RING finger (Really Interesting New Gene) domain and U-box domain superfamily; 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 different Cys/His patterns while some lack a single Cys or His residue at typical Zn ligand positions (the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can indeed chelate Zn in a RING finger as well). C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type RING fingers are closely related to RING-HC fingers. In contrast, C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type RING fingers are more closely related to RING-H2 fingers. However, not all RING finger-containing proteins display regular RING finger features, and the RING finger family has turned out to be multifarious. The degenerate RING fingers of the Siz/PIAS RING (SP-RING) family proteins and sporulation protein RMD5, are characterized by lacking the second, fifth, and sixth Zn2+ ion-coordinating residues. They bind only one Zn2+ ion. On the other hand, the RING fingers of the human APC11 and RBX1 proteins can bind a third Zn atom since they harbor four additional Zn ligands. U-box is a modified form of the RING finger domain that lacks metal chelating Cys and His residues. It resembles the cross-brace RING structure consisting of three beta-sheets and a single alpha-helix, which would be stabilized by salt bridges instead of chelated metal ions. U-box proteins are widely distributed among eukaryotic organisms and show a higher prevalence in plants than in other organisms. RING finger/U-box-containing proteins are 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 enable efficient transfer of ubiquitin from E2 to the substrates.

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2ECT_A      17 ECPVCKEDYALGESVRQLPCNHLFHDSCIVPWLEQHDSCPVCRK 60
Cdd:cd16801  1 ECPVCKEDYTVGENVRQLPCNHLFHNDCIVPWLEQHDTCPVCRK 44

RING finger, H2 subclass, found in RING finger protein 126 (RNF126) 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). Moreover, 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. In addition, RNF126 and the related protein, RNF115 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. RNF126 contains an N-terminal BCA2 Zinc-finger domain (BZF), the AKT-phosphorylation sites, and the C-terminal C3H2C3-type RING-H2 finger.

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2ECT_A      17 ECPVCKEDYALGESVRQLPCNHLFHDSCIVPWLEQHDSCPVCRK 60
Cdd:cd16801  1 ECPVCKEDYTVGENVRQLPCNHLFHNDCIVPWLEQHDTCPVCRK 44

Ring finger domain;

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2ECT_A        17 ECPVCKEDYALGESVRQLPCNHLFHDSCIVPWLEQHDSCPVCR 59
Cdd:pfam13639  2 ECPICLEEFEEGDKVVVLPCGHHFHRECLDKWLRSSNTCPLCR 44

N1R/p28-like protein; Provisional

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                 ....*....|....*....|....*....|....*....|....*....|.
2ECT_A        17 ECPVCKED-YAlgESVRQ-----LP-CNHLFHDSCIVPWLEQHDSCPVCRK 60
Cdd:PHA02929 176 ECAICMEKvYD--KEIKNmyfgiLSnCNHVFCIECIDIWKKEKNTCPVCRT 224

RING finger, H2 subclass, found in RING finger protein 126 (RNF126) 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). Moreover, 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. In addition, RNF126 and the related protein, RNF115 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. RNF126 contains an N-terminal BCA2 Zinc-finger domain (BZF), the AKT-phosphorylation sites, and the C-terminal C3H2C3-type RING-H2 finger.

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               ....*....|....*....|....*....|....*....|....
2ECT_A      17 ECPVCKEDYALGESVRQLPCNHLFHDSCIVPWLEQHDSCPVCRK 60
Cdd:cd16801  1 ECPVCKEDYTVGENVRQLPCNHLFHNDCIVPWLEQHDTCPVCRK 44

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.

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2ECT_A      17 ECPVCKEDYALGESVRQLPCNHLFHDSCIVPWLEQHDSCPVCR 59
Cdd:cd16667  1 ECAVCKEDFEVGEEVRQLPCKHLFHPDCIVPWLELHNSCPVCR 43

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.

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               ....*....|....*....|....*....|....*....|....*.
2ECT_A      17 ECPVCKEDYALGESVRQLPCNHLFHDSCIVPWLEQHDSCPVCRKSL 62
Cdd:cd16669  1 KCPICLLEFEEGETVKQLPCKHSFHSDCILPWLGKTNSCPLCRHEL 46

RING finger, H2 subclass, found in rice E3 ubiquitin-protein ligase EL5 and similar proteins; EL5, also known as protein ELICITOR 5, is an E3 ubiquitin-protein ligase containing an N-terminal transmembrane domain and a C3H2C3-type RING-H2 finger that is a binding site for ubiquitin-conjugating enzyme (E2). It can be rapidly induced by N-acetylchitooligosaccharide elicitor. EL5 catalyzes polyubiquitination via the Lys48 residue of ubiquitin, and thus plays a crucial role as a membrane-anchored E3 in the maintenance of cell viability after the initiation of root primordial formation in rice. It also acts as an anti-cell death enzyme that might be responsible for mediating the degradation of cytotoxic proteins produced in root cells after the actions of phytohormones. Moreover, EL5 interacts with UBC5b, a rice ubiquitin carrier protein, through its RING-H2 finger. EL5 is an unstable protein, and its degradation is regulated by the C3H2C3-type RING-H2 finger in a proteasome-independent manner.

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2ECT_A      17 ECPVCKEDYALGESVRQLP-CNHLFHDSCIVPWLEQHDSCPVCR 59
Cdd:cd16461  1 ECAICLSDYENGEELRRLPeCKHAFHKECIDEWLKSNSTCPLCR 44

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.

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2ECT_A      17 ECPVCKEDYALGESVRQLPCNHLFHDSCIVPWLEQHDSCPVCR 59
Cdd:cd16467  1 ECTICLGEYETGEKLRRLPCSHEFHSECVDRWLKENSSCPICR 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.

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2ECT_A      17 ECPVCKEDYALGESVRQLPCNHLFHDSCIVPWLEQ-HDSCPVCRK 60
Cdd:cd16473  6 ECAICLENYQNGDLLRGLPCGHVFHQNCIDVWLERdNHCCPVCRW 50

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

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2ECT_A        8 TEEHvGSGLECPVCKEDYALGESVRQLPCNHLFHDSCIVPWLEQH-DSCPVCRKSL 62
Cdd:COG5540 317 AVEA-DKGVECAICMSNFIKNDRLRVLPCDHRFHVGCVDKWLLGYsNKCPVCRTAI 371

RING finger, H2 subclass, found in E3 ubiquitin-protein ligase RNF6 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. Moreover, RNF6 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 also binds and upregulates the Inha promoter, and functions as a transcription regulatory protein in the mouse sertoli cell. RNF6 also acts as a potential tumor suppressor gene involved in the pathogenesis of esophageal squamous cell carcinoma (ESCC). RNF6 contains an N-terminal coiled-coil domain, a Lys-X-X-Leu/Ile-X-X-Leu/Ile (KIL) motif, and a C-terminal C3H2C3-type RING-H2 finger which is responsible for its ubiquitin ligase activity. The KIL motif is present in a subset of RING-H2 proteins from organisms as evolutionarily diverse as human, mouse, chicken, Drosophila, Caenorhabditis elegans, and Arabidopsis thaliana.

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2ECT_A      18 CPVCKEDYALGESVRQLPCNHLFHDSCIVPWLEQHDSCPVCRKSLTGQN 66
Cdd:cd16673  3 CSVCINEYATGNKLRRLPCAHEFHIHCIDRWLSENSTCPICRQPVLGSN 51

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.

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2ECT_A      18 CPVCKEDYALGESVRQLPCNHLFHDSCIVPWLEQHDSCPVCR 59
Cdd:cd16474  3 CTICLSDFEEGEDVRRLPCMHLFHQECVDQWLSTNKRCPICR 44

Ring finger domain;

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2ECT_A        17 ECPVCKEDYALGESVRQLPCNHLFHDSCIVPWLEQHDSCPVCR 59
Cdd:pfam13639  2 ECPICLEEFEEGDKVVVLPCGHHFHRECLDKWLRSSNTCPLCR 44

RING finger, H2 subclass, found in autocrine motility factor receptor (AMFR) and similar proteins; AMFR, also known as AMF receptor, or RING finger protein 45, or ER-protein gp78, is an internalizing cell surface glycoprotein localized in both plasma membrane caveolae and the endoplasmic reticulum (ER). It is involved in the regulation of cellular adhesion, proliferation, motility and apoptosis, as well as in the process of learning and memory. AMFR also functions as a RING finger-dependent ubiquitin protein ligase (E3) implicated in the degradation from the ER. AMFR contains an N-terminal RING-H2 finger and a C-terminal ubiquitin-associated (UBA)-like CUE domain.

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2ECT_A      17 ECPVCKEDYalgESVRQLPCNHLFHDSCIVPWLEQHDSCPVCRKSL 62
Cdd:cd16455  2 DCAICWESM---QSARKLPCGHLFHNSCLRSWLEQDTSCPTCRMSL 44

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.

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2ECT_A      17 ECPVCKEDYALGESVRQLPCNHLFHDSCIVPWLEQHDSCPVC 58
Cdd:cd16468  1 ECVICMADFVVGDPIRYLPCMHIYHVDCIDDWLMRSFTCPSC 42

RING finger, H2 subclass, found in RING finger protein 111 (RNF111) 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 acts as an amplifier of Nodal signals, and enhances the dorsalizing activity of limiting amounts of Xnr1, a Nodal homolog, and requires Nodal signaling for its function. The loss of RNF111 results in early embryonic lethality, with defects attributed to compromised Nodal signaling. RNF111 also regulates tumor metastasis by modulation of the TGF-beta pathway. Its ubiquitination can be modulated by the four and a half LIM-only protein 2 (FHL2) that activates TGF-beta signal transduction. Furthermore, RNF111 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. In addition, RNF111 has been identified as a small ubiquitin-like modifier (SUMO)-binding protein with clustered SUMO-interacting motifs (SIMs) that together form a SUMO-binding domain (SBD). 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). The N-terminal half of RNF111 harbors three SIMs. Its C-terminal half show high sequence similarity with RING finger protein 165 (RNF165), where it contains two serine rich domains, two nuclear localization signals, an NRG-TIER domain, and a C-terminal C3H2C3-type RING-H2 finger that is required for polyubiqutination and proteasome-dependent degradation of phosphorylated forms of Smad2/3 and three major negative regulators of TGF-beta signaling, Smad7, SnoN and c-Ski.

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2ECT_A       4 GSSGTEEHVGSglECPVCKEDYALGESVRQLPCNHLFHDSCIVPWLEQHDSCPVCRKSLTGQ 65
Cdd:cd16681  1 GEEGTEEDTEE--KCTICLSILEEGEDVRRLPCMHLFHQVCVDQWLITNKKCPICRVDIEAQ 60

RING finger, H2 subclass, found in RING finger protein 167 (RNF167) and similar proteins; RNF167, also known as RING105, is an endosomal/lysosomal E3 ubiquitin-protein ligase involved in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) ubiquitination. It ubiquitinates AMPA-type glutamate receptor subunit GluA2 and regulates its surface expression, and thus acts as a selective regulator of AMPAR-mediated neurotransmission. It acts as an endosomal membrane protein which ubiquitylates vesicle-associated membrane protein 3 (VAMP3) and regulates endosomal trafficking. Moreover, RNF167 plays a role in the regulation of TSSC5 (tumor-suppressing subchromosomal transferable fragment cDNA, also known as ORCTL2/IMPT1/BWR1A/SLC22A1L), which can function in concert with the ubiquitin-conjugating enzyme UbcH6. RNF167 is widely conserved in metazoans and contains an N-terminal signal peptide, a protease-associated (PA) domain, two transmembrane domains (TM1 and TM2), and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence.

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2ECT_A      18 CPVCKEDYALGESVRQLPCNHLFHDSCIVPWLEQ-HDSCPVCRK 60
Cdd:cd16797  3 CAICLDEYEEGDKLRVLPCSHAYHSKCVDPWLTQtKKTCPVCKQ 46

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.

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2ECT_A      18 CPVCKEDYALGESVRQLPCNHLFHDSCIVPWLEQHDSCPVCR 59
Cdd:cd16666  2 CAICLEEYEEGQELRVLPCQHEFHRKCVDPWLLQNHTCPLCL 43

RING finger, H2 subclass, found in RING finger protein 150 (RNF150) and similar proteins; RNF150 is a RING finger protein and its polymorphisms may be associated with chronic obstructive pulmonary disease (COPD) risk in the Chinese population. Further studies with larger numbers of participants worldwide are needed for validation of the relationships between RNF150 genetic variants and the pathogenesis of COPD. RNF150 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.

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2ECT_A      18 CPVCKEDYALGESVRQLPCNHLFHDSCIVPWLEQHDSCPVCRKSL 62
Cdd:cd16805  9 CAVCIEGYKPNDVVRILPCRHLFHKSCVDPWLLDHRTCPMCKMNI 53

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.

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2ECT_A       9 EEHVGSGLECPVCKEDYALGESVRQLPCNHLFHDSCIVPWLEQHDSCPVCR 59
Cdd:cd16680  1 ENHQSEQTLCVVCFSDFESRQLLRVLPCNHEFHTKCVDKWLKTNRTCPICR 51

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.

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2ECT_A      17 ECPVCKEDYalgESVRQLPCNHLFHDSCIVPWLEQHDSCPVCRKSLT 63
Cdd:cd16561  4 ECSICLEDL---NDPVKLPCDHVFCEECIRQWLPGQMSCPLCRTELP 47

RING finger, H2 subclass, found in Arabidopsis thaliana NEP1-interacting protein-like 1 (NIPL1) and similar proteins; This subfamily includes Arabidopsis thaliana NIPL1 and MISFOLDED PROTEIN SENSING RING E3 LIGASE 1 (MPSR1). NIPL1, also called RING-H2 finger protein ATL27, may be involved in the early steps of the plant defense signaling pathway. MPSR1 is a cytoplasmic E3 ubiquitin-protein ligase involved in protein quality control (PQC) under proteotoxic stress. It is essential for plant survival under proteotoxic stress. It functions by removing damaged proteins before they form cytotoxic aggregates. It recognizes misfolded proteins selectively and tethers polyubiquitin chains to the proteins directly for subsequent degradation by the 26S proteasome pathway. Members of this subfamily contain a C3H2C3-type RING-H2 finger.

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2ECT_A      17 ECPVCKEDYALGESVRQLP-CNHLFHDSCIVPWLEQHDSCPVCR 59
Cdd:cd23119  1 CCTICLQDLQVGEIARSLPhCHHTFHLGCVDKWLGRHGSCPVCR 44

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.

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               ....*....|....*....|....*....|....*....|.
2ECT_A      18 CPVCKEDYALGESVRQLPCNHLFHDSCIVPWLEQHDSCPVC 58
Cdd:cd16798  6 CAICLEEFSEGQELRIISCSHEFHRECVDPWLHQHRTCPLC 46

RING finger, H2 subclass, found in RING finger protein 122 (RNF122) and similar proteins; 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. It interacts with calcium-modulating cyclophilin ligand (CAML), which is not a substrate, but a stabilizer of RNF122. RNF122 contains an N-terminal transmembrane domain and a C-terminal C3H2C3-type RING-H2 finger.

                       10        20        30        40
               ....*....|....*....|....*....|....*....|....*
2ECT_A      18 CPVCKEDYALGESVRQLPCNHLFHDSCIVPWLEQHDSCPVCRKSL 62
Cdd:cd16676  3 CAVCLEDFKTKDELGVLPCQHAFHRKCLVKWLEIRCVCPMCNKPI 47

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
               ....*....|....*....|....*....|....*....|..
2ECT_A      18 CPVCKEDYALGESVRQLPCNHLFHDSCIVPWLEQHDSCPVCR 59
Cdd:cd16679 23 CVVCMCDFESRQLLRVLPCNHEFHAKCVDKWLKANRTCPICR 64

RING finger, H2 subclass, found in RING finger protein 215 (RNF215) and similar proteins; This family includes uncharacterized protein RNF215 and similar proteins. Although its biological function remains unclear, RNF215 shares high sequence similarity with PA-TM-RING ubiquitin ligases, which have 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.

                       10        20        30        40
               ....*....|....*....|....*....|....*....|....*..
2ECT_A      18 CPVCKEDYALGESVRQLPCNHLFHDSCIVPWLEQHDSCPVCRKSLTG 64
Cdd:cd16670  3 CAVCLDQFYKNQCLRVLPCLHEFHRDCVDPWLLLQQTCPLCKRNILG 49

RING finger, H2 subclass, found in RING finger protein 24 (RNF24) 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. RNF24 contains an N-terminal transmembrane domain and a C-terminal C3H2C3-type RING-H2 finger.

                       10        20        30        40
               ....*....|....*....|....*....|....*....|.
2ECT_A      18 CPVCKEDYALGESVRQLPCNHLFHDSCIVPWLEQHDSCPVC 58
Cdd:cd16675  3 CAVCLEEFKPKDELGICPCKHAFHRKCLIKWLEVRKVCPLC 43

RING finger, H2 subclass, found in Arabidopsis thaliana RING-H2 finger A1a (RHA1A), A1b (RHA1B) and similar proteins; This subfamily includes Arabidopsis thaliana RHA1A, RHA1B and XERICO. RHA1A is a probable E3 ubiquitin-protein ligase that may possess E3 ubiquitin ligase activity in vitro. RHA1B possesses E3 ubiquitin-protein ligase activity when associated with the E2 enzyme UBC8 in vitro. XERICO functions on abscisic acid homeostasis at post-translational level, probably through ubiquitin/proteasome-dependent substrate-specific degradation. Members of this subfamily contain a C3H2C3-type RING-H2 finger.

                       10        20        30        40
               ....*....|....*....|....*....|....*....|....*
2ECT_A      17 ECPVCKEDYALGESVRQLP-CNHLFHDSCIVPWLEQHDS-CPVCR 59
Cdd:cd23121  3 CCAICLSDFNSDEKLRQLPkCGHIFHHHCLDRWIRYNKItCPLCR 47

RING finger, H2 subclass, found in RING finger protein 139 (RNF139) and similar proteins; RNF139, also known as translocation in renal carcinoma on chromosome 8 protein (TRC8), is 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. It is a tumor suppressor that has been implicated in a novel regulatory relationship linking the cholesterol/lipid biosynthetic pathway with cellular growth control. A mutation in RNF139 has been identified in families with hereditary renal (RCC) and thyroid cancers. RNF139 physically and functionally interacts with von Hippel-Lindau (VHL), which is part of an SCF related E3-ubiquitin ligase complex with "gatekeeper" function in renal carcinoma and is defective in most sporadic clear-cell renal cell carcinomas (ccRCC). It suppresses growth and functions with VHL in a common pathway. RNF139 also suppresses tumorigenesis by targeting heme oxygenase-1 for ubiquitination and degradation. Moreover, RNF139 is a target of Translin (TSN), a posttranscriptional regulator of genes transcribed by the transcription factor CREM-tau in postmeiotic male germ cells, suggesting a role of RNF139 in dysgerminoma. In addition, RNF139 forms an integral part of a novel multi-protein ER complex, containing MHC I, US2, and signal peptide peptidase, which is associated with the ER-associated degradation (ERAD) pathway. It is required for the ubiquitination of MHC class I molecules before dislocation from the ER. As a novel sterol-sensing ER membrane protein, RNF139 hinders sterol regulatory element-binding protein-2 (SREBP-2) processing through interaction with SREBP-2 and SREBP cleavage-activated protein (SCAP), regulating its own turnover rate via its E3 ubiquitin ligase activity. RNF139 shows two regions of similarity with the receptor for sonic hedgehog (SHH), Patched. The first region corresponds to the second extracellular domain of Patched, which is involved in binding SHH. The second region is a putative sterol-sensing domain (SSD). The C-terminal half of RNF139 contains a C3H2C3-type RING-H2 finger with E3-ubiquitin ligase activity in vitro.

                       10        20        30        40
               ....*....|....*....|....*....|....*....|....*
2ECT_A      18 CPVCKEDYalGESVRQLPCNHLFHDSCIVPWLEQHDSCPVCRKSL 62
Cdd:cd16683  7 CAICYQEF--TTSARITPCNHYFHALCLRKWLYIQDTCPMCHQKV 49

Modified RING finger, C3HGC3-type, found in RING finger and WD repeat domain-containing protein 3 (RFWD3) and similar proteins; RFWD3, also known as RING finger protein 201 (RNF201) or FLJ10520, is an E3 ubiquitin-protein ligase that forms a complex with Mdm2 and p53 to synergistically ubiquitinate p53 and acts as a positive regulator of p53 stability in response to DNA damage. It is phosphorylated by checkpoint kinase ATM/ATR and the phosphorylation mutant fails to stimulate p53 ubiquitination. RFWD3 also functions as a novel replication protein A (RPA)-associated protein involved in DNA replication checkpoint control. RFWD3 contains an N-terminal SQ-rich region followed by a RING finger domain that exhibits robust E3 ubiquitin ligase activity toward p53, a coiled-coil domain and three WD40 repeats in the C-terminus, the latter two of which may be responsible for protein-protein interaction. The RING finger in this family is a modified C3HGC3-type RING finger, but not a canonical C3H2C3-type RING-H2 finger or C3HC4-type RING-HC finger.

                       10        20        30        40        50
               ....*....|....*....|....*....|....*....|....*....|
2ECT_A      15 GLECPVCKEDYALGESVR--QLPCNHLFHDSCIVPWL-EQHDSCPVCRKS 61
Cdd:cd16450  2 GNTCPICFEPWTSSGEHRlvSLKCGHLFGYSCIEKWLkGKGKKCPQCNKK 51

RING finger, H2 subclass, found in Saccharomyces cerevisiae transmembrane E3 ubiquitin-protein ligase 1 (TUL1) and similar proteins; This subfamily includes Saccharomyces cerevisiae TUL1, Schizosaccharomyces pombe DSC E3 ubiquitin ligase complex subunit 1 (DSC1), and Arabidopsis thaliana protein FLYING SAUCER 2 (FLY2). TUL1 is the catalytic component of DSC E3 ubiquitin ligase complexes that tag proteins present in Golgi, endosome and vacuole membranes and function in protein homeostasis under non-stress conditions, and support a role in protein quality control. It mediates ubiquitination of vacuolar proteins such as CPS1, PPN1, PEP12 and other proteins containing exposed hydrophilic residues within their transmembrane domains, leading to their sorting into internal vesicles in late endosomes. TUL1 also targets the unpalmitoylated endosomal SNARE TLG1 to the multivesicular body (MVB) pathway. DSC1, also known as defective for SREBP cleavage protein 1, is the catalytic component of the DSC E3 ubiquitin ligase complex required for the sre1 transcriptional activator proteolytic cleavage to release the soluble transcription factor from the membrane in low oxygen or sterol conditions. FLY2 acts as an E3 ubiquitin-protein ligase that may be involved in xylem development. Members of this subfamily contain a C3H2C3-type RING-H2 finger.

                       10        20        30        40        50
               ....*....|....*....|....*....|....*....|....*....|..
2ECT_A      17 ECPVCKEDYALGESVRQL------PCNHLFHDSCIVPWLEQHDSCPVCRKSL 62
Cdd:cd23117  6 DCVICMSDIELPSTNSVRrdymvtPCNHIFHTNCLERWMDIKLECPTCRRPL 57

RING finger, HC subclass, found in RING finger and transmembrane domain-containing protein RNFT1, RNFT2, and similar proteins; Both RNFT1 and RNFT2 are multi-pass membrane proteins containing a C3HC4-type RING-HC finger. Their biological roles remain unclear.

                       10        20        30        40
               ....*....|....*....|....*....|....*....|..
2ECT_A      18 CPVCKEDYAlgeSVRQLPCNHLFHDSCIVPWLEQHDSCPVCR 59
Cdd:cd16532  3 CPICQDEFK---DPVVLRCKHIFCEDCVSEWFERERTCPLCR 41

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
2ECT_A         9 EEHVGSGLECPVCkedYALGESV-RQLP------CNHLFHDSCIVPWLEQHDS--CPVCRKSLT 63
Cdd:COG5219 1463 DEKFSGHEECAIC---YSVLDMVdRSLPskrcatCKNKFHTRCLYKWFASSARsnCPLCRSEIT 1523

RING finger, H2 subclass, found in RING finger proteins RNF139, RNF145, and similar proteins; RNF139, also known as translocation in renal carcinoma on chromosome 8 protein (TRC8), is 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. It is a tumor suppressor that has been implicated in a novel regulatory relationship linking the cholesterol/lipid biosynthetic pathway with cellular growth control. A mutation in RNF139 has been identified in families with hereditary renal (RCC) and thyroid cancers. 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. Both RNF139 and RNF145 contain a C3H2C3-type RING-H2 finger with possible E3-ubiquitin ligase activity.

                       10        20        30        40
               ....*....|....*....|....*....|....*....|.
2ECT_A      18 CPVCKEDYalgESVRQLPCNHLFHDSCIVPWLEQHDSCPVC 58
Cdd:cd16476  3 CAICYQEM---KEARITPCNHFFHGLCLRKWLYVQDTCPLC 40

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
               ....*....|....*....|....*....|....*....|..
2ECT_A      18 CPVCKEDYALGESVRQLPCNHLFHDSCIVPWLEQHDSCPVCR 59
Cdd:cd16480  2 CTICSDFFDNSRDVAAIHCGHTFHYDCLLQWFDTSRTCPQCR 43

Modified RING-CH finger, H2 subclass (C4HC2H-type), found in zinc/RING finger protein 2 (ZNRF2) and similar proteins; ZNRF2, also known as protein Ells2 or RING finger protein 202 (RNF202), is an E3 ubiquitin-protein ligase that is highly expressed in the nervous system during development and is present in presynaptic plasma membranes. It is N-myrisotoylated and is also located in the endosome-lysosome compartment in fibroblasts. It contains an N-terminal MAGE domain, and a special C-terminal domain that combines a zinc finger and a modified C4HC2H-type RING-CH finger, rather than the typical C4HC3-type RING-CH finger, which is a variant of RING-H2 finger. Only the RING finger of the zinc finger-RING finger motif is required for its E3 ubiquitin ligase activity. Together with its sister protein ZNRF1, ZNRF2 regulates the ubiquitous Na+/K+ pump (Na+/K+ATPase).

                       10        20        30        40
               ....*....|....*....|....*....|....*....|
2ECT_A      17 ECPVCKEDYALGESVRQLPCNHLFHDSCIVPWLEQHDSCP 56
Cdd:cd16695 12 ECAICLEELQQGDTIARLPCLCIYHKGCIDEWFEVNRSCP 51

RING finger, HC subclass, found in RING finger protein 138 (RNF138) and similar proteins; RNF138, also known as Nemo-like kinase-associated RING finger protein (NARF) or NLK-associated RING finger protein, is an E3 ubiquitin-protein ligase that plays an important role in glioma cell proliferation, apoptosis, and cell cycle. It specifically cooperates with the E2 conjugating enzyme E2-25K (Hip-2/UbcH1), regulates the ubiquitylation and degradation of T cell factor/lymphoid enhancer factor (TCF/LEF), and further suppresses Wnt-beta-catenin signaling. RNF138, together with three closely related proteins: RNF114, RNF125 and RNF166, forms a novel family of ubiquitin ligases with a C3HC4-type RING-HC finger, a C2HC-, and two C2H2-type zinc fingers, as well as a ubiquitin interacting motif (UIM).

                       10        20        30        40        50
               ....*....|....*....|....*....|....*....|....*....|
2ECT_A      16 LECPVCKEDYAlgESVRQLPCNHLFHDSCIV-PWLEQHDSCPVCRKSLTG 64
Cdd:cd16544  3 LTCPVCQEVLK--DPVELPPCRHIFCKACILlALRSSGARCPLCRGPVGK 50

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        50
               ....*....|....*....|....*....|....*....|....*....|
2ECT_A      18 CPVCKEDYALGESVrQLPCNHLFHDSCivpwLEQ------HDSCPVCRKS 61
Cdd:cd16677  2 CPICLEDFGLQQQV-LLSCSHVFHRAC----LESferfsgKKTCPMCRKE 46

RING finger, HC subclass, found in RING finger protein 8 (RNF8) and similar proteins; RNF8 is a telomere-associated E3 ubiquitin-protein ligase that plays an important role in DNA double-strand break (DSB) repair via histone ubiquitination. It is localized in the nucleus and interacts with class III E2s (UBE2E2, UbcH6, and UBE2E3), but not with other E2s (UbcH5, UbcH7, UbcH10, hCdc34, and hBendless). It recruits UBC13 for lysine 63-based self polyubiquitylation. Its deficiency causes neuronal pathology and cognitive decline, and its loss results in neuron degeneration. RNF8, together with RNF168, catalyzes a series of ubiquitylation events on substrates such as H2A and H2AX, with the H2AK13/15 ubiquitylation being particularly important for recruitment of repair factors p53-binding protein 1 (53BP1) or the RAP80-BRCA1 complex to sites of DSBs. RNF8 mediates the ubiquitination of gammaH2AX, and recruits 53BP1 and BRCA1 to DNA damage sites which promotes DNA damage response (DDR) and inhibits chromosomal instability. Moreover, RNF8 interacts with retinoid X receptor alpha (RXR alpha) and enhances its transcription-stimulating activity. It also regulates the rate of exit from mitosis and cytokinesis. RNF8 contains an N-terminal forkhead-associated (FHA) domain and a C-terminal C3HC4-type RING-HC finger.

                       10        20        30        40        50
               ....*....|....*....|....*....|....*....|....*....|.
2ECT_A      16 LECPVCKEDYALGESvrqLPCNHLFHDSCIVPWLEQHDSCPVCRKSLTGQN 66
Cdd:cd16535  2 LQCSICSELFIEAVT---LNCSHSFCSYCITEWMKRKKECPICRKPITSKT 49

RING finger, HC subclass, found in RING finger protein 151 (RNF151) and similar proteins; RNF151 is a testis-specific RING finger protein that interacts with dysbindin, a synaptic and microtubular protein that binds brain snapin, a SNARE-binding protein that mediates intracellular membrane fusion in both neuronal and non-neuronal cells. Thus, it may be involved in acrosome formation of spermatids by interacting with multiple proteins participating in membrane biogenesis and microtubule organization. RNF151 contains a C3HC4-type RING finger domain, a putative nuclear localization signal (NLS), and a TNF receptor associated factor (TRAF)-type zinc finger domain.

                       10        20        30
               ....*....|....*....|....*....|.
2ECT_A      34 LPCNHLFHDSCIVPWLEQHDSCPVCRKSLTG 64
Cdd:cd16547 19 LSCSHIFCKKCILQWLKRQETCPCCRKEVKG 49

Zinc finger, C3HC4 type (RING finger); The C3HC4 type zinc-finger (RING finger) is a cysteine-rich domain of 40 to 60 residues that coordinates two zinc ions, and has the consensus sequence: C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C where X is any amino acid. Many proteins containing a RING finger play a key role in the ubiquitination pathway.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
2ECT_A        18 CPVCKEDYAlgESVRQLPCNHLFHDSCIVPWLE-QHDSCPVC 58
Cdd:pfam00097  1 CPICLEEPK--DPVTLLPCGHLFCSKCIRSWLEsGNVTCPLC 40

RING finger, H2 subclass, found in 43 kDa receptor-associated protein of the synapse (Rapsyn) and similar proteins; Rapsyn, also known as acetylcholine receptor (AChR)-associated 43 kDa protein or RING finger protein 205 (RNF205), is a 43 kDa postsynaptic protein that plays an essential role in the clustering and maintenance of AChR in the postsynaptic membrane of the motor endplate. AChRs enable the transport of rapsyn from the Golgi complex to the plasma membrane through a molecule-specific interaction. Rapsyn also mediates subsynaptic anchoring of protein kinase A (PKA) type I in close proximity to the postsynaptic membrane, which is essential for synapse maintenance. Its mutations in humans cause endplate AChR deficiency and myasthenic syndrome. Rapsyn contains an N-terminal myristoylation signal required for membrane association, seven tetratricopeptide repeats (TPRs) that subserve rapsyn self-association, a coiled-coil domain responsible for the binding of determinants within the long cytoplasmic loop of each AChR subunit, a C3H2C3-type RING-H2 finger that binds to the cytoplasmic domain of beta-dystroglycan and to S-NRAP and links rapsyn to the subsynaptic cytoskeleton, and a serine phosphorylation site.

                       10        20        30        40
               ....*....|....*....|....*....|....*....|....*...
2ECT_A      15 GLECPVCKEDYAL-GESVRQLPCNHLFHDSCIVPWLEQHD-SCPVCRK 60
Cdd:cd16478  1 ELFCGMCGESIGEkNEQLQALPCSHIFHLKCLQTNLRGGTrGCPNCRR 48

DNA repair protein rad18; All proteins in this family for which functions are known are involved in nucleotide excision repair.This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
2ECT_A         14 SGLECPVCKEDYalgESVRQLPCNHLFHDSCIVPWLEQHDSCPVCRKS 61
Cdd:TIGR00599  25 TSLRCHICKDFF---DVPVLTSCSHTFCSLCIRRCLSNQPKCPLCRAE 69

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

                       10        20        30        40        50
               ....*....|....*....|....*....|....*....|....*....|..
2ECT_A      16 LECPVCKEdyALGESVRQLPCNHLFHDSCIVPWLE-QHDSCPVCRKSLTGQN 66
Cdd:cd16503  3 LTCSICQD--LLHDCVSLQPCMHNFCAACYSDWMErSNTECPTCRATVQRVN 52

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
               ....*....|....*....|....*....|....*....|....
2ECT_A      16 LECPVCKEDYalgESVRQLPCNHLFHDSCIVPWLEQ-HDSCPVC 58
Cdd:cd16449  1 LECPICLERL---KDPVLLPCGHVFCRECIRRLLESgSIKCPIC 41

Modified RING finger, HC subclass (C3HC3D-type), found in tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) and similar proteins; TRAF6, also known as interleukin-1 signal transducer or RING finger protein 85 (RNF85), is a cytoplasmic adapter protein that mediates signals induced by the tumor necrosis factor receptor (TNFR) superfamily and Toll-like receptor (TLR)/interleukin-1 receptor (IL-1R) family. It functions as a mediator involved in the activation of mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), and interferon regulatory factor pathways, as well as in IL-1R-mediated activation of NF-kappaB. TRAF6 is also an oncogene that plays a vital role in K-RAS-mediated oncogenesis. TRAF6 contains an N-terminal domain with a modified C3HC3D-type RING-HC finger and several zinc fingers, and a C-terminal TRAF domain that comprises a coiled coil domain and a conserved TRAF-C domain.

                       10        20        30        40
               ....*....|....*....|....*....|....*....|...
2ECT_A      16 LECPVCKedYALGESVrQLPCNHLFHDSCIVPWL-EQHDSCPV 57
Cdd:cd16643  2 YECPICL--MALREPV-QTPCGHRFCKACILKSIrEAGHKCPV 41

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.

                       10        20        30
               ....*....|....*....|....*....|.
2ECT_A      35 PCNHLFHDSCIVPWLEQHDSCPVCRKSLTGQ 65
Cdd:cd16527 17 PCGHLFCWSCITEWCNEKPECPLCREPFQPQ 47

RING finger, HC subclass, found in ligand of numb protein X 3 (LNX3); LNX3, also known as PDZ domain-containing RING finger protein 3 (PDZRN3), or Semaphorin cytoplasmic domain-associated protein 3 (SEMACAP3), is an E3 ubiquitin-protein ligase that was first identified as a Semaphorin-binding partner. It is also responsible for the ubiquitination and degradation of Numb, a component of the Notch signaling pathway that functions in the specification of cell fates during development and is known to control cell numbers during neurogenesis in vertebrates. LNX3 acts as a negative regulator of osteoblast differentiation by inhibiting Wnt-beta-catenin signaling. LNX3 also plays an important role in neuromuscular junction formation. It interacts with and ubiquitinates the muscle specific tyrosine kinase (MuSK), thus promoting its endocytosis and negatively regulating the cell surface expression of this key regulator of postsynaptic assembly. LNX3 contains an N-terminal C3HC4-type RING-HC finger, two PDZ domains, and a C-terminal LNX3 homology (LNX3H) domain.

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2ECT_A      12 VGSGLECPVCKEdyaLGESVRQLPCNHLFHDSCIVPWLEQHDSCPV-CRK 60
Cdd:cd16718  1 VDPDFKCNLCNK---VLEDPLTTPCGHVFCAGCVLPWVVQQGSCPVkCQR 47

RING finger, H2 subclass, found in anaphase-promoting complex subunit 11 (APC11) and similar proteins; APC11, also known as cyclosome subunit 11, or hepatocellular carcinoma-associated RING finger protein, is a C3H2C3-type RING-H2 protein that facilitates ubiquitin chain formation by recruiting ubiquitin-charged ubiquitin conjugating enzymes (E2) through its RING-H2 domain. APC11 and its partner, the cullin-like subunit APC2, form the dynamic catalytic core of the gigantic, multisubunit 1.2-MDa anaphase-promoting complex/cyclosome (APC), also known as the cyclosome, which is a ubiquitin-protein ligase (E3) composed of at least 12 subunits and controls cell division by ubiquitinating cell cycle regulators, such as cyclin B and securin, to drive their timely degradation. APC11 can be inhibited by hydrogen peroxide, which may contribute to the delay in cell cycle progression through mitosis that is characteristic of cells subjected to oxidative stress. APC11 contains a canonical RING-H2-finger that coordinate two Zn2+ ions. In addition, it contains a third Zn2+-binding site that is not essential for its ligase activity.

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2ECT_A      36 CNHLFHDSCIVPWLEQ---HDSCPVCR 59
Cdd:cd16456 32 CSHCFHMHCILKWLNSqqvQQHCPMCR 58