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 972971476   6 YCTICSDFFDHSKDVAAIHCGHTFHYDCLLQWFQSapSKTCPQCR 50
Cdd:cd16480    1 YCTICSDFFDNSRDVAAIHCGHTFHYDCLLQWFDT--SRTCPQCR 43

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 972971476   6 YCTICSDFFDHSKDVAAIHCGHTFHYDCLLQWFQSapSKTCPQCR 50
Cdd:cd16480    1 YCTICSDFFDNSRDVAAIHCGHTFHYDCLLQWFDT--SRTCPQCR 43

Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and is likely to be a general function of this domain; Various RING fingers exhibit binding activity towards E2 ubiquitin-conjugating enzymes (Ubc' s)

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 972971476     7 CTICSDFFdhSKDVAAIHCGHTFHYDCLLQWFQSApSKTCPQC 49
Cdd:smart00184   1 CPICLEEY--LKDPVILPCGHTFCRSCIRKWLESG-NNTCPIC 40

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 972971476    78 ESLQNELDKFKALLSVKEKDRKGLQKVIEALRETVGRLNIDLECVKKELSEK-DMLCAALRKQMKFLENQQSETQSAKEE 156
Cdd:TIGR02169  233 EALERQKEAIERQLASLEEELEKLTEEISELEKRLEEIEQLLEELNKKIKDLgEEEQLRVKEKIGELEAEIASLERSIAE 312

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 972971476   157 A-RRLRTKMKTYESLDLLLQGQRSEVEAMIRDMGVGQAAVEQLSIFCISLKKEYENL--------------KISNKTSNE 221
Cdd:TIGR02169  313 KeRELEDAEERLAKLEAEIDKLLAEIEELEREIEEERKRRDKLTEEYAELKEELEDLraeleevdkefaetRDELKDYRE 392

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 972971476   222 MCEKLKREVfvsnNKLQKSALQVSRTKEELNAAQEDLKNADKQISSLQKKVE 273
Cdd:TIGR02169  393 KLEKLKREI----NELKRELDRLQEELQRLSEELADLNAAIAGIEAKINELE 440

DNA double-strand break repair ATPase Rad50;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 972971476  78 ESLQNELDKFKALLSVKEKDRKGLQKVIEALRETVGRLNIDLECVKKELSEkdmlcaaLRKQMKFLEnqqsETQSAKEEA 157
Cdd:PRK03918 227 EKEVKELEELKEEIEELEKELESLEGSKRKLEEKIRELEERIEELKKEIEE-------LEEKVKELK----ELKEKAEEY 295

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 972971476 158 RRLRTKMKTY-------ESLDLLLQGQRSEVEAMIRDMGVGQAAVEQLSIFCISLKKEYENLKISNKTSNEMCEKL---- 226
Cdd:PRK03918 296 IKLSEFYEEYldelreiEKRLSRLEEEINGIEERIKELEEKEERLEELKKKLKELEKRLEELEERHELYEEAKAKKeele 375

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 972971476 227 ---KREVFVSNNKLQKSALQVSRTKEELnaaQEDLKNADKQISSLQKKVEFLQKALS 280
Cdd:PRK03918 376 rlkKRLTGLTPEKLEKELEELEKAKEEI---EEEISKITARIGELKKEIKELKKAIE 429

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 972971476   6 YCTICSDFFDHSKDVAAIHCGHTFHYDCLLQWFQSapSKTCPQCR 50
Cdd:cd16480    1 YCTICSDFFDNSRDVAAIHCGHTFHYDCLLQWFDT--SRTCPQCR 43

Ring finger domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 972971476    7 CTICSDFFDHSKDVAAIHCGHTFHYDCLLQWFQSapSKTCPQCR 50
Cdd:pfam13639   3 CPICLEEFEEGDKVVVLPCGHHFHRECLDKWLRS--SNTCPLCR 44

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 972971476   7 CTICSDFFDHSKD--VAAIHCGHTFHYDCLLQWFQSApSKTCPQCRKQVSTKHIIN 60
Cdd:cd16450    5 CPICFEPWTSSGEhrLVSLKCGHLFGYSCIEKWLKGK-GKKCPQCNKKAKRSDIRP 59

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 972971476   7 CTICSDFFdHSKDVAAIHCGHTFHYDCLLQWFQSapSKTCPQCRKQV 53
Cdd:cd16481    2 CIICHDDL-KPDQLAKLECGHIFHKECIKQWLKE--QSTCPTCRVHV 45

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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 972971476   7 CTICSDFFD-HSKDVAAIHCGHTFHYDCLLQWFQSapskTCPQCR 50
Cdd:cd16457    3 CPVCLERMDeSVSGILTILCNHSFHCSCLSKWGDS----SCPVCR 43

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 972971476   7 CTICSDFFDHSKDVAAIHCGHTFHYDCLLQWFQSapSKTCPQCR 50
Cdd:cd16474    3 CTICLSDFEEGEDVRRLPCMHLFHQECVDQWLST--NKRCPICR 44

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 972971476   7 CTICSDFFdhSKDVAAIHCGHTFHYDCLLQWFQSApSKTCPQCRKQV 53
Cdd:cd16503    5 CSICQDLL--HDCVSLQPCMHNFCAACYSDWMERS-NTECPTCRATV 48

Zinc finger, C3HC4 type (RING finger);

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 972971476    6 YCTICSDFFDHSKDVAAihCGHTFHYDCLLQWFQSapSKTCPQC 49
Cdd:pfam13923   1 MCPICMDMLKDPSTTTP--CGHVFCQDCILRALRA--GNECPLC 40

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 972971476   7 CTICSDFFDHSKDVAAIHCGHTFHYDCLLQWFQSapSKTCPQCRKQV 53
Cdd:cd16460    3 CVICHEAFSDGDRLLVLPCAHKFHTQCIGPWLDG--QQTCPTCRLHV 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 972971476   7 CTIC-SDFFDHSKDVAAIHCGHTFHYDCLLQWFQSapSKTCPQCR 50
Cdd:cd16461    2 CAIClSDYENGEELRRLPECKHAFHKECIDEWLKS--NSTCPLCR 44

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 972971476   7 CTICSDFF---DHSK-DVAAIHCGHTFHYDCLLQWFQSAPSKTCPQCR 50
Cdd:cd16491    3 CPICYSVIhgsNHSLpKLKCKTCKNKFHSACLYKWFRSSNKSTCPLCR 50

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 972971476   7 CTICSDFFdhsKDVAAIHCGHTFHYDCLLQWFQSApSKTCPQC 49
Cdd:cd16449    3 CPICLERL---KDPVLLPCGHVFCRECIRRLLESG-SIKCPIC 41

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 972971476  71 DSARVDPESLQNELDKFKALLSVKEKDRKGLQKVIEALRETVGRLNIDLECVKKELSEKDMLCAALRKQmkfLENQQset 150
Cdd:COG4942   30 EQLQQEIAELEKELAALKKEEKALLKQLAALERRIAALARRIRALEQELAALEAELAELEKEIAELRAE---LEAQK--- 103

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 972971476 151 qsaKEEARRLRT--KMKTYESLDLLLQGQrsEVEAMIRDMGVGQAAVEQLSIFCISLKKEYENLKISNKTSNEMCEKLKR 228
Cdd:COG4942  104 ---EELAELLRAlyRLGRQPPLALLLSPE--DFLDAVRRLQYLKYLAPARREQAEELRADLAELAALRAELEAERAELEA 178

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 972971476 229 EVFVSNNKLQKSALQVSRTKEELNAAQEDLKNADKQISSLQKKVEFLQKALSTPSRTNEAISRMVFESPAP 299
Cdd:COG4942  179 LLAELEEERAALEALKAERQKLLARLEKELAELAAELAELQQEAEELEALIARLEAEAAAAAERTPAAGFA 249

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

                          10        20
                  ....*....|....*....|....*.
gi 972971476   25 CGHTFHYDCLLQWFQSapSKTCPQCR 50
Cdd:pfam12678  32 CGHAFHLHCISRWLKT--NNTCPLCR 55

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 972971476   7 CTICSDFFDHSKDVAAIHCGHTFHYDCLLQWFQSapSKTCPQCR 50
Cdd:cd16667    2 CAVCKEDFEVGEEVRQLPCKHLFHPDCIVPWLEL--HNSCPVCR 43

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 972971476   7 CTICSDFFDHSKDVAAIHCGHTFHYDCLLQWFQSapSKTCPQCRKQVS 54
Cdd:cd16800    3 CPVCKEDYTVGEQVRQLPCNHFFHSDCIVPWLEL--HDTCPVCRKSLN 48

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 972971476    78 ESLQNELDKFKALLSVKEKDRKGLQKVIEALRETVGRLNIDLECVKKELSEK-DMLCAALRKQMKFLENQQSETQSAKEE 156
Cdd:TIGR02169  233 EALERQKEAIERQLASLEEELEKLTEEISELEKRLEEIEQLLEELNKKIKDLgEEEQLRVKEKIGELEAEIASLERSIAE 312

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 972971476   157 A-RRLRTKMKTYESLDLLLQGQRSEVEAMIRDMGVGQAAVEQLSIFCISLKKEYENL--------------KISNKTSNE 221
Cdd:TIGR02169  313 KeRELEDAEERLAKLEAEIDKLLAEIEELEREIEEERKRRDKLTEEYAELKEELEDLraeleevdkefaetRDELKDYRE 392

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 972971476   222 MCEKLKREVfvsnNKLQKSALQVSRTKEELNAAQEDLKNADKQISSLQKKVE 273
Cdd:TIGR02169  393 KLEKLKREI----NELKRELDRLQEELQRLSEELADLNAAIAGIEAKINELE 440

RING finger (Really Interesting New Gene) domain and U-box domain superfamily; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers: some have different Cys/His patterns while some lack a single Cys or His residue at typical Zn ligand positions (the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can indeed chelate Zn in a RING finger as well). C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type RING fingers are closely related to RING-HC fingers. In contrast, C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type RING fingers are more closely related to RING-H2 fingers. However, not all RING finger-containing proteins display regular RING finger features, and the RING finger family has turned out to be multifarious. The degenerate RING fingers of the Siz/PIAS RING (SP-RING) family proteins and sporulation protein RMD5, are characterized by lacking the second, fifth, and sixth Zn2+ ion-coordinating residues. They bind only one Zn2+ ion. On the other hand, the RING fingers of the human APC11 and RBX1 proteins can bind a third Zn atom since they harbor four additional Zn ligands. U-box is a modified form of the RING finger domain that lacks metal chelating Cys and His residues. It resembles the cross-brace RING structure consisting of three beta-sheets and a single alpha-helix, which would be stabilized by salt bridges instead of chelated metal ions. U-box proteins are widely distributed among eukaryotic organisms and show a higher prevalence in plants than in other organisms. RING finger/U-box-containing proteins are a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serve as scaffolds for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enable efficient transfer of ubiquitin from E2 to the substrates.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 972971476   7 CTICSDFFDHSKDVAAIHCGHTFHYDCLLQWfQSAPSKTCPQC 49
Cdd:cd00162    1 CPICREEMNDRRPVVLLSCGHTFSRSAIARW-LEGSKQKCPFC 42

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        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 972971476   7 CTICSDFFDHSkdvAAIHCGHTFHYDCLLQWFQSAPSktCPQCRKQVSTKHII 59
Cdd:cd16527    3 CSLCLEERRHP---TATPCGHLFCWSCITEWCNEKPE--CPLCREPFQPQRLV 50

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
                 ....*....|....*....|....*....|....*....|....
gi 972971476   7 CTICSDFfDHSKDVAAIHCGHTFHYDCLLQWFQSAPSKTCPQCR 50
Cdd:cd23120    4 CPICLEE-MNSGTGYLADCGHEFHLTCIREWHNKSGNLDCPICR 46

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 972971476    7 CTICSDFFDHskdvAAIHCGHTFHYDCLLQWFQSAPSK-TCP 47
Cdd:pfam13445   1 CPICLELFTD----PVLPCGHTFCRECLEEMSQKKGGKfKCP 38

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 972971476   7 CTIC-SDFFDHSKDVAAIHCGHTFHYDCLLQWFQSApSKTCPQCR 50
Cdd:cd23121    4 CAIClSDFNSDEKLRQLPKCGHIFHHHCLDRWIRYN-KITCPLCR 47

RING finger, H2 subclass, found in Arabidopsis thaliana RING-H2 zinc finger protein RHF2A and similar proteins; RHF2A is an E3 ubiquitin-protein ligase involved in the positive regulation of the gametogenesis progression. It is required for the degradation of KRP6, a cyclin-dependent kinase inhibitor which accumulates during meiosis and blocks the progression of subsequent mitoses during gametophytes development. It functions in association with RHF1A. Members of this subfamily contain a C3H2C3-type RING-H2 finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 972971476   7 CTICSDFFDHSKDVAAIHCGHTFHYDCLLQWFQSapSKTCPQCRKQVSTK 56
Cdd:cd23122   14 CSICLESFCEADPATVTSCKHEYHLQCILEWSQR--SKECPMCWQALSLK 61

RING finger, H2 subclass, found in RING finger protein 111 (RNF111) and similar proteins; RNF111, also known as Arkadia, is a nuclear E3 ubiquitin-protein ligase that targets intracellular effectors and modulators of transforming growth factor beta (TGF-beta)/Nodal-related signaling for polyubiquitination and proteasome-dependent degradation. It acts as an amplifier of Nodal signals, and enhances the dorsalizing activity of limiting amounts of Xnr1, a Nodal homolog, and requires Nodal signaling for its function. The loss of RNF111 results in early embryonic lethality, with defects attributed to compromised Nodal signaling. RNF111 also regulates tumor metastasis by modulation of the TGF-beta pathway. Its ubiquitination can be modulated by the four and a half LIM-only protein 2 (FHL2) that activates TGF-beta signal transduction. Furthermore, RNF111 interacts with the clathrin-adaptor 2 (AP2) complex and regulates endocytosis of certain cell surface receptors, leading to modulation of epidermal growth factor (EGF) and possibly other signaling pathways. In addition, RNF111 has been identified as a small ubiquitin-like modifier (SUMO)-binding protein with clustered SUMO-interacting motifs (SIMs) that together form a SUMO-binding domain (SBD). It thus functions as a SUMO-targeted ubiquitin ligase (STUbL) that directly links nonproteolytic ubiquitylation and SUMOylation in the DNA damage response, as well as triggers degradation of signal-induced polysumoylated proteins, such as the promyelocytic leukemia protein (PML). The N-terminal half of RNF111 harbors three SIMs. Its C-terminal half show high sequence similarity with RING finger protein 165 (RNF165), where it contains two serine rich domains, two nuclear localization signals, an NRG-TIER domain, and a C-terminal C3H2C3-type RING-H2 finger that is required for polyubiqutination and proteasome-dependent degradation of phosphorylated forms of Smad2/3 and three major negative regulators of TGF-beta signaling, Smad7, SnoN and c-Ski.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 972971476   7 CTICSDFFDHSKDVAAIHCGHTFHYDCLLQWFQSapSKTCPQCRKQVSTK 56
Cdd:cd16681   13 CTICLSILEEGEDVRRLPCMHLFHQVCVDQWLIT--NKKCPICRVDIEAQ 60

RING finger, HC subclass, found in topoisomerase I-binding arginine/serine-rich protein (Topors) and similar proteins; Topors, also known as topoisomerase I-binding RING finger protein, tumor suppressor p53- binding protein 3, or p53-binding protein 3 (p53BP3), is a ubiquitously expressed nuclear E3 ubiquitin-protein ligase that can ligate both ubiquitin and small ubiquitin-like modifier (SUMO) to substrate proteins in the nucleus. It contains an N-terminal C3HC4-type RING-HC finger which ligates ubiquitin to its target proteins including DNA topoisomerase I, p53, NKX3.1, H2AX, and the AAV-2 Rep78/68 proteins. As a RING-dependent E3 ubiquitin ligase, Topors works with the E2 enzymes UbcH5a, UbcH5c, and UbcH6, but not with UbcH7, CDC34, or UbcH2b. Topors acts as a tumor suppressor in various malignancies. It regulates p53 modification, suggesting it may be responsible for astrocyte elevated gene-1 (AEG-1, also known as metadherin, or LYRIC) ubiquitin modification. Plk1-mediated phosphorylation of Topors inhibits Topors-mediated sumoylation of p53, whereas p53 ubiquitination is enhanced, leading to p53 degradation. It also functions as a negative regulator of the prostate tumor suppressor NKX3.1. Moreover, Topors is associated with promyelocytic leukemia nuclear bodies, and may be involved in the cellular response to camptothecin. It also plays a key role in the turnover of H2AX protein, discriminating the type of DNA damaging stress. Furthermore, Topors is a cilia-centrosomal protein associated with autosomal dominant retinal degeneration. Mutations in TOPORS cause autosomal dominant retinitis pigmentosa (adRP).

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 972971476   7 CTICSDFFDHSKdvAAIH-CGHTFHYDCLLQWfqSAPSKTCPQCR 50
Cdd:cd16574    4 CPICLDRFENEK--AFLDgCFHAFCFTCILEW--SKVKNECPLCK 44

RING finger, HC subclass, found in Arabidopsis thaliana RING membrane-anchor proteins (AtRMAs) and similar proteins; AtRMAs, including AtRma1, AtRma2, and AtRma3, are endoplasmic reticulum (ER)-localized Arabidopsis homologs of human outer membrane of the ER-anchor E3 ubiquitin-protein ligase, RING finger protein 5 (RNF5). AtRMAs possess E3 ubiquitin ligase activity, and may play a role in the growth and development of Arabidopsis. The AtRMA1 and AtRMA3 genes are predominantly expressed in major tissues, such as cotyledons, leaves, shoot-root junction, roots, and anthers, while AtRMA2 expression is restricted to the root tips and leaf hydathodes. AtRma1 probably functions with the Ubc4/5 subfamily of E2. AtRma2 is likely involved in the cellular regulation of ABP1 expression levels through interacting with auxin binding protein 1 (ABP1). AtRMA proteins contain an N-terminal C3HC4-type RING-HC finger and a trans-membrane-anchoring domain in their extreme C-terminal region.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 972971476   7 CTICsdfFDHSKDVAAIHCGHTFHYDCLLQWFQSAPSKT-CPQCR 50
Cdd:cd16745    3 CNIC---LDLAQDPVVTLCGHLFCWPCLHKWLRRQSSQPeCPVCK 44

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 972971476   7 CTICSDFFDHSKDVAAIHCGHTFHYDCLLQWFQSApSKTCPQCR 50
Cdd:cd23123    3 CCICLDKLKTGEEVKKLDCRHKFHKQCIEGWLKHL-NFNCPLCR 45

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 972971476   7 CTICSDFFDHSKDVAAIHCGHTFHYDCLLQWFQSapSKTCPQCR 50
Cdd:cd16669    2 CPICLLEFEEGETVKQLPCKHSFHSDCILPWLGK--TNSCPLCR 43

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 972971476   7 CTICSDFFDHSKDVAAIHCGHTFHYDCLLQWFQSapSKTCPQCRKQV 53
Cdd:cd16676    3 CAVCLEDFKTKDELGVLPCQHAFHRKCLVKWLEI--RCVCPMCNKPI 47

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 972971476    68 GEEDSARVDPESLQNELDKFKALLSV-------KEKDRKGLQKVIEALRETVGRLNIDLECVKKELSEKDMLCAALRKQM 140
Cdd:TIGR02169  688 RELSSLQSELRRIENRLDELSQELSDasrkigeIEKEIEQLEQEEEKLKERLEELEEDLSSLEQEIENVKSELKELEARI 767

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 972971476   141 KFLENQQSETQSAKE--EARRLRTKMKTYESLDLLLQGQRSEVEAMIRDMgvgQAAVEQLSIFCISLKKEYENLKISNKT 218
Cdd:TIGR02169  768 EELEEDLHKLEEALNdlEARLSHSRIPEIQAELSKLEEEVSRIEARLREI---EQKLNRLTLEKEYLEKEIQELQEQRID 844

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 972971476   219 SNEMCEKLKREVFVSNNKLQKSALQVSRTKEELNAAQEDLKNADKQISSLQKKVEFLQKALSTPSRTNEAISRMVFESPA 298
Cdd:TIGR02169  845 LKEQIKSIEKEIENLNGKKEELEEELEELEAALRDLESRLGDLKKERDELEAQLRELERKIEELEAQIEKKRKRLSELKA 924

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 972971476   299 PLELKQPRLHQPEDSQDVDLSITFD----------------------------IETPEQQEKKSIPVPSKKMRLEPAESP 350
Cdd:TIGR02169  925 KLEALEEELSEIEDPKGEDEEIPEEelsledvqaelqrveeeiralepvnmlaIQEYEEVLKRLDELKEKRAKLEEERKA 1004

                          330
                   ....*....|....*
gi 972971476   351 TLRHIGNCSTEKKNS 365
Cdd:TIGR02169 1005 ILERIEEYEKKKREV 1019

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 972971476   7 CTICSDFFDHSKdvaAIHCGHTFHYDCLLQWFQSAPSktCPQCRKQV 53
Cdd:cd16455    3 CAICWESMQSAR---KLPCGHLFHNSCLRSWLEQDTS--CPTCRMSL 44

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 972971476   7 CTICSDFFDHSKDVAAIHCGHTFHYDCLLQWFQSapSKTCPQC 49
Cdd:cd16468    2 CVICMADFVVGDPIRYLPCMHIYHVDCIDDWLMR--SFTCPSC 42

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 972971476   7 CTICSDFFDHSKDVAAIHCGHTFHYDCLLQWFQSapSKTCPQC 49
Cdd:cd16798    6 CAICLEEFSEGQELRIISCSHEFHRECVDPWLHQ--HRTCPLC 46

RING finger, HC subclass, found in RING finger protein 166 (RNF166) and similar proteins; RNF166 is encoded by the gene RNF166 targeted by thyroid hormone receptor alpha1 (TRalpha1), which is important in brain development. It plays an important role in RNA virus-induced interferon-beta production by enhancing the ubiquitination of TRAF3 and TRAF6. RNF166, together with three closely related proteins: RNF114, RNF125 and RNF138, forms a novel family of ubiquitin ligases with a C3HC4-type RING-HC finger, a C2HC-, and two C2H2-type zinc fingers, as well as a ubiquitin interacting motif (UIM).

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 972971476   7 CTICSDFFdhSKDVAAIHCGHTFHYDCLLQWFQsAPSKTCPQCR 50
Cdd:cd16549    4 CPICLEVY--HKPVVITSCGHTFCGECLQPCLQ-VASPLCPLCR 44

RING finger, H2 subclass, found in Arabidopsis thaliana protein ABA INSENSITIVE RING PROTEIN 1 (AIRP1) and similar proteins; This subfamily includes Arabidopsis thaliana AIRP1 and RING-H2 finger B1a (RHB1A). AIRP1, also known as RING-type E3 ubiquitin transferase AIRP1, possesses E3 ubiquitin-protein ligase activity in vitro when associated with the E2 enzyme UBC8. It plays combinatory roles with AIRP2 in the positive regulation of the abscisic acid-mediated drought stress response. RHB1A is a probable E3 ubiquitin-protein ligase. Members of this subfamily contain a C3H2C3-type RING-H2 finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 972971476   7 CTICSDFFDHSKDVAAIHCGHTFHYDCLLQWFQSapSKTCPQCRKQV 53
Cdd:cd23116    5 CPTCLEGYTEENPKLLTKCGHHFHLACIYEWMER--SERCPVCDKEM 49