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Conserved domains on  [gi|38016196|ref|NP_937894|]
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E3 ubiquitin-protein ligase RNF133 [Mus musculus]

Protein Classification

RING-H2 finger protein( domain architecture ID 11550656)

RING-H2 finger protein may function as an E3 ubiquitin-protein ligase that mediates E2-dependent protein ubiquitination by bringing the ubiquitin-charged E2 ubiquitin-conjugating enzyme and the acceptor protein together to enable the direct transfer of ubiquitin

CATH:  3.30.40.10
EC:  2.3.2.27
Gene Ontology:  GO:0008270|GO:0016567|GO:0004842
PubMed:  11007473|19489725
SCOP:  3000160

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PA_GRAIL_like cd02122
PA _GRAIL_like: Protease-associated (PA) domain GRAIL-like. This group includes PA domain ...
43-159 2.66e-55

PA _GRAIL_like: Protease-associated (PA) domain GRAIL-like. This group includes PA domain containing E3 (ubiquitin ligases) similar to human GRAIL (gene related to anergy in lymphocytes) protein. Proteins in this group contain a C3H2C3 RING finger. E3 ubiquitin ligase is part of an enzymic cascade, the end result of which is the ubiquitination of proteins. In this cascade, E1 activates the ubiquitin, the activated ubiquitin is carried by E2, and E3 recognizes the acceptor protein as well as catalyzes the transfer of the activated ubiquitin from E2 to this acceptor. GRAIL, a transmembrane protein localized in the endosomes, controls the development of T cell clonal anergy, and may ubiquitinate membrane-associated targets for T cell activation. GRAIL1 is associated with, and regulated by, two isoforms of otubain 1 (the ubiquitin-specific protease). Additional E3s belonging to this group include human (h)Goliath and Xenopus GREUL1 (Goliath Related E3 Ubiquitin Ligase 1). hGoliath and GRAIL both have the property of self-ubiquitination. hGoliath is expressed in leukocytes; its expression and localization is not modified in leukemia. GREUL1 may play a role in the generation of anterior ectoderm. The significance of the PA domain to these proteins has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.


:

Pssm-ID: 239037 [Multi-domain]  Cd Length: 138  Bit Score: 177.11  E-value: 2.66e-55
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38016196  43 NISF--HVGNRMLSELGETGVFGRSSILKRVAGVVVPP-EGKIQNACDPNTTFILPRNKEPWIALIERGGCAFTQKIKVA 119
Cdd:cd02122   1 NITYvdPISNELTTEKTESGRYGEHSPKEEAKGLVVVPdPPNDHYGCDPDTRFPIPPNGEPWIALIQRGNCTFEEKIKLA 80
                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 38016196 120 SEHGARGVIIYNFPGTGNQVFPMSHQAFEDIVVVMIGNIK 159
Cdd:cd02122  81 AERNASAVVIYNNPGTGNETVKMSHPGTGDIVAIMITNPK 120
RING-H2_RNF128-like cd16802
RING finger, H2 subclass, found in RING finger protein 128 (RNF128) and similar proteins; This ...
211-259 2.51e-29

RING finger, H2 subclass, found in RING finger protein 128 (RNF128) and similar proteins; This subfamily includes RING finger proteins RNF128, RNF133, RNF148, and similar proteins, which belong to a larger PA-TM-RING ubiquitin ligase family that has been characterized by containing an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger followed by a putative PEST sequence. RNF128, also known as gene related to anergy in lymphocytes protein (GRAIL), is a type 1 transmembrane E3 ubiquitin-protein ligase that is a critical regulator of adaptive immunity and development. It inhibits cytokine gene transcription, is expressed in anergic CD4+ T cells, and has been implicated in primary T cell activation, survival, and differentiation, as well as in T cell anergy and oral tolerance. It induces T cell anergy through the ubiquitination activity of its cytosolic RING finger. It regulates expression of the costimulatory molecule CD40L on CD4 T cells, and ubiquitinates the costimulatory molecule CD40 ligand (CD40L) during the induction of T cell anergy. Moreover, RNF128 interacts with the luminal/extracellular portion of both CD151 and the related tetraspanin CD81 via its PA domain, which promoted ubiquitination of cytosolic lysine residues. It also down-modulates the expression of CD83 (previously described as a cell surface marker for mature dendritic cells) on CD4 T cells. Furthermore, Rho guanine dissociation inhibitor (RhoGDI) has been identified as a potential substrate of RNF128, suggesting a role for Rho effector molecules in T cell anergy. In addition, RNF128 plays a role in environmental stress responses. It promotes environmental salinity tolerance in euryhaline tilapia. RNF133 is a testis-specific endoplasmic reticulum-associated E3 ubiquitin ligase that is mainly present in the cytoplasm of elongated spermatids. It may play a role in sperm maturation through an ER-associated degradation (ERAD) pathway. RNF148 is a testis-specific E3 ubiquitin ligase that is abundantly expressed in testes and slightly expressed in pancreas. Its expression is regulated by histone deacetylases.


:

Pssm-ID: 438454 [Multi-domain]  Cd Length: 49  Bit Score: 106.75  E-value: 2.51e-29
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 38016196 211 DSCVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCKCDILK 259
Cdd:cd16802   1 DSCAVCIEPYKPNDVVRILTCNHLFHKNCIDPWLLEHRTCPMCKCDILK 49
HRD1 super family cl34953
HRD ubiquitin ligase complex, ER membrane component [Posttranslational modification, protein ...
161-254 1.62e-04

HRD ubiquitin ligase complex, ER membrane component [Posttranslational modification, protein turnover, chaperones];


The actual alignment was detected with superfamily member COG5243:

Pssm-ID: 227568 [Multi-domain]  Cd Length: 491  Bit Score: 43.42  E-value: 1.62e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38016196 161 YFTFYHIRRLWvarienrRWKRLTRELKKAFGQLQVRVLKEGDeevnpnaDSCVICFEA--YKPNEIV--------RILT 230
Cdd:COG5243 252 YALFRRIREHA-------RFRRATKDLNAMYPTATEEQLTNSD-------RTCTICMDEmfHPDHEPLprgldmtpKRLP 317
                        90       100
                ....*....|....*....|....
gi 38016196 231 CKHFFHKNCIDPWILAHGTCPMCK 254
Cdd:COG5243 318 CGHILHLHCLKNWLERQQTCPICR 341
 
Name Accession Description Interval E-value
PA_GRAIL_like cd02122
PA _GRAIL_like: Protease-associated (PA) domain GRAIL-like. This group includes PA domain ...
43-159 2.66e-55

PA _GRAIL_like: Protease-associated (PA) domain GRAIL-like. This group includes PA domain containing E3 (ubiquitin ligases) similar to human GRAIL (gene related to anergy in lymphocytes) protein. Proteins in this group contain a C3H2C3 RING finger. E3 ubiquitin ligase is part of an enzymic cascade, the end result of which is the ubiquitination of proteins. In this cascade, E1 activates the ubiquitin, the activated ubiquitin is carried by E2, and E3 recognizes the acceptor protein as well as catalyzes the transfer of the activated ubiquitin from E2 to this acceptor. GRAIL, a transmembrane protein localized in the endosomes, controls the development of T cell clonal anergy, and may ubiquitinate membrane-associated targets for T cell activation. GRAIL1 is associated with, and regulated by, two isoforms of otubain 1 (the ubiquitin-specific protease). Additional E3s belonging to this group include human (h)Goliath and Xenopus GREUL1 (Goliath Related E3 Ubiquitin Ligase 1). hGoliath and GRAIL both have the property of self-ubiquitination. hGoliath is expressed in leukocytes; its expression and localization is not modified in leukemia. GREUL1 may play a role in the generation of anterior ectoderm. The significance of the PA domain to these proteins has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.


Pssm-ID: 239037 [Multi-domain]  Cd Length: 138  Bit Score: 177.11  E-value: 2.66e-55
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38016196  43 NISF--HVGNRMLSELGETGVFGRSSILKRVAGVVVPP-EGKIQNACDPNTTFILPRNKEPWIALIERGGCAFTQKIKVA 119
Cdd:cd02122   1 NITYvdPISNELTTEKTESGRYGEHSPKEEAKGLVVVPdPPNDHYGCDPDTRFPIPPNGEPWIALIQRGNCTFEEKIKLA 80
                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 38016196 120 SEHGARGVIIYNFPGTGNQVFPMSHQAFEDIVVVMIGNIK 159
Cdd:cd02122  81 AERNASAVVIYNNPGTGNETVKMSHPGTGDIVAIMITNPK 120
RING-H2_RNF128-like cd16802
RING finger, H2 subclass, found in RING finger protein 128 (RNF128) and similar proteins; This ...
211-259 2.51e-29

RING finger, H2 subclass, found in RING finger protein 128 (RNF128) and similar proteins; This subfamily includes RING finger proteins RNF128, RNF133, RNF148, and similar proteins, which belong to a larger PA-TM-RING ubiquitin ligase family that has been characterized by containing an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger followed by a putative PEST sequence. RNF128, also known as gene related to anergy in lymphocytes protein (GRAIL), is a type 1 transmembrane E3 ubiquitin-protein ligase that is a critical regulator of adaptive immunity and development. It inhibits cytokine gene transcription, is expressed in anergic CD4+ T cells, and has been implicated in primary T cell activation, survival, and differentiation, as well as in T cell anergy and oral tolerance. It induces T cell anergy through the ubiquitination activity of its cytosolic RING finger. It regulates expression of the costimulatory molecule CD40L on CD4 T cells, and ubiquitinates the costimulatory molecule CD40 ligand (CD40L) during the induction of T cell anergy. Moreover, RNF128 interacts with the luminal/extracellular portion of both CD151 and the related tetraspanin CD81 via its PA domain, which promoted ubiquitination of cytosolic lysine residues. It also down-modulates the expression of CD83 (previously described as a cell surface marker for mature dendritic cells) on CD4 T cells. Furthermore, Rho guanine dissociation inhibitor (RhoGDI) has been identified as a potential substrate of RNF128, suggesting a role for Rho effector molecules in T cell anergy. In addition, RNF128 plays a role in environmental stress responses. It promotes environmental salinity tolerance in euryhaline tilapia. RNF133 is a testis-specific endoplasmic reticulum-associated E3 ubiquitin ligase that is mainly present in the cytoplasm of elongated spermatids. It may play a role in sperm maturation through an ER-associated degradation (ERAD) pathway. RNF148 is a testis-specific E3 ubiquitin ligase that is abundantly expressed in testes and slightly expressed in pancreas. Its expression is regulated by histone deacetylases.


Pssm-ID: 438454 [Multi-domain]  Cd Length: 49  Bit Score: 106.75  E-value: 2.51e-29
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 38016196 211 DSCVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCKCDILK 259
Cdd:cd16802   1 DSCAVCIEPYKPNDVVRILTCNHLFHKNCIDPWLLEHRTCPMCKCDILK 49
zf-RING_2 pfam13639
Ring finger domain;
211-254 9.13e-14

Ring finger domain;


Pssm-ID: 433370 [Multi-domain]  Cd Length: 44  Bit Score: 64.74  E-value: 9.13e-14
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 38016196   211 DSCVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCK 254
Cdd:pfam13639   1 DECPICLEEFEEGDKVVVLPCGHHFHRECLDKWLRSSNTCPLCR 44
RING smart00184
Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and ...
213-253 1.94e-08

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: 49.81  E-value: 1.94e-08
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 38016196    213 CVICFEAYKPNeiVRILTCKHFFHKNCIDPWILAHG-TCPMC 253
Cdd:smart00184   1 CPICLEEYLKD--PVILPCGHTFCRSCIRKWLESGNnTCPIC 40
COG5540 COG5540
RING-finger-containing ubiquitin ligase [Posttranslational modification, protein turnover, ...
213-257 5.55e-08

RING-finger-containing ubiquitin ligase [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 227827 [Multi-domain]  Cd Length: 374  Bit Score: 53.85  E-value: 5.55e-08
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 38016196 213 CVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHG-TCPMCKCDI 257
Cdd:COG5540 326 CAICMSNFIKNDRLRVLPCDHRFHVGCVDKWLLGYSnKCPVCRTAI 371
PA pfam02225
PA domain; The PA (Protease associated) domain is found as an insert domain in diverse ...
73-157 8.91e-08

PA domain; The PA (Protease associated) domain is found as an insert domain in diverse proteases. The PA domain is also found in a plant vacuolar sorting receptor Swiss:O22925 and members of the RZF family Swiss:O43567. It has been suggested that this domain forms a lid-like structure that covers the active site in active proteases, and is involved in protein recognition in vacuolar sorting receptors.


Pssm-ID: 460499 [Multi-domain]  Cd Length: 91  Bit Score: 49.43  E-value: 8.91e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38016196    73 GVVVPPEGkiQNACDPNTTFILPRNKepwIALIERGGCAFTQKIKVASEHGARGVIIYNFP----GTGNQVFPMSHQAFE 148
Cdd:pfam02225   2 GPLVLAPG--CYAGDGIPADFDVKGK---IVLVRCTFGFRAEKVRNAQAAGAAGVIIYNNVeglgGPPGAGGNELYPDGI 76

                  ....*....
gi 38016196   149 DIVVVMIGN 157
Cdd:pfam02225  77 YIPAVGVSR 85
T9SSA_dep_M36 NF038113
T9SS-dependent M36 family metallopeptidase; Members of this family have an M36 family ...
74-137 1.20e-06

T9SS-dependent M36 family metallopeptidase; Members of this family have an M36 family metallopeptidase domain, like fungalysin (see PF02128), and a C-terminal T9SS type A sorting domain (see TIGR04131).


Pssm-ID: 468356 [Multi-domain]  Cd Length: 868  Bit Score: 50.04  E-value: 1.20e-06
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 38016196   74 VVVPPEGKIQNACDPNTTfilPRNKEPWIALIERGGCAFTQKIKVASEHGARGVIIYN-FPGTGN 137
Cdd:NF038113 446 LATDSSPDPNDGCDPILN---AAALAGKIAVIRRGSCEFAVKVLNAQNAGAIAVIIVNnVPGEPI 507
myxo_dep_M36 NF038112
myxosortase-dependent M36 family metallopeptidase; Members of this bacterial protein family ...
74-131 5.90e-06

myxosortase-dependent M36 family metallopeptidase; Members of this bacterial protein family have an M36 family metallopeptidase domain, like fungalysin (see PF02128), and a C-terminal MYXO-CTERM domain (see TIGR03901), suggesting processing and surface-anchoring by the still-unknown putative transpeptidase, myxosortase. Members of this family include MXAN_3564 (mepA), part of the effector cargo of outer membrane vesicles that the species produces in large numbers during predation on other microbes.


Pssm-ID: 468355 [Multi-domain]  Cd Length: 1597  Bit Score: 48.11  E-value: 5.90e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 38016196    74 VVVPPEG--KIQNACDPNTtfilprNKEPW---IALIERGGCAFTQKIKVASEHGARGVIIYN 131
Cdd:NF038112  521 VVLAPDGtgSDTDGCTPFT------NAAEVagkIALIDRGTCDFTVKALNAQNAGAIGVIIAN 577
HRD1 COG5243
HRD ubiquitin ligase complex, ER membrane component [Posttranslational modification, protein ...
161-254 1.62e-04

HRD ubiquitin ligase complex, ER membrane component [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 227568 [Multi-domain]  Cd Length: 491  Bit Score: 43.42  E-value: 1.62e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38016196 161 YFTFYHIRRLWvarienrRWKRLTRELKKAFGQLQVRVLKEGDeevnpnaDSCVICFEA--YKPNEIV--------RILT 230
Cdd:COG5243 252 YALFRRIREHA-------RFRRATKDLNAMYPTATEEQLTNSD-------RTCTICMDEmfHPDHEPLprgldmtpKRLP 317
                        90       100
                ....*....|....*....|....
gi 38016196 231 CKHFFHKNCIDPWILAHGTCPMCK 254
Cdd:COG5243 318 CGHILHLHCLKNWLERQQTCPICR 341
 
Name Accession Description Interval E-value
PA_GRAIL_like cd02122
PA _GRAIL_like: Protease-associated (PA) domain GRAIL-like. This group includes PA domain ...
43-159 2.66e-55

PA _GRAIL_like: Protease-associated (PA) domain GRAIL-like. This group includes PA domain containing E3 (ubiquitin ligases) similar to human GRAIL (gene related to anergy in lymphocytes) protein. Proteins in this group contain a C3H2C3 RING finger. E3 ubiquitin ligase is part of an enzymic cascade, the end result of which is the ubiquitination of proteins. In this cascade, E1 activates the ubiquitin, the activated ubiquitin is carried by E2, and E3 recognizes the acceptor protein as well as catalyzes the transfer of the activated ubiquitin from E2 to this acceptor. GRAIL, a transmembrane protein localized in the endosomes, controls the development of T cell clonal anergy, and may ubiquitinate membrane-associated targets for T cell activation. GRAIL1 is associated with, and regulated by, two isoforms of otubain 1 (the ubiquitin-specific protease). Additional E3s belonging to this group include human (h)Goliath and Xenopus GREUL1 (Goliath Related E3 Ubiquitin Ligase 1). hGoliath and GRAIL both have the property of self-ubiquitination. hGoliath is expressed in leukocytes; its expression and localization is not modified in leukemia. GREUL1 may play a role in the generation of anterior ectoderm. The significance of the PA domain to these proteins has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.


Pssm-ID: 239037 [Multi-domain]  Cd Length: 138  Bit Score: 177.11  E-value: 2.66e-55
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38016196  43 NISF--HVGNRMLSELGETGVFGRSSILKRVAGVVVPP-EGKIQNACDPNTTFILPRNKEPWIALIERGGCAFTQKIKVA 119
Cdd:cd02122   1 NITYvdPISNELTTEKTESGRYGEHSPKEEAKGLVVVPdPPNDHYGCDPDTRFPIPPNGEPWIALIQRGNCTFEEKIKLA 80
                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 38016196 120 SEHGARGVIIYNFPGTGNQVFPMSHQAFEDIVVVMIGNIK 159
Cdd:cd02122  81 AERNASAVVIYNNPGTGNETVKMSHPGTGDIVAIMITNPK 120
RING-H2_RNF128-like cd16802
RING finger, H2 subclass, found in RING finger protein 128 (RNF128) and similar proteins; This ...
211-259 2.51e-29

RING finger, H2 subclass, found in RING finger protein 128 (RNF128) and similar proteins; This subfamily includes RING finger proteins RNF128, RNF133, RNF148, and similar proteins, which belong to a larger PA-TM-RING ubiquitin ligase family that has been characterized by containing an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger followed by a putative PEST sequence. RNF128, also known as gene related to anergy in lymphocytes protein (GRAIL), is a type 1 transmembrane E3 ubiquitin-protein ligase that is a critical regulator of adaptive immunity and development. It inhibits cytokine gene transcription, is expressed in anergic CD4+ T cells, and has been implicated in primary T cell activation, survival, and differentiation, as well as in T cell anergy and oral tolerance. It induces T cell anergy through the ubiquitination activity of its cytosolic RING finger. It regulates expression of the costimulatory molecule CD40L on CD4 T cells, and ubiquitinates the costimulatory molecule CD40 ligand (CD40L) during the induction of T cell anergy. Moreover, RNF128 interacts with the luminal/extracellular portion of both CD151 and the related tetraspanin CD81 via its PA domain, which promoted ubiquitination of cytosolic lysine residues. It also down-modulates the expression of CD83 (previously described as a cell surface marker for mature dendritic cells) on CD4 T cells. Furthermore, Rho guanine dissociation inhibitor (RhoGDI) has been identified as a potential substrate of RNF128, suggesting a role for Rho effector molecules in T cell anergy. In addition, RNF128 plays a role in environmental stress responses. It promotes environmental salinity tolerance in euryhaline tilapia. RNF133 is a testis-specific endoplasmic reticulum-associated E3 ubiquitin ligase that is mainly present in the cytoplasm of elongated spermatids. It may play a role in sperm maturation through an ER-associated degradation (ERAD) pathway. RNF148 is a testis-specific E3 ubiquitin ligase that is abundantly expressed in testes and slightly expressed in pancreas. Its expression is regulated by histone deacetylases.


Pssm-ID: 438454 [Multi-domain]  Cd Length: 49  Bit Score: 106.75  E-value: 2.51e-29
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 38016196 211 DSCVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCKCDILK 259
Cdd:cd16802   1 DSCAVCIEPYKPNDVVRILTCNHLFHKNCIDPWLLEHRTCPMCKCDILK 49
RING-H2_PA-TM-RING cd16454
RING finger, H2 subclass, found in the PA-TM-RING ubiquitin ligase family; The PA-TM-RING ...
212-254 1.51e-21

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: 85.79  E-value: 1.51e-21
                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 38016196 212 SCVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCK 254
Cdd:cd16454   1 TCAICLEEFKEGEKVRVLPCNHLFHKDCIDPWLEQHNTCPLCR 43
RING-H2_RNF130 cd16803
RING finger, H2 subclass, found in RING finger protein 130 (RNF130) and similar proteins; ...
211-259 1.90e-21

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: 85.79  E-value: 1.90e-21
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 38016196 211 DSCVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCKCDILK 259
Cdd:cd16803   1 DHCAVCIEGYKQNDVVRILPCKHVFHKSCVDPWLNEHCTCPMCKLNILK 49
RING-H2_RNF130-like cd16668
RING finger, H2 subclass, found in RING finger proteins, RNF130, RNF149, RNF150 and similar ...
213-257 5.59e-21

RING finger, H2 subclass, found in RING finger proteins, RNF130, RNF149, RNF150 and similar proteins; This subfamily includes RING finger proteins, RNF130, RNF149 and RNF150, which belong to a larger PA-TM-RING ubiquitin ligase family that has been characterized by 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. RNF130, also known as Goliath homolog (H-Goliath), is a paralog of RNF128. 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. RNF133 is a testis-specific endoplasmic reticulum-associated E3 ubiquitin ligase that may play a role in sperm maturation through an ER-associated degradation (ERAD) pathway. RNF149, also known as DNA polymerase-transactivated protein 2, is an E3 ubiquitin-protein ligase that induces the ubiquitination of wild-type v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) and promotes its proteasome-dependent degradation. RNF150 polymorphisms may be associated with chronic obstructive pulmonary disease (COPD) risk in the Chinese population. This subfamily also includes Drosophila melanogaster protein goliath (d-goliath), also known as protein g1, which is one of the founding members of the group. It was originally identified as a transcription factor involved in the embryo mesoderm formation.


Pssm-ID: 438330 [Multi-domain]  Cd Length: 46  Bit Score: 84.37  E-value: 5.59e-21
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 38016196 213 CVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCKCDI 257
Cdd:cd16668   2 CAVCIEPYKPSDVIRILPCKHIFHKSCVDPWLLEHRTCPMCKLDI 46
RING-H2_RNF149 cd16804
RING finger, H2 subclass, found in RING finger protein 149 (RNF149) and similar proteins; ...
212-259 4.91e-20

RING finger, H2 subclass, found in RING finger protein 149 (RNF149) and similar proteins; RNF149, also known as DNA polymerase-transactivated protein 2, is an E3 ubiquitin-protein ligase that interacts with wild-type v-Raf murine sarcoma viral oncogene homolog B1 (BRAF), a RING domain-containing E3 ubiquitin ligase involved in control of gene transcription, translation, cytoskeletal organization, cell adhesion, and epithelial development. RNF149 induces the ubiquitination of wild-type BRAF and promotes its proteasome-dependent degradation. Mutated RNF149 has been found in some human breast, ovarian, and colorectal cancers. RNF149 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: 438455 [Multi-domain]  Cd Length: 48  Bit Score: 81.87  E-value: 4.91e-20
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 38016196 212 SCVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCKCDILK 259
Cdd:cd16804   1 NCAVCIENYKSKDVVRILPCKHVFHRICIDPWLLEHRTCPMCKLDVIK 48
RING-H2_RNF150 cd16805
RING finger, H2 subclass, found in RING finger protein 150 (RNF150) and similar proteins; ...
205-259 5.65e-20

RING finger, H2 subclass, found in RING finger protein 150 (RNF150) and similar proteins; RNF150 is a RING finger protein and its polymorphisms may be associated with chronic obstructive pulmonary disease (COPD) risk in the Chinese population. Further studies with larger numbers of participants worldwide are needed for validation of the relationships between RNF150 genetic variants and the pathogenesis of COPD. RNF150 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: 438456 [Multi-domain]  Cd Length: 55  Bit Score: 82.02  E-value: 5.65e-20
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 38016196 205 EVNPNADSCVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCKCDILK 259
Cdd:cd16805   1 ETESDFDNCAVCIEGYKPNDVVRILPCRHLFHKSCVDPWLLDHRTCPMCKMNILK 55
RING-H2_SIS3 cd23118
RING finger, H2 subclass, found in Arabidopsis thaliana protein SUGAR INSENSITIVE 3 (SIS3) and ...
211-257 1.89e-18

RING finger, H2 subclass, found in Arabidopsis thaliana protein SUGAR INSENSITIVE 3 (SIS3) and similar proteins; SIS3 is an E3 ubiquitin-protein ligase that acts as a positive regulator of sugar signaling during early seedling development. SIS3 contains a C3H2C3-type RING-H2 finger.


Pssm-ID: 438480 [Multi-domain]  Cd Length: 47  Bit Score: 77.79  E-value: 1.89e-18
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 38016196 211 DSCVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCKCDI 257
Cdd:cd23118   1 KTCTICLEDFEDGEKLRVLPCQHQFHSECVDQWLRRNPKCPVCRRDA 47
RING-H2_RNF215 cd16670
RING finger, H2 subclass, found in RING finger protein 215 (RNF215) and similar proteins; This ...
211-258 1.27e-16

RING finger, H2 subclass, found in RING finger protein 215 (RNF215) and similar proteins; This family includes uncharacterized protein RNF215 and similar proteins. Although its biological function remains unclear, RNF215 shares high sequence similarity with PA-TM-RING ubiquitin ligases, which have been characterized by containing an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger.


Pssm-ID: 438332 [Multi-domain]  Cd Length: 50  Bit Score: 72.87  E-value: 1.27e-16
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 38016196 211 DSCVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCKCDIL 258
Cdd:cd16670   1 ESCAVCLDQFYKNQCLRVLPCLHEFHRDCVDPWLLLQQTCPLCKRNIL 48
RING-H2_RNF103 cd16473
RING finger, H2 subclass, found in RING finger protein 103 (RNF103) and similar proteins; ...
211-260 6.66e-16

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: 70.77  E-value: 6.66e-16
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 38016196 211 DSCVICFEAYKPNEIVRILTCKHFFHKNCIDPWILA-HGTCPMCKCDILKA 260
Cdd:cd16473   5 EECAICLENYQNGDLLRGLPCGHVFHQNCIDVWLERdNHCCPVCRWPVYKD 55
RING-H2_RNF11 cd16468
RING finger, H2 subclass, found in RING finger protein 11 (RNF11) and similar proteins; RNF11 ...
213-254 1.50e-14

RING finger, H2 subclass, found in RING finger protein 11 (RNF11) and similar proteins; RNF11 is an E3 ubiquitin-protein ligase that acts both as an adaptor and a modulator of itch-mediated control of ubiquitination events underlying membrane traffic. It acts downstream of an enzymatic cascade for the ubiquitination of specific substrates. It is also a molecular adaptor of homologous to E6-associated protein C-terminus (HECT)-type ligases. RNF11 has been implicated in the regulation of several signaling pathways. It enhances transforming growth factor receptor (TGFR) signaling by both abrogating Smurf2-mediated receptor ubiquitination and by promoting the Smurf2-mediated degradation of AMSH (associated molecule with the SH3 domain of STAM), a de-ubiquitinating enzyme that enhances TGF-beta signaling and epidermal growth factor receptor (EGFR) endosomal recycling. It also acts directly on Smad4 to enhance Smad4 function, and plays a role in prolonged TGF-beta signaling. RNF11 also functions as a critical component of the A20 ubiquitin-editing protein complex that negatively regulates tumor necrosis factor (TNF)-mediated nuclear factor (NF)-kappaB activation. It interacts with Smad anchor for receptor activation (SARA) and the endosomal sorting complex required for transport (ESCRT)-0 complex, thus participating in the regulation of lysosomal degradation of EGFR. RNF11 acts as a novel GGA cargo actively participating in regulating the ubiquitination of the GGA protein family. RNF11 functions together with TAX1BP1 to target TANK-binding kinase 1 (TBK1)/IkappaB kinase IKKi, and further restricts antiviral signaling and type I interferon (IFN)-beta production. RNF11 contains an N-terminal PPPY motif that binds WW domain-containing proteins such as AIP4/itch, Nedd4 and Smurf1/2 (SMAD-specific E3 ubiquitin-protein ligase 1/2), and a C-terminal C3H2C3-type RING-H2 finger that functions as a scaffold for the coordinated transfer of ubiquitin to substrate proteins together with the E2 enzymes UbcH527 and Ubc13.


Pssm-ID: 438131 [Multi-domain]  Cd Length: 43  Bit Score: 67.00  E-value: 1.50e-14
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 38016196 213 CVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCK 254
Cdd:cd16468   2 CVICMADFVVGDPIRYLPCMHIYHVDCIDDWLMRSFTCPSCM 43
zf-RING_2 pfam13639
Ring finger domain;
211-254 9.13e-14

Ring finger domain;


Pssm-ID: 433370 [Multi-domain]  Cd Length: 44  Bit Score: 64.74  E-value: 9.13e-14
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 38016196   211 DSCVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCK 254
Cdd:pfam13639   1 DECPICLEEFEEGDKVVVLPCGHHFHRECLDKWLRSSNTCPLCR 44
RING-H2_RNF43-like cd16666
RING finger, H2 subclass, found in RING finger proteins RNF43, ZNRF3, and similar proteins; ...
212-256 1.05e-13

RING finger, H2 subclass, found in RING finger proteins RNF43, ZNRF3, and similar proteins; RNF43 and ZNRF3 (also known as RNF203) are transmembrane E3 ubiquitin-protein ligases that belong to the PA-TM-RING ubiquitin ligase family, characterized by containing an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C3H2C3-type RING-H2 finger followed by a long C-terminal region. Both RNF43 and RNF203 function as tumor suppressors involved in the regulation of Wnt/beta-catenin signaling. They negatively regulate Wnt signaling by interacting with complexes of frizzled (FZD) receptors and low-density lipoprotein receptor-related protein (LRP) 5/6, which leads to ubiquitination of FZD and endocytosis of the Wnt receptor. Dishevelled (DVL), a positive Wnt regulator, is required for ZNRF3/RNF43-mediated ubiquitination and degradation of FZD. They also associate with R-spondin 1 (RSPO1). This interaction may block FZD ubiquitination and enhances Wnt signaling.


Pssm-ID: 438328 [Multi-domain]  Cd Length: 45  Bit Score: 64.41  E-value: 1.05e-13
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 38016196 212 SCVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCKCD 256
Cdd:cd16666   1 VCAICLEEYEEGQELRVLPCQHEFHRKCVDPWLLQNHTCPLCLFN 45
RING-H2_RNF38-like cd16472
RING finger, H2 subclass, found in RING finger proteins RNF38, RNF44, and similar proteins; ...
212-254 1.44e-13

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: 64.27  E-value: 1.44e-13
                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 38016196 212 SCVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCK 254
Cdd:cd16472   4 QCVVCMCDYEKRQLLRVLPCSHEFHAKCIDKWLKTNRTCPICR 46
RING-H2_RNF126-like cd16667
RING finger, H2 subclass, found in RING finger proteins RNF126, RNF115, and similar proteins; ...
213-254 3.87e-13

RING finger, H2 subclass, found in RING finger proteins RNF126, RNF115, and similar proteins; This subfamily includes RING finger proteins RNF126, RNF115, and similar proteins. RNF126 is a Bag6-dependent E3 ubiquitin ligase that is involved in the mislocalized protein (MLP) pathway of quality control. It regulates the retrograde sorting of the cation-independent mannose 6-phosphate receptor (CI-MPR). RNF126 promotes cancer cell proliferation by targeting the tumor suppressor p21 for ubiquitin-mediated degradation, and could be a novel therapeutic target in breast and prostate cancers. It is also able to ubiquitylate cytidine deaminase (AID), a poorly soluble protein that is essential for antibody diversification. RNF115, also known as Rab7-interacting ring finger protein (Rabring 7), or zinc finger protein 364 (ZNF364), or breast cancer-associated gene 2 (BCA2), is an E3 ubiquitin-protein ligase that is an endogenous inhibitor of adenosine monophosphate-activated protein kinase (AMPK) activation; this inhibition increases the efficacy of metformin in breast cancer cells. It also functions as a cofactor in the restriction imposed by tetherin on HIV-1, and targets HIV-1 Gag for lysosomal degradation, impairing virus assembly and release, in a tetherin-independent manner. Moreover, RNF115 is a Rab7-binding protein that stimulates c-Myc degradation through mono-ubiquitination of MM-1. It also plays crucial roles as a Rab7 target protein in vesicle traffic to late endosome/lysosome and lysosome biogenesis. RNF115 and RNF126 associate with the epidermal growth factor receptor (EGFR) and promote ubiquitylation of EGFR, suggesting they play a role in the ubiquitin-dependent sorting and downregulation of membrane receptors. Both of them contain an N-terminal BCA2 Zinc-finger domain (BZF), AKT-phosphorylation sites, and a C-terminal C3H2C3-type RING-H2 finger.


Pssm-ID: 438329 [Multi-domain]  Cd Length: 43  Bit Score: 63.09  E-value: 3.87e-13
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 38016196 213 CVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCK 254
Cdd:cd16667   2 CAVCKEDFEVGEEVRQLPCKHLFHPDCIVPWLELHNSCPVCR 43
RING-H2_EL5-like cd16461
RING finger, H2 subclass, found in rice E3 ubiquitin-protein ligase EL5 and similar proteins; ...
212-253 5.84e-13

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: 62.28  E-value: 5.84e-13
                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 38016196 212 SCVICFEAYKPNEIVRIL-TCKHFFHKNCIDPWILAHGTCPMC 253
Cdd:cd16461   1 ECAICLSDYENGEELRRLpECKHAFHKECIDEWLKSNSTCPLC 43
RING-H2_RNF43 cd16798
RING finger, H2 subclass, found in RING finger protein 43 (RNF43) and similar proteins; RNF43 ...
213-259 6.20e-13

RING finger, H2 subclass, found in RING finger protein 43 (RNF43) and similar proteins; RNF43 is a transmembrane E3 ubiquitin-protein ligase that plays an important role in frizzled (FZD)-dependent regulation of the Wnt/beta-catenin pathway. It functions as a tumor suppressor that inhibits Wnt/beta-catenin signaling by ubiquitinating FZD receptor and targeting it to the lysosomal pathway for degradation. miR-550a-5p directly targeted the 3'-UTR of gene RNF43 and regulated its expression. Moreover, RNF43 interacts with NEDD-4-like ubiquitin-protein ligase-1 (NEDL1) and regulates p53-mediated transcription. It may also be involved in cell growth control through the interaction with HAP95, a chromatin-associated protein interfacing the nuclear envelope. Mutations of RNF43 have been identified in various tumors, including colorectal cancer (CRC), endometrial cancer, mucinous ovarian tumors, gastric adenocarcinoma, pancreatic ductal adenocarcinoma, liver fluke-associated cholangiocarcinoma, hepatocellular carcinoma, and glioma. RNF43 contains an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C3H2C3-type RING-H2 finger followed by a long C-terminal region.


Pssm-ID: 438451 [Multi-domain]  Cd Length: 53  Bit Score: 62.57  E-value: 6.20e-13
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 38016196 213 CVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCKCDILK 259
Cdd:cd16798   6 CAICLEEFSEGQELRIISCSHEFHRECVDPWLHQHRTCPLCMFNIIE 52
RING-H2_RNF24-like cd16469
RING finger, H2 subclass, found in RING finger proteins RNF24, RNF122, and similar proteins; ...
211-254 8.66e-13

RING finger, H2 subclass, found in RING finger proteins RNF24, RNF122, and similar proteins; This subfamily includes RNF24, RNF122, and similar proteins. RNF24 is an intrinsic membrane protein localized in the Golgi apparatus. It specifically interacts with the ankyrin-repeats domains (ARDs) of TRPC1, -3, -4, -5, -6, and -7, and affects TRPC intracellular trafficking without affecting their activity. RNF122 is a RING finger protein associated with HEK 293T cell viability. It is localized to the endoplasmic reticulum (ER) and the Golgi apparatus, and overexpressed in anaplastic thyroid cancer cells. RNF122 functions as an E3 ubiquitin ligase that can ubiquitinate itself and undergo degradation through its RING finger in a proteasome-dependent manner. Both RNF24 and RNF122 contain an N-terminal transmembrane domain and a C-terminal C3H2C3-type RING-H2 finger.


Pssm-ID: 438132 [Multi-domain]  Cd Length: 47  Bit Score: 62.02  E-value: 8.66e-13
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 38016196 211 DSCVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCK 254
Cdd:cd16469   1 DTCAVCLEEFKLKEELGVCPCGHAFHTKCLKKWLEVRNSCPICK 44
RING-H2 cd16448
H2 subclass of RING (RING-H2) fingers and its variants; The RING finger is a specialized type ...
213-254 1.71e-12

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: 61.26  E-value: 1.71e-12
                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 38016196 213 CVICFEAYKPNEIVRILTCKHFFHKNCIDPWI-LAHGTCPMCK 254
Cdd:cd16448   1 CVICLEEFEEGDVVRLLPCGHVFHLACILRWLeSGNNTCPLCR 43
PA_C_RZF_like cd02123
PA_C-RZF_ like: Protease-associated (PA) domain C_RZF-like. This group includes various PA ...
73-165 2.75e-12

PA_C-RZF_ like: Protease-associated (PA) domain C_RZF-like. This group includes various PA domain-containing proteins similar to C-RZF (chicken embryo RING zinc finger) protein. These proteins contain a C3H2C3 RING finger. C-RZF is expressed in embryo cells and is restricted mainly to brain and heart, it is localized to both the nucleus and endosomes. Additional C3H2C3 RING finger proteins belonging to this group, include Arabidopsis ReMembR-H2 protein and mouse sperizin. ReMembR-H2 is likely to be an integral membrane protein, and to traffic through the endosomal pathway. Sperizin is expressed in haploid germ cells and localized in the cytoplasm, it may participate in spermatogenesis. The significance of the PA domain to these proteins has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.


Pssm-ID: 239038 [Multi-domain]  Cd Length: 153  Bit Score: 63.90  E-value: 2.75e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38016196  73 GVVVPPEGKI--------QNACDPNTTFILPRNK-EPWIALIERGGCAFTQKIKVASEHGARGVIIYNFpgTGNQVFPMS 143
Cdd:cd02123  32 GPIPPGSGLKgvlvvaepLNACSPIENPPLNSNAsGSFIVLIRRGNCSFETKVRNAQRAGYKAAIVYND--ESNDLISMS 109
                        90       100       110
                ....*....|....*....|....*....|.
gi 38016196 144 HQAFE----DIVVVMIGN-----IKAYFTFY 165
Cdd:cd02123 110 GNDQEikgiDIPSVFVGKstgeiLKKYASYE 140
RING-H2_PJA1_2 cd16465
RING finger, H2 subclass, found in protein E3 ubiquitin-protein ligase Praja-1, Praja-2, and ...
212-255 4.64e-12

RING finger, H2 subclass, found in protein E3 ubiquitin-protein ligase Praja-1, Praja-2, and similar proteins; This family includes two highly similar E3 ubiquitin-protein ligases, Praja-1 and Praja-2. Praja-1, also known as RING finger protein 70, is a RING-H2 finger ubiquitin ligase encoded by gene PJA1, a novel human X chromosome gene abundantly expressed in the brain. It has been implicated in bone and liver development, as well as memory formation and X-linked mental retardation (MRX). Praja-1 interacts with and activates the ubiquitin-conjugating enzyme UbcH5B, and shows E2-dependent E3 ubiquitin ligase activity. It is a 3-deazaneplanocin A (DZNep)-induced ubiquitin ligase that directly ubiquitinates individual polycomb repressive complex 2 (PRC2) subunits in a cell free system, which leads to their proteasomal degradation. It also plays an important role in neuronal plasticity, which is the basis for learning and memory. Moreover, Praja-1 ubiquitinates embryonic liver fodrin (ELF) and Smad3, but not Smad4, in a transforming growth factor-beta (TGF-beta)-dependent manner. It controls ELF abundance through ubiquitin-mediated degradation, and further regulates TGF-beta signaling, which plays a key role in the suppression of gastric carcinoma. Praja-1 also regulates the transcription function of the homeodomain protein Dlx5 by controlling the stability of Dlxin-1, via a ubiquitin-dependent degradation pathway. Praja-2, also known as RING finger protein 131, NEURODAP1, or KIAA0438, is an E2-dependent E3 ubiquitin ligase that interacts with and activates the ubiquitin-conjugating enzyme UbcH5B. It functions as an A-kinase anchoring protein (AKAP)-like E3 ubiquitin ligase that plays a critical role in controlling cyclic AMP (cAMP)-dependent PKA activity and pro-survival signaling, and further promotes cell proliferation and growth. Praja-2 is also involved in protein sorting at the postsynaptic density region of axosomatic synapses and possibly plays a role in synaptic communication and plasticity. Together with the AMPK-related kinase SIK2 and the CDK5 activator CDK5R1/p35, it forms a SIK2-p35-PJA2 complex that plays an essential role for glucose homeostasis in pancreatic beta cell functional compensation. Praja-2 ubiquitylates and degrades Mob, a core component of NDR/LATS kinase and a positive regulator of the tumor-suppressor Hippo signaling. Both Praja-1 and Praja-2 contain a potential nuclear localization signal (NLS) and a C-terminal C3H2C3-type RING-H2 motif.


Pssm-ID: 438128 [Multi-domain]  Cd Length: 46  Bit Score: 60.16  E-value: 4.64e-12
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 38016196 212 SCVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCKC 255
Cdd:cd16465   1 CCPICCSEYVKDEIATELPCHHLFHKPCITAWLQKSGTCPVCRH 44
RING-H2_RNF44 cd16680
RING finger, H2 subclass, found in RING finger protein 44 (RNF44) and similar proteins; RNF44 ...
213-256 4.77e-12

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: 60.47  E-value: 4.77e-12
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 38016196 213 CVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCKCD 256
Cdd:cd16680  10 CVVCFSDFESRQLLRVLPCNHEFHTKCVDKWLKTNRTCPICRAD 53
RING-H2_RNF115 cd16800
RING finger, H2 subclass, found in RING finger protein 115 (RNF115) and similar proteins; ...
213-254 8.50e-12

RING finger, H2 subclass, found in RING finger protein 115 (RNF115) and similar proteins; RNF115, also known as Rab7-interacting ring finger protein (Rabring 7), or zinc finger protein 364 (ZNF364), or breast cancer-associated gene 2 (BCA2), is an E3 ubiquitin-protein ligase that is an endogenous inhibitor of adenosine monophosphate-activated protein kinase (AMPK) activation and its inhibition increases the efficacy of metformin in breast cancer cells. It also functions as a co-factor in the restriction imposed by tetherin on HIV-1, and targets HIV-1 Gag for lysosomal degradation, impairing virus assembly and release, in a tetherin-independent manner. Moreover, RNF115 is a Rab7-binding protein that stimulates c-Myc degradation through mono-ubiquitination of MM-1. It also plays crucial roles as a Rab7 target protein in vesicle traffic to late endosome/lysosome and lysosome biogenesis. Furthermore, RNF115 and the related protein, RNF126 associate with the epidermal growth factor receptor (EGFR) and promote ubiquitylation of EGFR, suggesting they play a role in the ubiquitin-dependent sorting and downregulation of membrane receptors. RNF115 contains an N-terminal BCA2 Zinc-finger domain (BZF), the AKT-phosphorylation sites, and the C-terminal C3H2C3-type RING-H2 finger.


Pssm-ID: 438452 [Multi-domain]  Cd Length: 50  Bit Score: 59.57  E-value: 8.50e-12
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 38016196 213 CVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCK 254
Cdd:cd16800   3 CPVCKEDYTVGEQVRQLPCNHFFHSDCIVPWLELHDTCPVCR 44
RING-H2_DZIP3 cd16460
RING finger, H2 subclass, found in DAZ (deleted in azoospermia)-interacting protein 3 (DZIP3) ...
213-254 9.86e-12

RING finger, H2 subclass, found in DAZ (deleted in azoospermia)-interacting protein 3 (DZIP3) and similar proteins; DZIP3, also known as RNA-binding ubiquitin ligase of 138 kDa (RUL138) or 2A-HUB protein, is an RNA-binding E3 ubiquitin-protein ligase that interacts with coactivator-associated arginine methyltransferase 1 (CARM1) and acts as a transcriptional coactivator of estrogen receptor (ER) alpha. It is also a histone H2A ubiquitin ligase that catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatorial component of the repression machinery required for repressing a specific chemokine gene expression program, critically modulating migratory responses to Toll-like receptors (TLR) activation. DZIP3 contains a C3H2C3-type RING-H2 finger at the C-terminus.


Pssm-ID: 438123 [Multi-domain]  Cd Length: 47  Bit Score: 59.09  E-value: 9.86e-12
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 38016196 213 CVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCK 254
Cdd:cd16460   3 CVICHEAFSDGDRLLVLPCAHKFHTQCIGPWLDGQQTCPTCR 44
RING-H2_RNF167 cd16797
RING finger, H2 subclass, found in RING finger protein 167 (RNF167) and similar proteins; ...
211-254 1.14e-11

RING finger, H2 subclass, found in RING finger protein 167 (RNF167) and similar proteins; RNF167, also known as RING105, is an endosomal/lysosomal E3 ubiquitin-protein ligase involved in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) ubiquitination. It ubiquitinates AMPA-type glutamate receptor subunit GluA2 and regulates its surface expression, and thus acts as a selective regulator of AMPAR-mediated neurotransmission. It acts as an endosomal membrane protein which ubiquitylates vesicle-associated membrane protein 3 (VAMP3) and regulates endosomal trafficking. Moreover, RNF167 plays a role in the regulation of TSSC5 (tumor-suppressing subchromosomal transferable fragment cDNA, also known as ORCTL2/IMPT1/BWR1A/SLC22A1L), which can function in concert with the ubiquitin-conjugating enzyme UbcH6. RNF167 is widely conserved in metazoans and contains an N-terminal signal peptide, a protease-associated (PA) domain, two transmembrane domains (TM1 and TM2), and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence.


Pssm-ID: 319711 [Multi-domain]  Cd Length: 46  Bit Score: 58.90  E-value: 1.14e-11
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 38016196 211 DSCVICFEAYKPNEIVRILTCKHFFHKNCIDPWIL-AHGTCPMCK 254
Cdd:cd16797   1 DVCAICLDEYEEGDKLRVLPCSHAYHSKCVDPWLTqTKKTCPVCK 45
RING-H2_RNF111-like cd16474
RING finger, H2 subclass, found in RING finger proteins RNF111, RNF165, and similar proteins; ...
211-256 1.54e-11

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: 58.57  E-value: 1.54e-11
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 38016196 211 DSCVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCKCD 256
Cdd:cd16474   1 EKCTICLSDFEEGEDVRRLPCMHLFHQECVDQWLSTNKRCPICRVD 46
PA cd00538
PA: Protease-associated (PA) domain. The PA domain is an insert domain in a diverse fraction ...
53-157 2.02e-11

PA: Protease-associated (PA) domain. The PA domain is an insert domain in a diverse fraction of proteases. The significance of the PA domain to many of the proteins in which it is inserted is undetermined. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate. Proteins into which the PA domain is inserted include the following: i) various signal peptide peptidases including, hSPPL2a and 2b which catalyze the intramembrane proteolysis of tumor necrosis factor alpha, ii) various proteins containing a C3H2C3 RING finger including, Arabidopsis ReMembR-H2 protein and various E3 ubiquitin ligases such as human GRAIL (gene related to anergy in lymphocytes), iii) EDEM3 (ER-degradation-enhancing mannosidase-like 3 protein), iv) various plant vacuolar sorting receptors such as Pisum sativum BP-80, v) glutamate carboxypeptidase II (GCPII), vi) yeast aminopeptidase Y, vii) Vibrio metschnikovii VapT, a sodium dodecyl sulfate (SDS) resistant extracellular alkaline serine protease, viii) lactocepin (a cell envelope-associated protease from Lactobacillus paracasei subsp. paracasei NCDO 151), ix) various subtilisin-like proteases such as melon Cucumisin, and x) human TfR (transferrin receptor) 1 and 2.


Pssm-ID: 238300 [Multi-domain]  Cd Length: 126  Bit Score: 60.61  E-value: 2.02e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38016196  53 LSELGETGVFGRSSILKRVAGVVVPPegkiQNACDPNTTFILPRNKEPWIALIERGGCAFTQKIKVASEHGARGVIIYN- 131
Cdd:cd00538   4 LATTGYAGSALLFNPPSSPVGVVAGP----LVGCGYGTTDDSGADVKGKIVLVRRGGCSFSEKVKNAQKAGAKAVIIYNn 79
                        90       100
                ....*....|....*....|....*..
gi 38016196 132 -FPGTGNQVFPMSHQAFEDIVVVMIGN 157
Cdd:cd00538  80 gDDPGPQMGSVGLESTDPSIPTVGISY 106
RING-H2_RNF13-like cd16665
RING finger, H2 subclass, found in RING finger protein 13 (RNF13), RING finger protein 167 ...
211-254 2.27e-11

RING finger, H2 subclass, found in RING finger protein 13 (RNF13), RING finger protein 167 (RNF167), and similar proteins; This subfamily includes RING finger protein 13 (RNF13), RING finger protein 167 (RNF167), Zinc/RING finger protein 4 (ZNRF4), and similar proteins, which belong to a larger PA-TM-RING ubiquitin ligase family that has been characterized by containing an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane domain (TM), and a C-terminal C3H2C3-type RING-H2 finger followed by a putative PEST sequence. RNF13 is a widely expressed membrane-associated E3 ubiquitin-protein ligase that functions in the regulation of cancer development, muscle cell growth, and neuronal development. Its expression is developmentally regulated during myogenesis and is upregulated in various tumors. RNF13 negatively regulates cell proliferation through its E3 ligase activity. RNF167, also known as RING105, is an endosomal/lysosomal E3 ubiquitin-protein ligase involved in the ubiquitination of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR). It acts as an endosomal membrane protein which ubiquitylates vesicle-associated membrane protein 3 (VAMP3) and regulates endosomal trafficking. Moreover, RNF167 plays a role in the regulation of TSSC5 (tumor-suppressing subchromosomal transferable fragment cDNA, also known as ORCTL2/IMPT1/BWR1A/SLC22A1L), which can function in concert with the ubiquitin-conjugating enzyme UbcH6. ZNRF4, also known as RING finger protein 204 (RNF204), or Nixin, is an endoplasmic reticulum (ER) membrane-anchored ubiquitin ligase that physically interacts with the ER-localized chaperone calnexin in a glycosylation-independent manner, inducing calnexin ubiquitination, and p97-dependent degradation. The murine protein sperizin (spermatid-specific ring zinc finger) is a homolog of human ZNRF4. It is specifically expressed in Haploid germ cells and is involved in spermatogenesis.


Pssm-ID: 438327 [Multi-domain]  Cd Length: 46  Bit Score: 58.21  E-value: 2.27e-11
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 38016196 211 DSCVICFEAYKPNEIVRILTCKHFFHKNCIDPWIL-AHGTCPMCK 254
Cdd:cd16665   1 DVCAICLDDYEEGDKLRILPCSHAYHCKCIDPWLTkNKRTCPVCK 45
RING-H2_RNF126 cd16801
RING finger, H2 subclass, found in RING finger protein 126 (RNF126) and similar proteins; ...
213-254 2.44e-11

RING finger, H2 subclass, found in RING finger protein 126 (RNF126) and similar proteins; RNF126 is a Bag6-dependent E3 ubiquitin ligase that is involved in the mislocalized protein (MLP) pathway of quality control. It regulates the retrograde sorting of the cation-independent mannose 6-phosphate receptor (CI-MPR). Moreover, RNF126 promotes cancer cell proliferation by targeting the tumor suppressor p21 for ubiquitin-mediated degradation, and could be a novel therapeutic target in breast and prostate cancers. It is also able to ubiquitylate cytidine deaminase (AID), a poorly soluble protein that is essential for antibody diversification. In addition, RNF126 and the related protein, RNF115 associate with the epidermal growth factor receptor (EGFR) and promote ubiquitylation of EGFR, suggesting they play a role in the ubiquitin-dependent sorting and downregulation of membrane receptors. RNF126 contains an N-terminal BCA2 Zinc-finger domain (BZF), the AKT-phosphorylation sites, and the C-terminal C3H2C3-type RING-H2 finger.


Pssm-ID: 438453 [Multi-domain]  Cd Length: 44  Bit Score: 58.08  E-value: 2.44e-11
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 38016196 213 CVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCK 254
Cdd:cd16801   2 CPVCKEDYTVGENVRQLPCNHLFHNDCIVPWLEQHDTCPVCR 43
RING-H2_ZNRF3 cd16799
RING finger, H2 subclass, found in zinc/RING finger protein 3 (ZNRF3) and similar proteins; ...
213-254 2.90e-11

RING finger, H2 subclass, found in zinc/RING finger protein 3 (ZNRF3) and similar proteins; ZNRF3, also known as RING finger protein 203 (RNF203), is a homolog of Ring finger protein 43 (RNF43). It is a transmembrane E3 ubiquitin-protein ligase that is associated with the Wnt receptor complex, and negatively regulates Wnt signaling by promoting the turnover of frizzled and lipoprotein receptor-related protein LRP6 in an R-spondin-sensitive manner. It inhibits gastric cancer cell growth and promotes cell apoptosis by affecting the Wnt/beta-catenin/TCF signaling pathway. ZNRF3 contains an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C3H2C3-type RING-H2 finger followed by a long C-terminal region.


Pssm-ID: 319713 [Multi-domain]  Cd Length: 45  Bit Score: 57.73  E-value: 2.90e-11
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 38016196 213 CVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCK 254
Cdd:cd16799   2 CAICLEKYIDGEELRVIPCTHRFHKKCVDPWLLQHHTCPHCR 43
RING-H2_RNF111 cd16681
RING finger, H2 subclass, found in RING finger protein 111 (RNF111) and similar proteins; ...
200-257 5.21e-11

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: 57.38  E-value: 5.21e-11
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 38016196 200 KEGDEEvnPNADSCVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCKCDI 257
Cdd:cd16681   2 EEGTEE--DTEEKCTICLSILEEGEDVRRLPCMHLFHQVCVDQWLITNKKCPICRVDI 57
RING-H2_RNF13 cd16796
RING finger, H2 subclass, found in RING finger protein 13 (RNF13) and similar proteins; RNF13 ...
199-260 1.21e-10

RING finger, H2 subclass, found in RING finger protein 13 (RNF13) and similar proteins; RNF13 is a widely expressed membrane-associated E3 ubiquitin-protein ligase that is functionally significant in the regulation of cancer development, muscle cell growth, and neuronal development. Its expression is developmentally regulated during myogenesis and is upregulated in various tumors. RNF13 negatively regulates cell proliferation through its E3 ligase activity. It functions as an important regulator of inositol-requiring transmembrane kinase/endonuclease IRE1alpha, mediating endoplasmic reticulum (ER) stress-induced apoptosis through the activation of the IRE1alpha-TRAF2-JNK signaling pathway. Moreover, RNF13 is involved in the regulation of the soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor (SNARE) complex via the ubiquitination of snapin, a SNAP25-interacting protein, which thereby controls synaptic function. In addition, RNF13 participates in regulating the function of satellite cells by modulating cytokine composition. RNF13 is evolutionarily conserved among many metazoans and 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: 438450 [Multi-domain]  Cd Length: 59  Bit Score: 56.59  E-value: 1.21e-10
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 38016196 199 LKEGDEevnpnADSCVICFEAYKPNEIVRILTCKHFFHKNCIDPWIL-AHGTCPMCKCDILKA 260
Cdd:cd16796   2 FKKGDE-----YDVCAICLDEYEEGDKLRILPCSHAYHCKCVDPWLTkTKKTCPVCKQKVVPS 59
RING-H2_RNF165 cd16682
RING finger, H2 subclass, found in RING finger protein 165 (RNF165) and similar proteins; ...
203-262 1.27e-10

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: 56.24  E-value: 1.27e-10
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 38016196 203 DEEVNPNaDSCVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCKCDILKALG 262
Cdd:cd16682   1 GEESDTD-EKCTICLSMLEDGEDVRRLPCMHLFHQLCVDQWLAMSKKCPICRVDIETQLG 59
PA_C5a_like cd02133
PA_C5a_like: Protease-associated domain containing proteins like Streptococcus pyogenes C5a ...
102-155 1.63e-10

PA_C5a_like: Protease-associated domain containing proteins like Streptococcus pyogenes C5a peptidase. This group contains various PA domain-containing proteins similar to S. pyogenes C5a, including, i) Vpr, a minor extracellular serine protease from Bacillus subtilis, ii) a large molecular mass collagenolytic protease from Geobacillus collagenovorans MO-1, and iii) PrtS, a cell envelope protease from Streptococcus thermophilus CNRZ 385. Proteins in this group belong to the peptidase S8 family. C5a peptidase is a cell surface serine protease which specifically inactivates C5a [a chemotactic peptide, which attracts polymorphonuclear leukocytes (PMNs)], by cleaving it to release a 7-residue carboxy-terminal fragment which contains the PMN binding site. The significance of the PA domain to these proteins has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.


Pssm-ID: 239048 [Multi-domain]  Cd Length: 143  Bit Score: 58.45  E-value: 1.63e-10
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 38016196 102 IALIERGGCAFTQKIKVASEHGARGVIIYNF-PGtgnqVFPMSHQAFEDIVVVMI 155
Cdd:cd02133  50 IALIQRGEITFVEKIANAKAAGAVGVIIYNNvDG----LIPGTLGEAVFIPVVFI 100
RING-H2_RNF181 cd16669
RING finger, H2 subclass, found in RING finger protein 181 (RNF181) and similar proteins; ...
212-254 1.83e-10

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: 55.46  E-value: 1.83e-10
                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 38016196 212 SCVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCK 254
Cdd:cd16669   1 KCPICLLEFEEGETVKQLPCKHSFHSDCILPWLGKTNSCPLCR 43
PA_subtilisin_1 cd04818
PA_subtilisin_1: Protease-associated domain containing subtilisin-like proteases, subgroup 1. ...
71-157 2.53e-10

PA_subtilisin_1: Protease-associated domain containing subtilisin-like proteases, subgroup 1. A subgroup of PA domain-containing subtilisin-like proteases. The significance of the PA domain to many of the proteins in which it is inserted is undetermined. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate. Proteins into which the PA domain is inserted include the following subtilisin-like proteases: i) melon cucumisin, ii) Arabidopsis thaliana Ara12, iii) Alnus glutinosa ag12, iv) members of the tomato P69 family, and v) tomato LeSBT2. However, these proteins belong to other subtilisin-like subgroups. Relatively little is known about proteins in this subgroup.


Pssm-ID: 240122 [Multi-domain]  Cd Length: 118  Bit Score: 57.34  E-value: 2.53e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38016196  71 VAGVVVPPEgkIQNACDPNTTFILPRNKepwIALIERGGCAFTQKIKVASEHGARGVIIYNFPGtGNQVFPMSHQAfEDI 150
Cdd:cd04818  17 VLAGAAPAS--NTDGCTAFTNAAAFAGK---IALIDRGTCNFTVKVLNAQNAGAIAVIVANNVA-GGAPITMGGDD-PDI 89

                ....*....
gi 38016196 151 VV--VMIGN 157
Cdd:cd04818  90 TIpaVMISQ 98
PA_hPAP21_like cd02127
PA_hPAP21_like: Protease-associated domain containing proteins like the human secreted ...
62-144 3.16e-10

PA_hPAP21_like: Protease-associated domain containing proteins like the human secreted glycoprotein hPAP21 (human protease-associated domain-containing protein, 21kDa). This group contains various PA domain-containing proteins similar to hPAP21. Complex N-glycosylation may be required for the secretion of hPAP21. The significance of the PA domain to hPAP21 has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.


Pssm-ID: 239042 [Multi-domain]  Cd Length: 118  Bit Score: 57.00  E-value: 3.16e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38016196  62 FGrSSILKRVAGV-VVPPEGKiqNACDP--NTTFIlprnkEPWIALIERGGCAFTQKIKVASEHGARGVIIYNF-PGTGN 137
Cdd:cd02127   2 FG-TIFNTRYKHVpLVPADPL--EACEElrNIHDI-----NGNIALIERGGCSFLTKAINAQKAGALAVIITDVnNDSDE 73

                ....*..
gi 38016196 138 QVFPMSH 144
Cdd:cd02127  74 YYVEMIQ 80
RING-H2_RNF6-like cd16467
RING finger, H2 subclass, found in E3 ubiquitin-protein ligase RNF6, RNF12, and similar ...
212-254 6.82e-10

RING finger, H2 subclass, found in E3 ubiquitin-protein ligase RNF6, RNF12, and similar proteins; RNF6 is an androgen receptor (AR)-associated protein that induces AR ubiquitination and promotes AR transcriptional activity. RNF6-induced ubiquitination may regulate AR transcriptional activity and specificity by modulating cofactor recruitment. RNF6 is overexpressed in hormone-refractory human prostate cancer tissues and required for prostate cancer cell growth under androgen-depleted conditions. RNF6 also regulates local serine/threonine kinase LIM kinase 1 (LIMK1) levels in axonal growth cones. RNF6-induced LIMK1 polyubiquitination is mediated via K48 of ubiquitin and leads to proteasomal degradation of the kinase. RNF6 binds and upregulates the Inha promoter, and functions as a transcription regulatory protein in the mouse sertoli cell. It acts as a potential tumor suppressor gene involved in the pathogenesis of esophageal squamous cell carcinoma (ESCC). RNF12, also known as LIM domain-interacting RING finger protein, or RING finger LIM domain-binding protein (R-LIM), is an E3 ubiquitin-protein ligase encoded by gene RLIM that is crucial for normal embryonic development in some species and for normal X inactivation in mice. It thus functions as a major sex-specific epigenetic regulator of female mouse nurturing tissues. RNF12 is widely expressed during embryogenesis, and mainly localizes to the cell nucleus, where it regulates the levels of many proteins, including CLIM, LMO, HDAC2, TRF1, SMAD7, and REX1, by proteasomal degradation. Both RNF6 and RNF12 contain a well conserved C3H2C3-type RING-H2 finger.


Pssm-ID: 438130 [Multi-domain]  Cd Length: 43  Bit Score: 54.00  E-value: 6.82e-10
                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 38016196 212 SCVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCK 254
Cdd:cd16467   1 ECTICLGEYETGEKLRRLPCSHEFHSECVDRWLKENSSCPICR 43
RING-H2_NIPL1-like cd23119
RING finger, H2 subclass, found in Arabidopsis thaliana NEP1-interacting protein-like 1 (NIPL1) ...
212-254 1.53e-09

RING finger, H2 subclass, found in Arabidopsis thaliana NEP1-interacting protein-like 1 (NIPL1) and similar proteins; This subfamily includes Arabidopsis thaliana NIPL1 and MISFOLDED PROTEIN SENSING RING E3 LIGASE 1 (MPSR1). NIPL1, also called RING-H2 finger protein ATL27, may be involved in the early steps of the plant defense signaling pathway. MPSR1 is a cytoplasmic E3 ubiquitin-protein ligase involved in protein quality control (PQC) under proteotoxic stress. It is essential for plant survival under proteotoxic stress. It functions by removing damaged proteins before they form cytotoxic aggregates. It recognizes misfolded proteins selectively and tethers polyubiquitin chains to the proteins directly for subsequent degradation by the 26S proteasome pathway. Members of this subfamily contain a C3H2C3-type RING-H2 finger.


Pssm-ID: 438481 [Multi-domain]  Cd Length: 44  Bit Score: 52.89  E-value: 1.53e-09
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 38016196 212 SCVICFEAYKPNEIVRIL-TCKHFFHKNCIDPWILAHGTCPMCK 254
Cdd:cd23119   1 CCTICLQDLQVGEIARSLpHCHHTFHLGCVDKWLGRHGSCPVCR 44
RING-H2_RNF38 cd16679
RING finger, H2 subclass, found in RING finger protein 38 (RNF38) and similar proteins; RNF38 ...
213-256 2.61e-09

RING finger, H2 subclass, found in RING finger protein 38 (RNF38) and similar proteins; RNF38 is a nuclear E3 ubiquitin protein ligase that is widely expressed throughout the human body, and is especially highly expressed in the heart, brain, placenta and the testis. It recognizes p53 as a substrate for ubiquitination, and thus plays a role in regulating p53. The overexpression of RNF38 increases p53 ubiquitination and alters p53 localization. It is also capable of autoubiquitination. RNF38 expression is negatively regulated by the serotonergic system. Induction of RNF38 may be involved in the anxiety-like behavior or non-cell autonomy in Oryzias latipes by the decline of serotonin (5-HT) levels. RNF38 contains a coiled-coil motif, a KIL motif (Lys-X2-Ile/Leu-X2-Ile/Leu, X can be any amino acid), a C3H2C3-type RING-H2 finger, as well as two potential nuclear localization signals.


Pssm-ID: 438341 [Multi-domain]  Cd Length: 67  Bit Score: 52.76  E-value: 2.61e-09
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 38016196 213 CVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCKCD 256
Cdd:cd16679  23 CVVCMCDFESRQLLRVLPCNHEFHAKCVDKWLKANRTCPICRAD 66
mRING-H2-C3H2C2D_ZSWM2 cd16486
Modified RING finger, H2 subclass (C3H2C2D-type), found in zinc finger SWIM domain-containing ...
213-253 2.68e-09

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: 52.38  E-value: 2.68e-09
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 38016196 213 CVICFEAYKPNEIVRILTCKHFFHKNCIDPWIL-AHGTCPMC 253
Cdd:cd16486   2 CRICLKAFQLGQHVRTLPCRHKFHRDCIDNWLLhSRNSCPID 43
RING-H2_BB-like cd23115
RING finger, H2 subclass, found in Arabidopsis thaliana RING-type E3 ubiquitin transferase BIG ...
211-254 5.17e-09

RING finger, H2 subclass, found in Arabidopsis thaliana RING-type E3 ubiquitin transferase BIG BROTHER (BB) and similar proteins; BB (also known as protein ENHANCER OF DA1-1 or EOD1) is an E3 ubiquitin-protein ligase that limits organ size, and possibly seed size, in a dose-dependent manner. It negatively regulates the duration of cell proliferation in leaves and petals independently of the major phytohormones (e.g. auxin, cytokinin, gibberellin, brassinosteroids, ethylene, abscisic acid, jasmonic acid), probably by targeting growth stimulators for degradation. It limits the proliferation of root meristematic cells. BB polyubiquitinates DA1. It is involved in the promotion of leaf senescence, in addition to its function in restricting plant growth. BB-related is an E3 ubiquitin-ligase probably involved in organ size regulation. Members of this subfamily contain a C3H2C3-type RING-H2 finger.


Pssm-ID: 438477 [Multi-domain]  Cd Length: 52  Bit Score: 51.68  E-value: 5.17e-09
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 38016196 211 DSCVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCK 254
Cdd:cd23115   5 ERCVICRLEYEEGEDLLTLPCKHCYHSECIQQWLQINKVCPVCS 48
mRING-CH-C4HC2H_ZNRF cd16489
Modified RING-CH finger, H2 subclass (C4HC2H-type), found in the ZNRF family; The ZNRF family ...
213-252 5.86e-09

Modified RING-CH finger, H2 subclass (C4HC2H-type), found in the ZNRF family; The ZNRF family includes zinc/RING finger proteins ZNRF1, ZNRF2, and similar proteins. It has been characterized by containing a unique combination of zinc finger-RING finger motifs in the C-terminal region, which is evolutionarily conserved in a wide range of species, including Caenorhabditis elegans and Drosophila. ZNRF proteins function as E3 ubiquitin ligases and are highly expressed in central nervous system (CNS) and peripheral nervous system (PNS) neurons, particularly during development and in adulthood. ZNRF1 and ZNRF2 are differentially localized within the synaptic region. ZNRF1 is associated with synaptic vesicle membranes, whereas ZNRF2 is present in presynaptic plasma membranes. They are N-myrisotoylated and also located in the endosome-lysosome compartment in fibroblasts. ZNRF proteins may play a role in the establishment and maintenance of neuronal transmission and plasticity via their ubiquitin ligase activity, as well as in regulating Ca2+-dependent exocytosis. The RING fingers found in ZNRF proteins are modified as C4HC2H-type RING-CH finger, rather than the typical C4HC3-type RING-CH finger, which is a variant of the RING-H2 finger.


Pssm-ID: 438152 [Multi-domain]  Cd Length: 43  Bit Score: 51.15  E-value: 5.86e-09
                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 38016196 213 CVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPM 252
Cdd:cd16489   2 CVICLEELEAGDTIARLPCLCIYHKKCIDDWFEVNRSCPE 41
RING-H2_TTC3 cd16481
RING finger, H2 subclass, found in Tetratricopeptide repeat protein 3 (TTC3) and similar ...
212-257 6.60e-09

RING finger, H2 subclass, found in Tetratricopeptide repeat protein 3 (TTC3) and similar proteins; TTC3, also known as protein DCRR1, TPR repeat protein D, TPR repeat protein 3, or RING finger protein 105 (RNF105), is an E3 ubiquitin-protein ligase encoded by a gene within the Down syndrome (DS) critical region on chromosome 21. It affects differentiation and Golgi compactness in neurons through specific actin-regulating pathways. It inhibits the neuronal-like differentiation of pheocromocytoma cells by activating RhoA and by binding to Citron proteins. TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. It contains four N-terminal TPR motifs, a potential coiled-coil region and a Citron binding region in the central part, and a C-terminal C3H2C2-type RING-H2 finger.


Pssm-ID: 438144 [Multi-domain]  Cd Length: 45  Bit Score: 51.20  E-value: 6.60e-09
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 38016196 212 SCVICFEAYKPNEiVRILTCKHFFHKNCIDPWILAHGTCPMCKCDI 257
Cdd:cd16481   1 PCIICHDDLKPDQ-LAKLECGHIFHKECIKQWLKEQSTCPTCRVHV 45
RING-H2_RNF24 cd16675
RING finger, H2 subclass, found in RING finger protein 24 (RNF24) and similar proteins; RNF24 ...
213-259 1.32e-08

RING finger, H2 subclass, found in RING finger protein 24 (RNF24) and similar proteins; RNF24 is an intrinsic membrane protein localized in the Golgi apparatus. It specifically interacts with the ankyrin-repeats domains (ARDs) of TRPC1, -3, -4, -5, -6, and -7, and affects TRPC intracellular trafficking without affecting their activity. RNF24 contains an N-terminal transmembrane domain and a C-terminal C3H2C3-type RING-H2 finger.


Pssm-ID: 438337 [Multi-domain]  Cd Length: 54  Bit Score: 50.40  E-value: 1.32e-08
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 38016196 213 CVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCKCDILK 259
Cdd:cd16675   3 CAVCLEEFKPKDELGICPCKHAFHRKCLIKWLEVRKVCPLCNMPVLQ 49
PA_SaNapH_like cd04816
PA_SaNapH_like: Protease-associated domain containing proteins like Streptomyces anulatus ...
102-131 1.79e-08

PA_SaNapH_like: Protease-associated domain containing proteins like Streptomyces anulatus N-acetylpuromycin N-acetylhydrolase (SaNapH).This group contains various PA domain-containing proteins similar SaNapH. Proteins in this group belong to the peptidase M28 family. NapH is a terminal enzyme in the puromycin biosynthetic pathway; NapH hydrolyzes N-acetylpuromycin to the active antibiotic. The significance of the PA domain to these proteins has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.


Pssm-ID: 240120 [Multi-domain]  Cd Length: 122  Bit Score: 51.94  E-value: 1.79e-08
                        10        20        30
                ....*....|....*....|....*....|
gi 38016196 102 IALIERGGCAFTQKIKVASEHGARGVIIYN 131
Cdd:cd04816  46 IVLVDRGGCPFADKQKVAAARGAVAVIVVN 75
RING smart00184
Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and ...
213-253 1.94e-08

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: 49.81  E-value: 1.94e-08
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 38016196    213 CVICFEAYKPNeiVRILTCKHFFHKNCIDPWILAHG-TCPMC 253
Cdd:smart00184   1 CPICLEEYLKD--PVILPCGHTFCRSCIRKWLESGNnTCPIC 40
RING-H2_RNF139-like cd16476
RING finger, H2 subclass, found in RING finger proteins RNF139, RNF145, and similar proteins; ...
211-253 1.98e-08

RING finger, H2 subclass, found in RING finger proteins RNF139, RNF145, and similar proteins; RNF139, also known as translocation in renal carcinoma on chromosome 8 protein (TRC8), is an endoplasmic reticulum (ER)-resident multi-transmembrane protein that functions as a potent growth suppressor in mammalian cells, inducing G2/M arrest, decreased DNA synthesis and increased apoptosis. It is a tumor suppressor that has been implicated in a novel regulatory relationship linking the cholesterol/lipid biosynthetic pathway with cellular growth control. A mutation in RNF139 has been identified in families with hereditary renal (RCC) and thyroid cancers. RNF145 is an uncharacterized RING finger protein encoded by the RNF145 gene, which is expressed in T lymphocytes, and its expression is altered in acute myelomonocytic and acute promyelocytic leukemias. Although its biological function remains unclear, RNF145 shows high sequence similarity with RNF139. Both RNF139 and RNF145 contain a C3H2C3-type RING-H2 finger with possible E3-ubiquitin ligase activity.


Pssm-ID: 438139 [Multi-domain]  Cd Length: 41  Bit Score: 49.76  E-value: 1.98e-08
                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 38016196 211 DSCVICFEAYKPneiVRILTCKHFFHKNCIDPWILAHGTCPMC 253
Cdd:cd16476   1 DVCAICYQEMKE---ARITPCNHFFHGLCLRKWLYVQDTCPLC 40
RING-HC_IRC20-like cd23135
RING finger, HC subclass, found in Saccharomyces cerevisiae increased recombination centers ...
212-254 2.17e-08

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: 49.82  E-value: 2.17e-08
                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 38016196 212 SCVICFEAYKpneIVRILTCKHFFHKNCIDPWILAHGTCPMCK 254
Cdd:cd23135   5 SCSICFSEIR---SGAILKCGHFFCLSCIASWLREKSTCPLCK 44
RING-H2_RHA2B cd23123
RING finger, H2 subclass, found in Saccharomyces cerevisiae RING-H2 zinc finger protein RHA2B ...
211-254 3.54e-08

RING finger, H2 subclass, found in Saccharomyces cerevisiae RING-H2 zinc finger protein RHA2B and similar proteins; RHA2B is an E3 ubiquitin-protein ligase involved in the positive regulation of abscisic acid (ABA) signaling and responses to salt and osmotic stresses during seed germination and early seedling development. It acts additively with RHA2A in regulating ABA signaling and drought response. RHA2B contains a C3H2C3-type RING-H2 finger.


Pssm-ID: 438485 [Multi-domain]  Cd Length: 47  Bit Score: 49.12  E-value: 3.54e-08
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 38016196 211 DSCVICFEAYKPNEIVRILTCKHFFHKNCIDPWI-LAHGTCPMCK 254
Cdd:cd23123   1 SDCCICLDKLKTGEEVKKLDCRHKFHKQCIEGWLkHLNFNCPLCR 45
COG5540 COG5540
RING-finger-containing ubiquitin ligase [Posttranslational modification, protein turnover, ...
213-257 5.55e-08

RING-finger-containing ubiquitin ligase [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 227827 [Multi-domain]  Cd Length: 374  Bit Score: 53.85  E-value: 5.55e-08
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 38016196 213 CVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHG-TCPMCKCDI 257
Cdd:COG5540 326 CAICMSNFIKNDRLRVLPCDHRFHVGCVDKWLLGYSnKCPVCRTAI 371
RING-H2_RNF122 cd16676
RING finger, H2 subclass, found in RING finger protein 122 (RNF122) and similar proteins; ...
212-253 5.78e-08

RING finger, H2 subclass, found in RING finger protein 122 (RNF122) and similar proteins; RNF122 is a RING finger protein associated with HEK 293T cell viability. It is localized to the endoplasmic reticulum (ER) and the Golgi apparatus, and overexpressed in anaplastic thyroid cancer cells. RNF122 functions as an E3 ubiquitin ligase that can ubiquitinate itself and undergo degradation through its RING finger in a proteasome-dependent manner. It interacts with calcium-modulating cyclophilin ligand (CAML), which is not a substrate, but a stabilizer of RNF122. RNF122 contains an N-terminal transmembrane domain and a C-terminal C3H2C3-type RING-H2 finger.


Pssm-ID: 438338 [Multi-domain]  Cd Length: 47  Bit Score: 48.42  E-value: 5.78e-08
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 38016196 212 SCVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMC 253
Cdd:cd16676   2 TCAVCLEDFKTKDELGVLPCQHAFHRKCLVKWLEIRCVCPMC 43
PA pfam02225
PA domain; The PA (Protease associated) domain is found as an insert domain in diverse ...
73-157 8.91e-08

PA domain; The PA (Protease associated) domain is found as an insert domain in diverse proteases. The PA domain is also found in a plant vacuolar sorting receptor Swiss:O22925 and members of the RZF family Swiss:O43567. It has been suggested that this domain forms a lid-like structure that covers the active site in active proteases, and is involved in protein recognition in vacuolar sorting receptors.


Pssm-ID: 460499 [Multi-domain]  Cd Length: 91  Bit Score: 49.43  E-value: 8.91e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38016196    73 GVVVPPEGkiQNACDPNTTFILPRNKepwIALIERGGCAFTQKIKVASEHGARGVIIYNFP----GTGNQVFPMSHQAFE 148
Cdd:pfam02225   2 GPLVLAPG--CYAGDGIPADFDVKGK---IVLVRCTFGFRAEKVRNAQAAGAAGVIIYNNVeglgGPPGAGGNELYPDGI 76

                  ....*....
gi 38016196   149 DIVVVMIGN 157
Cdd:pfam02225  77 YIPAVGVSR 85
RING-H2_RNF12 cd16674
RING finger, H2 subclass, found in RING finger protein 12 (RNF12) and similar proteins; RNF12, ...
212-260 1.16e-07

RING finger, H2 subclass, found in RING finger protein 12 (RNF12) and similar proteins; RNF12, also known as LIM domain-interacting RING finger protein or RING finger LIM domain-binding protein (R-LIM), is an E3 ubiquitin-protein ligase encoded by gene RLIM that is crucial for normal embryonic development in some species and for normal X inactivation in mice. It thus functions as a major sex-specific epigenetic regulator of female mouse nurturing tissues. RNF12 is widely expressed during embryogenesis, and mainly localizes to the cell nucleus, where it regulates the levels of many proteins, including CLIM, LMO, HDAC2, TRF1, SMAD7, and REX1, by proteasomal degradation. Its functional activity is regulated by phosphorylation-dependent nucleocytoplasmic shuttling. It is negatively regulated by pluripotency factors in embryonic stem cells. p53 represses its transcription through Sp1. RNF12 is the primary factor responsible for X chromosome inactivation (XCI) in female placental mammals. It is an indispensable factor in up-regulation of Xist transcription, thereby leading to initiation of random XCI. It also targets REX1, an inhibitor of XCI, for proteasomal degradation. RNF12 also acts as a co-regulator for a range of transcription factors, particularly those containing a LIM homeodomain, and modulates the formation of transcriptional multiprotein complexes. It is a negative regulator of Smad7, which in turn negatively regulates the signaling of type I receptors from the transforming growth factor beta (TGF-beta) superfamily. In addition, paternal RNF12 is a critical survival factor for milk-producing alveolar cells. RNF12 contains an nuclear localization signal (NLS) and a C3H2C3-type RING-H2 finger.


Pssm-ID: 438336 [Multi-domain]  Cd Length: 51  Bit Score: 47.79  E-value: 1.16e-07
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 38016196 212 SCVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCKCDILKA 260
Cdd:cd16674   2 TCSVCITEYTEGNKLRKLPCSHEYHVHCIDRWLSENSTCPICRRAVLAS 50
zf-C3HC4 pfam00097
Zinc finger, C3HC4 type (RING finger); The C3HC4 type zinc-finger (RING finger) is a ...
213-253 1.37e-07

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


Pssm-ID: 395049 [Multi-domain]  Cd Length: 40  Bit Score: 47.35  E-value: 1.37e-07
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 38016196   213 CVICFEAYKpnEIVRILTCKHFFHKNCIDPWILA-HGTCPMC 253
Cdd:pfam00097   1 CPICLEEPK--DPVTLLPCGHLFCSKCIRSWLESgNVTCPLC 40
RING-H2_RNF139 cd16683
RING finger, H2 subclass, found in RING finger protein 139 (RNF139) and similar proteins; ...
211-253 1.61e-07

RING finger, H2 subclass, found in RING finger protein 139 (RNF139) and similar proteins; RNF139, also known as translocation in renal carcinoma on chromosome 8 protein (TRC8), is an endoplasmic reticulum (ER)-resident multi-transmembrane protein that functions as a potent growth suppressor in mammalian cells, inducing G2/M arrest, decreased DNA synthesis and increased apoptosis. It is a tumor suppressor that has been implicated in a novel regulatory relationship linking the cholesterol/lipid biosynthetic pathway with cellular growth control. A mutation in RNF139 has been identified in families with hereditary renal (RCC) and thyroid cancers. RNF139 physically and functionally interacts with von Hippel-Lindau (VHL), which is part of an SCF related E3-ubiquitin ligase complex with "gatekeeper" function in renal carcinoma and is defective in most sporadic clear-cell renal cell carcinomas (ccRCC). It suppresses growth and functions with VHL in a common pathway. RNF139 also suppresses tumorigenesis by targeting heme oxygenase-1 for ubiquitination and degradation. Moreover, RNF139 is a target of Translin (TSN), a posttranscriptional regulator of genes transcribed by the transcription factor CREM-tau in postmeiotic male germ cells, suggesting a role of RNF139 in dysgerminoma. In addition, RNF139 forms an integral part of a novel multi-protein ER complex, containing MHC I, US2, and signal peptide peptidase, which is associated with the ER-associated degradation (ERAD) pathway. It is required for the ubiquitination of MHC class I molecules before dislocation from the ER. As a novel sterol-sensing ER membrane protein, RNF139 hinders sterol regulatory element-binding protein-2 (SREBP-2) processing through interaction with SREBP-2 and SREBP cleavage-activated protein (SCAP), regulating its own turnover rate via its E3 ubiquitin ligase activity. RNF139 shows two regions of similarity with the receptor for sonic hedgehog (SHH), Patched. The first region corresponds to the second extracellular domain of Patched, which is involved in binding SHH. The second region is a putative sterol-sensing domain (SSD). The C-terminal half of RNF139 contains a C3H2C3-type RING-H2 finger with E3-ubiquitin ligase activity in vitro.


Pssm-ID: 438345 [Multi-domain]  Cd Length: 54  Bit Score: 47.65  E-value: 1.61e-07
                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 38016196 211 DSCVICFEAYKPNeiVRILTCKHFFHKNCIDPWILAHGTCPMC 253
Cdd:cd16683   5 DVCAICYQEFTTS--ARITPCNHYFHALCLRKWLYIQDTCPMC 45
zf-RING_11 pfam17123
RING-like zinc finger;
213-240 1.88e-07

RING-like zinc finger;


Pssm-ID: 465355 [Multi-domain]  Cd Length: 29  Bit Score: 46.76  E-value: 1.88e-07
                          10        20
                  ....*....|....*....|....*...
gi 38016196   213 CVICFEAYKPNEIVRILTCKHFFHKNCI 240
Cdd:pfam17123   2 CSICLDEFKPGQALFVLPCSHVFHYKCI 29
PA_ScAPY_like cd02130
PA_ScAPY_like: Protease-associated domain containing proteins like Saccharomyces cerevisiae ...
74-131 1.97e-07

PA_ScAPY_like: Protease-associated domain containing proteins like Saccharomyces cerevisiae aminopeptidase Y (ScAPY). This group contains various PA domain-containing proteins similar to the S. cerevisiae APY, including Trichophyton rubrum leucine aminopeptidase 1(LAP1). Proteins in this group belong to the peptidase M28 family. ScAPY hydrolyzes amino acid-4-methylcoumaryl-7-amides (MCAs). ScAPY more rapidly hydrolyzes dipeptidyl-MCAs. Hydrolysis of amino acid-MCAs or dipeptides is stimulated by Co2+ while the hydrolysis of dipeptidyl-MCAs, tripeptides, and longer peptides is inhibited by Co2+. ScAPY is vacuolar and is activated by proteolytic processing. LAP1 is a secreted leucine aminopeptidase. The significance of the PA domain to these proteins has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.


Pssm-ID: 239045 [Multi-domain]  Cd Length: 122  Bit Score: 49.18  E-value: 1.97e-07
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 38016196  74 VVVPPEGkiqnaCDPnTTFilPRNKEPWIALIERGGCAFTQKIKVASEHGARGVIIYN 131
Cdd:cd02130  27 VVVPNLG-----CDA-ADY--PASVAGNIALIERGECPFGDKSALAGAAGAAAAIIYN 76
RING-H2_RNF6 cd16673
RING finger, H2 subclass, found in E3 ubiquitin-protein ligase RNF6 and similar proteins; RNF6 ...
212-260 2.20e-07

RING finger, H2 subclass, found in E3 ubiquitin-protein ligase RNF6 and similar proteins; RNF6 is an androgen receptor (AR)-associated protein that induces AR ubiquitination and promotes AR transcriptional activity. RNF6-induced ubiquitination may regulate AR transcriptional activity and specificity by modulating cofactor recruitment. RNF6 is overexpressed in hormone-refractory human prostate cancer tissues and required for prostate cancer cell growth under androgen-depleted conditions. Moreover, RNF6 regulates local serine/threonine kinase LIM kinase 1 (LIMK1) levels in axonal growth cones. RNF6-induced LIMK1 polyubiquitination is mediated via K48 of ubiquitin and leads to proteasomal degradation of the kinase. RNF6 also binds and upregulates the Inha promoter, and functions as a transcription regulatory protein in the mouse sertoli cell. RNF6 also acts as a potential tumor suppressor gene involved in the pathogenesis of esophageal squamous cell carcinoma (ESCC). RNF6 contains an N-terminal coiled-coil domain, a Lys-X-X-Leu/Ile-X-X-Leu/Ile (KIL) motif, and a C-terminal C3H2C3-type RING-H2 finger which is responsible for its ubiquitin ligase activity. The KIL motif is present in a subset of RING-H2 proteins from organisms as evolutionarily diverse as human, mouse, chicken, Drosophila, Caenorhabditis elegans, and Arabidopsis thaliana.


Pssm-ID: 438335 [Multi-domain]  Cd Length: 52  Bit Score: 46.87  E-value: 2.20e-07
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 38016196 212 SCVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCKCDILKA 260
Cdd:cd16673   2 TCSVCINEYATGNKLRRLPCAHEFHIHCIDRWLSENSTCPICRQPVLGS 50
RING-H2_TRAIP cd16480
RING finger, H2 subclass, found in TRAF-interacting protein (TRAIP) and similar proteins; ...
213-254 6.93e-07

RING finger, H2 subclass, found in TRAF-interacting protein (TRAIP) and similar proteins; TRAIP, also known as RING finger protein 206 (RNF206) or TRIP, is a ubiquitously expressed nucleolar E3 ubiquitin ligase important for cellular proliferation and differentiation. It is found near mitotic chromosomes and functions as a regulator of the spindle assembly checkpoint. TRAIP interacts with tumor necrosis factor (TNF)-receptor-associated factor (TRAF) proteins and inhibits TNF-alpha-mediated nuclear factor (NF)-kappaB activation. It also interacts with two tumor suppressors CYLD and spleen tyrosine kinase (Syk), and DNA polymerase eta, which facilitates translesional synthesis after DNA damage. TRAIP contains an N-terminal C3H2C2-type RING-H2 finger and an extended coiled-coil domain.


Pssm-ID: 438143 [Multi-domain]  Cd Length: 43  Bit Score: 45.50  E-value: 6.93e-07
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 38016196 213 CVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCK 254
Cdd:cd16480   2 CTICSDFFDNSRDVAAIHCGHTFHYDCLLQWFDTSRTCPQCR 43
T9SSA_dep_M36 NF038113
T9SS-dependent M36 family metallopeptidase; Members of this family have an M36 family ...
74-137 1.20e-06

T9SS-dependent M36 family metallopeptidase; Members of this family have an M36 family metallopeptidase domain, like fungalysin (see PF02128), and a C-terminal T9SS type A sorting domain (see TIGR04131).


Pssm-ID: 468356 [Multi-domain]  Cd Length: 868  Bit Score: 50.04  E-value: 1.20e-06
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 38016196   74 VVVPPEGKIQNACDPNTTfilPRNKEPWIALIERGGCAFTQKIKVASEHGARGVIIYN-FPGTGN 137
Cdd:NF038113 446 LATDSSPDPNDGCDPILN---AAALAGKIAVIRRGSCEFAVKVLNAQNAGAIAVIIVNnVPGEPI 507
zf-RING_5 pfam14634
zinc-RING finger domain;
213-254 1.23e-06

zinc-RING finger domain;


Pssm-ID: 434085 [Multi-domain]  Cd Length: 43  Bit Score: 44.73  E-value: 1.23e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 38016196   213 CVICFEAYKPNEIVRILTCKHFFHKNCIDPwILAHGTCPMCK 254
Cdd:pfam14634   2 CNKCFKELSKTRPFYLTSCGHIFCEECLTR-LLQERQCPICK 42
RING-H2_RHA1-like cd23121
RING finger, H2 subclass, found in Arabidopsis thaliana RING-H2 finger A1a (RHA1A), A1b (RHA1B) ...
211-256 1.92e-06

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: 44.40  E-value: 1.92e-06
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 38016196 211 DSCVICFEAYKPNEIVR-ILTCKHFFHKNCIDPWILAHG-TCPMCKCD 256
Cdd:cd23121   2 DCCAICLSDFNSDEKLRqLPKCGHIFHHHCLDRWIRYNKiTCPLCRAD 49
RING-HC_RNF141 cd16545
RING finger, HC subclass, found in RING finger protein 141 (RNF141) and similar proteins; ...
211-254 2.10e-06

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: 44.00  E-value: 2.10e-06
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 38016196 211 DSCVICFEAyKPnEIvrILTCKHFFHKNCIDPWILAHGTCPMCK 254
Cdd:cd16545   1 EECCICMDR-KA-DL--ILPCAHSYCQKCIDKWSDRHRTCPICR 40
RING-H2_MBR cd23113
RING finger, H2 subclass, found in Arabidopsis thaliana MED25-binding RING-H2 protein (MBR) ...
209-258 2.34e-06

RING finger, H2 subclass, found in Arabidopsis thaliana MED25-binding RING-H2 protein (MBR) and similar proteins; This subfamily includes MBR1 and MBR2 (also called HAL3-interacting protein 1 or AtHIP1). They are E3 ubiquitin-protein ligases that function as regulators of MED25 stability by targeting MED25 for degradation in a RING-H2-dependent manner. Proteasome-dependent degradation of MED25 seems to activate its function as a positive regulator of FLOWERING LOCUS T (FT) and is important to induce the expression of FT, and consequently to promote flowering. MBR2 may also function downstream of HAL3 and be required for HAL3-regulated plant growth. Activation of MBR2 by HAL3 may lead to the degradation of cell cycle suppressors, resulting in enhancement of cell division and plant growth. Both MBR1 and MBR2 contain a C3H2C3-type RING-H2 finger.


Pssm-ID: 438475 [Multi-domain]  Cd Length: 50  Bit Score: 44.10  E-value: 2.34e-06
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 38016196 209 NADSCVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCKCDIL 258
Cdd:cd23113   1 SDEKCCICQEEYEEGDELGTIECGHEYHSDCIKQWLVQKNLCPICKATAL 50
RING-H2_RHF2A cd23122
RING finger, H2 subclass, found in Arabidopsis thaliana RING-H2 zinc finger protein RHF2A and ...
207-253 2.64e-06

RING finger, H2 subclass, found in Arabidopsis thaliana RING-H2 zinc finger protein RHF2A and similar proteins; RHF2A is an E3 ubiquitin-protein ligase involved in the positive regulation of the gametogenesis progression. It is required for the degradation of KRP6, a cyclin-dependent kinase inhibitor which accumulates during meiosis and blocks the progression of subsequent mitoses during gametophytes development. It functions in association with RHF1A. Members of this subfamily contain a C3H2C3-type RING-H2 finger.


Pssm-ID: 438484 [Multi-domain]  Cd Length: 63  Bit Score: 44.20  E-value: 2.64e-06
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 38016196 207 NPNADSCVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCPMC 253
Cdd:cd23122   8 DACEDACSICLESFCEADPATVTSCKHEYHLQCILEWSQRSKECPMC 54
zf-C3HC4_2 pfam13923
Zinc finger, C3HC4 type (RING finger);
213-253 4.13e-06

Zinc finger, C3HC4 type (RING finger);


Pssm-ID: 404756 [Multi-domain]  Cd Length: 40  Bit Score: 43.19  E-value: 4.13e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 38016196   213 CVICFEAYKpnEIVRILTCKHFFHKNCIDPWILAHGTCPMC 253
Cdd:pfam13923   2 CPICMDMLK--DPSTTTPCGHVFCQDCILRALEASNECPLC 40
zf-rbx1 pfam12678
RING-H2 zinc finger domain; There are 8 cysteine/ histidine residues which are proposed to be ...
207-253 4.14e-06

RING-H2 zinc finger domain; There are 8 cysteine/ histidine residues which are proposed to be the conserved residues involved in zinc binding. The protein, of which this domain is the conserved region, participates in diverse functions relevant to chromosome metabolism and cell cycle control.


Pssm-ID: 463669 [Multi-domain]  Cd Length: 55  Bit Score: 43.47  E-value: 4.14e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 38016196   207 NPNADSCVICfeAYKPNEIVRILT--CKHFFHKNCIDPWILAHGTCPMC 253
Cdd:pfam12678   8 NPFMEPCPEC--QAPGDDECPVVWgeCGHAFHLHCISRWLKTNNTCPLC 54
myxo_dep_M36 NF038112
myxosortase-dependent M36 family metallopeptidase; Members of this bacterial protein family ...
74-131 5.90e-06

myxosortase-dependent M36 family metallopeptidase; Members of this bacterial protein family have an M36 family metallopeptidase domain, like fungalysin (see PF02128), and a C-terminal MYXO-CTERM domain (see TIGR03901), suggesting processing and surface-anchoring by the still-unknown putative transpeptidase, myxosortase. Members of this family include MXAN_3564 (mepA), part of the effector cargo of outer membrane vesicles that the species produces in large numbers during predation on other microbes.


Pssm-ID: 468355 [Multi-domain]  Cd Length: 1597  Bit Score: 48.11  E-value: 5.90e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 38016196    74 VVVPPEG--KIQNACDPNTtfilprNKEPW---IALIERGGCAFTQKIKVASEHGARGVIIYN 131
Cdd:NF038112  521 VVLAPDGtgSDTDGCTPFT------NAAEVagkIALIDRGTCDFTVKALNAQNAGAIGVIIAN 577
mRING-C3HGC3_RFWD3 cd16450
Modified RING finger, C3HGC3-type, found in RING finger and WD repeat domain-containing ...
210-254 7.20e-06

Modified RING finger, C3HGC3-type, found in RING finger and WD repeat domain-containing protein 3 (RFWD3) and similar proteins; RFWD3, also known as RING finger protein 201 (RNF201) or FLJ10520, is an E3 ubiquitin-protein ligase that forms a complex with Mdm2 and p53 to synergistically ubiquitinate p53 and acts as a positive regulator of p53 stability in response to DNA damage. It is phosphorylated by checkpoint kinase ATM/ATR and the phosphorylation mutant fails to stimulate p53 ubiquitination. RFWD3 also functions as a novel replication protein A (RPA)-associated protein involved in DNA replication checkpoint control. RFWD3 contains an N-terminal SQ-rich region followed by a RING finger domain that exhibits robust E3 ubiquitin ligase activity toward p53, a coiled-coil domain and three WD40 repeats in the C-terminus, the latter two of which may be responsible for protein-protein interaction. The RING finger in this family is a modified C3HGC3-type RING finger, but not a canonical C3H2C3-type RING-H2 finger or C3HC4-type RING-HC finger.


Pssm-ID: 438114 [Multi-domain]  Cd Length: 61  Bit Score: 42.99  E-value: 7.20e-06
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 38016196 210 ADSCVICFEAYKPNEIVRI--LTCKHFFHKNCIDPWIL-AHGTCPMCK 254
Cdd:cd16450   2 GNTCPICFEPWTSSGEHRLvsLKCGHLFGYSCIEKWLKgKGKKCPQCN 49
RING-H2_RNF32_rpt1 cd16677
first RING finger, H2 subclass, found in RING finger protein 32 (RNF32) and similar proteins; ...
212-255 7.66e-06

first RING finger, H2 subclass, found in RING finger protein 32 (RNF32) and similar proteins; RNF32 is mainly expressed in testis spermatogenesis, most likely in spermatocytes and/or in spermatids, suggesting a possible role in sperm formation. RNF32 contains two C3H2C3-type RING-H2 fingers separated by an IQ domain of unknown function. Although the biological function of RNF32 remains unclear, proteins with double RING-H2 fingers may act as scaffolds for binding several proteins that function in the same pathway. This model corresponds to the first RING-H2 finger.


Pssm-ID: 438339 [Multi-domain]  Cd Length: 49  Bit Score: 42.67  E-value: 7.66e-06
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 38016196 212 SCVICFEAYKPNEIVrILTCKHFFHKNCIDPW--ILAHGTCPMCKC 255
Cdd:cd16677   1 PCPICLEDFGLQQQV-LLSCSHVFHRACLESFerFSGKKTCPMCRK 45
RING-H2_RNF145 cd16684
RING finger, H2 subclass, found in RING finger protein 145 (RNF145) and similar proteins; ...
211-253 7.93e-06

RING finger, H2 subclass, found in RING finger protein 145 (RNF145) and similar proteins; RNF145 is an uncharacterized RING finger protein encoded by the RNF145 gene, which is expressed in T lymphocytes, and its expression is altered in acute myelomonocytic and acute promyelocytic leukemias. Although its biological function remains unclear, RNF145 shows high sequence similarity with RNF139, an endoplasmic reticulum (ER)-resident multi-transmembrane protein that functions as a potent growth suppressor in mammalian cells, inducing G2/M arrest, decreased DNA synthesis and increased apoptosis. Like RNF139, RNF145 contains a C3H2C3-type RING-H2 finger with possible E3-ubiquitin ligase activity.


Pssm-ID: 319598 [Multi-domain]  Cd Length: 43  Bit Score: 42.35  E-value: 7.93e-06
                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 38016196 211 DSCVICFEAYKPneiVRILTCKHFFHKNCIDPWILAHGTCPMC 253
Cdd:cd16684   3 DICSICYQDMKS---AVITPCSHFFHAGCLKKWLYVQETCPLC 42
PA_PoS1_like cd02124
PA_PoS1_like: Protease-associated (PA) domain PoS1-like. This group includes various PA ...
84-131 1.59e-05

PA_PoS1_like: Protease-associated (PA) domain PoS1-like. This group includes various PA domain-containing proteins similar to Pleurotus ostreatus (Po)S1. PoSl, the main extracellular protease in P. ostreatus is a subtilisin-like serine protease belonging to the peptidase S8 family. Ca2+ and Mn2+ both stimulate the protease activity of (Po)S1. Ca2+ protects PoS1 from autolysis. PoS1 is a monomeric glycoprotein, which may play a role in the regulation of laccases in lignin formation. (Po)S1 participates in the degradation of POXA1b, and in the activation of POXA3, (POXA1b and POXA3 are laccase isoenzymes), but its effect may be indirect. The significance of the PA domain to PoS1 has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.


Pssm-ID: 239039  Cd Length: 129  Bit Score: 43.86  E-value: 1.59e-05
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 38016196  84 NACDP---NTTFIlpRNKepwIALIERGGCAFTQKIKVASEHGARGVIIYN 131
Cdd:cd02124  42 DACQPlpdDTPDL--SGY---IVLVRRGTCTFATKAANAAAKGAKYVLIYN 87
RING-HC_RNFT1-like cd16532
RING finger, HC subclass, found in RING finger and transmembrane domain-containing protein ...
211-254 2.37e-05

RING finger, HC subclass, found in RING finger and transmembrane domain-containing protein RNFT1, RNFT2, and similar proteins; Both RNFT1 and RNFT2 are multi-pass membrane proteins containing a C3HC4-type RING-HC finger. Their biological roles remain unclear.


Pssm-ID: 438194 [Multi-domain]  Cd Length: 41  Bit Score: 41.13  E-value: 2.37e-05
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 38016196 211 DSCVICFEAYKpnEIVRiLTCKHFFHKNCIDPWILAHGTCPMCK 254
Cdd:cd16532   1 DICPICQDEFK--DPVV-LRCKHIFCEDCVSEWFERERTCPLCR 41
RING-H2_AMFR cd16455
RING finger, H2 subclass, found in autocrine motility factor receptor (AMFR) and similar ...
211-254 2.54e-05

RING finger, H2 subclass, found in autocrine motility factor receptor (AMFR) and similar proteins; AMFR, also known as AMF receptor, or RING finger protein 45, or ER-protein gp78, is an internalizing cell surface glycoprotein localized in both plasma membrane caveolae and the endoplasmic reticulum (ER). It is involved in the regulation of cellular adhesion, proliferation, motility and apoptosis, as well as in the process of learning and memory. AMFR also functions as a RING finger-dependent ubiquitin protein ligase (E3) implicated in the degradation from the ER. AMFR contains an N-terminal RING-H2 finger and a C-terminal ubiquitin-associated (UBA)-like CUE domain.


Pssm-ID: 438119 [Multi-domain]  Cd Length: 44  Bit Score: 40.89  E-value: 2.54e-05
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 38016196 211 DSCVICFEaykPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCK 254
Cdd:cd16455   1 DDCAICWE---SMQSARKLPCGHLFHNSCLRSWLEQDTSCPTCR 41
mRING-CH-C4HC2H_ZNRF1 cd16694
Modified RING-CH finger, H2 subclass (C4HC2H-type), found in zinc/RING finger protein 1 (ZNRF1) ...
213-251 2.80e-05

Modified RING-CH finger, H2 subclass (C4HC2H-type), found in zinc/RING finger protein 1 (ZNRF1) and similar proteins; ZNRF1, also known as Nerve injury-induced gene 283 protein (nin283), or peripheral nerve injury protein (PNIP), is an E3 ubiquitin-protein ligase that is highly expressed in the nervous system during development and is associated with synaptic vesicle membranes. It is N-myrisotoylated and is also located in the endosome-lysosome compartment in fibroblasts, suggesting it may participate in ubiquitin-mediated protein modification. It contains an N-terminal MAGE domain, and a special C-terminal domain that combines a zinc finger and a modified C4HC2H-type RING-CH finger, rather than the typical C4HC3-type RING-CH finger, which is a variant of the RING-H2 finger. Only the RING finger of the zinc finger-RING finger motif is required for its E3 ubiquitin ligase activity. ZNRF1 regulates Schwann cell differentiation by proteasomal degradation of glutamine synthetase (GS). It also mediates regulation of neuritogenesis via interaction with beta-tubulin type 2 (Tubb2). Moreover, ZNRF1 promotes Wallerian degeneration by degrading AKT to induce glycogen synthase kinase-3beta (GSK3B)-dependent CRMP2 phosphorylation. Furthermore, ZNRF1 and its sister protein ZNRF2 regulate the ubiquitous Na+/K+ pump (Na+/K+ATPase). In addition, ZNRF1 may be associated with leukemogenesis of acute lymphoblastic leukemia (ALL) with paired box domain gene 5 (PAX5) alteration.


Pssm-ID: 438355 [Multi-domain]  Cd Length: 45  Bit Score: 40.78  E-value: 2.80e-05
                        10        20        30
                ....*....|....*....|....*....|....*....
gi 38016196 213 CVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCP 251
Cdd:cd16694   2 CVICLEELLQGDTIARLPCLCIYHKSCIDSWFEVNRSCP 40
PA_GO-like cd02132
PA_GO-like: Protease-associated domain containing proteins like Arabidopsis thaliana growth-on ...
102-131 4.42e-05

PA_GO-like: Protease-associated domain containing proteins like Arabidopsis thaliana growth-on protein GRO10. This group contains various PA domain-containing proteins similar to the functionally uncharacterized Arabidopsis GRO10. The PA domain may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.


Pssm-ID: 239047 [Multi-domain]  Cd Length: 139  Bit Score: 42.80  E-value: 4.42e-05
                        10        20        30
                ....*....|....*....|....*....|
gi 38016196 102 IALIERGGCAFTQKIKVASEHGARGVIIYN 131
Cdd:cd02132  62 IALVERGECAFTEKAKIAEAGGASALLIIN 91
RING-H2_synoviolin cd16479
RING finger, H2 subclass, found in synoviolin and similar proteins; Synoviolin, also known as ...
211-254 8.04e-05

RING finger, H2 subclass, found in synoviolin and similar proteins; Synoviolin, also known as synovial apoptosis inhibitor 1 (Syvn1), Hrd1, or Der3, is an endoplasmic reticulum (ER)-anchoring E3 ubiquitin ligase that functions as a suppressor of ER stress-induced apoptosis and plays a role in homeostasis maintenance. It also targets tumor suppressor gene p53 for proteasomal degradation, suggesting crosstalk between ER associated degradation (ERAD) and p53 mediated apoptotic pathway under ER stress. Moreover, synoviolin controls body weight and mitochondrial biogenesis through negative regulation of the thermogenic coactivator peroxisome proliferator-activated receptor coactivator (PGC)-1beta. It upregulates amyloid beta production by targeting a negative regulator of gamma-secretase, Retention in endoplasmic reticulum 1 (Rer1), for degradation. It is also involved in the degradation of endogenous immature nicastrin, and affects amyloid beta-protein generation. Moreover, synoviolin is highly expressed in rheumatoid synovial cells and may be involved in the pathogenesis of rheumatoid arthritis (RA). It functions as an anti-apoptotic factor that is responsible for the outgrowth of synovial cells during the development of RA. It promotes inositol-requiring enzyme 1 (IRE1) ubiquitination and degradation in synovial fibroblasts with collagen-induced arthritis. Furthermore, the upregulation of synoviolin may represent a protective response against neurodegeneration in Parkinson's disease (PD). In addition, synoviolin is involved in liver fibrogenesis. Synoviolin contains a C3H2C2-type RING-H2 finger.


Pssm-ID: 438142 [Multi-domain]  Cd Length: 43  Bit Score: 39.65  E-value: 8.04e-05
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 38016196 211 DSCVICFEAYKPNEivRILTCKHFFHKNCIDPWILAHGTCPMCK 254
Cdd:cd16479   2 NTCIICREEMTVGA--KKLPCGHIFHLSCLRSWLQRQQTCPTCR 43
RING-HC_RNF213 cd16561
RING finger, HC subclass, found in RING finger protein 213 (RNF213) and similar proteins; ...
213-254 9.76e-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: 39.57  E-value: 9.76e-05
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 38016196 213 CVICFEayKPNEIVRiLTCKHFFHKNCIDPWILAHGTCPMCK 254
Cdd:cd16561   5 CSICLE--DLNDPVK-LPCDHVFCEECIRQWLPGQMSCPLCR 43
PA_VSR cd02125
PA_VSR: Protease-associated (PA) domain-containing plant vacuolar sorting receptor (VSR). This ...
62-129 1.15e-04

PA_VSR: Protease-associated (PA) domain-containing plant vacuolar sorting receptor (VSR). This group includes various PA domain-containing VSRs such as garden pea BP-80, pumpkin PV72, and various Arabidopsis VSRs including AtVSR1. In contrast to most eukaryotes, which only have one or two VSRs, plants have several. This may in part be a reflection of having a more complex vacuolar system with both lytic vacuoles and storage vacuoles. The lytic vacuole is thought to be equivalent to the mammalian lysosome and the yeast vacuole. Pea BP-80 is a type 1 transmembrane protein, involved in the targeting of proteins to the lytic vacuole; it has been suggested that this protein also mediates targeting to the storage vacuole. PV72 and AtVSR1 may mediate transport of seed storage proteins to protein storage vacuoles. The significance of the PA domain to VSRs has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.


Pssm-ID: 239040 [Multi-domain]  Cd Length: 127  Bit Score: 41.31  E-value: 1.15e-04
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 38016196  62 FGRSSILKRVAGVVVPPEGKiQNACDPNTTFILPRNKE----PWIALIERGGCAFTQKIKVASEHGARGVII 129
Cdd:cd02125   2 FGLPQYGGTLTGVVVYPKEN-RTGCKEFDVFFKPKKSEpgrrPVILLLDRGGCFFTLKAWNAQQAGAAAVLV 72
RING-H2_TUL1-like cd23117
RING finger, H2 subclass, found in Saccharomyces cerevisiae transmembrane E3 ubiquitin-protein ...
213-256 1.18e-04

RING finger, H2 subclass, found in Saccharomyces cerevisiae transmembrane E3 ubiquitin-protein ligase 1 (TUL1) and similar proteins; This subfamily includes Saccharomyces cerevisiae TUL1, Schizosaccharomyces pombe DSC E3 ubiquitin ligase complex subunit 1 (DSC1), and Arabidopsis thaliana protein FLYING SAUCER 2 (FLY2). TUL1 is the catalytic component of DSC E3 ubiquitin ligase complexes that tag proteins present in Golgi, endosome and vacuole membranes and function in protein homeostasis under non-stress conditions, and support a role in protein quality control. It mediates ubiquitination of vacuolar proteins such as CPS1, PPN1, PEP12 and other proteins containing exposed hydrophilic residues within their transmembrane domains, leading to their sorting into internal vesicles in late endosomes. TUL1 also targets the unpalmitoylated endosomal SNARE TLG1 to the multivesicular body (MVB) pathway. DSC1, also known as defective for SREBP cleavage protein 1, is the catalytic component of the DSC E3 ubiquitin ligase complex required for the sre1 transcriptional activator proteolytic cleavage to release the soluble transcription factor from the membrane in low oxygen or sterol conditions. FLY2 acts as an E3 ubiquitin-protein ligase that may be involved in xylem development. Members of this subfamily contain a C3H2C3-type RING-H2 finger.


Pssm-ID: 438479 [Multi-domain]  Cd Length: 59  Bit Score: 39.69  E-value: 1.18e-04
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 38016196 213 CVICFEA--YKPNEIVR----ILTCKHFFHKNCIDPWILAHGTCPMCKCD 256
Cdd:cd23117   7 CVICMSDieLPSTNSVRrdymVTPCNHIFHTNCLERWMDIKLECPTCRRP 56
PA_EDEM3_like cd02126
PA_EDEM3_like: protease associated domain (PA) domain-containing EDEM3-like proteins. This ...
102-143 1.38e-04

PA_EDEM3_like: protease associated domain (PA) domain-containing EDEM3-like proteins. This group contains various PA domain-containing proteins similar to mouse EDEM3 (ER-degradation-enhancing mannosidase-like 3 protein). EDEM3 contains a region, similar to Class I alpha-mannosidases (gylcosyl hydrolase family 47), N-terminal to the PA domain. EDEM3 accelerates glycoprotein ERAD (ER-associated degradation). In transfected mammalian cells, overexpression of EDEM3 enhances the mannose trimming from the N-glycans, of a model misfolded protein [alpha1-antitrypsin null (Hong Kong)] as well as, from total glycoproteins. Mannose trimming appears to be involved in the selection of ERAD substrates. EDEM3 has a different specificity of trimming than ER alpha-mannosidase 1. The significance of the PA domain to EDEM3 has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.


Pssm-ID: 239041 [Multi-domain]  Cd Length: 126  Bit Score: 41.19  E-value: 1.38e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 38016196 102 IALIERGGCAFTQKIKVASEHGARGVIIY-NFPGT---GNQVFPMS 143
Cdd:cd02126  43 IAIMERGDCMFVEKARRVQKAGAIGGIVIdNNEGSssdTAPMFAMS 88
RING-HC_EHV1-like cd23130
RING finger, HC subclass, found in Equid alphaherpesvirus 1 (Equine herpesvirus 1/EHV-1) ...
211-254 1.53e-04

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: 38.87  E-value: 1.53e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 38016196 211 DSCVICFEAykPNEIVRILTCKHFFHKNCIDPWILAHGTCPMCK 254
Cdd:cd23130   1 DVCPICLDD--PEDEAITLPCLHQFCYTCILRWLQTSPTCPLCK 42
HRD1 COG5243
HRD ubiquitin ligase complex, ER membrane component [Posttranslational modification, protein ...
161-254 1.62e-04

HRD ubiquitin ligase complex, ER membrane component [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 227568 [Multi-domain]  Cd Length: 491  Bit Score: 43.42  E-value: 1.62e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38016196 161 YFTFYHIRRLWvarienrRWKRLTRELKKAFGQLQVRVLKEGDeevnpnaDSCVICFEA--YKPNEIV--------RILT 230
Cdd:COG5243 252 YALFRRIREHA-------RFRRATKDLNAMYPTATEEQLTNSD-------RTCTICMDEmfHPDHEPLprgldmtpKRLP 317
                        90       100
                ....*....|....*....|....
gi 38016196 231 CKHFFHKNCIDPWILAHGTCPMCK 254
Cdd:COG5243 318 CGHILHLHCLKNWLERQQTCPICR 341
mRING-CH-C4HC2H_ZNRF2 cd16695
Modified RING-CH finger, H2 subclass (C4HC2H-type), found in zinc/RING finger protein 2 (ZNRF2) ...
203-251 1.84e-04

Modified RING-CH finger, H2 subclass (C4HC2H-type), found in zinc/RING finger protein 2 (ZNRF2) and similar proteins; ZNRF2, also known as protein Ells2 or RING finger protein 202 (RNF202), is an E3 ubiquitin-protein ligase that is highly expressed in the nervous system during development and is present in presynaptic plasma membranes. It is N-myrisotoylated and is also located in the endosome-lysosome compartment in fibroblasts. It contains an N-terminal MAGE domain, and a special C-terminal domain that combines a zinc finger and a modified C4HC2H-type RING-CH finger, rather than the typical C4HC3-type RING-CH finger, which is a variant of RING-H2 finger. Only the RING finger of the zinc finger-RING finger motif is required for its E3 ubiquitin ligase activity. Together with its sister protein ZNRF1, ZNRF2 regulates the ubiquitous Na+/K+ pump (Na+/K+ATPase).


Pssm-ID: 438356 [Multi-domain]  Cd Length: 56  Bit Score: 38.86  E-value: 1.84e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 38016196 203 DEEVNPNADSCVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHGTCP 251
Cdd:cd16695   3 EDVLSKDAGECAICLEELQQGDTIARLPCLCIYHKGCIDEWFEVNRSCP 51
APC11 COG5194
Component of SCF ubiquitin ligase and anaphase-promoting complex [Posttranslational ...
207-254 1.88e-04

Component of SCF ubiquitin ligase and anaphase-promoting complex [Posttranslational modification, protein turnover, chaperones / Cell division and chromosome partitioning];


Pssm-ID: 227521 [Multi-domain]  Cd Length: 88  Bit Score: 39.82  E-value: 1.88e-04
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 38016196 207 NPNADSCVICFEAYKPNE--IVRILTCKHFFHKNCIDPWILAHGTCPMCK 254
Cdd:COG5194  28 NHIMGTCPECQFGMTPGDecPVVWGVCNHAFHDHCIYRWLDTKGVCPLDR 77
RING-H2_ASR1 cd23120
RING finger, H2 subclass, found in Saccharomyces cerevisiae alcohol-sensitive RING finger ...
211-254 2.30e-04

RING finger, H2 subclass, found in Saccharomyces cerevisiae alcohol-sensitive RING finger protein 1 (ASR1) and similar proteins; ASR1 is required for tolerance to alcohol. It signals alcohol stress to the nucleus. ASR1 contains a C3H2C3-type RING-H2 finger.


Pssm-ID: 438482 [Multi-domain]  Cd Length: 54  Bit Score: 38.67  E-value: 2.30e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 38016196 211 DSCVICFEAyKPNEIVRILTCKHFFHKNCIDPWILAHGT--CPMCK 254
Cdd:cd23120   2 EECPICLEE-MNSGTGYLADCGHEFHLTCIREWHNKSGNldCPICR 46
RING-HC cd16449
HC subclass of RING (RING-HC) finger and its variants; The RING finger is a specialized type ...
212-253 2.58e-04

HC subclass of RING (RING-HC) finger and its variants; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers. Some have a different Cys/His pattern. Some lack a single Cys or His residue at typical Zn ligand positions, especially, the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can chelate Zn in a RING finger as well. This family corresponds to the HC subclass of RING (RING-HC) fingers that are characterized by containing C3HC4-type canonical RING-HC fingers or noncanonical RING-HC finger variants, including C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type modified RING-HC fingers. The canonical RING-HC finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-HC fingers can be found in a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle, and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serve as scaffolds for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enables efficient transfer of ubiquitin from E2 to the substrates.


Pssm-ID: 438113 [Multi-domain]  Cd Length: 41  Bit Score: 38.24  E-value: 2.58e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 38016196 212 SCVICFEAYKPneiVRILTCKHFFHKNCIDPWI-LAHGTCPMC 253
Cdd:cd16449   2 ECPICLERLKD---PVLLPCGHVFCRECIRRLLeSGSIKCPIC 41
RING-HC_Topors cd16574
RING finger, HC subclass, found in topoisomerase I-binding arginine/serine-rich protein ...
211-255 2.65e-04

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: 38.03  E-value: 2.65e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 38016196 211 DSCVICFEAYKpNEIVRILTCKHFFHKNCIDPWILAHGTCPMCKC 255
Cdd:cd16574   2 SSCPICLDRFE-NEKAFLDGCFHAFCFTCILEWSKVKNECPLCKQ 45
RING-H2_AIRP1-like cd23116
RING finger, H2 subclass, found in Arabidopsis thaliana protein ABA INSENSITIVE RING PROTEIN 1 ...
211-253 3.87e-04

RING finger, H2 subclass, found in Arabidopsis thaliana protein ABA INSENSITIVE RING PROTEIN 1 (AIRP1) and similar proteins; This subfamily includes Arabidopsis thaliana AIRP1 and RING-H2 finger B1a (RHB1A). AIRP1, also known as RING-type E3 ubiquitin transferase AIRP1, possesses E3 ubiquitin-protein ligase activity in vitro when associated with the E2 enzyme UBC8. It plays combinatory roles with AIRP2 in the positive regulation of the abscisic acid-mediated drought stress response. RHB1A is a probable E3 ubiquitin-protein ligase. Members of this subfamily contain a C3H2C3-type RING-H2 finger.


Pssm-ID: 438478 [Multi-domain]  Cd Length: 49  Bit Score: 37.83  E-value: 3.87e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 38016196 211 DSCVICFEAYKpNEIVRILT-CKHFFHKNCIDPWILAHGTCPMC 253
Cdd:cd23116   3 DVCPTCLEGYT-EENPKLLTkCGHHFHLACIYEWMERSERCPVC 45
RING-HC_ARI6-like cd23141
RING finger, HC subclass, found in Arabidopsis thaliana protein ariadne homolog 6 (ARI6) and ...
213-265 8.50e-04

RING finger, HC subclass, found in Arabidopsis thaliana protein ariadne homolog 6 (ARI6) and similar proteins; This subfamily includes ARI6 and ARI11. They might act as E3 ubiquitin-protein ligases, or as part of E3 complexes, which accept ubiquitin from specific E2 ubiquitin-conjugating enzymes and then transfer it to substrates. Members of this subfamily contain a typical C3HC4-type RING-HC finger.


Pssm-ID: 438503 [Multi-domain]  Cd Length: 62  Bit Score: 37.08  E-value: 8.50e-04
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 38016196 213 CVICFEAYKPNEIVRIlTCKHFFHKNCIDPWI---LAHG------TCPMCKCDIlkALGIQM 265
Cdd:cd23141   4 CGICFESFPVEEMRAA-SCGHYFCKTCWTGYIhtaISDGpgcldlRCPDPSCPA--AVGEDM 62
PA_1 cd04813
PA_1: Protease-associated (PA) domain subgroup 1. A subgroup of PA-domain containing proteins. ...
84-131 1.01e-03

PA_1: Protease-associated (PA) domain subgroup 1. A subgroup of PA-domain containing proteins. Proteins in this subgroup contain a RING-finger (Really Interesting New Gene) domain C-terminal to this PA domain. The PA domain is an insert domain in a diverse fraction of proteases. The significance of the PA domain to many of the proteins in which it is inserted is undetermined. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate. Proteins in this group contain a C-terminal RING-finger domain. Proteins into which the PA domain is inserted include the following: i) various signal peptide peptidases: such as hSPPL2a and 2b, ii) various E3 ubiquitin ligases similar to human GRAIL (gene related to anergy in lymphocytes) protein, iii) various proteins containing a RING finger motif such as Arabidopsis ReMembR-H2 protein, iv) EDEM3 (ER-degradation-enhancing mannosidase-like 3 protein), v) various plant vacuolar sorting receptors such as Pisum sativum BP-80, vi) prostate-specific membrane antigen (PSMA), vii) yeast aminopeptidase Y viii) Vibrio metschnikovii VapT, a sodium dodecyl sulfate (SDS) resistant extracellular alkaline serine protease, ix) various subtilisin-like proteases such as Cucumisin from the juice of melon fruits, and x) human TfR (transferrin receptor) 1 and human TfR2. The proteins listed above belong to other subgroups; relatively little is known about proteins in this subgroup.


Pssm-ID: 240117 [Multi-domain]  Cd Length: 117  Bit Score: 38.52  E-value: 1.01e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 38016196  84 NACDPNTTfilpRNKEPWIALIERGGCAFTQKIKVASEHGARGVIIYN 131
Cdd:cd04813  28 DACSLQEH----AEIDGKVALVLRGGCGFLDKVMWAQRRGAKAVIVGD 71
RING_Ubox cd00162
RING finger (Really Interesting New Gene) domain and U-box domain superfamily; The RING finger ...
213-253 1.31e-03

RING finger (Really Interesting New Gene) domain and U-box domain superfamily; 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). C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type RING fingers are closely related to RING-HC fingers. In contrast, C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type RING fingers are more closely related to RING-H2 fingers. However, not all RING finger-containing proteins display regular RING finger features, and the RING finger family has turned out to be multifarious. The degenerate RING fingers of the Siz/PIAS RING (SP-RING) family proteins and sporulation protein RMD5, are characterized by lacking the second, fifth, and sixth Zn2+ ion-coordinating residues. They bind only one Zn2+ ion. On the other hand, the RING fingers of the human APC11 and RBX1 proteins can bind a third Zn atom since they harbor four additional Zn ligands. U-box is a modified form of the RING finger domain that lacks metal chelating Cys and His residues. It resembles the cross-brace RING structure consisting of three beta-sheets and a single alpha-helix, which would be stabilized by salt bridges instead of chelated metal ions. U-box proteins are widely distributed among eukaryotic organisms and show a higher prevalence in plants than in other organisms. RING finger/U-box-containing proteins are 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 enable efficient transfer of ubiquitin from E2 to the substrates.


Pssm-ID: 438111 [Multi-domain]  Cd Length: 42  Bit Score: 35.90  E-value: 1.31e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 38016196 213 CVICFEAYKPNEIVRILTCKHFFHKNCIDPWILAHG-TCPMC 253
Cdd:cd00162   1 CPICREEMNDRRPVVLLSCGHTFSRSAIARWLEGSKqKCPFC 42
RING-HC_RBR_TRIAD1 cd16773
RING finger, HC subclass, found in two RING fingers and DRIL [double RING finger linked] 1 ...
212-257 1.37e-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: 1.37e-03
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 38016196 212 SCVICFEAYKPNEiVRILTCKHFFHKNCidpWI------LAHG-----TCPMCKCDI 257
Cdd:cd16773   2 TCGVCCEDVPKDE-LFSLACGHYFCNDC---WKqyltvkIKDGvstgiECMAPDCKV 54
RING-HC_HLTF cd16509
RING finger, HC subclass, found in helicase-like transcription factor (HLTF) and similar ...
213-257 1.44e-03

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: 36.13  E-value: 1.44e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 38016196 213 CVICFEAykPNEIVrILTCKHFFHKNCIDPWIL-AHGTCPMCKCDI 257
Cdd:cd16509   6 CAICLDS--LTNPV-ITPCAHVFCRRCICEVIQrEKAKCPMCRAPL 48
RING-H2_BRAP2 cd16457
RING finger, H2 subclass, found in BRCA1-associated protein (BRAP2) and similar proteins; ...
212-254 2.16e-03

RING finger, H2 subclass, found in BRCA1-associated protein (BRAP2) and similar proteins; BRAP2, also known as impedes mitogenic signal propagation (IMP), RING finger protein 52, or renal carcinoma antigen NY-REN-63, is a novel cytoplasmic protein interacting with the two functional nuclear localization signal (NLS) motifs of BRCA1, a nuclear protein linked to breast cancer. It also binds to the SV40 large T antigen NLS motif and the bipartite NLS motif found in mitosin. BRAP2 serves as a cytoplasmic retention protein and plays a role in the regulation of nuclear protein transport. It contains an N-terminal RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), followed by a C3H2C3-type RING-H2 finger and a UBP-type zinc finger.


Pssm-ID: 438121 [Multi-domain]  Cd Length: 44  Bit Score: 35.34  E-value: 2.16e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 38016196 212 SCVICFEAYKPNE--IVRILtCKHFFHKNCIDPWIlaHGTCPMCK 254
Cdd:cd16457   2 TCPVCLERMDESVsgILTIL-CNHSFHCSCLSKWG--DSSCPVCR 43
COG5219 COG5219
Uncharacterized conserved protein, contains RING Zn-finger [General function prediction only];
167-257 2.21e-03

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


Pssm-ID: 227544 [Multi-domain]  Cd Length: 1525  Bit Score: 40.04  E-value: 2.21e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38016196  167 IRRLWVARIENRRWKRLTR-ELKKAFGQL--QVRVLKEGDEEVNPNADSCVICF------EAYKPNEivRILTCKHFFHK 237
Cdd:COG5219 1423 IKRVGTSEIGWKSWINLRQnEMIKKNGSFmdLLGLWKKNIDEKFSGHEECAICYsvldmvDRSLPSK--RCATCKNKFHT 1500
                         90       100
                 ....*....|....*....|..
gi 38016196  238 NCIDPWILAHG--TCPMCKCDI 257
Cdd:COG5219 1501 RCLYKWFASSArsNCPLCRSEI 1522
RING-H2_WAVH2 cd23114
RING finger, H2 subclass, found in Arabidopsis thaliana protein WAV3 homolog 2 (WAVH2) and ...
207-257 2.46e-03

RING finger, H2 subclass, found in Arabidopsis thaliana protein WAV3 homolog 2 (WAVH2) and similar proteins; WAVH2, also known as RING-type E3 ubiquitin transferase WAVH2, is a probable E3 ubiquitin-protein ligase involved in the regulation of root growth. It acts as a positive regulator of root gravitropism. WAVH2 contains a C3H2C3-type RING-H2 finger.


Pssm-ID: 438476 [Multi-domain]  Cd Length: 56  Bit Score: 35.63  E-value: 2.46e-03
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 38016196 207 NPNADSCVICFEAYKPNEI--VRILTCKHFFHKNCIDPWIlAHGT--CPMCKCDI 257
Cdd:cd23114   1 KASSSECSICLETMKPGSGhaIFTAECSHSFHFECIAGNV-RHGNlrCPVCRAKW 54
RING-H2_APC11 cd16456
RING finger, H2 subclass, found in anaphase-promoting complex subunit 11 (APC11) and similar ...
231-254 2.71e-03

RING finger, H2 subclass, found in anaphase-promoting complex subunit 11 (APC11) and similar proteins; APC11, also known as cyclosome subunit 11, or hepatocellular carcinoma-associated RING finger protein, is a C3H2C3-type RING-H2 protein that facilitates ubiquitin chain formation by recruiting ubiquitin-charged ubiquitin conjugating enzymes (E2) through its RING-H2 domain. APC11 and its partner, the cullin-like subunit APC2, form the dynamic catalytic core of the gigantic, multisubunit 1.2-MDa anaphase-promoting complex/cyclosome (APC), also known as the cyclosome, which is a ubiquitin-protein ligase (E3) composed of at least 12 subunits and controls cell division by ubiquitinating cell cycle regulators, such as cyclin B and securin, to drive their timely degradation. APC11 can be inhibited by hydrogen peroxide, which may contribute to the delay in cell cycle progression through mitosis that is characteristic of cells subjected to oxidative stress. APC11 contains a canonical RING-H2-finger that coordinate two Zn2+ ions. In addition, it contains a third Zn2+-binding site that is not essential for its ligase activity.


Pssm-ID: 438120 [Multi-domain]  Cd Length: 63  Bit Score: 35.72  E-value: 2.71e-03
                        10        20
                ....*....|....*....|....*..
gi 38016196 231 CKHFFHKNCIDPWI---LAHGTCPMCK 254
Cdd:cd16456  32 CSHCFHMHCILKWLnsqQVQQHCPMCR 58
RING-HC_Cbl-c cd16710
RING finger, HC subclass, found in E3 ubiquitin-protein ligase Cbl-c and similar proteins; ...
206-257 3.53e-03

RING finger, HC subclass, found in E3 ubiquitin-protein ligase Cbl-c and similar proteins; Cbl-c, also known as RING finger protein 57 (RNF57), SH3-binding protein Cbl-3, SH3-binding protein Cbl-c, or signal transduction protein Cbl-c, is an E3 ubiquitin-protein ligase expressed exclusively in epithelial cells. It contains 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), a C3HC4-type RING-HC finger, and a short proline-rich region, but lacks the ubiquitin-associated (UBA) leucine zipper motif that are present in Cbl and Cbl-b. Cbl-c acts as a regulator of epidermal growth factor receptor (EGFR)-mediated signal transduction. It also suppresses v-Src-induced transformation through ubiquitin-dependent protein degradation. Moreover, Cbl-c ubiquitinates and downregulates RETMEN2A and implicates Enigma (PDLIM7) as a positive regulator of RETMEN2A by blocking Cbl-mediated ubiquitination and degradation. The ubiquitin ligase activity of Cbl-c is increased via the interaction of its RING-HC finger domain with a LIM domain of the paxillin homolog, hydrogen peroxide induced construct 5 (Hic-5).


Pssm-ID: 438370 [Multi-domain]  Cd Length: 65  Bit Score: 35.45  E-value: 3.53e-03
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 38016196 206 VNPNADSCVICFEAykpNEIVRILTCKHFFHKNCIDPWILAHG-TCPMCKCDI 257
Cdd:cd16710   9 MNSTFELCKICAER---DKDVRIEPCGHLLCSCCLAAWQHSDSqTCPFCRCEI 58
RING-H2_RNF121-like cd16475
RING finger, H2 subclass, found in RING finger proteins RNF121, RNF175 and similar proteins; ...
211-254 3.98e-03

RING finger, H2 subclass, found in RING finger proteins RNF121, RNF175 and similar proteins; This subfamily includes RNF121, RNF175 and similar proteins. RNF121 is an E3-ubiquitin ligase present in the endoplasmic reticulum (ER) and cis-Golgi compartments. It is a novel regulator of apoptosis. It also facilitates the degradation and membrane localization of voltage-gated sodium (NaV) channels, and thus plays a role in the quality control of NaV channels during their synthesis and subsequent transport to the membrane. Moreover, RNF121 acts as a broad regulator of nuclear factor kappaB (NF-kappaB) signaling since its silencing also dampens NF-kappaB activation following stimulation of toll-like receptors (TLRs), nod-like receptors (NLRs), RIG-I-like Receptors (RLRs) or after DNA damage. RNF121 contains five conserved transmembrane (TM) domains and a C3H2C2-type RING-H2 finger. RNF175 is an uncharacterized RING finger protein that shows high sequence similarity with RNF121. This family also includes Arabidopsis RING finger E3 ligase RHA2A, RHA2B, and their homologs. RHA2A is a positive regulator of abscisic acid (ABA) signaling during seed germination and early seedling development. RHA2B may play a role in the ubiquitin-dependent proteolysis pathway that respond to proteasome inhibition. All subfamily members contain a C3H2C3-type RING-H2 finger, which is responsible for E3-ubiquitin ligase activity.


Pssm-ID: 438138 [Multi-domain]  Cd Length: 55  Bit Score: 34.96  E-value: 3.98e-03
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 38016196 211 DSCVICFEAYKPNEIVR-------ILTCKHFFHKNCIDPWILAhG---TCPMCK 254
Cdd:cd16475   1 NVCAVCGQKLDVDDNEEgiiektyKLSCNHVFHEFCIRGWCIV-GkkqTCPYCK 53
RING-H2_Rapsyn cd16478
RING finger, H2 subclass, found in 43 kDa receptor-associated protein of the synapse (Rapsyn) ...
212-255 4.52e-03

RING finger, H2 subclass, found in 43 kDa receptor-associated protein of the synapse (Rapsyn) and similar proteins; Rapsyn, also known as acetylcholine receptor (AChR)-associated 43 kDa protein or RING finger protein 205 (RNF205), is a 43 kDa postsynaptic protein that plays an essential role in the clustering and maintenance of AChR in the postsynaptic membrane of the motor endplate. AChRs enable the transport of rapsyn from the Golgi complex to the plasma membrane through a molecule-specific interaction. Rapsyn also mediates subsynaptic anchoring of protein kinase A (PKA) type I in close proximity to the postsynaptic membrane, which is essential for synapse maintenance. Its mutations in humans cause endplate AChR deficiency and myasthenic syndrome. Rapsyn contains an N-terminal myristoylation signal required for membrane association, seven tetratricopeptide repeats (TPRs) that subserve rapsyn self-association, a coiled-coil domain responsible for the binding of determinants within the long cytoplasmic loop of each AChR subunit, a C3H2C3-type RING-H2 finger that binds to the cytoplasmic domain of beta-dystroglycan and to S-NRAP and links rapsyn to the subsynaptic cytoskeleton, and a serine phosphorylation site.


Pssm-ID: 438141 [Multi-domain]  Cd Length: 48  Bit Score: 34.74  E-value: 4.52e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 38016196 212 SCVICFEAY-KPNEIVRILTCKHFFHKNCIDPwILAHGT--CPMCKC 255
Cdd:cd16478   3 FCGMCGESIgEKNEQLQALPCSHIFHLKCLQT-NLRGGTrgCPNCRR 48
RING-HC_RNFT1 cd16741
RING finger, HC subclass, found in RING finger and transmembrane domain-containing protein 1 ...
211-257 4.96e-03

RING finger, HC subclass, found in RING finger and transmembrane domain-containing protein 1 (RNFT1); RNFT1, also known as protein PTD016, is a multi-pass membrane protein containing a C3HC4-type RING-HC finger. Its biological role remains unclear.


Pssm-ID: 438399 [Multi-domain]  Cd Length: 58  Bit Score: 34.86  E-value: 4.96e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 38016196 211 DSCVIC-FEAYKPneivRILTCKHFFHKNCIDPWILAHGTCPMCKCDI 257
Cdd:cd16741  15 DICAICqAEFRKP----ILLICQHVFCEECISLWFNREKTCPLCRTVI 58
PA_hSPPL_like cd02129
PA_hSPPL_like: Protease-associated domain containing human signal peptide peptidase-like ...
102-155 5.59e-03

PA_hSPPL_like: Protease-associated domain containing human signal peptide peptidase-like (hSPPL)-like. This group contains various PA domain-containing proteins similar to hSPPL2a and 2b. These SPPLs are GxGD aspartic proteases. SPPL2a is sorted to the late endosomes, SPPL2b to the plasma membrane. In activated dendritic cells, hSPPL2a and 2b catalyze the intramembrane proteolysis of tumor necrosis factor alpha triggering IL-12 production. hSPPL2a and 2b may have a broad substrate spectrum. The significance of the PA domain to these SPPLs has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.


Pssm-ID: 239044 [Multi-domain]  Cd Length: 120  Bit Score: 36.22  E-value: 5.59e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 38016196 102 IALIERGGCAFTQKIKVASEHGARGVIIYN----FPGTGNQvfpmshQAFE--DIVVVMI 155
Cdd:cd02129  47 AVVVMRGNCTFYEKARLAQSLGAEGLLIVSrerlVPPSGNR------SEYEkiDIPVALL 100
RING-HC_TRIM13_like_C-V cd16581
RING finger, HC subclass, found in tripartite motif-containing proteins TRIM13, TRIM59 and ...
212-254 6.14e-03

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: 34.41  E-value: 6.14e-03
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 38016196 212 SCVICFEAYKPNeivRILTCKHFFHKNCIDPWILAHGT-------CPMCK 254
Cdd:cd16581   4 TCSICYNIFDDP---KILPCSHTFCKNCLEKLLAASGYyllaslkCPTCR 50
RING-HC_RNF8 cd16535
RING finger, HC subclass, found in RING finger protein 8 (RNF8) and similar proteins; RNF8 is ...
213-257 6.17e-03

RING finger, HC subclass, found in RING finger protein 8 (RNF8) and similar proteins; RNF8 is a telomere-associated E3 ubiquitin-protein ligase that plays an important role in DNA double-strand break (DSB) repair via histone ubiquitination. It is localized in the nucleus and interacts with class III E2s (UBE2E2, UbcH6, and UBE2E3), but not with other E2s (UbcH5, UbcH7, UbcH10, hCdc34, and hBendless). It recruits UBC13 for lysine 63-based self polyubiquitylation. Its deficiency causes neuronal pathology and cognitive decline, and its loss results in neuron degeneration. RNF8, together with RNF168, catalyzes a series of ubiquitylation events on substrates such as H2A and H2AX, with the H2AK13/15 ubiquitylation being particularly important for recruitment of repair factors p53-binding protein 1 (53BP1) or the RAP80-BRCA1 complex to sites of DSBs. RNF8 mediates the ubiquitination of gammaH2AX, and recruits 53BP1 and BRCA1 to DNA damage sites which promotes DNA damage response (DDR) and inhibits chromosomal instability. Moreover, RNF8 interacts with retinoid X receptor alpha (RXR alpha) and enhances its transcription-stimulating activity. It also regulates the rate of exit from mitosis and cytokinesis. RNF8 contains an N-terminal forkhead-associated (FHA) domain and a C-terminal C3HC4-type RING-HC finger.


Pssm-ID: 438197 [Multi-domain]  Cd Length: 64  Bit Score: 34.68  E-value: 6.17e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 38016196 213 CVICFEAYKpnEIVrILTCKHFFHKNCIDPWILAHGTCPMCKCDI 257
Cdd:cd16535   4 CSICSELFI--EAV-TLNCSHSFCSYCITEWMKRKKECPICRKPI 45
mRING-H2-C3DHC3_ZFPL1 cd16487
Modified RING finger, H2 subclass (C3DHC3-type), found in zinc finger protein-like 1 (ZFPL1) ...
207-258 6.62e-03

Modified RING finger, H2 subclass (C3DHC3-type), found in zinc finger protein-like 1 (ZFPL1) and similar proteins; ZFPL1, also known as zinc finger protein MCG4, is a novel mitotic Golgi phosphoprotein required for cis-Golgi integrity and efficient endoplasmic reticulum (ER)-to-Golgi transport via directly interacting with the cis-Golgi matrix protein GM130. ZFPL1 is a widely expressed integral membrane protein with two predicted zinc fingers at its N-terminus. One is a novel type of zinc finger, and the other is a modified RING-H2 finger that lacks the fourth zinc-binding residue of the consensus C3H2C3-type RING-H2 finger. It also contains a bipartite nuclear localization signal (NLS), and a leucine zipper at the C-terminus.


Pssm-ID: 438150 [Multi-domain]  Cd Length: 57  Bit Score: 34.58  E-value: 6.62e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 38016196 207 NPNadsCVICFEAYKPNEIVRiLTCKHFFHKNCIDPWILAHG--------TCPMCKCDIL 258
Cdd:cd16487   1 DPN---CTLCNTSLANGDVVR-LVCYDLFHWSCLNEYAAQLPantapagyTCPQCKGPIF 56
zf-ANAPC11 pfam12861
Anaphase-promoting complex subunit 11 RING-H2 finger; Apc11 is one of the subunits of the ...
208-254 6.93e-03

Anaphase-promoting complex subunit 11 RING-H2 finger; Apc11 is one of the subunits of the anaphase-promoting complex or cyclosome. The APC subunits are cullin family proteins with ubiquitin ligase activity. Polyubiquitination marks proteins for degradation by the 26S proteasome and is carried out by a cascade of enzymes that includes ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), and ubiquitin ligases (E3s). Apc11 acts as an E3 enzyme and is responsible for recruiting E2s to the APC and for mediating the subsequent transfer of ubiquitin to APC substrates in vivo. In Saccharomyces cerevisiae this RING-H2 finger protein defines the minimal ubiquitin ligase activity of the APC, and the integrity of the RING-H2 finger is essential for budding yeast cell viability.


Pssm-ID: 403920 [Multi-domain]  Cd Length: 85  Bit Score: 35.15  E-value: 6.93e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 38016196   208 PNADSCVICFEAYK--------PNEIVRIL--TCKHFFHKNCIDPWILA---HGTCPMCK 254
Cdd:pfam12861  19 PSDDVCGICRVSFDgtcpdckfPGDDCPLVwgKCSHNFHMHCILKWLHTetsKGLCPMCR 78
RING-CH-C4HC3_LTN1 cd16491
RING-CH finger, H2 subclass (C4HC3-type), found in E3 ubiquitin-protein ligase listerin and ...
230-254 7.28e-03

RING-CH finger, H2 subclass (C4HC3-type), found in E3 ubiquitin-protein ligase listerin and similar proteins; Listerin, also known as RING finger protein 160 or zinc finger protein 294, is the mammalian homolog of yeast Ltn1. It is widely expressed in all tissues, but motor and sensory neurons and neuronal processes in the brainstem and spinal cord are primarily affected in the mutant. Listerin is required for embryonic development and plays an important role in neurodegeneration. It also functions as a critical E3 ligase involving quality control of nonstop proteins. It mediates ubiquitylation of aberrant proteins that become stalled on ribosomes during translation. Ltn1 works with several cofactors to form a large ribosomal subunit-associated quality control complex (RQC), which mediates the ubiquitylation and extraction of ribosome-stalled nascent polypeptide chains for proteasomal degradation. It appears to first associate with nascent chain-stalled 60S subunits together with two proteins of unknown function, Tae2 and Rqc1. Listerin contains a long stretch of HEAT (Huntingtin, Elongation factor 3, PR65/A subunit of protein phosphatase 2A, and TOR) or ARM (Armadillo) repeats in the N terminus and middle region, and a catalytic RING-CH finger, also known as vRING or RINGv, with an unusual arrangement of zinc-coordinating residues in the C-terminus . Its cysteines and histidines are arranged in the sequence as C4HC3-type, rather than the C3H2C3-type in canonical RING-H2 finger.


Pssm-ID: 438154 [Multi-domain]  Cd Length: 50  Bit Score: 34.16  E-value: 7.28e-03
                        10        20
                ....*....|....*....|....*..
gi 38016196 230 TCKHFFHKNCIDPWILAHG--TCPMCK 254
Cdd:cd16491  24 TCKNKFHSACLYKWFRSSNksTCPLCR 50
RING-H2_RNF32 cd16471
RING finger, H2 subclass, found in RING finger protein 32 (RNF32) and similar proteins; RNF32 ...
213-254 9.50e-03

RING finger, H2 subclass, found in RING finger protein 32 (RNF32) and similar proteins; RNF32 is mainly expressed in testis spermatogenesis, most likely in spermatocytes and/or in spermatids, suggesting a possible role in sperm formation. RNF32 contains two C3H2C3-type RING-H2 fingers separated by an IQ domain of unknown function. Although the biological function of RNF32 remains unclear, proteins with double RING-H2 fingers may act as scaffolds for binding several proteins that function in the same pathway.


Pssm-ID: 438134 [Multi-domain]  Cd Length: 46  Bit Score: 33.76  E-value: 9.50e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 38016196 213 CVICFEAYKPNEIVrILTCKHFFHKNCIDPW----ILAHGTCPMCK 254
Cdd:cd16471   2 CPICLCAFKGRKCT-LLSCSHVFHEACLSAFekfiESKNQKCPLCR 46
 
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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