N-terminal helicase domain of the DEAD-box helicase superfamily; The DEAD-like helicase superfamily is a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. The N-terminal domain contains the ATP-binding region.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469924198  376 AQGLLSEEMGLGKTIEILSLILLNKRNSRVTGP---------------SKSNLHKAKTTLIVCPDSILNQWIDEIEDHsY 440
Cdd:cd18070     15 PGGILADEMGLGKTVEVLALILLHPRPDNDLDAadddsdemvccpdclVAETPVSSKATLIVCPSAILAQWLDEINRH-V 93

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469924198  441 NNTLSIYHYPGFKqlsrtfdKDKLSANDISLKLLEYDIIITSYSVLSSEVHYTnfathrnrnvhnysDTVKTNDKKRHDI 520
Cdd:cd18070     94 PSSLKVLTYQGVK-------KDGALASPAPEILAEYDIVVTTYDVLRTELHYA--------------EANRSNRRRRRQK 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469924198  521 KY-DYSSPLALINFWRIVLDEVQMLgRSLTGNIIRCCNEISRVHTWGSSGTPVSTitkvthignndranaGAGtiakDLA 599
Cdd:cd18070    153 RYeAPPSPLVLVEWWRVCLDEAQMV-ESSTSKAAEMARRLPRVNRWCVSGTPIQR---------------GLD----DLF 212

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|..
gi 1469924198  600 MILSYLQFNPFMDSPNLINKMLKLQY------PICAELTQFF 635
Cdd:cd18070    213 GLLSFLGVEPFCDSDWWARVLIRPQGrnkarePLAALLKELL 254

C-terminal helicase domain of the SNF family helicases; The Sucrose Non-Fermenting (SNF) family includes chromatin-remodeling factors, such as CHD proteins and SMARCA proteins, recombination proteins Rad54, and many others. They are DEAD-like helicases belonging to superfamily (SF)2, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. Similar to SF1 helicases, SF2 helicases do not form toroidal structures like SF3-6 helicases. Their helicase core consists of two similar protein domains that resemble the fold of the recombination protein RecA. This model describes the C-terminal domain, also called HelicC.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469924198 1385 TKLDAIVKMVTYLLLNYEnntctadgnipppQILIYSHNVTFLDCLSHILSFNSINHRNV-SAVSSKVFNKLVELFRKDS 1463
Cdd:cd18793     11 GKLEALLELLEELREPGE-------------KVLIFSQFTDTLDILEEALRERGIKYLRLdGSTSSKERQKLVDRFNEDP 77

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1469924198 1464 TISCLLLDSKRQVSGLTLVNATNIFLVEPILNRSDELQAINRVSRFGQKYNTFVWQFM 1521
Cdd:cd18793     78 DIRVFLLSTKAGGVGLNLTAANRVILYDPWWNPAVEEQAIDRAHRIGQKKPVVVYRLI 135

RING-finger-containing E3 ubiquitin ligase [Posttranslational modification, protein turnover, chaperones];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469924198 1153 ATESDFETyLFSYSKELPA-LMQDVQK---------LKNYIKSLNTVYnAKVEYYKHLQKISDSLVSIVELDERMQAKIK 1222
Cdd:COG5574     87 DSLSRFNR-EETLSIEYSReTNIDKEGevlypcgifFCIGCDYIWSID-LKQTANTHEASPSQLLKFLPTIRLAMNIPEV 164

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469924198 1223 MNVKKSDEIVKKNTTKINNLRARCKYLNTLQKIKTEITDNGKK--------FKCSICFGSIKLGAILKCGHFFCQECAES 1294
Cdd:COG5574    165 ISDLTAVALSLDESRLQPILQPSNNLHTLFQVITKENLSKKNGlpfipladYKCFLCLEEPEVPSCTPCGHLFCLSCLLI 244

                          170       180
                   ....*....|....*....|..
gi 1469924198 1295 WLRHHST--CPMCKQTTVLEEI 1314
Cdd:COG5574    245 SWTKKKYefCPLCRAKVYPKKV 266

DEXQ-box helicase domain of SHPRH; E3 ubiquitin-protein ligase SHPRH is a ubiquitously expressed protein that contains motifs characteristic of several DNA repair proteins, transcription factors, and helicases. SHPRH is a functional homolog of S. cerevisiae RAD5 and is involved in DNA repair. SHPRH is a member of the DEAD-like helicase superfamily, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. This domain contains the ATP-binding region.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469924198  376 AQGLLSEEMGLGKTIEILSLILLNKRNSRVTGP---------------SKSNLHKAKTTLIVCPDSILNQWIDEIEDHsY 440
Cdd:cd18070     15 PGGILADEMGLGKTVEVLALILLHPRPDNDLDAadddsdemvccpdclVAETPVSSKATLIVCPSAILAQWLDEINRH-V 93

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469924198  441 NNTLSIYHYPGFKqlsrtfdKDKLSANDISLKLLEYDIIITSYSVLSSEVHYTnfathrnrnvhnysDTVKTNDKKRHDI 520
Cdd:cd18070     94 PSSLKVLTYQGVK-------KDGALASPAPEILAEYDIVVTTYDVLRTELHYA--------------EANRSNRRRRRQK 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469924198  521 KY-DYSSPLALINFWRIVLDEVQMLgRSLTGNIIRCCNEISRVHTWGSSGTPVSTitkvthignndranaGAGtiakDLA 599
Cdd:cd18070    153 RYeAPPSPLVLVEWWRVCLDEAQMV-ESSTSKAAEMARRLPRVNRWCVSGTPIQR---------------GLD----DLF 212

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|..
gi 1469924198  600 MILSYLQFNPFMDSPNLINKMLKLQY------PICAELTQFF 635
Cdd:cd18070    213 GLLSFLGVEPFCDSDWWARVLIRPQGrnkarePLAALLKELL 254

SNF2-related domain; This domain is found in proteins involved in a variety of processes including transcription regulation (e.g., SNF2, STH1, brahma, MOT1), DNA repair (e.g., ERCC6, RAD16, RAD5), DNA recombination (e.g., RAD54), and chromatin unwinding (e.g., ISWI) as well as a variety of other proteins with little functional information (e.g., lodestar, ETL1). SNF2 functions as the ATPase component of the SNF2/SWI multisubunit complex, which utilizes energy derived from ATP hydrolysis to disrupt histone-DNA interactions, resulting in the increased accessibility of DNA to transcription factors.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469924198  369 DAEVPHGaqGLLSEEMGLGKTIEILSLILLNKRNSRVTGpsksnlhkaKTTLIVCPDSILNQWIDEIEDHSYNNTLSIYH 448
Cdd:pfam00176   13 ENNLGRG--GILADEMGLGKTLQTISLLLYLKHVDKNWG---------GPTLIVVPLSLLHNWMNEFERWVSPPALRVVV 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469924198  449 YPGFKQLSRTFDKDKLSANDislklleYDIIITSYSVLSSevhytnfathrnrnvhnysdtvktndkkrhdikydYSSPL 528
Cdd:pfam00176   82 LHGNKRPQERWKNDPNFLAD-------FDVVITTYETLRK-----------------------------------HKELL 119

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469924198  529 ALINFWRIVLDEVQMLgRSLTGNIIRCCNEISRVHTWGSSGTPvstitkvthIGNNdranagagtiAKDLAMILSYLQFN 608
Cdd:pfam00176  120 KKVHWHRIVLDEGHRL-KNSKSKLSKALKSLKTRNRWILTGTP---------LQNN----------LEELWALLNFLRPG 179

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469924198  609 PF---------MDSPNLINKMLKLQYPIcAELTQFFIdndlcIRHTKLNVSdqINIPKQYQYLIPLALGPIEQDHYTScw 679
Cdd:pfam00176  180 PFgslstfrnwFDRPIERGGGKKGVSRL-HKLLKPFL-----LRRTKKDVE--KSLPPKVEYILFCRLSKLQRKLYQT-- 249

                          330       340       350
                   ....*....|....*....|....*....|....
gi 1469924198  680 tkFLNEAGYD--NNGNSTRSNSNDQMVDLMTMNK 711
Cdd:pfam00176  250 --FLLKKDLNaiKTGEGGREIKASLLNILMRLRK 281

Ring finger domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1469924198 1268 CSICFGSIKLGA---ILKCGHFFCQECAESWLRHHSTCPMCK 1306
Cdd:pfam13639    3 CPICLEEFEEGDkvvVLPCGHHFHRECLDKWLRSSNTCPLCR 44

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 1469924198  1268 CSICFG-SIKLGAILKCGHFFCQECAESWLR-HHSTCPMC 1305
Cdd:smart00184    1 CPICLEeYLKDPVILPCGHTFCRSCIRKWLEsGNNTCPIC 40

DEAD-like helicases superfamily;

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469924198   378 GLLSEEMGLGKTIEILSLILLNKRNsrvtgpsksnlHKAKTTLIVCPDSIL-NQWIDEIED---HSYNNTLSIYHypgfk 453
Cdd:smart00487   27 VILAAPTGSGKTLAALLPALEALKR-----------GKGGRVLVLVPTRELaEQWAEELKKlgpSLGLKVVGLYG----- 90

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469924198   454 QLSRTFDKDKLSANDislklleYDIIITSYSVLssevhytnfathrnrnvhnysdtvktndkkRHDIKydySSPLALINF 533
Cdd:smart00487   91 GDSKREQLRKLESGK-------TDILVTTPGRL------------------------------LDLLE---NDKLSLSNV 130

                           170       180       190       200       210
                    ....*....|....*....|....*....|....*....|....*....|....
gi 1469924198   534 WRIVLDEVQ-MLGRSLTGNIIRCCNEISR-VHTWGSSGTPVSTITKVTHIGNND 585
Cdd:smart00487  131 DLVILDEAHrLLDGGFGDQLEKLLKLLPKnVQLLLLSATPPEEIENLLELFLND 184

DNA repair protein rad18; All proteins in this family for which functions are known are involved in nucleotide excision repair.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 1469924198 1266 FKCSICFGSIKLGAILKCGHFFCQECAESWLRHHSTCPMCKQT---------TVLEEI---YK------FKFQVEEKCNN 1327
Cdd:TIGR00599   27 LRCHICKDFFDVPVLTSCSHTFCSLCIRRCLSNQPKCPLCRAEdqesklrsnWLVSEIvesFKnlrpslLEFLRIPKTTP 106

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1469924198 1328 SIADNLNGQSRELHDRPNAENTLDNSNAKSQD 1359
Cdd:TIGR00599  107 VENPDLAGPENSSKIELIEESESDGVDAEDED 138

RING-finger-containing E3 ubiquitin ligase [Signal transduction mechanisms];

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1469924198 1235 NTTKINNLrarcKYLNTLqkikteitdngkkFKCSICFGSIKLGAILKCGHFFCQECAESWLRHHSTCPMCK 1306
Cdd:COG5432     12 NQTKIPSL----KGLDSM-------------LRCRICDCRISIPCETTCGHTFCSLCIRRHLGTQPFCPVCR 66

DEXQ-box helicase domain of SHPRH; E3 ubiquitin-protein ligase SHPRH is a ubiquitously expressed protein that contains motifs characteristic of several DNA repair proteins, transcription factors, and helicases. SHPRH is a functional homolog of S. cerevisiae RAD5 and is involved in DNA repair. SHPRH is a member of the DEAD-like helicase superfamily, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. This domain contains the ATP-binding region.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469924198  376 AQGLLSEEMGLGKTIEILSLILLNKRNSRVTGP---------------SKSNLHKAKTTLIVCPDSILNQWIDEIEDHsY 440
Cdd:cd18070     15 PGGILADEMGLGKTVEVLALILLHPRPDNDLDAadddsdemvccpdclVAETPVSSKATLIVCPSAILAQWLDEINRH-V 93

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469924198  441 NNTLSIYHYPGFKqlsrtfdKDKLSANDISLKLLEYDIIITSYSVLSSEVHYTnfathrnrnvhnysDTVKTNDKKRHDI 520
Cdd:cd18070     94 PSSLKVLTYQGVK-------KDGALASPAPEILAEYDIVVTTYDVLRTELHYA--------------EANRSNRRRRRQK 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469924198  521 KY-DYSSPLALINFWRIVLDEVQMLgRSLTGNIIRCCNEISRVHTWGSSGTPVSTitkvthignndranaGAGtiakDLA 599
Cdd:cd18070    153 RYeAPPSPLVLVEWWRVCLDEAQMV-ESSTSKAAEMARRLPRVNRWCVSGTPIQR---------------GLD----DLF 212

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|..
gi 1469924198  600 MILSYLQFNPFMDSPNLINKMLKLQY------PICAELTQFF 635
Cdd:cd18070    213 GLLSFLGVEPFCDSDWWARVLIRPQGrnkarePLAALLKELL 254

RING finger, HC subclass, found in Saccharomyces cerevisiae increased recombination centers protein 20 (IRC20) and similar proteins; IRC20 is an uncharacterized ATP-dependent helicase that is probably involved in a pathway contributing to genomic integrity. IRC20 contains a typical C3HC4-type RING-HC finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1469924198 1263 GKKFKCSICFGSIKLGAILKCGHFFCQECAESWLRHHSTCPMCK 1306
Cdd:cd23135      1 KQKLSCSICFSEIRSGAILKCGHFFCLSCIASWLREKSTCPLCK 44

DEAH-box helicase domain of TTF2; Transcription termination factor 2 (TTF2 also called Forkhead-box E1/FOXE1 ) is a transcription termination factor that couples ATP hydrolysis with the removal of RNA polymerase II from the DNA template. Single nucleotide polymorphism (SNP) within the 5'-UTR of TTF2 is associated with thyroid cancer risk.TTF2 is a member of the DEAD-like helicase superfamily, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. This domain contains the ATP-binding region.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469924198  378 GLLSEEMGLGKTIEILSLILLNKRNSRVTGPSK------------SNLHKAKTTLIVCPDSILNQWIDEIEDHSYNNTLS 445
Cdd:cd18072     23 GILADDMGLGKTLTMIALILAQKNTQNRKEEEKekalteweskkdSTLVPSAGTLVVCPASLVHQWKNEVESRVASNKLR 102

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469924198  446 IYHYPGfkqlsrtFDKDKLSANdislkLLEYDIIITSYSVLSSEvhytnfathrnrnVHNYSDTVKtndkkrhdikydyS 525
Cdd:cd18072    103 VCLYHG-------PNRERIGEV-----LRDYDIVITTYSLVAKE-------------IPTYKEESR-------------S 144

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469924198  526 SPLALINFWRIVLDEVQMLGRSLTGNIIRCCNEISRVHtWGSSGTPvstitkvthIGNNdranagagtiAKDLAMILSYL 605
Cdd:cd18072    145 SPLFRIAWARIILDEAHNIKNPKVQASIAVCKLRAHAR-WALTGTP---------IQNN----------LLDMYSLLKFL 204

                   ....*..
gi 1469924198  606 QFNPFMD 612
Cdd:cd18072    205 RCSPFDD 211

DEXH/Q-box helicase domain of DEAD-like helicase Snf family proteins; Sucrose Non-Fermenting (SNF) proteins DEAD-like helicases superfamily. A diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. This domain contains the ATP-binding region.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469924198  374 HGAQGLLSEEMGLGKTIEILSLILLNKRNSRVTGPsksnlhkaktTLIVCPDSILNQWIDEIEDHSYNNTLSIYHypGfk 453
Cdd:cd17919     18 NGPGGILADEMGLGKTLQAIAFLAYLLKEGKERGP----------VLVVCPLSVLENWEREFEKWTPDLRVVVYH--G-- 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469924198  454 qlsrtfDKDKLSANDISLKLLEYDIIITSYSVLSSEVHYtnfathrnrnvhnysdtvktndkkRHDIKYDYssplalinf 533
Cdd:cd17919     84 ------SQRERAQIRAKEKLDKFDVVLTTYETLRRDKAS------------------------LRKFRWDL--------- 124

                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 1469924198  534 wrIVLDEVQMLgRSLTGNIIRCCNEISRVHTWGSSGTPV 572
Cdd:cd17919    125 --VVVDEAHRL-KNPKSQLSKALKALRAKRRLLLTGTPL 160

Ring finger domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1469924198 1268 CSICFGSIKLGA---ILKCGHFFCQECAESWLRHHSTCPMCK 1306
Cdd:pfam13639    3 CPICLEEFEEGDkvvVLPCGHHFHRECLDKWLRSSNTCPLCR 44

Superfamily II DNA or RNA helicase, SNF2 family [Transcription, Replication, recombination, and repair];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469924198  378 GLLSEEMGLGKTIEILSLILLNKRNsrvtgpsksnlHKAKTTLIVCPDSILNQWIDEIEDHsyNNTLSIYHYPGfkQLSR 457
Cdd:COG0553    263 GLLADDMGLGKTIQALALLLELKER-----------GLARPVLIVAPTSLVGNWQRELAKF--APGLRVLVLDG--TRER 327

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469924198  458 TFDKDKLSandislkllEYDIIITSYSVLssevhytnfathrnrnvhnysdtvktndkkRHDIKYdysspLALINFWRIV 537
Cdd:COG0553    328 AKGANPFE---------DADLVITSYGLL------------------------------RRDIEL-----LAAVDWDLVI 363

                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 1469924198  538 LDEVQML--GRSLTGniiRCCNEISRVHTWGSSGTPV 572
Cdd:COG0553    364 LDEAQHIknPATKRA---KAVRALKARHRLALTGTPV 397

HC subclass of RING (RING-HC) finger 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 a different Cys/His pattern. Some lack a single Cys or His residue at typical Zn ligand positions, especially, the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can chelate Zn in a RING finger as well. This family corresponds to the HC subclass of RING (RING-HC) fingers that are characterized by containing C3HC4-type canonical RING-HC fingers or noncanonical RING-HC finger variants, including C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type modified RING-HC fingers. The canonical RING-HC finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-HC fingers 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 serve as scaffolds 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 1469924198 1266 FKCSICFGSIKLGAILKCGHFFCQECAESWLRH-HSTCPMC 1305
Cdd:cd16449      1 LECPICLERLKDPVLLPCGHVFCRECIRRLLESgSIKCPIC 41

DEXH-box helicase domain of ERCC6; ERCC excision repair 6, chromatin remodeling factor (ERCC6, also known Cockayne syndrome group B (CSB), Rad26 in Saccharomyces cerevisiae, and Rhp26 in Schizosaccharomyces pombe) is a DNA-binding protein that is important in transcription-coupled excision repair. ERCC6 is a member of the DEAD-like helicase superfamily, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. This domain contains the ATP-binding region.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469924198  374 HGAQGLLSEEMGLGKTIEILSLILLNKRNSRVTGPSksnlhkakttLIVCPDSILNQWIDEIedHSYNNTL--SIYHYPG 451
Cdd:cd18000     18 QRVGGILGDEMGLGKTIQIIAFLAALHHSKLGLGPS----------LIVCPATVLKQWVKEF--HRWWPPFrvVVLHSSG 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469924198  452 -FKQLSRTFDKDKLSANDISLKLLEYDIIITSYSvlssevhytnfathrnrnvhnysdTVKTNDKKRHDIKYDYssplal 530
Cdd:cd18000     86 sGTGSEEKLGSIERKSQLIRKVVGDGGILITTYE------------------------GFRKHKDLLLNHNWQY------ 135

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|..
gi 1469924198  531 infwrIVLDEVQMLgRSLTGNIIRCCNEISRVHTWGSSGTPV 572
Cdd:cd18000    136 -----VILDEGHKI-RNPDAEITLACKQLRTPHRLILSGTPI 171

RING finger, HC subclass, found in RING finger protein 151 (RNF151) and similar proteins; RNF151 is a testis-specific RING finger protein that interacts with dysbindin, a synaptic and microtubular protein that binds brain snapin, a SNARE-binding protein that mediates intracellular membrane fusion in both neuronal and non-neuronal cells. Thus, it may be involved in acrosome formation of spermatids by interacting with multiple proteins participating in membrane biogenesis and microtubule organization. RNF151 contains a C3HC4-type RING finger domain, a putative nuclear localization signal (NLS), and a TNF receptor associated factor (TRAF)-type zinc finger domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1469924198 1266 FKCSICFGSIKLGAILKCGHFFCQECAESWLRHHSTCPMCKQ 1307
Cdd:cd16547      4 LICSICHGVLRCPVRLSCSHIFCKKCILQWLKRQETCPCCRK 45

Zinc finger, C3HC4 type (RING finger);

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1469924198 1264 KKFKCSICFGSIKLGAILKCGHF-FCQECAESWLRHHSTCPMCKQ 1307
Cdd:pfam13920    1 EDLLCVICLDRPRNVVLLPCGHLcLCEECAERLLRKKKKCPICRQ 45

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
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gi 1469924198  1268 CSICFG-SIKLGAILKCGHFFCQECAESWLR-HHSTCPMC 1305
Cdd:smart00184    1 CPICLEeYLKDPVILPCGHTFCRSCIRKWLEsGNNTCPIC 40

RING finger, HC subclass, found in RING finger proteins RNF113A, RNF113B, and similar proteins; RNF113A, also known as zinc finger protein 183 (ZNF183), is an E3 ubiquitin-protein ligase that physically interacts with the E2 protein, UBE2U. A nonsense mutation in RNF113A is associated with an X-linked trichothiodystrophy (TTD). Its yeast ortholog Cwc24p is predicted to have a spliceosome function and acts in a complex with Cef1p to participate in pre-U3 snoRNA splicing, indirectly affecting pre-rRNA processing. It is also important for the U2 snRNP binding to primary transcripts and co-migrates with spliceosomes. Moreover, the ortholog of RNF113A in fruit flies may also act as a spliceosome and is hypothesized to be involved in splicing, namely within the central nervous system. The ortholog in Caenorhabditis elegans is involved in DNA repair of inter-strand crosslinks. RNF113B, also known as zinc finger protein 183-like 1, shows high sequence similarity with RNF113A. Both RNF113A and RNF113B contain a CCCH-type zinc finger, which is commonly found in RNA-binding proteins involved in splicing, and a C3HC4-type RING-HC finger, which is frequently found in E3 ubiquitin ligases.

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gi 1469924198 1266 FKCSICFGSIKLGAILKCGHFFCQECAESWLRHHSTCPMCKQTT 1309
Cdd:cd16539      6 FACFICRKPFKNPVVTKCGHYFCEKCALKHYRKSKKCFVCGKQT 49

RING finger, HC subclass, found in RING finger and transmembrane domain-containing protein RNFT1, RNFT2, and similar proteins; Both RNFT1 and RNFT2 are multi-pass membrane proteins containing a C3HC4-type RING-HC finger. Their biological roles remain unclear.

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                   ....*....|....*....|....*....|....*....
gi 1469924198 1268 CSICFGSIKLGAILKCGHFFCQECAESWLRHHSTCPMCK 1306
Cdd:cd16532      3 CPICQDEFKDPVVLRCKHIFCEDCVSEWFERERTCPLCR 41

RING finger, HC subclass, found in topoisomerase I-binding arginine/serine-rich protein (Topors) and similar proteins; Topors, also known as topoisomerase I-binding RING finger protein, tumor suppressor p53- binding protein 3, or p53-binding protein 3 (p53BP3), is a ubiquitously expressed nuclear E3 ubiquitin-protein ligase that can ligate both ubiquitin and small ubiquitin-like modifier (SUMO) to substrate proteins in the nucleus. It contains an N-terminal C3HC4-type RING-HC finger which ligates ubiquitin to its target proteins including DNA topoisomerase I, p53, NKX3.1, H2AX, and the AAV-2 Rep78/68 proteins. As a RING-dependent E3 ubiquitin ligase, Topors works with the E2 enzymes UbcH5a, UbcH5c, and UbcH6, but not with UbcH7, CDC34, or UbcH2b. Topors acts as a tumor suppressor in various malignancies. It regulates p53 modification, suggesting it may be responsible for astrocyte elevated gene-1 (AEG-1, also known as metadherin, or LYRIC) ubiquitin modification. Plk1-mediated phosphorylation of Topors inhibits Topors-mediated sumoylation of p53, whereas p53 ubiquitination is enhanced, leading to p53 degradation. It also functions as a negative regulator of the prostate tumor suppressor NKX3.1. Moreover, Topors is associated with promyelocytic leukemia nuclear bodies, and may be involved in the cellular response to camptothecin. It also plays a key role in the turnover of H2AX protein, discriminating the type of DNA damaging stress. Furthermore, Topors is a cilia-centrosomal protein associated with autosomal dominant retinal degeneration. Mutations in TOPORS cause autosomal dominant retinitis pigmentosa (adRP).

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gi 1469924198 1267 KCSICFGSIKLG-AILK-CGHFFCQECAESWLRHHSTCPMCKQ 1307
Cdd:cd16574      3 SCPICLDRFENEkAFLDgCFHAFCFTCILEWSKVKNECPLCKQ 45

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.

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gi 1469924198 1267 KCSICFGSIKLG---AILKCGHFFCQECAESWLRHHSTCPMCK 1306
Cdd:cd16469      2 TCAVCLEEFKLKeelGVCPCGHAFHTKCLKKWLEVRNSCPICK 44

RING finger, HC subclass, found in RING finger and transmembrane domain-containing protein 2(RNFT2); RNFT2, also known as transmembrane protein 118 (TMEM118), is a multi-pass membrane protein containing a C3HC4-type RING-HC finger. Its biological role remains unclear.

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gi 1469924198 1268 CSICFGSIKLGAILKCGHFFCQECAESWLRHHSTCPMCKQTTV 1310
Cdd:cd16742     16 CAICQAEFREPLILICQHVFCEECLCLWFDRERTCPLCRSVVV 58

RING finger, H2 subclass, found in RING finger protein 128 (RNF128) and similar proteins; This subfamily includes RING finger proteins RNF128, RNF133, RNF148, and similar proteins, which belong to a larger PA-TM-RING ubiquitin ligase family that has been characterized by containing an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger followed by a putative PEST sequence. RNF128, also known as gene related to anergy in lymphocytes protein (GRAIL), is a type 1 transmembrane E3 ubiquitin-protein ligase that is a critical regulator of adaptive immunity and development. It inhibits cytokine gene transcription, is expressed in anergic CD4+ T cells, and has been implicated in primary T cell activation, survival, and differentiation, as well as in T cell anergy and oral tolerance. It induces T cell anergy through the ubiquitination activity of its cytosolic RING finger. It regulates expression of the costimulatory molecule CD40L on CD4 T cells, and ubiquitinates the costimulatory molecule CD40 ligand (CD40L) during the induction of T cell anergy. Moreover, RNF128 interacts with the luminal/extracellular portion of both CD151 and the related tetraspanin CD81 via its PA domain, which promoted ubiquitination of cytosolic lysine residues. It also down-modulates the expression of CD83 (previously described as a cell surface marker for mature dendritic cells) on CD4 T cells. Furthermore, Rho guanine dissociation inhibitor (RhoGDI) has been identified as a potential substrate of RNF128, suggesting a role for Rho effector molecules in T cell anergy. In addition, RNF128 plays a role in environmental stress responses. It promotes environmental salinity tolerance in euryhaline tilapia. RNF133 is a testis-specific endoplasmic reticulum-associated E3 ubiquitin ligase that is mainly present in the cytoplasm of elongated spermatids. It may play a role in sperm maturation through an ER-associated degradation (ERAD) pathway. RNF148 is a testis-specific E3 ubiquitin ligase that is abundantly expressed in testes and slightly expressed in pancreas. Its expression is regulated by histone deacetylases.

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gi 1469924198 1268 CSICFGSIKLG---AILKCGHFFCQECAESWLRHHSTCPMCK 1306
Cdd:cd16802      3 CAVCIEPYKPNdvvRILTCNHLFHKNCIDPWLLEHRTCPMCK 44

Modified RING finger, C3HGC3-type, found in RING finger and WD repeat domain-containing protein 3 (RFWD3) and similar proteins; RFWD3, also known as RING finger protein 201 (RNF201) or FLJ10520, is an E3 ubiquitin-protein ligase that forms a complex with Mdm2 and p53 to synergistically ubiquitinate p53 and acts as a positive regulator of p53 stability in response to DNA damage. It is phosphorylated by checkpoint kinase ATM/ATR and the phosphorylation mutant fails to stimulate p53 ubiquitination. RFWD3 also functions as a novel replication protein A (RPA)-associated protein involved in DNA replication checkpoint control. RFWD3 contains an N-terminal SQ-rich region followed by a RING finger domain that exhibits robust E3 ubiquitin ligase activity toward p53, a coiled-coil domain and three WD40 repeats in the C-terminus, the latter two of which may be responsible for protein-protein interaction. The RING finger in this family is a modified C3HGC3-type RING finger, but not a canonical C3H2C3-type RING-H2 finger or C3HC4-type RING-HC finger.

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                   ....*....|....*....|....*....|....*....|....*....|...
gi 1469924198 1268 CSICFGSIKLG-----AILKCGHFFCQECAESWLRHHS-TCPMCKQTTVLEEI 1314
Cdd:cd16450      5 CPICFEPWTSSgehrlVSLKCGHLFGYSCIEKWLKGKGkKCPQCNKKAKRSDI 57

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.

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gi 1469924198 1268 CSICFGSIKLG---AILKCGHFFCQECAESWLRH-HSTCPMCK 1306
Cdd:cd16448      1 CVICLEEFEEGdvvRLLPCGHVFHLACILRWLESgNNTCPLCR 43

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.

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gi 1469924198 1267 KCSICFGSIKLGAILK---CGHFFCQECAESWLRHHSTCPMCK 1306
Cdd:cd16467      1 ECTICLGEYETGEKLRrlpCSHEFHSECVDRWLKENSSCPICR 43

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.

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gi 1469924198 1267 KCSICFGSIKLG--AILKCGHFFCQECAESWLRHHSTCPMCKQ 1307
Cdd:cd16481      1 PCIICHDDLKPDqlAKLECGHIFHKECIKQWLKEQSTCPTCRV 43

RING finger, H2 subclass, found in autocrine motility factor receptor (AMFR) and similar proteins; AMFR, also known as AMF receptor, or RING finger protein 45, or ER-protein gp78, is an internalizing cell surface glycoprotein localized in both plasma membrane caveolae and the endoplasmic reticulum (ER). It is involved in the regulation of cellular adhesion, proliferation, motility and apoptosis, as well as in the process of learning and memory. AMFR also functions as a RING finger-dependent ubiquitin protein ligase (E3) implicated in the degradation from the ER. AMFR contains an N-terminal RING-H2 finger and a C-terminal ubiquitin-associated (UBA)-like CUE domain.