heme oxygenase in eukaryotes and some bacteria; This subfamily contains heme oxygenase (HO, EC 1.14.14.18) found in eukaryotes as well as some proteobacteria, including cyanobacteria. Heme oxygenase (HO) catalyzes the rate limiting step in the degradation of heme to biliverdin in a multi-step reaction. HO is essential for recycling of iron from heme which is used as a substrate and cofactor for its own degradation to biliverdin, iron, and carbon monoxide. In vertebrates, HO plays a role in heme homeostasis and oxidative stress response, and cellular signaling in mammals that include isoforms HO-1, HO-2 and HO-3. HO-1 is ubiquitously expressed after induction while HO-2 expression is constitutive, mostly limited to certain organs, such as the brain, testes, and the vascular system. HO-3 is non-functional in humans, suggesting that the Hmox3 gene is a pseudogene derived from HO-2 transcripts. In higher plants and cyanobacteria, heme oxygenase is required for the synthesis of light-harvesting pigments, which contain tetrapyrrols derived from biliverdin. Candida albicans expresses a heme oxygenase that is required for the utilization of heme as a nutritional iron source, whereas Saccharomyces cerevisiae responds to iron deprivation by increasing Hmx1p transcription, which is controlled by the major iron-dependent transcription factor, Aft1p, and promotes both the re-utilization of heme iron and the regulation of heme-dependent transcription during periods of iron scarcity. In pathogenic bacteria, HO is part of a pathway for iron acquisition from host heme. In Leptospira interrogans, a pathogenic spirochete that causes leptospirosis, HO is required for iron utilization when hemoglobin is the sole iron source, thus making HO an interesting target for novel antimicrobial agents. HO shares tertiary structure similarity to methane monooxygenase (EC 1.14.13.25), ribonucleotide reductase (EC 1.17.4.1) and thiaminase II (EC 3.5.99.2), but shares little sequence homology.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15222425  76 GFVEEMRFVAMRLHTKDQAREGekeSRSPEEGPvakwePTVEGYLHFLVDSKLVYDTLEGIIDGSNFPTYAG--FKNTGL 153
Cdd:cd19165   1 PLSERLREATRKLHTAAERSIF---AKLLLAGP-----LDREAYARLLVQLYFVYEALEEALDRLADDPVLAaaLYDPEL 72

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15222425 154 ERAESLRKDLEWFKEQGYEIPEPMAP-GKTYSEYLKDLAENDPQAFICHFYNIYFAHSAGGQMIGTKVSKK--ILDNKEL 230
Cdd:cd19165  73 ERSEALEADLAFLLGPDWREPIPPSPaTAAYVARIRELAEEKPHLLLAHAYVRYLGDLSGGQIIRRKLAKAygLFGGEGL 152

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 15222425 231 EFYKWDG--QLSQLLQNVRQKLNKVAewWTREEKSHCLEETEKSFKFSGEILRLI 283
Cdd:cd19165 153 SFYDFDGigDGKDLKDEYRARLDALE--LTEEEKDAIVEEAKLAFELNIALFEEL 205

heme oxygenase in eukaryotes and some bacteria; This subfamily contains heme oxygenase (HO, EC 1.14.14.18) found in eukaryotes as well as some proteobacteria, including cyanobacteria. Heme oxygenase (HO) catalyzes the rate limiting step in the degradation of heme to biliverdin in a multi-step reaction. HO is essential for recycling of iron from heme which is used as a substrate and cofactor for its own degradation to biliverdin, iron, and carbon monoxide. In vertebrates, HO plays a role in heme homeostasis and oxidative stress response, and cellular signaling in mammals that include isoforms HO-1, HO-2 and HO-3. HO-1 is ubiquitously expressed after induction while HO-2 expression is constitutive, mostly limited to certain organs, such as the brain, testes, and the vascular system. HO-3 is non-functional in humans, suggesting that the Hmox3 gene is a pseudogene derived from HO-2 transcripts. In higher plants and cyanobacteria, heme oxygenase is required for the synthesis of light-harvesting pigments, which contain tetrapyrrols derived from biliverdin. Candida albicans expresses a heme oxygenase that is required for the utilization of heme as a nutritional iron source, whereas Saccharomyces cerevisiae responds to iron deprivation by increasing Hmx1p transcription, which is controlled by the major iron-dependent transcription factor, Aft1p, and promotes both the re-utilization of heme iron and the regulation of heme-dependent transcription during periods of iron scarcity. In pathogenic bacteria, HO is part of a pathway for iron acquisition from host heme. In Leptospira interrogans, a pathogenic spirochete that causes leptospirosis, HO is required for iron utilization when hemoglobin is the sole iron source, thus making HO an interesting target for novel antimicrobial agents. HO shares tertiary structure similarity to methane monooxygenase (EC 1.14.13.25), ribonucleotide reductase (EC 1.17.4.1) and thiaminase II (EC 3.5.99.2), but shares little sequence homology.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15222425  76 GFVEEMRFVAMRLHTKDQAREGekeSRSPEEGPvakwePTVEGYLHFLVDSKLVYDTLEGIIDGSNFPTYAG--FKNTGL 153
Cdd:cd19165   1 PLSERLREATRKLHTAAERSIF---AKLLLAGP-----LDREAYARLLVQLYFVYEALEEALDRLADDPVLAaaLYDPEL 72

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15222425 154 ERAESLRKDLEWFKEQGYEIPEPMAP-GKTYSEYLKDLAENDPQAFICHFYNIYFAHSAGGQMIGTKVSKK--ILDNKEL 230
Cdd:cd19165  73 ERSEALEADLAFLLGPDWREPIPPSPaTAAYVARIRELAEEKPHLLLAHAYVRYLGDLSGGQIIRRKLAKAygLFGGEGL 152

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 15222425 231 EFYKWDG--QLSQLLQNVRQKLNKVAewWTREEKSHCLEETEKSFKFSGEILRLI 283
Cdd:cd19165 153 SFYDFDGigDGKDLKDEYRARLDALE--LTEEEKDAIVEEAKLAFELNIALFEEL 205

Heme oxygenase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15222425   115 TVEGYLHFLVDSKLVYDTLEGIID-GSNFPTYAGFKNTGLERAESLRKDLE-WFKEQGYEIPEPMAPGKTYSEYLKDLAE 192
Cdd:pfam01126  33 DKDAYAKLLANLYFVYSALEEELErNRDSPVAAPIYFPELNRKAALERDLAyLYGADWRADIQDSPATQEYVPRIREIGN 112

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15222425   193 NDPQAFICHFYNIYFAHSAGGQMIGTKVSKK-ILDNKE-LEFYKWDGQLS--QLLQNVRQKLNKVAEwwTREEKSHCLEE 268
Cdd:pfam01126 113 ESPELLVAHAYTRYLGDLSGGQLLKKIAQRAlGLPPGEgTAFYEFEGISDrkVFKQEYREALNALEL--DDEARARAVEE 190

                         170
                  ....*....|...
gi 15222425   269 TEKSFKFSGEILR 281
Cdd:pfam01126 191 ANDAFALNIQVFR 203

heme oxygenase in eukaryotes and some bacteria; This subfamily contains heme oxygenase (HO, EC 1.14.14.18) found in eukaryotes as well as some proteobacteria, including cyanobacteria. Heme oxygenase (HO) catalyzes the rate limiting step in the degradation of heme to biliverdin in a multi-step reaction. HO is essential for recycling of iron from heme which is used as a substrate and cofactor for its own degradation to biliverdin, iron, and carbon monoxide. In vertebrates, HO plays a role in heme homeostasis and oxidative stress response, and cellular signaling in mammals that include isoforms HO-1, HO-2 and HO-3. HO-1 is ubiquitously expressed after induction while HO-2 expression is constitutive, mostly limited to certain organs, such as the brain, testes, and the vascular system. HO-3 is non-functional in humans, suggesting that the Hmox3 gene is a pseudogene derived from HO-2 transcripts. In higher plants and cyanobacteria, heme oxygenase is required for the synthesis of light-harvesting pigments, which contain tetrapyrrols derived from biliverdin. Candida albicans expresses a heme oxygenase that is required for the utilization of heme as a nutritional iron source, whereas Saccharomyces cerevisiae responds to iron deprivation by increasing Hmx1p transcription, which is controlled by the major iron-dependent transcription factor, Aft1p, and promotes both the re-utilization of heme iron and the regulation of heme-dependent transcription during periods of iron scarcity. In pathogenic bacteria, HO is part of a pathway for iron acquisition from host heme. In Leptospira interrogans, a pathogenic spirochete that causes leptospirosis, HO is required for iron utilization when hemoglobin is the sole iron source, thus making HO an interesting target for novel antimicrobial agents. HO shares tertiary structure similarity to methane monooxygenase (EC 1.14.13.25), ribonucleotide reductase (EC 1.17.4.1) and thiaminase II (EC 3.5.99.2), but shares little sequence homology.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15222425  76 GFVEEMRFVAMRLHTKDQAREGekeSRSPEEGPvakwePTVEGYLHFLVDSKLVYDTLEGIIDGSNFPTYAG--FKNTGL 153
Cdd:cd19165   1 PLSERLREATRKLHTAAERSIF---AKLLLAGP-----LDREAYARLLVQLYFVYEALEEALDRLADDPVLAaaLYDPEL 72

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15222425 154 ERAESLRKDLEWFKEQGYEIPEPMAP-GKTYSEYLKDLAENDPQAFICHFYNIYFAHSAGGQMIGTKVSKK--ILDNKEL 230
Cdd:cd19165  73 ERSEALEADLAFLLGPDWREPIPPSPaTAAYVARIRELAEEKPHLLLAHAYVRYLGDLSGGQIIRRKLAKAygLFGGEGL 152

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 15222425 231 EFYKWDG--QLSQLLQNVRQKLNKVAewWTREEKSHCLEETEKSFKFSGEILRLI 283
Cdd:cd19165 153 SFYDFDGigDGKDLKDEYRARLDALE--LTEEEKDAIVEEAKLAFELNIALFEEL 205

Heme oxygenase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15222425   115 TVEGYLHFLVDSKLVYDTLEGIID-GSNFPTYAGFKNTGLERAESLRKDLE-WFKEQGYEIPEPMAPGKTYSEYLKDLAE 192
Cdd:pfam01126  33 DKDAYAKLLANLYFVYSALEEELErNRDSPVAAPIYFPELNRKAALERDLAyLYGADWRADIQDSPATQEYVPRIREIGN 112

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15222425   193 NDPQAFICHFYNIYFAHSAGGQMIGTKVSKK-ILDNKE-LEFYKWDGQLS--QLLQNVRQKLNKVAEwwTREEKSHCLEE 268
Cdd:pfam01126 113 ESPELLVAHAYTRYLGDLSGGQLLKKIAQRAlGLPPGEgTAFYEFEGISDrkVFKQEYREALNALEL--DDEARARAVEE 190

                         170
                  ....*....|...
gi 15222425   269 TEKSFKFSGEILR 281
Cdd:pfam01126 191 ANDAFALNIQVFR 203

heme oxygenase; Heme oxygenase (HO, EC 1.14.14.18) catalyzes the rate limiting step in the degradation of heme to biliverdin in a multi-step reaction. HO is essential for recycling iron from heme which is used as a substrate and cofactor for its own degradation to biliverdin, iron, and carbon monoxide. This family serves a variety of specific needs in different branches of life: in vertebrates, HO plays a role in heme homeostasis and oxidative stress response, and cellular signaling in mammals that include isoforms HO-1 and HO-2; in photosynthetic organisms including cyanobacteria, algae, and higher plants, biliverdin is used for photosynthetic pigment formation or light-sensing; and, in pathogenic bacteria, HO is part of a pathway for iron acquisition from host heme and heme products. HO shares tertiary structure similarity to methane monooxygenase (EC 1.14.13.25), ribonucleotide reductase (EC 1.17.4.1) and thiaminase II (EC 3.5.99.2), but shares little sequence homology.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15222425 117 EGYLHFLVDSKLVYDTLEGIIDgSNFPTYAGFKNTGLE---RAESLRKDLEWFKEQGYEIPEPMAPG-KTYSEYLKDLAE 192
Cdd:cd00232  32 DNYAKFLACQYYFFVALEAAYD-EALLKGDFDKDPLLEglaRADAFKQDLADLGGPTWQADLGTKSQaKDYEAHLAELGR 110

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15222425 193 NDPQAFICHFYNIYFAHSAGGQMIgTKVSKKILDNKELE----FYKWDGQLSQLLQNVRQKLNkvaEW-WTREEKSHCLE 267
Cdd:cd00232 111 SSPALLLAHLYTQELSMLSGGQFL-KKWAQKLFQLPDDVgaahFAYPGESRNKLWSAFVKQLD---ELeLTPELEDQAIS 186

                       170
                ....*....|....
gi 15222425 268 ETEKSFKFSGEILR 281
Cdd:cd00232 187 EALAAFGHNNALLE 200