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 6680177    8 EKTLINGLWSKVNVEEVGGEALGRLLVVYPWTHRFFDSFGNLSSASAIMGNPRVKAHGKKVLTAFGESIKNLDNLKSALA 87
Cdd:cd08925   1 EKAAITAVWGKVDVDEVGAEALARLLIVYPWTQRYFSSFGDLSSAAAIAGNPKVAAHGKKVLGALGEAIKHLDDIKATFA 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 6680177   88 KLSELHCDKLHVDPENFKLLGNVLVIVLASHFGNEFTAEMQAAWQKLVAGVATALSHKY 146
Cdd:cd08925  81 DLSEKHSEKLHVDPENFKLLGDCLVVVLAAHFGKEFTPEVQAAWEKFFAVVVDALSKGY 139

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 6680177    8 EKTLINGLWSKVNVEEVGGEALGRLLVVYPWTHRFFDSFGNLSSASAIMGNPRVKAHGKKVLTAFGESIKNLDNLKSALA 87
Cdd:cd08925   1 EKAAITAVWGKVDVDEVGAEALARLLIVYPWTQRYFSSFGDLSSAAAIAGNPKVAAHGKKVLGALGEAIKHLDDIKATFA 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 6680177   88 KLSELHCDKLHVDPENFKLLGNVLVIVLASHFGNEFTAEMQAAWQKLVAGVATALSHKY 146
Cdd:cd08925  81 DLSEKHSEKLHVDPENFKLLGDCLVVVLAAHFGKEFTPEVQAAWEKFFAVVVDALSKGY 139

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 6680177    8 EKTLINGLWSKVNVEEVGGEALGRLLVVYPWTHRFFDSFGNLSSASAIMGNPRVKAHGKKVLTAFGESIKNLDNLKSALA 87
Cdd:cd08925   1 EKAAITAVWGKVDVDEVGAEALARLLIVYPWTQRYFSSFGDLSSAAAIAGNPKVAAHGKKVLGALGEAIKHLDDIKATFA 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 6680177   88 KLSELHCDKLHVDPENFKLLGNVLVIVLASHFGNEFTAEMQAAWQKLVAGVATALSHKY 146
Cdd:cd08925  81 DLSEKHSEKLHVDPENFKLLGDCLVVVLAAHFGKEFTPEVQAAWEKFFAVVVDALSKGY 139

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 6680177    4 FTAEEKTLINGLWSKV--NVEEVGGEALGRLLVVYPWTHRFFDSFgNLSSasaimGNPRVKAHGKKVLTAFGESIKNLDN 81
Cdd:cd08927   1 LSAADKALIKALWGKIagHAEAIGAEALARMFLSFPQTKTYFPHF-DLSA-----GSAQVKAHGKKVMDALGDAVKHLDD 74

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 6680177   82 LKSALAKLSELHCDKLHVDPENFKLLGNVLVIVLASHFGNEFTAEMQAAWQKLVAGVATALSHKY 146
Cdd:cd08927  75 LPGALSKLSDLHAYKLRVDPVNFKLLSHCILVTLAAHLPEDFTPEVHAALDKFLAAVSHVLSSKY 139

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 6680177    5 TAEEKTLINGLWSKV--NVEEVGGEALGRLLVVYPWTHRFFDSFGNLSSASAIMGNPRVKAHGKKVLTAFGESIKNLDN- 81
Cdd:cd08924   2 TEAERKVIQDTWARVyaNCEDVGVAILVRFFVNFPSAKQYFSQFKHMEDPLEMERSSQLRKHARRVMGALNTVVENLHDp 81

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 6680177   82 --LKSALAKLSELHCDKLHVDPENFKLLGNVLVIVLASHFGNEFTAEMQAAWQKLVAGVATALSHKY 146
Cdd:cd08924  82 dkVSSVLALVGKAHALKHKVEPVYFKILSGVILEVLAEEFAQDFTPEVQSAWSKLRGLIYSHVTAAY 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 6680177   11 LINGLWSKV--NVEEVGGEALGRLLVVYPWTHRFFDSFGNLSSAsAIMGNPRVKAHGKKVLTAFGESIKNLDNLKSALAK 88
Cdd:cd08926   5 LVLKVWAKVeaDLTGIGQEVLLRLFKEHPETQEHFPKFKGISQD-DLKSNEDLKKHGVTVLTALGEILKQKGSHEAELKP 83

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 6680177   89 LSELHCDKLHVDPENFKLLGNVLVIVLASHFGNEFTAEMQAAWQKLVAGVATALSHKY 146
Cdd:cd08926  84 LAQTHATKHKIPPKYFELITEIIVKVLAEKHPSEMGAPAQAAFSKAFELICSDIEANY 141

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 6680177   62 KAHGKKVLTAFGESIKNLDNLKSALAKLSELHcdKLHVD----PENFKLLGNVLVIVLASHFGNEFTAEMQAAWQ---KL 134
Cdd:cd12131  44 EEQGRKLMAMLVLVVKGLDDLEALLPALQDLG--RRHVKygvkPEHYPLVGEALLWTLEEGLGDEWTPEVKQAWTdayGI 121

                ....*..
gi 6680177  135 VAGVATA 141
Cdd:cd12131 122 LAGTMIE 128

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 6680177   20 NVEEVGGEALGRLLVvYPWTHRFFDSFGNLSsasaimgnpRVKAHGKKVLTAFGESIKNLDNLKSALAKLSELHCDkLHV 99
Cdd:cd01067   8 NQEEIVDDFYDRLFA-LPSLSELFSPPGRLA---------KCIRKQMHFLRYALYGLVDGDSIEEGLAGLGEAHKS-LGV 76

                        90       100       110
                ....*....|....*....|....*....|....*
gi 6680177  100 DPENFKLLGNVLVIVLASHFGNEFTAEMQAAWQKL 134
Cdd:cd01067  77 PISYFIAALNVMKDVLTELLGDKFTPAAGEAWTKI 111

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 6680177    5 TAEEKTLINGLWSKV--NVEEVGGEALGRLLVVYPwthRFFDSFGNLSSA--SAIMGNPRVKAHGKKVLTAFGESIKNLD 80
Cdd:cd12137   2 TERQKQLIESSWSILqeDIAKVGVIMFVRLFETHP---DCKDAFFPFRDVdlEDLRHSKELRAHGLRVLSFVEKSLARLH 78

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 6680177   81 NLKSALAKLSEL---HCdKLHVDPENFKLLGNVLVIVLASHFGNEFTAEMQAAWQKLVA 136
Cdd:cd12137  79 QPDKLEELLHELgrkHY-RYNAKVKYVDLVGQQFIFAIEPVLKEQWTPELEEAWKTLFR 136

Globin domain of Pseudomonas aeruginosa flavohemoglobin (HmpPa) and related proteins; Flavohemoglobins (flavoHbs) function primarily as nitric oxide dioxygenases (NODs, EC 1.14.12.17), converting NO and O2 to inert NO3- (nitrate). They have an N-terminal globin domain and a C-terminal ferredoxin reductase-like NAD- and FAD-binding domain, and use the reducing power of cellular NAD(P)H to drive regeneration of the ferrous heme. They protect from nitrosative stress (the broad range of cellular toxicities caused by NO), and modulate NO signaling pathways. The physiological role of HmpPa is thought to be detoxification of NO under aerobic conditions.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6680177    5 TAEEKTLINglwSKVNVEEVGGEALGR-----LLVVYPWTHRFFDSFGNLSSAsaimgNPRVKAHGkkvLTAFGESIKNL 79
Cdd:cd14780   2 SPHQIAIIK---ATVPALEAHGEAITThfyplMFEEYPEVRALFNQAHQASGA-----QPRALANA---VLAYARHIDRL 70

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 6680177   80 DNLKSALAKLSELHCdKLHVDPENFKLLGNVLVIVLASHFGNEFTAEMQAAW 131
Cdd:cd14780  71 EVLGGAVSLIVNKHV-SLNILPEHYPIVGTCLLRAIREVLGDAATDEVIEAW 121

Globin domain of flavohemoglobins (flavoHbs); FlavoHbs function primarily as nitric oxide dioxygenases (NODs, EC 1.14.12.17), converting NO and O2 to inert NO3- (nitrate). They have an N-terminal globin domain and a C-terminal ferredoxin reductase-like NAD- and FAD-binding domain, and use the reducing power of cellular NAD(P)H to drive regeneration of the ferrous heme. 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. FlavoHb expression affects Aspergillus nidulans sexual development and mycotoxin production, and Dictyostelium discoideum development. This family also includes some single-domain goblins (SDgbs).

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 6680177   71 AFGESIKNLDNLKSALAKLSELHCdKLHVDPENFKLLGNVLVIVLASHFGNEFTAEMQAAW 131
Cdd:cd08922  62 AYAANIDNLEVLLPAVERIAHKHV-SLGVKPEHYPIVGEYLLEAIKEVLGDAATPEVLDAW 121