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 568997450 1800 SCEICHEIFKSKNMRVLKCGHKFHKGCFKQWLKGQSTCPTC 1840
Cdd:cd16481     1 PCIICHDDLKPDQLAKLECGHIFHKECIKQWLKEQSTCPTC 41

Outer membrane protein chaperone/metalloprotease BepA/YfgC, contains M48 and TPR domains [Cell wall/membrane/envelope biogenesis, Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997450  360 LRSLIQDGYTALLEQRCRSAAQAFTELLNgLDPqkikqlnlamiNYVLVVYGLAVSLLGIGRPEElseAENQFKRIIEHY 439
Cdd:COG4783     4 AEALYALAQALLLAGDYDEAEALLEKALE-LDP-----------DNPEAFALLGEILLQLGDLDE---AIVLLHEALELD 68

                          90       100       110
                  ....*....|....*....|....*....|...
gi 568997450  440 PNEGLdclAYCGIGKVYLKKNRFLEALNHFEKA 472
Cdd:COG4783    69 PDEPE---ARLNLGLALLKAGDYDEALALLEKA 98

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 568997450 1800 SCEICHEIFKSKNMRVLKCGHKFHKGCFKQWLKGQSTCPTC 1840
Cdd:cd16481     1 PCIICHDDLKPDQLAKLECGHIFHKECIKQWLKEQSTCPTC 41

Tetratricopeptide (TPR) repeat [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997450  107 RGNEEFSKEKFEIAVIYYTRAIEYRPENHLLYGNRALCFLRMGQFRNALSDGKRAIVLKNTWPKGHYRYCDALCMLGEYD 186
Cdd:COG0457    48 LGLAYLRLGRYEEALADYEQALELDPDDAEALNNLGLALQALGRYEEALEDYDKALELDPDDAEALYNLGLALLELGRYD 127

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 568997450  187 WALQANIKAQKLCKNDPEGIKDLIQQHVKLQKQIEDLQ 224
Cdd:COG0457   128 EAIEAYERALELDPDDADALYNLGIALEKLGRYEEALE 165

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 568997450   1801 CEICHEIFkSKNMRVLKCGHKFHKGCFKQWLK-GQSTCPTC 1840
Cdd:smart00184    1 CPICLEEY-LKDPVILPCGHTFCRSCIRKWLEsGNNTCPIC 40

mitochondrial precursor proteins import receptor (72 kDa mitochondrial outermembrane protein) (mitochondrial import receptor for the ADP/ATP carrier) (translocase of outermembrane tom70); [Transport and binding proteins, Amino acids, peptides and amines]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997450   104 MKMRGNEEFSKEKFEIAVIYYTRAIEYRPENhLLYGNRALCFLRMGQFRNALSDGKRAIVLKNTWPKGHYRYCDALCMLG 183
Cdd:TIGR00990  130 LKEKGNKAYRNKDFNKAIKLYSKAIECKPDP-VYYSNRAACHNALGDWEKVVEDTTAALELDPDYSKALNRRANAYDGLG 208

                   ....*.
gi 568997450   184 EYDWAL 189
Cdd:TIGR00990  209 KYADAL 214

MAEBL; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997450 1330 EVNTEPYEPFETQQGDLSQKEKECHLLREQLKVACE---NCEQIELRSSQEIKDLEEkLQRHTEENKISKTELDWFLQDL 1406
Cdd:PTZ00121 1595 EEVMKLYEEEKKMKAEEAKKAEEAKIKAEELKKAEEekkKVEQLKKKEAEEKKKAEE-LKKAEEENKIKAAEEAKKAEED 1673

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997450 1407 DR---EIKKWQQEKKEIQE---RLKALKKKIKKVINTSEMPAQKNDGFDKECEPHPDQSlgfssalTDEKTKVEESVRKG 1480
Cdd:PTZ00121 1674 KKkaeEAKKAEEDEKKAAEalkKEAEEAKKAEELKKKEAEEKKKAEELKKAEEENKIKA-------EEAKKEAEEDKKKA 1746

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997450 1481 KELYEESHQRAVAAEVSVLENWKEREVCKLQGVASQSEAYLKSLKLMSSDSATYPDVE---------------YDILSWE 1545
Cdd:PTZ00121 1747 EEAKKDEEEKKKIAHLKKEEEKKAEEIRKEKEAVIEEELDEEDEKRRMEVDKKIKDIFdnfaniieggkegnlVINDSKE 1826

                         250
                  ....*....|....*....
gi 568997450 1546 SFLSTVREEIESKKSQFEE 1564
Cdd:PTZ00121 1827 MEDSAIKEVADSKNMQLEE 1845

Tetratricopeptide repeat;

                           10        20
                   ....*....|....*....|....*...
gi 568997450   448 AYCGIGKVYLKKNRFLEALNHFEKAKTL 475
Cdd:pfam00515    3 ALYNLGNAYFKLGKYDEALEYYEKALEL 30

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 568997450 1800 SCEICHEIFKSKNMRVLKCGHKFHKGCFKQWLKGQSTCPTC 1840
Cdd:cd16481     1 PCIICHDDLKPDQLAKLECGHIFHKECIKQWLKEQSTCPTC 41

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 568997450 1801 CEICHEIFKSK-NMRVLKCGHKFHKGCFKQWLKGQSTCPTC 1840
Cdd:cd16460     3 CVICHEAFSDGdRLLVLPCAHKFHTQCIGPWLDGQQTCPTC 43

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 568997450 1801 CEICHEIFKSKN-MRVLKCGHKFHKGCFKQWLK-GQSTCPTC 1840
Cdd:cd16448     1 CVICLEEFEEGDvVRLLPCGHVFHLACILRWLEsGNNTCPLC 42

Tetratricopeptide (TPR) repeat [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997450  107 RGNEEFSKEKFEIAVIYYTRAIEYRPENHLLYGNRALCFLRMGQFRNALSDGKRAIVLKNTWPKGHYRYCDALCMLGEYD 186
Cdd:COG0457    82 LGLALQALGRYEEALEDYDKALELDPDDAEALYNLGLALLELGRYDEAIEAYERALELDPDDADALYNLGIALEKLGRYE 161

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 568997450  187 WALQANIKAQKLCKNDPEGIKDLIQQHVKLQKQIEDLQ 224
Cdd:COG0457   162 EALELLEKLEAAALAALLAAALGEAALALAAAEVLLAL 199

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 568997450   1801 CEICHEIFkSKNMRVLKCGHKFHKGCFKQWLK-GQSTCPTC 1840
Cdd:smart00184    1 CPICLEEY-LKDPVILPCGHTFCRSCIRKWLEsGNNTCPIC 40

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 568997450 1799 NSCEICHEIFKSKNMRvLKCGHKFHKGCFKQWLKGQSTCPTC 1840
Cdd:cd16479     2 NTCIICREEMTVGAKK-LPCGHIFHLSCLRSWLQRQQTCPTC 42

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 568997450 1797 DGNSCEICHEIFKSK-NMRV--LKCGHKFHKGCFKQWLKGQS-TCPTC 1840
Cdd:cd16450     1 EGNTCPICFEPWTSSgEHRLvsLKCGHLFGYSCIEKWLKGKGkKCPQC 48

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 568997450 1801 CEICHEIFK-SKNMRVLKCGHKFHKGCFKQWLKGQSTCPTC 1840
Cdd:cd16480     2 CTICSDFFDnSRDVAAIHCGHTFHYDCLLQWFDTSRTCPQC 42

RING finger, H2 subclass, found in RING finger proteins RNF24, RNF122, and similar proteins; This subfamily includes RNF24, RNF122, and similar proteins. RNF24 is an intrinsic membrane protein localized in the Golgi apparatus. It specifically interacts with the ankyrin-repeats domains (ARDs) of TRPC1, -3, -4, -5, -6, and -7, and affects TRPC intracellular trafficking without affecting their activity. RNF122 is a RING finger protein associated with HEK 293T cell viability. It is localized to the endoplasmic reticulum (ER) and the Golgi apparatus, and overexpressed in anaplastic thyroid cancer cells. RNF122 functions as an E3 ubiquitin ligase that can ubiquitinate itself and undergo degradation through its RING finger in a proteasome-dependent manner. Both RNF24 and RNF122 contain an N-terminal transmembrane domain and a C-terminal C3H2C3-type RING-H2 finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 568997450 1801 CEICHEIFKSKN-MRVLKCGHKFHKGCFKQWLKGQSTCPTCGSS 1843
Cdd:cd16469     3 CAVCLEEFKLKEeLGVCPCGHAFHTKCLKKWLEVRNSCPICKSP 46

RING finger, H2 subclass, found in RING finger protein 215 (RNF215) and similar proteins; This family includes uncharacterized protein RNF215 and similar proteins. Although its biological function remains unclear, RNF215 shares high sequence similarity with PA-TM-RING ubiquitin ligases, which have been characterized by containing an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 568997450 1800 SCEICHEIFKSKN-MRVLKCGHKFHKGCFKQWLKGQSTCPTC 1840
Cdd:cd16670     2 SCAVCLDQFYKNQcLRVLPCLHEFHRDCVDPWLLLQQTCPLC 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 568997450 1801 CEICHEIFKSknMRVLKCGHKFHKGCFKQWLKGQSTCPTC 1840
Cdd:cd16476     3 CAICYQEMKE--ARITPCNHFFHGLCLRKWLYVQDTCPLC 40

RING finger, H2 subclass, found in RING finger proteins RNF43, ZNRF3, and similar proteins; RNF43 and ZNRF3 (also known as RNF203) are transmembrane E3 ubiquitin-protein ligases that belong to the PA-TM-RING ubiquitin ligase family, characterized by containing an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C3H2C3-type RING-H2 finger followed by a long C-terminal region. Both RNF43 and RNF203 function as tumor suppressors involved in the regulation of Wnt/beta-catenin signaling. They negatively regulate Wnt signaling by interacting with complexes of frizzled (FZD) receptors and low-density lipoprotein receptor-related protein (LRP) 5/6, which leads to ubiquitination of FZD and endocytosis of the Wnt receptor. Dishevelled (DVL), a positive Wnt regulator, is required for ZNRF3/RNF43-mediated ubiquitination and degradation of FZD. They also associate with R-spondin 1 (RSPO1). This interaction may block FZD ubiquitination and enhances Wnt signaling.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 568997450 1800 SCEICHEIFKSKN-MRVLKCGHKFHKGCFKQWLKGQSTCPTC 1840
Cdd:cd16666     1 VCAICLEEYEEGQeLRVLPCQHEFHRKCVDPWLLQNHTCPLC 42

Outer membrane protein chaperone/metalloprotease BepA/YfgC, contains M48 and TPR domains [Cell wall/membrane/envelope biogenesis, Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997450  100 QGELMKMRGNEEFSKEKFEIAVIYYTRAIEYRPENHLLYGNRALCFLRMGQFRNALSDGKRAIVLKNTWPKGHYRYCDAL 179
Cdd:COG4783     3 CAEALYALAQALLLAGDYDEAEALLEKALELDPDNPEAFALLGEILLQLGDLDEAIVLLHEALELDPDEPEARLNLGLAL 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 568997450  180 CMLGEYDWALQANIKAQKLCKNDPEGIKDLIQQHVKLQKQIE 221
Cdd:COG4783    83 LKAGDYDEALALLEKALKLDPEHPEAYLRLARAYRALGRPDE 124

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 568997450 1801 CEICHEIFKSKN-MRVLKCGHKFHKGCFKQWLKGQSTCPTC 1840
Cdd:cd16474     3 CTICLSDFEEGEdVRRLPCMHLFHQECVDQWLSTNKRCPIC 43

first RING finger, H2 subclass, found in RING finger protein 32 (RNF32) and similar proteins; RNF32 is mainly expressed in testis spermatogenesis, most likely in spermatocytes and/or in spermatids, suggesting a possible role in sperm formation. RNF32 contains two C3H2C3-type RING-H2 fingers separated by an IQ domain of unknown function. Although the biological function of RNF32 remains unclear, proteins with double RING-H2 fingers may act as scaffolds for binding several proteins that function in the same pathway. This model corresponds to the first RING-H2 finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 568997450 1800 SCEICHEIFKSKNMRVLKCGHKFHKGCFKQWLK--GQSTCPTC 1840
Cdd:cd16677     1 PCPICLEDFGLQQQVLLSCSHVFHRACLESFERfsGKKTCPMC 43

RING finger, H2 subclass, found in RING finger protein 44 (RNF44) and similar proteins; RNF44 is an uncharacterized RING finger protein that shows high sequence similarity with RNF38, which is a nuclear E3 ubiquitin protein ligase that plays a role in regulating p53. RNF44 contains a coiled-coil motif, a KIL motif (Lys-X2-Ile/Leu-X2-Ile/Leu, X can be any amino acid), and a C3H2C2-type RING-H2 finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 568997450 1801 CEICHEIFKSKNM-RVLKCGHKFHKGCFKQWLKGQSTCPTC 1840
Cdd:cd16680    10 CVVCFSDFESRQLlRVLPCNHEFHTKCVDKWLKTNRTCPIC 50

RING finger, H2 subclass, found in RING finger protein 149 (RNF149) and similar proteins; RNF149, also known as DNA polymerase-transactivated protein 2, is an E3 ubiquitin-protein ligase that interacts with wild-type v-Raf murine sarcoma viral oncogene homolog B1 (BRAF), a RING domain-containing E3 ubiquitin ligase involved in control of gene transcription, translation, cytoskeletal organization, cell adhesion, and epithelial development. RNF149 induces the ubiquitination of wild-type BRAF and promotes its proteasome-dependent degradation. Mutated RNF149 has been found in some human breast, ovarian, and colorectal cancers. RNF149 contains an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 568997450 1800 SCEICHEIFKSKNM-RVLKCGHKFHKGCFKQWLKGQSTCPTC 1840
Cdd:cd16804     1 NCAVCIENYKSKDVvRILPCKHVFHRICIDPWLLEHRTCPMC 42

Outer membrane protein chaperone/metalloprotease BepA/YfgC, contains M48 and TPR domains [Cell wall/membrane/envelope biogenesis, Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997450  360 LRSLIQDGYTALLEQRCRSAAQAFTELLNgLDPqkikqlnlamiNYVLVVYGLAVSLLGIGRPEElseAENQFKRIIEHY 439
Cdd:COG4783     4 AEALYALAQALLLAGDYDEAEALLEKALE-LDP-----------DNPEAFALLGEILLQLGDLDE---AIVLLHEALELD 68

                          90       100       110
                  ....*....|....*....|....*....|...
gi 568997450  440 PNEGLdclAYCGIGKVYLKKNRFLEALNHFEKA 472
Cdd:COG4783    69 PDEPE---ARLNLGLALLKAGDYDEALALLEKA 98

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.

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gi 568997450 1800 SCEICHEIFKSKN-MRVLKCGHKFHKGCFKQWLKGQSTCPTC 1840
Cdd:cd16676     2 TCAVCLEDFKTKDeLGVLPCQHAFHRKCLVKWLEIRCVCPMC 43

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

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gi 568997450 1801 CEICHEIFK-SKNMRVLKCGHKFHKGCFKQWLKGQSTCPTC 1840
Cdd:cd16667     2 CAVCKEDFEvGEEVRQLPCKHLFHPDCIVPWLELHNSCPVC 42

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

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                  ....*....|....*....|....*....|....*....|.
gi 568997450 1801 CEICHEIFKSKN-MRVLKCGHKFHKGCFKQWLKGQSTCPTC 1840
Cdd:cd16468     2 CVICMADFVVGDpIRYLPCMHIYHVDCIDDWLMRSFTCPSC 42

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 568997450 1801 CEICHEIFKSKNMrvLKCGHKFHKGCFKQWLKGQSTCPTC 1840
Cdd:cd16547     6 CSICHGVLRCPVR--LSCSHIFCKKCILQWLKRQETCPCC 43

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

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gi 568997450 1797 DGNSCEIC-HEIFKSKNMRVLKCGHKFHKGCFKQWLKGQSTCPTCGSS 1843
Cdd:cd23115     3 DNERCVICrLEYEEGEDLLTLPCKHCYHSECIQQWLQINKVCPVCSAE 50

Tetratricopeptide (TPR) repeat [General function prediction only];

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568997450  128 IEYRPENHLLYGNRALCFLRMGQFRNALSDGKRAIVLKNTWPKGHYRYCDALCMLGEYDWALQANIKAQKLCKNDPE 204
Cdd:COG0457     1 LELDPDDAEAYNNLGLAYRRLGRYEEAIEDYEKALELDPDDAEALYNLGLAYLRLGRYEEALADYEQALELDPDDAE 77

mitochondrial precursor proteins import receptor (72 kDa mitochondrial outermembrane protein) (mitochondrial import receptor for the ADP/ATP carrier) (translocase of outermembrane tom70); [Transport and binding proteins, Amino acids, peptides and amines]

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997450   104 MKMRGNEEFSKEKFEIAVIYYTRAIEYRPENhLLYGNRALCFLRMGQFRNALSDGKRAIVLKNTWPKGHYRYCDALCMLG 183
Cdd:TIGR00990  130 LKEKGNKAYRNKDFNKAIKLYSKAIECKPDP-VYYSNRAACHNALGDWEKVVEDTTAALELDPDYSKALNRRANAYDGLG 208

                   ....*.
gi 568997450   184 EYDWAL 189
Cdd:TIGR00990  209 KYADAL 214

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 568997450 1799 NSCEICHEIFKSKN-MRVLKCGHKFHKGCFKQWLKGQSTCPTC 1840
Cdd:cd16802     1 DSCAVCIEPYKPNDvVRILTCNHLFHKNCIDPWLLEHRTCPMC 43

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.

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gi 568997450 1801 CEICHEIFKSKnmRVLKCGHKFHKGCFKQWLKGQSTCPTC 1840
Cdd:cd16684     5 CSICYQDMKSA--VITPCSHFFHAGCLKKWLYVQETCPLC 42

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 568997450 1800 SCEICHEIFKskNMRVLKCGHKFHKGCFKQWLK-GQSTCPTC 1840
Cdd:cd16449     2 ECPICLERLK--DPVLLPCGHVFCRECIRRLLEsGSIKCPIC 41

RING finger, HC subclass, found in Saccharomyces cerevisiae increased recombination centers protein 20 (IRC20) and similar proteins; IRC20 is an uncharacterized ATP-dependent helicase that is probably involved in a pathway contributing to genomic integrity. IRC20 contains a typical C3HC4-type RING-HC finger.