RING finger, HC subclass, found in RING domain ligase RGLG1, RGLG2 and similar proteins from plant; RGLG1 is a ubiquitously expressed E3 ubiquitin-protein ligase that interacts with UBC13 and, together with UBC13, catalyzes the formation of K63-linked polyubiquitin chains, which is involved in DNA damage repair. RGLG1 mediates the formation of canonical, K48-linked polyubiquitin chains that target proteins for degradation. It also regulates apical dominance by acting on the auxin transport proteins abundance. RGLG1 has overlapping functions with its closest sequelog, RGLG2. They both function as RING E3 ligases that interact with ethylene response factor 53 (ERF53) in the nucleus and negatively regulate the plant drought stress response. Members of this subfamily contain a Von Willebrand factor type A (vWA) domain and a C3HC4-type RING-HC finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1063708822 442 DIQLCPICLSNPKNMAFGCGHQTCCECGPDLKVCPICRAPIQTRIKLY 489
Cdd:cd16729     1 DDQLCPICLSNPKDMAFGCGHQTCCECGQSLTHCPICRQPITTRIKLY 48

Copine; This family represents a conserved region approximately 220 residues long within eukaryotic copines. Copines are Ca(2+)-dependent phospholipid-binding proteins that are thought to be involved in membrane-trafficking, and may also be involved in cell division and growth.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063708822 179 SLHHLS-NTPNPYEQAITIIGRTLAAFDEDNLIPCYGFGD-----ASTHDQDVFSFYPEGRFCNGFEEVLARYREIVPQL 252
Cdd:pfam07002   1 SLHYISpSQPNPYEQALRIVGEILQDYDSDKLFPAFGFGArippdATVSHCFVLNFNPENPECEGIEGVLEAYRSALPNL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063708822 253 KLAGPTSFAPIIEMAMTVVEQS---SGQYHVLVIIADGQVTrsvdtehgrlspQEQKTVDAIVKASTLPLSIVLVGVGDG 329
Cdd:pfam07002  81 QLYGPTNFAPIIDAAARIAKAStqnAGQYHVLLIITDGVVT------------DMKATIDAIVNASHLPLSIIIVGVGDG 148

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1063708822 330 PWDMMQEFDDN---------IPARafDNFQFVNFTEIMSKNkdqSRKETEFALSALMEIPPQYKATIELNL 391
Cdd:pfam07002 149 DFSDMRELDDDdrlrssdgrIAAR--DIVQFVPFRDIMSNA---DLKEAALALAVLAEIPDQYVAYMELRG 214

Zinc finger, C3HC4 type (RING finger);

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1063708822 442 DIQLCPICLSNPKNMAFG-CGHQTCC-ECGPDL----KVCPICRAPIQTR 485
Cdd:pfam13920   1 EDLLCVICLDRPRNVVLLpCGHLCLCeECAERLlrkkKKCPICRQPIESV 50

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 1063708822  446 CPICLSNPKNMAF--GCGHQTCCEC-----GPDLKVCPIC 478
Cdd:smart00184   1 CPICLEEYLKDPVilPCGHTFCRSCirkwlESGNNTCPIC 40

Copine; This family represents a conserved region approximately 220 residues long within eukaryotic copines. Copines are Ca(2+)-dependent phospholipid-binding proteins that are thought to be involved in membrane-trafficking, and may also be involved in cell division and growth.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063708822 179 SLHHLS-NTPNPYEQAITIIGRTLAAFDEDNLIPCYGFGD-----ASTHDQDVFSFYPEGRFCNGFEEVLARYREIVPQL 252
Cdd:pfam07002   1 SLHYISpSQPNPYEQALRIVGEILQDYDSDKLFPAFGFGArippdATVSHCFVLNFNPENPECEGIEGVLEAYRSALPNL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063708822 253 KLAGPTSFAPIIEMAMTVVEQS---SGQYHVLVIIADGQVTrsvdtehgrlspQEQKTVDAIVKASTLPLSIVLVGVGDG 329
Cdd:pfam07002  81 QLYGPTNFAPIIDAAARIAKAStqnAGQYHVLLIITDGVVT------------DMKATIDAIVNASHLPLSIIIVGVGDG 148

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1063708822 330 PWDMMQEFDDN---------IPARafDNFQFVNFTEIMSKNkdqSRKETEFALSALMEIPPQYKATIELNL 391
Cdd:pfam07002 149 DFSDMRELDDDdrlrssdgrIAAR--DIVQFVPFRDIMSNA---DLKEAALALAVLAEIPDQYVAYMELRG 214

RING finger, HC subclass, found in mind bomb MIB1, MIB2, RGLG1, RGLG2, and similar proteins; MIBs are large, multi-domain E3 ubiquitin-protein ligases that promote ubiquitination of the cytoplasmic tails of Notch ligands. They are also responsible for TBK1 K63-linked ubiquitination and activation, promoting interferon production and controlling antiviral immunity. Moreover, MIBs selectively control responses to cytosolic RNA and regulate type I interferon transcription. Both MIB1 and MIB2 have similar domain architectures, which consist of two Mib-Herc2 domains flanking a ZZ zinc finger, a REP region including two tandem Mib repeats, an ANK region that spans ankyrin repeats, and a RNG region, where MIB1 and MIB2 contain three and two C3HC4-type RING-HC fingers, respectively. This model corresponds to the third RING-HC finger of MIB1, as well as the second RING-HC finger of MIB2. In addition to MIB1 and MIB2, the RING-HC fingers of RING domain ligase RGLG1, RGLG2 and similar proteins from plant are also included in this model. RGLG1 is a ubiquitously expressed E3 ubiquitin-protein ligase that interacts with UBC13 and, together with UBC13, catalyzes the formation of K63-linked polyubiquitin chains, which is involved in DNA damage repair. RGLG1 mediates the formation of canonical, K48-linked polyubiquitin chains that target proteins for degradation. It also regulates apical dominance by acting on the auxin transport proteins abundance. RGLG1 has overlapping functions with its closest sequelog, RGLG2. They both function as RING E3 ligases that interact with ethylene response factor 53 (ERF53) in the nucleus and negatively regulate the plant drought stress response. All RGLG proteins contain a Von Willebrand factor type A (vWA) domain and a C3HC4-type RING-HC finger.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1063708822 444 QLCPICLSNPKNMAFGCGHQTCCECGPDLKVCPICRAPI 482
Cdd:cd16520     1 ILCPICMERKKNVVFLCGHGTCQKCAEKLKKCPICRKPI 39

second RING finger, HC subclass, found in mind bomb 2 (MIB2) and similar proteins; MIB2, also known as novel zinc finger protein (Novelzin), putative NF-kappa-B-activating protein 002N, skeletrophin, or zinc finger ZZ type with ankyrin repeat domain protein 1, is a large, multi-domain E3 ubiquitin-protein ligase that promotes ubiquitination of the cytoplasmic tails of Notch ligands. Especially, it promotes Delta ubiquitylation and endocytosis in Notch activation. Overexpression of MIB2, activates NF-kappaB and interferon-stimulated response element (ISRE) reporter activity. Moreover, MIB2 acts as a novel component of the activated B-cell CLL/lymphoma 10 (BCL10) complex and controls BCL10-dependent NF-kappaB activation. It also functions as a founder myoblast-specific protein that regulates myoblast fusion and muscle stability. MIB2 contains an MZM region with two Mib-Herc2 domains flanking a ZZ zinc finger, a REP region including two tandem Mib repeats, an ANK region that spans ankyrin repeats, and a RNG region consisting of two C3HC4-type RING-HC fingers. This model corresponds to the second RING-HC finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1063708822 446 CPICLSNPKNMAFGCGHQTCCECGPDLKVCPICRAPIQTRIKLY 489
Cdd:cd16728     7 CPICIDNHIKLVFQCGHGSCIECSSALKACPICRQAIRERIQIF 50

Modified RING finger, HC subclass (C3HC5-type), found in neuralized-like protein NEURL1A, NEURL1B, and similar proteins; This subfamily includes Drosophila neuralized (D-neu) protein, and its two mammalian homologs, NEURL1A and NEURL1B. D-neu is a regulator of the developmentally important Notch signaling pathway. NEURL1A, also known as NEURL1, NEU, neuralized 1, or RING finger protein 67 (RNF67), is a mammalian homolog of D-neu. It functions as an E3 ubiquitin-protein ligase that directly interacts with and monoubiquitinates cytoplasmic polyadenylation element-binding protein 3 (CPEB3), an RNA binding protein and a translational regulator of local protein synthesis, which facilitates hippocampal plasticity and hippocampal-dependent memory storage. It also acts as a potential tumor suppressor that causes apoptosis and downregulates Notch target genes in medulloblastoma. NEURL1B, also known as neuralized-2 (NEUR2) or neuralized-like protein 3, is another mammalian homolog of D-neu protein. It functions as an E3 ubiquitin-protein ligase that interacts with and ubiquitinates Delta. Thus, it plays a role in the endocytic pathways for Notch signaling by working cooperatively with another E3 ligase, Mind bomb-1 (Mib1), in Delta endocytosis to hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs)-positive vesicles. Members of this subfamily contain two neuralized homology regions (NHRs) responsible for Neural-ligand interactions and a modified C3HC5-type RING-HC finger required for ubiquitin ligase activity. The C3HC5-type RING-HC finger is distinguished from typical C3HC4-type RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1063708822 446 CPICLSNPKNMAF-GCGHQTCC-ECGPDLKV----CPICRAPIQTRIKLY 489
Cdd:cd16647     4 CVICYERPVDTVLyRCGHMCMCyDCALQLKRrggsCPICRAPIKDVIKIY 53

RING finger, HC subclass, found in inhibitor of apoptosis proteins (IAPs); IAPs are frequently overexpressed in cancer and associated with tumor cell survival, chemoresistance, disease progression, and poor prognosis. They function primarily as negative regulators of cell death. They regulate caspases and apoptosis through the inhibition of specific members of the caspase family of cysteine proteases. In addition, IAPs has been implicated in a multitude of other cellular processes, including inflammatory signalling and immunity, mitogenic kinase signalling, proliferation and mitosis, as well as cell invasion and metastasis. IAPs in this family includes cellular inhibitor of apoptosis protein c-IAP1 (BIRC2) and c-IAP2 (BIRC3), XIAP (BIRC4), BIRC7, and BIRC8, all of which contain three N-terminal baculoviral IAP repeat (BIR) domains that enable interactions with proteins, a ubiquitin-association (UBA) domain that is responsible for the binding of polyubiquitin (polyUb), and a C3HC4-type RING-HC finger at the carboxyl terminus that is required for ubiquitin ligase activity. The UBA domain is only absent in mammalian homologs of BIRC7. Moreover, c-IAPs contains an additional caspase activation and recruitment domain (CARD) between the UBA and C3HC4-type RING-HC domains. The CARD domain may serve as a protein interaction surface.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1063708822 444 QLCPICLSNPKNMAF-GCGHQTCC-ECGPDLKVCPICRA 480
Cdd:cd16510     2 KLCKICMDREVNIVFlPCGHLVTCaQCAASLRKCPICRT 40

Modified RING finger, HC subclass (C2H2C4-type), found in E3 ubiquitin-protein ligase MDM2, protein MDM4 and similar proteins; MDM2 (also known as HDM2) and MDM4 (also known as MDMX or HDMX) are the primary p53 tumor suppressor negative regulators. They have non-redundant roles in the regulation of p53. MDM2 mainly functions to control p53 stability, while MDM4 controls p53 transcriptional activity. Both MDM2 and MDM4 contain an N-terminal p53-binding domain, a RanBP2-type zinc finger (zf-RanBP2) domain near the central acidic region, and a C-terminal modified C2H2C4-type RING-HC finger. Mdm2 can form homo-oligomers through its RING domain and displays E3 ubiquitin ligase activity that catalyzes the attachment of ubiquitin to p53 as an essential step in the regulation of its levels in cells. Despite its RING domain and structural similarity with MDM2, MDM4 does not homo-oligomerize and lacks ubiquitin-ligase function, but inhibits the transcriptional activity of p53. In addition, both their RING domains are responsible for the hetero-oligomerization, which is crucial for the suppression of P53 activity during embryonic development and the recruitment of E2 ubiquitin-conjugating enzymes. Moreover, MDM2 and MDM4 can be phosphorylated and destabilized in response to DNA damage stress. In response to ribosomal stress, MDM2-mediated p53 ubiquitination and degradation can be inhibited through the interaction with ribosomal proteins L5, L11, and L23. However, MDM4 is not bound to ribosomal proteins, suggesting its different response to regulation by small basic proteins such as ribosomal proteins and ARF.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1063708822 445 LCPICLSNPKNMAF--GC-GHQTCC-ECGPDL----KVCPICRAPIQTRIK 487
Cdd:cd16646     2 LCVICLSRPRTAAIvhGKtGHQVACyTCAKKLkrrgKPCPVCRRPIQNVIK 52

RING finger, HC subclass, found in apoptosis protein c-IAP1, c-IAP2, livin, and similar proteins; The cellular inhibitor of apoptosis protein c-IAPs function as ubiquitin E3 ligases that mediate the ubiquitination of substrates involved in apoptosis, nuclear factor-kappaB (NF-kappaB) signaling, and oncogenesis. Unlike other IAPs, such as XIAP, c-IAPs exhibit minimal binding to caspases and may not play an important role in the inhibition of these proteases. c-IAP1, also known as baculoviral IAP repeat-containing protein BIRC2, IAP-2, RING finger protein 48, or TNFR2-TRAF-signaling complex protein 2, is a potent regulator of the tumor necrosis factor (TNF) receptor family and NF-kappaB signaling pathways in the cytoplasm. It can also regulate E2F1 transcription factor-mediated control of cyclin transcription in the nucleus. c-IAP2, also known as BIRC3, IAP-1, apoptosis inhibitor 2 (API2), or IAP homolog C, also influences ubiquitin-dependent pathways that modulate innate immune signalling by activation of NF-kappaB. c-IAPs contain three N-terminal baculoviral IAP repeat (BIR) domains that enable interactions with proteins, a ubiquitin-association (UBA) domain that is responsible for the binding of polyubiquitin (polyUb), a caspase activation and recruitment domain (CARD) that serves as a protein interaction surface, and a C3HC4-type RING-HC finger at the carboxyl terminus that is required for ubiquitin ligase activity. Livin, also known as baculoviral IAP repeat-containing protein 7 (BIRC7), kidney inhibitor of apoptosis protein (KIAP), melanoma inhibitor of apoptosis protein (ML-IAP), or RING finger protein 50, was identified as the melanoma IAP. It plays crucial roles in apoptosis, cell proliferation, and cell cycle control. Its anti-apoptotic activity is regulated by the inhibition of caspase-3, -7, and -9. Its E3 ubiquitin-ligase-like activity promotes degradation of Smac/DIABLO, a critical endogenous regulator of all IAPs. Unlike other family members, mammalian livin contains a single BIR domain and a C3HC4-type RING-HC finger. The UBA domain can be detected in non-mammalian homologs of livin.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1063708822 446 CPICLSNPKNMAF-GCGHQTCC-ECGPDLKVCPICRAPIQTRIKLY 489
Cdd:cd16713    10 CKVCMDKEVSIVFiPCGHLVVCtECAPSLRKCPICRATIKGTVRTF 55

RING finger, HC subclass, found in leucine-rich repeat and sterile alpha motif-containing protein 1 (LRSAM1) and similar proteins; LRSAM1, also known as Tsg101-associated ligase (TAL), or RIFLE, is an E3 ubiquitin-protein ligase that physically associates with, and selectively ubiquitylates, Tsg101, an E2-like molecule that regulates vesicular trafficking processes in yeast and mammals. It regulates a Tsg101-associated complex responsible for the sorting of cargo into cytoplasm-containing vesicles that bud at the multivesicular body and at the plasma membrane. LRSAM1 is a multidomain protein containing an N-terminal leucine-rich repeat (LRR), followed by several recognizable motifs, including an ezrin-radixin-moezin (ERM) domain, a coiled-coil (CC) region, a SAM domain, and a C-terminal C3HC4-type RING-HC finger domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1063708822 446 CPICLSNPKNMAF-GCGHQTCCE-CGPDLKVCPICRAPIQTRIKL 488
Cdd:cd16515     4 CVVCMDAESQVIFlPCGHVCCCQtCSSSLSTCPLCRADITQRVRI 48

vWA found in TerF C terminus; vWA domain fused to TerD domain typified by the TerF protein. Some times found as solos.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063708822 202 AAFDEDNLIPCYGFGD--ASTHDQDVFSFYpegRFCNGFEEVLARYReivpqlKLAGPTSFAPIIEMAMTVVEQSSGQYH 279
Cdd:pfam10138  35 AQLDDDGELDVWLFGTraARLPDVTLADLP---GWVERLHLGRDRYR------KLGGQNNEPPVMEAVIDYYRKNPADLP 105

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1063708822 280 VLVI-IADGQVTRSVDTEhgrlspqeqktvDAIVKASTLPLSIVLVGVGDGPWDMMQEFDDnIPARAFDNfqfVNF 354
Cdd:pfam10138 106 TLVLfITDGGVTDNAAIE------------RLLREASREPIFWQFVGIGRSGYGFLEKLDT-LRGRVVDN---AGF 165

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
                  ....*....|....*....|....*....|....*....
gi 1063708822 446 CPICLSNPKNMAF-GCGHQTCCEC-----GPDLKVCPIC 478
Cdd:cd16449     3 CPICLERLKDPVLlPCGHVFCRECirrllESGSIKCPIC 41

Modified RING finger, HC subclass (C3HC5-type), found in neuralized-like protein 1B (NEURL1B); NEURL1B, also known as neuralized-2 (NEUR2) or neuralized-like protein 3, is a mammalian homolog of the Drosophila neuralized (D-neu) protein. It functions as an E3 ubiquitin-protein ligase that interacts with and ubiquitinates Delta. Thus, it plays a role in the endocytic pathways for Notch signaling through working cooperatively with another E3 ligase, Mind bomb-1 (Mib1), in Delta endocytosis to hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs)-positive vesicles. NEURL1B contains two neuralized homology regions (NHRs) responsible for Neural-ligand interactions and a modified C3HC5-type RING-HC finger required for ubiquitin ligase activity. The C3HC5-type RING-HC finger is distinguished from typical C3HC4-type RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1063708822 446 CPICLSNP-KNMAFGCGHQTCC-ECGPDLK-----VCPICRAPIQTRIKLY 489
Cdd:cd16786     5 CTVCFDSEvDTVIYTCGHMCLCnSCGLKLKrqinaCCPICRRVIKDVIKIY 55

RING finger, HC subclass, found in E3 ubiquitin-protein ligase XIAP, baculoviral IAP repeat-containing protein 8 (BIRC8) and similar proteins; XIAP, also known as baculoviral IAP repeat-containing protein 4 (BIRC4), IAP-like protein (ILP), inhibitor of apoptosis protein 3 (IAP-3), or X-linked inhibitor of apoptosis protein (X-linked IAP), is a potent suppressor of apoptosis that directly inhibits specific members of the caspase family of cysteine proteases, including caspase-3, -7, and -9. It promotes proteasomal degradation of caspase-3 and enhances its anti-apoptotic effect in Fas-induced cell death. The ubiquitin-protein ligase (E3) activity of XIAP also exhibits in the ubiquitination of second mitochondria-derived activator of caspases (Smac). The mitochondrial proteins, Smac/DIABLO and Omi/HtrA2, can inhibit the antiapoptotic activity of XIAP. XIAP has also been implicated in several intracellular signaling cascades involved in the cellular response to stress, such as the c-Jun N-terminal kinase (JNK), the nuclear factor-kappaB (NF-kappaB), and the transforming growth factor-beta (TGF-beta) pathways. Moreover, XIAP can regulate copper homeostasis by interacting with MURR1. BIRC8, also known as inhibitor of apoptosis-like protein 2, IAP-like protein 2, ILP-2, or testis-specific inhibitor of apoptosis, is a tissue-specific homolog of E3 ubiquitin-protein ligase XIAP. It has been implicated in the control of apoptosis in the testis by direct inhibition of caspase 9. Both XIAP and BIRC8 contain three N-terminal baculoviral IAP repeat (BIR) domains, a ubiquitin-association (UBA) domain and a C3HC4-type RING-HC finger at the carboxyl terminus.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1063708822 444 QLCPICLSNPKNMAF-GCGHQ-TCCECGPDLKVCPICRAPIQTRIKLY 489
Cdd:cd16714    15 KLCKICMDRNISIVFiPCGHLvTCKQCAEALDKCPICCTVITFKQKIF 62

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 1063708822 444 QLCPICLSNPKN-MAF--GCGHQTCCECgpdLK-------VCPICRAPI 482
Cdd:cd16574     2 SSCPICLDRFENeKAFldGCFHAFCFTC---ILewskvknECPLCKQPF 47

Modified RING finger, HC subclass (C3HC5-type), found in cell growth regulator with RING finger domain protein 1 (CGRRF1) and similar proteins; CGRRF1, also known as cell growth regulatory gene 19 protein (CGR19) or RING finger protein 197 (RNF197), functions as a novel biomarker to monitor endometrial sensitivity and response to insulin-sensitizing drugs, such as metformin, in the context of obesity. CGRRF1 contains a C-terminal modified C3HC5-type RING-HC finger, which is distinguished from typical C3HC4 RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1063708822 444 QLCPICLSNPKNMAF-GCGHQTCC-ECGPDLKVCPICR 479
Cdd:cd16787     1 KDCVVCQNAPVNRVLlPCRHACVCdECFKRLQRCPMCR 38

RING finger, HC subclass, found in seven in absentia homolog 1 (SIAH1) and similar proteins; SIAH1, also known as Siah-1a, is an inducible E3 ubiquitin-protein ligase that contributes to proteasome-mediated degradation of multiple targets in numerous cellular processes including apoptosis, tumor suppression, cell cycle, axon guidance, transcription regulation, and tumor necrosis factor signaling. SIAH1 functions as a scaffolding protein and interacts with a variety of different substrates for ubiquitination and subsequent degradation. It regulates the oncoprotein p34SEI-1 polyubiquitination and its subsequent degradation in a p53-dependent manner, which mediates p53 preferential vitamin C cytotoxicity. It targets the nonreceptor tyrosine kinase activated Cdc42-associated kinase 1 (ACK1), a valid target in cancer therapy, for ubiquitinylation and proteasomal degradation. It also interacts with KLF10 and targets it for degradation. The CDK2 phosphorylation-mediated KLF10 dissociation from SIAH1 is linked to cell cycle progression. Moreover, SIAH1 is downregulated and associated with apoptosis and invasion in human breast cancer. It targets TAp73, a homolog of the tumor suppressor p53, for degradation. It is suppressed by hypoxia-inducible factor 1-alpha (HIF-1alpha) under hypoxic conditions to regulate TAp73 levels. It also promotes the migration and invasion of human glioma cells by regulating HIF-1alpha signaling under hypoxia. Furthermore, SIAH1 forms a protein complex with glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The apoptosis signal-regulating kinase 1 (ASK1) functions as an activator of the GAPDH-Siah1 stress-signaling cascade. It also plays an important role in ethanol-induced apoptosis in neural crest cells (NCCs). SIAH1 contains an N-terminal C3HC4-type RING-HC finger, two zinc-finger subdomains, and a C-terminal tumor necrosis factor (TNF) receptor associated factor (TRAF)-like substrate-binding domain (SBD) responsible for dimer formation.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1063708822 446 CPICLSN--PKNMAFGCGHQTCCECGPDLKVCPICRAP 481
Cdd:cd16751     8 CPVCFDYvlPPILQCQSGHLVCSNCRPKLTCCPTCRGP 45

first RING finger, HC subclass, found in mind bomb 1 (MIB1) and similar proteins; MIB1, also known as DAPK-interacting protein 1 (DIP-1) or zinc finger ZZ type with ankyrin repeat domain protein 2, is a large, multi-domain E3 ubiquitin-protein ligase that promotes ubiquitination of the cytoplasmic tails of Notch ligands, and thus plays an essential role in controlling metazoan development by Notch signaling. It is also involved in Wnt/beta-catenin signaling and nuclear factor (NF)-kappaB signaling, and has been implicated in innate immunity, neuronal function, genomic stability, and cell death. MIB1 contains an MZM region with two Mib-Herc2 domains flanking a ZZ zinc finger, a REP region including two tandem Mib repeats, an ANK region that spans ankyrin repeats, and a RNG region consisting of three C3HC4-type RING-HC fingers. This model corresponds to the first RING-HC finger.

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                  ....*....|....*....|....*....|....*.
gi 1063708822 446 CPICLSNPKNMAFG-CGHQTCCE-CGPDLKVCPICR 479
Cdd:cd16724     3 CMVCSDMKRDTLFGpCGHIATCSlCSPRVKKCLICK 38

RING finger, HC subclass, found in Casitas B-lineage lymphoma (Cbl) proteins; The Cbl adaptor protein family contains a small class of RING-type E3 ubiquitin ligases with oncogenic activity, which is represented by three mammalian members, c-Cbl, Cbl-b and Cbl-c, as well as two invertebrate Cbl-family proteins, D-Cbl in Drosophila and Sli-1 in C. elegans. Cbl proteins function as potent negative regulators of various signaling cascades in a wide range of cell types. They play roles in ubiquitinating activated tyrosine kinases and targeting them for degradation. D-Cbl associates with the Drosophila epidermal growth factor receptor (EGFR) and overexpression of D-Cbl in the eye of Drosophila embryos inhibits EGFR-dependent photoreceptor cell development. Sli-1 is a negative regulator of the Let-23 receptor tyrosine kinase, an EGFR homolog, in vulva development. Cbl proteins in this subfamily consist of a highly conserved N-terminal half that includes a tyrosine-kinase-binding domain (TKB, also known as the phosphotyrosine binding PTB domain, composed of a four helix-bundle, a Ca2+ binding EF-hand and a highly variant SH2 domain) and a C3HC4-type RING-HC finger, both of which are required for Cbl-mediated downregulation of RTKs, and a divergent C-terminal region.

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                  ....*....|....*....|....*....|....*....|..
gi 1063708822 444 QLCPICLSNPKNMAFG-CGHQTCCEC-----GPDLKVCPICR 479
Cdd:cd16502     2 QLCKICAENDKDVRIEpCGHLLCTPCltswqDSDGQTCPFCR 43

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.

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                  ....*....|....*....|....*....|....*....|....*....|
gi 1063708822 446 CPICL---SNPknMAFGCGHQTCCEC---------GPDLKVCPICRAPIQ 483
Cdd:cd16598     7 CSICLdylRDP--VTIDCGHNFCRSCitdycpisgGHERPVCPLCRKPFK 54

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

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                  ....*....|....*....|....*....|....*....|....*....|..
gi 1063708822 446 CPICLSNPKN--MAFGCGHQTCCEC-------GPdlKVCPICRAPIQTRIKL 488
Cdd:cd16531     4 CPICLGIIKNtmTVKECLHRFCAECiekalrlGN--KECPTCRKHLPSRRSL 53

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)

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                   ....*....|....*....|....*....|....*....|
gi 1063708822  446 CPICLSNPKNMAF--GCGHQTCCEC-----GPDLKVCPIC 478
Cdd:smart00184   1 CPICLEEYLKDPVilPCGHTFCRSCirkwlESGNNTCPIC 40

RING finger, HC subclass, found in peroxin-10 (PEX10) and similar proteins; PEX10, also known as peroxisome biogenesis factor 10, peroxisomal biogenesis factor 10, peroxisome assembly protein 10, or RING finger protein 69 (RNF69), is an integral peroxisomal membrane protein with two transmembrane regions and a C3HC4-type RING-HC finger within its cytoplasmically exposed C-terminus. It plays an essential role in peroxisome assembly, import of target substrates, and recycling or degradation of protein complexes and amino acids. It is an essential component of the spinal locomotor circuit, and thus its mutations may be involved in peroxisomal biogenesis disorders (PBD). Mutations in human PEX10 also result in autosomal recessive ataxia. Moreover, PEX10 functions as an E3-ubiquitin ligase with an E2, UBCH5C. It mono- or poly-ubiquitinates PEX5, a key player in peroxisomal matrix protein import, in a UBC4-dependent manner, to control PEX5 receptor recycling or degradation. It also links the E2 ubiquitin conjugating enzyme PEX4 to the protein import machinery of the peroxisome.

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                  ....*....|....*....|....*....|....*....|....*.
gi 1063708822 446 CPICLSNPKN-MAFGCGHQTCCEC-------GPDlkvCPICRAPIQ 483
Cdd:cd16527     3 CSLCLEERRHpTATPCGHLFCWSCitewcneKPE---CPLCREPFQ 45

Ring finger domain;

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                  ....*....|....*....|....*....|....*....|..
gi 1063708822 446 CPICLSNPKN----MAFGCGHQTCCECGPDL----KVCPICR 479
Cdd:pfam13639   3 CPICLEEFEEgdkvVVLPCGHHFHRECLDKWlrssNTCPLCR 44

RING finger, HC subclass, found in caspases-8 and -10-associated RING finger protein 1 (CARP1) and similar proteins; CARP1, also known as caspase regulator CARP1, FYVE-RING finger protein Momo, RING finger homologous to inhibitor of apoptosis protein (RFI), RING finger protein 34 (RNF34), or RING finger protein RIFF, is a nuclear protein that functions as a specific E3 ubiquitin ligase for the transcriptional coactivator PGC-1alpha, a master regulator of energy metabolism and adaptive thermogenesis in the brown fat cell which negatively regulates brown fat cell metabolism. It is preferentially expressed in esophageal, gastric, and colorectal cancers, suggesting a possible association with the development of digestive tract cancers. It regulates the p53 signaling pathway by degrading 14-3-3 sigma and stabilizing MDM2. CARP1 does not localize to membranes in the cell and is involved in the negative regulation of apoptosis, specifically targeting two initiator caspases, caspase 8 and caspase 10. CARP1 contains an N-terminal FYVE-like domain and a C-terminal C3HC4-type RING-HC finger domain.

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                  ....*....|....*....|....*....|....*....|.
gi 1063708822 441 DDIQLCPICLSNPKN-MAFGCGHQ-TCCECGPDLKVCPICR 479
Cdd:cd16706     2 SDDNLCRICMDAVIDcVLLECGHMvTCTKCGKRMSECPICR 42

RING finger, HC subclass, found in seven in absentia homolog 2 (SIAH2) and similar proteins; SIAH2 is an E3 ubiquitin-protein ligase that contributes to proteasome-mediated degradation of multiple targets in numerous cellular processes. It targets the ubiquitylation and degradation of tumor necrosis factor receptor-associated factor 2 (TRAF2) under stress conditions, which is required for the cell to commit to undergoing apoptosis. It is, therefore, a key regulator of TRAF2-dependent signaling in response to tumor necrosis factor-alpha (TNF-alpha) treatment and UV irradiation. SIAH2 modulates the polyubiquitination of G protein pathway suppressor 2 (GPS2), and targets it for proteasomal degradation. It is also a regulator of NF-E2-related factor 2 (Nrf2), a key regulator of cellular oxidative response, and contributes to the degradation of Nrf2 irrespective of its phosphorylation status. Moreover, SIAH2 contributes to castration-resistant prostate cancer (CRPC) by regulation of androgen receptor (AR) transcriptional activity. It enhances AR transcriptional activity and prostate cancer cell growth. Its stability can be regulated by AKR1C3. SIAH2 also inhibits tyrosine kinase-2 (TYK2)-STAT3 signaling in lung carcinoma cells. Furthermore, SIAH2 regulates obesity-induced adipose tissue inflammation by altering peroxisome proliferator-activated receptor gamma (PPAR gamma) protein levels and selectively regulating PPAR gamma activity. It also functions as a regulator of the nuclear hormone receptor RevErbalpha (Nr1d1) stability and rhythmicity, and overall circadian oscillator function. In addition, SIAH2 is an essential component of the hypoxia response Hippo signaling pathway and has been implicated in normal development and tumorigenesis. It modulates the hypoxia pathway upstream of hypoxia-induced transcription factor subunit HIF-1alpha, and therefore may play an important role in angiogenesis in response to hypoxic stress in endothelial cells. It also stimulates transcriptional coactivator YAP1 by destabilizing serine/threonine-protein kinase LATS2, a critical component of the Hippo pathway, in response to hypoxia. Meanwhile, SIAH2 is involved in regulation of tight junction integrity and cell polarity under hypoxia, through its regulation of apoptosis-stimulating proteins of p53 subunit 2 (ASPP2) stability. SIAH2 contains an N-terminal C3HC4-type RING-HC finger, two zinc-finger subdomains, and a C-terminal tumor necrosis factor (TNF) receptor associated factor (TRAF)-like substrate-binding domain (SBD) responsible for dimer formation.

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                  ....*....|....*....|....*....|....*....|....*
gi 1063708822 446 CPICLSN--PKNMAFGCGHQTCCECGPDLKVCPICRAPIQTRIKL 488
Cdd:cd16752     6 CPVCFDYvlPPILQCQAGHLVCNQCRQKLSCCPTCRGPLTPSIRN 50

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.

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                  ....*....|....*....|....*....|....*....|....*....|
gi 1063708822 446 CPICL---SNPknMAFGCGHQTCCEC------GPDLKV-CPICRAPIQTR 485
Cdd:cd16594     8 CPICLdyfTDP--VTLDCGHSFCRACiarcweEPETSAsCPQCRETCPQR 55

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

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                  ....*....|....*....|....*....|....*....|....
gi 1063708822 446 CPICLS---NPKNMAfGCGHQTCCEC-GPDLKV----CPICRAP 481
Cdd:cd16549     4 CPICLEvyhKPVVIT-SCGHTFCGEClQPCLQVasplCPLCRMP 46

RING finger, HC subclass, found in E3 ubiquitin-protein ligase Cbl-c and similar proteins; Cbl-c, also known as RING finger protein 57 (RNF57), SH3-binding protein Cbl-3, SH3-binding protein Cbl-c, or signal transduction protein Cbl-c, is an E3 ubiquitin-protein ligase expressed exclusively in epithelial cells. It contains a tyrosine-kinase-binding domain (TKB, also known as the phosphotyrosine binding PTB domain, composed of a four helix-bundle, a Ca2+ binding EF-hand and a highly variant SH2 domain), a C3HC4-type RING-HC finger, and a short proline-rich region, but lacks the ubiquitin-associated (UBA) leucine zipper motif that are present in Cbl and Cbl-b. Cbl-c acts as a regulator of epidermal growth factor receptor (EGFR)-mediated signal transduction. It also suppresses v-Src-induced transformation through ubiquitin-dependent protein degradation. Moreover, Cbl-c ubiquitinates and downregulates RETMEN2A and implicates Enigma (PDLIM7) as a positive regulator of RETMEN2A by blocking Cbl-mediated ubiquitination and degradation. The ubiquitin ligase activity of Cbl-c is increased via the interaction of its RING-HC finger domain with a LIM domain of the paxillin homolog, hydrogen peroxide induced construct 5 (Hic-5).

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                  ....*....|....*....|....*....|....*....|....*...
gi 1063708822 444 QLCPICLSNPKNMAFG-CGHQTCCEC-----GPDLKVCPICRAPIQTR 485
Cdd:cd16710    14 ELCKICAERDKDVRIEpCGHLLCSCClaawqHSDSQTCPFCRCEIKGR 61

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.

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                  ....*....|....*....|....*....|....*....|....*.
gi 1063708822 446 CPICLSNPKNMAFG-CGHQTCCEC-----GPDLKVCPICRAPIQTR 485
Cdd:cd16509     6 CAICLDSLTNPVITpCAHVFCRRCiceviQREKAKCPMCRAPLSAS 51

Prokaryotic RING finger family 4; RING finger family domain found sporadically in bacteria. The finger is fused to an N-terminal alpha-helical domain, ROT/Trove-like repeats and a C-terminal TerD domain. The architecture suggests a possible role in an RNA-processing complex.

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                  ....*....|....*....|....*....|....*..
gi 1063708822 446 CPICLSNPKNMAFG-CGHQTCCEC--GPDLKVCPICR 479
Cdd:pfam14447   1 CVLCGRNGTVHALIpCGHLVCRDCfdGSDFSACPICR 37