NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|359718938|ref|NP_001240776|]
View 

E3 ubiquitin-protein ligase Hakai isoform 1 [Mus musculus]

Protein Classification

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

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 ...
 107-161 1.36e-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: 1.36e-30
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 359718938 107 HFCDKCGLPIKVYGRMIPCKHVFCYDCAILHekkgDKMCPGCSDPVQRIEQCTRG 161
Cdd:cd16508    1 HFCDKCDLPIKIYGRMIPCKHVFCLDCARLH----DKICPRCDDPVQRIEQCTRG 51
zf_Hakai pfam18408
C2H2 Hakai zinc finger domain; This is the C2H2 zinc finger domain found in E3 ubiquitin ...
 161-192 8.50e-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: 70.98  E-value: 8.50e-16
                          10        20        30
                  ....*....|....*....|....*....|..
gi 359718938  161 GSLFMCSIVQGCKRTYLSQRDLQAHINHRHMR 192
Cdd:pfam18408   1 GTVFMCSVVQGCRRTYLSQRDLQAHINHRHLR 32
 
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 ...
 107-161 1.36e-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: 1.36e-30
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 359718938 107 HFCDKCGLPIKVYGRMIPCKHVFCYDCAILHekkgDKMCPGCSDPVQRIEQCTRG 161
Cdd:cd16508    1 HFCDKCDLPIKIYGRMIPCKHVFCLDCARLH----DKICPRCDDPVQRIEQCTRG 51
zf_Hakai pfam18408
C2H2 Hakai zinc finger domain; This is the C2H2 zinc finger domain found in E3 ubiquitin ...
 161-192 8.50e-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: 70.98  E-value: 8.50e-16
                          10        20        30
                  ....*....|....*....|....*....|..
gi 359718938  161 GSLFMCSIVQGCKRTYLSQRDLQAHINHRHMR 192
Cdd:pfam18408   1 GTVFMCSVVQGCRRTYLSQRDLQAHINHRHLR 32
zf-C3HC4 pfam00097
Zinc finger, C3HC4 type (RING finger); The C3HC4 type zinc-finger (RING finger) is a ...
 112-148 1.91e-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: 36.18  E-value: 1.91e-03
                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 359718938  112 CGLPIKVYGRMIPCKHVFCYDCAILHEKKGDKMCPGC 148
Cdd:pfam00097   4 CLEEPKDPVTLLPCGHLFCSKCIRSWLESGNVTCPLC 40
RING smart00184
Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and ...
 109-148 2.48e-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: 2.48e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 359718938   109 CDKCGLPIKVYGRMIPCKHVFCYDCAILHEKKGDKMCPGC 148
Cdd:smart00184   1 CPICLEEYLKDPVILPCGHTFCRSCIRKWLESGNNTCPIC 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 ...
 107-161 1.36e-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: 1.36e-30
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 359718938 107 HFCDKCGLPIKVYGRMIPCKHVFCYDCAILHekkgDKMCPGCSDPVQRIEQCTRG 161
Cdd:cd16508    1 HFCDKCDLPIKIYGRMIPCKHVFCLDCARLH----DKICPRCDDPVQRIEQCTRG 51
zf_Hakai pfam18408
C2H2 Hakai zinc finger domain; This is the C2H2 zinc finger domain found in E3 ubiquitin ...
 161-192 8.50e-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: 70.98  E-value: 8.50e-16
                          10        20        30
                  ....*....|....*....|....*....|..
gi 359718938  161 GSLFMCSIVQGCKRTYLSQRDLQAHINHRHMR 192
Cdd:pfam18408   1 GTVFMCSVVQGCRRTYLSQRDLQAHINHRHLR 32
RING-HC_MIP1-like cd23128
RING finger, HC subclass, found in Arabidopsis thaliana MND1-interacting protein 1 (MIP1) and ...
 123-154 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
                         10        20        30
                 ....*....|....*....|....*....|...
gi 359718938 123 IPCKH-VFCYDCAILHEKKGDKMCPGCSDPVQR 154
Cdd:cd23128   19 LPCAHqVVCSGCNDLHEKKGMRECPSCRGEIQE 51
RING-HC cd16449
HC subclass of RING (RING-HC) finger and its variants; The RING finger is a specialized type ...
 121-148 1.22e-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: 1.22e-04
                         10        20
                 ....*....|....*....|....*...
gi 359718938 121 RMIPCKHVFCYDCAILHEKKGDKMCPGC 148
Cdd:cd16449   14 VLLPCGHVFCRECIRRLLESGSIKCPIC 41
RING-HC_RNF10 cd16536
RING finger, HC subclass, found in RING finger protein 10 (RNF10) and similar proteins; RNF10 ...
 121-156 2.69e-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: 2.69e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 359718938 121 RMIPCKHVFCYDCaILH----EKKGDKMCPGCSDPVQRIE 156
Cdd:cd16536   14 RITRCGHIFCWPC-ILRylslSEKKWRKCPICFESIHKKD 52
zf-C3HC4 pfam00097
Zinc finger, C3HC4 type (RING finger); The C3HC4 type zinc-finger (RING finger) is a ...
 112-148 1.91e-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: 36.18  E-value: 1.91e-03
                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 359718938  112 CGLPIKVYGRMIPCKHVFCYDCAILHEKKGDKMCPGC 148
Cdd:pfam00097   4 CLEEPKDPVTLLPCGHLFCSKCIRSWLESGNVTCPLC 40
RING smart00184
Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and ...
 109-148 2.48e-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: 2.48e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 359718938   109 CDKCGLPIKVYGRMIPCKHVFCYDCAILHEKKGDKMCPGC 148
Cdd:smart00184   1 CPICLEEYLKDPVILPCGHTFCRSCIRKWLESGNNTCPIC 40
RING-HC_RNF138 cd16544
RING finger, HC subclass, found in RING finger protein 138 (RNF138) and similar proteins; ...
 121-156 3.21e-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: 35.84  E-value: 3.21e-03
                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 359718938 121 RMIPCKHVFCYDCAILHEKKGDKMCPGCSDPVQRIE 156
Cdd:cd16544   17 ELPPCRHIFCKACILLALRSSGARCPLCRGPVGKTE 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.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH