first BRCT domain of BRCA1-associated RING domain protein 1 (Bard1) and similar proteins; Bard1, also termed BARD-1, or RING-type E3 ubiquitin transferase BARD1, is a critical factor in BRCA1-mediated tumor suppression and may also serve as a target for tumorigenic lesions in some human cancers. It associates with BRCA1 (breast cancer-1) to form a heterodimeric BRCA1/BARD1 complex that is responsible for maintaining genomic stability through nuclear functions involving DNA damage signaling and repair, transcriptional regulation, and cell cycle control. The BRCA1/BARD1 complex catalyzes autoubiquitination of BRCA1 and trans ubiquitination of other protein substrates. Its E3 ligase activity is dramatically reduced in the presence of UBX domain protein 1 (UBXN1). BARD-1 contains an N-terminal C3HC4-type RING-HC finger that binds BRCA1, and a C-terminal region with three ankyrin repeats and tandem BRCT domains that bind CstF-50 (cleavage stimulation factor) to modulate mRNA processing and RNAP II stability in response to DNA damage. The family corresponds to the first BRCT domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1350206831 720 LVLCCSGLTNEEKIVISEFAELSGVTISRKWEPSVTHVIASINENGACKRTLKFMMGILEGKWILSIDWIKACLKNTKYV 799
Cdd:cd17734     1 LVLLGSGLSSEQKKLLEKLAQLLKAKVVTEFSPEVTHVVVPADERGVCPRTMKYLMGILAGKWIVSFEWVEACLKAKKLV 80

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1350206831 587 VHKNCAEWAPNVYFNNLNAVNLNVELTRSRRISCSGCGLKGAALGCYNKSCKNSFHVTCAKLiPECRWDNENFVMLCPL 665
Cdd:cd15668    25 VHEDCAVWAPGVYLVGGKLYGLEEAVWVAKQSVCSSCQQTGATIGCLHKGCKAKYHYPCAVE-SGCQLDEENFSLLCPK 102

C-terminal domain of the breast cancer suppressor protein (BRCA1) and related domains; The BRCT (BRCA1 C-terminus) domain is found within many DNA damage repair and cell cycle checkpoint proteins. BRCT domains interact with each other forming homo/hetero BRCT multimers, but are also involved in BRCT-non-BRCT interactions and interactions within DNA strand breaks. BRCT tandem repeats bind to phosphopeptides; it has been shown that the repeats in human BRCA1 bind specifically to pS-X-X-F motifs, mediating the interaction between BRCA1 and the DNA helicase BACH1, or BRCA1 and CtIP, a transcriptional corepressor. It is assumed that BRCT repeats play similar roles in many signaling pathways associated with the response to DNA damage.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1350206831 831 LFNELKFYIMGDF-ELAYKGYLQDLIVAAGGTILRRRPISNDNEASTI-VVFSVEPSKKKSLTQR-------RSDGEALA 901
Cdd:cd17720     1 LFDGCHFYFHGTFkPPTTKDDLEQLVKAGGGTVLSREPKPDSDVTQTInTVAYARPDSDLANCTHyiiydklNDKKPAKV 80

                          90
                  ....*....|....*...
gi 1350206831 902 KSARARAASSSWVLDSIA 919
Cdd:cd17720    81 RQGKVRVVPVSWLLDCIS 98

first BRCT domain of BRCA1-associated RING domain protein 1 (Bard1) and similar proteins; Bard1, also termed BARD-1, or RING-type E3 ubiquitin transferase BARD1, is a critical factor in BRCA1-mediated tumor suppression and may also serve as a target for tumorigenic lesions in some human cancers. It associates with BRCA1 (breast cancer-1) to form a heterodimeric BRCA1/BARD1 complex that is responsible for maintaining genomic stability through nuclear functions involving DNA damage signaling and repair, transcriptional regulation, and cell cycle control. The BRCA1/BARD1 complex catalyzes autoubiquitination of BRCA1 and trans ubiquitination of other protein substrates. Its E3 ligase activity is dramatically reduced in the presence of UBX domain protein 1 (UBXN1). BARD-1 contains an N-terminal C3HC4-type RING-HC finger that binds BRCA1, and a C-terminal region with three ankyrin repeats and tandem BRCT domains that bind CstF-50 (cleavage stimulation factor) to modulate mRNA processing and RNAP II stability in response to DNA damage. The family corresponds to the first BRCT domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1350206831 720 LVLCCSGLTNEEKIVISEFAELSGVTISRKWEPSVTHVIASINENGACKRTLKFMMGILEGKWILSIDWIKACLKNTKYV 799
Cdd:cd17734     1 LVLLGSGLSSEQKKLLEKLAQLLKAKVVTEFSPEVTHVVVPADERGVCPRTMKYLMGILAGKWIVSFEWVEACLKAKKLV 80

Extended PHD finger found in retinoic acid-induced protein 1 (RAI1), transcription factor 20 (TCF-20) and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the C-terminal ePHD/ADD (ATRX-DNMT3-DNMT3L) domain of RAI1 and TCF-20. RAI1, a homolog of stromelysin-1 PDGF (platelet-derived growth factor)-responsive element-binding protein (SPBP, also termed TCF-20), is a chromatin-binding protein implicated in the regulation of gene expression. TCF-20 is involved in transcriptional activation of the MMP3 (matrix metalloprotease 3) promoter. It also functions as a transcriptional co-regulator that enhances or represses the transcriptional activity of certain transcription factors/cofactors, such as specificity protein 1 (Sp1), E twenty-six 1 (Ets1), paired box protein 6 (Pax6), small nuclear RING-finger (SNURF)/RNF4, c-Jun, androgen receptor (AR) and estrogen receptor alpha (ERalpha). Both RAI1 and TCF-20 are strongly enriched in chromatin in interphase HeLa cells, and display low nuclear mobility, and have been implicated in Smith-Magenis syndrome and Potocki-Lupski syndrome.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1350206831 587 VHKNCAEWAPNVYFNNLNAVNLNVELTRSRRISCSGCGLKGAALGCYNKSCKNSFHVTCAKLiPECRWDNENFVMLCPL 665
Cdd:cd15668    25 VHEDCAVWAPGVYLVGGKLYGLEEAVWVAKQSVCSSCQQTGATIGCLHKGCKAKYHYPCAVE-SGCQLDEENFSLLCPK 102

breast cancer carboxy-terminal domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1350206831  710 SKPLHGLpkklVLCCSG-LTNEEKIVISEFAELSGVTISRKW-EPSVTHVIASINENgackRTLKFMMGILEGKWILSID 787
Cdd:smart00292   1 PKLFKGK----TFYITGsFDKEERDELKELIEALGGKVTSSLsSKTTTHVIVGSPEG----GKLELLKAIALGIPIVKEE 72

                   ....*.
gi 1350206831  788 WIKACL 793
Cdd:smart00292  73 WLLDCL 78

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 1350206831  14 LKCPICLSLFNSAVSLSCNHVFCNACIVKSMKMDATCPVCKIPYHRREIRGAPHMDSLVSIYKN----------MENASG 83
Cdd:TIGR00599  27 LRCHICKDFFDVPVLTSCSHTFCSLCIRRCLSNQPKCPLCRAEDQESKLRSNWLVSEIVESFKNlrpslleflrIPKTTP 106

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1350206831  84 VNMFVSQNKPSPSGKEKHVRDAS-----------IDKTSEKN---------RQGSRKGRTSKRKEYRKTKETDVDAPGPI 143
Cdd:TIGR00599 107 VENPDLAGPENSSKIELIEESESdgvdaededlqRSATSSRAlaarstadiLQLSSDPSKRNDADYRSEPPNEGLVQCPI 186

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1350206831 144 VmkpsSQTKKRVQLLQNHSSESLTKSTESAEKLKDYTENTvirlNEDPSlnkygnlaPFFWLRDEDDGKSLSQPESDQLL 223
Cdd:TIGR00599 187 C----QQRMPEKAVERHLDSECLGSPSLGASTTFPTESNP----HNKSS--------SRFSFRTVDKSSTGETSHVDKYL 250

                         250       260
                  ....*....|....*....|..
gi 1350206831 224 DVTPVDVP------SFSDLKDS 239
Cdd:TIGR00599 251 NSMMSKPPerlpkiNYSLLTDS 272

Ring finger domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1350206831  16 CPICLSLFN---SAVSLSCNHVFCNACIVKSMKMDATCPVCK 54
Cdd:pfam13639   3 CPICLEEFEegdKVVVLPCGHHFHRECLDKWLRSSNTCPLCR 44

N1R/p28-like protein; Provisional

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1350206831   3 ETNHLEKMGRElkCPICL---------SLFNSAVSlSCNHVFCNACIVKSMKMDATCPVCKIPY 57
Cdd:PHA02929  166 EKLYNRSKDKE--CAICMekvydkeikNMYFGILS-NCNHVFCIECIDIWKKEKNTCPVCRTPF 226

Uncharacterized conserved protein, contains RING Zn-finger [General function prediction only];

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1350206831  14 LKCPICLSLFNSAV-SLSCNHVFCNACIVKSM-KMDATCPVCkipyHRREI 62
Cdd:COG5222   275 LKCPLCHCLLRNPMkTPCCGHTFCDECIGTALlDSDFKCPNC----SRKDV 321

PHD zinc finger-containing protein [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1350206831 536 LLRRCDGPPIDKFTCAFCQSSEDTeasgemahyhrgepvsadFNGGSKVIHVHKNCAEWAPNVYFNNLNAV---NLNVEL 612
Cdd:COG5141   236 LCRKCIYGEYQIRCCSFCPSSDGA------------------FKQTSDGRWGHVICAMFNPELSFGHLLSKdpiDNIASV 297

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1350206831 613 TRSR-RISCSGCGLK-GAALGCYNKSCKNSFHVTCAK 647
Cdd:COG5141   298 SSSRwKLGCLICKEFgGTCIQCSYFNCTRAYHVTCAR 334

first BRCT domain of BRCA1-associated RING domain protein 1 (Bard1) and similar proteins; Bard1, also termed BARD-1, or RING-type E3 ubiquitin transferase BARD1, is a critical factor in BRCA1-mediated tumor suppression and may also serve as a target for tumorigenic lesions in some human cancers. It associates with BRCA1 (breast cancer-1) to form a heterodimeric BRCA1/BARD1 complex that is responsible for maintaining genomic stability through nuclear functions involving DNA damage signaling and repair, transcriptional regulation, and cell cycle control. The BRCA1/BARD1 complex catalyzes autoubiquitination of BRCA1 and trans ubiquitination of other protein substrates. Its E3 ligase activity is dramatically reduced in the presence of UBX domain protein 1 (UBXN1). BARD-1 contains an N-terminal C3HC4-type RING-HC finger that binds BRCA1, and a C-terminal region with three ankyrin repeats and tandem BRCT domains that bind CstF-50 (cleavage stimulation factor) to modulate mRNA processing and RNAP II stability in response to DNA damage. The family corresponds to the first BRCT domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1350206831 720 LVLCCSGLTNEEKIVISEFAELSGVTISRKWEPSVTHVIASINENGACKRTLKFMMGILEGKWILSIDWIKACLKNTKYV 799
Cdd:cd17734     1 LVLLGSGLSSEQKKLLEKLAQLLKAKVVTEFSPEVTHVVVPADERGVCPRTMKYLMGILAGKWIVSFEWVEACLKAKKLV 80

first BRCT domain of breast cancer type 1 susceptibility protein (BRCA1) and similar proteins; BRCA1, also termed RING finger protein 53 (RNF53), is a RING finger protein encoded by BRCA1, a tumor suppressor gene 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. The family corresponds to the first BRCT domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1350206831 725 SGLTNEEKIVISEFAELSGVTISRKWEPSVTHVIASINENGACKRTLKFMMGILEGKWILSIDWIKACLKNTKYVSEEPY 804
Cdd:cd17735     6 SGLTPEELMLVQKFARKTGSTLTSQFTEETTHVIMKTDAELVCERTLKYFLGIAGRKWVVSYQWITQSIKEGKILPEHDF 85

                  ....*.
gi 1350206831 805 EIYMDV 810
Cdd:cd17735    86 EVRGDV 91

Extended PHD finger found in retinoic acid-induced protein 1 (RAI1), transcription factor 20 (TCF-20) and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the C-terminal ePHD/ADD (ATRX-DNMT3-DNMT3L) domain of RAI1 and TCF-20. RAI1, a homolog of stromelysin-1 PDGF (platelet-derived growth factor)-responsive element-binding protein (SPBP, also termed TCF-20), is a chromatin-binding protein implicated in the regulation of gene expression. TCF-20 is involved in transcriptional activation of the MMP3 (matrix metalloprotease 3) promoter. It also functions as a transcriptional co-regulator that enhances or represses the transcriptional activity of certain transcription factors/cofactors, such as specificity protein 1 (Sp1), E twenty-six 1 (Ets1), paired box protein 6 (Pax6), small nuclear RING-finger (SNURF)/RNF4, c-Jun, androgen receptor (AR) and estrogen receptor alpha (ERalpha). Both RAI1 and TCF-20 are strongly enriched in chromatin in interphase HeLa cells, and display low nuclear mobility, and have been implicated in Smith-Magenis syndrome and Potocki-Lupski syndrome.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1350206831 587 VHKNCAEWAPNVYFNNLNAVNLNVELTRSRRISCSGCGLKGAALGCYNKSCKNSFHVTCAKLiPECRWDNENFVMLCPL 665
Cdd:cd15668    25 VHEDCAVWAPGVYLVGGKLYGLEEAVWVAKQSVCSSCQQTGATIGCLHKGCKAKYHYPCAVE-SGCQLDEENFSLLCPK 102

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        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1350206831   7 LEKMGRELKCPICLSLFNSAVSLSCNHVFCNACIVKSMKM---DATCPVCKIPYHRREIRGAPHMDSLVSIYKNMENA 81
Cdd:cd16498    10 ISAMQKNLECPICLELLKEPVSTKCDHQFCRFCILKLLQKkkkPAPCPLCKKSVTKRSLQESTRFKQLVEAVKKLIDA 87

Extended PHD finger (ePHD) found in transcription factor 20 (TCF-20); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model corresponds to the C-terminal ePHD/ADD (ATRX-DNMT3-DNMT3L) domain of TCF-20. TCF-20, also termed nuclear factor SPBP, or protein AR1, or stromelysin-1 PDGF (platelet-derived growth factor)-responsive element-binding protein (SPRE-binding protein), is involved in transcriptional activation of the MMP3 (matrix metalloprotease 3) promoter. It is strongly enriched on chromatin in interphase HeLa cells, and displays low nuclear mobility, and has been implicated in Smith-Magenis syndrome and Potocki-Lupski syndrome. As a chromatin-binding protein, TCF-20 plays a role in the regulation of gene expression. It also functions as a transcriptional co-regulator that enhances or represses the transcriptional activity of certain transcription factors/cofactors, such as specificity protein 1 (Sp1), E twenty-six 1 (Ets1), paired box protein 6 (Pax6), small nuclear RING-finger (SNURF)/RNF4, c-Jun, androgen receptor (AR) and estrogen receptor alpha (ERalpha). TCF-20 contains an N-terminal transactivation domain, a novel DNA-binding domain with an AT-hook motif, three nuclear localization signals (NLSs) and a C-terminal ePHD/ADD domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1350206831 587 VHKNCAEWAPNVYFNNLNAVNLNVELTRSRRISCSGCGLKGAALGCYNKSCKNSFHVTCAkLIPECRWDNENFVMLCP 664
Cdd:cd15699    25 VHEGCILWANGIYLVCGRLYGLQEALDIAREMKCSHCQEAGATLGCYNKGCSFRYHYPCA-IDADCLLNEENFSVRCP 101

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM5, TRIM6, TRIM22, TRIM34 and similar proteins; TRIM5, TRIM6, TRIM22, and TRIM34, four 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, 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. TRIM5, also known as RING finger protein 88 (RNF88), is a capsid-specific restriction factor that prevents infection from non-host-adapted retroviruses in a species-specific manner by binding to and destabilizing the retroviral capsid lattice before reverse transcription is completed. Its retroviral restriction activity correlates with the ability to activate TAK1-dependent innate immune signaling. TRIM5 also acts as a pattern recognition receptor that activates innate immune signaling in response to the retroviral capsid lattice. Moreover, TRIM5 plays a role in regulating autophagy through activation of autophagy regulator BECN1 by causing its dissociation from its inhibitors BCL2 and TAB2. It also plays a role in autophagy by acting as a selective autophagy receptor which recognizes and targets HIV-1 capsid protein p24 for autophagic destruction. TRIM6, also known as RING finger protein 89 (RNF89), is an E3-ubiquitin ligase that cooperates with the E2-ubiquitin conjugase UbE2K to catalyze the synthesis of unanchored K48-linked polyubiquitin chains, and further stimulates the interferon-I kappa B kinase epsilon (IKKepsilon) kinase-mediated antiviral response. It also regulates the transcriptional activity of Myc during the maintenance of embryonic stem (ES) cell pluripotency, and may act as a novel regulator for Myc-mediated transcription in ES cells. TRIM22, also known as 50 kDa-stimulated trans-acting factor (Staf-50) or RING finger protein 94 (RNF94), is an E3 ubiquitin-protein ligase that plays an integral role in the host innate immune response to viruses. It has been shown to inhibit the replication of a number of viruses, including HIV-1, hepatitis B, and influenza A. TRIM22 acts as a suppressor of basal HIV-1 long terminal repeat (LTR)-driven transcription by preventing the transcription factor specificity protein 1 (Sp1) binding to the HIV-1 promoter. It also controls FoxO4 activity and cell survival by directing Toll-like receptor 3 (TLR3)-stimulated cells toward type I interferon (IFN) type I gene induction or apoptosis. Moreover, TRIM22 can activate the noncanonical nuclear factor-kappaB (NF-kappaB) pathway by activating I kappa B kinase alpha (IKKalpha). It also regulates nucleotide binding oligomerization domain containing 2 (NOD2)-dependent activation of interferon-beta signaling and nuclear factor-kappaB. TRIM34, also known as interferon-responsive finger protein 1 or RING finger protein 21 (RNF21), may function as antiviral protein that contribute to the defense against retroviral infections.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1350206831  13 ELKCPICLSLFNSAVSLSCNHVFCNACIV----KSMKMD--ATCPVCKIPYHRREIRGAPHMDSLV 72
Cdd:cd16591     6 EVTCPICLELLTEPLSLDCGHSFCQACITanhkESVNQEgeSSCPVCRTSYQPENLRPNRHLANIV 71

PHD-like zinc-binding domain; The members of this family are annotated as containing PHD domain, but the zinc-binding region here is not typical of PHD domains. The conformation here is a well-conserved cysteine-histidine rich region spanning 90 residues, where the Cys and His are arranged as HxxC(31)CxxC(6)CxxCxxxxCxxxxHxxC (21)CxxH.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1350206831 588 HKNCAEWAPNVYFNNLNAVNL-----NVELTRSRRISCSGCGLK-GAALGCYNKSCKNSFHVTCAK---LIPECRWDNEN 658
Cdd:pfam13771   1 HVVCALWSPELVQRGNDSMGFpiediEKIPKRRWKLKCYLCKKKgGACIQCSKKNCRRAFHVTCALeagLLMQFDEDNGT 80

                  ....*.
gi 1350206831 659 FVMLCP 664
Cdd:pfam13771  81 FKSYCK 86

BRCT domain of nibrin and similar proteins; Nibrin (NBN), also termed Nijmegen breakage syndrome protein 1 (NBS1), or cell cycle regulatory protein p95, is a novel DNA double-strand break repair protein that is mutated in Nijmegen breakage syndrome. It is a component of the MRE11-RAD50-NBN (MRN complex) which plays a critical role in the cellular response to DNA damage and the maintenance of chromosome integrity. The BRCT (Breast Cancer Suppressor Protein BRCA1, carboxy-terminal) domain is found within many DNA damage repair and cell cycle checkpoint proteins. The unique diversity of this domain superfamily allows BRCT modules to interact forming homo/hetero BRCT multimers, BRCT-non-BRCT interactions, and interactions within DNA strand breaks. The Trp-X-X-X-Cys/Ser signature motif of the BRCT family is absent in this group.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1350206831 718 KKLVLCCSGLTNEEKIVISEFAELSGVTISRKWEPSVTHVIASINengacKRTLKFMMGILEGKWILSIDWIKACLK 794
Cdd:cd17741     1 EPLVVCSSCLDSEEKKKLKQIIAKLGGKVVNEWTEECTHLVMSKI-----KVTVKVICALISGKPIVTPEYLDALLE 72

RING finger, HC subclass, found in tripartite motif-containing protein 35 (TRIM35) and similar proteins; TRIM35, also known as hemopoietic lineage switch protein 5 (HLS5), is a putative hepatocellular carcinoma (HCC) suppressor that inhibits phosphorylation of pyruvate kinase isoform M2 (PKM2), which is involved in aerobic glycolysis of cancer cells and further suppresses the Warburg effect and tumorigenicity in HCC. It also negatively regulates Toll-like receptor 7 (TLR7)- and TLR9-mediated type I interferon production by suppressing the stability of interferon regulatory factor 7 (IRF7). Moreover, TRIM35 regulates erythroid differentiation by modulating globin transcription factor 1 (GATA-1) activity. TRIM35 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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1350206831  13 ELKCPICLSLFNSAVSLSCNHVFCNACIVKS--MKMDATCPVCKIPYHRREIRGAPHMDSLV 72
Cdd:cd16599     4 ELLCPICYEPFREAVTLRCGHNFCKGCVSRSweRQPRAPCPVCKEASSSDDLRTNHTLNNLV 65

breast cancer carboxy-terminal domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1350206831  710 SKPLHGLpkklVLCCSG-LTNEEKIVISEFAELSGVTISRKW-EPSVTHVIASINENgackRTLKFMMGILEGKWILSID 787
Cdd:smart00292   1 PKLFKGK----TFYITGsFDKEERDELKELIEALGGKVTSSLsSKTTTHVIVGSPEG----GKLELLKAIALGIPIVKEE 72

                   ....*.
gi 1350206831  788 WIKACL 793
Cdd:smart00292  73 WLLDCL 78

BRCA1 C Terminus (BRCT) domain; The BRCT domain is found predominantly in proteins involved in cell cycle checkpoint functions responsive to DNA damage. The BRCT domain of XRCC1 forms a homodimer in the crystal structure. This suggests that pairs of BRCT domains associate as homo- or heterodimers. BRCT domains are often found as tandem-repeat pairs. Structures of the BRCA1 BRCT domains revealed a basis for a widely utilized head-to-tail BRCT-BRCT oligomerization mode. This conserved tandem BRCT architecture facilitates formation of the canonical BRCT phospho-peptide interaction cleft at a groove between the BRCT domains. Disease associated missense and nonsense mutations in the BRCA1 BRCT domains disrupt peptide binding by directly occluding this peptide binding groove, or by disrupting key conserved BRCT core folding determinants.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1350206831 709 QSKPLHGLpkklVLCCSGLTNEEKIVISEFAELSGVTISRKWEPSVTHVIAsinengaCKRTLKFMMGILEGKWILSIDW 788
Cdd:pfam00533   2 KEKLFSGK----TFVITGLDGLERDELKELIEKLGGKVTDSLSKKTTHVIV-------EARTKKYLKAKELGIPIVTEEW 70

                  ....*
gi 1350206831 789 IKACL 793
Cdd:pfam00533  71 LLDCI 75

RING finger, HC subclass, found in tripartite motif-containing protein TRIM21 and similar proteins; TRIM21, also known as 52 kDa Ro protein, 52 kDa ribonucleoprotein autoantigen Ro/SS-A, Ro(SS-A), RING finger protein 81 (RNF81), or Sjoegren syndrome type A antigen (SS-A), is a ubiquitously expressed E3 ubiquitin-protein ligase and a high affinity antibody receptor uniquely expressed in the cytosol of mammalian cells. As a cytosolic Fc receptor, TRIM21 binds the Fc of virus-associated antibodies and targets the complex in the cytosol for proteasomal degradation in a process known as antibody-dependent intracellular neutralization (ADIN), and provides an intracellular immune response to protect host defense against pathogen infection. It shows remarkably broad isotype specificity as it does not only bind IgG, but also IgM and IgA. Moreover, TRIM21 promotes the cytosolic DNA sensor cGAS and the cytosolic RNA sensor RIG-I sensing of viral genomes during infection by antibody-opsonized virus. It stimulates inflammatory signaling and activates innate transcription factors, such as nuclear factor-kappaB (NF-kappaB). TRIM21 also plays an essential role in p62-regulated redox homeostasis, suggesting it may be a viable target for treating pathological conditions resulting from oxidative damage. Furthermore, TRIM21 may have implications for various autoimmune diseases associated with uncontrolled antiviral signaling through the regulation of Nmi-IFI35 complex-mediated inhibition of innate antiviral response. TRIM21 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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1350206831   7 LEKMGRELKCPICLSLFNSAVSLSCNHVFCNACIVKSMK-MDATCPVCKIPYHRREIRGAPHMDSLV 72
Cdd:cd16596     3 LTMMWEEVTCPICLDPFVEPVSIECGHSFCQECISQVGKgGGSVCPVCRQRFLLKNLRPNRQLANMV 69

RING finger, HC subclass, found in RING finger protein 213 (RNF213) and similar proteins; RNF213, also known as ALK lymphoma oligomerization partner on chromosome 17 or Moyamoya steno-occlusive disease-associated AAA+ and RING finger protein (mysterin), is an intracellular soluble protein that functions as an E3 ubiquitin-protein ligase and AAA+ ATPase, which possibly contributes to vascular development through mechanical processes in the cell. It plays a unique role in endothelial cells for proper gene expression in response to inflammatory signals from the environment. Mutations in RNF213 may be associated with Moyamoya disease (MMD), an idiopathic cerebrovascular occlusive disorder prevalent in East Asia. It also acts as a nuclear marker for acanthomorph phylogeny. RNF213 contains two tandem enzymatically active AAA+ ATPase modules and a C3HC4-type RING-HC finger. It can form a huge ring-shaped oligomeric complex.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1350206831  16 CPICLSLFNSAVSLSCNHVFCNACIVKSMKMDATCPVCK 54
Cdd:cd16561     5 CSICLEDLNDPVKLPCDHVFCEECIRQWLPGQMSCPLCR 43

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 1350206831  10 MGRELKCPICLSLFNSAVSLSCNHVFCNACIVKSMKMDAT----CPVCKIPYH 58
Cdd:cd16612     1 MHQDLSCPLCLKLFQSPVTTECGHTFCQDCLSRVPKEEDGgstsCPTCQAPTK 53

RING finger, HC subclass, found in BRCA1-associated RING domain protein 1 (BARD-1) and similar proteins; BARD-1 is a critical factor in BRCA1-mediated tumor suppression and may also serve as a target for tumorigenic lesions in some human cancers. It associates with BRCA1 (breast cancer-1) to form a heterodimeric BRCA1/BARD1 complex that is responsible for maintaining genomic stability through nuclear functions involving DNA damage signaling and repair, transcriptional regulation, and cell cycle control. The BRCA1/BARD1 complex catalyzes autoubiquitination of BRCA1 and trans ubiquitination of other protein substrates. Its E3 ligase activity is dramatically reduced in the presence of UBX domain protein 1 (UBXN1). BARD-1 contains an C3HC4-type RING-HC finger that binds BRCA1 at its N-terminus and three tandem ankyrin repeats and tandem BRCT repeat domains at its C-terminus. The BRCT repeats bind CstF-50 (cleavage stimulation factor) to modulate mRNA processing and RNAP II stability in response to DNA damage.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1350206831   7 LEKMGRELKCPICLSLFNSAVSL-SCNHVFCNACIVKSMkmDATCPVCKIPYHRREIRGAPHMDSLVSIYKNMEN 80
Cdd:cd16496     9 LDELENLLRCSRCASILKEPVTLgGCEHVFCRSCVGDRL--GNGCPVCDTPAWARDLQINRQLDSMVQLCRKLRN 81

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 1350206831   16 CPICLSLF-NSAVSLSCNHVFCNACIVKSMKMD-ATCPVC 53
Cdd:smart00184   1 CPICLEEYlKDPVILPCGHTFCRSCIRKWLESGnNTCPIC 40

RING finger, HC subclass, found in tripartite motif-containing protein 69 (TRIM69) and similar proteins; TRIM69, also known as RFP-like domain-containing protein trimless or RING finger protein 36 (RNF36), is a testis E3 ubiquitin-protein ligase that plays a specific role in apoptosis and may also play an important role in germ cell homeostasis during spermatogenesis. TRIM69 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 1350206831  13 ELKCPICLSLFNSAVSLSCNHVFCNACIV---KSMKMDATCPVCKIPYHRREIR 63
Cdd:cd16611     4 ELHCPLCLDFFRDPVMLSCGHNFCQSCITgfwELQAEDTTCPECRELCQYRNLT 57

Extended PHD finger found in PHD finger protein 6 (PHF6) and PHD finger protein 11 (PHF11); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the two ePHD fingers of PFH6 and the single ePHD finger of PFH11. PHF6, also termed the X-linked mental retardation disorder Borjeson-Forssman-Lehmann syndrome-associated protein, is a nucleolus, ribosomal RNA promoter-associated protein that regulates cell cycle progression by suppressing ribosomal RNA synthesis. It has been implicated in cell cycle control, genomic maintenance, and tumor suppression. PHF6 shows transcriptional repression activity through directly interacting with the nucleosome remodeling and deacetylation complex component RBBP4. PHF6 contains two non-canonical ePHD fingers. PHF11, also termed BRCA1 C-terminus-associated protein, or renal carcinoma antigen NY-REN-34, is a transcriptional co-activator of the Th1 effector cytokine genes, interleukin-2 (IL2) and interferon-gamma (IFNG), co-operating with nuclear factor kappa B (NF-kappaB). It is involved in T-cell activation and viability. Polymorphisms within PHF11 are associated with total IgE, allergic asthma and eczema.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1350206831 550 CAFCQSSEDTEASGEMAHyhRGEPVSAdfnggskvihvHKNCAEWAPNVY---------FNNLNAVNLNVELTRSRRISC 620
Cdd:cd15673     1 CGFCKSGEENKETGGKLA--SGEKIAA-----------HHNCMLFSSGLVqyvspnendFGGFDIEDVKKEIKRGRKLKC 67

                          90       100
                  ....*....|....*....|....*...
gi 1350206831 621 SGCGLKGAALGCYNKSCKNSFHVTCAKL 648
Cdd:cd15673    68 NLCKKTGATIGCDVKQCKKTYHYHCAKK 95

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        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1350206831  13 ELKCPICLSLFNSAVSLSCNHVFCNACIVKSMKMDAT-----CPVCKIPYHRREIR 63
Cdd:cd16598     4 EVTCSICLDYLRDPVTIDCGHNFCRSCITDYCPISGGherpvCPLCRKPFKKENIR 59

RING finger, HC subclass, found in Arabidopsis thaliana proteolysis 1 protein (PRT1) and similar proteins; PRT1, also called RING-type E3 ubiquitin transferase PRT1, is an E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. It functions in the N-end rule pathway of protein degradation, where it specifically recognizes and ubiquitinates proteins with an N-terminal bulky aromatic amino acid (Phe). It does not act on aliphatic hydrophobic and basic N-terminal residues (Arg or Leu) containing proteins. PRT1 contains a typical C3HC4-type RING-HC finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1350206831  12 RELKCPICLSLFNSAVSLSCNHVFCNACIVKSMKM--DATCPVCKIPY 57
Cdd:cd23132     1 EEFLCCICLDLLYKPVVLECGHVFCFWCVHRCMNGydESHCPLCRRPY 48

RING finger, HC subclass, found in E3 ubiquitin-protein ligase Deltex3 (DTX3), Deltex-3-like (DTX3L) and similar proteins; This subfamily contains Deltex3 (DTX3) and Deltex-3-like (DTX3L), both of which are E3 ubiquitin-protein ligases belonging to the Deltex (DTX) family. DTX3, also known as RING finger protein 154 (RNF154), has a biological function that remains unclear. DTX3L, also known as B-lymphoma- and BAL-associated protein (BBAP) or Rhysin-2 (Rhysin2), regulates endosomal sorting of the G protein-coupled receptor CXCR4 from endosomes to lysosomes. It also regulates subcellular localization of its partner protein, B aggressive lymphoma (BAL), by a dynamic nucleocytoplasmic trafficking mechanism. In contrast to other DTXs, both DTX3 and DTX3L contain a C3HC4-type RING-HC finger, and a previously unidentified C-terminal domain. DTX3L can associate with DTX1 through its unique N termini and further enhance self-ubiquitination.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1350206831  15 KCPICLSLFNSAVSL-SCNHVFCNACIVKSMKMDATCPVCKIPY 57
Cdd:cd16506     2 TCPICLDEIQNKKTLeKCKHSFCEDCIDRALQVKPVCPVCGVVY 45

RING finger, HC subclass, found in tripartite motif-containing protein 8 (TRIM8) and similar proteins; TRIM8, also known as glioblastoma-expressed RING finger protein (GERP) or RING finger protein 27 (RNF27), is a probable E3 ubiquitin-protein ligase that may promote proteasomal degradation of suppressor of cytokine signaling 1 (SOCS1) and further regulate interferon-gamma signaling. It functions as a new p53 modulator that stabilizes p53 impairing its association with MDM2 and inducing the reduction of cell proliferation. TRIM8 deficit dramatically impairs p53 stabilization and activation in response to chemotherapeutic drugs. TRIM8 also modulates tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta)-triggered nuclear factor-kappaB (NF- kappa B) activation by targeting transforming growth factor beta (TGFbeta) activated kinase 1 (TAK1) for K63-linked polyubiquitination. Moreover, TRIM8 modulates translocation of phosphorylated STAT3 into the nucleus through interaction with Hsp90beta and consequently regulates transcription of Nanog in embryonic stem cells. It also interacts with protein inhibitor of activated STAT3 (PIAS3), which inhibits IL-6-dependent activation of STAT3. TRIM8 belongs to the C-V 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 domain, as well as an uncharacterized region positioned C-terminal to the RBCC domain. The coiled coil domain is required for homodimerization and the region immediately C-terminal to the RING motif is sufficient to mediate the interaction with SOCS1.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1350206831  13 ELKCPICLSLFNSAVSLSCNHVFCNACIVKSMKMDAT---CPVCKIPYHRR 60
Cdd:cd16580    11 ELICPICLHVFVEPVQLPCKHNFCRGCIGEAWAKDAGlvrCPECNQAYNQK 61

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.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1350206831  16 CPICLSLFNSAVSLSCNHVFCNACIVKSMKMDATCPVCK 54
Cdd:cd16532     3 CPICQDEFKDPVVLRCKHIFCEDCVSEWFERERTCPLCR 41

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 1350206831  12 RELKCPICLSLFNSAVSLSCNHVFCNACIVKSMKMDAT---------CPVCKIP 56
Cdd:cd16592     3 EETTCPICLGYFKDPVILDCEHSFCRACIARHWGQEAMegngaegvfCPQCGEP 56

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).

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1350206831  15 KCPICLSLFNSAVSL--SCNHVFCNACIVKSMKMDATCPVCKIPY 57
Cdd:cd16574     3 SCPICLDRFENEKAFldGCFHAFCFTCILEWSKVKNECPLCKQPF 47

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1350206831  13 ELKCPICLSLFNSAVSLSCNHVFCNACIVKSMKMdaTCPVCKIPYHRREIR 63
Cdd:cd16602     3 EAVCAICLDYFKDPVSIGCGHNFCRVCVTQLWGF--TCPQCRKSFPRRSFR 51

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1350206831  16 CPICLSLFNSA---VSLSCNHVFCNACIVKSMKMDATCPVCK 54
Cdd:cd16454     2 CAICLEEFKEGekvRVLPCNHLFHKDCIDPWLEQHNTCPLCR 43

RING finger, HC subclass, found in RING finger protein 125 (RNF125); RNF125, also known as T-cell RING activation protein 1 (TRAC-1), is an E3 ubiquitin-protein ligase that is predominantly expressed in lymphoid cells, and functions as a positive regulator of T cell activation. It also down-modulates HIV replication and inhibits pathogen-induced cytokine production. It negatively regulates type I interferon signaling, which conjugates Lys(48)-linked ubiquitination to retinoic acid-inducible gene-I (RIG-I) and subsequently leads to the proteasome-dependent degradation of RIG-I. Further, RNF125 conjugates ubiquitin to melanoma differentiation-associated gene 5 (MDA5), a family protein of RIG-I. It thus acts as a negative regulator of RIG-I signaling, and is a direct target of miR-15b in the context of Japanese encephalitis virus (JEV) infection. Moreover, RNF125 binds to and ubiquitinates JAK1, prompting its degradation and inhibition of receptor tyrosine kinase (RTK) expression. It also negatively regulates p53 function through physical interaction and ubiquitin-mediated proteasome degradation. Mutations in RNF125 may lead to overgrowth syndromes (OGS). RNF125, together with three closely related proteins: RNF114, RNF138 and RNF166, 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). The UIM of RNF125 binds K48-linked poly-ubiquitin chains and is, together with the RING domain, required for auto-ubiquitination.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1350206831  14 LKCPICLSLFNSAVSLSCNHVFCNACIVKSMKMD-ATCPVCKIPYHR 59
Cdd:cd16542     2 FDCAVCLEVLHQPVRTRCGHVFCRPCIATSLRNNtWTCPYCRAYLSS 48

RING finger, HC subclass, found in tripartite motif-containing protein 38 (TRIM38) and similar proteins; TRIM38, also known as RING finger protein 15 (RNF15) or zinc finger protein RoRet, is an E3 ubiquitin-protein ligase that promotes K63- and K48-linked ubiquitination of cellular proteins and also catalyzes self-ubiquitination. It negatively regulates Tumor necrosis factor alpha (TNF-alpha)- and interleukin-1beta-triggered Nuclear factor-kappaB (NF-kappaB) activation by mediating lysosomal-dependent degradation of transforming growth factor beta (TGFbeta)-activated kinase 1 (TAK1)-binding protein (TAB)2/3, two critical components of the TAK1 kinase complex. It also inhibits TLR3/4-mediated activation of NF-kappaB and interferon regulatory factor 3 (IRF3) by mediating ubiquitin-proteasomal degradation of TNF receptor-associated factor 6 (Traf6) and NAK-associated protein 1 (Nap1), respectively. Moreover, TRIM38 negatively regulates TLR3-mediated interferon beta (IFN-beta) signaling by targeting ubiquitin-proteasomal degradation of TIR domain-containing adaptor inducing IFN-beta (TRIF). It functions as a valid target for autoantibodies in primary Sjogren's Syndrome. TRIM38 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        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1350206831   9 KMGRELKCPICLSLFNSAVSLSCNHVFCNACIVKSMKMDA---------TCPVCKIPY 57
Cdd:cd16600     1 KMREEATCSICLQLMTEPVSINCGHSYCKRCIVSFLENQSqlepgletfSCPQCRAPF 58