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Conserved domains on  [gi|767939571|ref|XP_011512730|]
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cullin-9 isoform X13 [Homo sapiens]

Protein Classification

cullin-9( domain architecture ID 13773699)

cullin-9 (CUL-9) is a cytoplasmic RBR-type E3 ubiquitin-protein ligase that is a tumor suppressor and promotes p53-dependent apoptosis

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
APC10-like super family cl02148
APC10-like DOC1 domains in E3 ubiquitin ligases that mediate substrate ubiquitination; This ...
 1167-1297 2.68e-90

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.


The actual alignment was detected with superfamily member cd08665:

Pssm-ID: 382862  Cd Length: 131  Bit Score: 288.75  E-value: 2.68e-90
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939571 1167 DKCWEKVEVSSNPHRASKLTDHNPKTYWESNGSTGSHYITLHMHRGVLVRQLTLLVASEDSSYMPARVVVFGGDSTSCIG 1246
Cdd:cd08665     1 DKCWEKVEVSSNPHRANKLTDGNPKTYWESNGSTGSHYINIHMHRGVVIRQLYMLVASEDSSYMPARVVVLGGDSPSCIT 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 767939571 1247 TELNTVNVMPSASRVILLENLNRFWPIIQIRIKRCQQGGIDTRVRGVEVLG 1297
Cdd:cd08665    81 TELNAVNVSPTASRVVLLENMTRFWPIIQIRIKRCQQGGIDTRVRGLEILG 131
Cul7 pfam11515
Mouse development and cellular proliferation protein Cullin-7; The Cullin Ring Ligase family ...
 366-440 4.38e-44

Mouse development and cellular proliferation protein Cullin-7; The Cullin Ring Ligase family member, Cul7, is required for normal mouse development and cellular proliferation. Cul7 has a CPH domain which is a p53 interaction domain. The CPH domain interaction surface of P53 is present in the tetramerization domain.


:

Pssm-ID: 463286  Cd Length: 78  Bit Score: 154.43  E-value: 4.38e-44
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767939571   366 RSEFSSRSGYGEYVQQTLQPGMRVRMLDDYEEISAGDEGEFRQSNNGI---PPVQVFWQSTGRTYWVHWHMLEILGPE 440
Cdd:pfam11515    1 RSDFASRDDYAEYVRDNLAPGMRVRCCRDYEEVSAGDEGEVIQSNRGGlhdLNVQVDWQSKGRTYWVHWHHVEILGFP 78
Cullin super family cl38017
Cullin family;
1595-1835 3.25e-12

Cullin family;


The actual alignment was detected with superfamily member pfam00888:

Pssm-ID: 459983 [Multi-domain]  Cd Length: 610  Bit Score: 71.44  E-value: 3.25e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939571  1595 SEQFARYIDQQIQGGLIGGAPGvemlgQLQRHLEPIMVL----SGLELattFEHFYQHYMADRLLSFGS----------S 1660
Cdd:pfam00888  353 PELLAKYIDDLLKKGLKGKSEE-----ELEEKLDKVITLfryiQDKDV---FEAFYKKHLAKRLLLGKSasddaersmiS 424

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939571  1661 WLEGAVleqiGLCFPNRLpQLMLQSLSTSEELQRQFhlfqlqrldKLFLEQEDEeekrleeeeeeeeeeeaekelfiEDP 1740
Cdd:pfam00888  425 KLKEEC----GSEFTSKL-EGMFKDMELSKDLMKEF---------KEHLSENKS-----------------------SKK 467

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939571  1741 SPAISILVLSPRCWPvsplcyLYHPRKC-LPTEFCDALDRFSSFYSQSQNHpvldmgphRRLQWTW-LGRAEL--QFGK- 1815
Cdd:pfam00888  468 GIDLSVNVLTSGAWP------TYLTSDFiLPPELEKAIERFEKFYLSKHSG--------RKLTWLHsLGTAELkaTFPKg 533

                          250       260
                   ....*....|....*....|..
gi 767939571  1816 --QILHVSTVQMWLLLKFNQTE 1835
Cdd:pfam00888  534 kkHELNVSTYQMAILLLFNDDG 555
 
Name Accession Description Interval E-value
APC10-CUL7 cd08665
APC10-like DOC1 domain of CUL7, subunit of the SCF-ROC1-like E3 ubiquitin ligase complex that ...
 1167-1297 2.68e-90

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.


Pssm-ID: 176486  Cd Length: 131  Bit Score: 288.75  E-value: 2.68e-90
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939571 1167 DKCWEKVEVSSNPHRASKLTDHNPKTYWESNGSTGSHYITLHMHRGVLVRQLTLLVASEDSSYMPARVVVFGGDSTSCIG 1246
Cdd:cd08665     1 DKCWEKVEVSSNPHRANKLTDGNPKTYWESNGSTGSHYINIHMHRGVVIRQLYMLVASEDSSYMPARVVVLGGDSPSCIT 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 767939571 1247 TELNTVNVMPSASRVILLENLNRFWPIIQIRIKRCQQGGIDTRVRGVEVLG 1297
Cdd:cd08665    81 TELNAVNVSPTASRVVLLENMTRFWPIIQIRIKRCQQGGIDTRVRGLEILG 131
Cul7 pfam11515
Mouse development and cellular proliferation protein Cullin-7; The Cullin Ring Ligase family ...
 366-440 4.38e-44

Mouse development and cellular proliferation protein Cullin-7; The Cullin Ring Ligase family member, Cul7, is required for normal mouse development and cellular proliferation. Cul7 has a CPH domain which is a p53 interaction domain. The CPH domain interaction surface of P53 is present in the tetramerization domain.


Pssm-ID: 463286  Cd Length: 78  Bit Score: 154.43  E-value: 4.38e-44
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767939571   366 RSEFSSRSGYGEYVQQTLQPGMRVRMLDDYEEISAGDEGEFRQSNNGI---PPVQVFWQSTGRTYWVHWHMLEILGPE 440
Cdd:pfam11515    1 RSDFASRDDYAEYVRDNLAPGMRVRCCRDYEEVSAGDEGEVIQSNRGGlhdLNVQVDWQSKGRTYWVHWHHVEILGFP 78
Cullin pfam00888
Cullin family;
1595-1835 3.25e-12

Cullin family;


Pssm-ID: 459983 [Multi-domain]  Cd Length: 610  Bit Score: 71.44  E-value: 3.25e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939571  1595 SEQFARYIDQQIQGGLIGGAPGvemlgQLQRHLEPIMVL----SGLELattFEHFYQHYMADRLLSFGS----------S 1660
Cdd:pfam00888  353 PELLAKYIDDLLKKGLKGKSEE-----ELEEKLDKVITLfryiQDKDV---FEAFYKKHLAKRLLLGKSasddaersmiS 424

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939571  1661 WLEGAVleqiGLCFPNRLpQLMLQSLSTSEELQRQFhlfqlqrldKLFLEQEDEeekrleeeeeeeeeeeaekelfiEDP 1740
Cdd:pfam00888  425 KLKEEC----GSEFTSKL-EGMFKDMELSKDLMKEF---------KEHLSENKS-----------------------SKK 467

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939571  1741 SPAISILVLSPRCWPvsplcyLYHPRKC-LPTEFCDALDRFSSFYSQSQNHpvldmgphRRLQWTW-LGRAEL--QFGK- 1815
Cdd:pfam00888  468 GIDLSVNVLTSGAWP------TYLTSDFiLPPELEKAIERFEKFYLSKHSG--------RKLTWLHsLGTAELkaTFPKg 533

                          250       260
                   ....*....|....*....|..
gi 767939571  1816 --QILHVSTVQMWLLLKFNQTE 1835
Cdd:pfam00888  534 kkHELNVSTYQMAILLLFNDDG 555
ANAPC10 pfam03256
Anaphase-promoting complex, subunit 10 (APC10);
1185-1298 1.57e-06

Anaphase-promoting complex, subunit 10 (APC10);


Pssm-ID: 367420  Cd Length: 185  Bit Score: 50.52  E-value: 1.57e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939571  1185 LTDHNPKTYWESNGSTgSHYITLHMHRGVLVRQLTLLVASE-DSSYMPARVVVFGGDSTSCIgTELNTVNV-MPSA-SRV 1261
Cdd:pfam03256   45 LRDDNLDTYWQSDGSQ-PHLVNIQFRKKTPVKYVAIYLDYKlDESYTPSKISVRAGTGFNDL-QEVRVVDLeEPTGwVHI 122

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 767939571  1262 ILLENLNRFWPI--IQIRIKRCQQGGIDTRVRGVEVLGP 1298
Cdd:pfam03256  123 PLRDANGKPLRTfmLQIAVLSNHQNGRDTHVRQIKIYGP 161
CULLIN smart00182
Cullin;
1642-1813 1.59e-06

Cullin;


Pssm-ID: 214545 [Multi-domain]  Cd Length: 143  Bit Score: 49.63  E-value: 1.59e-06
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939571   1642 FEHFYQHYMADRLLSFGS----------SWLEgavlEQIGLCFPNRLpQLMLQSLSTSEELQRQF-HLFQLQRLDKlfle 1710
Cdd:smart00182    8 FEKYYKKHLAKRLILNRSasddaeenmiTKLK----QECGYEFTSKL-ERMFRDISLSKDLNQSFkDMLENNPSAK---- 78

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939571   1711 qedeeekrleeeeeeeeeeeaekelfiedPSPAISILVLSPRCWPVSPLCYLYHprkcLPTEFCDALDRFSSFYSQSQNh 1790
Cdd:smart00182   79 -----------------------------PIIDLNVRVLTSGYWPTSSTEVEIN----LPQELEDALEEFEEFYLAKHS- 124

                           170       180
                    ....*....|....*....|....
gi 767939571   1791 pvldmgpHRRLQWTW-LGRAELQF 1813
Cdd:smart00182  125 -------GRKLTWLHsLGRGEVKA 141
COG5647 COG5647
Cullin, a subunit of E3 ubiquitin ligase [Posttranslational modification, protein turnover, ...
 1595-1836 2.41e-06

Cullin, a subunit of E3 ubiquitin ligase [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 227934 [Multi-domain]  Cd Length: 773  Bit Score: 52.50  E-value: 2.41e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939571 1595 SEQFARYIDqqiqgGLIGGAPGVEMLGQLQRHLEPIMVLSG-LELATTFEHFYQHYMADRLLSFGS------SWLEGAVL 1667
Cdd:COG5647   419 SEYLAKYID-----GLLKKDGKQSFIGKIKDLLQDIITLFRyVEEKDVFEKYYKKLLAKRLLNGRSasaqaeLKMISMLK 493

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939571 1668 EQIGLCFPNRLpQLMLQSLSTSEELQRQFHLFQLQRldklfleqedeeekrleeeeeeeeeeeaekelfieDPSPAISIL 1747
Cdd:COG5647   494 KVCGQEFTSKL-EGMFRDISLSSEFTEAFQHSPQSY-----------------------------------NKYLDLFVW 537

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939571 1748 VLSPRCWPVSPlcylyHPRKC-LPTEFCDALDRFSSFYSQSQNhpvldmgpHRRLQWTW-LGRAEL--QFGKQ-----IL 1818
Cdd:COG5647   538 VLTQAYWPLSP-----EEVSIrLPKELVPILEGFKKFYSSKHN--------GRKLKWYWhLGSGEVkaRFNEGqkyleIS 604

                         250
                  ....*....|....*...
gi 767939571 1819 HVSTVQMWLLLKFNQTES 1836
Cdd:COG5647   605 TFSVYQLLVFLLFNDHEE 622
 
Name Accession Description Interval E-value
APC10-CUL7 cd08665
APC10-like DOC1 domain of CUL7, subunit of the SCF-ROC1-like E3 ubiquitin ligase complex that ...
 1167-1297 2.68e-90

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.


Pssm-ID: 176486  Cd Length: 131  Bit Score: 288.75  E-value: 2.68e-90
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939571 1167 DKCWEKVEVSSNPHRASKLTDHNPKTYWESNGSTGSHYITLHMHRGVLVRQLTLLVASEDSSYMPARVVVFGGDSTSCIG 1246
Cdd:cd08665     1 DKCWEKVEVSSNPHRANKLTDGNPKTYWESNGSTGSHYINIHMHRGVVIRQLYMLVASEDSSYMPARVVVLGGDSPSCIT 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 767939571 1247 TELNTVNVMPSASRVILLENLNRFWPIIQIRIKRCQQGGIDTRVRGVEVLG 1297
Cdd:cd08665    81 TELNAVNVSPTASRVVLLENMTRFWPIIQIRIKRCQQGGIDTRVRGLEILG 131
APC10-like1 cd08365
APC10-like DOC1 domains of E3 ubiquitin ligases that mediate substrate ubiquitination; This ...
 1167-1296 3.20e-65

APC10-like DOC1 domains of E3 ubiquitin ligases that mediate substrate ubiquitination; This model represens the APC10-like 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. APC10/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 here. 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/DOC1 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.


Pssm-ID: 176483  Cd Length: 131  Bit Score: 216.99  E-value: 3.20e-65
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939571 1167 DKCW-EKVEVSSNPHRASKLTDHNPKTYWESNGSTGSHYITLHMHRGVLVRQLTLLVASEDSSYMPARVVVFGGDSTSCI 1245
Cdd:cd08365     1 TKCYvESIEVSSNPADASRLTDGNTSTYWQSDGSQGSHWIRLKMKPDVLVRHLSLAVDATDSSYMPQRVVVAGGRSASNL 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 767939571 1246 gTELNTVNVMPS-ASRVILLENLNRFWPIIQIRIKRCQQGGIDTRVRGVEVL 1296
Cdd:cd08365    81 -QELRDVNIPPSvTGYVTLLEDATISQPYIEIRIKRCRSDGIDTRIHGLRIL 131
APC10-like cd08159
APC10-like DOC1 domains in E3 ubiquitin ligases that mediate substrate ubiquitination; This ...
 1168-1296 7.73e-61

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.


Pssm-ID: 176482  Cd Length: 129  Bit Score: 204.24  E-value: 7.73e-61
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939571 1168 KCW-EKVEVSSNPHRASKLTDHNPKTYWESNGSTGSHYITLHMHRGVLVRQLTLLVASEDSSYMPARVVVFGGDSTSCIg 1246
Cdd:cd08159     1 KCYtASIEVSSNPLPVSRLTDGNYDTYWQSDGSQGSHWIRLFMKKDVLIRVLAIFVDMADSSYMPSLVVVYGGHSPSDL- 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 767939571 1247 TELNTVNVMPSASRVILLENLNRFWPIIQIRIKRCQQGGIDTRVRGVEVL 1296
Cdd:cd08159    80 RELKDVNIRPSNGWVALLEDDTLKCPYIEIRIKRCRSDGIDTRIRGLRLL 129
Cul7 pfam11515
Mouse development and cellular proliferation protein Cullin-7; The Cullin Ring Ligase family ...
 366-440 4.38e-44

Mouse development and cellular proliferation protein Cullin-7; The Cullin Ring Ligase family member, Cul7, is required for normal mouse development and cellular proliferation. Cul7 has a CPH domain which is a p53 interaction domain. The CPH domain interaction surface of P53 is present in the tetramerization domain.


Pssm-ID: 463286  Cd Length: 78  Bit Score: 154.43  E-value: 4.38e-44
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767939571   366 RSEFSSRSGYGEYVQQTLQPGMRVRMLDDYEEISAGDEGEFRQSNNGI---PPVQVFWQSTGRTYWVHWHMLEILGPE 440
Cdd:pfam11515    1 RSDFASRDDYAEYVRDNLAPGMRVRCCRDYEEVSAGDEGEVIQSNRGGlhdLNVQVDWQSKGRTYWVHWHHVEILGFP 78
APC10-HERC2 cd08664
APC10-like DOC1 domain present in HERC2 (HECT domain and RLD2); This model represents the ...
 1154-1296 1.18e-35

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.


Pssm-ID: 176485  Cd Length: 152  Bit Score: 133.27  E-value: 1.18e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939571 1154 RHLCQGSSVEVKE-DKCWEKVEVSSNPHRASKLTDHNpKTYWESNGSTGSHYITLHMHRGVLVRQLTLLVASEDSSYMPA 1232
Cdd:cd08664    11 PELNAGEGDLIDDwSRCVRSLTVSSNENQAKRLIDGS-GSYWQSSGSQGKHWIRLELHPDVLIHSLKIIVDPADSSYMPS 89

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767939571 1233 RVVVFGGDSTSCIgTELNTVNVMPSASRVILLENLNRFWPIIQIRIKRCQQGGIDTRVRGVEVL 1296
Cdd:cd08664    90 LVVVSGGDSLNSL-KELKTINVNATDTLVTLLQDVKEYYRYIEIAIKQCRNNGIDCKIHGLNII 152
APC10-HECTD3 cd08666
APC10-like DOC1 domain of HECTD3, a HECT E3 ubiquitin ligase protein that mediates substrate ...
 1171-1295 1.15e-33

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.


Pssm-ID: 176487  Cd Length: 134  Bit Score: 126.76  E-value: 1.15e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939571 1171 EKVEVSS--NPHRASKLTDHNPKTYWESNGSTGSHYITLHMHRGVLVRQLTLLVASEDSSYMPARVVVFGGDSTSCigTE 1248
Cdd:cd08666     8 ESIEVSSytDDFNVSCLTDGDPDTYWESDGSQGQHWIRLHMKKGTIIKKLLLTVDATDDNYMPKRVAVYGGEGDNL--KK 85

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 767939571 1249 LNTVNV-MPSASRVILLENLNRFWPIIQIRIKRCQQGGIDTRVRGVEV 1295
Cdd:cd08666    86 LNDVSIdETLIGDVCILEDMTTHLPVIEIRIKECKDEGIDVRIRGIKI 133
APC10-ZZEF1 cd08667
APC10/DOC1-like domain of uncharacterized Zinc finger ZZ-type and EF-hand domain-containing ...
 1168-1297 7.90e-33

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.


Pssm-ID: 176488  Cd Length: 131  Bit Score: 124.25  E-value: 7.90e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939571 1168 KCWEKVEVSSNPHRASKLTDHNPKTYWESNGSTGSHYITLHMHRGVLVRQLTLLVASEDSSYMPARVVVFGGDSTSCIgT 1247
Cdd:cd08667     2 KCYAYIEVSSNSADIDRMTDGETSTYWQSDGSARSHWIRLKMKPDVVLRHLSIAVAATDQSYMPQQVTVSVGRSASSL-Q 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 767939571 1248 ELNTVNVmPS--ASRVILLENLNRFWPIIQIRIKRCQQGGIDTRVRGVEVLG 1297
Cdd:cd08667    81 EVRDVHI-PSnvTGYVTLLENANISYLVVQINIKRCHSDGCDTRIHGLKTIG 131
APC10 cd08366
APC10 subunit of the anaphase-promoting complex (APC) that mediates substrate ubiquitination; ...
 1185-1297 1.59e-12

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.


Pssm-ID: 176484  Cd Length: 139  Bit Score: 66.43  E-value: 1.59e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939571 1185 LTDHNPKTYWESNGSTgSHYITLHMHRGVLVRQLTLLVA-SEDSSYMPARVVVFGGDSTSCIgTELNTVNV-MPSASRVI 1262
Cdd:cd08366    23 LRDDSLDTYWQSDGPQ-PHLINIQFSKKTDISAVALYLDyKLDESYTPSKISIRAGTSPHDL-QEVRTVELeEPNGWVHI 100

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 767939571 1263 LLENLNRFWPI----IQIRIKRCQQGGIDTRVRGVEVLG 1297
Cdd:cd08366   101 PLEDNRDGKPLrtffLQIAILSNHQNGRDTHIRQIKVYG 139
Cullin pfam00888
Cullin family;
1595-1835 3.25e-12

Cullin family;


Pssm-ID: 459983 [Multi-domain]  Cd Length: 610  Bit Score: 71.44  E-value: 3.25e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939571  1595 SEQFARYIDQQIQGGLIGGAPGvemlgQLQRHLEPIMVL----SGLELattFEHFYQHYMADRLLSFGS----------S 1660
Cdd:pfam00888  353 PELLAKYIDDLLKKGLKGKSEE-----ELEEKLDKVITLfryiQDKDV---FEAFYKKHLAKRLLLGKSasddaersmiS 424

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939571  1661 WLEGAVleqiGLCFPNRLpQLMLQSLSTSEELQRQFhlfqlqrldKLFLEQEDEeekrleeeeeeeeeeeaekelfiEDP 1740
Cdd:pfam00888  425 KLKEEC----GSEFTSKL-EGMFKDMELSKDLMKEF---------KEHLSENKS-----------------------SKK 467

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939571  1741 SPAISILVLSPRCWPvsplcyLYHPRKC-LPTEFCDALDRFSSFYSQSQNHpvldmgphRRLQWTW-LGRAEL--QFGK- 1815
Cdd:pfam00888  468 GIDLSVNVLTSGAWP------TYLTSDFiLPPELEKAIERFEKFYLSKHSG--------RKLTWLHsLGTAELkaTFPKg 533

                          250       260
                   ....*....|....*....|..
gi 767939571  1816 --QILHVSTVQMWLLLKFNQTE 1835
Cdd:pfam00888  534 kkHELNVSTYQMAILLLFNDDG 555
ANAPC10 pfam03256
Anaphase-promoting complex, subunit 10 (APC10);
1185-1298 1.57e-06

Anaphase-promoting complex, subunit 10 (APC10);


Pssm-ID: 367420  Cd Length: 185  Bit Score: 50.52  E-value: 1.57e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939571  1185 LTDHNPKTYWESNGSTgSHYITLHMHRGVLVRQLTLLVASE-DSSYMPARVVVFGGDSTSCIgTELNTVNV-MPSA-SRV 1261
Cdd:pfam03256   45 LRDDNLDTYWQSDGSQ-PHLVNIQFRKKTPVKYVAIYLDYKlDESYTPSKISVRAGTGFNDL-QEVRVVDLeEPTGwVHI 122

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 767939571  1262 ILLENLNRFWPI--IQIRIKRCQQGGIDTRVRGVEVLGP 1298
Cdd:pfam03256  123 PLRDANGKPLRTfmLQIAVLSNHQNGRDTHVRQIKIYGP 161
CULLIN smart00182
Cullin;
1642-1813 1.59e-06

Cullin;


Pssm-ID: 214545 [Multi-domain]  Cd Length: 143  Bit Score: 49.63  E-value: 1.59e-06
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939571   1642 FEHFYQHYMADRLLSFGS----------SWLEgavlEQIGLCFPNRLpQLMLQSLSTSEELQRQF-HLFQLQRLDKlfle 1710
Cdd:smart00182    8 FEKYYKKHLAKRLILNRSasddaeenmiTKLK----QECGYEFTSKL-ERMFRDISLSKDLNQSFkDMLENNPSAK---- 78

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939571   1711 qedeeekrleeeeeeeeeeeaekelfiedPSPAISILVLSPRCWPVSPLCYLYHprkcLPTEFCDALDRFSSFYSQSQNh 1790
Cdd:smart00182   79 -----------------------------PIIDLNVRVLTSGYWPTSSTEVEIN----LPQELEDALEEFEEFYLAKHS- 124

                           170       180
                    ....*....|....*....|....
gi 767939571   1791 pvldmgpHRRLQWTW-LGRAELQF 1813
Cdd:smart00182  125 -------GRKLTWLHsLGRGEVKA 141
COG5647 COG5647
Cullin, a subunit of E3 ubiquitin ligase [Posttranslational modification, protein turnover, ...
 1595-1836 2.41e-06

Cullin, a subunit of E3 ubiquitin ligase [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 227934 [Multi-domain]  Cd Length: 773  Bit Score: 52.50  E-value: 2.41e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939571 1595 SEQFARYIDqqiqgGLIGGAPGVEMLGQLQRHLEPIMVLSG-LELATTFEHFYQHYMADRLLSFGS------SWLEGAVL 1667
Cdd:COG5647   419 SEYLAKYID-----GLLKKDGKQSFIGKIKDLLQDIITLFRyVEEKDVFEKYYKKLLAKRLLNGRSasaqaeLKMISMLK 493

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939571 1668 EQIGLCFPNRLpQLMLQSLSTSEELQRQFHLFQLQRldklfleqedeeekrleeeeeeeeeeeaekelfieDPSPAISIL 1747
Cdd:COG5647   494 KVCGQEFTSKL-EGMFRDISLSSEFTEAFQHSPQSY-----------------------------------NKYLDLFVW 537

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939571 1748 VLSPRCWPVSPlcylyHPRKC-LPTEFCDALDRFSSFYSQSQNhpvldmgpHRRLQWTW-LGRAEL--QFGKQ-----IL 1818
Cdd:COG5647   538 VLTQAYWPLSP-----EEVSIrLPKELVPILEGFKKFYSSKHN--------GRKLKWYWhLGSGEVkaRFNEGqkyleIS 604

                         250
                  ....*....|....*...
gi 767939571 1819 HVSTVQMWLLLKFNQTES 1836
Cdd:COG5647   605 TFSVYQLLVFLLFNDHEE 622
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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