2.5 s465 PROTEIN pr15 s35 PROTEIN pr15 s35 ION Fe_super_3+_endsuper_ s250 PROTEIN pr15 s250 ION Fe_super_3+_endsuper_ s51 PROTEIN pr2 s51 ION Fe_super_3+_endsuper_ s69 PROTEIN pr16 s249 PROTEIN pr15 s249 ION Fe_super_3+_endsuper_ s385 ION Fe_super_2+_endsuper_ s150 PROTEIN pr2 s166 PROTEIN pr2 s69 ION Fe_super_2+_endsuper_ s295 ION Fe_super_3+_endsuper_ s166 SIMPLE_MOLECULE PP_IX s166 ION Fe_super_2+_endsuper_ s221 SIMPLE_MOLECULE S s147 ION Fe_super_2+_endsuper_ s147 SIMPLE_MOLECULE S s219 SIMPLE_MOLECULE PP_IX s219 ION Fe_super_2+_endsuper_ s221 ION Fe_super_2+_endsuper_ s150 ION Fe_super_2+_endsuper_ s150 SIMPLE_MOLECULE S s225 SIMPLE_MOLECULE PP_IX s225 ION Fe_super_2+_endsuper_ s228 SIMPLE_MOLECULE S s234 ION Fe_super_2+_endsuper_ s234 SIMPLE_MOLECULE PP_IX s249 PROTEIN pr13 s250 PROTEIN pr13 s465 PROTEIN pr1 s262 PROTEIN pr56 s262 PROTEIN pr13 s295 PROTEIN pr58 s450 ION Fe_super_3+_endsuper_ s295 PROTEIN pr25 s147 PROTEIN pr2 s450 PROTEIN pr25 s208 PROTEIN pr25 s208 ION Fe_super_3+_endsuper_ s273 PROTEIN pr58 s273 PROTEIN pr25 s273 ION Fe_super_3+_endsuper_ s431 ION Fe_super_3+_endsuper_ s432 SIMPLE_MOLECULE siderophore s444 SIMPLE_MOLECULE siderophore s444 ION Fe_super_3+_endsuper_ s444 PROTEIN pr63 s441 PROTEIN pr63 s82 PROTEIN pr12 s83 PROTEIN pr12 s241 PROTEIN pr12 s385 PROTEIN pr30 s228 ION Fe_super_2+_endsuper_ s443 PROTEIN pr63 s431 PROTEIN pr63 s431 SIMPLE_MOLECULE siderophore s443 PROTEIN pr62 s444 PROTEIN pr62 s441 PROTEIN pr62 s427 PROTEIN pr63 s427 PROTEIN pr62 s427 SIMPLE_MOLECULE siderophore s432 PROTEIN pr63 s432 ION Fe_super_3+_endsuper_ s439 PROTEIN pr62 s439 ION Fe_super_3+_endsuper_ s439 PROTEIN pr63 s439 SIMPLE_MOLECULE siderophore s498 ION Fe_super_2+_endsuper_ s450 PROTEIN pr58 s440 PROTEIN pr62 s440 ION Fe_super_3+_endsuper_ s440 PROTEIN pr63 s440 SIMPLE_MOLECULE siderophore s476 PROTEIN pr62 s476 PROTEIN pr63 s476 SIMPLE_MOLECULE siderophore s463 ION Fe_super_2+_endsuper_ s466 PROTEIN pr62 s466 ION Fe_super_3+_endsuper_ s466 PROTEIN pr63 s466 SIMPLE_MOLECULE siderophore s463 PROTEIN pr62 s463 PROTEIN pr63 s463 SIMPLE_MOLECULE siderophore s82 SIMPLE_MOLECULE FeOOH s83 SIMPLE_MOLECULE FeOOH s241 SIMPLE_MOLECULE FeOOH s506 ION Fe_super_2+_endsuper_ s498 PROTEIN pr2 s506 PROTEIN pr68 s521 PROTEIN pr72 s521 ION Fe_super_2+_endsuper_ s535 PROTEIN pr77 s535 ION Fe_super_2+_endsuper_ SQUARE SQUARE SQUARE SQUARE inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive cell Endosome compartment represents the early, recycling, and late endosome. The pH ranges from 6.5 in the early endosome to 5 in the late endosome. Iron does not fall of LfR or 24p3R in the endosome as a pH lower than 5 is necessary for this process. endosome mitochondrion lysosome inside PROTEIN pr15 inside DEGRADED sa109_degraded inside PROTEIN pr17 inside COMPLEX Tf-Fe inside ION Fe_super_3+_endsuper_ inside ION Fe_super_2+_endsuper_ inside COMPLEX proteins-Fe_super_3+_endsuper_ inside PROTEIN pr2 inside SIMPLE_MOLECULE O_sub_2_endsub_ inside COMPLEX cytoplasmic_br_aconitase inside PROTEIN pr16 inside COMPLEX LOW_Iron_br_Ferritin inside COMPLEX HIGH_Iron_br_Ferritin inside ION Fe_super_3+_endsuper_ inside ION Fe_super_3+_endsuper_ inside ION Fe_super_2+_endsuper_ inside PROTEIN pr23 transmembrane PROTEIN pr29 inside PROTEIN pr31 inside ION Fe_super_2+_endsuper_ inside SIMPLE_MOLECULE O_sub_2_endsub_ inside DEGRADED sa109_degraded inside COMPLEX proteins-Fe-S inside COMPLEX proteins-Fe-S inside PROTEIN pr2 inside COMPLEX heme-proteins 5-aminolevulinate synthase inside PROTEIN pr38 name: protoporphyrin IX inside SIMPLE_MOLECULE PP_IX inside SIMPLE_MOLECULE glycine inside SIMPLE_MOLECULE succinyl_br_CoA name: 5-aminolevulinic acid inside SIMPLE_MOLECULE ALA inside PROTEIN pr40 name: delta-aminolevulinic acid inside SIMPLE_MOLECULE ALA name: coproporphyrinogen III inside SIMPLE_MOLECULE COPRO_III name: protoporphyrinogen IX inside SIMPLE_MOLECULE PPG_IX name: prophobilinogen inside SIMPLE_MOLECULE PBG name: uroporphyrinogen III inside SIMPLE_MOLECULE URO_III name: hydroxymethylbilane inside SIMPLE_MOLECULE HMB name: hydroxymethylbilane synthase inside PROTEIN pr44 name: uroporphyrinogen III synthase inside PROTEIN pr45 uroporphyrinogen decarboxylase inside PROTEIN pr46 name: protoporphyriogen oxidase inside PROTEIN pr47 name: coproporphyrinogen oxidase inside PROTEIN pr48 name: delta-aminolevulinate dehydratase inside PROTEIN pr50 inside COMPLEX Lf-Fe inside SIMPLE_MOLECULE O_sub_2_endsub_ inside SIMPLE_MOLECULE S inside COMPLEX heme inside COMPLEX Fe-S inside COMPLEX heme inside COMPLEX Fe-S inside GENE gn3 transmembrane PROTEIN pr52 inside COMPLEX heme name: coproporphyrinogen III inside SIMPLE_MOLECULE COPRO_III outerSurface PROTEIN pr53 inside COMPLEX Ferritin_Iron inside ION Fe_super_2+_endsuper_ outerSurface PROTEIN pr13 transmembrane COMPLEX TfR1-Tf-Fe inside COMPLEX TfR1-Tf-Fe innerSurface PROTEIN pr56 transmembrane COMPLEX HFE-TfR1 name: coproporphyrinogen III inside SIMPLE_MOLECULE COPRO_III found in intestinal epithelial cells transmembrane PROTEIN pr57 transmembrane COMPLEX LfR-Lf-Fe transmembrane PROTEIN pr58 inside PROTEIN pr25 inside COMPLEX LfR-Lf-Fe inside SIMPLE_MOLECULE siderophore transmembrane PROTEIN pr64 transmembrane PROTEIN pr14 inside PROTEIN pr27 inside RNA rn6 transmembrane PROTEIN pr19 inside PROTEIN pr63 inside PROTEIN pr20 inside RNA rn4 inside PROTEIN pr41 inside PROTEIN pr42 inside RNA rn5 inside PROTEIN pr12 inside RNA rn2 inside GENE gn2 inside COMPLEX Fxn-Fe inside PROTEIN pr30 inside PROTEIN pr35 inside PROTEIN pr22 inside SIMPLE_MOLECULE siderophore transmembrane PROTEIN pr62 inside COMPLEX NGAL+R+sid inside COMPLEX exported_br_Fe-NGAL inside COMPLEX Fe-NGAL inside COMPLEX imported_br_Fe-NGAL+R inside COMPLEX Fe-NGAL+R inside COMPLEX NGAL+R transmembrane COMPLEX NGAL+R transmembrane COMPLEX Fe-NGAL+R inside ION Fe_super_3+_endsuper_ inside ION Fe_super_2+_endsuper_ inside SIMPLE_MOLECULE cysteine inside COMPLEX LfR-Lf-Fe transmembrane PROTEIN pr65 inside RNA rn9 transmembrane PROTEIN pr66 inside COMPLEX Fe_super_+2_endsuper_-NGAL+R_br_pH<5 inside COMPLEX TfR1-Tf_br_pH=5.5 inside COMPLEX imported_br_Fe-NGAL+R inside COMPLEX NGAL+R+sid inside ION Fe_super_3+_endsuper_ inside COMPLEX ROS_br__br_ inside COMPLEX ROS_br_ inside GENE gn5 inside COMPLEX proteins_br_Fe_super_2+_endsuper_ inside GENE gn7 inside PROTEIN pr68 inside COMPLEX cytoplasmic_br_aconitase-P inside GENE gn8 inside PROTEIN pr73 inside PROTEIN pr74 inside PROTEIN pr72 inside COMPLEX active_PHD inside SIMPLE_MOLECULE 2-oxoglutarate inside SIMPLE_MOLECULE succinate inside SIMPLE_MOLECULE CO_sub_2_endsub_ inside PROTEIN pr75 inside RNA rn10 inside PROTEIN pr76 inside PROTEIN pr77 inside COMPLEX active_br_FIH1 inside PROTEIN pr79 PMID: 10522551 TRANSLATIONAL_ACTIVATION sa27 sa28 sa26 sa54 sa279 PMID: 10522551 TRANSLATIONAL_ACTIVATION sa29 sa30 sa26 sa54 sa279 PMID: 16054062 PMID: 10747949 TRANSPORT 0.20004235299985007,-0.019334887624969155 0.8081603252911183,-0.0011075323568718876 sa34 sa39 sa36 PMID: 14729944 STATE_TRANSITION sa26 sa25 sa34 PMID: 14769051 STATE_TRANSITION 0.9703568618867626,-0.11504015960339764 sa28 csa7 csa8 STATE_TRANSITION 0.7888409060991887,-0.040941740790246595 0.9375033218488064,-0.013674932972222997 sa34 sa48 csa12 STATE_TRANSITION 0.4208316462108357,0.29953015661255833 sa38 sa48 csa10 PMID: 10401608 STATE_TRANSITION 0.09955635724722167,0.010133941565733107 0.6057698176022394,-0.001552615191096507 sa34 csa9 sa38 csa9 PMID: 8668195 PMID: 10522551 PMID: 1946430 PMID: 1502165 PMID: 1447194 PMID: 8269957 STATE_TRANSITION -0.07213011507776601,0.025791707495955052 0.0016780981444772802,-0.23586243164413023 0.8388179701232032,0.06180254930592799 csa13 sa34 sa54 csa9 PMID: 10522551 PMID: 1946430 PMID: 1502165 PMID: 1447194 PMID: 8269957 STATE_TRANSITION 0.2141844296621449,-0.09144710129199796 0.9441779160205859,0.02711090102084812 sa34 sa54 csa13 PMID: 12627982 PMID: 10441528 PMID: 15771525 PMID: 17881115 STATE_TRANSITION 0.11875533372986091,-0.038117096382115356 0.4397359642090565,-0.14430034394476232 1.0182355375106673,-0.10525097623419288 0.9968592412526897,-0.044199487961920525 sa34 sa30 sa52 csa14 csa9 PMID: 12627982 PMID: 10441528 PMID: 15771525 PMID: 17881115 STATE_TRANSITION 0.0965980429753841,-0.07438904590738371 0.5348361164854685,-0.3091978452507673 0.82986751817488,-0.3175286926428056 sa34 csa14 sa52 csa15 csa9 PMID: 12627982 PMID: 15771525 PMID: 17881115 STATE_TRANSITION 1.0366986022814755,0.20132549675968558 1.082710010053541,0.060239023902135536 sa34 csa9 csa15 csa15 PMID: 12627982 PMID: 10441528 PMID: 15771525 PMID: 17881115 STATE_TRANSITION 0.1614679823106271,-0.08395200045855233 0.6751435284361775,-0.24687368121164077 0.8887638824811548,-0.22286884262090467 sa34 csa15 sa52 csa15 csa9 PMID: 5925868 PMID: 6027241 PMID: 9988272 STATE_TRANSITION sa39 sa76 sa61 sa63 sa62 PMID: 16793765 STATE_TRANSITION 0.7900324359925048,0.3199137172100156 sa61 sa24 csa7 TRANSPORT csa8 csa16 PMID: 1988034 PMID: 16564538 PMID: 16271884 STATE_TRANSITION 0.03340428770560955,0.20368318062015867 csa16 sa69 csa6 enzyme is tissue specific--could be Steap2 or Steap4, two homologs of Steap3 PMID: 16227996 STATE_TRANSITION sa69 sa70 PMID: 17109629 PMID: 16475818 TRANSPORT 0.21272126467050545,-0.09451111452685979 sa70 sa34 sa64 PMID: 10913165 TRANSCRIPTIONAL_ACTIVATION sa72 sa29 csa9 PMID: 17632513 TRANSPORT sa81 sa36 sa71 TRANSPORT 0.0607338919387459,0.2203216796686922 csa32 csa30 sa83 mitoferrin exists in human erythroids, not sure about other human tissue/cells PMID: 16511496 PMID: 16843431 TRANSPORT 0.33372288348575063,0.030169225653738696 0.7297246585544928,0.04896165380985629 sa34 sa89 PMID: 12785837 PMID: 12221295 PMID: 17476391 STATE_TRANSITION 0.5027570105141503,0.5309176820680621 0.9071273725438065,0.14402422794599487 1.0323803423967064,0.02948893608061584 sa89 sa84 csa18 PMID: 12785837 PMID: 12221295 PMID: 16517407 PMID: 17476391 STATE_TRANSITION 0.25848201319564623,-0.013562672001150133 0.6730578682709112,-0.12759831917434106 csa18 sa154 sa84 csa32 sa88 PMID: 10942769 PMID: 16475818 TRANSPORT 0.21139739173909838,0.0031183639385100603 0.7837041793158102,0.025735498240480048 sa39 sa34 sa98 PMID: 9806901 PMID: 16611735 STATE_TRANSITION 0.14949649979966395,0.6381993084159641 csa21 sa75 sa258 PMID: 9806901 PMID: 16611735 TRANSPORT 0.19255352350040877,0.4018382123462955 csa15 csa21 PMID: 9806901 PMID: 16611735 TRANSPORT 0.08432968062468804,0.28806663970599045 csa14 csa21 STATE_TRANSITION 0.930208971057089,0.35588364479870127 1.024020078561488,0.08774710682913778 csa30 sa48 csa22 PMID: 17476391 PMID: 15123683 MetaCyc pathway heme biosynthesis II http://metacyc.org STATE_TRANSITION 0.29116165884957335,-0.032281915417279095 0.6289115304799986,-0.007513608057519328 csa18 sa123 sa84 csa31 sa108 PMID: 17194590 (a review) The protein which transports heme into cytosol is not determined. Three proteins are possible: ABCG2 ABC-me FLVCR TRANSPORT csa31 csa29 STATE_TRANSITION 0.8870194691435564,0.1414239910091588 sa48 csa29 csa25 PMID: 7354050 PMID: 15482256 PMID: 15496594 TRANSPORT sa120 sa118 csa29 TRANSLATIONAL_ACTIVATION sa121 sa120 csa29 Metacyc pathway: tetrapyrrole biosynthesis II http://metacyc.org STATE_TRANSITION sa125 sa124 sa126 sa118 TRANSPORT sa126 sa135 PMID: 17368550 TRANSPORT sa136 sa137 MetaCyc Pathway heme biosynthesis II http://metacyc.org STATE_TRANSITION sa137 sa153 sa138 sa147 MetaCyc pathway heme biosynthesis II http://metacyc.org STATE_TRANSITION sa138 sa153 sa123 sa146 MetaCyc pathway tetrapyrrole biosynthesis II http://metacyc.org STATE_TRANSITION sa135 sa139 sa149 MetaCyc pathway tetrapyrrole biosynthesis II http://metacyc.org STATE_TRANSITION sa139 sa141 sa143 MetaCyc pathway tetrapyrrole biosynthesis II http://metacyc.org STATE_TRANSITION sa141 sa140 sa144 MetaCyc pathway: heme biosynthesis II http://metacyc.org STATE_TRANSITION sa140 sa136 sa145 PMID: 4390967 This reaction has additional reactants and products. NADPH is also a reactant. CO, H2O, NADP+, and Biliverdin are products. In a second reaction, Biliverdin is converted to Bilirubin (an anti-oxidant). This second reaction has NADPH as a product, NADP+ as a reactant, and is catalyzed by biliverdin reductase. STATE_TRANSITION -0.009221490908672969,0.024119012445942722 0.15170317630205754,0.13641801496837092 0.5404801518811162,0.06241517960176335 0.6594443782013832,0.04189437805874219 csa29 sa52 sa34 sa122 sa127 PMID: 9652407 PMID: 9427294 PMID: 10828980 PMID: 15222467 STATE_TRANSITION 0.5687553746592879,-0.2975189846063042 sa61 sa80 csa28 PMID: 1988141 PMID: 2388632 PMID: 3345742 PMID: 17064313 TRANSCRIPTIONAL_ACTIVATION sa171 sa122 csa9 csa29 sa127 sa286 sa307 PMID: 16402910 PMID: 15044468 PMID: 17368550 PMID: 15369674 TRANSPORT csa29 csa33 sa172 sa176 PMID: 16402910 PMID: 15044468 PMID: 17368550 TRANSPORT 0.3090658325691642,-9.97948291604267E-4 sa136 sa175 sa172 PMID: 14568251 PMID: 10882071 TRANSLATIONAL_ACTIVATION sa177 sa81 sa54 sa26 sa279 PMID: 14769051 STATE_TRANSITION 0.1775711031231246,-0.22658345358880227 0.34226607058380676,-0.4062617196636147 csa6 sa24 sa28 PMID: 11800564 PMID: 10638746 PMID: 10085150 STATE_TRANSITION 0.9931806438899642,0.23067887892578298 sa28 sa187 csa37 PMID: 17156779 PMID: 16143108 PMID: 16143096 TRANSPORT csa33 csa29 sa190 PMID: 11747454 PMID: 15222483 STATE_TRANSITION sa194 csa28 csa38 TRANSLATIONAL_ACTIVATION sa202 sa98 sa26 sa54 sa279 PMID: 16261254 TRANSPORT csa38 csa41 PMID: 16261254 TRANSPORT 0.009589799948693134,0.07784077494952035 0.686814607783857,0.09116032782754113 csa41 csa44 PMID: 16261254 PMID: 15222467 PMID: 11023790 STATE_TRANSITION 0.40449204345081435,-0.0023132914814176786 csa44 sa257 sa75 STATE_TRANSITION 0.7191725604770696,0.06306424777445474 sa61 sa218 sa219 csa46 PMID: 16377569 STATE_TRANSITION sa220 sa219 csa45 PMID: 15282194 STATE_TRANSITION sa220 csa46 csa48 PMID: 16377569 TRANSPORT csa45 csa49 PMID: 15282194 TRANSPORT csa48 csa53 PMID: 16377569 STATE_TRANSITION 0.17004848267193307,-0.20949302687496285 csa49 sa251 csa55 PMID: 16377569 STATE_TRANSITION 0.010834709124992403,-0.045273339489414144 0.2892539011855113,-0.40058016434880717 0.6445607260449019,-0.12216097228829159 0.7228661238119221,-0.22209101677999477 0.9264176250571171,-0.05989945061606594 sa38 csa55 csa50 STATE_TRANSITION 0.38113062333433656,-0.027534841577089075 csa50 csa47 sa220 PMID: 18259769 STATE_TRANSITION sa257 sa258 sa259 PMID: 9806901 PMID: 16611735 PMID: 18259769 PMID: 16261254 TRANSPORT 0.04924025859545078,-0.08200118826389546 0.41371602814708175,-0.4843653703959513 0.9083727804394057,-0.013607980560609523 sa258 sa34 STATE_TRANSITION csa53 csa56 STATE_TRANSITION 0.04886349071807916,-0.005330425911151737 0.07339520719655424,-0.26919129345539483 0.8220883197845457,-0.31279168923849654 csa56 csa58 sa70 TRANSPORT csa53 csa57 STATE_TRANSITION 0.5842013160673614,0.23138669524380528 csa57 sa258 csa58 STATE_TRANSITION csa58 sa75 STATE_TRANSITION 0.9173152950408747,-0.12782035942462383 1.100748773226917,-0.04032055495099823 sa61 sa39 sa244 STATE_TRANSITION csa32 sa107 csa23 STATE_TRANSITION 0.5401268848690135,0.054142617227263656 sa89 csa60 sa277 csa60 TRANSCRIPTIONAL_ACTIVATION sa278 sa202 sa65 STATE_TRANSITION sa54 sa279 STATE_TRANSITION 0.22428613662166486,-0.05259657813511809 0.7559989433668046,0.22106608742124023 0.9180897559614336,0.0656082114552603 sa34 sa279 csa61 STATE_TRANSITION -0.07041060387628417,-0.012960924336854696 0.21737710480281014,-0.4415694555871672 0.871108416445505,-0.010635576678261982 csa61 sa34 sa279 csa9 TRANSCRIPTIONAL_ACTIVATION sa288 sa27 sa286 sa307 TRANSLATIONAL_ACTIVATION sa289 sa287 sa26 sa54 sa279 TRANSCRIPTIONAL_ACTIVATION 0.6233390297492463,-7.105427357601002E-15 sa290 sa84 sa287 STATE_TRANSITION 0.1241117020944138,0.7249979687119126 1.3205091345462723,0.608120777264574 1.3136340056376028,0.537744457708583 sa286 sa52 sa298 sa294 sa300 sa299 csa62 STATE_TRANSITION 0.8054632952777205,-0.10901972976082863 sa34 sa293 csa62 STATE_TRANSITION 0.4250646666045279,-0.4778419572265542 0.8315212596674453,-0.14890924367402292 0.9166115325626714,-0.07370255494976719 sa52 sa287 sa298 sa301 sa300 sa299 csa62 STATE_TRANSITION sa294 sa302 STATE_TRANSITION sa301 sa302 STATE_TRANSITION sa34 sa303 csa63 STATE_TRANSITION -0.12838723202502944,0.30796289043280867 0.3551432875330294,0.5095428435188372 0.49141239373666323,0.37716313982129757 0.5240367019578089,0.36373692237024846 sa286 sa298 sa52 sa307 sa299 sa300 csa63