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Conserved domains on  [gi|4389013|pdb|3LHB|A]
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Chain A, PROTEIN (HEMOGLOBIN)

Protein Classification

globin family protein( domain architecture ID 229384)

globin family protein is an all-helical protein that may bind porphyrins, phycobilins, and other non-heme cofactors, and may play various roles including as a sensor or transporter of oxygen

CATH:  1.10.490.10
Gene Ontology:  GO:0019825|GO:0020037
PubMed:  32863222|16061809|19281958
SCOP:  3000554

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
Globin-like super family cl21461
Globin-like protein superfamily; This globin-like domain superfamily contains a wide variety ...
 11-149 4.64e-32

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).


The actual alignment was detected with superfamily member cd08924:

Pssm-ID: 473869  Cd Length: 153  Bit Score: 111.47  E-value: 4.64e-32
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LHB_A       11 LSAAEKTKIRSAWAPVYSTYETSGVDILVKFFTSTPAAQEFFPKFKGLTTADELKKSADVRWHAERIINAVDDAVASMDD 90
Cdd:cd08924   1 LTEAERKVIQDTWARVYANCEDVGVAILVRFFVNFPSAKQYFSQFKHMEDPLEMERSSQLRKHARRVMGALNTVVENLHD 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
3LHB_A       91 TEKMSMKLrNLSGK-HAKSFQVDPEYFKVLAAVIADTVAAG---------DAGFEKLMSMICILLRSAY 149
Cdd:cd08924  81 PDKVSSVL-ALVGKaHALKHKVEPVYFKILSGVILEVLAEEfaqdftpevQSAWSKLRGLIYSHVTAAY 148
 
Name Accession Description Interval E-value
Cygb cd08924
Cytoglobin and related globins; Cygb is a hexacoordinated heme-containing protein, able to ...
 11-149 4.64e-32

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.


Pssm-ID: 271275  Cd Length: 153  Bit Score: 111.47  E-value: 4.64e-32
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LHB_A       11 LSAAEKTKIRSAWAPVYSTYETSGVDILVKFFTSTPAAQEFFPKFKGLTTADELKKSADVRWHAERIINAVDDAVASMDD 90
Cdd:cd08924   1 LTEAERKVIQDTWARVYANCEDVGVAILVRFFVNFPSAKQYFSQFKHMEDPLEMERSSQLRKHARRVMGALNTVVENLHD 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
3LHB_A       91 TEKMSMKLrNLSGK-HAKSFQVDPEYFKVLAAVIADTVAAG---------DAGFEKLMSMICILLRSAY 149
Cdd:cd08924  81 PDKVSSVL-ALVGKaHALKHKVEPVYFKILSGVILEVLAEEfaqdftpevQSAWSKLRGLIYSHVTAAY 148
Globin pfam00042
Globin;
35-129 4.92e-21

Globin;


Pssm-ID: 459646 [Multi-domain]  Cd Length: 117  Bit Score: 81.95  E-value: 4.92e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LHB_A         35 VDILVKFFTSTPAAQEFFPKFKGltTADELKKSADVRWHAERIINAVDDAVASMDDTEKMSMKLRNLSGKHAKSFQVDPE 114
Cdd:pfam00042   1 AEILARLFTAYPDTKAYFPRFEK--SADDLKGSPKFKAHGKKVLAALGEAVKHLDDLAALNAALKKLGARHKEKRGVDPA 78

                          90
                  ....*....|....*
3LHB_A        115 YFKVLAAVIADTVAA 129
Cdd:pfam00042  79 NFKLFGEALLVVLAE 93
 
Name Accession Description Interval E-value
Cygb cd08924
Cytoglobin and related globins; Cygb is a hexacoordinated heme-containing protein, able to ...
 11-149 4.64e-32

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.


Pssm-ID: 271275  Cd Length: 153  Bit Score: 111.47  E-value: 4.64e-32
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LHB_A       11 LSAAEKTKIRSAWAPVYSTYETSGVDILVKFFTSTPAAQEFFPKFKGLTTADELKKSADVRWHAERIINAVDDAVASMDD 90
Cdd:cd08924   1 LTEAERKVIQDTWARVYANCEDVGVAILVRFFVNFPSAKQYFSQFKHMEDPLEMERSSQLRKHARRVMGALNTVVENLHD 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
3LHB_A       91 TEKMSMKLrNLSGK-HAKSFQVDPEYFKVLAAVIADTVAAG---------DAGFEKLMSMICILLRSAY 149
Cdd:cd08924  81 PDKVSSVL-ALVGKaHALKHKVEPVYFKILSGVILEVLAEEfaqdftpevQSAWSKLRGLIYSHVTAAY 148
Mb-like cd01040
myoglobin-like; M family globin domain; This family includes chimeric (FHbs/flavohemoglobins) ...
 19-129 6.61e-24

myoglobin-like; M family globin domain; This 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 M family exhibits 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). In Adgbs, the globin domain is split into two: helices C-H are followed by helices A-B and the two parts are separated by the IQ motif. Although rearranged, the globin domain of most Adgbs contains a number of conserved residues which play critical roles in heme-coordination and gas ligand binding. Adgbs have been omitted from this A-H helix cd.


Pssm-ID: 381254  Cd Length: 133  Bit Score: 89.82  E-value: 6.61e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LHB_A       19 IRSAWAPVYSTYETSGVDILVKFFTSTPAAQEFFPKFKGLTtaDELKKSADVRWHAERIINAVDDAVASMDDTEKMSMKL 98
Cdd:cd01040   1 VKSSWARVKKDKEEFGVAIFLRLFEANPELKKLFPKFAGVD--LDLKGSPEFKAHAKRVVGALDSLIDNLDDPEALDALL 78

                        90       100       110
                ....*....|....*....|....*....|.
3LHB_A       99 RNLSGKHAKsFQVDPEYFKVLAAVIADTVAA 129
Cdd:cd01040  79 RKLGKRHKR-RGVTPEHFEVFGEALLETLEE 108
Globin pfam00042
Globin;
35-129 4.92e-21

Globin;


Pssm-ID: 459646 [Multi-domain]  Cd Length: 117  Bit Score: 81.95  E-value: 4.92e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LHB_A         35 VDILVKFFTSTPAAQEFFPKFKGltTADELKKSADVRWHAERIINAVDDAVASMDDTEKMSMKLRNLSGKHAKSFQVDPE 114
Cdd:pfam00042   1 AEILARLFTAYPDTKAYFPRFEK--SADDLKGSPKFKAHGKKVLAALGEAVKHLDDLAALNAALKKLGARHKEKRGVDPA 78

                          90
                  ....*....|....*
3LHB_A        115 YFKVLAAVIADTVAA 129
Cdd:pfam00042  79 NFKLFGEALLVVLAE 93
Hb-alpha-like cd08927
Hemoglobin alpha, zeta, mu, theta, and related Hb subunits; Hb is the oxygen transport protein ...
 11-149 2.69e-19

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.


Pssm-ID: 381263  Cd Length: 140  Bit Score: 78.38  E-value: 2.69e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LHB_A       11 LSAAEKTKIRSAWAPVYSTYETSGVDILVKFFTSTPAAQEFFPKFKglTTADelkkSADVRWHAERIINAVDDAVASMDD 90
Cdd:cd08927   1 LSAADKALIKALWGKIAGHAEAIGAEALARMFLSFPQTKTYFPHFD--LSAG----SAQVKAHGKKVMDALGDAVKHLDD 74

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
3LHB_A       91 tekMSMKLRNLSGKHAKSFQVDPEYFKVLAAVIADTVAA---GD------AGFEKLMSMICILLRSAY 149
Cdd:cd08927  75 ---LPGALSKLSDLHAYKLRVDPVNFKLLSHCILVTLAAhlpEDftpevhAALDKFLAAVSHVLSSKY 139
Hb cd14765
Hemoglobins; Hb is the oxygen transport protein of erythrocytes. It is an allosterically ...
 15-129 2.40e-18

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.


Pssm-ID: 381278  Cd Length: 131  Bit Score: 75.47  E-value: 2.40e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LHB_A       15 EKTKIRSAWAPVysTYETSGVDILVKFFTSTPAAQEFFPKFKGLTTADelkksADVRWHAERIINAVDDAVASMDDtekM 94
Cdd:cd14765   1 EKSTIKALWGKV--NVEEYGAEALARLFVVYPWTKRYFPKFDDSSSGN-----PKVKAHGKKVLGALGDAVKHLDD---L 70

                        90       100       110
                ....*....|....*....|....*....|....*
3LHB_A       95 SMKLRNLSGKHAKSFQVDPEYFKVLAAVIADTVAA 129
Cdd:cd14765  71 KNTFSDLSELHADKLHVDPENFKLLSDCLIVVLAA 105
Mb cd08926
Animal Myoglobins; Myoglobin (Mb) is a monomeric pentacoordinate heme-bound globin protein ...
 14-149 9.97e-17

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.


Pssm-ID: 271277  Cd Length: 148  Bit Score: 71.72  E-value: 9.97e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LHB_A       14 AEKTKIRSAWAPVYSTYETSGVDILVKFFTSTPAAQEFFPKFKGLTTaDELKKSADVRWHAERIINAVDDAVASMDdteK 93
Cdd:cd08926   1 ADWDLVLKVWAKVEADLTGIGQEVLLRLFKEHPETQEHFPKFKGISQ-DDLKSNEDLKKHGVTVLTALGEILKQKG---S 76

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
3LHB_A       94 MSMKLRNLSGKHAKSFQVDPEYFKVLAAVI---------ADTVAAGDAGFEKLMSMICILLRSAY 149
Cdd:cd08926  77 HEAELKPLAQTHATKHKIPPKYFELITEIIvkvlaekhpSEMGAPAQAAFSKAFELICSDIEANY 141
Hb-beta-like cd08925
Hemoglobin beta, gamma, delta, epsilon, and related Hb subunits; Hb is the oxygen transport ...
 15-149 2.90e-16

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.


Pssm-ID: 381262  Cd Length: 139  Bit Score: 70.36  E-value: 2.90e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LHB_A       15 EKTKIRSAWAPVysTYETSGVDILVKFFTSTPAAQEFFPKFKGLTTADELKKSADVRWHAERIINAVDDAVASMDDTEKM 94
Cdd:cd08925   1 EKAAITAVWGKV--DVDEVGAEALARLLIVYPWTQRYFSSFGDLSSAAAIAGNPKVAAHGKKVLGALGEAIKHLDDIKAT 78

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
3LHB_A       95 smkLRNLSGKHAKSFQVDPEYFKVLAAVIADTVAA--GD-------AGFEKLMSMICILLRSAY 149
Cdd:cd08925  79 ---FADLSEKHSEKLHVDPENFKLLGDCLVVVLAAhfGKeftpevqAAWEKFFAVVVDALSKGY 139
GbX cd12137
Globin_X (GbX); Zebrafish globin X (GbX) is expressed at low levels in neurons of the central ...
 11-115 6.71e-11

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.


Pssm-ID: 271287  Cd Length: 145  Bit Score: 56.54  E-value: 6.71e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LHB_A       11 LSAAEKTKIRSAWAPVYSTYETSGVDILVKFFTSTPAAQEFFPKFKGLTTADeLKKSADVRWHAERIINAVDDAVASMDD 90
Cdd:cd12137   1 LTERQKQLIESSWSILQEDIAKVGVIMFVRLFETHPDCKDAFFPFRDVDLED-LRHSKELRAHGLRVLSFVEKSLARLHQ 79

                        90       100
                ....*....|....*....|....*
3LHB_A       91 TEKMSMKLRNLSGKHAkSFQVDPEY 115
Cdd:cd12137  80 PDKLEELLHELGRKHY-RYNAKVKY 103
CeGLB25-like cd14766
Caenorhabditis elegans globin GLB-25, and related globins; The C. elegans genome contains 33 ...
 19-117 1.69e-10

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.


Pssm-ID: 381279  Cd Length: 137  Bit Score: 55.41  E-value: 1.69e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3LHB_A       19 IRSAWAPVYSTYETSGVDILVKFFTSTPAAQEFFPKFKGL-TTADELKKSADVRWHAERIINAVDDAVASMDDTEKMSMK 97
Cdd:cd14766   1 LKKSWKGIARKIDETGKTMFLRMLTENPELKELFPKLKNLeDEEDELRSSEILENHAARVMDTLDEAISNIENVDYVIDL 80

                        90       100
                ....*....|....*....|
3LHB_A       98 LRNLSGKHAKSFQVDPEYFK 117
Cdd:cd14766  81 LHKVGKMHAKKPGFRPEMFW 100
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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