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Conserved domains on  [gi|564365498|ref|XP_006243847|]
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E3 ubiquitin-protein ligase ARIH2 isoform X1 [Rattus norvegicus]

Protein Classification

ariadne family E3 ubiquitin-protein ligase( domain architecture ID 17725850)

RBR-type ariadne family E3 ubiquitin-protein ligase catalyzes the ubiquitination of target proteins together with ubiquitin-conjugating enzyme E2; similar to Drosophila melanogaster ariadne-2 and its homolog ARIH2

CATH:  3.30.40.10
EC:  2.3.2.31
Gene Ontology:  GO:0008270|GO:0004842|GO:0016567
SCOP:  3000160

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
BRcat_RBR_TRIAD1 cd20344
BRcat domain found in two RING fingers and DRIL [double RING finger linked] 1 (TRIAD1); TRIAD1, ...
216-287 1.01e-45

BRcat domain found in two RING fingers and DRIL [double RING finger linked] 1 (TRIAD1); TRIAD1, also called 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the BRcat domain of TRIAD1 that adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.


:

Pssm-ID: 439005  Cd Length: 72  Bit Score: 153.63  E-value: 1.01e-45
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 564365498 216 DYVESHYQLQLCPGADCPMVIRVQEPRARRVQCNRCNEVFCFKCRQMYHAPTDCATIRKWLTKCADDSETAN 287
Cdd:cd20344    1 DYVKSHPQLRFCPGPDCPVVIRALEPKAKRVQCKRCKTSFCFKCGEDYHAPTDCETIKKWLTKCADDSETAN 72
Rcat_RBR_TRIAD1 cd20360
Rcat domain found in two RING fingers and DRIL [double RING finger linked] 1 (TRIAD1); TRIAD1, ...
291-346 6.46e-37

Rcat domain found in two RING fingers and DRIL [double RING finger linked] 1 (TRIAD1); TRIAD1, also called 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain of TRIAD1 that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.


:

Pssm-ID: 439021  Cd Length: 56  Bit Score: 129.82  E-value: 6.46e-37
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 564365498 291 AHTKDCPKCNICIEKNGGCNHMQCSKCKHDFCWMCLGDWKTHGSEYYECSRYKENP 346
Cdd:cd20360    1 AHTKDCPKCHVCIEKNGGCNHMQCSKCKHEFCWMCLGDWKTHGSEYYECSRYKENP 56
RING-HC_RBR_TRIAD1 cd16773
RING finger, HC subclass, found in two RING fingers and DRIL [double RING finger linked] 1 ...
136-189 6.87e-22

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: 88.56  E-value: 6.87e-22
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 564365498 136 HHCAVCMQFVRKENLLSLTCQHQFCRSCWEQHCSVLVKDGVGVGISCMAQDCPL 189
Cdd:cd16773    1 VTCGVCCEDVPKDELFSLACGHYFCNDCWKQYLTVKIKDGVSTGIECMAPDCKV 54
Ariadne super family cl44843
Ariadne domain; This entry represents the Ariadne domain found in the Ariadne subfamily E3 ...
351-477 5.94e-13

Ariadne domain; This entry represents the Ariadne domain found in the Ariadne subfamily E3 ubiquitin ligase proteins. The C-terminal Ariadne domain adopts an elongated four-helix bundle consisting of an antiparallel arrangement of seven-to-ten-turn long helices. The Ariadne domain is straddled on one side by the IBR domain, and on the other by the RING2 domain. Notably, the Ariadne domain embraces the surface of RING2 containing the catalytic Cys357. The ariadne Domain Masks the HHARI Catalytic Cys357 and Inhibits Intrinsic E3 Activity.


The actual alignment was detected with superfamily member pfam19422:

Pssm-ID: 466073  Cd Length: 261  Bit Score: 68.91  E-value: 5.94e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564365498  351 QSQQA-QAREALKKYLFYFERWENHNKSLQLEAqtyqRIHEKIQERVM---NNLGTWIDWQYLQNAAKLLAKCRYTLQYT 426
Cdd:pfam19422   4 REKKAeRAKRDLYRYMHYHNRYKAHTDSFKLES----KLKETIQEKISileERDSKLRDFSWVTNGLYRLFRSRRVLSYS 79
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 564365498  427 YPYAYYM-------------ESGPRKKLFEYQQAQLEAEIENLSWKVERA-DSYDRGD-LENQMHI 477
Cdd:pfam19422  80 YPFAFYMfgdelfkdemtkeEREIKQNLFEDQQQQLEANVEKLSKFLEEPfDEYSEDKvMEIRMQV 145
 
Name Accession Description Interval E-value
BRcat_RBR_TRIAD1 cd20344
BRcat domain found in two RING fingers and DRIL [double RING finger linked] 1 (TRIAD1); TRIAD1, ...
216-287 1.01e-45

BRcat domain found in two RING fingers and DRIL [double RING finger linked] 1 (TRIAD1); TRIAD1, also called 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the BRcat domain of TRIAD1 that adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.


Pssm-ID: 439005  Cd Length: 72  Bit Score: 153.63  E-value: 1.01e-45
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 564365498 216 DYVESHYQLQLCPGADCPMVIRVQEPRARRVQCNRCNEVFCFKCRQMYHAPTDCATIRKWLTKCADDSETAN 287
Cdd:cd20344    1 DYVKSHPQLRFCPGPDCPVVIRALEPKAKRVQCKRCKTSFCFKCGEDYHAPTDCETIKKWLTKCADDSETAN 72
Rcat_RBR_TRIAD1 cd20360
Rcat domain found in two RING fingers and DRIL [double RING finger linked] 1 (TRIAD1); TRIAD1, ...
291-346 6.46e-37

Rcat domain found in two RING fingers and DRIL [double RING finger linked] 1 (TRIAD1); TRIAD1, also called 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain of TRIAD1 that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.


Pssm-ID: 439021  Cd Length: 56  Bit Score: 129.82  E-value: 6.46e-37
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 564365498 291 AHTKDCPKCNICIEKNGGCNHMQCSKCKHDFCWMCLGDWKTHGSEYYECSRYKENP 346
Cdd:cd20360    1 AHTKDCPKCHVCIEKNGGCNHMQCSKCKHEFCWMCLGDWKTHGSEYYECSRYKENP 56
RING-HC_RBR_TRIAD1 cd16773
RING finger, HC subclass, found in two RING fingers and DRIL [double RING finger linked] 1 ...
136-189 6.87e-22

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: 88.56  E-value: 6.87e-22
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 564365498 136 HHCAVCMQFVRKENLLSLTCQHQFCRSCWEQHCSVLVKDGVGVGISCMAQDCPL 189
Cdd:cd16773    1 VTCGVCCEDVPKDELFSLACGHYFCNDCWKQYLTVKIKDGVSTGIECMAPDCKV 54
IBR smart00647
In Between Ring fingers; the domains occurs between pairs og RING fingers
207-269 1.01e-17

In Between Ring fingers; the domains occurs between pairs og RING fingers


Pssm-ID: 214763 [Multi-domain]  Cd Length: 64  Bit Score: 77.07  E-value: 1.01e-17
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564365498   207 DKYRRYLFRDYVESHYQLQLCPGADCPMVIRVQEP-RARRVQCNRCNEVFCFKCRQMYHAPTDC 269
Cdd:smart00647   1 EKYERLLLESYVESNPDLKWCPAPDCSAAIIVTEEeGCNRVTCPKCGFSFCFRCKVPWHSPVSC 64
IBR pfam01485
IBR domain, a half RING-finger domain; The IBR (In Between Ring fingers) domain is often found ...
207-269 2.89e-13

IBR domain, a half RING-finger domain; The IBR (In Between Ring fingers) domain is often found to occur between pairs of ring fingers (pfam00097). This domain has also been called the C6HC domain and DRIL (for double RING finger linked) domain. Proteins that contain two Ring fingers and an IBR domain (these proteins are also termed RBR family proteins) are thought to exist in all eukaryotic organizms. RBR family members play roles in protein quality control and can indirectly regulate transcription. Evidence suggests that RBR proteins are often parts of cullin-containing ubiquitin ligase complexes. The ubiquitin ligase Parkin is an RBR family protein whose mutations are involved in forms of familial Parkinson's disease.


Pssm-ID: 460227  Cd Length: 65  Bit Score: 64.49  E-value: 2.89e-13
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 564365498  207 DKYRRYLFRDYVESHYQLQLCPGADCPMVIRVQEPRAR--RVQCNRCNEVFCFKCRQMYHAPTDC 269
Cdd:pfam01485   1 EKYEKLLLKSYVESDPNLKWCPTPDCGYIIELTDGCSNtsHVTCSKCGHEFCFNCKEEWHEGLTC 65
Ariadne pfam19422
Ariadne domain; This entry represents the Ariadne domain found in the Ariadne subfamily E3 ...
351-477 5.94e-13

Ariadne domain; This entry represents the Ariadne domain found in the Ariadne subfamily E3 ubiquitin ligase proteins. The C-terminal Ariadne domain adopts an elongated four-helix bundle consisting of an antiparallel arrangement of seven-to-ten-turn long helices. The Ariadne domain is straddled on one side by the IBR domain, and on the other by the RING2 domain. Notably, the Ariadne domain embraces the surface of RING2 containing the catalytic Cys357. The ariadne Domain Masks the HHARI Catalytic Cys357 and Inhibits Intrinsic E3 Activity.


Pssm-ID: 466073  Cd Length: 261  Bit Score: 68.91  E-value: 5.94e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564365498  351 QSQQA-QAREALKKYLFYFERWENHNKSLQLEAqtyqRIHEKIQERVM---NNLGTWIDWQYLQNAAKLLAKCRYTLQYT 426
Cdd:pfam19422   4 REKKAeRAKRDLYRYMHYHNRYKAHTDSFKLES----KLKETIQEKISileERDSKLRDFSWVTNGLYRLFRSRRVLSYS 79
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 564365498  427 YPYAYYM-------------ESGPRKKLFEYQQAQLEAEIENLSWKVERA-DSYDRGD-LENQMHI 477
Cdd:pfam19422  80 YPFAFYMfgdelfkdemtkeEREIKQNLFEDQQQQLEANVEKLSKFLEEPfDEYSEDKvMEIRMQV 145
IBR pfam01485
IBR domain, a half RING-finger domain; The IBR (In Between Ring fingers) domain is often found ...
297-329 1.83e-04

IBR domain, a half RING-finger domain; The IBR (In Between Ring fingers) domain is often found to occur between pairs of ring fingers (pfam00097). This domain has also been called the C6HC domain and DRIL (for double RING finger linked) domain. Proteins that contain two Ring fingers and an IBR domain (these proteins are also termed RBR family proteins) are thought to exist in all eukaryotic organizms. RBR family members play roles in protein quality control and can indirectly regulate transcription. Evidence suggests that RBR proteins are often parts of cullin-containing ubiquitin ligase complexes. The ubiquitin ligase Parkin is an RBR family protein whose mutations are involved in forms of familial Parkinson's disease.


Pssm-ID: 460227  Cd Length: 65  Bit Score: 39.45  E-value: 1.83e-04
                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 564365498  297 PKCNICIEKNGGCN---HMQCSKCKHDFCWMCLGDW 329
Cdd:pfam01485  24 PDCGYIIELTDGCSntsHVTCSKCGHEFCFNCKEEW 59
 
Name Accession Description Interval E-value
BRcat_RBR_TRIAD1 cd20344
BRcat domain found in two RING fingers and DRIL [double RING finger linked] 1 (TRIAD1); TRIAD1, ...
216-287 1.01e-45

BRcat domain found in two RING fingers and DRIL [double RING finger linked] 1 (TRIAD1); TRIAD1, also called 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the BRcat domain of TRIAD1 that adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.


Pssm-ID: 439005  Cd Length: 72  Bit Score: 153.63  E-value: 1.01e-45
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 564365498 216 DYVESHYQLQLCPGADCPMVIRVQEPRARRVQCNRCNEVFCFKCRQMYHAPTDCATIRKWLTKCADDSETAN 287
Cdd:cd20344    1 DYVKSHPQLRFCPGPDCPVVIRALEPKAKRVQCKRCKTSFCFKCGEDYHAPTDCETIKKWLTKCADDSETAN 72
Rcat_RBR_TRIAD1 cd20360
Rcat domain found in two RING fingers and DRIL [double RING finger linked] 1 (TRIAD1); TRIAD1, ...
291-346 6.46e-37

Rcat domain found in two RING fingers and DRIL [double RING finger linked] 1 (TRIAD1); TRIAD1, also called 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain of TRIAD1 that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.


Pssm-ID: 439021  Cd Length: 56  Bit Score: 129.82  E-value: 6.46e-37
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 564365498 291 AHTKDCPKCNICIEKNGGCNHMQCSKCKHDFCWMCLGDWKTHGSEYYECSRYKENP 346
Cdd:cd20360    1 AHTKDCPKCHVCIEKNGGCNHMQCSKCKHEFCWMCLGDWKTHGSEYYECSRYKENP 56
Rcat_RBR_HHARI-like cd20356
Rcat domain found in human homolog of Drosophila Ariadne (HHARI) and similar proteins; This ...
288-343 1.37e-27

Rcat domain found in human homolog of Drosophila Ariadne (HHARI) and similar proteins; This subfamily includes Drosophila melanogaster protein ariadne-1 (ARI-1), and its eukaryotic homologs, such as HHARI. ARI-1 is a widely expressed Drosophila RING-finger protein that localizes mainly in the cytoplasm, and is required for neural development. It interacts with the ubiquitin-conjugating enzyme, UbcD10. HHARI is also called H7-AP2, monocyte protein 6 (MOP-6), protein ariadne-1 homolog, Ariadne RBR E3 ubiquitin protein ligase 1 (ARIH1), ariadne-1 (ARI-1), UbcH7-binding protein, UbcM4-interacting protein, or ubiquitin-conjugating enzyme E2-binding protein. It is an RBR-type E3 ubiquitin-protein ligase highly expressed in nuclei, where it is co-localized with nuclear bodies including Cajal, PML, and Lewy bodies. It interacts with the E2 conjugating enzymes UbcH7, UbcH8, UbcM4 and UbcD10 in human, mouse and fly, and modulates the ubiquitylation of substrate proteins including single-minded 2 (SIM2) and translation initiation factor 4E homologous protein (4EHP). It functions as a potent mediator of DNA damage-induced translation arrest, which protects stem and cancer cells against genotoxic stress by initiating a 4EHP-mediated mRNA translation arrest. HHARI 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain of HHARI and similar proteins that are essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.


Pssm-ID: 439017  Cd Length: 58  Bit Score: 104.75  E-value: 1.37e-27
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 564365498 288 YISAHTKDCPKCNICIEKNGGCNHMQC--SKCKHDFCWMCLGDWKTHGSEYYECSRYK 343
Cdd:cd20356    1 WIAANTKECPKCHVTIEKNGGCNHMVCrnQNCKYEFCWVCLGPWEPHGSSWYNCNRYD 58
Rcat_RBR_ANKIB1 cd20361
Rcat domain found in ankyrin repeat and IBR domain-containing protein 1 (ANKIB1) and similar ...
288-343 3.76e-22

Rcat domain found in ankyrin repeat and IBR domain-containing protein 1 (ANKIB1) and similar proteins; ANKIB1 is an RBR-type E3 ubiquitin-protein ligase that may function as part of an E3 complex, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes and then transfers it to substrates. It contains N-terminal ankyrin repeats, and 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain of ANKIB1 that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.


Pssm-ID: 439022  Cd Length: 62  Bit Score: 89.44  E-value: 3.76e-22
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 564365498 288 YISAHTKDCPKCNICIEKNGGCNHMQCSKCKHDFCWMCLGDWKTHGSE---YYECSRYK 343
Cdd:cd20361    4 WLVTNSKPCPNCKSPIQKNEGCNHMKCSKCKYDFCWVCLEEWKKHSSStggYFRCNRYE 62
RING-HC_RBR_TRIAD1 cd16773
RING finger, HC subclass, found in two RING fingers and DRIL [double RING finger linked] 1 ...
136-189 6.87e-22

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: 88.56  E-value: 6.87e-22
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 564365498 136 HHCAVCMQFVRKENLLSLTCQHQFCRSCWEQHCSVLVKDGVGVGISCMAQDCPL 189
Cdd:cd16773    1 VTCGVCCEDVPKDELFSLACGHYFCNDCWKQYLTVKIKDGVSTGIECMAPDCKV 54
BRcat_RBR_HHARI-like cd20343
BRcat domain found in human homolog of Drosophila Ariadne (HHARI) and similar proteins; This ...
202-284 1.58e-21

BRcat domain found in human homolog of Drosophila Ariadne (HHARI) and similar proteins; This subfamily includes Drosophila melanogaster protein ariadne-1 (ARI-1), and its eukaryotic homologs, such as HHARI. ARI-1 is a widely expressed Drosophila RING-finger protein that localizes mainly in the cytoplasm, and is required for neural development. It interacts with the ubiquitin-conjugating enzyme, UbcD10. HHARI is also called H7-AP2, monocyte protein 6 (MOP-6), protein ariadne-1 homolog, Ariadne RBR E3 ubiquitin protein ligase 1 (ARIH1), ariadne-1 (ARI-1), UbcH7-binding protein, UbcM4-interacting protein, or ubiquitin-conjugating enzyme E2-binding protein 1. It is an RBR-type E3 ubiquitin-protein ligase highly expressed in nuclei, where it is co-localized with nuclear bodies including Cajal, PML, and Lewy bodies. It interacts with the E2 conjugating enzymes UbcH7, UbcH8, UbcM4, and UbcD10 in human, mouse and fly, and modulates the ubiquitylation of substrate proteins including single-minded 2 (SIM2) and translation initiation factor 4E homologous protein (4EHP). It functions as a potent mediator of DNA damage-induced translation arrest, which protects stem and cancer cells against genotoxic stress by initiating a 4EHP-mediated mRNA translation arrest. HHARI 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the BRcat domain of HHARI and similar proteins that adopt the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.


Pssm-ID: 439004  Cd Length: 82  Bit Score: 88.47  E-value: 1.58e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564365498 202 NEELRDKYRRYLFRDYVESHYQLQLCPGADCPMVIRVQEPRARRVQCnRCNEVFCFKCRQMYHAPTDCATIRKWLTKCAD 281
Cdd:cd20343    1 DSKVRLKYQHLITNSFVECNRLLKWCPAPDCGHAVKVQYPDARPVTC-KCGHTFCFACGENWHEPVKCRLLKKWIKKCDD 79

                 ...
gi 564365498 282 DSE 284
Cdd:cd20343   80 DSE 82
Rcat_RBR_ARI7-like cd22583
Rcat domain found in E3 ubiquitin-protein ligase ARI7 and similar proteins; This subfamily ...
292-342 3.28e-20

Rcat domain found in E3 ubiquitin-protein ligase ARI7 and similar proteins; This subfamily contains probable RBR-type E3 ubiquitin-protein ligases (EC 2.3.2.31) including Arabidopsis thaliana ARI5, ARI6, ARI7, and ARI8, as well as Dictyostelium discoideum RbrA (also called Ariadne-like ubiquitin ligase). They may function as part of E3 complexes, which accept ubiquitin from E2 ubiquitin-conjugating enzymes and then transfer it to substrates. RbrA may be required for normal cell-type proportioning and cell sorting during multicellular development, and is also necessary for spore cell viability. Members of this subfamily contain 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain of ARI7-like proteins that are essential for RBR E3 ligase activity and adopt the same fold as the BRcat domain.


Pssm-ID: 439034  Cd Length: 55  Bit Score: 84.04  E-value: 3.28e-20
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 564365498 292 HTKDCPKCNICIEKNGGCNHMQCS-KCKHDFCWMCLGDWKTHGSE---YYECSRY 342
Cdd:cd22583    1 NTKPCPKCKRPIEKNQGCMHMTCSpPCKHEFCWLCLGPWSEHGERtggFYACNRY 55
IBR smart00647
In Between Ring fingers; the domains occurs between pairs og RING fingers
207-269 1.01e-17

In Between Ring fingers; the domains occurs between pairs og RING fingers


Pssm-ID: 214763 [Multi-domain]  Cd Length: 64  Bit Score: 77.07  E-value: 1.01e-17
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564365498   207 DKYRRYLFRDYVESHYQLQLCPGADCPMVIRVQEP-RARRVQCNRCNEVFCFKCRQMYHAPTDC 269
Cdd:smart00647   1 EKYERLLLESYVESNPDLKWCPAPDCSAAIIVTEEeGCNRVTCPKCGFSFCFRCKVPWHSPVSC 64
Rcat_RBR cd20336
Rcat (required-for-catalysis) domain, part of the RBR (RING1-BRcat-Rcat) domain; The RBR ...
292-329 2.27e-17

Rcat (required-for-catalysis) domain, part of the RBR (RING1-BRcat-Rcat) domain; The RBR family of RING-type E3 ligases are characterized by containing an RBR domain, which was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. It is composed of an extended RING domain (RING1) followed by an in-between RING (IBR) domain and the catalytic domain, which is structurally an IBR domain but is commonly designated RING2. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently, where the IBR and RING2 domains have been renamed as BRcat and Rcat domains, respectively. The RBR 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 functions to facilitate the ubiquitination reaction. The Rcat domain contains the catalytic cysteine residue and ubiquitination activity. RBR family members play roles in protein quality control and can indirectly regulate transcription. Evidence suggests that RBR proteins are often parts of cullin-containing ubiquitin ligase complexes. This model corresponds to the Rcat domain that adopts the same fold as the BRcat domain.


Pssm-ID: 438997  Cd Length: 38  Bit Score: 75.33  E-value: 2.27e-17
                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 564365498 292 HTKDCPKCNICIEKNGGCNHMQCSKCKHDFCWMCLGDW 329
Cdd:cd20336    1 NTKKCPKCKVPIEKNGGCNHMTCSRCGTEFCWLCGKPW 38
Rcat_RBR_RNF14 cd20354
Rcat domain found in RING finger protein 14 (RNF14); RNF14, also called androgen receptor (AR) ...
281-326 1.04e-14

Rcat domain found in RING finger protein 14 (RNF14); RNF14, also called androgen receptor (AR)-associated protein 54 (ARA54), HFB30, or Triad2 protein, is an RBR-type E3 ubiquitin-protein ligase that is highly expressed in the testis and interacts with class III E2s (UBE2E2, UbcH6, and UBE2E3). Its differential localization may play an important role in testicular development and spermatogenesis in humans. RNF14 functions as a transcriptional regulator of mitochondrial and immune function in muscles. It is a ligand-dependent AR co-activator that enhances AR-dependent transcriptional activation. It also may participate in enhancing cell cycle progression and cell proliferation via induction of cyclin D1. Moreover, RNF14 is crucial for colon cancer cell survival. It acts as a new enhancer of the Wnt-dependent transcriptional outputs that acts at the level of the T-cell factor/lymphoid enhancer factor (TCF/LEF)-beta-catenin complex. RNF14 contains an N-terminal RWD domain, and a C-terminal RBR domain. The RBR domain 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain of RNF14 that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.


Pssm-ID: 439015  Cd Length: 68  Bit Score: 68.53  E-value: 1.04e-14
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 564365498 281 DDSETANYISAHTKDCPKCNICIEKNGGCNHMQCSKCKHDFCWMCL 326
Cdd:cd20354    1 EEKLSEEWLEKNSKPCPGCGTLIEKIDGCNKMTCTKCRTYFCWLCL 46
Rcat_RBR_CUL9 cd20359
Rcat domain found in cullin-9 (CUL-9) and similar proteins; CUL-9, also called ...
293-340 2.23e-14

Rcat domain found in cullin-9 (CUL-9) and similar proteins; CUL-9, also called UbcH7-associated protein 1 (H7-AP1), p53-associated parkin-like cytoplasmic protein, or PARC, is a cytoplasmic RBR-type E3 ubiquitin-protein ligase that function as a tumor suppressor and promotes p53-dependent apoptosis. It mediates the ubiquitination and degradation of cytosolic cytochrome c to promote survival in neurons and cancer cells. It is also a critical downstream effector of the 3M complex in the maintenance of microtubules and genome integrity. Moreover, CUL-9, together with CUL-7, forms homodimers and heterodimers, as well as some atypical cullin RING ligase complexes, which may exhibit ubiquitin ligase activity. CUL-9 contains a CPH domain (conserved in Cul7, PARC, and HERC2 proteins), a DOC (DOC1/APC10) domain, cullin homology domains linked with E3 ligase function, and a C-terminal RBR domain 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain of CUL-9 that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.


Pssm-ID: 439020  Cd Length: 58  Bit Score: 67.65  E-value: 2.23e-14
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 564365498 293 TKDCPKCNICIEKNGGCNHMQCSKCKHDFCWMCLGDWKTHGSEYYECS 340
Cdd:cd20359    7 SKRCPSCQAQIEKNEGCLHMTCAKCNHGFCWRCLKPWKPTHKDYYNCS 54
IBR pfam01485
IBR domain, a half RING-finger domain; The IBR (In Between Ring fingers) domain is often found ...
207-269 2.89e-13

IBR domain, a half RING-finger domain; The IBR (In Between Ring fingers) domain is often found to occur between pairs of ring fingers (pfam00097). This domain has also been called the C6HC domain and DRIL (for double RING finger linked) domain. Proteins that contain two Ring fingers and an IBR domain (these proteins are also termed RBR family proteins) are thought to exist in all eukaryotic organizms. RBR family members play roles in protein quality control and can indirectly regulate transcription. Evidence suggests that RBR proteins are often parts of cullin-containing ubiquitin ligase complexes. The ubiquitin ligase Parkin is an RBR family protein whose mutations are involved in forms of familial Parkinson's disease.


Pssm-ID: 460227  Cd Length: 65  Bit Score: 64.49  E-value: 2.89e-13
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 564365498  207 DKYRRYLFRDYVESHYQLQLCPGADCPMVIRVQEPRAR--RVQCNRCNEVFCFKCRQMYHAPTDC 269
Cdd:pfam01485   1 EKYEKLLLKSYVESDPNLKWCPTPDCGYIIELTDGCSNtsHVTCSKCGHEFCFNCKEEWHEGLTC 65
Ariadne pfam19422
Ariadne domain; This entry represents the Ariadne domain found in the Ariadne subfamily E3 ...
351-477 5.94e-13

Ariadne domain; This entry represents the Ariadne domain found in the Ariadne subfamily E3 ubiquitin ligase proteins. The C-terminal Ariadne domain adopts an elongated four-helix bundle consisting of an antiparallel arrangement of seven-to-ten-turn long helices. The Ariadne domain is straddled on one side by the IBR domain, and on the other by the RING2 domain. Notably, the Ariadne domain embraces the surface of RING2 containing the catalytic Cys357. The ariadne Domain Masks the HHARI Catalytic Cys357 and Inhibits Intrinsic E3 Activity.


Pssm-ID: 466073  Cd Length: 261  Bit Score: 68.91  E-value: 5.94e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564365498  351 QSQQA-QAREALKKYLFYFERWENHNKSLQLEAqtyqRIHEKIQERVM---NNLGTWIDWQYLQNAAKLLAKCRYTLQYT 426
Cdd:pfam19422   4 REKKAeRAKRDLYRYMHYHNRYKAHTDSFKLES----KLKETIQEKISileERDSKLRDFSWVTNGLYRLFRSRRVLSYS 79
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 564365498  427 YPYAYYM-------------ESGPRKKLFEYQQAQLEAEIENLSWKVERA-DSYDRGD-LENQMHI 477
Cdd:pfam19422  80 YPFAFYMfgdelfkdemtkeEREIKQNLFEDQQQQLEANVEKLSKFLEEPfDEYSEDKvMEIRMQV 145
Rcat_RBR_parkin cd20357
Rcat domain found in parkin and similar proteins; Parkin, also called Parkinson juvenile ...
288-330 1.74e-12

Rcat domain found in parkin and similar proteins; Parkin, also called Parkinson juvenile disease protein 2, is an RBR-type E3 ubiquitin-protein ligase that is associated with recessive early onset Parkinson's disease (PD), and exerts a protective effect against dopamine-induced alpha-synuclein-dependent cell toxicity. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Parkin functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPT5, TOMM20, USP30, ZNF746, and AIMP2. It mediates monoubiquitination as well as Lys6-, Lys11-, Lys48- and Lys63-linked polyubiquitination of substrates depending on the context. Parkin may enhance cell viability and protects dopaminergic neurons from oxidative stress-mediated death by regulating mitochondrial function. It also limits the production of reactive oxygen species (ROS), and regulates cyclin-E during neuronal apoptosis. Moreover, parkin displays a ubiquitin ligase-independent function in transcriptional repression of p53. Parkin contains an N-terminal ubiquitin-like domain and a C-terminal 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain of parkin that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.


Pssm-ID: 439018  Cd Length: 55  Bit Score: 62.02  E-value: 1.74e-12
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 564365498 288 YISAHTKDCPKCNICIEKNGGCNHMQCS--KCKHDFCWMCLGDWK 330
Cdd:cd20357    2 TIKKTTKPCPKCKVPTEKNGGCMHMKCPrpQCGLEWCWICGCEWN 46
Rcat_RBR_RNF144 cd20352
Rcat domain found in the RNF144 protein subfamily; The RNF144 subfamily includes RNF144A and ...
291-326 4.41e-11

Rcat domain found in the RNF144 protein subfamily; The RNF144 subfamily includes RNF144A and RNF144B, which are transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligases. RNF144A, also called UbcM4-interacting protein 4 (UIP4), or ubiquitin-conjugating enzyme 7-interacting protein 4, targets DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and thus promotes DNA damage-induced cell apoptosis. It is transcriptionally repressed by metastasis-associated protein 1 (MTA1) and inhibits MTA1-driven cancer cell migration and invasion. RNF144B, also called PIR2, IBR domain-containing protein 2 (IBRDC2), or p53-inducible RING finger protein (p53RFP), induces p53-dependent but caspase-independent apoptosis. It interacts with E2 ubiquitin-conjugating enzymes UbcH7 and UbcH8, but not with UbcH5. It is involved in ubiquitination and degradation of p21, a p53 downstream protein promoting growth arrest and antagonizing apoptosis, suggesting a role in switching a cell from p53-mediated growth arrest to apoptosis. Moreover, RNF144B regulates the levels of Bax, a pro-apoptotic protein from the Bcl-2 family, and protects cells from unprompted Bax activation and cell death. It also regulates epithelial homeostasis by mediating degradation of p21WAF1 and p63. Both RNF144A and RNF144B contain an RBR domain followed by a potential single-TM domain. The RBR domain 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain of the RNF144 protein subfamily that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.


Pssm-ID: 439013  Cd Length: 70  Bit Score: 58.59  E-value: 4.41e-11
                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 564365498 291 AHTKDCPKCNICIEKNGGCNHMQCSKCKHDFCWMCL 326
Cdd:cd20352    3 APIKRCPMCHVPIERDEGCAQMMCKNCKHVFCWYCL 38
BRcat_RBR_ANKIB1 cd20346
BRcat domain found in ankyrin repeat and IBR domain-containing protein 1 (ANKIB1) and similar ...
215-278 5.50e-11

BRcat domain found in ankyrin repeat and IBR domain-containing protein 1 (ANKIB1) and similar proteins; ANKIB1 is an RBR-type E3 ubiquitin-protein ligase that may function as part of the E3 complex, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes and then transfers it to substrates. It contains N-terminal ankyrin repeats, and 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the BRcat domain of ANKIB1 that adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.


Pssm-ID: 439007 [Multi-domain]  Cd Length: 68  Bit Score: 58.04  E-value: 5.50e-11
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 564365498 215 RDYVESHYQLQLCPGADCPMVIRV----QEPRARRVQCNrCNEVFCFKCRQMYHAPTDCATIRKWLTK 278
Cdd:cd20346    2 RSYVEDNPNLKWCPAPGCGRAVELpgggSEEGSPEVDCG-CGHSFCFNCGEEAHRPVDCETVKKWLKK 68
Rcat_RBR_DEAH12-like cd22585
Rcat domain of ATP-dependent RNA helicase DEAH12 and similar proteins; This group includes ...
294-326 7.50e-11

Rcat domain of ATP-dependent RNA helicase DEAH12 and similar proteins; This group includes Arabidopsis thaliana ATP-dependent RNA helicases DEAH11 and DEAH12, which may be bifunctional proteins that function as DEAD-box RNA helicases (EC 3.6.4.13) and RBR-type E3 ubiquitin-protein ligases (EC 2.3.2.31). As RNA helicases, they may utilize the energy from ATP hydrolysis to unwind RNA (or DNA). DEAD-box RNA helicases participate in every aspect of RNA metabolism. As E3 ubiquitin-protein ligase, they may function as part of E3 complexes, which accept ubiquitin from specific E2 ubiquitin-conjugating enzymes and then transfer it to substrates. Other members of this group may not have an RNA helicase domain. All members contain 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.


Pssm-ID: 439036  Cd Length: 52  Bit Score: 57.35  E-value: 7.50e-11
                         10        20        30
                 ....*....|....*....|....*....|...
gi 564365498 294 KDCPKCNICIEKNGGCNHMQCSKCKHDFCWMCL 326
Cdd:cd22585    3 KRCPKCKSLIEKIDGCNHVTCTRCGTHICWVCL 35
Rcat_RBR_ARI1-like cd22586
Rcat domain found in E3 ubiquitin-protein ligase ARI1 and similar proteins; This subfamily ...
290-325 1.17e-10

Rcat domain found in E3 ubiquitin-protein ligase ARI1 and similar proteins; This subfamily contains probable RBR-type E3 ubiquitin-protein ligases (EC 2.3.2.31) including Arabidopsis thaliana ARI1, ARI2, and ARI3. They may function as part of E3 complexes, which accept ubiquitin from E2 ubiquitin-conjugating enzymes and then transfer it to substrates. Members of this subfamily contain 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain of ARI1-like proteins that are essential for RBR E3 ligase activity and adopt the same fold as the BRcat domain.


Pssm-ID: 439037  Cd Length: 54  Bit Score: 56.77  E-value: 1.17e-10
                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 564365498 290 SAHTKDCPKCNICIEKNGGCNHMQCsKCKHDFCWMC 325
Cdd:cd22586    1 TVNTKLCPKCSKPVEKNGGCNLVTC-RCGQHFCWLC 35
Rcat_RBR_unk cd22584
Rcat domain found in an uncharacterized subfamily of RBR proteins; This subfamily contains ...
294-325 8.73e-09

Rcat domain found in an uncharacterized subfamily of RBR proteins; This subfamily contains uncharacterized members of the RBR family, including Arabidopsis thaliana mutator-like transposase and hypothetical protein At2g19610/F3P11.21. The RBR family of RING-type E3 ligases are characterized by containing a RBR domain, which was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. It is composed of an extended RING domain (RING1) followed by an in-between RING (IBR) domain and the catalytic domain, which is structurally an IBR domain but is commonly designated RING2. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been corrected as RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently, where the IBR and RING2 domains have been renamed as BRcat and Rcat domains, respectively. The RBR 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 functions to facilitate the ubiquitination reaction. RBR family members play roles in protein quality control and can indirectly regulate transcription. Evidence suggests that RBR proteins are often parts of cullin-containing ubiquitin ligase complexes. This model corresponds to the Rcat domain that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.


Pssm-ID: 439035  Cd Length: 37  Bit Score: 51.07  E-value: 8.73e-09
                         10        20        30
                 ....*....|....*....|....*....|..
gi 564365498 294 KDCPKCNICIEKNGGCNHMQCsKCKHDFCWMC 325
Cdd:cd22584    3 RRCPQCGHMVELSEGCNHMTC-RCGYEFCYLC 33
Rcat_RBR_RNF217 cd20350
Rcat domain found in RING finger protein 217 (RNF217); RNF217, also called IBR ...
296-325 1.44e-08

Rcat domain found in RING finger protein 217 (RNF217); RNF217, also called IBR domain-containing protein 1 (IBRDC1), is a transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligase, with different splice variants, that is mainly expressed in testis and skeletal muscle. It interacts with the anti-apoptotic protein HAX1, and is adjacent to a translocation breakpoint involving ETV6 in childhood acute lymphoblastic leukemia (ALL). RNF217 contains an RBR domain followed by TMs. The RBR domain 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain of RNF217 that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.


Pssm-ID: 439011  Cd Length: 68  Bit Score: 51.20  E-value: 1.44e-08
                         10        20        30
                 ....*....|....*....|....*....|
gi 564365498 296 CPKCNICIEKNGGCNHMQCSKCKHDFCWMC 325
Cdd:cd20350    8 CPKCKVYIQRSEGCDHMTCSQCNTNFCYRC 37
BRcat_Rcat_RBR cd14799
BRcat (benign-catalytic) and Rcat (required-for-catalysis) domains, part of the RBR ...
293-327 1.63e-08

BRcat (benign-catalytic) and Rcat (required-for-catalysis) domains, part of the RBR (RING1-BRcat-Rcat) domain; The RBR family of RING-type E3 ligases are characterized by containing an RBR (RING1-BRcat-Rcat) domain, which was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. It is composed of an extended RING domain (RING1) followed by an in-between RING (IBR) domain and the catalytic domain, which is structurally an IBR domain but is commonly designated as RING2. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBRs has been changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis), where the IBR and RING2 domains have been renamed as BRcat and Rcat domains, respectively. The RBR 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 functions to facilitate the ubiquitination reaction. The BRcat domain adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity. RBR family members play roles in protein quality control and can indirectly regulate transcription. Evidence suggests that RBR proteins are often parts of cullin-containing ubiquitin ligase complexes.


Pssm-ID: 438995  Cd Length: 37  Bit Score: 50.19  E-value: 1.63e-08
                         10        20        30
                 ....*....|....*....|....*....|....*
gi 564365498 293 TKDCPKCNICIEKNGGCNHMQCSKCKHDFCWMCLG 327
Cdd:cd14799    2 TKWCPKCHFGFEKERGCMHATCPQCRQEFCWRCKR 36
BRcat_RBR cd20335
BRcat (benign-catalytic) domain, part of the RBR (RING1-BRcat-Rcat) domain; The RBR family of ...
227-270 1.79e-08

BRcat (benign-catalytic) domain, part of the RBR (RING1-BRcat-Rcat) domain; The RBR family of RING-type E3 ligases are characterized by containing an RBR domain, which was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. It is composed of an extended RING domain (RING1) followed by an in-between RING (IBR) domain and the catalytic domain, which is structurally an IBR domain but is commonly designated as RING2. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently, where the IBR and RING2 domains have been renamed as BRcat and Rcat domains, respectively. The RBR 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 functions to facilitate the ubiquitination reaction. The BRcat domain adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity. RBR family members play roles in protein quality control and can indirectly regulate transcription. Evidence suggests that RBR proteins are often parts of cullin-containing ubiquitin ligase complexes. The model corresponds to the BRcat domain.


Pssm-ID: 438996  Cd Length: 53  Bit Score: 50.61  E-value: 1.79e-08
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 564365498 227 CPGADCPMVIRVQEP-RARRVQCNRCNEVFCFKCRQMYHAPTDCA 270
Cdd:cd20335    7 CPTPDCGGVIRVEEPgDGPRVTCPSCGTSFCFKCKEEWHEGLTCE 51
Rcat_RBR_RNF144B cd20369
Rcat domain found in RING finger protein 144B (RNF144B); RNF144B, also called PIR2, IBR ...
291-326 2.50e-08

Rcat domain found in RING finger protein 144B (RNF144B); RNF144B, also called PIR2, IBR domain-containing protein 2 (IBRDC2), or p53-inducible RING finger protein (p53RFP), is a transmembrane (TM) domain-containing RBR E3 ubiquitin-protein ligase that induces p53-dependent but caspase-independent apoptosis. It interacts with E2 ubiquitin-conjugating enzymes UbcH7 and UbcH8, but not with UbcH5. It is involved in ubiquitination and degradation of p21, a p53 downstream protein promoting growth arrest and antagonizing apoptosis, suggesting a role in switching a cell from p53-mediated growth arrest to apoptosis. Moreover, RNF144B regulates the levels of Bax, a pro-apoptotic protein from the Bcl-2 family, and protects cells from unprompted Bax activation and cell death. It also regulates epithelial homeostasis by mediating degradation of p21WAF1 and p63. RNF144B contains an RBR domain followed by a potential single-TM domain. The RBR domain 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain of RNF144B that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.


Pssm-ID: 439030  Cd Length: 71  Bit Score: 50.79  E-value: 2.50e-08
                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 564365498 291 AHTKDCPKCNICIEKNGGCNHMQCSKCKHDFCWMCL 326
Cdd:cd20369    4 APIKQCPVCRVYIERNEGCAQMMCKNCKHTFCWYCL 39
Rcat_RBR_RNF144A cd20368
Rcat domain found in RING finger protein 144A (RNF144A); RNF144A, also called ...
294-326 3.98e-07

Rcat domain found in RING finger protein 144A (RNF144A); RNF144A, also called UbcM4-interacting protein 4 (UIP4), or ubiquitin-conjugating enzyme 7-interacting protein 4, is a transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligase that targets DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and thus promotes DNA damage-induced cell apoptosis. It is transcriptionally repressed by metastasis-associated protein 1 (MTA1) and inhibits MTA1-driven cancer cell migration and invasion. RNF144A contains an RBR domain followed by a potential single-TM domain. The RBR domain 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain of RNF144A that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.


Pssm-ID: 439029  Cd Length: 76  Bit Score: 47.71  E-value: 3.98e-07
                         10        20        30
                 ....*....|....*....|....*....|...
gi 564365498 294 KDCPKCNICIEKNGGCNHMQCSKCKHDFCWMCL 326
Cdd:cd20368    7 KRCPKCKVYIERDEGCAQMMCKNCKHAFCWYCL 39
Rcat_RBR_RNF19 cd20355
Rcat domain found in the RING finger protein 19 (RNF19) subfamily; This subfamily includes ...
294-326 8.18e-07

Rcat domain found in the RING finger protein 19 (RNF19) subfamily; This subfamily includes RING finger protein RNF19A and RNF19B, which are transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligases. RNF19A, also called double ring-finger protein (Dorfin) or p38, localizes to the ubiquitylated inclusions in Parkinson's disease (PD), dementia with Lewy bodies (LBs), multiple system atrophy, and amyotrophic lateral sclerosis (ALS). It interacts with Psmc3, a protein component of the 19S regulatory cap of the 26S proteasome, and further participates in the ubiquitin-proteasome system in acrosome biogenesis, spermatid head shaping, and development of the head-tail coupling apparatus and tail. It modulates the ubiquitination and degradation of calcium-sensing receptor (CaR), which may contribute to a general mechanism for CaR quality control during biosynthesis. Moreover, RNF19A can also ubiquitylate mutant superoxide dismutase 1 (SOD1), the causative gene of familial ALS. It may associate with the endoplasmic reticulum-associated degradation (ERAD) pathway, which is related to the pathogenesis of neurodegenerative disorders, such as PD or Alzheimer's disease. It is also involved in the pathogenic process of PD and LB formation by ubiquitylation of synphilin-1. RNF19B, also called IBR domain-containing protein 3, or natural killer (NK) lytic-associated molecule (NKLAM), plays a role in controlling tumor dissemination and metastasis. It is involved in the cytolytic function of NK cells and cytotoxic T lymphocytes (CTLs). It interacts with ubiquitin conjugates UbcH7 and UbcH8, and ubiquitinates uridine kinase like-1 protein, targeting it for degradation. RNF19B is a novel component of macrophage phagosomes and plays a role in macrophage anti-bacterial activity. It functions as a novel modulator of macrophage inducible nitric oxide synthase (iNOS) expression. Both RNF19A and RNF19B contain an RBR domain followed by three TMs. The RBR domain 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain of the RNF19 subfamily that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.


Pssm-ID: 439016  Cd Length: 69  Bit Score: 46.32  E-value: 8.18e-07
                         10        20        30
                 ....*....|....*....|....*....|....*
gi 564365498 294 KDCPKCNICIEK--NGGCNHMQCSKCKHDFCWMCL 326
Cdd:cd20355    5 KPCPRCGALIIKmdDGSCNHMTCAVCGAEFCWLCM 39
RING-HC_RBR_ANKIB1 cd16774
RING finger, HC subclass, found in ankyrin repeat and IBR domain-containing protein 1 (ANKIB1) ...
138-187 6.00e-06

RING finger, HC subclass, found in ankyrin repeat and IBR domain-containing protein 1 (ANKIB1) and similar proteins; ANKIB1 is an RBR-type E3 ubiquitin-protein ligase that may function as part of an E3 complex, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes and then transfers it to substrates. It contains an N-terminal ankyrin repeat domain and 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: 438430  Cd Length: 58  Bit Score: 43.56  E-value: 6.00e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 564365498 138 CAVCM-QFVRKENLLSLTCQHQFCRSCWEQHCSVLVKDGVGVGISCMAQDC 187
Cdd:cd16774    3 CDICMcSISVFEDPVDMPCGHEFCRACWEGYLNLKIQEGEAHNIFCPAYDC 53
Rcat_RBR_HOIL1 cd20358
Rcat domain found in heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1) and similar proteins; ...
296-323 1.25e-05

Rcat domain found in heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1) and similar proteins; HOIL-1 is also called RBCK1, HOIL-1L, RanBP-type and C3HC4-type zinc finger-containing protein 1, HBV-associated factor 4, Hepatitis B virus X-associated protein 4, RING finger protein 54 (RNF54), ubiquitin-conjugating enzyme 7-interacting protein 3, or UbcM4-interacting protein 28 (UIP28). Together with the E3 ubiquitin-protein ligase RNF31 (also known as HOIP) and SHANK-associated RH domain interacting protein (SHARPIN), it forms the E3-ligase complex (also known as linear-ubiquitin-chain assembly complex LUBAC) that regulates NF-kappaB activity and apoptosis through conjugation of linear polyubiquitin chains to NF-kappaB essential modulator (also known as NEMO or IKBKG). HOIL-1 plays a crucial role in TNF-alpha-mediated NF-kappaB activation. It also functions as an ubiquitin-protein ligase E3 that interacts with not only PKCbeta but also PKCzeta. It can recognize heme-oxidized IRP2 (iron regulatory protein2) and is thought to affect the turnover of oxidatively damaged proteins. HOIL-1 contains an N-terminal ubiqutin-like (UBL) domain and an Npl4 zinc-finger (NZF) domain, which regulate the interaction with the LUBAC subunit RNF31 and ubiquitin, respectively. The NZF domain belongs to RanBP2-type zinc finger (zf-RanBP2) domain superfamily. In addition, HOIL-1 has 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain of HOIL1 that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.


Pssm-ID: 439019  Cd Length: 73  Bit Score: 43.12  E-value: 1.25e-05
                         10        20
                 ....*....|....*....|....*...
gi 564365498 296 CPKCNICIEKNGGCNHMQCSKCKHDFCW 323
Cdd:cd20358   10 CPQCQVIVQKKDGCDWIRCSMCKTEICW 37
Rcat_RBR_HOIP cd20351
Rcat domain found in HOIL-1-interacting protein (HOIP) and similar proteins; HOIP, also called ...
286-325 1.52e-05

Rcat domain found in HOIL-1-interacting protein (HOIP) and similar proteins; HOIP, also called RING finger protein 31 (RNF31) or zinc in-between-RING-finger ubiquitin-associated domain protein, together with HOIL-1 and SHARPIN, forms the E3-ligase complex (also known as linear-ubiquitin-chain assembly complex LUBAC) that regulates NF-kappaB activity and apoptosis. It also interacts with the atypical mammalian orphan receptor DAX-1, trigger DAX-1 ubiquitination and stabilization, and participate in repressing steroidogenic gene expression. HOIP contains three Npl4 zinc fingers, a central ubiquitin-associated (UBA) domain responsible for the interaction with the N-terminal ubiquitin-like domain (UBL) of HOIL-1L, an RBR domain, and a C-terminal linear chain determining domain (LDD). The RBR domain 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain of HOIP that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.


Pssm-ID: 439012  Cd Length: 85  Bit Score: 43.39  E-value: 1.52e-05
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 564365498 286 ANYISAHTKDCPKCNICIE-KNGGCNHMQCSKCKHDFCWMC 325
Cdd:cd20351    9 AAYLAENGIDCPKCKFRYAlAKGGCMHFTCTQCRHEFCSGC 49
RING-HC_ITT1-like cd23134
RING finger, HC subclass, found in Saccharomyces cerevisiae translation termination inhibitor ...
136-187 1.72e-05

RING finger, HC subclass, found in Saccharomyces cerevisiae translation termination inhibitor protein ITT1 and similar proteins; ITT1 is a protein that modulates the efficiency of translation termination, resulting in the readthrough of all three types of nonsense codons UAA, UAG and UGA. ITT1 contains a typical C3HC4-type RING-HC finger.


Pssm-ID: 438496  Cd Length: 60  Bit Score: 42.31  E-value: 1.72e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 564365498 136 HHCAVCMQFVRKENLLSLTCQHQFCRSCWEQHCSVLVKDGVGVGISCMAQDC 187
Cdd:cd23134    5 YHCGICFEEKKGSDFIKLPCGHVFCRECLQDYYTIHIQEGEVSSVKCPDPNC 56
BRcat_RBR_RNF144 cd20349
BRcat domain found in the RNF144 protein subfamily; The RNF144 subfamily includes RNF144A and ...
227-269 3.55e-05

BRcat domain found in the RNF144 protein subfamily; The RNF144 subfamily includes RNF144A and RNF144B, which are transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligases. RNF144A, also called UbcM4-interacting protein 4 (UIP4), or ubiquitin-conjugating enzyme 7-interacting protein 4, targets DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and thus promotes DNA damage-induced cell apoptosis. It is transcriptionally repressed by metastasis-associated protein 1 (MTA1) and inhibits MTA1-driven cancer cell migration and invasion. RNF144B, also called PIR2, IBR domain-containing protein 2 (IBRDC2), or p53-inducible RING finger protein (p53RFP), induces p53-dependent but caspase-independent apoptosis. It interacts with E2 ubiquitin-conjugating enzymes UbcH7 and UbcH8, but not with UbcH5. It is involved in ubiquitination and degradation of p21, a p53 downstream protein promoting growth arrest and antagonizing apoptosis, suggesting a role in switching a cell from p53-mediated growth arrest to apoptosis. Moreover, RNF144B regulates the levels of Bax, a pro-apoptotic protein from the Bcl-2 family, and protects cells from unprompted Bax activation and cell death. It also regulates epithelial homeostasis by mediating degradation of p21WAF1 and p63. Both RNF144A and RNF144B contain an RBR domain followed by a potential single-TM domain. The RBR domain 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the BRcat domain of the RNF144 protein subfamily that adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.


Pssm-ID: 439010  Cd Length: 64  Bit Score: 41.60  E-value: 3.55e-05
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 564365498 227 CPGADCPMVIRVQEP------RARRVQCNRCNEVFCFKCRQMYHAPTDC 269
Cdd:cd20349   11 CPRAGCETVCHVCPPsgsapvTAVPVQCPKCGLTFCSICKAAWHAGQSC 59
Rcat_RBR_RNF19B cd20371
Rcat domain found in RING finger protein 19B (RNF19B); RNF19B, also called IBR ...
294-326 4.20e-05

Rcat domain found in RING finger protein 19B (RNF19B); RNF19B, also called IBR domain-containing protein 3, or natural killer (NK) lytic-associated molecule (NKLAM), is a transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligase that plays a role in controlling tumor dissemination and metastasis. It is involved in the cytolytic function of NK cells and cytotoxic T lymphocytes (CTLs). It interacts with ubiquitin conjugates UbcH7 and UbcH8, and ubiquitinates uridine kinase like-1 protein, targeting it for degradation. Moreover, RNF19B is a novel component of macrophage phagosomes and plays a role in macrophage anti-bacterial activity. It functions as a novel modulator of macrophage inducible nitric oxide synthase (iNOS) expression. RNF19B contains an RBR domain followed by three TMs. The RBR domain 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain of RNF19B that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.


Pssm-ID: 439032  Cd Length: 70  Bit Score: 41.62  E-value: 4.20e-05
                         10        20        30
                 ....*....|....*....|....*....|....*
gi 564365498 294 KDCPKCNICIEK--NGGCNHMQCSKCKHDFCWMCL 326
Cdd:cd20371    5 KPCPRCSAYIIKmnDGSCNHMTCAVCGCEFCWLCM 39
Rcat_RBR_RNF19A cd20370
Rcat domain found in RING finger protein 19A (RNF19A); RNF19A, also called double ring-finger ...
294-326 1.22e-04

Rcat domain found in RING finger protein 19A (RNF19A); RNF19A, also called double ring-finger protein (Dorfin), or p38, is a transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligase that localizes to the ubiquitylated inclusions in Parkinson's disease (PD), dementia with Lewy bodies (LBs), multiple system atrophy, and amyotrophic lateral sclerosis (ALS). It interacts with Psmc3, a protein component of the 19S regulatory cap of the 26S proteasome, and further participates in the ubiquitin-proteasome system in acrosome biogenesis, spermatid head shaping, and development of the head-tail coupling apparatus and tail. It modulates the ubiquitination and degradation of calcium-sensing receptor (CaR), which may contribute to a general mechanism for CaR quality control during biosynthesis. Moreover, RNF19A can also ubiquitylate mutant superoxide dismutase 1 (SOD1), the causative gene of familial ALS. It may associate with endoplasmic reticulum-associated degradation (ERAD) pathway, which is related to the pathogenesis of neurodegenerative disorders, such as PD or Alzheimer's disease. It is also involved in the pathogenic process of PD and LB formation by ubiquitylation of synphilin-1. RNF19A contains an RBR domain followed by three TMs. The RBR domain 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain of RNF19A that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.


Pssm-ID: 439031  Cd Length: 74  Bit Score: 40.41  E-value: 1.22e-04
                         10        20        30
                 ....*....|....*....|....*....|....*
gi 564365498 294 KDCPKCNICIEK--NGGCNHMQCSKCKHDFCWMCL 326
Cdd:cd20370   10 KPCPRCAAYIIKmnDGSCNHMTCAVCGCEFCWLCM 44
BRcat_RBR_RNF19 cd20338
BRcat domain found in the RING finger protein 19 (RNF19) subfamily; This subfamily includes ...
205-274 1.24e-04

BRcat domain found in the RING finger protein 19 (RNF19) subfamily; This subfamily includes RING finger protein RNF19A and RNF19B, both of which are transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligases. RNF19A, also called double ring-finger protein (Dorfin), or p38, localizes to the ubiquitylated inclusions in Parkinson's disease (PD), dementia with Lewy bodies (LBs), multiple system atrophy, and amyotrophic lateral sclerosis (ALS). It interacts with Psmc3, a protein component of the 19S regulatory cap of the 26S proteasome, and further participates in the ubiquitin-proteasome system in acrosome biogenesis, spermatid head shaping, and development of the head-tail coupling apparatus and tail. It modulates the ubiquitination and degradation of Calcium-sensing receptor (CaR), which may contribute to a general mechanism for CaR quality control during biosynthesis. Moreover, RNF19A can also ubiquitylate mutant superoxide dismutase 1 (SOD1), the causative gene of familial ALS. It may associate with the endoplasmic reticulum-associated degradation (ERAD) pathway, which is related to the pathogenesis of neurodegenerative disorders, such as PD or Alzheimer's disease. It is also involved in the pathogenic process of PD and LB formation by ubiquitylation of synphilin-1. RNF19B, also called IBR domain-containing protein 3 or natural killer (NK) lytic-associated molecule (NKLAM), plays a role in controlling tumor dissemination and metastasis. It is involved in the cytolytic function of NK cells and cytotoxic T lymphocytes (CTLs). It interacts with ubiquitin conjugates UbcH7 and UbcH8, and ubiquitinates uridine kinase like-1 (URKL-1) protein, targeting it for degradation. Moreover, RNF19B is a novel component of macrophage phagosomes and plays a role in macrophage anti-bacterial activity. It functions as a novel modulator of macrophage inducible nitric oxide synthase (iNOS) expression. Both RNF19A and RNF19B contain an RBR domain followed by three TMs. The RBR domain 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the BRcat domain of the RNF19 subfamily that adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.


Pssm-ID: 438999  Cd Length: 75  Bit Score: 40.35  E-value: 1.24e-04
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 564365498 205 LRDKYRRYLFRDYVESHYQLQLCPGADCPMVIRVQEPRAR-RVQCNR--CNEVFCFKCRQMYHAPTDCATIRK 274
Cdd:cd20338    1 LLEKYEEFMLRRVLVRDPDARWCPAPDCGYAVIATGCASCpKLTCQRpgCGTEFCYHCKQPWHPNQTCDAARL 73
BRcat-RBR_RNF19B cd20363
BRcat domain found in RING finger protein 19B (RNF19B); RNF19B, also called IBR ...
205-274 1.28e-04

BRcat domain found in RING finger protein 19B (RNF19B); RNF19B, also called IBR domain-containing protein 3 or natural killer (NK) lytic-associated molecule (NKLAM), is a transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligase that plays a role in controlling tumor dissemination and metastasis. It is involved in the cytolytic function of NK cells and cytotoxic T lymphocytes (CTLs). It interacts with ubiquitin conjugates UbcH7 and UbcH8, and ubiquitinates uridine kinase like-1 (URKL-1) protein, targeting it for degradation. Moreover, RNF19B is a novel component of macrophage phagosomes and plays a role in macrophage anti-bacterial activity. It functions as a novel modulator of macrophage inducible nitric oxide synthase (iNOS) expression. RNF19B contains an RBR domain followed by three TMs. The RBR domain 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the BRcat domain of RNF19B that adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.


Pssm-ID: 439024  Cd Length: 75  Bit Score: 40.39  E-value: 1.28e-04
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 564365498 205 LRDKYRRYLFRDYVESHYQLQLCPGADCPM-VIRVQEPRARRVQCNR--CNEVFCFKCRQMYHAPTDCATIRK 274
Cdd:cd20363    1 LMHKYEEFMLRRYLASDPDCRWCPAPDCGYaVIAYGCASCPKLTCERegCQTEFCYHCKQIWHPNQTCDMARQ 73
IBR pfam01485
IBR domain, a half RING-finger domain; The IBR (In Between Ring fingers) domain is often found ...
297-329 1.83e-04

IBR domain, a half RING-finger domain; The IBR (In Between Ring fingers) domain is often found to occur between pairs of ring fingers (pfam00097). This domain has also been called the C6HC domain and DRIL (for double RING finger linked) domain. Proteins that contain two Ring fingers and an IBR domain (these proteins are also termed RBR family proteins) are thought to exist in all eukaryotic organizms. RBR family members play roles in protein quality control and can indirectly regulate transcription. Evidence suggests that RBR proteins are often parts of cullin-containing ubiquitin ligase complexes. The ubiquitin ligase Parkin is an RBR family protein whose mutations are involved in forms of familial Parkinson's disease.


Pssm-ID: 460227  Cd Length: 65  Bit Score: 39.45  E-value: 1.83e-04
                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 564365498  297 PKCNICIEKNGGCN---HMQCSKCKHDFCWMCLGDW 329
Cdd:pfam01485  24 PDCGYIIELTDGCSntsHVTCSKCGHEFCFNCKEEW 59
RING-HC_RBR_HEL2-like cd16625
RING finger, HC subclass, found in Saccharomyces cerevisiae histone E3 ligase 2 (HEL2) and ...
146-190 4.06e-04

RING finger, HC subclass, found in Saccharomyces cerevisiae histone E3 ligase 2 (HEL2) and similar proteins; HEL2 is an E3 ubiquitin-protein ligase that interacts with the E2 ubiquitin-conjugating enzyme UBC4 and histones H3 and H4. It plays an important role in regulating histone protein levels and also likely to contribute to the maintenance of genomic stability in the budding yeast. HEL2 can be phosphorylated by the DNA damage checkpoint kinase and histone protein regulator Rad53. This subfamily also includes Schizosaccharomyces pombe histone E3 ligase 1 (HEL1), also known as DNA-break-localizing protein 4 (dbl4), and Dictyostelium discoideum Ariadne-like ubiquitin ligase (RbrA). RbrA may act as an E3 ubiquitin-protein ligase that appears to be required for normal cell-type proportioning and cell sorting during multicellular development, and is also necessary for spore cell viability. Members of this subfamily contain 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: 438287  Cd Length: 57  Bit Score: 38.51  E-value: 4.06e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 564365498 146 RKENLLSLTCQHQFCRSCWEQHC-SVLVKDGVGVGISCMAQDCPLR 190
Cdd:cd16625   10 GELETFSLECGHEFCVDCYSQYLtSKIKEEGEGCRITCPGEKCNLI 55
BRcat_RBR_parkin cd20340
BRcat domain found in parkin and similar proteins; Parkin, also called Parkinson juvenile ...
203-264 5.12e-04

BRcat domain found in parkin and similar proteins; Parkin, also called Parkinson juvenile disease protein 2, is an RBR-type E3 ubiquitin-protein ligase that is associated with recessive early onset Parkinson's disease (PD), and exerts a protective effect against dopamine-induced alpha-synuclein-dependent cell toxicity. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Parkin functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPT5, TOMM20, USP30, ZNF746 and AIMP2. It mediates monoubiquitination as well as Lys6-, Lys11-, Lys48- and Lys63-linked polyubiquitination of substrates depending on the context. Parkin may enhance cell viability and protects dopaminergic neurons from oxidative stress-mediated death by regulating mitochondrial function. It also limits the production of reactive oxygen species (ROS), and regulates cyclin-E during neuronal apoptosis. Moreover, parkin displays a ubiquitin ligase-independent function in transcriptional repression of p53. Parkin contains an N-terminal ubiquitin-like domain and a C-terminal 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the BRcat domain of parkin that adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.


Pssm-ID: 439001  Cd Length: 77  Bit Score: 38.80  E-value: 5.12e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 564365498 203 EELRDKYRRYLFRDYVeshyqLQ----LCPGADCPMVIRVqEPRARRVQC-NRCNEVFCFKCRQMYH 264
Cdd:cd20340    9 DEQYERYQRFGAEECV-----LQmggvLCPQPGCGAGLLP-EDECNRVTCeLGCGFVFCRECLEAYH 69
RING-HC_RBR_HHARI cd16626
RING finger, HC subclass, found in human homolog of Drosophila ariadne (HHARI) and similar ...
138-187 6.90e-04

RING finger, HC subclass, found in human homolog of Drosophila ariadne (HHARI) and similar proteins; This subfamily includes Drosophila melanogaster protein ariadne-1 (ARI-1), and its eukaryotic homologs, such as HHARI. ARI-1 is a widely expressed Drosophila RING-finger protein that localizes mainly in the cytoplasm and is required for neural development. It interacts with a novel ubiquitin-conjugating enzyme, UbcD10. HHARI, also known as H7-AP2, monocyte protein 6 (MOP-6), protein ariadne-1 homolog, Ariadne RBR E3 ubiquitin protein ligase 1 (ARIH1), ariadne-1 (ARI-1), UbcH7-binding protein, UbcM4-interacting protein, or ubiquitin-conjugating enzyme E2-binding protein 1, is an RBR-type E3 ubiquitin-protein ligase highly expressed in nuclei, where it is co-localized with nuclear bodies including Cajal, PML, and Lewy bodies. It interacts with the E2 conjugating enzymes UbcH7, UbcH8, UbcM4, and UbcD10 in human, mouse, and fly, and modulates the ubiquitylation of substrate proteins including single-minded 2 (SIM2) and translation initiation factor 4E homologous protein (4EHP). It functions as a potent mediator of DNA damage-induced translation arrest, which protects stem and cancer cells against genotoxic stress by initiating a 4EHP-mediated mRNA translation arrest. HHARI 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: 438288  Cd Length: 59  Bit Score: 37.71  E-value: 6.90e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 564365498 138 CAVCMQFVRKENLLSLTCQHQFCRSCWEQHCSV-LVKDGVGVGISCMAQDC 187
Cdd:cd16626    3 CDICYLNYPNSYMTGLECGHKFCMQCWKEYLTTkIMEEGMGQTISCPAHGC 53
mRING-HC-C4C4_RBR_RNF144A cd16777
Modified RING finger, HC subclass (C4C4-type), found in RING finger protein 144A (RNF144A); ...
138-188 2.52e-03

Modified RING finger, HC subclass (C4C4-type), found in RING finger protein 144A (RNF144A); RNF144A, also known as UbcM4-interacting protein 4 (UIP4) or ubiquitin-conjugating enzyme 7-interacting protein 4, is a transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligase that targets DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and thus promotes DNA damage-induced cell apoptosis. It is transcriptionally repressed by metastasis-associated protein 1 (MTA1) and inhibits MTA1-driven cancer cell migration and invasion. RNF144A contains an RBR domain followed by a potential single-TM domain. The RBR domain 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 C4C4-type RING finger whose overall folding is similar to that of the C3HC4-type RING-HC finger. It is responsible for the interaction of E2-conjugating enzymes UbcH7 and UbcH8.


Pssm-ID: 438433  Cd Length: 55  Bit Score: 36.11  E-value: 2.52e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 564365498 138 CAVCMQFVRKENLLSLT-CQHQFCRSCWEQHCSVLVKDGVGVGISCMAQDCP 188
Cdd:cd16777    3 CKLCLGEYPVEQMTTIAqCQCIFCTLCLKQYVELLIKEGLETAISCPDAACP 54
BRcat_RBR_RNF14 cd20341
BRcat domain found in RING finger protein 14 (RNF14); RNF14, also called androgen receptor (AR) ...
227-272 2.59e-03

BRcat domain found in RING finger protein 14 (RNF14); RNF14, also called androgen receptor (AR)-associated protein 54 (ARA54), HFB30, or Triad2 protein, is an RBR-type E3 ubiquitin-protein ligase that is highly expressed in the testis and interacts with class III E2s (UBE2E2, UbcH6, and UBE2E3). Its differential localization may play an important role in testicular development and spermatogenesis in humans. RNF14 functions as a transcriptional regulator of mitochondrial and immune function in muscles. It is a ligand-dependent AR co-activator that enhances AR-dependent transcriptional activation. It may also participate in enhancing cell cycle progression and cell proliferation via induction of cyclin D1. Moreover, RNF14 is crucial for colon cancer cell survival. It acts as a new enhancer of the Wnt-dependent transcriptional outputs that acts at the level of the T-cell factor/lymphoid enhancer factor (TCF/LEF)-beta-catenin complex. RNF14 contains an N-terminal RWD domain, and a C-terminal RBR domain. The RBR domain 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 BRcat domain of RNF14 that adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.


Pssm-ID: 439002  Cd Length: 57  Bit Score: 36.13  E-value: 2.59e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 564365498 227 CPGADCPMVIrVQEPRARRVQCNRCNEVFCFKCRQMYHAPTDCATI 272
Cdd:cd20341   10 CPRPSCQTPV-ILEPDENLGICPSCNYAFCTLCRETYHGVSPCKIK 54
BRcat_RBR_RNF19A cd20362
BRcat domain found in RING finger protein 19A (RNF19A); RNF19A, also called double ring-finger ...
199-274 2.73e-03

BRcat domain found in RING finger protein 19A (RNF19A); RNF19A, also called double ring-finger protein (Dorfin) or p38, is a transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligase that localizes to the ubiquitylated inclusions in Parkinson's disease (PD), dementia with Lewy bodies (LBs), multiple system atrophy, and amyotrophic lateral sclerosis (ALS). It interacts with Psmc3, a protein component of the 19S regulatory cap of the 26S proteasome, and further participates in the ubiquitin-proteasome system in acrosome biogenesis, spermatid head shaping, and development of the head-tail coupling apparatus and tail. It modulates the ubiquitination and degradation of Calcium-sensing receptor (CaR), which may contribute to a general mechanism for CaR quality control during biosynthesis. Moreover, RNF19A can also ubiquitylate mutant superoxide dismutase 1 (SOD1), the causative gene of familial ALS. It may associate with the endoplasmic reticulum-associated degradation (ERAD) pathway, which is related to the pathogenesis of neurodegenerative disorders, such as PD or Alzheimer's disease. It is also involved in the pathogenic process of PD and LB formation by ubiquitylation of synphilin-1. RNF19A contains an RBR domain followed by three TMs. The RBR domain 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the BRcat domain of RNF19A that adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.


Pssm-ID: 439023  Cd Length: 83  Bit Score: 36.95  E-value: 2.73e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564365498 199 LLPNEELRDKYRRYLFRDYVESHYQLQLCPGADCP-MVIRVQEPRARRVQCNR--CNEVFCFKCRQMYHAPTDCATIRK 274
Cdd:cd20362    1 ILNDDVLMEKYEEFMLRRWLVADPDCRWCPAPDCGyAVIAFGCASCPKLTCGRegCGTEFCYHCKQIWHPNQTCDAARQ 79
RING-HC_ARI6-like cd23141
RING finger, HC subclass, found in Arabidopsis thaliana protein ariadne homolog 6 (ARI6) and ...
138-194 4.98e-03

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: 35.54  E-value: 4.98e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 564365498 138 CAVCMQFVRKENLLSLTCQHQFCRSCWEQHCSVLVKDGVG-VGISCMAQDCPLRTPED 194
Cdd:cd23141    4 CGICFESFPVEEMRAASCGHYFCKTCWTGYIHTAISDGPGcLDLRCPDPSCPAAVGED 61
mRING-HC-C4C4_RBR_HOIP cd16631
Modified RING finger, HC subclass (C4C4-type), found in HOIL-1-interacting protein (HOIP) and ...
136-174 6.37e-03

Modified RING finger, HC subclass (C4C4-type), found in HOIL-1-interacting protein (HOIP) and similar proteins; HOIP, also known as RING finger protein 31 (RNF31) or zinc in-between-RING-finger ubiquitin-associated domain protein, together with HOIL-1 and SHARPIN, forms the E3-ligase complex (also known as linear-ubiquitin-chain assembly complex LUBAC) that regulates NF-kappaB activity and apoptosis. It also interacts with the atypical mammalian orphan receptor DAX-1, trigger DAX-1 ubiquitination and stabilization, and participate in repressing steroidogenic gene expression. HOIP contains three Npl4 zinc fingers, a central ubiquitin-associated (UBA) domain responsible for the interaction with the N-terminal ubiquitin-like domain (UBL) of HOIL-1L, an RBR domain, and a C-terminal linear chain determining domain (LDD). The RBR domain 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 C4C4-type RING finger motif whose overall folding is similar to that of the C3HC4-type RING-HC finger. It is required for RBR-mediated ubiquitination.


Pssm-ID: 438293  Cd Length: 54  Bit Score: 34.95  E-value: 6.37e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 564365498 136 HHCAVCMQFVRKENLLSLT-CQHQFCRSCWEQHCSVLVKD 174
Cdd:cd16631    1 QECPICFNSFPRNKMVSLTsCECKICPDCFKQYFTVVIKE 40
RING-HC_TRIM69_C-IV cd16611
RING finger, HC subclass, found in tripartite motif-containing protein 69 (TRIM69) and similar ...
137-166 8.58e-03

RING finger, HC subclass, found in tripartite motif-containing protein 69 (TRIM69) and similar proteins; TRIM69, also known as RFP-like domain-containing protein trimless or RING finger protein 36 (RNF36), is a testis E3 ubiquitin-protein ligase that plays a specific role in apoptosis and may also play an important role in germ cell homeostasis during spermatogenesis. TRIM69 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.


Pssm-ID: 438273 [Multi-domain]  Cd Length: 59  Bit Score: 34.73  E-value: 8.58e-03
                         10        20        30
                 ....*....|....*....|....*....|....
gi 564365498 137 HCAVCMQFVRKENLLSltCQHQFCRSC----WEQ 166
Cdd:cd16611    6 HCPLCLDFFRDPVMLS--CGHNFCQSCitgfWEL 37
 
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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