BRCA1-associated protein 2; These proteins include BRCA1-associated protein 2 (BRAP2), which binds nuclear localization signals (NLSs) in vitro and in yeast two-hybrid screening. These proteins share a region of sequence similarity at their N terminus. They also have pfam02148 at the C terminus.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 79323080    57 GRNPLVCVLGVPNHMTYADFCQFCGSFIQHILDMRTVRnDDIENRYSILIRFDSQESTDTFFQHFRGKQFNSLDEDVCRL 136
Cdd:pfam07576   1 GRSTLLCILAVPNYMSPADFLQFCGSFLEHISHIRIIR-DGMENRYMVLIKFDDQNSADEFYEEFNGKPFSSLEPEVCHV 79

                          90
                  ....*....|..
gi 79323080   137 LFALDVQFTGYS 148
Cdd:pfam07576  80 LFVKSVEYTESA 91

Zn-finger in ubiquitin-hydrolases and other protein;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 79323080   218 CCVCQTTENLWMCVICGVVGCGRYKEGHARRHWEETEHCYSLELETQRVWDYAGDNYVHRLIQ 280
Cdd:pfam02148   1 CSLCGNTSNLWLCLTCGHVGCGRYQNSHALEHYEETGHPLAVNLSTLTVYCYPCDDYVHDPSL 63

BRCA1-associated protein 2; These proteins include BRCA1-associated protein 2 (BRAP2), which binds nuclear localization signals (NLSs) in vitro and in yeast two-hybrid screening. These proteins share a region of sequence similarity at their N terminus. They also have pfam02148 at the C terminus.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 79323080    57 GRNPLVCVLGVPNHMTYADFCQFCGSFIQHILDMRTVRnDDIENRYSILIRFDSQESTDTFFQHFRGKQFNSLDEDVCRL 136
Cdd:pfam07576   1 GRSTLLCILAVPNYMSPADFLQFCGSFLEHISHIRIIR-DGMENRYMVLIKFDDQNSADEFYEEFNGKPFSSLEPEVCHV 79

                          90
                  ....*....|..
gi 79323080   137 LFALDVQFTGYS 148
Cdd:pfam07576  80 LFVKSVEYTESA 91

RING finger, H2 subclass, found in BRCA1-associated protein (BRAP2) and similar proteins; BRAP2, also known as impedes mitogenic signal propagation (IMP), RING finger protein 52, or renal carcinoma antigen NY-REN-63, is a novel cytoplasmic protein interacting with the two functional nuclear localization signal (NLS) motifs of BRCA1, a nuclear protein linked to breast cancer. It also binds to the SV40 large T antigen NLS motif and the bipartite NLS motif found in mitosin. BRAP2 serves as a cytoplasmic retention protein and plays a role in the regulation of nuclear protein transport. It contains an N-terminal RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), followed by a C3H2C3-type RING-H2 finger and a UBP-type zinc finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 79323080 165 PTCPVCLERLDQDTGGILTTMCNHSFHCSCISNWPDSSCPVCRY 208
Cdd:cd16457   1 PTCPVCLERMDESVSGILTILCNHSFHCSCLSKWGDSSCPVCRY 44

Ubiquitin Carboxyl-terminal Hydrolase-like zinc finger;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 79323080    218 CCVCQTTENLWMCVICGVVGCGRYKEGHARRHWEETEHCYSLELETQRV 266
Cdd:smart00290   2 CSVCGTIENLWLCLTCGQVGCGRYQNGHALEHFEETGHPLVVKLGTQRV 50

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 79323080    167 CPVCLERLDQDTggiLTTMCNHSFHCSCISNWPDS---SCPVC 206
Cdd:smart00184   1 CPICLEEYLKDP---VILPCGHTFCRSCIRKWLESgnnTCPIC 40

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 79323080 107 RFDSQESTDTFFQHFRGKQFNSLDEdvCRLLFalDVQFTGYSGSI-DHTQ-----PSAAGPIEQPT----CPVCLE---R 173
Cdd:COG5540 260 RIPSQELRFLFLTQSKGSRFNIILE--IQINF--DVGFYSSSEAIpTTTTkgslkPLSIERAVEADkgveCAICMSnfiK 335

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 79323080 174 LDQdtggILTTMCNHSFHCSCISNWPDS---SCPVCR 207
Cdd:COG5540 336 NDR----LRVLPCDHRFHVGCVDKWLLGysnKCPVCR 368

Uncharacterized protein, contains DUF3084 domain [Function unknown];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 79323080 309 SGMTDALLNSKVDMIISEYNEL------LQAQLENQKQYFEKL---LQNVKEE---TEQKISEAAS-------------- 362
Cdd:COG4372  22 TGILIAALSEQLRKALFELDKLqeeleqLREELEQAREELEQLeeeLEQARSEleqLEEELEELNEqlqaaqaelaqaqe 101

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 79323080 363 --KAISQRLQKLQTRFDRCVKEKQFLEDLNENLVKNKDVWSTKITEmKEREKKAVRakdEKIQGLEEQLGNLMAQMDGES 440
Cdd:COG4372 102 elESLQEEAEELQEELEELQKERQDLEQQRKQLEAQIAELQSEIAE-REEELKELE---EQLESLQEELAALEQELQALS 177

                ....*....
gi 79323080 441 EVSETKEVQ 449
Cdd:COG4372 178 EAEAEQALD 186

Component of SCF ubiquitin ligase and anaphase-promoting complex [Posttranslational modification, protein turnover, chaperones / Cell division and chromosome partitioning];

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 79323080 166 TCPVCLERLDQ-DTGGILTTMCNHSFHCSCISNWPDSS--CPVCR 207
Cdd:COG5194  33 TCPECQFGMTPgDECPVVWGVCNHAFHDHCIYRWLDTKgvCPLDR 77

BRCA1-associated protein 2; These proteins include BRCA1-associated protein 2 (BRAP2), which binds nuclear localization signals (NLSs) in vitro and in yeast two-hybrid screening. These proteins share a region of sequence similarity at their N terminus. They also have pfam02148 at the C terminus.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 79323080    57 GRNPLVCVLGVPNHMTYADFCQFCGSFIQHILDMRTVRnDDIENRYSILIRFDSQESTDTFFQHFRGKQFNSLDEDVCRL 136
Cdd:pfam07576   1 GRSTLLCILAVPNYMSPADFLQFCGSFLEHISHIRIIR-DGMENRYMVLIKFDDQNSADEFYEEFNGKPFSSLEPEVCHV 79

                          90
                  ....*....|..
gi 79323080   137 LFALDVQFTGYS 148
Cdd:pfam07576  80 LFVKSVEYTESA 91

RING finger, H2 subclass, found in BRCA1-associated protein (BRAP2) and similar proteins; BRAP2, also known as impedes mitogenic signal propagation (IMP), RING finger protein 52, or renal carcinoma antigen NY-REN-63, is a novel cytoplasmic protein interacting with the two functional nuclear localization signal (NLS) motifs of BRCA1, a nuclear protein linked to breast cancer. It also binds to the SV40 large T antigen NLS motif and the bipartite NLS motif found in mitosin. BRAP2 serves as a cytoplasmic retention protein and plays a role in the regulation of nuclear protein transport. It contains an N-terminal RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), followed by a C3H2C3-type RING-H2 finger and a UBP-type zinc finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 79323080 165 PTCPVCLERLDQDTGGILTTMCNHSFHCSCISNWPDSSCPVCRY 208
Cdd:cd16457   1 PTCPVCLERMDESVSGILTILCNHSFHCSCLSKWGDSSCPVCRY 44

Ubiquitin Carboxyl-terminal Hydrolase-like zinc finger;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 79323080    218 CCVCQTTENLWMCVICGVVGCGRYKEGHARRHWEETEHCYSLELETQRV 266
Cdd:smart00290   2 CSVCGTIENLWLCLTCGQVGCGRYQNGHALEHFEETGHPLVVKLGTQRV 50

RNA recognition motif (RRM) found in yeast RING finger protein ETP1 and similar proteins; This subgroup corresponds to the RRM of ETP1, also termed BRAP2 homolog, or ethanol tolerance protein 1, the yeast homolog of BRCA1-associated protein (BRAP2) found in vertebrates. It may be involved in ethanol and salt-induced transcriptional activation of the NHA1 promoter and heat shock protein genes (HSP12 and HSP26), and participate in ethanol-induced turnover of the low-affinity hexose transporter Hxt3p. ETP1 contains an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), followed by a C3HC4-type ring finger domain and a UBP-type zinc finger.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 79323080  62 VCVLGVPNHMTYADFCQFCG----SFIQHIldmRTVRNDDiENRYSILIRFDSQESTDTFFQHFRGKQFNSLDEDVCRLL 137
Cdd:cd12717   2 LAILAVPSYMTPSDLLGFVGgatlEQVSHF---RLIRTSR-PNRYMVLLKFRDAKSAKEFQKEFNGKKFNSIDPETCHVV 77

                ....*.
gi 79323080 138 FALDVQ 143
Cdd:cd12717  78 FIKEII 83

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 79323080 167 CPVCLerLDQDTGGILTTM-CNHSFHCSCISNW--PDSSCPVCRY 208
Cdd:cd16669   2 CPICL--LEFEEGETVKQLpCKHSFHSDCILPWlgKTNSCPLCRH 44

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 79323080 166 TCPVCLERLDqdTGGILTTM-CNHSFHCSCISNW--PDSSCPVCR 207
Cdd:cd16454   1 TCAICLEEFK--EGEKVRVLpCNHLFHKDCIDPWleQHNTCPLCR 43

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 79323080 166 TCPVCLERL-DQDTGGILTtmCNHSFHCSCISNWPDS--SCPVC 206
Cdd:cd16469   2 TCAVCLEEFkLKEELGVCP--CGHAFHTKCLKKWLEVrnSCPIC 43

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 79323080 164 QPTCPVCLERLDQDTGGIltTMCNHSFHCSCISNW----PDSSCPVCR 207
Cdd:cd23120   1 IEECPICLEEMNSGTGYL--ADCGHEFHLTCIREWhnksGNLDCPICR 46

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 79323080 163 EQPTCPVCLERLDQDTGGIlTTMCNHSFHCSCISNWPDSS--CPVC 206
Cdd:cd23116   1 DEDVCPTCLEGYTEENPKL-LTKCGHHFHLACIYEWMERSerCPVC 45

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 79323080 167 CPVCLErlDQDTGGILTTM-CNHSFHCSCISNWPD--SSCPVCR 207
Cdd:cd16801   2 CPVCKE--DYTVGENVRQLpCNHLFHNDCIVPWLEqhDTCPVCR 43

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM5, TRIM6, TRIM22, TRIM34 and similar proteins; TRIM5, TRIM6, TRIM22, and TRIM34, four closely related tripartite motif-containing proteins, belong 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. TRIM5, also known as RING finger protein 88 (RNF88), is a capsid-specific restriction factor that prevents infection from non-host-adapted retroviruses in a species-specific manner by binding to and destabilizing the retroviral capsid lattice before reverse transcription is completed. Its retroviral restriction activity correlates with the ability to activate TAK1-dependent innate immune signaling. TRIM5 also acts as a pattern recognition receptor that activates innate immune signaling in response to the retroviral capsid lattice. Moreover, TRIM5 plays a role in regulating autophagy through activation of autophagy regulator BECN1 by causing its dissociation from its inhibitors BCL2 and TAB2. It also plays a role in autophagy by acting as a selective autophagy receptor which recognizes and targets HIV-1 capsid protein p24 for autophagic destruction. TRIM6, also known as RING finger protein 89 (RNF89), is an E3-ubiquitin ligase that cooperates with the E2-ubiquitin conjugase UbE2K to catalyze the synthesis of unanchored K48-linked polyubiquitin chains, and further stimulates the interferon-I kappa B kinase epsilon (IKKepsilon) kinase-mediated antiviral response. It also regulates the transcriptional activity of Myc during the maintenance of embryonic stem (ES) cell pluripotency, and may act as a novel regulator for Myc-mediated transcription in ES cells. TRIM22, also known as 50 kDa-stimulated trans-acting factor (Staf-50) or RING finger protein 94 (RNF94), is an E3 ubiquitin-protein ligase that plays an integral role in the host innate immune response to viruses. It has been shown to inhibit the replication of a number of viruses, including HIV-1, hepatitis B, and influenza A. TRIM22 acts as a suppressor of basal HIV-1 long terminal repeat (LTR)-driven transcription by preventing the transcription factor specificity protein 1 (Sp1) binding to the HIV-1 promoter. It also controls FoxO4 activity and cell survival by directing Toll-like receptor 3 (TLR3)-stimulated cells toward type I interferon (IFN) type I gene induction or apoptosis. Moreover, TRIM22 can activate the noncanonical nuclear factor-kappaB (NF-kappaB) pathway by activating I kappa B kinase alpha (IKKalpha). It also regulates nucleotide binding oligomerization domain containing 2 (NOD2)-dependent activation of interferon-beta signaling and nuclear factor-kappaB. TRIM34, also known as interferon-responsive finger protein 1 or RING finger protein 21 (RNF21), may function as antiviral protein that contribute to the defense against retroviral infections.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 79323080 163 EQPTCPVCLERLDQDtggiLTTMCNHSFHCSCIS--------NWPDSSCPVCRyCQQQPEN 215
Cdd:cd16591   5 EEVTCPICLELLTEP----LSLDCGHSFCQACITanhkesvnQEGESSCPVCR-TSYQPEN 60

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 79323080 167 CPVCLERLDQDTGgILTTMCNHSFHCSCISNWPD--SSCPVCR 207
Cdd:cd16667   2 CAVCKEDFEVGEE-VRQLPCKHLFHPDCIVPWLElhNSCPVCR 43

DNA double-strand break repair ATPase Rad50;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 79323080  324 ISEYNELLQAQlENqkqyFEKLLQNVKEETEQKISEAasKAISQRLQKLQTRFDRCVKEKQFLEDLNEnlvknkdvwstK 403
Cdd:PRK03918 178 IERLEKFIKRT-EN----IEELIKEKEKELEEVLREI--NEISSELPELREELEKLEKEVKELEELKE-----------E 239

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 79323080  404 ITEMKERE---KKAVRAKDEKIQGLEEQLGNLMAQM-DGESEVSETKEVQ 449
Cdd:PRK03918 240 IEELEKELeslEGSKRKLEEKIRELEERIEELKKEIeELEEKVKELKELK 289

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 79323080 107 RFDSQESTDTFFQHFRGKQFNSLDEdvCRLLFalDVQFTGYSGSI-DHTQ-----PSAAGPIEQPT----CPVCLE---R 173
Cdd:COG5540 260 RIPSQELRFLFLTQSKGSRFNIILE--IQINF--DVGFYSSSEAIpTTTTkgslkPLSIERAVEADkgveCAICMSnfiK 335

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 79323080 174 LDQdtggILTTMCNHSFHCSCISNWPDS---SCPVCR 207
Cdd:COG5540 336 NDR----LRVLPCDHRFHVGCVDKWLLGysnKCPVCR 368

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 79323080    326 EYNELLQAQLENQKQYFEklLQNVKEETEQKISE--AASKAISQRLQKLQTRF-------DRCVKEKQFLEDLNENLVKN 396
Cdd:TIGR02168  240 ELEELQEELKEAEEELEE--LTAELQELEEKLEElrLEVSELEEEIEELQKELyalaneiSRLEQQKQILRERLANLERQ 317

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 79323080    397 KDVWSTKITEMKEREKKAVRAKDEkiqgLEEQLGNLMAQMDGESEVSETKE 447
Cdd:TIGR02168  318 LEELEAQLEELESKLDELAEELAE----LEEKLEELKEELESLEAELEELE 364

RING finger, HC subclass, found in tripartite motif-containing proteins, TRIM7, TRIM11 and TRIM27, and similar proteins; TRIM7, TRIM11 and TRIM27, closely related tripartite motif-containing proteins, belong 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, Bbox2, and a coiled coil region, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain. TRIM7, also known as glycogenin-interacting protein (GNIP) or RING finger protein 90 (RNF90), is an E3 ubiquitin-protein ligase that mediates c-Jun/AP-1 activation by Ras signalling. Its phosphorylation and activation by MSK1 in response to direct activation by the Ras-Raf-MEK-ERK pathway can stimulate TRIM7 E3 ubiquitin ligase activity in mediating Lys63-linked ubiquitination of the AP-1 coactivator RACO-1, leading to RACO-1 protein stabilization. Moreover, TRIM7 binds and activates glycogenin, the self-glucosylating initiator of glycogen biosynthesis. TRIM11, also known as protein BIA1, or RING finger protein 92 (RNF92), is an E3 ubiquitin-protein ligase involved in the development of the central nervous system. It is overexpressed in high-grade gliomas and promotes proliferation, invasion, migration and glial tumor growth. TRIM11 acts as a potential therapeutic target for congenital central hypoventilation syndrome (CCHS) by mediating the degradation of CCHS-associated polyalanine-expanded Phox2b. TRIM11 modulates the function of neurogenic transcription factor Pax6 through the ubiquitin-proteosome system, and thus plays an essential role for Pax6-dependent neurogenesis. It also binds to and destabilizes a key component of the activator-mediated cofactor complex (ARC105), humanin, a neuroprotective peptide against Alzheimer's disease-relevant insults, and further regulates ARC105 function in transforming growth factor beta (TGFbeta) signaling. Moreover, TRIM11 negatively regulates retinoic acid-inducible gene-I (RIG-I)-mediated interferon-beta (IFNbeta) production and antiviral activity by targeting TANK-binding kinase-1 (TBK1). It may contribute to the endogenous restriction of retroviruses in cells. It enhances N-tropic murine leukemia virus (N-MLV) entry by interfering with Ref1 restriction. It also suppresses the early steps of human immunodeficiency virus HIV-1 transduction, resulting in decreased reverse transcripts. TRIM27, also known as RING finger protein 76 (RNF76), RET finger protein (RFP), or zinc finger protein RFP, is a nuclear E3 ubiquitin-protein ligase that is highly expressed in testis and in various tumor cell lines. Expression of TRIM27 is associated with prognosis of colon and endometrial cancers. TRIM27 was first identified as a fusion partner of the RET receptor tyrosine kinase. It functions as a transcriptional repressor and associates with several proteins involved in transcriptional activity, such as enhancer of polycomb 1 (Epc1), a member of the Polycomb group proteins, and Mi-2beta, a main component of the nucleosome remodeling and deacetylase (NuRD) complex, and the cell cycle regulator retinoblastoma protein (RB1). It also interacts with HDAC1, leading to downregulation of thioredoxin binding protein 2 (TBP-2), which inhibits the function of thioredoxin. Moreover, TRIM27 mediates Pax7-induced ubiquitination of MyoD in skeletal muscle atrophy. In addition, it inhibits muscle differentiation by modulating serum response factor (SRF) and Epc1. TRIM27 promotes a non-canonical polyubiquitination of PTEN, a lipid phosphatase that catalyzes PtdIns(3,4,5)P3 (PIP3) to PtdIns(4,5)P2 (PIP2). It is an IKKepsilon-interacting protein that regulates IkappaB kinase (IKK) function and negatively regulates signaling involved in the antiviral response and inflammation. TRIM27 also forms a protein complex with MBD4 or MBD2 or MBD3, and thus plays an important role in the enhancement of transcriptional repression through MBD proteins in tumorigenesis, spermatogenesis, and embryogenesis. It is a component of an estrogen receptor 1 (ESR1) regulatory complex that is involved in estrogen receptor-mediated transcription in MCF-7 cells.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 79323080 166 TCPVCLERLdQDTggiLTTMCNHSFHCSCISN-WPDS----SCPVCR 207
Cdd:cd16594   7 TCPICLDYF-TDP---VTLDCGHSFCRACIARcWEEPetsaSCPQCR 49

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        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 79323080   161 PIEQPtCPVCLERLDQDTGgILTTMCNHSFHCSCISNWPDSS--CPVCR 207
Cdd:pfam12678   9 PFMEP-CPECQAPGDDECP-VVWGECGHAFHLHCISRWLKTNntCPLCR 55

phosphodiesterase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 79323080  319 KVDMIISEYnellQAQLENQKQyfEKLLQ------NVKEETEQKISEAASKaISQRLQKLQTRFDRCVKEKQFLEDLNEN 392
Cdd:PRK12704  39 EAKRILEEA----KKEAEAIKK--EALLEakeeihKLRNEFEKELRERRNE-LQKLEKRLLQKEENLDRKLELLEKREEE 111

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 79323080  393 LVKNKDVWSTKITEMKEREKKAVRAKDEKIQGLEE 427
Cdd:PRK12704 112 LEKKEKELEQKQQELEKKEEELEELIEEQLQELER 146

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM60, TRIM61, TRIM75 and similar proteins; TRIM60, also known as RING finger protein 129 (RNF129) or RING finger protein 33 (RNF33), is a cytoplasmic protein expressed in the testis. It may play an important role in the spermatogenesis process, the development of the preimplantation embryo, and in testicular functions. RNF33 interacts with the cytoplasmic kinesin motor proteins KIF3A and KIF3B suggesting possible contribution to cargo movement along the microtubule in the expressed sites. It is also involved in spermatogenesis in Sertoli cells under the regulation of nuclear factor-kappaB (NF-kappaB). TRIM75 mainly localizes within spindles, suggesting it may function in spindle organization and thereby affect meiosis. Both TRIM60 and TRIM75 belong 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, a B2-box, and two coiled coil domains, as well as a PRY domain and a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. In contrast, TRIM61 belongs to the C-V subclass of the TRIM family that contains RBCC domains only. Its biological function remains unclear.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 79323080 167 CPVCLERLDQDtggiLTTMCNHSFHCSCIS-NWPDSS----CPVCRYC 209
Cdd:cd16607   4 CPICLDYLKDP----VTINCGHNFCRSCISmSWKDLQdtfpCPVCRFC 47

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 79323080 166 TCPVCLERLD-QDTGGILTtmCNHSFHCSCISNW--PDSSCPVCRY 208
Cdd:cd16802   2 SCAVCIEPYKpNDVVRILT--CNHLFHKNCIDPWllEHRTCPMCKC 45

RING finger, H2 subclass, found in Saccharomyces cerevisiae transmembrane E3 ubiquitin-protein ligase 1 (TUL1) and similar proteins; This subfamily includes Saccharomyces cerevisiae TUL1, Schizosaccharomyces pombe DSC E3 ubiquitin ligase complex subunit 1 (DSC1), and Arabidopsis thaliana protein FLYING SAUCER 2 (FLY2). TUL1 is the catalytic component of DSC E3 ubiquitin ligase complexes that tag proteins present in Golgi, endosome and vacuole membranes and function in protein homeostasis under non-stress conditions, and support a role in protein quality control. It mediates ubiquitination of vacuolar proteins such as CPS1, PPN1, PEP12 and other proteins containing exposed hydrophilic residues within their transmembrane domains, leading to their sorting into internal vesicles in late endosomes. TUL1 also targets the unpalmitoylated endosomal SNARE TLG1 to the multivesicular body (MVB) pathway. DSC1, also known as defective for SREBP cleavage protein 1, is the catalytic component of the DSC E3 ubiquitin ligase complex required for the sre1 transcriptional activator proteolytic cleavage to release the soluble transcription factor from the membrane in low oxygen or sterol conditions. FLY2 acts as an E3 ubiquitin-protein ligase that may be involved in xylem development. Members of this subfamily contain a C3H2C3-type RING-H2 finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 79323080 165 PTCPVCLERLD-----QDTGGILTTMCNHSFHCSCISNWPD--SSCPVCR 207
Cdd:cd23117   5 VDCVICMSDIElpstnSVRRDYMVTPCNHIFHTNCLERWMDikLECPTCR 54

Uncharacterized protein, contains DUF3084 domain [Function unknown];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 79323080 309 SGMTDALLNSKVDMIISEYNEL------LQAQLENQKQYFEKL---LQNVKEE---TEQKISEAAS-------------- 362
Cdd:COG4372  22 TGILIAALSEQLRKALFELDKLqeeleqLREELEQAREELEQLeeeLEQARSEleqLEEELEELNEqlqaaqaelaqaqe 101

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 79323080 363 --KAISQRLQKLQTRFDRCVKEKQFLEDLNENLVKNKDVWSTKITEmKEREKKAVRakdEKIQGLEEQLGNLMAQMDGES 440
Cdd:COG4372 102 elESLQEEAEELQEELEELQKERQDLEQQRKQLEAQIAELQSEIAE-REEELKELE---EQLESLQEELAALEQELQALS 177

                ....*....
gi 79323080 441 EVSETKEVQ 449
Cdd:COG4372 178 EAEAEQALD 186

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 79323080 167 CPVCLERLD-QDTggILTTMCNHSFHCSCISNW---PDSSCPVCR 207
Cdd:cd16486   2 CRICLKAFQlGQH--VRTLPCRHKFHRDCIDNWllhSRNSCPIDG 44

RING finger, HC subclass, found in RING finger protein 141 (RNF141) and similar proteins; RNF141, also known as zinc finger protein 230 (ZNF230), is a RING finger protein present primarily in the nuclei of spermatogonia, the acrosome, and the tail of spermatozoa. It may have a broad function during early development of vertebrates. It plays an important role in spermatogenesis, including spermatogenic cell proliferation and sperm maturation, as well as motility and fertilization. It also exhibits DNA binding activity. RNF141/ZNF230 gene mutations may be associated with azoospermia. RNF141 contains a C3HC4-type RING finger domain that may function as an activator module in transcription.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 79323080 167 CPVCLERldqDTGGILTtmCNHSFHCSCISNWPDSS--CPVCR 207
Cdd:cd16545   3 CCICMDR---KADLILP--CAHSYCQKCIDKWSDRHrtCPICR 40

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 79323080 166 TCPVCLERLDQdtGGILTTM-CNHSFHCSCISNW--PDSSCPVCR 207
Cdd:cd16674   2 TCSVCITEYTE--GNKLRKLpCSHEYHVHCIDRWlsENSTCPICR 44

Ezrin/radixin/moesin, alpha-helical domain; The ERM family consists of three closely-related proteins, ezrin, radixin and moesin. Ezrin was first identified as a constituent of microvilli, radixin as a barbed, end-capping actin-modulating protein from isolated junctional fractions, and moesin as a heparin binding protein. A tumour suppressor molecule responsible for neurofibromatosis type 2 (NF2) is highly similar to ERM proteins and has been designated merlin (moesin-ezrin-radixin-like protein). ERM molecules contain 3 domains, an N-terminal globular domain, an extended alpha-helical domain and a charged C-terminal domain (pfam00769). Ezrin, radixin and merlin also contain a polyproline linker region between the helical and C-terminal domains. The N-terminal domain is highly conserved and is also found in merlin, band 4.1 proteins and members of the band 4.1 superfamily, designated the FERM domain. ERM proteins crosslink actin filaments with plasma membranes. They co-localize with CD44 at actin filament plasma membrane interaction sites, associating with CD44 via their N-terminal domains and with actin filaments via their C-terminal domains. This is the alpha-helical domain, which is involved in intramolecular masking of protein-protein interaction sites, regulating the activity of this proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 79323080   336 ENQKQYFEKLLQNVKEETE---QKISEAASKAIS--QRLQKLQTRFDRCVKEKQFLEDLNENLVKnkdvwsTKITEMKER 410
Cdd:pfam20492   5 EREKQELEERLKQYEEETKkaqEELEESEETAEEleEERRQAEEEAERLEQKRQEAEEEKERLEE------SAEMEAEEK 78

                          90
                  ....*....|....*....
gi 79323080   411 EKKA--VRAKDEKIQGLEE 427
Cdd:pfam20492  79 EQLEaeLAEAQEEIARLEE 97

RING finger, H2 subclass, found in Arabidopsis thaliana NEP1-interacting protein-like 1 (NIPL1) and similar proteins; This subfamily includes Arabidopsis thaliana NIPL1 and MISFOLDED PROTEIN SENSING RING E3 LIGASE 1 (MPSR1). NIPL1, also called RING-H2 finger protein ATL27, may be involved in the early steps of the plant defense signaling pathway. MPSR1 is a cytoplasmic E3 ubiquitin-protein ligase involved in protein quality control (PQC) under proteotoxic stress. It is essential for plant survival under proteotoxic stress. It functions by removing damaged proteins before they form cytotoxic aggregates. It recognizes misfolded proteins selectively and tethers polyubiquitin chains to the proteins directly for subsequent degradation by the 26S proteasome pathway. Members of this subfamily contain a C3H2C3-type RING-H2 finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 79323080 167 CPVCLERLDQDTGGILTTMCNHSFHCSCISNW--PDSSCPVCR 207
Cdd:cd23119   2 CTICLQDLQVGEIARSLPHCHHTFHLGCVDKWlgRHGSCPVCR 44

Anaphase-promoting complex subunit 11 RING-H2 finger; Apc11 is one of the subunits of the anaphase-promoting complex or cyclosome. The APC subunits are cullin family proteins with ubiquitin ligase activity. Polyubiquitination marks proteins for degradation by the 26S proteasome and is carried out by a cascade of enzymes that includes ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), and ubiquitin ligases (E3s). Apc11 acts as an E3 enzyme and is responsible for recruiting E2s to the APC and for mediating the subsequent transfer of ubiquitin to APC substrates in vivo. In Saccharomyces cerevisiae this RING-H2 finger protein defines the minimal ubiquitin ligase activity of the APC, and the integrity of the RING-H2 finger is essential for budding yeast cell viability.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 79323080   166 TCPVCleRLDQDTGGILTTMCNHSFHCSCISNWPDSS-----CPVCR 207
Cdd:pfam12861  34 TCPDC--KFPGDDCPLVWGKCSHNFHMHCILKWLHTEtskglCPMCR 78

Phage shock protein A [Transcription, Signal transduction mechanisms];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 79323080 329 ELLQAQLENQKQYFEKLLQNVkEETEQKISEAASKAIS----QRLQKLQTRfdrcvkekqfledLNENL--VKNKDVWST 402
Cdd:COG1842 101 EALEAQLAQLEEQVEKLKEAL-RQLESKLEELKAKKDTlkarAKAAKAQEK-------------VNEALsgIDSDDATSA 166

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 79323080 403 kITEMKER--EKKA-VRAKDEKIQG--LEEQLGNLMAQMDGESEVSETKE 447
Cdd:COG1842 167 -LERMEEKieEMEArAEAAAELAAGdsLDDELAELEADSEVEDELAALKA 215

RING finger, H2 subclass, found in Arabidopsis thaliana RING-H2 zinc finger protein RHF2A and similar proteins; RHF2A is an E3 ubiquitin-protein ligase involved in the positive regulation of the gametogenesis progression. It is required for the degradation of KRP6, a cyclin-dependent kinase inhibitor which accumulates during meiosis and blocks the progression of subsequent mitoses during gametophytes development. It functions in association with RHF1A. Members of this subfamily contain a C3H2C3-type RING-H2 finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 79323080 167 CPVCLERLDQDTGGILTTmCNHSFHCSCISNWPDSS--CPVC 206
Cdd:cd23122  14 CSICLESFCEADPATVTS-CKHEYHLQCILEWSQRSkeCPMC 54

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.