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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28573741  31 REVGAQAVWSLSSCKPGFGVERLRDNIMDTYWQSDGQLPHLVNIQFHKRTNISQIYIYTDYKLDESYTPSRISIRSGTNF 110
Cdd:cd08366   1 REIGSLAVWSLSSAKPGNGVDQLRDDSLDTYWQSDGPQPHLINIQFSKKTDISAVALYLDYKLDESYTPSKISIRAGTSP 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 28573741 111 NDLQELQVMDLTEPTGWVQIPIKDGNV-KSIRTFMLQIAVISNHQNGRDTHMRQIRIHA 168
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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28573741  31 REVGAQAVWSLSSCKPGFGVERLRDNIMDTYWQSDGQLPHLVNIQFHKRTNISQIYIYTDYKLDESYTPSRISIRSGTNF 110
Cdd:cd08366   1 REIGSLAVWSLSSAKPGNGVDQLRDDSLDTYWQSDGPQPHLINIQFSKKTDISAVALYLDYKLDESYTPSKISIRAGTSP 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 28573741 111 NDLQELQVMDLTEPTGWVQIPIKDGNV-KSIRTFMLQIAVISNHQNGRDTHMRQIRIHA 168
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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28573741  37 AVWSLSSCKpgFGVERLRDNIMDTYWQSDG-QLPHLVNIQFHKRTNISQIYIYTDYKlDESYTPSRISIRSGTNFNDLQE 115
Cdd:cd08159   5 ASIEVSSNP--LPVSRLTDGNYDTYWQSDGsQGSHWIRLFMKKDVLIRVLAIFVDMA-DSSYMPSLVVVYGGHSPSDLRE 81

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|.
gi 28573741 116 LQVMDLTEPTGWVQIpIKDGNVKSIrtfMLQIAVISNHQNGRDTHMRQIRI 166
Cdd:cd08159  82 LKDVNIRPSNGWVAL-LEDDTLKCP---YIEIRIKRCRSDGIDTRIRGLRL 128

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 28573741  40 SLSSCKPGFGVERLRDNIMDTYWQSDG-QLPHLVNIQFHKRTNISQIYIYTDYKlDESYTPSRISIRSGTNfNDLQEL 116
Cdd:cd08666  11 EVSSYTDDFNVSCLTDGDPDTYWESDGsQGQHWIRLHMKKGTIIKKLLLTVDAT-DDNYMPKRVAVYGGEG-DNLKKL 86

APC10-like DOC1 domain of CUL7, subunit of the SCF-ROC1-like E3 ubiquitin ligase complex that mediates substrate ubiquitination; This model represents the APC10/DOC1 domain present in CUL7, a subunit of the SCF-ROC1-like E3 Ubiquitin (Ub) ligase complex, which mediates substrate ubiquitination (or ubiquitylation), and is a component of the ubiquitin-26S proteasome pathway for selective proteolytic degradation. CUL7 is a member of the Cullin-RING ligase family and functions as a molecular scaffold assembling the SCF-ROC1-like E3 Ub ligase complex consisting of the adapter protein Skp1, CUL7, the WD40 repeat-containing F-box Fbw8 (also known as Fbx29), and ROC1 (RING-box protein 1). CUL7 is a large protein with a C-terminal cullin domain that binds ROC1 and additional domains, including an APC10/DOC1 domain. While the Fbw8 protein is responsible for substrate protein recognition, the ROC1 RING domain recruits an Ub-charged E2 Ub-conjugating enzyme for substrate ubiquitination. It remains to be determined how CUL7 binds to the Skp1-Fbw8 heterodimer. The CUL7 E3 Ub ligase has been implicated in the proteasomal degradation of the cellular proteins, cyclin D1, an important regulator of the G1 to S-phase cell cycle progression, and insulin receptor substrate 1, a critical component of the signaling pathways downstream of the insulin and insulin-like growth factor 1 receptor. CUL7 appears to be an important regulator of placental development. Germ line mutations of CUL7 are linked to 3-M syndrome and Yakuts short stature syndrome.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28573741  52 RLRDNIMDTYWQSDGQL-PHLVNIQFHKRTNISQIYIYTDYKlDESYTPSRISIRSGTNFNDLQ-ELQVMDLTEPTGWVQ 129
Cdd:cd08665  18 KLTDGNPKTYWESNGSTgSHYINIHMHRGVVIRQLYMLVASE-DSSYMPARVVVLGGDSPSCITtELNAVNVSPTASRVV 96

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 28573741 130 IpikdgnVKSIRTF--MLQIAVISNHQNGRDTHMRQIRI 166
Cdd:cd08665  97 L------LENMTRFwpIIQIRIKRCQQGGIDTRVRGLEI 129