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 1039753947 146 FFIYCKGPCHKVQPGKLRVQCGTCKQATLTLAQGPSCWDDVLIPNRMSGECQSPDCPGTRAEFFFKCGAHPTSDKDTSVA 225
Cdd:cd21382     1 FYVYCKGPCKKVQPGKLRVRCATCKQGAFTLDRGPSCWDDVLIPNRISGVCQSPDCPGTRAEFYFKCASHPTSDKDTSVA 80

                  ....
gi 1039753947 226 LNLI 229
Cdd:cd21382    81 LNLI 84

BRcat domain found in parkin and similar proteins; Parkin, also called Parkinson juvenile disease protein 2, is an 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 Lys6-, Lys11-, Lys48- and Lys63-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 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR domain uses an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase functions to facilitate the ubiquitination reaction. This model corresponds to the BRcat domain of parkin that adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039753947 301 LHHFRILGEEQYTRYQQYGAEECVLQMGGVLCPRPGCGAGLLPEQGQRKVTCEggngLGCGFVFCRDCKEAYHEGDCDSL 380
Cdd:cd20340     1 THHFRILGDEQYERYQRFGAEECVLQMGGVLCPQPGCGAGLLPEDECNRVTCE----LGCGFVFCRECLEAYHEGECRSF 76

                  .
gi 1039753947 381 L 381
Cdd:cd20340    77 L 77

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 1039753947 146 FFIYCKGPCHKVQPGKLRVQCGTCKQATLTLAQGPSCWDDVLIPNRMSGECQSPDCPGTRAEFFFKCGAHPTSDKDTSVA 225
Cdd:cd21382     1 FYVYCKGPCKKVQPGKLRVRCATCKQGAFTLDRGPSCWDDVLIPNRISGVCQSPDCPGTRAEFYFKCASHPTSDKDTSVA 80

                  ....
gi 1039753947 226 LNLI 229
Cdd:cd21382    81 LNLI 84

BRcat domain found in parkin and similar proteins; Parkin, also called Parkinson juvenile disease protein 2, is an 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 Lys6-, Lys11-, Lys48- and Lys63-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 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR domain uses an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase functions to facilitate the ubiquitination reaction. This model corresponds to the BRcat domain of parkin that adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039753947 301 LHHFRILGEEQYTRYQQYGAEECVLQMGGVLCPRPGCGAGLLPEQGQRKVTCEggngLGCGFVFCRDCKEAYHEGDCDSL 380
Cdd:cd20340     1 THHFRILGDEQYERYQRFGAEECVLQMGGVLCPQPGCGAGLLPEDECNRVTCE----LGCGFVFCRECLEAYHEGECRSF 76

                  .
gi 1039753947 381 L 381
Cdd:cd20340    77 L 77

RING finger, HC subclass, found in parkin and similar proteins; Parkin, also known as Parkinson juvenile disease protein 2, is an 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 protect 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 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 uses 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. This model corresponds to the RING domain, a C3HC4-type RING-HC finger required for RBR-mediated ubiquitination.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1039753947 236 IPCIACTDVRSPVLVFQCNHRHVICLDCFHLYCVTRLNDRQFVHDAQLGYSLPCVAGCP 294
Cdd:cd16627     1 VPCITCTDVRSPVLVFPCESRHVICLDCFHLYCVTRLNDRQFVHDPQLGYTLPCPAGCE 59

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 1039753947    1 MIVFVRFNSSYGFPVEVDSDTSILQLKEVVAKRQGVPADQLRVIFAGKELPNHLTVQNCDLEQQSIVHIVQR 72
Cdd:smart00213   1 IELTVKTLDGKTITLEVKPSDTVSELKEKIAELTGIPPEQQRLIYKGKVLEDDRTLADYGIQDGSTIHLVLR 72

IBR domain, a half RING-finger domain; The IBR (In Between Ring fingers) domain is often found to occur between pairs of ring fingers (pfam00097). This domain has also been called the C6HC domain and DRIL (for double RING finger linked) domain. Proteins that contain two Ring fingers and an IBR domain (these proteins are also termed RBR family proteins) are thought to exist in all eukaryotic organizms. RBR family members play roles in protein quality control and can indirectly regulate transcription. Evidence suggests that RBR proteins are often parts of cullin-containing ubiquitin ligase complexes. The ubiquitin ligase Parkin is an RBR family protein whose mutations are involved in forms of familial Parkinson's disease.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1039753947 314 RYQQYGAEECVLQMGGVL-CPRPGCGAGLLPEQGQRK---VTCEGgnglgCGFVFCRDCKEAYHEG-DC 377
Cdd:pfam01485   2 KYEKLLLKSYVESDPNLKwCPTPDCGYIIELTDGCSNtshVTCSK-----CGHEFCFNCKEEWHEGlTC 65

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 1039753947  13 FPVEVDSDTSILQLKEVVAKRQGV---PADQLRVIFAGKELPNHLTVQNCDL-EQQSIVHIVQRPRRrshETNASGGDEP 88
Cdd:TIGR00601  13 FKIDMEPDETVKELKEKIEAEQGKdayPVAQQKLIYSGKILSDDKTVKEYKIkEKDFVVVMVSKPKT---GTGKVAPPAA 89

                  ....
gi 1039753947  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 1039753947 146 FFIYCKGPCHKVQPGKLRVQCGTCKQATLTLAQGPSCWDDVLIPNRMSGECQSPDCPGTRAEFFFKCGAHPTSDKDTSVA 225
Cdd:cd21382     1 FYVYCKGPCKKVQPGKLRVRCATCKQGAFTLDRGPSCWDDVLIPNRISGVCQSPDCPGTRAEFYFKCASHPTSDKDTSVA 80

                  ....
gi 1039753947 226 LNLI 229
Cdd:cd21382    81 LNLI 84

BRcat domain found in parkin and similar proteins; Parkin, also called Parkinson juvenile disease protein 2, is an 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 Lys6-, Lys11-, Lys48- and Lys63-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 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR domain uses an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase functions to facilitate the ubiquitination reaction. This model corresponds to the BRcat domain of parkin that adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039753947 301 LHHFRILGEEQYTRYQQYGAEECVLQMGGVLCPRPGCGAGLLPEQGQRKVTCEggngLGCGFVFCRDCKEAYHEGDCDSL 380
Cdd:cd20340     1 THHFRILGDEQYERYQRFGAEECVLQMGGVLCPQPGCGAGLLPEDECNRVTCE----LGCGFVFCRECLEAYHEGECRSF 76

                  .
gi 1039753947 381 L 381
Cdd:cd20340    77 L 77

RING finger, HC subclass, found in parkin and similar proteins; Parkin, also known as Parkinson juvenile disease protein 2, is an 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 protect 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 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 uses 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. This model corresponds to the RING domain, a C3HC4-type RING-HC finger required for RBR-mediated ubiquitination.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1039753947 236 IPCIACTDVRSPVLVFQCNHRHVICLDCFHLYCVTRLNDRQFVHDAQLGYSLPCVAGCP 294
Cdd:cd16627     1 VPCITCTDVRSPVLVFPCESRHVICLDCFHLYCVTRLNDRQFVHDPQLGYTLPCPAGCE 59

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 1039753947    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 1039753947   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 1039753947   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 1039753947   1 MIVFVRFNSSYGFPVEVDSDTSILQLKEVVAKRQGVPADQLRVIFAGKELPNHLTVQNCDLEQQSIVHIVQRPR 74
Cdd:cd01810     1 LSIFVRNEKGQSHTYEVRLTQTVDQLKQKVSGREGVHDDQFWLTFEGRPLEDQLPLGEYGLKPQSTIHMNLRLR 74

ubiquitin-like (Ubl) domain found in ubiquitin-like protein FUBI and similar proteins; FUBI is a pro-apoptotic regulatory gene FAU encoding ubiquitin-like protein with ribosomal protein S30 as a C-terminal extension. FUBI functions as a tumor suppressor protein that may be involved in the ATP-dependent proteolytic activity of ubiquitin. The N-terminal ubiquitin-like (Ubl) domain of FUBI has the beta-grasp Ubl fold, and it may act as a substitute or an inhibitor of ubiquitin or one of ubiquitin's close relatives UCRP, FAT10, and Nedd8.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1039753947   1 MIVFVRFNSSYGFpvEVDSDTSILQLKEVVAKRQGVPADQLRVIFAGKELPNHLTVQNCDLEQQSIVHIVQR 72
Cdd:cd01793     1 MQLFVRAQSLHTL--EVSGNETVADIKAHIAALEGIAVEDQVLLYAGAPLEDDVVLGQCGIPDLATLEVAVR 70

ubiquitin-like (Ubl) domain found in the Rad23 protein family; The Rad23 family includes the yeast nucleotide excision repair (NER) proteins, Rad23p (in Saccharomyces cerevisiae) and Rhp23p (in Schizosaccharomyces pombe), their mammalian orthologs HR23A and HR23B, and putative DNA repair proteins from plants. Rad23 proteins play dual roles in DNA repair as well as in proteosomal degradation. They have affinity for both the proteasome and ubiquitinylated proteins and participate in translocating polyubiquitinated proteins to the proteasome. Rad23 proteins carry an ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, and two ubiquitin-associated (UBA) domains, as well as a xeroderma pigmentosum group C (XPC) protein-binding domain. The Ubl domain is responsible for the binding to proteasome. The UBA domains are important for binding of ubiquitin (Ub) or multi-ubiquitinated substrates, which suggests Rad23 proteins might be involved in certain pathways of Ub metabolism. Both the Ubl domain and the XPC-binding domain are necessary for efficient NER function of Rad23 proteins.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039753947  13 FPVEVDSDTSILQLKEVVAKRQGV-PADQLRVIFAGKELPNHLTVQNCDLEQQS--IVHI 69
Cdd:cd01805    13 FEIEVEPSDTVLELKEKIEQEQGDfPASGQKLIYSGKVLKDDKTLSEYNIKEKDfvVVMV 72

BRcat domain found in RING finger protein 14 (RNF14); RNF14, also called androgen receptor (AR)-associated protein 54 (ARA54), HFB30, or Triad2 protein, is an RBR-type E3 ubiquitin-protein ligase that is highly expressed in the testis and interacts with class III E2s (UBE2E2, UbcH6, and UBE2E3). Its differential localization may play an important role in testicular development and spermatogenesis in humans. RNF14 functions as a transcriptional regulator of mitochondrial and immune function in muscles. It is a ligand-dependent AR co-activator that enhances AR-dependent transcriptional activation. It may also participate in enhancing cell cycle progression and cell proliferation via induction of cyclin D1. Moreover, RNF14 is crucial for colon cancer cell survival. It acts as a new enhancer of the Wnt-dependent transcriptional outputs that acts at the level of the T-cell factor/lymphoid enhancer factor (TCF/LEF)-beta-catenin complex. RNF14 contains an N-terminal RWD domain, and a C-terminal RBR domain. The RBR domain 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR domain uses 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. This model corresponds to the BRcat domain of RNF14 that adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1039753947 330 VLCPRPGCGAGLLPEQGQRKVTCeggngLGCGFVFCRDCKEAYH 373
Cdd:cd20341     8 VYCPRPSCQTPVILEPDENLGIC-----PSCNYAFCTLCRETYH 46

Ubiquitin-2 like Rad60 SUMO-like; The small ubiquitin-related modifier SUMO-1 is a Ub/Ubl family member, and although SUMO-1 shares structural similarity to Ub, SUMO's cellular functions remain distinct insomuch as SUMO modification alters protein function through changes in activity, cellular localization, or by protecting substrates from ubiquitination. Rad60 family members contain functionally enigmatic, integral SUMO-like domains (SLDs). Despite their divergence from SUMO, each Rad60 SLD interacts with a subset of SUMO pathway enzymes: SLD2 specifically binds the SUMO E2 conjugating enzyme (Ubc9)), whereas SLD1 binds the SUMO E1 (Fub2, also called Uba2) activating and E3 (Pli1, also called Siz1 and Siz2) specificity enzymes. Structural analysis of PDB:2uyz reveals a mechanistic basis for the near-synonymous roles of Rad60 and SUMO in survival of genotoxic stress and suggest unprecedented DNA-damage-response functions for SLDs in regulating SUMOylation. The Rad60 branch of this family is also known as RENi (Rad60-Esc2-Nip45), and biologically it should be two distinct families SUMO and RENi (Rad60-Esc2-Nip45).

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1039753947  15 VEVDSDTSILQLKEVVAKRQGVPAD-QLRVIFAGKELPNHLTVQNCDLEQQSIVHIV 70
Cdd:pfam11976  15 IKVKPTTTVSKLINAYRKKRGIPPSqQVRLIFDGERLDPNSTVEDLDIEDGDTIDVV 71

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]

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039753947  13 FPVEVDSDTSILQLKEVVAKRQGV---PADQLRVIFAGKELPNHLTVQNCDL-EQQSIVHIVQRPRRrshETNASGGDEP 88
Cdd:TIGR00601  13 FKIDMEPDETVKELKEKIEAEQGKdayPVAQQKLIYSGKILSDDKTVKEYKIkEKDFVVVMVSKPKT---GTGKVAPPAA 89

                  ....
gi 1039753947  89 QSTS 92
Cdd:TIGR00601  90 TPTS 93

ubiquitin-like (Ubl) domain found in Arabidopsis thaliana ubiquitin-protein ligase 5 (AtUPL5) and similar proteins; Arabidopsis thaliana AtUPL5, also termed HECT-type E3 ubiquitin transferase UPL5, is an E3 ubiquitin-protein ligase that contains a ubiquitin-like domain (Ubl), a C-type lectin-binding domain, a leucine zipper and a HECT domain. HECT domain containing-ubiquitin-protein ligases have more than one member in different genomes, these proteins have been classified into four sub-families (UPL1/2, UPL3/4, UPL5 and UPL6/7). AtUPL5 fUPL5 regulates leaf senescence in Arabidopsis through degradation of the transcription factor WRKY53.

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gi 1039753947   3 VFVRFNSSYGFPVEVDSDTSILQLKEVVAKRQGVPADQLRVIFAGKELPNHLTVQNCDLEQQSIVHIV 70
Cdd:cd16107     2 IFVRTYCGKTIVLHAKASDTVESLHQQIEARTGIPSLEQRLIFGGRQLQHSQSLESCKMENDATLFLV 69

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1039753947   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.

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gi 1039753947  13 FPVEVDSDTSILQLKEVVAKRQGVPADQLRVIFAGKELPN-HLTVQNCDLEQQSIVHIVQ 71
Cdd:cd01796    14 FSLEVSPDMTLEDLKALCEAETGIPAAEQVLLHNGQPLTDdKKTLEALGLKDGDLLLLRP 73