E3 ubiquitin-protein ligase Hakai isoform 5 [Mus musculus]
Protein Classification
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 ... |
103-157 | 1.74e-30 | ||
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 arranged in an anti-parallel configuration with a novel HYB (Hakai pTyr-binding) domain that forms a phosphotyrosine-binding pocket. 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: 438171 [Multi-domain] Cd Length: 51 Bit Score: 112.44 E-value: 1.74e-30
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| zf_Hakai | pfam18408 | C2H2 Hakai zinc finger domain; This is the C2H2 zinc finger domain found in E3 ubiquitin ... |
157-188 | 9.76e-16 | ||
C2H2 Hakai zinc finger domain; This is the C2H2 zinc finger domain found in E3 ubiquitin ligase Hakai. Hakai targets tyrosine-phosphorylated E-cadherin. It carries a Tyr(P)-binding domain, coined the HYB domain for Hakai phosphotyrosine (Tyr(P)) binding. HYB domain structure illustrates that it forms a zinc-coordinated homodimer in an antiparallel, intertwined configuration, utilizing residues from the Tyr(P)-binding region of two Hakai monomers. The C-terminal region of the HYB domain, which harbors the atypical zinc-coordination motif and key residues involved in the Tyr(P) interaction, plays an important role in the dimerization observed in the HYB domain. : Pssm-ID: 465753 Cd Length: 32 Bit Score: 70.60 E-value: 9.76e-16
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| 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 ... |
103-157 | 1.74e-30 | ||
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 arranged in an anti-parallel configuration with a novel HYB (Hakai pTyr-binding) domain that forms a phosphotyrosine-binding pocket. 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: 438171 [Multi-domain] Cd Length: 51 Bit Score: 112.44 E-value: 1.74e-30
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| zf_Hakai | pfam18408 | C2H2 Hakai zinc finger domain; This is the C2H2 zinc finger domain found in E3 ubiquitin ... |
157-188 | 9.76e-16 | ||
C2H2 Hakai zinc finger domain; This is the C2H2 zinc finger domain found in E3 ubiquitin ligase Hakai. Hakai targets tyrosine-phosphorylated E-cadherin. It carries a Tyr(P)-binding domain, coined the HYB domain for Hakai phosphotyrosine (Tyr(P)) binding. HYB domain structure illustrates that it forms a zinc-coordinated homodimer in an antiparallel, intertwined configuration, utilizing residues from the Tyr(P)-binding region of two Hakai monomers. The C-terminal region of the HYB domain, which harbors the atypical zinc-coordination motif and key residues involved in the Tyr(P) interaction, plays an important role in the dimerization observed in the HYB domain. Pssm-ID: 465753 Cd Length: 32 Bit Score: 70.60 E-value: 9.76e-16
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| zf-C3HC4 | pfam00097 | Zinc finger, C3HC4 type (RING finger); The C3HC4 type zinc-finger (RING finger) is a ... |
108-144 | 2.10e-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: 395049 [Multi-domain] Cd Length: 40 Bit Score: 35.79 E-value: 2.10e-03
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| RING | smart00184 | Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and ... |
105-144 | 2.71e-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: 2.71e-03
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| 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 ... |
103-157 | 1.74e-30 | ||
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 arranged in an anti-parallel configuration with a novel HYB (Hakai pTyr-binding) domain that forms a phosphotyrosine-binding pocket. 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: 438171 [Multi-domain] Cd Length: 51 Bit Score: 112.44 E-value: 1.74e-30
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| zf_Hakai | pfam18408 | C2H2 Hakai zinc finger domain; This is the C2H2 zinc finger domain found in E3 ubiquitin ... |
157-188 | 9.76e-16 | ||
C2H2 Hakai zinc finger domain; This is the C2H2 zinc finger domain found in E3 ubiquitin ligase Hakai. Hakai targets tyrosine-phosphorylated E-cadherin. It carries a Tyr(P)-binding domain, coined the HYB domain for Hakai phosphotyrosine (Tyr(P)) binding. HYB domain structure illustrates that it forms a zinc-coordinated homodimer in an antiparallel, intertwined configuration, utilizing residues from the Tyr(P)-binding region of two Hakai monomers. The C-terminal region of the HYB domain, which harbors the atypical zinc-coordination motif and key residues involved in the Tyr(P) interaction, plays an important role in the dimerization observed in the HYB domain. Pssm-ID: 465753 Cd Length: 32 Bit Score: 70.60 E-value: 9.76e-16
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| RING-HC_MIP1-like | cd23128 | RING finger, HC subclass, found in Arabidopsis thaliana MND1-interacting protein 1 (MIP1) and ... |
119-150 | 1.09e-04 | ||
RING finger, HC subclass, found in Arabidopsis thaliana MND1-interacting protein 1 (MIP1) and similar proteins; This subfamily includes Arabidopsis thaliana MIP1, RING finger protein 4 (RF4) and RING finger protein 298 (RF298). MIP1 interacts with MND1, HOP2 and XRI1. RF4 and RF298 are putative E3 ubiquitin-protein ligase that may mediate E2-dependent protein ubiquitination. Members of this subfamily contain a typical C3HC4-type RING-HC finger. Pssm-ID: 438490 [Multi-domain] Cd Length: 55 Bit Score: 39.80 E-value: 1.09e-04
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| RING-HC | cd16449 | HC subclass of RING (RING-HC) finger and its variants; The RING finger is a specialized type ... |
117-144 | 1.37e-04 | ||
HC subclass of RING (RING-HC) finger 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 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 the HC subclass of RING (RING-HC) fingers 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 fingers 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: 438113 [Multi-domain] Cd Length: 41 Bit Score: 39.39 E-value: 1.37e-04
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| RING-HC_RNF10 | cd16536 | RING finger, HC subclass, found in RING finger protein 10 (RNF10) and similar proteins; RNF10 ... |
117-152 | 3.06e-04 | ||
RING finger, HC subclass, found in RING finger protein 10 (RNF10) and similar proteins; RNF10 is an E3 ubiquitin-protein ligase that interacts with mesenchyme Homeobox 2 (MEOX2) transcription factor, a regulator of the proliferation, differentiation and migration of vascular smooth muscle cells and cardiomyocytes; it enhances Meox2 activation of the p21 promoter. It also regulates the expression of myelin-associated glycoprotein (MAG) genes and is required for myelin production in Schwann cells of the peripheral nervous system. Moreover, RNF10 regulates retinoic acid-induced neuronal differentiation and the cell cycle exit of P19 embryonic carcinoma cells. RNF10 contains a C3HC4-type RING-HC finger and three putative nuclear localization signals. Pssm-ID: 438198 [Multi-domain] Cd Length: 54 Bit Score: 38.76 E-value: 3.06e-04
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| zf-C3HC4 | pfam00097 | Zinc finger, C3HC4 type (RING finger); The C3HC4 type zinc-finger (RING finger) is a ... |
108-144 | 2.10e-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: 395049 [Multi-domain] Cd Length: 40 Bit Score: 35.79 E-value: 2.10e-03
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| RING | smart00184 | Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and ... |
105-144 | 2.71e-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: 2.71e-03
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| RING-HC_RNF138 | cd16544 | RING finger, HC subclass, found in RING finger protein 138 (RNF138) and similar proteins; ... |
117-152 | 3.51e-03 | ||
RING finger, HC subclass, found in RING finger protein 138 (RNF138) and similar proteins; RNF138, also known as Nemo-like kinase-associated RING finger protein (NARF) or NLK-associated RING finger protein, is an E3 ubiquitin-protein ligase that plays an important role in glioma cell proliferation, apoptosis, and cell cycle. It specifically cooperates with the E2 conjugating enzyme E2-25K (Hip-2/UbcH1), regulates the ubiquitylation and degradation of T cell factor/lymphoid enhancer factor (TCF/LEF), and further suppresses Wnt-beta-catenin signaling. RNF138, together with three closely related proteins: RNF114, RNF125 and RNF166, forms a novel family of ubiquitin ligases with a C3HC4-type RING-HC finger, a C2HC-, and two C2H2-type zinc fingers, as well as a ubiquitin interacting motif (UIM). Pssm-ID: 438206 [Multi-domain] Cd Length: 53 Bit Score: 35.46 E-value: 3.51e-03
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