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Conserved domains on  [gi|512749776|ref|NP_001265466|]
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RING finger and CHY zinc finger domain-containing protein 1 isoform 5 [Homo sapiens]

Protein Classification

RING_Ubox and zinc_ribbon_6 domain-containing protein( domain architecture ID 11691138)

RING_Ubox and zinc_ribbon_6 domain-containing protein

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
zinc_ribbon_6 pfam14599
Zinc-ribbon; This is a typical zinc-ribbon finger, with each pair of zinc-ligands coming from ...
142-200 5.95e-31

Zinc-ribbon; This is a typical zinc-ribbon finger, with each pair of zinc-ligands coming from more-or-less either side of two knuckles. It is found in eukaryotes.


:

Pssm-ID: 464215  Cd Length: 59  Bit Score: 107.63  E-value: 5.95e-31
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 512749776  142 LDMTRYWRQLDDEVAQTPMPSEYQNMTVDILCNDCNGRSTVQFHILGMKCKICESYNTA 200
Cdd:pfam14599   1 VDMEAYWRALDAEIAAQPMPEEYANWRVVILCNDCEAKSEVPFHFLGLKCSHCGSYNTR 59
RING_Ubox super family cl17238
RING finger (Really Interesting New Gene) domain and U-box domain superfamily; The RING finger ...
104-138 4.06e-11

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 cd16464:

Pssm-ID: 473075 [Multi-domain]  Cd Length: 45  Bit Score: 56.13  E-value: 4.06e-11
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 512749776 104 NCPICLEDIHTSRVVAHVLPCGHLLH----------RGYRCPLCM 138
Cdd:cd16464    1 NCPVCLEDLFTSREPVHVLPCGHLMHstcfeeylksGNYRCPLCS 45
 
Name Accession Description Interval E-value
zinc_ribbon_6 pfam14599
Zinc-ribbon; This is a typical zinc-ribbon finger, with each pair of zinc-ligands coming from ...
142-200 5.95e-31

Zinc-ribbon; This is a typical zinc-ribbon finger, with each pair of zinc-ligands coming from more-or-less either side of two knuckles. It is found in eukaryotes.


Pssm-ID: 464215  Cd Length: 59  Bit Score: 107.63  E-value: 5.95e-31
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 512749776  142 LDMTRYWRQLDDEVAQTPMPSEYQNMTVDILCNDCNGRSTVQFHILGMKCKICESYNTA 200
Cdd:pfam14599   1 VDMEAYWRALDAEIAAQPMPEEYANWRVVILCNDCEAKSEVPFHFLGLKCSHCGSYNTR 59
RING-H2_Pirh2-like cd16464
RING finger, H2 subclass, found in p53-induced RING-H2 protein (Pirh2) and similar proteins; ...
104-138 4.06e-11

RING finger, H2 subclass, found in p53-induced RING-H2 protein (Pirh2) and similar proteins; Pirh2, also known as RING finger and CHY zinc finger domain-containing protein 1 (Rchy1), androgen receptor N-terminal-interacting protein, CH-rich-interacting match with PLAG1, RING finger protein 199 (RNF199), or zinc finger protein 363 (ZNF363), is a p53 inducible E3 ubiquitin-protein ligase that functions as a negative regulator of p53. It preferably ubiquitylates the tetrameric form of p53 in vitro and in vivo, suggesting a role of Pirh2 in downregulating the transcriptionally active form of p53 in the cell. Moreover, Pirh2 inhibits the transcriptional activity of p73, a homolog of the tumor suppressor p53, by promoting its ubiquitination. It also monoubiquitinates DNA polymerase eta (PolH) to suppress translesion DNA synthesis. Furthermore, Pirh2 functions as a negative regulator of the cyclin-dependent kinase inhibitor p27(Kip1) function by promoting ubiquitin-dependent proteasomal degradation. Pirh2 enhances androgen receptor (AR) signaling through inhibition of histone deacetylase 1 (HDAC1) and is overexpressed in prostate cancer. It interacts with TIP60 and this association may regulate Pirh2 stability. In addition, the oncoprotein pleomorphic adenoma gene like 2 (PLAGL2) can bind to the Pirh2 dimer and therefore control the stability of Pirh2. Pirh2 contains a total of nine zinc-binding sites with six located at the N-terminal region, two in the C3H2C3-type RING-H2 domain, and one in the C-terminal region. Nine zinc binding sites comprise three different zinc coordination schemes, including RING type cross-brace zinc coordination, C4 zinc finger, and a novel left-handed beta-spiral zinc-binding motif formed by three recurrent CCHC sequence motifs. This subfamily also includes Drosophila melanogaster Deltex, a ubiquitously expressed cytoplasmic ubiquitin E3 ligase that mediates Notch activation in Drosophila. It selectively suppresses T-cell activation through degradation of a key signaling molecule, MAP kinase kinase kinase 1 (MEKK1). It also inhibits Jun-mediated transcription at the stage of Ras-dependent Jun N-terminal protein kinase (JNK) activation. Deltex contains N-terminal two Notch-binding WWE domains that physically interact with the Notch ankyrin domains, a proline-rich motif that shares homology with SH3-binding domains, and a RING finger at the C-terminus.


Pssm-ID: 438127 [Multi-domain]  Cd Length: 45  Bit Score: 56.13  E-value: 4.06e-11
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 512749776 104 NCPICLEDIHTSRVVAHVLPCGHLLH----------RGYRCPLCM 138
Cdd:cd16464    1 NCPVCLEDLFTSREPVHVLPCGHLMHstcfeeylksGNYRCPLCS 45
 
Name Accession Description Interval E-value
zinc_ribbon_6 pfam14599
Zinc-ribbon; This is a typical zinc-ribbon finger, with each pair of zinc-ligands coming from ...
142-200 5.95e-31

Zinc-ribbon; This is a typical zinc-ribbon finger, with each pair of zinc-ligands coming from more-or-less either side of two knuckles. It is found in eukaryotes.


Pssm-ID: 464215  Cd Length: 59  Bit Score: 107.63  E-value: 5.95e-31
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 512749776  142 LDMTRYWRQLDDEVAQTPMPSEYQNMTVDILCNDCNGRSTVQFHILGMKCKICESYNTA 200
Cdd:pfam14599   1 VDMEAYWRALDAEIAAQPMPEEYANWRVVILCNDCEAKSEVPFHFLGLKCSHCGSYNTR 59
RING-H2_Pirh2-like cd16464
RING finger, H2 subclass, found in p53-induced RING-H2 protein (Pirh2) and similar proteins; ...
104-138 4.06e-11

RING finger, H2 subclass, found in p53-induced RING-H2 protein (Pirh2) and similar proteins; Pirh2, also known as RING finger and CHY zinc finger domain-containing protein 1 (Rchy1), androgen receptor N-terminal-interacting protein, CH-rich-interacting match with PLAG1, RING finger protein 199 (RNF199), or zinc finger protein 363 (ZNF363), is a p53 inducible E3 ubiquitin-protein ligase that functions as a negative regulator of p53. It preferably ubiquitylates the tetrameric form of p53 in vitro and in vivo, suggesting a role of Pirh2 in downregulating the transcriptionally active form of p53 in the cell. Moreover, Pirh2 inhibits the transcriptional activity of p73, a homolog of the tumor suppressor p53, by promoting its ubiquitination. It also monoubiquitinates DNA polymerase eta (PolH) to suppress translesion DNA synthesis. Furthermore, Pirh2 functions as a negative regulator of the cyclin-dependent kinase inhibitor p27(Kip1) function by promoting ubiquitin-dependent proteasomal degradation. Pirh2 enhances androgen receptor (AR) signaling through inhibition of histone deacetylase 1 (HDAC1) and is overexpressed in prostate cancer. It interacts with TIP60 and this association may regulate Pirh2 stability. In addition, the oncoprotein pleomorphic adenoma gene like 2 (PLAGL2) can bind to the Pirh2 dimer and therefore control the stability of Pirh2. Pirh2 contains a total of nine zinc-binding sites with six located at the N-terminal region, two in the C3H2C3-type RING-H2 domain, and one in the C-terminal region. Nine zinc binding sites comprise three different zinc coordination schemes, including RING type cross-brace zinc coordination, C4 zinc finger, and a novel left-handed beta-spiral zinc-binding motif formed by three recurrent CCHC sequence motifs. This subfamily also includes Drosophila melanogaster Deltex, a ubiquitously expressed cytoplasmic ubiquitin E3 ligase that mediates Notch activation in Drosophila. It selectively suppresses T-cell activation through degradation of a key signaling molecule, MAP kinase kinase kinase 1 (MEKK1). It also inhibits Jun-mediated transcription at the stage of Ras-dependent Jun N-terminal protein kinase (JNK) activation. Deltex contains N-terminal two Notch-binding WWE domains that physically interact with the Notch ankyrin domains, a proline-rich motif that shares homology with SH3-binding domains, and a RING finger at the C-terminus.


Pssm-ID: 438127 [Multi-domain]  Cd Length: 45  Bit Score: 56.13  E-value: 4.06e-11
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 512749776 104 NCPICLEDIHTSRVVAHVLPCGHLLH----------RGYRCPLCM 138
Cdd:cd16464    1 NCPVCLEDLFTSREPVHVLPCGHLMHstcfeeylksGNYRCPLCS 45
mRING-C3HGC3_RFWD3 cd16450
Modified RING finger, C3HGC3-type, found in RING finger and WD repeat domain-containing ...
103-141 2.01e-03

Modified RING finger, C3HGC3-type, found in RING finger and WD repeat domain-containing protein 3 (RFWD3) and similar proteins; RFWD3, also known as RING finger protein 201 (RNF201) or FLJ10520, is an E3 ubiquitin-protein ligase that forms a complex with Mdm2 and p53 to synergistically ubiquitinate p53 and acts as a positive regulator of p53 stability in response to DNA damage. It is phosphorylated by checkpoint kinase ATM/ATR and the phosphorylation mutant fails to stimulate p53 ubiquitination. RFWD3 also functions as a novel replication protein A (RPA)-associated protein involved in DNA replication checkpoint control. RFWD3 contains an N-terminal SQ-rich region followed by a RING finger domain that exhibits robust E3 ubiquitin ligase activity toward p53, a coiled-coil domain and three WD40 repeats in the C-terminus, the latter two of which may be responsible for protein-protein interaction. The RING finger in this family is a modified C3HGC3-type RING finger, but not a canonical C3H2C3-type RING-H2 finger or C3HC4-type RING-HC finger.


Pssm-ID: 438114 [Multi-domain]  Cd Length: 61  Bit Score: 35.28  E-value: 2.01e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 512749776 103 QNCPICLEDIHTS---RVVAhvLPCGHL----------LHRGYRCPLCMHSA 141
Cdd:cd16450    3 NTCPICFEPWTSSgehRLVS--LKCGHLfgysciekwlKGKGKKCPQCNKKA 52
 
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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