PHR domain; This domain is called PHR as it was original found in the proteins PAM, highwire and RPM. This domain can be duplicated in the highwire, PFAM and PRM sequence. The C-terminal region of the protein BTBD1 includes the PHR domain and is known to interact with Topoisomerase I, an enzyme which relaxes DNA supercoils.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291190787  1235 NRFESHGGGWGYSAHSVEAIRFSADTDILLGGLG---LFGGRGEYTAKIKLfelgPDGGDHETDGDLLAETDVLAYDCAA 1311
Cdd:pfam08005    1 NRFQSTGGGWGYSGGSPDAIRFSVDRDIFLVGFGlygSIGGPADYSVKIEL----IDGERWESLGEVLGENDTTFSSDGS 76

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 291190787  1312 REKYAMMFDEPVLLQAGWWYVAWARVSGPSSDCGSHGQASITTDDGVVFQFKSSKKSNNGTDVNAGQIPQLLYR 1385
Cdd:pfam08005   77 NDIFRVLFDEPVEIEPNVKYTASAKIKGPSSYYGTNGLREVTCDGGVTFQFSSSSLSNNGTSVNRGQIPELLYY 150

RING finger, H2 subclass, found in the PHR (Pam/Highwire/RPM-1) protein family; The PHR protein family represents an evolutionally conserved family of large proteins including human E3 ubiquitin ligase protein associated with Myc (Pam) and its homologs, Phr1 in mouse, Highwire (HIW) in Drosophila, RPM-1 (regulator of presynaptic morphology 1) in Caenorhabditis elegans, and Esrom in zebrafish. Those proteins are large E3 ubiquitin ligases containing regulator of chromosome condensation (RCC) homology domains (RHD-1 and RHD-2) with inferred guanine exchange factor (GEF) activity, a Myc-binding domain, a B-box zinc finger, and a C-terminal C3H2C3-type RING-H2 finger with E3 ubiquitin (Ub) ligase activity. They play an important role in axon guidance and synaptogenesis. They regulate synapse formation and growth in mammals, zebrafish, Drosophila, and Caenorhabditis elegans, and may control a variety of signaling pathways, including cAMP signaling in mammalian cells, JNK/p38 MAPK signaling in Drosophila and C. elegans, and bone morphogenetic protein signaling in Drosophila. Pam also known as Myc-binding protein 2 (MYCBP2), or Pam/highwire/rpm-1 protein (PHR1), negatively regulates neuronal growth, synaptogenesis and synaptic plasticity by modulating several signaling pathways including the p38 MAPK signaling cascade. It also participates in receptor and ion channel internalization, such as regulating internalization of transient receptor potential vanilloid receptor 1 (TRPV1) in peripheral sensory neurons, as well as duration of thermal hyperalgesia through p38 MAPK. It interacts with neuron-specific electroneutral potassium (K+) and chloride (Cl-) cotransporter KCC2 and modulates its function. Moreover, Pam genetically interacts with Robo2 to modulate axon guidance in the olfactory system. It also associates with tuberous sclerosis complex (TSC) proteins, ubiquitinating TSC2 and regulating mammalian/mechanistic target of rapamycin (mTOR) signaling. Furthermore, Pam is the longest lasting nontranscriptional regulator of adenylyl cyclase activity, and can mediate sustained inhibition of cAMP signaling by sphingosine-1-phosphate. It is also involved in spinal nociceptive processing. Phr1 is an essential regulator of retinal ganglion cell projection during both dorsal lateral geniculate nucleus (dLGN) and superior colliculus (SC) topographic map development. RPM-1 positively regulates a Rab GTPase pathway to promote vesicular trafficking via late endosomes, thereby regulating synapse formation and axon termination. Esrom has E3 ligase activity and modulates the amount of phosphorylated Tuberin, a tumor suppressor, in growth cones. It is required for the formation of the retinotectal projection.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 291190787 4425 DDMCMICFTEALSAAPAIQLDCSHIFHLQCCRRVLENRWLGPRITFGFISCPICK 4479
Cdd:cd16463     1 DDMCMICFTEALSAAPAIQLDCGHVFHLHCCRRVLENRWPGPRITFGFLKCPICK 55

Alpha-tubulin suppressor ATS1 and related RCC1 domain-containing proteins [Cell cycle control, cell division, chromosome partitioning, Cytoskeleton];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291190787  941 RAVQVSCGFHHSVVLMENGDVYTFGYGQHGQLGHGDVNSRGCPTLVQALPGPsTQVTAGSNHTAVLLMDGQVFTFGSFSK 1020
Cdd:COG5184   250 GVVAIAAGGSHTCALKSDGTVWCWGDNSYGQLGDGTTTDRSTPVKVPGLSGV-VAVAAGSSHTCALLTDGTVWCWGDNAY 328

                  ....*
gi 291190787 1021 GQLGR 1025
Cdd:COG5184   329 GQLGD 333

Filamin-type immunoglobulin domains; These form a rod-like structure in the actin-binding cytoskeleton protein, filamin. The C-terminal repeats of filamin bind beta1-integrin (CD29).

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 291190787   2394 PKRPSENMLIRVNNDGTYCANWTPGAIGLYTLHVTIDGIEIDAG-LEVKVKDP 2445
Cdd:smart00557   41 PSGKKVPVEVKDNGDGTYTVSYTPTEPGDYTVTVKFGGEHIPGSpFTVKVGPA 93

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 291190787 3748 IKTSSRPAMIGSLTDGSTETFWESgdEDKNKTKNITINCVKGINARYVSVHVdNSRDLGNKVTSMTFLTGKAVEDLCRIK 3827
Cdd:cd08667     7 IEVSSNSADIDRMTDGETSTYWQS--DGSARSHWIRLKMKPDVVLRHLSIAV-AATDQSYMPQQVTVSVGRSASSLQEVR 83

                          90
                  ....*....|...
gi 291190787 3828 QVDLDSRHIGWVT 3840
Cdd:cd08667    84 DVHIPSNVTGYVT 96

PHR domain; This domain is called PHR as it was original found in the proteins PAM, highwire and RPM. This domain can be duplicated in the highwire, PFAM and PRM sequence. The C-terminal region of the protein BTBD1 includes the PHR domain and is known to interact with Topoisomerase I, an enzyme which relaxes DNA supercoils.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291190787  1235 NRFESHGGGWGYSAHSVEAIRFSADTDILLGGLG---LFGGRGEYTAKIKLfelgPDGGDHETDGDLLAETDVLAYDCAA 1311
Cdd:pfam08005    1 NRFQSTGGGWGYSGGSPDAIRFSVDRDIFLVGFGlygSIGGPADYSVKIEL----IDGERWESLGEVLGENDTTFSSDGS 76

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 291190787  1312 REKYAMMFDEPVLLQAGWWYVAWARVSGPSSDCGSHGQASITTDDGVVFQFKSSKKSNNGTDVNAGQIPQLLYR 1385
Cdd:pfam08005   77 NDIFRVLFDEPVEIEPNVKYTASAKIKGPSSYYGTNGLREVTCDGGVTFQFSSSSLSNNGTSVNRGQIPELLYY 150

RING finger, H2 subclass, found in the PHR (Pam/Highwire/RPM-1) protein family; The PHR protein family represents an evolutionally conserved family of large proteins including human E3 ubiquitin ligase protein associated with Myc (Pam) and its homologs, Phr1 in mouse, Highwire (HIW) in Drosophila, RPM-1 (regulator of presynaptic morphology 1) in Caenorhabditis elegans, and Esrom in zebrafish. Those proteins are large E3 ubiquitin ligases containing regulator of chromosome condensation (RCC) homology domains (RHD-1 and RHD-2) with inferred guanine exchange factor (GEF) activity, a Myc-binding domain, a B-box zinc finger, and a C-terminal C3H2C3-type RING-H2 finger with E3 ubiquitin (Ub) ligase activity. They play an important role in axon guidance and synaptogenesis. They regulate synapse formation and growth in mammals, zebrafish, Drosophila, and Caenorhabditis elegans, and may control a variety of signaling pathways, including cAMP signaling in mammalian cells, JNK/p38 MAPK signaling in Drosophila and C. elegans, and bone morphogenetic protein signaling in Drosophila. Pam also known as Myc-binding protein 2 (MYCBP2), or Pam/highwire/rpm-1 protein (PHR1), negatively regulates neuronal growth, synaptogenesis and synaptic plasticity by modulating several signaling pathways including the p38 MAPK signaling cascade. It also participates in receptor and ion channel internalization, such as regulating internalization of transient receptor potential vanilloid receptor 1 (TRPV1) in peripheral sensory neurons, as well as duration of thermal hyperalgesia through p38 MAPK. It interacts with neuron-specific electroneutral potassium (K+) and chloride (Cl-) cotransporter KCC2 and modulates its function. Moreover, Pam genetically interacts with Robo2 to modulate axon guidance in the olfactory system. It also associates with tuberous sclerosis complex (TSC) proteins, ubiquitinating TSC2 and regulating mammalian/mechanistic target of rapamycin (mTOR) signaling. Furthermore, Pam is the longest lasting nontranscriptional regulator of adenylyl cyclase activity, and can mediate sustained inhibition of cAMP signaling by sphingosine-1-phosphate. It is also involved in spinal nociceptive processing. Phr1 is an essential regulator of retinal ganglion cell projection during both dorsal lateral geniculate nucleus (dLGN) and superior colliculus (SC) topographic map development. RPM-1 positively regulates a Rab GTPase pathway to promote vesicular trafficking via late endosomes, thereby regulating synapse formation and axon termination. Esrom has E3 ligase activity and modulates the amount of phosphorylated Tuberin, a tumor suppressor, in growth cones. It is required for the formation of the retinotectal projection.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 291190787 4425 DDMCMICFTEALSAAPAIQLDCSHIFHLQCCRRVLENRWLGPRITFGFISCPICK 4479
Cdd:cd16463     1 DDMCMICFTEALSAAPAIQLDCGHVFHLHCCRRVLENRWPGPRITFGFLKCPICK 55

Alpha-tubulin suppressor ATS1 and related RCC1 domain-containing proteins [Cell cycle control, cell division, chromosome partitioning, Cytoskeleton];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291190787  941 RAVQVSCGFHHSVVLMENGDVYTFGYGQHGQLGHGDVNSRGCPTLVQALPGPsTQVTAGSNHTAVLLMDGQVFTFGSFSK 1020
Cdd:COG5184   250 GVVAIAAGGSHTCALKSDGTVWCWGDNSYGQLGDGTTTDRSTPVKVPGLSGV-VAVAAGSSHTCALLTDGTVWCWGDNAY 328

                  ....*
gi 291190787 1021 GQLGR 1025
Cdd:COG5184   329 GQLGD 333

Alpha-tubulin suppressor ATS1 and related RCC1 domain-containing proteins [Cell cycle control, cell division, chromosome partitioning, Cytoskeleton];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291190787  534 LGAGREFALMKTANGKIYYTGK--YQSLGIkqgGPSAGKWVELPITKSPKIVHFSVGhdGSHALLVAEDGSIFFTGSASK 611
Cdd:COG5184   154 IAAGGYHTCALKSDGTVWCWGAnsYGQLGD---GTTTDRPTPVQVGGLSGVVAVAAG--GDHSCALKSDGTVWCWGSNSS 228

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291190787  612 GEDGESTKSRRQSKPYKPKkiikmeGKIVVYTACNNGSSSVISKDGELYMFGK-------DAIYSDSSS--LVTDLKGhf 682
Cdd:COG5184   229 GQLGDGTTTDRATPVQVAG------LTGVVAIAAGGSHTCALKSDGTVWCWGDnsygqlgDGTTTDRSTpvKVPGLSG-- 300

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 291190787  683 VTQVAMGKAHTCVLMKNGEVWTFGVNNKGQCGRDT 717
Cdd:COG5184   301 VVAVAAGSSHTCALLTDGTVWCWGDNAYGQLGDGT 335

Ring finger domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 291190787  4426 DMCMICFTEALSAAPAIQLDCSHIFHLQCCRRVLENRwlgpritfgfISCPICK 4479
Cdd:pfam13639    1 DECPICLEEFEEGDKVVVLPCGHHFHRECLDKWLRSS----------NTCPLCR 44

Filamin-type immunoglobulin domains; These form a rod-like structure in the actin-binding cytoskeleton protein, filamin. The C-terminal repeats of filamin bind beta1-integrin (CD29).

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 291190787   2394 PKRPSENMLIRVNNDGTYCANWTPGAIGLYTLHVTIDGIEIDAG-LEVKVKDP 2445
Cdd:smart00557   41 PSGKKVPVEVKDNGDGTYTVSYTPTEPGDYTVTVKFGGEHIPGSpFTVKVGPA 93

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 291190787 3748 IKTSSRPAMIGSLTDGSTETFWESgdEDKNKTKNITINCVKGINARYVSVHVdNSRDLGNKVTSMTFLTGKAVEDLCRIK 3827
Cdd:cd08667     7 IEVSSNSADIDRMTDGETSTYWQS--DGSARSHWIRLKMKPDVVLRHLSIAV-AATDQSYMPQQVTVSVGRSASSLQEVR 83

                          90
                  ....*....|...
gi 291190787 3828 QVDLDSRHIGWVT 3840
Cdd:cd08667    84 DVHIPSNVTGYVT 96

PHR domain; This domain is called PHR as it was original found in the proteins PAM, highwire and RPM. This domain can be duplicated in the highwire, PFAM and PRM sequence. The C-terminal region of the protein BTBD1 includes the PHR domain and is known to interact with Topoisomerase I, an enzyme which relaxes DNA supercoils.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291190787  1235 NRFESHGGGWGYSAHSVEAIRFSADTDILLGGLG---LFGGRGEYTAKIKLfelgPDGGDHETDGDLLAETDVLAYDCAA 1311
Cdd:pfam08005    1 NRFQSTGGGWGYSGGSPDAIRFSVDRDIFLVGFGlygSIGGPADYSVKIEL----IDGERWESLGEVLGENDTTFSSDGS 76

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 291190787  1312 REKYAMMFDEPVLLQAGWWYVAWARVSGPSSDCGSHGQASITTDDGVVFQFKSSKKSNNGTDVNAGQIPQLLYR 1385
Cdd:pfam08005   77 NDIFRVLFDEPVEIEPNVKYTASAKIKGPSSYYGTNGLREVTCDGGVTFQFSSSSLSNNGTSVNRGQIPELLYY 150

RING finger, H2 subclass, found in the PHR (Pam/Highwire/RPM-1) protein family; The PHR protein family represents an evolutionally conserved family of large proteins including human E3 ubiquitin ligase protein associated with Myc (Pam) and its homologs, Phr1 in mouse, Highwire (HIW) in Drosophila, RPM-1 (regulator of presynaptic morphology 1) in Caenorhabditis elegans, and Esrom in zebrafish. Those proteins are large E3 ubiquitin ligases containing regulator of chromosome condensation (RCC) homology domains (RHD-1 and RHD-2) with inferred guanine exchange factor (GEF) activity, a Myc-binding domain, a B-box zinc finger, and a C-terminal C3H2C3-type RING-H2 finger with E3 ubiquitin (Ub) ligase activity. They play an important role in axon guidance and synaptogenesis. They regulate synapse formation and growth in mammals, zebrafish, Drosophila, and Caenorhabditis elegans, and may control a variety of signaling pathways, including cAMP signaling in mammalian cells, JNK/p38 MAPK signaling in Drosophila and C. elegans, and bone morphogenetic protein signaling in Drosophila. Pam also known as Myc-binding protein 2 (MYCBP2), or Pam/highwire/rpm-1 protein (PHR1), negatively regulates neuronal growth, synaptogenesis and synaptic plasticity by modulating several signaling pathways including the p38 MAPK signaling cascade. It also participates in receptor and ion channel internalization, such as regulating internalization of transient receptor potential vanilloid receptor 1 (TRPV1) in peripheral sensory neurons, as well as duration of thermal hyperalgesia through p38 MAPK. It interacts with neuron-specific electroneutral potassium (K+) and chloride (Cl-) cotransporter KCC2 and modulates its function. Moreover, Pam genetically interacts with Robo2 to modulate axon guidance in the olfactory system. It also associates with tuberous sclerosis complex (TSC) proteins, ubiquitinating TSC2 and regulating mammalian/mechanistic target of rapamycin (mTOR) signaling. Furthermore, Pam is the longest lasting nontranscriptional regulator of adenylyl cyclase activity, and can mediate sustained inhibition of cAMP signaling by sphingosine-1-phosphate. It is also involved in spinal nociceptive processing. Phr1 is an essential regulator of retinal ganglion cell projection during both dorsal lateral geniculate nucleus (dLGN) and superior colliculus (SC) topographic map development. RPM-1 positively regulates a Rab GTPase pathway to promote vesicular trafficking via late endosomes, thereby regulating synapse formation and axon termination. Esrom has E3 ligase activity and modulates the amount of phosphorylated Tuberin, a tumor suppressor, in growth cones. It is required for the formation of the retinotectal projection.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 291190787 4425 DDMCMICFTEALSAAPAIQLDCSHIFHLQCCRRVLENRWLGPRITFGFISCPICK 4479
Cdd:cd16463     1 DDMCMICFTEALSAAPAIQLDCGHVFHLHCCRRVLENRWPGPRITFGFLKCPICK 55

Alpha-tubulin suppressor ATS1 and related RCC1 domain-containing proteins [Cell cycle control, cell division, chromosome partitioning, Cytoskeleton];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291190787  941 RAVQVSCGFHHSVVLMENGDVYTFGYGQHGQLGHGDVNSRGCPTLVQALPGPsTQVTAGSNHTAVLLMDGQVFTFGSFSK 1020
Cdd:COG5184   250 GVVAIAAGGSHTCALKSDGTVWCWGDNSYGQLGDGTTTDRSTPVKVPGLSGV-VAVAAGSSHTCALLTDGTVWCWGDNAY 328

                  ....*
gi 291190787 1021 GQLGR 1025
Cdd:COG5184   329 GQLGD 333

Alpha-tubulin suppressor ATS1 and related RCC1 domain-containing proteins [Cell cycle control, cell division, chromosome partitioning, Cytoskeleton];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291190787  942 AVQVSCGFHHSVVLMENGDVYTFGYGQHGQLGHGDVNSRGCPTLVQALPGPSTQVTAGSNHTAVLLMDGQVFTFGSFSKG 1021
Cdd:COG5184   100 VVAVAAGYYHSCALKSDGTVWCWGDNSSGQLGDGTTTNRLTPVQVDAGLSGVVAIAAGGYHTCALKSDGTVWCWGANSYG 179

                  ...
gi 291190787 1022 QLG 1024
Cdd:COG5184   180 QLG 182

Alpha-tubulin suppressor ATS1 and related RCC1 domain-containing proteins [Cell cycle control, cell division, chromosome partitioning, Cytoskeleton];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291190787  941 RAVQVSCGFHHSVVLMENGDVYTFGYGQHGQLGHGDVNSRGCPTLVQALpGPSTQVTAGSNHTAVLLMDGQVFTFGSFSK 1020
Cdd:COG5184    49 NVVAVAAGGDHTCALKADGTVWCWGNNSYGQLGDGTTTDRTTPVKVPGL-TGVVAVAAGYYHSCALKSDGTVWCWGDNSS 127

                  ....*.
gi 291190787 1021 GQLGRP 1026
Cdd:COG5184   128 GQLGDG 133

Regulator of chromosome condensation (RCC1) repeat;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 291190787   958 NGDVYTFGYGQHGQLGHGDVNSRGCPTLVQALPG-PSTQVTAGSNHTAVL 1006
Cdd:pfam00415    1 DGRVYTWGRNDYGQLGLGTTENVLVPQKVEGLSGnKVVQVACGGDHTVAL 50

Alpha-tubulin suppressor ATS1 and related RCC1 domain-containing proteins [Cell cycle control, cell division, chromosome partitioning, Cytoskeleton];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291190787  534 LGAGREFALMKTANGKIYYTGK--YQSLGIkqgGPSAGKWVELPITKSPKIVHFSVGhdGSHALLVAEDGSIFFTGSASK 611
Cdd:COG5184   154 IAAGGYHTCALKSDGTVWCWGAnsYGQLGD---GTTTDRPTPVQVGGLSGVVAVAAG--GDHSCALKSDGTVWCWGSNSS 228

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291190787  612 GEDGESTKSRRQSKPYKPKkiikmeGKIVVYTACNNGSSSVISKDGELYMFGK-------DAIYSDSSS--LVTDLKGhf 682
Cdd:COG5184   229 GQLGDGTTTDRATPVQVAG------LTGVVAIAAGGSHTCALKSDGTVWCWGDnsygqlgDGTTTDRSTpvKVPGLSG-- 300

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 291190787  683 VTQVAMGKAHTCVLMKNGEVWTFGVNNKGQCGRDT 717
Cdd:COG5184   301 VVAVAAGSSHTCALLTDGTVWCWGDNAYGQLGDGT 335

H2 subclass of RING (RING-H2) fingers and its variants; 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). This family corresponds to the H2 subclass of RING (RING-H2) finger proteins that are characterized by containing C3H2C3-type canonical RING-H2 fingers or noncanonical RING-H2 finger variants, including C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type modified RING-H2 fingers. The canonical RING-H2 finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-H-X2-C-X(4-48)-C-X2-C, X is any amino acid and the number of X residues varies in different fingers. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-H2 finger can be found in 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 serves as a scaffold for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enables efficient transfer of ubiquitin from E2 to the substrates.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 291190787 4428 CMICFTEALSAAPAIQLDCSHIFHLQCCRRVLENrwlgpritfGFISCPICK 4479
Cdd:cd16448     1 CVICLEEFEEGDVVRLLPCGHVFHLACILRWLES---------GNNTCPLCR 43

Regulator of chromosome condensation (RCC1) repeat;

                           10        20        30
                   ....*....|....*....|....*....|
gi 291190787   683 VTQVAMGKAHTCVLMKNGEVWTFGVNNKGQ 712
Cdd:pfam13540    1 VVSVAAGDNHTLALTSDGRVYCWGDNSYGQ 30

RING finger, H2 subclass, found in Arabidopsis thaliana RING-H2 finger A1a (RHA1A), A1b (RHA1B) and similar proteins; This subfamily includes Arabidopsis thaliana RHA1A, RHA1B and XERICO. RHA1A is a probable E3 ubiquitin-protein ligase that may possess E3 ubiquitin ligase activity in vitro. RHA1B possesses E3 ubiquitin-protein ligase activity when associated with the E2 enzyme UBC8 in vitro. XERICO functions on abscisic acid homeostasis at post-translational level, probably through ubiquitin/proteasome-dependent substrate-specific degradation. Members of this subfamily contain a C3H2C3-type RING-H2 finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 291190787 4425 DDMCMICFTEALSAAPAIQL-DCSHIFHLQCCrrvleNRWlgprITFGFISCPICKN 4480
Cdd:cd23121     1 DDCCAICLSDFNSDEKLRQLpKCGHIFHHHCL-----DRW----IRYNKITCPLCRA 48

Regulator of chromosome condensation (RCC1) repeat;

                           10        20
                   ....*....|....*....|....*....
gi 291190787   994 TQVTAGSNHTAVLLMDGQVFTFGSFSKGQ 1022
Cdd:pfam13540    2 VSVAAGDNHTLALTSDGRVYCWGDNSYGQ 30

Bacterial SH3 domain;

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                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 291190787  2477 AGLRIRSHPSLQSEQIGIVKVNGTITFIDEihnDDGVWLRLNDEtikkyvpnmNGYTeAWCLS 2539
Cdd:pfam08239    1 SGLNVRSGPSTSSEVVGTLPKGEKVEVLEE---QGGGWYKVRTY---------DGYE-GWVSS 50

RING finger, H2 subclass, found in Arabidopsis thaliana protein WAV3 homolog 2 (WAVH2) and similar proteins; WAVH2, also known as RING-type E3 ubiquitin transferase WAVH2, is a probable E3 ubiquitin-protein ligase involved in the regulation of root growth. It acts as a positive regulator of root gravitropism. WAVH2 contains a C3H2C3-type RING-H2 finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 291190787 4428 CMICF--TEALSAAPAIQLDCSHIFHLQCCRRVLENRWLgpritfgfiSCPICKNKINH 4484
Cdd:cd23114     7 CSICLetMKPGSGHAIFTAECSHSFHFECIAGNVRHGNL---------RCPVCRAKWKE 56

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 291190787 3748 IKTSSRPAMIGSLTDGSTETFWESgdEDKNKTKNITINCVKGINARYVSVHVdNSRDLGNKVTSMTFLTGKAVEDLCRIK 3827
Cdd:cd08667     7 IEVSSNSADIDRMTDGETSTYWQS--DGSARSHWIRLKMKPDVVLRHLSIAV-AATDQSYMPQQVTVSVGRSASSLQEVR 83

                          90
                  ....*....|...
gi 291190787 3828 QVDLDSRHIGWVT 3840
Cdd:cd08667    84 DVHIPSNVTGYVT 96

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*
gi 291190787 4425 DDMCMICFTEALSAAPaiQLDCSHIFHLQCCRRVLENRWlgpritfgfiSCPICK 4479
Cdd:cd16479     1 DNTCIICREEMTVGAK--KLPCGHIFHLSCLRSWLQRQQ----------TCPTCR 43

RING finger, H2 subclass, found in RING finger protein 12 (RNF12) and similar proteins; RNF12, also known as LIM domain-interacting RING finger protein or RING finger LIM domain-binding protein (R-LIM), is an E3 ubiquitin-protein ligase encoded by gene RLIM that is crucial for normal embryonic development in some species and for normal X inactivation in mice. It thus functions as a major sex-specific epigenetic regulator of female mouse nurturing tissues. RNF12 is widely expressed during embryogenesis, and mainly localizes to the cell nucleus, where it regulates the levels of many proteins, including CLIM, LMO, HDAC2, TRF1, SMAD7, and REX1, by proteasomal degradation. Its functional activity is regulated by phosphorylation-dependent nucleocytoplasmic shuttling. It is negatively regulated by pluripotency factors in embryonic stem cells. p53 represses its transcription through Sp1. RNF12 is the primary factor responsible for X chromosome inactivation (XCI) in female placental mammals. It is an indispensable factor in up-regulation of Xist transcription, thereby leading to initiation of random XCI. It also targets REX1, an inhibitor of XCI, for proteasomal degradation. RNF12 also acts as a co-regulator for a range of transcription factors, particularly those containing a LIM homeodomain, and modulates the formation of transcriptional multiprotein complexes. It is a negative regulator of Smad7, which in turn negatively regulates the signaling of type I receptors from the transforming growth factor beta (TGF-beta) superfamily. In addition, paternal RNF12 is a critical survival factor for milk-producing alveolar cells. RNF12 contains an nuclear localization signal (NLS) and a C3H2C3-type RING-H2 finger.

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                  ....*....|....*....|....*....|....*....|....*....|....*
gi 291190787 4428 CMICFTEALSAAPAIQLDCSHIFHLQCCrrvleNRWLGPRITfgfisCPICKNKI 4482
Cdd:cd16674     3 CSVCITEYTEGNKLRKLPCSHEYHVHCI-----DRWLSENST-----CPICRRAV 47