Proton-coupled folate transporter (HsPCFT) (hPCFT) (Heme carrier protein 1) (PCFT/HCP1) (Solute carrier family 46 member 1)
1_MEGSA 6_ SPPEK 11_ PRARP 16_ AAAVL 21_ CRGPV 26_ EPLVF 31_ LANFA 36_ LVLQG 41_ PLTTQ 46_ YLWHR 51_ FSADL 56_ GYNGT 61_ RQRGG 66_ CSNRS 71_ ADPTM 76_ QEVET 81_ LTSHW 86_ TLYMN 91_ VGGFL 96_ VGLFS 101_ STLLG 106_ AWSDS 111_ VGRRP 116_ LLVLA 121_ SLGLL 126_ LQALV 131_ SVFVV 136_ QLQLH 141_ VGYFV 146_ LGRIL 151_ CALLG 156_ DFGGL 161_ LAASF 166_ ASVAD 171_ VSSSR 176_ SRTFR 181_ MALLE 186_ ASIGV 191_ AGMLA 196_ SLLGG 201_ HWLRA 206_ QGYAN 211_ PFWLA 216_ LALLI 221_ AMTLY 226_ AAFCF 231_ GETLK 236_ EPKST 241_ RLFTF 246_ RHHRS 251_ IVQLY 256_ VAPAP 261_ EKSRK 266_ HLALY 271_ SLAIF 276_ VVITV 281_ HFGAQ 286_ DILTL 291_ YELST 296_ PLCWD 301_ SKLIG 306_ YGSAA 311_ QHLPY 316_ LTSLL 321_ ALKLL 326_ QYCLA 331_ DAWVA 336_ EIGLA 341_ FNILG 346_ MVVFA 351_ FATIT 356_ PLMFT 361_ GYGLL 366_ FLSLV 371_ ITPVI 376_ RAKLS 381_ KLVRE 386_ TEQGA 391_ LFSAV 396_ ACVNS 401_ LAMLT 406_ ASGIF 411_ NSLYP 416_ ATLNF 421_ MKGFP 426_ FLLGA 431_ GLLLI 436_ PAVLI 441_ GMLEK 446_ ADPHL 451_EFQQF
1: Proton-coupled folate symporter that mediates folate absorption using an H(+) gradient as a driving force (PubMed:17129779, PubMed:17446347, PubMed:17475902, PubMed:19389703, PubMed:19762432, PubMed:25504888, PubMed:29344585, PubMed:30858177, PubMed:31494288, PubMed:31792273, PubMed:32893190, PubMed:34619546). Involved in the intestinal absorption of folates at the brush-border membrane of the proximal jejunum, and the transport from blood to cerebrospinal fluid across the choroid plexus (PubMed:17129779, PubMed:17446347, PubMed:17475902, PubMed:19389703, PubMed:25504888, PubMed:29344585, PubMed:30858177, PubMed:31494288, PubMed:32893190). Functions at acidic pH via alternate outward- and inward-open conformation states (PubMed:32893190, PubMed:34040256). Protonation of residues in the outward open state primes the protein for transport (PubMed:34040256). Binding of folate promotes breaking of salt bridge network and subsequent closure of the extracellular gate, leading to the inward-open state and release of protons and folate (PubMed:34040256). Also able to transport antifolate drugs, such as methotrexate and pemetrexed, which are established treatments for cancer and autoimmune diseases (PubMed:18524888, PubMed:19762432, PubMed:22345511, PubMed:25608532, PubMed:28802835, PubMed:29326243, PubMed:34040256, PubMed:34619546). Involved in FOLR1-mediated endocytosis by serving as a route of export of folates from acidified endosomes (PubMed:19074442). Also acts as a lower-affinity, pH-independent heme carrier protein and constitutes the main importer of heme in the intestine (PubMed:17156779). Imports heme in the retina and retinal pigment epithelium, in neurons of the hippocampus, in hepatocytes and in the renal epithelial cells (PubMed:32621820). Hence, participates in the trafficking of heme and increases intracellular iron content (PubMed:32621820)
2: Inactive isoform which is not able to mediate proton-coupled folate transport