RING finger, H2 subclass, found in 43 kDa receptor-associated protein of the synapse (Rapsyn) and similar proteins; Rapsyn, also known as acetylcholine receptor (AChR)-associated 43 kDa protein or RING finger protein 205 (RNF205), is a 43 kDa postsynaptic protein that plays an essential role in the clustering and maintenance of AChR in the postsynaptic membrane of the motor endplate. AChRs enable the transport of rapsyn from the Golgi complex to the plasma membrane through a molecule-specific interaction. Rapsyn also mediates subsynaptic anchoring of protein kinase A (PKA) type I in close proximity to the postsynaptic membrane, which is essential for synapse maintenance. Its mutations in humans cause endplate AChR deficiency and myasthenic syndrome. Rapsyn contains an N-terminal myristoylation signal required for membrane association, seven tetratricopeptide repeats (TPRs) that subserve rapsyn self-association, a coiled-coil domain responsible for the binding of determinants within the long cytoplasmic loop of each AChR subunit, a C3H2C3-type RING-H2 finger that binds to the cytoplasmic domain of beta-dystroglycan and to S-NRAP and links rapsyn to the subsynaptic cytoskeleton, and a serine phosphorylation site.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 530395607 342 ELYCGLCGESIGEKNSRLQALPCSHIFHLRCLQNN---GTRSCPNCRR 386
Cdd:cd16478    1 ELFCGMCGESIGEKNEQLQALPCSHIFHLKCLQTNlrgGTRGCPNCRR 48

RING finger, H2 subclass, found in 43 kDa receptor-associated protein of the synapse (Rapsyn) and similar proteins; Rapsyn, also known as acetylcholine receptor (AChR)-associated 43 kDa protein or RING finger protein 205 (RNF205), is a 43 kDa postsynaptic protein that plays an essential role in the clustering and maintenance of AChR in the postsynaptic membrane of the motor endplate. AChRs enable the transport of rapsyn from the Golgi complex to the plasma membrane through a molecule-specific interaction. Rapsyn also mediates subsynaptic anchoring of protein kinase A (PKA) type I in close proximity to the postsynaptic membrane, which is essential for synapse maintenance. Its mutations in humans cause endplate AChR deficiency and myasthenic syndrome. Rapsyn contains an N-terminal myristoylation signal required for membrane association, seven tetratricopeptide repeats (TPRs) that subserve rapsyn self-association, a coiled-coil domain responsible for the binding of determinants within the long cytoplasmic loop of each AChR subunit, a C3H2C3-type RING-H2 finger that binds to the cytoplasmic domain of beta-dystroglycan and to S-NRAP and links rapsyn to the subsynaptic cytoskeleton, and a serine phosphorylation site.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 530395607 342 ELYCGLCGESIGEKNSRLQALPCSHIFHLRCLQNN---GTRSCPNCRR 386
Cdd:cd16478    1 ELFCGMCGESIGEKNEQLQALPCSHIFHLKCLQTNlrgGTRGCPNCRR 48

Tetratricopeptide repeat;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 530395607  204 YRAMSQYHMAVAYRLLGRLGSAMECCEESMKIA--LQHGDRPLQALCLLCFADIHRSRGDLETAFPRYDSAMSIMTE 278
Cdd:pfam13424   1 DVATALNNLAAVLRRLGRYDEALELLEKALEIArrLLGPDHPLTATTLLNLGRLYLELGRYEEALELLERALALAEK 77

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 530395607 345 CGLCGESIgEKNSRLQALPCSHIFHLRCLQN--NGTR-SCPNCR 385
Cdd:COG5540  326 CAICMSNF-IKNDRLRVLPCDHRFHVGCVDKwlLGYSnKCPVCR 368

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530395607   62 MLKFAVVQIDTARELEDADFL----------LESYLNLARSNEKLCEFHKTISYCKTCLglpgtrAGAQLGGQVSLSMGN 131
Cdd:TIGR02917 536 ILALAGLYLRTGNEEEAVAWLekaaelnpqeIEPALALAQYYLGKGQLKKALAILNEAA------DAAPDSPEAWLMLGR 609

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530395607  132 AFLGLSVFQKALESFEKALRYAHNNDDAMLEcrvccsLGSFYAQVKDYEKALffpckaaelvnnygkgWSLKyRAMSQY- 210
Cdd:TIGR02917 610 AQLAAGDLNKAVSSFKKLLALQPDSALALLL------LADAYAVMKNYAKAI----------------TSLK-RALELKp 666

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530395607  211 HMAVAYRLLGRLGSAMECCEESMKIALQ-HGDRPLQALCLLCFADIHRSRGDLETAFPRYDSAMSIMTEIGNRLGQVQAL 289
Cdd:TIGR02917 667 DNTEAQIGLAQLLLAAKRTESAKKIAKSlQKQHPKAALGFELEGDLYLRQKDYPAAIQAYRKALKRAPSSQNAIKLHRAL 746

                         250       260
                  ....*....|....*....|...
gi 530395607  290 LGVAKcwvARKALDKLSQ-LKLH 311
Cdd:TIGR02917 747 LASGN---TAEAVKTLEAwLKTH 766

RING finger, H2 subclass, found in 43 kDa receptor-associated protein of the synapse (Rapsyn) and similar proteins; Rapsyn, also known as acetylcholine receptor (AChR)-associated 43 kDa protein or RING finger protein 205 (RNF205), is a 43 kDa postsynaptic protein that plays an essential role in the clustering and maintenance of AChR in the postsynaptic membrane of the motor endplate. AChRs enable the transport of rapsyn from the Golgi complex to the plasma membrane through a molecule-specific interaction. Rapsyn also mediates subsynaptic anchoring of protein kinase A (PKA) type I in close proximity to the postsynaptic membrane, which is essential for synapse maintenance. Its mutations in humans cause endplate AChR deficiency and myasthenic syndrome. Rapsyn contains an N-terminal myristoylation signal required for membrane association, seven tetratricopeptide repeats (TPRs) that subserve rapsyn self-association, a coiled-coil domain responsible for the binding of determinants within the long cytoplasmic loop of each AChR subunit, a C3H2C3-type RING-H2 finger that binds to the cytoplasmic domain of beta-dystroglycan and to S-NRAP and links rapsyn to the subsynaptic cytoskeleton, and a serine phosphorylation site.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 530395607 342 ELYCGLCGESIGEKNSRLQALPCSHIFHLRCLQNN---GTRSCPNCRR 386
Cdd:cd16478    1 ELFCGMCGESIGEKNEQLQALPCSHIFHLKCLQTNlrgGTRGCPNCRR 48

Lipopolysaccharide biosynthesis regulator YciM/LapB, contains six TPR domains and a C-terminal metal-binding domain [Cell wall/membrane/envelope biogenesis];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530395607   9 QIEKGLQLYQSNQTEKALQVWTKVLEKSSDlmgrfrvlgcLVTAHSEMGRYKEMLKfavvqidtarELEDAdflLESYLN 88
Cdd:COG2956   11 WYFKGLNYLLNGQPDKAIDLLEEALELDPE----------TVEAHLALGNLYRRRG----------EYDRA---IRIHQK 67

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530395607  89 LARSNEKlcefhktisycktclglpgtRAGAQLG-GQVSLSMGNaflglsvFQKALESFEKALRYAHNNDDAMLEcrvcc 167
Cdd:COG2956   68 LLERDPD--------------------RAEALLElAQDYLKAGL-------LDRAEELLEKLLELDPDDAEALRL----- 115

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530395607 168 sLGSFYAQVKDYEKALFFpckAAELVNNYGKgwslkyRAMSQYHMAVAYRLLGRLGSAMECCEEsmkiALQHGDRPLQAL 247
Cdd:COG2956  116 -LAEIYEQEGDWEKAIEV---LERLLKLGPE------NAHAYCELAELYLEQGDYDEAIEALEK----ALKLDPDCARAL 181

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530395607 248 CLLcfADIHRSRGDLETA----------FPRYDSAMSIMTEIGNRLGQVQALLGVAKCWVARKALDKLsqlkLHCLSESI 317
Cdd:COG2956  182 LLL--AELYLEQGDYEEAiaaleraleqDPDYLPALPRLAELYEKLGDPEEALELLRKALELDPSDDL----LLALADLL 255

                        330       340
                 ....*....|....*....|
gi 530395607 318 YRSKG-------LQRELRAH 330
Cdd:COG2956  256 ERKEGleaalalLERQLRRH 275

H2 subclass of RING (RING-H2) fingers and its variants; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers: some have different Cys/His patterns while some lack a single Cys or His residue at typical Zn ligand positions (the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can indeed chelate Zn in a RING finger as well). This family corresponds to the H2 subclass of RING (RING-H2) finger proteins that are characterized by containing C3H2C3-type canonical RING-H2 fingers or noncanonical RING-H2 finger variants, including C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type modified RING-H2 fingers. The canonical RING-H2 finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-H-X2-C-X(4-48)-C-X2-C, X is any amino acid and the number of X residues varies in different fingers. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-H2 finger can be found in a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serves as a scaffold for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enables efficient transfer of ubiquitin from E2 to the substrates.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 530395607 345 CGLCGESIGEKnSRLQALPCSHIFHLRCLQN---NGTRSCPNCR 385
Cdd:cd16448    1 CVICLEEFEEG-DVVRLLPCGHVFHLACILRwleSGNNTCPLCR 43

first RING finger, H2 subclass, found in RING finger protein 32 (RNF32) and similar proteins; RNF32 is mainly expressed in testis spermatogenesis, most likely in spermatocytes and/or in spermatids, suggesting a possible role in sperm formation. RNF32 contains two C3H2C3-type RING-H2 fingers separated by an IQ domain of unknown function. Although the biological function of RNF32 remains unclear, proteins with double RING-H2 fingers may act as scaffolds for binding several proteins that function in the same pathway. This model corresponds to the first RING-H2 finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 530395607 345 CGLCGESIGEKNSRLqaLPCSHIFHLRCLQN----NGTRSCPNCRRS 387
Cdd:cd16677    2 CPICLEDFGLQQQVL--LSCSHVFHRACLESferfSGKKTCPMCRKE 46

Tetratricopeptide repeat;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 530395607  204 YRAMSQYHMAVAYRLLGRLGSAMECCEESMKIA--LQHGDRPLQALCLLCFADIHRSRGDLETAFPRYDSAMSIMTE 278
Cdd:pfam13424   1 DVATALNNLAAVLRRLGRYDEALELLEKALEIArrLLGPDHPLTATTLLNLGRLYLELGRYEEALELLERALALAEK 77

RING finger, HC subclass, found in the makorin (MKRN) proteins; The MKRN protein subfamily includes ribonucleoproteins that are characterized by a variety of zinc-finger motifs, including typical arrays of one to four C3H1-type zinc fingers and a C3HC4-type RING-HC finger. Another motif rich in Cys and His residues (CH), with so far unknown function, is also generally present in MKRN proteins. MKRN proteins may have E3 ubiquitin ligase activity.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 530395607 345 CGLCGESIGEKNSRLQALP-CSHIFHLRCL---------QNNGTRSCPNCR 385
Cdd:cd16521    3 CGICMEVVLEKERRFGILSnCNHVFCLECIrewrsskdfENSIVRSCPICR 53

Outer membrane protein chaperone/metalloprotease BepA/YfgC, contains M48 and TPR domains [Cell wall/membrane/envelope biogenesis, Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530395607   5 QTKQQIEKGLQLYQSNQTEKALQVWTKVLEKSSDLMGRFRVLGclvTAHSEMGRYKEmlkfAVVQIDTARELEDADFllE 84
Cdd:COG4783    3 CAEALYALAQALLLAGDYDEAEALLEKALELDPDNPEAFALLG---EILLQLGDLDE----AIVLLHEALELDPDEP--E 73

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 530395607  85 SYLNLARSNEKLCEFHKTISYCKTCLGLPGTRAGAQLGgqvslsMGNAFLGLSVFQKALESFEKALRYAHNN 156
Cdd:COG4783   74 ARLNLGLALLKAGDYDEALALLEKALKLDPEHPEAYLR------LARAYRALGRPDEAIAALEKALELDPDD 139

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 530395607 345 CGLCGESIGEKNSRLQALPCSHIFHLRCLQNNGTRSCPNCR 385
Cdd:cd16457    3 CPVCLERMDESVSGILTILCNHSFHCSCLSKWGDSSCPVCR 43

HRD ubiquitin ligase complex, ER membrane component [Posttranslational modification, protein turnover, chaperones];

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 530395607 355 KNSRLQALPCSHIFHLRCLQNNGTRS--CPNCRRS 387
Cdd:COG5243  309 LDMTPKRLPCGHILHLHCLKNWLERQqtCPICRRP 343

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

                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 530395607 354 EKNSRLQALPCSHIFHLRC----LQNNgtRSCPNCR 385
Cdd:cd16472   13 EKRQLLRVLPCSHEFHAKCidkwLKTN--RTCPICR 46

Cytochrome c-type biogenesis protein CcmH/NrfG [Energy production and conversion, Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530395607  83 LESYLNLARSNEKLCEFHKTISYCKTCLGLPGTRAGAQLGgqvslsMGNAFLGLSVFQKALESFEKALRYAHNNDDAMLE 162
Cdd:COG4235   17 AEGWLLLGRAYLRLGRYDEALAAYEKALRLDPDNADALLD------LAEALLAAGDTEEAEELLERALALDPDNPEALYL 90

                         90       100
                 ....*....|....*....|.
gi 530395607 163 crvccsLGSFYAQVKDYEKAL 183
Cdd:COG4235   91 ------LGLAAFQQGDYAEAI 105

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530395607   62 MLKFAVVQIDTARELEDADFL----------LESYLNLARSNEKLCEFHKTISYCKTCLglpgtrAGAQLGGQVSLSMGN 131
Cdd:TIGR02917 536 ILALAGLYLRTGNEEEAVAWLekaaelnpqeIEPALALAQYYLGKGQLKKALAILNEAA------DAAPDSPEAWLMLGR 609

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530395607  132 AFLGLSVFQKALESFEKALRYAHNNDDAMLEcrvccsLGSFYAQVKDYEKALffpckaaelvnnygkgWSLKyRAMSQY- 210
Cdd:TIGR02917 610 AQLAAGDLNKAVSSFKKLLALQPDSALALLL------LADAYAVMKNYAKAI----------------TSLK-RALELKp 666

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530395607  211 HMAVAYRLLGRLGSAMECCEESMKIALQ-HGDRPLQALCLLCFADIHRSRGDLETAFPRYDSAMSIMTEIGNRLGQVQAL 289
Cdd:TIGR02917 667 DNTEAQIGLAQLLLAAKRTESAKKIAKSlQKQHPKAALGFELEGDLYLRQKDYPAAIQAYRKALKRAPSSQNAIKLHRAL 746

                         250       260
                  ....*....|....*....|...
gi 530395607  290 LGVAKcwvARKALDKLSQ-LKLH 311
Cdd:TIGR02917 747 LASGN---TAEAVKTLEAwLKTH 766

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530395607 139 FQKALESFEKALRYAHNNDDAMLecrvccSLGSFYAQVKDYEKALFFPCKAAELVNNYgkgwslkyrAMSQYHMAVAYRL 218
Cdd:COG5010   70 FEESLALLEQALQLDPNNPELYY------NLALLYSRSGDKDEAKEYYEKALALSPDN---------PNAYSNLAALLLS 134

                         90
                 ....*....|....*...
gi 530395607 219 LGRLGSAMECCEESMKIA 236
Cdd:COG5010  135 LGQDDEAKAALQRALGTS 152

Outer membrane protein chaperone/metalloprotease BepA/YfgC, contains M48 and TPR domains [Cell wall/membrane/envelope biogenesis, Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530395607 124 QVSLSMGNAFLGLSVFQKALESFEKALRYAHNNDDAMlecrvcCSLGSFYAQVKDYEKALffpckaaelvNNYGKGWSL- 202
Cdd:COG4783    5 EALYALAQALLLAGDYDEAEALLEKALELDPDNPEAF------ALLGEILLQLGDLDEAI----------VLLHEALELd 68

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 530395607 203 KYRAMSQYHMAVAYRLLGRLGSAMECCEESMKIALQHGDrplqALCLLcfADIHRSRGDLETAFPRYDSAMSIMTE 278
Cdd:COG4783   69 PDEPEARLNLGLALLKAGDYDEALALLEKALKLDPEHPE----AYLRL--ARAYRALGRPDEAIAALEKALELDPD 138

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 530395607 339 EETELYCGLCgESIGEKNSRLQALPCSHIFHLRCLQN--NGTRSCPNCR 385
Cdd:cd16681    7 EDTEEKCTIC-LSILEEGEDVRRLPCMHLFHQVCVDQwlITNKKCPICR 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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 530395607 345 CGLCGESIgeknSRLQALPCSHIFHLRCLQN--NGTRSCPNCRRS 387
Cdd:cd16455    3 CAICWESM----QSARKLPCGHLFHNSCLRSwlEQDTSCPTCRMS 43

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 530395607 345 CGLCGESIGEKNSRLQALPCSHIFHLRCL-----QNNGTrsCPNCR 385
Cdd:cd23121    4 CAICLSDFNSDEKLRQLPKCGHIFHHHCLdrwirYNKIT--CPLCR 47

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 530395607 345 CGLCGESIgEKNSRLQALPCSHIFHLRCLQ---NNGTRSCPNCRRSSMK 390
Cdd:cd16796   11 CAICLDEY-EEGDKLRILPCSHAYHCKCVDpwlTKTKKTCPVCKQKVVP 58