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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 530409257 124 QPSVKLCCQLCCSVFKDPVITTCGHTFCRRCALKS--EKCPVDNVKL 168
Cdd:cd16644    1 PPSVKLYCPLCQRVFKDPVITSCGHTFCRRCALTApgEKCPVDNMKL 47

Dimerization/Docking domain of Cyclic GMP-dependent Protein Kinase I; Cyclic GMP-dependent Protein Kinase I (PKG1 or cGKI) is a Serine/Threonine Kinase (STK), catalyzing the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. cGKI exists as two splice variants, cGKI-alpha and cGKI-beta. They contain an N-terminal regulatory domain containing a dimerization/docking region and an autoinhibitory pseudosubstrate region, two cGMP-binding domains, and a C-terminal catalytic domain. Binding of cGMP to both binding sites releases the inhibition of the catalytic center by the pseudosubstrate region, allowing autophosphorylation and activation of the kinase. cGKI is a soluble protein expressed in all smooth muscles, platelets, cerebellum, and kidney. It is also expressed at lower concentrations in other tissues. It is involved in the regulation of smooth muscle tone, smooth cell proliferation, and platelet activation. The dimerization/docking (D/D) domain is a leucine/isoleucine zipper that mediates both homodimerization and interaction with isotype-specific G-kinase-anchoring proteins (GKAPs). The D/D domain of the two variants (alpha and beta) differ, allowing their targeting to different subcellular compartments and intracellular substrates.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 530409257 280 CRFEGLKEFLQQTDDRFHEMHVALAQKDQEIAFLRSMLGKL 320
Cdd:cd12085    2 GSVEELQKLLQAKEERIRELEQLLQQRDEEIQELRSQLDKF 42

WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from its N-terminus and the WD dipeptide at its C-terminus and is 40 residues long, hence the name WD40; between GH and WD lies a conserved core; serves as a stable propeller-like platform to which proteins can bind either stably or reversibly; forms a propeller-like structure with several blades where each blade is composed of a four-stranded anti-parallel b-sheet; instances with few detectable copies are hypothesized to form larger structures by dimerization; each WD40 sequence repeat forms the first three strands of one blade and the last strand in the next blade; the last C-terminal WD40 repeat completes the blade structure of the first WD40 repeat to create the closed ring propeller-structure; residues on the top and bottom surface of the propeller are proposed to coordinate interactions with other proteins and/or small ligands; 7 copies of the repeat are present in this alignment.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530409257 386 CKGTFVGHQGPVWCLCVYSMGDLLFSGSSDKTIKVWDTCTTyKCQKTLEGHDGIV--LALCIQGCKLYSGSADCTIIVWD 463
Cdd:cd00200    1 LRRTLKGHTGGVTCVAFSPDGKLLATGSGDGTIKVWDLETG-ELLRTLKGHTGPVrdVAASADGTYLASGSSDKTIRLWD 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530409257 464 IQNLQKVNTIRAHDNPV--CTLVSSHNVLFSGSL-KAIKVWDIvgTELKLKKELTGLNHWVRALVAAQS--YLYSGSY-Q 537
Cdd:cd00200   80 LETGECVRTLTGHTSYVssVAFSPDGRILSSSSRdKTIKVWDV--ETGKCLTTLRGHTDWVNSVAFSPDgtFVASSSQdG 157

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530409257 538 TIKIWDIRTLDCIHVLQTSGGSVYSIAV--TNHHIVCGTYENLIHVWDIESKEQVRTLTGHVGTVYALAVisTPDQTKVF 615
Cdd:cd00200  158 TIKLWDLRTGKCVATLTGHTGEVNSVAFspDGEKLLSSSSDGTIKLWDLSTGKCLGTLRGHENGVNSVAF--SPDGYLLA 235

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|...
gi 530409257 616 SASYDRSLRVWSMDNMICTQTLLRHQGSVTALAVS--RGRLFSGAVDSTVKVW 666
Cdd:cd00200  236 SGSEDGTIRVWDLRTGECVQTLSGHTNSVTSLAWSpdGKRLASGSADGTIRIW 288

WD domain, G-beta repeat;

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 530409257  384 FKCKGTFVGHQGPVWCLCVYSMGDLLFSGSSDKTIKVWD 422
Cdd:pfam00400   1 GKLLKTLEGHTGSVTSLAFSPDGKLLASGSDDGTVKVWD 39

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
                  ....*....|....*....|....*....|....*...
gi 530409257  129 LCCQLCCSVFKDPVITTCGHTFC----RRCALKSEKCP 162
Cdd:TIGR00599  27 LRCHICKDFFDVPVLTSCSHTFCslciRRCLSNQPKCP 64

Seven in absentia protein family; The seven in absentia (sina) gene was first identified in Drosophila. The Drosophila Sina protein is essential for the determination of the R7 pathway in photoreceptor cell development: the loss of functional Sina results in the transformation of the R7 precursor cell to a non- neuronal cell type. The Sina protein contains an N-terminal RING finger domain pfam00097. Through this domain, Sina binds E2 ubiquitin-conjugating enzymes (UbcD1) Sina also interacts with Tramtrack (TTK88) via PHYL. Tramtrack is a transcriptional repressor that blocks photoreceptor determination, while PHYL down-regulates the activity of TTK88. In turn, the activity of PHYL requires the activation of the Sevenless receptor tyrosine kinase, a process essential for R7 determination. It is thought that thus Sina targets TTK88 for degradation, therefore promoting the R7 pathway. Murine and human homologs of Sina have also been identified. The human homolog Siah-1 also binds E2 enzymes (UbcH5) and through a series of physical interactions, targets beta-catenin for ubiquitin degradation. Siah-1 expression is enhanced by p53, itself promoted by DNA damage. Thus this pathway links DNA damage to beta-catenin degradation. Sina proteins, therefore, physically interact with a variety of proteins. The N-terminal RING finger domain that binds ubiquitin conjugating enzymes is described in pfam00097, and does not form part of the alignment for this family. The remainder C-terminal part is involved in interactions with other proteins, and is included in this alignment. In addition to the Drosophila protein and mammalian homologs, whose similarity was noted previously, this family also includes putative homologs from Caenorhabditis elegans, Arabidopsis thaliana.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530409257  208 RGCPFTIKLSARKDHEGSCDYRPVRCPnnpscppllrmnleahlkecehikCPHSKCTFIGNQDTYETHL 277
Cdd:pfam03145  22 SGCSETLPYTEKADHEERCEFRPYSCP------------------------CPGSSCTWQGSLDAVMPHL 67

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
                   ....*....|....*....|....*....|....*....
gi 530409257   131 CQLCCSVF-KDPVITTCGHTFCRRCALK-----SEKCPV 163
Cdd:smart00184   1 CPICLEEYlKDPVILPCGHTFCRSCIRKwlesgNNTCPI 39

DNA double-strand break repair ATPase Rad50;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530409257 281 RFEGLKEFLQQT---DDRFHEMHVALAQKDQEIAFLRSMLGKLSEKIDQLEKSLElKFDVLDENQSKLSEDLMEFRRDAS 357
Cdd:PRK03918 177 RIERLEKFIKRTeniEELIKEKEKELEEVLREINEISSELPELREELEKLEKEVK-ELEELKEEIEELEKELESLEGSKR 255

                         90
                 ....*....|....
gi 530409257 358 MLNDELSHINARLN 371
Cdd:PRK03918 256 KLEEKIRELEERIE 269

WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from its N-terminus and the WD dipeptide at its C-terminus and is 40 residues long, hence the name WD40; between GH and WD lies a conserved core; serves as a stable propeller-like platform to which proteins can bind either stably or reversibly; forms a propeller-like structure with several blades where each blade is composed of a four-stranded anti-parallel b-sheet; instances with few detectable copies are hypothesized to form larger structures by dimerization; each WD40 sequence repeat forms the first three strands of one blade and the last strand in the next blade; the last C-terminal WD40 repeat completes the blade structure of the first WD40 repeat to create the closed ring propeller-structure; residues on the top and bottom surface of the propeller are proposed to coordinate interactions with other proteins and/or small ligands; 7 copies of the repeat are present in this alignment.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530409257 386 CKGTFVGHQGPVWCLCVYSMGDLLFSGSSDKTIKVWDTCTTyKCQKTLEGHDGIV--LALCIQGCKLYSGSADCTIIVWD 463
Cdd:cd00200    1 LRRTLKGHTGGVTCVAFSPDGKLLATGSGDGTIKVWDLETG-ELLRTLKGHTGPVrdVAASADGTYLASGSSDKTIRLWD 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530409257 464 IQNLQKVNTIRAHDNPV--CTLVSSHNVLFSGSL-KAIKVWDIvgTELKLKKELTGLNHWVRALVAAQS--YLYSGSY-Q 537
Cdd:cd00200   80 LETGECVRTLTGHTSYVssVAFSPDGRILSSSSRdKTIKVWDV--ETGKCLTTLRGHTDWVNSVAFSPDgtFVASSSQdG 157

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530409257 538 TIKIWDIRTLDCIHVLQTSGGSVYSIAV--TNHHIVCGTYENLIHVWDIESKEQVRTLTGHVGTVYALAVisTPDQTKVF 615
Cdd:cd00200  158 TIKLWDLRTGKCVATLTGHTGEVNSVAFspDGEKLLSSSSDGTIKLWDLSTGKCLGTLRGHENGVNSVAF--SPDGYLLA 235

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|...
gi 530409257 616 SASYDRSLRVWSMDNMICTQTLLRHQGSVTALAVS--RGRLFSGAVDSTVKVW 666
Cdd:cd00200  236 SGSEDGTIRVWDLRTGECVQTLSGHTNSVTSLAWSpdGKRLASGSADGTIRIW 288

WD40 repeat [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530409257 385 KCKGTFVGHQGPVWCLcVYS-MGDLLFSGSSDKTIKVWDTCTTyKCQKTLEGHDGIVLALCI--QGCKLYSGSADCTIIV 461
Cdd:COG2319  153 KLLRTLTGHSGAVTSV-AFSpDGKLLASGSDDGTVRLWDLATG-KLLRTLTGHTGAVRSVAFspDGKLLASGSADGTVRL 230

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530409257 462 WDIQNLQKVNTIRAHDNPVCTLVSSHN--VLFSGSL-KAIKVWDIVGTELKlkKELTGLNHWVRALVAAQ--SYLYSGSY 536
Cdd:COG2319  231 WDLATGKLLRTLTGHSGSVRSVAFSPDgrLLASGSAdGTVRLWDLATGELL--RTLTGHSGGVNSVAFSPdgKLLASGSD 308

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530409257 537 -QTIKIWDIRTLDCIHVLQTSGGSVYSIAVT--NHHIVCGTYENLIHVWDIESKEQVRTLTGHVGTVYALAVisTPDQTK 613
Cdd:COG2319  309 dGTVRLWDLATGKLLRTLTGHTGAVRSVAFSpdGKTLASGSDDGTVRLWDLATGELLRTLTGHTGAVTSVAF--SPDGRT 386

                        250
                 ....*....|....*..
gi 530409257 614 VFSASYDRSLRVWSMDN 630
Cdd:COG2319  387 LASGSADGTVRLWDLAT 403

WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from its N-terminus and the WD dipeptide at its C-terminus and is 40 residues long, hence the name WD40; between GH and WD lies a conserved core; serves as a stable propeller-like platform to which proteins can bind either stably or reversibly; forms a propeller-like structure with several blades where each blade is composed of a four-stranded anti-parallel b-sheet; instances with few detectable copies are hypothesized to form larger structures by dimerization; each WD40 sequence repeat forms the first three strands of one blade and the last strand in the next blade; the last C-terminal WD40 repeat completes the blade structure of the first WD40 repeat to create the closed ring propeller-structure; residues on the top and bottom surface of the propeller are proposed to coordinate interactions with other proteins and/or small ligands; 7 copies of the repeat are present in this alignment.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530409257 384 FKCKGTFVGHQGPVWCLCVYSMGDLLFSGSSDKTIKVWDTcTTYKCQKTLEGHDGIVLALCI--QGCKLYSGSADCTIIV 461
Cdd:cd00200  125 GKCLTTLRGHTDWVNSVAFSPDGTFVASSSQDGTIKLWDL-RTGKCVATLTGHTGEVNSVAFspDGEKLLSSSSDGTIKL 203

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530409257 462 WDIQNLQKVNTIRAHDNPVCTLVSSHN--VLFSGSL-KAIKVWDIVGTElkLKKELTGLNHWVRALVAAQS--YLYSGSY 536
Cdd:cd00200  204 WDLSTGKCLGTLRGHENGVNSVAFSPDgyLLASGSEdGTIRVWDLRTGE--CVQTLSGHTNSVTSLAWSPDgkRLASGSA 281

                 ....*...
gi 530409257 537 -QTIKIWD 543
Cdd:cd00200  282 dGTIRIWD 289

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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 530409257 124 QPSVKLCCQLCCSVFKDPVITTCGHTFCRRCALKS--EKCPVDNVKL 168
Cdd:cd16644    1 PPSVKLYCPLCQRVFKDPVITSCGHTFCRRCALTApgEKCPVDNMKL 47

WD40 repeats; Note that these repeats are permuted with respect to the structural repeats (blades) of the beta propeller domain.

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 530409257   384 FKCKGTFVGHQGPVWCLCVYSMGDLLFSGSSDKTIKVWD 422
Cdd:smart00320   2 GELLKTLKGHTGPVTSVAFSPDGKYLASGSDDGTIKLWD 40

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 530409257 129 LCCQLCCSVFKDPVITTCGHTFCRRCALK-----SEKCPVD 164
Cdd:cd16449    1 LECPICLERLKDPVLLPCGHVFCRECIRRllesgSIKCPIC 41

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
                 ....*....|....*....|....*.
gi 530409257 129 LCCQLCCSVFKDPVITTCGHTFCRRC 154
Cdd:cd16611    5 LHCPLCLDFFRDPVMLSCGHNFCQSC 30

RING finger, HC subclass, found in tripartite motif-containing protein TRIM17 and similar proteins; TRIM17, also known as RING finger protein 16 (RNF16) or testis RING finger protein (Terf), is a crucial E3 ubiquitin ligase that is necessary and sufficient for neuronal apoptosis and contributes to Mcl-1 ubiquitination in cerebellar granule neurons (CGNs). It interacts in a SUMO-dependent manner with nuclear factor of activated T cell NFATc3 transcription factor, and thus inhibits the activity of NFATc3 by preventing its nuclear localization. In contrast, it binds to and inhibits NFATc4 transcription factor in a SUMO-independent manner. Moreover, TRIM17 stimulates degradation of kinetochore protein ZW10 interacting protein (ZWINT), a known component of the kinetochore complex required for the mitotic spindle checkpoint, and negatively regulates cell proliferation. TRIM17 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
                 ....*....|....*....|....*...
gi 530409257 131 CQLCCSVFKDPVITTCGHTFCRRCALKS 158
Cdd:cd16595    8 CSICLDYFTDPVMTTCGHNFCRACIQLS 35

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
                 ....*....|....*....|....*.
gi 530409257 129 LCCQLCCSVFKDPVITTCGHTFCRRC 154
Cdd:cd16608    7 LLCSICLSIYQDPVSLGCEHYFCRQC 32

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
                 ....*....|....*....|....
gi 530409257 131 CQLCCSVFKDPVITTCGHTFCRRC 154
Cdd:cd16592    7 CPICLGYFKDPVILDCEHSFCRAC 30

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
                 ....*....|....*....|....*....
gi 530409257 129 LCCQLCCSVFKDPVITTCGHTFCRRCALK 157
Cdd:cd16594    6 LTCPICLDYFTDPVTLDCGHSFCRACIAR 34

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
                 ....*....|....*....|....
gi 530409257 131 CQLCCSVFKDPVITTCGHTFCRRC 154
Cdd:cd16601    4 CSLCKEYLKDPVIIECGHNFCRAC 27

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
                 ....*....|....*....|....*....|....*...
gi 530409257 131 CQLCCSVFKDPVITTCGHTFCRRCALKS-----EKCPV 163
Cdd:cd16509    6 CAICLDSLTNPVITPCAHVFCRRCICEViqrekAKCPM 43

RING finger, HC subclass, found in constitutive photomorphogenesis protein 1 (COP1) and similar proteins; COP1, also known as RING finger and WD repeat domain protein 2 (RFWD2) or RING finger protein 200 (RNF200), is a central regulator of photomorphogenic development in plants, which targets key transcription factors for proteasome-dependent degradation. It is localized predominantly in the nucleus, but may also be present in the cytosol. Mammalian COP1 functions as an E3 ubiquitin-protein ligase that interacts with Jun transcription factors and modulates their transcriptional activity. It also interacts with and negatively regulates the tumor-suppressor protein p53. Moreover, COP1 associates with COP9 signalosome subunit 6 (CSN6), and is involved in 14-3-3sigma ubiquitin-mediated degradation. The CSN6-COP1 link enhances ubiquitin-mediated degradation of p27(Kip1), a critical CDK inhibitor involved in cell cycle regulation, to promote cancer cell growth. Furthermore, COP1 functions as the negative regulator of ETV1 and influences prognosis in triple-negative breast cancer. COP1 contains an N-terminal extension, a C3HC4-type RING-HC finger, a coiled coil domain, and seven WD40 repeats. In human COP1, a classic leucine-rich NES, and a novel bipartite NLS is bridged by the RING-HC finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 530409257 131 CQLCCSVFKDPVITTCGHTFCRRCALKS----EKCPVDNVKLT 169
Cdd:cd16504    5 CPICFDIIKEAFVTKCGHSFCYKCIVKHleqkNRCPKCNFYLT 47

RING finger, HC subclass, found in tripartite motif-containing protein TRIM65 and similar proteins; TRIM65 is an E3 ubiquitin-protein ligase that interacts with the innate immune receptor MDA5, enhancing its ability to stimulate interferon-beta signaling. It functions as a potential oncogenic protein that negatively regulates p53 through ubiquitination, providing insight into the development of novel approaches targeting TRIM65 for non-small cell lung carcinoma (NSCLC) treatment, and also overcoming chemotherapy resistance. Moreover, TRIM65 negatively regulates microRNA-driven suppression of mRNA translation by targeting TNRC6 proteins for ubiquitination and degradation. TRIM65 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
                 ....*....|....*....|....*..
gi 530409257 128 KLCCQLCCSVFKDPVITTCGHTFCRRC 154
Cdd:cd16609    3 ELTCSICLGLYQDPVTLPCQHSFCRAC 29

Seven in absentia protein family; The seven in absentia (sina) gene was first identified in Drosophila. The Drosophila Sina protein is essential for the determination of the R7 pathway in photoreceptor cell development: the loss of functional Sina results in the transformation of the R7 precursor cell to a non- neuronal cell type. The Sina protein contains an N-terminal RING finger domain pfam00097. Through this domain, Sina binds E2 ubiquitin-conjugating enzymes (UbcD1) Sina also interacts with Tramtrack (TTK88) via PHYL. Tramtrack is a transcriptional repressor that blocks photoreceptor determination, while PHYL down-regulates the activity of TTK88. In turn, the activity of PHYL requires the activation of the Sevenless receptor tyrosine kinase, a process essential for R7 determination. It is thought that thus Sina targets TTK88 for degradation, therefore promoting the R7 pathway. Murine and human homologs of Sina have also been identified. The human homolog Siah-1 also binds E2 enzymes (UbcH5) and through a series of physical interactions, targets beta-catenin for ubiquitin degradation. Siah-1 expression is enhanced by p53, itself promoted by DNA damage. Thus this pathway links DNA damage to beta-catenin degradation. Sina proteins, therefore, physically interact with a variety of proteins. The N-terminal RING finger domain that binds ubiquitin conjugating enzymes is described in pfam00097, and does not form part of the alignment for this family. The remainder C-terminal part is involved in interactions with other proteins, and is included in this alignment. In addition to the Drosophila protein and mammalian homologs, whose similarity was noted previously, this family also includes putative homologs from Caenorhabditis elegans, Arabidopsis thaliana.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530409257  208 RGCPFTIKLSARKDHEGSCDYRPVRCPnnpscppllrmnleahlkecehikCPHSKCTFIGNQDTYETHL 277
Cdd:pfam03145  22 SGCSETLPYTEKADHEERCEFRPYSCP------------------------CPGSSCTWQGSLDAVMPHL 67

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
                 ....*....|....*....|....*.
gi 530409257 129 LCCQLCCSVFKDPVITTCGHTFCRRC 154
Cdd:cd16597    6 LTCSICLELFKDPVTLPCGHNFCGVC 31

WD40 repeats; Note that these repeats are permuted with respect to the structural repeats (blades) of the beta propeller domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 530409257   586 SKEQVRTLTGHVGTVYALAVisTPDQTKVFSASYDRSLRVWS 627
Cdd:smart00320   1 SGELLKTLKGHTGPVTSVAF--SPDGKYLASGSDDGTIKLWD 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
                   ....*....|....*....|....*....|....*....
gi 530409257   131 CQLCCSVF-KDPVITTCGHTFCRRCALK-----SEKCPV 163
Cdd:smart00184   1 CPICLEEYlKDPVILPCGHTFCRSCIRKwlesgNNTCPI 39

RING finger, HC subclass, found in tripartite motif-containing protein TRIM4 and similar proteins; TRIM4 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, Bbox2, and a coiled coil region, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain. TRIM4, also known as RING finger protein 87 (RNF87), is a cytoplasmic E3 ubiquitin-protein ligase that has recently evolved and is present only in higher mammals. It transiently interacts with mitochondria, induces mitochondrial aggregation and sensitizes the cells to hydrogen peroxide (H2O2) induced death. Its interaction with peroxiredoxin 1 (PRX1) is critical for the regulation of H2O2 induced cell death. Moreover, TRIM4 functions as a positive regulator of RIG-I-mediated type I interferon induction. It regulates the K63-linked ubiquitination of RIG-1 and assembly of antiviral signaling complex at the mitochondria.

                         10        20
                 ....*....|....*....|....*..
gi 530409257 128 KLCCQLCCSVFKDPVITTCGHTFCRRC 154
Cdd:cd16590    6 ELTCPICLDYFQDPVSIECGHNFCRGC 32

WD domain, G-beta repeat;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 530409257  587 KEQVRTLTGHVGTVYALAVisTPDQTKVFSASYDRSLRVWS 627
Cdd:pfam00400   1 GKLLKTLEGHTGSVTSLAF--SPDGKLLASGSDDGTVKVWD 39

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
                 ....*....|....*....|....*.
gi 530409257 129 LCCQLCCSVFKDPVITTCGHTFCRRC 154
Cdd:cd16604    1 LSCPICLDLLKDPVTLPCGHSFCMGC 26

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.

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                 ....*....|....*....|....*....|....*....|...
gi 530409257 131 CQLCCSVFKDPVITTCGHTFCRRC---ALKSEK--CPVDNVKL 168
Cdd:cd16542    4 CAVCLEVLHQPVRTRCGHVFCRPCiatSLRNNTwtCPYCRAYL 46

Modified RING finger, HC subclass (C3HC3D-type), found in Roquin-1, Roquin-2, and similar proteins; The ROQUIN family includes Roquin-1, Roquin-2, and similar proteins, which localize to the cytoplasm and upon stress, are concentrated in stress granules. They may play essential roles in preventing T-cell-mediated autoimmune disease and in microRNA-mediated repression of inducible costimulator (Icos) mRNA. They function as E3 ubiquitin ligases consisting of an N-terminal modified C3HC3D-type RING-HC finger with a potential E3 activity, a highly conserved ROQ domain required for RNA binding and localization to stress granules, and a CCCH-type zinc finger involved in RNA recognition.

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                 ....*....|....*....|....*....|....*....|..
gi 530409257 129 LCCQLCCSVFKD----PVITTCGHTFCRRC--ALKSEKCPVD 164
Cdd:cd16638    2 LSCPVCTNEFDGtqrkPISLGCGHTVCKTClsKLHRKQCPFD 43

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
                  ....*....|....*....|....*....|....*....
gi 530409257  131 CQLCCSVFKDPV-ITTCGHTFCRRCALK-----SEKCPV 163
Cdd:pfam00097   1 CPICLEEPKDPVtLLPCGHLFCSKCIRSwlesgNVTCPL 39

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).