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Conserved domains on  [gi|45356139|ref|NP_987103|]
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RWD domain-containing protein 4 [Mus musculus]

Protein Classification

RWD domain-containing protein( domain architecture ID 10530492)

RWD domain-containing protein similar to Saccharomyces cerevisiae protein GIR2 that acts as a negative regulator of the GCN2 kinase activity by disrupting the GCN1-GCN2 interaction in amino acid-starved cells

CATH:  3.10.110.10
Gene Ontology:  GO:0005515
PubMed:  26495453|26276859|25918163

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
RWD-RWDD4 cd23817
RWD domain of RWD domain-containing protein 4 (RWDD4) and related proteins; RWDD4, also called ...
 8-111 3.63e-62

RWD domain of RWD domain-containing protein 4 (RWDD4) and related proteins; RWDD4, also called protein FAM28A, is a target of the tumor suppressor MicroRNA (MiR)-506 in bladder cancer cells. Downregulation of RWDD4 suppresses bladder cancer cell proliferation, migration and invasion. RWDD4 has also been identified as a modifier of metastasis in human prostate cancer.


:

Pssm-ID: 467653  Cd Length: 104  Bit Score: 187.72  E-value: 3.63e-62
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45356139   8 EMELEALRSIYEGDNSFRELSPVSFQYRIGEDGDPKAFLIEVSWTETYPQTAPVISMNAFFNNTISSAVKQSILAKLQEA 87
Cdd:cd23817   1 EEELEVLLSIYEGDENFKQISDTTFQYKYGEDGDPKSFLLEISWPENYPEEPPIINLDAFYNKHISSSVKEKIVSKLNEE 80

                        90       100
                ....*....|....*....|....
gi 45356139  88 VEVNLGTAMTYTLFEYAKDHKEQF 111
Cdd:cd23817  81 AEQNLGSAMTYTLFEWAKENAEEL 104
 
Name Accession Description Interval E-value
RWD-RWDD4 cd23817
RWD domain of RWD domain-containing protein 4 (RWDD4) and related proteins; RWDD4, also called ...
 8-111 3.63e-62

RWD domain of RWD domain-containing protein 4 (RWDD4) and related proteins; RWDD4, also called protein FAM28A, is a target of the tumor suppressor MicroRNA (MiR)-506 in bladder cancer cells. Downregulation of RWDD4 suppresses bladder cancer cell proliferation, migration and invasion. RWDD4 has also been identified as a modifier of metastasis in human prostate cancer.


Pssm-ID: 467653  Cd Length: 104  Bit Score: 187.72  E-value: 3.63e-62
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45356139   8 EMELEALRSIYEGDNSFRELSPVSFQYRIGEDGDPKAFLIEVSWTETYPQTAPVISMNAFFNNTISSAVKQSILAKLQEA 87
Cdd:cd23817   1 EEELEVLLSIYEGDENFKQISDTTFQYKYGEDGDPKSFLLEISWPENYPEEPPIINLDAFYNKHISSSVKEKIVSKLNEE 80

                        90       100
                ....*....|....*....|....
gi 45356139  88 VEVNLGTAMTYTLFEYAKDHKEQF 111
Cdd:cd23817  81 AEQNLGSAMTYTLFEWAKENAEEL 104
RWD pfam05773
RWD domain; This domain was identified in WD40 repeat proteins and Ring finger domain proteins. ...
 5-107 6.55e-22

RWD domain; This domain was identified in WD40 repeat proteins and Ring finger domain proteins. The function of this domain is unknown. GCN2 is the alpha-subunit of the only translation initiation factor (eIF2 alpha) kinase that appears in all eukaryotes. Its function requires an interaction with GCN1 via the domain at its N-terminus, which is termed the RWD domain after three major RWD-containing proteins: RING finger-containing proteins, WD-repeat-containing proteins, and yeast DEAD (DEXD)-like helicases. The structure forms an alpha + beta sandwich fold consisting of two layers: a four-stranded antiparallel beta-sheet, and three side-by-side alpha-helices.


Pssm-ID: 399058  Cd Length: 111  Bit Score: 85.45  E-value: 6.55e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45356139     5 EDQEMELEALRSIYEGDNSFRELSP---VSFQYRIGEDGD------PKAFLIEVSWTETYPQTAPVISMNAFFNntISSA 75
Cdd:pfam05773   1 EEQEEELEALESIYPDEFEVISDSPyesLEIEIKLSLDSDesdsshLPPLVLKFTLPEDYPDEPPKISLSSPWN--LSDE 78

                          90       100       110
                  ....*....|....*....|....*....|..
gi 45356139    76 VKQSILAKLQEAVEVNLGTAMTYTLFEYAKDH 107
Cdd:pfam05773  79 QVLSLLEELEELAEENLGEVMIFELIEWLQEN 110
RWD smart00591
domain in RING finger and WD repeat containing proteins and DEXDc-like helicases subfamily ...
 10-111 1.01e-15

domain in RING finger and WD repeat containing proteins and DEXDc-like helicases subfamily related to the UBCc domain;


Pssm-ID: 214735  Cd Length: 107  Bit Score: 69.31  E-value: 1.01e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45356139     10 ELEALRSIYEGDNSFRELSPVSFQYRI--------GEDGDPKAFLiEVSWTETYPQTAPVISMNAFFNntISSAVKQSIL 81
Cdd:smart00591   1 ELEALESIYPEDFEVIDEDARIPEITIklspssdeGEDQYVSLTL-QVKLPENYPDEAPPISLLNSEG--LSDEQLAELL 77

                           90       100       110
                   ....*....|....*....|....*....|
gi 45356139     82 AKLQEAVEVNLGTAMTYTLFEYAKDHKEQF 111
Cdd:smart00591  78 KKLEEIAEENLGEVMIFELVEKLQEFLSEF 107
 
Name Accession Description Interval E-value
RWD-RWDD4 cd23817
RWD domain of RWD domain-containing protein 4 (RWDD4) and related proteins; RWDD4, also called ...
 8-111 3.63e-62

RWD domain of RWD domain-containing protein 4 (RWDD4) and related proteins; RWDD4, also called protein FAM28A, is a target of the tumor suppressor MicroRNA (MiR)-506 in bladder cancer cells. Downregulation of RWDD4 suppresses bladder cancer cell proliferation, migration and invasion. RWDD4 has also been identified as a modifier of metastasis in human prostate cancer.


Pssm-ID: 467653  Cd Length: 104  Bit Score: 187.72  E-value: 3.63e-62
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45356139   8 EMELEALRSIYEGDNSFRELSPVSFQYRIGEDGDPKAFLIEVSWTETYPQTAPVISMNAFFNNTISSAVKQSILAKLQEA 87
Cdd:cd23817   1 EEELEVLLSIYEGDENFKQISDTTFQYKYGEDGDPKSFLLEISWPENYPEEPPIINLDAFYNKHISSSVKEKIVSKLNEE 80

                        90       100
                ....*....|....*....|....
gi 45356139  88 VEVNLGTAMTYTLFEYAKDHKEQF 111
Cdd:cd23817  81 AEQNLGSAMTYTLFEWAKENAEEL 104
RWD pfam05773
RWD domain; This domain was identified in WD40 repeat proteins and Ring finger domain proteins. ...
 5-107 6.55e-22

RWD domain; This domain was identified in WD40 repeat proteins and Ring finger domain proteins. The function of this domain is unknown. GCN2 is the alpha-subunit of the only translation initiation factor (eIF2 alpha) kinase that appears in all eukaryotes. Its function requires an interaction with GCN1 via the domain at its N-terminus, which is termed the RWD domain after three major RWD-containing proteins: RING finger-containing proteins, WD-repeat-containing proteins, and yeast DEAD (DEXD)-like helicases. The structure forms an alpha + beta sandwich fold consisting of two layers: a four-stranded antiparallel beta-sheet, and three side-by-side alpha-helices.


Pssm-ID: 399058  Cd Length: 111  Bit Score: 85.45  E-value: 6.55e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45356139     5 EDQEMELEALRSIYEGDNSFRELSP---VSFQYRIGEDGD------PKAFLIEVSWTETYPQTAPVISMNAFFNntISSA 75
Cdd:pfam05773   1 EEQEEELEALESIYPDEFEVISDSPyesLEIEIKLSLDSDesdsshLPPLVLKFTLPEDYPDEPPKISLSSPWN--LSDE 78

                          90       100       110
                  ....*....|....*....|....*....|..
gi 45356139    76 VKQSILAKLQEAVEVNLGTAMTYTLFEYAKDH 107
Cdd:pfam05773  79 QVLSLLEELEELAEENLGEVMIFELIEWLQEN 110
RWD smart00591
domain in RING finger and WD repeat containing proteins and DEXDc-like helicases subfamily ...
 10-111 1.01e-15

domain in RING finger and WD repeat containing proteins and DEXDc-like helicases subfamily related to the UBCc domain;


Pssm-ID: 214735  Cd Length: 107  Bit Score: 69.31  E-value: 1.01e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45356139     10 ELEALRSIYEGDNSFRELSPVSFQYRI--------GEDGDPKAFLiEVSWTETYPQTAPVISMNAFFNntISSAVKQSIL 81
Cdd:smart00591   1 ELEALESIYPEDFEVIDEDARIPEITIklspssdeGEDQYVSLTL-QVKLPENYPDEAPPISLLNSEG--LSDEQLAELL 77

                           90       100       110
                   ....*....|....*....|....*....|
gi 45356139     82 AKLQEAVEVNLGTAMTYTLFEYAKDHKEQF 111
Cdd:smart00591  78 KKLEEIAEENLGEVMIFELVEKLQEFLSEF 107
RWD_GCN2 cd23823
RWD domain of eIF-2-alpha kinase GCN2 and related proteins; GCN2 (EC 2.7.11.1), also called ...
 4-116 3.79e-15

RWD domain of eIF-2-alpha kinase GCN2 and related proteins; GCN2 (EC 2.7.11.1), also called eukaryotic translation initiation factor 2-alpha kinase 4 (EIF2AK4), acts as a metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to low amino acid availability. It also plays a role in modulating the adaptive immune response to yellow fever virus infection and promotes dendritic cells to initiate autophagy and antigene presentation to both CD4(+) and CD8(+) T-cells under amino acid starvation.


Pssm-ID: 467659  Cd Length: 117  Bit Score: 68.01  E-value: 3.79e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45356139   4 NEDQEMELEALRSIYEGDnsFRELS-------PVSFQYRIG--EDGDPKAFL---IEVSWTETYPQTAPVISMNAffNNT 71
Cdd:cd23823   1 EEEQEEELEALQSIYGDD--FEDLSskkavwsPPEFRIRLRpqEGESEENHVsvdLHVKFPPTYPDVPPEIELEN--VKG 76

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 45356139  72 ISSAVKQSILAKLQEAVEVNLGTAMTYTLFEYAKDhkeqFMENHH 116
Cdd:cd23823  77 LSDEQLEELLKELEELAKELLGEEMIFELAEAVQE----FLEEHN 117
RWD_RWDD1 cd23816
RWD domain of RWD domain-containing protein 1 (RWDD1) and related proteins; RWDD1, also called ...
 4-100 2.76e-11

RWD domain of RWD domain-containing protein 1 (RWDD1) and related proteins; RWDD1, also called DRG family-regulatory protein 2 (DFRP2), or PTD013, interacts with DRG2 and protects DRG2 from proteolytic degradation. It is an androgen receptor-interacting protein that functions as a coactivator of androgen-dependent transcription.


Pssm-ID: 467652  Cd Length: 118  Bit Score: 58.07  E-value: 2.76e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45356139   4 NEDQEMELEALRSIYEgdNSFRELS---PVSFQYRIGEDGDPK-----AFLIEVSWTETYPQTAPVISMNAFFNNTISSA 75
Cdd:cd23816   2 KEEQRNELEALESIYP--DEFTVLSeepPISFTITVTSEEEENedetvSVTLKFTYTEKYPDEAPLIEIISHENLEDEDI 79

                        90       100
                ....*....|....*....|....*
gi 45356139  76 vkQSILAKLQEAVEVNLGTAMTYTL 100
Cdd:cd23816  80 --EDLLELLEQQAEENLGMVMVFTI 102
RWD_YLR419W-like cd23827
RWD domain of Saccharomyces cerevisiae putative ATP-dependent RNA helicase YLR419W and related ...
 8-107 6.49e-10

RWD domain of Saccharomyces cerevisiae putative ATP-dependent RNA helicase YLR419W and related proteins; YLR419W (EC 3.6.4.13) may act as an ATP-binding RNA helicase. The RWD domain may mediate protein-protein interactions.


Pssm-ID: 467662  Cd Length: 104  Bit Score: 53.79  E-value: 6.49e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45356139   8 EMELEALRSIYEgdNSFRELSPVSFQYRI-GEDGDPKAFLIEVSWTETYPQTAPVISMNAFfnNTISSAVKQSILAKL-Q 85
Cdd:cd23827   2 DEEIEALEAIYG--EKFEVISDDSCEITLnSPTKTKPSLKLKFYKSSSYPNSLPGIFISSS--DKLPAYIKLAIIRQLlQ 77

                        90       100
                ....*....|....*....|..
gi 45356139  86 EAVEVNLGTAMTYTLFEYAKDH 107
Cdd:cd23827  78 YARDNLLGDPMIFSIVEWLEEN 99
RWD_RNF25 cd23818
RWD domain of RING finger protein 25 (RNF25) and related proteins; RNF25 (EC 2.3.2.27), also ...
 8-107 1.44e-09

RWD domain of RING finger protein 25 (RNF25) and related proteins; RNF25 (EC 2.3.2.27), also known as AO7, is a putative E3 ubiquitin-protein ligase that was initially identified as an interacting protein of the E2 ubiquitin-conjugating enzyme, Ubc5B. It is ubiquitously expressed in various tissues and is predominantly localized in the nucleus. RNF25 activates nuclear factor (NF)-kappaB-dependent gene expression upon stimulation with interleukin-1 beta (IL-1beta), or tumor necrosis factor (TNF), or overexpression of NF-kappaB-inducing kinase. It interacts with the p65 transactivation domain (TAD) and modulates its transcriptional activity.


Pssm-ID: 467654  Cd Length: 109  Bit Score: 52.93  E-value: 1.44e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45356139   8 EMELEALRSIYEGDnsFRELSPVSFQYRI--------GEDGDPK--AFLIEVSWTETYPQTAPVISM-NAffnNTISSAV 76
Cdd:cd23818   2 EEELEALEAIYPDE--LKVVSEDGAPTELsitlhpatADDESEQyvRLTLVITLPPGYPEEPPKISLrNP---RGLSDAR 76

                        90       100       110
                ....*....|....*....|....*....|.
gi 45356139  77 KQSILAKLQEAVEVNLGTAMTYTLFEYAKDH 107
Cdd:cd23818  77 LARLLSLLKELAEERAGEPMLFELIELAKEF 107
RWD_DRWD_ELF-like cd11605
RWD, DRWD, and ELF domain family; The family includes the RWD, double-RWD (DRWD), and ELF ...
 13-104 1.38e-08

RWD, DRWD, and ELF domain family; The family includes the RWD, double-RWD (DRWD), and ELF domains. They belong to the ubiquitin-conjugating (UBC) superfamily that represents a structural domain with an alpha-beta(4)-alpha(3) core fold. The RWD domain (named after three major RWD-containing proteins: RING finger, WD-repeat-containing proteins and DEXD-like helicases) mediates protein-protein interactions in a variety of pathways in eukaryotes. The DRWD domain is responsible for substrate binding. It is involved in interactions with other kinetochore proteins. The ELF (N-terminal E2-like fold) domain is found in all Fanconi anemia group L protein (FANCL) homologs. It is required to promote efficient DNA damage-induced FANCD2 (Fanconi anemia group D2 protein) monoubiquitination in vertebrate cells.


Pssm-ID: 467641  Cd Length: 94  Bit Score: 50.26  E-value: 1.38e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45356139  13 ALRSIYEGDNSFRELS-PVSFQYRIG--EDGDPKAFLIEVSWTETY-PQTAPVISMNAFFNntISSAVKQSILAKLQEAV 88
Cdd:cd11605   1 ALESIYGDELEVLSDDsPLRFSIRLSpeEEEDDPPLELEFTLPPGYpPEEPPLITLRSPKL--SSAERLSLLKLELEEAA 78

                        90
                ....*....|....*.
gi 45356139  89 EVNLGTAMTYTLFEYA 104
Cdd:cd11605  79 EENLGEPMLFDLVEAL 94
RWD_RWDD3 cd23819
RWD domain of RWD domain-containing protein 3 (RWDD3) and related proteins; RWDD3, also called ...
 10-107 6.80e-08

RWD domain of RWD domain-containing protein 3 (RWDD3) and related proteins; RWDD3, also called RWD domain-containing sumoylation enhancer (RSUME), acts as an enhancer of SUMO conjugation and has no effect on ubiquitination. It increases protein sumoylation (a dynamic ubiquitin-like post translational modification) of several proteins including HIF1alpha and I-kappa-B, through direct interaction with UBC9. Its RWD domain is required for the sumoylation enhancement activity.


Pssm-ID: 467655  Cd Length: 106  Bit Score: 48.48  E-value: 6.80e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45356139  10 ELEALRSIYEGDNSFRELSP------VSFQYRIGEDGDPKAFLIE--VSWTETYPQTAPVISMNAffnNTISSAVKQSIL 81
Cdd:cd23819   2 ELSVLQAIFCGPGEFEVLSSsetsdgVSFKIQISVEGFDEDIVLKltFHLSPNYPSSLPDISVSS---EQLTRAQCNDLQ 78

                        90       100
                ....*....|....*....|....*.
gi 45356139  82 AKLQEAVEVNLGTAMTYTLFEYAKDH 107
Cdd:cd23819  79 DSLLEYANSLLGEPMVLELVLWLQEN 104
RWD_IMPACT cd23821
RWD domain of protein IMPACT and related proteins; IMPACT, also imprinted and ancient gene ...
 10-93 4.33e-04

RWD domain of protein IMPACT and related proteins; IMPACT, also imprinted and ancient gene protein homolog, acts as a translational regulator that ensures constant high levels of translation upon a variety of stress conditions, such as amino acid starvation, UV-C irradiation, proteasome inhibitor treatment, and glucose deprivation. It plays a role as a negative regulator of EIF2AK4/GCN2 kinase activity. It impairs GCN1-mediated EIF2AK4/GCN2 activation, and hence EIF2AK4/GCN2-mediated eIF-2-alpha phosphorylation and subsequent down-regulation of protein synthesis. IMPACT may be required to regulate translation in specific neuronal cells under amino acid starvation conditions by preventing GCN2 activation and therefore ATF4 synthesis. Through its inhibitory action on EIF2AK4/GCN2, IMPACT plays a role in differentiation of neuronal cells by stimulating neurite outgrowth.


Pssm-ID: 467657  Cd Length: 101  Bit Score: 37.99  E-value: 4.33e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45356139  10 ELEALRSIYEGDnsFRELSPVSFQYRI----GEDGDPKAFLiEVSWTETYPQTAPVISmnaffnnTISSA-----VKQSI 80
Cdd:cd23821   3 EIEALEAIYGED--FVVIDESARSFVIrielDGPHLPPLVL-RVHLPPDYPSHSPPIF-------ELSAPwlsgeERSEL 72

                        90
                ....*....|...
gi 45356139  81 LAKLQEAVEVNLG 93
Cdd:cd23821  73 CAELDEIWEENAG 85
RWD_ScGIR2-like cd23824
RWD domain of Saccharomyces cerevisiae genetically interacts with ribosomal genes protein 2 ...
 5-67 4.14e-03

RWD domain of Saccharomyces cerevisiae genetically interacts with ribosomal genes protein 2 (GIR2) and related proteins; GIR2, also called DRG family-regulatory protein 2, acts as a negative regulator of GCN2 kinase activity by interacting with GCN1 and disrupting the GCN1-GCN2 interaction in amino acid-starved cells. It also interacts with RBG1. The RBG1-GIR2 complex is responsible for efficient cell growth under conditions of amino acid depletion and binds the activator GCN1. Critical mutations in the RWD domain of GIR2 abolishes its interaction with GCN1. GIR2 may interact with ribosomes through GCN1, which binds directly to ribosomes.


Pssm-ID: 467660  Cd Length: 159  Bit Score: 36.14  E-value: 4.14e-03
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 45356139   5 EDQEMELEALRSIYEGDNSF--RELSPVSFQYRIGEDGDP---------KAFLIEVSWT--ETYPQTAPVISMNAF 67
Cdd:cd23824   3 EEQEQELEVLESIYPDELTVlnDEYPNIQFEVDLKLELDPlddtadslsKEHTLVVDFQlpENYPDEAPIISIEPQ 78
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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