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Conserved domains on  [gi|2240474248|ref|XP_048176930|]
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E3 ubiquitin-protein ligase MGRN1 isoform X4 [Corvus hawaiiensis]

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
mRING-HC-C3HC5_MGRN1 cd16816
Modified RING finger, HC subclass (C3HC5-type), found in mahogunin RING finger protein 1 ...
269-326 2.83e-35

Modified RING finger, HC subclass (C3HC5-type), found in mahogunin RING finger protein 1 (MGRN1) and similar proteins; MGRN1, also known as RING finger protein 156 (RNF156), is a cytosolic E3 ubiquitin-protein ligase that inhibits signaling through the G protein-coupled melanocortin receptors-1 (MC1R), -2 (MC2R) and -4 (MC4R) via ubiquitylation-dependent and -independent processes. It suppresses chaperone-associated misfolded protein aggregation and toxicity. MGRN1 interacts with cytosolic prion proteins (PrPs) that are linked with neurodegeneration. It also interacts with expanded polyglutamine proteins, and suppresses misfolded polyglutamine aggregation and cytotoxicity. Moreover, MGRN1 inhibits melanocortin receptor signaling by competition with Galphas, suggesting a novel pathway for melanocortin signaling from the cell surface to the nucleus. Furthermore, MGRN1 interacts with and ubiquitylates TSG101, a key component of the endosomal sorting complex required for transport (ESCRT)-I, and regulates endosomal trafficking. A null mutation in the gene encoding MGRN1 causes spongiform neurodegeneration, suggesting a link between dysregulation of endosomal trafficking and spongiform neurodegeneration. MGRN1 contains a modified C3HC5-type RING-HC finger, a conserved PSAP motif necessary for interaction between MGRN1 and TSG101. In addition, MGRN1 harbors a functionally uncharacterized region, as known as the domain associated with RING2 (DAR2), N-terminal to the RING finger. The C3HC5-type RING-HC finger is distinguished from typical C3HC4 RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.


:

Pssm-ID: 438465  Cd Length: 58  Bit Score: 126.33  E-value: 2.83e-35
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2240474248 269 DDENSDNSNECVVCLSDLRDTLILPCRHLCLCNSCADTLRYQANNCPICRLPFRALLQ 326
Cdd:cd16816     1 DDENSDNSNECVVCLSDLRDTLILPCRHLCLCNSCADTLRYQANNCPICRLPFRALLQ 58
 
Name Accession Description Interval E-value
mRING-HC-C3HC5_MGRN1 cd16816
Modified RING finger, HC subclass (C3HC5-type), found in mahogunin RING finger protein 1 ...
269-326 2.83e-35

Modified RING finger, HC subclass (C3HC5-type), found in mahogunin RING finger protein 1 (MGRN1) and similar proteins; MGRN1, also known as RING finger protein 156 (RNF156), is a cytosolic E3 ubiquitin-protein ligase that inhibits signaling through the G protein-coupled melanocortin receptors-1 (MC1R), -2 (MC2R) and -4 (MC4R) via ubiquitylation-dependent and -independent processes. It suppresses chaperone-associated misfolded protein aggregation and toxicity. MGRN1 interacts with cytosolic prion proteins (PrPs) that are linked with neurodegeneration. It also interacts with expanded polyglutamine proteins, and suppresses misfolded polyglutamine aggregation and cytotoxicity. Moreover, MGRN1 inhibits melanocortin receptor signaling by competition with Galphas, suggesting a novel pathway for melanocortin signaling from the cell surface to the nucleus. Furthermore, MGRN1 interacts with and ubiquitylates TSG101, a key component of the endosomal sorting complex required for transport (ESCRT)-I, and regulates endosomal trafficking. A null mutation in the gene encoding MGRN1 causes spongiform neurodegeneration, suggesting a link between dysregulation of endosomal trafficking and spongiform neurodegeneration. MGRN1 contains a modified C3HC5-type RING-HC finger, a conserved PSAP motif necessary for interaction between MGRN1 and TSG101. In addition, MGRN1 harbors a functionally uncharacterized region, as known as the domain associated with RING2 (DAR2), N-terminal to the RING finger. The C3HC5-type RING-HC finger is distinguished from typical C3HC4 RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.


Pssm-ID: 438465  Cd Length: 58  Bit Score: 126.33  E-value: 2.83e-35
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2240474248 269 DDENSDNSNECVVCLSDLRDTLILPCRHLCLCNSCADTLRYQANNCPICRLPFRALLQ 326
Cdd:cd16816     1 DDENSDNSNECVVCLSDLRDTLILPCRHLCLCNSCADTLRYQANNCPICRLPFRALLQ 58
zf-C3HC4_3 pfam13920
Zinc finger, C3HC4 type (RING finger);
275-320 1.20e-17

Zinc finger, C3HC4 type (RING finger);


Pssm-ID: 464042 [Multi-domain]  Cd Length: 50  Bit Score: 76.65  E-value: 1.20e-17
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 2240474248 275 NSNECVVCLSDLRDTLILPCRHLCLCNSCADTLRYQANNCPICRLP 320
Cdd:pfam13920   1 EDLLCVICLDRPRNVVLLPCGHLCLCEECAERLLRKKKKCPICRQP 46
RING smart00184
Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and ...
279-317 8.60e-07

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: 45.58  E-value: 8.60e-07
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 2240474248  279 CVVCLSD-LRDTLILPCRHLcLCNSCADT-LRYQANNCPIC 317
Cdd:smart00184   1 CPICLEEyLKDPVILPCGHT-FCRSCIRKwLESGNNTCPIC 40
PHA02929 PHA02929
N1R/p28-like protein; Provisional
233-332 2.88e-04

N1R/p28-like protein; Provisional


Pssm-ID: 222944 [Multi-domain]  Cd Length: 238  Bit Score: 42.46  E-value: 2.88e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2240474248 233 FSVKPLKQKQIVDRVSYL--LQE---IYGIENKNNQETK------PS------DDENSDNSNECVVCLSDLRDTL----- 290
Cdd:PHA02929  114 YNQKILKNKPSNDKINYIymRKEedmFYAIINKKGKNYKkflktiPSvlseyeKLYNRSKDKECAICMEKVYDKEiknmy 193
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 2240474248 291 --ILP-CRHLcLCNSCADTLRYQANNCPICRLPFRALLQIRAVRK 332
Cdd:PHA02929  194 fgILSnCNHV-FCIECIDIWKKEKNTCPVCRTPFISVIKSRFFTK 237
COG5236 COG5236
Uncharacterized conserved protein, contains RING Zn-finger [General function prediction only];
260-318 1.34e-03

Uncharacterized conserved protein, contains RING Zn-finger [General function prediction only];


Pssm-ID: 227561 [Multi-domain]  Cd Length: 493  Bit Score: 41.54  E-value: 1.34e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2240474248 260 KNNQETKP------SDDENSDNSNeCVVCLSDLRDTLILPCRHLcLCNSCADTLR--YQANNCPICR 318
Cdd:COG5236    40 KNNLSAEPnlttssADDTDEENMN-CQICAGSTTYSARYPCGHQ-ICHACAVRLRalYMQKGCPLCR 104
 
Name Accession Description Interval E-value
mRING-HC-C3HC5_MGRN1 cd16816
Modified RING finger, HC subclass (C3HC5-type), found in mahogunin RING finger protein 1 ...
269-326 2.83e-35

Modified RING finger, HC subclass (C3HC5-type), found in mahogunin RING finger protein 1 (MGRN1) and similar proteins; MGRN1, also known as RING finger protein 156 (RNF156), is a cytosolic E3 ubiquitin-protein ligase that inhibits signaling through the G protein-coupled melanocortin receptors-1 (MC1R), -2 (MC2R) and -4 (MC4R) via ubiquitylation-dependent and -independent processes. It suppresses chaperone-associated misfolded protein aggregation and toxicity. MGRN1 interacts with cytosolic prion proteins (PrPs) that are linked with neurodegeneration. It also interacts with expanded polyglutamine proteins, and suppresses misfolded polyglutamine aggregation and cytotoxicity. Moreover, MGRN1 inhibits melanocortin receptor signaling by competition with Galphas, suggesting a novel pathway for melanocortin signaling from the cell surface to the nucleus. Furthermore, MGRN1 interacts with and ubiquitylates TSG101, a key component of the endosomal sorting complex required for transport (ESCRT)-I, and regulates endosomal trafficking. A null mutation in the gene encoding MGRN1 causes spongiform neurodegeneration, suggesting a link between dysregulation of endosomal trafficking and spongiform neurodegeneration. MGRN1 contains a modified C3HC5-type RING-HC finger, a conserved PSAP motif necessary for interaction between MGRN1 and TSG101. In addition, MGRN1 harbors a functionally uncharacterized region, as known as the domain associated with RING2 (DAR2), N-terminal to the RING finger. The C3HC5-type RING-HC finger is distinguished from typical C3HC4 RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.


Pssm-ID: 438465  Cd Length: 58  Bit Score: 126.33  E-value: 2.83e-35
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2240474248 269 DDENSDNSNECVVCLSDLRDTLILPCRHLCLCNSCADTLRYQANNCPICRLPFRALLQ 326
Cdd:cd16816     1 DDENSDNSNECVVCLSDLRDTLILPCRHLCLCNSCADTLRYQANNCPICRLPFRALLQ 58
mRING-HC-C3HC5_RNF157 cd16817
Modified RING finger, HC subclass (C3HC5-type), found in RING finger protein 157 (RNF157) and ...
273-332 8.46e-35

Modified RING finger, HC subclass (C3HC5-type), found in RING finger protein 157 (RNF157) and similar proteins; RNF157 is a cytoplasmic E3 ubiquitin ligase predominantly expressed in brain. It is a homolog of the E3 ligase mahogunin ring finger-1 (MGRN1). In cultured neurons, it promotes neuronal survival in an E3 ligase-dependent manner. In contrast, it supports growth and maintenance of dendrites independent of its E3 ligase activity. RNF157 interacts with and ubiquitinates the adaptor protein APBB1 (amyloid beta precursor protein-binding, family B, member 1 or Fe65), which regulates neuronal survival, but not dendritic growth downstream of RNF157. The nuclear localization of APBB1 together with its interaction partner RNA-binding protein SART3 (squamous cell carcinoma antigen recognized by T cells 3 or Tip110) is crucial to trigger apoptosis. RNF157 contains a modified C3HC5-type RING-HC finger, and a functionally uncharacterized region, known as domain associated with RING2 (DAR2), N-terminal to the RING finger. The C3HC5-type RING-HC finger is distinguished from typical C3HC4 RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.


Pssm-ID: 438466 [Multi-domain]  Cd Length: 60  Bit Score: 125.20  E-value: 8.46e-35
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2240474248 273 SDNSNECVVCLSDLRDTLILPCRHLCLCNSCADTLRYQANNCPICRLPFRALLQIRAVRK 332
Cdd:cd16817     1 SDNSAECVVCLSDVRDTLILPCRHLCLCNACADTLRYQANNCPICRLPFRALLQIRAMRK 60
mRING-HC-C3HC5_MGRN1-like cd16789
Modified RING finger, HC subclass (C3HC5-type), found in mahogunin RING finger protein 1 ...
277-318 3.27e-28

Modified RING finger, HC subclass (C3HC5-type), found in mahogunin RING finger protein 1 (MGRN1), RING finger protein 157 (RNF157) and similar proteins; MGRN1, also known as RING finger protein 156 (RNF156), is a cytosolic E3 ubiquitin-protein ligase that inhibits signaling through the G protein-coupled melanocortin receptors-1 (MC1R), -2 (MC2R) and -4 (MC4R) via ubiquitylation-dependent and -independent processes. It suppresses chaperone-associated misfolded protein aggregation and toxicity. MGRN1 interacts with cytosolic prion proteins (PrPs) that are linked with neurodegeneration. It also interacts with expanded polyglutamine proteins, and suppresses misfolded polyglutamine aggregation and cytotoxicity. Moreover, MGRN1 inhibits melanocortin receptor signaling by competition with Galphas, suggesting a novel pathway for melanocortin signaling from the cell surface to the nucleus. MGRN1 also interacts with and ubiquitylates TSG101, a key component of the endosomal sorting complex required for transport (ESCRT)-I, and regulates endosomal trafficking. A null mutation in the gene encoding MGRN1 causes spongiform neurodegeneration, suggesting a link between dysregulation of endosomal trafficking and spongiform neurodegeneration. RNF157 is a cytoplasmic E3 ubiquitin ligase predominantly expressed in the brain. It is a homolog of the E3 ligase mahogunin ring finger-1 (MGRN1). In cultured neurons, it promotes neuronal survival in an E3 ligase-dependent manner. In contrast, it supports growth and maintenance of dendrites independent of its E3 ligase activity. RNF157 interacts with and ubiquitinates the adaptor protein APBB1 (amyloid beta precursor protein-binding, family B, member 1 or Fe65), which regulates neuronal survival, but not dendritic growth downstream of RNF157. The nuclear localization of APBB1 together with its interaction partner RNA-binding protein SART3 (squamous cell carcinoma antigen recognized by T cells 3 or Tip110) is crucial to trigger apoptosis. Both MGRN1 and RNF157 contain a modified C3HC5-type RING-HC finger, and a functionally uncharacterized region, known as domain associated with RING2 (DAR2), N-terminal to the RING finger. The C3HC5-type RING-HC finger is distinguished from typical C3HC4 RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.


Pssm-ID: 438443 [Multi-domain]  Cd Length: 42  Bit Score: 106.23  E-value: 3.27e-28
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 2240474248 277 NECVVCLSDLRDTLILPCRHLCLCNSCADTLRYQANNCPICR 318
Cdd:cd16789     1 SECVICLSDPRDTAVLPCRHLCLCSDCAEVLRYQSNKCPICR 42
zf-C3HC4_3 pfam13920
Zinc finger, C3HC4 type (RING finger);
275-320 1.20e-17

Zinc finger, C3HC4 type (RING finger);


Pssm-ID: 464042 [Multi-domain]  Cd Length: 50  Bit Score: 76.65  E-value: 1.20e-17
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 2240474248 275 NSNECVVCLSDLRDTLILPCRHLCLCNSCADTLRYQANNCPICRLP 320
Cdd:pfam13920   1 EDLLCVICLDRPRNVVLLPCGHLCLCEECAERLLRKKKKCPICRQP 46
mRING-HC-C3HC5_CGRF1-like cd16649
Modified RING finger, HC subclass (C3HC5-type), found in RING finger proteins, RNF26, RNF197 ...
277-318 2.16e-16

Modified RING finger, HC subclass (C3HC5-type), found in RING finger proteins, RNF26, RNF197 (CGRRF1), RNF156 (MGRN1), RNF157 and similar proteins; This subfamily corresponds to a group of RING finger proteins containing a modified C3HC5-type RING-HC finger, which is distinguished from typical C3HC4 RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain. Cell growth regulator with RING finger domain protein 1 (CGRRF1), also known as cell growth regulatory gene 19 protein (CGR19) or RING finger protein 197 (RNF197), functions as a novel biomarker to monitor endometrial sensitivity and response to insulin-sensitizing drugs, such as metformin, in the context of obesity. RNF26 is an E3 ubiquitin ligase that temporally regulates virus-triggered type I interferon induction by increasing the stability of Mediator of IRF3 activation, MITA, also known as STING, through K11-linked polyubiquitination after viral infection and promoting degradation of IRF3, another important component required for virus-triggered interferon induction. Mahogunin ring finger-1 (MGRN1), also known as RING finger protein 156 (RNF156), is a cytosolic E3 ubiquitin-protein ligase that inhibits signaling through the G protein-coupled melanocortin receptors-1 (MC1R), -2 (MC2R) and -4 (MC4R) via ubiquitylation-dependent and -independent processes. It suppresses chaperone-associated misfolded protein aggregation and toxicity. RNF157 is a cytoplasmic E3 ubiquitin ligase predominantly expressed in the brain. It is a homolog of the E3 ligase MGRN1. In cultured neurons, it promotes neuronal survival in an E3 ligase-dependent manner. In contrast, it supports growth and maintenance of dendrites independent of its E3 ligase activity. RNF157 interacts with and ubiquitinates the adaptor protein APBB1 (amyloid beta precursor protein-binding, family B, member 1 or Fe65), which regulates neuronal survival, but not dendritic growth downstream of RNF157. The nuclear localization of APBB1 together with its interaction partner RNA-binding protein SART3 (squamous cell carcinoma antigen recognized by T cells 3 or Tip110) is crucial to trigger apoptosis.


Pssm-ID: 438311 [Multi-domain]  Cd Length: 40  Bit Score: 72.74  E-value: 2.16e-16
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 2240474248 277 NECVVCLSDLRDTLILPCRHLCLCNSCADTLRYQanNCPICR 318
Cdd:cd16649     1 GLCVVCLENPASVLLLPCRHLCLCEVCAKGLRGK--TCPICR 40
mRING-HC-C3HC5_RNF26 cd16788
Modified RING finger, HC subclass (C3HC5-type), found in RING finger protein 26 (RNF26) and ...
279-327 3.43e-14

Modified RING finger, HC subclass (C3HC5-type), found in RING finger protein 26 (RNF26) and similar proteins; RNF26 is an E3 ubiquitin ligase that temporally regulates virus-triggered type I interferon induction by increasing the stability of Mediator of IRF3 activation, MITA, also known as STING, through K11-linked polyubiquitination of MITA after viral infection, and promoting the degradation of IRF3, another important component required for virus-triggered interferon induction. Although RNF26 substrates of ubiquitination remain unclear at present, RNF26 upregulation in gastric cancer might be implicated in carcinogenesis through dysregulation of growth regulators. RNF26 contains an N-terminal leucine zipper domain and a C-terminal modified C3HC5-type RING-HC finger, which is distinguished from typical C3HC4 RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.


Pssm-ID: 438442 [Multi-domain]  Cd Length: 60  Bit Score: 67.06  E-value: 3.43e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2240474248 279 CVVCLSDLRDTLILPCRHLCLCNSCADTLRYQA---NNCPICRLPFRALLQI 327
Cdd:cd16788     8 CVICQDQSKTVLILPCRHMCLCRQCANILLQQPvyrRNCPLCRTMILQTLDV 59
mRING-HC-C3HC5_NEU1 cd16647
Modified RING finger, HC subclass (C3HC5-type), found in neuralized-like protein NEURL1A, ...
276-327 1.07e-13

Modified RING finger, HC subclass (C3HC5-type), found in neuralized-like protein NEURL1A, NEURL1B, and similar proteins; This subfamily includes Drosophila neuralized (D-neu) protein, and its two mammalian homologs, NEURL1A and NEURL1B. D-neu is a regulator of the developmentally important Notch signaling pathway. NEURL1A, also known as NEURL1, NEU, neuralized 1, or RING finger protein 67 (RNF67), is a mammalian homolog of D-neu. It functions as an E3 ubiquitin-protein ligase that directly interacts with and monoubiquitinates cytoplasmic polyadenylation element-binding protein 3 (CPEB3), an RNA binding protein and a translational regulator of local protein synthesis, which facilitates hippocampal plasticity and hippocampal-dependent memory storage. It also acts as a potential tumor suppressor that causes apoptosis and downregulates Notch target genes in medulloblastoma. NEURL1B, also known as neuralized-2 (NEUR2) or neuralized-like protein 3, is another mammalian homolog of D-neu protein. It functions as an E3 ubiquitin-protein ligase that interacts with and ubiquitinates Delta. Thus, it plays a role in the endocytic pathways for Notch signaling by working cooperatively with another E3 ligase, Mind bomb-1 (Mib1), in Delta endocytosis to hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs)-positive vesicles. Members of this subfamily contain two neuralized homology regions (NHRs) responsible for Neural-ligand interactions and a modified C3HC5-type RING-HC finger required for ubiquitin ligase activity. The C3HC5-type RING-HC finger is distinguished from typical C3HC4-type RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.


Pssm-ID: 438309 [Multi-domain]  Cd Length: 53  Bit Score: 65.40  E-value: 1.07e-13
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2240474248 276 SNECVVCLSDLRDTLILPCRHLCLCNSCADTLRYQANNCPICRLPFRALLQI 327
Cdd:cd16647     1 GSECVICYERPVDTVLYRCGHMCMCYDCALQLKRRGGSCPICRAPIKDVIKI 52
RING-HC_XBAT35-like cd23129
RING finger, HC subclass, found in Arabidopsis thaliana protein XB3 homolog 5 (XBAT35) and ...
275-327 2.87e-12

RING finger, HC subclass, found in Arabidopsis thaliana protein XB3 homolog 5 (XBAT35) and similar proteins; XBAT35, also known as ankyrin repeat domain and RING finger-containing protein XBAT35, or RING-type E3 ubiquitin transferase XBAT35, has no E3 ubiquitin-protein ligase activity observed when associated with the E2 enzyme UBC8 in vitro. It contains a typical C3HC4-type RING-HC finger.


Pssm-ID: 438491 [Multi-domain]  Cd Length: 54  Bit Score: 61.51  E-value: 2.87e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2240474248 275 NSNECVVCLSDLRDTLILPCRHLCLCNSCADTLRYQANNCPICRLPFRALLQI 327
Cdd:cd23129     1 QRDECVVCMDAPRDAVCVPCGHVAGCMSCLKALMQSSPLCPICRAPVRQVIKV 53
mRING-HC-C3HC5_NEU1B cd16786
Modified RING finger, HC subclass (C3HC5-type), found in neuralized-like protein 1B (NEURL1B); ...
276-327 8.17e-12

Modified RING finger, HC subclass (C3HC5-type), found in neuralized-like protein 1B (NEURL1B); NEURL1B, also known as neuralized-2 (NEUR2) or neuralized-like protein 3, is a mammalian homolog of the Drosophila neuralized (D-neu) protein. It functions as an E3 ubiquitin-protein ligase that interacts with and ubiquitinates Delta. Thus, it plays a role in the endocytic pathways for Notch signaling through working cooperatively with another E3 ligase, Mind bomb-1 (Mib1), in Delta endocytosis to hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs)-positive vesicles. NEURL1B contains two neuralized homology regions (NHRs) responsible for Neural-ligand interactions and a modified C3HC5-type RING-HC finger required for ubiquitin ligase activity. The C3HC5-type RING-HC finger is distinguished from typical C3HC4-type RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.


Pssm-ID: 438440 [Multi-domain]  Cd Length: 57  Bit Score: 60.34  E-value: 8.17e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2240474248 276 SNECVVCLSDLRDTLILPCRHLCLCNSCADTLRYQANN-CPICRLPFRALLQI 327
Cdd:cd16786     2 NGECTVCFDSEVDTVIYTCGHMCLCNSCGLKLKRQINAcCPICRRVIKDVIKI 54
mRING-HC-C3HC5_CGRF1 cd16787
Modified RING finger, HC subclass (C3HC5-type), found in cell growth regulator with RING ...
277-318 3.90e-10

Modified RING finger, HC subclass (C3HC5-type), found in cell growth regulator with RING finger domain protein 1 (CGRRF1) and similar proteins; CGRRF1, also known as cell growth regulatory gene 19 protein (CGR19) or RING finger protein 197 (RNF197), functions as a novel biomarker to monitor endometrial sensitivity and response to insulin-sensitizing drugs, such as metformin, in the context of obesity. CGRRF1 contains a C-terminal modified C3HC5-type RING-HC finger, which is distinguished from typical C3HC4 RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.


Pssm-ID: 438441 [Multi-domain]  Cd Length: 38  Bit Score: 55.07  E-value: 3.90e-10
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 2240474248 277 NECVVCLSDLRDTLILPCRHLCLCNSCAdtlrYQANNCPICR 318
Cdd:cd16787     1 KDCVVCQNAPVNRVLLPCRHACVCDECF----KRLQRCPMCR 38
mRING-HC-C3HC5_MAPL cd16648
Modified RING finger, HC subclass (C3HC5-type), found in mitochondrial-anchored protein ligase ...
277-318 6.37e-10

Modified RING finger, HC subclass (C3HC5-type), found in mitochondrial-anchored protein ligase (MAPL) and similar proteins; MAPL, also known as MULAN, mitochondrial ubiquitin ligase activator of NFKB 1, E3 SUMO-protein ligase MUL1, E3 ubiquitin-protein ligase MUL1, growth inhibition and death E3 ligase (GIDE), putative NF-kappa-B-activating protein 266, or RING finger protein 218 (RNF218), is a multifunctional mitochondrial outer membrane protein involved in several processes specific to metazoan (multicellular animal) cells, such as NF-kappaB activation, innate immunity and antiviral signaling, suppression of PINK1/parkin defects, mitophagy in skeletal muscle, and caspase-dependent apoptosis. MAPL contains a unique BAM (beside a membrane)/GIDE (growth inhibition death E3 ligase) domain and a C-terminal modified cytosolic C3HC5-type RING-HC finger which is distinguished from typical C3HC4-type RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.


Pssm-ID: 438310 [Multi-domain]  Cd Length: 52  Bit Score: 54.78  E-value: 6.37e-10
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 2240474248 277 NECVVCLSDLRDTLILPCRHLCLCNSCADTLRyQANNCPICR 318
Cdd:cd16648     2 NACVICLSNPRSCVFLECGHVCSCIECYEALP-SPKKCPICR 42
RING-HC_MIP1-like cd23128
RING finger, HC subclass, found in Arabidopsis thaliana MND1-interacting protein 1 (MIP1) and ...
278-318 9.56e-10

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: 54.44  E-value: 9.56e-10
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 2240474248 278 ECVVCLSDLRDTLILPCRHLCLCNSCADTLRYQA-NNCPICR 318
Cdd:cd23128     5 ECVMCMEEERSVVFLPCAHQVVCSGCNDLHEKKGmRECPSCR 46
mRING-HC-C3HC5_NEU1A cd16785
Modified RING finger, HC subclass (C3HC5-type), found in neuralized-like protein 1A (NEURL1A) ...
276-326 1.42e-09

Modified RING finger, HC subclass (C3HC5-type), found in neuralized-like protein 1A (NEURL1A) and similar proteins; NEURL1A, also known as NEURL1, NEU, neuralized 1, or RING finger protein 67 (RNF67), is a mammalian homolog of the Drosophila neuralized (D-neu) protein. It functions as an E3 ubiquitin-protein ligase that directly interacts with and monoubiquitinates cytoplasmic polyadenylation element-binding protein 3 (CPEB3), an RNA binding protein and a translational regulator of local protein synthesis, which facilitates hippocampal plasticity and hippocampal-dependent memory storage. It also acts as a potential tumor suppressor that causes apoptosis and downregulates Notch target genes in the medulloblastoma. NEURL1A contains two neuralized homology regions (NHRs) responsible for Neural-ligand interactions and a modified C3HC5-type RING-HC finger required for ubiquitin ligase activity. The C3HC5-type RING-HC finger is distinguished from typical C3HC4-type RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.


Pssm-ID: 438439 [Multi-domain]  Cd Length: 59  Bit Score: 54.22  E-value: 1.42e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2240474248 276 SNECVVCLSDLRDTLILPCRHLCLCNSCADTLRYQAN-NCPICRLPFRALLQ 326
Cdd:cd16785     4 SDECTICYENAVDTVIYTCGHMCLCYACGLRLKKMLNaCCPICRRAIKDIIK 55
RING-HC_LRSAM1 cd16515
RING finger, HC subclass, found in leucine-rich repeat and sterile alpha motif-containing ...
276-318 2.62e-09

RING finger, HC subclass, found in leucine-rich repeat and sterile alpha motif-containing protein 1 (LRSAM1) and similar proteins; LRSAM1, also known as Tsg101-associated ligase (TAL), or RIFLE, is an E3 ubiquitin-protein ligase that physically associates with, and selectively ubiquitylates, Tsg101, an E2-like molecule that regulates vesicular trafficking processes in yeast and mammals. It regulates a Tsg101-associated complex responsible for the sorting of cargo into cytoplasm-containing vesicles that bud at the multivesicular body and at the plasma membrane. LRSAM1 is a multidomain protein containing an N-terminal leucine-rich repeat (LRR), followed by several recognizable motifs, including an ezrin-radixin-moezin (ERM) domain, a coiled-coil (CC) region, a SAM domain, and a C-terminal C3HC4-type RING-HC finger domain.


Pssm-ID: 438178 [Multi-domain]  Cd Length: 48  Bit Score: 53.07  E-value: 2.62e-09
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 2240474248 276 SNECVVCLSDLRDTLILPCRHLCLCNSCADTLRyqanNCPICR 318
Cdd:cd16515     1 ESECVVCMDAESQVIFLPCGHVCCCQTCSSSLS----TCPLCR 39
RING-HC cd16449
HC subclass of RING (RING-HC) finger and its variants; The RING finger is a specialized type ...
278-317 7.06e-09

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: 51.72  E-value: 7.06e-09
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 2240474248 278 ECVVCLSDLRDTLILPCRHLClCNSCADTL-RYQANNCPIC 317
Cdd:cd16449     2 ECPICLERLKDPVLLPCGHVF-CRECIRRLlESGSIKCPIC 41
zf-RING_2 pfam13639
Ring finger domain;
277-318 7.51e-09

Ring finger domain;


Pssm-ID: 433370 [Multi-domain]  Cd Length: 44  Bit Score: 51.64  E-value: 7.51e-09
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 2240474248 277 NECVVCLSDL---RDTLILPCRHlCLCNSCADTLRYQANNCPICR 318
Cdd:pfam13639   1 DECPICLEEFeegDKVVVLPCGH-HFHRECLDKWLRSSNTCPLCR 44
RING-HC_CblA-like cd16501
RING finger, HC subclass, found in Dictyostelium discoideum Cbl-like protein A (CblA) and ...
275-327 1.73e-07

RING finger, HC subclass, found in Dictyostelium discoideum Cbl-like protein A (CblA) and similar proteins; CblA is a Dictyostelium homolog of the Cbl proteins which are multi-domain proteins acting as key negative regulators of various receptor and non-receptor tyrosine kinase signaling. CblA upregulates STATc tyrosine phosphorylation by downregulating PTP3, the protein tyrosine phosphatase responsible for dephosphorylating STATc. STATc is a signal transducer and activator of transcription protein. Like other Cbl proteins, CblA contains a tyrosine-kinase-binding domain (TKB), a proline-rich domain, a C3HC4-type RING-HC finger, and an ubiquitin-associated (UBA) domain. TKB, also known as a phosphotyrosine binding PTB domain, is composed of a four helix-bundle, a Ca2+ binding EF-hand and a highly variant SH2 domain. This family also includes Drosophila melanogaster defense repressor 1 (Dnr1) that was identified as an inhibitor of Dredd activity in the absence of a microbial insult in Drosophila S2 cells. It inhibits the Drosophila initiator caspases Dredd and Dronc. Moreover, Dnr1 acts as a negative regulator of the Imd (immune deficiency) innate immune-response pathway. Its mutations cause neurodegeneration in Drosophila by activating the innate immune response in the brain. Dnr1 contains a FERM N-terminal domain followed by a region rich in glutamine and serine residues, a central FERM domain, and a C-terminal C3HC4-type RING-HC finger.


Pssm-ID: 438164 [Multi-domain]  Cd Length: 53  Bit Score: 47.87  E-value: 1.73e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2240474248 275 NSNECVVCLSDLRDTLILPCRHLCLCNSCADTLRyqanNCPICRLPFRALLQI 327
Cdd:cd16501     4 DADLCVVCMDAPIDTVFLECGHLACCRLCSKRLR----VCPICRQPISRVVRI 52
mRING-HC-C2H2C4_MDM2-like cd16646
Modified RING finger, HC subclass (C2H2C4-type), found in E3 ubiquitin-protein ligase MDM2, ...
279-326 2.06e-07

Modified RING finger, HC subclass (C2H2C4-type), found in E3 ubiquitin-protein ligase MDM2, protein MDM4 and similar proteins; MDM2 (also known as HDM2) and MDM4 (also known as MDMX or HDMX) are the primary p53 tumor suppressor negative regulators. They have non-redundant roles in the regulation of p53. MDM2 mainly functions to control p53 stability, while MDM4 controls p53 transcriptional activity. Both MDM2 and MDM4 contain an N-terminal p53-binding domain, a RanBP2-type zinc finger (zf-RanBP2) domain near the central acidic region, and a C-terminal modified C2H2C4-type RING-HC finger. Mdm2 can form homo-oligomers through its RING domain and displays E3 ubiquitin ligase activity that catalyzes the attachment of ubiquitin to p53 as an essential step in the regulation of its levels in cells. Despite its RING domain and structural similarity with MDM2, MDM4 does not homo-oligomerize and lacks ubiquitin-ligase function, but inhibits the transcriptional activity of p53. In addition, both their RING domains are responsible for the hetero-oligomerization, which is crucial for the suppression of P53 activity during embryonic development and the recruitment of E2 ubiquitin-conjugating enzymes. Moreover, MDM2 and MDM4 can be phosphorylated and destabilized in response to DNA damage stress. In response to ribosomal stress, MDM2-mediated p53 ubiquitination and degradation can be inhibited through the interaction with ribosomal proteins L5, L11, and L23. However, MDM4 is not bound to ribosomal proteins, suggesting its different response to regulation by small basic proteins such as ribosomal proteins and ARF.


Pssm-ID: 438308 [Multi-domain]  Cd Length: 52  Bit Score: 47.71  E-value: 2.06e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 2240474248 279 CVVCLSDLRDTLILPCR--HLCLCNSCADTLRYQANNCPICRLPFRALLQ 326
Cdd:cd16646     3 CVICLSRPRTAAIVHGKtgHQVACYTCAKKLKRRGKPCPVCRRPIQNVIK 52
RING-HC_RNF141 cd16545
RING finger, HC subclass, found in RING finger protein 141 (RNF141) and similar proteins; ...
277-318 3.27e-07

RING finger, HC subclass, found in RING finger protein 141 (RNF141) and similar proteins; RNF141, also known as zinc finger protein 230 (ZNF230), is a RING finger protein present primarily in the nuclei of spermatogonia, the acrosome, and the tail of spermatozoa. It may have a broad function during early development of vertebrates. It plays an important role in spermatogenesis, including spermatogenic cell proliferation and sperm maturation, as well as motility and fertilization. It also exhibits DNA binding activity. RNF141/ZNF230 gene mutations may be associated with azoospermia. RNF141 contains a C3HC4-type RING finger domain that may function as an activator module in transcription.


Pssm-ID: 438207 [Multi-domain]  Cd Length: 40  Bit Score: 46.70  E-value: 3.27e-07
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 2240474248 277 NECVVCLsDLRDTLILPCRHLcLCNSCADTLRYQANNCPICR 318
Cdd:cd16545     1 EECCICM-DRKADLILPCAHS-YCQKCIDKWSDRHRTCPICR 40
RING-HC_IAPs cd16510
RING finger, HC subclass, found in inhibitor of apoptosis proteins (IAPs); IAPs are frequently ...
279-318 3.92e-07

RING finger, HC subclass, found in inhibitor of apoptosis proteins (IAPs); IAPs are frequently overexpressed in cancer and associated with tumor cell survival, chemoresistance, disease progression, and poor prognosis. They function primarily as negative regulators of cell death. They regulate caspases and apoptosis through the inhibition of specific members of the caspase family of cysteine proteases. In addition, IAPs has been implicated in a multitude of other cellular processes, including inflammatory signalling and immunity, mitogenic kinase signalling, proliferation and mitosis, as well as cell invasion and metastasis. IAPs in this family includes cellular inhibitor of apoptosis protein c-IAP1 (BIRC2) and c-IAP2 (BIRC3), XIAP (BIRC4), BIRC7, and BIRC8, all of which contain three N-terminal baculoviral IAP repeat (BIR) domains that enable interactions with proteins, a ubiquitin-association (UBA) domain that is responsible for the binding of polyubiquitin (polyUb), and a C3HC4-type RING-HC finger at the carboxyl terminus that is required for ubiquitin ligase activity. The UBA domain is only absent in mammalian homologs of BIRC7. Moreover, c-IAPs contains an additional caspase activation and recruitment domain (CARD) between the UBA and C3HC4-type RING-HC domains. The CARD domain may serve as a protein interaction surface.


Pssm-ID: 438173 [Multi-domain]  Cd Length: 40  Bit Score: 46.48  E-value: 3.92e-07
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 2240474248 279 CVVCLSDLRDTLILPCRHLCLCNSCADTLRyqanNCPICR 318
Cdd:cd16510     4 CKICMDREVNIVFLPCGHLVTCAQCAASLR----KCPICR 39
RING smart00184
Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and ...
279-317 8.60e-07

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: 45.58  E-value: 8.60e-07
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 2240474248  279 CVVCLSD-LRDTLILPCRHLcLCNSCADT-LRYQANNCPIC 317
Cdd:smart00184   1 CPICLEEyLKDPVILPCGHT-FCRSCIRKwLESGNNTCPIC 40
RING-HC_SPL2-like cd23145
RING finger, HC subclass, found in Arabidopsis thaliana SP1-like protein 2 (SPL2) and similar ...
279-318 1.33e-06

RING finger, HC subclass, found in Arabidopsis thaliana SP1-like protein 2 (SPL2) and similar proteins; SPL2, also known as RING-type E3 ubiquitin transferase SPL2, acts as an E3 ubiquitin-protein ligase that mediates E2-dependent protein ubiquitination. SPL2 contains a typical C3HC4-type RING-HC finger.


Pssm-ID: 438507 [Multi-domain]  Cd Length: 47  Bit Score: 45.27  E-value: 1.33e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 2240474248 279 CVVCLSDLRDTLILPCRHLCLCNSCADTLRYQAN-NCPICR 318
Cdd:cd23145     6 CVVCLLRRRRVAFIECGHRVCCELCARRVTREANpRCPVCR 46
RING-HC_EHV1-like cd23130
RING finger, HC subclass, found in Equid alphaherpesvirus 1 (Equine herpesvirus 1/EHV-1) ...
277-325 2.04e-06

RING finger, HC subclass, found in Equid alphaherpesvirus 1 (Equine herpesvirus 1/EHV-1) regulatory protein and similar proteins; EHV-1 regulatory protein belongs to the Vmw110 (IPC0) protein family. It contains a typical C3HC4-type RING-HC finger and binds zinc stably.


Pssm-ID: 438492 [Multi-domain]  Cd Length: 51  Bit Score: 45.04  E-value: 2.04e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 2240474248 277 NECVVCLSDLRD-TLILPCRHLcLCNSCADTLRYQANNCPICRLPFRALL 325
Cdd:cd23130     1 DVCPICLDDPEDeAITLPCLHQ-FCYTCILRWLQTSPTCPLCKTPVTSII 49
RING-HC_HLTF cd16509
RING finger, HC subclass, found in helicase-like transcription factor (HLTF) and similar ...
278-323 2.80e-06

RING finger, HC subclass, found in helicase-like transcription factor (HLTF) and similar proteins; HLTF, also known as DNA-binding protein/plasminogen activator inhibitor 1 regulator, HIP116, RING finger protein 80, SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 3, or sucrose nonfermenting protein 2-like 3, is a yeast RAD5 homolog found in mammals. It has both E3 ubiquitin ligase and DNA helicase activities, and plays a pivotal role in the template-switching pathway of DNA damage tolerance. It is involved in Lys-63-linked poly-ubiquitination of proliferating cell nuclear antigen (PCNA) at Lys-164 and in the regulation of DNA damage tolerance. It shows double-stranded DNA translocase activity with 3'-5' polarity, thereby facilitating regression of the replication fork. HLTF contains an N-terminal HIRAN (HIP116 and RAD5 N-terminal) domain, a SWI/SNF helicase domain that is divided into N- and C-terminal parts by an insertion of a C3HC4-type RING-HC finger involved in the poly-ubiquitination of PCNA.


Pssm-ID: 438172 [Multi-domain]  Cd Length: 53  Bit Score: 44.60  E-value: 2.80e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 2240474248 278 ECVVCLSDLRDTLILPCRHLcLCNSC-ADTLRYQANNCPICRLPFRA 323
Cdd:cd16509     5 ECAICLDSLTNPVITPCAHV-FCRRCiCEVIQREKAKCPMCRAPLSA 50
RING-H2_RNF165 cd16682
RING finger, H2 subclass, found in RING finger protein 165 (RNF165) and similar proteins; ...
270-325 2.92e-06

RING finger, H2 subclass, found in RING finger protein 165 (RNF165) and similar proteins; RNF165, also known as Arkadia-like 2, Arkadia2, or Ark2C, is an E3 ubiquitin ligase with homology to the C-terminal half of RNF111. It is expressed specifically in the nervous system, and can serve to amplify neuronal responses to specific signals. It acts as a positive regulator of bone morphogenetic protein (BMP)-Smad signaling that is involved in motor neuron (MN) axon elongation. RNF165 contains two serine rich domains, a nuclear localization signal, an NRG-TIER domain, and a C-terminal C3H2C3-type RING-H2 finger that is responsible for the enhancement of BMP-Smad1/5/8 signaling in the spinal cord.


Pssm-ID: 438344 [Multi-domain]  Cd Length: 59  Bit Score: 44.68  E-value: 2.92e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2240474248 270 DENSDNSNECVVCLS---DLRDTLILPCRHLcLCNSCADTLRYQANNCPICRLPFRALL 325
Cdd:cd16682     1 GEESDTDEKCTICLSmleDGEDVRRLPCMHL-FHQLCVDQWLAMSKKCPICRVDIETQL 58
RING-HC_BIRC2_3_7 cd16713
RING finger, HC subclass, found in apoptosis protein c-IAP1, c-IAP2, livin, and similar ...
279-322 4.45e-06

RING finger, HC subclass, found in apoptosis protein c-IAP1, c-IAP2, livin, and similar proteins; The cellular inhibitor of apoptosis protein c-IAPs function as ubiquitin E3 ligases that mediate the ubiquitination of substrates involved in apoptosis, nuclear factor-kappaB (NF-kappaB) signaling, and oncogenesis. Unlike other IAPs, such as XIAP, c-IAPs exhibit minimal binding to caspases and may not play an important role in the inhibition of these proteases. c-IAP1, also known as baculoviral IAP repeat-containing protein BIRC2, IAP-2, RING finger protein 48, or TNFR2-TRAF-signaling complex protein 2, is a potent regulator of the tumor necrosis factor (TNF) receptor family and NF-kappaB signaling pathways in the cytoplasm. It can also regulate E2F1 transcription factor-mediated control of cyclin transcription in the nucleus. c-IAP2, also known as BIRC3, IAP-1, apoptosis inhibitor 2 (API2), or IAP homolog C, also influences ubiquitin-dependent pathways that modulate innate immune signalling by activation of NF-kappaB. c-IAPs contain three N-terminal baculoviral IAP repeat (BIR) domains that enable interactions with proteins, a ubiquitin-association (UBA) domain that is responsible for the binding of polyubiquitin (polyUb), a caspase activation and recruitment domain (CARD) that serves as a protein interaction surface, and a C3HC4-type RING-HC finger at the carboxyl terminus that is required for ubiquitin ligase activity. Livin, also known as baculoviral IAP repeat-containing protein 7 (BIRC7), kidney inhibitor of apoptosis protein (KIAP), melanoma inhibitor of apoptosis protein (ML-IAP), or RING finger protein 50, was identified as the melanoma IAP. It plays crucial roles in apoptosis, cell proliferation, and cell cycle control. Its anti-apoptotic activity is regulated by the inhibition of caspase-3, -7, and -9. Its E3 ubiquitin-ligase-like activity promotes degradation of Smac/DIABLO, a critical endogenous regulator of all IAPs. Unlike other family members, mammalian livin contains a single BIR domain and a C3HC4-type RING-HC finger. The UBA domain can be detected in non-mammalian homologs of livin.


Pssm-ID: 438373 [Multi-domain]  Cd Length: 57  Bit Score: 44.00  E-value: 4.45e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 2240474248 279 CVVCLSDLRDTLILPCRHLCLCNSCADTLRyqanNCPICRLPFR 322
Cdd:cd16713    10 CKVCMDKEVSIVFIPCGHLVVCTECAPSLR----KCPICRATIK 49
RING-HC_UNK-like cd16614
RING finger, HC subclass, found in RING finger protein unkempt (UNK), unkempt-like (UNKL), and ...
278-317 5.14e-06

RING finger, HC subclass, found in RING finger protein unkempt (UNK), unkempt-like (UNKL), and similar proteins; UNK, also known as zinc finger CCCH domain-containing protein 5, is a metazoan-specific zinc finger protein enriched in embryonic brains. It may play a broad regulatory role during the formation of the central nervous system (CNS). It is a sequence-specific RNA-binding protein required for early neuronal morphology. UNK is a neurogenic component of the mTOR pathway, and functions as a negative regulator of the timing of photoreceptor differentiation. It also specifically binds to Brg/Brm-associated factor BAF60b and promotes its ubiquitination in a Rac1-dependent manner. UNKL, also known as zinc finger CCCH domain-containing protein 5-like, is a putative E3 ubiquitin-protein ligase that may participate in a protein complex showing an E3 ligase activity regulated by RAC1. Both UNK and UNKL contain several tandem CCCH-type zinc fingers at the N-terminus, and a C3HC4-type RING-HC finger at its C-terminus.


Pssm-ID: 438276  Cd Length: 38  Bit Score: 43.32  E-value: 5.14e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 2240474248 278 ECVVCLSDLRDTLILPCRHLCLCNSCADTlryqANNCPIC 317
Cdd:cd16614     2 KCMKCEERNRSVAVLPCQHYVLCEQCAET----ATECPYC 37
mRING-HC-C4C4_Asi1p-like cd16616
Modified RING finger, HC subclass (C4C4-type), found in Saccharomyces cerevisiae amino acid ...
279-318 6.65e-06

Modified RING finger, HC subclass (C4C4-type), found in Saccharomyces cerevisiae amino acid sensor-independent protein Asi1p, Asi3p and similar proteins; Asi1p and Asi3p are inner nuclear membrane proteins that act as negative regulators of SPS (Ssy1-Ptr3-Ssy5)-sensor signaling in yeast. Together with Asi2p, they assemble into an Asi complex that functions in the SPS amino acid sensing pathway involved in degradation of Stp1 and Stp2 transcription factors. Both Asi1p and Asi3p contain five membrane-spanning domains, as well as highly conserved RING fingers at their extreme C termini, which are C4C4-type RING finger motifs whose overall folding is similar to that of the C3HC4-type RING-HC finger.


Pssm-ID: 438278  Cd Length: 53  Bit Score: 43.49  E-value: 6.65e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 2240474248 279 CVVCLSDLRDTLILPCRHLCLCNSCADTLRYQA-NNCPICR 318
Cdd:cd16616     4 CVICKSNPRNIVLWPCRCLALCDDCRLSLAMRGfHTCVCCR 44
RING-HC_NEURL3 cd16552
RING finger, HC subclass, found in neuralized-like protein 3 (NEURL3) and similar proteins; ...
278-318 8.50e-06

RING finger, HC subclass, found in neuralized-like protein 3 (NEURL3) and similar proteins; NEURL3, also known as lung-inducible neuralized-related C3HC4 RING domain protein (LINCR), is a novel inflammation-induced E3 ubiquitin-protein ligase encoded by LINCR, a glucocorticoid-attenuated response gene induced in the lung during endotoxemia. It is expressed in alveolar epithelial type II cells, preferentially interacts with the ubiquitin-conjugating enzyme UbcH6, and generates polyubiquitin chains linked via non-canonical lysine residues. Overexpression of NEURL3 in the developing lung epithelium inhibits distal differentiation and induces cystic changes in the Notch signaling pathway. NEURL3 contains an N-terminal neuralized homology repeat (NHR) domain similar to the SPRY (SPla and the RYanodine receptor) domain and a C-terminal C3HC4-type RING-HC finger.


Pssm-ID: 438214 [Multi-domain]  Cd Length: 50  Bit Score: 42.99  E-value: 8.50e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 2240474248 278 ECVVCLSDLRDTLILPCRHLCLCNSCADTLRYQANNCPICR 318
Cdd:cd16552     3 ECAICFHHTANTRLVPCGHSHFCGSCAWHIFRDTARCPVCR 43
RING-HC_MIBs-like cd16520
RING finger, HC subclass, found in mind bomb MIB1, MIB2, RGLG1, RGLG2, and similar proteins; ...
278-320 1.31e-05

RING finger, HC subclass, found in mind bomb MIB1, MIB2, RGLG1, RGLG2, and similar proteins; MIBs are large, multi-domain E3 ubiquitin-protein ligases that promote ubiquitination of the cytoplasmic tails of Notch ligands. They are also responsible for TBK1 K63-linked ubiquitination and activation, promoting interferon production and controlling antiviral immunity. Moreover, MIBs selectively control responses to cytosolic RNA and regulate type I interferon transcription. Both MIB1 and MIB2 have similar domain architectures, which consist of two Mib-Herc2 domains flanking a ZZ zinc finger, a REP region including two tandem Mib repeats, an ANK region that spans ankyrin repeats, and a RNG region, where MIB1 and MIB2 contain three and two C3HC4-type RING-HC fingers, respectively. This model corresponds to the third RING-HC finger of MIB1, as well as the second RING-HC finger of MIB2. In addition to MIB1 and MIB2, the RING-HC fingers of RING domain ligase RGLG1, RGLG2 and similar proteins from plant are also included in this model. RGLG1 is a ubiquitously expressed E3 ubiquitin-protein ligase that interacts with UBC13 and, together with UBC13, catalyzes the formation of K63-linked polyubiquitin chains, which is involved in DNA damage repair. RGLG1 mediates the formation of canonical, K48-linked polyubiquitin chains that target proteins for degradation. It also regulates apical dominance by acting on the auxin transport proteins abundance. RGLG1 has overlapping functions with its closest sequelog, RGLG2. They both function as RING E3 ligases that interact with ethylene response factor 53 (ERF53) in the nucleus and negatively regulate the plant drought stress response. All RGLG proteins contain a Von Willebrand factor type A (vWA) domain and a C3HC4-type RING-HC finger.


Pssm-ID: 438183 [Multi-domain]  Cd Length: 39  Bit Score: 42.28  E-value: 1.31e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 2240474248 278 ECVVCLSDLRDTLILpCRHlCLCNSCADTLRyqanNCPICRLP 320
Cdd:cd16520     2 LCPICMERKKNVVFL-CGH-GTCQKCAEKLK----KCPICRKP 38
RING-HC_CARP cd16500
RING finger, HC subclass, found in caspases-8 and -10-associated RING finger protein CARP-1, ...
279-318 1.37e-05

RING finger, HC subclass, found in caspases-8 and -10-associated RING finger protein CARP-1, CARP-2 and similar proteins; The CARP subfamily includes CARP-1 and CARP-2 proteins, both of which are E3 ubiquitin ligases that ubiquitinate apical caspases and target them for proteasome-mediated degradation. As a novel group of caspase regulators with a FYVE-type zinc finger domain, they do not localize to membranes in the cell and are involved in the negative regulation of apoptosis, specifically targeting two initiator caspases, caspase 8, and caspase 10. Moreover, they stabilize MDM2 by inhibiting MDM2 self-ubiquitination, as well as by targeting 14-3-3sigma for degradation. They work together with MDM2 to enhance p53 degradation, thereby inhibiting p53-mediated cell death. CARPs contain an N-terminal FYVE-like domain that can serve as a membrane-targeting or endosome localizing signal and a C-terminal C3HC4-type RING-HC finger domain.


Pssm-ID: 438163 [Multi-domain]  Cd Length: 48  Bit Score: 42.37  E-value: 1.37e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 2240474248 279 CVVCLSDLRDTLILPCRHLCLCNSCADTLryqaNNCPICR 318
Cdd:cd16500     3 CKICMDAAIDCVLLECGHMVTCTDCGKKL----SECPICR 38
RING-HC_SpRad8-like cd16572
RING finger, HC subclass, found in Schizosaccharomyces pombe DNA repair protein Rad8 (SpRad8) ...
273-321 1.51e-05

RING finger, HC subclass, found in Schizosaccharomyces pombe DNA repair protein Rad8 (SpRad8) and similar proteins; SpRad8 is a conserved protein homologous to Saccharomyces cerevisiae DNA repair protein Rad5 and human helicase-like transcription factor (HLTF) that is required for error-free postreplication repair by contributing to polyubiquitylation of PCNA. SpRad8 contains a C3HC4-type RING-HC finger responsible for the E3 ubiquitin ligase activity, a SNF2-family helicase domain including an ATP binding site, and a family-specific HIRAN domain (HIP116, Rad5p N-terminal domain) that contributes to nuclear localization.


Pssm-ID: 438234 [Multi-domain]  Cd Length: 61  Bit Score: 42.88  E-value: 1.51e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2240474248 273 SDNSNECVVCLSD-LRDTLILPCRHLClCNSC-ADTLRYQANN-----CPICRLPF 321
Cdd:cd16572     1 EDAENECPICAEEpISELALTRCWHSA-CKDClLDHIEFQKSKnevplCPTCRQPI 55
RING-HC_RSPRY1 cd16566
RING finger, HC subclass, found in RING finger and SPRY domain-containing protein 1 (RSPRY1) ...
277-320 1.79e-05

RING finger, HC subclass, found in RING finger and SPRY domain-containing protein 1 (RSPRY1) and similar proteins; RSPRY1 is a hypothetical RING and SPRY domain-containing protein of unknown physiological function. Mutations in its corresponding gene RSPRY1 may associate with a distinct skeletal dysplasia syndrome. RSPRY1 contains a B30.2/SPRY domain and a C3HC4-type RING-HC finger.


Pssm-ID: 438228 [Multi-domain]  Cd Length: 43  Bit Score: 41.96  E-value: 1.79e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 2240474248 277 NECVVCLSDLRDTLILPCRHLCLCNSCAdtlrYQANNCPICRLP 320
Cdd:cd16566     3 DSCTLCFDKVADTELRPCGHSGFCMECA----LQLETCPLCRQP 42
RING-HC_ZNF598 cd16615
RING finger, HC subclass, found in zinc finger protein 598 (ZNF598) and similar proteins; ...
277-318 2.10e-05

RING finger, HC subclass, found in zinc finger protein 598 (ZNF598) and similar proteins; ZNF598 associates with eukaryotic initiation factor 4E (eIF4E) homologous protein from mammals (m4EHP) by binding to Grb10-interacting GYF protein 2 (GIGYF2). The m4EHP-GIGYF2 complex functions as a translational repressor and is essential for normal embryonic development of mammalian. ZNF598 harbors a C3HC4-type RING-HC finger at its N-terminus.


Pssm-ID: 438277 [Multi-domain]  Cd Length: 51  Bit Score: 41.83  E-value: 2.10e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 2240474248 277 NECVVCLSDLRDTLILPCRHLClCNSCADTLR--YQANNCPICR 318
Cdd:cd16615     1 ETCVICCEEIEYFAVGPCNHPV-CYKCSLRMRvlYKDKYCPICR 43
Prok-RING_4 pfam14447
Prokaryotic RING finger family 4; RING finger family domain found sporadically in bacteria. ...
279-318 2.71e-05

Prokaryotic RING finger family 4; RING finger family domain found sporadically in bacteria. The finger is fused to an N-terminal alpha-helical domain, ROT/Trove-like repeats and a C-terminal TerD domain. The architecture suggests a possible role in an RNA-processing complex.


Pssm-ID: 433959 [Multi-domain]  Cd Length: 46  Bit Score: 41.64  E-value: 2.71e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 2240474248 279 CVVCLSDLRDTLILPCRHLcLCNSCADTLRYQAnnCPICR 318
Cdd:pfam14447   1 CVLCGRNGTVHALIPCGHL-VCRDCFDGSDFSA--CPICR 37
RING-HC_TRIM62_C-IV cd16608
RING finger, HC subclass, found in tripartite motif-containing protein 62 (TRIM62) and similar ...
279-321 3.19e-05

RING finger, HC subclass, found in tripartite motif-containing protein 62 (TRIM62) and similar proteins; TRIM62, also known as Ductal Epithelium Associated Ring Chromosome 1 (DEAR1), is a cytoplasmic E3 ubiquitin-protein ligase that was identified as a dominant regulator of acinar morphogenesis in the mammary gland. It is implicated in the inflammatory response of immune cells by regulating the Toll-like receptor 4 (TLR4) signaling pathway, leading to increased activity of the activator protein 1 (AP-1) transcription factor in primary macrophages. It is also involved in muscular protein homeostasis, especially during inflammation-induced atrophy, and may play a role in the pathogenesis of ICU-acquired weakness (ICUAW) by activating and maintaining inflammation in myocytes. Moreover, TRIM62 facilitates K27-linked poly-ubiquitination of CARD9 and also regulates CARD9-mediated anti-fungal immunity and intestinal inflammation. It also functions as a chromosome 1p35 tumor suppressor and negatively regulates transforming growth factor beta (TGFbeta)-driven epithelial-mesenchymal transition (EMT) by binding to and promoting the ubiquitination of SMAD3, a major effector of TGFbeta-mediated EMT. TRIM62 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.


Pssm-ID: 438270 [Multi-domain]  Cd Length: 52  Bit Score: 41.72  E-value: 3.19e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 2240474248 279 CVVCLSDLRDTLILPCRHLcLCNSCADT--LRYQANNCPICRLPF 321
Cdd:cd16608     9 CSICLSIYQDPVSLGCEHY-FCRQCITEhwSRSEHRDCPECRRTF 52
mRING-H2-C3H2C2D_ZSWM2 cd16486
Modified RING finger, H2 subclass (C3H2C2D-type), found in zinc finger SWIM domain-containing ...
278-321 3.47e-05

Modified RING finger, H2 subclass (C3H2C2D-type), found in zinc finger SWIM domain-containing protein 2 (ZSWIM2) and similar proteins; ZSWIM2, also known as MEKK1-related protein X (MEX) or ZZ-type zinc finger-containing protein 2, is a testis-specific E3 ubiquitin ligase that promotes death receptor-induced apoptosis through Fas, death receptor (DR) 3 and DR4 signaling. ZSWIM2 is self-ubiquitinated and targeted for degradation through the proteasome pathway. It acts as an E3 ubiquitin ligase, through the E2, Ub-conjugating enzymes UbcH5a, UbcH5c, or UbcH6. ZSWIM2 contains four putative zinc-binding domains including an N-terminal SWIM (SWI2/SNF2 and MuDR) domain critical for its ubiquitination, and two modified RING-H2 fingers separated by a ZZ zinc finger domain, which was required for interaction with UbcH5a and its self-association. This model corresponds to the second RING-H2 finger, which is not a canonical C3H2C3-type, but a modified C3H2C2D-type.


Pssm-ID: 438149 [Multi-domain]  Cd Length: 49  Bit Score: 41.20  E-value: 3.47e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 2240474248 278 ECVVCLS--DLRDTL-ILPCRHlCLCNSCADT-LRYQANNCPICRLPF 321
Cdd:cd16486     1 QCRICLKafQLGQHVrTLPCRH-KFHRDCIDNwLLHSRNSCPIDGQVV 47
RING-HC_RNF213 cd16561
RING finger, HC subclass, found in RING finger protein 213 (RNF213) and similar proteins; ...
278-318 4.07e-05

RING finger, HC subclass, found in RING finger protein 213 (RNF213) and similar proteins; RNF213, also known as ALK lymphoma oligomerization partner on chromosome 17 or Moyamoya steno-occlusive disease-associated AAA+ and RING finger protein (mysterin), is an intracellular soluble protein that functions as an E3 ubiquitin-protein ligase and AAA+ ATPase, which possibly contributes to vascular development through mechanical processes in the cell. It plays a unique role in endothelial cells for proper gene expression in response to inflammatory signals from the environment. Mutations in RNF213 may be associated with Moyamoya disease (MMD), an idiopathic cerebrovascular occlusive disorder prevalent in East Asia. It also acts as a nuclear marker for acanthomorph phylogeny. RNF213 contains two tandem enzymatically active AAA+ ATPase modules and a C3HC4-type RING-HC finger. It can form a huge ring-shaped oligomeric complex.


Pssm-ID: 438223 [Multi-domain]  Cd Length: 50  Bit Score: 41.11  E-value: 4.07e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 2240474248 278 ECVVCLSDLRDTLILPCRHLcLCNSCADTLRYQANNCPICR 318
Cdd:cd16561     4 ECSICLEDLNDPVKLPCDHV-FCEECIRQWLPGQMSCPLCR 43
RING-HC_MIB1_rpt1 cd16724
first RING finger, HC subclass, found in mind bomb 1 (MIB1) and similar proteins; MIB1, also ...
277-318 4.29e-05

first RING finger, HC subclass, found in mind bomb 1 (MIB1) and similar proteins; MIB1, also known as DAPK-interacting protein 1 (DIP-1) or zinc finger ZZ type with ankyrin repeat domain protein 2, is a large, multi-domain E3 ubiquitin-protein ligase that promotes ubiquitination of the cytoplasmic tails of Notch ligands, and thus plays an essential role in controlling metazoan development by Notch signaling. It is also involved in Wnt/beta-catenin signaling and nuclear factor (NF)-kappaB signaling, and has been implicated in innate immunity, neuronal function, genomic stability, and cell death. MIB1 contains an MZM region with two Mib-Herc2 domains flanking a ZZ zinc finger, a REP region including two tandem Mib repeats, an ANK region that spans ankyrin repeats, and a RNG region consisting of three C3HC4-type RING-HC fingers. This model corresponds to the first RING-HC finger.


Pssm-ID: 438384  Cd Length: 38  Bit Score: 40.93  E-value: 4.29e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 2240474248 277 NECVVCLSDLRDTLILPCRHLCLCNSCADTLRyqanNCPICR 318
Cdd:cd16724     1 EECMVCSDMKRDTLFGPCGHIATCSLCSPRVK----KCLICK 38
RING-H2_PA-TM-RING cd16454
RING finger, H2 subclass, found in the PA-TM-RING ubiquitin ligase family; The PA-TM-RING ...
278-318 6.95e-05

RING finger, H2 subclass, found in the PA-TM-RING ubiquitin ligase family; The PA-TM-RING family represents a group of transmembrane-type E3 ubiquitin ligases, which has been characterized by an N-terminal transient signal peptide, a PA (protease-associated) domain, a TM (transmembrane) domain, as well as a C-terminal C3H2C3-type RING-H2 finger domain. It includes RNF13, RNF167, ZNRF4 (zinc and RING finger 4), GRAIL (gene related to anergy in lymphocytes)/RNF128, RNF130, RNF133, RNF148, RNF149 and RNF150 (which are more closely related), as well as RNF43 and ZNRF3, which have substantially longer C-terminal tail extensions compared with the others. PA-TM-RING proteins are expressed at low levels in all mammalian tissues and species, but they are not present in yeast. They play a common regulatory role in intracellular trafficking/sorting, suggesting that abrogation of their function may result in dysregulation of cellular signaling events in cancer.


Pssm-ID: 438118 [Multi-domain]  Cd Length: 43  Bit Score: 40.34  E-value: 6.95e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 2240474248 278 ECVVCLSDLRD---TLILPCRHLCLCNsCADTLRYQANNCPICR 318
Cdd:cd16454     1 TCAICLEEFKEgekVRVLPCNHLFHKD-CIDPWLEQHNTCPLCR 43
RING-HC_RNF146 cd16546
RING finger, HC subclass, found in RING finger protein 146 (RNF146) and similar proteins; ...
278-321 7.89e-05

RING finger, HC subclass, found in RING finger protein 146 (RNF146) and similar proteins; RNF146, also known as dactylidin, or iduna, is a cytoplasmic E3 ubiquitin-protein ligase that is responsible for PARylation-dependent ubiquitination (PARdU). It displays neuroprotective property due to its inhibition of Parthanatos, a PAR dependent cell death, via binding with Poly(ADP-ribose) (PAR). It also modulates PAR polymerase-1 (PARP-1)-mediated oxidative cell injury in cardiac myocytes. Moreover, RNF146 mediates tankyrase-dependent degradation of axin, thereby positively regulating Wnt signaling. It also facilitates DNA repair and protects against cell death induced by DNA damaging agents or gamma-irradiation by translocating to the nucleus after cellular injury and promoting the ubiquitination and degradation of various nuclear proteins involved in DNA damage repair. Furthermore, RNF146 is implicated in neurodegenerative disease and cancer development. It regulates the development and progression of non-small cell lung cancer (NSCLC) by enhancing cell growth, invasion, and survival. RNF146 contains an N-terminal C3HC4-type RING-HC finger followed by a WWE domain with a poly(ADP-ribose) (PAR) binding motif at the tail.


Pssm-ID: 438208 [Multi-domain]  Cd Length: 50  Bit Score: 40.45  E-value: 7.89e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 2240474248 278 ECVVCLSDLRDTLILPCRHLcLCNSCADTLRYQANNCPICRLPF 321
Cdd:cd16546     2 ECPICLQTCIHPVKLPCGHI-FCYLCVKGVAWQSKRCALCRQEI 44
RING-HC_TRIM9-like_C-I cd16576
RING finger, HC subclass, found in tripartite motif-containing proteins TRIM9, TRIM67, and ...
279-318 8.63e-05

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM9, TRIM67, and similar proteins; Tripartite motif-containing proteins TRIM9 and TRIM67 belong to the C-I subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, consisting of three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, and a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. TRIM9 (the human ortholog of rat Spring), also known as RING finger protein 91 (RNF91), is a brain-specific E3 ubiquitin-protein ligase collaborating with an E2 ubiquitin conjugating enzyme UBCH5b. TRIM9 plays an important role in the regulation of neuronal functions and participates in neurodegenerative disorders through its ligase activity. TRIM67, also known as TRIM9-like protein (TNL), is a protein selectively expressed in the cerebellum. It interacts with PRG-1, an important molecule in the control of hippocampal excitability dependent on presynaptic LPA2 receptor signaling, and 80K-H, also known as glucosidase II beta, a protein kinase C substrate.


Pssm-ID: 438238 [Multi-domain]  Cd Length: 42  Bit Score: 40.09  E-value: 8.63e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 2240474248 279 CVVCLSDLRDTLILPCRHlCLCNSCADTLRYqanNCPICR 318
Cdd:cd16576     6 CPVCGSLFTEPVILPCSH-NLCLGCALNIQL---TCPICH 41
RING-HC_AtBARD1-like cd23146
RING finger, HC subclass, found in Arabidopsis thaliana BRCA1-associated RING domain protein 1 ...
279-321 1.25e-04

RING finger, HC subclass, found in Arabidopsis thaliana BRCA1-associated RING domain protein 1 (AtBARD1) and similar proteins; AtBARD1, also called protein REPRESSOR OF WUSCHEL 1, binds specifically to H3K4me3 regions of target gene (e.g. WUS and WOX5) promoters to repress their transcription via chromatin remodeling. It is required for the shoot apical meristem (SAM) organization and maintenance, by confining WUS expression to the organizing center, and for the quiescent center (QC) development in the root apical meristem (RAM), by repressing WOX5 expression in the root proximal meristem. AtBARD1 plays a role in DNA repair and in cell-cycle control. It is required for the repair of DNA double-strand breaks (DSBs), both natural and induced by genotoxic stress, by homologous recombination (HR). AtBARD1 contains a typical C3HC4-type RING-HC finger.


Pssm-ID: 438508 [Multi-domain]  Cd Length: 54  Bit Score: 39.76  E-value: 1.25e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 2240474248 279 CVVCLSDLRDTLILPCRHLcLCNSCADTLRYQANNCPICRLPF 321
Cdd:cd23146     7 CPICLKLLNRPVLLPCDHI-FCSSCITDSTKVGSDCPVCKLPY 48
RING-HC_CeBARD1-like cd23143
RING finger, HC subclass, found in Caenorhabditis elegans BRCA1-associated RING domain protein ...
277-321 1.33e-04

RING finger, HC subclass, found in Caenorhabditis elegans BRCA1-associated RING domain protein 1 (CeBARD1) and similar proteins; CeBARD1, also called Ce-BRD-1, Cebrd-1, or RING-type E3 ubiquitin transferase BARD1, is a constituent of the CeBCD complex that possesses E3 ubiquitin-protein ligase activity. It plays a role in triggering cellular responses at damage sites in response to DNA damage that may be induced by ionizing radiation. It protects against chromosome non-disjunction and nuclear fragmentation during meiotic double-strand break repair to ensure sister chromatid recombination and aid chromosome stability. CeBARD1 contains a typical C3HC4-type RING-HC finger.


Pssm-ID: 438505 [Multi-domain]  Cd Length: 47  Bit Score: 39.45  E-value: 1.33e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 2240474248 277 NECVVCLSDLRDT-LILPCRHLcLCNSCADTLRYQANNCPICRLPF 321
Cdd:cd23143     2 IECVICSEPQIDTfLLSSCGHI-YCWECFTEFIEKRHMCPSCRFPL 46
RING-HC_Bre1-like cd16499
RING finger, HC subclass, found in yeast Bre1 and its homologs from eukaryotes; Bre1 is an E3 ...
279-321 1.42e-04

RING finger, HC subclass, found in yeast Bre1 and its homologs from eukaryotes; Bre1 is an E3 ubiquitin-protein ligase that catalyzes monoubiquitination of histone H2B in concert with the E2 ubiquitin-conjugating enzyme, Rad6. The Rad6-Bre1-mediated histone H2B ubiquitylation modulates the formation of double-strand breaks (DSBs) during meiosis in yeast. it is also required, indirectly, for the methylation of histone 3 on lysine 4 (H3K4) and 79. RNF20, also known as BRE1A and RNF40, also known as BRE1B, are the mammalian homologs of Bre1. They work together to form a heterodimeric Bre1 complex that facilitate the K120 monoubiquitination of histone H2B (H2Bub1), a DNA damage-induced histone modification that is crucial for recruitment of the chromatin remodeler SNF2h to DNA double-strand break (DSB) damage sites. Moreover, the Bre1 complex acts as a tumor suppressor, augmenting expression of select tumor suppressor genes and suppressing select oncogenes. Deficiency in the mammalian histone H2B ubiquitin ligase Bre1 leads to replication stress and chromosomal instability. All subfamily members contain a C3HC4-type RING-HC finger at its C-terminus.


Pssm-ID: 438162 [Multi-domain]  Cd Length: 59  Bit Score: 39.85  E-value: 1.42e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 2240474248 279 CVVCLSDLRDTLILPCRHlCLCNSCADTlRYQANN--CPICRLPF 321
Cdd:cd16499     9 CSVCNDRFKDVIITKCGH-VFCNECVQK-RLETRQrkCPGCGKAF 51
RING-HC_RNF138 cd16544
RING finger, HC subclass, found in RING finger protein 138 (RNF138) and similar proteins; ...
278-320 2.65e-04

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: 38.92  E-value: 2.65e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 2240474248 278 ECVVCLSDLRDTLIL-PCRHLcLCNSCA-DTLRYQANNCPICRLP 320
Cdd:cd16544     4 TCPVCQEVLKDPVELpPCRHI-FCKACIlLALRSSGARCPLCRGP 47
RING-H2_RHA1-like cd23121
RING finger, H2 subclass, found in Arabidopsis thaliana RING-H2 finger A1a (RHA1A), A1b (RHA1B) ...
277-321 2.70e-04

RING finger, H2 subclass, found in Arabidopsis thaliana RING-H2 finger A1a (RHA1A), A1b (RHA1B) and similar proteins; This subfamily includes Arabidopsis thaliana RHA1A, RHA1B and XERICO. RHA1A is a probable E3 ubiquitin-protein ligase that may possess E3 ubiquitin ligase activity in vitro. RHA1B possesses E3 ubiquitin-protein ligase activity when associated with the E2 enzyme UBC8 in vitro. XERICO functions on abscisic acid homeostasis at post-translational level, probably through ubiquitin/proteasome-dependent substrate-specific degradation. Members of this subfamily contain a C3H2C3-type RING-H2 finger.


Pssm-ID: 438483 [Multi-domain]  Cd Length: 50  Bit Score: 39.01  E-value: 2.70e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 2240474248 277 NECVVCLSDLRDTLILP----CRHLcLCNSCADT-LRYQANNCPICRLPF 321
Cdd:cd23121     2 DCCAICLSDFNSDEKLRqlpkCGHI-FHHHCLDRwIRYNKITCPLCRADL 50
PHA02929 PHA02929
N1R/p28-like protein; Provisional
233-332 2.88e-04

N1R/p28-like protein; Provisional


Pssm-ID: 222944 [Multi-domain]  Cd Length: 238  Bit Score: 42.46  E-value: 2.88e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2240474248 233 FSVKPLKQKQIVDRVSYL--LQE---IYGIENKNNQETK------PS------DDENSDNSNECVVCLSDLRDTL----- 290
Cdd:PHA02929  114 YNQKILKNKPSNDKINYIymRKEedmFYAIINKKGKNYKkflktiPSvlseyeKLYNRSKDKECAICMEKVYDKEiknmy 193
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 2240474248 291 --ILP-CRHLcLCNSCADTLRYQANNCPICRLPFRALLQIRAVRK 332
Cdd:PHA02929  194 fgILSnCNHV-FCIECIDIWKKEKNTCPVCRTPFISVIKSRFFTK 237
RING-HC_TRIM65_C-IV cd16609
RING finger, HC subclass, found in tripartite motif-containing protein TRIM65 and similar ...
279-322 3.35e-04

RING finger, HC subclass, found in tripartite motif-containing protein TRIM65 and similar proteins; TRIM65 is an E3 ubiquitin-protein ligase that interacts with the innate immune receptor MDA5, enhancing its ability to stimulate interferon-beta signaling. It functions as a potential oncogenic protein that negatively regulates p53 through ubiquitination, providing insight into the development of novel approaches targeting TRIM65 for non-small cell lung carcinoma (NSCLC) treatment, and also overcoming chemotherapy resistance. Moreover, TRIM65 negatively regulates microRNA-driven suppression of mRNA translation by targeting TNRC6 proteins for ubiquitination and degradation. TRIM65 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.


Pssm-ID: 438271 [Multi-domain]  Cd Length: 58  Bit Score: 38.89  E-value: 3.35e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2240474248 279 CVVCLSDLRDTLILPCRHlCLCNSC-------ADTLRYQannCPICRLPFR 322
Cdd:cd16609     6 CSICLGLYQDPVTLPCQH-SFCRACiedhwrqKDEGSFS---CPECRAPFP 52
RING-H2_RNF103 cd16473
RING finger, H2 subclass, found in RING finger protein 103 (RNF103) and similar proteins; ...
276-320 3.46e-04

RING finger, H2 subclass, found in RING finger protein 103 (RNF103) and similar proteins; RNF103, also known as KF-1 or zinc finger protein 103 homolog (Zfp-103), is an endoplasmic reticulum (ER)-resident E3 ubiquitin-protein ligase that is widely expressed in many different organs, including brain, heart, kidney, spleen, and lung. It is involved in the ER-associated degradation (ERAD) pathway by interacting with components of the ERAD pathway, including Derlin-1 and VCP. RNF103 contains several hydrophobic regions at its N-terminal and middle regions, as well as a C-terminal C3H2C3-type RING-H2 finger.


Pssm-ID: 438136 [Multi-domain]  Cd Length: 55  Bit Score: 38.79  E-value: 3.46e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2240474248 276 SNECVVCLSDLRDT---LILPCRHL----CLCnscaDTLRYQANNCPICRLP 320
Cdd:cd16473     4 CEECAICLENYQNGdllRGLPCGHVfhqnCID----VWLERDNHCCPVCRWP 51
RING-H2_RNF111 cd16681
RING finger, H2 subclass, found in RING finger protein 111 (RNF111) and similar proteins; ...
269-325 3.53e-04

RING finger, H2 subclass, found in RING finger protein 111 (RNF111) and similar proteins; RNF111, also known as Arkadia, is a nuclear E3 ubiquitin-protein ligase that targets intracellular effectors and modulators of transforming growth factor beta (TGF-beta)/Nodal-related signaling for polyubiquitination and proteasome-dependent degradation. It acts as an amplifier of Nodal signals, and enhances the dorsalizing activity of limiting amounts of Xnr1, a Nodal homolog, and requires Nodal signaling for its function. The loss of RNF111 results in early embryonic lethality, with defects attributed to compromised Nodal signaling. RNF111 also regulates tumor metastasis by modulation of the TGF-beta pathway. Its ubiquitination can be modulated by the four and a half LIM-only protein 2 (FHL2) that activates TGF-beta signal transduction. Furthermore, RNF111 interacts with the clathrin-adaptor 2 (AP2) complex and regulates endocytosis of certain cell surface receptors, leading to modulation of epidermal growth factor (EGF) and possibly other signaling pathways. In addition, RNF111 has been identified as a small ubiquitin-like modifier (SUMO)-binding protein with clustered SUMO-interacting motifs (SIMs) that together form a SUMO-binding domain (SBD). It thus functions as a SUMO-targeted ubiquitin ligase (STUbL) that directly links nonproteolytic ubiquitylation and SUMOylation in the DNA damage response, as well as triggers degradation of signal-induced polysumoylated proteins, such as the promyelocytic leukemia protein (PML). The N-terminal half of RNF111 harbors three SIMs. Its C-terminal half show high sequence similarity with RING finger protein 165 (RNF165), where it contains two serine rich domains, two nuclear localization signals, an NRG-TIER domain, and a C-terminal C3H2C3-type RING-H2 finger that is required for polyubiqutination and proteasome-dependent degradation of phosphorylated forms of Smad2/3 and three major negative regulators of TGF-beta signaling, Smad7, SnoN and c-Ski.


Pssm-ID: 438343 [Multi-domain]  Cd Length: 61  Bit Score: 38.89  E-value: 3.53e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2240474248 269 DDENSDNSNECVVCLSDLR---DTLILPCRHLcLCNSCADTLRYQANNCPICRLPFRALL 325
Cdd:cd16681     3 EGTEEDTEEKCTICLSILEegeDVRRLPCMHL-FHQVCVDQWLITNKKCPICRVDIEAQL 61
RING-HC_MIBs cd16519
RING finger, HC subclass, found in mind bomb MIB1, MIB2, and similar proteins; MIBs are large, ...
278-318 3.67e-04

RING finger, HC subclass, found in mind bomb MIB1, MIB2, and similar proteins; MIBs are large, multi-domain E3 ubiquitin-protein ligases that promote ubiquitination of the cytoplasmic tails of Notch ligands. They are also responsible for TBK1 K63-linked ubiquitination and activation, promoting interferon production and controlling antiviral immunity. Moreover, MIBs selectively control responses to cytosolic RNA and regulate type I interferon transcription. Both MIB1 and MIB2 have similar domain architectures, which consist of two Mib-Herc2 domains flanking a ZZ zinc finger, a REP region including two tandem Mib repeats, an ANK region that spans ankyrin repeats, and a RNG region, where MIB1 and MIB2 contain three and two C3HC4-type RING-HC fingers, respectively. This model corresponds to the first RING-HC finger of MIB1 and MIB2, as well as the second RING-HC finger of MIB1.


Pssm-ID: 438182  Cd Length: 38  Bit Score: 38.23  E-value: 3.67e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 2240474248 278 ECVVCLSDLRDTLILPCRHLCLCNSCAdtlrYQANNCPICR 318
Cdd:cd16519     2 ECRVCSDKKALVLFQPCGHVVACEECS----LRMKKCLQCK 38
RING-HC_TRIM25_C-IV cd16597
RING finger, HC subclass, found in tripartite motif-containing protein TRIM25 and similar ...
279-328 3.70e-04

RING finger, HC subclass, found in tripartite motif-containing protein TRIM25 and similar proteins; TRIM25, also known as estrogen-responsive finger protein (EFP), RING finger protein 147 (RNF147), or RING-type E3 ubiquitin transferase, is an E3 ubiquitin/ISG15 ligase that is induced by estrogen and is therefore particularly abundant in placenta and uterus. TRIM25 regulates various cellular processes through E3 ubiquitin ligase activity, transferring ubiquitin and ISG15 to target proteins. It mediates K63-linked polyubiquitination of retinoic acid inducible gene I (RIG-I) that is crucial for downstream antiviral interferon signaling. It is also required for melanoma differentiation-associated gene 5 (MDA5) and mitochondrial antiviral signaling (MAVS, also known as IPS-1, VISA, Cardiff) mediated activation of nuclear factor-kappaB (NF-kappaB) and interferon production. Upon UV irradiation, TRIM25 interacts with mono-ubiquitinated PCNA and promotes its ISG15 modification (ISGylation), suggesting a crucial role in termination of error-prone translesion DNA synthesis. TRIM25 also functions as a novel regulator of p53 and Mdm2. It enhances p53 and Mdm2 abundance by inhibiting their ubiquitination and degradation in 26S proteasomes. Meanwhile, it inhibits p53's transcriptional activity and dampens the response to DNA damage, and is essential for medaka development and this dependence is rescued by silencing of p53. Moreover, TRIM25 is involved in the host cellular innate immune response against retroviral infection. It interferes with the late stage of feline leukemia virus (FeLV) replication. Furthermore, TRIM25 acts as an oncogene in gastric cancer. Its blockade by RNA interference inhibits migration and invasion of gastric cancer cells through transforming growth factor-beta (TGF-beta) signaling, suggesting it presents a novel target for the detection and treatment of gastric cancer. In addition, TRIM25 acts as an RNA-specific activator for Lin28a/TuT4-mediated uridylation. TRIM25 belongs to the C-IV subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.


Pssm-ID: 438259 [Multi-domain]  Cd Length: 71  Bit Score: 39.22  E-value: 3.70e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2240474248 279 CVVCLSDLRDTLILPCRH----LCLCNSCaDTLRYQANNCPICRLPFRALLQIR 328
Cdd:cd16597     8 CSICLELFKDPVTLPCGHnfcgVCIEKTW-DSQHGSEYSCPQCRATFPRRPELH 60
RING-HC_RNF168 cd16550
RING finger, HC subclass, found in RING finger protein 168 (RNF168) and similar proteins; ...
279-319 4.32e-04

RING finger, HC subclass, found in RING finger protein 168 (RNF168) and similar proteins; RNF168 is an E3 ubiquitin-protein ligase that promotes noncanonical K27 ubiquitination to signal DNA damage. It, together with RNF8, functions as a DNA damage response (DDR) factor that promotes a series of ubiquitylation events on substrates, such as H2A and H2AX with H2AK13/15 ubiquitylation, facilitates recruitment of repair factors p53-binding protein 1 (53BP1) or the RAP80-BRCA1 complex to sites of double-strand breaks (DSBs), and inhibits homologous recombination (HR) in cells deficient in the tumor suppressor BRCA1. RNF168 also promotes H2A neddylation, which antagonizes ubiquitylation of H2A and regulates DNA damage repair. Moreover, RNF168 forms a functional complex with RAD6A or RAD6B during the DNA damage response. RNF168 contains an N-terminal C3HC4-type RING-HC finger that catalyzes H2A-K15ub and interacts with H2A, and two MIU (motif interacting with ubiquitin) domains responsible for the interaction with K63 linked poly-ubiquitin.


Pssm-ID: 438212 [Multi-domain]  Cd Length: 48  Bit Score: 38.13  E-value: 4.32e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 2240474248 279 CVVCLSDLRDTLILPCRHlCLCNSCADTLRYQAN-NCPICRL 319
Cdd:cd16550     3 CPICLEILVEPVTLPCNH-TLCMPCFQSTVEKASlCCPLCRL 43
RING-HC_IRC20-like cd23135
RING finger, HC subclass, found in Saccharomyces cerevisiae increased recombination centers ...
279-318 5.95e-04

RING finger, HC subclass, found in Saccharomyces cerevisiae increased recombination centers protein 20 (IRC20) and similar proteins; IRC20 is an uncharacterized ATP-dependent helicase that is probably involved in a pathway contributing to genomic integrity. IRC20 contains a typical C3HC4-type RING-HC finger.


Pssm-ID: 438497 [Multi-domain]  Cd Length: 44  Bit Score: 37.88  E-value: 5.95e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 2240474248 279 CVVCLSDLRDTLILPCRHLcLCNSCADTLRYQANNCPICR 318
Cdd:cd23135     6 CSICFSEIRSGAILKCGHF-FCLSCIASWLREKSTCPLCK 44
RING-HC_UNK cd16771
RING finger, HC subclass, found in RING finger protein unkempt (UNK) and similar proteins; UNK, ...
279-317 7.13e-04

RING finger, HC subclass, found in RING finger protein unkempt (UNK) and similar proteins; UNK, also known as zinc finger CCCH domain-containing protein 5, is a metazoan-specific zinc finger protein enriched in embryonic brains. It may play a broad regulatory role during the formation of the central nervous system (CNS). It is a sequence-specific RNA-binding protein required for early neuronal morphology. UNK is a neurogenic component of the mTOR pathway, and functions as a negative regulator of the timing of photoreceptor differentiation. It also specifically binds to Brg/Brm-associated factor BAF60b and promotes its ubiquitination in a Rac1-dependent manner. UNK contains six tandem CCCH-type zinc fingers at the N-terminus, and a C3HC4-type RING-HC finger at its C-terminus.


Pssm-ID: 438427  Cd Length: 42  Bit Score: 37.50  E-value: 7.13e-04
                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 2240474248 279 CVVClsDLRDTLILPCRHLCLCNSCAdtlryQANNCPIC 317
Cdd:cd16771     5 CLKC--QELKRVTLPCQHALLCETCA-----TSEECPIC 36
RING-HC_Cbl-like cd16502
RING finger, HC subclass, found in Casitas B-lineage lymphoma (Cbl) proteins; The Cbl adaptor ...
279-318 7.88e-04

RING finger, HC subclass, found in Casitas B-lineage lymphoma (Cbl) proteins; The Cbl adaptor protein family contains a small class of RING-type E3 ubiquitin ligases with oncogenic activity, which is represented by three mammalian members, c-Cbl, Cbl-b and Cbl-c, as well as two invertebrate Cbl-family proteins, D-Cbl in Drosophila and Sli-1 in C. elegans. Cbl proteins function as potent negative regulators of various signaling cascades in a wide range of cell types. They play roles in ubiquitinating activated tyrosine kinases and targeting them for degradation. D-Cbl associates with the Drosophila epidermal growth factor receptor (EGFR) and overexpression of D-Cbl in the eye of Drosophila embryos inhibits EGFR-dependent photoreceptor cell development. Sli-1 is a negative regulator of the Let-23 receptor tyrosine kinase, an EGFR homolog, in vulva development. Cbl proteins in this subfamily consist of a highly conserved N-terminal half that includes a tyrosine-kinase-binding domain (TKB, also known as the phosphotyrosine binding PTB domain, composed of a four helix-bundle, a Ca2+ binding EF-hand and a highly variant SH2 domain) and a C3HC4-type RING-HC finger, both of which are required for Cbl-mediated downregulation of RTKs, and a divergent C-terminal region.


Pssm-ID: 438165 [Multi-domain]  Cd Length: 43  Bit Score: 37.33  E-value: 7.88e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 2240474248 279 CVVCLSDLRDTLILPCRHLcLCNSCadTLRYQ---ANNCPICR 318
Cdd:cd16502     4 CKICAENDKDVRIEPCGHL-LCTPC--LTSWQdsdGQTCPFCR 43
RING-HC_TRIM13_like_C-V cd16581
RING finger, HC subclass, found in tripartite motif-containing proteins TRIM13, TRIM59 and ...
279-318 8.14e-04

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM13, TRIM59 and similar proteins; TRIM13 and TRIM59, two closely related tripartite motif-containing proteins, belong to the C-V subclass of the TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domain, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, followed by a C-terminal transmembrane domain. TRIM13, also known as B-cell chronic lymphocytic leukemia tumor suppressor Leu5, leukemia-associated protein 5, putative tumor suppressor RFP2, RING finger protein 77 (RNF77), or Ret finger protein 2, is an endoplasmic reticulum (ER) membrane anchored E3 ubiquitin-protein ligase that interacts with proteins localized to the ER, including valosin-containing protein (VCP), a protein indispensable for ER-associated degradation (ERAD). TRIM59, also known as RING finger protein 104 (RNF104) or tumor suppressor TSBF-1, is a putative E3 ubiquitin-protein ligase that functions as a novel multiple cancer biomarker for immunohistochemical detection of early tumorigenesis.


Pssm-ID: 438243 [Multi-domain]  Cd Length: 50  Bit Score: 37.49  E-value: 8.14e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 2240474248 279 CVVCLSDLRDTLILPCRHL----CLCNSCADTLRYQANN--CPICR 318
Cdd:cd16581     5 CSICYNIFDDPKILPCSHTfcknCLEKLLAASGYYLLASlkCPTCR 50
RING-HC_AtBRCA1-like cd23147
RING finger, HC subclass, found in Arabidopsis thaliana protein BREAST CANCER SUSCEPTIBILITY 1 ...
279-323 8.29e-04

RING finger, HC subclass, found in Arabidopsis thaliana protein BREAST CANCER SUSCEPTIBILITY 1 homolog (AtBRCA1) and similar proteins; AtBRCA1 plays a role in DNA repair and in cell-cycle control. It is required for the repair of DNA double-strand breaks (DSBs), both natural and induced by genotoxic stress, by homologous recombination (HR). AtBRCA1 contains a typical C3HC4-type RING-HC finger.


Pssm-ID: 438509 [Multi-domain]  Cd Length: 54  Bit Score: 37.45  E-value: 8.29e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 2240474248 279 CVVCLSDLRDTLILPCRHlCLCNSCADTLRYQANNCPICRLPFRA 323
Cdd:cd23147     7 CPICLSLFKSAANLSCNH-CFCAGCIGESLKLSAICPVCKIPATR 50
RING-HC_RNFT2 cd16742
RING finger, HC subclass, found in RING finger and transmembrane domain-containing protein 2 ...
279-318 9.27e-04

RING finger, HC subclass, found in RING finger and transmembrane domain-containing protein 2(RNFT2); RNFT2, also known as transmembrane protein 118 (TMEM118), is a multi-pass membrane protein containing a C3HC4-type RING-HC finger. Its biological role remains unclear.


Pssm-ID: 438400 [Multi-domain]  Cd Length: 67  Bit Score: 37.94  E-value: 9.27e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 2240474248 279 CVVCLSDLRDTLILPCRHLcLCNSCADTLRYQANNCPICR 318
Cdd:cd16742    16 CAICQAEFREPLILICQHV-FCEECLCLWFDRERTCPLCR 54
RING-HC_TRIM47-like_C-IV cd16604
RING finger, HC subclass, found in tripartite motif-containing protein 47 (TRIM47) and similar ...
279-322 9.33e-04

RING finger, HC subclass, found in tripartite motif-containing protein 47 (TRIM47) and similar proteins; TRIM47, also known as gene overexpressed in astrocytoma protein (GOA) or RING finger protein 100 (RNF100), belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, a B-box, and two coiled coil domains, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. It plays an important role in the process of dedifferentiation that is associated with astrocytoma tumorigenesis. This subfamily also includes RING finger protein 135 (RNF135). RNF135, also known as RIG-I E3 ubiquitin ligase (REUL) or Riplet, is a widely expressed E3 ubiquitin-protein ligase that consists of an N-terminal C3HC4-type RING-HC finger and C-terminal B30.2/SPRY and PRY motifs, but lacks the B-box and coiled-coil domains that are also typically present in TRIM proteins. RNF135 serves as a specific retinoic acid-inducible gene-I (RIG-I)-interacting protein that ubiquitinates RIG-I and specifically stimulates RIG-I-mediated innate antiviral activity to produce antiviral type-I interferon (IFN) during the early phase of viral infection. It also has been identified as a bio-marker and therapy target of glioblastoma. It associates with the ERK signal transduction pathway and plays a role in glioblastoma cell proliferation, migration and cell cycle.


Pssm-ID: 438266 [Multi-domain]  Cd Length: 49  Bit Score: 37.40  E-value: 9.33e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 2240474248 279 CVVCLSDLRDTLILPCRHlCLCNSCA----DTLRYQANNCPICRLPFR 322
Cdd:cd16604     3 CPICLDLLKDPVTLPCGH-SFCMGCLgalwGAGRGGRASCPLCRQTFP 49
RING-HC_BIRC4_8 cd16714
RING finger, HC subclass, found in E3 ubiquitin-protein ligase XIAP, baculoviral IAP ...
279-318 9.57e-04

RING finger, HC subclass, found in E3 ubiquitin-protein ligase XIAP, baculoviral IAP repeat-containing protein 8 (BIRC8) and similar proteins; XIAP, also known as baculoviral IAP repeat-containing protein 4 (BIRC4), IAP-like protein (ILP), inhibitor of apoptosis protein 3 (IAP-3), or X-linked inhibitor of apoptosis protein (X-linked IAP), is a potent suppressor of apoptosis that directly inhibits specific members of the caspase family of cysteine proteases, including caspase-3, -7, and -9. It promotes proteasomal degradation of caspase-3 and enhances its anti-apoptotic effect in Fas-induced cell death. The ubiquitin-protein ligase (E3) activity of XIAP also exhibits in the ubiquitination of second mitochondria-derived activator of caspases (Smac). The mitochondrial proteins, Smac/DIABLO and Omi/HtrA2, can inhibit the antiapoptotic activity of XIAP. XIAP has also been implicated in several intracellular signaling cascades involved in the cellular response to stress, such as the c-Jun N-terminal kinase (JNK), the nuclear factor-kappaB (NF-kappaB), and the transforming growth factor-beta (TGF-beta) pathways. Moreover, XIAP can regulate copper homeostasis by interacting with MURR1. BIRC8, also known as inhibitor of apoptosis-like protein 2, IAP-like protein 2, ILP-2, or testis-specific inhibitor of apoptosis, is a tissue-specific homolog of E3 ubiquitin-protein ligase XIAP. It has been implicated in the control of apoptosis in the testis by direct inhibition of caspase 9. Both XIAP and BIRC8 contain three N-terminal baculoviral IAP repeat (BIR) domains, a ubiquitin-association (UBA) domain and a C3HC4-type RING-HC finger at the carboxyl terminus.


Pssm-ID: 438374 [Multi-domain]  Cd Length: 64  Bit Score: 37.81  E-value: 9.57e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 2240474248 279 CVVCLSDLRDTLILPCRHLCLCNSCADTLryqaNNCPICR 318
Cdd:cd16714    17 CKICMDRNISIVFIPCGHLVTCKQCAEAL----DKCPICC 52
RING-HC_CARP2 cd16707
RING finger, HC subclass, found in caspases-8 and -10-associated RING finger protein 2 (CARP-2) ...
275-318 9.60e-04

RING finger, HC subclass, found in caspases-8 and -10-associated RING finger protein 2 (CARP-2) and similar proteins; CARP-2, also known as rififylin, caspase regulator CARP2, FYVE-RING finger protein Sakura (Fring), RING finger and FYVE-like domain-containing protein 1, RING finger protein 189 (RNF189), or RING finger protein 34-like, is an endosome-associated E3 ubiquitin-protein ligase that targets internalized receptor interacting kinase (RIP) for proteasome-mediated degradation. It acts as a negative regulator of tumor necrosis factor (TNF)-induced nuclear factor (NF)-kappaB activation. It also regulates the p53 signaling pathway by degrading 14-3-3sigma and stabilizing MDM2. As a caspase regulator, CARP2 does not localize to membranes in the cell and is involved in the negative regulation of apoptosis, specifically targeting two initiator caspases, caspase 8 and caspase 10. CARP2 contains an N-terminal FYVE-like domain and a C-terminal C3HC4-type RING-HC finger domain.


Pssm-ID: 438367 [Multi-domain]  Cd Length: 50  Bit Score: 37.26  E-value: 9.60e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 2240474248 275 NSNECVVCLSDLRDTLILPCRHLCLCNSCADTLryqaNNCPICR 318
Cdd:cd16707     1 DENLCKICMDSPIDCVLLECGHMVTCTKCGKRM----SECPICR 40
mRING-HC-C2H2C4_MDM2 cd16783
Modified RING finger, HC subclass (C2H2C4-type), found in E3 ubiquitin-protein ligase MDM2 and ...
279-325 9.66e-04

Modified RING finger, HC subclass (C2H2C4-type), found in E3 ubiquitin-protein ligase MDM2 and similar proteins; MDM2, also known as double minute 2 protein (Hdm2), oncoprotein MDM2, or p53-binding protein, exerts its oncogenic activity predominantly by binding p53 tumor suppressor and blocking its transcriptional activity. It forms homo-oligomers and displays E3 ubiquitin ligase activity that catalyzes the attachment of ubiquitin to p53 as an essential step in the regulation of its levels in cells. Moreover, in response to ribosomal stress, MDM2-mediated p53 ubiquitination and degradation can be inhibited through its interaction with ribosomal proteins L5, L11, and L23. MDM2 can be phosphorylated in the DNA damage. Meanwhile, MDM2 has a p53-independent role in tumorigenesis and cell growth regulation. In addition, it binds interferon (IFN) regulatory factor-2 (IRF-2), an IFN-regulated transcription factor, and mediates its ubiquitination. MDM2 contains an N-terminal p53-binding domain, and a C-terminal modified C2H2C4-type RING-HC finger conferring E3 ligase activity that is required for ubiquitination and nuclear export of p53. It is also responsible for the hetero-oligomerization of MDM2, which is crucial for the suppression of P53 activity during embryonic development, and the recruitment of E2 ubiquitin-conjugating enzymes. MDM2 also harbors a RanBP2-type zinc finger (zf-RanBP2) domain, as well as a nuclear localization signal (NLS) and a nuclear export signal (NES), near the central acidic region. The zf-RanBP2 domain plays an important role in mediating MDM2 binding to ribosomal proteins and thus is involved in MDM2-mediated p53 suppression.


Pssm-ID: 438438  Cd Length: 57  Bit Score: 37.62  E-value: 9.66e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 2240474248 279 CVVCLSDLRDTLILPCR--HLCLCNSCADTLRYQANNCPICRLPFRALL 325
Cdd:cd16783     4 CVICQTRPKNGCIVHGKtgHLMACFTCAKKLKKRNKPCPVCRQPIQMIV 52
RING-HC_UNKL cd16772
RING finger, HC subclass, found in RING finger protein unkempt-like (UNKL) and similar ...
278-318 1.08e-03

RING finger, HC subclass, found in RING finger protein unkempt-like (UNKL) and similar proteins; UNKL, also known as zinc finger CCCH domain-containing protein 5-like, is a putative E3 ubiquitin-protein ligase that may participate in a protein complex showing an E3 ligase activity regulated by RAC1. It shows high sequence similarity with RING finger protein unkempt (UNK), which is a metazoan-specific zinc finger protein enriched in embryonic brains, and may play a broad regulatory role during the formation of the central nervous system (CNS). UNKL contains several CCCH-type zinc fingers at the N-terminus, and a C3HC4-type RING-HC finger at its C-terminus.


Pssm-ID: 438428  Cd Length: 44  Bit Score: 37.07  E-value: 1.08e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 2240474248 278 ECVVCLSDLRDTLILPCRHLCLCNSCADTlryqANNCPICR 318
Cdd:cd16772     2 KCIVCQERDRSIVLQPCQHYVLCEHCAAS----KPECPYCK 38
RING-HC_RAG1 cd16530
RING finger, HC subclass, found in recombination activating gene-1 (RAG-1) and similar ...
276-320 1.21e-03

RING finger, HC subclass, found in recombination activating gene-1 (RAG-1) and similar proteins; RAG-1, also known as V(D)J recombination-activating protein 1, RING finger protein 74 (RNF74), or endonuclease RAG1, is the catalytic component of the RAG complex, a multiprotein complex that mediates the DNA cleavage phase during V(D)J recombination. RAG1 is a lymphoid-specific factor that mediates DNA-binding to conserved recombination signal sequences (RSS) and catalyzes DNA cleavage activities by introducing a double-strand break between the RSS and the adjacent coding segment. It also functions as an E3 ubiquitin-protein ligase that mediates monoubiquitination of histone H3, which is required for the joining step of V(D)J recombination. RAG-1 contains an N-terminal C3HC4-type RING-HC finger that mediates monoubiquitylation of histone H3, an adjacent C2H2-type zinc finger, and a nonamer binding (NBD) DNA-binding domain.


Pssm-ID: 319444 [Multi-domain]  Cd Length: 46  Bit Score: 37.04  E-value: 1.21e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 2240474248 276 SNECVVCLSDLRDTLILPCRHLcLCNSC-ADTLRYQANNCPICRLP 320
Cdd:cd16530     2 SVSCQVCEHILADPVQTPCKHL-FCRTCiLKCLKVMGSYCPSCRYP 46
RING-HC_MYLIP cd16523
RING finger, HC subclass, found in myosin regulatory light chain interacting protein (MYLIP) ...
279-318 1.21e-03

RING finger, HC subclass, found in myosin regulatory light chain interacting protein (MYLIP) and similar proteins; MYLIP, also known as inducible degrader of the low-density lipoprotein (LDL)-receptor (IDOL), or MIR, is an E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of myosin regulatory light chain (MRLC), LDLR, VLDLR, and LRP8. Its activity depends on E2 ubiquitin-conjugating enzymes of the UBE2D family. MYLIP stimulates clathrin-independent endocytosis and acts as a sterol-dependent inhibitor of cellular cholesterol uptake by binding directly to the cytoplasmic tail of the LDLR and promoting its ubiquitination via the UBE2D1/E1 complex. The ubiquitinated LDLR then enters the multivesicular body (MVB) protein-sorting pathway and is shuttled to the lysosome for degradation. Moreover, MYLIP has been identified as a novel ERM-like protein that affects cytoskeleton interactions regulating cell motility, such as neurite outgrowth. The ERM proteins includes ezrin, radixin, and moesin, which are cytoskeletal effector proteins linking actin to membrane-bound proteins at the cell surface. MYLIP contains an ERM-homology domain and a C-terminal C3HC4-type RING-HC finger.


Pssm-ID: 438186 [Multi-domain]  Cd Length: 52  Bit Score: 37.17  E-value: 1.21e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 2240474248 279 CVVCLSDLRDTLILPCRHLCLCNSCADtlryQANNCPICR 318
Cdd:cd16523     5 CMVCCEEEINSAFCPCGHMVCCESCAA----QLQSCPVCR 40
RING-HC_MIB1_rpt2 cd16725
second RING finger, HC subclass, found in mind bomb 1 (MIB1) and similar proteins; MIB1, also ...
278-318 1.23e-03

second RING finger, HC subclass, found in mind bomb 1 (MIB1) and similar proteins; MIB1, also known as DAPK-interacting protein 1 (DIP-1) or zinc finger ZZ type with ankyrin repeat domain protein 2, is a large, multi-domain E3 ubiquitin-protein ligase that promotes ubiquitination of the cytoplasmic tails of Notch ligands, and thus plays an essential role in controlling metazoan development by Notch signaling. It is also involved in Wnt/beta-catenin signaling and nuclear factor (NF)-kappaB signaling, and has been implicated in innate immunity, neuronal function, genomic stability, and cell death. MIB1 contains an MZM region with two Mib-Herc2 domains flanking a ZZ zinc finger, a REP region including two tandem Mib repeats, an ANK region that spans ankyrin repeats, and a RNG region consisting of three C3HC4-type RING-HC fingers. This model corresponds to the second RING-HC finger.


Pssm-ID: 438385  Cd Length: 38  Bit Score: 36.70  E-value: 1.23e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 2240474248 278 ECVVCLSDLRDTLILPCRHLCLCNSCADTLRyqanNCPICR 318
Cdd:cd16725     2 ECVVCSDKKASVLFKPCGHMCACEGCAALMK----KCVQCR 38
COG5236 COG5236
Uncharacterized conserved protein, contains RING Zn-finger [General function prediction only];
260-318 1.34e-03

Uncharacterized conserved protein, contains RING Zn-finger [General function prediction only];


Pssm-ID: 227561 [Multi-domain]  Cd Length: 493  Bit Score: 41.54  E-value: 1.34e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2240474248 260 KNNQETKP------SDDENSDNSNeCVVCLSDLRDTLILPCRHLcLCNSCADTLR--YQANNCPICR 318
Cdd:COG5236    40 KNNLSAEPnlttssADDTDEENMN-CQICAGSTTYSARYPCGHQ-ICHACAVRLRalYMQKGCPLCR 104
RING-HC_RNF222 cd16564
RING finger, HC subclass, found in RING finger protein 222 (RNF222) and similar proteins; ...
277-318 1.38e-03

RING finger, HC subclass, found in RING finger protein 222 (RNF222) and similar proteins; RNF222 is an uncharacterized C3HC4-type RING-HC finger-containing protein. It may function as an E3 ubiquitin-protein ligase.


Pssm-ID: 438226 [Multi-domain]  Cd Length: 50  Bit Score: 37.00  E-value: 1.38e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 2240474248 277 NECVVCLSDLRDTL-ILPCRHLcLCNSC-ADTLRYQANNCPICR 318
Cdd:cd16564     1 SECPVCYEDFDDAPrILSCGHS-FCEDClVKQLVSMTISCPICR 43
RING-H2_RNF38-like cd16472
RING finger, H2 subclass, found in RING finger proteins RNF38, RNF44, and similar proteins; ...
275-318 1.44e-03

RING finger, H2 subclass, found in RING finger proteins RNF38, RNF44, and similar proteins; This subfamily includes RING finger proteins RNF38, RNF44, and similar proteins. RNF38 is a nuclear E3 ubiquitin protein ligase that plays a role in regulating p53. RNF44 is an uncharacterized RING finger protein that shows high sequence similarity to RNF38. Both RNF38 and RNF44 contain a coiled-coil motif, a KIL motif (Lys-X2-Ile/Leu-X2-Ile/Leu, X can be any amino acid), and a C3H2C3-type RING-H2 finger. In addition, RNF38 harbors two potential nuclear localization signals.


Pssm-ID: 438135 [Multi-domain]  Cd Length: 46  Bit Score: 36.54  E-value: 1.44e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 2240474248 275 NSNECVVCLSDL--RDTL-ILPCRHLcLCNSCADtlRYQANN--CPICR 318
Cdd:cd16472     1 DQTQCVVCMCDYekRQLLrVLPCSHE-FHAKCID--KWLKTNrtCPICR 46
RING-H2_EL5-like cd16461
RING finger, H2 subclass, found in rice E3 ubiquitin-protein ligase EL5 and similar proteins; ...
278-318 1.47e-03

RING finger, H2 subclass, found in rice E3 ubiquitin-protein ligase EL5 and similar proteins; EL5, also known as protein ELICITOR 5, is an E3 ubiquitin-protein ligase containing an N-terminal transmembrane domain and a C3H2C3-type RING-H2 finger that is a binding site for ubiquitin-conjugating enzyme (E2). It can be rapidly induced by N-acetylchitooligosaccharide elicitor. EL5 catalyzes polyubiquitination via the Lys48 residue of ubiquitin, and thus plays a crucial role as a membrane-anchored E3 in the maintenance of cell viability after the initiation of root primordial formation in rice. It also acts as an anti-cell death enzyme that might be responsible for mediating the degradation of cytotoxic proteins produced in root cells after the actions of phytohormones. Moreover, EL5 interacts with UBC5b, a rice ubiquitin carrier protein, through its RING-H2 finger. EL5 is an unstable protein, and its degradation is regulated by the C3H2C3-type RING-H2 finger in a proteasome-independent manner.


Pssm-ID: 438124 [Multi-domain]  Cd Length: 44  Bit Score: 36.47  E-value: 1.47e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 2240474248 278 ECVVCLSD--LRDTL--ILPCRHlCLCNSCADTLRYQANNCPICR 318
Cdd:cd16461     1 ECAICLSDyeNGEELrrLPECKH-AFHKECIDEWLKSNSTCPLCR 44
RING-HC_Topors cd16574
RING finger, HC subclass, found in topoisomerase I-binding arginine/serine-rich protein ...
277-321 1.55e-03

RING finger, HC subclass, found in topoisomerase I-binding arginine/serine-rich protein (Topors) and similar proteins; Topors, also known as topoisomerase I-binding RING finger protein, tumor suppressor p53- binding protein 3, or p53-binding protein 3 (p53BP3), is a ubiquitously expressed nuclear E3 ubiquitin-protein ligase that can ligate both ubiquitin and small ubiquitin-like modifier (SUMO) to substrate proteins in the nucleus. It contains an N-terminal C3HC4-type RING-HC finger which ligates ubiquitin to its target proteins including DNA topoisomerase I, p53, NKX3.1, H2AX, and the AAV-2 Rep78/68 proteins. As a RING-dependent E3 ubiquitin ligase, Topors works with the E2 enzymes UbcH5a, UbcH5c, and UbcH6, but not with UbcH7, CDC34, or UbcH2b. Topors acts as a tumor suppressor in various malignancies. It regulates p53 modification, suggesting it may be responsible for astrocyte elevated gene-1 (AEG-1, also known as metadherin, or LYRIC) ubiquitin modification. Plk1-mediated phosphorylation of Topors inhibits Topors-mediated sumoylation of p53, whereas p53 ubiquitination is enhanced, leading to p53 degradation. It also functions as a negative regulator of the prostate tumor suppressor NKX3.1. Moreover, Topors is associated with promyelocytic leukemia nuclear bodies, and may be involved in the cellular response to camptothecin. It also plays a key role in the turnover of H2AX protein, discriminating the type of DNA damaging stress. Furthermore, Topors is a cilia-centrosomal protein associated with autosomal dominant retinal degeneration. Mutations in TOPORS cause autosomal dominant retinitis pigmentosa (adRP).


Pssm-ID: 438236 [Multi-domain]  Cd Length: 47  Bit Score: 36.49  E-value: 1.55e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 2240474248 277 NECVVCLSDLRD--TLILPCRHLcLCNSCADTLRYQANNCPICRLPF 321
Cdd:cd16574     2 SSCPICLDRFENekAFLDGCFHA-FCFTCILEWSKVKNECPLCKQPF 47
RING-HC_CARP1 cd16706
RING finger, HC subclass, found in caspases-8 and -10-associated RING finger protein 1 (CARP1) ...
274-318 1.80e-03

RING finger, HC subclass, found in caspases-8 and -10-associated RING finger protein 1 (CARP1) and similar proteins; CARP1, also known as caspase regulator CARP1, FYVE-RING finger protein Momo, RING finger homologous to inhibitor of apoptosis protein (RFI), RING finger protein 34 (RNF34), or RING finger protein RIFF, is a nuclear protein that functions as a specific E3 ubiquitin ligase for the transcriptional coactivator PGC-1alpha, a master regulator of energy metabolism and adaptive thermogenesis in the brown fat cell which negatively regulates brown fat cell metabolism. It is preferentially expressed in esophageal, gastric, and colorectal cancers, suggesting a possible association with the development of digestive tract cancers. It regulates the p53 signaling pathway by degrading 14-3-3 sigma and stabilizing MDM2. CARP1 does not localize to membranes in the cell and is involved in the negative regulation of apoptosis, specifically targeting two initiator caspases, caspase 8 and caspase 10. CARP1 contains an N-terminal FYVE-like domain and a C-terminal C3HC4-type RING-HC finger domain.


Pssm-ID: 438366 [Multi-domain]  Cd Length: 54  Bit Score: 36.54  E-value: 1.80e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 2240474248 274 DNSNECVVCLSDLRDTLILPCRHLCLCNSCADTLryqaNNCPICR 318
Cdd:cd16706     2 SDDNLCRICMDAVIDCVLLECGHMVTCTKCGKRM----SECPICR 42
RING-HC_TRIM77_C-IV cd16543
RING finger, HC subclass, found in tripartite motif-containing protein 77 (TRIM77) and similar ...
279-321 2.30e-03

RING finger, HC subclass, found in tripartite motif-containing protein 77 (TRIM77) and similar proteins; TRIM77 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including two consecutive zinc-binding domains, a C3HC4-type RING-HC finger and Bbox2, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain.


Pssm-ID: 438205 [Multi-domain]  Cd Length: 54  Bit Score: 36.22  E-value: 2.30e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 2240474248 279 CVVCLSDLRDTLILPCRHlCLCNSCADTL--RYQANN-CPICRLPF 321
Cdd:cd16543     6 CSICLDLLKDPVTIPCGH-SFCMNCITLLwdRKQGVPsCPQCRESF 50
RING-HC_RNF219 cd16562
RING finger, HC subclass, found in RING finger protein 219 (RNF219) and similar proteins; ...
279-320 2.51e-03

RING finger, HC subclass, found in RING finger protein 219 (RNF219) and similar proteins; RNF219 may function as a modulator of late-onset Alzheimer's disease (LOAD) associated amyloid beta A4 precursor protein (APP) endocytosis and metabolism. It genetically interacts with apolipoprotein E epsilon4 allele (APOE4). Thus, a genetic variant of RNF219 was found to affect amyloid deposition in human brain and LOAD age-of-onset. Moreover, common genetic variants at the RNF219 locus had been associated with alternations in lipid metabolism, cognitive performance and central nervous system ventricle volume. RNF219 contains a C3HC4-type RING-HC finger.


Pssm-ID: 438224 [Multi-domain]  Cd Length: 45  Bit Score: 35.87  E-value: 2.51e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 2240474248 279 CVVCLSDLRDTLILPCRHLcLCNSCADTLRYQANNCPICRLP 320
Cdd:cd16562     4 CHICLGKVRQPVICSNNHV-FCSSCMDVWLKNNNQCPACRVP 44
RING-HC_RBR_TRIAD1 cd16773
RING finger, HC subclass, found in two RING fingers and DRIL [double RING finger linked] 1 ...
278-303 2.96e-03

RING finger, HC subclass, found in two RING fingers and DRIL [double RING finger linked] 1 (TRIAD1); TRIAD1, also known as ariadne-2 (ARI-2), protein ariadne-2 homolog, Ariadne RBR E3 ubiquitin protein ligase 2 (ARIH2), or UbcM4-interacting protein 48, is an RBR-type E3 ubiquitin-protein ligase that catalyzes the formation of polyubiquitin chains linked via lysine-48, as well as lysine-63 residues. Its auto-ubiquitylation can be catalyzed by the E2 conjugating enzyme UBCH7. TRIAD1 has been implicated in hematopoiesis, specifically in myelopoiesis, as well as in embryogenesis. It functions as a regulator of endosomal transport and is required for the proper function of multivesicular bodies. It also acts as a novel ubiquitination target for proteasome-dependent degradation by murine double minute 2 (MDM2). As a proapoptotic protein, TRIAD1 promotes p53 activation, and inhibits MDM2-mediated p53 ubiquitination and degradation. Furthermore, TRIAD1 can inhibit the ubiquitination and proteasomal degradation of growth factor independence 1 (Gfi1), a transcriptional repressor essential for the function and development of many different hematopoietic lineages. TRIAD1 contains an RBR domain that was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain uses an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase function to facilitate the ubiquitination reaction. This model corresponds to the RING domain, a C3HC4-type RING-HC finger required for RBR-mediated ubiquitination.


Pssm-ID: 438429 [Multi-domain]  Cd Length: 54  Bit Score: 36.18  E-value: 2.96e-03
                          10        20
                  ....*....|....*....|....*...
gi 2240474248 278 ECVVCLSDLR--DTLILPCRHlCLCNSC 303
Cdd:cd16773     2 TCGVCCEDVPkdELFSLACGH-YFCNDC 28
RING-HC_MEX3D cd16723
RING finger, HC subclass, found in RNA-binding protein MEX3D; MEX3D, also known as RING finger ...
267-320 3.23e-03

RING finger, HC subclass, found in RNA-binding protein MEX3D; MEX3D, also known as RING finger and KH domain-containing protein 1 (RKHD1), RING finger protein 193 (RNF193), or TINO, is an RNA-binding phosphoprotein that controls the stability of the transcripts coding for the anti-apoptotic protein BCL-2, and negatively regulates BCL-2 in HeLa cells. MEX3D contains two K homology (KH) domains that provide RNA-binding capacity, and a C-terminal C3HC4-type RING-HC finger. Like other MEX-3 family proteins, MEX3D shuttles between the nucleus and the cytoplasm via the CRM1-dependent export pathway.


Pssm-ID: 438383 [Multi-domain]  Cd Length: 64  Bit Score: 36.43  E-value: 3.23e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2240474248 267 PSDDENSDNSNECVVCLSDLRDTLILPCRHLCLCNSCADTLRYQAN-NCPICRLP 320
Cdd:cd16723     1 SSSDGARKSARECVVCFESEVIAALVPCGHNLFCMECAIRICGKSEpECPACHTP 55
RING-HC_RING1-like cd16531
RING finger, HC subclass, found in really interesting new gene proteins RING1, RING2 and ...
279-334 3.26e-03

RING finger, HC subclass, found in really interesting new gene proteins RING1, RING2 and similar proteins; RING1, also known as polycomb complex protein RING1, RING finger protein 1 (RNF1), or RING finger protein 1A (RING1A), is a transcriptional repressor that is associated with the Polycomb group (PcG) protein complex involved in stable repression of gene activity. RING2, also known as huntingtin-interacting protein 2-interacting protein 3, HIP2-interacting protein 3, protein DinG, RING finger protein 1B (RING1B), RING finger protein 2 (RNF2), or RING finger protein BAP-1, is an E3 ubiquitin-protein ligase that interacts with both nucleosomal DNA and an acidic patch on histone H4 to achieve the specific monoubiquitination of K119 on histone H2A (H2AK119ub), thereby playing a central role in histone code and gene regulation. Both RING1 and RING2 are core components of polycomb repressive complex 1 (PRC1) that functions as an E3-ubuiquitin ligase transferring the mono-ubuiquitin mark to the C-terminal tail of Histone H2A at K118/K119. PRC1 is also capable of chromatin compaction, a function not requiring histone tails, and this activity appears important in gene silencing. RING2 acts as the main E3 ubiquitin ligase on histone H2A of the PRC1 complex, while RING1 may rather act as a modulator of RNF2/RING2 activity. Members of this family contain a C3HC4-type RING-HC finger.


Pssm-ID: 438193 [Multi-domain]  Cd Length: 66  Bit Score: 36.09  E-value: 3.26e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2240474248 279 CVVCLSDLRDTL-ILPCRHLcLCNSCADT-LRYQANNCPICRLPfraLLQIRAVRKKP 334
Cdd:cd16531     4 CPICLGIIKNTMtVKECLHR-FCAECIEKaLRLGNKECPTCRKH---LPSRRSLRPDP 57
RING-HC_MID1 cd16753
RING finger, HC subclass, found in midline-1 (MID1) and similar proteins; MID1, also known as ...
279-318 3.40e-03

RING finger, HC subclass, found in midline-1 (MID1) and similar proteins; MID1, also known as midin, midline 1 RING finger protein, putative transcription factor XPRF, RING finger protein 59 (RNF59), or tripartite motif-containing protein 18 (TRIM18), is a microtubule-associated E3 ubiquitin-protein ligase implicated in epithelial-mesenchymal differentiation, cell migration and adhesion, and programmed cell death along specific regions of the ventral midline during embryogenesis. It monoubiquinates the alpha4 subunit of protein phosphatase 2A (PP2A), promoting proteosomal degradation of the catalytic subunit of PP2A (PP2Ac) and preventing the A and B subunits from forming an active complex. It promotes allergen and rhinovirus-induced asthma through the inhibition of PP2A activity. It is strongly upregulated in cytotoxic lymphocytes (CTLs) and directs lytic granule exocytosis and cytotoxicity of killer T cells. Loss-of-function mutations in MID1 lead to the human X-linked Opitz G/BBB (XLOS) syndrome characterized by defective midline development during embryogenesis. MID1 belongs to the C-I subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, and a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. MID1 hetero-dimerizes in vitro with its paralog MID2.


Pssm-ID: 438411 [Multi-domain]  Cd Length: 72  Bit Score: 36.56  E-value: 3.40e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2240474248 279 CVVCLSDLRDTLILPCRHlCLCNSCADTL--RYQANN----------CPICR 318
Cdd:cd16753     8 CPICLELFEDPLLLPCAH-SLCFNCAHRIlvSHCASNesvesitafqCPTCR 58
RING-HC_PML_C-V cd16579
RING finger, HC subclass, found in promyelocytic leukemia protein (PML) and similar proteins; ...
279-320 4.01e-03

RING finger, HC subclass, found in promyelocytic leukemia protein (PML) and similar proteins; Protein PML, also known as RING finger protein 71 (RNF71) or tripartite motif-containing protein 19 (TRIM19), is predominantly a nuclear protein with a broad intrinsic antiviral activity. It is the eponymous component of PML nuclear bodies (PML NBs) and has been implicated in a wide variety of cell processes, including DNA damage signaling, apoptosis, and transcription. PML interferes with the replication of many unrelated viruses, including human immunodeficiency virus 1 (HIV-1), human foamy virus (HFV), poliovirus, influenza virus, rabies virus, EMCV, adeno-associated virus (AAV), and vesicular stomatitis virus (VSV). It also selectively interacts with misfolded proteins through distinct substrate recognition sites and conjugates these proteins with the small ubiquitin-like modifiers (SUMOs) through its SUMO ligase activity. PML belongs to the C-V subclass of the TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domain, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as an uncharacterized region positioned C-terminal to the RBCC domain.


Pssm-ID: 438241 [Multi-domain]  Cd Length: 52  Bit Score: 35.61  E-value: 4.01e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 2240474248 279 CVVCLSDLRDTLILPCRHlCLCNSCADTLRYQANN-----CPICRLP 320
Cdd:cd16579     7 CPGCKAEYKCPKLLPCLH-TVCSGCLEALAEQASEttefqCPICKAS 52
RING-HC_BARD1 cd16496
RING finger, HC subclass, found in BRCA1-associated RING domain protein 1 (BARD-1) and similar ...
275-327 4.15e-03

RING finger, HC subclass, found in BRCA1-associated RING domain protein 1 (BARD-1) and similar proteins; BARD-1 is a critical factor in BRCA1-mediated tumor suppression and may also serve as a target for tumorigenic lesions in some human cancers. It associates with BRCA1 (breast cancer-1) to form a heterodimeric BRCA1/BARD1 complex that is responsible for maintaining genomic stability through nuclear functions involving DNA damage signaling and repair, transcriptional regulation, and cell cycle control. The BRCA1/BARD1 complex catalyzes autoubiquitination of BRCA1 and trans ubiquitination of other protein substrates. Its E3 ligase activity is dramatically reduced in the presence of UBX domain protein 1 (UBXN1). BARD-1 contains an C3HC4-type RING-HC finger that binds BRCA1 at its N-terminus and three tandem ankyrin repeats and tandem BRCT repeat domains at its C-terminus. The BRCT repeats bind CstF-50 (cleavage stimulation factor) to modulate mRNA processing and RNAP II stability in response to DNA damage.


Pssm-ID: 438159 [Multi-domain]  Cd Length: 86  Bit Score: 36.54  E-value: 4.15e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2240474248 275 NSNECVVCLSDLRDTLIL-PCRHlCLCNSCADTlrYQANNCPICRLPFRA-LLQI 327
Cdd:cd16496    14 NLLRCSRCASILKEPVTLgGCEH-VFCRSCVGD--RLGNGCPVCDTPAWArDLQI 65
RING-H2_RNF44 cd16680
RING finger, H2 subclass, found in RING finger protein 44 (RNF44) and similar proteins; RNF44 ...
270-318 4.28e-03

RING finger, H2 subclass, found in RING finger protein 44 (RNF44) and similar proteins; RNF44 is an uncharacterized RING finger protein that shows high sequence similarity with RNF38, which is a nuclear E3 ubiquitin protein ligase that plays a role in regulating p53. RNF44 contains a coiled-coil motif, a KIL motif (Lys-X2-Ile/Leu-X2-Ile/Leu, X can be any amino acid), and a C3H2C2-type RING-H2 finger.


Pssm-ID: 438342 [Multi-domain]  Cd Length: 62  Bit Score: 35.81  E-value: 4.28e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2240474248 270 DENSDNSNECVVCLSDL--RDTL-ILPCRHLcLCNSCADTLRYQANNCPICR 318
Cdd:cd16680     1 ENHQSEQTLCVVCFSDFesRQLLrVLPCNHE-FHTKCVDKWLKTNRTCPICR 51
RING-HC_PEX10 cd16527
RING finger, HC subclass, found in peroxin-10 (PEX10) and similar proteins; PEX10, also known ...
279-322 4.93e-03

RING finger, HC subclass, found in peroxin-10 (PEX10) and similar proteins; PEX10, also known as peroxisome biogenesis factor 10, peroxisomal biogenesis factor 10, peroxisome assembly protein 10, or RING finger protein 69 (RNF69), is an integral peroxisomal membrane protein with two transmembrane regions and a C3HC4-type RING-HC finger within its cytoplasmically exposed C-terminus. It plays an essential role in peroxisome assembly, import of target substrates, and recycling or degradation of protein complexes and amino acids. It is an essential component of the spinal locomotor circuit, and thus its mutations may be involved in peroxisomal biogenesis disorders (PBD). Mutations in human PEX10 also result in autosomal recessive ataxia. Moreover, PEX10 functions as an E3-ubiquitin ligase with an E2, UBCH5C. It mono- or poly-ubiquitinates PEX5, a key player in peroxisomal matrix protein import, in a UBC4-dependent manner, to control PEX5 receptor recycling or degradation. It also links the E2 ubiquitin conjugating enzyme PEX4 to the protein import machinery of the peroxisome.


Pssm-ID: 438190 [Multi-domain]  Cd Length: 52  Bit Score: 35.28  E-value: 4.93e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 2240474248 279 CVVCLSDLRDTLILPCRHLcLCNSC-ADTLRYQAnNCPICRLPFR 322
Cdd:cd16527     3 CSLCLEERRHPTATPCGHL-FCWSCiTEWCNEKP-ECPLCREPFQ 45
vRING-HC-C4C4_RBBP6 cd16620
Variant RING finger, HC subclass (C4C4-type), found in retinoblastoma-binding protein 6 (RBBP6) ...
279-318 5.13e-03

Variant RING finger, HC subclass (C4C4-type), found in retinoblastoma-binding protein 6 (RBBP6) and similar proteins; RBBP6, also known as proliferation potential-related protein, protein P2P-R, retinoblastoma-binding Q protein 1 (RBQ-1), or p53-associated cellular protein of testis (PACT), is a nuclear E3 ubiquitin-protein ligase involved in multiple processes, such as the control of gene expression, mitosis, cell differentiation, and cell apoptosis. It plays a role in both promoting and inhibiting apoptosis in many human cancers, including esophageal, lung, hepatocellular, and colon cancers, familial myeloproliferative neoplasms, as well as in human immunodeficiency virus-associated nephropathy (HIVAN). It functions as an Rb- and p53-binding protein that plays an important role in chaperone-mediated ubiquitination and possibly in protein quality control. It acts as a scaffold protein to promote the assembly of the p53/TP53-MDM2 complex, resulting in an increase of MDM2-mediated ubiquitination and degradation of p53/TP53, and leading to both apoptosis and cell growth. It is also a double-stranded RNA-binding protein that plays a role in mRNA processing by regulating the human polyadenylation machinery and modulating expression of mRNAs with AU-rich 3' untranslated regions (UTRs). Moreover, RBBP6 ubiquitinates and destabilizes the transcriptional repressor ZBTB38 that negatively regulates transcription and levels of the MCM10 replication factor on chromatin. Furthermore, RBBP6 is involved in tunicamycin-induced apoptosis by mediating protein kinase (PKR) activation. RBBP6 contains an N-terminal ubiquitin-like domain and a C4C4-type RING finger, whose overall folding is similar to that of the typical C3HC4-type RING-HC finger. RBBP6 interacts with chaperones Hsp70 and Hsp40 through its N-terminal ubiquitin-like domain. It promotes the ubiquitination of p53 by Hdm2 in an E4-like manner through its RING finger. It also interacts directly with the pro-proliferative transcription factor Y-box-binding protein-1 (YB-1) via its RING finger.


Pssm-ID: 438282 [Multi-domain]  Cd Length: 55  Bit Score: 35.46  E-value: 5.13e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 2240474248 279 CVVCLSDLRDTLILPCRHLCLCNSCADT-LRYQANNCPICR 318
Cdd:cd16620     6 CPICKDLMKDAVLTPCCGNSFCDECIRTaLLEEDFTCPTCK 46
RING-H2_RNF111-like cd16474
RING finger, H2 subclass, found in RING finger proteins RNF111, RNF165, and similar proteins; ...
279-319 5.32e-03

RING finger, H2 subclass, found in RING finger proteins RNF111, RNF165, and similar proteins; The family includes RING finger proteins RNF111, RNF165, and similar proteins. RNF111, also known as Arkadia, is a nuclear E3 ubiquitin-protein ligase that targets intracellular effectors and modulators of transforming growth factor beta (TGF-beta)/Nodal-related signaling for polyubiquitination and proteasome-dependent degradation. It also interacts with the clathrin-adaptor 2 (AP2) complex and regulates endocytosis of certain cell surface receptors, leading to modulation of epidermal growth factor (EGF) and possibly other signaling pathways. The N-terminal half of RNF111 harbors three SUMO-interacting motifs (SIMs). It thus functions as a SUMO-targeted ubiquitin ligase (STUbL) that directly links nonproteolytic ubiquitylation and SUMOylation in the DNA damage response, as well as triggers degradation of signal-induced polysumoylated proteins, such as the promyelocytic leukemia protein (PML). RNF165, also known as Arkadia-like 2, Arkadia2, or Ark2C, is an E3 ubiquitin ligase with homology to the C-terminal half of RNF111. It is expressed specifically in the nervous system, and can serve to amplify neuronal responses to specific signals. It acts as a positive regulator of bone morphogenetic protein (BMP)-Smad signaling that is involved in motor neuron (MN) axon elongation. Both RNF165 and RNF111 contain a C-terminal C3H2C3-type RING-H2 finger.


Pssm-ID: 438137 [Multi-domain]  Cd Length: 46  Bit Score: 35.08  E-value: 5.32e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 2240474248 279 CVVCLSDLRDTLI---LPCRHLcLCNSCADTLRYQANNCPICRL 319
Cdd:cd16474     3 CTICLSDFEEGEDvrrLPCMHL-FHQECVDQWLSTNKRCPICRV 45
RING-H2 cd16448
H2 subclass of RING (RING-H2) fingers and its variants; The RING finger is a specialized type ...
279-318 5.89e-03

H2 subclass of RING (RING-H2) fingers 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 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). This family corresponds to the H2 subclass of RING (RING-H2) finger proteins that are characterized by containing C3H2C3-type canonical RING-H2 fingers or noncanonical RING-H2 finger variants, including C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type modified RING-H2 fingers. The canonical RING-H2 finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-H-X2-C-X(4-48)-C-X2-C, X is any amino acid and the number of X residues varies in different fingers. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-H2 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 serves as a scaffold 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: 438112 [Multi-domain]  Cd Length: 43  Bit Score: 34.68  E-value: 5.89e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 2240474248 279 CVVCLSDLRD---TLILPCRHL----CLcNSCadtLRYQANNCPICR 318
Cdd:cd16448     1 CVICLEEFEEgdvVRLLPCGHVfhlaCI-LRW---LESGNNTCPLCR 43
RING-HC_MEX3C cd16722
RING finger, HC subclass, found in RNA-binding protein MEX3C; MEX3C, also known as RING finger ...
277-327 5.90e-03

RING finger, HC subclass, found in RNA-binding protein MEX3C; MEX3C, also known as RING finger and KH domain-containing protein 2 (RKHD2), or RING finger protein 194 (RNF194), is an RNA-binding phosphoprotein that acts as a suppressor of chromosomal instability. It functions as an ubiquitin E3 ligase responsible for the post-transcriptional, HLA-A allotype-specific regulation of MHC class I molecules (MHC-I). It also modifies retinoic acid inducible gene-1 (RIG-I) in stress granules and plays a critical role in eliciting antiviral immune responses. Moreover, MEX3C plays an essential role in normal postnatal growth via enhancing the local expression of insulin-like growth factor 1 (IGF1) in bone. It may also be involved in metabolic regulation of energy balance. MEX3C contains two K homology (KH) domains that provide RNA-binding capacity, and a C-terminal C3HC4-type RING-HC finger. Like other MEX-3 family proteins, MEX3C shuttles between the nucleus and the cytoplasm via the CRM1-dependent export pathway.


Pssm-ID: 438382 [Multi-domain]  Cd Length: 55  Bit Score: 35.34  E-value: 5.90e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2240474248 277 NECVVCLSDLRDTLILPCRHLCLCNSCADTL-RYQANNCPICRLPFRALLQI 327
Cdd:cd16722     2 HDCVICFENEVIAALVPCGHNLFCMECANKIcEKETPSCPVCQTAVTQAIQI 53
RING-HC_TRIM40-C-V cd16583
RING finger, HC subclass, found in tripartite motif-containing protein 40 (TRIM40) and similar ...
272-320 7.29e-03

RING finger, HC subclass, found in tripartite motif-containing protein 40 (TRIM40) and similar proteins; TRIM40, also known as probable E3 NEDD8-protein ligase or RING finger protein 35 (RNF35), is highly expressed in the gastrointestinal tract including the stomach, small intestine, and large intestine. It enhances neddylation of inhibitor of nuclear factor kappaB kinase subunit gamma (IKKgamma), inhibits the activity of nuclear factor-kappaB (NF-kappaB)-mediated transcription, and thus prevents inflammation-associated carcinogenesis in the gastrointestinal tract. TRIM40 belongs to the C-V subclass of the TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domain, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as an uncharacterized region positioned C-terminal to the RBCC domain.


Pssm-ID: 438245 [Multi-domain]  Cd Length: 63  Bit Score: 35.19  E-value: 7.29e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2240474248 272 NSDNSNECVVCLSDLRDTLILPCRHL----CLCNSCADTLRYQANNCPICRLP 320
Cdd:cd16583     1 DSDEEGVCPICQEPLKEAVSTDCGHLfcrmCLTQHAKKASASGVFSCPVCRKP 53
RING-H2_RNF181 cd16669
RING finger, H2 subclass, found in RING finger protein 181 (RNF181) and similar proteins; ...
278-318 8.51e-03

RING finger, H2 subclass, found in RING finger protein 181 (RNF181) and similar proteins; RNF181, also known as HSPC238, is a platelet E3 ubiquitin-protein ligase containing a C3H2C3-type RING-H2 finger. It interacts with the KVGFFKR motif of platelet integrin alpha(IIb)beta3, suggesting a role for RNF181-mediated ubiquitination in integrin and platelet signaling. It also suppresses the tumorigenesis of hepatocellular carcinoma (HCC) through the inhibition of extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling in the liver.


Pssm-ID: 438331 [Multi-domain]  Cd Length: 46  Bit Score: 34.65  E-value: 8.51e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 2240474248 278 ECVVCLSDLRD---TLILPCRHlCLCNSCADTLRYQANNCPICR 318
Cdd:cd16669     1 KCPICLLEFEEgetVKQLPCKH-SFHSDCILPWLGKTNSCPLCR 43
RING-H2_RNF130 cd16803
RING finger, H2 subclass, found in RING finger protein 130 (RNF130) and similar proteins; ...
277-319 8.82e-03

RING finger, H2 subclass, found in RING finger protein 130 (RNF130) and similar proteins; RNF130, also known as Goliath homolog (H-Goliath), is a paralog of RNF128, also known as gene related to anergy in lymphocytes protein (GRAIL). It is a transmembrane E3 ubiquitin-protein ligase expressed in leukocytes. It has a self-ubiquitination property, and controls the development of T cell clonal anergy by ubiquitination. RNF130 contains an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence.


Pssm-ID: 319717 [Multi-domain]  Cd Length: 49  Bit Score: 34.56  E-value: 8.82e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 2240474248 277 NECVVCLS--DLRDTL-ILPCRHLcLCNSCADTLRYQANNCPICRL 319
Cdd:cd16803     1 DHCAVCIEgyKQNDVVrILPCKHV-FHKSCVDPWLNEHCTCPMCKL 45
RING-HC_RNF5-like cd16534
RING finger, HC subclass, found in RING finger protein RNF5, RNF185 and similar proteins; RNF5 ...
278-318 9.98e-03

RING finger, HC subclass, found in RING finger protein RNF5, RNF185 and similar proteins; RNF5 and RNF185 are E3 ubiquitin-protein ligases that are anchored to the outer membrane of the endoplasmic reticulum (ER). RNF5 acts at early stages of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) biosynthesis, and functions as a target for therapeutic modalities to antagonize mutant CFTR proteins in CF patients carrying the F508del allele. RNF185 controls the degradation of CFTR and CFTR F508del allele in a RING- and proteasome-dependent manner, but does not control that of other classical endoplasmic reticulum-associated degradation (ERAD) model substrates. Moreover, both RNF5 and RNF185 play important roles in cell adhesion and migration through the modulation of cell migration by ubiquitinating paxillin. Arabidopsis thaliana RING membrane-anchor proteins (AtRMAs) are also included in this family. They possess E3 ubiquitin-protein ligase activity and may play a role in the growth and development of Arabidopsis. All members of this family contain a C3HC4-type RING-HC finger.


Pssm-ID: 438196 [Multi-domain]  Cd Length: 44  Bit Score: 34.20  E-value: 9.98e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 2240474248 278 ECVVCLSDLRDTLILPCRHLcLCNSCADT---LRYQANNCPICR 318
Cdd:cd16534     2 ECNICLDTASDPVVTMCGHL-FCWPCLYQwleTRPDRQTCPVCK 44
 
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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