APC10 subunit of the anaphase-promoting complex (APC) that mediates substrate ubiquitination; This model represents the single domain protein APC10, a subunit of the anaphase-promoting complex (APC), which is a multi-subunit E3 ubiquitin ligase. E3 ubiquitin ligases mediate substrate ubiquitination (or ubiquitylation), a vital component of the ubiquitin-26S proteasome pathway for selective proteolytic degradation. The APC (also known as the cyclosome), is a cell cycle-regulated E3 ubiquitin ligase that controls important transitions in mitosis and the G1 phase by ubiquitinating regulatory proteins, thereby targeting them for degradation. In mitosis, the APC initiates sister chromatid separation by ubiquitinating the anaphase inhibitor securin and triggers exit from mitosis by ubiquitinating cyclin B. The C-terminus of APC10 binds to CDC27/APC3, an APC subunit that contains multiple tetratrico peptide repeats. APC10 domains are homologous to the DOC1 domains present in the HECT (Homologous to the E6-AP Carboxyl Terminus) E3 ubiquitin ligase protein, and the Cullin-RING (Really Interesting New Gene) E3 ubiquitin ligase complex. The APC10/DOC1 domain forms a beta-sandwich structure that is related in architecture to the galactose-binding domain-like fold; their sequences are quite dissimilar, however, and are not included here.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5G05_L       23 REIGSQAVWSLSSCKPGFGVDQLRDDNLETYWQSDGSQPHLVNIQFRRKTTVKTLCIYADYKSDESYTPSKISVRVGNNF 102
Cdd:cd08366   1 REIGSLAVWSLSSAKPGNGVDQLRDDSLDTYWQSDGPQPHLINIQFSKKTDISAVALYLDYKLDESYTPSKISIRAGTSP 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
5G05_L      103 HNLQEIRQLELVEPSGWIHVPLTDNHK-KPTRTFMIQIAVLANHQNGRDTHMRQIKIYT 160
Cdd:cd08366  81 HDLQEVRTVELEEPNGWVHIPLEDNRDgKPLRTFFLQIAILSNHQNGRDTHIRQIKVYG 139

APC10 subunit of the anaphase-promoting complex (APC) that mediates substrate ubiquitination; This model represents the single domain protein APC10, a subunit of the anaphase-promoting complex (APC), which is a multi-subunit E3 ubiquitin ligase. E3 ubiquitin ligases mediate substrate ubiquitination (or ubiquitylation), a vital component of the ubiquitin-26S proteasome pathway for selective proteolytic degradation. The APC (also known as the cyclosome), is a cell cycle-regulated E3 ubiquitin ligase that controls important transitions in mitosis and the G1 phase by ubiquitinating regulatory proteins, thereby targeting them for degradation. In mitosis, the APC initiates sister chromatid separation by ubiquitinating the anaphase inhibitor securin and triggers exit from mitosis by ubiquitinating cyclin B. The C-terminus of APC10 binds to CDC27/APC3, an APC subunit that contains multiple tetratrico peptide repeats. APC10 domains are homologous to the DOC1 domains present in the HECT (Homologous to the E6-AP Carboxyl Terminus) E3 ubiquitin ligase protein, and the Cullin-RING (Really Interesting New Gene) E3 ubiquitin ligase complex. The APC10/DOC1 domain forms a beta-sandwich structure that is related in architecture to the galactose-binding domain-like fold; their sequences are quite dissimilar, however, and are not included here.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5G05_L       23 REIGSQAVWSLSSCKPGFGVDQLRDDNLETYWQSDGSQPHLVNIQFRRKTTVKTLCIYADYKSDESYTPSKISVRVGNNF 102
Cdd:cd08366   1 REIGSLAVWSLSSAKPGNGVDQLRDDSLDTYWQSDGPQPHLINIQFSKKTDISAVALYLDYKLDESYTPSKISIRAGTSP 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
5G05_L      103 HNLQEIRQLELVEPSGWIHVPLTDNHK-KPTRTFMIQIAVLANHQNGRDTHMRQIKIYT 160
Cdd:cd08366  81 HDLQEVRTVELEEPNGWVHIPLEDNRDgKPLRTFFLQIAILSNHQNGRDTHIRQIKVYG 139

APC10-like DOC1 domains in E3 ubiquitin ligases that mediate substrate ubiquitination; This family contains the single domain protein, APC10, a subunit of the anaphase-promoting complex (APC), as well as the DOC1 domain of multi-domain proteins present in E3 ubiquitin ligases. E3 ubiquitin ligases mediate substrate ubiquitination (or ubiquitylation), a component of the ubiquitin-26S proteasome pathway for selective proteolytic degradation. The APC, a multi-protein complex (or cyclosome), is a cell cycle-regulated, E3 ubiquitin ligase that controls important transitions in mitosis and the G1 phase by ubiquitinating regulatory proteins, thereby targeting them for degradation. APC10-like DOC1 domains such as those present in HECT (Homologous to the E6-AP Carboxyl Terminus) and Cullin-RING (Really Interesting New Gene) E3 ubiquitin ligase proteins, HECTD3, and CUL7, respectively, are also included in this hierarchy. CUL7 is a member of the Cullin-RING ligase family and functions as a molecular scaffold assembling a SCF-ROC1-like E3 ubiquitin ligase complex consisting of Skp1, CUL7, Fbx29 F-box protein, and ROC1 (RING-box protein 1) and promotes ubiquitination. CUL7 is a multi-domain protein with a C-terminal cullin domain that binds ROC1 and a centrally positioned APC10/DOC1 domain. HECTD3 contains a C-terminal HECT domain which contains the active site for ubiquitin transfer onto substrates, and an N-terminal APC10 domain which is responsible for substrate recognition and binding. An APC10/DOC1 domain homolog is also present in HERC2 (HECT domain and RLD2), a large multi-domain protein with three RCC1-like domains (RLDs), additional internal domains including zinc finger ZZ-type and Cyt-b5 (Cytochrome b5-like Heme/Steroid binding) domains, and a C-terminal HECT domain. Recent studies have shown that the protein complex HERC2-RNF8 coordinates ubiquitin-dependent assembly of DNA repair factors on damaged chromosomes. Also included in this hierarchy is an uncharacterized APC10/DOC1-like domain found in a multi-domain protein, which also contains CUB, zinc finger ZZ-type, and EF-hand domains. The APC10/DOC1 domain forms a beta-sandwich structure that is related in architecture to the galactose-binding domain-like fold; their sequences are quite dissimilar, however, and are not included here.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5G05_L       29 AVWSLSSCKpgFGVDQLRDDNLETYWQSDGSQP-HLVNIQFRRKTTVKTLCIYADyKSDESYTPSKISVRVGNNFHNLQE 107
Cdd:cd08159   5 ASIEVSSNP--LPVSRLTDGNYDTYWQSDGSQGsHWIRLFMKKDVLIRVLAIFVD-MADSSYMPSLVVVYGGHSPSDLRE 81

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
5G05_L      108 IRQLELVEPSGWIHVPLTDNHKKPtrtfMIQIAVLANHQNGRDTHMRQIKIY 159
Cdd:cd08159  82 LKDVNIRPSNGWVALLEDDTLKCP----YIEIRIKRCRSDGIDTRIRGLRLL 129

APC10-like DOC1 domain of HECTD3, a HECT E3 ubiquitin ligase protein that mediates substrate ubiquitination; This model represents the APC10/DOC1 domain present in HECTD3, a HECT (Homologous to the E6-AP Carboxyl Terminus) E3 ubiquitin ligase protein. HECT E3 ubiquitin ligases mediate substrate ubiquitination (or ubiquitylation), and are a component of the ubiquitin-26S proteasome pathway for selective proteolytic degradation. They also regulate the trafficking of many receptors, channels, transporters and viral proteins. HECTD3 (HECT domain-containing protein3) contains a C-terminal HECT domain with the active site for ubiquitin transfer onto substrates, and an N-terminal APC10/DOC1 domain, which is responsible for substrate recognition and binding. HECTD3 specifically recognizes the Trio-binding protein, Tara (Trio-associated repeat on actin), implicated in regulating actin cytoskeletal, cell motility and cell growth. Tara also binds to TRF1 and may participate in telomere maintenance and/or mitotic regulation through interacting with TRF1. HECTD3 interacts with and promotes the ubiquitination of Syntaxin 8, an endosomal syntaxin proposed to mediate distinct steps of endosomal protein trafficking. HECTD3-mediated Syntaxin 8 degradation has been suggested to contribute to the pathophysiology of neurodegenerative diseases.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5G05_L       32 SLSSCKPGFGVDQLRDDNLETYWQSDGSQ-PHLVNIQFRRKTTVKTLCIYADyKSDESYTPSKISVRVG--NNFHNLQEI 108
Cdd:cd08666  11 EVSSYTDDFNVSCLTDGDPDTYWESDGSQgQHWIRLHMKKGTIIKKLLLTVD-ATDDNYMPKRVAVYGGegDNLKKLNDV 89

                .
5G05_L      109 R 109
Cdd:cd08666  90 S 90

APC10-like DOC1 domain present in HERC2 (HECT domain and RLD2); This model represents the APC10/DOC1 domain present in HERC2 (HECT domain and RLD2), a large multi-domain protein with three RCC1-like domains (RLDs), additional internal domains including a zinc finger ZZ-type and Cyt-b5 (Cytochrome b5-like Heme/Steroid binding) domains, and a C-terminal HECT (Homologous to the E6-AP Carboxyl Terminus) domain. The APC10/DOC1 domain of HERC2 is a homolog of the APC10 subunit and the DOC1 domain present in E3 ubiquitin ligases which mediate substrate ubiquitination (or ubiquitylation), a component of the ubiquitin-26S proteasome pathway for selective proteolytic degradation. As suggested by structural relationships between HERC2 and other proteins such as HERC1, the proposed role for HERC2 in protein trafficking and degradation pathways is consistent with observations that mutations in HERC2 lead to neuromuscular secretory vesicle and sperm acrosome defects, other developmental abnormalities, and juvenile lethality of jdf2 mice. Recent studies have shown that the protein complex, HERC2-RNF8, coordinates ubiquitin-dependent assembly of DNA repair factors on damaged chromosomes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5G05_L       48 DNLETYWQSDGSQP-HLVNIQFRRKTTVKTLCIYADyKSDESYTPSKISVRVGNNFHNLQEIRqlelvepsgWIHVPLTD 126
Cdd:cd08664  45 DGSGSYWQSSGSQGkHWIRLELHPDVLIHSLKIIVD-PADSSYMPSLVVVSGGDSLNSLKELK---------TINVNATD 114