Src homology 2 (SH2) domain found in the Cbl-b TKB domain; SH2 found in the Cbl-b TKB domain. The Cbl (for Casitas B-lineage lymphoma) family of E3 ubiquitin ligases contains three members Cbl, Cbl-b and Cbl-c. The founding member Cbl was discovered first as the oncogenic protein v-Cbl, a Gag-fusion transforming protein of Cas NS-1 retrovirus, which causes pre- and pro-B lymphomas in mice. The N-terminus of the Cbl proteins is composed of a tyrosine kinase-binding (TKB) domain, also called phosphotyrosine binding (PTB) domain, a short linker region and the RING-type zinc finger. In addition, Cbl and Cbl-b contain a leucine zipper motif and a proline-rich domain in the C-terminus. The TKB domain consists of a four-helix bundle (4H), a calcium-binding EF hand and a divergent SH2 domain. Cbl-b plays a role in early hematopoietic development and is a negative regulator of T-cell receptor, B-cell receptor and high affinity immunoglobulin epsilon receptor signal transduction pathways. It also negatively regulates insulin-like growth factor 1 signaling during muscle atrophy caused by unloading and is involved in EGFR ubiquitination and internalization. Diseases associated with defects in Cbl-b include: multiple sclerosis, autoimmune diseases, including type 1 diabetes, and a craniofacial phenotype. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50315    254 RNWNSLAVTHPGYMAFLTYDEVKARLQKFIHKPGSYIFRLSCTRLGQWAIGYVTADGNILQTIPHNKPLFQALIDGFREG 333
Cdd:cd09920   1 RNWQVLAVTHPGYMAFLTYDEVKARLQKFRDKPGSYVFRLSCTRLGQWAIGYVTADGKILQTIPQNKSLCQALIDGSREG 80

                        90
                ....*....|....*..
gi 50315    334 FYLFPDGRNQNPDLTGL 350
Cdd:cd09920  81 FYLYPDGRLDNPDLSGA 97

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        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 50315    356 QDHIKVTQ-----------------ICAENDKDVKIEPCGHLMCTSCLTSWQESEGQGCPFCRCEIKGTEPIVVDPF 415
Cdd:cd16708   1 QDHIKVTQeqyelycemgstfqlckICAENDKDVKIEPCGHLMCTSCLTSWQESEGQGCPFCRCEIKGTEPIVVDPF 77

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50315      461 RPSSPFSMAPQASL--PPVPPRLDLLQQRAPVPASTSVLGTASKAASGSLHKDKPLPIPPTLRDLPPppppdrpysvGAE 538
Cdd:PHA03247 2685 RRAARPTVGSLTSLadPPPPPPTPEPAPHALVSATPLPPGPAAARQASPALPAAPAPPAVPAGPATP----------GGP 2754

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50315      539 TRPQRRPLPCTPGD-CPSRDKL--PPVPSSRPGDSWLSRTIPKVPvATPNPGDPWNGRELTNRHSLPFSLPSQME--PRA 613
Cdd:PHA03247 2755 ARPARPPTTAGPPApAPPAAPAagPPRRLTRPAVASLSESRESLP-SPWDPADPPAAVLAPAAALPPAASPAGPLppPTS 2833

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50315      614 DVPRLGSTFS--LDTSMTMNSSPVAG------PESEHPKIKPSSSANAIYSLAARP--------LPMPKLPPGEQGESEE 677
Cdd:PHA03247 2834 AQPTAPPPPPgpPPPSLPLGGSVAPGgdvrrrPPSRSPAAKPAAPARPPVRRLARPavsrstesFALPPDQPERPPQPQA 2913

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50315      678 DTEYMTPTSRPVGVQKPEPKRPLEATQSSRACDCDQQIDSCTYEAMYTIQSQALSVAENSASGEGNLATAHTSTGPEESE 757
Cdd:PHA03247 2914 PPPPQPQPQPPPPPQPQPPPPPPPRPQPPLAPTTDPAGAGEPSGAVPQPWLGALVPGRVAVPRFRVPQPAPSREAPASST 2993

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50315      758 NEDDGYDVPK-------------PPVPAVLARRTLSDISNASSSFGWLSLDGDPTNFNEGSQVPERPP-------KPFPR 817
Cdd:PHA03247 2994 PPLTGHSLSRvsswasslalheeTDPPPVSLKQTLWPPDDTEDSDADSLFDSDSERSDLEALDPLPPEphdpfahEPDPA 3073

                         410
                  ....*....|....*
gi 50315      818 RINSERKASSYQQGG 832
Cdd:PHA03247 3074 TPEAGARESPSSQFG 3088

Src homology 2 (SH2) domain found in the Cbl-b TKB domain; SH2 found in the Cbl-b TKB domain. The Cbl (for Casitas B-lineage lymphoma) family of E3 ubiquitin ligases contains three members Cbl, Cbl-b and Cbl-c. The founding member Cbl was discovered first as the oncogenic protein v-Cbl, a Gag-fusion transforming protein of Cas NS-1 retrovirus, which causes pre- and pro-B lymphomas in mice. The N-terminus of the Cbl proteins is composed of a tyrosine kinase-binding (TKB) domain, also called phosphotyrosine binding (PTB) domain, a short linker region and the RING-type zinc finger. In addition, Cbl and Cbl-b contain a leucine zipper motif and a proline-rich domain in the C-terminus. The TKB domain consists of a four-helix bundle (4H), a calcium-binding EF hand and a divergent SH2 domain. Cbl-b plays a role in early hematopoietic development and is a negative regulator of T-cell receptor, B-cell receptor and high affinity immunoglobulin epsilon receptor signal transduction pathways. It also negatively regulates insulin-like growth factor 1 signaling during muscle atrophy caused by unloading and is involved in EGFR ubiquitination and internalization. Diseases associated with defects in Cbl-b include: multiple sclerosis, autoimmune diseases, including type 1 diabetes, and a craniofacial phenotype. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50315    254 RNWNSLAVTHPGYMAFLTYDEVKARLQKFIHKPGSYIFRLSCTRLGQWAIGYVTADGNILQTIPHNKPLFQALIDGFREG 333
Cdd:cd09920   1 RNWQVLAVTHPGYMAFLTYDEVKARLQKFRDKPGSYVFRLSCTRLGQWAIGYVTADGKILQTIPQNKSLCQALIDGSREG 80

                        90
                ....*....|....*..
gi 50315    334 FYLFPDGRNQNPDLTGL 350
Cdd:cd09920  81 FYLYPDGRLDNPDLSGA 97

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 50315      177 FRITKADAAEFWRKAFGEKTIVPWKSFRQALHEVHPISSGLEAMALKSTIDLTCNDYISVFEFDIFTRLFQPWSSLLRNW 256
Cdd:pfam02761   1 FRITKSEAAEFWKKSFGKRTIVPWKEFRTALQQVHGIESGLEAMALKSTIDLTCNDHISIFEFDVFTRLFQPWSTLLRNW 80

                  ....
gi 50315      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 50315    847 LSSEIERLMSQGYSYQDIQKALVIAHNNIEMAKNILREFV 886
Cdd:cd14393   1 LSSEIENLMSQGYSYQDIQKALVIAQNNIEMAKNILREFV 40

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
                   ....*....|....*....|....*....|....*...
gi 50315       364 ICAEN-DKDVKIEPCGHLMCTSCLTSWQESEGQGCPFC 400
Cdd:smart00184   3 ICLEEyLKDPVILPCGHTFCRSCIRKWLESGNNTCPIC 40

Ubiquitin associated domain; Present in Rad23, SNF1-like kinases. The newly-found UBA in p62 is known to bind ubiquitin.

                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 50315       847 LSSEIERLMSQGYSYQDIQKALVIAHNNIEMAKNIL 882
Cdd:smart00165   1 DEEKIDQLLEMGFSREEALKALRAANGNVERAAEYL 36

Family of unknown function (DUF5585); This is a family of unknown function found in chordata.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50315      563 PSSRPG--DSWLSRTIpkvpvATPNPGDPWNGRELTNRHSLPFSLPSQMEPRADVPRLGSTFSLDTSMTMNSSPVAGpeS 640
Cdd:pfam17823 100 PATREGaaDGAASRAL-----AAAASSSPSSAAQSLPAAIAALPSEAFSAPRAAACRANASAAPRAAIAAASAPHAA--S 172

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50315      641 EHPKIKPSSSANAIYSLAARPLPM------PKLPPGEQGESEEDTEYMTPTSRPVGVQKPepkrpleaTQSSRACDCDQQ 714
Cdd:pfam17823 173 PAPRTAASSTTAASSTTAASSAPTtaassaPATLTPARGISTAATATGHPAAGTALAAVG--------NSSPAAGTVTAA 244

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50315      715 IDSCTYEAMYTIQSQALSVAenSASGEGNLATAHTST-GPEESENEDDGYDVPKPPVPAvlarRTLSDISNASSSFGWLS 793
Cdd:pfam17823 245 VGTVTPAALATLAAAAGTVA--SAAGTINMGDPHARRlSPAKHMPSDTMARNPAAPMGA----QAQGPIIQVSTDQPVHN 318

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 50315      794 LDGDPTNFNEGSQVPERPPKPFPrRINSERKASSYQQGGGATANPVATAPSpQLSSEIE 852
Cdd:pfam17823 319 TAGEPTPSPSNTTLEPNTPKSVA-STNLAVVTTTKAQAKEPSASPVPVLHT-SMIPEVE 375

Src homology 2 (SH2) domain found in the Cbl-b TKB domain; SH2 found in the Cbl-b TKB domain. The Cbl (for Casitas B-lineage lymphoma) family of E3 ubiquitin ligases contains three members Cbl, Cbl-b and Cbl-c. The founding member Cbl was discovered first as the oncogenic protein v-Cbl, a Gag-fusion transforming protein of Cas NS-1 retrovirus, which causes pre- and pro-B lymphomas in mice. The N-terminus of the Cbl proteins is composed of a tyrosine kinase-binding (TKB) domain, also called phosphotyrosine binding (PTB) domain, a short linker region and the RING-type zinc finger. In addition, Cbl and Cbl-b contain a leucine zipper motif and a proline-rich domain in the C-terminus. The TKB domain consists of a four-helix bundle (4H), a calcium-binding EF hand and a divergent SH2 domain. Cbl-b plays a role in early hematopoietic development and is a negative regulator of T-cell receptor, B-cell receptor and high affinity immunoglobulin epsilon receptor signal transduction pathways. It also negatively regulates insulin-like growth factor 1 signaling during muscle atrophy caused by unloading and is involved in EGFR ubiquitination and internalization. Diseases associated with defects in Cbl-b include: multiple sclerosis, autoimmune diseases, including type 1 diabetes, and a craniofacial phenotype. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50315    254 RNWNSLAVTHPGYMAFLTYDEVKARLQKFIHKPGSYIFRLSCTRLGQWAIGYVTADGNILQTIPHNKPLFQALIDGFREG 333
Cdd:cd09920   1 RNWQVLAVTHPGYMAFLTYDEVKARLQKFRDKPGSYVFRLSCTRLGQWAIGYVTADGKILQTIPQNKSLCQALIDGSREG 80

                        90
                ....*....|....*..
gi 50315    334 FYLFPDGRNQNPDLTGL 350
Cdd:cd09920  81 FYLYPDGRLDNPDLSGA 97

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 50315      177 FRITKADAAEFWRKAFGEKTIVPWKSFRQALHEVHPISSGLEAMALKSTIDLTCNDYISVFEFDIFTRLFQPWSSLLRNW 256
Cdd:pfam02761   1 FRITKSEAAEFWKKSFGKRTIVPWKEFRTALQQVHGIESGLEAMALKSTIDLTCNDHISIFEFDVFTRLFQPWSTLLRNW 80

                  ....
gi 50315      257 NSLA 260
Cdd:pfam02761  81 NLLA 84

RING finger, HC subclass, found in E3 ubiquitin-protein ligase Cbl-b and similar proteins; Cbl-b, also known as Casitas B-lineage lymphoma proto-oncogene b, RING finger protein 56 (RNF56), SH3-binding protein Cbl-b, or signal transduction protein Cbl-b, has been identified as a regulator of antigen-specific, T cell-intrinsic, peripheral immune tolerance, a state also known as clonal anergy. It may inhibit activation of the p85 subunit of phosphoinositide 3-kinase (PI3K), protein kinase C-theta (PKC-theta), and phospholipase C-gamma1 (PLC-gamma1) and negatively regulates T-cell receptor-induced transcription factor nuclear factor kappaB (NF-kappaB) activation. In addition, Cbl-b may target multiple signaling molecules involved in transforming growth factor (TGF)-beta-mediated transactivation pathways. Cbl-b contains a tyrosine-kinase-binding domain (TKB, also known as the phosphotyrosine binding PTB domain, is composed of a four helix-bundle, a Ca2+ binding EF-hand and a highly variant SH2 domain), a proline rich domain, a nuclear localization signal, a C3HC4-type RING-HC finger and an ubiquitin-associated (UBA) domain.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 50315    357 DHIKVTQ-----------------ICAENDKDVKIEPCGHLMCTSCLTSWQESEGQGCPFCRCEIKGTEPIVVDPF 415
Cdd:cd16709   1 DHIKVTQeqyelycemgstfqlckICAENDKDVKIEPCGHLMCTSCLTAWQESDGQGCPFCRCEIKGTEPIIVDPF 76

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
                ....*....|....*....|....*....|....*....|....*....|.
gi 50315    360 KVTQICAENDKDVKIEPCGHLMCTSCLTSWQESEGQGCPFCRCEIKGTEPI 410
Cdd:cd16710  14 ELCKICAERDKDVRIEPCGHLLCSCCLAAWQHSDSQTCPFCRCEIKGREAV 64

UBA domain found in casitas B-lineage lymphoma (Cbl) proteins; The Cbl adaptor proteins family contains a small class of RING-type E3 ubiquitin ligases with oncogenic activity which is represented by three mammalian members, c-Cbl, Cbl-b and Cbl-3. Cbl proteins function as potent negative regulators of various signaling cascades in a wide range of cell types. They play roles in ubiquitinating the activated tyrosine kinases and targeting them for degradation. Cbl proteins in this family consists of a highly conserved N-terminal half that includes a tyrosine-kinase-binding (TKB) domain and a RING finger domain, both of which are required for Cbl-mediated downregulation of RTKs, and a C-terminal half that includes a ubiquitin-associated (UBA) domain and other protein interaction motifs. The UBA domain contains leucine/isoleucine repeats and may play a role in dimerization of Cbl proteins. In addition, although both c-Cbl and Cbl-b have the C-terminal UBA domain, only the UBA domain from Cbl-b can bind ubiquitin.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 50315    847 LSSEIERLMSQGYSYQDIQKALVIAHNNIEMAKNILREFV 886
Cdd:cd14318   1 LLSYIAKLVGEGYSKEDVIRALGIARNNVEMARDILREFA 40

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 50315      364 ICAENDKDVKIEPCGHLMCTSCLTSWQESegqGCPFCRCEIKGTEPI 410
Cdd:pfam14447   3 LCGRNGTVHALIPCGHLVCRDCFDGSDFS---ACPICRRRIDADDPF 46

UBA domain found in E3 ubiquitin-protein ligase Cbl-b and similar proteins; Cbl-b, also called casitas B-lineage lymphoma proto-oncogene b, RING finger protein 56, SH3-binding protein Cbl-b, or signal transduction protein Cbl-b, has been identified as a regulator of antigen-specific, T cell-intrinsic, peripheral immune tolerance (a state also called clonal anergy). It may inhibit activation of the p85 subunit of phosphoinositide 3-kinase (PI3K), protein kinase C-theta (PKC-theta), and phospholipase C-gamma1 (PLC-gamma1) and negatively regulates T-cell receptor-induced transcription factor nuclear factor-kappaB (NF-kappaB) activation. In addition, Cbl-b may target multiple signaling molecules involved in transforming growth factor (TGF)-beta-mediated transactivation pathways. Cbl-b contains a proline rich domain, a nuclear localization signal, a C3HC4 zinc finger and a ubiquitin-associated (UBA) domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 50315    847 LSSEIERLMSQGYSYQDIQKALVIAHNNIEMAKNILREFV 886
Cdd:cd14392   2 VDAKIAKLMGEGYSFEEVKRALEIAQNNVEVARSILREFA 41

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50315      461 RPSSPFSMAPQASL--PPVPPRLDLLQQRAPVPASTSVLGTASKAASGSLHKDKPLPIPPTLRDLPPppppdrpysvGAE 538
Cdd:PHA03247 2685 RRAARPTVGSLTSLadPPPPPPTPEPAPHALVSATPLPPGPAAARQASPALPAAPAPPAVPAGPATP----------GGP 2754

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50315      539 TRPQRRPLPCTPGD-CPSRDKL--PPVPSSRPGDSWLSRTIPKVPvATPNPGDPWNGRELTNRHSLPFSLPSQME--PRA 613
Cdd:PHA03247 2755 ARPARPPTTAGPPApAPPAAPAagPPRRLTRPAVASLSESRESLP-SPWDPADPPAAVLAPAAALPPAASPAGPLppPTS 2833

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50315      614 DVPRLGSTFS--LDTSMTMNSSPVAG------PESEHPKIKPSSSANAIYSLAARP--------LPMPKLPPGEQGESEE 677
Cdd:PHA03247 2834 AQPTAPPPPPgpPPPSLPLGGSVAPGgdvrrrPPSRSPAAKPAAPARPPVRRLARPavsrstesFALPPDQPERPPQPQA 2913

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50315      678 DTEYMTPTSRPVGVQKPEPKRPLEATQSSRACDCDQQIDSCTYEAMYTIQSQALSVAENSASGEGNLATAHTSTGPEESE 757
Cdd:PHA03247 2914 PPPPQPQPQPPPPPQPQPPPPPPPRPQPPLAPTTDPAGAGEPSGAVPQPWLGALVPGRVAVPRFRVPQPAPSREAPASST 2993

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50315      758 NEDDGYDVPK-------------PPVPAVLARRTLSDISNASSSFGWLSLDGDPTNFNEGSQVPERPP-------KPFPR 817
Cdd:PHA03247 2994 PPLTGHSLSRvsswasslalheeTDPPPVSLKQTLWPPDDTEDSDADSLFDSDSERSDLEALDPLPPEphdpfahEPDPA 3073

                         410
                  ....*....|....*
gi 50315      818 RINSERKASSYQQGG 832
Cdd:PHA03247 3074 TPEAGARESPSSQFG 3088

Zinc finger, C3HC4 type (RING finger);

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 50315      363 QICAENDKDVKIEPCGHL-MCTSCLTSWqESEGQGCPFCRCEIKGT 407
Cdd:pfam13920   6 VICLDRPRNVVLLPCGHLcLCEECAERL-LRKKKKCPICRQPIESV 50

RING finger, HC subclass, found in peroxin-10 (PEX10) and similar proteins; PEX10, also known as peroxisome biogenesis factor 10, peroxisomal biogenesis factor 10, peroxisome assembly protein 10, or RING finger protein 69 (RNF69), is an integral peroxisomal membrane protein with two transmembrane regions and a C3HC4-type RING-HC finger within its cytoplasmically exposed C-terminus. It plays an essential role in peroxisome assembly, import of target substrates, and recycling or degradation of protein complexes and amino acids. It is an essential component of the spinal locomotor circuit, and thus its mutations may be involved in peroxisomal biogenesis disorders (PBD). Mutations in human PEX10 also result in autosomal recessive ataxia. Moreover, PEX10 functions as an E3-ubiquitin ligase with an E2, UBCH5C. It mono- or poly-ubiquitinates PEX5, a key player in peroxisomal matrix protein import, in a UBC4-dependent manner, to control PEX5 receptor recycling or degradation. It also links the E2 ubiquitin conjugating enzyme PEX4 to the protein import machinery of the peroxisome.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 50315    364 ICAENDKDVKIEPCGHLMCTSCLTSWQESEGQgCPFCRCEIK 405
Cdd:cd16527   5 LCLEERRHPTATPCGHLFCWSCITEWCNEKPE-CPLCREPFQ 45

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 50315    364 ICAENDKDVKIEPCGHL-MCTSCLTSWQESEGqGCPFCRCEIKGT 407
Cdd:cd23129   7 VCMDAPRDAVCVPCGHVaGCMSCLKALMQSSP-LCPICRAPVRQV 50

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
                ....*....|....*....|....*....|....*....|....*....
gi 50315    364 ICAENDKDVKIEPCGHLMCTSCLTSWQESE--GQGCPFCRCEIKGTEPI 410
Cdd:cd16744   5 ICLDTAKDAVVSLCGHLFCWPCLHQWLETRpnRQVCPVCKAGISRDKVI 53

RING finger, HC subclass, found in RING finger protein 5 (RNF5) and similar proteins; RNF5, also known as protein G16 or Ram1, is an E3 ubiquitin-protein ligase anchored to the outer membrane of the endoplasmic reticulum (ER). It acts at early stages of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) biosynthesis and functions as a target for therapeutic modalities to antagonize mutant CFTR proteins in CF patients carrying the F508del allele. It also regulates the turnover of specific G protein-coupled receptors by ubiquitinating JNK-associated membrane protein (JAMP) and preventing proteasome recruitment. RNF5 limits basal levels of autophagy and influences susceptibility to bacterial infection through the regulation of ATG4B stability. It is also involved in the degradation of Pendrin, a transmembrane chloride/anion exchanger highly expressed in thyroid, kidney, and inner ear. RNF5 plays an important role in cell adhesion and migration. It can modulate cell migration by ubiquitinating paxillin. Furthermore, RNF5 interacts with virus-induced signaling adaptor (VISA) at mitochondria in a viral infection-dependent manner, and further targets VISA at K362 and K461 for K48-linked ubiquitination and degradation after viral infection. It also negatively regulates virus-triggered signaling by targeting MITA, also known as STING, for ubiquitination and degradation at the mitochondria. In addition, RNF5 determines breast cancer response to ER stress-inducing chemotherapies through the regulation of the L-glutamine carrier proteins SLC1A5 and SLC38A2 (SLC1A5/38A2). It also has been implicated in muscle organization and in recognition and processing of misfolded proteins. RNF5 contains a C3HC4-type RING-HC finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 50315    364 ICAENDKDVKIEPCGHLMCTSCLTSWQES--EGQGCPFCRCEI 404
Cdd:cd16743   5 ICLETARDAVVSLCGHLFCWPCLHQWLETrpERQECPVCKAGI 47

Family of unknown function (DUF5585); This is a family of unknown function found in chordata.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50315      563 PSSRPG--DSWLSRTIpkvpvATPNPGDPWNGRELTNRHSLPFSLPSQMEPRADVPRLGSTFSLDTSMTMNSSPVAGpeS 640
Cdd:pfam17823 100 PATREGaaDGAASRAL-----AAAASSSPSSAAQSLPAAIAALPSEAFSAPRAAACRANASAAPRAAIAAASAPHAA--S 172

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50315      641 EHPKIKPSSSANAIYSLAARPLPM------PKLPPGEQGESEEDTEYMTPTSRPVGVQKPepkrpleaTQSSRACDCDQQ 714
Cdd:pfam17823 173 PAPRTAASSTTAASSTTAASSAPTtaassaPATLTPARGISTAATATGHPAAGTALAAVG--------NSSPAAGTVTAA 244

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50315      715 IDSCTYEAMYTIQSQALSVAenSASGEGNLATAHTST-GPEESENEDDGYDVPKPPVPAvlarRTLSDISNASSSFGWLS 793
Cdd:pfam17823 245 VGTVTPAALATLAAAAGTVA--SAAGTINMGDPHARRlSPAKHMPSDTMARNPAAPMGA----QAQGPIIQVSTDQPVHN 318

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 50315      794 LDGDPTNFNEGSQVPERPPKPFPrRINSERKASSYQQGGGATANPVATAPSpQLSSEIE 852
Cdd:pfam17823 319 TAGEPTPSPSNTTLEPNTPKSVA-STNLAVVTTTKAQAKEPSASPVPVLHT-SMIPEVE 375

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
                ....*....|....*....|....*....|....*....|....*..
gi 50315    364 ICAENDKD-VKIEPCGHLMCTSCLTSWQESEGQGCPFCRCEIKGTEP 409
Cdd:cd16544   7 VCQEVLKDpVELPPCRHIFCKACILLALRSSGARCPLCRGPVGKTER 53

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
                ....*....|....*....|....*....|....*....
gi 50315    364 ICAEN-DKDVKIEPCGHLMCTSCLTSWQESEgQGCPFCR 401
Cdd:cd16479   6 ICREEmTVGAKKLPCGHIFHLSCLRSWLQRQ-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
                ....*....|....*....|....*....|....*...
gi 50315    364 ICAENDKDVKIEPCGHLMCTSCLTSWQEsEGQGCPFCR 401
Cdd:cd16455   5 ICWESMQSARKLPCGHLFHNSCLRSWLE-QDTSCPTCR 41

RING finger, HC subclass, found in RING finger protein 213 (RNF213) and similar proteins; RNF213, also known as ALK lymphoma oligomerization partner on chromosome 17 or Moyamoya steno-occlusive disease-associated AAA+ and RING finger protein (mysterin), is an intracellular soluble protein that functions as an E3 ubiquitin-protein ligase and AAA+ ATPase, which possibly contributes to vascular development through mechanical processes in the cell. It plays a unique role in endothelial cells for proper gene expression in response to inflammatory signals from the environment. Mutations in RNF213 may be associated with Moyamoya disease (MMD), an idiopathic cerebrovascular occlusive disorder prevalent in East Asia. It also acts as a nuclear marker for acanthomorph phylogeny. RNF213 contains two tandem enzymatically active AAA+ ATPase modules and a C3HC4-type RING-HC finger. It can form a huge ring-shaped oligomeric complex.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 50315    364 ICAENDKDVKIEPCGHLMCTSCLTSWQESEGQgCPFCRCEIK 405
Cdd:cd16561   7 ICLEDLNDPVKLPCDHVFCEECIRQWLPGQMS-CPLCRTELP 47

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 50315    363 QICAENDKDVKIEPCGHLM-CTSCLTSWQEsegqgCPFCRCEIKGT 407
Cdd:cd16713  11 KVCMDKEVSIVFIPCGHLVvCTECAPSLRK-----CPICRATIKGT 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
                ....*....|....*....|....*....|....*....|....*....
gi 50315    364 ICAENDKDVKIEPCGHL-MCTSC----LTSWQESegQGCPFCRCEIKGT 407
Cdd:cd16788  10 ICQDQSKTVLILPCRHMcLCRQCanilLQQPVYR--RNCPLCRTMILQT 56

RING finger, HC subclass, found in inhibitor of apoptosis proteins (IAPs); IAPs are frequently overexpressed in cancer and associated with tumor cell survival, chemoresistance, disease progression, and poor prognosis. They function primarily as negative regulators of cell death. They regulate caspases and apoptosis through the inhibition of specific members of the caspase family of cysteine proteases. In addition, IAPs has been implicated in a multitude of other cellular processes, including inflammatory signalling and immunity, mitogenic kinase signalling, proliferation and mitosis, as well as cell invasion and metastasis. IAPs in this family includes cellular inhibitor of apoptosis protein c-IAP1 (BIRC2) and c-IAP2 (BIRC3), XIAP (BIRC4), BIRC7, and BIRC8, all of which 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), and a C3HC4-type RING-HC finger at the carboxyl terminus that is required for ubiquitin ligase activity. The UBA domain is only absent in mammalian homologs of BIRC7. Moreover, c-IAPs contains an additional caspase activation and recruitment domain (CARD) between the UBA and C3HC4-type RING-HC domains. The CARD domain may serve as a protein interaction surface.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 50315    360 KVTQICAENDKDVKIEPCGHLM-CTSCLTSWQEsegqgCPFCR 401
Cdd:cd16510   2 KLCKICMDREVNIVFLPCGHLVtCAQCAASLRK-----CPICR 39

RING finger, HC subclass, found in Saccharomyces cerevisiae POB3/SPT16 histone-associated protein 1 (ScPSH1) and similar proteins; ScPSH1 is a Cse4-specific E3 ubiquitin ligase that interacts with the kinetochore protein Pat1 and targets the degradation of budding yeast centromeric histone H3 variant, CENP-ACse4, which is essential for faithful chromosome segregation. ScPSH1 contains a C3HC4-type RING-HC finger and a DNA directed RNA polymerase domain.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 50315    359 IKVTQICAENDKDVK---IEPCGHLMCTSCLTSWQES-EGQGCPFCRCEIKgTEP 409
Cdd:cd16568   1 ILETQECIICHEYLYepmVTTCGHTYCYTCLNTWFKSnRSLSCPDCRTKIT-TQP 54

RING finger, HC subclass, found in RING finger protein 37 (RNF37); RNF37, also known as KIAA0860, U-box domain-containing protein 5 (UBOX5), UbcM4-interacting protein 5 (UIP5), or ubiquitin-conjugating enzyme 7-interacting protein 5, is an E3 ubiquitin-protein ligase found exclusively in the nucleus as part of a nuclear dot-like structure. It interacts with the molecular chaperone VCP/p97 protein. RNF37 contains a U-box domain followed by a potential nuclear location signal (NLS) and a C-terminal C3HC4-type RING-HC finger. The U-box domain is a modified RING finger domain that lacks the hallmark metal-chelating cysteines and histidines of the latter, and is likely to adopt a RING finger-like conformation. The presence of the U-box, but not of the RING finger, is required for the E3 activity. The U-box domain can directly interact with several E2 enzymes, including UbcM2, UbcM3, UbcM4, UbcH5, and UbcH8, suggesting a similar function as the RING finger in the ubiquitination pathway. This model corresponds to the RING-HC finger.

                        10        20
                ....*....|....*....|....*
gi 50315    376 PCGHLMCTSCLTSWQESEGQGCPFC 400
Cdd:cd16537  23 PCGHLLCRPCLAEKQKSLAILCPTC 47

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

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 50315    364 ICAENDKDVKIEPCGHLMCTSCL-TSWQESEGQGCPFCR 401
Cdd:COG5574 220 LCLEEPEVPSCTPCGHLFCLSCLlISWTKKKYEFCPLCR 258

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 50315    364 ICAENDKDVKIEPCGHLMCTSCLTSW--QESEGQGCPFCRCEIKG 406
Cdd:cd16611   9 LCLDFFRDPVMLSCGHNFCQSCITGFweLQAEDTTCPECRELCQY 53

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 50315    364 ICAENDKDVKIEPCGHL-MCTSCLTSWQESEGQGCPFCRCEIK 405
Cdd:cd23128   8 MCMEEERSVVFLPCAHQvVCSGCNDLHEKKGMRECPSCRGEIQ 50

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM13, TRIM59 and similar proteins; TRIM13 and TRIM59, two closely related tripartite motif-containing proteins, belong to the C-V subclass of the TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domain, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, followed by a C-terminal transmembrane domain. TRIM13, also known as B-cell chronic lymphocytic leukemia tumor suppressor Leu5, leukemia-associated protein 5, putative tumor suppressor RFP2, RING finger protein 77 (RNF77), or Ret finger protein 2, is an endoplasmic reticulum (ER) membrane anchored E3 ubiquitin-protein ligase that interacts with proteins localized to the ER, including valosin-containing protein (VCP), a protein indispensable for ER-associated degradation (ERAD). TRIM59, also known as RING finger protein 104 (RNF104) or tumor suppressor TSBF-1, is a putative E3 ubiquitin-protein ligase that functions as a novel multiple cancer biomarker for immunohistochemical detection of early tumorigenesis.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 50315    363 QICAENDKDVKIEPCGHLMCTSCLTSWQESEGQG------CPFCR 401
Cdd:cd16581   6 SICYNIFDDPKILPCSHTFCKNCLEKLLAASGYYllaslkCPTCR 50

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
                ....*....|....*....|....*....|....*....
gi 50315    364 ICAENDKDVKIEPCGHLMCTSCLTSWQESEGQG--CPFC 400
Cdd:cd16601   6 LCKEYLKDPVIIECGHNFCRACITRFWEELDGDfpCPQC 44

RING finger, HC subclass, found in RING finger protein 8 (RNF8) and similar proteins; RNF8 is a telomere-associated E3 ubiquitin-protein ligase that plays an important role in DNA double-strand break (DSB) repair via histone ubiquitination. It is localized in the nucleus and interacts with class III E2s (UBE2E2, UbcH6, and UBE2E3), but not with other E2s (UbcH5, UbcH7, UbcH10, hCdc34, and hBendless). It recruits UBC13 for lysine 63-based self polyubiquitylation. Its deficiency causes neuronal pathology and cognitive decline, and its loss results in neuron degeneration. RNF8, together with RNF168, catalyzes a series of ubiquitylation events on substrates such as H2A and H2AX, with the H2AK13/15 ubiquitylation being particularly important for recruitment of repair factors p53-binding protein 1 (53BP1) or the RAP80-BRCA1 complex to sites of DSBs. RNF8 mediates the ubiquitination of gammaH2AX, and recruits 53BP1 and BRCA1 to DNA damage sites which promotes DNA damage response (DDR) and inhibits chromosomal instability. Moreover, RNF8 interacts with retinoid X receptor alpha (RXR alpha) and enhances its transcription-stimulating activity. It also regulates the rate of exit from mitosis and cytokinesis. RNF8 contains an N-terminal forkhead-associated (FHA) domain and a C-terminal C3HC4-type RING-HC finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 50315    364 ICAENDKDVKIEPCGHLMCTSCLTSWQESEGQgCPFCRCEIKG-TEPIVVD 413
Cdd:cd16535   6 ICSELFIEAVTLNCSHSFCSYCITEWMKRKKE-CPICRKPITSkTRSLVLD 55

RING finger, HC subclass, found in tripartite motif-containing protein 62 (TRIM62) and similar proteins; TRIM62, also known as Ductal Epithelium Associated Ring Chromosome 1 (DEAR1), is a cytoplasmic E3 ubiquitin-protein ligase that was identified as a dominant regulator of acinar morphogenesis in the mammary gland. It is implicated in the inflammatory response of immune cells by regulating the Toll-like receptor 4 (TLR4) signaling pathway, leading to increased activity of the activator protein 1 (AP-1) transcription factor in primary macrophages. It is also involved in muscular protein homeostasis, especially during inflammation-induced atrophy, and may play a role in the pathogenesis of ICU-acquired weakness (ICUAW) by activating and maintaining inflammation in myocytes. Moreover, TRIM62 facilitates K27-linked poly-ubiquitination of CARD9 and also regulates CARD9-mediated anti-fungal immunity and intestinal inflammation. It also functions as a chromosome 1p35 tumor suppressor and negatively regulates transforming growth factor beta (TGFbeta)-driven epithelial-mesenchymal transition (EMT) by binding to and promoting the ubiquitination of SMAD3, a major effector of TGFbeta-mediated EMT. TRIM62 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
                ....*....|....*....|....*....|....*....
gi 50315    364 ICAENDKDVKIEPCGHLMCTSCLTS-WQESEGQGCPFCR 401
Cdd:cd16608  11 ICLSIYQDPVSLGCEHYFCRQCITEhWSRSEHRDCPECR 49

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50315      417 PRGSGSLLRQGAEGAPSPNYDDDDDERADDSLFMMKELA--GAKVERPSSPFSMAPQASLPPVPPRLDL----------- 483
Cdd:PHA03247 2784 TRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAAspAGPLPPPTSAQPTAPPPPPGPPPPSLPLggsvapggdvr 2863

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50315      484 ----LQQRAPVPASTSVLGTASKAASGSLHKDKPLPIPPTLRDLPPPPPpdrpysvgaetrPQRRPLPCTPGDCPSRDKL 559
Cdd:PHA03247 2864 rrppSRSPAAKPAAPARPPVRRLARPAVSRSTESFALPPDQPERPPQPQ------------APPPPQPQPQPPPPPQPQP 2931