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 1844139515   1 MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYLEFISECIIQVLQSKHPGDFGADAQGAMNKA 80
Cdd:cd08926    50 LKSNEDLKKHGVTVLTALGEILKQKGSHEAELKPLAQTHATKHKIPPKYFELITEIIVKVLAEKHPSEMGAPAQAAFSKA 129

                          90
                  ....*....|....*....
gi 1844139515  81 LELFRKDMASNYKELGFQG 99
Cdd:cd08926   130 FELICSDIEANYKELGFQG 148

Animal Myoglobins; Myoglobin (Mb) is a monomeric pentacoordinate heme-bound globin protein whose expression has long been considered limited to cardiomyocytes and striated skeletal muscle cell, however it has recently been found localized in a wide variety of tissues including smooth muscle cells. As a physiological catalyst, it can modulate reactive oxygen species levels, facilitate oxygen diffusion within the cell, and scavenge or generate NO depending on oxygen tensions within the cell. Through its NO dioxygenase and nitrite reductase activities, Mb regulates mitochondrial function in energy-demanding tissues.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139515   1 MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYLEFISECIIQVLQSKHPGDFGADAQGAMNKA 80
Cdd:cd08926    50 LKSNEDLKKHGVTVLTALGEILKQKGSHEAELKPLAQTHATKHKIPPKYFELITEIIVKVLAEKHPSEMGAPAQAAFSKA 129

                          90
                  ....*....|....*....
gi 1844139515  81 LELFRKDMASNYKELGFQG 99
Cdd:cd08926   130 FELICSDIEANYKELGFQG 148

Animal Myoglobins; Myoglobin (Mb) is a monomeric pentacoordinate heme-bound globin protein whose expression has long been considered limited to cardiomyocytes and striated skeletal muscle cell, however it has recently been found localized in a wide variety of tissues including smooth muscle cells. As a physiological catalyst, it can modulate reactive oxygen species levels, facilitate oxygen diffusion within the cell, and scavenge or generate NO depending on oxygen tensions within the cell. Through its NO dioxygenase and nitrite reductase activities, Mb regulates mitochondrial function in energy-demanding tissues.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139515   1 MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYLEFISECIIQVLQSKHPGDFGADAQGAMNKA 80
Cdd:cd08926    50 LKSNEDLKKHGVTVLTALGEILKQKGSHEAELKPLAQTHATKHKIPPKYFELITEIIVKVLAEKHPSEMGAPAQAAFSKA 129

                          90
                  ....*....|....*....
gi 1844139515  81 LELFRKDMASNYKELGFQG 99
Cdd:cd08926   130 FELICSDIEANYKELGFQG 148

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 1844139515   1 MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQ---SHATKHKIPVKYLEFISECIIQVLQSKHPGDFGADAQGAM 77
Cdd:cd08924    54 MERSSQLRKHARRVMGALNTVVENLHDPDKVSSVLALvgkAHALKHKVEPVYFKILSGVILEVLAEEFAQDFTPEVQSAW 133

                          90       100
                  ....*....|....*....|
gi 1844139515  78 NKALELFRKDMASNYKELGF 97
Cdd:cd08924   134 SKLRGLIYSHVTAAYKEVGW 153

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 1844139515   3 ASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYLEFISECIIQVLQSKHPGDFGADAQGAMNKALE 82
Cdd:cd14765    45 GNPKVKAHGKKVLGALGDAVKHLDDLKNTFSDLSELHADKLHVDPENFKLLSDCLIVVLAAHLGKEFTPEVHAAWDKFLA 124

                  .
gi 1844139515  83 L 83
Cdd:cd14765   125 V 125