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Conserved domains on  [gi|1039749415|ref|XP_017172226|]
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E3 SUMO-protein ligase NSE2 isoform X2 [Mus musculus]

Protein Classification

RING finger protein( domain architecture ID 106764)

RING finger protein may function as an E3 ubiquitin protein ligase that mediates the ubiquitination of target proteins by bringing the ubiquitin-charged E2 ubiquitin-conjugating enzyme and the acceptor protein together to enable the direct transfer of ubiquitin

EC:  2.3.2.27
Gene Ontology:  GO:0061630

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
RING_Ubox super family cl17238
RING finger (Really Interesting New Gene) domain and U-box domain superfamily; The RING finger ...
182-231 4.32e-16

RING finger (Really Interesting New Gene) domain and U-box domain superfamily; 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). C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type RING fingers are closely related to RING-HC fingers. In contrast, C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type RING fingers are more closely related to RING-H2 fingers. However, not all RING finger-containing proteins display regular RING finger features, and the RING finger family has turned out to be multifarious. The degenerate RING fingers of the Siz/PIAS RING (SP-RING) family proteins and sporulation protein RMD5, are characterized by lacking the second, fifth, and sixth Zn2+ ion-coordinating residues. They bind only one Zn2+ ion. On the other hand, the RING fingers of the human APC11 and RBX1 proteins can bind a third Zn atom since they harbor four additional Zn ligands. U-box is a modified form of the RING finger domain that lacks metal chelating Cys and His residues. It resembles the cross-brace RING structure consisting of three beta-sheets and a single alpha-helix, which would be stabilized by salt bridges instead of chelated metal ions. U-box proteins are widely distributed among eukaryotic organisms and show a higher prevalence in plants than in other organisms. RING finger/U-box-containing proteins are 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 serve as scaffolds for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enable efficient transfer of ubiquitin from E2 to the substrates.


The actual alignment was detected with superfamily member pfam11789:

Pssm-ID: 450175 [Multi-domain]  Cd Length: 57  Bit Score: 70.01  E-value: 4.32e-16
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1039749415 182 EDMIVTQSQTNFICPITQLEMKKPVKNKMCGHTYEEEAIVRMIESKHKRK 231
Cdd:pfam11789   1 DDLQIEGETISLTCPLTLQPFVEPVTSKKCNHVFEKDAILEMLKRNPTVK 50
 
Name Accession Description Interval E-value
zf-Nse pfam11789
Zinc-finger of the MIZ type in Nse subunit; Nse1 and Nse2 are novel non-SMC subunits of the ...
182-231 4.32e-16

Zinc-finger of the MIZ type in Nse subunit; Nse1 and Nse2 are novel non-SMC subunits of the fission yeast Smc5-6 DNA repair complex. This family is the zinc-finger domain similar to the MIZ type of zinc-finger.


Pssm-ID: 403098 [Multi-domain]  Cd Length: 57  Bit Score: 70.01  E-value: 4.32e-16
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1039749415 182 EDMIVTQSQTNFICPITQLEMKKPVKNKMCGHTYEEEAIVRMIESKHKRK 231
Cdd:pfam11789   1 DDLQIEGETISLTCPLTLQPFVEPVTSKKCNHVFEKDAILEMLKRNPTVK 50
SPL-RING_NSE2 cd16651
SPL-RING finger found in E3 SUMO-protein ligase NSE2 and similar proteins; NSE2, also known as ...
193-232 6.13e-16

SPL-RING finger found in E3 SUMO-protein ligase NSE2 and similar proteins; NSE2, also known as MMS21 homolog (MMS21) or non-structural maintenance of chromosomes element 2 homolog (Non-SMC element 2 homolog, NSMCE2), is an autosumoylating small ubiquitin-like modifier (SUMO) ligase required for the response to DNA damage. It regulates sumoylation and nuclear-to-cytoplasmic translocation of skeletal and heart muscle-specific variant of the alpha subunit of nascent polypeptide associated complex (skNAC)-Smyd1 in myogenesis. It is also required for resisting extrinsically induced genotoxic stress. Moreover, NSE2 together with its partner proteins SMC6 and SMC5 form a tight subcomplex of the structural maintenance of chromosomes SMC5-6 complex, which includes another two subcomplexes, NSE1-NSE3-NSE4 and NSE5-NSE6. SMC6 and NSE3 are sumoylated in an NSE2-dependent manner, but SMC5 and NSE1 are not. NSE2-dependent E3 SUMO ligase activity is required for efficient DNA repair, but not for SMC5-6 complex stability. NSE2 contains a RING variant known as a Siz/PIAS (protein inhibitor of activated signal transducer and activator of transcription)-like RING (SPL-RING) finger that is likely shared by the SP-RING type SUMO E3 ligases, such as PIAS family proteins. The SPL-RING finger is a variant of the RING finger, which lacks the second, fifth, and sixth zinc-binding residues of the consensus C3H2C3-/C3HC4-type RING fingers. It harbors only one Zn binding site and is required for the sumoylating activity.


Pssm-ID: 438313 [Multi-domain]  Cd Length: 67  Bit Score: 69.98  E-value: 6.13e-16
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1039749415 193 FICPITQLEMKKPVKNKMCGHTYEEEAIVRMIESKHKRKK 232
Cdd:cd16651     1 LKCPITQQLMVDPVRNKKCGHTYEKAAILQYLQSRKKKAK 40
Ubox smart00504
Modified RING finger domain; Modified RING finger domain, without the full complement of Zn2 ...
193-226 1.09e-03

Modified RING finger domain; Modified RING finger domain, without the full complement of Zn2+-binding ligands. Probable involvement in E2-dependent ubiquitination.


Pssm-ID: 128780 [Multi-domain]  Cd Length: 63  Bit Score: 36.44  E-value: 1.09e-03
                           10        20        30
                   ....*....|....*....|....*....|....
gi 1039749415  193 FICPITQLEMKKPVKNKMcGHTYEEEAIVRMIES 226
Cdd:smart00504   2 FLCPISLEVMKDPVILPS-GQTYERSAIEKWLLS 34
 
Name Accession Description Interval E-value
zf-Nse pfam11789
Zinc-finger of the MIZ type in Nse subunit; Nse1 and Nse2 are novel non-SMC subunits of the ...
182-231 4.32e-16

Zinc-finger of the MIZ type in Nse subunit; Nse1 and Nse2 are novel non-SMC subunits of the fission yeast Smc5-6 DNA repair complex. This family is the zinc-finger domain similar to the MIZ type of zinc-finger.


Pssm-ID: 403098 [Multi-domain]  Cd Length: 57  Bit Score: 70.01  E-value: 4.32e-16
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1039749415 182 EDMIVTQSQTNFICPITQLEMKKPVKNKMCGHTYEEEAIVRMIESKHKRK 231
Cdd:pfam11789   1 DDLQIEGETISLTCPLTLQPFVEPVTSKKCNHVFEKDAILEMLKRNPTVK 50
SPL-RING_NSE2 cd16651
SPL-RING finger found in E3 SUMO-protein ligase NSE2 and similar proteins; NSE2, also known as ...
193-232 6.13e-16

SPL-RING finger found in E3 SUMO-protein ligase NSE2 and similar proteins; NSE2, also known as MMS21 homolog (MMS21) or non-structural maintenance of chromosomes element 2 homolog (Non-SMC element 2 homolog, NSMCE2), is an autosumoylating small ubiquitin-like modifier (SUMO) ligase required for the response to DNA damage. It regulates sumoylation and nuclear-to-cytoplasmic translocation of skeletal and heart muscle-specific variant of the alpha subunit of nascent polypeptide associated complex (skNAC)-Smyd1 in myogenesis. It is also required for resisting extrinsically induced genotoxic stress. Moreover, NSE2 together with its partner proteins SMC6 and SMC5 form a tight subcomplex of the structural maintenance of chromosomes SMC5-6 complex, which includes another two subcomplexes, NSE1-NSE3-NSE4 and NSE5-NSE6. SMC6 and NSE3 are sumoylated in an NSE2-dependent manner, but SMC5 and NSE1 are not. NSE2-dependent E3 SUMO ligase activity is required for efficient DNA repair, but not for SMC5-6 complex stability. NSE2 contains a RING variant known as a Siz/PIAS (protein inhibitor of activated signal transducer and activator of transcription)-like RING (SPL-RING) finger that is likely shared by the SP-RING type SUMO E3 ligases, such as PIAS family proteins. The SPL-RING finger is a variant of the RING finger, which lacks the second, fifth, and sixth zinc-binding residues of the consensus C3H2C3-/C3HC4-type RING fingers. It harbors only one Zn binding site and is required for the sumoylating activity.


Pssm-ID: 438313 [Multi-domain]  Cd Length: 67  Bit Score: 69.98  E-value: 6.13e-16
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1039749415 193 FICPITQLEMKKPVKNKMCGHTYEEEAIVRMIESKHKRKK 232
Cdd:cd16651     1 LKCPITQQLMVDPVRNKKCGHTYEKAAILQYLQSRKKKAK 40
SP-RING-like cd16452
SP-RING finger and SPL-RING finger, variants of RING fingers; This family corresponds to a ...
193-232 2.91e-13

SP-RING finger and SPL-RING finger, variants of RING fingers; This family corresponds to a group of proteins with variants of RING fingers that are characterized by lacking the second, fifth, and sixth Zn2+ ion-coordinating residues compared with the classic C3H2C3-/C3HC4-type RING fingers. They include SP-RING finger found in the Siz/PIAS RING (SP-RING) family of SUMO E3 ligases and SPL-RING finger found in E3 SUMO-protein ligase NSE2. The SP-RING family includes PIAS (protein inhibitor of activated STAT) proteins, Zmiz proteins, and Siz proteins from plants and fungi. The PIAS (protein inhibitor of activated STAT) protein family modulates the activity of several transcription factors and acts as an E3 ubiquitin ligase in the sumoylation pathway. NSE2, also known as MMS21 homolog (MMS21) or non-structural maintenance of chromosomes element 2 homolog (Non-SMC element 2 homolog, NSMCE2), is an autosumoylating small ubiquitin-like modifier (SUMO) ligase required for the response to DNA damage. It regulates sumoylation and nuclear-to-cytoplasmic translocation of skeletal and heart muscle-specific variant of the alpha subunit of nascent polypeptide associated complex (skNAC)-Smyd1 in myogenesis. It is also required for resisting extrinsically induced genotoxic stress.


Pssm-ID: 438116 [Multi-domain]  Cd Length: 45  Bit Score: 62.27  E-value: 2.91e-13
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1039749415 193 FICPITQLEMKKPVKNKMCGHTYEEEAIVRMIESKHKRKK 232
Cdd:cd16452     1 LKCPITQKRMKDPVRGKHCGHCFDLEAILQYLKRRKKKWK 40
RING_Ubox cd00162
RING finger (Really Interesting New Gene) domain and U-box domain superfamily; The RING finger ...
195-227 4.74e-07

RING finger (Really Interesting New Gene) domain and U-box domain superfamily; 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). C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type RING fingers are closely related to RING-HC fingers. In contrast, C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type RING fingers are more closely related to RING-H2 fingers. However, not all RING finger-containing proteins display regular RING finger features, and the RING finger family has turned out to be multifarious. The degenerate RING fingers of the Siz/PIAS RING (SP-RING) family proteins and sporulation protein RMD5, are characterized by lacking the second, fifth, and sixth Zn2+ ion-coordinating residues. They bind only one Zn2+ ion. On the other hand, the RING fingers of the human APC11 and RBX1 proteins can bind a third Zn atom since they harbor four additional Zn ligands. U-box is a modified form of the RING finger domain that lacks metal chelating Cys and His residues. It resembles the cross-brace RING structure consisting of three beta-sheets and a single alpha-helix, which would be stabilized by salt bridges instead of chelated metal ions. U-box proteins are widely distributed among eukaryotic organisms and show a higher prevalence in plants than in other organisms. RING finger/U-box-containing proteins are 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 serve as scaffolds for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enable efficient transfer of ubiquitin from E2 to the substrates.


Pssm-ID: 438111 [Multi-domain]  Cd Length: 42  Bit Score: 45.14  E-value: 4.74e-07
                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1039749415 195 CPITQLEMKK--PVKNKMCGHTYEEEAIVRMIESK 227
Cdd:cd00162     1 CPICREEMNDrrPVVLLSCGHTFSRSAIARWLEGS 35
RING-Ubox_WDSUB1-like cd16655
U-box domain, a modified RING finger, found in WD repeat, SAM and U-box domain-containing ...
193-228 1.36e-06

U-box domain, a modified RING finger, found in WD repeat, SAM and U-box domain-containing protein 1 (WDSUB1) and similar proteins; WDSUB1 is an uncharacterized protein containing seven WD40 repeats and a SAM domain in addition to the U-box. Its biological role remains unclear. This subfamily also includes many uncharacterized kinase domain-containing U-box (AtPUB) proteins and several MIF4G motif-containing AtPUB proteins from Arabidopsis.


Pssm-ID: 438317 [Multi-domain]  Cd Length: 55  Bit Score: 44.42  E-value: 1.36e-06
                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1039749415 193 FICPITQLEMKKPVknkMC--GHTYEEEAIVRMIESKH 228
Cdd:cd16655     4 FLCPITQELMRDPV---VAadGHTYERSAIEEWLETHN 38
RING-Ubox_PUB cd16664
U-box domain, a modified RING finger, found in Arabidopsis plant U-box proteins (AtPUB) and ...
193-230 3.17e-05

U-box domain, a modified RING finger, found in Arabidopsis plant U-box proteins (AtPUB) and similar proteins; The plant PUB proteins, also known as U-box domain-containing proteins, are much more numerous in Arabidopsis which has 62 in comparison with the typical 6 in most animals. The majority of AtPUBs in this subfamily are known as ARM domain-containing PUB proteins, containing a C-terminally-located, tandem ARM (armadillo) repeat protein-interaction region in addition to the U-box domain. They have been implicated in the regulation of cell death and defense. They also play important roles in other plant-specific pathways, such as controlling both self-incompatibility and pseudo-self-incompatibility, as well as acting in abiotic stress. A subgroup of ARM domain-containing PUB proteins harbors a plant-specific U-box N-terminal domain.


Pssm-ID: 438326 [Multi-domain]  Cd Length: 53  Bit Score: 40.24  E-value: 3.17e-05
                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1039749415 193 FICPITQLEMKKPVKNKMcGHTYEEEAIVRMIESKHKR 230
Cdd:cd16664     4 FICPISLELMKDPVILAT-GQTYERAAIEKWLDSGNNT 40
zf-RING_UBOX pfam13445
RING-type zinc-finger; This zinc-finger is a typical RING-type of plant ubiquitin ligases.
195-232 2.15e-04

RING-type zinc-finger; This zinc-finger is a typical RING-type of plant ubiquitin ligases.


Pssm-ID: 433213 [Multi-domain]  Cd Length: 38  Bit Score: 37.76  E-value: 2.15e-04
                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1039749415 195 CPITQLEMKKPVKNkmCGHTYEEEAIVRMIESKHKRKK 232
Cdd:pfam13445   1 CPICLELFTDPVLP--CGHTFCRECLEEMSLLKGGRFK 36
Ubox smart00504
Modified RING finger domain; Modified RING finger domain, without the full complement of Zn2 ...
193-226 1.09e-03

Modified RING finger domain; Modified RING finger domain, without the full complement of Zn2+-binding ligands. Probable involvement in E2-dependent ubiquitination.


Pssm-ID: 128780 [Multi-domain]  Cd Length: 63  Bit Score: 36.44  E-value: 1.09e-03
                           10        20        30
                   ....*....|....*....|....*....|....
gi 1039749415  193 FICPITQLEMKKPVKNKMcGHTYEEEAIVRMIES 226
Cdd:smart00504   2 FLCPISLEVMKDPVILPS-GQTYERSAIEKWLLS 34
RING-Ubox_LubX-like_rpt1 cd23149
first U-box domain, a modified RING finger, found in Legionella pneumophila U-box protein LubX ...
193-227 1.82e-03

first U-box domain, a modified RING finger, found in Legionella pneumophila U-box protein LubX and similar proteins; LubX, also called RING-type E3 ubiquitin transferase LubX, is part of the large arsenal of effectors in Legionella pneumophila that are translocated into the host cytosol during infection. LubX acts as an E3 ubiquitin-protein ligase (EC 2.3.2.27) that interferes with the host's ubiquitination pathway. LubX contains two RING-like U-box domains. U-box 1 is critical to the ubiquitin ligase activity, and U-box 2 mediates interaction with host target. This model corresponds to the first one.


Pssm-ID: 438511 [Multi-domain]  Cd Length: 55  Bit Score: 35.54  E-value: 1.82e-03
                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1039749415 193 FICPITQLEMKKPVKNKMcGHTYEEEAIVRMIESK 227
Cdd:cd23149     1 FTCPITSGFMEDPVITPS-GFSYERSAIERWLETK 34
RING-Ubox cd16453
U-box domain, a modified RING finger; The U-box protein family is a family of E3 enzymes that ...
193-228 1.85e-03

U-box domain, a modified RING finger; The U-box protein family is a family of E3 enzymes that also includes the HECT family and the RING finger family. The E3 enzyme is ubiquitin-protein ligase that cooperates with a ubiquitin-activating enzyme (E1) and a ubiquitin-conjugating enzyme (E2), and plays a central role in determining the specificity of the ubiquitination system. It removes the ubiquitin molecule from the E2 enzyme and attaches it to the target substrate, forming a covalent bond between ubiquitin and the target. U-box proteins are characterized by the presence of a U-box domain of approximately 70 amino acids. The U-box is a modified form of the RING finger domain that lacks metal chelating cysteines and histidines. It resembles the cross-brace RING structure consisting of three beta-sheets and a single alpha-helix, which would be stabilized by salt bridges instead of chelated metal ions. U-box proteins are widely distributed among eukaryotic organisms and show a higher prevalence in plants than in other organisms.


Pssm-ID: 438117 [Multi-domain]  Cd Length: 44  Bit Score: 35.22  E-value: 1.85e-03
                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 1039749415 193 FICPITQLEMKKPVKNKmCGHTYEEEAIVRMIESKH 228
Cdd:cd16453     1 FLCPISGELMKDPVITP-SGITYDRSAIERWLLSDN 35
RING-like_Rtf2 cd16653
RING-like Rtf2 domain, C2HC2-type, found in the replication termination factor 2 (Rtf2) ...
193-220 9.21e-03

RING-like Rtf2 domain, C2HC2-type, found in the replication termination factor 2 (Rtf2) protein family; The Rtf2 protein family includes a group of conserved proteins found in eukaryotes ranging from fission yeast to humans. The defining member of the family is Schizosaccharomyces pombe Rtf2 (SpRtf2), which is a proliferating cell nuclear antigen-interacting protein that functions as a key requirement for efficient replication termination at the site-specific replication barrier RTS1. It promotes termination at RTS1 by preventing replication restart. SpRtf2 contains a RING-like Rtf2 domain that is characterized by a C2HC2 motif similar to C3HC4 RING-HC finger motif known to bind two Zn2+ ions and mediate protein-protein interactions. The C2HC2 motif lacks three of the seven conserved cysteines of the C3HC4 motif, and forms only one functional Zn2+ ion-binding site. The RING-like Rtf2 domain in fission yeast is required to stabilize a paused DNA replication fork during imprinting at the mating type locus, possibly by facilitating sumoylation of PCNA. The family also includes Arabidopsis RTF2 (AtRTF2), an essential nuclear protein required for both normal embryo development and for proper expression of the GFP reporter gene. It plays a critical role in splicing the GFP pre-mRNA, and may also have a more transient regulatory role during the spliceosome cycle. The biological function of Rtf2 homologs found in eumetazoa remains unclear. They contain a variant C2HC2 motif where the middle conserved histidine has been replaced by cysteine.


Pssm-ID: 438315  Cd Length: 47  Bit Score: 33.38  E-value: 9.21e-03
                          10        20        30
                  ....*....|....*....|....*....|.
gi 1039749415 193 FICPITQLEMK---KPVKNKMCGHTYEEEAI 220
Cdd:cd16653     1 FICPITGLEMNgkyKFVYLWPCGCVFSERAL 31
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.20
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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