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Conserved domains on  [gi|122937349|ref|NP_001073945|]
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glutaredoxin domain-containing cysteine-rich protein 1 [Homo sapiens]

Protein Classification

glutaredoxin family protein( domain architecture ID 10122541)

glutaredoxin (GRX) family protein belonging to the thioredoxin superfamily, may function as a glutathione (GSH) dependent reductase, catalyzing the disulfide reduction of target proteins using an active site dithiol, present in a CXXC motif

CATH:  3.40.30.10
Gene Ontology:  GO:0015036
SCOP:  4000237

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
GRX_GRX_like cd03031
Glutaredoxin (GRX) family, GRX-like domain containing protein subfamily; composed of ...
138-285 1.04e-74

Glutaredoxin (GRX) family, GRX-like domain containing protein subfamily; composed of uncharacterized eukaryotic proteins containing a GRX-like domain having only one conserved cysteine, aligning to the C-terminal cysteine of the CXXC motif of GRXs. This subfamily is predominantly composed of plant proteins. GRX is a glutathione (GSH) dependent reductase, catalyzing the disulfide reduction of target proteins via a redox active CXXC motif using a similar dithiol mechanism employed by TRXs. GRX has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. Proteins containing only the C-terminal cysteine are generally redox inactive.


:

Pssm-ID: 239329 [Multi-domain]  Cd Length: 147  Bit Score: 225.19  E-value: 1.04e-74
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 122937349 138 RVVIYTTCLRVVRTTFERCELVRKIFQNHRVKFEEKNIALNGEYGKELDERCRRVSEAPSLPVVFIDGHYLGGAEKILSM 217
Cdd:cd03031    1 RVVLYTTSLRGVRKTFEDCNNVRAILESFRVKFDERDVSMDSGFREELRELLGAELKAVSLPRVFVDGRYLGGAEEVLRL 80
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 122937349 218 NESGELQDILTKIERVQHPHECPSCGGFGFLPCSVCHGSKMSMFRNCFtDSFKALKCTACNENGLQRC 285
Cdd:cd03031   81 NESGELRKLLKGIRARAGGGVCEGCGGARFVPCSECNGSCKVFAENAT-AAGGFLRCPECNENGLVRC 147
 
Name Accession Description Interval E-value
GRX_GRX_like cd03031
Glutaredoxin (GRX) family, GRX-like domain containing protein subfamily; composed of ...
138-285 1.04e-74

Glutaredoxin (GRX) family, GRX-like domain containing protein subfamily; composed of uncharacterized eukaryotic proteins containing a GRX-like domain having only one conserved cysteine, aligning to the C-terminal cysteine of the CXXC motif of GRXs. This subfamily is predominantly composed of plant proteins. GRX is a glutathione (GSH) dependent reductase, catalyzing the disulfide reduction of target proteins via a redox active CXXC motif using a similar dithiol mechanism employed by TRXs. GRX has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. Proteins containing only the C-terminal cysteine are generally redox inactive.


Pssm-ID: 239329 [Multi-domain]  Cd Length: 147  Bit Score: 225.19  E-value: 1.04e-74
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 122937349 138 RVVIYTTCLRVVRTTFERCELVRKIFQNHRVKFEEKNIALNGEYGKELDERCRRVSEAPSLPVVFIDGHYLGGAEKILSM 217
Cdd:cd03031    1 RVVLYTTSLRGVRKTFEDCNNVRAILESFRVKFDERDVSMDSGFREELRELLGAELKAVSLPRVFVDGRYLGGAEEVLRL 80
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 122937349 218 NESGELQDILTKIERVQHPHECPSCGGFGFLPCSVCHGSKMSMFRNCFtDSFKALKCTACNENGLQRC 285
Cdd:cd03031   81 NESGELRKLLKGIRARAGGGVCEGCGGARFVPCSECNGSCKVFAENAT-AAGGFLRCPECNENGLVRC 147
Glutaredoxin pfam00462
Glutaredoxin;
139-207 2.86e-08

Glutaredoxin;


Pssm-ID: 425695 [Multi-domain]  Cd Length: 60  Bit Score: 49.43  E-value: 2.86e-08
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 122937349  139 VVIYTTclrvvrTTFERCELVRKIFQNHRVKFEEKNIALNGEYGKELdercRRVSEAPSLPVVFIDGHY 207
Cdd:pfam00462   1 VVLYTK------PTCPFCKRAKRLLKSLGVDFEEIDVDEDPEIREEL----KELSGWPTVPQVFIDGEH 59
GrxC COG0695
Glutaredoxin [Posttranslational modification, protein turnover, chaperones];
138-210 3.39e-07

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 440459 [Multi-domain]  Cd Length: 74  Bit Score: 46.73  E-value: 3.39e-07
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 122937349 138 RVVIYTT--ClrvvrttfERCELVRKIFQNHRVKFEEKNIALNGEYGKELdercRRVSEAPSLPVVFIDGHYLGG 210
Cdd:COG0695    1 KVTLYTTpgC--------PYCARAKRLLDEKGIPYEEIDVDEDPEAREEL----RERSGRRTVPVIFIGGEHLGG 63
GlrX-like_plant TIGR02189
Glutaredoxin-like family; This family of glutaredoxin-like proteins is aparrently limited to ...
139-229 6.20e-06

Glutaredoxin-like family; This family of glutaredoxin-like proteins is aparrently limited to plants. Multiple isoforms are found in A. thaliana and O.sativa.


Pssm-ID: 274023 [Multi-domain]  Cd Length: 99  Bit Score: 43.98  E-value: 6.20e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 122937349  139 VVIYTT---CLrvvrttferCELVRKIFQNHRVKFEEKNIAlNGEYGKELDERCRRVSEAPSLPVVFIDGHYLGGAEKIL 215
Cdd:TIGR02189  10 VVIFSRsscCM---------CHVVKRLLLTLGVNPAVHEID-KEPAGKDIENALSRLGCSPAVPAVFVGGKLVGGLENVM 79
                          90
                  ....*....|....
gi 122937349  216 SMNESGELQDILTK 229
Cdd:TIGR02189  80 ALHISGSLVPMLKQ 93
 
Name Accession Description Interval E-value
GRX_GRX_like cd03031
Glutaredoxin (GRX) family, GRX-like domain containing protein subfamily; composed of ...
138-285 1.04e-74

Glutaredoxin (GRX) family, GRX-like domain containing protein subfamily; composed of uncharacterized eukaryotic proteins containing a GRX-like domain having only one conserved cysteine, aligning to the C-terminal cysteine of the CXXC motif of GRXs. This subfamily is predominantly composed of plant proteins. GRX is a glutathione (GSH) dependent reductase, catalyzing the disulfide reduction of target proteins via a redox active CXXC motif using a similar dithiol mechanism employed by TRXs. GRX has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. Proteins containing only the C-terminal cysteine are generally redox inactive.


Pssm-ID: 239329 [Multi-domain]  Cd Length: 147  Bit Score: 225.19  E-value: 1.04e-74
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 122937349 138 RVVIYTTCLRVVRTTFERCELVRKIFQNHRVKFEEKNIALNGEYGKELDERCRRVSEAPSLPVVFIDGHYLGGAEKILSM 217
Cdd:cd03031    1 RVVLYTTSLRGVRKTFEDCNNVRAILESFRVKFDERDVSMDSGFREELRELLGAELKAVSLPRVFVDGRYLGGAEEVLRL 80
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 122937349 218 NESGELQDILTKIERVQHPHECPSCGGFGFLPCSVCHGSKMSMFRNCFtDSFKALKCTACNENGLQRC 285
Cdd:cd03031   81 NESGELRKLLKGIRARAGGGVCEGCGGARFVPCSECNGSCKVFAENAT-AAGGFLRCPECNENGLVRC 147
GRX_family cd02066
Glutaredoxin (GRX) family; composed of GRX, approximately 10 kDa in size, and proteins ...
138-219 1.51e-16

Glutaredoxin (GRX) family; composed of GRX, approximately 10 kDa in size, and proteins containing a GRX or GRX-like domain. GRX is a glutathione (GSH) dependent reductase, catalyzing the disulfide reduction of target proteins such as ribonucleotide reductase. It contains a redox active CXXC motif in a TRX fold and uses a similar dithiol mechanism employed by TRXs for intramolecular disulfide bond reduction of protein substrates. Unlike TRX, GRX has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. The flow of reducing equivalents in the GRX system goes from NADPH -> GSH reductase -> GSH -> GRX -> protein substrates. By altering the redox state of target proteins, GRX is involved in many cellular functions including DNA synthesis, signal transduction and the defense against oxidative stress. Different classes are known including human GRX1 and GRX2, as well as E. coli GRX1 and GRX3, which are members of this family. E. coli GRX2, however, is a 24-kDa protein that belongs to the GSH S-transferase (GST) family.


Pssm-ID: 239017 [Multi-domain]  Cd Length: 72  Bit Score: 72.50  E-value: 1.51e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 122937349 138 RVVIYTTclrvvrTTFERCELVRKIFQNHRVKFEEKNIALNGEYGKELdercRRVSEAPSLPVVFIDGHYLGGAEKILSM 217
Cdd:cd02066    1 KVVVFSK------STCPYCKRAKRLLESLGIEFEEIDILEDGELREEL----KELSGWPTVPQIFINGEFIGGYDDLKAL 70

                 ..
gi 122937349 218 NE 219
Cdd:cd02066   71 HE 72
Glutaredoxin pfam00462
Glutaredoxin;
139-207 2.86e-08

Glutaredoxin;


Pssm-ID: 425695 [Multi-domain]  Cd Length: 60  Bit Score: 49.43  E-value: 2.86e-08
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 122937349  139 VVIYTTclrvvrTTFERCELVRKIFQNHRVKFEEKNIALNGEYGKELdercRRVSEAPSLPVVFIDGHY 207
Cdd:pfam00462   1 VVLYTK------PTCPFCKRAKRLLKSLGVDFEEIDVDEDPEIREEL----KELSGWPTVPQVFIDGEH 59
GrxC COG0695
Glutaredoxin [Posttranslational modification, protein turnover, chaperones];
138-210 3.39e-07

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 440459 [Multi-domain]  Cd Length: 74  Bit Score: 46.73  E-value: 3.39e-07
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 122937349 138 RVVIYTT--ClrvvrttfERCELVRKIFQNHRVKFEEKNIALNGEYGKELdercRRVSEAPSLPVVFIDGHYLGG 210
Cdd:COG0695    1 KVTLYTTpgC--------PYCARAKRLLDEKGIPYEEIDVDEDPEAREEL----RERSGRRTVPVIFIGGEHLGG 63
GRX_PICOT_like cd03028
Glutaredoxin (GRX) family, PKC-interacting cousin of TRX (PICOT)-like subfamily; composed of ...
162-224 1.88e-06

Glutaredoxin (GRX) family, PKC-interacting cousin of TRX (PICOT)-like subfamily; composed of PICOT and GRX-PICOT-like proteins. The non-PICOT members of this family contain only the GRX-like domain, whereas PICOT contains an N-terminal TRX-like domain followed by one to three GRX-like domains. It is interesting to note that PICOT from plants contain three repeats of the GRX-like domain, metazoan proteins (except for insect) have two repeats, while fungal sequences contain only one copy of the domain. PICOT is a protein that interacts with protein kinase C (PKC) theta, a calcium independent PKC isoform selectively expressed in skeletal muscle and T lymphocytes. PICOT inhibits the activation of c-Jun N-terminal kinase and the transcription factors, AP-1 and NF-kB, induced by PKC theta or T-cell activating stimuli. Both GRX and TRX domains of PICOT are required for its activity. Characterized non-PICOT members of this family include CXIP1, a CAX-interacting protein in Arabidopsis thaliana, and PfGLP-1, a GRX-like protein from Plasmodium falciparum.


Pssm-ID: 239326  Cd Length: 90  Bit Score: 45.18  E-value: 1.88e-06
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 122937349 162 IFQNHRVKFEEKNIALNgeygKELDERCRRVSEAPSLPVVFIDGHYLGGAEKILSMNESGELQ 224
Cdd:cd03028   32 ILNQLGVDFGTFDILED----EEVRQGLKEYSNWPTFPQLYVNGELVGGCDIVKEMHESGELQ 90
GRX_GRXh_1_2_like cd03419
Glutaredoxin (GRX) family, GRX human class 1 and 2 (h_1_2)-like subfamily; composed of ...
180-226 3.88e-06

Glutaredoxin (GRX) family, GRX human class 1 and 2 (h_1_2)-like subfamily; composed of proteins similar to human GRXs, approximately 10 kDa in size, and proteins containing a GRX or GRX-like domain. GRX is a glutathione (GSH) dependent reductase, catalyzing the disulfide reduction of target proteins such as ribonucleotide reductase. It contains a redox active CXXC motif in a TRX fold and uses a similar dithiol mechanism employed by TRXs for intramolecular disulfide bond reduction of protein substrates. Unlike TRX, GRX has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. The flow of reducing equivalents in the GRX system goes from NADPH -> GSH reductase -> GSH -> GRX -> protein substrates. By altering the redox state of target proteins, GRX is involved in many cellular functions including DNA synthesis, signal transduction and the defense against oxidative stress. Different classes are known including human GRX1 and GRX2, which are members of this subfamily. Also included in this subfamily are the N-terminal GRX domains of proteins similar to human thioredoxin reductase 1 and 3.


Pssm-ID: 239511 [Multi-domain]  Cd Length: 82  Bit Score: 44.07  E-value: 3.88e-06
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 122937349 180 EYGKELDERCRRVSEAPSLPVVFIDGHYLGGAEKILSMNESGELQDI 226
Cdd:cd03419   36 EDGSEIQDYLQELTGQRTVPNVFIGGKFIGGCDDLMALHKSGKLVKL 82
GlrX-like_plant TIGR02189
Glutaredoxin-like family; This family of glutaredoxin-like proteins is aparrently limited to ...
139-229 6.20e-06

Glutaredoxin-like family; This family of glutaredoxin-like proteins is aparrently limited to plants. Multiple isoforms are found in A. thaliana and O.sativa.


Pssm-ID: 274023 [Multi-domain]  Cd Length: 99  Bit Score: 43.98  E-value: 6.20e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 122937349  139 VVIYTT---CLrvvrttferCELVRKIFQNHRVKFEEKNIAlNGEYGKELDERCRRVSEAPSLPVVFIDGHYLGGAEKIL 215
Cdd:TIGR02189  10 VVIFSRsscCM---------CHVVKRLLLTLGVNPAVHEID-KEPAGKDIENALSRLGCSPAVPAVFVGGKLVGGLENVM 79
                          90
                  ....*....|....
gi 122937349  216 SMNESGELQDILTK 229
Cdd:TIGR02189  80 ALHISGSLVPMLKQ 93
GRX_SH3BGR cd03030
Glutaredoxin (GRX) family, SH3BGR (SH3 domain binding glutamic acid-rich protein) subfamily; a ...
167-227 2.85e-04

Glutaredoxin (GRX) family, SH3BGR (SH3 domain binding glutamic acid-rich protein) subfamily; a recently-identified subfamily composed of SH3BGR and similar proteins possessing significant sequence similarity to GRX, but without a redox active CXXC motif. The SH3BGR gene was cloned in an effort to identify genes mapping to chromosome 21, which could be involved in the pathogenesis of congenital heart disease affecting Down syndrome newborns. Several human SH3BGR-like (SH3BGRL) genes have been identified since, mapping to different locations in the chromosome. Of these, SH3BGRL3 was identified as a tumor necrosis factor (TNF) alpha inhibitory protein and was also named TIP-B1. Upregulation of expression of SH3BGRL3 is associated with differentiation. It has been suggested that it functions as a regulator of differentiation-related signal transduction pathways.


Pssm-ID: 239328 [Multi-domain]  Cd Length: 92  Bit Score: 39.18  E-value: 2.85e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 122937349 167 RVKFEEKNIALNGEYGKELDERCRRVSEAPSLPVVFIDGHYLGGAEKILSMNESGELQDIL 227
Cdd:cd03030   30 KIEFEEVDISMNEENRQWMRENVPNENGKPLPPQIFNGDEYCGDYEAFFEAKENNTLEEFL 90
GRX_hybridPRX5 cd03029
Glutaredoxin (GRX) family, PRX5 hybrid subfamily; composed of hybrid proteins containing ...
156-214 1.00e-03

Glutaredoxin (GRX) family, PRX5 hybrid subfamily; composed of hybrid proteins containing peroxiredoxin (PRX) and GRX domains, which is found in some pathogenic bacteria and cyanobacteria. PRXs are thiol-specific antioxidant (TSA) proteins that confer a protective antioxidant role in cells through their peroxidase activity in which hydrogen peroxide, peroxynitrate, and organic hydroperoxides are reduced and detoxified using reducing equivalents derived from either thioredoxin, glutathione, trypanothione and AhpF. GRX is a glutathione (GSH) dependent reductase, catalyzing the disulfide reduction of target proteins. PRX-GRX hybrid proteins from Haemophilus influenza and Neisseria meningitis exhibit GSH-dependent peroxidase activity. The flow of reducing equivalents in the catalytic cycle of the hybrid protein goes from NADPH -> GSH reductase -> GSH -> GRX domain of hybrid -> PRX domain of hybrid -> peroxide substrate.


Pssm-ID: 239327 [Multi-domain]  Cd Length: 72  Bit Score: 37.11  E-value: 1.00e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 122937349 156 CELVRKIFQNHRVKFEEknIAL-NGEYGKELdercRRVSEAPSLPVVFIDGHYLGGAEKI 214
Cdd:cd03029   14 CARAKAALQENGISYEE--IPLgKDITGRSL----RAVTGAMTVPQVFIDGELIGGSDDL 67
NrdH cd02976
NrdH-redoxin (NrdH) family; NrdH is a small monomeric protein with a conserved redox active ...
138-210 2.26e-03

NrdH-redoxin (NrdH) family; NrdH is a small monomeric protein with a conserved redox active CXXC motif within a TRX fold, characterized by a glutaredoxin (GRX)-like sequence and TRX-like activity profile. In vitro, it displays protein disulfide reductase activity that is dependent on TRX reductase, not glutathione (GSH). It is part of the NrdHIEF operon, where NrdEF codes for class Ib ribonucleotide reductase (RNR-Ib), an efficient enzyme at low oxygen levels. Under these conditions when GSH is mostly conjugated to spermidine, NrdH can still function and act as a hydrogen donor for RNR-Ib. It has been suggested that the NrdHEF system may be the oldest RNR reducing system, capable of functioning in a microaerophilic environment, where GSH was not yet available. NrdH from Corynebacterium ammoniagenes can form domain-swapped dimers, although it is unknown if this happens in vivo. Domain-swapped dimerization, which results in the blocking of the TRX reductase binding site, could be a mechanism for regulating the oxidation state of the protein.


Pssm-ID: 239274 [Multi-domain]  Cd Length: 73  Bit Score: 36.05  E-value: 2.26e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 122937349 138 RVVIYTTclrvvrTTFERCELVRKIFQNHRVKFEEKNIALNGEYGKELdercRRVSEAPSLPVVFIDGHYLGG 210
Cdd:cd02976    1 EVTVYTK------PDCPYCKATKRFLDERGIPFEEVDVDEDPEALEEL----KKLNGYRSVPVVVIGDEHLSG 63
 
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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