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Conserved domains on  [gi|546230945|ref|NP_001271220|]
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E3 ubiquitin-protein ligase Hakai isoform 2 [Homo sapiens]

Protein Classification

RING-HC_HAKAI_like domain-containing protein (domain architecture ID 11613637)

RING-HC_HAKAI_like domain-containing protein

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
RING-HC_HAKAI_like cd16508
RING finger, HC subclass, found in E3 ubiquitin-protein ligase Hakai, zinc finger protein 645 ...
106-147 2.24e-22

RING finger, HC subclass, found in E3 ubiquitin-protein ligase Hakai, zinc finger protein 645 (ZNF645), and similar proteins; Hakai, also known as Casitas B-lineage lymphoma-transforming sequence-like protein 1, RING finger protein 188 (RNF188), or c-Cbl-like protein 1 (CBLL1), is an E3 ubiquitin ligase that disrupts cell-cell contacts in epithelial cells and is upregulated in human colon and gastric adenocarcinomas. It was identified to mediate the posttranslational downregulation of E-cadherin (CDH1), a major component of adherens junctions in epithelial cells and a potent tumor suppressor. It also promotes ubiquitination of several other tyrosine-phosphorylated Src substrates, including cortactin (CTTN) and DOK1. Hakai acts as a homodimer with a novel HYB (Hakai pTyr-binding) domain that forms a phosphotyrosine-binding pocket upon, and consists of a pair of monomers arranged in an anti-parallel configuration. Each monomer contains a C3HC4-type RING-HC finger and a short pTyr-B domain that incorporates a novel, atypical C2H2-type Zn-finger coordination motif. Both domains are important for dimerization. ZNF645 is a novel testis-specific E3 ubiquitin-protein ligase that plays a role in sperm production and quality control. It has a structure similar to that of the c-Cbl-like protein Hakai. In contrast to Hakai, its HYB domain demonstrates different target specificities. It interacts with v-Src-phosphorylated E-cadherin, but not to cortactin.


:

Pssm-ID: 319422  Cd Length: 38  Bit Score: 89.36  E-value: 2.24e-22
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 546230945 106 HFCDKCGLPIKIYGRMIPCKHVFCYDCAilheKKGDKMCPGC 147
Cdd:cd16508    1 HFCDKCDLPILIYGRMIPCKHVFCYDCA----KLGDKICPRC 38
 
Name Accession Description Interval E-value
RING-HC_HAKAI_like cd16508
RING finger, HC subclass, found in E3 ubiquitin-protein ligase Hakai, zinc finger protein 645 ...
106-147 2.24e-22

RING finger, HC subclass, found in E3 ubiquitin-protein ligase Hakai, zinc finger protein 645 (ZNF645), and similar proteins; Hakai, also known as Casitas B-lineage lymphoma-transforming sequence-like protein 1, RING finger protein 188 (RNF188), or c-Cbl-like protein 1 (CBLL1), is an E3 ubiquitin ligase that disrupts cell-cell contacts in epithelial cells and is upregulated in human colon and gastric adenocarcinomas. It was identified to mediate the posttranslational downregulation of E-cadherin (CDH1), a major component of adherens junctions in epithelial cells and a potent tumor suppressor. It also promotes ubiquitination of several other tyrosine-phosphorylated Src substrates, including cortactin (CTTN) and DOK1. Hakai acts as a homodimer with a novel HYB (Hakai pTyr-binding) domain that forms a phosphotyrosine-binding pocket upon, and consists of a pair of monomers arranged in an anti-parallel configuration. Each monomer contains a C3HC4-type RING-HC finger and a short pTyr-B domain that incorporates a novel, atypical C2H2-type Zn-finger coordination motif. Both domains are important for dimerization. ZNF645 is a novel testis-specific E3 ubiquitin-protein ligase that plays a role in sperm production and quality control. It has a structure similar to that of the c-Cbl-like protein Hakai. In contrast to Hakai, its HYB domain demonstrates different target specificities. It interacts with v-Src-phosphorylated E-cadherin, but not to cortactin.


Pssm-ID: 319422  Cd Length: 38  Bit Score: 89.36  E-value: 2.24e-22
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 546230945 106 HFCDKCGLPIKIYGRMIPCKHVFCYDCAilheKKGDKMCPGC 147
Cdd:cd16508    1 HFCDKCDLPILIYGRMIPCKHVFCYDCA----KLGDKICPRC 38
zf-C3HC4 pfam00097
Zinc finger, C3HC4 type (RING finger); The C3HC4 type zinc-finger (RING finger) is a ...
111-147 1.31e-03

Zinc finger, C3HC4 type (RING finger); The C3HC4 type zinc-finger (RING finger) is a cysteine-rich domain of 40 to 60 residues that coordinates two zinc ions, and has the consensus sequence: C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C where X is any amino acid. Many proteins containing a RING finger play a key role in the ubiquitination pathway.


Pssm-ID: 333836 [Multi-domain]  Cd Length: 40  Bit Score: 36.18  E-value: 1.31e-03
                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 546230945  111 CGLPIKIYGRMIPCKHVFCYDCAILHEKKGDKMCPGC 147
Cdd:pfam00097   4 CLEEPKDPVTILPCGHLFCSKCILSWLESGNVTCPLC 40
RING smart00184
Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and ...
120-147 2.57e-03

Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and is likely to be a general function of this domain; Various RING fingers exhibit binding activity towards E2 ubiquitin-conjugating enzymes (Ubc' s)


Pssm-ID: 214546 [Multi-domain]  Cd Length: 40  Bit Score: 35.56  E-value: 2.57e-03
                           10        20
                   ....*....|....*....|....*...
gi 546230945   120 RMIPCKHVFCYDCAILHEKKGDKMCPGC 147
Cdd:smart00184  13 VILPCGHTFCRSCIRKWLESGNNTCPIC 40
 
Name Accession Description Interval E-value
RING-HC_HAKAI_like cd16508
RING finger, HC subclass, found in E3 ubiquitin-protein ligase Hakai, zinc finger protein 645 ...
106-147 2.24e-22

RING finger, HC subclass, found in E3 ubiquitin-protein ligase Hakai, zinc finger protein 645 (ZNF645), and similar proteins; Hakai, also known as Casitas B-lineage lymphoma-transforming sequence-like protein 1, RING finger protein 188 (RNF188), or c-Cbl-like protein 1 (CBLL1), is an E3 ubiquitin ligase that disrupts cell-cell contacts in epithelial cells and is upregulated in human colon and gastric adenocarcinomas. It was identified to mediate the posttranslational downregulation of E-cadherin (CDH1), a major component of adherens junctions in epithelial cells and a potent tumor suppressor. It also promotes ubiquitination of several other tyrosine-phosphorylated Src substrates, including cortactin (CTTN) and DOK1. Hakai acts as a homodimer with a novel HYB (Hakai pTyr-binding) domain that forms a phosphotyrosine-binding pocket upon, and consists of a pair of monomers arranged in an anti-parallel configuration. Each monomer contains a C3HC4-type RING-HC finger and a short pTyr-B domain that incorporates a novel, atypical C2H2-type Zn-finger coordination motif. Both domains are important for dimerization. ZNF645 is a novel testis-specific E3 ubiquitin-protein ligase that plays a role in sperm production and quality control. It has a structure similar to that of the c-Cbl-like protein Hakai. In contrast to Hakai, its HYB domain demonstrates different target specificities. It interacts with v-Src-phosphorylated E-cadherin, but not to cortactin.


Pssm-ID: 319422  Cd Length: 38  Bit Score: 89.36  E-value: 2.24e-22
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 546230945 106 HFCDKCGLPIKIYGRMIPCKHVFCYDCAilheKKGDKMCPGC 147
Cdd:cd16508    1 HFCDKCDLPILIYGRMIPCKHVFCYDCA----KLGDKICPRC 38
RING-HC cd16449
HC subclass of RING (RING-HC) finger and its variants; RING finger is a specialized type of ...
120-147 9.67e-05

HC subclass of RING (RING-HC) finger and its variants; 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 a different Cys/His pattern. Some lack a single Cys or His residue at typical Zn ligand positions, especially, the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can chelate Zn in a RING finger as well. This family corresponds to HC subclass of RING (RING-HC) finger proteins that are characterized by containing C3HC4-type canonical RING-HC fingers or noncanonical RING-HC finger variants, including C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type modified RING-HC fingers. The canonical RING-HC finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-HC 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 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 enables efficient transfer of ubiquitin from E2 to the substrates.


Pssm-ID: 319363 [Multi-domain]  Cd Length: 39  Bit Score: 39.37  E-value: 9.67e-05
                         10        20
                 ....*....|....*....|....*...
gi 546230945 120 RMIPCKHVFCYDCAILHEKKGDKMCPGC 147
Cdd:cd16449   12 VLLPCGHTFCRSCLRRLLKEGKKKCPIC 39
zf-C3HC4 pfam00097
Zinc finger, C3HC4 type (RING finger); The C3HC4 type zinc-finger (RING finger) is a ...
111-147 1.31e-03

Zinc finger, C3HC4 type (RING finger); The C3HC4 type zinc-finger (RING finger) is a cysteine-rich domain of 40 to 60 residues that coordinates two zinc ions, and has the consensus sequence: C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C where X is any amino acid. Many proteins containing a RING finger play a key role in the ubiquitination pathway.


Pssm-ID: 333836 [Multi-domain]  Cd Length: 40  Bit Score: 36.18  E-value: 1.31e-03
                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 546230945  111 CGLPIKIYGRMIPCKHVFCYDCAILHEKKGDKMCPGC 147
Cdd:pfam00097   4 CLEEPKDPVTILPCGHLFCSKCILSWLESGNVTCPLC 40
RING smart00184
Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and ...
120-147 2.57e-03

Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and is likely to be a general function of this domain; Various RING fingers exhibit binding activity towards E2 ubiquitin-conjugating enzymes (Ubc' s)


Pssm-ID: 214546 [Multi-domain]  Cd Length: 40  Bit Score: 35.56  E-value: 2.57e-03
                           10        20
                   ....*....|....*....|....*...
gi 546230945   120 RMIPCKHVFCYDCAILHEKKGDKMCPGC 147
Cdd:smart00184  13 VILPCGHTFCRSCIRKWLESGNNTCPIC 40
RING-HC_RNF113A_B cd16539
RING finger, HC subclass, found in RING finger proteins RNF113A, RNF113B, and similar proteins; ...
124-148 5.53e-03

RING finger, HC subclass, found in RING finger proteins RNF113A, RNF113B, and similar proteins; RNF113A, also known as zinc finger protein 183 (ZNF183), is an E3 ubiquitin-protein ligase that physically interacts with the E2 protein, UBE2U. A nonsense mutation in RNF113A is associated with an X-linked trichothiodystrophy (TTD). Its yeast ortholog Cwc24p is predicted to have a spliceosome function and acts in a complex with Cef1p to participate in pre-U3 snoRNA splicing, indirectly affecting pre-rRNA processing. It is also important for the U2 snRNP binding to primary transcripts and co-migrates with spliceosomes. Moreover, the ortholog of RNF113A in fruit flies may also act as a spliceosome and is hypothesized to be involved in splicing, namely within the central nervous system. The ortholog in Caenorhabditis elegans is involved in DNA repair of inter-strand crosslinks. RNF113B, also known as zinc finger protein 183-like 1, shows high sequence similarity with RNF113A. Both RNF113A and RNF113B contain a CCCH-type zinc finger, which is commonly found in RNA-binding proteins involved in splicing, and a C3HC4-type RING-HC finger, which is frequently found in E3 ubiquitin ligases.


Pssm-ID: 319453 [Multi-domain]  Cd Length: 41  Bit Score: 34.51  E-value: 5.53e-03
                         10        20
                 ....*....|....*....|....*
gi 546230945 124 CKHVFCYDCAILHEKKGDKmCPGCS 148
Cdd:cd16539   18 CGHYFCEKCALKHYRKSKR-CFVCG 41
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.17
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
  • Marchler-Bauer A et al. (2015), "CDD: NCBI's conserved domain database.", Nucleic Acids Res.43(D)222-6.
  • Marchler-Bauer A et al. (2011), "CDD: a Conserved Domain Database for the functional annotation of proteins.", Nucleic Acids Res.39(D)225-9.
  • Marchler-Bauer A, Bryant SH (2004), "CD-Search: protein domain annotations on the fly.", Nucleic Acids Res.32(W)327-331.
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