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        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2217312632 267 SSAPVCAICLEEFSEGQELRVISCLHEFHRNCVDPWLHQHRTCPLCMFNITEG 319
Cdd:cd16798     1 SSAPVCAICLEEFSEGQELRIISCSHEFHRECVDPWLHQHRTCPLCMFNIIEG 53

transcriptional regulator ICP4; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217312632  312 CMFNITEGDSFSQSLGPSRSYQEPGRRLHLIRQHPGHAHYHLPAAYLLGPSRSAVARPPRPGPFLPSQEPGMGPRHHRFP 391
Cdd:PHA03307    66 EPPTGPPPGPGTEAPANESRSTPTWSLSTLAPASPAREGSPTPPGPSSPDPPPPTPPPASPPPSPAPDLSEMLRPVGSPG 145

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217312632  392 RAAHPRAPGEQQRLAGAQHPYAQGWGLSHLQSTSQHPAACPVPLRRARPPDSS-GSGESYCTERSGYLADGPASDSSSGP 470
Cdd:PHA03307   146 PPPAASPPAAGASPAAVASDAASSRQAALPLSSPEETARAPSSPPAEPPPSTPpAAASPRPPRRSSPISASASSPAPAPG 225

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217312632  471 ------CHGSSSDSVVNCTDISLQGVHG--------------SSSTFCSSLSSDFDPLVYCSPKGDPQR-------VDMQ 523
Cdd:PHA03307   226 rsaaddAGASSSDSSSSESSGCGWGPENecplprpapitlptRIWEASGWNGPSSRPGPASSSSSPRERspspspsSPGS 305

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217312632  524 PSVTSRPRSLDSVVPTGETQVSSHVHYHRHRHHHYKKRFQWHGRKPGPETGVPQSRPPIPRTQPQPEPPSPDQQVTRSNS 603
Cdd:PHA03307   306 GPAPSSPRASSSSSSSRESSSSSTSSSSESSRGAAVSPGPSPSRSPSPSRPPPPADPSSPRKRPRPSRAPSSPAASAGRP 385

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2217312632  604 AAPSGRLSNPqcPRALPEPAPGPVDASSICPSTSSlfnlqKSSLSARHPQRKRRGGPS-EPTPGSRP 669
Cdd:PHA03307   386 TRRRARAAVA--GRARRRDATGRFPAGRPRPSPLD-----AGAASGAFYARYPLLTPSgEPWPGSPP 445

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        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2217312632 267 SSAPVCAICLEEFSEGQELRVISCLHEFHRNCVDPWLHQHRTCPLCMFNITEG 319
Cdd:cd16798     1 SSAPVCAICLEEFSEGQELRIISCSHEFHRECVDPWLHQHRTCPLCMFNIIEG 53

RING-finger-containing ubiquitin ligase [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 2217312632 272 CAICLEEFSEGQELRVISCLHEFHRNCVDPWLHQHR-TCPLC 312
Cdd:COG5540   326 CAICMSNFIKNDRLRVLPCDHRFHVGCVDKWLLGYSnKCPVC 367

large tegument protein UL36; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217312632  570 GPETGVPQSRPPIPRTQPQPEPPSPdqqVTRSNSAAPSGRLSNPQCPRAlpePAPGPVDASSICPSTsslfnlqksslSA 649
Cdd:PHA03247  2693 GSLTSLADPPPPPPTPEPAPHALVS---ATPLPPGPAAARQASPALPAA---PAPPAVPAGPATPGG-----------PA 2755

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217312632  650 RHPQRKRRGGPSEPT----PGSRPQDATVHPACQIFPHYTPSVAYPWSPEAHPLICGPP--GLDKRLLPETPGPCYSNSQ 723
Cdd:PHA03247  2756 RPARPPTTAGPPAPAppaaPAAGPPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPaaALPPAASPAGPLPPPTSAQ 2835

                          170       180
                   ....*....|....*....|....
gi 2217312632  724 PVwlclTPRQPLEPHPPGEGPSEW 747
Cdd:PHA03247  2836 PT----APPPPPGPPPPSLPLGGS 2855

PA: Protease-associated (PA) domain. The PA domain is an insert domain in a diverse fraction of proteases. The significance of the PA domain to many of the proteins in which it is inserted is undetermined. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate. Proteins into which the PA domain is inserted include the following: i) various signal peptide peptidases including, hSPPL2a and 2b which catalyze the intramembrane proteolysis of tumor necrosis factor alpha, ii) various proteins containing a C3H2C3 RING finger including, Arabidopsis ReMembR-H2 protein and various E3 ubiquitin ligases such as human GRAIL (gene related to anergy in lymphocytes), iii) EDEM3 (ER-degradation-enhancing mannosidase-like 3 protein), iv) various plant vacuolar sorting receptors such as Pisum sativum BP-80, v) glutamate carboxypeptidase II (GCPII), vi) yeast aminopeptidase Y, vii) Vibrio metschnikovii VapT, a sodium dodecyl sulfate (SDS) resistant extracellular alkaline serine protease, viii) lactocepin (a cell envelope-associated protease from Lactobacillus paracasei subsp. paracasei NCDO 151), ix) various subtilisin-like proteases such as melon Cucumisin, and x) human TfR (transferrin receptor) 1 and 2.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217312632  87 PLYLCNA---SDDDNLEPGFISIVKlesprrapRPCLSLASKARMAGERGASAVLFdITEDRAAAEQLQQPLGLTW---- 159
Cdd:cd00538    29 PLVGCGYgttDDSGADVKGKIVLVR--------RGGCSFSEKVKNAQKAGAKAVII-YNNGDDPGPQMGSVGLESTdpsi 99

                          90       100
                  ....*....|....*....|....*..
gi 2217312632 160 PVVLIWGNDAEKLMEFVYKNQKAHVRI 186
Cdd:cd00538   100 PTVGISYADGEALLSLLEAGKTVTVDL 126

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        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2217312632 267 SSAPVCAICLEEFSEGQELRVISCLHEFHRNCVDPWLHQHRTCPLCMFNITEG 319
Cdd:cd16798     1 SSAPVCAICLEEFSEGQELRIISCSHEFHRECVDPWLHQHRTCPLCMFNIIEG 53

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 2217312632 271 VCAICLEEFSEGQELRVISCLHEFHRNCVDPWLHQHRTCPLCM 313
Cdd:cd16454     1 TCAICLEEFKEGEKVRVLPCNHLFHKDCIDPWLEQHNTCPLCR 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 2217312632 272 CAICLEEFSEGQELRVISCLHEFHRNCVDPWLHQHRTCPLCMFNI 316
Cdd:cd16670     3 CAVCLDQFYKNQCLRVLPCLHEFHRDCVDPWLLLQQTCPLCKRNI 47

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 2217312632 271 VCAICLEEFSEGQELRVISCLHEFHRNCVDPWLHQHR-TCPLC 312
Cdd:cd16797     2 VCAICLDEYEEGDKLRVLPCSHAYHSKCVDPWLTQTKkTCPVC 44

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 2217312632 272 CAICLEEFSEGQELRVISCLHEFHRNCVDPWLHQHRTCPLCMFN 315
Cdd:cd16799     2 CAICLEKYIDGEELRVIPCTHRFHKKCVDPWLLQHHTCPHCRHN 45

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 2217312632 272 CAICLEEFSEGQELRVI-SCLHEFHRNCVDPWLHQHRTCPLC 312
Cdd:cd16461     2 CAICLSDYENGEELRRLpECKHAFHKECIDEWLKSNSTCPLC 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 2217312632 272 CAICLEEFSEGQELRVISCLHEFHRNCVDPWLHQHRTCPLCMFNI 316
Cdd:cd16802     3 CAVCIEPYKPNDVVRILTCNHLFHKNCIDPWLLEHRTCPMCKCDI 47

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 2217312632 271 VCAICLEEFSEGQELRVISCLHEFHRNCVDPWLHQHRTCPLCM 313
Cdd:cd16469     2 TCAVCLEEFKLKEELGVCPCGHAFHTKCLKKWLEVRNSCPICK 44

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 2217312632 272 CAICLEEFSEGQELRVISCLHEFHRNCVDPWLHQHRTCPLCMFNI 316
Cdd:cd16804     2 CAVCIENYKSKDVVRILPCKHVFHRICIDPWLLEHRTCPMCKLDV 46

RING finger, H2 subclass, found in RING finger protein 103 (RNF103) and similar proteins; RNF103, also known as KF-1 or zinc finger protein 103 homolog (Zfp-103), is an endoplasmic reticulum (ER)-resident E3 ubiquitin-protein ligase that is widely expressed in many different organs, including brain, heart, kidney, spleen, and lung. It is involved in the ER-associated degradation (ERAD) pathway by interacting with components of the ERAD pathway, including Derlin-1 and VCP. RNF103 contains several hydrophobic regions at its N-terminal and middle regions, as well as a C-terminal C3H2C3-type RING-H2 finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 2217312632 272 CAICLEEFSEGQELRVISCLHEFHRNCVDPWLHQHR-TCPLC 312
Cdd:cd16473     7 CAICLENYQNGDLLRGLPCGHVFHQNCIDVWLERDNhCCPVC 48

Ring finger domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 2217312632 272 CAICLEEFSEGQELRVISCLHEFHRNCVDPWLHQHRTCPLC 312
Cdd:pfam13639   3 CPICLEEFEEGDKVVVLPCGHHFHRECLDKWLRSSNTCPLC 43

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2217312632 267 SSAPVCAICLEEFSEGQELRVISCLHEFHRNCVDPWLHQHRTCPLCMFNITE 318
Cdd:cd16680     5 SEQTLCVVCFSDFESRQLLRVLPCNHEFHTKCVDKWLKTNRTCPICRADASE 56

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 2217312632 272 CAICLEEFSEGQELRVISCLHEFHRNCVDPWLHQHRTCPLC 312
Cdd:cd16667     2 CAVCKEDFEVGEEVRQLPCKHLFHPDCIVPWLELHNSCPVC 42

RING finger, H2 subclass, found in RING finger protein 150 (RNF150) and similar proteins; RNF150 is a RING finger protein and its polymorphisms may be associated with chronic obstructive pulmonary disease (COPD) risk in the Chinese population. Further studies with larger numbers of participants worldwide are needed for validation of the relationships between RNF150 genetic variants and the pathogenesis of COPD. RNF150 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 2217312632 272 CAICLEEFSEGQELRVISCLHEFHRNCVDPWLHQHRTCPLCMFNI 316
Cdd:cd16805     9 CAVCIEGYKPNDVVRILPCRHLFHKSCVDPWLLDHRTCPMCKMNI 53

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 2217312632 271 VCAICLEEFSEGQELRVISCLHEFHRNCVDPWLHQHRTCPLC 312
Cdd:cd16673     2 TCSVCINEYATGNKLRRLPCAHEFHIHCIDRWLSENSTCPIC 43

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 2217312632 272 CAICLEEFSEGQELRVISCLHEFHRNCVDPWLHQHRTCPLCMFNI 316
Cdd:cd16681    13 CTICLSILEEGEDVRRLPCMHLFHQVCVDQWLITNKKCPICRVDI 57

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 2217312632 272 CAICLEEFSEGQELRVISCLHEFHRNCVDPWLHQHRTCPLC 312
Cdd:cd16801     2 CPVCKEDYTVGENVRQLPCNHLFHNDCIVPWLEQHDTCPVC 42

RING finger, H2 subclass, found in RING finger protein 165 (RNF165) and similar proteins; RNF165, also known as Arkadia-like 2, Arkadia2, or Ark2C, is an E3 ubiquitin ligase with homology to the C-terminal half of RNF111. It is expressed specifically in the nervous system, and can serve to amplify neuronal responses to specific signals. It acts as a positive regulator of bone morphogenetic protein (BMP)-Smad signaling that is involved in motor neuron (MN) axon elongation. RNF165 contains two serine rich domains, a nuclear localization signal, an NRG-TIER domain, and a C-terminal C3H2C3-type RING-H2 finger that is responsible for the enhancement of BMP-Smad1/5/8 signaling in the spinal cord.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 2217312632 272 CAICLEEFSEGQELRVISCLHEFHRNCVDPWLHQHRTCPLCMFNI 316
Cdd:cd16682    10 CTICLSMLEDGEDVRRLPCMHLFHQLCVDQWLAMSKKCPICRVDI 54

RING finger, H2 subclass, found in RING finger protein 38 (RNF38) and similar proteins; RNF38 is a nuclear E3 ubiquitin protein ligase that is widely expressed throughout the human body, and is especially highly expressed in the heart, brain, placenta and the testis. It recognizes p53 as a substrate for ubiquitination, and thus plays a role in regulating p53. The overexpression of RNF38 increases p53 ubiquitination and alters p53 localization. It is also capable of autoubiquitination. RNF38 expression is negatively regulated by the serotonergic system. Induction of RNF38 may be involved in the anxiety-like behavior or non-cell autonomy in Oryzias latipes by the decline of serotonin (5-HT) levels. RNF38 contains a coiled-coil motif, a KIL motif (Lys-X2-Ile/Leu-X2-Ile/Leu, X can be any amino acid), a C3H2C3-type RING-H2 finger, as well as two potential nuclear localization signals.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 2217312632 267 SSAPVCAICLEEFSEGQELRVISCLHEFHRNCVDPWLHQHRTCPLC 312
Cdd:cd16679    18 SEQTLCVVCMCDFESRQLLRVLPCNHEFHAKCVDKWLKANRTCPIC 63

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 2217312632 272 CAICLEEFSEGQELRVISCLHEFHRNCVDPWLHQHRTCPLC 312
Cdd:cd16676     3 CAVCLEDFKTKDELGVLPCQHAFHRKCLVKWLEIRCVCPMC 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 2217312632 272 CAICLEEFSEGQELRVISCLHEFHRNCVDPWLHQHRTCPLCMFNIT 317
Cdd:cd23115     7 CVICRLEYEEGEDLLTLPCKHCYHSECIQQWLQINKVCPVCSAEVT 52

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 2217312632 271 VCAICLEEFSEGQeLRVISCLHEFHRNCVDPWLHQHRTCPLC 312
Cdd:cd16481     1 PCIICHDDLKPDQ-LAKLECGHIFHKECIKQWLKEQSTCPTC 41

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 2217312632 271 VCAICLEEFSEGQELRVI-SCLHEFHRNCVDPWLHQHR-TCPLC 312
Cdd:cd23121     3 CCAICLSDFNSDEKLRQLpKCGHIFHHHCLDRWIRYNKiTCPLC 46

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 2217312632  272 CAICLEEFSEgqELRVISCLHEFHRNCVDPWLHQH-RTCPLC 312
Cdd:smart00184   1 CPICLEEYLK--DPVILPCGHTFCRSCIRKWLESGnNTCPIC 40

Zinc finger, C3HC4 type (RING finger); The C3HC4 type zinc-finger (RING finger) is a cysteine-rich domain of 40 to 60 residues that coordinates two zinc ions, and has the consensus sequence: C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C where X is any amino acid. Many proteins containing a RING finger play a key role in the ubiquitination pathway.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 2217312632 272 CAICLEEFSEgqELRVISCLHEFHRNCVDPWL-HQHRTCPLC 312
Cdd:pfam00097   1 CPICLEEPKD--PVTLLPCGHLFCSKCIRSWLeSGNVTCPLC 40

Modified RING-CH finger, H2 subclass (C4HC2H-type), found in zinc/RING finger protein 1 (ZNRF1) and similar proteins; ZNRF1, also known as Nerve injury-induced gene 283 protein (nin283), or peripheral nerve injury protein (PNIP), is an E3 ubiquitin-protein ligase that is highly expressed in the nervous system during development and is associated with synaptic vesicle membranes. It is N-myrisotoylated and is also located in the endosome-lysosome compartment in fibroblasts, suggesting it may participate in ubiquitin-mediated protein modification. It contains an N-terminal MAGE domain, and a special C-terminal domain that combines a zinc finger and a modified C4HC2H-type RING-CH finger, rather than the typical C4HC3-type RING-CH finger, which is a variant of the RING-H2 finger. Only the RING finger of the zinc finger-RING finger motif is required for its E3 ubiquitin ligase activity. ZNRF1 regulates Schwann cell differentiation by proteasomal degradation of glutamine synthetase (GS). It also mediates regulation of neuritogenesis via interaction with beta-tubulin type 2 (Tubb2). Moreover, ZNRF1 promotes Wallerian degeneration by degrading AKT to induce glycogen synthase kinase-3beta (GSK3B)-dependent CRMP2 phosphorylation. Furthermore, ZNRF1 and its sister protein ZNRF2 regulate the ubiquitous Na+/K+ pump (Na+/K+ATPase). In addition, ZNRF1 may be associated with leukemogenesis of acute lymphoblastic leukemia (ALL) with paired box domain gene 5 (PAX5) alteration.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 2217312632 272 CAICLEEFSEGQELRVISCLHEFHRNCVDPWLHQHRTCP 310
Cdd:cd16694     2 CVICLEELLQGDTIARLPCLCIYHKSCIDSWFEVNRSCP 40

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 2217312632 271 VCAICLEEFseGQELRVISCLHEFHRNCVDPWLHQHRTCPLC 312
Cdd:cd16683     6 VCAICYQEF--TTSARITPCNHYFHALCLRKWLYIQDTCPMC 45

RING finger, H2 subclass, found in Saccharomyces cerevisiae alcohol-sensitive RING finger protein 1 (ASR1) and similar proteins; ASR1 is required for tolerance to alcohol. It signals alcohol stress to the nucleus. ASR1 contains a C3H2C3-type RING-H2 finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 2217312632 270 PVCAICLEEFSEGqELRVISCLHEFHRNCVDPWLHQH--RTCPLC 312
Cdd:cd23120     2 EECPICLEEMNSG-TGYLADCGHEFHLTCIREWHNKSgnLDCPIC 45

Modified RING-CH finger, H2 subclass (C4HC2H-type), found in zinc/RING finger protein 2 (ZNRF2) and similar proteins; ZNRF2, also known as protein Ells2 or RING finger protein 202 (RNF202), is an E3 ubiquitin-protein ligase that is highly expressed in the nervous system during development and is present in presynaptic plasma membranes. It is N-myrisotoylated and is also located in the endosome-lysosome compartment in fibroblasts. It contains an N-terminal MAGE domain, and a special C-terminal domain that combines a zinc finger and a modified C4HC2H-type RING-CH finger, rather than the typical C4HC3-type RING-CH finger, which is a variant of RING-H2 finger. Only the RING finger of the zinc finger-RING finger motif is required for its E3 ubiquitin ligase activity. Together with its sister protein ZNRF1, ZNRF2 regulates the ubiquitous Na+/K+ pump (Na+/K+ATPase).

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 2217312632 272 CAICLEEFSEGQELRVISCLHEFHRNCVDPWLHQHRTCP 310
Cdd:cd16695    13 CAICLEELQQGDTIARLPCLCIYHKGCIDEWFEVNRSCP 51

RING finger, HC subclass, found in RING finger and transmembrane domain-containing protein RNFT1, RNFT2, and similar proteins; Both RNFT1 and RNFT2 are multi-pass membrane proteins containing a C3HC4-type RING-HC finger. Their biological roles remain unclear.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 2217312632 270 PVCAICLEEFsegQELRVISCLHEFHRNCVDPWLHQHRTCPLC 312
Cdd:cd16532     1 DICPICQDEF---KDPVVLRCKHIFCEDCVSEWFERERTCPLC 40

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 2217312632 272 CAICLEEFSEGQELRVIS--CLHEFHRNCVDPWL-HQHRTCPLC 312
Cdd:cd16450     5 CPICFEPWTSSGEHRLVSlkCGHLFGYSCIEKWLkGKGKKCPQC 48

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 2217312632 270 PVCAICLEEFseGQELRVI-SCLHEFHRNCVDPWLHQHRTCPLC 312
Cdd:cd16574     2 SSCPICLDRF--ENEKAFLdGCFHAFCFTCILEWSKVKNECPLC 43

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 2217312632 271 VCAICLEEFSEGQELRVISCLHEFHRNCVDPWLHQHRTCPLC 312
Cdd:cd23116     4 VCPTCLEGYTEENPKLLTKCGHHFHLACIYEWMERSERCPVC 45

RING finger, HC subclass, found in RING finger and transmembrane domain-containing protein 1 (RNFT1); RNFT1, also known as protein PTD016, is a multi-pass membrane protein containing a C3HC4-type RING-HC finger. Its biological role remains unclear.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2217312632 262 SGSSCSSA-PVCAICLEEFsegQELRVISCLHEFHRNCVDPWLHQHRTCPLC 312
Cdd:cd16741     6 SKRQCSEAdDICAICQAEF---RKPILLICQHVFCEECISLWFNREKTCPLC 54

RING finger, HC subclass, found in Equid alphaherpesvirus 1 (Equine herpesvirus 1/EHV-1) regulatory protein and similar proteins; EHV-1 regulatory protein belongs to the Vmw110 (IPC0) protein family. It contains a typical C3HC4-type RING-HC finger and binds zinc stably.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 2217312632 271 VCAICLEE-FSEGQELrviSCLHEFHRNCVDPWLHQHRTCPLC 312
Cdd:cd23130     2 VCPICLDDpEDEAITL---PCLHQFCYTCILRWLQTSPTCPLC 41