RING finger, H2 subclass, found in Tetratricopeptide repeat protein 3 (TTC3) and similar proteins; TTC3, also known as protein DCRR1, TPR repeat protein D, TPR repeat protein 3, or RING finger protein 105 (RNF105), is an E3 ubiquitin-protein ligase encoded by a gene within the Down syndrome (DS) critical region on chromosome 21. It affects differentiation and Golgi compactness in neurons through specific actin-regulating pathways. It inhibits the neuronal-like differentiation of pheocromocytoma cells by activating RhoA and by binding to Citron proteins. TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. It contains four N-terminal TPR motifs, a potential coiled-coil region and a Citron binding region in the central part, and a C-terminal C3H2C2-type RING-H2 finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1226253906 1234 SCEICHEVFKSKNVRVLKCGHKYHKGCFKQWLKGQSACPACQGRD 1278
Cdd:cd16481      1 PCIICHDDLKPDQLAKLECGHIFHKECIKQWLKEQSTCPTCRVHV 45

RING finger, H2 subclass, found in Tetratricopeptide repeat protein 3 (TTC3) and similar proteins; TTC3, also known as protein DCRR1, TPR repeat protein D, TPR repeat protein 3, or RING finger protein 105 (RNF105), is an E3 ubiquitin-protein ligase encoded by a gene within the Down syndrome (DS) critical region on chromosome 21. It affects differentiation and Golgi compactness in neurons through specific actin-regulating pathways. It inhibits the neuronal-like differentiation of pheocromocytoma cells by activating RhoA and by binding to Citron proteins. TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. It contains four N-terminal TPR motifs, a potential coiled-coil region and a Citron binding region in the central part, and a C-terminal C3H2C2-type RING-H2 finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1226253906 1234 SCEICHEVFKSKNVRVLKCGHKYHKGCFKQWLKGQSACPACQGRD 1278
Cdd:cd16481      1 PCIICHDDLKPDQLAKLECGHIFHKECIKQWLKEQSTCPTCRVHV 45

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 1226253906  1235 CEICHEVFkSKNVRVLKCGHKYHKGCFKQWLKGQSA-CPAC 1274
Cdd:smart00184    1 CPICLEEY-LKDPVILPCGHTFCRSCIRKWLESGNNtCPIC 40

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1226253906 1209 VVAPSPKTKG--QKAEDVPVRIALGASSCEICHEVF-KSKNVRVLKCGHKYHKGCFKQWLKGQS-ACPACQ 1275
Cdd:COG5540    298 EAIPTTTTKGslKPLSIERAVEADKGVECAICMSNFiKNDRLRVLPCDHRFHVGCVDKWLLGYSnKCPVCR 368

Septation ring formation regulator, EzrA; During the bacterial cell cycle, the tubulin-like cell-division protein FtsZ polymerizes into a ring structure that establishes the location of the nascent division site. EzrA modulates the frequency and position of FtsZ ring formation. The structure contains 5 spectrin like alpha helical repeats.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1226253906  773 IEKEHQVLQDQLQEVYENYEQIKLKG--------LEETRDLEEKLKRHL------------EENKISKTELDWFLQDLER 832
Cdd:pfam06160  202 YEELKTELPDQLEELKEGYREMEEEGyalehlnvDKEIQQLEEQLEENLallenleldeaeEALEEIEERIDQLYDLLEK 281

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1226253906  833 EIKKwqqeKKEIQErlkslkkkikkvsNASEMYTQKNDGKEKEHEL-----HLDQSLEISNTLTNEKMKIEEYIKKGKED 907
Cdd:pfam06160  282 EVDA----KKYVEK-------------NLPEIEDYLEHAEEQNKELkeeleRVQQSYTLNENELERVRGLEKQLEELEKR 344

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1226253906  908 YEESHQRAVAAEV---SVLENWKESEvYKLQIMESQAEAFLKKLGLISRDpaaypdmESDIR----SWELFLSNVTKEIE 980
Cdd:pfam06160  345 YDEIVERLEEKEVaysELQEELEEIL-EQLEEIEEEQEEFKESLQSLRKD-------ELEARekldEFKLELREIKRLVE 416

                          250       260       270
                   ....*....|....*....|....*....|....
gi 1226253906  981 KAK-----SQFEEQIKAIKNG-SRLS-ELSKVQI 1007
Cdd:pfam06160  417 KSNlpglpESYLDYFFDVSDEiEDLAdELNEVPL 450

RING finger, H2 subclass, found in Tetratricopeptide repeat protein 3 (TTC3) and similar proteins; TTC3, also known as protein DCRR1, TPR repeat protein D, TPR repeat protein 3, or RING finger protein 105 (RNF105), is an E3 ubiquitin-protein ligase encoded by a gene within the Down syndrome (DS) critical region on chromosome 21. It affects differentiation and Golgi compactness in neurons through specific actin-regulating pathways. It inhibits the neuronal-like differentiation of pheocromocytoma cells by activating RhoA and by binding to Citron proteins. TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. It contains four N-terminal TPR motifs, a potential coiled-coil region and a Citron binding region in the central part, and a C-terminal C3H2C2-type RING-H2 finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1226253906 1234 SCEICHEVFKSKNVRVLKCGHKYHKGCFKQWLKGQSACPACQGRD 1278
Cdd:cd16481      1 PCIICHDDLKPDQLAKLECGHIFHKECIKQWLKEQSTCPTCRVHV 45

Ring finger domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1226253906 1234 SCEICHEVF-KSKNVRVLKCGHKYHKGCFKQWLKGQSACPAC 1274
Cdd:pfam13639    2 ECPICLEEFeEGDKVVVLPCGHHFHRECLDKWLRSSNTCPLC 43

RING finger, H2 subclass, found in RING finger proteins RNF24, RNF122, and similar proteins; This subfamily includes RNF24, RNF122, and similar proteins. RNF24 is an intrinsic membrane protein localized in the Golgi apparatus. It specifically interacts with the ankyrin-repeats domains (ARDs) of TRPC1, -3, -4, -5, -6, and -7, and affects TRPC intracellular trafficking without affecting their activity. RNF122 is a RING finger protein associated with HEK 293T cell viability. It is localized to the endoplasmic reticulum (ER) and the Golgi apparatus, and overexpressed in anaplastic thyroid cancer cells. RNF122 functions as an E3 ubiquitin ligase that can ubiquitinate itself and undergo degradation through its RING finger in a proteasome-dependent manner. Both RNF24 and RNF122 contain an N-terminal transmembrane domain and a C-terminal C3H2C3-type RING-H2 finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1226253906 1235 CEICHEVFKSKN-VRVLKCGHKYHKGCFKQWLKGQSACPACQ 1275
Cdd:cd16469      3 CAVCLEEFKLKEeLGVCPCGHAFHTKCLKKWLEVRNSCPICK 44

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 1226253906  1235 CEICHEVFkSKNVRVLKCGHKYHKGCFKQWLKGQSA-CPAC 1274
Cdd:smart00184    1 CPICLEEY-LKDPVILPCGHTFCRSCIRKWLESGNNtCPIC 40

RING finger, H2 subclass, found in Arabidopsis thaliana protein SUGAR INSENSITIVE 3 (SIS3) and similar proteins; SIS3 is an E3 ubiquitin-protein ligase that acts as a positive regulator of sugar signaling during early seedling development. SIS3 contains a C3H2C3-type RING-H2 finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1226253906 1234 SCEICHEVFKSKN-VRVLKCGHKYHKGCFKQWLKGQSACPAC 1274
Cdd:cd23118      2 TCTICLEDFEDGEkLRVLPCQHQFHSECVDQWLRRNPKCPVC 43

RING finger, H2 subclass, found in RING finger protein 103 (RNF103) and similar proteins; RNF103, also known as KF-1 or zinc finger protein 103 homolog (Zfp-103), is an endoplasmic reticulum (ER)-resident E3 ubiquitin-protein ligase that is widely expressed in many different organs, including brain, heart, kidney, spleen, and lung. It is involved in the ER-associated degradation (ERAD) pathway by interacting with components of the ERAD pathway, including Derlin-1 and VCP. RNF103 contains several hydrophobic regions at its N-terminal and middle regions, as well as a C-terminal C3H2C3-type RING-H2 finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1226253906 1233 SSCEICHEVFKSKN-VRVLKCGHKYHKGCFKQWL-KGQSACPAC 1274
Cdd:cd16473      5 EECAICLENYQNGDlLRGLPCGHVFHQNCIDVWLeRDNHCCPVC 48

RING finger, H2 subclass, found in RING finger proteins RNF43, ZNRF3, and similar proteins; RNF43 and ZNRF3 (also known as RNF203) are transmembrane E3 ubiquitin-protein ligases that belong to the PA-TM-RING ubiquitin ligase family, characterized by containing an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C3H2C3-type RING-H2 finger followed by a long C-terminal region. Both RNF43 and RNF203 function as tumor suppressors involved in the regulation of Wnt/beta-catenin signaling. They negatively regulate Wnt signaling by interacting with complexes of frizzled (FZD) receptors and low-density lipoprotein receptor-related protein (LRP) 5/6, which leads to ubiquitination of FZD and endocytosis of the Wnt receptor. Dishevelled (DVL), a positive Wnt regulator, is required for ZNRF3/RNF43-mediated ubiquitination and degradation of FZD. They also associate with R-spondin 1 (RSPO1). This interaction may block FZD ubiquitination and enhances Wnt signaling.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1226253906 1234 SCEICHEVFKSKNV-RVLKCGHKYHKGCFKQWLKGQSACPACQ 1275
Cdd:cd16666      1 VCAICLEEYEEGQElRVLPCQHEFHRKCVDPWLLQNHTCPLCL 43

RING finger, H2 subclass, found in RING finger proteins RNF111, RNF165, and similar proteins; The family includes RING finger proteins RNF111, RNF165, and similar proteins. RNF111, also known as Arkadia, is a nuclear E3 ubiquitin-protein ligase that targets intracellular effectors and modulators of transforming growth factor beta (TGF-beta)/Nodal-related signaling for polyubiquitination and proteasome-dependent degradation. It also interacts with the clathrin-adaptor 2 (AP2) complex and regulates endocytosis of certain cell surface receptors, leading to modulation of epidermal growth factor (EGF) and possibly other signaling pathways. The N-terminal half of RNF111 harbors three SUMO-interacting motifs (SIMs). It thus functions as a SUMO-targeted ubiquitin ligase (STUbL) that directly links nonproteolytic ubiquitylation and SUMOylation in the DNA damage response, as well as triggers degradation of signal-induced polysumoylated proteins, such as the promyelocytic leukemia protein (PML). RNF165, also known as Arkadia-like 2, Arkadia2, or Ark2C, is an E3 ubiquitin ligase with homology to the C-terminal half of RNF111. It is expressed specifically in the nervous system, and can serve to amplify neuronal responses to specific signals. It acts as a positive regulator of bone morphogenetic protein (BMP)-Smad signaling that is involved in motor neuron (MN) axon elongation. Both RNF165 and RNF111 contain a C-terminal C3H2C3-type RING-H2 finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1226253906 1235 CEICHEVFKSKN-VRVLKCGHKYHKGCFKQWLKGQSACPACQ 1275
Cdd:cd16474      3 CTICLSDFEEGEdVRRLPCMHLFHQECVDQWLSTNKRCPICR 44

RING finger, H2 subclass, found in TRAF-interacting protein (TRAIP) and similar proteins; TRAIP, also known as RING finger protein 206 (RNF206) or TRIP, is a ubiquitously expressed nucleolar E3 ubiquitin ligase important for cellular proliferation and differentiation. It is found near mitotic chromosomes and functions as a regulator of the spindle assembly checkpoint. TRAIP interacts with tumor necrosis factor (TNF)-receptor-associated factor (TRAF) proteins and inhibits TNF-alpha-mediated nuclear factor (NF)-kappaB activation. It also interacts with two tumor suppressors CYLD and spleen tyrosine kinase (Syk), and DNA polymerase eta, which facilitates translesional synthesis after DNA damage. TRAIP contains an N-terminal C3H2C2-type RING-H2 finger and an extended coiled-coil domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 1226253906 1235 CEICHEVFK-SKNVRVLKCGHKYHKGCFKQWLKGQSACPAC 1274
Cdd:cd16480      2 CTICSDFFDnSRDVAAIHCGHTFHYDCLLQWFDTSRTCPQC 42

RING finger, H2 subclass, found in RING finger protein 130 (RNF130) and similar proteins; RNF130, also known as Goliath homolog (H-Goliath), is a paralog of RNF128, also known as gene related to anergy in lymphocytes protein (GRAIL). It is a transmembrane E3 ubiquitin-protein ligase expressed in leukocytes. It has a self-ubiquitination property, and controls the development of T cell clonal anergy by ubiquitination. RNF130 contains an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1226253906 1235 CEICHEVFKSKN-VRVLKCGHKYHKGCFKQWLKGQSACPACQ 1275
Cdd:cd16803      3 CAVCIEGYKQNDvVRILPCKHVFHKSCVDPWLNEHCTCPMCK 44

RING finger, H2 subclass, found in p53-induced RING-H2 protein (Pirh2) and similar proteins; Pirh2, also known as RING finger and CHY zinc finger domain-containing protein 1 (Rchy1), androgen receptor N-terminal-interacting protein, CH-rich-interacting match with PLAG1, RING finger protein 199 (RNF199), or zinc finger protein 363 (ZNF363), is a p53 inducible E3 ubiquitin-protein ligase that functions as a negative regulator of p53. It preferably ubiquitylates the tetrameric form of p53 in vitro and in vivo, suggesting a role of Pirh2 in downregulating the transcriptionally active form of p53 in the cell. Moreover, Pirh2 inhibits the transcriptional activity of p73, a homolog of the tumor suppressor p53, by promoting its ubiquitination. It also monoubiquitinates DNA polymerase eta (PolH) to suppress translesion DNA synthesis. Furthermore, Pirh2 functions as a negative regulator of the cyclin-dependent kinase inhibitor p27(Kip1) function by promoting ubiquitin-dependent proteasomal degradation. Pirh2 enhances androgen receptor (AR) signaling through inhibition of histone deacetylase 1 (HDAC1) and is overexpressed in prostate cancer. It interacts with TIP60 and this association may regulate Pirh2 stability. In addition, the oncoprotein pleomorphic adenoma gene like 2 (PLAGL2) can bind to the Pirh2 dimer and therefore control the stability of Pirh2. Pirh2 contains a total of nine zinc-binding sites with six located at the N-terminal region, two in the C3H2C3-type RING-H2 domain, and one in the C-terminal region. Nine zinc binding sites comprise three different zinc coordination schemes, including RING type cross-brace zinc coordination, C4 zinc finger, and a novel left-handed beta-spiral zinc-binding motif formed by three recurrent CCHC sequence motifs. This subfamily also includes Drosophila melanogaster Deltex, a ubiquitously expressed cytoplasmic ubiquitin E3 ligase that mediates Notch activation in Drosophila. It selectively suppresses T-cell activation through degradation of a key signaling molecule, MAP kinase kinase kinase 1 (MEKK1). It also inhibits Jun-mediated transcription at the stage of Ras-dependent Jun N-terminal protein kinase (JNK) activation. Deltex contains N-terminal two Notch-binding WWE domains that physically interact with the Notch ankyrin domains, a proline-rich motif that shares homology with SH3-binding domains, and a RING finger at the C-terminus.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1226253906 1235 CEICHE-VFKSK-NVRVLKCGHKYHKGCFKQWLKGQS-ACPACQ 1275
Cdd:cd16464      2 CPVCLEdLFTSRePVHVLPCGHLMHSTCFEEYLKSGNyRCPLCS 45

RING finger, H2 subclass, found in Arabidopsis thaliana RING-type E3 ubiquitin transferase BIG BROTHER (BB) and similar proteins; BB (also known as protein ENHANCER OF DA1-1 or EOD1) is an E3 ubiquitin-protein ligase that limits organ size, and possibly seed size, in a dose-dependent manner. It negatively regulates the duration of cell proliferation in leaves and petals independently of the major phytohormones (e.g. auxin, cytokinin, gibberellin, brassinosteroids, ethylene, abscisic acid, jasmonic acid), probably by targeting growth stimulators for degradation. It limits the proliferation of root meristematic cells. BB polyubiquitinates DA1. It is involved in the promotion of leaf senescence, in addition to its function in restricting plant growth. BB-related is an E3 ubiquitin-ligase probably involved in organ size regulation. Members of this subfamily contain a C3H2C3-type RING-H2 finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1226253906 1234 SCEIC-HEVFKSKNVRVLKCGHKYHKGCFKQWLKGQSACPACQ 1275
Cdd:cd23115      6 RCVICrLEYEEGEDLLTLPCKHCYHSECIQQWLQINKVCPVCS 48

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 1226253906 1234 SCEICHEVFKskNVRVLKCGHKYHKGCFKQWLK-GQSACPAC 1274
Cdd:cd16449      2 ECPICLERLK--DPVLLPCGHVFCRECIRRLLEsGSIKCPIC 41

RING finger, H2 subclass, found in RING finger proteins RNF126, RNF115, and similar proteins; This subfamily includes RING finger proteins RNF126, RNF115, and similar proteins. RNF126 is a Bag6-dependent E3 ubiquitin ligase that is involved in the mislocalized protein (MLP) pathway of quality control. It regulates the retrograde sorting of the cation-independent mannose 6-phosphate receptor (CI-MPR). RNF126 promotes cancer cell proliferation by targeting the tumor suppressor p21 for ubiquitin-mediated degradation, and could be a novel therapeutic target in breast and prostate cancers. It is also able to ubiquitylate cytidine deaminase (AID), a poorly soluble protein that is essential for antibody diversification. RNF115, also known as Rab7-interacting ring finger protein (Rabring 7), or zinc finger protein 364 (ZNF364), or breast cancer-associated gene 2 (BCA2), is an E3 ubiquitin-protein ligase that is an endogenous inhibitor of adenosine monophosphate-activated protein kinase (AMPK) activation; this inhibition increases the efficacy of metformin in breast cancer cells. It also functions as a cofactor in the restriction imposed by tetherin on HIV-1, and targets HIV-1 Gag for lysosomal degradation, impairing virus assembly and release, in a tetherin-independent manner. Moreover, RNF115 is a Rab7-binding protein that stimulates c-Myc degradation through mono-ubiquitination of MM-1. It also plays crucial roles as a Rab7 target protein in vesicle traffic to late endosome/lysosome and lysosome biogenesis. RNF115 and RNF126 associate with the epidermal growth factor receptor (EGFR) and promote ubiquitylation of EGFR, suggesting they play a role in the ubiquitin-dependent sorting and downregulation of membrane receptors. Both of them contain an N-terminal BCA2 Zinc-finger domain (BZF), AKT-phosphorylation sites, and a C-terminal C3H2C3-type RING-H2 finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 1226253906 1235 CEICHEVFK-SKNVRVLKCGHKYHKGCFKQWLKGQSACPAC 1274
Cdd:cd16667      2 CAVCKEDFEvGEEVRQLPCKHLFHPDCIVPWLELHNSCPVC 42

RING finger, H2 subclass, found in RING finger protein 11 (RNF11) and similar proteins; RNF11 is an E3 ubiquitin-protein ligase that acts both as an adaptor and a modulator of itch-mediated control of ubiquitination events underlying membrane traffic. It acts downstream of an enzymatic cascade for the ubiquitination of specific substrates. It is also a molecular adaptor of homologous to E6-associated protein C-terminus (HECT)-type ligases. RNF11 has been implicated in the regulation of several signaling pathways. It enhances transforming growth factor receptor (TGFR) signaling by both abrogating Smurf2-mediated receptor ubiquitination and by promoting the Smurf2-mediated degradation of AMSH (associated molecule with the SH3 domain of STAM), a de-ubiquitinating enzyme that enhances TGF-beta signaling and epidermal growth factor receptor (EGFR) endosomal recycling. It also acts directly on Smad4 to enhance Smad4 function, and plays a role in prolonged TGF-beta signaling. RNF11 also functions as a critical component of the A20 ubiquitin-editing protein complex that negatively regulates tumor necrosis factor (TNF)-mediated nuclear factor (NF)-kappaB activation. It interacts with Smad anchor for receptor activation (SARA) and the endosomal sorting complex required for transport (ESCRT)-0 complex, thus participating in the regulation of lysosomal degradation of EGFR. RNF11 acts as a novel GGA cargo actively participating in regulating the ubiquitination of the GGA protein family. RNF11 functions together with TAX1BP1 to target TANK-binding kinase 1 (TBK1)/IkappaB kinase IKKi, and further restricts antiviral signaling and type I interferon (IFN)-beta production. RNF11 contains an N-terminal PPPY motif that binds WW domain-containing proteins such as AIP4/itch, Nedd4 and Smurf1/2 (SMAD-specific E3 ubiquitin-protein ligase 1/2), and a C-terminal C3H2C3-type RING-H2 finger that functions as a scaffold for the coordinated transfer of ubiquitin to substrate proteins together with the E2 enzymes UbcH527 and Ubc13.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 1226253906 1235 CEICHEVFKSKN-VRVLKCGHKYHKGCFKQWLKGQSACPAC 1274
Cdd:cd16468      2 CVICMADFVVGDpIRYLPCMHIYHVDCIDDWLMRSFTCPSC 42

RING finger, H2 subclass, found in RING finger protein 128 (RNF128) and similar proteins; This subfamily includes RING finger proteins RNF128, RNF133, RNF148, and similar proteins, which belong to a larger PA-TM-RING ubiquitin ligase family that has been characterized by containing an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger followed by a putative PEST sequence. RNF128, also known as gene related to anergy in lymphocytes protein (GRAIL), is a type 1 transmembrane E3 ubiquitin-protein ligase that is a critical regulator of adaptive immunity and development. It inhibits cytokine gene transcription, is expressed in anergic CD4+ T cells, and has been implicated in primary T cell activation, survival, and differentiation, as well as in T cell anergy and oral tolerance. It induces T cell anergy through the ubiquitination activity of its cytosolic RING finger. It regulates expression of the costimulatory molecule CD40L on CD4 T cells, and ubiquitinates the costimulatory molecule CD40 ligand (CD40L) during the induction of T cell anergy. Moreover, RNF128 interacts with the luminal/extracellular portion of both CD151 and the related tetraspanin CD81 via its PA domain, which promoted ubiquitination of cytosolic lysine residues. It also down-modulates the expression of CD83 (previously described as a cell surface marker for mature dendritic cells) on CD4 T cells. Furthermore, Rho guanine dissociation inhibitor (RhoGDI) has been identified as a potential substrate of RNF128, suggesting a role for Rho effector molecules in T cell anergy. In addition, RNF128 plays a role in environmental stress responses. It promotes environmental salinity tolerance in euryhaline tilapia. RNF133 is a testis-specific endoplasmic reticulum-associated E3 ubiquitin ligase that is mainly present in the cytoplasm of elongated spermatids. It may play a role in sperm maturation through an ER-associated degradation (ERAD) pathway. RNF148 is a testis-specific E3 ubiquitin ligase that is abundantly expressed in testes and slightly expressed in pancreas. Its expression is regulated by histone deacetylases.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1226253906 1234 SCEICHEVFKSKN-VRVLKCGHKYHKGCFKQWLKGQSACPACQ 1275
Cdd:cd16802      2 SCAVCIEPYKPNDvVRILTCNHLFHKNCIDPWLLEHRTCPMCK 44

RING finger, H2 subclass, found in RING finger protein 44 (RNF44) and similar proteins; RNF44 is an uncharacterized RING finger protein that shows high sequence similarity with RNF38, which is a nuclear E3 ubiquitin protein ligase that plays a role in regulating p53. RNF44 contains a coiled-coil motif, a KIL motif (Lys-X2-Ile/Leu-X2-Ile/Leu, X can be any amino acid), and a C3H2C2-type RING-H2 finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1226253906 1235 CEICHEVFKSKNV-RVLKCGHKYHKGCFKQWLKGQSACPACQG 1276
Cdd:cd16680     10 CVVCFSDFESRQLlRVLPCNHEFHTKCVDKWLKTNRTCPICRA 52

RING finger, H2 subclass, found in RING finger protein 181 (RNF181) and similar proteins; RNF181, also known as HSPC238, is a platelet E3 ubiquitin-protein ligase containing a C3H2C3-type RING-H2 finger. It interacts with the KVGFFKR motif of platelet integrin alpha(IIb)beta3, suggesting a role for RNF181-mediated ubiquitination in integrin and platelet signaling. It also suppresses the tumorigenesis of hepatocellular carcinoma (HCC) through the inhibition of extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling in the liver.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1226253906 1234 SCEICHEVF-KSKNVRVLKCGHKYHKGCFKQWLKGQSACPAC 1274
Cdd:cd16669      1 KCPICLLEFeEGETVKQLPCKHSFHSDCILPWLGKTNSCPLC 42

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1226253906 1209 VVAPSPKTKG--QKAEDVPVRIALGASSCEICHEVF-KSKNVRVLKCGHKYHKGCFKQWLKGQS-ACPACQ 1275
Cdd:COG5540    298 EAIPTTTTKGslKPLSIERAVEADKGVECAICMSNFiKNDRLRVLPCDHRFHVGCVDKWLLGYSnKCPVCR 368

RING finger, H2 subclass, found in E3 ubiquitin-protein ligase RNF6, RNF12, and similar proteins; RNF6 is an androgen receptor (AR)-associated protein that induces AR ubiquitination and promotes AR transcriptional activity. RNF6-induced ubiquitination may regulate AR transcriptional activity and specificity by modulating cofactor recruitment. RNF6 is overexpressed in hormone-refractory human prostate cancer tissues and required for prostate cancer cell growth under androgen-depleted conditions. RNF6 also regulates local serine/threonine kinase LIM kinase 1 (LIMK1) levels in axonal growth cones. RNF6-induced LIMK1 polyubiquitination is mediated via K48 of ubiquitin and leads to proteasomal degradation of the kinase. RNF6 binds and upregulates the Inha promoter, and functions as a transcription regulatory protein in the mouse sertoli cell. It acts as a potential tumor suppressor gene involved in the pathogenesis of esophageal squamous cell carcinoma (ESCC). RNF12, also known as LIM domain-interacting RING finger protein, or RING finger LIM domain-binding protein (R-LIM), is an E3 ubiquitin-protein ligase encoded by gene RLIM that is crucial for normal embryonic development in some species and for normal X inactivation in mice. It thus functions as a major sex-specific epigenetic regulator of female mouse nurturing tissues. RNF12 is widely expressed during embryogenesis, and mainly localizes to the cell nucleus, where it regulates the levels of many proteins, including CLIM, LMO, HDAC2, TRF1, SMAD7, and REX1, by proteasomal degradation. Both RNF6 and RNF12 contain a well conserved C3H2C3-type RING-H2 finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1226253906 1234 SCEICHEVFKSKN-VRVLKCGHKYHKGCFKQWLKGQSACPAC 1274
Cdd:cd16467      1 ECTICLGEYETGEkLRRLPCSHEFHSECVDRWLKENSSCPIC 42

RING-H2 zinc finger domain; There are 8 cysteine/ histidine residues which are proposed to be the conserved residues involved in zinc binding. The protein, of which this domain is the conserved region, participates in diverse functions relevant to chromosome metabolism and cell cycle control.

                           10        20
                   ....*....|....*....|....*
gi 1226253906 1251 KCGHKYHKGCFKQWLKGQSACPACQ 1275
Cdd:pfam12678   31 ECGHAFHLHCISRWLKTNNTCPLCR 55

RING finger, HC subclass, found in Saccharomyces cerevisiae POB3/SPT16 histone-associated protein 1 (ScPSH1) and similar proteins; ScPSH1 is a Cse4-specific E3 ubiquitin ligase that interacts with the kinetochore protein Pat1 and targets the degradation of budding yeast centromeric histone H3 variant, CENP-ACse4, which is essential for faithful chromosome segregation. ScPSH1 contains a C3HC4-type RING-HC finger and a DNA directed RNA polymerase domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1226253906 1235 CEICHEVFKSKnvRVLKCGHKYHKGCFKQWLKGQ--SACPAC 1274
Cdd:cd16568      7 CIICHEYLYEP--MVTTCGHTYCYTCLNTWFKSNrsLSCPDC 46

RING finger, H2 subclass, found in Saccharomyces cerevisiae alcohol-sensitive RING finger protein 1 (ASR1) and similar proteins; ASR1 is required for tolerance to alcohol. It signals alcohol stress to the nucleus. ASR1 contains a C3H2C3-type RING-H2 finger.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1226253906 1235 CEICHEVFKSKNVRVLKCGHKYHKGCFKQWLK--GQSACPACQGRDLLTEE 1283
Cdd:cd23120      4 CPICLEEMNSGTGYLADCGHEFHLTCIREWHNksGNLDCPICRVESLLLED 54

RING finger, H2 subclass, found in RING finger protein 145 (RNF145) and similar proteins; RNF145 is an uncharacterized RING finger protein encoded by the RNF145 gene, which is expressed in T lymphocytes, and its expression is altered in acute myelomonocytic and acute promyelocytic leukemias. Although its biological function remains unclear, RNF145 shows high sequence similarity with RNF139, an endoplasmic reticulum (ER)-resident multi-transmembrane protein that functions as a potent growth suppressor in mammalian cells, inducing G2/M arrest, decreased DNA synthesis and increased apoptosis. Like RNF139, RNF145 contains a C3H2C3-type RING-H2 finger with possible E3-ubiquitin ligase activity.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 1226253906 1235 CEICHEVFKSknVRVLKCGHKYHKGCFKQWLKGQSACPACQ 1275
Cdd:cd16684      5 CSICYQDMKS--AVITPCSHFFHAGCLKKWLYVQETCPLCH 43

RING finger, H2 subclass, found in RING finger protein 43 (RNF43) and similar proteins; RNF43 is a transmembrane E3 ubiquitin-protein ligase that plays an important role in frizzled (FZD)-dependent regulation of the Wnt/beta-catenin pathway. It functions as a tumor suppressor that inhibits Wnt/beta-catenin signaling by ubiquitinating FZD receptor and targeting it to the lysosomal pathway for degradation. miR-550a-5p directly targeted the 3'-UTR of gene RNF43 and regulated its expression. Moreover, RNF43 interacts with NEDD-4-like ubiquitin-protein ligase-1 (NEDL1) and regulates p53-mediated transcription. It may also be involved in cell growth control through the interaction with HAP95, a chromatin-associated protein interfacing the nuclear envelope. Mutations of RNF43 have been identified in various tumors, including colorectal cancer (CRC), endometrial cancer, mucinous ovarian tumors, gastric adenocarcinoma, pancreatic ductal adenocarcinoma, liver fluke-associated cholangiocarcinoma, hepatocellular carcinoma, and glioma. RNF43 contains an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C3H2C3-type RING-H2 finger followed by a long C-terminal region.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 1226253906 1235 CEICHEVFKS-KNVRVLKCGHKYHKGCFKQWLKGQSACPAC 1274
Cdd:cd16798      6 CAICLEEFSEgQELRIISCSHEFHRECVDPWLHQHRTCPLC 46

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1226253906 1231 GASSCEICHEVFKSKnVRvLKCGHKYHKGCFKQWLKGQSACPAC 1274
Cdd:cd16561      1 GEQECSICLEDLNDP-VK-LPCDHVFCEECIRQWLPGQMSCPLC 42

first RING finger, H2 subclass, found in RING finger protein 32 (RNF32) and similar proteins; RNF32 is mainly expressed in testis spermatogenesis, most likely in spermatocytes and/or in spermatids, suggesting a possible role in sperm formation. RNF32 contains two C3H2C3-type RING-H2 fingers separated by an IQ domain of unknown function. Although the biological function of RNF32 remains unclear, proteins with double RING-H2 fingers may act as scaffolds for binding several proteins that function in the same pathway. This model corresponds to the first RING-H2 finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1226253906 1234 SCEICHEVFKSKNVRVLKCGHKYHKGCFKQWLK--GQSACPAC 1274
Cdd:cd16677      1 PCPICLEDFGLQQQVLLSCSHVFHRACLESFERfsGKKTCPMC 43

RING finger, H2 subclass, found in RING finger protein 38 (RNF38) and similar proteins; RNF38 is a nuclear E3 ubiquitin protein ligase that is widely expressed throughout the human body, and is especially highly expressed in the heart, brain, placenta and the testis. It recognizes p53 as a substrate for ubiquitination, and thus plays a role in regulating p53. The overexpression of RNF38 increases p53 ubiquitination and alters p53 localization. It is also capable of autoubiquitination. RNF38 expression is negatively regulated by the serotonergic system. Induction of RNF38 may be involved in the anxiety-like behavior or non-cell autonomy in Oryzias latipes by the decline of serotonin (5-HT) levels. RNF38 contains a coiled-coil motif, a KIL motif (Lys-X2-Ile/Leu-X2-Ile/Leu, X can be any amino acid), a C3H2C3-type RING-H2 finger, as well as two potential nuclear localization signals.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1226253906 1235 CEICHEVFKSKNV-RVLKCGHKYHKGCFKQWLKGQSACPACQG 1276
Cdd:cd16679     23 CVVCMCDFESRQLlRVLPCNHEFHAKCVDKWLKANRTCPICRA 65

RING finger, H2 subclass, found in RING finger protein 165 (RNF165) and similar proteins; RNF165, also known as Arkadia-like 2, Arkadia2, or Ark2C, is an E3 ubiquitin ligase with homology to the C-terminal half of RNF111. It is expressed specifically in the nervous system, and can serve to amplify neuronal responses to specific signals. It acts as a positive regulator of bone morphogenetic protein (BMP)-Smad signaling that is involved in motor neuron (MN) axon elongation. RNF165 contains two serine rich domains, a nuclear localization signal, an NRG-TIER domain, and a C-terminal C3H2C3-type RING-H2 finger that is responsible for the enhancement of BMP-Smad1/5/8 signaling in the spinal cord.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1226253906 1235 CEICHEVFKS-KNVRVLKCGHKYHKGCFKQWLKGQSACPACQ 1275
Cdd:cd16682     10 CTICLSMLEDgEDVRRLPCMHLFHQLCVDQWLAMSKKCPICR 51

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1226253906  763 FEERQGEISRIEKEHQVLQDQLQEVYENYEQIKLKGLEETRDLEEKLKR---HLEENKISKTELDWFLQDLEREIKKWQQ 839
Cdd:TIGR02168  801 LREALDELRAELTLLNEEAANLRERLESLERRIAATERRLEDLEEQIEElseDIESLAAEIEELEELIEELESELEALLN 880

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1226253906  840 EKKEIQERLKSLKKKIKKVSNASEMYTQKNDGKEKEHElHLDQSLE-ISNTLTNEKMKIEEYIKKGKEDYEeshqrAVAA 918
Cdd:TIGR02168  881 ERASLEEALALLRSELEELSEELRELESKRSELRRELE-ELREKLAqLELRLEGLEVRIDNLQERLSEEYS-----LTLE 954

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1226253906  919 EVSVLENWKESEVYKLQIMESQAEAFLKKLGLIsrDPAAYPDMEsDIRSWELFLSNVTKEIEKAKSQFEEQIKAI 993
Cdd:TIGR02168  955 EAEALENKIEDDEEEARRRLKRLENKIKELGPV--NLAAIEEYE-ELKERYDFLTAQKEDLTEAKETLEEAIEEI 1026

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1226253906  767 QGEISRIEKEHQVLQDQLQEVYENYEQIKlKGLEETRDLEEKLKRHLEenkisktELDWFLQDLEREIKKWQQEKKEIQE 846
Cdd:TIGR02169  694 QSELRRIENRLDELSQELSDASRKIGEIE-KEIEQLEQEEEKLKERLE-------ELEEDLSSLEQEIENVKSELKELEA 765

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1226253906  847 RLkslkkkikkvsnaSEMYTQKNDGKEKEHELHLDQSLEISNTLTNEKMKIEEYIKKGKEDYEESHQR--AVAAEVSVLE 924
Cdd:TIGR02169  766 RI-------------EELEEDLHKLEEALNDLEARLSHSRIPEIQAELSKLEEEVSRIEARLREIEQKlnRLTLEKEYLE 832

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1226253906  925 NWKESEVYKLQIMESQAEAFLKKLGLISRDPAaypDMESDIRSWELF-------LSNVTKEIEKAKSQFEEQIKAIKNGS 997
Cdd:TIGR02169  833 KEIQELQEQRIDLKEQIKSIEKEIENLNGKKE---ELEEELEELEAAlrdlesrLGDLKKERDELEAQLRELERKIEELE 909

                          250
                   ....*....|...
gi 1226253906  998 RLSELSKVQISEL 1010
Cdd:TIGR02169  910 AQIEKKRKRLSEL 922