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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148694518   6 VVRVFVASCSGFVAIKKKQQDVVRFLEANKIEFEEVDITMSEEQRQWMYKNIPPEkkpaQGNPLPPQIFNGDRYCGDYDS 85
Cdd:cd03030    1 VIKVYIASSSGSTEIKKRQQEVLGFLEAKKIEFEEVDISMNEENRQWMRENVPNE----NGKPLPPQIFNGDEYCGDYEA 76

                         90
                 ....*....|....*.
gi 148694518  86 FFESKESNTVFSFLGL 101
Cdd:cd03030   77 FFEAKENNTLEEFLKL 92

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148694518   6 VVRVFVASCSGFVAIKKKQQDVVRFLEANKIEFEEVDITMSEEQRQWMYKNIPPEkkpaQGNPLPPQIFNGDRYCGDYDS 85
Cdd:cd03030    1 VIKVYIASSSGSTEIKKRQQEVLGFLEAKKIEFEEVDISMNEENRQWMRENVPNE----NGKPLPPQIFNGDEYCGDYEA 76

                         90
                 ....*....|....*.
gi 148694518  86 FFESKESNTVFSFLGL 101
Cdd:cd03030   77 FFEAKENNTLEEFLKL 92

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 148694518  27 VVRFLEANKIEFEEVDITMSEEQRQWMYKnippekkpAQGNPLPPQIFNGDRYCGDYDS 85
Cdd:COG0695   16 AKRLLDEKGIPYEEIDVDEDPEAREELRE--------RSGRRTVPVIFIGGEHLGGFDE 66

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148694518   6 VVRVFVASCSGFVAIKKKQQDVVRFLEANKIEFEEVDITMSEEQRQWMYKNIPPEkkpaQGNPLPPQIFNGDRYCGDYDS 85
Cdd:cd03030    1 VIKVYIASSSGSTEIKKRQQEVLGFLEAKKIEFEEVDISMNEENRQWMRENVPNE----NGKPLPPQIFNGDEYCGDYEA 76

                         90
                 ....*....|....*.
gi 148694518  86 FFESKESNTVFSFLGL 101
Cdd:cd03030   77 FFEAKENNTLEEFLKL 92

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148694518   6 VVRVFVASCsgfvaiKKKQQDVVRFLEANKIEFEEVDITMSEEQRQWMYKNIppekkpaqGNPLPPQIFNGDRYCGDYDS 85
Cdd:cd02066    1 KVVVFSKST------CPYCKRAKRLLESLGIEFEEIDILEDGELREELKELS--------GWPTVPQIFINGEFIGGYDD 66

                 ....*.
gi 148694518  86 FFESKE 91
Cdd:cd02066   67 LKALHE 72

Glutaredoxin;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 148694518   27 VVRFLEANKIEFEEVDITMSEEQRQWMYKNIppekkpaqGNPLPPQIFNGDRY 79
Cdd:pfam00462  15 AKRLLKSLGVDFEEIDVDEDPEIREELKELS--------GWPTVPQVFIDGEH 59

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.

                         10        20
                 ....*....|....*....|....*..
gi 148694518  27 VVRFLEANKIEFEEVDITMSEEQRQWM 53
Cdd:cd02976   16 TKRFLDERGIPFEEVDVDEDPEALEEL 42