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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 18417587 133 DCAVCLCEFETEDKLRLLPKCSHAFHMDCIDTWLLSHSTCPLCR 176
Cdd:cd16461   1 ECAICLSDYENGEELRRLPECKHAFHKECIDEWLKSNSTCPLCR 44

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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 18417587 133 DCAVCLCEFETEDKLRLLPKCSHAFHMDCIDTWLLSHSTCPLCR 176
Cdd:cd16461   1 ECAICLSDYENGEELRRLPECKHAFHKECIDEWLKSNSTCPLCR 44

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 18417587 133 DCAVCLCEFETEDKLRLLPkCSHAFHMDCIDTWLLSHS-TCPLCR 176
Cdd:COG5540 325 ECAICMSNFIKNDRLRVLP-CDHRFHVGCVDKWLLGYSnKCPVCR 368

N1R/p28-like protein; Provisional

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 18417587  133 DCAVCLCE-FETEDKLR---LLPKCSHAFHMDCIDTWLLSHSTCPLCR 176
Cdd:PHA02929 176 ECAICMEKvYDKEIKNMyfgILSNCNHVFCIECIDIWKKEKNTCPVCR 223

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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 18417587 133 DCAVCLCEFETEDKLRLLPKCSHAFHMDCIDTWLLSHSTCPLCR 176
Cdd:cd16461   1 ECAICLSDYENGEELRRLPECKHAFHKECIDEWLKSNSTCPLCR 44

RING finger, H2 subclass, found in RING finger proteins RNF38, RNF44, and similar proteins; This subfamily includes RING finger proteins RNF38, RNF44, and similar proteins. RNF38 is a nuclear E3 ubiquitin protein ligase that plays a role in regulating p53. RNF44 is an uncharacterized RING finger protein that shows high sequence similarity to RNF38. Both RNF38 and RNF44 contain a coiled-coil motif, a KIL motif (Lys-X2-Ile/Leu-X2-Ile/Leu, X can be any amino acid), and a C3H2C3-type RING-H2 finger. In addition, RNF38 harbors two potential nuclear localization signals.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 18417587 133 DCAVCLCEFETEDKLRLLPkCSHAFHMDCIDTWLLSHSTCPLCR 176
Cdd:cd16472   4 QCVVCMCDYEKRQLLRVLP-CSHEFHAKCIDKWLKTNRTCPICR 46

Ring finger domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 18417587   132 FDCAVCLCEFETEDKLRLLPkCSHAFHMDCIDTWLLSHSTCPLCR 176
Cdd:pfam13639   1 DECPICLEEFEEGDKVVVLP-CGHHFHRECLDKWLRSSNTCPLCR 44

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 18417587 133 DCAVCLCEFETEDKLRLLPkCSHAFHMDCIDTWLLSHSTCPLCR 176
Cdd:cd16474   2 KCTICLSDFEEGEDVRRLP-CMHLFHQECVDQWLSTNKRCPICR 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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 18417587 134 CAVCLCEFETEDKLRLLPkCSHAFHMDCIDTWLLSHSTCPLC 175
Cdd:cd16468   2 CVICMADFVVGDPIRYLP-CMHIYHVDCIDDWLMRSFTCPSC 42

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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 18417587 134 CAVCLCEFETEDKLRLLPkCSHAFHMDCIDTWLL-SHSTCPLCR 176
Cdd:cd16797   3 CAICLDEYEEGDKLRVLP-CSHAYHSKCVDPWLTqTKKTCPVCK 45

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 18417587 133 DCAVCLCEFETEDKLRLLPkCSHAFHMDCIDTWLLS-HSTCPLCR 176
Cdd:cd16473   6 ECAICLENYQNGDLLRGLP-CGHVFHQNCIDVWLERdNHCCPVCR 49

RING finger, H2 subclass, found in RING finger protein 149 (RNF149) and similar proteins; RNF149, also known as DNA polymerase-transactivated protein 2, is an E3 ubiquitin-protein ligase that interacts with wild-type v-Raf murine sarcoma viral oncogene homolog B1 (BRAF), a RING domain-containing E3 ubiquitin ligase involved in control of gene transcription, translation, cytoskeletal organization, cell adhesion, and epithelial development. RNF149 induces the ubiquitination of wild-type BRAF and promotes its proteasome-dependent degradation. Mutated RNF149 has been found in some human breast, ovarian, and colorectal cancers. RNF149 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 18417587 133 DCAVCLCEFETEDKLRLLPkCSHAFHMDCIDTWLLSHSTCPLCR 176
Cdd:cd16804   1 NCAVCIENYKSKDVVRILP-CKHVFHRICIDPWLLEHRTCPMCK 43

RING finger, H2 subclass, found in RING finger protein 13 (RNF13), RING finger protein 167 (RNF167), and similar proteins; This subfamily includes RING finger protein 13 (RNF13), RING finger protein 167 (RNF167), Zinc/RING finger protein 4 (ZNRF4), 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 domain (TM), and a C-terminal C3H2C3-type RING-H2 finger followed by a putative PEST sequence. RNF13 is a widely expressed membrane-associated E3 ubiquitin-protein ligase that functions in the regulation of cancer development, muscle cell growth, and neuronal development. Its expression is developmentally regulated during myogenesis and is upregulated in various tumors. RNF13 negatively regulates cell proliferation through its E3 ligase activity. RNF167, also known as RING105, is an endosomal/lysosomal E3 ubiquitin-protein ligase involved in the ubiquitination of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR). 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. ZNRF4, also known as RING finger protein 204 (RNF204), or Nixin, is an endoplasmic reticulum (ER) membrane-anchored ubiquitin ligase that physically interacts with the ER-localized chaperone calnexin in a glycosylation-independent manner, inducing calnexin ubiquitination, and p97-dependent degradation. The murine protein sperizin (spermatid-specific ring zinc finger) is a homolog of human ZNRF4. It is specifically expressed in Haploid germ cells and is involved in spermatogenesis.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 18417587 134 CAVCLCEFETEDKLRLLPkCSHAFHMDCIDTWLL-SHSTCPLCR 176
Cdd:cd16665   3 CAICLDDYEEGDKLRILP-CSHAYHCKCIDPWLTkNKRTCPVCK 45

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
                ....*....|....*....|....*....|....*....|...
gi 18417587 134 CAVCLCEFETEDKLRLLPkCSHAFHMDCIDTWLLSHSTCPLCR 176
Cdd:cd16670   3 CAVCLDQFYKNQCLRVLP-CLHEFHRDCVDPWLLLQQTCPLCK 44

RING finger, H2 subclass, found in RING finger proteins, RNF130, RNF149, RNF150 and similar proteins; This subfamily includes RING finger proteins, RNF130, RNF149 and RNF150, which belong to a larger PA-TM-RING ubiquitin ligase family that has been characterized by 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. RNF130, also known as Goliath homolog (H-Goliath), is a paralog of RNF128. 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. RNF133 is a testis-specific endoplasmic reticulum-associated E3 ubiquitin ligase that may play a role in sperm maturation through an ER-associated degradation (ERAD) pathway. RNF149, also known as DNA polymerase-transactivated protein 2, is an E3 ubiquitin-protein ligase that induces the ubiquitination of wild-type v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) and promotes its proteasome-dependent degradation. RNF150 polymorphisms may be associated with chronic obstructive pulmonary disease (COPD) risk in the Chinese population. This subfamily also includes Drosophila melanogaster protein goliath (d-goliath), also known as protein g1, which is one of the founding members of the group. It was originally identified as a transcription factor involved in the embryo mesoderm formation.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 18417587 133 DCAVCLCEFETEDKLRLLPkCSHAFHMDCIDTWLLSHSTCPLCR 176
Cdd:cd16668   1 CCAVCIEPYKPSDVIRILP-CKHIFHKSCVDPWLLEHRTCPMCK 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 18417587 134 CAVCLCEFETEDKLRLLPkCSHAFHMDCIDTWLLSHSTCPLC 175
Cdd:cd16469   3 CAVCLEEFKLKEELGVCP-CGHAFHTKCLKKWLEVRNSCPIC 43

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 18417587 134 CAVCLCEFETEDKLRLLPkCSHAFHMDCIDTWLLSHSTCPLCR 176
Cdd:cd16803   3 CAVCIEGYKQNDVVRILP-CKHVFHKSCVDPWLNEHCTCPMCK 44

RING finger, H2 subclass, found in RING finger protein 13 (RNF13) and similar proteins; RNF13 is a widely expressed membrane-associated E3 ubiquitin-protein ligase that is functionally significant in the regulation of cancer development, muscle cell growth, and neuronal development. Its expression is developmentally regulated during myogenesis and is upregulated in various tumors. RNF13 negatively regulates cell proliferation through its E3 ligase activity. It functions as an important regulator of inositol-requiring transmembrane kinase/endonuclease IRE1alpha, mediating endoplasmic reticulum (ER) stress-induced apoptosis through the activation of the IRE1alpha-TRAF2-JNK signaling pathway. Moreover, RNF13 is involved in the regulation of the soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor (SNARE) complex via the ubiquitination of snapin, a SNAP25-interacting protein, which thereby controls synaptic function. In addition, RNF13 participates in regulating the function of satellite cells by modulating cytokine composition. RNF13 is evolutionarily conserved among many metazoans and 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 18417587 134 CAVCLCEFETEDKLRLLPkCSHAFHMDCIDTWLL-SHSTCPLCR 176
Cdd:cd16796  11 CAICLDEYEEGDKLRILP-CSHAYHCKCVDPWLTkTKKTCPVCK 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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 18417587 134 CAVCLCEFETEDKLRLLPkCSHAFHMDCIDTWLLSHSTCPLCR 176
Cdd:cd16680  10 CVVCFSDFESRQLLRVLP-CNHEFHTKCVDKWLKTNRTCPICR 51

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        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 18417587   133 DCAVCL---------CEFETEDKLRL-LPKCSHAFHMDCIDTWLLSHSTCPLCR 176
Cdd:pfam12678   2 TCAICRnpfmepcpeCQAPGDDECPVvWGECGHAFHLHCISRWLKTNNTCPLCR 55

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 18417587 134 CAVCLCEFETEDKLRLLPkCSHAFHMDCIDTWLLSHSTCPLCR 176
Cdd:cd16802   3 CAVCIEPYKPNDVVRILT-CNHLFHKNCIDPWLLEHRTCPMCK 44

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
                ....*....|....*....|....*....|....*....|..
gi 18417587 134 CAVCLCEFETEDKLRLLPkCSHAFHMDCIDTWLLSHSTCPLC 175
Cdd:cd16675   3 CAVCLEEFKPKDELGICP-CKHAFHRKCLIKWLEVRKVCPLC 43

RING finger, H2 subclass, found in zinc/RING finger protein 3 (ZNRF3) and similar proteins; ZNRF3, also known as RING finger protein 203 (RNF203), is a homolog of Ring finger protein 43 (RNF43). It is a transmembrane E3 ubiquitin-protein ligase that is associated with the Wnt receptor complex, and negatively regulates Wnt signaling by promoting the turnover of frizzled and lipoprotein receptor-related protein LRP6 in an R-spondin-sensitive manner. It inhibits gastric cancer cell growth and promotes cell apoptosis by affecting the Wnt/beta-catenin/TCF signaling pathway. ZNRF3 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 18417587 133 DCAVCLCEFETEDKLRLLPkCSHAFHMDCIDTWLLSHSTCPLCR 176
Cdd:cd16799   1 DCAICLEKYIDGEELRVIP-CTHRFHKKCVDPWLLQHHTCPHCR 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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 18417587 133 DCAVCLCEFETEDKLRLLPkCSHAFHMDCIDTWLLSHSTCPLCR 176
Cdd:cd16805   8 NCAVCIEGYKPNDVVRILP-CRHLFHKSCVDPWLLDHRTCPMCK 50

RING-like zinc finger;

                          10        20        30
                  ....*....|....*....|....*....|
gi 18417587   133 DCAVCLCEFETEDKLRLLPkCSHAFHMDCI 162
Cdd:pfam17123   1 ECSICLDEFKPGQALFVLP-CSHVFHYKCI 29

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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 18417587 134 CAVCLCEFETEDKLRLLPkCSHAFHMDCIDTWLLSHSTCPLCR 176
Cdd:cd16681  13 CTICLSILEEGEDVRRLP-CMHLFHQVCVDQWLITNKKCPICR 54

RING finger, H2 subclass, found in Arabidopsis thaliana MED25-binding RING-H2 protein (MBR) and similar proteins; This subfamily includes MBR1 and MBR2 (also called HAL3-interacting protein 1 or AtHIP1). They are E3 ubiquitin-protein ligases that function as regulators of MED25 stability by targeting MED25 for degradation in a RING-H2-dependent manner. Proteasome-dependent degradation of MED25 seems to activate its function as a positive regulator of FLOWERING LOCUS T (FT) and is important to induce the expression of FT, and consequently to promote flowering. MBR2 may also function downstream of HAL3 and be required for HAL3-regulated plant growth. Activation of MBR2 by HAL3 may lead to the degradation of cell cycle suppressors, resulting in enhancement of cell division and plant growth. Both MBR1 and MBR2 contain a C3H2C3-type RING-H2 finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 18417587 134 CAVCLCEFETEDKLRLLpKCSHAFHMDCIDTWLLSHSTCPLCR 176
Cdd:cd23113   5 CCICQEEYEEGDELGTI-ECGHEYHSDCIKQWLVQKNLCPICK 46

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 18417587 134 CAVCLCEFETEDKLRLLPkCSHAFHMDCIDTWLLSHSTCPLCR 176
Cdd:cd16682  10 CTICLSMLEDGEDVRRLP-CMHLFHQLCVDQWLAMSKKCPICR 51

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 18417587    134 CAVCLCEFETedKLRLLPkCSHAFHMDCIDTWLLSHS-TCPLC 175
Cdd:smart00184   1 CPICLEEYLK--DPVILP-CGHTFCRSCIRKWLESGNnTCPIC 40

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 18417587 133 DCAVCLCEFETEDKLrllpKCSHAFHMDCIDTWLLSHSTCPLCR 176
Cdd:cd16561   4 ECSICLEDLNDPVKL----PCDHVFCEECIRQWLPGQMSCPLCR 43

RING finger, HC subclass, found in E3 ubiquitin-protein ligase Deltex3 (DTX3), Deltex-3-like (DTX3L) and similar proteins; This subfamily contains Deltex3 (DTX3) and Deltex-3-like (DTX3L), both of which are E3 ubiquitin-protein ligases belonging to the Deltex (DTX) family. DTX3, also known as RING finger protein 154 (RNF154), has a biological function that remains unclear. DTX3L, also known as B-lymphoma- and BAL-associated protein (BBAP) or Rhysin-2 (Rhysin2), regulates endosomal sorting of the G protein-coupled receptor CXCR4 from endosomes to lysosomes. It also regulates subcellular localization of its partner protein, B aggressive lymphoma (BAL), by a dynamic nucleocytoplasmic trafficking mechanism. In contrast to other DTXs, both DTX3 and DTX3L contain a C3HC4-type RING-HC finger, and a previously unidentified C-terminal domain. DTX3L can associate with DTX1 through its unique N termini and further enhance self-ubiquitination.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 18417587 134 CAVCLCEFEteDKLRLlPKCSHAFHMDCIDTWLLSHSTCPLCR 176
Cdd:cd16506   3 CPICLDEIQ--NKKTL-EKCKHSFCEDCIDRALQVKPVCPVCG 42

RING finger, H2 subclass, found in synoviolin and similar proteins; Synoviolin, also known as synovial apoptosis inhibitor 1 (Syvn1), Hrd1, or Der3, is an endoplasmic reticulum (ER)-anchoring E3 ubiquitin ligase that functions as a suppressor of ER stress-induced apoptosis and plays a role in homeostasis maintenance. It also targets tumor suppressor gene p53 for proteasomal degradation, suggesting crosstalk between ER associated degradation (ERAD) and p53 mediated apoptotic pathway under ER stress. Moreover, synoviolin controls body weight and mitochondrial biogenesis through negative regulation of the thermogenic coactivator peroxisome proliferator-activated receptor coactivator (PGC)-1beta. It upregulates amyloid beta production by targeting a negative regulator of gamma-secretase, Retention in endoplasmic reticulum 1 (Rer1), for degradation. It is also involved in the degradation of endogenous immature nicastrin, and affects amyloid beta-protein generation. Moreover, synoviolin is highly expressed in rheumatoid synovial cells and may be involved in the pathogenesis of rheumatoid arthritis (RA). It functions as an anti-apoptotic factor that is responsible for the outgrowth of synovial cells during the development of RA. It promotes inositol-requiring enzyme 1 (IRE1) ubiquitination and degradation in synovial fibroblasts with collagen-induced arthritis. Furthermore, the upregulation of synoviolin may represent a protective response against neurodegeneration in Parkinson's disease (PD). In addition, synoviolin is involved in liver fibrogenesis. Synoviolin contains a C3H2C2-type RING-H2 finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 18417587 134 CAVCLCEFETEDKLrlLPkCSHAFHMDCIDTWLLSHSTCPLCR 176
Cdd:cd16479   4 CIICREEMTVGAKK--LP-CGHIFHLSCLRSWLQRQQTCPTCR 43

RING finger, H2 subclass, found in Saccharomyces cerevisiae RING-H2 zinc finger protein RHA2B and similar proteins; RHA2B is an E3 ubiquitin-protein ligase involved in the positive regulation of abscisic acid (ABA) signaling and responses to salt and osmotic stresses during seed germination and early seedling development. It acts additively with RHA2A in regulating ABA signaling and drought response. RHA2B contains a C3H2C3-type RING-H2 finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 18417587 133 DCAVCLCEFETEDKLRLLpKCSHAFHMDCIDTWL-LSHSTCPLCR 176
Cdd:cd23123   2 DCCICLDKLKTGEEVKKL-DCRHKFHKQCIEGWLkHLNFNCPLCR 45

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
                ....*....|....*....|....*....|....*....|..
gi 18417587 134 CAVCLCEFETEdkLRLLPkCSHAFHMDCIDTWLLSHSTCPLC 175
Cdd:cd16683   7 CAICYQEFTTS--ARITP-CNHYFHALCLRKWLYIQDTCPMC 45

N1R/p28-like protein; Provisional

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 18417587  133 DCAVCLCE-FETEDKLR---LLPKCSHAFHMDCIDTWLLSHSTCPLCR 176
Cdd:PHA02929 176 ECAICMEKvYDKEIKNMyfgILSNCNHVFCIECIDIWKKEKNTCPVCR 223

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
                ....*....|....*....|....*....|....*....|..
gi 18417587 134 CAVCLCEFetedKLRLLPKCSHAFHMDCIDTWLLSHSTCPLC 175
Cdd:cd16476   3 CAICYQEM----KEARITPCNHFFHGLCLRKWLYVQDTCPLC 40

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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 18417587 133 DCAVClceFETEDKLRLLPkCSHAFHMDCIDTWLLSHSTCPLCR 176
Cdd:cd16455   2 DCAIC---WESMQSARKLP-CGHLFHNSCLRSWLEQDTSCPTCR 41

Anaphase-promoting complex subunit 11 RING-H2 finger; Apc11 is one of the subunits of the anaphase-promoting complex or cyclosome. The APC subunits are cullin family proteins with ubiquitin ligase activity. Polyubiquitination marks proteins for degradation by the 26S proteasome and is carried out by a cascade of enzymes that includes ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), and ubiquitin ligases (E3s). Apc11 acts as an E3 enzyme and is responsible for recruiting E2s to the APC and for mediating the subsequent transfer of ubiquitin to APC substrates in vivo. In Saccharomyces cerevisiae this RING-H2 finger protein defines the minimal ubiquitin ligase activity of the APC, and the integrity of the RING-H2 finger is essential for budding yeast cell viability.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 18417587   126 GLKNYPFDCAVCLCEFETEDKLRLLPKCSHAFHMDCIDTWLLSHST---CPLCR 176
Cdd:pfam12861  25 GICRVSFDGTCPDCKFPGDDCPLVWGKCSHNFHMHCILKWLHTETSkglCPMCR 78

RING finger, HC subclass, found in RING finger and transmembrane domain-containing protein 1 (RNFT1); RNFT1, also known as protein PTD016, is a multi-pass membrane protein containing a C3HC4-type RING-HC finger. Its biological role remains unclear.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 18417587 134 CAVCLCEFETEdklrLLPKCSHAFHMDCIDTWLLSHSTCPLCR 176
Cdd:cd16741  17 CAICQAEFRKP----ILLICQHVFCEECISLWFNREKTCPLCR 55

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 18417587 134 CAVCLCEFETEDKLrLLPkCSHAFHMDCIDTW--LLSHSTCPLCR 176
Cdd:cd16677   2 CPICLEDFGLQQQV-LLS-CSHVFHRACLESFerFSGKKTCPMCR 44

Modified RING-CH finger, H2 subclass (C4HC2H-type), found in the ZNRF family; The ZNRF family includes zinc/RING finger proteins ZNRF1, ZNRF2, and similar proteins. It has been characterized by containing a unique combination of zinc finger-RING finger motifs in the C-terminal region, which is evolutionarily conserved in a wide range of species, including Caenorhabditis elegans and Drosophila. ZNRF proteins function as E3 ubiquitin ligases and are highly expressed in central nervous system (CNS) and peripheral nervous system (PNS) neurons, particularly during development and in adulthood. ZNRF1 and ZNRF2 are differentially localized within the synaptic region. ZNRF1 is associated with synaptic vesicle membranes, whereas ZNRF2 is present in presynaptic plasma membranes. They are N-myrisotoylated and also located in the endosome-lysosome compartment in fibroblasts. ZNRF proteins may play a role in the establishment and maintenance of neuronal transmission and plasticity via their ubiquitin ligase activity, as well as in regulating Ca2+-dependent exocytosis. The RING fingers found in ZNRF proteins are modified as C4HC2H-type RING-CH finger, rather than the typical C4HC3-type RING-CH finger, which is a variant of the RING-H2 finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 18417587 134 CAVCLCEFETEDKLRLLPkCSHAFHMDCIDTWLLSHSTCP 173
Cdd:cd16489   2 CVICLEELEAGDTIARLP-CLCIYHKKCIDDWFEVNRSCP 40

RING finger, HC subclass, found in RING finger and transmembrane domain-containing protein 2(RNFT2); RNFT2, also known as transmembrane protein 118 (TMEM118), is a multi-pass membrane protein containing a C3HC4-type RING-HC finger. Its biological role remains unclear.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 18417587 134 CAVCLCEFEteDKLRLLpkCSHAFHMDCIDTWLLSHSTCPLCR 176
Cdd:cd16742  16 CAICQAEFR--EPLILI--CQHVFCEECLCLWFDRERTCPLCR 54

second 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 second RING-H2 finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 18417587 133 DCAVCLCEFE----TEDKLRLLPK------CSHAFHMDCIDTW----LLSHSTCPLCR 176
Cdd:cd16678   1 DCPICLTPLQssgdSSDAKRVSSRptvllsCSHVFHATCLEAFeefsVGEELVCPVCR 58

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
                ....*....|....*....|....*....|....*....|....*....
gi 18417587 133 DCAVC-----LCEFETEDKLRLLPKCSHAFHMDCIDTWLLSHSTCPLCR 176
Cdd:cd23117   6 DCVICmsdieLPSTNSVRRDYMVTPCNHIFHTNCLERWMDIKLECPTCR 54

RING-CH finger, H2 subclass (C4HC3-type), found in E3 ubiquitin-protein ligase listerin and similar proteins; Listerin, also known as RING finger protein 160 or zinc finger protein 294, is the mammalian homolog of yeast Ltn1. It is widely expressed in all tissues, but motor and sensory neurons and neuronal processes in the brainstem and spinal cord are primarily affected in the mutant. Listerin is required for embryonic development and plays an important role in neurodegeneration. It also functions as a critical E3 ligase involving quality control of nonstop proteins. It mediates ubiquitylation of aberrant proteins that become stalled on ribosomes during translation. Ltn1 works with several cofactors to form a large ribosomal subunit-associated quality control complex (RQC), which mediates the ubiquitylation and extraction of ribosome-stalled nascent polypeptide chains for proteasomal degradation. It appears to first associate with nascent chain-stalled 60S subunits together with two proteins of unknown function, Tae2 and Rqc1. Listerin contains a long stretch of HEAT (Huntingtin, Elongation factor 3, PR65/A subunit of protein phosphatase 2A, and TOR) or ARM (Armadillo) repeats in the N terminus and middle region, and a catalytic RING-CH finger, also known as vRING or RINGv, with an unusual arrangement of zinc-coordinating residues in the C-terminus . Its cysteines and histidines are arranged in the sequence as C4HC3-type, rather than the C3H2C3-type in canonical RING-H2 finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 18417587 133 DCAVCLCEFETEDklRLLPK-----CSHAFHMDCIDTWLLS--HSTCPLCR 176
Cdd:cd16491   2 ECPICYSVIHGSN--HSLPKlkcktCKNKFHSACLYKWFRSsnKSTCPLCR 50

Modified RING-CH finger, H2 subclass (C4HC2H-type), found in zinc/RING finger protein 1 (ZNRF1) and similar proteins; ZNRF1, also known as Nerve injury-induced gene 283 protein (nin283), or peripheral nerve injury protein (PNIP), is an E3 ubiquitin-protein ligase that is highly expressed in the nervous system during development and is associated with synaptic vesicle membranes. It is N-myrisotoylated and is also located in the endosome-lysosome compartment in fibroblasts, suggesting it may participate in ubiquitin-mediated protein modification. 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 the RING-H2 finger. Only the RING finger of the zinc finger-RING finger motif is required for its E3 ubiquitin ligase activity. ZNRF1 regulates Schwann cell differentiation by proteasomal degradation of glutamine synthetase (GS). It also mediates regulation of neuritogenesis via interaction with beta-tubulin type 2 (Tubb2). Moreover, ZNRF1 promotes Wallerian degeneration by degrading AKT to induce glycogen synthase kinase-3beta (GSK3B)-dependent CRMP2 phosphorylation. Furthermore, ZNRF1 and its sister protein ZNRF2 regulate the ubiquitous Na+/K+ pump (Na+/K+ATPase). In addition, ZNRF1 may be associated with leukemogenesis of acute lymphoblastic leukemia (ALL) with paired box domain gene 5 (PAX5) alteration.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 18417587 133 DCAVCLCEFETEDKLRLLPkCSHAFHMDCIDTWLLSHSTCP 173
Cdd:cd16694   1 ECVICLEELLQGDTIARLP-CLCIYHKSCIDSWFEVNRSCP 40

RING finger, HC subclass, found in the makorin (MKRN) proteins; The MKRN protein subfamily includes ribonucleoproteins that are characterized by a variety of zinc-finger motifs, including typical arrays of one to four C3H1-type zinc fingers and a C3HC4-type RING-HC finger. Another motif rich in Cys and His residues (CH), with so far unknown function, is also generally present in MKRN proteins. MKRN proteins may have E3 ubiquitin ligase activity.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 18417587 134 CAVCLcEFETEDKLR--LLPKCSHAFHMDCIDTWLLSHS-------TCPLCR 176
Cdd:cd16521   3 CGICM-EVVLEKERRfgILSNCNHVFCLECIREWRSSKDfensivrSCPICR 53

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 18417587 133 DCAVCLCE-FETEDKLRLLPkCSHAFHMDCIDTWLLSHS-TCPLCR 176
Cdd:cd16464   1 NCPVCLEDlFTSREPVHVLP-CGHLMHSTCFEEYLKSGNyRCPLCS 45

RING finger, HC subclass, found in protein Deltex-3-like (DTX3L) and similar proteins; DTX3L, also known as B-lymphoma- and BAL-associated protein (BBAP) or Rhysin-2 (Rhysin2), is a RING-domain E3 ubiquitin-protein ligase that regulates endosomal sorting of the G protein-coupled receptor CXCR4 from endosomes to lysosomes. It also regulates subcellular localization of its partner protein, B aggressive lymphoma (BAL), by a dynamic nucleocytoplasmic trafficking mechanism. DTX3L has a unique N-terminus, but lacks the highly basic N-terminal motif and the central proline-rich motif present in other Deltex (DTX) family members, such as DTX1, DTX2, and DTX4. Moreover, its C-terminal region is highly homologous to DTX3. It includes a C3HC4-type RING-HC finger, and a previously unidentified C-terminal domain. DTX3L can associate with DTX1 through its unique N-terminus and further enhance self-ubiquitination.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 18417587 134 CAVCLCEfeTEDKLRLlPKCSHAFHMDCIDTWLLSHSTCPLC 175
Cdd:cd16712   6 CPICMDR--ISNKKVL-PKCKHVFCAACIDKAMKYKPVCPVC 44