E3 ubiquitin-protein ligase TTC3/DZIP3 domain; This domain is found in E3 ubiquitin-protein ligases TTC3 and DZIP3 and its function is unknown. TTC3 mediates ubiquitination and degradation of phosphorylated Akt, apparently its preferable target. DZIP3 is also able to bind RNA through a Lys-rich region which enhances is ubiquitination activity. It is suggested that RNA-binding proteins or ribonucleoprotein particles might be physiological targets for this enzyme, which could be important during viral infections, especially for those replicating through RNA intermediates. This domain is also found in uncharacterized proteins found in viruses.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720386819  221 IEESKPEKVKVMLEKFVEECKFPPVPDAVCCYQKCRGYSKIQIYLTDPDFKGFIRISCCQYCKVEFHMNCWKKLKTTTFN 300
Cdd:pfam19179    1 IEETQPEKLKELLESLIELCKFPPKPDAVCRYQKCLGHSKIEIYFTDPDFKGFIRVSCCQSCKVEFHINCWKKLKTTSFS 80

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1720386819  301 DKIDKDFLQGICLTPDCEGIISKIIIYSSGGQVKCE 336
Cdd:pfam19179   81 DKNDKDFLQESCLTPDCRGQICKIVIFGSTGLVKCE 116

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 1720386819   89 LRSLIQDGYTALLEQRCRSAAQAFTELLNgLDPqkikqlnlamiNYVLVVYGLAVSLLGIGRPEElseAENQFKRIIEHY 168
Cdd:COG4783      4 AEALYALAQALLLAGDYDEAEALLEKALE-LDP-----------DNPEAFALLGEILLQLGDLDE---AIVLLHEALELD 68

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1720386819  169 PNEGLdclAYCGIGKVYLKKNRFLEALNHFEKA 201
Cdd:COG4783     69 PDEPE---ARLNLGLALLKAGDYDEALALLEKA 98

E3 ubiquitin-protein ligase TTC3/DZIP3 domain; This domain is found in E3 ubiquitin-protein ligases TTC3 and DZIP3 and its function is unknown. TTC3 mediates ubiquitination and degradation of phosphorylated Akt, apparently its preferable target. DZIP3 is also able to bind RNA through a Lys-rich region which enhances is ubiquitination activity. It is suggested that RNA-binding proteins or ribonucleoprotein particles might be physiological targets for this enzyme, which could be important during viral infections, especially for those replicating through RNA intermediates. This domain is also found in uncharacterized proteins found in viruses.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720386819  221 IEESKPEKVKVMLEKFVEECKFPPVPDAVCCYQKCRGYSKIQIYLTDPDFKGFIRISCCQYCKVEFHMNCWKKLKTTTFN 300
Cdd:pfam19179    1 IEETQPEKLKELLESLIELCKFPPKPDAVCRYQKCLGHSKIEIYFTDPDFKGFIRVSCCQSCKVEFHINCWKKLKTTSFS 80

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1720386819  301 DKIDKDFLQGICLTPDCEGIISKIIIYSSGGQVKCE 336
Cdd:pfam19179   81 DKNDKDFLQESCLTPDCRGQICKIVIFGSTGLVKCE 116

Ring finger domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1720386819 1528 NSCEICHEIF-KSKNMRVLKCGHKFHKGCFKQWLKGQSTCPTC 1569
Cdd:pfam13639    1 DECPICLEEFeEGDKVVVLPCGHHFHRECLDKWLRSSNTCPLC 43

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 1720386819   89 LRSLIQDGYTALLEQRCRSAAQAFTELLNgLDPqkikqlnlamiNYVLVVYGLAVSLLGIGRPEElseAENQFKRIIEHY 168
Cdd:COG4783      4 AEALYALAQALLLAGDYDEAEALLEKALE-LDP-----------DNPEAFALLGEILLQLGDLDE---AIVLLHEALELD 68

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1720386819  169 PNEGLdclAYCGIGKVYLKKNRFLEALNHFEKA 201
Cdd:COG4783     69 PDEPE---ARLNLGLALLKAGDYDEALALLEKA 98

MAEBL; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720386819 1059 EVNTEPYEPFETQQGDLSQKEKECHLLREQLKVACE---NCEQIELRSSQEIKDLEEkLQRHTEENKISKTELDWFLQDL 1135
Cdd:PTZ00121  1595 EEVMKLYEEEKKMKAEEAKKAEEAKIKAEELKKAEEekkKVEQLKKKEAEEKKKAEE-LKKAEEENKIKAAEEAKKAEED 1673

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720386819 1136 DR---EIKKWQQEKKEIQE---RLKALKKKIKKVINTSEMPAQKNDGFDKECEPHPDQSlgfssalTDEKTKVEESVRKG 1209
Cdd:PTZ00121  1674 KKkaeEAKKAEEDEKKAAEalkKEAEEAKKAEELKKKEAEEKKKAEELKKAEEENKIKA-------EEAKKEAEEDKKKA 1746

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720386819 1210 KELYEESHQRAVAAEVSVLENWKEREVCKLQGVASQSEAYLKSLKLMSSDSATYPDVE---------------YDILSWE 1274
Cdd:PTZ00121  1747 EEAKKDEEEKKKIAHLKKEEEKKAEEIRKEKEAVIEEELDEEDEKRRMEVDKKIKDIFdnfaniieggkegnlVINDSKE 1826

                          250
                   ....*....|....*....
gi 1720386819 1275 SFLSTVREEIESKKSQFEE 1293
Cdd:PTZ00121  1827 MEDSAIKEVADSKNMQLEE 1845

Tetratricopeptide repeat;

                           10        20
                   ....*....|....*....|....*...
gi 1720386819  177 AYCGIGKVYLKKNRFLEALNHFEKAKTL 204
Cdd:pfam00515    3 ALYNLGNAYFKLGKYDEALEYYEKALEL 30

E3 ubiquitin-protein ligase TTC3/DZIP3 domain; This domain is found in E3 ubiquitin-protein ligases TTC3 and DZIP3 and its function is unknown. TTC3 mediates ubiquitination and degradation of phosphorylated Akt, apparently its preferable target. DZIP3 is also able to bind RNA through a Lys-rich region which enhances is ubiquitination activity. It is suggested that RNA-binding proteins or ribonucleoprotein particles might be physiological targets for this enzyme, which could be important during viral infections, especially for those replicating through RNA intermediates. This domain is also found in uncharacterized proteins found in viruses.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720386819  221 IEESKPEKVKVMLEKFVEECKFPPVPDAVCCYQKCRGYSKIQIYLTDPDFKGFIRISCCQYCKVEFHMNCWKKLKTTTFN 300
Cdd:pfam19179    1 IEETQPEKLKELLESLIELCKFPPKPDAVCRYQKCLGHSKIEIYFTDPDFKGFIRVSCCQSCKVEFHINCWKKLKTTSFS 80

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1720386819  301 DKIDKDFLQGICLTPDCEGIISKIIIYSSGGQVKCE 336
Cdd:pfam19179   81 DKNDKDFLQESCLTPDCRGQICKIVIFGSTGLVKCE 116

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 1720386819 1530 CEICHEIFKSK-NMRVLKCGHKFHKGCFKQWLKGQSTCPTC 1569
Cdd:cd16460      3 CVICHEAFSDGdRLLVLPCAHKFHTQCIGPWLDGQQTCPTC 43

Ring finger domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1720386819 1528 NSCEICHEIF-KSKNMRVLKCGHKFHKGCFKQWLKGQSTCPTC 1569
Cdd:pfam13639    1 DECPICLEEFeEGDKVVVLPCGHHFHRECLDKWLRSSNTCPLC 43

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 1720386819 1529 SCEICHEIFKSKNM-RVLKCGHKFHKGCFKQWLKGQSTCPTC 1569
Cdd:cd16454      1 TCAICLEEFKEGEKvRVLPCNHLFHKDCIDPWLEQHNTCPLC 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 1720386819 1526 DGNSCEICHEIFKSK-NMRV--LKCGHKFHKGCFKQWLKGQS-TCPTC 1569
Cdd:cd16450      1 EGNTCPICFEPWTSSgEHRLvsLKCGHLFGYSCIEKWLKGKGkKCPQC 48

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 1720386819 1529 SCEICHEIFKSKNM--RVLKCGHKFHKGCFKQWLKGQSTCPTC 1569
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 1720386819 1529 SCEICHEIFKSKN-MRVLKCGHKFHKGCFKQWLKGQSTCPTC 1569
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 1720386819 1530 CEICHEIFKSknMRVLKCGHKFHKGCFKQWLKGQSTCPTC 1569
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 1720386819 1529 SCEICHEIFKSKN-MRVLKCGHKFHKGCFKQWLKGQSTCPTC 1569
Cdd:cd16666      1 VCAICLEEYEEGQeLRVLPCQHEFHRKCVDPWLLQNHTCPLC 42

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 1720386819 1528 NSCEICHEIFKSKNM-RVLKCGHKFHKGCFKQWLKGQSTCPTC 1569
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 1720386819 1530 CEICHEIFKSKN-MRVLKCGHKFHKGCFKQWLKGQSTCPTC 1569
Cdd:cd16668      2 CAVCIEPYKPSDvIRILPCKHIFHKSCVDPWLLEHRTCPMC 42

RING finger, H2 subclass, found in p53-induced RING-H2 protein (Pirh2) and similar proteins; Pirh2, also known as RING finger and CHY zinc finger domain-containing protein 1 (Rchy1), androgen receptor N-terminal-interacting protein, CH-rich-interacting match with PLAG1, RING finger protein 199 (RNF199), or zinc finger protein 363 (ZNF363), is a p53 inducible E3 ubiquitin-protein ligase that functions as a negative regulator of p53. It preferably ubiquitylates the tetrameric form of p53 in vitro and in vivo, suggesting a role of Pirh2 in downregulating the transcriptionally active form of p53 in the cell. Moreover, Pirh2 inhibits the transcriptional activity of p73, a homolog of the tumor suppressor p53, by promoting its ubiquitination. It also monoubiquitinates DNA polymerase eta (PolH) to suppress translesion DNA synthesis. Furthermore, Pirh2 functions as a negative regulator of the cyclin-dependent kinase inhibitor p27(Kip1) function by promoting ubiquitin-dependent proteasomal degradation. Pirh2 enhances androgen receptor (AR) signaling through inhibition of histone deacetylase 1 (HDAC1) and is overexpressed in prostate cancer. It interacts with TIP60 and this association may regulate Pirh2 stability. In addition, the oncoprotein pleomorphic adenoma gene like 2 (PLAGL2) can bind to the Pirh2 dimer and therefore control the stability of Pirh2. Pirh2 contains a total of nine zinc-binding sites with six located at the N-terminal region, two in the C3H2C3-type RING-H2 domain, and one in the C-terminal region. Nine zinc binding sites comprise three different zinc coordination schemes, including RING type cross-brace zinc coordination, C4 zinc finger, and a novel left-handed beta-spiral zinc-binding motif formed by three recurrent CCHC sequence motifs. This subfamily also includes Drosophila melanogaster Deltex, a ubiquitously expressed cytoplasmic ubiquitin E3 ligase that mediates Notch activation in Drosophila. It selectively suppresses T-cell activation through degradation of a key signaling molecule, MAP kinase kinase kinase 1 (MEKK1). It also inhibits Jun-mediated transcription at the stage of Ras-dependent Jun N-terminal protein kinase (JNK) activation. Deltex contains N-terminal two Notch-binding WWE domains that physically interact with the Notch ankyrin domains, a proline-rich motif that shares homology with SH3-binding domains, and a RING finger at the C-terminus.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1720386819 1530 CEICHE-IFKSK-NMRVLKCGHKFHKGCFKQWLKGQS-TCPTCG 1570
Cdd:cd16464      2 CPVCLEdLFTSRePVHVLPCGHLMHSTCFEEYLKSGNyRCPLCS 45

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 1720386819 1530 CEICHEIFKSKNM-RVLKCGHKFHKGCFKQWLKGQSTCPTC 1569
Cdd:cd16680     10 CVVCFSDFESRQLlRVLPCNHEFHTKCVDKWLKTNRTCPIC 50

RING finger, H2 subclass, found in Arabidopsis thaliana MED25-binding RING-H2 protein (MBR) and similar proteins; This subfamily includes MBR1 and MBR2 (also called HAL3-interacting protein 1 or AtHIP1). They are E3 ubiquitin-protein ligases that function as regulators of MED25 stability by targeting MED25 for degradation in a RING-H2-dependent manner. Proteasome-dependent degradation of MED25 seems to activate its function as a positive regulator of FLOWERING LOCUS T (FT) and is important to induce the expression of FT, and consequently to promote flowering. MBR2 may also function downstream of HAL3 and be required for HAL3-regulated plant growth. Activation of MBR2 by HAL3 may lead to the degradation of cell cycle suppressors, resulting in enhancement of cell division and plant growth. Both MBR1 and MBR2 contain a C3H2C3-type RING-H2 finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1720386819 1530 CEICHEIF-KSKNMRVLKCGHKFHKGCFKQWLKGQSTCPTCGSSDL 1574
Cdd:cd23113      5 CCICQEEYeEGDELGTIECGHEYHSDCIKQWLVQKNLCPICKATAL 50

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 1720386819 1529 SCEICHEIFKSKN-MRVLKCGHKFHKGCFKQWLKGQSTCPTC 1569
Cdd:cd16676      2 TCAVCLEDFKTKDeLGVLPCQHAFHRKCLVKWLEIRCVCPMC 43

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 1720386819 1530 CEICHEIFKSKN-MRVLKCGHKFHKGCFKQWLKGQSTCPTC 1569
Cdd:cd16468      2 CVICMADFVVGDpIRYLPCMHIYHVDCIDDWLMRSFTCPSC 42

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 1720386819 1546 KCGHKFHKGCFKQWLKGQSTCPTC 1569
Cdd:pfam12678   31 ECGHAFHLHCISRWLKTNNTCPLC 54

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 1720386819 1530 CEICHEIFKS-KNMRVLKCGHKFHKGCFKQWLKGQSTCPTC 1569
Cdd:cd16798      6 CAICLEEFSEgQELRIISCSHEFHRECVDPWLHQHRTCPLC 46

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1720386819 1517 QKKDDVpapdgnsCEICHEIFKSkNMRVLKCGHKFHKGCFKQWLKGQSTCPTC 1569
Cdd:cd16683      1 REIDDV-------CAICYQEFTT-SARITPCNHYFHALCLRKWLYIQDTCPMC 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 1720386819 1529 SCEICHEIF-KSKNMRVLKCGHKFHKGCFKQWLKGQSTCPTC 1569
Cdd:cd16669      1 KCPICLLEFeEGETVKQLPCKHSFHSDCILPWLGKTNSCPLC 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.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1720386819 1529 SCEICHEIFKskNMRVLKCGHKFHKGCFKQWLK-GQSTCPTC 1569
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.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 1720386819 1529 SCEICHEIFKSKNmrVLKCGHKFHKGCFKQWLKGQSTCPTC 1569
Cdd:cd23135      5 SCSICFSEIRSGA--ILKCGHFFCLSCIASWLREKSTCPLC 43

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 1720386819 1528 NSCEIC-HEIFKSKNMRVLKCGHKFHKGCFKQWLKGQS-TCPTCGS 1571
Cdd:cd23123      1 SDCCIClDKLKTGEEVKKLDCRHKFHKQCIEGWLKHLNfNCPLCRS 46

RING finger, H2 subclass, found in RING finger protein 126 (RNF126) 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). Moreover, 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. In addition, RNF126 and the related protein, RNF115 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. RNF126 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 1720386819 1530 CEICHEIFK-SKNMRVLKCGHKFHKGCFKQWLKGQSTCPTC 1569
Cdd:cd16801      2 CPVCKEDYTvGENVRQLPCNHLFHNDCIVPWLEQHDTCPVC 42

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1720386819 1529 SCEIC-HEIFKSKNMRVLKCGHKFHKGCFKQWLKGQSTCPTC 1569
Cdd:cd16465      1 CCPICcSEYVKDEIATELPCHHLFHKPCITAWLQKSGTCPVC 42

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720386819   96 GYTALLEQRCRSAAQAFTELLNgLDPqkikqlnlamiNYVLVVYGLAVSLLGIGRPEElseAENQFKRIIEHYPNeglDC 175
Cdd:COG0457     15 GLAYRRLGRYEEAIEDYEKALE-LDP-----------DDAEALYNLGLAYLRLGRYEE---ALADYEQALELDPD---DA 76

                           90       100
                   ....*....|....*....|....*.
gi 1720386819  176 LAYCGIGKVYLKKNRFLEALNHFEKA 201
Cdd:COG0457     77 EALNNLGLALQALGRYEEALEDYDKA 102

RING finger, H2 subclass, found in E3 ubiquitin-protein ligase RNF6 and similar proteins; RNF6 is an androgen receptor (AR)-associated protein that induces AR ubiquitination and promotes AR transcriptional activity. RNF6-induced ubiquitination may regulate AR transcriptional activity and specificity by modulating cofactor recruitment. RNF6 is overexpressed in hormone-refractory human prostate cancer tissues and required for prostate cancer cell growth under androgen-depleted conditions. Moreover, RNF6 regulates local serine/threonine kinase LIM kinase 1 (LIMK1) levels in axonal growth cones. RNF6-induced LIMK1 polyubiquitination is mediated via K48 of ubiquitin and leads to proteasomal degradation of the kinase. RNF6 also binds and upregulates the Inha promoter, and functions as a transcription regulatory protein in the mouse sertoli cell. RNF6 also acts as a potential tumor suppressor gene involved in the pathogenesis of esophageal squamous cell carcinoma (ESCC). RNF6 contains an N-terminal coiled-coil domain, a Lys-X-X-Leu/Ile-X-X-Leu/Ile (KIL) motif, and a C-terminal C3H2C3-type RING-H2 finger which is responsible for its ubiquitin ligase activity. The KIL motif is present in a subset of RING-H2 proteins from organisms as evolutionarily diverse as human, mouse, chicken, Drosophila, Caenorhabditis elegans, and Arabidopsis thaliana.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1720386819 1529 SCEIC-HEIFKSKNMRVLKCGHKFHKGCFKQWLKGQSTCPTC 1569
Cdd:cd16673      2 TCSVCiNEYATGNKLRRLPCAHEFHIHCIDRWLSENSTCPIC 43

RING finger, H2 subclass, found in RING finger protein 12 (RNF12) and similar proteins; RNF12, also known as LIM domain-interacting RING finger protein or RING finger LIM domain-binding protein (R-LIM), is an E3 ubiquitin-protein ligase encoded by gene RLIM that is crucial for normal embryonic development in some species and for normal X inactivation in mice. It thus functions as a major sex-specific epigenetic regulator of female mouse nurturing tissues. RNF12 is widely expressed during embryogenesis, and mainly localizes to the cell nucleus, where it regulates the levels of many proteins, including CLIM, LMO, HDAC2, TRF1, SMAD7, and REX1, by proteasomal degradation. Its functional activity is regulated by phosphorylation-dependent nucleocytoplasmic shuttling. It is negatively regulated by pluripotency factors in embryonic stem cells. p53 represses its transcription through Sp1. RNF12 is the primary factor responsible for X chromosome inactivation (XCI) in female placental mammals. It is an indispensable factor in up-regulation of Xist transcription, thereby leading to initiation of random XCI. It also targets REX1, an inhibitor of XCI, for proteasomal degradation. RNF12 also acts as a co-regulator for a range of transcription factors, particularly those containing a LIM homeodomain, and modulates the formation of transcriptional multiprotein complexes. It is a negative regulator of Smad7, which in turn negatively regulates the signaling of type I receptors from the transforming growth factor beta (TGF-beta) superfamily. In addition, paternal RNF12 is a critical survival factor for milk-producing alveolar cells. RNF12 contains an nuclear localization signal (NLS) and a C3H2C3-type RING-H2 finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1720386819 1529 SCEIC-HEIFKSKNMRVLKCGHKFHKGCFKQWLKGQSTCPTCGSSDLLS 1576
Cdd:cd16674      2 TCSVCiTEYTEGNKLRKLPCSHEYHVHCIDRWLSENSTCPICRRAVLAS 50

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 1720386819 1526 DGNSCEICHEIFKSKNMRVL-KCGHKFHKGCFKQWLKGQSTCPTCGS 1571
Cdd:cd23116      1 DEDVCPTCLEGYTEENPKLLtKCGHHFHLACIYEWMERSERCPVCDK 47

RING finger, H2 subclass, found in RING finger protein 24 (RNF24) and similar proteins; RNF24 is an intrinsic membrane protein localized in the Golgi apparatus. It specifically interacts with the ankyrin-repeats domains (ARDs) of TRPC1, -3, -4, -5, -6, and -7, and affects TRPC intracellular trafficking without affecting their activity. RNF24 contains an N-terminal transmembrane domain and a C-terminal C3H2C3-type RING-H2 finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 1720386819 1530 CEICHEIFKSKN-MRVLKCGHKFHKGCFKQWLKGQSTCPTC 1569
Cdd:cd16675      3 CAVCLEEFKPKDeLGICPCKHAFHRKCLIKWLEVRKVCPLC 43

MAEBL; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720386819 1059 EVNTEPYEPFETQQGDLSQKEKECHLLREQLKVACE---NCEQIELRSSQEIKDLEEkLQRHTEENKISKTELDWFLQDL 1135
Cdd:PTZ00121  1595 EEVMKLYEEEKKMKAEEAKKAEEAKIKAEELKKAEEekkKVEQLKKKEAEEKKKAEE-LKKAEEENKIKAAEEAKKAEED 1673

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720386819 1136 DR---EIKKWQQEKKEIQE---RLKALKKKIKKVINTSEMPAQKNDGFDKECEPHPDQSlgfssalTDEKTKVEESVRKG 1209
Cdd:PTZ00121  1674 KKkaeEAKKAEEDEKKAAEalkKEAEEAKKAEELKKKEAEEKKKAEELKKAEEENKIKA-------EEAKKEAEEDKKKA 1746

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720386819 1210 KELYEESHQRAVAAEVSVLENWKEREVCKLQGVASQSEAYLKSLKLMSSDSATYPDVE---------------YDILSWE 1274
Cdd:PTZ00121  1747 EEAKKDEEEKKKIAHLKKEEEKKAEEIRKEKEAVIEEELDEEDEKRRMEVDKKIKDIFdnfaniieggkegnlVINDSKE 1826

                          250
                   ....*....|....*....
gi 1720386819 1275 SFLSTVREEIESKKSQFEE 1293
Cdd:PTZ00121  1827 MEDSAIKEVADSKNMQLEE 1845

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720386819   96 GYTALLEQRCRSAAQAFTELLNgLDPqkikqlnlamiNYVLVVYGLAVSLLGIGRPEElseAENQFKRIIEHYPNeglDC 175
Cdd:COG0457     49 GLAYLRLGRYEEALADYEQALE-LDP-----------DDAEALNNLGLALQALGRYEE---ALEDYDKALELDPD---DA 110

                           90       100
                   ....*....|....*....|....*.
gi 1720386819  176 LAYCGIGKVYLKKNRFLEALNHFEKA 201
Cdd:COG0457    111 EALYNLGLALLELGRYDEAIEAYERA 136

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 1720386819 1530 CEICHEIFKSKNMRVLK-----CGHKFHKGCFKQWLK--GQSTCPTC 1569
Cdd:cd16491      3 CPICYSVIHGSNHSLPKlkcktCKNKFHSACLYKWFRssNKSTCPLC 49

RING finger, H2 subclass, found in RING finger protein 167 (RNF167) and similar proteins; RNF167, also known as RING105, is an endosomal/lysosomal E3 ubiquitin-protein ligase involved in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) ubiquitination. It ubiquitinates AMPA-type glutamate receptor subunit GluA2 and regulates its surface expression, and thus acts as a selective regulator of AMPAR-mediated neurotransmission. It acts as an endosomal membrane protein which ubiquitylates vesicle-associated membrane protein 3 (VAMP3) and regulates endosomal trafficking. Moreover, RNF167 plays a role in the regulation of TSSC5 (tumor-suppressing subchromosomal transferable fragment cDNA, also known as ORCTL2/IMPT1/BWR1A/SLC22A1L), which can function in concert with the ubiquitin-conjugating enzyme UbcH6. RNF167 is widely conserved in metazoans and contains an N-terminal signal peptide, a protease-associated (PA) domain, two transmembrane domains (TM1 and TM2), and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1720386819 1530 CEICHEIFKSKN-MRVLKCGHKFHKGCFKQWL-KGQSTCPTC 1569
Cdd:cd16797      3 CAICLDEYEEGDkLRVLPCSHAYHSKCVDPWLtQTKKTCPVC 44

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 1720386819 1528 NSCEICHEIFKS--KNMRVLKCGHKFHKGCFKQWLK-GQSTCPTC 1569
Cdd:cd23121      2 DCCAICLSDFNSdeKLRQLPKCGHIFHHHCLDRWIRyNKITCPLC 46