CBL proto-oncogene N-terminal domain 1; Cbl is an adaptor protein that binds EGF receptors (or other tyrosine kinases) and SH3 domains, functioning as a negative regulator of many signaling pathways. The N-terminal domain is evolutionarily conserved, and is known to bind to phosphorylated tyrosine residues. Cbl_N is comprised of 3 structural domains of which this is the first - a four helix bundle.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 80978932    49 VDKKMVEKCWKLMDKVVRLCQNPKLALKNSPPYILDLLPDTYQHLRTVLSRYEGKMETLGENEYFRVFMENLMKKTKQTI 128
Cdd:pfam02262   1 IDRRTLDKAVKLLDKLVKLCQDPRLNLKNSPPYLLDLLPDTYQHLRLVAEKYRGRLDALGENEYLRIYLANLLAKCKQAA 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 80978932   129 SLFKEGKERMYEENSQPRRNLTKLSLIFSHMLAELKGIFPSGLFQ 173
Cdd:pfam02262  81 KLFKEGKEKMFDEGSRYRRQLTKLSLIFSHMLAELKALFPDGKFC 125

CBL proto-oncogene N-terminus, EF hand-like domain; Cbl is an adaptor protein that binds EGF receptors (or other tyrosine kinases) and SH3 domains, functioning as a negative regulator of many signaling pathways. The N-terminal domain is evolutionarily conserved, and is known to bind to phosphorylated tyrosine residues. The so called N-terminal domain is actually 3 structural domains, of which this is the central EF hand domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 80978932   177 FRITKADAAEFWRKAFGEKTIVPWKSFRQALHEVHPISSGLEAMALKSTIDLTCNDYISVFEFDIFTRLFQPWSSLLRNW 256
Cdd:pfam02761   1 FRITKSEAAEFWKKSFGKRTIVPWKEFRTALQQVHGIESGLEAMALKSTIDLTCNDHISIFEFDVFTRLFQPWSTLLRNW 80

                  ....
gi 80978932   257 NSLA 260
Cdd:pfam02761  81 NLLA 84

UBA domain found in E3 ubiquitin-protein ligase Cbl and similar proteins; Cbl, also called casitas B-lineage lymphoma proto-oncogene, proto-oncogene c-Cbl, RING finger protein 55, or signal transduction protein Cbl, is a multi-domain protein that acts as a key negative regulator of various receptor and non-receptor tyrosine kinases signaling. It contains a tyrosine kinase-binding domain (TKB), a proline-rich domain, a RING domain, and a ubiquitin-associated (UBA) domain. The TKB is responsible for the interactions with many tyrosine kinases, such as the colony-stimulating factor-1 (CSF-1) receptor, Syk/ZAP-70 and Src-family of protein tyrosine kinases. The proline-rich domain can recruit proteins with SH3 domain. Moreover, Cbl functions as an E3 ubiquitin ligase that can bind ubiquitin-conjugating enzymes (E2s) through RING domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 80978932 864 LSSEIERLMSQGYSYQDIQKALVIAHNNIEMAKNILREFV 903
Cdd:cd14393   1 LSSEIENLMSQGYSYQDIQKALVIAQNNIEMAKNILREFV 40

CBL proto-oncogene N-terminal domain 1; Cbl is an adaptor protein that binds EGF receptors (or other tyrosine kinases) and SH3 domains, functioning as a negative regulator of many signaling pathways. The N-terminal domain is evolutionarily conserved, and is known to bind to phosphorylated tyrosine residues. Cbl_N is comprised of 3 structural domains of which this is the first - a four helix bundle.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 80978932    49 VDKKMVEKCWKLMDKVVRLCQNPKLALKNSPPYILDLLPDTYQHLRTVLSRYEGKMETLGENEYFRVFMENLMKKTKQTI 128
Cdd:pfam02262   1 IDRRTLDKAVKLLDKLVKLCQDPRLNLKNSPPYLLDLLPDTYQHLRLVAEKYRGRLDALGENEYLRIYLANLLAKCKQAA 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 80978932   129 SLFKEGKERMYEENSQPRRNLTKLSLIFSHMLAELKGIFPSGLFQ 173
Cdd:pfam02262  81 KLFKEGKEKMFDEGSRYRRQLTKLSLIFSHMLAELKALFPDGKFC 125

CBL proto-oncogene N-terminus, SH2-like domain; Cbl is an adaptor protein that binds EGF receptors (or other tyrosine kinases) and SH3 domains, functioning as a negative regulator of many signaling pathways. The N-terminal domain is evolutionarily conserved, and is known to bind to phosphorylated tyrosine residues. The so called N-terminal domain is actually 3 structural domains, of which this is the C-terminal SH2 domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 80978932   262 THPGYMAFLTYDEVKARLQKFIHKPGSYIFRLSCTRLGQWAIGYVTADGNILQTIPHNKPLFQALIDGFREGFYLFPDGR 341
Cdd:pfam02762   1 THPGYMAFLTYDEVKARLEKFRHKPGSYVFRLSCTRLGQWAIGYVTPDGKIVQTIPQNKSLYQALIDGFREGFYLYPDGR 80

                  ....*.
gi 80978932   342 NQNPDL 347
Cdd:pfam02762  81 DANPDL 86

RING finger, HC subclass, found in E3 ubiquitin-protein ligase Cbl and similar proteins; Cbl, also known as Casitas B-lineage lymphoma proto-oncogene, proto-oncogene c-Cbl, RING finger protein 55 (RNF55), or signal transduction protein Cbl, is a multi-domain protein that acts as a key negative regulator of various receptor and non-receptor tyrosine kinase signaling. It contains a tyrosine kinase-binding domain (TKB, also known as the phosphotyrosine binding PTB domain, composed of a four helix-bundle, a Ca2+ binding EF-hand and a highly variant SH2 domain), a proline-rich domain, a C3HC4-type RING-HC finger, and an ubiquitin-associated (UBA) domain. TKB is responsible for the interactions with many tyrosine kinases, such as the colony-stimulating factor-1 (CSF-1) receptor, Syk/ZAP-70, and Src-family of protein tyrosine kinases. The proline-rich domain can recruit proteins with a SH3 domain. Moreover, Cbl functions as an E3 ubiquitin ligase that can bind ubiquitin-conjugating enzymes (E2s) through the RING-HC finger.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 80978932 356 QDHIKVTQEQYELYCEMGSTFQLCKICAENDKDVKIEPCGHLMCTSCLTSWQESEGQGCPFCRCEIKGTEPIVVDPF 432
Cdd:cd16708   1 QDHIKVTQEQYELYCEMGSTFQLCKICAENDKDVKIEPCGHLMCTSCLTSWQESEGQGCPFCRCEIKGTEPIVVDPF 77

Prokaryotic RING finger family 4; RING finger family domain found sporadically in bacteria. The finger is fused to an N-terminal alpha-helical domain, ROT/Trove-like repeats and a C-terminal TerD domain. The architecture suggests a possible role in an RNA-processing complex.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 80978932   379 CKICAENDKDVKIEPCGHLMCTSCLTSWQESegqGCPFCRCEIKGTEPI 427
Cdd:pfam14447   1 CVLCGRNGTVHALIPCGHLVCRDCFDGSDFS---ACPICRRRIDADDPF 46

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 80978932   478 RPSSPFSMAPQASL--PPVPPRLDLLQQRAPVPASTSVLGTASKAASGSLHKDKPLPIPPTLRDLPPppppdrpysvGAE 555
Cdd:PHA03247 2685 RRAARPTVGSLTSLadPPPPPPTPEPAPHALVSATPLPPGPAAARQASPALPAAPAPPAVPAGPATP----------GGP 2754

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 80978932   556 TRPQRRPLPCTPGD-CPSRD-------KLPPVPSSRPGDSWLSRPIPKVPVATPNPGDPWNGRE-LTNRHSLPFSLPSQM 626
Cdd:PHA03247 2755 ARPARPPTTAGPPApAPPAApaagpprRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALpPAASPAGPLPPPTSA 2834

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 80978932   627 EPRAdvPRLGSTFsLDTSMTMNSSPVAG------PESEHPKIKPSSSANAIYSLAARP--------LPMPKLPPGEQGES 692
Cdd:PHA03247 2835 QPTA--PPPPPGP-PPPSLPLGGSVAPGgdvrrrPPSRSPAAKPAAPARPPVRRLARPavsrstesFALPPDQPERPPQP 2911

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 80978932   693 EEDTEYMTPTSRPVGVQKPEPKRPLEATQSSRACDCDQQIDSCTYEAMYNIQSQALSVAENSASGEGNLATAHTSTGPEE 772
Cdd:PHA03247 2912 QAPPPPQPQPQPPPPPQPQPPPPPPPRPQPPLAPTTDPAGAGEPSGAVPQPWLGALVPGRVAVPRFRVPQPAPSREAPAS 2991

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 80978932   773 SENEDDGYDVPK-------------PPVPAVLARRTLSDISNASSSFGWLSLDGDPTNFNEGSQVPERPP-------KPF 832
Cdd:PHA03247 2992 STPPLTGHSLSRvsswasslalheeTDPPPVSLKQTLWPPDDTEDSDADSLFDSDSERSDLEALDPLPPEphdpfahEPD 3071

                         410
                  ....*....|....*..
gi 80978932   833 PRRINSERKASSYQQGG 849
Cdd:PHA03247 3072 PATPEAGARESPSSQFG 3088

UBA/TS-N domain; This small domain is composed of three alpha helices. This family includes the previously defined UBA and TS-N domains. The UBA-domain (ubiquitin associated domain) is a novel sequence motif found in several proteins having connections to ubiquitin and the ubiquitination pathway. The structure of the UBA domain consists of a compact three helix bundle. This domain is found at the N terminus of EF-TS hence the name TS-N. The structure of EF-TS is known and this domain is implicated in its interaction with EF-TU. The domain has been found in non EF-TS proteins such as alpha-NAC and MJ0280.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 80978932   865 SSEIERLMSQGYSYQDIQKALVIAHNNIEMAKNIL 899
Cdd:pfam00627   3 EEAIQRLVEMGFDREQVREALRATGNNVERAAEYL 37

RING-finger-containing E3 ubiquitin ligase [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 80978932 379 CKICAENDKDVKIEPCGHLMCTSCL-TSWQESEGQGCPFCR 418
Cdd:COG5574 218 CFLCLEEPEVPSCTPCGHLFCLSCLlISWTKKKYEFCPLCR 258

CBL proto-oncogene N-terminal domain 1; Cbl is an adaptor protein that binds EGF receptors (or other tyrosine kinases) and SH3 domains, functioning as a negative regulator of many signaling pathways. The N-terminal domain is evolutionarily conserved, and is known to bind to phosphorylated tyrosine residues. Cbl_N is comprised of 3 structural domains of which this is the first - a four helix bundle.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 80978932    49 VDKKMVEKCWKLMDKVVRLCQNPKLALKNSPPYILDLLPDTYQHLRTVLSRYEGKMETLGENEYFRVFMENLMKKTKQTI 128
Cdd:pfam02262   1 IDRRTLDKAVKLLDKLVKLCQDPRLNLKNSPPYLLDLLPDTYQHLRLVAEKYRGRLDALGENEYLRIYLANLLAKCKQAA 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 80978932   129 SLFKEGKERMYEENSQPRRNLTKLSLIFSHMLAELKGIFPSGLFQ 173
Cdd:pfam02262  81 KLFKEGKEKMFDEGSRYRRQLTKLSLIFSHMLAELKALFPDGKFC 125

CBL proto-oncogene N-terminus, SH2-like domain; Cbl is an adaptor protein that binds EGF receptors (or other tyrosine kinases) and SH3 domains, functioning as a negative regulator of many signaling pathways. The N-terminal domain is evolutionarily conserved, and is known to bind to phosphorylated tyrosine residues. The so called N-terminal domain is actually 3 structural domains, of which this is the C-terminal SH2 domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 80978932   262 THPGYMAFLTYDEVKARLQKFIHKPGSYIFRLSCTRLGQWAIGYVTADGNILQTIPHNKPLFQALIDGFREGFYLFPDGR 341
Cdd:pfam02762   1 THPGYMAFLTYDEVKARLEKFRHKPGSYVFRLSCTRLGQWAIGYVTPDGKIVQTIPQNKSLYQALIDGFREGFYLYPDGR 80

                  ....*.
gi 80978932   342 NQNPDL 347
Cdd:pfam02762  81 DANPDL 86

RING finger, HC subclass, found in E3 ubiquitin-protein ligase Cbl and similar proteins; Cbl, also known as Casitas B-lineage lymphoma proto-oncogene, proto-oncogene c-Cbl, RING finger protein 55 (RNF55), or signal transduction protein Cbl, is a multi-domain protein that acts as a key negative regulator of various receptor and non-receptor tyrosine kinase signaling. It contains a tyrosine kinase-binding domain (TKB, also known as the phosphotyrosine binding PTB domain, composed of a four helix-bundle, a Ca2+ binding EF-hand and a highly variant SH2 domain), a proline-rich domain, a C3HC4-type RING-HC finger, and an ubiquitin-associated (UBA) domain. TKB is responsible for the interactions with many tyrosine kinases, such as the colony-stimulating factor-1 (CSF-1) receptor, Syk/ZAP-70, and Src-family of protein tyrosine kinases. The proline-rich domain can recruit proteins with a SH3 domain. Moreover, Cbl functions as an E3 ubiquitin ligase that can bind ubiquitin-conjugating enzymes (E2s) through the RING-HC finger.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 80978932 356 QDHIKVTQEQYELYCEMGSTFQLCKICAENDKDVKIEPCGHLMCTSCLTSWQESEGQGCPFCRCEIKGTEPIVVDPF 432
Cdd:cd16708   1 QDHIKVTQEQYELYCEMGSTFQLCKICAENDKDVKIEPCGHLMCTSCLTSWQESEGQGCPFCRCEIKGTEPIVVDPF 77

RING finger, HC subclass, found in E3 ubiquitin-protein ligase Cbl-c and similar proteins; Cbl-c, also known as RING finger protein 57 (RNF57), SH3-binding protein Cbl-3, SH3-binding protein Cbl-c, or signal transduction protein Cbl-c, is an E3 ubiquitin-protein ligase expressed exclusively in epithelial cells. It contains a tyrosine-kinase-binding domain (TKB, also known as the phosphotyrosine binding PTB domain, composed of a four helix-bundle, a Ca2+ binding EF-hand and a highly variant SH2 domain), a C3HC4-type RING-HC finger, and a short proline-rich region, but lacks the ubiquitin-associated (UBA) leucine zipper motif that are present in Cbl and Cbl-b. Cbl-c acts as a regulator of epidermal growth factor receptor (EGFR)-mediated signal transduction. It also suppresses v-Src-induced transformation through ubiquitin-dependent protein degradation. Moreover, Cbl-c ubiquitinates and downregulates RETMEN2A and implicates Enigma (PDLIM7) as a positive regulator of RETMEN2A by blocking Cbl-mediated ubiquitination and degradation. The ubiquitin ligase activity of Cbl-c is increased via the interaction of its RING-HC finger domain with a LIM domain of the paxillin homolog, hydrogen peroxide induced construct 5 (Hic-5).

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 80978932 364 EQYELYCEMGSTFQLCKICAENDKDVKIEPCGHLMCTSCLTSWQESEGQGCPFCRCEIKGTEPI 427
Cdd:cd16710   1 EQLQLYQAMNSTFELCKICAERDKDVRIEPCGHLLCSCCLAAWQHSDSQTCPFCRCEIKGREAV 64

UBA domain found in E3 ubiquitin-protein ligase Cbl and similar proteins; Cbl, also called casitas B-lineage lymphoma proto-oncogene, proto-oncogene c-Cbl, RING finger protein 55, or signal transduction protein Cbl, is a multi-domain protein that acts as a key negative regulator of various receptor and non-receptor tyrosine kinases signaling. It contains a tyrosine kinase-binding domain (TKB), a proline-rich domain, a RING domain, and a ubiquitin-associated (UBA) domain. The TKB is responsible for the interactions with many tyrosine kinases, such as the colony-stimulating factor-1 (CSF-1) receptor, Syk/ZAP-70 and Src-family of protein tyrosine kinases. The proline-rich domain can recruit proteins with SH3 domain. Moreover, Cbl functions as an E3 ubiquitin ligase that can bind ubiquitin-conjugating enzymes (E2s) through RING domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 80978932 864 LSSEIERLMSQGYSYQDIQKALVIAHNNIEMAKNILREFV 903
Cdd:cd14393   1 LSSEIENLMSQGYSYQDIQKALVIAQNNIEMAKNILREFV 40

RING finger (Really Interesting New Gene) domain and U-box domain superfamily; 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). C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type RING fingers are closely related to RING-HC fingers. In contrast, C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type RING fingers are more closely related to RING-H2 fingers. However, not all RING finger-containing proteins display regular RING finger features, and the RING finger family has turned out to be multifarious. The degenerate RING fingers of the Siz/PIAS RING (SP-RING) family proteins and sporulation protein RMD5, are characterized by lacking the second, fifth, and sixth Zn2+ ion-coordinating residues. They bind only one Zn2+ ion. On the other hand, the RING fingers of the human APC11 and RBX1 proteins can bind a third Zn atom since they harbor four additional Zn ligands. U-box is a modified form of the RING finger domain that lacks metal chelating Cys and His residues. It resembles the cross-brace RING structure consisting of three beta-sheets and a single alpha-helix, which would be stabilized by salt bridges instead of chelated metal ions. U-box proteins are widely distributed among eukaryotic organisms and show a higher prevalence in plants than in other organisms. RING finger/U-box-containing proteins are a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serve as scaffolds for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enable efficient transfer of ubiquitin from E2 to the substrates.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 80978932 379 CKICAENDKD---VKIEPCGHLMCTSCLTSWQESEGQGCPFC 417
Cdd:cd00162   1 CPICREEMNDrrpVVLLSCGHTFSRSAIARWLEGSKQKCPFC 42

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 80978932   379 CKICAENDKD-VKIEPCGHLMCTSCLTSWQESEGQGCPFC 417
Cdd:pfam00097   1 CPICLEEPKDpVTLLPCGHLFCSKCIRSWLESGNVTCPLC 40

Zinc finger, C3HC4 type (RING finger);

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 80978932   377 QLCKICAENDKDVKIEPCGHL-MCTSCLTSWqESEGQGCPFCRCEIKGT 424
Cdd:pfam13920   3 LLCVICLDRPRNVVLLPCGHLcLCEECAERL-LRKKKKCPICRQPIESV 50

HC subclass of RING (RING-HC) finger and its variants; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers. Some have a different Cys/His pattern. Some lack a single Cys or His residue at typical Zn ligand positions, especially, the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can chelate Zn in a RING finger as well. This family corresponds to the HC subclass of RING (RING-HC) fingers that are characterized by containing C3HC4-type canonical RING-HC fingers or noncanonical RING-HC finger variants, including C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type modified RING-HC fingers. The canonical RING-HC finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-HC fingers can be found in a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle, and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serve as scaffolds for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enables efficient transfer of ubiquitin from E2 to the substrates.

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 80978932 379 CKICAENDKDVKIEPCGHLMCTSCLTSWQESEGQGCPFC 417
Cdd:cd16449   3 CPICLERLKDPVLLPCGHVFCRECIRRLLESGSIKCPIC 41

Modified RING finger, HC subclass (C3HC5-type), found in RING finger proteins, RNF26, RNF197 (CGRRF1), RNF156 (MGRN1), RNF157 and similar proteins; This subfamily corresponds to a group of RING finger proteins containing a modified C3HC5-type RING-HC finger, which is distinguished from typical C3HC4 RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain. Cell growth regulator with RING finger domain protein 1 (CGRRF1), also known as cell growth regulatory gene 19 protein (CGR19) or RING finger protein 197 (RNF197), functions as a novel biomarker to monitor endometrial sensitivity and response to insulin-sensitizing drugs, such as metformin, in the context of obesity. RNF26 is an E3 ubiquitin ligase that temporally regulates virus-triggered type I interferon induction by increasing the stability of Mediator of IRF3 activation, MITA, also known as STING, through K11-linked polyubiquitination after viral infection and promoting degradation of IRF3, another important component required for virus-triggered interferon induction. Mahogunin ring finger-1 (MGRN1), also known as RING finger protein 156 (RNF156), is a cytosolic E3 ubiquitin-protein ligase that inhibits signaling through the G protein-coupled melanocortin receptors-1 (MC1R), -2 (MC2R) and -4 (MC4R) via ubiquitylation-dependent and -independent processes. It suppresses chaperone-associated misfolded protein aggregation and toxicity. RNF157 is a cytoplasmic E3 ubiquitin ligase predominantly expressed in the brain. It is a homolog of the E3 ligase MGRN1. In cultured neurons, it promotes neuronal survival in an E3 ligase-dependent manner. In contrast, it supports growth and maintenance of dendrites independent of its E3 ligase activity. RNF157 interacts with and ubiquitinates the adaptor protein APBB1 (amyloid beta precursor protein-binding, family B, member 1 or Fe65), which regulates neuronal survival, but not dendritic growth downstream of RNF157. The nuclear localization of APBB1 together with its interaction partner RNA-binding protein SART3 (squamous cell carcinoma antigen recognized by T cells 3 or Tip110) is crucial to trigger apoptosis.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 80978932 377 QLCKICAENDKDVKIEPCGHL-MCTSCLtswQESEGQGCPFCR 418
Cdd:cd16649   1 GLCVVCLENPASVLLLPCRHLcLCEVCA---KGLRGKTCPICR 40

RING finger, HC subclass, found in RING finger protein 185 (RNF185) and similar proteins; RNF185 is an E3 ubiquitin-protein ligase of endoplasmic reticulum-associated degradation (ERAD) that targets cystic fibrosis transmembrane conductance regulator (CFTR). It controls the degradation of CFTR and CFTR F508del allele in a RING- and proteasome-dependent manner, but does not control that of other classical ERAD model substrates. It also negatively regulates osteogenic differentiation by targeting dishevelled2 (Dvl2), a key mediator of the Wnt signaling pathway, for degradation. Moreover, RNF185 regulates selective mitochondrial autophagy through interaction with the Bcl-2 family protein BNIP1. It also plays an important role in cell adhesion and migration through the modulation of cell migration by ubiquitinating paxillin. RNF185 contains a C3HC4-type RING-HC finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 80978932 379 CKICAENDKDVKIEPCGHLMCTSCLTSWQESE--GQGCPFCRCEIKGTEPI 427
Cdd:cd16744   3 CNICLDTAKDAVVSLCGHLFCWPCLHQWLETRpnRQVCPVCKAGISRDKVI 53

RING finger, HC subclass, found in Arabidopsis thaliana protein XB3 homolog 5 (XBAT35) and similar proteins; XBAT35, also known as ankyrin repeat domain and RING finger-containing protein XBAT35, or RING-type E3 ubiquitin transferase XBAT35, has no E3 ubiquitin-protein ligase activity observed when associated with the E2 enzyme UBC8 in vitro. It contains a typical C3HC4-type RING-HC finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 80978932 379 CKICAENDKDVKIEPCGHL-MCTSCLTSWQESEGqGCPFCRCEIKGT 424
Cdd:cd23129   5 CVVCMDAPRDAVCVPCGHVaGCMSCLKALMQSSP-LCPICRAPVRQV 50

Modified RING finger, HC subclass (C3HC5-type), found in neuralized-like protein NEURL1A, NEURL1B, and similar proteins; This subfamily includes Drosophila neuralized (D-neu) protein, and its two mammalian homologs, NEURL1A and NEURL1B. D-neu is a regulator of the developmentally important Notch signaling pathway. NEURL1A, also known as NEURL1, NEU, neuralized 1, or RING finger protein 67 (RNF67), is a mammalian homolog of D-neu. It functions as an E3 ubiquitin-protein ligase that directly interacts with and monoubiquitinates cytoplasmic polyadenylation element-binding protein 3 (CPEB3), an RNA binding protein and a translational regulator of local protein synthesis, which facilitates hippocampal plasticity and hippocampal-dependent memory storage. It also acts as a potential tumor suppressor that causes apoptosis and downregulates Notch target genes in medulloblastoma. NEURL1B, also known as neuralized-2 (NEUR2) or neuralized-like protein 3, is another mammalian homolog of D-neu protein. It functions as an E3 ubiquitin-protein ligase that interacts with and ubiquitinates Delta. Thus, it plays a role in the endocytic pathways for Notch signaling by working cooperatively with another E3 ligase, Mind bomb-1 (Mib1), in Delta endocytosis to hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs)-positive vesicles. Members of this subfamily contain two neuralized homology regions (NHRs) responsible for Neural-ligand interactions and a modified C3HC5-type RING-HC finger required for ubiquitin ligase activity. The C3HC5-type RING-HC finger is distinguished from typical C3HC4-type RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 80978932 379 CKICAENDKDVKIEPCGHL-MCTSCLTSWQESEGQgCPFCRCEIK 422
Cdd:cd16647   4 CVICYERPVDTVLYRCGHMcMCYDCALQLKRRGGS-CPICRAPIK 47

UBA/TS-N domain; This small domain is composed of three alpha helices. This family includes the previously defined UBA and TS-N domains. The UBA-domain (ubiquitin associated domain) is a novel sequence motif found in several proteins having connections to ubiquitin and the ubiquitination pathway. The structure of the UBA domain consists of a compact three helix bundle. This domain is found at the N terminus of EF-TS hence the name TS-N. The structure of EF-TS is known and this domain is implicated in its interaction with EF-TU. The domain has been found in non EF-TS proteins such as alpha-NAC and MJ0280.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 80978932   865 SSEIERLMSQGYSYQDIQKALVIAHNNIEMAKNIL 899
Cdd:pfam00627   3 EEAIQRLVEMGFDREQVREALRATGNNVERAAEYL 37

RING finger, HC subclass, found in RING finger protein 138 (RNF138) and similar proteins; RNF138, also known as Nemo-like kinase-associated RING finger protein (NARF) or NLK-associated RING finger protein, is an E3 ubiquitin-protein ligase that plays an important role in glioma cell proliferation, apoptosis, and cell cycle. It specifically cooperates with the E2 conjugating enzyme E2-25K (Hip-2/UbcH1), regulates the ubiquitylation and degradation of T cell factor/lymphoid enhancer factor (TCF/LEF), and further suppresses Wnt-beta-catenin signaling. RNF138, together with three closely related proteins: RNF114, RNF125 and RNF166, forms a novel family of ubiquitin ligases with a C3HC4-type RING-HC finger, a C2HC-, and two C2H2-type zinc fingers, as well as a ubiquitin interacting motif (UIM).

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 80978932 378 LCKICAENDKD-VKIEPCGHLMCTSCLTSWQESEGQGCPFCRCEIKGTEP 426
Cdd:cd16544   4 TCPVCQEVLKDpVELPPCRHIFCKACILLALRSSGARCPLCRGPVGKTER 53

RING finger, HC subclass, found in apoptosis protein c-IAP1, c-IAP2, livin, and similar proteins; The cellular inhibitor of apoptosis protein c-IAPs function as ubiquitin E3 ligases that mediate the ubiquitination of substrates involved in apoptosis, nuclear factor-kappaB (NF-kappaB) signaling, and oncogenesis. Unlike other IAPs, such as XIAP, c-IAPs exhibit minimal binding to caspases and may not play an important role in the inhibition of these proteases. c-IAP1, also known as baculoviral IAP repeat-containing protein BIRC2, IAP-2, RING finger protein 48, or TNFR2-TRAF-signaling complex protein 2, is a potent regulator of the tumor necrosis factor (TNF) receptor family and NF-kappaB signaling pathways in the cytoplasm. It can also regulate E2F1 transcription factor-mediated control of cyclin transcription in the nucleus. c-IAP2, also known as BIRC3, IAP-1, apoptosis inhibitor 2 (API2), or IAP homolog C, also influences ubiquitin-dependent pathways that modulate innate immune signalling by activation of NF-kappaB. c-IAPs contain three N-terminal baculoviral IAP repeat (BIR) domains that enable interactions with proteins, a ubiquitin-association (UBA) domain that is responsible for the binding of polyubiquitin (polyUb), a caspase activation and recruitment domain (CARD) that serves as a protein interaction surface, and a C3HC4-type RING-HC finger at the carboxyl terminus that is required for ubiquitin ligase activity. Livin, also known as baculoviral IAP repeat-containing protein 7 (BIRC7), kidney inhibitor of apoptosis protein (KIAP), melanoma inhibitor of apoptosis protein (ML-IAP), or RING finger protein 50, was identified as the melanoma IAP. It plays crucial roles in apoptosis, cell proliferation, and cell cycle control. Its anti-apoptotic activity is regulated by the inhibition of caspase-3, -7, and -9. Its E3 ubiquitin-ligase-like activity promotes degradation of Smac/DIABLO, a critical endogenous regulator of all IAPs. Unlike other family members, mammalian livin contains a single BIR domain and a C3HC4-type RING-HC finger. The UBA domain can be detected in non-mammalian homologs of livin.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 80978932 379 CKICAENDKDVKIEPCGHLM-CTSCLTSWQEsegqgCPFCRCEIKGT 424
Cdd:cd16713  10 CKVCMDKEVSIVFIPCGHLVvCTECAPSLRK-----CPICRATIKGT 51

RING finger, H2 subclass, found in TRAF-interacting protein (TRAIP) and similar proteins; TRAIP, also known as RING finger protein 206 (RNF206) or TRIP, is a ubiquitously expressed nucleolar E3 ubiquitin ligase important for cellular proliferation and differentiation. It is found near mitotic chromosomes and functions as a regulator of the spindle assembly checkpoint. TRAIP interacts with tumor necrosis factor (TNF)-receptor-associated factor (TRAF) proteins and inhibits TNF-alpha-mediated nuclear factor (NF)-kappaB activation. It also interacts with two tumor suppressors CYLD and spleen tyrosine kinase (Syk), and DNA polymerase eta, which facilitates translesional synthesis after DNA damage. TRAIP contains an N-terminal C3H2C2-type RING-H2 finger and an extended coiled-coil domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 80978932 378 LCKICAE---NDKDVKIEPCGHLMCTSCLTSWQESEgQGCPFCR 418
Cdd:cd16480   1 YCTICSDffdNSRDVAAIHCGHTFHYDCLLQWFDTS-RTCPQCR 43

RING finger, H2 subclass, found in synoviolin and similar proteins; Synoviolin, also known as synovial apoptosis inhibitor 1 (Syvn1), Hrd1, or Der3, is an endoplasmic reticulum (ER)-anchoring E3 ubiquitin ligase that functions as a suppressor of ER stress-induced apoptosis and plays a role in homeostasis maintenance. It also targets tumor suppressor gene p53 for proteasomal degradation, suggesting crosstalk between ER associated degradation (ERAD) and p53 mediated apoptotic pathway under ER stress. Moreover, synoviolin controls body weight and mitochondrial biogenesis through negative regulation of the thermogenic coactivator peroxisome proliferator-activated receptor coactivator (PGC)-1beta. It upregulates amyloid beta production by targeting a negative regulator of gamma-secretase, Retention in endoplasmic reticulum 1 (Rer1), for degradation. It is also involved in the degradation of endogenous immature nicastrin, and affects amyloid beta-protein generation. Moreover, synoviolin is highly expressed in rheumatoid synovial cells and may be involved in the pathogenesis of rheumatoid arthritis (RA). It functions as an anti-apoptotic factor that is responsible for the outgrowth of synovial cells during the development of RA. It promotes inositol-requiring enzyme 1 (IRE1) ubiquitination and degradation in synovial fibroblasts with collagen-induced arthritis. Furthermore, the upregulation of synoviolin may represent a protective response against neurodegeneration in Parkinson's disease (PD). In addition, synoviolin is involved in liver fibrogenesis. Synoviolin contains a C3H2C2-type RING-H2 finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 80978932 377 QLCKICAEN-DKDVKIEPCGHLMCTSCLTSWQESEgQGCPFCR 418
Cdd:cd16479   2 NTCIICREEmTVGAKKLPCGHIFHLSCLRSWLQRQ-QTCPTCR 43

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 80978932 379 CKICAENDKDVKIEPCGHLMCTSCLTSWQEsEGQGCPFCR 418
Cdd:cd16455   3 CAICWESMQSARKLPCGHLFHNSCLRSWLE-QDTSCPTCR 41

Modified RING finger, HC subclass (C3HC5-type), found in neuralized-like protein 1A (NEURL1A) and similar proteins; NEURL1A, also known as NEURL1, NEU, neuralized 1, or RING finger protein 67 (RNF67), is a mammalian homolog of the Drosophila neuralized (D-neu) protein. It functions as an E3 ubiquitin-protein ligase that directly interacts with and monoubiquitinates cytoplasmic polyadenylation element-binding protein 3 (CPEB3), an RNA binding protein and a translational regulator of local protein synthesis, which facilitates hippocampal plasticity and hippocampal-dependent memory storage. It also acts as a potential tumor suppressor that causes apoptosis and downregulates Notch target genes in the medulloblastoma. NEURL1A contains two neuralized homology regions (NHRs) responsible for Neural-ligand interactions and a modified C3HC5-type RING-HC finger required for ubiquitin ligase activity. The C3HC5-type RING-HC finger is distinguished from typical C3HC4-type RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 80978932 373 GSTFQLCKICAENDKDVKIEPCGHL-MCTSCLTSWQESEGQGCPFCRCEIK 422
Cdd:cd16785   1 GSWSDECTICYENAVDTVIYTCGHMcLCYACGLRLKKMLNACCPICRRAIK 51

Modified RING finger, HC subclass (C3HC5-type), found in RING finger protein 26 (RNF26) and similar proteins; RNF26 is an E3 ubiquitin ligase that temporally regulates virus-triggered type I interferon induction by increasing the stability of Mediator of IRF3 activation, MITA, also known as STING, through K11-linked polyubiquitination of MITA after viral infection, and promoting the degradation of IRF3, another important component required for virus-triggered interferon induction. Although RNF26 substrates of ubiquitination remain unclear at present, RNF26 upregulation in gastric cancer might be implicated in carcinogenesis through dysregulation of growth regulators. RNF26 contains an N-terminal leucine zipper domain and a C-terminal modified C3HC5-type RING-HC finger, which is distinguished from typical C3HC4 RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 80978932 378 LCKICAENDKDVKIEPCGHL-MCTSC----LTSWQESegQGCPFCRCEIKGT 424
Cdd:cd16788   7 KCVICQDQSKTVLILPCRHMcLCRQCanilLQQPVYR--RNCPLCRTMILQT 56

RING finger, HC subclass, found in tripartite motif-containing protein TRIM25 and similar proteins; TRIM25, also known as estrogen-responsive finger protein (EFP), RING finger protein 147 (RNF147), or RING-type E3 ubiquitin transferase, is an E3 ubiquitin/ISG15 ligase that is induced by estrogen and is therefore particularly abundant in placenta and uterus. TRIM25 regulates various cellular processes through E3 ubiquitin ligase activity, transferring ubiquitin and ISG15 to target proteins. It mediates K63-linked polyubiquitination of retinoic acid inducible gene I (RIG-I) that is crucial for downstream antiviral interferon signaling. It is also required for melanoma differentiation-associated gene 5 (MDA5) and mitochondrial antiviral signaling (MAVS, also known as IPS-1, VISA, Cardiff) mediated activation of nuclear factor-kappaB (NF-kappaB) and interferon production. Upon UV irradiation, TRIM25 interacts with mono-ubiquitinated PCNA and promotes its ISG15 modification (ISGylation), suggesting a crucial role in termination of error-prone translesion DNA synthesis. TRIM25 also functions as a novel regulator of p53 and Mdm2. It enhances p53 and Mdm2 abundance by inhibiting their ubiquitination and degradation in 26S proteasomes. Meanwhile, it inhibits p53's transcriptional activity and dampens the response to DNA damage, and is essential for medaka development and this dependence is rescued by silencing of p53. Moreover, TRIM25 is involved in the host cellular innate immune response against retroviral infection. It interferes with the late stage of feline leukemia virus (FeLV) replication. Furthermore, TRIM25 acts as an oncogene in gastric cancer. Its blockade by RNA interference inhibits migration and invasion of gastric cancer cells through transforming growth factor-beta (TGF-beta) signaling, suggesting it presents a novel target for the detection and treatment of gastric cancer. In addition, TRIM25 acts as an RNA-specific activator for Lin28a/TuT4-mediated uridylation. TRIM25 belongs to the C-IV subclass of 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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 80978932 379 CKICAENDKDVKIEPCGHLMCTSCLTS---WQESEGQGCPFCRCE 420
Cdd:cd16597   8 CSICLELFKDPVTLPCGHNFCGVCIEKtwdSQHGSEYSCPQCRAT 52

RING finger, HC subclass, found in RING finger protein 123 (RNF123) and similar proteins; RNF123, also known as Kip1 ubiquitination-promoting complex protein 1 (KPC1), is an E3 ubiquitin-protein ligase that mediates ubiquitination and proteasomal processing of the nuclear factor-kappaB 1 (NF-kappaB1) precursor p105 to the p50 active subunit that restricts tumor growth. It also regulates degradation of heterochromatin protein 1alpha (HP1alpha) and 1beta (HP1beta) in lamin A/C knock-down cells. Moreover, RNF123, together with Kip1 ubiquitylation-promoting complex 2 (KPC2), forms the Kip1 ubiquitination-promoting complex (KPC), acting as a cytoplasmic ubiquitin ligase that regulates degradation of the cyclin-dependent kinase inhibitor p27 (Kip1) at the G1 phase of the cell cycle. RNF123 may also function as a clinically relevant, peripheral state marker of depression. RNF123 contains a C3HC4-type RING-HC finger at the C-terminus.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 80978932 377 QLCKICAENDKDVKIEPCGHLMCTSCLTSWQESeGQGCPFCRCEI 421
Cdd:cd16541   1 DLCPICYAHPIDAVFLPCGHKSCRSCINRHLMN-NKECFFCKATI 44

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 80978932 379 CKICAENDKDVKIEPCGHLMCTSCLTSW--QESEGQGCPFCRCEIKG 423
Cdd:cd16611   7 CPLCLDFFRDPVMLSCGHNFCQSCITGFweLQAEDTTCPECRELCQY 53

RING finger, HC subclass, found in tripartite motif-containing protein 39 (TRIM39) and similar proteins; TRIM39, also known as RING finger protein 23 (RNF23) or testis-abundant finger protein, is an E3 ubiquitin-protein ligase that plays a role in controlling DNA damage-induced apoptosis through inhibition of the anaphase promoting complex (APC/C), a multiprotein ubiquitin ligase that controls multiple cell cycle regulators, including cyclins, geminin, and others. TRIM39 also functions as a regulator of several key processes in the proliferative cycle. It directly regulates p53 stability. It modulates cell cycle progression and DNA damage responses via stabilizing p21. Moreover, TRIM39 negatively regulates the nuclear factor kappaB (NFkappaB)-mediated signaling pathway through stabilization of Cactin, an inhibitor of NFkappaB- and Toll-like receptor (TLR)-mediated transcription, which is induced by inflammatory stimulants such as tumor necrosis factor alpha. Furthermore, TRIM39 is a MOAP-1-binding protein that can promote apoptosis signaling through stabilization of MOAP-1 via the inhibition of its poly-ubiquitination process. TRIM39 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 80978932 378 LCKICAENDKDVKIEPCGHLMCTSCLTSWQESEGQG--CPFC 417
Cdd:cd16601   3 SCSLCKEYLKDPVIIECGHNFCRACITRFWEELDGDfpCPQC 44

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 80978932   479 PSSPFSMAPQASLPPVPPrldLLQQRAPVPASTSVLGTASKAASGSLH--KDKPLPIPPTLRDLPPPPPPDRPYSVGAET 556
Cdd:pfam03154 294 PPQPFPLTPQSSQSQVPP---GPSPAAPGQSQQRIHTPPSQSQLQSQQppREQPLPPAPLSMPHIKPPPTTPIPQLPNPQ 370

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 80978932   557 RPQRRPLPCTPGDCPSRDKLPPVPSSRPGDSWLSR--------PIPKVPVATPNPGDPWNGRELTNRHSLP--------- 619
Cdd:pfam03154 371 SHKHPPHLSGPSPFQMNSNLPPPPALKPLSSLSTHhppsahppPLQLMPQSQQLPPPPAQPPVLTQSQSLPppaashppt 450

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 80978932   620 ---FSLPSQME-PRADVPRLGSTFSLDTSMTMNSSPVAGPESEHPKIKPSSSANAIYSLAARPLPMPKLPPGEQGESEED 695
Cdd:pfam03154 451 sglHQVPSQSPfPQHPFVPGGPPPITPPSGPPTSTSSAMPGIQPPSSASVSSSGPVPAAVSCPLPPVQIKEEALDEAEEP 530

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 80978932   696 TEYMTPTSRPvgvqKPEP---KRPLEATQSSRACD-CDQQIDSCTYEAMY 741
Cdd:pfam03154 531 ESPPPPPRSP----SPEPtvvNTPSHASQSARFYKhLDRGYNSCARTDLY 576

RING finger, HC subclass, found in yeast Bre1 and its homologs from eukaryotes; Bre1 is an E3 ubiquitin-protein ligase that catalyzes monoubiquitination of histone H2B in concert with the E2 ubiquitin-conjugating enzyme, Rad6. The Rad6-Bre1-mediated histone H2B ubiquitylation modulates the formation of double-strand breaks (DSBs) during meiosis in yeast. it is also required, indirectly, for the methylation of histone 3 on lysine 4 (H3K4) and 79. RNF20, also known as BRE1A and RNF40, also known as BRE1B, are the mammalian homologs of Bre1. They work together to form a heterodimeric Bre1 complex that facilitate the K120 monoubiquitination of histone H2B (H2Bub1), a DNA damage-induced histone modification that is crucial for recruitment of the chromatin remodeler SNF2h to DNA double-strand break (DSB) damage sites. Moreover, the Bre1 complex acts as a tumor suppressor, augmenting expression of select tumor suppressor genes and suppressing select oncogenes. Deficiency in the mammalian histone H2B ubiquitin ligase Bre1 leads to replication stress and chromosomal instability. All subfamily members contain a C3HC4-type RING-HC finger at its C-terminus.

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 80978932 379 CKICAENDKDVKIEPCGHLMCTSCLTSWQESEGQGCPFC 417
Cdd:cd16499   9 CSVCNDRFKDVIITKCGHVFCNECVQKRLETRQRKCPGC 47

RING finger, HC subclass, found in Caenorhabditis elegans BRCA1-associated RING domain protein 1 (CeBARD1) and similar proteins; CeBARD1, also called Ce-BRD-1, Cebrd-1, or RING-type E3 ubiquitin transferase BARD1, is a constituent of the CeBCD complex that possesses E3 ubiquitin-protein ligase activity. It plays a role in triggering cellular responses at damage sites in response to DNA damage that may be induced by ionizing radiation. It protects against chromosome non-disjunction and nuclear fragmentation during meiotic double-strand break repair to ensure sister chromatid recombination and aid chromosome stability. CeBARD1 contains a typical C3HC4-type RING-HC finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 80978932 376 FQLCKICAENDKDV-KIEPCGHLMCTSCLTSWQESEGQgCPFCR 418
Cdd:cd23143   1 LIECVICSEPQIDTfLLSSCGHIYCWECFTEFIEKRHM-CPSCR 43

RING finger, HC subclass, found in Arabidopsis thaliana MND1-interacting protein 1 (MIP1) and similar proteins; This subfamily includes Arabidopsis thaliana MIP1, RING finger protein 4 (RF4) and RING finger protein 298 (RF298). MIP1 interacts with MND1, HOP2 and XRI1. RF4 and RF298 are putative E3 ubiquitin-protein ligase that may mediate E2-dependent protein ubiquitination. Members of this subfamily contain a typical C3HC4-type RING-HC finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 80978932 379 CKICAENDKDVKIEPCGHL-MCTSCLTSWQESEGQGCPFCRCEIK 422
Cdd:cd23128   6 CVMCMEEERSVVFLPCAHQvVCSGCNDLHEKKGMRECPSCRGEIQ 50

RING finger, HC subclass, found in RING finger and SPRY domain-containing protein 1 (RSPRY1) and similar proteins; RSPRY1 is a hypothetical RING and SPRY domain-containing protein of unknown physiological function. Mutations in its corresponding gene RSPRY1 may associate with a distinct skeletal dysplasia syndrome. RSPRY1 contains a B30.2/SPRY domain and a C3HC4-type RING-HC finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 80978932 379 CKICAENDKDVKIEPCGH----LMCTSCLTSwqesegqgCPFCRCEI 421
Cdd:cd16566   5 CTLCFDKVADTELRPCGHsgfcMECALQLET--------CPLCRQPI 43

RING finger, HC subclass, found in Arabidopsis thaliana protein XB3 homolog 1 (XBAT31) and similar proteins; XBAT31, also called ankyrin repeat domain and RING finger-containing protein XBAT31, or RING-type E3 ubiquitin transferase XB31, has no E3 ubiquitin-protein ligase activity observed when associated with the E2 enzyme UBC8 in vitro. XBAT31 contains a typical C3HC4-type RING-HC finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 80978932 374 STFQLCKICAENDKDVKIEPCGHLMCTSCL----------TSWQESEGQGCPFCRCEI 421
Cdd:cd23144   4 SDEDVCCICFEHLCTIEIKDCGHQMCATCAlklcchnkpnPSSSPPRPPACPFCRQDI 61