Protein of unknown function (DUF3583); This domain is found in eukaryotes, and is typically between 302 and 338 amino acids in length. It is found in association with pfam00097 and pfam00643. Most members are promyelocytic leukemia proteins, and this family lies towards the C-terminus.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960843  244 LGTMTQTLEEQGRTFDSAHAQMCSAIGQLDHARADIEKQIRARVRQVVDYVQAQERELLEAVNDRYQRDYQEIAGQLSCL 323
Cdd:pfam12126   1 LDTMTQALQEQDGAFGAAHAQMRSAISQLGRARADTEELIRARVRQVVAHVQAQERELLEAVNARYQRDYEEMAGQLGRL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960843  324 EAVLQRIRTSGALVKRMKLYASDQEVLDMHSFLRKALCSLRQEEPQNQKVQLLTRGFEEFKLCLQDFISCITQRINAAV- 402
Cdd:pfam12126  81 DAVLQRIRTGGALVQRMKRYASDQEVLDMHGFLREALCRLRQEEPQNLQAAVRTDGFDEFKVRLQDLVSCITQGTDAAVs 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960843  403 --ASPEAASnqpeaasthpvTTSTPEDLEQPKEVQSVQAQALELSKTQPVAMVKTVPGAHPVPVYAFSMQGPTYREEASQ 480
Cdd:pfam12126 161 rrASPEAAS-----------TPRDPSDVDLPEEVQRVQAQALGLAETQPVAVVQSVPGAHPVPVYAFSIKDPSYREEVSN 229

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960843  481 TVGSMKRKCSHEDCSRKIIKMESTEENEDRLATSSPEQSWPSTFKATSPPHLDGTSNPESTVPEKKILLPNNNHVTSDTG 560
Cdd:pfam12126 230 TVTPQKRKSCQTECPRKVIKMESEEEKEARLARSSPEQPRPSTSKAVSPPHLDGPPSPESPIVGKEVLLPNSNHVTSDPG 309

                         330       340
                  ....*....|....*....|
gi 568960843  561 ETEERVVVISSSEDSDTENL 580
Cdd:pfam12126 310 EAEERIVVISSSEDSDAENS 329

B-box-type zinc finger superfamily; The B-box-type zinc finger is a short zinc binding domain of around 40 amino acid residues in length. It has been found in transcription factors, ribonucleoproteins and proto-oncoproteins, such as in TRIM (tripartite motif) proteins that consist of an N-terminal RING finger (originally called an A-box), followed by 1-2 B-box domains and a coiled-coil domain (also called RBCC for Ring, B-box, Coiled-Coil). The B-box-type zinc finger often presents in combination with other motifs, like RING zinc finger, NHL motif, coiled-coil or RFP domain in functionally unrelated proteins, most likely mediating protein-protein interactions. Based on different consensus sequences and the spacing of the 7-8 zinc-binding residues, B-box-type zinc fingers can be divided into two groups, type 1 (Bbox1: C6H2) and type 2 (Bbox2: CHC3H2).

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 568960843 191 IFCSNTNHRNPaLTDIYCRGCAKPLCCTCALLDRNHSHLHCDIGEEIQQ 239
Cdd:cd19770    1 PFCPSPNHETQ-MISIYCRQCSKSVCCTCALLDSSHKGQHCDIKAEIQR 48

Protein of unknown function (DUF3583); This domain is found in eukaryotes, and is typically between 302 and 338 amino acids in length. It is found in association with pfam00097 and pfam00643. Most members are promyelocytic leukemia proteins, and this family lies towards the C-terminus.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960843  244 LGTMTQTLEEQGRTFDSAHAQMCSAIGQLDHARADIEKQIRARVRQVVDYVQAQERELLEAVNDRYQRDYQEIAGQLSCL 323
Cdd:pfam12126   1 LDTMTQALQEQDGAFGAAHAQMRSAISQLGRARADTEELIRARVRQVVAHVQAQERELLEAVNARYQRDYEEMAGQLGRL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960843  324 EAVLQRIRTSGALVKRMKLYASDQEVLDMHSFLRKALCSLRQEEPQNQKVQLLTRGFEEFKLCLQDFISCITQRINAAV- 402
Cdd:pfam12126  81 DAVLQRIRTGGALVQRMKRYASDQEVLDMHGFLREALCRLRQEEPQNLQAAVRTDGFDEFKVRLQDLVSCITQGTDAAVs 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960843  403 --ASPEAASnqpeaasthpvTTSTPEDLEQPKEVQSVQAQALELSKTQPVAMVKTVPGAHPVPVYAFSMQGPTYREEASQ 480
Cdd:pfam12126 161 rrASPEAAS-----------TPRDPSDVDLPEEVQRVQAQALGLAETQPVAVVQSVPGAHPVPVYAFSIKDPSYREEVSN 229

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960843  481 TVGSMKRKCSHEDCSRKIIKMESTEENEDRLATSSPEQSWPSTFKATSPPHLDGTSNPESTVPEKKILLPNNNHVTSDTG 560
Cdd:pfam12126 230 TVTPQKRKSCQTECPRKVIKMESEEEKEARLARSSPEQPRPSTSKAVSPPHLDGPPSPESPIVGKEVLLPNSNHVTSDPG 309

                         330       340
                  ....*....|....*....|
gi 568960843  561 ETEERVVVISSSEDSDTENL 580
Cdd:pfam12126 310 EAEERIVVISSSEDSDAENS 329

B-box-type 2 zinc finger found in tripartite motif-containing protein 19, also called promyelocytic leukemia protein (PML), and similar proteins; Protein PML, also known as RING finger protein 71 (RNF71) or tripartite motif-containing protein 19 (TRIM19), is predominantly a nuclear protein with a broad intrinsic antiviral activity. It is the eponymous component of PML nuclear bodies (PML NBs) and has been implicated in a wide variety of cell processes, including DNA damage signaling, apoptosis, and transcription. PML interferes with the replication of many unrelated viruses, including human immunodeficiency virus 1 (HIV-1), human foamy virus (HFV), poliovirus, influenza virus, rabies virus, EMCV, adeno-associated virus (AAV), and vesicular stomatitis virus (VSV). It also selectively interacts with misfolded proteins through distinct substrate recognition sites and conjugates these proteins with the small ubiquitin-like modifiers (SUMOs) through its SUMO ligase activity. PML belongs to the C-V subclass of TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox1 and Bbox2, and a coiled coil region, as well as an uncharacterized region positioned C-terminal to the RBCC domain. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 568960843 191 IFCSNTNHRNPaLTDIYCRGCAKPLCCTCALLDRNHSHLHCDIGEEIQQ 239
Cdd:cd19770    1 PFCPSPNHETQ-MISIYCRQCSKSVCCTCALLDSSHKGQHCDIKAEIQR 48

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 568960843   62 CPSCQAQAKCP-KLLPCLHTLCSGCL----EAPGLQCPIC 96
Cdd:pfam00097   1 CPICLEEPKDPvTLLPCGHLFCSKCIrswlESGNVTCPLC 40

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 568960843    62 CPSC-QAQAKCPKLLPCLHTLCSGC----LEAPGLQCPIC 96
Cdd:smart00184   1 CPIClEEYLKDPVILPCGHTFCRSCirkwLESGNNTCPIC 40

B-box zinc finger;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 568960843  134 CTRCKG-LADFWCFECEQLICSKCF-EAHQwylKHEARPL 171
Cdd:pfam00643   6 CPEHEEePLTLYCNDCQELLCEECSvGEHR---GHTVVPL 42

Protein of unknown function (DUF3583); This domain is found in eukaryotes, and is typically between 302 and 338 amino acids in length. It is found in association with pfam00097 and pfam00643. Most members are promyelocytic leukemia proteins, and this family lies towards the C-terminus.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960843  244 LGTMTQTLEEQGRTFDSAHAQMCSAIGQLDHARADIEKQIRARVRQVVDYVQAQERELLEAVNDRYQRDYQEIAGQLSCL 323
Cdd:pfam12126   1 LDTMTQALQEQDGAFGAAHAQMRSAISQLGRARADTEELIRARVRQVVAHVQAQERELLEAVNARYQRDYEEMAGQLGRL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960843  324 EAVLQRIRTSGALVKRMKLYASDQEVLDMHSFLRKALCSLRQEEPQNQKVQLLTRGFEEFKLCLQDFISCITQRINAAV- 402
Cdd:pfam12126  81 DAVLQRIRTGGALVQRMKRYASDQEVLDMHGFLREALCRLRQEEPQNLQAAVRTDGFDEFKVRLQDLVSCITQGTDAAVs 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960843  403 --ASPEAASnqpeaasthpvTTSTPEDLEQPKEVQSVQAQALELSKTQPVAMVKTVPGAHPVPVYAFSMQGPTYREEASQ 480
Cdd:pfam12126 161 rrASPEAAS-----------TPRDPSDVDLPEEVQRVQAQALGLAETQPVAVVQSVPGAHPVPVYAFSIKDPSYREEVSN 229

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960843  481 TVGSMKRKCSHEDCSRKIIKMESTEENEDRLATSSPEQSWPSTFKATSPPHLDGTSNPESTVPEKKILLPNNNHVTSDTG 560
Cdd:pfam12126 230 TVTPQKRKSCQTECPRKVIKMESEEEKEARLARSSPEQPRPSTSKAVSPPHLDGPPSPESPIVGKEVLLPNSNHVTSDPG 309

                         330       340
                  ....*....|....*....|
gi 568960843  561 ETEERVVVISSSEDSDTENL 580
Cdd:pfam12126 310 EAEERIVVISSSEDSDAENS 329

B-box-type 2 zinc finger found in tripartite motif-containing protein 19, also called promyelocytic leukemia protein (PML), and similar proteins; Protein PML, also known as RING finger protein 71 (RNF71) or tripartite motif-containing protein 19 (TRIM19), is predominantly a nuclear protein with a broad intrinsic antiviral activity. It is the eponymous component of PML nuclear bodies (PML NBs) and has been implicated in a wide variety of cell processes, including DNA damage signaling, apoptosis, and transcription. PML interferes with the replication of many unrelated viruses, including human immunodeficiency virus 1 (HIV-1), human foamy virus (HFV), poliovirus, influenza virus, rabies virus, EMCV, adeno-associated virus (AAV), and vesicular stomatitis virus (VSV). It also selectively interacts with misfolded proteins through distinct substrate recognition sites and conjugates these proteins with the small ubiquitin-like modifiers (SUMOs) through its SUMO ligase activity. PML belongs to the C-V subclass of TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox1 and Bbox2, and a coiled coil region, as well as an uncharacterized region positioned C-terminal to the RBCC domain. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 568960843 191 IFCSNTNHRNPaLTDIYCRGCAKPLCCTCALLDRNHSHLHCDIGEEIQQ 239
Cdd:cd19770    1 PFCPSPNHETQ-MISIYCRQCSKSVCCTCALLDSSHKGQHCDIKAEIQR 48

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM9, TRIM67, and similar proteins; Tripartite motif-containing proteins TRIM9 and TRIM67 belong to the C-I subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, consisting of three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, and a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. TRIM9 (the human ortholog of rat Spring), also known as RING finger protein 91 (RNF91), is a brain-specific E3 ubiquitin-protein ligase collaborating with an E2 ubiquitin conjugating enzyme UBCH5b. TRIM9 plays an important role in the regulation of neuronal functions and participates in neurodegenerative disorders through its ligase activity. TRIM67, also known as TRIM9-like protein (TNL), is a protein selectively expressed in the cerebellum. It interacts with PRG-1, an important molecule in the control of hippocampal excitability dependent on presynaptic LPA2 receptor signaling, and 80K-H, also known as glucosidase II beta, a protein kinase C substrate.

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 568960843  60 LRCPSCQAQAKCPKLLPCLHTLCSGCLEAPGLQCPICK 97
Cdd:cd16576    4 LKCPVCGSLFTEPVILPCSHNLCLGCALNIQLTCPICH 41

RING finger, HC subclass, found in tripartite motif-containing protein TRIM2, TRIM3, and similar proteins; TRIM2, also known as RING finger protein 86 (RNF86), is an E3 ubiquitin-protein ligase that ubiquitinates the neurofilament light chain, a component of the intermediate filament in axons. Loss of function of TRIM2 results in early-onset axonal neuropathy. TRIM3, also known as brain-expressed RING finger protein (BERP), RING finger protein 97 (RNF97), or RING finger protein 22 (RNF22), is an E3 ubiquitin-protein ligase involved in the pathogenesis of various cancers. It also plays an important role in the central nervous system (CNS). In addition, TRIM3 may be involved in vesicular trafficking via its association with the cytoskeleton-associated-recycling or transport (CART) complex that is necessary for efficient transferrin receptor recycling, but not for epidermal growth factor receptor (EGFR) degradation. Both TRIM2 and TRIM3 belong to the C-VII subclass of the TRIM (tripartite motif)-NHL family that is 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 a NHL (named after proteins NCL-1, HT2A and Lin-41 that contain repeats folded into a six-bladed beta propeller) repeat domain positioned C-terminal to the RBCC domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 568960843  59 FLRCPSCQAQAKCPKLLPCLHTLCSGCL------EAPGLQCPICK 97
Cdd:cd16586    1 FLSCGICLERYKNPKVLPCLHTFCERCLqnyipaESLSLSCPVCR 45

B-box-type zinc finger superfamily; The B-box-type zinc finger is a short zinc binding domain of around 40 amino acid residues in length. It has been found in transcription factors, ribonucleoproteins and proto-oncoproteins, such as in TRIM (tripartite motif) proteins that consist of an N-terminal RING finger (originally called an A-box), followed by 1-2 B-box domains and a coiled-coil domain (also called RBCC for Ring, B-box, Coiled-Coil). The B-box-type zinc finger often presents in combination with other motifs, like RING zinc finger, NHL motif, coiled-coil or RFP domain in functionally unrelated proteins, most likely mediating protein-protein interactions. Based on different consensus sequences and the spacing of the 7-8 zinc-binding residues, B-box-type zinc fingers can be divided into two groups, type 1 (Bbox1: C6H2) and type 2 (Bbox2: CHC3H2).

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 568960843 134 CTRCK-GLADFWCFECEQLICSKCFE--AHQWylkHEARPL 171
Cdd:cd00021    2 CQEHDeEKANKYCVTCEVLYCALCKKsgAHPD---HEVAPL 39

RING finger, HC subclass, found in tripartite motif-containing protein 2 (TRIM2); TRIM2, also known as RING finger protein 86 (RNF86), is an E3 ubiquitin-protein ligase that ubiquitinates the neurofilament light chain, a component of the intermediate filament in axons. Loss of function of TRIM2 results in early-onset axonal neuropathy. TRIM2 also plays a role in mediating the p42/p44 MAPK-dependent ubiquitination of the cell death-promoting protein Bcl-2-interacting mediator of cell death (Bim) in rapid ischemic tolerance. TRIM2 belongs to the C-VII subclass of the TRIM (tripartite motif)-NHL family that is 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 a NHL (named after proteins NCL-1, HT2A and Lin-41 that contain repeats folded into a six-bladed beta propeller) repeat domain positioned C-terminal to the RBCC domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 568960843  54 QEEFQFLRCPSCQAQAKCPKLLPCLHTLCSGCLE------APGLQCPICK 97
Cdd:cd16767    1 QIDKQFLICSICLDRYKNPKVLPCLHTFCERCLQnyipahSLTLSCPVCR 50

RING finger, HC subclass, found in tripartite motif-containing protein 56 (TRIM56) and similar proteins; TRIM56, also known as RING finger protein 109 (RNF109), is a virus-inducible E3 ubiquitin ligase that restricts pestivirus infection. It positively regulates the Toll-like receptor 3 (TLR3) antiviral signaling pathway, and possesses antiviral activity against bovine viral diarrhea virus (BVDV), a ruminant pestivirus classified within the family Flaviviridae shared by tick-borne encephalitis virus (TBEV). It also possesses antiviral activity against two classical flaviviruses, yellow fever virus (YFV) and dengue virus (DENV), as well as a human coronavirus, HCoV-OC43, which is responsible for a significant share of common cold cases. It may not act on positive-strand RNA viruses indiscriminately. Moreover, TRIM56 is an interferon-inducible E3 ubiquitin ligase that modulates STING to confer double-stranded DNA-mediated innate immune responses. TRIM56 belongs to the C-V subclass of the TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domain, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as an uncharacterized region positioned C-terminal to the RBCC domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 568960843  59 FLRCPSCQAQAKCPKLLPCLHTLCSGC----LEAPGLQCPICK 97
Cdd:cd16584    1 FLACKICLEQLRAPKTLPCLHTYCQDClaqlADGGRVRCPECR 43

RING finger, HC subclass, found in Caenorhabditis elegans RING finger protein NHL-1 and similar proteins; NHL-1 functions as an E3 ubiquitin-protein ligase in the presence of both UBC-13 and UBC-1 within the ubiquitin pathway of Caenorhabditis elegans. It acts in chemosensory neurons to promote stress resistance in distal tissues by the transcription factor DAF-16 activation but is dispensable for the activation of heat shock factor 1 (HSF-1). NHL-1 belongs to the TRIM (tripartite motif)-NHL 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 NHL (named after proteins NCL-1, HT2A and Lin-41 that contain repeats folded into a six-bladed beta propeller) repeat domain positioned C-terminal to the RBCC domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 568960843  58 QFLRCPSCQAQAKCPKLLPCLHTLC-SGCLE------APGLQCPICKA 98
Cdd:cd16524    4 QLLTCPICLDRYRRPKLLPCQHTFClSPCLEglvdyvTRKLKCPECRA 51

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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 568960843  60 LRCPSCQAQAKCPKLLPCLHTLCSGCLEA-------PGLQCPICKAP 99
Cdd:cd16604    1 LSCPICLDLLKDPVTLPCGHSFCMGCLGAlwgagrgGRASCPLCRQT 47

RING finger, HC subclass, found in tripartite motif-containing protein 71 (TRIM71) and similar proteins; TRIM71, also known as protein lineage variant 41 (lin-41), is an E3 ubiquitin-protein ligase that may play essential roles in embryonic stem cells, cellular reprogramming and the timing of embryonic neurogenesis. It was first identified in the nematode Caenorhabditis elegans as a target of the differentiation-associated microRNA (miRNA) let-7 (lethal 7) and is therefore part of a heterochronic gene network that controls larval development. In humans, it regulates let-7 microRNA biogenesis via modulation of Lin28B protein polyubiquitination. TRIM71 localizes to cytoplasmic P-bodies and directly interacts with the miRNA pathway proteins Argonaute 2 (AGO2) and DICER. It represses miRNA activity by promoting degradative ubiquitination of AGO2. Moreover, TRIM71 associates with SHCBP1, a novel component of the fibroblast growth factor (FGF) signaling pathway, and regulates its non-degradative polyubiquitination. It is also involved in the post-transcriptional regulation of the CDKN1A, RBL1 and RBL2 or EGR1 mRNAs by mediating RNA-binding in embryonic stem cells. TRIM71 belongs to the C-VII subclass of the TRIM (tripartite motif)-NHL family that is 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 a NHL (named after proteins NCL-1, HT2A and Lin-41 that contain repeats folded into a six-bladed beta propeller) repeat domain positioned C-terminal to the RBCC domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 568960843  64 SCQAQAKCPKLLPCLHTLCSGCLEA---------PGLQCPIC 96
Cdd:cd16589   42 SAGAATRRLHVLPCLHAFCRQCLEAqrspgagpaLKLRCPVC 83

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568960843   58 QFLRCPSCQAQAKCPKLLPCLHTLCSGCL-----EAPglQCPICKAPGQadangealdnvffESLQRRLAVFRQIVDA 130
Cdd:TIGR00599  25 TSLRCHICKDFFDVPVLTSCSHTFCSLCIrrclsNQP--KCPLCRAEDQ-------------ESKLRSNWLVSEIVES 87

RING finger, HC subclass, found in Drosophila melanogaster Bre1 (dBre1) and similar proteins; dBre1 is the functional homolog of yeast Bre1, an E3 ubiquitin ligase required for the monoubiquitination of histone H2B and, indirectly, for H3K4 methylation. dBre1 acts as a nuclear component required for the expression of Notch target genes in Drosophila development. dBre1 contains a C3HC4-type RING-HC finger at its C-terminus.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 568960843  51 QAIQEEFQFLRCPSCQAQAKCPKLLPCLHTLCSGCL----EAPGLQCPICKAP 99
Cdd:cd16705    6 EEIREYKEQLTCPSCKVKRKDAVLTKCFHVFCLDCLrtryETRQRKCPKCNAA 58

RING finger, HC subclass, found in the transcriptional inknown asiary factor 1 (TIF1) subfamily and similar proteins; The TIF1 subfamily of transcriptional cofactors containing RING-HC fingers includes TIF1alpha (TRIM24), TIF1beta (TRIM28), and TIF1gamma (TRIM33), which belong to the C-VI 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 plant homeodomain (PHD), and a bromodomain (Bromo) positioned C-terminal to the RBCC domain. TIF1 proteins couple chromatin modifications to transcriptional regulation, signaling, and tumor suppression. They exert a deacetylase-dependent silencing effect when tethered to a promoter region. TIF1alpha and TIF1beta can homodimerize and contain a PXVXL motif necessary and sufficient for heterochromatin protein 1(HP1) binding. They bind nuclear receptors and Kruppel-associated boxes (KRAB) specifically and respectively. TIF1gamma is structurally closely related to TIF1alpha and TIF1beta, but has very little functional features in common with them. It does not interact with the KRAB silencing domain of KOX1 or the heterochromatin proteins HP1alpha, beta and gamma. It cannot bind to nuclear receptors (NRs). TIF1delta (TRIM66) doesn't have a RING-HC finger and is not included in this model.

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gi 568960843  62 CPSCQA--QAKCPKLLPCLHTLCSGCLEAP 89
Cdd:cd16585    4 CAVCKQsfQSREPKLLPCLHSFCKRCLPPA 33

RING finger, HC subclass, found in tripartite motif-containing protein 46 (TRIM46) and similar proteins; TRIM46, also known as gene Y protein (GeneY) or tripartite, fibronectin type-III and C-terminal SPRY motif protein (TRIFIC), is a microtubule-associated protein that specifically localizes to the proximal axon, partly overlaps with the axon initial segment (AIS) at later stages, and organizes uniform microtubule orientation in axons. It controls neuronal polarity and axon specification by driving the formation of parallel microtubule arrays. TRIM46 belongs to the C-I subclass of the TRIM (tripartite motif) family of proteins, which 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 COS (carboxyl-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, a PRY domain and a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

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gi 568960843  60 LRCPSCQAQAKCPKLLPCLHTLCSGCLEAPGLQCPICK 97
Cdd:cd16757    5 LLCPVCKEMYKQPLVLPCMHNVCQVCASEVLFPCPPCQ 42

RING finger, HC subclass, found in RING finger protein 207 (RNF207) and similar proteins; RNF207 is a cardiac-specific E3 ubiquitin-protein ligase that plays an important role in the regulation of cardiac repolarization. It regulates action potential duration, likely via effects on human ether-a-go-go-related gene (HERG) trafficking and localization in a heat shock protein-dependent manner. RNF207 contains a C3HC4-type RING-HC finger, Bbox 1 and Bbox C-terminal (BBC) domain, as well as a C-terminal non-homologous region (CNHR).

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gi 568960843  60 LRCPSCQAQAKCPKLLPCLHTLCSGCLEAPG----LQCPIC 96
Cdd:cd16558    2 LVCYLCHEQYEHPCLLDCYHTFCASCLRGRAadgrLTCPLC 42

RING finger, HC subclass, found in tripartite motif-containing protein 9 (TRIM9) and similar proteins; TRIM9, human ortholog of rat Spring, also known as RING finger protein 91 (RNF91), is a brain-specific E3 ubiquitin-protein ligase collaborating with an E2 ubiquitin conjugating enzyme UBCH5b. TRIM9 plays an important role in the regulation of neuronal functions and participates in the neurodegenerative disorders through its ligase activity. It interacts with the WD repeat region of beta-transducin repeat-containing protein (beta-TrCP) through its N-terminal degron motif depending on the phosphorylation status, and thus negatively regulates nuclear factor-kappaB (NF-kappaB) activation in the NF-kappaB pro-inflammatory signaling pathway. Moreover, TRIM9 acts as a critical catalytic link between Netrin-1 and the exocytic soluble NSF attachment receptor protein (SNARE) machinery in murine cortical neurons. It promotes SNARE-mediated vesicle fusion and axon branching in a Netrin-dependent manner. TRIM9 belongs to the C-I 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 COS (carboxyl-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, and a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

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gi 568960843  60 LRCPSCQAQAKCPKLLPCLHTLCSGCLEAPGLQCPICKAP 99
Cdd:cd16755    4 LKCPVCGSFYREPIILPCSHNLCLACARNILVQTPEAESP 43

RING finger, HC subclass, found in RING finger protein 138 (RNF138) and similar proteins; RNF138, also known as Nemo-like kinase-associated RING finger protein (NARF) or NLK-associated RING finger protein, is an E3 ubiquitin-protein ligase that plays an important role in glioma cell proliferation, apoptosis, and cell cycle. It specifically cooperates with the E2 conjugating enzyme E2-25K (Hip-2/UbcH1), regulates the ubiquitylation and degradation of T cell factor/lymphoid enhancer factor (TCF/LEF), and further suppresses Wnt-beta-catenin signaling. RNF138, together with three closely related proteins: RNF114, RNF125 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).

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gi 568960843  60 LRCPSCQAQAKCP-KLLPCLHTLCSGCLE----APGLQCPICKAPGQ 101
Cdd:cd16544    3 LTCPVCQEVLKDPvELPPCRHIFCKACILlalrSSGARCPLCRGPVG 49

RING finger, HC subclass, found in checkpoint with forkhead and RING finger domains protein (CHFR); CHFR, also known as RING finger protein 196 (RNF196), is a checkpoint protein that delays entry into mitosis in response to stress. It functions as an E3 ubiquitin ligase that ubiquitinates and degrades its target proteins, such as Aurora-A, Plk1, Kif22, and PARP-1, which are critical for proper mitotic transitions. It also plays an important role in cell cycle progression and tumor suppression, and is negatively regulated by SUMOylation-mediated proteasomal ubiquitylation. Moreover, CHFR is involved in the early stage of the DNA damage response, which mediates the crosstalk between ubiquitination and poly-ADP-ribosylation. CHFR contains a fork head associated (FHA) domain and a C3HC4-type RING-HC finger.

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gi 568960843  60 LRCPSCQAQ-AKCPKLLPCLHTLCSGCL----EAPGLQCPICKAP 99
Cdd:cd16503    3 LTCSICQDLlHDCVSLQPCMHNFCAACYsdwmERSNTECPTCRAT 47

RING finger, HC subclass, found in transcription inknown asiary factor 1-alpha (TIF1-alpha); TIF1-alpha, also known as tripartite motif-containing protein 24 (TRIM24), E3 ubiquitin-protein ligase TRIM24, or RING finger protein 82, belongs to the C-VI 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 plant homeodomain (PHD), and a bromodomain (Bromo) positioned C-terminal to the RBCC domain. It interacts specifically and in a ligand-dependent manner with the ligand binding domain (LBD) of several nuclear receptors (NRs), including retinoid X (RXR), retinoic acid (RAR), vitamin D3 (VDR), estrogen (ER), and progesterone (PR) receptors. It also associates with heterochromatin-associated factors HP1alpha, MOD1 (HP1beta), and MOD2 (HP1gamma), as well as the vertebrate Kruppel-type (C2H2) zinc finger proteins that contain the transcriptional silencing domain KRAB. TIF1-alpha is a ligand-dependent co-repressor of RAR that interacts with multiple nuclear receptors in vitro via an LXXLL motif and further acts as a gatekeeper of liver carcinogenesis. It also functions as an E3-ubiquitin ligase targeting p53, and is broadly associated with chromatin silencing. Moreover, it is a chromatin regulator that recognizes specific, combinatorial histone modifications through its C-terminal PHD-Bromo region. In addition, it interacts with chromatin and estrogen receptor to activate estrogen-dependent genes associated with cellular proliferation and tumor development.

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gi 568960843  68 QAKCPKLLPCLHTLCSGCLEAP 89
Cdd:cd16764   12 QSREPRLLPCLHSFCQRCLPQP 33

RING finger, HC subclass, found in tripartite motif-containing protein 32 (TRIM32) and similar proteins; TRIM32, also known as 72 kDa Tat-interacting protein, zinc finger protein HT2A, or BBS11, is an E3 ubiquitin-protein ligase that promotes degradation of several targets, including actin, PIASgamma, Abl interactor 2, dysbindin, X-linked inhibitor of apoptosis (XIAP), p73 transcription factor, thin filaments and Z-bands during fasting. It plays important roles in neuronal differentiation of neural progenitor cells, as well as in controlling cell fate in skeletal muscle progenitor cells. It reduces PI3K-Akt-FoxO signaling in muscle atrophy by promoting plakoglobin-PI3K dissociation. It also functions as a pluripotency-reprogramming roadblock that facilitates cellular transition towards differentiation by modulating the levels of Oct4 and cMyc. Moreover, TRIM32 is an intrinsic influenza A virus (IAV) restriction factor which senses and targets the polymerase basic protein 1 (PB1) for ubiquitination and protein degradation. It also plays a significant role in mediating the biological activity of the HIV-1 Tat protein in vivo, binds specifically to the activation domain of HIV-1 Tat, and can also interact with the HIV-2 and EIAV Tat proteins in vivo. Furthermore, TRIM32 regulates myoblast proliferation by controlling turnover of NDRG2 (N-myc downstream-regulated gene). It negatively regulates tumor suppressor p53 to promote tumorigenesis. It also facilitates degradation of MYCN on spindle poles and induces asymmetric cell division in human neuroblastoma cells. In addition, TRIM32 plays important roles in regulation of hyperactivities and positively regulates the development of anxiety and depression disorders induced by chronic stress. It also plays a role in regeneration by affecting satellite cell cycle progression via modulation of the SUMO ligase PIASy (PIAS4). Defects in TRIM32 leads to limb-girdle muscular dystrophy type 2H (LGMD2H), sarcotubular myopathies (STM) and Bardet-Biedl syndrome. TRIM32 belongs to the C-VII subclass of the TRIM (tripartite motif)-NHL family that is 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 a NHL (named after proteins NCL-1, HT2A and Lin-41 that contain repeats folded into a six-bladed beta propeller) repeat domain positioned C-terminal to the RBCC domain. The NHL domain mediates the interaction with Argonaute proteins and consequently allows TRIM32 to modulate the activity of certain miRNAs.

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gi 568960843  60 LRCPSC-----QAQAKcPKLLPCLHTLCSGCLEA-------PGLQCPICKA 98
Cdd:cd16587    1 LECPIClesfdEGQLR-PKLLHCGHTICEQCLEKllaslsiNGVRCPFCRK 50