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Conserved domains on  [gi|2032630016|ref|NP_001381714|]
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NFATC2-interacting protein isoform 3 [Homo sapiens]

Protein Classification

ubiquitin family protein( domain architecture ID 1000087)

ubiquitin family protein belongs to an diverse class of protein modifier and gene expression regulatory proteins that participate in a number of cellular processes

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
Ubl1_cv_Nsp3_N-like super family cl28922
first ubiquitin-like (Ubl) domain located at the N-terminus of coronavirus SARS-CoV ...
278-333 5.01e-27

first ubiquitin-like (Ubl) domain located at the N-terminus of coronavirus SARS-CoV non-structural protein 3 (Nsp3) and related proteins; This ubiquitin-like (Ubl) domain (Ubl1) is found at the N-terminus of coronavirus Nsp3, a large multi-functional multi-domain protein which is an essential component of the replication/transcription complex (RTC). The functions of Ubl1 in CoVs are related to single-stranded RNA (ssRNA) binding and to interacting with the nucleocapsid (N) protein. SARS-CoV Ubl1 has been shown to bind ssRNA having AUA patterns, and since the 5'-UTR of the SARS-CoV genome has a number of AUA repeats, it may bind there. In mouse hepatitis virus (MHV), this Ubl1 domain binds the cognate N protein. Adjacent to Ubl1 is a Glu-rich acidic region (also referred to as hypervariable region, HVR); Ubl1 together with HVR has been called Nsp3a. Currently, the function of HVR in CoVs is unknown. This model corresponds to one of two Ubl domains in Nsp3; the other is located N-terminal to the papain-like protease (PLpro) and is not represented by this model.


The actual alignment was detected with superfamily member cd17079:

Pssm-ID: 475130  Cd Length: 73  Bit Score: 101.37  E-value: 5.01e-27
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2032630016 278 LPLRMDSPLKTLMSHYEEAMGLSGRKLSFFFDGTKLSGRELPADLGMESGDLIEVW 333
Cdd:cd17079    18 VSVSKTAPLKSLMSQYEEAMGLSGRKLSFFFDGTKLSGKETPADLGMESGDVIEVW 73
 
Name Accession Description Interval E-value
Ubl_SLD2_NFATC2ip cd17079
SUMO-like domain 2 (SLD2), structurally similar to a beta-grasp ubiquitin-like fold, found in ...
278-333 5.01e-27

SUMO-like domain 2 (SLD2), structurally similar to a beta-grasp ubiquitin-like fold, found in nuclear factor of activated T-cells 2 interacting protein (NFATC2ip) and similar proteins; NFATC2ip, also termed nuclear factor of activated T cells (NFAT), cytoplasmic, calcineurin dependent 2 interacting protein, or 45 kDa NF-AT-interacting protein, or 45 kDa NFAT-interacting protein (Nip45), or nuclear factor of activated T-cells, or cytoplasmic 2-interacting protein, belongs to the eukaryotic-specific Rad60-Esc2-Nip45 (RENi) protein family. The family members may act as factors in transcriptional regulation, chromatin silencing and genomic stability, and typically contain an N-terminal polar/charged low-complexity segment and two C-terminal consecutive unique small ubiquitin-related modifier (SUMO)-like domains (SLD1 and SLD2) with beta-grasp fold. NFATC2ip was firstly identified as a co-regulator with NFAT and the T helper 2 (Th2)-specific transcription factor, c-Maf, to induce IL-4 production. NFATC2ip has also been involved in cellular differentiation and coordination of the immune response in humans and mice. NFATC2ip SLD2 domain binds to E2 SUMOylation enzyme, Ubc9, in an almost identical manner to that of SUMO and thereby inhibits elongation of poly-SUMO chains.


Pssm-ID: 340599  Cd Length: 73  Bit Score: 101.37  E-value: 5.01e-27
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2032630016 278 LPLRMDSPLKTLMSHYEEAMGLSGRKLSFFFDGTKLSGRELPADLGMESGDLIEVW 333
Cdd:cd17079    18 VSVSKTAPLKSLMSQYEEAMGLSGRKLSFFFDGTKLSGKETPADLGMESGDVIEVW 73
Rad60-SLD pfam11976
Ubiquitin-2 like Rad60 SUMO-like; The small ubiquitin-related modifier SUMO-1 is a Ub/Ubl ...
283-332 3.83e-08

Ubiquitin-2 like Rad60 SUMO-like; The small ubiquitin-related modifier SUMO-1 is a Ub/Ubl family member, and although SUMO-1 shares structural similarity to Ub, SUMO's cellular functions remain distinct insomuch as SUMO modification alters protein function through changes in activity, cellular localization, or by protecting substrates from ubiquitination. Rad60 family members contain functionally enigmatic, integral SUMO-like domains (SLDs). Despite their divergence from SUMO, each Rad60 SLD interacts with a subset of SUMO pathway enzymes: SLD2 specifically binds the SUMO E2 conjugating enzyme (Ubc9)), whereas SLD1 binds the SUMO E1 (Fub2, also called Uba2) activating and E3 (Pli1, also called Siz1 and Siz2) specificity enzymes. Structural analysis of PDB:2uyz reveals a mechanistic basis for the near-synonymous roles of Rad60 and SUMO in survival of genotoxic stress and suggest unprecedented DNA-damage-response functions for SLDs in regulating SUMOylation. The Rad60 branch of this family is also known as RENi (Rad60-Esc2-Nip45), and biologically it should be two distinct families SUMO and RENi (Rad60-Esc2-Nip45).


Pssm-ID: 403255 [Multi-domain]  Cd Length: 72  Bit Score: 49.87  E-value: 3.83e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2032630016 283 DSPLKTLMSHYEEAMGLS-GRKLSFFFDGTKLSGRELPADLGMESGDLIEV 332
Cdd:pfam11976  20 TTTVSKLINAYRKKRGIPpSQQVRLIFDGERLDPNSTVEDLDIEDGDTIDV 70
SMT3 COG5227
Ubiquitin-like protein (sentrin) [Posttranslational modification, protein turnover, chaperones] ...
280-332 3.65e-05

Ubiquitin-like protein (sentrin) [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 227552  Cd Length: 103  Bit Score: 42.22  E-value: 3.65e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2032630016 280 LRMDSPLKTLMSHYEEAMGLSGRKLSFFFDGTKLSGRELPADLGMESGDLIEV 332
Cdd:COG5227    41 IKKTTTFKKLMDAFSRRQGKNMSSLRFLFDGKRIDLDQTPGDLDMEDNDEIEA 93
 
Name Accession Description Interval E-value
Ubl_SLD2_NFATC2ip cd17079
SUMO-like domain 2 (SLD2), structurally similar to a beta-grasp ubiquitin-like fold, found in ...
278-333 5.01e-27

SUMO-like domain 2 (SLD2), structurally similar to a beta-grasp ubiquitin-like fold, found in nuclear factor of activated T-cells 2 interacting protein (NFATC2ip) and similar proteins; NFATC2ip, also termed nuclear factor of activated T cells (NFAT), cytoplasmic, calcineurin dependent 2 interacting protein, or 45 kDa NF-AT-interacting protein, or 45 kDa NFAT-interacting protein (Nip45), or nuclear factor of activated T-cells, or cytoplasmic 2-interacting protein, belongs to the eukaryotic-specific Rad60-Esc2-Nip45 (RENi) protein family. The family members may act as factors in transcriptional regulation, chromatin silencing and genomic stability, and typically contain an N-terminal polar/charged low-complexity segment and two C-terminal consecutive unique small ubiquitin-related modifier (SUMO)-like domains (SLD1 and SLD2) with beta-grasp fold. NFATC2ip was firstly identified as a co-regulator with NFAT and the T helper 2 (Th2)-specific transcription factor, c-Maf, to induce IL-4 production. NFATC2ip has also been involved in cellular differentiation and coordination of the immune response in humans and mice. NFATC2ip SLD2 domain binds to E2 SUMOylation enzyme, Ubc9, in an almost identical manner to that of SUMO and thereby inhibits elongation of poly-SUMO chains.


Pssm-ID: 340599  Cd Length: 73  Bit Score: 101.37  E-value: 5.01e-27
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2032630016 278 LPLRMDSPLKTLMSHYEEAMGLSGRKLSFFFDGTKLSGRELPADLGMESGDLIEVW 333
Cdd:cd17079    18 VSVSKTAPLKSLMSQYEEAMGLSGRKLSFFFDGTKLSGKETPADLGMESGDVIEVW 73
Ubl_SUMO_like cd01763
ubiquitin-like (Ubl) domain found in small ubiquitin-related modifier (SUMO) and similar ...
265-333 5.66e-16

ubiquitin-like (Ubl) domain found in small ubiquitin-related modifier (SUMO) and similar proteins; SUMO (also known as "Smt3" and "sentrin" in other organisms) resembles ubiquitin (Ub) in structure, ligation to other proteins, and the mechanism of ligation. Ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair. Ubiquitination is comprised of a cascade of E1, E2 and E3 enzymes that results in a covalent bond between the C-terminus of Ub and the epsilon-amino group of a substrate lysine. SUMOs, like Ub, are covalently conjugated to lysine residues in a wide variety of target proteins in eukaryotic cells and regulate numerous cellular processes, such as transcription, epigenetic gene control, genomic instability, and protein degradation. The mammalian SUMOs have four paralogs, SUMO1 through SUMO4, which all regulate different cellular functions by conjugating to different proteins. SUMO2-4 are more closely related to each other than to SUMO1.


Pssm-ID: 340462 [Multi-domain]  Cd Length: 72  Bit Score: 71.46  E-value: 5.66e-16
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2032630016 265 FPLKIRCR--ADLVRLPLRMDSPLKTLMSHYEEAMGLSGRKLSFFFDGTKLSGRELPADLGMESGDLIEVW 333
Cdd:cd01763     2 ITIKVRGQdgGKKVRFKVKKTTKLKKLFDAYAEKKGLDPDSLRFTFDGERISPNDTPESLGLEDGDIIDVV 72
Ubl_Smt3_like cd16116
ubiquitin-like (Ubl) domain found in Saccharomyces cerevisiae ubiquitin-like protein Smt3p and ...
285-332 3.36e-09

ubiquitin-like (Ubl) domain found in Saccharomyces cerevisiae ubiquitin-like protein Smt3p and similar proteins; Smt3 (Suppressor of Mif Two 3) was originally isolated as a high-copy suppressor of a mutation in MIF2, the gene of a centromere binding protein in S. cerevisiae. Smt3p is the yeast homolog of small ubiquitin-related modifier (SUMO) proteins that are involved in post-translational protein modification called SUMOylation, covalently attaching to and detaching from other proteins in cells to modify their function. SUMO resembles ubiquitin (Ub) in its structure, its ability to be ligated to other proteins, as well as in the mechanism of ligation. Ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair. Ubiquitination is comprised of a cascade of E1, E2 and E3 enzymes that results in a covalent bond between the C-terminus of Ub and the epsilon-amino group of a substrate lysine. Smt3p plays essential roles in cell-cycle regulation and chromosome segregation in budding yeast. It interacts with different modification enzymes, and regulates their functions through linking covalently to its targets.


Pssm-ID: 340533 [Multi-domain]  Cd Length: 74  Bit Score: 52.62  E-value: 3.36e-09
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 2032630016 285 PLKTLMSHYEEAMGLSGRKLSFFFDGTKLSGRELPADLGMESGDLIEV 332
Cdd:cd16116    24 PLRKLMEAYCKRQGKSMDSVRFLFDGERIREDQTPEDLGMEDGDEIDA 71
Ubl_SUMO2_3_4 cd16115
ubiquitin-like (Ubl) domain found in small ubiquitin-related modifier SUMO-2, SUMO-3, SUMO-4, ...
276-332 1.11e-08

ubiquitin-like (Ubl) domain found in small ubiquitin-related modifier SUMO-2, SUMO-3, SUMO-4, and similar proteins; SUMO (also known as "Smt3" and "sentrin" in other organisms) resembles ubiquitin (Ub) in structure, ligation to other proteins and the mechanism of ligation. Ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair. Ubiquitination is comprised of a cascade of E1, E2 and E3 enzymes that results in a covalent bond between the C-terminus of Ub and the epsilon-amino group of a substrate lysine. SUMOs, like Ub, are covalently conjugated to lysine residues in a wide variety of target proteins in eukaryotic cells and regulate numerous cellular processes, such as transcription, epigenetic gene control, genomic instability, and protein degradation. The mammalian SUMOs have four paralogs, SUMO1 through SUMO4. SUMO2 and SUMO3 are more closely related to each other than they are to SUMO1. SUMO2/3 are capable of forming chains on substrate proteins through internal lysine residues. The basic biology of SUMO4 remains unclear. A M55V polymorphism in SUMO4 has been associated with susceptibility to type I diabetes in some genetic studies.


Pssm-ID: 340532 [Multi-domain]  Cd Length: 72  Bit Score: 51.21  E-value: 1.11e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 2032630016 276 VRLPLRMDSPLKTLMSHYEEAMGLSGRKLSFFFDGTKLSGRELPADLGMESGDLIEV 332
Cdd:cd16115    14 VQFKIKRHTPLSKLMKAYCDRQGLSMRQIRFRFDGQPINETDTPAQLEMEDEDTIDV 70
Rad60-SLD pfam11976
Ubiquitin-2 like Rad60 SUMO-like; The small ubiquitin-related modifier SUMO-1 is a Ub/Ubl ...
283-332 3.83e-08

Ubiquitin-2 like Rad60 SUMO-like; The small ubiquitin-related modifier SUMO-1 is a Ub/Ubl family member, and although SUMO-1 shares structural similarity to Ub, SUMO's cellular functions remain distinct insomuch as SUMO modification alters protein function through changes in activity, cellular localization, or by protecting substrates from ubiquitination. Rad60 family members contain functionally enigmatic, integral SUMO-like domains (SLDs). Despite their divergence from SUMO, each Rad60 SLD interacts with a subset of SUMO pathway enzymes: SLD2 specifically binds the SUMO E2 conjugating enzyme (Ubc9)), whereas SLD1 binds the SUMO E1 (Fub2, also called Uba2) activating and E3 (Pli1, also called Siz1 and Siz2) specificity enzymes. Structural analysis of PDB:2uyz reveals a mechanistic basis for the near-synonymous roles of Rad60 and SUMO in survival of genotoxic stress and suggest unprecedented DNA-damage-response functions for SLDs in regulating SUMOylation. The Rad60 branch of this family is also known as RENi (Rad60-Esc2-Nip45), and biologically it should be two distinct families SUMO and RENi (Rad60-Esc2-Nip45).


Pssm-ID: 403255 [Multi-domain]  Cd Length: 72  Bit Score: 49.87  E-value: 3.83e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2032630016 283 DSPLKTLMSHYEEAMGLS-GRKLSFFFDGTKLSGRELPADLGMESGDLIEV 332
Cdd:pfam11976  20 TTTVSKLINAYRKKRGIPpSQQVRLIFDGERLDPNSTVEDLDIEDGDTIDV 70
Ubl_SUMO1 cd16114
ubiquitin-like (Ubl) domain found in small ubiquitin-related modifier 1 (SUMO-1) and similar ...
276-333 5.64e-07

ubiquitin-like (Ubl) domain found in small ubiquitin-related modifier 1 (SUMO-1) and similar proteins; SUMO (also known as "Smt3" and "sentrin" in other organisms) resembles ubiquitin (Ub) in structure, ligation to other proteins and the mechanism of ligation. Ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair. Ubiquitination is comprised of a cascade of E1, E2 and E3 enzymes that results in a covalent bond between the C-terminus of Ub and the epsilon-amino group of a substrate lysine. SUMOs, like Ub, are covalently conjugated to lysine residues in a wide variety of target proteins in eukaryotic cells and regulate numerous cellular processes, such as transcription, epigenetic gene control, genomic instability, and protein degradation. Four SUMO paralogs exist in mammals, SUMO1 through SUMO4. SUMO2-SUMO4 are more closely related to each other than they are to SUMO1. SUMO1 is a binding partner of the RAD51/52 nucleoprotein filament proteins, which mediate DNA strand exchange. SUMO1 conjugation to cellular proteins has been implicated in multiple important cellular processes, such as nuclear transport, cell cycle control, oncogenesis, inflammation, and the response to virus infection.


Pssm-ID: 340531 [Multi-domain]  Cd Length: 76  Bit Score: 46.68  E-value: 5.64e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2032630016 276 VRLPLRMDSPLKTLMSHYEEAMGLSGRKLSFFFDGTKLSGRELPADLGMESGDLIEVW 333
Cdd:cd16114    14 IHFKVKMTTHLKKLKESYCQRQGVPMNSLRFLFEGQRINDNHTPKELGMEEEDVIEVY 71
Ubl_SLD2_Esc2_like cd17080
SUMO-like domain 2 (SLD2), structurally similar to a beta-grasp ubiquitin-like fold, found in ...
264-332 1.48e-06

SUMO-like domain 2 (SLD2), structurally similar to a beta-grasp ubiquitin-like fold, found in Saccharomyces cerevisiae establishes silent chromatin protein 2 (Esc2p) and similar proteins; Protein Esc2p belongs to the eukaryotic-specific Rad60-Esc2-Nip45 (RENi) protein family, whose members may act as factors in transcriptional regulation, chromatin silencing and genomic stability, and typically contain an N-terminal polar/charged low-complexity segment and two C-terminal consecutive unique small ubiquitin-related modifier (SUMO)-like domains (SLD1 and SLD2) with beta-grasp fold. Yeast Esc2p was identified as a factor promoting gene silencing. It is also required for genome integrity during DNA replication and sister chromatid cohesion in Saccharomyces cerevisiae. Esc2p promotes Mus81p complex-activity via its SUMO-like and DNA binding domains. It also acts as a novel structure-specific DNA-binding factor implicated in the local regulation of the Srs2p helicase through promoting recombination at sites of stalled replication. In addition, Esc2p specifically promotes the accumulation of SUMOylated Mms21-specific substrates and functions with Mms21p to suppress gross chromosomal rearrangements (GCRs). This family also includes DNA repair protein Rad60p from Schizosaccharomyces pombe. It is a SUMO mimetic and SUMO-targeted ubiquitin ligase (STUbL)-interacting protein that is required for the repair of DNA double strand breaks, recovery from S phase replication arrest, and plays an essential role in cell viability. Like other RENi family members, Rad60p has two SLD domains.


Pssm-ID: 340600  Cd Length: 74  Bit Score: 45.29  E-value: 1.48e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2032630016 264 LFPLKIR-CRADLVRLPLRMDSPLKTLMSHYEEAMGLS--GRKLSFFFDGTKLSGRELPADLGMESGDLIEV 332
Cdd:cd17080     2 LIKLKLRgKDNKRLSLKVKPSTTLSDLVEAYKIKKKLSlaAAKVKLEFDGEPLDLSETVEDLDLEDEDMLEV 73
SMT3 COG5227
Ubiquitin-like protein (sentrin) [Posttranslational modification, protein turnover, chaperones] ...
280-332 3.65e-05

Ubiquitin-like protein (sentrin) [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 227552  Cd Length: 103  Bit Score: 42.22  E-value: 3.65e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2032630016 280 LRMDSPLKTLMSHYEEAMGLSGRKLSFFFDGTKLSGRELPADLGMESGDLIEV 332
Cdd:COG5227    41 IKKTTTFKKLMDAFSRRQGKNMSSLRFLFDGKRIDLDQTPGDLDMEDNDEIEA 93
Ubl_SLD1_NFATC2ip cd17078
SUMO-like domain 1 (SLD1), structurally similar to a beta-grasp ubiquitin-like fold, found in ...
263-331 2.45e-04

SUMO-like domain 1 (SLD1), structurally similar to a beta-grasp ubiquitin-like fold, found in nuclear factor of activated T-cells 2 interacting protein (NFATC2ip) and similar proteins; NFATC2ip, also termed nuclear factor of activated T cells (NFAT), cytoplasmic, calcineurin dependent 2 interacting protein, or 45 kDa NF-AT-interacting protein, or 45 kDa NFAT-interacting protein (Nip45), or nuclear factor of activated T-cells, or cytoplasmic 2-interacting protein, belongs to the eukaryotic-specific Rad60-Esc2-Nip45 (RENi) protein family. The family members may act as factors in transcriptional regulation, chromatin silencing and genomic stability, and typically contain an N-terminal polar/charged low-complexity segment and two C-terminal consecutive unique small ubiquitin-related modifier (SUMO)-like domains (SLD1 and SLD2) with beta-grasp fold. NFATC2ip was firstly identified as a co-regulator with NFAT and the T helper 2 (Th2)-specific transcription factor, c-Maf, to induce IL-4 production. NFATC2ip has also been involved in cellular differentiation and coordination of the immune response in humans and mice.


Pssm-ID: 340598  Cd Length: 74  Bit Score: 39.10  E-value: 2.45e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2032630016 263 RLFPLKIRCRADLVRLPLRMDSPLKTLMSHYEEAMGLSGRKLSFFFDGTKLSGRELPADLGMESGDLIE 331
Cdd:cd17078     1 RTITVKVRCRSGIKRIPLKPTDPFEKIFETLARLLGVPPSRILLLLNDQLLHLDDTPKSLNLGIADIID 69
 
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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