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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 998516791 269 RDDIKPCPRCQVLIVKMDDGSCNHMTCAVCGAEFCWLCMKEISDLHYLSPSGCTFWGKKPWSRKKKILW 337
Cdd:cd20355    1 ADDIKPCPRCGALIIKMDDGSCNHMTCAVCGAEFCWLCMKEISDLHYLSPSGCTFWGKKPWSRKKKILW 69

RING finger, HC subclass, found in the family of RING finger proteins RNF19A, RNF19B and similar proteins; The family includes RING finger protein RNF19A and RNF19B, both of which are transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligases. RNF19A, also known as double ring-finger protein (Dorfin) or p38, localizes to the ubiquitylated inclusions in Parkinson's disease (PD), dementia with Lewy bodies, 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. RNF19B, also known as IBR domain-containing protein 3 or natural killer lytic-associated molecule (NKLAM), plays a role in controlling tumor dissemination and metastasis. It is involved in the cytolytic function of natural killer (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 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 998516791 108 MECPLCLAELSAESFPVVQSCDHRSCYDCYQQYLKVEISESRVNIACPECSELLHP 163
Cdd:cd16629    1 LECPLCLDDLSPEFFPILLSCEHRSCRDCLRQYLTIEISESRVNISCPECSERFHP 56

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 998516791 269 RDDIKPCPRCQVLIVKMDDGSCNHMTCAVCGAEFCWLCMKEISDLHYLSPSGCTFWGKKPWSRKKKILW 337
Cdd:cd20355    1 ADDIKPCPRCGALIIKMDDGSCNHMTCAVCGAEFCWLCMKEISDLHYLSPSGCTFWGKKPWSRKKKILW 69

RING finger, HC subclass, found in the family of RING finger proteins RNF19A, RNF19B and similar proteins; The family includes RING finger protein RNF19A and RNF19B, both of which are transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligases. RNF19A, also known as double ring-finger protein (Dorfin) or p38, localizes to the ubiquitylated inclusions in Parkinson's disease (PD), dementia with Lewy bodies, 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. RNF19B, also known as IBR domain-containing protein 3 or natural killer lytic-associated molecule (NKLAM), plays a role in controlling tumor dissemination and metastasis. It is involved in the cytolytic function of natural killer (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 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 998516791 108 MECPLCLAELSAESFPVVQSCDHRSCYDCYQQYLKVEISESRVNIACPECSELLHP 163
Cdd:cd16629    1 LECPLCLDDLSPEFFPILLSCEHRSCRDCLRQYLTIEISESRVNISCPECSERFHP 56

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 998516791  177 EKYEDFMVRRVLAVEPDTRWCPAPDCSFAVIAT-GCASCPKLRCERlgCDSYFCYHCKAKWHPNQTC 242
Cdd:pfam01485   1 EKYEKLLLKSYVESDPNLKWCPTPDCGYIIELTdGCSNTSHVTCSK--CGHEFCFNCKEEWHEGLTC 65

Ring finger domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 998516791  109 ECPLCLAELSAESFPVVQSCDHRSCYDCYQQYLkveisesRVNIACPEC 157
Cdd:pfam13639   2 ECPICLEEFEEGDKVVVLPCGHHFHRECLDKWL-------RSSNTCPLC 43

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 998516791 269 RDDIKPCPRCQVLIVKMDDGSCNHMTCAVCGAEFCWLCMKEISDLHYLSPSGCTFWGKKPWSRKKKILW 337
Cdd:cd20355    1 ADDIKPCPRCGALIIKMDDGSCNHMTCAVCGAEFCWLCMKEISDLHYLSPSGCTFWGKKPWSRKKKILW 69

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 998516791 270 DDIKPCPRCQVLIVKMDDGSCNHMTCAVCGAEFCWLCMKEISDLHYLSPSGCTFWGKKPWSRKKKILWQ 338
Cdd:cd20371    2 DDIKPCPRCSAYIIKMNDGSCNHMTCAVCGCEFCWLCMKEISDLHYLSPSGCTFWGKKPWSRKKKILWQ 70

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 998516791 177 EKYEDFMVRRVLAVEPDTRWCPAPDCSFAVIATGCASCPKLRCERLGCDSYFCYHCKAKWHPNQTCDAARAQR 249
Cdd:cd20363    3 HKYEEFMLRRYLASDPDCRWCPAPDCGYAVIAYGCASCPKLTCEREGCQTEFCYHCKQIWHPNQTCDMARQQR 75

RING finger, HC subclass, found in the family of RING finger proteins RNF19A, RNF19B and similar proteins; The family includes RING finger protein RNF19A and RNF19B, both of which are transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligases. RNF19A, also known as double ring-finger protein (Dorfin) or p38, localizes to the ubiquitylated inclusions in Parkinson's disease (PD), dementia with Lewy bodies, 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. RNF19B, also known as IBR domain-containing protein 3 or natural killer lytic-associated molecule (NKLAM), plays a role in controlling tumor dissemination and metastasis. It is involved in the cytolytic function of natural killer (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 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 998516791 108 MECPLCLAELSAESFPVVQSCDHRSCYDCYQQYLKVEISESRVNIACPECSELLHP 163
Cdd:cd16629    1 LECPLCLDDLSPEFFPILLSCEHRSCRDCLRQYLTIEISESRVNISCPECSERFHP 56

RING finger, HC subclass, found in RING finger protein 19A (RNF19A) and similar proteins; RNF19A, also known as 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, 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. 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 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 998516791 108 MECPLCLAELSAESFPVVQSCDHRSCYDCYQQYLKVEISESRVNIACPECSELLHP 163
Cdd:cd16775    1 MECPLCLLRHSKDRFPDIMTCHHRSCADCLRQYLRIEISESRVNISCPECSERFNP 56

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 998516791  177 EKYEDFMVRRVLAVEPDTRWCPAPDCSFAVIAT-GCASCPKLRCERlgCDSYFCYHCKAKWHPNQTC 242
Cdd:pfam01485   1 EKYEKLLLKSYVESDPNLKWCPTPDCGYIIELTdGCSNTSHVTCSK--CGHEFCFNCKEEWHEGLTC 65

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 998516791 272 IKPCPRCQVLIVKmDDGsCNHMTCAVCGAEFCWLCMKEISD----LHY-LSPSGC 321
Cdd:cd20354   13 SKPCPGCGTLIEK-IDG-CNKMTCTKCRTYFCWLCLKVLSRtnpySHFsDPNSPC 65

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 998516791 192 PDTRWCPAPDCSFAVIATGCASCPKLRCERlgCDSYFCYHCKAKWHPNQTCDAA 245
Cdd:cd20335    2 PNLRWCPTPDCGGVIRVEEPGDGPRVTCPS--CGTSFCFKCKEEWHEGLTCEEY 53

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.

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 998516791 273 KPCPRCQVLIVKmdDGSCNHMTCAVCGAEFCWLCM 307
Cdd:cd20360    4 KDCPKCHVCIEK--NGGCNHMQCSKCKHEFCWMCL 36

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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 998516791 273 KPCPRCQVLIVKmdDGSCNHMTCAV-CGAEFCWLCMKEISD 312
Cdd:cd22583    3 KPCPKCKRPIEK--NQGCMHMTCSPpCKHEFCWLCLGPWSE 41

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 998516791 275 CPRCQVLIVKmdDGSCNHMTCAVCGAEFCWLC------MKEISDlHY--LSPSGCTF 323
Cdd:cd20350    8 CPKCKVYIQR--SEGCDHMTCSQCNTNFCYRCgeryrqLKFIGD-HYsrLSIFGCKY 61

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 998516791 270 DDIKPCPRCQVLIVKmdDGSCNHMTCAVCGAEFCWLCMKEISD----LHY 315
Cdd:cd20352    3 APIKRCPMCHVPIER--DEGCAQMMCKNCKHVFCWYCLASLDDdfllRHY 50

BRcat domain found in an uncharacterized subfamily of RBR proteins; This subfamily contains uncharacterized members of the RBR family, including Arabidopsis thaliana mutator-like transposase, hypothetical protein F9K21.90, and hypothetical protein T16H5.30. 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. 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 998516791 197 CPAPDCSFAVIAT--------GCASCPKlrcerlgCDSYFCYHCKAKWHPNQTCD 243
Cdd:cd22582    7 CPNPDCSALMSKDelleaeddTPRECPK-------CRRLFCARCKVPWHAGLSCA 54

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.

                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 998516791 273 KPCPRCQVLIVKmdDGSCNHMTCAVCGAEFCWLCMKE 309
Cdd:cd14799    3 KWCPKCHFGFEK--ERGCMHATCPQCRQEFCWRCKRQ 37

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.

                         10        20        30
                 ....*....|....*....|....*....|....
gi 998516791 273 KPCPRCQVLIVKmdDGSCNHMTCaVCGAEFCWLC 306
Cdd:cd22586    5 KLCPKCSKPVEK--NGGCNLVTC-RCGQHFCWLC 35

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 998516791 192 PDTRWCPAPDCSFAVIATG---CASCPKlrcerlgCDSYFCYHCKAKWHPNQTCD 243
Cdd:cd20341    5 PDVVYCPRPSCQTPVILEPdenLGICPS-------CNYAFCTLCRETYHGVSPCK 52

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 998516791  271 DIKPCPR--CQVLIVKMDDGS-CNHMTCAVCGAEFCWLCMKE 309
Cdd:pfam01485  17 NLKWCPTpdCGYIIELTDGCSnTSHVTCSKCGHEFCFNCKEE 58

Modified RING finger, HC subclass (C4C4-type), found in RNF144 proteins; This group includes RNF144A and RNF144B, both of which are transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligases. RNF144A, also known as UbcM4-interacting protein 4 (UIP4) or ubiquitin-conjugating enzyme 7-interacting protein 4, targets DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and thus promote 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 known as 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 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 required for RBR-mediated ubiquitination.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 998516791 110 CPLCLAELSAESFPVVQSCDHRSCYDCYQQYLKVEISESRVN-IACP 155
Cdd:cd16632    3 CKLCLEEVPLREMYTLQSCGCIFCLQCLKQYVEVLIREGNVSsITCP 49

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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 998516791 270 DDIKPCPR--CQVLIVKMDDGSCNHMTCAVCGAEFCWLCMKE 309
Cdd:cd20335    2 PNLRWCPTpdCGGVIRVEEPGDGPRVTCPSCGTSFCFKCKEE 43

Rcat domain found in RING finger protein 216 (RNF216); RNF216, also called Triad domain-containing protein 3 (Triad3A), ubiquitin-conjugating enzyme 7-interacting protein 1, or zinc finger protein inhibiting NF-kappa-B (ZIN), is an RBR-type E3 ubiquitin-protein ligase that interacts with several components of the Toll-like receptor (TLR) signaling and promotes their proteolytic degradation. It negatively regulates the RIG-I RNA sensing pathway through Lys48-linked, ubiquitin-mediated degradation of the tumor necrosis factor receptor-associated factor 3 (TRAF3) adapter following RNA virus infection. It also controls ubiquitination and proteasomal degradation of receptor-interacting protein 1 (RIP1), a serine/threonine protein kinase that is critically involved in tumor necrosis factor receptor-1 (TNF-R1)-induced NF-kappa B activation, following disruption of Hsp90 binding. Moreover, RNF216 is involved in inflammatory diseases by strongly inhibiting autophagy in macrophages. It interacts with and ubiquitinates BECN1, a key regulator in autophagy, thereby contributing to BECN1 degradation. It regulates synaptic strength by ubiquitination of Arc, resulting in its rapid proteasomal degradation. It is also a key negative regulator of sustained 2DL4/KIR2DL4 (killer cell Ig-like receptor with two Ig-like domains and a long cytoplasmic domain 4)-mediated NF-kappaB signaling from internalized 2DL4, which functions by promoting ubiquitylation and degradation of endocytosed receptor from early endosomes. Furthermore, RNF216 interacts with human immunodeficiency virus type 1 (HIV-1) virion infectivity factor (Vif) protein, which is essential for the productive infection of primary human CD4 T lymphocytes and macrophages. Mutations in RNF216 may result in Gordon Holmes syndrome, a condition defined by hypogonadotropic hypogonadism and cerebellar ataxia, as well as in autosomal recessive Huntington-like disorder. RNF216 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. The family corresponds to the Rcat domain of RNF216 that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 998516791 272 IKPCPRCQVLIVKmDDGsCNHMTCAvCGAEFCWLCMKEISD 312
Cdd:cd20353    9 IRTCPKCKTKFIK-SEG-CNKMTCR-CGAKMCYICRKPIKG 46

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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 998516791 272 IKPCPRCQVLIVKmdDGSCNHMTCAVCGAEFCWLCMKEISD----LHY 315
Cdd:cd20368    6 IKRCPKCKVYIER--DEGCAQMMCKNCKHAFCWYCLESLDDdfllIHY 51

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 998516791 172 DQAQFEKYEDFMVRRVLAVEPDTRWCPAPDCSFAVIATgCASCPKLRCErlgCDSYFCYHCKAKWHPNQTCD 243
Cdd:cd20343    1 DSKVRLKYQHLITNSFVECNRLLKWCPAPDCGHAVKVQ-YPDARPVTCK---CGHTFCFACGENWHEPVKCR 68

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 998516791 192 PDTRWCPAPDCSFAVIATGCAScPKLRCERlgCDSYFCYHCKAKWHPNQTCD 243
Cdd:cd20344    7 PQLRFCPGPDCPVVIRALEPKA-KRVQCKR--CKTSFCFKCGEDYHAPTDCE 55

BRcat 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 BRcat domain of RNF144B that adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 998516791 191 EPDTRWCPAPDC-SFAVIATGCASCP-KLRCERlgCDSYFCYHCKAKWHPNQTC 242
Cdd:cd20367    5 DPCRTWCPVADCqTVCHVEASDSGQPvLVECPS--CHLKFCSVCKDAWHPEHSC 56

Ring finger domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 998516791  109 ECPLCLAELSAESFPVVQSCDHRSCYDCYQQYLkveisesRVNIACPEC 157
Cdd:pfam13639   2 ECPICLEEFEEGDKVVVLPCGHHFHRECLDKWL-------RSSNTCPLC 43

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

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gi 998516791 110 CPLCLaELSAEsfPVVQSCDHRSCYDCYQQylKVEISesrvNIACPEC 157
Cdd:cd16550    3 CPICL-EILVE--PVTLPCNHTLCMPCFQS--TVEKA----SLCCPLC 41

RING finger, HC subclass, found in SH3 domain-containing RING finger protein 1 (SH3RF1) and similar proteins; SH3RF1, also known as plenty of SH3s (POSH), RING finger protein 142 (RNF142), or SH3 multiple domains protein 2 (SH3MD2), is a trans-Golgi network-associated pro-apoptotic scaffold protein with E3 ubiquitin-protein ligase activity. It also plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and c-Jun N-terminal kinase (JNK) mediated apoptosis, linking Rac1 to downstream components. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. Moreover, SH3RF1 assembles an inhibitory complex with the actomyosin regulatory protein Shroom3, which links to the actin-myosin network to regulate neuronal process outgrowth. It also forms a complex with apoptosis-linked gene-2 (ALG-2) and ALG-2-interacting protein (ALIX/AIP1) in a calcium-dependent manner to play a role in the regulation of the JNK pathway. Furthermore, direct interaction of SH3RF1 and another molecular scaffold JNK-interacting protein (JIP) is required for apoptotic activation of JNKs. Interaction of SH3RF1 and E3 ubiquitin-protein isopeptide ligases, Siah proteins, further promotes JNK activation and apoptosis. In addition, SH3RF1 binds to and degrades TAK1, a crucial activator of both the JNK and the Relish signaling pathways. SH3RF1 contains an N-terminal C3HC4-type RING-HC finger responsible for the E3 ligase activity and four Src Homology 3 (SH3) domains, which are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs.

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gi 998516791 107 LMECPLCLAELSAESfpVVQSCDHRSCYDCYQQylkveISESRVNIACPECSEL 160
Cdd:cd16748    2 LLECPVCLERLDATA--KVLPCQHTFCRRCLLG-----IVGSRSELRCPECRTL 48

RING finger, HC subclass, found in Saccharomyces cerevisiae POB3/SPT16 histone-associated protein 1 (ScPSH1) and similar proteins; ScPSH1 is a Cse4-specific E3 ubiquitin ligase that interacts with the kinetochore protein Pat1 and targets the degradation of budding yeast centromeric histone H3 variant, CENP-ACse4, which is essential for faithful chromosome segregation. ScPSH1 contains a C3HC4-type RING-HC finger and a DNA directed RNA polymerase domain.

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gi 998516791 109 ECPLCLAELSAesfPVVQSCDHRSCYDCYQQYLKveiseSRVNIACPEC 157
Cdd:cd16568    6 ECIICHEYLYE---PMVTTCGHTYCYTCLNTWFK-----SNRSLSCPDC 46

BRcat 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 BRcat domain of RNF144A that adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.

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gi 998516791 185 RRVLaVEPDTRWCPAPDC-SFAVIATGCASCPKL-RCErlGCDSYFCYHCKAKWHPNQTC 242
Cdd:cd20366    2 REVL-LDPCRTWCPSSTCqAVCQLQEVGLQNPQLvQCK--ACDLEFCSACKANWHPGQGC 58

RING finger, HC subclass, found in SH3 domain-containing RING finger protein 2 (SH3RF2) and similar proteins; SH3RF2, also known as heart protein phosphatase 1-binding protein (HEPP1), plenty of SH3s (POSH)-eliminating RING protein (POSHER), protein phosphatase 1 regulatory subunit 39, or RING finger protein 158 (RNF158), is a putative E3 ubiquitin-protein ligase that acts as an anti-apoptotic regulator for the c-Jun N-terminal kinase (JNK) pathway by binding to and promoting the proteasomal degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal C3HC4-type RING-HC finger responsible for the E3 ligase activity and four Src Homology 3 (SH3) domains, which are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs.

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gi 998516791 108 MECPLCLAELSAESfpVVQSCDHRSCYDCYQQYLKveiseSRVNIACPEC 157
Cdd:cd16749    1 LECPVCFEKLDVTA--KVLPCQHTFCKPCLQRIFK-----ARKELRCPEC 43