Soluble N-ethylmaleimide-sensitive factor (NSF) Attachment Protein family; Members of the soluble NSF attachment protein (SNAP) family are involved in intracellular membrane trafficking, including vesicular transport between the endoplasmic reticulum and Golgi apparatus. Higher eukaryotes contain three isoforms of SNAPs: alpha, beta, and gamma. Alpha-SNAP is universally present in eukaryotes and acts as an adaptor protein between SNARE (integral membrane SNAP receptor) and NSF for recruitment to the 20S complex. Beta-SNAP is brain-specific and shares high sequence identity (about 85%) with alpha-SNAP. Gamma-SNAP is weakly related (about 20-25% identity) to the two other isoforms, and is ubiquitous. It may help regulate the activity of the 20S complex. The X-ray structures of vertebrate gamma-SNAP and yeast Sec17, a SNAP family member, show similar all-helical structures consisting of an N-terminal extended twisted sheet of four Tetratricopeptide repeat (TPR)-like helical hairpins and a C-terminal helical bundle.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1972246578  20 MGQRQAKQHMQAGVKLYHQRHYAQAINKWRQSLNRLNNAEDRFITLGYLAQALCDQGEYEGMLSYALSQMQLATDQND 97
Cdd:pfam10579   1 LGQDIAKQKIEKGLKLYEQNDQEAALRTWMKALKGTCDPEDCFQLLGCLIQAHMDMGKFKEAIEFGHAQIGIAEELDD 78

Tetratricopeptide repeat;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972246578 222 YRCLILYHLSVALRMKGSLVDAKEACDEASQLA--VEMGNRAIHARCMCSLADIYRELGESEAKEtitkswARYEDAYRV 299
Cdd:pfam13424   1 DVATALNNLAAVLRRLGRYDEALELLEKALEIArrLLGPDHPLTATTLLNLGRLYLELGRYEEAL------ELLERALAL 74

                  ..
gi 1972246578 300 MR 301
Cdd:pfam13424  75 AE 76

Rapsyn N-terminal myristoylation and linker region; Neuromuscular junction formation relies upon the clustering of acetylcholine receptors and other proteins in the muscle membrane. Rapsyn is a peripheral membrane protein that is selectively concentrated at the neuromuscular junction and is essential for the formation of synaptic acetylcholine receptor aggregates. Acetylcholine receptors fail to aggregate beneath nerve terminals in mice where rapsyn has been knocked out. The N-terminal six amino acids of rapsyn are its myristoylation site, and myristoylation is necessary for the targeting of the protein to the membrane.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1972246578  20 MGQRQAKQHMQAGVKLYHQRHYAQAINKWRQSLNRLNNAEDRFITLGYLAQALCDQGEYEGMLSYALSQMQLATDQND 97
Cdd:pfam10579   1 LGQDIAKQKIEKGLKLYEQNDQEAALRTWMKALKGTCDPEDCFQLLGCLIQAHMDMGKFKEAIEFGHAQIGIAEELDD 78

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 1972246578  22 QRQAKQHMQAGVKLYHQRHYAQAINKWRQSLNRLNNAEDRFITLGYLAQAlcdQGEYEGmlsyALSQMQ--LATDQNDSa 99
Cdd:COG4783     1 AACAEALYALAQALLLAGDYDEAEALLEKALELDPDNPEAFALLGEILLQ---LGDLDE----AIVLLHeaLELDPDEP- 72

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1972246578 100 mkcEAFLNLAKAYERLADFTKALQYGKASLEhpsMDPRTPgYAHLTIALAHLGMSQFQQCLESFESAM 167
Cdd:COG4783    73 ---EARLNLGLALLKAGDYDEALALLEKALK---LDPEHP-EAYLRLARAYRALGRPDEAIAALEKAL 133

PHD zinc finger; The plant homeodomain (PHD) finger is a C4HC3 zinc-finger-like motif found in nuclear proteins thought to be involved in epigenetics and chromatin-mediated transcriptional regulation. The PHD finger binds two zinc ions using the so-called 'cross-brace' motif and is thus structurally related to the RING finger and the FYVE finger. It is not yet known if PHD fingers have a common molecular function. Several reports suggest that it can function as a protein-protein interacton domain and it was recently demonstrated that the PHD finger of p300 can cooperate with the adjacent BROMO domain in nucleosome binding in vitro. Other reports suggesting that the PHD finger is a ubiquitin ligase have been refuted as these domains were RING fingers misidentified as PHD fingers.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1972246578  392 FCNFCGQRYGlKDESLQALRCSHIFHEKCLHTYLL---QRTDQTCPKC 436
Cdd:smart00249   1 YCSVCGKPDD-GGELLQCDGCDRWYHQTCLGPPLLeeePDGKWYCPKC 47

putative PEP-CTERM system TPR-repeat lipoprotein; This protein family occurs in strictly within a subset of Gram-negative bacterial species with the proposed PEP-CTERM/exosortase system, analogous to the LPXTG/sortase system common in Gram-positive bacteria. This protein occurs in a species if and only if a transmembrane histidine kinase (TIGR02916) and a DNA-binding response regulator (TIGR02915) also occur. The present of tetratricopeptide repeats (TPR) suggests protein-protein interaction, possibly for the regulation of PEP-CTERM protein expression, since many PEP-CTERM proteins in these genomes are preceded by a proposed DNA binding site for the response regulator.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972246578  31 AGVKLYHQRHYAQAINKWRQSLNRLNNAED--RFITLGYLAQALCDQGEyegmlsyALSQMQLATDQNDSAmkceaFLNL 108
Cdd:TIGR02917 301 AGASEYQLGNLEQAYQYLNQILKYAPNSHQarRLLASIQLRLGRVDEAI-------ATLSPALGLDPDDPA-----ALSL 368

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972246578 109 A-KAYERLADFTKALQY-GKASlehpSMDPRTPGyAHLTIALAHLGMSQFQQCLESFESAMNVANETSDrllelqicVGL 186
Cdd:TIGR02917 369 LgEAYLALGDFEKAAEYlAKAT----ELDPENAA-ARTQLGISKLSQGDPSEAIADLETAAQLDPELGR--------ADL 435

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972246578 187 GSLFTLLR--DITKALIFLRNALAivqsvtvddvHAKYRCLILYHLSVALRMKGSLVDAKEACDEAsqLAVEMGN-RAIH 263
Cdd:TIGR02917 436 LLILSYLRsgQFDKALAAAKKLEK----------KQPDNASLHNLLGAIYLGKGDLAKAREAFEKA--LSIEPDFfPAAA 503

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972246578 264 arcmcSLADIyrelgeSEAKETITKSWARYEDAYRVMRGANDKMGEVLVLSSMAKSASESRSHYTgqcecQAIQLNKKCI 343
Cdd:TIGR02917 504 -----NLARI------DIQEGNPDDAIQRFEKVLTIDPKNLRAILALAGLYLRTGNEEEAVAWLE-----KAAELNPQEI 567

                         330
                  ....*....|....
gi 1972246578 344 EIANQIGCKHVVLK 357
Cdd:TIGR02917 568 EPALALAQYYLGKG 581

Rapsyn N-terminal myristoylation and linker region; Neuromuscular junction formation relies upon the clustering of acetylcholine receptors and other proteins in the muscle membrane. Rapsyn is a peripheral membrane protein that is selectively concentrated at the neuromuscular junction and is essential for the formation of synaptic acetylcholine receptor aggregates. Acetylcholine receptors fail to aggregate beneath nerve terminals in mice where rapsyn has been knocked out. The N-terminal six amino acids of rapsyn are its myristoylation site, and myristoylation is necessary for the targeting of the protein to the membrane.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1972246578  20 MGQRQAKQHMQAGVKLYHQRHYAQAINKWRQSLNRLNNAEDRFITLGYLAQALCDQGEYEGMLSYALSQMQLATDQND 97
Cdd:pfam10579   1 LGQDIAKQKIEKGLKLYEQNDQEAALRTWMKALKGTCDPEDCFQLLGCLIQAHMDMGKFKEAIEFGHAQIGIAEELDD 78

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972246578  28 HMQAGVKLYHQRHYAQAINKWRQSLnRLNnaEDRFITLGYLAQALCDQGEYEGMLSYAlsQMQLATDQNDSamkcEAFLN 107
Cdd:COG0457    11 YNNLGLAYRRLGRYEEAIEDYEKAL-ELD--PDDAEALYNLGLAYLRLGRYEEALADY--EQALELDPDDA----EALNN 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972246578 108 LAKAYERLADFTKALQYGKASLEhpsMDPRTPgYAHLTIALAHLGMSQFQQCLESFESAMNVANETSDRLlelqicVGLG 187
Cdd:COG0457    82 LGLALQALGRYEEALEDYDKALE---LDPDDA-EALYNLGLALLELGRYDEAIEAYERALELDPDDADAL------YNLG 151

                         170       180
                  ....*....|....*....|.
gi 1972246578 188 SLFTLLRDITKALIFLRNALA 208
Cdd:COG0457   152 IALEKLGRYEEALELLEKLEA 172

Ring finger domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1972246578 393 CNFCGQRYgLKDESLQALRCSHIFHEKCLHTYLlqRTDQTCPKCR 437
Cdd:pfam13639   3 CPICLEEF-EEGDKVVVLPCGHHFHRECLDKWL--RSSNTCPLCR 44

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 1972246578 393 CNFCGQRYGLKDESLQALRCSHIFHEKCLHTYLLQRTdqTCPKCR 437
Cdd:cd16461     2 CAICLSDYENGEELRRLPECKHAFHKECIDEWLKSNS--TCPLCR 44

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 1972246578 392 FCNFCGQRYGLKDEsLQALRCSHIFHEKCLHTYLlqRTDQTCPKCR 437
Cdd:cd16480     1 YCTICSDFFDNSRD-VAAIHCGHTFHYDCLLQWF--DTSRTCPQCR 43

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 1972246578 393 CNFCGQRYGLkDESLQALRCSHIFHEKCLHTYLLQRtdQTCPKCR 437
Cdd:cd16801     2 CPVCKEDYTV-GENVRQLPCNHLFHNDCIVPWLEQH--DTCPVCR 43

Predicted O-linked N-acetylglucosamine transferase, SPINDLY family [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972246578  24 QAKQHMQAGVKLYHQRHYAQAINKWRQSLNRLNNAEDRFITLGYLAQALCDQGEYEGMLSYALSQmQLATDQNDSAMKC- 102
Cdd:COG3914    23 AAELALAAELEAAALAAALGLALLLLAALAEAAAAALLALAAGEAAAAAAALLLLAALLELAALL-LQALGRYEEALALy 101

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972246578 103 -----------EAFLNLAKAYERLADFTKALQYGKASLEhpsMDPRTPGyAHLTIALAHLGMSQFQQCLESFESAMNVAN 171
Cdd:COG3914   102 rralalnpdnaEALFNLGNLLLALGRLEEALAALRRALA---LNPDFAE-AYLNLGEALRRLGRLEEAIAALRRALELDP 177

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1972246578 172 EtsdrllELQICVGLGSLFTLLRDITKALIFLRNALAIVQSvtvddvHAKYRCLILYHL 230
Cdd:COG3914   178 D------NAEALNNLGNALQDLGRLEEAIAAYRRALELDPD------NADAHSNLLFAL 224

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 1972246578 393 CNFCGQRYGLKDEsLQALRCSHIFHEKCLHTYlLQRTDQTCPKCR 437
Cdd:cd16797     3 CAICLDEYEEGDK-LRVLPCSHAYHSKCVDPW-LTQTKKTCPVCK 45

RING finger, H2 subclass, found in zinc/RING finger protein 3 (ZNRF3) and similar proteins; ZNRF3, also known as RING finger protein 203 (RNF203), is a homolog of Ring finger protein 43 (RNF43). It is a transmembrane E3 ubiquitin-protein ligase that is associated with the Wnt receptor complex, and negatively regulates Wnt signaling by promoting the turnover of frizzled and lipoprotein receptor-related protein LRP6 in an R-spondin-sensitive manner. It inhibits gastric cancer cell growth and promotes cell apoptosis by affecting the Wnt/beta-catenin/TCF signaling pathway. ZNRF3 contains an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C3H2C3-type RING-H2 finger followed by a long C-terminal region.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1972246578 393 CNFCGQRYgLKDESLQALRCSHIFHEKCLHTYLLQrtDQTCPKCR 437
Cdd:cd16799     2 CAICLEKY-IDGEELRVIPCTHRFHKKCVDPWLLQ--HHTCPHCR 43

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1972246578 393 CNFCGQRYGLKDEsLQALRCSHIFHEKCLHTYLLQRtdQTCPKCRC 438
Cdd:cd16802     3 CAVCIEPYKPNDV-VRILTCNHLFHKNCIDPWLLEH--RTCPMCKC 45

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 1972246578 393 CNFCGQRYGLKDESLqaLRCSHIFHEKCLHTYLLQRTDQTCPKCRC 438
Cdd:cd16677     2 CPICLEDFGLQQQVL--LSCSHVFHRACLESFERFSGKKTCPMCRK 45

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1972246578 393 CNFCGQRYGLkDESLQALRCSHIFHEKCLHTYLLQRTdqTCPKCR 437
Cdd:cd16667     2 CAVCKEDFEV-GEEVRQLPCKHLFHPDCIVPWLELHN--SCPVCR 43

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 1972246578 393 CNFCGQRYgLKDESLQALRCSHIFHEKCLHTYLlqRTDQTCPKCRC 438
Cdd:cd16465     2 CPICCSEY-VKDEIATELPCHHLFHKPCITAWL--QKSGTCPVCRH 44

Tetratricopeptide repeat;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1972246578  60 DRFITLGYLAQALCDQGEYEGMLSYALSQMQLATDQ--NDSAMKCEAFLNLAKAYERLADFTKALQYGKASLE 130
Cdd:pfam13424   1 DVATALNNLAAVLRRLGRYDEALELLEKALEIARRLlgPDHPLTATTLLNLGRLYLELGRYEEALELLERALA 73

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 1972246578 393 CNFCGQRYGLKDeSLQALRCSHIFHEKCLHTYLLQRtdQTCPKCR 437
Cdd:cd16804     2 CAVCIENYKSKD-VVRILPCKHVFHRICIDPWLLEH--RTCPMCK 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
                  ....*....|....*....|....*....|....*
gi 1972246578 403 KDESLQALRCSHIFHEKCLHTYLlqRTDQTCPKCR 437
Cdd:cd16472    14 KRQLLRVLPCSHEFHAKCIDKWL--KTNRTCPICR 46

RING finger, H2 subclass, found in RING finger protein 13 (RNF13) and similar proteins; RNF13 is a widely expressed membrane-associated E3 ubiquitin-protein ligase that is functionally significant in the regulation of cancer development, muscle cell growth, and neuronal development. Its expression is developmentally regulated during myogenesis and is upregulated in various tumors. RNF13 negatively regulates cell proliferation through its E3 ligase activity. It functions as an important regulator of inositol-requiring transmembrane kinase/endonuclease IRE1alpha, mediating endoplasmic reticulum (ER) stress-induced apoptosis through the activation of the IRE1alpha-TRAF2-JNK signaling pathway. Moreover, RNF13 is involved in the regulation of the soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor (SNARE) complex via the ubiquitination of snapin, a SNAP25-interacting protein, which thereby controls synaptic function. In addition, RNF13 participates in regulating the function of satellite cells by modulating cytokine composition. RNF13 is evolutionarily conserved among many metazoans and contains an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence.

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                  ....*....|....*....|....*....|....*....|....*....|.
gi 1972246578 393 CNFCGQRYGlKDESLQALRCSHIFHEKCLHTYlLQRTDQTCPKCRCRAVLS 443
Cdd:cd16796    11 CAICLDEYE-EGDKLRILPCSHAYHCKCVDPW-LTKTKKTCPVCKQKVVPS 59

Tetratricopeptide repeat;

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972246578 222 YRCLILYHLSVALRMKGSLVDAKEACDEASQLA--VEMGNRAIHARCMCSLADIYRELGESEAKEtitkswARYEDAYRV 299
Cdd:pfam13424   1 DVATALNNLAAVLRRLGRYDEALELLEKALEIArrLLGPDHPLTATTLLNLGRLYLELGRYEEAL------ELLERALAL 74

                  ..
gi 1972246578 300 MR 301
Cdd:pfam13424  75 AE 76

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.

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                  ....*....|....*....|....*....|....*....|....*..
gi 1972246578 393 CNFCGQRYGLKDESLqaLRCSHIFHEKCLHTY--LLQRTDQTCPKCR 437
Cdd:cd16471     2 CPICLCAFKGRKCTL--LSCSHVFHEACLSAFekFIESKNQKCPLCR 46

RING finger, H2 subclass, found in Arabidopsis thaliana RING-H2 finger A1a (RHA1A), A1b (RHA1B) and similar proteins; This subfamily includes Arabidopsis thaliana RHA1A, RHA1B and XERICO. RHA1A is a probable E3 ubiquitin-protein ligase that may possess E3 ubiquitin ligase activity in vitro. RHA1B possesses E3 ubiquitin-protein ligase activity when associated with the E2 enzyme UBC8 in vitro. XERICO functions on abscisic acid homeostasis at post-translational level, probably through ubiquitin/proteasome-dependent substrate-specific degradation. Members of this subfamily contain a C3H2C3-type RING-H2 finger.

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                  ....*....|....*....|....*....|....*....|....*...
gi 1972246578 393 CNFCGQRYGLKDESLQALRCSHIFHEKCLHTYLLQRTdQTCPKCRCRA 440
Cdd:cd23121     4 CAICLSDFNSDEKLRQLPKCGHIFHHHCLDRWIRYNK-ITCPLCRADL 50

RING finger, H2 subclass, found in RING finger protein 115 (RNF115) and similar proteins; RNF115, also known as Rab7-interacting ring finger protein (Rabring 7), or zinc finger protein 364 (ZNF364), or breast cancer-associated gene 2 (BCA2), is an E3 ubiquitin-protein ligase that is an endogenous inhibitor of adenosine monophosphate-activated protein kinase (AMPK) activation and its inhibition increases the efficacy of metformin in breast cancer cells. It also functions as a co-factor in the restriction imposed by tetherin on HIV-1, and targets HIV-1 Gag for lysosomal degradation, impairing virus assembly and release, in a tetherin-independent manner. Moreover, RNF115 is a Rab7-binding protein that stimulates c-Myc degradation through mono-ubiquitination of MM-1. It also plays crucial roles as a Rab7 target protein in vesicle traffic to late endosome/lysosome and lysosome biogenesis. Furthermore, RNF115 and the related protein, RNF126 associate with the epidermal growth factor receptor (EGFR) and promote ubiquitylation of EGFR, suggesting they play a role in the ubiquitin-dependent sorting and downregulation of membrane receptors. RNF115 contains an N-terminal BCA2 Zinc-finger domain (BZF), the AKT-phosphorylation sites, and the C-terminal C3H2C3-type RING-H2 finger.

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                  ....*....|....*....|....*....|....*....|....*..
gi 1972246578 391 LFCNFCGQRYGLKdESLQALRCSHIFHEKCLHTYLlqRTDQTCPKCR 437
Cdd:cd16800     1 LECPVCKEDYTVG-EQVRQLPCNHFFHSDCIVPWL--ELHDTCPVCR 44

RING finger, H2 subclass, found in autocrine motility factor receptor (AMFR) and similar proteins; AMFR, also known as AMF receptor, or RING finger protein 45, or ER-protein gp78, is an internalizing cell surface glycoprotein localized in both plasma membrane caveolae and the endoplasmic reticulum (ER). It is involved in the regulation of cellular adhesion, proliferation, motility and apoptosis, as well as in the process of learning and memory. AMFR also functions as a RING finger-dependent ubiquitin protein ligase (E3) implicated in the degradation from the ER. AMFR contains an N-terminal RING-H2 finger and a C-terminal ubiquitin-associated (UBA)-like CUE domain.

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                  ....*....|....*....|....*....|...
gi 1972246578 405 ESLQALRCSHIFHEKCLHTYLLQrtDQTCPKCR 437
Cdd:cd16455    11 QSARKLPCGHLFHNSCLRSWLEQ--DTSCPTCR 41

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.

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                  ....*....|....*....|....*....|....*....|....*...
gi 1972246578 393 CNFCGQRYGLKDEsLQALRCSHIFHEKCLHTYLLQRtdQTCPKCRCRA 440
Cdd:cd16469     3 CAVCLEEFKLKEE-LGVCPCGHAFHTKCLKKWLEVR--NSCPICKSPV 47

RING finger, HC subclass, found in tripartite motif-containing protein 69 (TRIM69) and similar proteins; TRIM69, also known as RFP-like domain-containing protein trimless or RING finger protein 36 (RNF36), is a testis E3 ubiquitin-protein ligase that plays a specific role in apoptosis and may also play an important role in germ cell homeostasis during spermatogenesis. TRIM69 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

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                  ....*....|....*....|....*....|....*....|....*....|
gi 1972246578 389 MQLFCNFCGQRYglKDESLqaLRCSHIFHEKCLHTYL-LQRTDQTCPKCR 437
Cdd:cd16611     3 EELHCPLCLDFF--RDPVM--LSCGHNFCQSCITGFWeLQAEDTTCPECR 48

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

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                  ....*....|....*....|....*....|....*..
gi 1972246578 404 DESLQALRCSHIFHEKCLHTYLlqRTDQTCPKCRCRA 440
Cdd:cd23118    13 GEKLRVLPCQHQFHSECVDQWL--RRNPKCPVCRRDA 47