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Conserved domains on  [gi|22749189|ref|NP_689790|]
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E3 ubiquitin-protein ligase CBLL2 [Homo sapiens]

Protein Classification

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 ...
 55-109 6.14e-27

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: 102.04  E-value: 6.14e-27
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 22749189  55 HFCDKCDLPIKIYGRIIPCKHAFCYHCANLYDkvgyKVCPRCRYPVLRIEAHKRG 109
Cdd:cd16508   1 HFCDKCDLPIKIYGRMIPCKHVFCLDCARLHD----KICPRCDDPVQRIEQCTRG 51
zf_Hakai pfam18408
C2H2 Hakai zinc finger domain; This is the C2H2 zinc finger domain found in E3 ubiquitin ...
 109-140 2.25e-13

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: 63.67  E-value: 2.25e-13
                          10        20        30
                  ....*....|....*....|....*....|..
gi 22749189   109 GSVFMCSIVQQCKRTYLSQKSLQAHIKRRHKR 140
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 ...
 55-109 6.14e-27

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: 102.04  E-value: 6.14e-27
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 22749189  55 HFCDKCDLPIKIYGRIIPCKHAFCYHCANLYDkvgyKVCPRCRYPVLRIEAHKRG 109
Cdd:cd16508   1 HFCDKCDLPIKIYGRMIPCKHVFCLDCARLHD----KICPRCDDPVQRIEQCTRG 51
zf_Hakai pfam18408
C2H2 Hakai zinc finger domain; This is the C2H2 zinc finger domain found in E3 ubiquitin ...
 109-140 2.25e-13

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: 63.67  E-value: 2.25e-13
                          10        20        30
                  ....*....|....*....|....*....|..
gi 22749189   109 GSVFMCSIVQQCKRTYLSQKSLQAHIKRRHKR 140
Cdd:pfam18408   1 GTVFMCSVVQGCRRTYLSQRDLQAHINHRHLR 32
RING smart00184
Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and ...
 57-96 3.87e-04

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: 37.87  E-value: 3.87e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 22749189     57 CDKCDLPIKIYGRIIPCKHAFCYHCANLYDKVGYKVCPRC 96
Cdd:smart00184   1 CPICLEEYLKDPVILPCGHTFCRSCIRKWLESGNNTCPIC 40
zf-C3HC4 pfam00097
Zinc finger, C3HC4 type (RING finger); The C3HC4 type zinc-finger (RING finger) is a ...
 63-96 2.51e-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: 35.41  E-value: 2.51e-03
                          10        20        30
                  ....*....|....*....|....*....|....
gi 22749189    63 PIKIYGRIIPCKHAFCYHCANLYDKVGYKVCPRC 96
Cdd:pfam00097   7 EPKDPVTLLPCGHLFCSKCIRSWLESGNVTCPLC 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 ...
 55-109 6.14e-27

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: 102.04  E-value: 6.14e-27
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 22749189  55 HFCDKCDLPIKIYGRIIPCKHAFCYHCANLYDkvgyKVCPRCRYPVLRIEAHKRG 109
Cdd:cd16508   1 HFCDKCDLPIKIYGRMIPCKHVFCLDCARLHD----KICPRCDDPVQRIEQCTRG 51
zf_Hakai pfam18408
C2H2 Hakai zinc finger domain; This is the C2H2 zinc finger domain found in E3 ubiquitin ...
 109-140 2.25e-13

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: 63.67  E-value: 2.25e-13
                          10        20        30
                  ....*....|....*....|....*....|..
gi 22749189   109 GSVFMCSIVQQCKRTYLSQKSLQAHIKRRHKR 140
Cdd:pfam18408   1 GTVFMCSVVQGCRRTYLSQRDLQAHINHRHLR 32
RING smart00184
Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and ...
 57-96 3.87e-04

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: 37.87  E-value: 3.87e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 22749189     57 CDKCDLPIKIYGRIIPCKHAFCYHCANLYDKVGYKVCPRC 96
Cdd:smart00184   1 CPICLEEYLKDPVILPCGHTFCRSCIRKWLESGNNTCPIC 40
RING-HC cd16449
HC subclass of RING (RING-HC) finger and its variants; The RING finger is a specialized type ...
 69-96 9.74e-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: 36.69  E-value: 9.74e-04
                        10        20
                ....*....|....*....|....*...
gi 22749189  69 RIIPCKHAFCYHCANLYDKVGYKVCPRC 96
Cdd:cd16449  14 VLLPCGHVFCRECIRRLLESGSIKCPIC 41
zf-C3HC4 pfam00097
Zinc finger, C3HC4 type (RING finger); The C3HC4 type zinc-finger (RING finger) is a ...
 63-96 2.51e-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: 35.41  E-value: 2.51e-03
                          10        20        30
                  ....*....|....*....|....*....|....
gi 22749189    63 PIKIYGRIIPCKHAFCYHCANLYDKVGYKVCPRC 96
Cdd:pfam00097   7 EPKDPVTLLPCGHLFCSKCIRSWLESGNVTCPLC 40
RING-HC_PEX2 cd16526
RING finger, HC subclass, found in peroxin-2 (PEX2) and similar proteins; PEX2, also known as ...
 70-100 4.70e-03

RING finger, HC subclass, found in peroxin-2 (PEX2) and similar proteins; PEX2, also known as peroxisome biogenesis factor 2, 35 kDa peroxisomal membrane protein, peroxisomal membrane protein 3, peroxisome assembly factor 1 (PAF-1), or RING finger protein 72 (RNF72), is an integral peroxisomal membrane protein with two transmembrane regions and a C3HC4-type RING-HC finger within its cytoplasmically exposed C-terminus. It may be involved in the biogenesis of peroxisomes, as well as in peroxisomal matrix protein import. Mutations in the PEX2 gene are the primary defect in a subset of patients with Zellweger syndrome and related peroxisome biogenesis disorders. Moreover, PEX2 functions as an E3-ubiquitin ligase that mediates the UBC4-dependent polyubiquitination of PEX5, a key player in peroxisomal matrix protein import, to control PEX5 receptor recycling or degradation.


Pssm-ID: 438189 [Multi-domain]  Cd Length: 49  Bit Score: 35.05  E-value: 4.70e-03
                        10        20        30
                ....*....|....*....|....*....|...
gi 22749189  70 IIPCKHAFCYHC--ANLYDKVGYKvCPRCRYPV 100
Cdd:cd16526  17 STGCGHVYCYYCikSNLLADDSFT-CPRCGSPV 48
 
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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