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        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831677272 228 LITTNSRDITCITCMDIRSPVLVFQCNYRHVICLDCFHLYCVTRLNDRQFVHDPQLGYSLPCVAGCPNSLIKELHHFRIL 307
Cdd:pfam17978   1 LIKSNSRDVPCLACTDVSSPVLVFPCEDRHVICLDCFHQYCVSRLNERQFVQHPEIGYTLPCPAGCPDSLIKEVHHFRLL 80

                  ....*....
gi 1831677272 308 GEEQYNRYQ 316
Cdd:pfam17978  81 GDEQYERYQ 89

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1831677272 301 LHHFRILGEEQYNRYQQYGAEECVLQMGGVLCPSPGCGAGLLPEPSQRKVTCEggsgLGCGFVFCRDCKEPYHEGECSA 379
Cdd:cd20340     1 THHFRILGDEQYERYQRFGAEECVLQMGGVLCPQPGCGAGLLPEDECNRVTCE----LGCGFVFCRECLEAYHEGECRS 75

BRcat (benign-catalytic) and Rcat (required-for-catalysis) domains, part of the RBR (RING1-BRcat-Rcat) domain; The RBR family of RING-type E3 ligases are characterized by containing an RBR (RING1-BRcat-Rcat) domain, which was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. It is composed of an extended RING domain (RING1) followed by an in-between RING (IBR) domain and the catalytic domain, which is structurally an IBR domain but is commonly designated as RING2. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBRs has been changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis), where the IBR and RING2 domains have been renamed as BRcat and Rcat domains, respectively. 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. The BRcat domain adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity. 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.

                          10        20
                  ....*....|....*....|.
gi 1831677272 409 ETIKKTSKPCPRCHVPVEKHG 429
Cdd:cd20357     1 ETIKKTTKPCPKCKVPTEKNG 21

1-acyl-sn-glycerol-3-phosphate acyltransferase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831677272 477 VFIASGLIINTIQL-FTLLLWPINKQLFRKINCRLSYCISSQLVMLLEWWSGTECIIHTDPRAYPKYGKENAIVVLNHKF 555
Cdd:PLN02380   15 LFLLSGLIVNLIQAvCFILVRPLSKSLYRRINRAVAELLWLELIWLVDWWAGVKVQLYADEETFELMGKEHALVISNHRS 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831677272 556 EIDFLCGWSLAERFGVLGGSKVLAKKELAYVPIIGW-MWyFTEMVFCTRKWEQDRKTVSESLLHLRDYPEKYFFLIHCEG 634
Cdd:PLN02380   95 DIDWLVGWILAQRSGCLGSALAVMKKSSKFLPVIGWsMW-FSEYVFLERSWAKDENTLKSGFQRLKDFPRPFWLALFVEG 173

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831677272 635 TRFTEKKHQISMQVAQAKGLPSLKHHLLPRTKGFAITVRSLRNVVSAVYDCTLNF-RNNENPTLLGVLNGKKYHADLYVR 713
Cdd:PLN02380  174 TRFTQAKLLAAQEYAASRGLPVPRNVLIPRTKGFVSAVSNMRSFVPAIYDVTVAVpKGQPAPTMLRIFRGQSSVVHVHIK 253

                         250
                  ....*....|....*....
gi 1831677272 714 TPSRRSTPARAPSPGRpWC 732
Cdd:PLN02380  254 RHSMKELPETDDGIAQ-WC 271

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 1831677272 146 FFVYCKGPCQGVQPGKLRVRCSTCQQATLTLAQGPSRWEDVLIPNQMSGECQSPNCPGTRAEFFFKCGAHPTSDKETSVA 225
Cdd:cd21382     1 FYVYCKGPCKKVQPGKLRVRCATCKQGAFTLDRGPSCWDDVLIPNRISGVCQSPDCPGTRAEFYFKCASHPTSDKDTSVA 80

                  ....
gi 1831677272 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 1831677272   3 VFVRFNSSHGFPVEVDSDTSIFQLKEVVAKQQGVPADQLRVIFAGKELRNDLTVRSCDLDQQSIVHIVLRPQRK 76
Cdd:cd01798     1 VFVRFNSSHGFPVEVDSDWSILQLKEVVAKRQGVPPDQLRIIFAGKELSDDLTLQNCDLGQQSIVHAVQGPKRK 74

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 1831677272 236 ITCITCMDIRSPVLVFQCNYRHVICLDCFHLYCVTRLNDRQFVHDPQLGYSLPCVAGCP 294
Cdd:cd16627     1 VPCITCTDVRSPVLVFPCESRHVICLDCFHLYCVTRLNDRQFVHDPQLGYTLPCPAGCE 59

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 1831677272   3 VFVRFNSSHGFPVEVDSDTSIFQLKEVVAKQQGVPADQLRVIFAGKELRNDLTVRSCDLDQQSIVHIVLRPQ 74
Cdd:pfam00240   1 ITVKTLDGKKITLEVDPTDTVLELKEKIAEKEGVPPEQQRLIYSGKVLEDDQTLGEYGIEDGSTIHLVLRQR 72

Acyltransferase; This family contains acyltransferases involved in phospholipid biosynthesis and other proteins of unknown function. This family also includes tafazzin, the Barth syndrome gene.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831677272 544 KENAIVVLNHKFEIDFLCGWSLAERFGVLGgsKVLAKKELAYVPIIGWMWYFTEMVFCTRKWEQDRKTVSESLLHLRDyp 623
Cdd:pfam01553  13 GGPAIVVANHQSYLDVLLLSLALYKRGRPL--VFVAKKELFDIPLVGWLMRLLGCIFIDRKNRKDAAGTLEYLVELLR-- 88

                          90
                  ....*....|....*.
gi 1831677272 624 EKYFFLIHCEGTRFTE 639
Cdd:pfam01553  89 EGKLVVIFPEGTRSRE 104

Rcat 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 Rcat domain of parkin that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

                          10        20
                  ....*....|....*....|.
gi 1831677272 409 ETIKKTSKPCPRCHVPVEKHG 429
Cdd:cd20357     1 ETIKKTTKPCPKCKVPTEKNG 21

ubiquitin; Provisional

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1831677272  18 DSDTSIFQLKEVVAKQQGVPADQLRVIFAGKELRNDLTVRSCDLDQQSIVHIVLR 72
Cdd:PTZ00044   18 EPDNTVQQVKMALQEKEGIDVKQIRLIYSGKQMSDDLKLSDYKVVPGSTIHMVLQ 72

1-acyl-sn-glycerol-3-phosphate acyltransferases; This model describes the core homologous region of a collection of related proteins, several of which are known to act as 1-acyl-sn-glycerol-3-phosphate acyltransferases (EC 2.3.1.51). Proteins scoring above the trusted cutoff are likely to have the same general activity. However, there is variation among characterized members as to whether the acyl group can be donated by acyl carrier protein or coenzyme A, and in the length and saturation of the donated acyl group. 1-acyl-sn-glycerol-3-phosphate acyltransferase is also called 1-AGP acyltransferase, lysophosphatidic acid acyltransferase, and LPA acyltransferase. [Fatty acid and phospholipid metabolism, Biosynthesis]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831677272 531 IIHTDPRAYPKYGkeNAIVVLNHKFEIDFLcgwSLAERFGVlgGSKVLAKKELAYVPIIGWMWYFTEMVFCTRKWEQDRK 610
Cdd:TIGR00530   4 VEVVGPENLPAKS--PVLVVANHQSNLDPL---TLSAAFPP--PIVFIAKKELKWIPFFGIMLWLTGAIFIDRENIRAIA 76

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1831677272 611 TVSESLLH-LRDYPEKYFFLihcEGTRFTEKK----HQISMQVAQAKGLP 655
Cdd:TIGR00530  77 TALKAAIEvLKQGRSIGVFP---EGTRSRGRDilpfKKGAFHIAIKAGVP 123

1-acyl-sn-glycerol-3-phosphate acyltransferase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831677272 477 VFIASGLIINTIQL-FTLLLWPINKQLFRKINCRLSYCISSQLVMLLEWWSGTECIIHTDPRAYPKYGKENAIVVLNHKF 555
Cdd:PLN02380   15 LFLLSGLIVNLIQAvCFILVRPLSKSLYRRINRAVAELLWLELIWLVDWWAGVKVQLYADEETFELMGKEHALVISNHRS 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831677272 556 EIDFLCGWSLAERFGVLGGSKVLAKKELAYVPIIGW-MWyFTEMVFCTRKWEQDRKTVSESLLHLRDYPEKYFFLIHCEG 634
Cdd:PLN02380   95 DIDWLVGWILAQRSGCLGSALAVMKKSSKFLPVIGWsMW-FSEYVFLERSWAKDENTLKSGFQRLKDFPRPFWLALFVEG 173

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831677272 635 TRFTEKKHQISMQVAQAKGLPSLKHHLLPRTKGFAITVRSLRNVVSAVYDCTLNF-RNNENPTLLGVLNGKKYHADLYVR 713
Cdd:PLN02380  174 TRFTQAKLLAAQEYAASRGLPVPRNVLIPRTKGFVSAVSNMRSFVPAIYDVTVAVpKGQPAPTMLRIFRGQSSVVHVHIK 253

                         250
                  ....*....|....*....
gi 1831677272 714 TPSRRSTPARAPSPGRpWC 732
Cdd:PLN02380  254 RHSMKELPETDDGIAQ-WC 271

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 1831677272 146 FFVYCKGPCQGVQPGKLRVRCSTCQQATLTLAQGPSRWEDVLIPNQMSGECQSPNCPGTRAEFFFKCGAHPTSDKETSVA 225
Cdd:cd21382     1 FYVYCKGPCKKVQPGKLRVRCATCKQGAFTLDRGPSCWDDVLIPNRISGVCQSPDCPGTRAEFYFKCASHPTSDKDTSVA 80

                  ....
gi 1831677272 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 1831677272   3 VFVRFNSSHGFPVEVDSDTSIFQLKEVVAKQQGVPADQLRVIFAGKELRNDLTVRSCDLDQQSIVHIVLRPQRK 76
Cdd:cd01798     1 VFVRFNSSHGFPVEVDSDWSILQLKEVVAKRQGVPPDQLRIIFAGKELSDDLTLQNCDLGQQSIVHAVQGPKRK 74

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 1831677272 236 ITCITCMDIRSPVLVFQCNYRHVICLDCFHLYCVTRLNDRQFVHDPQLGYSLPCVAGCP 294
Cdd:cd16627     1 VPCITCTDVRSPVLVFPCESRHVICLDCFHLYCVTRLNDRQFVHDPQLGYTLPCPAGCE 59

Phosphate acyltransferases; Function in phospholipid biosynthesis and have either glycerolphosphate, 1-acylglycerolphosphate, or 2-acylglycerolphosphoethanolamine acyltransferase activities. Tafazzin, the product of the gene mutated in patients with Barth syndrome, is a member of this family.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831677272  547 AIVVLNHKFEIDFLCGWSLAERFGvlGGSKVLAKKELAYVPIIGWMWYFTEMVFCTRKWE-QDRKTVSESLLHLRDypeK 625
Cdd:smart00563   1 ALVVANHQSFLDPLVLSALLPRKL--GRVRFVAKKELFYVPLLGWLLRLLGAIFIDRSNGrKARAALREAVELLKE---G 75

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1831677272  626 YFFLIHCEGTRFTEKKHQ-----ISMQVAQAkglpslKHHLLPRTKGFA 669
Cdd:smart00563  76 EWLLIFPEGTRSRPGKLLpfkkgAARLALEA------GVPIVPVAIRGT 118

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 1831677272    1 MIVFVRFNSSHGFPVEVDSDTSIFQLKEVVAKQQGVPADQLRVIFAGKELRNDLTVRSCDLDQQSIVHIVLR 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1831677272   5 VRFNSSHG--FPVEVDSDTSIFQLKEVVAKQQGVPADQLRVIFAGKELRNDLTVRSCDLDQQSIVHIV 70
Cdd:cd16106     3 VTVKCSNGkkFTVEVEPDATVLELKELIAEKSDIPAEQQRLIYKGKILKDEETLSSYKIQDGHTVHLV 70

Acyltransferase; This family contains acyltransferases involved in phospholipid biosynthesis and other proteins of unknown function. This family also includes tafazzin, the Barth syndrome gene.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831677272 544 KENAIVVLNHKFEIDFLCGWSLAERFGVLGgsKVLAKKELAYVPIIGWMWYFTEMVFCTRKWEQDRKTVSESLLHLRDyp 623
Cdd:pfam01553  13 GGPAIVVANHQSYLDVLLLSLALYKRGRPL--VFVAKKELFDIPLVGWLMRLLGCIFIDRKNRKDAAGTLEYLVELLR-- 88

                          90
                  ....*....|....*.
gi 1831677272 624 EKYFFLIHCEGTRFTE 639
Cdd:pfam01553  89 EGKLVVIFPEGTRSRE 104

putative acyltransferase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831677272 576 KVLAKKELAYVPIIGWMWYFTEMVFCTR-----------KWEQDRKTVSESLLHLRDYPEKYF-FLihcEGTRFTEKKHQ 643
Cdd:PRK14014  116 KFFLKQELIWVPFLGLAWWALDFPFMKRyskaylaknpeLKGKDLETTRRACEKFKRMPTTIVnFV---EGTRFTPEKHQ 192

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1831677272 644 ismqvAQAkglpSLKHHLL-PRTKGFAITVRSLRNVVSAVYDCTLNFRnNENPTLLGVLNGK 704
Cdd:PRK14014  193 -----QQQ----SPYQHLLkPKAGGIAFALNAMGEQFDGLLDVTIVYP-DGRPSFWDLLSGR 244

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 1831677272   1 MIVFVRFNSSHGFpvEVDSDTSIFQLKEVVAKQQGVPADQLRVIFAGKELRNDLTVRSCDLDQQSIVHIVLR 72
Cdd:cd01793     1 MQLFVRAQSLHTL--EVSGNETVADIKAHIAALEGIAVEDQVLLYAGAPLEDDVVLGQCGIPDLATLEVAVR 70

ubiquitin-like (Ubl) domain found in eukaryotic protein linking integrin-associated protein (IAP, also known as CD47) with cytoskeleton (PLIC) proteins; The PLIC proteins (or ubiquilins) family contains human homologs of the yeast ubiquitin-like (Ubl) Dsk2 protein, PLIC-1 (also termed ubiquilin-1), PLIC-2 (also termed ubiquilin-2, or Chap1), PLIC-3 (also termed ubiquilin-3) and PLIC-4 (also termed ubiquilin-4, ataxin-1 interacting ubiquitin-like protein, A1Up, connexin43-interacting protein of 75 kDa, or CIP75), and mouse PLIC proteins. They are ubiquitin (Ub)-binding adaptor proteins involved in all protein degradation pathways through delivering ubiquitinated substrates to proteasomes. They also promote autophagy-dependent cell survival during nutrient starvation. PLIC-1 regulates the function of the thrombospondin receptor CD47 and G protein signaling. It plays a role in TLR4-mediated signaling through interacting with the Toll/interleukin-1 receptor (TIR) domain of TLR4. It also inhibits the TLR3-Trif antiviral pathway by reducing the abundance of Trif. Moreover, PLIC-1 binds to gamma-aminobutyric acid receptors (GABAARs) and modulates the Ub-dependent, proteasomal degradation of GABAARs. Furthermore, PLIC-1 acts as a molecular chaperone regulating amyloid precursor protein (APP) biosynthesis, trafficking, and degradation by stimulating K63-linked polyubiquitination of lysine 688 in the APP intracellular domain. In addition, PLIC-1 is involved in the protein aggregation-stress pathway via associating with the Ub-interacting motif (UIM) proteins ataxin 3, HSJ1a, and epidermal growth factor substrate 15 (EPS15). PLIC-2 is a protein that binds the ATPase domain of the HSP70-like Stch protein. It functions as a negative regulator of G protein-coupled receptor (GPCR) endocytosis. It also involved in amyotrophic lateral sclerosis (ALS)-related dementia. PLIC-3 is encoded by UbiquilinN3, a testis-specific gene. It shows high sequence similarity with the Xenopus protein XDRP1, a nuclear phosphoprotein that binds to the N-terminus of cyclin A and inhibits Ca2+-induced degradation of cyclin A, but not cyclin B. PLIC-4 is an ubiquitin-like (Ubl) nuclear protein that interacts with ataxin-1 and further links ataxin-1 with the chaperone and Ub-proteasome pathways. It also binds to the non-ubiquitinated gap junction protein connexin43 (Cx43) and regulates the turnover of Cx43 through the proteasomal pathway. PLIC proteins contain an N-terminal Ubl domain that is responsible for the binding of Ub-interacting motifs (UIMs) expressed by proteasomes and endocytic adaptors, and C-terminal Ub-associated (UBA) domain that interacts with Ub chains present on proteins destined for proteasomal degradation. In addition, mammalian PLIC2 proteins have an extra collagen-like motif region, which is absent in other PLIC proteins and the yeast Dsk2 protein.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1831677272  15 VEVDSDTSIFQLKEVVAKQQGVPADQLRVIFAGKELRNDLTVRSCDLDQQSIVHIVLR 72
Cdd:cd01808    16 FEVPEDSSVKEFKEEISKKFKAPVEQLVLIFAGKILKDQDTLSQHGIKDGLTVHLVIK 73

Rcat 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 Rcat domain of parkin that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

                          10        20
                  ....*....|....*....|.
gi 1831677272 409 ETIKKTSKPCPRCHVPVEKHG 429
Cdd:cd20357     1 ETIKKTTKPCPKCKVPTEKNG 21

ubiquitin; Provisional

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1831677272  18 DSDTSIFQLKEVVAKQQGVPADQLRVIFAGKELRNDLTVRSCDLDQQSIVHIVLR 72
Cdd:PTZ00044   18 EPDNTVQQVKMALQEKEGIDVKQIRLIYSGKQMSDDLKLSDYKVVPGSTIHMVLQ 72

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 1831677272   3 VFVRFNSSHGFPVEVDSDTSIFQLKEVVAKQQGVPADQLRVIFAGKELRNDLTVRSCDLDQQSIVHIV 70
Cdd:cd00196     1 VKVETPSLKKIVVAVPPSTTLRQVLEKVAKRIGLPPDVIRLLFNGQVLDDLMTAKQVGLEPGEELHFV 68

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 1831677272 330 VLCPSPGCGAGLLPEPSQRKVTCeggsgLGCGFVFCRDCKEPYHEGE 376
Cdd:cd20341     8 VYCPRPSCQTPVILEPDENLGIC-----PSCNYAFCTLCRETYHGVS 49

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
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1831677272   2 IVFVRFNSSHGFPVEVDSDTSIFQLKEVVAKQQGVPADQLRVIFAGKELRNDLTVRS 58
Cdd:cd16103     3 QIFVKFPDGTSKPYAINPEDTILDLKEKIEEQGGPPVEDQILLFQGQELRDKKSLKY 59

1-acyl-sn-glycerol-3-phosphate acyltransferases; This model describes the core homologous region of a collection of related proteins, several of which are known to act as 1-acyl-sn-glycerol-3-phosphate acyltransferases (EC 2.3.1.51). Proteins scoring above the trusted cutoff are likely to have the same general activity. However, there is variation among characterized members as to whether the acyl group can be donated by acyl carrier protein or coenzyme A, and in the length and saturation of the donated acyl group. 1-acyl-sn-glycerol-3-phosphate acyltransferase is also called 1-AGP acyltransferase, lysophosphatidic acid acyltransferase, and LPA acyltransferase. [Fatty acid and phospholipid metabolism, Biosynthesis]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831677272 531 IIHTDPRAYPKYGkeNAIVVLNHKFEIDFLcgwSLAERFGVlgGSKVLAKKELAYVPIIGWMWYFTEMVFCTRKWEQDRK 610
Cdd:TIGR00530   4 VEVVGPENLPAKS--PVLVVANHQSNLDPL---TLSAAFPP--PIVFIAKKELKWIPFFGIMLWLTGAIFIDRENIRAIA 76

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1831677272 611 TVSESLLH-LRDYPEKYFFLihcEGTRFTEKK----HQISMQVAQAKGLP 655
Cdd:TIGR00530  77 TALKAAIEvLKQGRSIGVFP---EGTRSRGRDilpfKKGAFHIAIKAGVP 123

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1831677272   3 VFVRFNSSHGFPVEVDSDTSIFQLKEVVAKQQGVPADQLRVIFAGKELRNDLTVRSCDLDQQSIVHIV 70
Cdd:cd16107     2 IFVRTYCGKTIVLHAKASDTVESLHQQIEARTGIPSLEQRLIFGGRQLQHSQSLESCKMENDATLFLV 69

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
                  ....*....|....*....|....*....|....*....|.
gi 1831677272  13 FPVEVDSDTSIFQLKEVVAKQQGVPADQLRVIFAGKELRND 53
Cdd:cd01796    14 FSLEVSPDMTLEDLKALCEAETGIPAAEQVLLHNGQPLTDD 54

Rcat 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 also may 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 functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain of RNF14 that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

                          10        20
                  ....*....|....*....|....
gi 1831677272 404 EHASKETIKKTSKPCPRCHVPVEK 427
Cdd:cd20354     2 EKLSEEWLEKNSKPCPGCGTLIEK 25