Recombination-activation protein 1 (RAG1), recombinase; This family is one of the two different components of the RAG1-RAG2 V(D)J recombinase complex. The RAG complex, consisting of two RAG1 and two RAG2 proteins is a multi-protein complex that mediates DNA cleavage during V(D)J (variable-diversity-joining) recombination. RAG1 mediates DNA-binding to the conserved recombination signal sequences (RSS). Many of the proteins in this family are fragments. Solution of the structure of the complex of RAG1 and RAG2 shows that each protein dimerizes with itself and each pair then complexes together to from the RAG1-RAG2 V(D)J recombinase enzyme. The different structural elements in RAG1 for UniProtKB:P15919 are: an N-terminal nonamer-binding domain from residues 391-459; a dimerization and DNA-binding domain from 459-515; an extended pre-RNase H domain from 515-588; the catalytic RNase H domain from 588-719; a ZnC2 domain from 719-791; and ZnH2 domain from 791-962; and a three-helix C-terminal domain from 962-1008.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1787508884  386 FVHINKGGRPRQHLLSLTRRAQKHRLRELKLQVKAFADKEEGGDVKSVCMTLFLLALRARNEHRQADELEAIMQGKGSGL 465
Cdd:pfam12940    3 FLLTNKGGRPRQHLLSLTRRAQKHRLRDLKHQVKVFADKEEGGDIKSVCLTLFLLALRAGNEHRQADELEAMMQGRGFGL 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1787508884  466 QPAVCLAIRVNTFLSCSQYHKMYRTVKAITGRQIFQPLHALRNAEKVLLPGYHHFEWQPPLKNVSSSTDVGIIDGLSGLS 545
Cdd:pfam12940   83 HPAVCLAIRVNTFLSCSQYHKMYRTVKATSGRQIFQPLHTLRAAEKALLPGFHHFEWQPALKNVSPSCDVGIIDGLSGWS 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1787508884  546 SSVDDYPVDTIAKRFRYDSALVSALMDMEEDILEGMRSQDLDDY-LNGPFTVVVKESCDGMGDVSEKHGSGPVVPEKAVR 624
Cdd:pfam12940  163 PSVDDQPADTITRRFRYDVALVAALKDLEEDILEGLKEQGLDDSaCTEGFSVMIKECCDGMGDVSEKHGGGPAVPEKAVR 242

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1787508884  625 FSFTIMKITIA---HSSQNVKVFEEAKPNSELCCKPLCLMLADESDHETLTAILSPLIAEREAMKSSELMLELGGILRTF 701
Cdd:pfam12940  243 FSFTIMSVSILaddEEGEEVAIFHELKPNSELCCKPLCLMFADESDHETLTAILAPIMAEREAMKESRLILSIGGLLRSF 322

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1787508884  702 KFIFRGTGYDEKLVREVEGLEASGSVYICTLCDATRLEASQNLVFHSITRSHAENLERYEVWRSNPYHESVEELRDRVKG 781
Cdd:pfam12940  323 RFHFRGTGYDEKLVRDMEGLEASGSTYICTLCDSSRAEASKNKVLHAITRSHEENLERYEIWRTNPFSESADDLRDRVKG 402

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1787508884  782 VSAKPFIETVPSIDALHCDIGNAAEFYKIFQLEIGEVYKNPNASKEERKRWQATLDKHLRKKMNLKPIMRMNGNFARKLM 861
Cdd:pfam12940  403 ISAKPFLETQACIDALHCDIGNATEFYKIFQDEIGEVHKKANPSKEERKRWQAALDKQLRKKMKLKPVMRMNGNFARKLM 482

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1787508884  862 TKETVDAVCELIPSEERHEALRELMDLYLKMKPVWRSSCPAKECPESLCQYSFNSQRFAELLSTKFKYRYEGKITNYFHK 941
Cdd:pfam12940  483 TQEAVDAVCELVPSEERQEALRELMHLYLQMKPVWRATCPAKECPDLLCRYSFNSQRFADLLSTTFKYRYDGKITNYLHK 562

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1787508884  942 TLAHVPEIIERDGSIGAWASEGNESGNKLFRRFRKMNARQSKCYEMEDVLKHHWLYTSKYLQKFMNAH-NALKTSGFTMN 1020
Cdd:pfam12940  563 TLAHVPEIIERDGSIGAWASEGNESANKLFRRFRKMNARQSKSFELEDILKHHWLYTSKYLQKFMEAHkDSAKALEATID 642

                   .
gi 1787508884 1021 P 1021
Cdd:pfam12940  643 P 643

RING finger, HC subclass, found in recombination activating gene-1 (RAG-1) and similar proteins; RAG-1, also known as V(D)J recombination-activating protein 1, RING finger protein 74 (RNF74), or endonuclease RAG1, is the catalytic component of the RAG complex, a multiprotein complex that mediates the DNA cleavage phase during V(D)J recombination. RAG1 is a lymphoid-specific factor that mediates DNA-binding to conserved recombination signal sequences (RSS) and catalyzes DNA cleavage activities by introducing a double-strand break between the RSS and the adjacent coding segment. It also functions as an E3 ubiquitin-protein ligase that mediates monoubiquitination of histone H3, which is required for the joining step of V(D)J recombination. RAG-1 contains an N-terminal C3HC4-type RING-HC finger that mediates monoubiquitylation of histone H3, an adjacent C2H2-type zinc finger, and a nonamer binding (NBD) DNA-binding domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1787508884  289 KSISCQICEHILADPVETNCKHVFCRVCILRCLKVMGSYCPSCRYP 334
Cdd:cd16530      1 KSVSCQVCEHILADPVQTPCKHLFCRTCILKCLKVMGSYCPSCRYP 46

Recombination-activation protein 1 (RAG1), recombinase; This family is one of the two different components of the RAG1-RAG2 V(D)J recombinase complex. The RAG complex, consisting of two RAG1 and two RAG2 proteins is a multi-protein complex that mediates DNA cleavage during V(D)J (variable-diversity-joining) recombination. RAG1 mediates DNA-binding to the conserved recombination signal sequences (RSS). Many of the proteins in this family are fragments. Solution of the structure of the complex of RAG1 and RAG2 shows that each protein dimerizes with itself and each pair then complexes together to from the RAG1-RAG2 V(D)J recombinase enzyme. The different structural elements in RAG1 for UniProtKB:P15919 are: an N-terminal nonamer-binding domain from residues 391-459; a dimerization and DNA-binding domain from 459-515; an extended pre-RNase H domain from 515-588; the catalytic RNase H domain from 588-719; a ZnC2 domain from 719-791; and ZnH2 domain from 791-962; and a three-helix C-terminal domain from 962-1008.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1787508884  386 FVHINKGGRPRQHLLSLTRRAQKHRLRELKLQVKAFADKEEGGDVKSVCMTLFLLALRARNEHRQADELEAIMQGKGSGL 465
Cdd:pfam12940    3 FLLTNKGGRPRQHLLSLTRRAQKHRLRDLKHQVKVFADKEEGGDIKSVCLTLFLLALRAGNEHRQADELEAMMQGRGFGL 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1787508884  466 QPAVCLAIRVNTFLSCSQYHKMYRTVKAITGRQIFQPLHALRNAEKVLLPGYHHFEWQPPLKNVSSSTDVGIIDGLSGLS 545
Cdd:pfam12940   83 HPAVCLAIRVNTFLSCSQYHKMYRTVKATSGRQIFQPLHTLRAAEKALLPGFHHFEWQPALKNVSPSCDVGIIDGLSGWS 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1787508884  546 SSVDDYPVDTIAKRFRYDSALVSALMDMEEDILEGMRSQDLDDY-LNGPFTVVVKESCDGMGDVSEKHGSGPVVPEKAVR 624
Cdd:pfam12940  163 PSVDDQPADTITRRFRYDVALVAALKDLEEDILEGLKEQGLDDSaCTEGFSVMIKECCDGMGDVSEKHGGGPAVPEKAVR 242

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1787508884  625 FSFTIMKITIA---HSSQNVKVFEEAKPNSELCCKPLCLMLADESDHETLTAILSPLIAEREAMKSSELMLELGGILRTF 701
Cdd:pfam12940  243 FSFTIMSVSILaddEEGEEVAIFHELKPNSELCCKPLCLMFADESDHETLTAILAPIMAEREAMKESRLILSIGGLLRSF 322

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1787508884  702 KFIFRGTGYDEKLVREVEGLEASGSVYICTLCDATRLEASQNLVFHSITRSHAENLERYEVWRSNPYHESVEELRDRVKG 781
Cdd:pfam12940  323 RFHFRGTGYDEKLVRDMEGLEASGSTYICTLCDSSRAEASKNKVLHAITRSHEENLERYEIWRTNPFSESADDLRDRVKG 402

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1787508884  782 VSAKPFIETVPSIDALHCDIGNAAEFYKIFQLEIGEVYKNPNASKEERKRWQATLDKHLRKKMNLKPIMRMNGNFARKLM 861
Cdd:pfam12940  403 ISAKPFLETQACIDALHCDIGNATEFYKIFQDEIGEVHKKANPSKEERKRWQAALDKQLRKKMKLKPVMRMNGNFARKLM 482

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1787508884  862 TKETVDAVCELIPSEERHEALRELMDLYLKMKPVWRSSCPAKECPESLCQYSFNSQRFAELLSTKFKYRYEGKITNYFHK 941
Cdd:pfam12940  483 TQEAVDAVCELVPSEERQEALRELMHLYLQMKPVWRATCPAKECPDLLCRYSFNSQRFADLLSTTFKYRYDGKITNYLHK 562

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1787508884  942 TLAHVPEIIERDGSIGAWASEGNESGNKLFRRFRKMNARQSKCYEMEDVLKHHWLYTSKYLQKFMNAH-NALKTSGFTMN 1020
Cdd:pfam12940  563 TLAHVPEIIERDGSIGAWASEGNESANKLFRRFRKMNARQSKSFELEDILKHHWLYTSKYLQKFMEAHkDSAKALEATID 642

                   .
gi 1787508884 1021 P 1021
Cdd:pfam12940  643 P 643

RING finger, HC subclass, found in recombination activating gene-1 (RAG-1) and similar proteins; RAG-1, also known as V(D)J recombination-activating protein 1, RING finger protein 74 (RNF74), or endonuclease RAG1, is the catalytic component of the RAG complex, a multiprotein complex that mediates the DNA cleavage phase during V(D)J recombination. RAG1 is a lymphoid-specific factor that mediates DNA-binding to conserved recombination signal sequences (RSS) and catalyzes DNA cleavage activities by introducing a double-strand break between the RSS and the adjacent coding segment. It also functions as an E3 ubiquitin-protein ligase that mediates monoubiquitination of histone H3, which is required for the joining step of V(D)J recombination. RAG-1 contains an N-terminal C3HC4-type RING-HC finger that mediates monoubiquitylation of histone H3, an adjacent C2H2-type zinc finger, and a nonamer binding (NBD) DNA-binding domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1787508884  289 KSISCQICEHILADPVETNCKHVFCRVCILRCLKVMGSYCPSCRYP 334
Cdd:cd16530      1 KSVSCQVCEHILADPVQTPCKHLFCRTCILKCLKVMGSYCPSCRYP 46

Zinc finger, C3HC4 type (RING finger); The C3HC4 type zinc-finger (RING finger) is a cysteine-rich domain of 40 to 60 residues that coordinates two zinc ions, and has the consensus sequence: C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C where X is any amino acid. Many proteins containing a RING finger play a key role in the ubiquitination pathway.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1787508884  293 CQICEHILADPV-ETNCKHVFCRVCILRCLKVMGSYCPSC 331
Cdd:pfam00097    1 CPICLEEPKDPVtLLPCGHLFCSKCIRSWLESGNVTCPLC 40

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
                   ....*....|....*....|....*....|....*....|....*
gi 1787508884  290 SISCQICEHILADPVETNCKHVFCRVCILRCLKVMGSyCPSCRYP 334
Cdd:TIGR00599   26 SLRCHICKDFFDVPVLTSCSHTFCSLCIRRCLSNQPK-CPLCRAE 69

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1787508884  159 FRIDVKADVDSIHPTEFCHNCWSIMHRKFSSapcevyfprnvTMEWHPHTPS--CDICNTARrglkrksLQPNLQlsKKL 236
Cdd:COG5574    106 TNIDKEGEVLYPCGIFFCIGCDYIWSIDLKQ-----------TANTHEASPSqlLKFLPTIR-------LAMNIP--EVI 165

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1787508884  237 KTVLDQARQARQHKRRAQARISSKDvMKKIANCSKIHLSTKLLAVDFPEHFVKsisCQICEHILADPVETNCKHVFCRVC 316
Cdd:COG5574    166 SDLTAVALSLDESRLQPILQPSNNL-HTLFQVITKENLSKKNGLPFIPLADYK---CFLCLEEPEVPSCTPCGHLFCLSC 241

                          170       180
                   ....*....|....*....|....*
gi 1787508884  317 IL--RCLKVMGsYCPSCRYPCFPTD 339
Cdd:COG5574    242 LLisWTKKKYE-FCPLCRAKVYPKK 265

Recombination-activation protein 1 (RAG1), recombinase; This family is one of the two different components of the RAG1-RAG2 V(D)J recombinase complex. The RAG complex, consisting of two RAG1 and two RAG2 proteins is a multi-protein complex that mediates DNA cleavage during V(D)J (variable-diversity-joining) recombination. RAG1 mediates DNA-binding to the conserved recombination signal sequences (RSS). Many of the proteins in this family are fragments. Solution of the structure of the complex of RAG1 and RAG2 shows that each protein dimerizes with itself and each pair then complexes together to from the RAG1-RAG2 V(D)J recombinase enzyme. The different structural elements in RAG1 for UniProtKB:P15919 are: an N-terminal nonamer-binding domain from residues 391-459; a dimerization and DNA-binding domain from 459-515; an extended pre-RNase H domain from 515-588; the catalytic RNase H domain from 588-719; a ZnC2 domain from 719-791; and ZnH2 domain from 791-962; and a three-helix C-terminal domain from 962-1008.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1787508884  386 FVHINKGGRPRQHLLSLTRRAQKHRLRELKLQVKAFADKEEGGDVKSVCMTLFLLALRARNEHRQADELEAIMQGKGSGL 465
Cdd:pfam12940    3 FLLTNKGGRPRQHLLSLTRRAQKHRLRDLKHQVKVFADKEEGGDIKSVCLTLFLLALRAGNEHRQADELEAMMQGRGFGL 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1787508884  466 QPAVCLAIRVNTFLSCSQYHKMYRTVKAITGRQIFQPLHALRNAEKVLLPGYHHFEWQPPLKNVSSSTDVGIIDGLSGLS 545
Cdd:pfam12940   83 HPAVCLAIRVNTFLSCSQYHKMYRTVKATSGRQIFQPLHTLRAAEKALLPGFHHFEWQPALKNVSPSCDVGIIDGLSGWS 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1787508884  546 SSVDDYPVDTIAKRFRYDSALVSALMDMEEDILEGMRSQDLDDY-LNGPFTVVVKESCDGMGDVSEKHGSGPVVPEKAVR 624
Cdd:pfam12940  163 PSVDDQPADTITRRFRYDVALVAALKDLEEDILEGLKEQGLDDSaCTEGFSVMIKECCDGMGDVSEKHGGGPAVPEKAVR 242

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1787508884  625 FSFTIMKITIA---HSSQNVKVFEEAKPNSELCCKPLCLMLADESDHETLTAILSPLIAEREAMKSSELMLELGGILRTF 701
Cdd:pfam12940  243 FSFTIMSVSILaddEEGEEVAIFHELKPNSELCCKPLCLMFADESDHETLTAILAPIMAEREAMKESRLILSIGGLLRSF 322

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1787508884  702 KFIFRGTGYDEKLVREVEGLEASGSVYICTLCDATRLEASQNLVFHSITRSHAENLERYEVWRSNPYHESVEELRDRVKG 781
Cdd:pfam12940  323 RFHFRGTGYDEKLVRDMEGLEASGSTYICTLCDSSRAEASKNKVLHAITRSHEENLERYEIWRTNPFSESADDLRDRVKG 402

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1787508884  782 VSAKPFIETVPSIDALHCDIGNAAEFYKIFQLEIGEVYKNPNASKEERKRWQATLDKHLRKKMNLKPIMRMNGNFARKLM 861
Cdd:pfam12940  403 ISAKPFLETQACIDALHCDIGNATEFYKIFQDEIGEVHKKANPSKEERKRWQAALDKQLRKKMKLKPVMRMNGNFARKLM 482

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1787508884  862 TKETVDAVCELIPSEERHEALRELMDLYLKMKPVWRSSCPAKECPESLCQYSFNSQRFAELLSTKFKYRYEGKITNYFHK 941
Cdd:pfam12940  483 TQEAVDAVCELVPSEERQEALRELMHLYLQMKPVWRATCPAKECPDLLCRYSFNSQRFADLLSTTFKYRYDGKITNYLHK 562

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1787508884  942 TLAHVPEIIERDGSIGAWASEGNESGNKLFRRFRKMNARQSKCYEMEDVLKHHWLYTSKYLQKFMNAH-NALKTSGFTMN 1020
Cdd:pfam12940  563 TLAHVPEIIERDGSIGAWASEGNESANKLFRRFRKMNARQSKSFELEDILKHHWLYTSKYLQKFMEAHkDSAKALEATID 642

                   .
gi 1787508884 1021 P 1021
Cdd:pfam12940  643 P 643

RING finger, HC subclass, found in recombination activating gene-1 (RAG-1) and similar proteins; RAG-1, also known as V(D)J recombination-activating protein 1, RING finger protein 74 (RNF74), or endonuclease RAG1, is the catalytic component of the RAG complex, a multiprotein complex that mediates the DNA cleavage phase during V(D)J recombination. RAG1 is a lymphoid-specific factor that mediates DNA-binding to conserved recombination signal sequences (RSS) and catalyzes DNA cleavage activities by introducing a double-strand break between the RSS and the adjacent coding segment. It also functions as an E3 ubiquitin-protein ligase that mediates monoubiquitination of histone H3, which is required for the joining step of V(D)J recombination. RAG-1 contains an N-terminal C3HC4-type RING-HC finger that mediates monoubiquitylation of histone H3, an adjacent C2H2-type zinc finger, and a nonamer binding (NBD) DNA-binding domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1787508884  289 KSISCQICEHILADPVETNCKHVFCRVCILRCLKVMGSYCPSCRYP 334
Cdd:cd16530      1 KSVSCQVCEHILADPVQTPCKHLFCRTCILKCLKVMGSYCPSCRYP 46

Recombination-activating protein 1 zinc-finger domain; This is a C2-H2 zinc-finger domain closely resembling the classical TFIIIA-type zinc-finger, CX3FX5LX2-3H, despite having a valine and a tyrosine at the core instead of a phenylalanine and a leucine, hence CX3VX1LX2YX2H. The structure, nevertheless, contains the characteriztic two-stranded beta-sheet and alpha-helix of a classical zinc-finger. The domain binds one zinc and, in complex with the zinc-RING-finger domain, helps to stabilize the whole of the dimerization region of recombination activating protein 1 (RAG1). The function of the whole is to bind double-stranded DNA.

                           10        20        30
                   ....*....|....*....|....*....|
gi 1787508884  354 LMVKCPAKECNEEVSLEKYNHHISSHKESK 383
Cdd:pfam10426    1 LVIRCPAKDCDEEVRLEKYGQHLSSHKEGK 30

second RING finger, HC subclass, found in the LON peptidase N-terminal domain and RING finger protein family; The LON peptidase N-terminal domain and RING finger protein family includes LONRF1 (also known as RING finger protein 191 or RNF191), LONRF2 (also known as RING finger protein 192, RNF192, or neuroblastoma apoptosis-related protease), LONRF3 (also known as RING finger protein 127 or RNF127), which are characterized by containing two C3HC4-type RING-HC fingers, four tetratricopeptide (TPR) repeats, and an ATP-dependent protease La (LON) substrate-binding domain at the C-terminus. Their biological functions remain unclear. This model corresponds to the second RING-HC finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1787508884  293 CQICEHILADPVETNCKHVFCRVCILRCLKvMGSYCPSCRYP 334
Cdd:cd16514      4 CSLCLRLLYEPVTTPCGHTFCRACLERCLD-HSPKCPLCRTS 44

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 1787508884  292 SCQICEHILADPVETNCKHVFCRVCILRCLKVMGSYCPSC 331
Cdd:cd16449      2 ECPICLERLKDPVLLPCGHVFCRECIRRLLESGSIKCPIC 41

RING finger, HC subclass, found in tripartite motif-containing proteins, TRIM7, TRIM11 and TRIM27, and similar proteins; TRIM7, TRIM11 and TRIM27, closely related tripartite motif-containing proteins, belong to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox2, and a coiled coil region, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain. TRIM7, also known as glycogenin-interacting protein (GNIP) or RING finger protein 90 (RNF90), is an E3 ubiquitin-protein ligase that mediates c-Jun/AP-1 activation by Ras signalling. Its phosphorylation and activation by MSK1 in response to direct activation by the Ras-Raf-MEK-ERK pathway can stimulate TRIM7 E3 ubiquitin ligase activity in mediating Lys63-linked ubiquitination of the AP-1 coactivator RACO-1, leading to RACO-1 protein stabilization. Moreover, TRIM7 binds and activates glycogenin, the self-glucosylating initiator of glycogen biosynthesis. TRIM11, also known as protein BIA1, or RING finger protein 92 (RNF92), is an E3 ubiquitin-protein ligase involved in the development of the central nervous system. It is overexpressed in high-grade gliomas and promotes proliferation, invasion, migration and glial tumor growth. TRIM11 acts as a potential therapeutic target for congenital central hypoventilation syndrome (CCHS) by mediating the degradation of CCHS-associated polyalanine-expanded Phox2b. TRIM11 modulates the function of neurogenic transcription factor Pax6 through the ubiquitin-proteosome system, and thus plays an essential role for Pax6-dependent neurogenesis. It also binds to and destabilizes a key component of the activator-mediated cofactor complex (ARC105), humanin, a neuroprotective peptide against Alzheimer's disease-relevant insults, and further regulates ARC105 function in transforming growth factor beta (TGFbeta) signaling. Moreover, TRIM11 negatively regulates retinoic acid-inducible gene-I (RIG-I)-mediated interferon-beta (IFNbeta) production and antiviral activity by targeting TANK-binding kinase-1 (TBK1). It may contribute to the endogenous restriction of retroviruses in cells. It enhances N-tropic murine leukemia virus (N-MLV) entry by interfering with Ref1 restriction. It also suppresses the early steps of human immunodeficiency virus HIV-1 transduction, resulting in decreased reverse transcripts. TRIM27, also known as RING finger protein 76 (RNF76), RET finger protein (RFP), or zinc finger protein RFP, is a nuclear E3 ubiquitin-protein ligase that is highly expressed in testis and in various tumor cell lines. Expression of TRIM27 is associated with prognosis of colon and endometrial cancers. TRIM27 was first identified as a fusion partner of the RET receptor tyrosine kinase. It functions as a transcriptional repressor and associates with several proteins involved in transcriptional activity, such as enhancer of polycomb 1 (Epc1), a member of the Polycomb group proteins, and Mi-2beta, a main component of the nucleosome remodeling and deacetylase (NuRD) complex, and the cell cycle regulator retinoblastoma protein (RB1). It also interacts with HDAC1, leading to downregulation of thioredoxin binding protein 2 (TBP-2), which inhibits the function of thioredoxin. Moreover, TRIM27 mediates Pax7-induced ubiquitination of MyoD in skeletal muscle atrophy. In addition, it inhibits muscle differentiation by modulating serum response factor (SRF) and Epc1. TRIM27 promotes a non-canonical polyubiquitination of PTEN, a lipid phosphatase that catalyzes PtdIns(3,4,5)P3 (PIP3) to PtdIns(4,5)P2 (PIP2). It is an IKKepsilon-interacting protein that regulates IkappaB kinase (IKK) function and negatively regulates signaling involved in the antiviral response and inflammation. TRIM27 also forms a protein complex with MBD4 or MBD2 or MBD3, and thus plays an important role in the enhancement of transcriptional repression through MBD proteins in tumorigenesis, spermatogenesis, and embryogenesis. It is a component of an estrogen receptor 1 (ESR1) regulatory complex that is involved in estrogen receptor-mediated transcription in MCF-7 cells.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1787508884  291 ISCQICEHILADPVETNCKHVFCRVCILRCLKVMG--SYCPSCRYPC 335
Cdd:cd16594      6 LTCPICLDYFTDPVTLDCGHSFCRACIARCWEEPEtsASCPQCRETC 52

RING finger, HC subclass, found in helicase-like transcription factor (HLTF) and similar proteins; HLTF, also known as DNA-binding protein/plasminogen activator inhibitor 1 regulator, HIP116, RING finger protein 80, SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 3, or sucrose nonfermenting protein 2-like 3, is a yeast RAD5 homolog found in mammals. It has both E3 ubiquitin ligase and DNA helicase activities, and plays a pivotal role in the template-switching pathway of DNA damage tolerance. It is involved in Lys-63-linked poly-ubiquitination of proliferating cell nuclear antigen (PCNA) at Lys-164 and in the regulation of DNA damage tolerance. It shows double-stranded DNA translocase activity with 3'-5' polarity, thereby facilitating regression of the replication fork. HLTF contains an N-terminal HIRAN (HIP116 and RAD5 N-terminal) domain, a SWI/SNF helicase domain that is divided into N- and C-terminal parts by an insertion of a C3HC4-type RING-HC finger involved in the poly-ubiquitination of PCNA.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1787508884  293 CQICEHILADPVETNCKHVFCRVCILRCLKVMGSYCPSCRYPCFPTDL 340
Cdd:cd16509      6 CAICLDSLTNPVITPCAHVFCRRCICEVIQREKAKCPMCRAPLSASDL 53

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
                   ....*....|....*....|....*....|....*....|....*
gi 1787508884  290 SISCQICEHILADPVETNCKHVFCRVCILRCLKVMGSyCPSCRYP 334
Cdd:TIGR00599   26 SLRCHICKDFFDVPVLTSCSHTFCSLCIRRCLSNQPK-CPLCRAE 69

RING finger, HC subclass, found in breast cancer type 1 susceptibility protein (BRCA1) and similar proteins; BRCA1, also known as RING finger protein 53 (RNF53), is a RING finger protein encoded by the tumor suppressor gene BRCA1 that regulates all DNA double-strand break (DSB) repair pathways. BRCA1 is frequently mutated in patients with hereditary breast and ovarian cancer (HBOC). Its mutation is also associated with an increased risk of pancreatic, stomach, laryngeal, fallopian tube, and prostate cancer. It plays an important role in the DNA damage response signaling and has been implicated in various cellular processes such as cell cycle regulation, transcriptional regulation, chromatin remodeling, DNA DSBs, and apoptosis. BRCA1 contains an N-terminal C3HC4-type RING-HC finger, and two BRCT (BRCA1 C-terminus domain) repeats at the C-terminus.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1787508884  289 KSISCQICEHILADPVETNCKHVFCRVCILRCL--KVMGSYCPSCRYP 334
Cdd:cd16498     15 KNLECPICLELLKEPVSTKCDHQFCRFCILKLLqkKKKPAPCPLCKKS 62

RING finger, HC subclass, found in RING finger protein 39 (RNF39) and similar proteins; RNF39, also called protein HZFw, may play a role in prolonged long term-potentiation (LTP) maintenance. It is involved in the etiology of Behcet's disease (BD). It may also be involved in HIV-1 replication. RNF39 acts as an E3 ubiquitin ligase that inhibits retinoic acid-inducible gene-I (RIG-I)-like receptor (RLR) pathways by mediating K48-linked ubiquitination and proteasomal degradation of DDX3X (DEAD-box RNA helicase 3, X-linked). RNF39 contains a typical C3HC4-type RING-HC finger.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1787508884  293 CQICEHILADPVETNCKHVFCRVCILRCLKV--------MGSYCPSCRYPC 335
Cdd:cd16592      7 CPICLGYFKDPVILDCEHSFCRACIARHWGQeamegngaEGVFCPQCGEPC 57

RING finger, HC subclass, found in Mus musculus tripartite motif-containing protein 43 (TRIM43) and similar propteins; This subfamily includes TRIM43A, TRIM43B and TRIM43C, which are expressed specifically in mouse preimplantation embryos. They contain a typical C3HC4-type RING-HC finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1787508884  289 KSISCQICEHILADPVETNCKHVFCRVCILRCLKVM--GSYCPSCRYPC 335
Cdd:cd23133      2 ETLTCSICQGIFMNPVYLRCGHKFCEACLLLFQEDIkfPAYCPMCRQPF 50

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM60, TRIM61, TRIM75 and similar proteins; TRIM60, also known as RING finger protein 129 (RNF129) or RING finger protein 33 (RNF33), is a cytoplasmic protein expressed in the testis. It may play an important role in the spermatogenesis process, the development of the preimplantation embryo, and in testicular functions. RNF33 interacts with the cytoplasmic kinesin motor proteins KIF3A and KIF3B suggesting possible contribution to cargo movement along the microtubule in the expressed sites. It is also involved in spermatogenesis in Sertoli cells under the regulation of nuclear factor-kappaB (NF-kappaB). TRIM75 mainly localizes within spindles, suggesting it may function in spindle organization and thereby affect meiosis. Both TRIM60 and TRIM75 belong the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, a B2-box, and two coiled coil domains, as well as a PRY domain and a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. In contrast, TRIM61 belongs to the C-V subclass of the TRIM family that contains RBCC domains only. Its biological function remains unclear.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1787508884  291 ISCQICEHILADPVETNCKHVFCRVCI-LRCLKVMGSY-CPSCRYPC 335
Cdd:cd16607      2 ASCPICLDYLKDPVTINCGHNFCRSCIsMSWKDLQDTFpCPVCRFCC 48

RING finger, HC subclass, found in tripartite motif-containing protein 26 (TRIM26) and similar proteins; TRIM26, also known as acid finger protein (AFP), RING finger protein 95 (RNF95), or zinc finger protein 173 (ZNF173), is an E3 ubiquitin-protein ligase that negatively regulates interferon-beta production and antiviral response through polyubiquitination and degradation of nuclear transcription factor IRF3. It functions as an important regulator for RNA virus-triggered innate immune response by bridging TBK1 to NEMO (NF-kappaB essential modulator, also known as IKKgamma) and mediating TBK1 activation. It also acts as a novel tumor suppressor of hepatocellular carcinoma by regulating cancer cell proliferation, colony forming ability, migration, and invasion. TRIM26 belongs the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, a B-box, and two coiled coil domains, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1787508884  291 ISCQICEHILADPVETNCKHVFCRVCILRCLKVMGSY----CPSCRYP 334
Cdd:cd16598      5 VTCSICLDYLRDPVTIDCGHNFCRSCITDYCPISGGHerpvCPLCRKP 52

RING finger, HC subclass, found in Saccharomyces cerevisiae DNA repair protein RAD16, Schizosaccharomyces pombe rhp16, and similar proteins; Budding yeast RAD16, also known as ATP-dependent helicase RAD16, is encoded by a yeast excision repair gene homologous to the recombinational repair gene RAD54 and to the SNF2 gene involved in transcriptional activation. It is a component of the global genome repair (GGR) complex that promotes global genome nucleotide excision repair (GG-NER) by removing DNA damage from non-transcribing DNA. RAD16 is involved in differential repair of DNA after UV damage, and repairs preferentially the MAT-alpha locus compared with the HML-alpha locus. Fission yeast rhp16, also known as ATP-dependent helicase rhp16, is a RAD16 homolog. It is involved in GGR via nucleotide excision repair (NER), in conjunction with rhp7, after UV irradiation. Both RAD16 and rhp16 contain a C3HC4-type RING-HC finger, as well as a DEAD-like helicase domain and a helicase superfamily C-terminal domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1787508884  291 ISCQICEHILADPVETNCKHVFCRVCI---LRCLKVMGSYCPSCRYP 334
Cdd:cd16567      1 LVCGICHEEAEDPVVARCHHVFCRACVkeyIESAPGGKVTCPTCHKP 47

RING finger, HC subclass, found in RING finger protein 170 (RNF170) and similar proteins; RNF170, also known as putative LAG1-interacting protein, is an endoplasmic reticulum (ER) membrane-bound E3 ubiquitin-protein ligase that mediates ubiquitination-dependent degradation of type-I inositol 1,4,5-trisphosphate (IP3) receptors (ITPR1) via the endoplasmic-reticulum-associated protein degradation (ERAD) pathway. A point mutation (arginine to cysteine at position 199) in the RNF170 gene is linked with autosomal-dominant sensory ataxia (ADSA), a disease characterized by neurodegeneration in the posterior columns of the spinal cord. RNF170 contains a C3HC4-type RING-HC finger.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1787508884  290 SISCQICEHILADPVETNCKHVFCRVCIL---RCLKVMGSY-CPSCR------YPCF 336
Cdd:cd16553      1 DMECPICLQDARFPVETNCGHLFCGPCIItywRHGSWLGAVsCPVCRqtvtllLPVF 57

RING finger, HC subclass, found in RING finger protein 166 (RNF166) and similar proteins; RNF166 is encoded by the gene RNF166 targeted by thyroid hormone receptor alpha1 (TRalpha1), which is important in brain development. It plays an important role in RNA virus-induced interferon-beta production by enhancing the ubiquitination of TRAF3 and TRAF6. RNF166, together with three closely related proteins: RNF114, RNF125 and RNF138, forms a novel family of ubiquitin ligases with a C3HC4-type RING-HC finger, a C2HC-, and two C2H2-type zinc fingers, as well as a ubiquitin interacting motif (UIM).

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                   ....*....|....*....|....*....|....*....|....
gi 1787508884  292 SCQICEHILADPVET-NCKHVFCRVCILRCLKVMGSYCPSCRYP 334
Cdd:cd16549      3 SCPICLEVYHKPVVItSCGHTFCGECLQPCLQVASPLCPLCRMP 46

RING finger, HC subclass, found in tripartite motif-containing protein 62 (TRIM62) and similar proteins; TRIM62, also known as Ductal Epithelium Associated Ring Chromosome 1 (DEAR1), is a cytoplasmic E3 ubiquitin-protein ligase that was identified as a dominant regulator of acinar morphogenesis in the mammary gland. It is implicated in the inflammatory response of immune cells by regulating the Toll-like receptor 4 (TLR4) signaling pathway, leading to increased activity of the activator protein 1 (AP-1) transcription factor in primary macrophages. It is also involved in muscular protein homeostasis, especially during inflammation-induced atrophy, and may play a role in the pathogenesis of ICU-acquired weakness (ICUAW) by activating and maintaining inflammation in myocytes. Moreover, TRIM62 facilitates K27-linked poly-ubiquitination of CARD9 and also regulates CARD9-mediated anti-fungal immunity and intestinal inflammation. It also functions as a chromosome 1p35 tumor suppressor and negatively regulates transforming growth factor beta (TGFbeta)-driven epithelial-mesenchymal transition (EMT) by binding to and promoting the ubiquitination of SMAD3, a major effector of TGFbeta-mediated EMT. TRIM62 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1787508884  289 KSISCQICEHILADPVETNCKHVFCRVCILRCLKVMGSY-CPSCRYPC 335
Cdd:cd16608      5 DELLCSICLSIYQDPVSLGCEHYFCRQCITEHWSRSEHRdCPECRRTF 52

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM41, TRIM52 and similar proteins; TRIM41 and TRIM52, two closely related tripartite motif-containing proteins, have dramatically expanded RING domains compared with the rest of the TRIM family proteins. TRIM41 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. In contrast, TRIM52 lacks the putative viral recognition SPRY/B30.2 domain, and thus has been classified to the C-V subclass of the TRIM family that contains only RBCC domains. TRIM41, also known as RING finger-interacting protein with C kinase (RINCK), is an E3 ubiquitin-protein ligase that promotes the ubiquitination of protein kinase C (PKC) isozymes in cells. It specifically recognizes the C1 domain of PKC isozymes. It controls the amplitude of PKC signaling by controlling the amount of PKC in the cell. TRIM52, also known as RING finger protein 102 (RNF102), is encoded by a novel, noncanonical antiviral TRIM52 gene in primate genomes with unique specificity determined by the rapidly evolving RING domain.

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                   ....*....|....*....|....*....|....*....|
gi 1787508884  293 CQICEHILADPVETNCKHVFCRVCIlrcLKVMGSYCPSCR 332
Cdd:cd16602      6 CAICLDYFKDPVSIGCGHNFCRVCV---TQLWGFTCPQCR 42

RING finger, HC subclass, found in tripartite motif-containing protein 72 (TRIM72) and similar proteins; TRIM72, also known as Mitsugumin-53 (MG53), is a muscle-specific protein that plays a central role in cell membrane repair by nucleating the assembly of the repair machinery at muscle injury sites. It is required in repair of alveolar epithelial cells under plasma membrane stress failure. It interacts with dysferlin to regulate sarcolemmal repair. Upregulation of TRIM72 develops obesity, systemic insulin resistance, dyslipidemia, and hyperglycemia, as well as induces diabetic cardiomyopathy through transcriptional activation of the peroxisome proliferation-activated receptor alpha (PPAR-alpha) signaling pathway. Compensation for the absence of AKT signaling by ERK signaling during TRIM72 overexpression leads to pathological hypertrophy. Moreover, TRIM72 functions as a novel negative feedback regulator of myogenesis by targeting insulin receptor substrate-1 (IRS-1). It is transcriptionally activated by the synergism of myogenin (MyoD) and myocyte enhancer factor 2 (MEF2). TRIM72 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1787508884  289 KSISCQICEHILADPVETNCKHVFCRVCILRCLK---VMGSYCPSCRYPCFPTDL 340
Cdd:cd16612      3 QDLSCPLCLKLFQSPVTTECGHTFCQDCLSRVPKeedGGSTSCPTCQAPTKPEQL 57

RING finger, HC subclass, found in RING finger protein 168 (RNF168) and similar proteins; RNF168 is an E3 ubiquitin-protein ligase that promotes noncanonical K27 ubiquitination to signal DNA damage. It, together with RNF8, functions as a DNA damage response (DDR) factor that promotes a series of ubiquitylation events on substrates, such as H2A and H2AX with H2AK13/15 ubiquitylation, facilitates recruitment of repair factors p53-binding protein 1 (53BP1) or the RAP80-BRCA1 complex to sites of double-strand breaks (DSBs), and inhibits homologous recombination (HR) in cells deficient in the tumor suppressor BRCA1. RNF168 also promotes H2A neddylation, which antagonizes ubiquitylation of H2A and regulates DNA damage repair. Moreover, RNF168 forms a functional complex with RAD6A or RAD6B during the DNA damage response. RNF168 contains an N-terminal C3HC4-type RING-HC finger that catalyzes H2A-K15ub and interacts with H2A, and two MIU (motif interacting with ubiquitin) domains responsible for the interaction with K63 linked poly-ubiquitin.

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                   ....*....|....*....|....*....|....*....|
gi 1787508884  293 CQICEHILADPVETNCKHVFCRVCILRCLKVMGSYCPSCR 332
Cdd:cd16550      3 CPICLEILVEPVTLPCNHTLCMPCFQSTVEKASLCCPLCR 42

RING finger, HC subclass, found in tripartite motif-containing protein 77 (TRIM77) and similar proteins; TRIM77 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including two consecutive zinc-binding domains, a C3HC4-type RING-HC finger and Bbox2, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1787508884  290 SISCQICEHILADPVETNCKHVFCRVCIlRCL---KVMGSYCPSCRYPcFPT 338
Cdd:cd16543      3 QLTCSICLDLLKDPVTIPCGHSFCMNCI-TLLwdrKQGVPSCPQCRES-FPP 52

RING finger, HC subclass, found in tripartite motif-containing protein 39 (TRIM39) and similar proteins; TRIM39, also known as RING finger protein 23 (RNF23) or testis-abundant finger protein, is an E3 ubiquitin-protein ligase that plays a role in controlling DNA damage-induced apoptosis through inhibition of the anaphase promoting complex (APC/C), a multiprotein ubiquitin ligase that controls multiple cell cycle regulators, including cyclins, geminin, and others. TRIM39 also functions as a regulator of several key processes in the proliferative cycle. It directly regulates p53 stability. It modulates cell cycle progression and DNA damage responses via stabilizing p21. Moreover, TRIM39 negatively regulates the nuclear factor kappaB (NFkappaB)-mediated signaling pathway through stabilization of Cactin, an inhibitor of NFkappaB- and Toll-like receptor (TLR)-mediated transcription, which is induced by inflammatory stimulants such as tumor necrosis factor alpha. Furthermore, TRIM39 is a MOAP-1-binding protein that can promote apoptosis signaling through stabilization of MOAP-1 via the inhibition of its poly-ubiquitination process. TRIM39 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1787508884  292 SCQICEHILADPVETNCKHVFCRVCILRCL-KVMGSY-CPSC 331
Cdd:cd16601      3 SCSLCKEYLKDPVIIECGHNFCRACITRFWeELDGDFpCPQC 44

RING finger, HC subclass, found in really interesting new gene proteins RING1, RING2 and similar proteins; RING1, also known as polycomb complex protein RING1, RING finger protein 1 (RNF1), or RING finger protein 1A (RING1A), is a transcriptional repressor that is associated with the Polycomb group (PcG) protein complex involved in stable repression of gene activity. RING2, also known as huntingtin-interacting protein 2-interacting protein 3, HIP2-interacting protein 3, protein DinG, RING finger protein 1B (RING1B), RING finger protein 2 (RNF2), or RING finger protein BAP-1, is an E3 ubiquitin-protein ligase that interacts with both nucleosomal DNA and an acidic patch on histone H4 to achieve the specific monoubiquitination of K119 on histone H2A (H2AK119ub), thereby playing a central role in histone code and gene regulation. Both RING1 and RING2 are core components of polycomb repressive complex 1 (PRC1) that functions as an E3-ubuiquitin ligase transferring the mono-ubuiquitin mark to the C-terminal tail of Histone H2A at K118/K119. PRC1 is also capable of chromatin compaction, a function not requiring histone tails, and this activity appears important in gene silencing. RING2 acts as the main E3 ubiquitin ligase on histone H2A of the PRC1 complex, while RING1 may rather act as a modulator of RNF2/RING2 activity. Members of this family contain a C3HC4-type RING-HC finger.

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                   ....*....|....*....|....*....|....*....|....*.
gi 1787508884  291 ISCQICEHILADPVET-NCKHVFCRVCILRCLKVMGSYCPSCRYPC 335
Cdd:cd16531      2 LMCPICLGIIKNTMTVkECLHRFCAECIEKALRLGNKECPTCRKHL 47

RING finger, HC subclass, found in Arabidopsis thaliana protein BREAST CANCER SUSCEPTIBILITY 1 homolog (AtBRCA1) and similar proteins; AtBRCA1 plays a role in DNA repair and in cell-cycle control. It is required for the repair of DNA double-strand breaks (DSBs), both natural and induced by genotoxic stress, by homologous recombination (HR). AtBRCA1 contains a typical C3HC4-type RING-HC finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1787508884  289 KSISCQICEHILADPVETNCKHVFCRVCILRCLKVMgSYCPSCRYP 334
Cdd:cd23147      3 KELKCPICLSLFKSAANLSCNHCFCAGCIGESLKLS-AICPVCKIP 47

RING finger, HC subclass, found in tripartite motif-containing protein TRIM25 and similar proteins; TRIM25, also known as estrogen-responsive finger protein (EFP), RING finger protein 147 (RNF147), or RING-type E3 ubiquitin transferase, is an E3 ubiquitin/ISG15 ligase that is induced by estrogen and is therefore particularly abundant in placenta and uterus. TRIM25 regulates various cellular processes through E3 ubiquitin ligase activity, transferring ubiquitin and ISG15 to target proteins. It mediates K63-linked polyubiquitination of retinoic acid inducible gene I (RIG-I) that is crucial for downstream antiviral interferon signaling. It is also required for melanoma differentiation-associated gene 5 (MDA5) and mitochondrial antiviral signaling (MAVS, also known as IPS-1, VISA, Cardiff) mediated activation of nuclear factor-kappaB (NF-kappaB) and interferon production. Upon UV irradiation, TRIM25 interacts with mono-ubiquitinated PCNA and promotes its ISG15 modification (ISGylation), suggesting a crucial role in termination of error-prone translesion DNA synthesis. TRIM25 also functions as a novel regulator of p53 and Mdm2. It enhances p53 and Mdm2 abundance by inhibiting their ubiquitination and degradation in 26S proteasomes. Meanwhile, it inhibits p53's transcriptional activity and dampens the response to DNA damage, and is essential for medaka development and this dependence is rescued by silencing of p53. Moreover, TRIM25 is involved in the host cellular innate immune response against retroviral infection. It interferes with the late stage of feline leukemia virus (FeLV) replication. Furthermore, TRIM25 acts as an oncogene in gastric cancer. Its blockade by RNA interference inhibits migration and invasion of gastric cancer cells through transforming growth factor-beta (TGF-beta) signaling, suggesting it presents a novel target for the detection and treatment of gastric cancer. In addition, TRIM25 acts as an RNA-specific activator for Lin28a/TuT4-mediated uridylation. TRIM25 belongs to the C-IV subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1787508884  292 SCQICEHILADPVETNCKHVFCRVCILRCLKVMGS---YCPSCRyPCFPTDLE 341
Cdd:cd16597      7 TCSICLELFKDPVTLPCGHNFCGVCIEKTWDSQHGseySCPQCR-ATFPRRPE 58

RING finger, HC subclass, found in ubiquitin-like PHD and RING finger domain-containing proteins, UHRF1 and UHRF2, and similar proteins; UHRF1 is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma (LSCC), gastric cancer (GC), esophageal squamous cell carcinoma (ESCC), colorectal cancer, prostate cancer, and breast cancer. UHRF1 acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumor suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21. Moreover, UHRF1-dependent repression of transcription factors can facilitate the G1-S transition. It interacts with Tat-interacting protein of 60 kDa (TIP60) and induces degradation-independent ubiquitination of TIP60. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53 status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF2 was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131 (ZNF131) SUMOylation, but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. Moreover, UHRF2 functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs, p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Furthermore, UHRF2 is a direct transcriptional target of the transcription factor E2F-1 in the induction of apoptosis. It recruits HDAC1 and binds to methyl-CpG. UHRF2 also participates in the maturation of Hepatitis B virus (HBV) by interacting with the HBV core protein and promoting its degradation. Both UHRF1 and UHRF2 contain an N-terminal ubiquitin-like domain (UBL), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a SET- and RING-associated (SRA) domain, and a C-terminal C3HC4-type RING-HC finger.

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gi 1787508884  293 CQICEHILADPVETNCKHVFCRVCILRCLKVMGSYCPSCRY 333
Cdd:cd16613      3 CICCQELVYKPITTPCKHNICKSCLQRSFKAEVYTCPACRH 43

Modified RING finger, HC subclass (C3HC3D-type), found in tumor necrosis factor (TNF) receptor-associated factor 7 (TRAF7) and similar proteins; TRAF7, also known as RING finger and WD repeat-containing protein 1 or RING finger protein 119 (RNF119), is an E3 ubiquitin-protein ligase involved in signal transduction pathways that lead either to activation or repression of NF-kappaB transcription factor by promoting K29-linked ubiquitination of several cellular targets, including the NF-kappaB essential modulator (NEMO) and the p65 subunit of NF-kappaB transcription factor. It is also involved in K29-linked polyubiquitination that has been implicated in lysosomal degradation of proteins. Moreover, TRAF7 is required for K48-linked ubiquitination of p53, a key tumor suppressor and a master regulator of various signaling pathways, such as those related to apoptosis, cell cycle and DNA repair. It is also required for tumor necrosis factor alpha (TNFalpha)-induced Jun N-terminal kinase activation and promotes cell death by regulating polyubiquitination and lysosomal degradation of c-FLIP protein. Furthermore, TRAF7 functions as small ubiquitin-like modifier (SUMO) E3 ligase involved in other post-translational modification, such as sumoylation. It binds to and stimulates sumoylation of the proto-oncogene product c-Myb, a transcription factor regulating proliferation and differentiation of hematopoietic cells. It potentiates MEKK3-induced AP1 and CHOP activation and induces apoptosis. Meanwhile, TRAF7 mediates MyoD1 regulation of the pathway and cell-cycle progression in myoblasts. It also plays a role in Toll-like receptors (TLR) signaling. TRAF7 contains an N-terminal domain with a modified C3HC3D-type RING-HC finger and an adjacent zinc finger, and a unique C-terminal domain that comprises a coiled coil domain and seven WD40 repeats.

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gi 1787508884  293 CQICEHILADPVETNCKHVFCRVCILRclkVMGSYCPS 330
Cdd:cd16644      8 CPLCQRVFKDPVITSCGHTFCRRCALT---APGEKCPV 42

RING finger, HC subclass, found in tripartite motif-containing protein 47 (TRIM47) and similar proteins; TRIM47, also known as gene overexpressed in astrocytoma protein (GOA) or RING finger protein 100 (RNF100), belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, a B-box, and two coiled coil domains, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. It plays an important role in the process of dedifferentiation that is associated with astrocytoma tumorigenesis. This subfamily also includes RING finger protein 135 (RNF135). RNF135, also known as RIG-I E3 ubiquitin ligase (REUL) or Riplet, is a widely expressed E3 ubiquitin-protein ligase that consists of an N-terminal C3HC4-type RING-HC finger and C-terminal B30.2/SPRY and PRY motifs, but lacks the B-box and coiled-coil domains that are also typically present in TRIM proteins. RNF135 serves as a specific retinoic acid-inducible gene-I (RIG-I)-interacting protein that ubiquitinates RIG-I and specifically stimulates RIG-I-mediated innate antiviral activity to produce antiviral type-I interferon (IFN) during the early phase of viral infection. It also has been identified as a bio-marker and therapy target of glioblastoma. It associates with the ERK signal transduction pathway and plays a role in glioblastoma cell proliferation, migration and cell cycle.

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gi 1787508884  291 ISCQICEHILADPVETNCKHVFCRVCI--LRCLKVMGSY-CPSCRYP 334
Cdd:cd16604      1 LSCPICLDLLKDPVTLPCGHSFCMGCLgaLWGAGRGGRAsCPLCRQT 47