA 80

                ....
gi 10179811 226 LNLI 229
Cdd:cd21382  81 LNLI 84

RING/Ubox like zinc-binding domain; This is a RING zinc finger domain found in parkin proteins. Parkin consists of a ubiquitin-like (Ubl) domain and a 60-amino acid linker followed by RING0 and three additional zinc finger domains characteriztic of the RBR family. This entry relates to RING1 zinc binding domain. The RING1 domain displays the C3HC4 cross-brace motif characteriztic of RING domains. The N-terminal Ubl domain binds to RING1.

                          10
                  ....*....|....*...
gi 10179811   228 LITSNRRSIPCIACTDVS 245
Cdd:pfam17978   1 LIKSNSRDVPCLACTDVS 18

RING finger-like zinc-binding domain 0 of parkin; Parkin, also called Parkinson juvenile disease protein 2, is a RBR (RING1-BRcat-Rcat)-type E3 ubiquitin-protein ligase that is associated with recessive early onset Parkinson's disease (PD), and exerts a protective effect against dopamine-induced alpha-synuclein-dependent cell toxicity. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Parkin functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. It is involved in regulating mitochondrial quality control. Its activation is a key regulatory event in the pathway to the clearance of depolarized or damaged mitochondria. Parkin contains an N-terminal ubiquitin-like domain, an acid linker, a RING finger-like domain 0 (RING0), and a C-terminal RBR domain that was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. This model represents RING0 of parkin.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10179811 146 FFIYCKGPCHKVQPGKLRVQCGTCKQATLTLAQGPSCWDDVLIPNRMSGECQSPDCPGTRAEFFFKCGAHPTSDKDTSVA 225
Cdd:cd21382   1 FYVYCKGPCKKVQPGKLRVRCATCKQGAFTLDRGPSCWDDVLIPNRISGVCQSPDCPGTRAEFYFKCASHPTSDKDTSVA 80

                ....
gi 10179811 226 LNLI 229
Cdd:cd21382  81 LNLI 84

ubiquitin-like (Ubl) domain found in parkin and similar proteins; Parkin, also termed Parkinson juvenile disease protein 2, is a RBR-type E3 ubiquitin-protein ligase that is associated with recessive early onset Parkinson's disease (PD), and exerts a protective effect against dopamine-induced alpha-synuclein-dependent cell toxicity. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Parkin functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPT5, TOMM20, USP30, ZNF746 and AIMP2. It mediates monoubiquitination as well as Lys-6-, Lys-11-, Lys-48- and Lys-63-linked polyubiquitination of substrates depending on the context. Parkin may enhance cell viability and protects dopaminergic neurons from oxidative stress-mediated death by regulating mitochondrial function. It also limits the production of reactive oxygen species (ROS), and regulates cyclin-E during neuronal apoptosis. Moreover, parkin displays a ubiquitin ligase-independent function in transcriptional repression of p53. Parkin contains an N-terminal ubiquitin-like (Ubl) domain and a C-terminal RBR domain that was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain use an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase function to facilitate the ubiquitination reaction.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 10179811   3 VFVRFNSSYGFPVEVDSDTSILQLKEVVAKRQGVPADQLRVIFAGKELPNHLTVQNCDLEQQSIVHIVQRPRRR 76
Cdd:cd01798   1 VFVRFNSSHGFPVEVDSDWSILQLKEVVAKRQGVPPDQLRIIFAGKELSDDLTLQNCDLGQQSIVHAVQGPKRK 74

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 10179811      1 MIVFVRFNSSYGFPVEVDSDTSILQLKEVVAKRQGVPADQLRVIFAGKELPNHLTVQNCDLEQQSIVHIVQR 72
Cdd:smart00213   1 IELTVKTLDGKTITLEVKPSDTVSELKEKIAELTGIPPEQQRLIYKGKVLEDDRTLADYGIQDGSTIHLVLR 72

UV excision repair protein Rad23; All proteins in this family for which functions are known are components of a multiprotein complex used for targeting nucleotide excision repair to specific parts of the genome. In humans, Rad23 complexes with the XPC protein. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10179811    13 FPVEVDSDTSILQLKEVVAKRQGV---PADQLRVIFAGKELPNHLTVQNCDL-EQQSIVHIVQRPRRrshETNASGGDEP 88
Cdd:TIGR00601  13 FKIDMEPDETVKELKEKIEAEQGKdayPVAQQKLIYSGKILSDDKTVKEYKIkEKDFVVVMVSKPKT---GTGKVAPPAA 89

                  ....
gi 10179811    89 QSTS 92
Cdd:TIGR00601  90 TPTS 93

RING finger-like zinc-binding domain 0 of parkin; Parkin, also called Parkinson juvenile disease protein 2, is a RBR (RING1-BRcat-Rcat)-type E3 ubiquitin-protein ligase that is associated with recessive early onset Parkinson's disease (PD), and exerts a protective effect against dopamine-induced alpha-synuclein-dependent cell toxicity. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Parkin functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. It is involved in regulating mitochondrial quality control. Its activation is a key regulatory event in the pathway to the clearance of depolarized or damaged mitochondria. Parkin contains an N-terminal ubiquitin-like domain, an acid linker, a RING finger-like domain 0 (RING0), and a C-terminal RBR domain that was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. This model represents RING0 of parkin.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10179811 146 FFIYCKGPCHKVQPGKLRVQCGTCKQATLTLAQGPSCWDDVLIPNRMSGECQSPDCPGTRAEFFFKCGAHPTSDKDTSVA 225
Cdd:cd21382   1 FYVYCKGPCKKVQPGKLRVRCATCKQGAFTLDRGPSCWDDVLIPNRISGVCQSPDCPGTRAEFYFKCASHPTSDKDTSVA 80

                ....
gi 10179811 226 LNLI 229
Cdd:cd21382  81 LNLI 84

ubiquitin-like (Ubl) domain found in parkin and similar proteins; Parkin, also termed Parkinson juvenile disease protein 2, is a RBR-type E3 ubiquitin-protein ligase that is associated with recessive early onset Parkinson's disease (PD), and exerts a protective effect against dopamine-induced alpha-synuclein-dependent cell toxicity. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Parkin functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPT5, TOMM20, USP30, ZNF746 and AIMP2. It mediates monoubiquitination as well as Lys-6-, Lys-11-, Lys-48- and Lys-63-linked polyubiquitination of substrates depending on the context. Parkin may enhance cell viability and protects dopaminergic neurons from oxidative stress-mediated death by regulating mitochondrial function. It also limits the production of reactive oxygen species (ROS), and regulates cyclin-E during neuronal apoptosis. Moreover, parkin displays a ubiquitin ligase-independent function in transcriptional repression of p53. Parkin contains an N-terminal ubiquitin-like (Ubl) domain and a C-terminal RBR domain that was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain use an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase function to facilitate the ubiquitination reaction.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 10179811   3 VFVRFNSSYGFPVEVDSDTSILQLKEVVAKRQGVPADQLRVIFAGKELPNHLTVQNCDLEQQSIVHIVQRPRRR 76
Cdd:cd01798   1 VFVRFNSSHGFPVEVDSDWSILQLKEVVAKRQGVPPDQLRIIFAGKELSDDLTLQNCDLGQQSIVHAVQGPKRK 74

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 10179811      1 MIVFVRFNSSYGFPVEVDSDTSILQLKEVVAKRQGVPADQLRVIFAGKELPNHLTVQNCDLEQQSIVHIVQR 72
Cdd:smart00213   1 IELTVKTLDGKTITLEVKPSDTVSELKEKIAELTGIPPEQQRLIYKGKVLEDDRTLADYGIQDGSTIHLVLR 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 10179811   5 VRFNSSYG--FPVEVDSDTSILQLKEVVAKRQGVPADQLRVIFAGKELPNHLTVQNCDLEQQSIVHIVQRP 73
Cdd:cd16106   3 VTVKCSNGkkFTVEVEPDATVLELKELIAEKSDIPAEQQRLIYKGKILKDEETLSSYKIQDGHTVHLVKGA 73

ubiquitin-like (Ubl) domain found in ubiquitin; Ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair. Ubiquitination is comprised of a cascade of E1, E2 and E3 enzymes that results in a covalent bond between the C-terminus of ubiquitin and the epsilon-amino group of a substrate lysine. Ubiquitin-like (Ubl) proteins have similar ubiquitin beta-grasp fold and attach to other proteins in a Ubl manner but with biochemically distinct roles. Ubiquitin (Ub)and Ubl proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Ub includes Ubq/RPL40e and Ubq/RPS27a fusions as well as homopolymeric multiubiquitin protein chains.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 10179811   1 MIVFVRFNSSYGFPVEVDSDTSILQLKEVVAKRQGVPADQLRVIFAGKELPNHLTVQNCDLEQQSIVHIVQRPR 74
Cdd:cd01803   1 MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLR 74

ubiquitin-like (Ubl) domain 2 found in interferon-stimulated gene 15 (ISG15) and similar proteins; ISG15, also termed interferon-induced 15 kDa protein, or interferon-induced 17 kDa protein (IP17), or ubiquitin cross-reactive protein (UCRP), is an antiviral interferon-induced ubiquitin-like protein that upon viral infection it modifies cellular and viral proteins by mechanisms similar to ubiquitination. Although ISG15 has properties similar to those of other ubiquitin-like (Ubl) molecules, it is a unique member of the Ubl superfamily, whose expression and conjugation to target proteins are tightly regulated by specific signaling pathways, indicating it may have specialized functions in the immune system. ISG15 contains two tandem Ubl domains with a beta-grasp Ubl fold. This family corresponds to the second Ubl domain.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 10179811   1 MIVFVRFNSSYGFPVEVDSDTSILQLKEVVAKRQGVPADQLRVIFAGKELPNHLTVQNCDLEQQSIVHIVQRPR 74
Cdd:cd01810   1 LSIFVRNEKGQSHTYEVRLTQTVDQLKQKVSGREGVHDDQFWLTFEGRPLEDQLPLGEYGLKPQSTIHMNLRLR 74

Beta-grasp ubiquitin-like fold; Ubiquitin is a protein modifier that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes. The ubiquitination process comprises a cascade of E1, E2 and E3 enzymes that results in a covalent bond between the C-terminus of ubiquitin and the epsilon-amino group of a substrate lysine. Ubiquitin-like proteins have similar ubiquitin beta-grasp fold and attach to other proteins in a ubiquitin-like manner but with biochemically distinct roles. Ubiquitin and ubiquitin-like proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Some other ubiquitin-like domains have adaptor roles in ubiquitin-signaling by mediating protein-protein interaction. In addition to Ubiquitin-like (Ubl) domain, Ras-associating (RA) domain, F0/F1 sub-domain of FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, TGS (ThrRS, GTPase and SpoT) domain, Ras-binding domain (RBD), Ubiquitin regulatory domain X (UBX), Dublecortin-like domain, and RING finger- and WD40-associated ubiquitin-like (RAWUL) domain have beta-grasp ubiquitin-like folds, and are included in this superfamily.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 10179811   3 VFVRFNSSYGFPVEVDSDTSILQLKEVVAKRQGVPADQLRVIFAGKELPNHLTVQNCDLEQQSIVHIV 70
Cdd:cd00196   1 VKVETPSLKKIVVAVPPSTTLRQVLEKVAKRIGLPPDVIRLLFNGQVLDDLMTAKQVGLEPGEELHFV 68

ubiquitin; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 10179811    9 SSYGFpvevDSDTSILQLKEVVAKRQGVPADQLRVIFAGKELPNHLTVQNCDLEQQSIVHIVQRPR 74
Cdd:PTZ00044  13 QSFNF----EPDNTVQQVKMALQEKEGIDVKQIRLIYSGKQMSDDLKLSDYKVVPGSTIHMVLQLR 74

ubiquitin-like (Ubl) domain found in BCL2-associated athanogene 6 (BAG6) and similar proteins; BAG6, also termed large proline-rich protein BAG6, or BAG family molecular chaperone regulator 6, or HLA-B-associated transcript 3 (Bat3), or protein Scythe, or protein G3, is a nucleo-cytoplasmic shuttling chaperone protein that is highly conserved in eukaryotes. It functions in two distinct biological pathways, ubiquitin-mediated protein degradation of defective polypeptides and tail-anchored transmembrane protein biogenesis in mammals. BAG6 is a component of the heterotrimeric BAG6 sortase complex composed of BAG6, transmembrane recognition complex 35 (TRC35) and ubiquitin-like protein 4A (UBL4A). The BAG6 complex together with the cochaperone small, glutamine-rich, tetratricopeptide repeat-containing, protein alpha (SGTA) plays a role in the biogenesis of tail-anchored membrane proteins and subsequently shown to regulate the ubiquitination and proteasomal degradation of mislocalized proteins. Moreover, BAG6 acts as an apoptotic regulator that binds reaper, a potent apoptotic inducer. BAG6/reaper is thought to signal apoptosis, in part through regulating the folding and activity of apoptotic signaling molecules. It is also likely a key regulator of the molecular chaperone Heat Shock Protein A2 (HSPA2) stability/function in human germ cells. Furthermore, aspartyl protease-mediated cleavage of BAG6 is necessary for autophagy and fungal resistance in plants. BAG6 contains a ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, which provides a platform for discriminating substrates with shorter hydrophobicity stretches as a signal for defective proteins.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 10179811  17 VDSDTSILQLKEVVAKRQGVPADQLRVIFAGKELPNHLTVQNCDLeQQSIVHIVQR 72
Cdd:cd01809  17 VPEEITVKEFKEHIASSVNIPAEKQRLIFQGRVLQDDKKLKEYDV-DGKVIHLVER 71

ubiquitin-like (Ubl) domain found in small ubiquitin-related modifier 1 (SUMO-1) and similar proteins; SUMO (also known as "Smt3" and "sentrin" in other organisms) resembles ubiquitin (Ub) in structure, ligation to other proteins and the mechanism of ligation. Ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair. Ubiquitination is comprised of a cascade of E1, E2 and E3 enzymes that results in a covalent bond between the C-terminus of Ub and the epsilon-amino group of a substrate lysine. SUMOs, like Ub, are covalently conjugated to lysine residues in a wide variety of target proteins in eukaryotic cells and regulate numerous cellular processes, such as transcription, epigenetic gene control, genomic instability, and protein degradation. Four SUMO paralogs exist in mammals, SUMO1 through SUMO4. SUMO2-SUMO4 are more closely related to each other than they are to SUMO1. SUMO1 is a binding partner of the RAD51/52 nucleoprotein filament proteins, which mediate DNA strand exchange. SUMO1 conjugation to cellular proteins has been implicated in multiple important cellular processes, such as nuclear transport, cell cycle control, oncogenesis, inflammation, and the response to virus infection.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 10179811  17 VDSDTSILQLKEVVAKRQGVPADQLRVIFAGKELPNHLTVQNCDLEQQSIVHIVQ 71
Cdd:cd16114  18 VKMTTHLKKLKESYCQRQGVPMNSLRFLFEGQRINDNHTPKELGMEEEDVIEVYQ 72

ubiquitin-like (Ubl) domain 2 found in 2'-5'-oligoadenylate synthase-like protein (OASL) and similar proteins; OASL, also termed 2'-5'-OAS-related protein (2'-5'-OAS-RP), or 59 kDa 2'-5'-oligoadenylate synthase-like protein, or thyroid receptor-interacting protein 14, or TR-interacting protein 14 (TRIP-14), or p59 OASL (p59OASL), is an interferon (IFN)-induced antiviral protein that plays an important role in the IFNs-mediated antiviral signaling pathway. It inhibits respiratory syncytial virus replication and is targeted by the viral nonstructural protein 1 (NS1). It also displays antiviral activity against encephalomyocarditis virus (EMCV) and hepatitis C virus (HCV) via an alternative antiviral pathway independent of RNase L. Moreover, OASL does not have 2'-5'-OAS activity, but can bind double-stranded RNA (dsRNA) to enhance RIG-I signaling. OASL belongs to the 2'-5' oligoadenylate synthase (OAS) family. While each member of this family has a conserved N-terminal OAS catalytic domain, only OASL has two tandem C-terminal ubiquitin-like (Ubl) repeats, which are required for its antiviral activity. This family corresponds to the second Ubl domain.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 10179811   2 IVFVRFNSSYGFPVEVDSDTSILQLKEVVAKRQGVPADQLRVIFAGKELPNHLT-----VQNCD 60
Cdd:cd16103   3 QIFVKFPDGTSKPYAINPEDTILDLKEKIEEQGGPPVEDQILLFQGQELRDKKSlkyygIKDGD 66

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
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 10179811  13 FPVEVDSDTSILQLKEVVAKRQGVPADQLRVIFAGKELPN-HLTVQNCDLEQQSIVHIVQ 71
Cdd:cd01796  14 FSLEVSPDMTLEDLKALCEAETGIPAAEQVLLHNGQPLTDdKKTLEALGLKDGDLLLLRP 73

ubiquitin-like (Ubl) domain found in BAG family molecular chaperone regulator 1 (BAG1) and similar proteins; BAG1, also termed Bcl-2-associated athanogene 1, or HAP, is a multifunctional protein involved in a variety of cellular functions such as apoptosis, transcription, and proliferative pathways, as well as in cell signaling and differentiation. It delivers chaperone-recognized unfolded substrates to the proteasome for degradation. BAG1 functions as a co-chaperone for Hsp70/Hsc70 to increase Hsp70 foldase activity. It also suppresses apoptosis and enhances neuronal differentiation. As an anti-apoptotic factor, BAG1 interacts with tau and regulates its proteasomal degradation. It also binds to BCR-ABL with a high affinity, and directly routes immature BCR-ABL for proteasomal degradation. It acts as a potential therapeutic target in Parkinson's disease. It also modulates huntingtin toxicity, aggregation, degradation, and subcellular distribution, suggesting a role in Huntington's disease. There are at least four isoforms of Bag1 protein that are formed by alternative initiation of translation within a common mRNA. BAG1 contains an N-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, and a C-terminal BAG domain.

                        10        20        30
                ....*....|....*....|....*....|....*..
gi 10179811  14 PVEVDSDTSILQLKEVVAKRQGVPADQLRVIFAGKEL 50
Cdd:cd01812  17 PSQDEDEPTLQDLAEAIEEVTGVPVENQKLIFKGKSL 53