ATP-dependent Clp protease, ATP-binding subunit ClpA [Posttranslational modification, protein turnover, chaperones];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734317970 1276 RARMETISRFETFEvqvSSESRIEQLQGRIDELIRERNNLVKE---EIKEEKALMERQINEMKAKHlQQTRKMADEILRL 1352
Cdd:COG0542    401 RVRMEIDSKPEELD---ELERRLEQLEIEKEALKKEQDEASFErlaELRDELAELEEELEALKARW-EAEKELIEEIQEL 476

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1734317970 1353 KQQSAQLATARDELLRGISELDNNSQRSAPLNIPVPTAKE 1392
Cdd:COG0542    477 KEELEQRYGKIPELEKELAELEEELAELAPLLREEVTEED 516

Sine oculis-binding protein; SOBP is associated with syndromic and nonsyndromic intellectual disability. It carries a zinc-finger of the zf-C2H2 type at the N-terminus, and a highly characteriztic C-terminal PhPhPhPhPhPh motif. The deduced 873-amino acid protein contains an N-terminal nuclear localization signal (NLS), followed by 2 FCS-type zinc finger motifs, a proline-rich region (PR1), a putative RNA-binding motif region, and a C-terminal NLS embedded in a second proline-rich motif. SOBP is expressed in various human tissues, including developing mouse brain at embryonic day 14. In postnatal and adult mouse brain SOBP is expressed in all neurons, with intense staining in the limbic system. Highest expression is in layer V cortical neurons, hippocampus, pyriform cortex, dorsomedial nucleus of thalamus, amygdala, and hypothalamus. Postnatal expression of SOBP in the limbic system corresponds to a time of active synaptogenesis. the family is also referred to as Jackson circler, JXC1. In seven affected siblings from a consanguineous Israeli Arab family with mental retardation, anterior maxillary protrusion, and strabismus mutations were found in this protein.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734317970  316 LDADTSVNLsITTDgVHLMMCVDKAAQGVVVEATHVGE---SENTIEV--VEDAEKSFEILVCGQRRKVTPftprRKQDS 390
Cdd:pfam15279   60 KSAGSSAQL-ITPD-LWLSDCRRKSASPASTRSESVSPgpsSSASPSSspTSSNSSKPLISVASSSKLLAP----KPHEP 133

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734317970  391 SSGDEQPASESTSAFDIPE-HPPVIVPFRNAPIV-YSSQTSNIPQIHPplpppRFLAMPMQFSGH---PPPVIMGPPIIR 465
Cdd:pfam15279  134 PSLPPPPLPPKKGRRHRPGlHPPLGRPPGSPPMSmTPRGLLGKPQQHP-----PPSPLPAFMEPSsmpPPFLRPPPSIPQ 208

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734317970  466 PFGAPPPQFIPIQsnyGRPPQFP-PIGVVPIPIQRLPMQRMSGPPVMMSRGPVycSQPVPMHPMQQNVQNMQSSSRQDfG 544
Cdd:pfam15279  209 PNSPLSNPMLPGI---GPPPKPPrNLGPPSNPMHRPPFSPHHPPPPPTPPGPP--PGLPPPPPRGFTPPFGPPFPPVN-M 282

                          250       260
                   ....*....|....*....|.
gi 1734317970  545 MNERLLIRPNQKPLEITAPPV 565
Cdd:pfam15279  283 MPNPPEMNFGLPSLAPLVPPV 303

modified RING finger, H2 subclass (C3H2C2D-type), found in RING-box protein 1 (RBX1) and similar proteins; RBX1, also known as Hrt1, protein ZYP, RING finger protein 75 (RNF75), or regulator of cullins 1 (ROC1), is an E3 ubiquitin-protein ligase necessary for ubiquitin ligation activity of multimeric cullin (Cul)-RING E3 ligases (CRLs). RBX1-containing CRLs are involved in the NEDD8 pathway; RBX1 specifically regulates NEDD8ylation of Cul1-4. It can also bind and activate HIV-1 Vif-Cullin5 E3 ligase complex in vitro. Moreover, RBX1 is an essential element of Skp1/Cullin/F-box (SCF) E3-ubiquitin ligase complexes that target diverse proteins for proteasome-mediated degradation. It is a direct functional target of miR-194 and plays an important role in proliferation and migration of gastric cancer (GC) cells. RBX1 is also an essential component of KEAP1/CUL3/RBX1 E3-ubiquitin ligase complex that functions as a regulator of NFE2-related factor 2 (NRF2) and plays a key role in NRF2 pathway deregulation in multiple tumor types, including ovarian carcinomas (OVCA) and papillary thyroid carcinoma (PTC). Furthermore, RBX1 associates with DDB1, Cul4A, and Fbxw5 to form the Fbxw5-DDB1-Cul4A-Rbx1 complex that may function as a dual SUMO/ubiquitin ligase suppressing c-Myb activity through sumoylation or ubiquitination. RBX1 contains a C-terminal modified RING-H2 finger that is of C3H2C2D-type, rather than the canonical C3H2C3-type. The modified RING-H2 finger is essential for its ligase activity.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734317970 1551 DGCLIC-TEIIEEAVE-------------TVTCDTCTREYHYHCISRWLKINSVCPQCSR 1596
Cdd:cd16485      1 DNCAICrNHIMDLCIEcqanqasatseecTVAWGVCNHAFHFHCISRWLKTRQVCPLDNR 60

Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and is likely to be a general function of this domain; Various RING fingers exhibit binding activity towards E2 ubiquitin-conjugating enzymes (Ubc' s)

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|...
gi 1734317970  1553 CLICTEIIEEaveTVTCDTCTREYHYHCISRWLKINSV-CPQC 1594
Cdd:smart00184    1 CPICLEEYLK---DPVILPCGHTFCRSCIRKWLESGNNtCPIC 40

Component of SCF ubiquitin ligase and anaphase-promoting complex [Posttranslational modification, protein turnover, chaperones / Cell division and chromosome partitioning];

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1734317970 1551 DGCLICTEIIEEAVE-TVTCDTCTREYHYHCISRWLKINSVCPQCSR 1596
Cdd:COG5194     32 GTCPECQFGMTPGDEcPVVWGVCNHAFHDHCIYRWLDTKGVCPLDRQ 78

EBNA-3B; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734317970  375 QRRKVTPFTPRRKQDSSSGDEQPASESTsafdiPEHPPVIVPFRNAPIVYSSQTSNIPQIHPPLPPPRFLAMPMQFSGHP 454
Cdd:PHA03378   675 QPSPTGANTMLPIQWAPGTMQPPPRAPT-----PMRPPAAPPGRAQRPAAATGRARPPAAAPGRARPPAAAPGRARPPAA 749

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1734317970  455 PPVIMGPPIIRPFGAPPPQFIPiqsnyGRPPQFPPIGVVPIPIQR-----LPMQRMSGPPVMMSRGP 516
Cdd:PHA03378   750 APGRARPPAAAPGRARPPAAAP-----GAPTPQPPPQAPPAPQQRprgapTPQPPPQAGPTSMQLMP 811

Sine oculis-binding protein; SOBP is associated with syndromic and nonsyndromic intellectual disability. It carries a zinc-finger of the zf-C2H2 type at the N-terminus, and a highly characteriztic C-terminal PhPhPhPhPhPh motif. The deduced 873-amino acid protein contains an N-terminal nuclear localization signal (NLS), followed by 2 FCS-type zinc finger motifs, a proline-rich region (PR1), a putative RNA-binding motif region, and a C-terminal NLS embedded in a second proline-rich motif. SOBP is expressed in various human tissues, including developing mouse brain at embryonic day 14. In postnatal and adult mouse brain SOBP is expressed in all neurons, with intense staining in the limbic system. Highest expression is in layer V cortical neurons, hippocampus, pyriform cortex, dorsomedial nucleus of thalamus, amygdala, and hypothalamus. Postnatal expression of SOBP in the limbic system corresponds to a time of active synaptogenesis. the family is also referred to as Jackson circler, JXC1. In seven affected siblings from a consanguineous Israeli Arab family with mental retardation, anterior maxillary protrusion, and strabismus mutations were found in this protein.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734317970  316 LDADTSVNLsITTDgVHLMMCVDKAAQGVVVEATHVGE---SENTIEV--VEDAEKSFEILVCGQRRKVTPftprRKQDS 390
Cdd:pfam15279   60 KSAGSSAQL-ITPD-LWLSDCRRKSASPASTRSESVSPgpsSSASPSSspTSSNSSKPLISVASSSKLLAP----KPHEP 133

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734317970  391 SSGDEQPASESTSAFDIPE-HPPVIVPFRNAPIV-YSSQTSNIPQIHPplpppRFLAMPMQFSGH---PPPVIMGPPIIR 465
Cdd:pfam15279  134 PSLPPPPLPPKKGRRHRPGlHPPLGRPPGSPPMSmTPRGLLGKPQQHP-----PPSPLPAFMEPSsmpPPFLRPPPSIPQ 208

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734317970  466 PFGAPPPQFIPIQsnyGRPPQFP-PIGVVPIPIQRLPMQRMSGPPVMMSRGPVycSQPVPMHPMQQNVQNMQSSSRQDfG 544
Cdd:pfam15279  209 PNSPLSNPMLPGI---GPPPKPPrNLGPPSNPMHRPPFSPHHPPPPPTPPGPP--PGLPPPPPRGFTPPFGPPFPPVN-M 282

                          250       260
                   ....*....|....*....|.
gi 1734317970  545 MNERLLIRPNQKPLEITAPPV 565
Cdd:pfam15279  283 MPNPPEMNFGLPSLAPLVPPV 303

modified RING finger, H2 subclass (C3H2C2D-type), found in RING-box protein 1 (RBX1) and similar proteins; RBX1, also known as Hrt1, protein ZYP, RING finger protein 75 (RNF75), or regulator of cullins 1 (ROC1), is an E3 ubiquitin-protein ligase necessary for ubiquitin ligation activity of multimeric cullin (Cul)-RING E3 ligases (CRLs). RBX1-containing CRLs are involved in the NEDD8 pathway; RBX1 specifically regulates NEDD8ylation of Cul1-4. It can also bind and activate HIV-1 Vif-Cullin5 E3 ligase complex in vitro. Moreover, RBX1 is an essential element of Skp1/Cullin/F-box (SCF) E3-ubiquitin ligase complexes that target diverse proteins for proteasome-mediated degradation. It is a direct functional target of miR-194 and plays an important role in proliferation and migration of gastric cancer (GC) cells. RBX1 is also an essential component of KEAP1/CUL3/RBX1 E3-ubiquitin ligase complex that functions as a regulator of NFE2-related factor 2 (NRF2) and plays a key role in NRF2 pathway deregulation in multiple tumor types, including ovarian carcinomas (OVCA) and papillary thyroid carcinoma (PTC). Furthermore, RBX1 associates with DDB1, Cul4A, and Fbxw5 to form the Fbxw5-DDB1-Cul4A-Rbx1 complex that may function as a dual SUMO/ubiquitin ligase suppressing c-Myb activity through sumoylation or ubiquitination. RBX1 contains a C-terminal modified RING-H2 finger that is of C3H2C2D-type, rather than the canonical C3H2C3-type. The modified RING-H2 finger is essential for its ligase activity.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734317970 1551 DGCLIC-TEIIEEAVE-------------TVTCDTCTREYHYHCISRWLKINSVCPQCSR 1596
Cdd:cd16485      1 DNCAICrNHIMDLCIEcqanqasatseecTVAWGVCNHAFHFHCISRWLKTRQVCPLDNR 60

RING finger, H2 subclass, found in RING finger protein 12 (RNF12) and similar proteins; RNF12, also known as LIM domain-interacting RING finger protein or RING finger LIM domain-binding protein (R-LIM), is an E3 ubiquitin-protein ligase encoded by gene RLIM that is crucial for normal embryonic development in some species and for normal X inactivation in mice. It thus functions as a major sex-specific epigenetic regulator of female mouse nurturing tissues. RNF12 is widely expressed during embryogenesis, and mainly localizes to the cell nucleus, where it regulates the levels of many proteins, including CLIM, LMO, HDAC2, TRF1, SMAD7, and REX1, by proteasomal degradation. Its functional activity is regulated by phosphorylation-dependent nucleocytoplasmic shuttling. It is negatively regulated by pluripotency factors in embryonic stem cells. p53 represses its transcription through Sp1. RNF12 is the primary factor responsible for X chromosome inactivation (XCI) in female placental mammals. It is an indispensable factor in up-regulation of Xist transcription, thereby leading to initiation of random XCI. It also targets REX1, an inhibitor of XCI, for proteasomal degradation. RNF12 also acts as a co-regulator for a range of transcription factors, particularly those containing a LIM homeodomain, and modulates the formation of transcriptional multiprotein complexes. It is a negative regulator of Smad7, which in turn negatively regulates the signaling of type I receptors from the transforming growth factor beta (TGF-beta) superfamily. In addition, paternal RNF12 is a critical survival factor for milk-producing alveolar cells. RNF12 contains an nuclear localization signal (NLS) and a C3H2C3-type RING-H2 finger.

                           10        20
                   ....*....|....*....|....*..
gi 1734317970 1572 CTREYHYHCISRWLKINSVCPQCSRAL 1598
Cdd:cd16674     21 CSHEYHVHCIDRWLSENSTCPICRRAV 47

RING finger, H2 subclass, found in Arabidopsis thaliana RING-type E3 ubiquitin transferase BIG BROTHER (BB) and similar proteins; BB (also known as protein ENHANCER OF DA1-1 or EOD1) is an E3 ubiquitin-protein ligase that limits organ size, and possibly seed size, in a dose-dependent manner. It negatively regulates the duration of cell proliferation in leaves and petals independently of the major phytohormones (e.g. auxin, cytokinin, gibberellin, brassinosteroids, ethylene, abscisic acid, jasmonic acid), probably by targeting growth stimulators for degradation. It limits the proliferation of root meristematic cells. BB polyubiquitinates DA1. It is involved in the promotion of leaf senescence, in addition to its function in restricting plant growth. BB-related is an E3 ubiquitin-ligase probably involved in organ size regulation. Members of this subfamily contain a C3H2C3-type RING-H2 finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1734317970 1553 CLICTEIIEEAvETVTCDTCTREYHYHCISRWLKINSVCPQCS 1595
Cdd:cd23115      7 CVICRLEYEEG-EDLLTLPCKHCYHSECIQQWLQINKVCPVCS 48

H2 subclass of RING (RING-H2) fingers and its variants; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers: some have different Cys/His patterns while some lack a single Cys or His residue at typical Zn ligand positions (the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can indeed chelate Zn in a RING finger as well). This family corresponds to the H2 subclass of RING (RING-H2) finger proteins that are characterized by containing C3H2C3-type canonical RING-H2 fingers or noncanonical RING-H2 finger variants, including C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type modified RING-H2 fingers. The canonical RING-H2 finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-H-X2-C-X(4-48)-C-X2-C, X is any amino acid and the number of X residues varies in different fingers. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-H2 finger can be found in a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serves as a scaffold for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enables efficient transfer of ubiquitin from E2 to the substrates.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1734317970 1553 CLICTEIIEEAVETVTCdTCTREYHYHCISRWLK-INSVCPQC 1594
Cdd:cd16448      1 CVICLEEFEEGDVVRLL-PCGHVFHLACILRWLEsGNNTCPLC 42

RING finger, H2 subclass, found in E3 ubiquitin-protein ligase RNF6, RNF12, and similar proteins; RNF6 is an androgen receptor (AR)-associated protein that induces AR ubiquitination and promotes AR transcriptional activity. RNF6-induced ubiquitination may regulate AR transcriptional activity and specificity by modulating cofactor recruitment. RNF6 is overexpressed in hormone-refractory human prostate cancer tissues and required for prostate cancer cell growth under androgen-depleted conditions. RNF6 also regulates local serine/threonine kinase LIM kinase 1 (LIMK1) levels in axonal growth cones. RNF6-induced LIMK1 polyubiquitination is mediated via K48 of ubiquitin and leads to proteasomal degradation of the kinase. RNF6 binds and upregulates the Inha promoter, and functions as a transcription regulatory protein in the mouse sertoli cell. It acts as a potential tumor suppressor gene involved in the pathogenesis of esophageal squamous cell carcinoma (ESCC). RNF12, also known as LIM domain-interacting RING finger protein, or RING finger LIM domain-binding protein (R-LIM), is an E3 ubiquitin-protein ligase encoded by gene RLIM that is crucial for normal embryonic development in some species and for normal X inactivation in mice. It thus functions as a major sex-specific epigenetic regulator of female mouse nurturing tissues. RNF12 is widely expressed during embryogenesis, and mainly localizes to the cell nucleus, where it regulates the levels of many proteins, including CLIM, LMO, HDAC2, TRF1, SMAD7, and REX1, by proteasomal degradation. Both RNF6 and RNF12 contain a well conserved C3H2C3-type RING-H2 finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1734317970 1553 CLICTEIIEEAVETVTCdTCTREYHYHCISRWLKINSVCPQC 1594
Cdd:cd16467      2 CTICLGEYETGEKLRRL-PCSHEFHSECVDRWLKENSSCPIC 42

RING finger, H2 subclass, found in the PA-TM-RING ubiquitin ligase family; The PA-TM-RING family represents a group of transmembrane-type E3 ubiquitin ligases, which has been characterized by an N-terminal transient signal peptide, a PA (protease-associated) domain, a TM (transmembrane) domain, as well as a C-terminal C3H2C3-type RING-H2 finger domain. It includes RNF13, RNF167, ZNRF4 (zinc and RING finger 4), GRAIL (gene related to anergy in lymphocytes)/RNF128, RNF130, RNF133, RNF148, RNF149 and RNF150 (which are more closely related), as well as RNF43 and ZNRF3, which have substantially longer C-terminal tail extensions compared with the others. PA-TM-RING proteins are expressed at low levels in all mammalian tissues and species, but they are not present in yeast. They play a common regulatory role in intracellular trafficking/sorting, suggesting that abrogation of their function may result in dysregulation of cellular signaling events in cancer.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1734317970 1553 CLICTEIIEEAvETVTCDTCTREYHYHCISRWLKINSVCPQC 1594
Cdd:cd16454      2 CAICLEEFKEG-EKVRVLPCNHLFHKDCIDPWLEQHNTCPLC 42

PHD finger superfamily; The PHD finger superfamily includes a canonical plant homeodomain (PHD) finger typically characterized as Cys4HisCys3, and a non-canonical extended PHD finger, characterized as Cys2HisCys5HisCys2His. Variations include the RAG2 PHD finger characterized by Cys3His2Cys2His and the PHD finger 5 found in nuclear receptor-binding SET domain-containing proteins characterized by Cys4HisCys2His. The PHD finger is also termed LAP (leukemia-associated protein) motif or TTC (trithorax consensus) domain. Single or multiple copies of PHD fingers have been found in a variety of eukaryotic proteins involved in the control of gene transcription and chromatin dynamics. PHD fingers can recognize the unmodified and modified histone H3 tail, and some have been found to interact with non-histone proteins. They also function as epigenome readers controlling gene expression through molecular recruitment of multi-protein complexes of chromatin regulators and transcription factors. The PHD finger domain SF is structurally similar to the RING and FYVE_like superfamilies.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1734317970 1553 CLICTEIIEEAVETVTCDTCTREYHYHCISRWLKINS-----VCPQC 1594
Cdd:cd15489      2 CIVCGKGGDLGGELLQCDGCGKWFHADCLGPPLSSFVpngkwICPVC 48

RING finger, H2 subclass, found in E3 ubiquitin-protein ligase RNF6 and similar proteins; RNF6 is an androgen receptor (AR)-associated protein that induces AR ubiquitination and promotes AR transcriptional activity. RNF6-induced ubiquitination may regulate AR transcriptional activity and specificity by modulating cofactor recruitment. RNF6 is overexpressed in hormone-refractory human prostate cancer tissues and required for prostate cancer cell growth under androgen-depleted conditions. Moreover, RNF6 regulates local serine/threonine kinase LIM kinase 1 (LIMK1) levels in axonal growth cones. RNF6-induced LIMK1 polyubiquitination is mediated via K48 of ubiquitin and leads to proteasomal degradation of the kinase. RNF6 also binds and upregulates the Inha promoter, and functions as a transcription regulatory protein in the mouse sertoli cell. RNF6 also acts as a potential tumor suppressor gene involved in the pathogenesis of esophageal squamous cell carcinoma (ESCC). RNF6 contains an N-terminal coiled-coil domain, a Lys-X-X-Leu/Ile-X-X-Leu/Ile (KIL) motif, and a C-terminal C3H2C3-type RING-H2 finger which is responsible for its ubiquitin ligase activity. The KIL motif is present in a subset of RING-H2 proteins from organisms as evolutionarily diverse as human, mouse, chicken, Drosophila, Caenorhabditis elegans, and Arabidopsis thaliana.

                           10        20
                   ....*....|....*....|...
gi 1734317970 1572 CTREYHYHCISRWLKINSVCPQC 1594
Cdd:cd16673     21 CAHEFHIHCIDRWLSENSTCPIC 43

RING finger, H2 subclass, found in Arabidopsis thaliana MED25-binding RING-H2 protein (MBR) and similar proteins; This subfamily includes MBR1 and MBR2 (also called HAL3-interacting protein 1 or AtHIP1). They are E3 ubiquitin-protein ligases that function as regulators of MED25 stability by targeting MED25 for degradation in a RING-H2-dependent manner. Proteasome-dependent degradation of MED25 seems to activate its function as a positive regulator of FLOWERING LOCUS T (FT) and is important to induce the expression of FT, and consequently to promote flowering. MBR2 may also function downstream of HAL3 and be required for HAL3-regulated plant growth. Activation of MBR2 by HAL3 may lead to the degradation of cell cycle suppressors, resulting in enhancement of cell division and plant growth. Both MBR1 and MBR2 contain a C3H2C3-type RING-H2 finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1734317970 1553 CLICTEIIEEAVETVTCDtCTREYHYHCISRWLKINSVCPQC 1594
Cdd:cd23113      5 CCICQEEYEEGDELGTIE-CGHEYHSDCIKQWLVQKNLCPIC 45

RING finger, H2 subclass, found in Tetratricopeptide repeat protein 3 (TTC3) and similar proteins; TTC3, also known as protein DCRR1, TPR repeat protein D, TPR repeat protein 3, or RING finger protein 105 (RNF105), is an E3 ubiquitin-protein ligase encoded by a gene within the Down syndrome (DS) critical region on chromosome 21. It affects differentiation and Golgi compactness in neurons through specific actin-regulating pathways. It inhibits the neuronal-like differentiation of pheocromocytoma cells by activating RhoA and by binding to Citron proteins. TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. It contains four N-terminal TPR motifs, a potential coiled-coil region and a Citron binding region in the central part, and a C-terminal C3H2C2-type RING-H2 finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1734317970 1553 CLICTEIIEEavETVTCDTCTREYHYHCISRWLKINSVCPQC 1594
Cdd:cd16481      2 CIICHDDLKP--DQLAKLECGHIFHKECIKQWLKEQSTCPTC 41

Component of SCF ubiquitin ligase and anaphase-promoting complex [Posttranslational modification, protein turnover, chaperones / Cell division and chromosome partitioning];

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1734317970 1551 DGCLICTEIIEEAVE-TVTCDTCTREYHYHCISRWLKINSVCPQCSR 1596
Cdd:COG5194     32 GTCPECQFGMTPGDEcPVVWGVCNHAFHDHCIYRWLDTKGVCPLDRQ 78

RING finger, H2 subclass, found in RING finger protein 122 (RNF122) and similar proteins; RNF122 is a RING finger protein associated with HEK 293T cell viability. It is localized to the endoplasmic reticulum (ER) and the Golgi apparatus, and overexpressed in anaplastic thyroid cancer cells. RNF122 functions as an E3 ubiquitin ligase that can ubiquitinate itself and undergo degradation through its RING finger in a proteasome-dependent manner. It interacts with calcium-modulating cyclophilin ligand (CAML), which is not a substrate, but a stabilizer of RNF122. RNF122 contains an N-terminal transmembrane domain and a C-terminal C3H2C3-type RING-H2 finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1734317970 1553 CLICTEIIEEAVETVTCdTCTREYHYHCISRWLKINSVCPQCSRAL 1598
Cdd:cd16676      3 CAVCLEDFKTKDELGVL-PCQHAFHRKCLVKWLEIRCVCPMCNKPI 47

RING finger, H2 subclass, found in RING finger proteins RNF111, RNF165, and similar proteins; The family includes RING finger proteins RNF111, RNF165, and similar proteins. RNF111, also known as Arkadia, is a nuclear E3 ubiquitin-protein ligase that targets intracellular effectors and modulators of transforming growth factor beta (TGF-beta)/Nodal-related signaling for polyubiquitination and proteasome-dependent degradation. It also interacts with the clathrin-adaptor 2 (AP2) complex and regulates endocytosis of certain cell surface receptors, leading to modulation of epidermal growth factor (EGF) and possibly other signaling pathways. The N-terminal half of RNF111 harbors three SUMO-interacting motifs (SIMs). It thus functions as a SUMO-targeted ubiquitin ligase (STUbL) that directly links nonproteolytic ubiquitylation and SUMOylation in the DNA damage response, as well as triggers degradation of signal-induced polysumoylated proteins, such as the promyelocytic leukemia protein (PML). RNF165, also known as Arkadia-like 2, Arkadia2, or Ark2C, is an E3 ubiquitin ligase with homology to the C-terminal half of RNF111. It is expressed specifically in the nervous system, and can serve to amplify neuronal responses to specific signals. It acts as a positive regulator of bone morphogenetic protein (BMP)-Smad signaling that is involved in motor neuron (MN) axon elongation. Both RNF165 and RNF111 contain a C-terminal C3H2C3-type RING-H2 finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1734317970 1553 CLICTEIIEEAvETVTCDTCTREYHYHCISRWLKINSVCPQC 1594
Cdd:cd16474      3 CTICLSDFEEG-EDVRRLPCMHLFHQECVDQWLSTNKRCPIC 43

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734317970 1184 DLEKEVIRQ---LKRDnitfaefikSEDAREmHQFLADTFKKMDLKYFAF---------------ILEKAMVESREQSWK 1245
Cdd:COG1196    193 DILGELERQlepLERQ---------AEKAER-YRELKEELKELEAELLLLklreleaeleeleaeLEELEAELEELEAEL 262

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734317970 1246 DTIQLRLA-AEEAHLQLDLARGQFKKEFGDLRARMETISRFETFEVQ--VSSESRIEQLQGRIDELIRERNNLVKE---- 1318
Cdd:COG1196    263 AELEAELEeLRLELEELELELEEAQAEEYELLAELARLEQDIARLEErrRELEERLEELEEELAELEEELEELEEEleel 342

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1734317970 1319 -----EIKEEKALMERQINEMKAKHLQQTRKMADEILRLKQQSAQLATARDELLRGISELDNNSQR 1379
Cdd:COG1196    343 eeeleEAEEELEEAEAELAEAEEALLEAEAELAEAEEELEELAEELLEALRAAAELAAQLEELEEA 408

Myosin tail; The myosin molecule is a multi-subunit complex made up of two heavy chains and four light chains it is a fundamental contractile protein found in all eukaryote cell types. This family consists of the coiled-coil myosin heavy chain tail region. The coiled-coil is composed of the tail from two molecules of myosin. These can then assemble into the macromolecular thick filament. The coiled-coil region provides the structural backbone the thick filament.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734317970 1246 DTIQLRLAAEEAHLQ-LDLARGQFKKEFGDLRAR---METISRfETFEVQVSS-ESRIEQLQGRIDELIRERNNLVKEEI 1320
Cdd:pfam01576  920 EQLTTELAAERSTSQkSESARQQLERQNKELKAKlqeMEGTVK-SKFKSSIAAlEAKIAQLEEQLEQESRERQAANKLVR 998

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734317970 1321 KEEKALMERQIN-EMKAKHLQQTRKMADEI-LRLKQQSAQLATARDELLRGIS-------ELDNNSQRSAPLNIPVPTAK 1391
Cdd:pfam01576  999 RTEKKLKEVLLQvEDERRHADQYKDQAEKGnSRMKQLKRQLEEAEEEASRANAarrklqrELDDATESNESMNREVSTLK 1078

RING finger, H2 subclass, found in RING finger proteins RNF24, RNF122, and similar proteins; This subfamily includes RNF24, RNF122, and similar proteins. RNF24 is an intrinsic membrane protein localized in the Golgi apparatus. It specifically interacts with the ankyrin-repeats domains (ARDs) of TRPC1, -3, -4, -5, -6, and -7, and affects TRPC intracellular trafficking without affecting their activity. RNF122 is a RING finger protein associated with HEK 293T cell viability. It is localized to the endoplasmic reticulum (ER) and the Golgi apparatus, and overexpressed in anaplastic thyroid cancer cells. RNF122 functions as an E3 ubiquitin ligase that can ubiquitinate itself and undergo degradation through its RING finger in a proteasome-dependent manner. Both RNF24 and RNF122 contain an N-terminal transmembrane domain and a C-terminal C3H2C3-type RING-H2 finger.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1734317970 1551 DGCLICTE--IIEEAVETVTCDtctREYHYHCISRWLKINSVCPQCSRAL 1598
Cdd:cd16469      1 DTCAVCLEefKLKEELGVCPCG---HAFHTKCLKKWLEVRNSCPICKSPV 47

EBNA-3B; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734317970  375 QRRKVTPFTPRRKQDSSSGDEQPASESTsafdiPEHPPVIVPFRNAPIVYSSQTSNIPQIHPPLPPPRFLAMPMQFSGHP 454
Cdd:PHA03378   675 QPSPTGANTMLPIQWAPGTMQPPPRAPT-----PMRPPAAPPGRAQRPAAATGRARPPAAAPGRARPPAAAPGRARPPAA 749

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1734317970  455 PPVIMGPPIIRPFGAPPPQFIPiqsnyGRPPQFPPIGVVPIPIQR-----LPMQRMSGPPVMMSRGP 516
Cdd:PHA03378   750 APGRARPPAAAPGRARPPAAAP-----GAPTPQPPPQAPPAPQQRprgapTPQPPPQAGPTSMQLMP 811

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734317970 1232 LEKAMVESREQ---------SWKDTIQLRLAAEEAHLQLDLARGQF-KKEFGDLRARMETI-SRFETFEVQVSS-ESRIE 1299
Cdd:COG4913    240 AHEALEDAREQiellepireLAERYAAARERLAELEYLRAALRLWFaQRRLELLEAELEELrAELARLEAELERlEARLD 319

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734317970 1300 QLQGRIDELIRERNNL---VKEEIKEEKALMERQINEMKAKHLQQTRKM----------ADEILRLKQQSAQLATARDEL 1366
Cdd:COG4913    320 ALREELDELEAQIRGNggdRLEQLEREIERLERELEERERRRARLEALLaalglplpasAEEFAALRAEAAALLEALEEE 399

                   ....*.
gi 1734317970 1367 LRGISE 1372
Cdd:COG4913    400 LEALEE 405

RING finger, HC subclass, found in RING finger protein 8 (RNF8) and similar proteins; RNF8 is a telomere-associated E3 ubiquitin-protein ligase that plays an important role in DNA double-strand break (DSB) repair via histone ubiquitination. It is localized in the nucleus and interacts with class III E2s (UBE2E2, UbcH6, and UBE2E3), but not with other E2s (UbcH5, UbcH7, UbcH10, hCdc34, and hBendless). It recruits UBC13 for lysine 63-based self polyubiquitylation. Its deficiency causes neuronal pathology and cognitive decline, and its loss results in neuron degeneration. RNF8, together with RNF168, catalyzes a series of ubiquitylation events on substrates such as H2A and H2AX, with the H2AK13/15 ubiquitylation being particularly important for recruitment of repair factors p53-binding protein 1 (53BP1) or the RAP80-BRCA1 complex to sites of DSBs. RNF8 mediates the ubiquitination of gammaH2AX, and recruits 53BP1 and BRCA1 to DNA damage sites which promotes DNA damage response (DDR) and inhibits chromosomal instability. Moreover, RNF8 interacts with retinoid X receptor alpha (RXR alpha) and enhances its transcription-stimulating activity. It also regulates the rate of exit from mitosis and cytokinesis. RNF8 contains an N-terminal forkhead-associated (FHA) domain and a C-terminal C3HC4-type RING-HC finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1734317970 1553 CLICTEIIeeaVETVTCDtCTREYHYHCISRWLKINSVCPQCSRALK 1599
Cdd:cd16535      4 CSICSELF---IEAVTLN-CSHSFCSYCITEWMKRKKECPICRKPIT 46

RING finger, H2 subclass, found in RING-box protein 2 (RBX2) and similar proteins; RBX2, also known as CKII beta-binding protein 1 (CKBBP1), RING finger protein 7 (RNF7), regulator of cullins 2 (ROC2), or sensitive to apoptosis gene protein (SAG), is an E3 ubiquitin-protein ligase that protects cells from apoptosis, confers radioresistance, and plays an essential and non-redundant role in embryogenesis and vasculogenesis. It promotes ubiquitination and degradation of a number of protein substrates, including c-JUN, DEPTOR, HIF-1alpha, IkappaBalpha, NF1, NOXA, p27, and procaspase-3, thus regulating various signaling pathways and biological processes. RBX2 is necessary for ubiquitin ligation activity of the multimeric cullin (Cul)-RING E3 ligases (CRLs). RBX2-containing CRLs are involved in the NEDD8 pathway and RBX2 specifically regulates NEDD8ylation of Cul5. It can bind and activate the HIV-1 Vif-Cullin5 E3 ligase complex in vitro. It is also a substrate of NEDD4-1 E3 ubiquitin ligase and mediates NEDD4-1 induced chemosensitization. The inactivation of RBX2 E3 ubiquitin ligase activity triggers senescence and inhibits Kras-induced immortalization. Endothelial deletion of RBX2 causes embryonic lethality and blocks tumor angiogenesis, and may have potential use in anti-angiogenesis therapy of human cancers. Moreover, as a component of the Cullin 5-RING E3 ubiquitin ligase (CRL5) complex, RBX2 regulates neuronal migration through different CRL5 adaptors, such as SOCS7. RBX2 also functions as a redox inducible antioxidant protein that scavenges oxygen radicals by forming inter- and intra-molecular disulfide bonds when acting alone. It contains a C-terminal C3H2C3-type RING-H2 finger that is essential for its ligase activity.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1734317970 1551 DGCLICTEIIEEAVETVTCDTCTREYHYHCISRWLKINSVCPQCSR 1596
Cdd:cd16466     13 DACLRCQAENKQEDCVVVWGECNHSFHNCCMSLWVKQNNRCPLCQQ 58

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734317970 1182 IWDLEKEVIRQLKRDNITFAEFIKSEDAREMHQFLADtfkkmdlKYFAFILEKAMVESREQSWKDTIQLRLAAEEAHLQL 1261
Cdd:COG4717    291 LLLAREKASLGKEAEELQALPALEELEEEELEELLAA-------LGLPPDLSPEELLELLDRIEELQELLREAEELEEEL 363

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734317970 1262 DLArgQFKKEFGDLRARM------ETISRFETFEVQVSSESRIEQLQGRIDELIRERNNLV----KEEIKEEKALMERQI 1331
Cdd:COG4717    364 QLE--ELEQEIAALLAEAgvedeeELRAALEQAEEYQELKEELEELEEQLEELLGELEELLealdEEELEEELEELEEEL 441

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|
gi 1734317970 1332 NEMKAKHLQQTRKMADEILRLKQ--QSAQLATARDELLRGISELDNNSQR 1379
Cdd:COG4717    442 EELEEELEELREELAELEAELEQleEDGELAELLQELEELKAELRELAEE 491

RING finger, H2 subclass, found in RING finger protein 24 (RNF24) and similar proteins; RNF24 is an intrinsic membrane protein localized in the Golgi apparatus. It specifically interacts with the ankyrin-repeats domains (ARDs) of TRPC1, -3, -4, -5, -6, and -7, and affects TRPC intracellular trafficking without affecting their activity. RNF24 contains an N-terminal transmembrane domain and a C-terminal C3H2C3-type RING-H2 finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1734317970 1553 CLICTEIIEEAVETVTCdTCTREYHYHCISRWLKINSVCPQCS 1595
Cdd:cd16675      3 CAVCLEEFKPKDELGIC-PCKHAFHRKCLIKWLEVRKVCPLCN 44

RING finger, H2 subclass, found in RING finger protein 44 (RNF44) and similar proteins; RNF44 is an uncharacterized RING finger protein that shows high sequence similarity with RNF38, which is a nuclear E3 ubiquitin protein ligase that plays a role in regulating p53. RNF44 contains a coiled-coil motif, a KIL motif (Lys-X2-Ile/Leu-X2-Ile/Leu, X can be any amino acid), and a C3H2C2-type RING-H2 finger.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1734317970 1553 CLICTEIIEeAVETVTCDTCTREYHYHCISRWLKINSVCPQCsRAlkDPNEYP 1605
Cdd:cd16680     10 CVVCFSDFE-SRQLLRVLPCNHEFHTKCVDKWLKTNRTCPIC-RA--DASEVH 58

Variant RING finger, HC subclass (C4C4-type), found in retinoblastoma-binding protein 6 (RBBP6) and similar proteins; RBBP6, also known as proliferation potential-related protein, protein P2P-R, retinoblastoma-binding Q protein 1 (RBQ-1), or p53-associated cellular protein of testis (PACT), is a nuclear E3 ubiquitin-protein ligase involved in multiple processes, such as the control of gene expression, mitosis, cell differentiation, and cell apoptosis. It plays a role in both promoting and inhibiting apoptosis in many human cancers, including esophageal, lung, hepatocellular, and colon cancers, familial myeloproliferative neoplasms, as well as in human immunodeficiency virus-associated nephropathy (HIVAN). It functions as an Rb- and p53-binding protein that plays an important role in chaperone-mediated ubiquitination and possibly in protein quality control. It acts as a scaffold protein to promote the assembly of the p53/TP53-MDM2 complex, resulting in an increase of MDM2-mediated ubiquitination and degradation of p53/TP53, and leading to both apoptosis and cell growth. It is also a double-stranded RNA-binding protein that plays a role in mRNA processing by regulating the human polyadenylation machinery and modulating expression of mRNAs with AU-rich 3' untranslated regions (UTRs). Moreover, RBBP6 ubiquitinates and destabilizes the transcriptional repressor ZBTB38 that negatively regulates transcription and levels of the MCM10 replication factor on chromatin. Furthermore, RBBP6 is involved in tunicamycin-induced apoptosis by mediating protein kinase (PKR) activation. RBBP6 contains an N-terminal ubiquitin-like domain and a C4C4-type RING finger, whose overall folding is similar to that of the typical C3HC4-type RING-HC finger. RBBP6 interacts with chaperones Hsp70 and Hsp40 through its N-terminal ubiquitin-like domain. It promotes the ubiquitination of p53 by Hdm2 in an E4-like manner through its RING finger. It also interacts directly with the pro-proliferative transcription factor Y-box-binding protein-1 (YB-1) via its RING finger.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1734317970 1552 GCLICTEIIEEAVeTVTCdtCTREYHYHCI-SRWLKINSVCPQCSRALKDP 1601
Cdd:cd16620      5 KCPICKDLMKDAV-LTPC--CGNSFCDECIrTALLEEDFTCPTCKEPDVSP 52

Zinc finger, C3HC4 type (RING finger);

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1734317970 1553 CLICTEIIEEAVETVTCdtcTREYHYHCISRWLKINSVCPQC 1594
Cdd:pfam13923    2 CPICMDMLKDPSTTTPC---GHVFCQDCILRALEASNECPLC 40