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 1025326532 338 DDCAICWDSMTTARKLPCGHLFHNSCLRSWLEQDTSCPTCRMSL 381
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 1025326532 457 NAMAHQIQEMFPQVPYHLILQDLQLTRSVEVTTDNILEGRI 497
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 1025326532 338 DDCAICWDSMTTARKLPCGHLFHNSCLRSWLEQDTSCPTCRMSL 381
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 1025326532 457 NAMAHQIQEMFPQVPYHLILQDLQLTRSVEVTTDNILEGRI 497
Cdd:cd14421     1 DAMAHQVQEMFPQVPLSVILADLRLTRSVEVTIENILEGRL 41

Ring finger domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1025326532 338 DDCAICWDSMTTARK---LPCGHLFHNSCLRSWLEQDTSCPTCR 378
Cdd:pfam13639   1 DECPICLEEFEEGDKvvvLPCGHHFHRECLDKWLRSSNTCPLCR 44

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 1025326532  455 QLNAMAHQIQEMFPQVPYHLILQDL-QLTRSVEVTTDNILEGR 496
Cdd:smart00546   1 ENDEALHDLKEMFPNLDEEVIEAVLeANTGNVEATINNLLEGS 43

RING-finger-containing E3 ubiquitin ligase [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1025326532 310 RHKNYLRVIDNMESRFAVATPDELLANND---------DCAICWDSMTTARKLPCGHLFHNSCLRSW--LEQDTSCPTCR 378
Cdd:COG5574   179 RLQPILQPSNNLHTLFQVITKENLSKKNGlpfipladyKCFLCLEEPEVPSCTPCGHLFCLSCLLISwtKKKYEFCPLCR 258

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 1025326532 338 DDCAICWDSMTTARKLPCGHLFHNSCLRSWLEQDTSCPTCRMSL 381
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 1025326532 457 NAMAHQIQEMFPQVPYHLILQDLQLTRSVEVTTDNILEGRI 497
Cdd:cd14421     1 DAMAHQVQEMFPQVPLSVILADLRLTRSVEVTIENILEGRL 41

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 1025326532 457 NAMAHQIQEMFPQVPYHLILQDLQLTRSVEVTTDNIL 493
Cdd:cd14376     1 EEMVEQVQEVFPHIPREAIRRDLQRTNSVDLTINNIL 37

CUE domain found in ancient ubiquitous protein 1 (AUP1) 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. It also binds to the membrane-proximal KVGFFKR motif of the cytoplasmic tail of the integrin alphaCTs that plays a crucial role in the inside-out signaling of alpha(IIb)beta(3). AUP1 is found in both the ER and in lipid droplets. It contains two conserved cytoplasmic domains, an acyltransferase domain, a CUE domain and an E2 ubiquitin conjugase G2 (Ube2g2)-binding domain (G2BR). The acyltransferase domain transfers fatty acids onto phospholipids and CUE domain participates in ubiquitin binding or in recruitment of ubiquitin-conjugating enzymes to the site of dislocation.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1025326532 459 MAHQIQEMFPQVPYHLILQDLQLTRSVEVTTDNILEGRIQ 498
Cdd:cd14420     5 MAQQVKEVLPHVPLHVIRRDLEKTRNVDTTITNILEGRVK 44

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 1025326532 548 ADERQRMLMQRKEELLQRARRRYLHK 573
Cdd:pfam18442   1 ADERQRMLVQRKEELLQQARRRYLNK 26

H2 subclass of RING (RING-H2) fingers and its variants; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers: some have different Cys/His patterns while some lack a single Cys or His residue at typical Zn ligand positions (the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can indeed chelate Zn in a RING finger as well). This family corresponds to the H2 subclass of RING (RING-H2) finger proteins that are characterized by containing C3H2C3-type canonical RING-H2 fingers or noncanonical RING-H2 finger variants, including C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type modified RING-H2 fingers. The canonical RING-H2 finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-H-X2-C-X(4-48)-C-X2-C, X is any amino acid and the number of X residues varies in different fingers. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-H2 finger can be found in a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serves as a scaffold for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enables efficient transfer of ubiquitin from E2 to the substrates.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1025326532 340 CAICWDSMTT---ARKLPCGHLFHNSCLRSWLE-QDTSCPTCR 378
Cdd:cd16448     1 CVICLEEFEEgdvVRLLPCGHVFHLACILRWLEsGNNTCPLCR 43

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 1025326532 338 DDCAICWDSMTTARKLPCGHLFHNSCLRSWLEQDTSCPTC 377
Cdd:cd16476     1 DVCAICYQEMKEARITPCNHFFHGLCLRKWLYVQDTCPLC 40

RING finger, H2 subclass, found in RING finger protein 115 (RNF115) and similar proteins; 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 and its inhibition increases the efficacy of metformin in breast cancer cells. It also functions as a co-factor 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. Furthermore, RNF115 and the related protein, 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. RNF115 contains an N-terminal BCA2 Zinc-finger domain (BZF), the AKT-phosphorylation sites, and the C-terminal C3H2C3-type RING-H2 finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1025326532 339 DCAICWDSMTTA---RKLPCGHLFHNSCLRSWLEQDTSCPTCRMSLN 382
Cdd:cd16800     2 ECPVCKEDYTVGeqvRQLPCNHFFHSDCIVPWLELHDTCPVCRKSLN 48

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 1025326532 339 DCAICWDSMTTARKLPCGHLFHNSCLRSWLEQDTSCPTCRMSLN 382
Cdd:cd16561     4 ECSICLEDLNDPVKLPCDHVFCEECIRQWLPGQMSCPLCRTELP 47

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 1025326532 340 CAICWDSMTTARK-----LPCGHLFHNSCLRSWL-EQDTSCPTCR 378
Cdd:cd16450     5 CPICFEPWTSSGEhrlvsLKCGHLFGYSCIEKWLkGKGKKCPQCN 49

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 1025326532 338 DDCAICWDSMTTARKLPCGHLFHNSCLRSWLEQDTSCPTCR 378
Cdd:cd16532     1 DICPICQDEFKDPVVLRCKHIFCEDCVSEWFERERTCPLCR 41

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1025326532 336 NNDDCAICWDSMTTARKLPCGHLFHNSCLRSWLEQDTSCPTC 377
Cdd:cd16684     1 HNDICSICYQDMKSAVITPCSHFFHAGCLKKWLYVQETCPLC 42

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 1025326532 340 CAICWDSMTTARK---LPCGHLFHNSCLRSWLEQDTSCPTCRMSL 381
Cdd:cd16460     3 CVICHEAFSDGDRllvLPCAHKFHTQCIGPWLDGQQTCPTCRLHV 47

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1025326532 340 CAICWDSMTTARKL---PCGHLFHNSCLRSWLEQDTSCPTCR 378
Cdd:cd16480     2 CTICSDFFDNSRDVaaiHCGHTFHYDCLLQWFDTSRTCPQCR 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 1025326532 338 DDCAICWDSMT---TARKLPCGHLFHNSCLRSWLEQDTSCPTCRMSL 381
Cdd:cd16803     1 DHCAVCIEGYKqndVVRILPCKHVFHKSCVDPWLNEHCTCPMCKLNI 47

RING finger, H2 subclass, found in protein E3 ubiquitin-protein ligase Praja-1, Praja-2, and similar proteins; This family includes two highly similar E3 ubiquitin-protein ligases, Praja-1 and Praja-2. Praja-1, also known as RING finger protein 70, is a RING-H2 finger ubiquitin ligase encoded by gene PJA1, a novel human X chromosome gene abundantly expressed in the brain. It has been implicated in bone and liver development, as well as memory formation and X-linked mental retardation (MRX). Praja-1 interacts with and activates the ubiquitin-conjugating enzyme UbcH5B, and shows E2-dependent E3 ubiquitin ligase activity. It is a 3-deazaneplanocin A (DZNep)-induced ubiquitin ligase that directly ubiquitinates individual polycomb repressive complex 2 (PRC2) subunits in a cell free system, which leads to their proteasomal degradation. It also plays an important role in neuronal plasticity, which is the basis for learning and memory. Moreover, Praja-1 ubiquitinates embryonic liver fodrin (ELF) and Smad3, but not Smad4, in a transforming growth factor-beta (TGF-beta)-dependent manner. It controls ELF abundance through ubiquitin-mediated degradation, and further regulates TGF-beta signaling, which plays a key role in the suppression of gastric carcinoma. Praja-1 also regulates the transcription function of the homeodomain protein Dlx5 by controlling the stability of Dlxin-1, via a ubiquitin-dependent degradation pathway. Praja-2, also known as RING finger protein 131, NEURODAP1, or KIAA0438, is an E2-dependent E3 ubiquitin ligase that interacts with and activates the ubiquitin-conjugating enzyme UbcH5B. It functions as an A-kinase anchoring protein (AKAP)-like E3 ubiquitin ligase that plays a critical role in controlling cyclic AMP (cAMP)-dependent PKA activity and pro-survival signaling, and further promotes cell proliferation and growth. Praja-2 is also involved in protein sorting at the postsynaptic density region of axosomatic synapses and possibly plays a role in synaptic communication and plasticity. Together with the AMPK-related kinase SIK2 and the CDK5 activator CDK5R1/p35, it forms a SIK2-p35-PJA2 complex that plays an essential role for glucose homeostasis in pancreatic beta cell functional compensation. Praja-2 ubiquitylates and degrades Mob, a core component of NDR/LATS kinase and a positive regulator of the tumor-suppressor Hippo signaling. Both Praja-1 and Praja-2 contain a potential nuclear localization signal (NLS) and a C-terminal C3H2C3-type RING-H2 motif.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1025326532 340 CAICWDSMT---TARKLPCGHLFHNSCLRSWLEQDTSCPTCR 378
Cdd:cd16465     2 CPICCSEYVkdeIATELPCHHLFHKPCITAWLQKSGTCPVCR 43

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 1025326532 458 AMAHQIQEMFPQVPYHLILQDLQLTRSVEVTTDNIL 493
Cdd:cd14424     2 AMIESVQTMFPQLSVAQIRYDLLRTGSVEATVERIL 37

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 1025326532 340 CAICWDSMTTA---RKLPCGHLFHNSCLRSWLEQDTSCPTCRMSL 381
Cdd:cd16674     3 CSVCITEYTEGnklRKLPCSHEYHVHCIDRWLSENSTCPICRRAV 47

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 1025326532 338 DDCAICWDSMTTA---RKLPCGHLFHNSCLRSWLEQ-DTSCPTCR 378
Cdd:cd16797     1 DVCAICLDEYEEGdklRVLPCSHAYHSKCVDPWLTQtKKTCPVCK 45

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

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                  ....*....|....*....|....*....|....*....|....
gi 1025326532 338 DDCAIC---WDSMTTARKLPCGHLFHNSCLRSWLEQDTSCPTCR 378
Cdd:cd16474     1 EKCTIClsdFEEGEDVRRLPCMHLFHQECVDQWLSTNKRCPICR 44

RING finger, H2 subclass, found in BRCA1-associated protein (BRAP2) and similar proteins; BRAP2, also known as impedes mitogenic signal propagation (IMP), RING finger protein 52, or renal carcinoma antigen NY-REN-63, is a novel cytoplasmic protein interacting with the two functional nuclear localization signal (NLS) motifs of BRCA1, a nuclear protein linked to breast cancer. It also binds to the SV40 large T antigen NLS motif and the bipartite NLS motif found in mitosin. BRAP2 serves as a cytoplasmic retention protein and plays a role in the regulation of nuclear protein transport. It contains an N-terminal RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), followed by a C3H2C3-type RING-H2 finger and a UBP-type zinc finger.

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                  ....*....|....*....|....*....|....*....|...
gi 1025326532 340 CAICWDSMTTARK----LPCGHLFHNSCLRSWleQDTSCPTCR 378
Cdd:cd16457     3 CPVCLERMDESVSgiltILCNHSFHCSCLSKW--GDSSCPVCR 43

Zinc finger, C3HC4 type (RING finger);

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1025326532 340 CAICWDSMTTARKL-PCGHLFHNSCLRSWLEQDTSCPTC 377
Cdd:pfam13923   2 CPICMDMLKDPSTTtPCGHVFCQDCILRALEASNECPLC 40

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.

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                  ....*....|....*....|....*....|....*....|....*.
gi 1025326532 339 DCAICWDSMT---TARKLPCGHLFHNSCLRSWLEQDTSCPTCRMSL 381
Cdd:cd16668     1 CCAVCIEPYKpsdVIRILPCKHIFHKSCVDPWLLEHRTCPMCKLDI 46

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.

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                  ....*....|....*....|....*....|....*....|....*..
gi 1025326532 339 DCAIC----WDSMTTarklPCGHLFHNSCLRSWLEQDTSCPTCRMSL 381
Cdd:cd16514     3 ECSLClrllYEPVTT----PCGHTFCRACLERCLDHSPKCPLCRTSL 45

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.

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                  ....*....|....*....|....*....|....*....|....*..
gi 1025326532 337 NDDCAICWDSMTTARKLP----CGHLFHNSCLRSWLEQDTS-CPTCR 378
Cdd:cd23121     1 DDCCAICLSDFNSDEKLRqlpkCGHIFHHHCLDRWIRYNKItCPLCR 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.

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                  ....*....|....*....|....*....|....*....|....*....|...
gi 1025326532 332 ELLANNDDCAIC---WDSMTTARKLPCGHLFHNSCLRSWLEQDTSCPTCRMSL 381
Cdd:cd16805     1 ETESDFDNCAVCiegYKPNDVVRILPCRHLFHKSCVDPWLLDHRTCPMCKMNI 53

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.

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                  ....*....|....*....|....*....|....*....|...
gi 1025326532 340 CAICWDSMTTARKL---PCGHLFHNSCLRSWLEQDTSCPTCRM 379
Cdd:cd16675     3 CAVCLEEFKPKDELgicPCKHAFHRKCLIKWLEVRKVCPLCNM 45

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.

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gi 1025326532 338 DDCAICWDSMT---TARKLPCGHLFHNSCLRSWLEQDTSCPTCR 378
Cdd:cd23118     1 KTCTICLEDFEdgeKLRVLPCQHQFHSECVDQWLRRNPKCPVCR 44

HC subclass of RING (RING-HC) finger and its variants; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers. Some have a different Cys/His pattern. Some lack a single Cys or His residue at typical Zn ligand positions, especially, the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can chelate Zn in a RING finger as well. This family corresponds to the HC subclass of RING (RING-HC) fingers that are characterized by containing C3HC4-type canonical RING-HC fingers or noncanonical RING-HC finger variants, including C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type modified RING-HC fingers. The canonical RING-HC finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-HC fingers can be found in a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle, and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serve as scaffolds for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enables efficient transfer of ubiquitin from E2 to the substrates.

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                  ....*....|....*....|....*....|....*....
gi 1025326532 340 CAICWDSMTTARKLPCGHLFHNSCLRSWLEQDT-SCPTC 377
Cdd:cd16449     3 CPICLERLKDPVLLPCGHVFCRECIRRLLESGSiKCPIC 41

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.

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                  ....*....|....*....|....*....|....*....|...
gi 1025326532 339 DCAIC---WDSMTTARKLPCGHLFHNSCLRSWLEQDTSCPTCR 378
Cdd:cd16472     4 QCVVCmcdYEKRQLLRVLPCSHEFHAKCIDKWLKTNRTCPICR 46

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.

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                  ....*....|....*....|....*....|....*....|....*
gi 1025326532 338 DDCAICWDSMTTA---RKLPCGHLFHNSCLRSWLEQDT-SCPTCR 378
Cdd:cd23123     1 SDCCICLDKLKTGeevKKLDCRHKFHKQCIEGWLKHLNfNCPLCR 45

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.

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                  ....*....|....*....|....*....|....*....|....*.
gi 1025326532 339 DCAIC---WDSMTTARKLPCGHLFHNSCLRSWLEQDTSCPTCRMSL 381
Cdd:cd16804     1 NCAVCienYKSKDVVRILPCKHVFHRICIDPWLLEHRTCPMCKLDV 46

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.

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                  ....*....|....*....|....*....|....*....|
gi 1025326532 339 DCAICWDSMT---TARKLPCGHLFHNSCLRSWLEQDTSCP 375
Cdd:cd16694     1 ECVICLEELLqgdTIARLPCLCIYHKSCIDSWFEVNRSCP 40

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

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gi 1025326532 340 CAIC---WDSMTTARKLP-CGHLFHNSCLRSWLEQDTSCPTCR 378
Cdd:cd23119     2 CTIClqdLQVGEIARSLPhCHHTFHLGCVDKWLGRHGSCPVCR 44

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

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                  ....*....|....*....|....*....|....*....|
gi 1025326532 340 CAICWDSMTTARK-LPCGHLFHNSCLRSWLE-QDTSCPTC 377
Cdd:pfam00097   1 CPICLEEPKDPVTlLPCGHLFCSKCIRSWLEsGNVTCPLC 40

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

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gi 1025326532 340 CAICWDSMTTARKL-PCGHLFHNSCLRSWLE-QDTSCPTCRMSL 381
Cdd:cd16503     5 CSICQDLLHDCVSLqPCMHNFCAACYSDWMErSNTECPTCRATV 48

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.

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                  ....*....|....*....|....*....|....*....|....*....|..
gi 1025326532 340 CAIC-------WDSMTTARK---LPCGHLFHNSCLRSWL---EQDTsCPTCR 378
Cdd:cd16475     3 CAVCgqkldvdDNEEGIIEKtykLSCNHVFHEFCIRGWCivgKKQT-CPYCK 53

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.

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gi 1025326532 339 DCAICWDSMTTA---RKLPCGHLFHNSCLRSWLEQDTSCPTCR 378
Cdd:cd16799     1 DCAICLEKYIDGeelRVIPCTHRFHKKCVDPWLLQHHTCPHCR 43

RING-type zinc-finger; This zinc-finger is a typical RING-type of plant ubiquitin ligases.

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                  ....*....|....*....|....*....|....*...
gi 1025326532 340 CAICWDSMTTARkLPCGHLFHNSCLRSWLEQDTSCPTC 377
Cdd:pfam13445   1 CPICLELFTDPV-LPCGHTFCRECLEEMSQKKGGKFKC 37

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.

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gi 1025326532 338 DDCAICWDSMT---TARKLPCGHLFHNSCLRSWLEQDTSCPTCR 378
Cdd:cd16802     1 DSCAVCIEPYKpndVVRILTCNHLFHKNCIDPWLLEHRTCPMCK 44

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.

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gi 1025326532 340 CAICWDSMTTARKLPCGHLFHNSCLRSWLEQDTSCPTCRMSLN 382
Cdd:cd16547     6 CSICHGVLRCPVRLSCSHIFCKKCILQWLKRQETCPCCRKEVK 48

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.

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                  ....*....|....*....|....*....|....*....|....*.
gi 1025326532 338 DDCAICWDSmttarklpCGHLFHNSCLRSWLEQDTS---CPTCRMS 380
Cdd:pfam12861  43 DDCPLVWGK--------CSHNFHMHCILKWLHTETSkglCPMCRQT 80