Detail Information for IndEnz0002006266
IED ID IndEnz0002006266
Enzyme Type ID protease006266
Protein Name Hemoglobin subunit beta
Beta-globin
Hemoglobin beta chain

Cleaved into: LVV-hemorphin-7; Spinorphin
Gene Name HBB
Organism Homo sapiens (Human)
Taxonomic Lineage cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human)
Enzyme Sequence MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH
Enzyme Length 147
Uniprot Accession Number P68871
Absorption
Active Site
Activity Regulation
Binding Site BINDING 2; /note="2,3-bisphosphoglycerate; via amino nitrogen"; BINDING 3; /note="2,3-bisphosphoglycerate"; BINDING 83; /note="2,3-bisphosphoglycerate"; BINDING 144; /note="2,3-bisphosphoglycerate"
Calcium Binding
catalytic Activity
DNA Binding
EC Number
Enzyme Function FUNCTION: Involved in oxygen transport from the lung to the various peripheral tissues. {ECO:0000269|PubMed:28066926}.; FUNCTION: LVV-hemorphin-7 potentiates the activity of bradykinin, causing a decrease in blood pressure.; FUNCTION: [Spinorphin]: Functions as an endogenous inhibitor of enkephalin-degrading enzymes such as DPP3, and as a selective antagonist of the P2RX3 receptor which is involved in pain signaling, these properties implicate it as a regulator of pain and inflammation.
Temperature Dependency
PH Dependency
Pathway
nucleotide Binding
Features Binding site (4); Chain (1); Glycosylation (6); Helix (11); Initiator methionine (1); Metal binding (2); Modified residue (11); Natural variant (261); Peptide (2); Sequence conflict (2); Site (22); Turn (1)
Keywords 3D-structure;Acetylation;Congenital dyserythropoietic anemia;Direct protein sequencing;Disease variant;Glycation;Glycoprotein;Heme;Hereditary hemolytic anemia;Hypotensive agent;Iron;Metal-binding;Oxygen transport;Phosphoprotein;Pyruvate;Reference proteome;S-nitrosylation;Transport;Vasoactive
Interact With P69905; Q6B0K9; P09105; P02008
Induction
Subcellular Location
Modified Residue MOD_RES 2; /note="N-acetylvaline"; /evidence="ECO:0000250|UniProtKB:P02086"; MOD_RES 2; /note="N-pyruvate 2-iminyl-valine; in Hb A1b"; MOD_RES 10; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:24275569"; MOD_RES 13; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:24275569"; MOD_RES 45; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:24275569"; MOD_RES 51; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:24275569"; MOD_RES 60; /note="N6-acetyllysine"; /evidence="ECO:0000269|PubMed:4531009"; MOD_RES 83; /note="N6-acetyllysine"; /evidence="ECO:0000269|PubMed:4531009"; MOD_RES 88; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:24275569"; MOD_RES 94; /note="S-nitrosocysteine"; /evidence="ECO:0000269|PubMed:8637569, ECO:0000269|PubMed:9843411"; MOD_RES 145; /note="N6-acetyllysine; alternate"; /evidence="ECO:0000269|PubMed:4531009"
Post Translational Modification PTM: Glucose reacts non-enzymatically with the N-terminus of the beta chain to form a stable ketoamine linkage. This takes place slowly and continuously throughout the 120-day life span of the red blood cell. The rate of glycation is increased in patients with diabetes mellitus.; PTM: S-nitrosylated; a nitric oxide group is first bound to Fe(2+) and then transferred to Cys-94 to allow capture of O(2). {ECO:0000269|PubMed:1520632, ECO:0000269|PubMed:8637569, ECO:0000269|PubMed:9843411}.; PTM: Acetylated on Lys-60, Lys-83 and Lys-145 upon aspirin exposure. {ECO:0000269|PubMed:4531009}.
Signal Peptide
Structure 3D Neutron diffraction (2); NMR spectroscopy (2); Electron microscopy (3); X-ray crystallography (283)
Cross Reference PDB 1A00; 1A01; 1A0U; 1A0Z; 1A3N; 1A3O; 1ABW; 1ABY; 1AJ9; 1B86; 1BAB; 1BBB; 1BIJ; 1BUW; 1BZ0; 1BZ1; 1BZZ; 1C7B; 1C7C; 1C7D; 1CBL; 1CBM; 1CH4; 1CLS; 1CMY; 1COH; 1DKE; 1DXT; 1DXU; 1DXV; 1FN3; 1G9V; 1GBU; 1GBV; 1GLI; 1GZX; 1HAB; 1HAC; 1HBA; 1HBB; 1HBS; 1HCO; 1HDB; 1HGA; 1HGB; 1HGC; 1HHO; 1IRD; 1J3Y; 1J3Z; 1J40; 1J41; 1J7S; 1J7W; 1J7Y; 1JY7; 1K0Y; 1K1K; 1KD2; 1LFL; 1LFQ; 1LFT; 1LFV; 1LFY; 1LFZ; 1LJW; 1M9P; 1MKO; 1NEJ; 1NIH; 1NQP; 1O1I; 1O1J; 1O1K; 1O1L; 1O1M; 1O1N; 1O1O; 1O1P; 1QI8; 1QSH; 1QSI; 1QXD; 1QXE; 1R1X; 1R1Y; 1RPS; 1RQ3; 1RQ4; 1RQA; 1RVW; 1SDK; 1SDL; 1THB; 1UIW; 1VWT; 1XXT; 1XY0; 1XYE; 1XZ2; 1XZ4; 1XZ5; 1XZ7; 1XZU; 1XZV; 1Y09; 1Y0A; 1Y0C; 1Y0D; 1Y0T; 1Y0W; 1Y22; 1Y2Z; 1Y31; 1Y35; 1Y45; 1Y46; 1Y4B; 1Y4F; 1Y4G; 1Y4P; 1Y4Q; 1Y4R; 1Y4V; 1Y5F; 1Y5J; 1Y5K; 1Y7C; 1Y7D; 1Y7G; 1Y7Z; 1Y83; 1Y85; 1Y8W; 1YDZ; 1YE0; 1YE1; 1YE2; 1YEN; 1YEO; 1YEQ; 1YEU; 1YEV; 1YFF; 1YG5; 1YGD; 1YGF; 1YH9; 1YHE; 1YHR; 1YIE; 1YIH; 1YVQ; 1YVT; 1YZI; 2D5Z; 2D60; 2DN1; 2DN2; 2DN3; 2DXM; 2H35; 2HBC; 2HBD; 2HBE; 2HBF; 2HBS; 2HCO; 2HHB; 2HHD; 2HHE; 2M6Z; 2W6V; 2W72; 2YRS; 3B75; 3D17; 3D7O; 3DUT; 3HHB; 3HXN; 3IC0; 3IC2; 3KMF; 3NL7; 3NMM; 3ODQ; 3ONZ; 3OO4; 3OO5; 3P5Q; 3QJB; 3QJC; 3QJD; 3QJE; 3R5I; 3S65; 3S66; 3SZK; 3W4U; 3WCP; 3WHM; 4FC3; 4HHB; 4IJ2; 4L7Y; 4M4A; 4M4B; 4MQC; 4MQG; 4MQH; 4MQI; 4N7N; 4N7O; 4N7P; 4N8T; 4NI0; 4NI1; 4ROL; 4ROM; 4WJG; 4X0L; 4XS0; 5E29; 5E6E; 5E83; 5EE4; 5HU6; 5HY8; 5JDO; 5KDQ; 5KSI; 5KSJ; 5NI1; 5SW7; 5U3I; 5UCU; 5UFJ; 5URC; 5VMM; 5WOG; 5WOH; 5X2R; 5X2S; 5X2T; 5X2U; 6BB5; 6BNR; 6BWP; 6BWU; 6DI4; 6FQF; 6HAL; 6HBW; 6HK2; 6KA9; 6KAE; 6KAH; 6KAI; 6KAO; 6KAP; 6KAQ; 6KAR; 6KAS; 6KAT; 6KAU; 6KAV; 6KYE; 6L5V; 6L5W; 6L5X; 6L5Y; 6LCW; 6LCX; 6NBC; 6NBD; 6NQ5; 6TB2; 6XD9; 6XDT; 6XE7; 7AET; 7AEU; 7AEV; 7CUE; 7JJQ; 7JXZ; 7JY0; 7JY1; 7JY3;
Mapped Pubmed ID 10080899; 10390349; 10512707; 10529219; 10611283; 10698631; 10791557; 10794410; 10856700; 10930827; 10930828; 11043018; 11082038; 11111119; 11132230; 11132233; 11159543; 11186256; 11196644; 11300346; 11316875; 11480785; 11570721; 11582643; 11724557; 11741197; 11778661; 11782463; 11800015; 11804203; 11804364; 11812133; 11822023; 11823440; 11827978; 11833853; 11843288; 11843884; 11857746; 11860449; 11869935; 11877258; 11890201; 11895428; 11909945; 11914488; 11939510; 11939511; 11939513; 11965279; 11971871; 11997516; 11999355; 12034837; 12054662; 12077435; 12082507; 12217699; 12217813; 12242335; 12360531; 12394345; 12419253; 12454461; 1252417; 12555809; 12581187; 12581188; 12629213; 12659864; 12709368; 12709369; 12736816; 12773618; 12799453; 12846902; 12865230; 12920025; 12941700; 12955718; 13342742; 13472068; 1390648; 1395; 14529320; 1453464; 14585970; 14587041; 14627823; 14642006; 14645507; 14649314; 14649315; 14649317; 14649318; 14649320; 14705937; 14722738; 14738432; 14958; 15060158; 15073633; 15084587; 1512262; 15131110; 15147217; 15153712; 15174051; 15198986; 15236579; 15256071; 15307413; 15315795; 15327529; 15341482; 15385559; 15448162; 15476181; 15481884; 15481897; 15482674; 15495251; 1552945; 15538648; 15555579; 15565159; 15591902; 15599663; 15607699; 15609277; 15615768; 15658186; 15692663; 15713129; 15727248; 15727901; 15741796; 15751957; 15767753; 15793780; 15795541; 15795925; 15835899; 15858218; 15858266; 15870261; 15882059; 15885239; 15921164; 15938624; 15948210; 15956966; 15973412; 15979088; 16046400; 16085752; 16103715; 16156863; 16156939; 16169070; 16184579; 1618774; 16189277; 16199858; 16227618; 16254903; 16356170; 16403522; 16418531; 16466947; 16470532; 16480967; 16508016; 16537808; 16637741; 16722361; 16765986; 16778136; 16798637; 16848606; 16855288; 16858401; 16859949; 16877501; 16885058; 16898315; 16943425; 16956833; 16990440; 16992238; 16994616; 17008602; 17056066; 17060917; 17096035; 17102136; 17133428; 17135308; 17140342; 17158930; 17160997; 17196618; 17301974; 17339197; 17394396; 17445142; 17446270; 17486493; 17486497; 17490901; 17508724; 17516066; 17519411; 17564253; 17565724; 17612748; 17637845; 17654071; 17654072; 17654503; 17665502; 17720709; 17724704; 17767159; 17845074; 17881306; 17894837; 17916326; 17918249; 17920577; 17925082; 17961316; 17990881; 18022136; 18026953; 18056715; 18071703; 18080800; 18081706; 18096416; 18235968; 18245381; 18257074; 18266765; 18291005; 18294253; 18308336; 18339318; 18381244; 18391696; 18392554; 18392622; 18414926; 18419131; 18428016; 18443145; 18458302; 18461170; 18473240; 18473247; 18473248; 18473944; 18498386; 18586828; 18603555; 18630930; 18644871; 18654889; 18667698; 18694524; 18728021; 18752444; 18759082; 18772456; 18928603; 18932071; 18951049; 1896430; 19065337; 19066892; 19122960; 19127788; 19149873; 19205970; 19205975; 19205976; 19205978; 19215610; 19230568; 19245215; 19247486; 19254853; 19269866; 19288145; 19290524; 19317913; 19320245; 19324878; 19333781; 19346882; 19359777; 19365817; 19372376; 19373584; 19397368; 19465909; 19474452; 19479992; 19488752; 19503809; 19533614; 19556751; 19609526; 19615732; 19618018; 19657833; 19775947; 19843387; 19903589; 19913121; 19954365; 19958184; 19958185; 19958186; 19958187; 19958196; 19958198; 19958201; 19968714; 20036801; 20068219; 20080971; 20113286; 20113295; 20113296; 20162361; 20181291; 20193381; 20230396; 20230836; 20231425; 20305663; 20336466; 20353347; 20353350; 20353351; 20353353; 20353593; 20395516; 20406103; 20430887; 20524821; 20552021; 20557680; 20598923; 20628086; 20628988; 20642332; 20676097; 20711500; 20739079; 20797626; 20798489; 20830473; 20938172; 20943106; 21034280; 21041929; 21068433; 21075280; 21075281; 21075288; 21077758; 21077760; 21086180; 21123872; 21129264; 21173165; 21193395; 21194254; 21194265; 21219849; 21232998; 21238931; 21250885; 21282471; 21333566; 21378272; 21389146; 21523319; 21636902; 21703224; 21757944; 21797700; 21797703; 21801233; 21816820; 21828133; 21863786; 21881051; 21917915; 21931690; 21947948; 21978377; 22028795; 22036762; 2204156; 22075726; 22117603; 22164220; 22178075; 22183073; 22216176; 22217259; 22260316; 22273838; 22289203; 22323332; 22324317; 22427940; 22524255; 22563936; 22625666; 22654577; 22672614; 22675570; 22705794; 22734501; 22734587; 22738610; 22862814; 22898041; 22922649; 22943051; 22981786; 23085440; 23089702; 23101664; 23215760; 23235792; 23272095; 23281611; 23349856; 23361909; 23398055; 23437895; 23457306; 23470150; 23500448; 23577918; 23586372; 23600595; 23638175; 23650620; 23671278; 23683733; 2370669; 23826747; 2383372; 23889802; 23901897; 23915319; 23925429; 23952145; 24074341; 24074398; 24080366; 24080465; 24086375; 24120603; 24149619; 24182909; 24401016; 24425866; 24471793; 24471820; 24578002; 24599423; 24635037; 24769418; 24795058; 24802353; 24857170; 24878022; 25061917; 2506737; 25123009; 25139985; 25155404; 25155936; 25170120; 25183384; 25188417; 25222042; 25222044; 25238043; 25268796; 25271992; 25287606; 25347256; 25370867; 25405919; 25410714; 25412720; 25469539; 25476778; 25497229; 25523871; 25572182; 25572184; 25572186; 25572187; 25617386; 25681747; 25712976; 25849334; 25856402; 25898735; 25918715; 25961502; 25974708; 25976460; 26042536; 26057669; 26097845; 26182728; 26214904; 26292035; 26372288; 26375765; 26445879; 26524961; 26554738; 26582149; 26671256; 26754300; 26840243; 26866725; 26890443; 26928674; 26949259; 26995402; 26997009; 27026582; 27083048; 27085422; 27105433; 27301940; 27377386; 27378309; 2738915; 27529207; 27739611; 27793844; 27828729; 2799391; 28003571; 28181495; 28199095; 28213526; 28224676; 28337324; 28366026; 28374749; 28385923; 28399542; 28465180; 28475449; 28595636; 28665412; 28772282; 28800727; 28858508; 28883619; 28931607; 29064674; 29109153; 29127281; 29127676; 29157167; 29240028; 29246762; 29626215; 29634905; 29655608; 29710269; 29857171; 29964138; 30183107; 30289405; 30289410; 30309760; 30622282; 30833564; 30844732; 31084366; 31146650; 31167908; 3119859; 31246535; 31275994; 31304856; 3136125; 31509281; 31636731; 31793705; 31840728; 31869403; 31899996; 31903828; 31914830; 31939318; 32001505; 32071219; 32078010; 32079421; 32091272; 32108581; 32172616; 32219817; 32370567; 32433728; 32527859; 32638316; 32664780; 32674615; 32679799; 32755585; 33049600; 33066815; 33198537; 33205981; 33219275; 33356244; 33440169; 33476375; 33556202; 33723266; 33726930; 33734896; 33798832; 33851260; 3427020; 34389729; 34585664; 3938604; 4008491; 4203704; 4327491; 4514311; 4647257; 4975618; 5135507; 5656372; 6094553; 6417382; 6644819; 6683087; 7263686; 7378053; 7541176; 7723849; 7929044; 8114096; 8114097; 8300612; 8415693; 8448109; 8639491; 8639677; 8647854; 8662539; 8855948; 9032082; 9038169; 9151685; 9223274; 9325099; 9441940; 9649306; 9761903; 9876125; 9894000;
Motif
Gene Encoded By
Mass 15,998
Kinetics
Metal Binding METAL 64; /note=Iron (heme distal ligand); METAL 93; /note=Iron (heme proximal ligand)
Rhea ID
Cross Reference Brenda