Cytoglobin and related globins; Cygb is a hexacoordinated heme-containing protein, able to bind O2, NO and carbon monoxide. It has both nitric oxide dioxygenase and lipid peroxidase activities, and potentially participates in the maintenance of normal phenotype by implementing a homeostatic effect, to counteract stress conditions imposed on a cell. Cygb is implicated in multiple human pathologies: it is up-regulated in fibrosis and neurodegenerative disorders, and down-regulated in multiple cancer types, and may have a tumor suppressor role. It is expressed ubiquitously across a broad range of vertebrate organs including liver, heart, brain, lung, retina, and gut. In the human brain, it was detected at high levels in the habenula, hypothalamus, thalamus, hippocampus and pontine tegmental nuclei, detected at a low level in the cerebral cortex, and undetected in the cerebellar cortex.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549320  22 AERKAVQATWARLYANCEDVGVAILVRFFVNFPSAKQYFSQFRHMEDPLEMERSPQLRKHACRVMGALNTVVENLHDPDK 101
Cdd:cd08924   4 AERKVIQDTWARVYANCEDVGVAILVRFFVNFPSAKQYFSQFKHMEDPLEMERSSQLRKHARRVMGALNTVVENLHDPDK 83

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549320 102 VSSVLALVGKAHALKHKVEPMYFKILSGVILEVIAEEFANDFPVETQKAWAKLRGLIYSHVTAAYKEVGW 171
Cdd:cd08924  84 VSSVLALVGKAHALKHKVEPVYFKILSGVILEVLAEEFAQDFTPEVQSAWSKLRGLIYSHVTAAYKEVGW 153

Cytoglobin and related globins; Cygb is a hexacoordinated heme-containing protein, able to bind O2, NO and carbon monoxide. It has both nitric oxide dioxygenase and lipid peroxidase activities, and potentially participates in the maintenance of normal phenotype by implementing a homeostatic effect, to counteract stress conditions imposed on a cell. Cygb is implicated in multiple human pathologies: it is up-regulated in fibrosis and neurodegenerative disorders, and down-regulated in multiple cancer types, and may have a tumor suppressor role. It is expressed ubiquitously across a broad range of vertebrate organs including liver, heart, brain, lung, retina, and gut. In the human brain, it was detected at high levels in the habenula, hypothalamus, thalamus, hippocampus and pontine tegmental nuclei, detected at a low level in the cerebral cortex, and undetected in the cerebellar cortex.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549320  22 AERKAVQATWARLYANCEDVGVAILVRFFVNFPSAKQYFSQFRHMEDPLEMERSPQLRKHACRVMGALNTVVENLHDPDK 101
Cdd:cd08924   4 AERKVIQDTWARVYANCEDVGVAILVRFFVNFPSAKQYFSQFKHMEDPLEMERSSQLRKHARRVMGALNTVVENLHDPDK 83

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549320 102 VSSVLALVGKAHALKHKVEPMYFKILSGVILEVIAEEFANDFPVETQKAWAKLRGLIYSHVTAAYKEVGW 171
Cdd:cd08924  84 VSSVLALVGKAHALKHKVEPVYFKILSGVILEVLAEEFAQDFTPEVQSAWSKLRGLIYSHVTAAYKEVGW 153

Cytoglobin and related globins; Cygb is a hexacoordinated heme-containing protein, able to bind O2, NO and carbon monoxide. It has both nitric oxide dioxygenase and lipid peroxidase activities, and potentially participates in the maintenance of normal phenotype by implementing a homeostatic effect, to counteract stress conditions imposed on a cell. Cygb is implicated in multiple human pathologies: it is up-regulated in fibrosis and neurodegenerative disorders, and down-regulated in multiple cancer types, and may have a tumor suppressor role. It is expressed ubiquitously across a broad range of vertebrate organs including liver, heart, brain, lung, retina, and gut. In the human brain, it was detected at high levels in the habenula, hypothalamus, thalamus, hippocampus and pontine tegmental nuclei, detected at a low level in the cerebral cortex, and undetected in the cerebellar cortex.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549320  22 AERKAVQATWARLYANCEDVGVAILVRFFVNFPSAKQYFSQFRHMEDPLEMERSPQLRKHACRVMGALNTVVENLHDPDK 101
Cdd:cd08924   4 AERKVIQDTWARVYANCEDVGVAILVRFFVNFPSAKQYFSQFKHMEDPLEMERSSQLRKHARRVMGALNTVVENLHDPDK 83

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549320 102 VSSVLALVGKAHALKHKVEPMYFKILSGVILEVIAEEFANDFPVETQKAWAKLRGLIYSHVTAAYKEVGW 171
Cdd:cd08924  84 VSSVLALVGKAHALKHKVEPVYFKILSGVILEVLAEEFAQDFTPEVQSAWSKLRGLIYSHVTAAYKEVGW 153

Globin;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549320    43 VAILVRFFVNFPSAKQYFSQFRHMEDplEMERSPQLRKHACRVMGALNTVVENLHDPDKVSSVLALVGKAHALKHKVEPM 122
Cdd:pfam00042   1 AEILARLFTAYPDTKAYFPRFEKSAD--DLKGSPKFKAHGKKVLAALGEAVKHLDDLAALNAALKKLGARHKEKRGVDPA 78

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 19549320   123 YFKILSGVILEVIAEEFAnDFPVETQKAWAKLRGLIYS 160
Cdd:pfam00042  79 NFKLFGEALLVVLAEHLG-EFTPETKAAWDKALDVIAA 115

Globin-like protein superfamily; This globin-like domain superfamily contains a wide variety of all-helical proteins that bind porphyrins, phycobilins, and other non-heme cofactors, and play various roles in all three kingdoms of life, including sensors or transporters of oxygen. It includes the M/myoglobin-like, S/sensor globin, and T/truncated globin (TrHb) families, and the phycobiliproteins (PBPs). The M family includes chimeric (FHbs/flavohemoglobins) and single-domain globins: FHbs, Ngbs/neuroglobins, Cygb/cytoglobins, GbE/avian eye specific globin E, GbX/globin X, amphibian GbY/globin Y, Mb/myoglobin, HbA/hemoglobin-alpha, HbB/hemoglobin-beta, SDgbs/single-domain globins related to FHbs, and Adgb/androglobin. The S family includes GCS/globin-coupled sensors, Pgbs/protoglobins, and SSDgbs/sensor single domain globins. The T family is classified into three main groups: TrHb1s (N), TrHb2s (O) and TrHb3s (P). The M- and S families exhibit the canonical secondary structure of hemoglobins, a 3-over-3 alpha-helical sandwich structure (3/3 Mb-fold), built by eight alpha-helical segments (named A through H). For M family Adgbs, this globin domain is permuted, such that C-H are followed by A-B. The T family globins adopt a 2-on-2 alpha-helical sandwich structure, resulting from extensive and complex modifications of the canonical 3-on-3 alpha-helical sandwich that are distributed throughout the whole protein molecule. PBPs bind the linear tetrapyrrole chromophore, phycobilin, a prosthetic group chemically and metabolically related to iron protoporphyrin IX/protoheme. Examples of other globin-like domains which bind non-heme cofactors include those of the Bacillus anthracis sporulation inhibitors pXO1-118 and pXO2-61 which bind fatty acid and halide in vitro, and the globin-like domain of Bacillus subtilis RsbRA which is presumed to channel sensory input to the C-terminal sulfate transporter/ anti-sigma factor antagonist (STAT) domain. RsbRA is a component of the sigma B-activating stressosome, and a regulator of the RNA polymerase sigma factor subunit sigma (B).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549320  31 WARLYANCEDVGVAILVRFFVNfPSAKQYFSQFRhmedplemerspQLRKHACRVMGALNTVVENLHDPDKVSSVLALVG 110
Cdd:cd01067   2 WGYLEENQEEIVDDFYDRLFAL-PSLSELFSPPG------------RLAKCIRKQMHFLRYALYGLVDGDSIEEGLAGLG 68

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 19549320 111 KAHALKHkVEPMYFKILSGVILEVIAEEFANDFPVETQKAWAKLRGLIYSHV 162
Cdd:cd01067  69 EAHKSLG-VPISYFIAALNVMKDVLTELLGDKFTPAAGEAWTKIFDYIISSM 119

Hemoglobin beta, gamma, delta, epsilon, and related Hb subunits; Hb is the oxygen transport protein of erythrocytes. It is an allosterically modulated heterotetramer. Hemoglobin A (HbA) is the most common Hb in adult humans, and is formed from two alpha-chains and two beta-chains (alpha2beta2). An equilibrium exists between deoxygenated/unliganded/T(tense state) Hb having low oxygen affinity, and oxygenated /liganded/R(relaxed state) Hb having a high oxygen affinity. Various endogenous heterotropic effectors bind Hb to modulate its oxygen affinity and cooperative behavior, e.g. hydrogen ions, chloride ions, carbon dioxide and 2,3-bisphosphoglycerate. Hb is also an allosterically regulated nitrite reductase; the plasma nitrite anion may be activated by hemoglobin in areas of hypoxia to bring about vasodilation. Other Hb types are: HbA2 (alpha2delta2) which in normal individuals, is naturally expressed at a low level; Hb Portland-1 (zeta2gamma2), Hb Gower-1 (zeta2epsilon2), and Hb Gower-2 (alpha2epsilon2), which are Hbs present during the embryonic period; and fetal hemoglobin (HbF, alpha2gamma2), the primary hemoglobin throughout most of gestation. These Hbs types have differences in O2 affinity and in their interactions with allosteric effectors.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549320  23 ERKAVQATWARLyaNCEDVGVAILVRFFVNFPSAKQYFSQFRHMEDPLEMERSPQLRKHACRVMGALntvVENLHDPDKV 102
Cdd:cd08925   1 EKAAITAVWGKV--DVDEVGAEALARLLIVYPWTQRYFSSFGDLSSAAAIAGNPKVAAHGKKVLGAL---GEAIKHLDDI 75

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 19549320 103 SSVLALVGKAHALKHKVEPMYFKILSGVILEVIAEEFANDFPVETQKAWAKL 154
Cdd:cd08925  76 KATFADLSEKHSEKLHVDPENFKLLGDCLVVVLAAHFGKEFTPEVQAAWEKF 127

Globin_X (GbX); Zebrafish globin X (GbX) is expressed at low levels in neurons of the central nervous system, and appears to be associated with the sensory system. GbX is likely to be attached to the cell membrane via S-palmitoylation and N-myristoylation. It's unlikely to have a true respiratory function as it is membrane-associated. It has been suggested that it may protect the lipids in the cell membrane from oxidation or act as a redox-sensing or signaling protein. Zebrafish GbX is hexacoordinate, and displays cooperative O2 binding.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549320  22 AERKAVQATWARLYANCEDVGVAILVRFFVNFPSAKQYFSQFRHMeDPLEMERSPQLRKHACRVMGALNTVVENLHDPDK 101
Cdd:cd12137   4 RQKQLIESSWSILQEDIAKVGVIMFVRLFETHPDCKDAFFPFRDV-DLEDLRHSKELRAHGLRVLSFVEKSLARLHQPDK 82

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|...
gi 19549320 102 VSSVLALVGKAHaLKHKVEPMYFKILSGVILEVIAEEFANDFPVETQKAWAKL 154
Cdd:cd12137  83 LEELLHELGRKH-YRYNAKVKYVDLVGQQFIFAIEPVLKEQWTPELEEAWKTL 134

Hell's gate globin I (HGbI) from Methylacidophilum infernorum and related proteins; HGbI is a single-domain heme-containing protein isolated from Methylacidiphilum infernorum, an aerobic acidophilic and thermophilic methanotroph. M. infernorum grows optimally at pH 2.0 and 60C and its home is New Zealand's Hell's Gate geothermal park. The physiological role of HGbI has yet to be determined. It has an extremely strong resistance to auto-oxidation, and has fast oxygen-binding/slow release characteristics. Its CO on-rate is comparable to the O2 on-rate, and it is able to bind acetate with high affinity in the ferric state. The coordination of the heme iron changes in the ferrous form from pentacoordinate at low pH to predominantly hexacoordinate at high pH; in the ferric form, it is predominantly hexacoordinate at all pH.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549320  27 VQATWARLYANCEDVGVAILVRFFVNFPSAKQYFSQfRHMEDplemerspQLRKhacrVMGALNTVVENLHDPDKVSSVL 106
Cdd:cd12131   5 VQQSFAKVEPIADEAAALFYERLFELDPELKPLFKG-TDMEE--------QGRK----LMAMLVLVVKGLDDLEALLPAL 71

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 19549320 107 ALVGKAHAlKHKVEPMYFKILSGVILEVIAEEFANDFPVETQKAW 151
Cdd:cd12131  72 QDLGRRHV-KYGVKPEHYPLVGEALLWTLEEGLGDEWTPEVKQAW 115

Class1 nonsymbiotic hemoglobins (nsHbs), class II nsHbs, leghemoglobins (Lbs,) and related proteins; Class1 nsHbs include the dimeric hexacoordinate Trema tomentosa nsHb and the dimeric hexacoordinate nsHb from monocot barley. Also belonging to this family is ParaHb, a dimeric pentacoordinate Hb from the root nodules of Parasponia andersonii, a non-legume capable of symbiotic nitrogen fixation. ParaHb is unusual in that it has different heme redox potentials for each subunit; it may have evolved from class1 nsHbs. Lbs are pentacoordinate, and facilitate the diffusion of O2 to the respiring Rhizobium bacteroids within root nodules. They may have evolved from class 2 nonsymbiotic hemoglobins (class2 nsHb).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549320  27 VQATWARLYANCEDVGVAILVRFFVNFPSAKQYFSQFRHMEDPLemERSPQLRKHACRVMGALNTVVENLHDPDKV---S 103
Cdd:cd08923   9 VKSSWEVLKKNIPQLSLRFFLLILEIAPAAKDMFSFLKDSDEIP--ENNPKLKAHAMKVFKMTCESAIQLRKKGKVvvaD 86

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 19549320 104 SVLALVGKAHaLKHKVEPMYFKILSGVILEVIAEEFANDFPVETQKAWaklrGLIYSHVTAAYK 167
Cdd:cd08923  87 TTLKRLGSVH-LKKGVADPHFEVVKEALLKTIKEAVGDKWSEEMKCAW----GEAYDQLAAAIK 145

Globin domain of uncharacterized oxidoreductases containing a FAD/NADH binding domain; This subfamily is composed of uncharacterized proteins containing an N-terminal myoglobin-like (M family globin) domain and a C-terminal oxygenase reductase FAD/NADH binding domain belonging to the ferredoxin reductase (FNR) family and is usually part of multi-component bacterial oxygenases which oxidize hydrocarbons using oxygen as the oxidant. The domain architecture of this subfamily is similar to flavohemoglobins, which function primarily as nitric oxide dioxygenases (NODs, EC 1.14.12.17), converting NO and O2 to inert NO3- (nitrate). They protect from nitrosative stress (the broad range of cellular toxicities caused by NO), and modulate NO signaling pathways. NO scavenging by flavoHb attenuates the expression of the nitrosative stress response, affects the swarming behavior of Escherichia coli, and maintains squid-Vibrio fischeri and Medicago truncatula-Sinorhizobium meliloti symbioses.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19549320  27 VQATWARLYANCEDVGVAILVRFFVNFPSAKQYFsqfrhmedPLEMErsPQLRkhacRVMGALNTVVENLHDPDKVSSVL 106
Cdd:cd19753   1 LRASLAAVEDGPDELARRFYARLFAEAPELRDLF--------PADMD--AQRD----RLARALTHVVENLDDPDGLVPFL 66

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 19549320 107 ALVGKAHAlKHKVEPMYFKILSGVILEVIAEEFANDFPVETQKAWAKLRGLIYSH 161
Cdd:cd19753  67 AQLGRDHR-KYGVAPEHYPAVGAALLAALRHFAGEAWTPELEAAWAEAYTLIAGV 120