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 568997442 1931 SCEICHEIFKSKNMRVLKCGHKFHKGCFKQWLKGQSTCPTC 1971
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 568997442  491 LRSLIQDGYTALLEQRCRSAAQAFTELLNgLDPqkikqlnlamiNYVLVVYGLAVSLLGIGRPEElseAENQFKRIIEHY 570
Cdd:COG4783     4 AEALYALAQALLLAGDYDEAEALLEKALE-LDP-----------DNPEAFALLGEILLQLGDLDE---AIVLLHEALELD 68

                          90       100       110
                  ....*....|....*....|....*....|...
gi 568997442  571 PNEGLdclAYCGIGKVYLKKNRFLEALNHFEKA 603
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 568997442 1931 SCEICHEIFKSKNMRVLKCGHKFHKGCFKQWLKGQSTCPTC 1971
Cdd:cd16481     1 PCIICHDDLKPDQLAKLECGHIFHKECIKQWLKEQSTCPTC 41

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997442  238 RGNEEFSKEKFEIAVIYYTRAIEYRPENHLLYGNRALCFLRMGQFRNALSDGKRAIVLKNTWPKGHYRYCDALCMLGEYD 317
Cdd:COG0457    48 LGLAYLRLGRYEEALADYEQALELDPDDAEALNNLGLALQALGRYEEALEDYDKALELDPDDAEALYNLGLALLELGRYD 127

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 568997442  318 WALQANIKAQKLCKNDPEGIKDLIQQHVKLQKQIEDLQ 355
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 568997442   1932 CEICHEIFkSKNMRVLKCGHKFHKGCFKQWLK-GQSTCPTC 1971
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 568997442   235 MKMRGNEEFSKEKFEIAVIYYTRAIEYRPENhLLYGNRALCFLRMGQFRNALSDGKRAIVLKNTWPKGHYRYCDALCMLG 314
Cdd:TIGR00990  130 LKEKGNKAYRNKDFNKAIKLYSKAIECKPDP-VYYSNRAACHNALGDWEKVVEDTTAALELDPDYSKALNRRANAYDGLG 208

                   ....*.
gi 568997442   315 EYDWAL 320
Cdd:TIGR00990  209 KYADAL 214

MAEBL; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997442 1461 EVNTEPYEPFETQQGDLSQKEKECHLLREQLKVACE---NCEQIELRSSQEIKDLEEkLQRHTEENKISKTELDWFLQDL 1537
Cdd:PTZ00121 1595 EEVMKLYEEEKKMKAEEAKKAEEAKIKAEELKKAEEekkKVEQLKKKEAEEKKKAEE-LKKAEEENKIKAAEEAKKAEED 1673

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997442 1538 DR---EIKKWQQEKKEIQE---RLKALKKKIKKVINTSEMPAQKNDGFDKECEPHPDQSlgfssalTDEKTKVEESVRKG 1611
Cdd:PTZ00121 1674 KKkaeEAKKAEEDEKKAAEalkKEAEEAKKAEELKKKEAEEKKKAEELKKAEEENKIKA-------EEAKKEAEEDKKKA 1746

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997442 1612 KELYEESHQRAVAAEVSVLENWKEREVCKLQGVASQSEAYLKSLKLMSSDSATYPDVE---------------YDILSWE 1676
Cdd:PTZ00121 1747 EEAKKDEEEKKKIAHLKKEEEKKAEEIRKEKEAVIEEELDEEDEKRRMEVDKKIKDIFdnfaniieggkegnlVINDSKE 1826

                         250
                  ....*....|....*....
gi 568997442 1677 SFLSTVREEIESKKSQFEE 1695
Cdd:PTZ00121 1827 MEDSAIKEVADSKNMQLEE 1845

Tetratricopeptide repeat;

                           10        20
                   ....*....|....*....|....*...
gi 568997442   579 AYCGIGKVYLKKNRFLEALNHFEKAKTL 606
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 568997442 1931 SCEICHEIFKSKNMRVLKCGHKFHKGCFKQWLKGQSTCPTC 1971
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 568997442 1932 CEICHEIFKSK-NMRVLKCGHKFHKGCFKQWLKGQSTCPTC 1971
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 568997442 1932 CEICHEIFKSKN-MRVLKCGHKFHKGCFKQWLK-GQSTCPTC 1971
Cdd:cd16448     1 CVICLEEFEEGDvVRLLPCGHVFHLACILRWLEsGNNTCPLC 42

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997442  238 RGNEEFSKEKFEIAVIYYTRAIEYRPENHLLYGNRALCFLRMGQFRNALSDGKRAIVLKNTWPKGHYRYCDALCMLGEYD 317
Cdd:COG0457    82 LGLALQALGRYEEALEDYDKALELDPDDAEALYNLGLALLELGRYDEAIEAYERALELDPDDADALYNLGIALEKLGRYE 161

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 568997442  318 WALQANIKAQKLCKNDPEGIKDLIQQHVKLQKQIEDLQ 355
Cdd:COG0457   162 EALELLEKLEAAALAALLAAALGEAALALAAAEVLLAL 199

RING finger, H2 subclass, found in the PA-TM-RING ubiquitin ligase family; The PA-TM-RING family represents a group of transmembrane-type E3 ubiquitin ligases, which has been characterized by an N-terminal transient signal peptide, a PA (protease-associated) domain, a TM (transmembrane) domain, as well as a C-terminal C3H2C3-type RING-H2 finger domain. It includes RNF13, RNF167, ZNRF4 (zinc and RING finger 4), GRAIL (gene related to anergy in lymphocytes)/RNF128, RNF130, RNF133, RNF148, RNF149 and RNF150 (which are more closely related), as well as RNF43 and ZNRF3, which have substantially longer C-terminal tail extensions compared with the others. PA-TM-RING proteins are expressed at low levels in all mammalian tissues and species, but they are not present in yeast. They play a common regulatory role in intracellular trafficking/sorting, suggesting that abrogation of their function may result in dysregulation of cellular signaling events in cancer.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 568997442 1931 SCEICHEIFKSKNM-RVLKCGHKFHKGCFKQWLKGQSTCPTC 1971
Cdd:cd16454     1 TCAICLEEFKEGEKvRVLPCNHLFHKDCIDPWLEQHNTCPLC 42

Flp pilus assembly protein TadD, contains TPR repeats [Intracellular trafficking, secretion, and vesicular transport, Extracellular structures];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997442  243 FSKEKFEIAVIYYTRAIEYRPENHLLYGNRALCFLRMGQFRNALSDGKRAIVLKNTWPKGHYRYCDALCMLGEYDWALQA 322
Cdd:COG5010    65 NKLGDFEESLALLEQALQLDPNNPELYYNLALLYSRSGDKDEAKEYYEKALALSPDNPNAYSNLAALLLSLGQDDEAKAA 144

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 568997442 1928 DGNSCEICHEIFKSK-NMRV--LKCGHKFHKGCFKQWLKGQS-TCPTC 1971
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 568997442 1932 CEICHEIFK-SKNMRVLKCGHKFHKGCFKQWLKGQSTCPTC 1971
Cdd:cd16480     2 CTICSDFFDnSRDVAAIHCGHTFHYDCLLQWFDTSRTCPQC 42

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 568997442 1931 SCEICHEIFKSKNM--RVLKCGHKFHKGCFKQWLKGQSTCPTC 1971
Cdd:cd16461     1 ECAICLSDYENGEElrRLPECKHAFHKECIDEWLKSNSTCPLC 43

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 568997442 1931 SCEICHEIFKSKN-MRVLKCGHKFHKGCFKQWLKGQSTCPTC 1971
Cdd:cd16670     2 SCAVCLDQFYKNQcLRVLPCLHEFHRDCVDPWLLLQQTCPLC 43

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 568997442 1931 SCEICHEIFKSKN-MRVLKCGHKFHKGCFKQWLKGQSTCPTC 1971
Cdd:cd23118     2 TCTICLEDFEDGEkLRVLPCQHQFHSECVDQWLRRNPKCPVC 43

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 568997442 1931 SCEICHEIFKSKN-MRVLKCGHKFHKGCFKQWLKGQSTCPTC 1971
Cdd:cd16666     1 VCAICLEEYEEGQeLRVLPCQHEFHRKCVDPWLLQNHTCPLC 42

Modified RING finger, H2 subclass (C3H2C2D-type), found in zinc finger SWIM domain-containing protein 2 (ZSWIM2) and similar proteins; ZSWIM2, also known as MEKK1-related protein X (MEX) or ZZ-type zinc finger-containing protein 2, is a testis-specific E3 ubiquitin ligase that promotes death receptor-induced apoptosis through Fas, death receptor (DR) 3 and DR4 signaling. ZSWIM2 is self-ubiquitinated and targeted for degradation through the proteasome pathway. It acts as an E3 ubiquitin ligase, through the E2, Ub-conjugating enzymes UbcH5a, UbcH5c, or UbcH6. ZSWIM2 contains four putative zinc-binding domains including an N-terminal SWIM (SWI2/SNF2 and MuDR) domain critical for its ubiquitination, and two modified RING-H2 fingers separated by a ZZ zinc finger domain, which was required for interaction with UbcH5a and its self-association. This model corresponds to the second RING-H2 finger, which is not a canonical C3H2C3-type, but a modified C3H2C2D-type.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 568997442 1932 CEICHEIFK-SKNMRVLKCGHKFHKGCFKQWLKGQS-TCPTCG 1972
Cdd:cd16486     2 CRICLKAFQlGQHVRTLPCRHKFHRDCIDNWLLHSRnSCPIDG 44

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 568997442 1930 NSCEICHEIFKSKNM-RVLKCGHKFHKGCFKQWLKGQSTCPTC 1971
Cdd:cd16803     1 DHCAVCIEGYKQNDVvRILPCKHVFHKSCVDPWLNEHCTCPMC 43

RING finger, H2 subclass, found in RING finger proteins, RNF130, RNF149, RNF150 and similar proteins; This subfamily includes RING finger proteins, RNF130, RNF149 and RNF150, which belong to a larger PA-TM-RING ubiquitin ligase family that has been characterized by an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence. RNF130, also known as Goliath homolog (H-Goliath), is a paralog of RNF128. It is a transmembrane E3 ubiquitin-protein ligase expressed in leukocytes. It has a self-ubiquitination property and controls the development of T cell clonal anergy by ubiquitination. RNF133 is a testis-specific endoplasmic reticulum-associated E3 ubiquitin ligase that may play a role in sperm maturation through an ER-associated degradation (ERAD) pathway. RNF149, also known as DNA polymerase-transactivated protein 2, is an E3 ubiquitin-protein ligase that induces the ubiquitination of wild-type v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) and promotes its proteasome-dependent degradation. RNF150 polymorphisms may be associated with chronic obstructive pulmonary disease (COPD) risk in the Chinese population. This subfamily also includes Drosophila melanogaster protein goliath (d-goliath), also known as protein g1, which is one of the founding members of the group. It was originally identified as a transcription factor involved in the embryo mesoderm formation.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 568997442 1932 CEICHEIFKSKN-MRVLKCGHKFHKGCFKQWLKGQSTCPTC 1971
Cdd:cd16668     2 CAVCIEPYKPSDvIRILPCKHIFHKSCVDPWLLEHRTCPMC 42

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 568997442 1932 CEICHEIFKSKNM-RVLKCGHKFHKGCFKQWLKGQSTCPTC 1971
Cdd:cd16680    10 CVVCFSDFESRQLlRVLPCNHEFHTKCVDKWLKTNRTCPIC 50

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 568997442  237 MRGNEEFSKEKFEIAVIYYTRAIEYRPENHLLYGNRALCFLRMGQFRNALSDGKRAIVLKNTWPKGHYRYCDALCMLGEY 316
Cdd:COG4783    43 LLGEILLQLGDLDEAIVLLHEALELDPDEPEARLNLGLALLKAGDYDEALALLEKALKLDPEHPEAYLRLARAYRALGRP 122

                          90
                  ....*....|....*....
gi 568997442  317 DWALQAnikAQKLCKNDPE 335
Cdd:COG4783   123 DEAIAA---LEKALELDPD 138

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 568997442 1931 SCEICHEIFKSKNM-RVLKCGHKFHKGCFKQWLKGQSTCPTC 1971
Cdd:cd16804     1 NCAVCIENYKSKDVvRILPCKHVFHRICIDPWLLEHRTCPMC 42

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 568997442 1931 SCEICHEIFKSKN-MRVLKCGHKFHKGCFKQWLKGQSTCPTC 1971
Cdd:cd16676     2 TCAVCLEDFKTKDeLGVLPCQHAFHRKCLVKWLEIRCVCPMC 43

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 568997442 1928 DGNSCEICHEIFKSK-NMRVLKCGHKFHKGCFKQWLKGQSTCPTC 1971
Cdd:cd16472     1 DQTQCVVCMCDYEKRqLLRVLPCSHEFHAKCIDKWLKTNRTCPIC 45

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 568997442 1932 CEICHEIFKSKN-MRVLKCGHKFHKGCFKQWLKGQSTCPTC 1971
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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 568997442 1932 CEICHEIFKSKNMrvLKCGHKFHKGCFKQWLKGQSTCPTC 1971
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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997442 1928 DGNSCEIC-HEIFKSKNMRVLKCGHKFHKGCFKQWLKGQSTCPTCGSS 1974
Cdd:cd23115     3 DNERCVICrLEYEEGEDLLTLPCKHCYHSECIQQWLQINKVCPVCSAE 50

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568997442  259 IEYRPENHLLYGNRALCFLRMGQFRNALSDGKRAIVLKNTWPKGHYRYCDALCMLGEYDWALQANIKAQKLCKNDPE 335
Cdd:COG0457     1 LELDPDDAEAYNNLGLAYRRLGRYEEAIEDYEKALELDPDDAEALYNLGLAYLRLGRYEEALADYEQALELDPDDAE 77

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 568997442 1931 SCEICHEIF-KSKNMRVLKCGHKFHKGCFKQWLKGQSTCPTC 1971
Cdd:cd16669     1 KCPICLLEFeEGETVKQLPCKHSFHSDCILPWLGKTNSCPLC 42

RING finger, H2 subclass, found in RING finger protein 139 (RNF139) and similar proteins; RNF139, also known as translocation in renal carcinoma on chromosome 8 protein (TRC8), is an endoplasmic reticulum (ER)-resident multi-transmembrane protein that functions as a potent growth suppressor in mammalian cells, inducing G2/M arrest, decreased DNA synthesis and increased apoptosis. It is a tumor suppressor that has been implicated in a novel regulatory relationship linking the cholesterol/lipid biosynthetic pathway with cellular growth control. A mutation in RNF139 has been identified in families with hereditary renal (RCC) and thyroid cancers. RNF139 physically and functionally interacts with von Hippel-Lindau (VHL), which is part of an SCF related E3-ubiquitin ligase complex with "gatekeeper" function in renal carcinoma and is defective in most sporadic clear-cell renal cell carcinomas (ccRCC). It suppresses growth and functions with VHL in a common pathway. RNF139 also suppresses tumorigenesis by targeting heme oxygenase-1 for ubiquitination and degradation. Moreover, RNF139 is a target of Translin (TSN), a posttranscriptional regulator of genes transcribed by the transcription factor CREM-tau in postmeiotic male germ cells, suggesting a role of RNF139 in dysgerminoma. In addition, RNF139 forms an integral part of a novel multi-protein ER complex, containing MHC I, US2, and signal peptide peptidase, which is associated with the ER-associated degradation (ERAD) pathway. It is required for the ubiquitination of MHC class I molecules before dislocation from the ER. As a novel sterol-sensing ER membrane protein, RNF139 hinders sterol regulatory element-binding protein-2 (SREBP-2) processing through interaction with SREBP-2 and SREBP cleavage-activated protein (SCAP), regulating its own turnover rate via its E3 ubiquitin ligase activity. RNF139 shows two regions of similarity with the receptor for sonic hedgehog (SHH), Patched. The first region corresponds to the second extracellular domain of Patched, which is involved in binding SHH. The second region is a putative sterol-sensing domain (SSD). The C-terminal half of RNF139 contains a C3H2C3-type RING-H2 finger with E3-ubiquitin ligase activity in vitro.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 568997442 1932 CEICHEIFKSkNMRVLKCGHKFHKGCFKQWLKGQSTCPTC 1971
Cdd:cd16683     7 CAICYQEFTT-SARITPCNHYFHALCLRKWLYIQDTCPMC 45

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 568997442 1930 NSCEIC-HEIFKSKNMRVLKCGHKFHKGCFKQWLKGQS-TCPTCGS 1973
Cdd:cd23123     1 SDCCIClDKLKTGEEVKKLDCRHKFHKQCIEGWLKHLNfNCPLCRS 46

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 568997442 1931 SCEICHEIFKSKNmrVLKCGHKFHKGCFKQWLKGQSTCPTC 1971
Cdd:cd23135     5 SCSICFSEIRSGA--ILKCGHFFCLSCIASWLREKSTCPLC 43

Zinc finger, C3HC4 type (RING finger);

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 568997442  1932 CEICHEIFKSKnMRVLKCGHKFHKGCFKQWLKGQSTCPTC 1971
Cdd:pfam13923    2 CPICMDMLKDP-STTTPCGHVFCQDCILRALRAGNECPLC 40