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 1034597991   1 MEDPLEMERSPQLRKHACRVMGALNTVVENLHDPDKVSSVLALVGKAHALKHKVEPVYFKILSGVILEVVAEEFASDFPP 80
Cdd:cd08924    48 MEDPLEMERSSQLRKHARRVMGALNTVVENLHDPDKVSSVLALVGKAHALKHKVEPVYFKILSGVILEVLAEEFAQDFTP 127

                          90       100
                  ....*....|....*....|....*.
gi 1034597991  81 ETQRAWAKLRGLIYSHVTAAYKEVGW 106
Cdd:cd08924   128 EVQSAWSKLRGLIYSHVTAAYKEVGW 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 1034597991   1 MEDPLEMERSPQLRKHACRVMGALNTVVENLHDPDKVSSVLALVGKAHALKHKVEPVYFKILSGVILEVVAEEFASDFPP 80
Cdd:cd08924    48 MEDPLEMERSSQLRKHARRVMGALNTVVENLHDPDKVSSVLALVGKAHALKHKVEPVYFKILSGVILEVLAEEFAQDFTP 127

                          90       100
                  ....*....|....*....|....*.
gi 1034597991  81 ETQRAWAKLRGLIYSHVTAAYKEVGW 106
Cdd:cd08924   128 EVQSAWSKLRGLIYSHVTAAYKEVGW 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 1034597991   1 MEDPLEMERSPQLRKHACRVMGALNTVVENLHDPDKVSSVLALVGKAHALKHKVEPVYFKILSGVILEVVAEEFASDFPP 80
Cdd:cd08924    48 MEDPLEMERSSQLRKHARRVMGALNTVVENLHDPDKVSSVLALVGKAHALKHKVEPVYFKILSGVILEVLAEEFAQDFTP 127

                          90       100
                  ....*....|....*....|....*.
gi 1034597991  81 ETQRAWAKLRGLIYSHVTAAYKEVGW 106
Cdd:cd08924   128 EVQSAWSKLRGLIYSHVTAAYKEVGW 153

Globin;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034597991   6 EMERSPQLRKHACRVMGALNTVVENLHDPDKVSSVLALVGKAHALKHKVEPVYFKILSGVILEVVAEEFaSDFPPETQRA 85
Cdd:pfam00042  27 DLKGSPKFKAHGKKVLAALGEAVKHLDDLAALNAALKKLGARHKEKRGVDPANFKLFGEALLVVLAEHL-GEFTPETKAA 105

                          90
                  ....*....|
gi 1034597991  86 WAKLRGLIYS 95
Cdd:pfam00042 106 WDKALDVIAA 115

Hemoglobin alpha, zeta, mu, theta, 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 1034597991  10 SPQLRKHACRVMGALNTVVENLHDPDKVSSVLALVgkaHALKHKVEPVYFKILSGVILEVVAEEFASDFPPETQRAWAKL 89
Cdd:cd08927    51 SAQVKAHGKKVMDALGDAVKHLDDLPGALSKLSDL---HAYKLRVDPVNFKLLSHCILVTLAAHLPEDFTPEVHAALDKF 127

Hemoglobins; 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 Hb throughout most of gestation. These Hb types have differences in O2 affinity and in their interactions with allosteric effectors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034597991  10 SPQLRKHACRVMGALNTVVENLhdpDKVSSVLALVGKAHALKHKVEPVYFKILSGVILEVVAEEFASDFPPETQRAWAKL 89
Cdd:cd14765    46 NPKVKAHGKKVLGALGDAVKHL---DDLKNTFSDLSELHADKLHVDPENFKLLSDCLIVVLAAHLGKEFTPEVHAAWDKF 122

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034597991  19 RVMGALNTVVENLHDPDKVSSVLALVGKAHAlKHKVEPVYFKILSGVILEVVAEEFASDFPPETQRAW 86
Cdd:cd12131    49 KLMAMLVLVVKGLDDLEALLPALQDLGRRHV-KYGVKPEHYPLVGEALLWTLEEGLGDEWTPEVKQAW 115

Caenorhabditis elegans globin GLB-25, and related globins; The C. elegans genome contains 33 genes encoding globins that are all transcribed. These are very diverse in gene and protein structure and are localized in a variety of cells. The C. elegans globin GLB-25 (locus tag T06A1.3), like the majority of them, was expressed in neuronal cells in the head and tail portions of the body and in the nerve cord.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034597991   6 EMERSPQLRKHACRVMGALNTVVENLHDPDKVSSVLALVGKAHALKHKVEPVYFKILSGVILEVVAE 72
Cdd:cd14766    46 ELRSSEILENHAARVMDTLDEAISNIENVDYVIDLLHKVGKMHAKKPGFRPEMFWKIEEPFLEAVSE 112

Class 1 nonsymbiotic hemoglobins and related proteins; Class1 nsHbs include the dimeric hexacoordinate Trema tomentosa nsHb and the dimeric hexacoordinate nsHb from monocot barley. This subfamily also includes 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034597991   4 PLEMERSPQLRKHACRVMGALNTVVENLHDPDKVS---SVLALVGKAHaLKHKVEPVYFKILSGVILEVVAEEFASDFPP 80
Cdd:cd14784    49 TVPLEKNPKLKPHAMSVFVMTCEAAVQLRKAGKVTvreSKLKRLGATH-VKYGVVDEHFEVVKFALLETIKEAVPDMWSP 127

                          90       100
                  ....*....|....*....|..
gi 1034597991  81 ETQRAWAKlrglIYSHVTAAYK 102
Cdd:cd14784   128 EMKSAWGE----AYDQLVAAIK 145