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 375493585  34 REIGSQAVWSLSSCKPGFGVDQLRDDNLETYWQSDGSQPHLVNIQFRRKTTVKTLCIYADYKSDESYTPSKISVRVGNNF 113
Cdd:cd08366    1 REIGSLAVWSLSSAKPGNGVDQLRDDSLDTYWQSDGPQPHLINIQFSKKTDISAVALYLDYKLDESYTPSKISIRAGTSP 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 375493585 114 HNLQEIRQLELVEPSGWIHVPLTDNHK-KPTRTFMIQIAVLANHQNGRDTHMRQIKIYT 171
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 375493585  34 REIGSQAVWSLSSCKPGFGVDQLRDDNLETYWQSDGSQPHLVNIQFRRKTTVKTLCIYADYKSDESYTPSKISVRVGNNF 113
Cdd:cd08366    1 REIGSLAVWSLSSAKPGNGVDQLRDDSLDTYWQSDGPQPHLINIQFSKKTDISAVALYLDYKLDESYTPSKISIRAGTSP 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 375493585 114 HNLQEIRQLELVEPSGWIHVPLTDNHK-KPTRTFMIQIAVLANHQNGRDTHMRQIKIYT 171
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 375493585  40 AVWSLSSCKpgFGVDQLRDDNLETYWQSDGSQP-HLVNIQFRRKTTVKTLCIYADyKSDESYTPSKISVRVGNNFHNLQE 118
Cdd:cd08159    5 ASIEVSSNP--LPVSRLTDGNYDTYWQSDGSQGsHWIRLFMKKDVLIRVLAIFVD-MADSSYMPSLVVVYGGHSPSDLRE 81

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 375493585 119 IRQLELVEPSGWIHVPLTDNHKKPtrtfMIQIAVLANHQNGRDTHMRQIKIY 170
Cdd:cd08159   82 LKDVNIRPSNGWVALLEDDTLKCP----YIEIRIKRCRSDGIDTRIRGLRLL 129

APC10/DOC1-like domain of uncharacterized Zinc finger ZZ-type and EF-hand domain-containing protein 1 (ZZEF1) and homologs; This model represents the APC10/DOC1-like domain present in the uncharacterized Zinc finger ZZ-type and EF-hand domain-containing protein 1 (ZZEF1) of Mus musculus. Members of this family contain EF-hand, APC10, CUB, and zinc finger ZZ-type domains. ZZEF1-like APC10 domains are homologous to the APC10 subunit/DOC1 domains present in E3 ubiquitin ligases, which mediate substrate ubiquitination (or ubiquitylation), and are components of the ubiquitin-26S proteasome pathway for selective proteolytic degradation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 375493585  53 VDQLRDDNLETYWQSDGS-QPHLVNIQFRRKTTVKTLCIYAdYKSDESYTPSKISVRVGNNFHNLQEIRQLELvePSGWI 131
Cdd:cd08667   16 IDRMTDGETSTYWQSDGSaRSHWIRLKMKPDVVLRHLSIAV-AATDQSYMPQQVTVSVGRSASSLQEVRDVHI--PSNVT 92

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 375493585 132 -HVPLTDNHKkpTRTFMIQIAVLANHQNGRDTHMRQIK 168
Cdd:cd08667   93 gYVTLLENAN--ISYLVVQINIKRCHSDGCDTRIHGLK 128

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 375493585  59 DNLETYWQSDGSQP-HLVNIQFRRKTTVKTLCIYADyKSDESYTPSKISVRVGNNFHNLQEIRqlelvepsgWIHVPLTD 137
Cdd:cd08664   45 DGSGSYWQSSGSQGkHWIRLELHPDVLIHSLKIIVD-PADSSYMPSLVVVSGGDSLNSLKELK---------TINVNATD 114