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 34922250 339 DDCAICWDSMQAARKLPCGHLFHNSCLRSWLEQDTSCPTCRMSL 382
Cdd:cd16455   1 DDCAICWESMQSARKLPCGHLFHNSCLRSWLEQDTSCPTCRMSL 44

CUE domain found in autocrine motility factor receptor (AMFR) and similar proteins; AMFR is an internalizing cell surface glycoprotein that is localized in both plasma membrane caveolae and the endoplasmic reticulum (ER), and involves in the regulation of cellular adhesion, proliferation, motility and apoptosis, as well as in the process of learning and memory. It is also called ER-protein gp78 that has been identified as a RING finger-dependent ubiquitin protein ligase (E3) implicated in degradation from the ER. AMFR contains an N-terminal RING-finger domain and a C-terminal CUE domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 34922250 458 NAMAHQIQEMFPQVPYHLVLQDLQLTRSVEITTDNILEGRI 498
Cdd:cd14421   1 DAMAHQVQEMFPQVPLSVILADLRLTRSVEVTIENILEGRL 41

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 34922250 339 DDCAICWDSMQAARKLPCGHLFHNSCLRSWLEQDTSCPTCRMSL 382
Cdd:cd16455   1 DDCAICWESMQSARKLPCGHLFHNSCLRSWLEQDTSCPTCRMSL 44

CUE domain found in autocrine motility factor receptor (AMFR) and similar proteins; AMFR is an internalizing cell surface glycoprotein that is localized in both plasma membrane caveolae and the endoplasmic reticulum (ER), and involves in the regulation of cellular adhesion, proliferation, motility and apoptosis, as well as in the process of learning and memory. It is also called ER-protein gp78 that has been identified as a RING finger-dependent ubiquitin protein ligase (E3) implicated in degradation from the ER. AMFR contains an N-terminal RING-finger domain and a C-terminal CUE domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 34922250 458 NAMAHQIQEMFPQVPYHLVLQDLQLTRSVEITTDNILEGRI 498
Cdd:cd14421   1 DAMAHQVQEMFPQVPLSVILADLRLTRSVEVTIENILEGRL 41

E3 gp78 Ube2g2-binding region (G2BR); The activity of RING finger ubiquitin ligases (E3) is dependent on their ability to facilitate transfer of ubiquitin from ubiquitin-conjugating enzymes (E2) to substrates. The G2BR domain within the E3 gp78 binds selectively and with high affinity to the E2 Ube2g2. Binding to the G2BR results in conformational changes in Ube2g2 that affect ubiquitin loading. The Ube2g2-G2BR interaction also causes a 50-fold increase in affinity between the E2 and RING finger. Hence, the Ube2g2-binding region (G2BR) is required for the function of gp78. In yeast, Ubc7p, the ortholog of Ube2g2, is recruited by Cue1p to the ER membrane. Cue1p directly binds Ubc7p through a stretch of 50 aa domain analogous to G2BR, i.e. suggesting that this domain which activates ERAD and Hrd1p stimulating ubiquitylation, might be the yeast equivalent of the G2BR domain.

                          10        20
                  ....*....|....*....|....*.
gi 34922250   575 ADERQRMLVQRKDELLQQARKRFLNK 600
Cdd:pfam18442   1 ADERQRMLVQRKEELLQQARRRYLNK 26

Domain that may be involved in binding ubiquitin-conjugating enzymes (UBCs); CUE domains also occur in two protein of the IL-1 signal transduction pathway, tollip and TAB2. Ponting (Biochem. J.) "Proteins of the Endoplasmic reticulum" (in press)

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 34922250    456 QLNAMAHQIQEMFPQVPYHLVLQDL-QLTRSVEITTDNILEGR 497
Cdd:smart00546   1 ENDEALHDLKEMFPNLDEEVIEAVLeANTGNVEATINNLLEGS 43

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 34922250 340 DCAICWDSM---QAARKLPCGHLFHNSCLRSWL-EQDTSCPTCRMSL 382
Cdd:COG5540 325 ECAICMSNFiknDRLRVLPCDHRFHVGCVDKWLlGYSNKCPVCRTAI 371

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 34922250 339 DDCAICWDSMQAARKLPCGHLFHNSCLRSWLEQDTSCPTCRMSL 382
Cdd:cd16455   1 DDCAICWESMQSARKLPCGHLFHNSCLRSWLEQDTSCPTCRMSL 44

CUE domain found in autocrine motility factor receptor (AMFR) and similar proteins; AMFR is an internalizing cell surface glycoprotein that is localized in both plasma membrane caveolae and the endoplasmic reticulum (ER), and involves in the regulation of cellular adhesion, proliferation, motility and apoptosis, as well as in the process of learning and memory. It is also called ER-protein gp78 that has been identified as a RING finger-dependent ubiquitin protein ligase (E3) implicated in degradation from the ER. AMFR contains an N-terminal RING-finger domain and a C-terminal CUE domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 34922250 458 NAMAHQIQEMFPQVPYHLVLQDLQLTRSVEITTDNILEGRI 498
Cdd:cd14421   1 DAMAHQVQEMFPQVPLSVILADLRLTRSVEVTIENILEGRL 41

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 34922250 340 DCAICWDSM---QAARKLPCGHLFHNSCLRSWLEQDTSCPTCR 379
Cdd:cd16667   1 ECAVCKEDFevgEEVRQLPCKHLFHPDCIVPWLELHNSCPVCR 43

CUE domain found in ancient ubiquitous protein 1 (AUP1), autocrine motility factor receptor (AMFR) and similar proteins; AUP1 is a component of the HRD1-SEL1L endoplasmic reticulum (ER) quality control complex and is essential for US11-mediated dislocation of class I MHC heavy chains. AMFR is an internalizing cell surface glycoprotein that is localized in both plasma membrane caveolae and the ER, and involves in the regulation of cellular adhesion, proliferation, motility and apoptosis, as well as in the process of learning and memory. Cue1p is an N-terminally membrane-anchored endoplasmic reticulum (ER) protein essential for the activity of the two major yeast RING finger ubiquitin ligases (E3s) implicated in ER-associated degradation (ERAD). This family also includes plant E3 ubiquitin protein ligases RIN2, RIN3, and similar proteins. Comparing with other CUE domain-containing proteins, some family members from higher eukaryotes do not bind monoubiquitin efficiently, since they carry LP, rather than FP among CUE domains.

                        10        20        30
                ....*....|....*....|....*....|....*..
gi 34922250 458 NAMAHQIQEMFPQVPYHLVLQDLQLTRSVEITTDNIL 494
Cdd:cd14376   1 EEMVEQVQEVFPHIPREAIRRDLQRTNSVDLTINNIL 37

Ring finger domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 34922250   339 DDCAICWDSM---QAARKLPCGHLFHNSCLRSWLEQDTSCPTCR 379
Cdd:pfam13639   1 DECPICLEEFeegDKVVVLPCGHHFHRECLDKWLRSSNTCPLCR 44

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 34922250 339 DDCAICWDSMQAARKLPCGHLFHNSCLRSWLE-QDTsCPTC 378
Cdd:cd16476   1 DVCAICYQEMKEARITPCNHFFHGLCLRKWLYvQDT-CPLC 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 34922250 340 DCAICWDSMQAARKLPCGHLFHNSCLRSWLEQDTSCPTCRMSLN 383
Cdd:cd16561   4 ECSICLEDLNDPVKLPCDHVFCEECIRQWLPGQMSCPLCRTELP 47

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 34922250 341 CAICWDSMQA--ARKLPCGHLFHNSCLRSWLEQDTSCPTCR 379
Cdd:cd16481   2 CIICHDDLKPdqLAKLECGHIFHKECIKQWLKEQSTCPTCR 42

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 34922250 339 DDCAICWDSMQAA---RKLPCGHLFHNSCLRSWLEQD-TSCPTCR 379
Cdd:cd16473   5 EECAICLENYQNGdllRGLPCGHVFHQNCIDVWLERDnHCCPVCR 49

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 34922250 339 DDCAICWDSMQA--ARKLPCGHLFHNSCLRSWLEQ--DTSCPTCRMSLNI 384
Cdd:cd23120   2 EECPICLEEMNSgtGYLADCGHEFHLTCIREWHNKsgNLDCPICRVESLL 51

RING finger, H2 subclass, found in DAZ (deleted in azoospermia)-interacting protein 3 (DZIP3) and similar proteins; DZIP3, also known as RNA-binding ubiquitin ligase of 138 kDa (RUL138) or 2A-HUB protein, is an RNA-binding E3 ubiquitin-protein ligase that interacts with coactivator-associated arginine methyltransferase 1 (CARM1) and acts as a transcriptional coactivator of estrogen receptor (ER) alpha. It is also a histone H2A ubiquitin ligase that catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatorial component of the repression machinery required for repressing a specific chemokine gene expression program, critically modulating migratory responses to Toll-like receptors (TLR) activation. DZIP3 contains a C3H2C3-type RING-H2 finger at the C-terminus.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 34922250 341 CAICWDSMQAARK---LPCGHLFHNSCLRSWLEQDTSCPTCRMSL 382
Cdd:cd16460   3 CVICHEAFSDGDRllvLPCAHKFHTQCIGPWLDGQQTCPTCRLHV 47

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 34922250 339 DDCAICWDSMQ---AARKLPCGHLFHNSCLRSWLEQDTSCPTCRMSL 382
Cdd:cd16803   1 DHCAVCIEGYKqndVVRILPCKHVFHKSCVDPWLNEHCTCPMCKLNI 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        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 34922250 338 NDDCAICWDSM-QAARKLPCGHLFHNSCLRSWLEQDTSCPTCRMSLNIADN 387
Cdd:cd16683   4 DDVCAICYQEFtTSARITPCNHYFHALCLRKWLYIQDTCPMCHQKVYIEDD 54

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
                ....*....|....*....|....*....|....*....|.
gi 34922250 339 DDCAICWDSMQAARKLPCGHLFHNSCLRSWLEQDTSCPTCR 379
Cdd:cd16532   1 DICPICQDEFKDPVVLRCKHIFCEDCVSEWFERERTCPLCR 41

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 34922250 341 CAIC---WDSMQAARKLPCGHLFHNSCLRSWLEQDTSCPTCR 379
Cdd:cd16467   2 CTIClgeYETGEKLRRLPCSHEFHSECVDRWLKENSSCPICR 43

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
                ....*....|....*....|....*....|....*....|....*
gi 34922250 341 CAICWDSMQAARK-----LPCGHLFHNSCLRSWL-EQDTSCPTCR 379
Cdd:cd16450   5 CPICFEPWTSSGEhrlvsLKCGHLFGYSCIEKWLkGKGKKCPQCN 49

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 34922250 340 DCAICWDSMQAA---RKLPCGHLFHNSCLRSWLEQDTSCPTCRMSL 382
Cdd:cd16668   1 CCAVCIEPYKPSdviRILPCKHIFHKSCVDPWLLEHRTCPMCKLDI 46

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
                ....*....|....*....|....*....|....*....|....*..
gi 34922250 338 NDDCAICWDSMQAARKLP----CGHLFHNSCLRSWLEQDTS-CPTCR 379
Cdd:cd23121   1 DDCCAICLSDFNSDEKLRqlpkCGHIFHHHCLDRWIRYNKItCPLCR 47

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 34922250 338 NDDCAICWDSMQAA---RKLPCGHLFHNSCLRSWLEQDTSCPTCRMSL 382
Cdd:cd16682   7 DEKCTICLSMLEDGedvRRLPCMHLFHQLCVDQWLAMSKKCPICRVDI 54

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 34922250 341 CAICWDSMQAARKLPCGHLFHNSCLRSWLEQDT-SCPTCR 379
Cdd:cd16502   4 CKICAENDKDVRIEPCGHLLCTPCLTSWQDSDGqTCPFCR 43

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 34922250 339 DDCAICWDSMQAA---RKLPCGHLFHNSCLRSWLEQ-DTSCPTCR 379
Cdd:cd16797   1 DVCAICLDEYEEGdklRVLPCSHAYHSKCVDPWLTQtKKTCPVCK 45

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 34922250 338 NDDCAIC---WDSMQAARKLPCGHLFHNSCLRSWLEQDTSCPTC 378
Cdd:cd23115   4 NERCVICrleYEEGEDLLTLPCKHCYHSECIQQWLQINKVCPVC 47

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 34922250 340 DCAICWDSMQA---ARKLP-CGHLFHNSCLRSWLEQDTSCPTCR 379
Cdd:cd16461   1 ECAICLSDYENgeeLRRLPeCKHAFHKECIDEWLKSNSTCPLCR 44

RING finger, H2 subclass, found in RING finger protein 12 (RNF12) and similar proteins; 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. Its functional activity is regulated by phosphorylation-dependent nucleocytoplasmic shuttling. It is negatively regulated by pluripotency factors in embryonic stem cells. p53 represses its transcription through Sp1. RNF12 is the primary factor responsible for X chromosome inactivation (XCI) in female placental mammals. It is an indispensable factor in up-regulation of Xist transcription, thereby leading to initiation of random XCI. It also targets REX1, an inhibitor of XCI, for proteasomal degradation. RNF12 also acts as a co-regulator for a range of transcription factors, particularly those containing a LIM homeodomain, and modulates the formation of transcriptional multiprotein complexes. It is a negative regulator of Smad7, which in turn negatively regulates the signaling of type I receptors from the transforming growth factor beta (TGF-beta) superfamily. In addition, paternal RNF12 is a critical survival factor for milk-producing alveolar cells. RNF12 contains an nuclear localization signal (NLS) and a C3H2C3-type RING-H2 finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 34922250 341 CAICWDSMQAA---RKLPCGHLFHNSCLRSWLEQDTSCPTCRMSL 382
Cdd:cd16674   3 CSVCITEYTEGnklRKLPCSHEYHVHCIDRWLSENSTCPICRRAV 47

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 34922250 339 DDCAICWDSMQ---AARKLPCGHLFHNSCLRSWLEQDTSCPTCRMSL 382
Cdd:cd16805   7 DNCAVCIEGYKpndVVRILPCRHLFHKSCVDPWLLDHRTCPMCKMNI 53

CUE domain found in yeast ubiquitin-binding protein CUE1 (Cue1p), CUE4 (Cue4p) and similar proteins; Cue1p, also called coupling of ubiquitin conjugation to ER degradation protein 1 or kinetochore-defect suppressor 4, is encoded by the open reading frame (ORF) YMR264W in yeast. It is an N-terminally membrane-anchored endoplasmic reticulum (ER) protein essential for the activity of the two major yeast RING finger ubiquitin ligases (E3s) implicated in ER-associated degradation (ERAD). It interacts with the ERAD ubiquitin-conjugating enzyme (E2) Ubc7p in vivo, stimulates Ubc7p E2 activity, and further activates ER-associated protein degradation. Cue1p contains a CUE domain which binds ubiquitin much more weakly than those of other CUE domain containing proteins. It also has an Ubc7p binding-domain at the C-terminal region which is required for Ubc7p-dependent ubiquitylation and for degradation of substrates in the ER. This family also includes Cue4p, also called coupling of ubiquitin conjugation to ER degradation protein 4. It is encoded by the open reading frame (ORF) YML101C in yeast. Cue4p contains a CUE domain which shows high level of similarity with that of Cue1p.

                        10        20        30
                ....*....|....*....|....*....|....*.
gi 34922250 459 AMAHQIQEMFPQVPYHLVLQDLQLTRSVEITTDNIL 494
Cdd:cd14424   2 AMIESVQTMFPQLSVAQIRYDLLRTGSVEATVERIL 37

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
                ....*....|....*....|....*....|....*....|....*....|....*
gi 34922250 340 DCAICwdsMQA--------ARK----LPCGHLFHNSCLRSWLEQDTSCPTCRMSL 382
Cdd:cd23117   6 DCVIC---MSDielpstnsVRRdymvTPCNHIFHTNCLERWMDIKLECPTCRRPL 57

Variant RING finger, HC subclass (C4C4-type), found in retinoblastoma-binding protein 6 (RBBP6) and similar proteins; RBBP6, also known as proliferation potential-related protein, protein P2P-R, retinoblastoma-binding Q protein 1 (RBQ-1), or p53-associated cellular protein of testis (PACT), is a nuclear E3 ubiquitin-protein ligase involved in multiple processes, such as the control of gene expression, mitosis, cell differentiation, and cell apoptosis. It plays a role in both promoting and inhibiting apoptosis in many human cancers, including esophageal, lung, hepatocellular, and colon cancers, familial myeloproliferative neoplasms, as well as in human immunodeficiency virus-associated nephropathy (HIVAN). It functions as an Rb- and p53-binding protein that plays an important role in chaperone-mediated ubiquitination and possibly in protein quality control. It acts as a scaffold protein to promote the assembly of the p53/TP53-MDM2 complex, resulting in an increase of MDM2-mediated ubiquitination and degradation of p53/TP53, and leading to both apoptosis and cell growth. It is also a double-stranded RNA-binding protein that plays a role in mRNA processing by regulating the human polyadenylation machinery and modulating expression of mRNAs with AU-rich 3' untranslated regions (UTRs). Moreover, RBBP6 ubiquitinates and destabilizes the transcriptional repressor ZBTB38 that negatively regulates transcription and levels of the MCM10 replication factor on chromatin. Furthermore, RBBP6 is involved in tunicamycin-induced apoptosis by mediating protein kinase (PKR) activation. RBBP6 contains an N-terminal ubiquitin-like domain and a C4C4-type RING finger, whose overall folding is similar to that of the typical C3HC4-type RING-HC finger. RBBP6 interacts with chaperones Hsp70 and Hsp40 through its N-terminal ubiquitin-like domain. It promotes the ubiquitination of p53 by Hdm2 in an E4-like manner through its RING finger. It also interacts directly with the pro-proliferative transcription factor Y-box-binding protein-1 (YB-1) via its RING finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 34922250 331 PEELAvnnddCAICWDSMQAARKLPC-GHLFHNSCLRSWL-EQDTSCPTCRMSLNIAD 386
Cdd:cd16620   1 PDELK-----CPICKDLMKDAVLTPCcGNSFCDECIRTALlEEDFTCPTCKEPDVSPD 53

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 34922250 340 DCAIC---WDSMQAARKLPCGHLFHNSCLRSWLEQDTSCPTCRMSL 382
Cdd:cd16804   1 NCAVCienYKSKDVVRILPCKHVFHRICIDPWLLEHRTCPMCKLDV 46

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        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 34922250 339 DDCAICWD---SMQAARKLPCGHLFHNSCLRSWLEQDTSCPTCRMslNIADN 387
Cdd:cd16670   1 ESCAVCLDqfyKNQCLRVLPCLHEFHRDCVDPWLLLQQTCPLCKR--NILGN 50

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 34922250 339 DDCAICWDSMQAA---RKLPCGHLFHNSCLRSWLEQDTSCPTCR 379
Cdd:cd23118   1 KTCTICLEDFEDGeklRVLPCQHQFHSECVDQWLRRNPKCPVCR 44

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
                ....*....|....*....|....*....|....*....
gi 34922250 341 CAICWDSMQAARKLPCGHLFHNSCLRSWLEQDTSCPTCR 379
Cdd:cd16527   3 CSLCLEERRHPTATPCGHLFCWSCITEWCNEKPECPLCR 41

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 34922250 341 CAICWDSMQAARKL---PCGHLFHNSCLRSWLEQDTSCPTCRM 380
Cdd:cd16675   3 CAVCLEEFKPKDELgicPCKHAFHRKCLIKWLEVRKVCPLCNM 45

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 34922250 340 DCAICWDSMQAA---RKLPCGHLFHNSCLRSWLEQDTSCP 376
Cdd:cd16694   1 ECVICLEELLQGdtiARLPCLCIYHKSCIDSWFEVNRSCP 40

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 34922250   339 DDCAICWDSM-----QAARKL---------PCGHLFHNSCLRSWLEQDTSCPTCR 379
Cdd:pfam12678   1 DTCAICRNPFmepcpECQAPGddecpvvwgECGHAFHLHCISRWLKTNNTCPLCR 55

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
                ....*....|....*....|....*....|....*....|.
gi 34922250 341 CAICWDSMQAARKL---PCGHLFHNSCLRSWLEQDTSCPTC 378
Cdd:cd16676   3 CAVCLEDFKTKDELgvlPCQHAFHRKCLVKWLEIRCVCPMC 43

RING finger, H2 subclass, found in RING finger proteins RNF121, RNF175 and similar proteins; This subfamily includes RNF121, RNF175 and similar proteins. RNF121 is an E3-ubiquitin ligase present in the endoplasmic reticulum (ER) and cis-Golgi compartments. It is a novel regulator of apoptosis. It also facilitates the degradation and membrane localization of voltage-gated sodium (NaV) channels, and thus plays a role in the quality control of NaV channels during their synthesis and subsequent transport to the membrane. Moreover, RNF121 acts as a broad regulator of nuclear factor kappaB (NF-kappaB) signaling since its silencing also dampens NF-kappaB activation following stimulation of toll-like receptors (TLRs), nod-like receptors (NLRs), RIG-I-like Receptors (RLRs) or after DNA damage. RNF121 contains five conserved transmembrane (TM) domains and a C3H2C2-type RING-H2 finger. RNF175 is an uncharacterized RING finger protein that shows high sequence similarity with RNF121. This family also includes Arabidopsis RING finger E3 ligase RHA2A, RHA2B, and their homologs. RHA2A is a positive regulator of abscisic acid (ABA) signaling during seed germination and early seedling development. RHA2B may play a role in the ubiquitin-dependent proteolysis pathway that respond to proteasome inhibition. All subfamily members contain a C3H2C3-type RING-H2 finger, which is responsible for E3-ubiquitin ligase activity.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 34922250 341 CAICWDSM----------QAARKLPCGHLFHNSCLRSWL---EQDTsCPTCR 379
Cdd:cd16475   3 CAVCGQKLdvddneegiiEKTYKLSCNHVFHEFCIRGWCivgKKQT-CPYCK 53

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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 34922250 341 CAIC---WDSMQAARKLP-CGHLFHNSCLRSWLEQDTSCPTCR 379
Cdd:cd23119   2 CTIClqdLQVGEIARSLPhCHHTFHLGCVDKWLGRHGSCPVCR 44

second RING finger, HC subclass, found in the LON peptidase N-terminal domain and RING finger protein family; The LON peptidase N-terminal domain and RING finger protein family includes LONRF1 (also known as RING finger protein 191 or RNF191), LONRF2 (also known as RING finger protein 192, RNF192, or neuroblastoma apoptosis-related protease), LONRF3 (also known as RING finger protein 127 or RNF127), which are characterized by containing two C3HC4-type RING-HC fingers, four tetratricopeptide (TPR) repeats, and an ATP-dependent protease La (LON) substrate-binding domain at the C-terminus. Their biological functions remain unclear. This model corresponds to the second RING-HC finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 34922250 340 DCAICWDSMQAARKLPCGHLFHNSCLRSWLEQDTSCPTCRMSL 382
Cdd:cd16514   3 ECSLCLRLLYEPVTTPCGHTFCRACLERCLDHSPKCPLCRTSL 45

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        40
                ....*....|....*....|....*....|....*....|...
gi 34922250 341 CAICWDSMQAARKLPCGHLFHNSCLRSWLEQDTSCPTCRMSLN 383
Cdd:cd16547   6 CSICHGVLRCPVRLSCSHIFCKKCILQWLKRQETCPCCRKEVK 48

RING finger, HC subclass, found in Saccharomyces cerevisiae radiation sensitivity protein 18 (RAD18) and similar proteins; RAD18, also called RING-type E3 ubiquitin transferase RAD18, acts as a postreplication repair E3 ubiquitin-protein ligase that associates with the E2 ubiquitin conjugating enzyme UBC2/RAD6 to form the UBC2-RAD18 ubiquitin ligase complex involved in postreplicative repair (PRR) of damaged DNA. The UBC2-RAD18 complex cooperates with RAD5 and the UBC13-MMS2 dimer to attach mono-ubiquitin chains on 'Lys-164' of POL30, which is necessary for PRR. The UBC2-RAD18 complex is also involved in prevention of spontaneous mutations caused by 7,8-dihydro-8-oxoguanine. RAD18 is an E3 RING-finger protein belonging to the UBC2/RAD6 epistasis group. It contains a typical C3HC4-type RING-HC finger.

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 34922250 341 CAICWDSMQAARKLPCGHLFHNSCLRSWLEQDTSCPTCR 379
Cdd:cd23148   6 CHICKDLLKAPMRTPCNHTFCSFCIRTHLNNDARCPLCK 44