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Conserved domains on  [gi|188219577|ref|NP_699172|]
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E3 ubiquitin-protein ligase RNF19B isoform a [Homo sapiens]

Protein Classification

RING-HC_RBR_RNF19B and IBR domain-containing protein (domain architecture ID 11617049)

protein containing domains RING-HC_RBR_RNF19B, IBR, and AzlC

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
RING-HC_RBR_RNF19B cd16776
RING finger, HC subclass, found in RING finger protein 19B (RNF19B) and similar proteins; ...
118-172 2.25e-29

RING finger, HC subclass, found in RING finger protein 19B (RNF19B) and similar proteins; RNF19B, also known as IBR domain-containing protein 3 or natural killer 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 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. RNF19B contains a 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 use 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 family corresponds to the RING domain, a C3HC4-type RING-HC finger required for RBR-mediated ubiquitination.


:

Pssm-ID: 319690  Cd Length: 55  Bit Score: 110.45  E-value: 2.25e-29
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 188219577 118 ECPLCLVRLPPERAPRLLSCPHRSCRDCLRHYLRLEISESRVPISCPECSERLNP 172
Cdd:cd16776    1 ECPLCLVRQPPERAPELLSCPHRSCLDCLRQYLRIEISESRVPLSCPECAERLNP 55
IBR smart00647
In Between Ring fingers; the domains occurs between pairs og RING fingers
187-251 5.65e-22

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


:

Pssm-ID: 214763  Cd Length: 64  Bit Score: 89.78  E-value: 5.65e-22
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 188219577   187 KYEEFMLRRYLASDPDCRWCPAPDCGYAVIAYGCASCPKLTCerEGCQTEFCYHCKQIWHPNQTC 251
Cdd:smart00647   2 KYERLLLESYVESNPDLKWCPAPDCSAAIIVTEEEGCNRVTC--PKCGFSFCFRCKVPWHSPVSC 64
IBR pfam01485
IBR domain, a half RING-finger domain; The IBR (In Between Ring fingers) domain is often found ...
283-321 2.20e-06

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 organisms. 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: 396187  Cd Length: 59  Bit Score: 45.21  E-value: 2.20e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 188219577  283 DIKPCPR--CSAYIIKmnDGSCNHMTCAVCGCEFCWLCMKE 321
Cdd:pfam01485  17 NLKWCPTpdCGSIIQQ--SKQCNRVTCSKCGFEFCFNCRAP 55
AzlC super family cl00570
AzlC protein;
347-436 1.09e-03

AzlC protein;


The actual alignment was detected with superfamily member COG1296:

Pssm-ID: 412452  Cd Length: 238  Bit Score: 41.13  E-value: 1.09e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188219577 347 ILWQLGTLIGAPVGISLIA------GIAIPAMVIG--IPVYVGRKIHSRyegrktskhkrnlaitggVTLSVIASpVIAA 418
Cdd:COG1296  145 LYWVVGTLIGALLGSLLPDpetiglDFALPALFIVlvIPQFKRRKTLLS------------------VLASLVLA-LVAL 205
                         90
                 ....*....|....*...
gi 188219577 419 VSVGIGVPIMLAYVYGVV 436
Cdd:COG1296  206 VLFGGPWAVLAGILAGLL 223
 
Name Accession Description Interval E-value
RING-HC_RBR_RNF19B cd16776
RING finger, HC subclass, found in RING finger protein 19B (RNF19B) and similar proteins; ...
118-172 2.25e-29

RING finger, HC subclass, found in RING finger protein 19B (RNF19B) and similar proteins; RNF19B, also known as IBR domain-containing protein 3 or natural killer 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 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. RNF19B contains a 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 use 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 family corresponds to the RING domain, a C3HC4-type RING-HC finger required for RBR-mediated ubiquitination.


Pssm-ID: 319690  Cd Length: 55  Bit Score: 110.45  E-value: 2.25e-29
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 188219577 118 ECPLCLVRLPPERAPRLLSCPHRSCRDCLRHYLRLEISESRVPISCPECSERLNP 172
Cdd:cd16776    1 ECPLCLVRQPPERAPELLSCPHRSCLDCLRQYLRIEISESRVPLSCPECAERLNP 55
IBR smart00647
In Between Ring fingers; the domains occurs between pairs og RING fingers
187-251 5.65e-22

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


Pssm-ID: 214763  Cd Length: 64  Bit Score: 89.78  E-value: 5.65e-22
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 188219577   187 KYEEFMLRRYLASDPDCRWCPAPDCGYAVIAYGCASCPKLTCerEGCQTEFCYHCKQIWHPNQTC 251
Cdd:smart00647   2 KYERLLLESYVESNPDLKWCPAPDCSAAIIVTEEEGCNRVTC--PKCGFSFCFRCKVPWHSPVSC 64
IBR pfam01485
IBR domain, a half RING-finger domain; The IBR (In Between Ring fingers) domain is often found ...
187-248 5.63e-16

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 organisms. 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: 396187  Cd Length: 59  Bit Score: 72.56  E-value: 5.63e-16
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 188219577  187 KYEEFMLRRYLASDPDCRWCPAPDCGYAVIAYGcaSCPKLTCERegCQTEFCYHCKQIWHPN 248
Cdd:pfam01485   2 KYEKLKLADLLESDPNLKWCPTPDCGSIIQQSK--QCNRVTCSK--CGFEFCFNCRAPWHEG 59
IBR pfam01485
IBR domain, a half RING-finger domain; The IBR (In Between Ring fingers) domain is often found ...
283-321 2.20e-06

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 organisms. 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: 396187  Cd Length: 59  Bit Score: 45.21  E-value: 2.20e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 188219577  283 DIKPCPR--CSAYIIKmnDGSCNHMTCAVCGCEFCWLCMKE 321
Cdd:pfam01485  17 NLKWCPTpdCGSIIQQ--SKQCNRVTCSKCGFEFCFNCRAP 55
AzlC COG1296
Predicted branched-chain amino acid permease (azaleucine resistance) [Amino acid transport and ...
347-436 1.09e-03

Predicted branched-chain amino acid permease (azaleucine resistance) [Amino acid transport and metabolism];


Pssm-ID: 224215  Cd Length: 238  Bit Score: 41.13  E-value: 1.09e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188219577 347 ILWQLGTLIGAPVGISLIA------GIAIPAMVIG--IPVYVGRKIHSRyegrktskhkrnlaitggVTLSVIASpVIAA 418
Cdd:COG1296  145 LYWVVGTLIGALLGSLLPDpetiglDFALPALFIVlvIPQFKRRKTLLS------------------VLASLVLA-LVAL 205
                         90
                 ....*....|....*...
gi 188219577 419 VSVGIGVPIMLAYVYGVV 436
Cdd:COG1296  206 VLFGGPWAVLAGILAGLL 223
 
Name Accession Description Interval E-value
RING-HC_RBR_RNF19B cd16776
RING finger, HC subclass, found in RING finger protein 19B (RNF19B) and similar proteins; ...
118-172 2.25e-29

RING finger, HC subclass, found in RING finger protein 19B (RNF19B) and similar proteins; RNF19B, also known as IBR domain-containing protein 3 or natural killer 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 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. RNF19B contains a 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 use 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 family corresponds to the RING domain, a C3HC4-type RING-HC finger required for RBR-mediated ubiquitination.


Pssm-ID: 319690  Cd Length: 55  Bit Score: 110.45  E-value: 2.25e-29
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 188219577 118 ECPLCLVRLPPERAPRLLSCPHRSCRDCLRHYLRLEISESRVPISCPECSERLNP 172
Cdd:cd16776    1 ECPLCLVRQPPERAPELLSCPHRSCLDCLRQYLRIEISESRVPLSCPECAERLNP 55
RING-HC_RBR_RNF19 cd16629
RING finger, HC subclass, found in the family of RING finger proteins RNF19A, RNF19B and ...
118-172 2.36e-29

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. It is also involved in the pathogenic process of PD and Lewy body (LB) formation by ubiquitylation of synphilin-1. 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 a 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 use 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 family corresponds to the RING domain, a C3HC4-type RING-HC finger required for RBR-mediated ubiquitination.


Pssm-ID: 319543  Cd Length: 55  Bit Score: 110.59  E-value: 2.36e-29
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 188219577 118 ECPLCLVRLPPERAPRLLSCPHRSCRDCLRHYLRLEISESRVPISCPECSERLNP 172
Cdd:cd16629    1 ECPLCLLPKPPSAFPRLLSCEHRSCRDCLRQYLRIEISESRVNISCPECSEYLHP 55
RING-HC_RBR_RNF19A cd16775
RING finger, HC subclass, found in RING finger protein 19A (RNF19A) and similar proteins; ...
118-172 1.67e-27

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. It is also involved in the pathogenic process of PD and Lewy body (LB) formation by ubiquitylation of synphilin-1. RNF19A contains a 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 use 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 family corresponds to the RING domain, a C3HC4-type RING-HC finger required for RBR-mediated ubiquitination.


Pssm-ID: 319689  Cd Length: 55  Bit Score: 105.22  E-value: 1.67e-27
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 188219577 118 ECPLCLVRLPPERAPRLLSCPHRSCRDCLRHYLRLEISESRVPISCPECSERLNP 172
Cdd:cd16775    1 ECPLCLLEQPKENFPDIMTCHHRSCRDCLRQYLRIEITESRVNISCPECSERFHP 55
IBR smart00647
In Between Ring fingers; the domains occurs between pairs og RING fingers
187-251 5.65e-22

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


Pssm-ID: 214763  Cd Length: 64  Bit Score: 89.78  E-value: 5.65e-22
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 188219577   187 KYEEFMLRRYLASDPDCRWCPAPDCGYAVIAYGCASCPKLTCerEGCQTEFCYHCKQIWHPNQTC 251
Cdd:smart00647   2 KYERLLLESYVESNPDLKWCPAPDCSAAIIVTEEEGCNRVTC--PKCGFSFCFRCKVPWHSPVSC 64
IBR pfam01485
IBR domain, a half RING-finger domain; The IBR (In Between Ring fingers) domain is often found ...
187-248 5.63e-16

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 organisms. 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: 396187  Cd Length: 59  Bit Score: 72.56  E-value: 5.63e-16
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 188219577  187 KYEEFMLRRYLASDPDCRWCPAPDCGYAVIAYGcaSCPKLTCERegCQTEFCYHCKQIWHPN 248
Cdd:pfam01485   2 KYEKLKLADLLESDPNLKWCPTPDCGSIIQQSK--QCNRVTCSK--CGFEFCFNCRAPWHEG 59
IBR pfam01485
IBR domain, a half RING-finger domain; The IBR (In Between Ring fingers) domain is often found ...
283-321 2.20e-06

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 organisms. 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: 396187  Cd Length: 59  Bit Score: 45.21  E-value: 2.20e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 188219577  283 DIKPCPR--CSAYIIKmnDGSCNHMTCAVCGCEFCWLCMKE 321
Cdd:pfam01485  17 NLKWCPTpdCGSIIQQ--SKQCNRVTCSKCGFEFCFNCRAP 55
mRING-HC-C4C4_RBR_HOIP cd16631
Modified RING finger, HC subclass (C4C4-type), found in HOIL-1-interacting protein (HOIP) and ...
118-168 1.07e-05

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, a 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 use 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 family 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: 319545  Cd Length: 53  Bit Score: 43.09  E-value: 1.07e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 188219577 118 ECPLCLVRLPPERAPRLLSCPHRSCRDCLRHYLRLEISESRV-PISCPECSE 168
Cdd:cd16631    1 ECAVCFTSLPRNKMQTLTSCQCKICPDCFKQYFTIIIKEKHIrDLVCPICSE 52
mRING-HC-C3HC3D_RBR_HOIL1 cd16633
Modified RING finger, HC subclass (C3HC3D-type), found in heme-oxidized IRP2 ubiquitin ligase ...
115-164 6.48e-05

Modified RING finger, HC subclass (C3HC3D-type), found in heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1) and similar proteins; HOIL-1, also known as 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 E3 ubiquitin-protein ligase RNF31 (also known as HOIP) and SHANK-associated RH domain interacting protein (SHARPIN), form 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 a 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 use 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 family corresponds to the RING domain, a modified C3HC3D-type RING-HC finger required for RBR-mediated ubiquitination.


Pssm-ID: 319547  Cd Length: 55  Bit Score: 41.14  E-value: 6.48e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 188219577 115 EEVECPLCLVRLPPERAPRLLSCPHRSCRDCLRHYLRLEiSESRVpiSCP 164
Cdd:cd16633    1 EPFECPICFVDIPPGEGVVLRECLHSFCRECLRGTILNS-EEAEV--KCP 47
RING-HC_TRIM56_C-V cd16584
RING finger, HC subclass, found in tripartite motif-containing protein 56 (TRIM56) and similar ...
118-167 1.38e-04

RING finger, HC subclass, found in tripartite motif-containing protein 56 (TRIM56) and similar proteins; TRIM56, also known as RING finger protein 109 (RNF109), is a virus-inducible E3 ubiquitin ligase that restricts pestivirus infection. It positively regulates the Toll-like receptor 3 (TLR3) antiviral signaling pathway, and possesses antiviral activity against bovine viral diarrhea virus (BVDV), a ruminant pestivirus classified within the family Flaviviridae shared by tick-borne encephalitis virus (TBEV). It also possesses antiviral activity against two classical flaviviruses, yellow fever virus (YFV) and dengue virus (DENV), as well as a human coronavirus, HCoV-OC43, which is responsible for a significant share of common cold cases. It may do not act on positive-strand RNA viruses indiscriminately. Moreover, TRIM56 is an interferon-inducible E3 ubiquitin ligase that modulates STING to confer double-stranded DNA-mediated innate immune responses. TRIM56 belongs to the C-V subclass of TRIM (tripartite motif) family of proteins that are defined by an 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 an uncharacterized region positioned C-terminal to the RBCC domain.


Pssm-ID: 319498 [Multi-domain]  Cd Length: 44  Bit Score: 39.68  E-value: 1.38e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 188219577 118 ECPLCLVRLppeRAPRLLSCPHRSCRDCLRHYlrleISESRVPISCPECS 167
Cdd:cd16584    2 NCPICLEHY---TKPKSLPCLHTFCEDCLEQL----IDHNSRRFSCPICR 44
RING-HC cd16449
HC subclass of RING (RING-HC) finger and its variants; RING finger is a specialized type of ...
119-166 3.12e-04

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


Pssm-ID: 319363 [Multi-domain]  Cd Length: 39  Bit Score: 38.60  E-value: 3.12e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 188219577 119 CPLCLVRLppeRAPRLLSCPHRSCRDCLRHYLRLEisesrvPISCPEC 166
Cdd:cd16449    1 CPICLELL---KDPVLLPCGHTFCRSCLRRLLKEG------KKKCPIC 39
RING-HC_TRIM10_C-IV cd16593
RING finger, HC subclass, found in tripartite motif-containing protein 10 (TRIM10) and similar ...
116-166 3.26e-04

RING finger, HC subclass, found in tripartite motif-containing protein 10 (TRIM10) and similar proteins; TRIM10, also known as B30-RING finger protein (RFB30), RING finger protein 9 (RNF9), or hematopoietic RING finger 1 (HERF1), is a novel hematopoiesis-specific RING finger protein required for terminal differentiation of erythroid cells. TRIM10 belongs to the C-IV subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.


Pssm-ID: 319507 [Multi-domain]  Cd Length: 49  Bit Score: 38.83  E-value: 3.26e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 188219577 116 EVECPLCLVRLppeRAPRLLSCPHRSCRDCLRHYLRLEISESRVPISCPEC 166
Cdd:cd16593    1 EVNCPICQGTL---REPVTIDCGHNFCRACLTRYCEIPGPDLEEPPTCPLC 48
RING-HC_SH3RF1 cd16748
RING finger, HC subclass, found in SH3 domain-containing RING finger protein 1 (SH3RF1) and ...
117-166 4.44e-04

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, also needs to promote 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 that are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs.


Pssm-ID: 319662 [Multi-domain]  Cd Length: 48  Bit Score: 38.47  E-value: 4.44e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 188219577 117 VECPLCLVRLppERAPRLLSCPHRSCRDCLrhylrLEISESRVPISCPEC 166
Cdd:cd16748    3 LECPVCLERL--DASAKVLPCQHTFCKRCL-----LGIVGSRNELRCPEC 45
RING-HC_TRIM32_C-VII cd16587
RING finger, HC subclass, found in tripartite motif-containing protein 32 (TRIM32) and similar ...
118-167 6.12e-04

RING finger, HC subclass, found in tripartite motif-containing protein 32 (TRIM32) and similar proteins; TRIM32, also known as 72 kDa Tat-interacting protein, or zinc finger protein HT2A, or BBS11, is an E3 ubiquitin-protein ligase that promotes degradation of several targets, including actin, PIASgamma, Abl interactor 2, dysbindin, X-linked inhibitor of apoptosis (XIAP), p73 transcription factor, thin filaments and Z-bands during fasting. It plays important roles in neuronal differentiation of neural progenitor cells, as well as in controlling cell fate in skeletal muscle progenitor cells. It reduces PI3K-Akt-FoxO signaling in muscle atrophy by promoting plakoglobin-PI3K dissociation. It also functions as a pluripotency-reprogramming roadblock that facilitates cellular transition towards differentiation via modulating the levels of Oct4 and cMyc. Moreover, TRIM32 is an intrinsic influenza A virus (IAV) restriction factor which senses and targets the polymerase basic protein 1 (PB1) polymerase for ubiquitination and protein degradation. It also plays a significant role in mediating the biological activity of the HIV-1 Tat protein in vivo, binds specifically to the activation domain of HIV-1 Tat, and can also interact with the HIV-2 and EIAV Tat proteins in vivo. Furthermore, Trim32 regulates myoblast proliferation by controlling turnover of NDRG2 (N-myc downstream-regulated gene). It negatively regulates tumor suppressor p53 to promote tumorigenesis. It also facilitates degradation of MYCN on spindle poles and induces asymmetric cell division in human neuroblastoma cells. In addition, TRIM32 plays important roles in regulation of hyperactivities and positively regulates the development of anxiety and depression disorders induced by chronic stress. It also plays a role in regeneration by affecting satellite cell cycle progression via modulation of the SUMO ligase PIASy (PIAS4). Defects in TRIM32 leads to limb-girdle muscular dystrophy type 2H (LGMD2H), sarcotubular myopathies (STM) and Bardet-Biedl syndrome. TRIM32 belongs to the C-VII subclass of TRIM (tripartite motif)-NHL family that is 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 domain, as well as a NHL (named after proteins NCL-1, HT2A and Lin-41 that contain repeats folded into a six-bladed beta propeller) repeat domain positioned C-terminal to the RBCC domain. The NHL domain mediates the interaction with Argonaute proteins and consequently allows TRIM32 to modulate the activity of certain miRNAs.


Pssm-ID: 319501 [Multi-domain]  Cd Length: 47  Bit Score: 38.17  E-value: 6.12e-04
                         10        20        30        40        50
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gi 188219577 118 ECPLCL-VRLPPERAPRLLSCPHRSCRDCLRHYLRLEISESRvpisCPECS 167
Cdd:cd16587    1 ECPICLeSYDEEEHTPKLLQCGHTVCQQCLEKLLASSINGIR----CPFCR 47
AzlC COG1296
Predicted branched-chain amino acid permease (azaleucine resistance) [Amino acid transport and ...
347-436 1.09e-03

Predicted branched-chain amino acid permease (azaleucine resistance) [Amino acid transport and metabolism];


Pssm-ID: 224215  Cd Length: 238  Bit Score: 41.13  E-value: 1.09e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188219577 347 ILWQLGTLIGAPVGISLIA------GIAIPAMVIG--IPVYVGRKIHSRyegrktskhkrnlaitggVTLSVIASpVIAA 418
Cdd:COG1296  145 LYWVVGTLIGALLGSLLPDpetiglDFALPALFIVlvIPQFKRRKTLLS------------------VLASLVLA-LVAL 205
                         90
                 ....*....|....*...
gi 188219577 419 VSVGIGVPIMLAYVYGVV 436
Cdd:COG1296  206 VLFGGPWAVLAGILAGLL 223
RING-HC_SH3RFs cd16570
RING finger, HC subclass, found in SH3 domain-containing RING finger proteins SH3RF1, SH3RF2, ...
117-166 1.17e-03

RING finger, HC subclass, found in SH3 domain-containing RING finger proteins SH3RF1, SH3RF2, SH3RF3, 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. 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. SH3RF3, also known as plenty of SH3s 2 (POSH2) or SH3 multiple domains protein 4 (SH3MD4), is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2) and may play a role in regulating c-Jun N-terminal kinase (JNK) mediated apoptosis in certain conditions. Members in this family contain an N-terminal C3HC4-type RING-HC finger responsible for the E3 ligase activity and four Src Homology 3 (SH3) domains that are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs.


Pssm-ID: 319484  Cd Length: 46  Bit Score: 37.09  E-value: 1.17e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 188219577 117 VECPLCLVRLppERAPRLLSCPHRSCRDCLrhylrLEISESRVPISCPEC 166
Cdd:cd16570    3 LECPVCLEPL--DVSAKVLPCQHTFCKRCL-----QEIVASRSELRCPEC 45
RING-HC_RNF186 cd16557
RING finger, HC subclass, found in RING finger protein 186 (RNF186) and similar proteins; ...
116-166 1.26e-03

RING finger, HC subclass, found in RING finger protein 186 (RNF186) and similar proteins; RNF186 is an E3 ubiquitin-protein ligase with an N-terminal C3HC4-type RING-HC finger and two putative C-terminal transmembrane domains which enable it to localize in a certain organelle. It regulates RING-dependent self-ubiquitination, as well as endoplasmic reticulum (ER) stress-mediated apoptosis through interaction with the Bcl-2 family protein BNip1.


Pssm-ID: 319471 [Multi-domain]  Cd Length: 51  Bit Score: 37.12  E-value: 1.26e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 188219577 116 EVECPLCLVRLPPERAPRLLSCPHRSCRDCLRhyLRLEISESRVPISCPEC 166
Cdd:cd16557    1 DLECLVCFNSYEFVRKPKLLACQHAFCAICLK--LILEEKDNTWVITCPLC 49
RING-HC_RBR_ANKIB1 cd16774
RING finger, HC subclass, found in ankyrin repeat and IBR domain-containing protein 1 (ANKIB1) ...
118-168 1.35e-03

RING finger, HC subclass, found in ankyrin repeat and IBR domain-containing protein 1 (ANKIB1) and similar proteins; ANKIB1 is a RBR-type E3 ubiquitin-protein ligase that may function as part of E3 complex, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes and then transfers it to substrates. It contains an N-terminal ankyrin repeats domain and a 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 use 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 family corresponds to the RING domain, a C3HC4-type RING-HC finger required for RBR-mediated ubiquitination.


Pssm-ID: 319688  Cd Length: 57  Bit Score: 37.42  E-value: 1.35e-03
                         10        20        30        40        50
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gi 188219577 118 ECPLCLVRLPPERAPRLLSCPHRSCRDCLRHYLRLEISESRV-PISCP--ECSE 168
Cdd:cd16774    1 LCDICACSISVFEEPVDMPCGHQFCRACWERYLNLKIQEGEAhNIFCPayDCFQ 54
RING-HC_RNF183_like cd16556
RING finger, HC subclass, found in RING finger protein RNF183, RNF223 and similar proteins; ...
118-166 1.42e-03

RING finger, HC subclass, found in RING finger protein RNF183, RNF223 and similar proteins; RNF183 is an E3 ubiquitin-protein ligase that is upregulated during intestinal inflammation and is negatively regulated by miR-7. It promotes intestinal inflammation by increasing the ubiquitination and degradation of inhibitor of kappa B, thereby resulting in secondary activation of the Nuclear factor-kappaB (NF-kB) pathway. The interaction between RNF183-mediated ubiquitination and miRNA may be an important novel epigenetic mechanism in the pathogenesis of inflammatory bowel disease (IBD). The biological function of RNF223 remains unclear. Both RNF183 and RNF223 contain an N-terminal C3HC4-type RING-HC finger and a C-terminal transmembrane domain.


Pssm-ID: 319470 [Multi-domain]  Cd Length: 54  Bit Score: 37.07  E-value: 1.42e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 188219577 118 ECPLCLVRLPPE-RAPRLLSCPHRSCRDCLRHYLRLEISESRVPISCPEC 166
Cdd:cd16556    1 ECSICFNKYDNTfKTPKELSCTHTFCLECLARLSLALPSPQAERLPCPLC 50
RING-HC_RNF222 cd16564
RING finger, HC subclass, found in RING finger protein 222 (RNF222) and similar proteins; ...
118-166 1.87e-03

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


Pssm-ID: 319478 [Multi-domain]  Cd Length: 47  Bit Score: 36.69  E-value: 1.87e-03
                         10        20        30        40
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gi 188219577 118 ECPLCLVRLppERAPRLLSCPHRSCRDCLRHYLrLEISESRVPISCPEC 166
Cdd:cd16564    1 ECPVCYEKF--SAAARSLSCGHVFCHDCLVKYL-LSARVDKKRIVCPIC 46
RING-HC_RNF208 cd16559
RING finger, HC subclass, found in RING finger protein 208 (RNF208) and similar proteins; ...
116-168 2.10e-03

RING finger, HC subclass, found in RING finger protein 208 (RNF208) and similar proteins; RNF208 is an E3 ubiquitin-protein ligase whose activity can be modulated by S-nitrosylation. It contains a C3HC4-type RING-HC finger.


Pssm-ID: 319473 [Multi-domain]  Cd Length: 50  Bit Score: 36.69  E-value: 2.10e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 188219577 116 EVECPLCLVRLppeRAPRLLSCPHRSCRDCLRHYlrLEISESRVPISCPECSE 168
Cdd:cd16559    1 SLECPLCGETY---NRPRILSCLHSFCEPCLQKL--YESCPKYKFISCPTCKR 48
RING-HC_TRIM59_C-V cd16763
RING finger, HC subclass, found in tripartite motif-containing protein 59 (TRIM59) and similar ...
115-166 2.11e-03

RING finger, HC subclass, found in tripartite motif-containing protein 59 (TRIM59) and similar proteins; TRIM59, also known as RING finger protein 104 (RNF104) or tumor suppressor TSBF-1, is a putative E3 ubiquitin-protein ligase that functions as a novel multiple cancer biomarker for immunohistochemical detection of early tumorigenesis. It is upregulated in gastric cancer and promotes gastric carcinogenesis by interacting with and targeting the P53 tumor suppressor for its ubiquitination and degradation. It also acts as a novel accessory molecule involved in cytotoxicity of BCG-activated macrophages (BAM). Moreover, TRIM59 may serve as a multifunctional regulator for innate immune signaling pathways. It interacts with ECSIT and negatively regulates nuclear factor-kappaB (NF- kappa B) and interferon regulatory factor (IRF)-3/7-mediated signal pathways. TRIM59 belongs to the C-V subclass of TRIM (tripartite motif) family of proteins that are defined by an 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. In addition, TRIM59 contains a C-terminal transmembrane domain.


Pssm-ID: 319677 [Multi-domain]  Cd Length: 56  Bit Score: 36.76  E-value: 2.11e-03
                         10        20        30        40        50
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gi 188219577 115 EEVECPLCLVRLppeRAPRLLSCPHRSCRDCLRHYLRLEISES-----RVPISCPEC 166
Cdd:cd16763    2 EELTCSVCYSIF---EDPRVLPCSHTFCRNCLENVIQSSGNFSlwrplRAPLKCPNC 55
RING-HC_TRIM13_like_C-V cd16581
RING finger, HC subclass, found in tripartite motif-containing proteins TRIM13, TRIM59 and ...
115-166 2.37e-03

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


Pssm-ID: 319495 [Multi-domain]  Cd Length: 45  Bit Score: 36.28  E-value: 2.37e-03
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gi 188219577 115 EEVECPLCLVRLppeRAPRLLSCPHRSCRDCLRhylrlEISESRVPISCPEC 166
Cdd:cd16581    1 EKLTCSICLDIF---NDPRVLPCLHTFCKNCLE-----GRAAESGPLKCPTC 44
RING-HC_SH3RF2 cd16749
RING finger, HC subclass, found in SH3 domain-containing RING finger protein 2 (SH3RF2) and ...
117-166 2.72e-03

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 that are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs.


Pssm-ID: 319663 [Multi-domain]  Cd Length: 48  Bit Score: 36.45  E-value: 2.72e-03
                         10        20        30        40        50
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gi 188219577 117 VECPLCLVRLppERAPRLLSCPHRSCRDCLRhylrlEISESRVPISCPEC 166
Cdd:cd16749    3 LECPVCFEKL--DVTAKVLPCQHTFCKPCLQ-----RIFKARKELRCPEC 45
RING-HC_RBR_HHARI cd16626
RING finger, HC subclass, found in human homolog of Drosophila ariadne (HHARI) and similar ...
118-166 3.67e-03

RING finger, HC subclass, found in human homolog of Drosophila ariadne (HHARI) and similar proteins; The family includes Drosophila melanogaster protein ariadne-1 (ARI-1), and its eukaryotic homologs, such as HHARI. ARI-1 is a novel 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 a 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 a 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 use 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 family corresponds to the RING domain, a C3HC4-type RING-HC finger required for RBR-mediated ubiquitination.


Pssm-ID: 319540  Cd Length: 58  Bit Score: 36.20  E-value: 3.67e-03
                         10        20        30        40        50
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gi 188219577 118 ECPLCLVRLPPERAPRLlSCPHRSCRDCLRHYLRLEISESRV--PISCPEC 166
Cdd:cd16626    1 ECEICYLNYPESYMTGL-ECGHRFCKNCWTEYLTTKIMEEGMgqTISCAAH 50
mRING-HC-C4C4_RBR_RNF144 cd16632
Modified RING finger, HC subclass (C4C4-type), found in the RNF144 protein family; The RNF144 ...
119-165 3.75e-03

Modified RING finger, HC subclass (C4C4-type), found in the RNF144 protein family; The RNF144 family 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 a 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 use 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 family 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.


Pssm-ID: 319546  Cd Length: 51  Bit Score: 35.78  E-value: 3.75e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 188219577 119 CPLCLVRLPPERAPRLLSCPHRSCRDCLRHYLRLEISESRV-PISCPE 165
Cdd:cd16632    1 CKLCLAECPLEEMYELQQCGCIFCTECLKQYLEVLIREGNVlVITCPD 48
RING-HC_SH3RF3 cd16750
RING finger, HC subclass, found in SH3 domain-containing RING finger protein 3 (SH3RF3) and ...
117-166 3.87e-03

RING finger, HC subclass, found in SH3 domain-containing RING finger protein 3 (SH3RF3) and similar proteins; SH3RF3, also known as plenty of SH3s 2 (POSH2) or SH3 multiple domains protein 4 (SH3MD4), is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating c-Jun N-terminal kinase (JNK) mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1. Both of them contain an N-terminal C3HC4-type RING-HC finger responsible for the E3 ligase activity and four Src Homology 3 (SH3) domains that are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs.


Pssm-ID: 319664 [Multi-domain]  Cd Length: 46  Bit Score: 35.86  E-value: 3.87e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 188219577 117 VECPLCLVRLppERAPRLLSCPHRSCRDCLRhylrlEISESRVPISCPEC 166
Cdd:cd16750    3 LECSVCLERL--DTTSKVLPCQHTFCRRCLE-----EIVSSRKELRCPEC 45
RING-HC_TIF1beta cd16765
RING finger, HC subclass, found in transcription inknown asiary factor 1-beta (TIF1-beta); ...
119-146 6.48e-03

RING finger, HC subclass, found in transcription inknown asiary factor 1-beta (TIF1-beta); TIF1-beta, also known as Kruppel-associated Box (KRAB)-associated protein 1 (KAP-1), KRAB-interacting protein 1 (KRIP-1), nuclear co-repressor KAP-1, RING finger protein 96, tripartite motif-containing protein 28 (TRIM28), or E3 SUMO-protein ligase TRIM28, belongs to the C-VI subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a plant homeodomain (PHD), and a bromodomain (Bromo) positioned C-terminal to the RBCC domain. It acts as a nuclear co-repressor that plays a role in transcription and in the DNA damage response. Upon DNA damage, the phosphorylation of KAP-1 on serine 824 by the ataxia telangiectasia-mutated (ATM) kinase enhances cell survival and facilitates chromatin relaxation and heterochromatic DNA repair. It also regulates CHD3 nucleosome remodeling during the DNA double-strand break (DSB) response. Meanwhile, KAP-1 can be dephosphorylated by protein phosphatase PP4C in the DNA damage response. Moreover, KAP-1 is a co-activator of the orphan nuclear receptor NGFI-B (or Nur77) and is involved in NGFI-B-dependent transcription. It is also a coiled-coil binding partner, substrate and activator of the c-Fes protein tyrosine kinase. The N-terminal RBCC domains of TIF1-beta are responsible for the interaction with KRAB zinc finger proteins (KRAB-ZFPs), MDM2, MM1, C/EBPbeta, and the regulation of homo- and heterodimerization. The C-terminal PHD/Bromo domains are involved in interacting with SETDB1, Mi-2alpha and other proteins to form complexes with histone deacetylase or methyltransferase activity.


Pssm-ID: 319679  Cd Length: 61  Bit Score: 35.79  E-value: 6.48e-03
                         10        20
                 ....*....|....*....|....*...
gi 188219577 119 CPLCLVRLPPERAPRLLSCPHRSCRDCL 146
Cdd:cd16765    4 CGVCCTELRPDREPQLLPCLHSVCQACL 31
RING-HC_RNF152 cd16548
RING finger, HC subclass, found in RING finger protein 152 (RNF152) and similar proteins; ...
118-166 6.68e-03

RING finger, HC subclass, found in RING finger protein 152 (RNF152) and similar proteins; RNF152 is a lysosome-anchored E3 ubiquitin-protein ligase involved in apoptosis. It is polyubiquitinated through K48 linkage. It negatively regulates the activation of the mTORC1 pathway by targeting RagA GTPase for K63-linked ubiquitination. It interacts with and ubiquitinates RagA in an amino-acid-sensitive manner. The ubiquitination of RagA recruits its inhibitor GATOR1, a GAP complex for Rag GTPases to the Rag complex, thereby inactivating mTORC1 signaling. RNF152 contains an N-terminal C3HC4-type RING-HC finger and a C-terminal transmembrane domain, both of which are responsible for its E3 ligase activity.


Pssm-ID: 319462 [Multi-domain]  Cd Length: 45  Bit Score: 34.99  E-value: 6.68e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 188219577 118 ECPLCLVRLPPERAPRLLSCPHRSCRDCLRhylrlEISESRVPISCPEC 166
Cdd:cd16548    1 ECQICFNYYSPRRRPKLLDCKHTCCSVCLQ-----QMRTSQKDLRCPWC 44
mRING-HC-C3HC3D_TRAF6 cd16643
Modified RING finger, HC subclass (C3HC3D-type), found in tumor necrosis factor (TNF) ...
118-151 6.76e-03

Modified RING finger, HC subclass (C3HC3D-type), found in tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) and similar proteins; TRAF6, also known as interleukin-1 signal transducer or RING finger protein 85 (RNF85), is a cytoplasmic adapter protein that mediates signals induced by the tumor necrosis factor receptor (TNFR) superfamily and Toll-like receptor (TLR)/interleukin-1 receptor (IL-1R) family. It functions as a mediator involved in the activation of mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), and interferon regulatory factor pathways, as well as in IL-1R-mediated activation of NF-kappaB. TRAF6 is also an oncogene that plays a vital role in K-RAS-mediated oncogenesis. TRAF6 contains an N-terminal domain with a modified C3HC3D-type RING-HC finger and several zinc fingers, and a C-terminal TRAF domain that comprises a coiled coil domain and a conserved TRAF-C domain.


Pssm-ID: 319557 [Multi-domain]  Cd Length: 58  Bit Score: 35.43  E-value: 6.76e-03
                         10        20        30
                 ....*....|....*....|....*....|....
gi 188219577 118 ECPLCLVRLppeRAPRLLSCPHRSCRDCLRHYLR 151
Cdd:cd16643    3 ECPICLMAL---REPVQTPCGHRFCKSCIKKSIR 33
RING-HC_TRIM9 cd16755
RING finger, HC subclass, found in tripartite motif-containing protein 9 (TRIM9) and similar ...
115-166 8.01e-03

RING finger, HC subclass, found in tripartite motif-containing protein 9 (TRIM9) and similar proteins; TRIM9, human ortholog of rat Spring, also known as RING finger protein 91 (RNF91), is a brain-specific E3 ubiquitin-protein ligase collaborating with an E2 ubiquitin conjugating enzyme UBCH5b. TRIM9 plays an important role in the regulation of neuronal functions and participates in the neurodegenerative disorders through its ligase activity. It interacts with the WD repeat region of beta-transducin repeat-containing protein (beta-TrCP) through its N-terminal degron motif depending on the phosphorylation status, and thus negatively regulates nuclear factor-kappaB (NF-kappaB) activation in the NF-kappaB pro-inflammatory signaling pathway. Moreover, TRIM9 acts as a critical catalytic link between Netrin-1 and exocytic soluble NSF attachment receptor protein (SNARE) machinery in murine cortical neurons. It promotes SNARE-mediated vesicle fusion and axon branching in a Netrin-dependent manner. TRIM9 belongs to the C-I subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, and a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.


Pssm-ID: 319669 [Multi-domain]  Cd Length: 52  Bit Score: 35.02  E-value: 8.01e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 188219577 115 EEVECPLCLVRLppeRAPRLLSCPHRSCRDCLRHYLrLEISESRVPISCPEC 166
Cdd:cd16755    2 EELKCPVCGSFY---REPIILPCSHNLCLACARNIL-VQTPERNSCLTCPQC 49
RING-HC_TRIM13_C-V cd16762
RING finger, HC subclass, found in tripartite motif-containing protein 13 (TRIM13) and similar ...
115-166 9.38e-03

RING finger, HC subclass, found in tripartite motif-containing protein 13 (TRIM13) and similar proteins; TRIM13, also known as B-cell chronic lymphocytic leukemia tumor suppressor Leu5, leukemia-associated protein 5, putative tumor suppressor RFP2, RING finger protein 77 (RNF77), or Ret finger protein 2, is an endoplasmic reticulum (ER) membrane anchored E3 ubiquitin-protein ligase that interacts proteins localized to the ER, including valosin-containing protein (VCP), a protein indispensable for ER-associated degradation (ERAD). It also targets the known ER proteolytic substrate CD3-delta, but not the N-end rule substrate Ub-R-YFP (yellow fluorescent protein) for its degradation. Moreover, TRIM13 regulates ubiquitination and degradation of NEMO to suppress tumor necrosis factor (TNF) induced nuclear factor-kappaB (NF- kappa B) activation. It is also involved in NF-kappaB p65 activation and nuclear factor of activated T-cells (NFAT)-dependent activation of c-Rel upon T-cell receptor engagement. Furthermore, TRIM13 negatively regulates lanoma differentiation-associated gene 5 (MDA5)-mediated type I interferon production. It also regulates caspase-8 ubiquitination, translocation to autophagosomes, and activation during ER stress induced cell death. Meanwhile, TRIM13 enhances ionizing radiation-induced apoptosis by increasing p53 stability and decreasing AKT kinase activity through MDM2 and AKT degradation. TRIM13 belongs to the C-V subclass of TRIM (tripartite motif) family of proteins that are defined by an 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. In addition, TRIM13 contains a C-terminal transmembrane domain.


Pssm-ID: 319676 [Multi-domain]  Cd Length: 57  Bit Score: 34.96  E-value: 9.38e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 188219577 115 EEVECPLCLVRLppeRAPRLLSCPHRSCRDCLRHYLRLEISES---RVPISCPEC 166
Cdd:cd16762    2 EDLTCPICCSLF---DDPRVLPCSHNFCKKCLEGILEGNVRNMlwrPAPFKCPTC 53
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.19
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
  • Marchler-Bauer A et al. (2015), "CDD: NCBI's conserved domain database.", Nucleic Acids Res.43(D)222-6.
  • Marchler-Bauer A et al. (2011), "CDD: a Conserved Domain Database for the functional annotation of proteins.", Nucleic Acids Res.39(D)225-9.
  • Marchler-Bauer A, Bryant SH (2004), "CD-Search: protein domain annotations on the fly.", Nucleic Acids Res.32(W)327-331.
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