ID FLVC2_HUMAN Reviewed; 526 AA. AC Q9UPI3; B7Z485; Q53ZT9; Q96JY3; Q9NX90; DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 27-MAR-2024, entry version 171. DE RecName: Full=Heme transporter FLVCR2 {ECO:0000305|PubMed:20823265}; DE AltName: Full=Calcium-chelate transporter {ECO:0000303|PubMed:14729055}; DE Short=CCT {ECO:0000303|PubMed:14729055}; DE AltName: Full=Feline leukemia virus subgroup C receptor-related protein 2; GN Name=FLVCR2; Synonyms=C14orf58; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE RP SPECIFICITY, DEVELOPMENTAL STAGE, AND CHARACTERIZATION. RC TISSUE=Pituitary; RX PubMed=14729055; DOI=10.1016/j.yexcr.2003.10.002; RA Brasier G., Tikellis C., Xuereb L., Craigie J., Casley D., Kovacs C.S., RA Fudge N.J., Kalnins R., Cooper M.E., Wookey P.J.; RT "Novel hexad repeats conserved in a putative transporter with restricted RT expression in cell types associated with growth, calcium exchange and RT homeostasis."; RL Exp. Cell Res. 293:31-42(2004). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Brown J., Pirani H., Tailor C.S.; RT "An aspartic acid in the presumptive extracellular loop six of subgroup C RT feline leukemia virus receptor FLVCR1 is involved in virus infection."; RL Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT RP ALA-16. RC TISSUE=Placenta, and Umbilical cord blood; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12508121; DOI=10.1038/nature01348; RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., RA Waterston R., Hood L., Weissenbach J.; RT "The DNA sequence and analysis of human chromosome 14."; RL Nature 421:601-607(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Colon; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP FUNCTION, TRANSPORTER ACTIVITY, AND TISSUE SPECIFICITY. RX PubMed=20823265; DOI=10.1128/mcb.00690-10; RA Duffy S.P., Shing J., Saraon P., Berger L.C., Eiden M.V., Wilde A., RA Tailor C.S.; RT "The Fowler syndrome-associated protein FLVCR2 is an importer of heme."; RL Mol. Cell. Biol. 30:5318-5324(2010). RN [8] RP FUNCTION, SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF 30-HIS--HIS-66. RX PubMed=32973183; DOI=10.1038/s41467-020-18607-1; RA Li Y., Ivica N.A., Dong T., Papageorgiou D.P., He Y., Brown D.R., RA Kleyman M., Hu G., Chen W.W., Sullivan L.B., Del Rosario A., Hammond P.T., RA Vander Heiden M.G., Chen J.; RT "MFSD7C switches mitochondrial ATP synthesis to thermogenesis in response RT to heme."; RL Nat. Commun. 11:4837-4837(2020). RN [9] RP VARIANTS PVHH ARG-280; VAL-398 AND ARG-430. RX PubMed=20206334; DOI=10.1016/j.ajhg.2010.02.004; RA Meyer E., Ricketts C., Morgan N.V., Morris M.R., Pasha S., Tee L.J., RA Rahman F., Bazin A., Bessieres B., Dechelotte P., Yacoubi M.T., RA Al-Adnani M., Marton T., Tannahill D., Trembath R.C., Fallet-Bianco C., RA Cox P., Williams D., Maher E.R.; RT "Mutations in FLVCR2 are associated with proliferative vasculopathy and RT hydranencephaly-hydrocephaly syndrome (Fowler syndrome)."; RL Am. J. Hum. Genet. 86:471-478(2010). RN [10] RP VARIANTS PVHH 110-ASN--PHE-112 DELINS ILE; VAL-326 AND VAL-398. RX PubMed=20518025; DOI=10.1002/humu.21293; RA Lalonde E., Albrecht S., Ha K.C., Jacob K., Bolduc N., Polychronakos C., RA Dechelotte P., Majewski J., Jabado N.; RT "Unexpected allelic heterogeneity and spectrum of mutations in Fowler RT syndrome revealed by next-generation exome sequencing."; RL Hum. Mutat. 31:918-923(2010). RN [11] RP VARIANTS PVHH HIS-84; ARG-352; VAL-398; ARG-412 AND MET-430. RX PubMed=20690116; DOI=10.1002/humu.21329; RA Thomas S., Encha-Razavi F., Devisme L., Etchevers H., RA Bessieres-Grattagliano B., Goudefroye G., Elkhartoufi N., Pateau E., RA Ichkou A., Bonniere M., Marcorelle P., Parent P., Manouvrier S., Holder M., RA Laquerriere A., Loeuillet L., Roume J., Martinovic J., Mougou-Zerelli S., RA Gonzales M., Meyer V., Wessner M., Feysot C.B., Nitschke P., Leticee N., RA Munnich A., Lyonnet S., Wookey P., Gyapay G., Foliguet B., Vekemans M., RA Attie-Bitach T.; RT "High-throughput sequencing of a 4.1 Mb linkage interval reveals FLVCR2 RT deletions and mutations in lethal cerebral vasculopathy."; RL Hum. Mutat. 31:1134-1141(2010). CC -!- FUNCTION: Putative heme b importer/sensor involved in heme homeostasis CC in response to the metabolic state of the cell and to diet. May act as CC a sensor of cytosolic and/or mitochondrial heme levels to regulate CC mitochondrial respiration processes, ATP synthesis and thermogenesis. CC At low heme levels, interacts with components of electron transfer CC chain (ETC) complexes and ATP2A2, leading to ubiquitin-mediated CC degradation of ATP2A2 and inhibition of thermogenesis. Upon heme CC binding, dissociates from ETC complexes to allow switching from CC mitochondrial ATP synthesis to thermogenesis. Alternatively, in CC coordination with ATP2A2 may mediate calcium transport and signaling in CC response to heme. {ECO:0000269|PubMed:20823265, CC ECO:0000269|PubMed:32973183}. CC -!- CATALYTIC ACTIVITY: CC Reaction=heme b(in) = heme b(out); Xref=Rhea:RHEA:75443, CC ChEBI:CHEBI:60344; Evidence={ECO:0000305|PubMed:20823265}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75444; CC Evidence={ECO:0000305|PubMed:20823265}; CC -!- SUBUNIT: Interacts with components of electron transfer chain complexes CC III, IV and V including CYC1, NDUFA4, COX4I1, ATP5PD and ATP5F1C; these CC interactions occur in the absence of heme and are disrupted upon heme CC binding (By similarity). Interacts with ATP2A2; this interaction occurs CC in the absence of heme and promotes ATP2A2 proteasomal degradation; the CC complex is dissociated upon heme binding (By similarity). Interacts CC with HMOX1; this interaction is potentiated in the presence of heme (By CC similarity). {ECO:0000250|UniProtKB:Q91X85}. CC -!- SUBCELLULAR LOCATION: Mitochondrion membrane CC {ECO:0000269|PubMed:32973183}; Multi-pass membrane protein CC {ECO:0000255}. Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:32973183}; Multi-pass membrane protein CC {ECO:0000255}. Cell membrane {ECO:0000305|PubMed:14729055}; Multi-pass CC membrane protein {ECO:0000255}. Note=Primarily resides in mitochondria CC where it interacts with components of the electron transfer chain CC complexes III, IV and V. Colocalizes with ATP2A2 at the mitochondrial- CC ER contact junction. {ECO:0000269|PubMed:32973183}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9UPI3-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9UPI3-2; Sequence=VSP_043048, VSP_043049; CC -!- TISSUE SPECIFICITY: Expressed in non-hematopoietic tissues, with CC relative abundant expression in brain, placenta, lung, liver and kidney CC (PubMed:20823265). Also expressed in hematopoietic tissues (fetal CC liver, spleen, lymph node, thymus, leukocytes and bone marrow) CC (PubMed:20823265). Found in acidophil cells of the pituitary that CC secrete growth hormone and prolactin (at protein level) CC (PubMed:14729055). {ECO:0000269|PubMed:14729055, CC ECO:0000269|PubMed:20823265}. CC -!- DEVELOPMENTAL STAGE: Expressed in follicular cells of the developing CC thyroid at 18 dpc (at protein level). {ECO:0000269|PubMed:14729055}. CC -!- DOMAIN: The N-terminus contains histidine-proline motifs involved in CC heme binding. Can bind 2 to 3 heme molecules. CC {ECO:0000269|PubMed:32973183}. CC -!- DISEASE: Proliferative vasculopathy and hydranencephaly-hydrocephaly CC syndrome (PVHH) [MIM:225790]: A rare prenatally lethal disorder CC characterized by hydranencephaly, a distinctive glomerular vasculopathy CC in the central nervous system and retina, and diffuse ischemic lesions CC of the brain stem, basal ganglia, and spinal cord with calcifications. CC Hydranencephaly is a condition where the greater portions of the CC cerebral hemispheres and corpus striatum are replaced by cerebrospinal CC fluid and glial tissue. {ECO:0000269|PubMed:20206334, CC ECO:0000269|PubMed:20518025, ECO:0000269|PubMed:20690116}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the major facilitator superfamily. Feline CC leukemia virus subgroup C receptor (TC 2.A.1.28.1) family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAB55381.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY260572; AAP86633.1; -; mRNA. DR EMBL; AY260577; AAP86638.1; -; mRNA. DR EMBL; AF456126; AAO15528.1; -; mRNA. DR EMBL; AK000378; BAA91126.1; -; mRNA. DR EMBL; AK027804; BAB55381.1; ALT_INIT; mRNA. DR EMBL; AK297002; BAH12471.1; -; mRNA. DR EMBL; AC007182; AAD51374.1; -; Genomic_DNA. DR EMBL; CH471061; EAW81235.1; -; Genomic_DNA. DR EMBL; BC019087; AAH19087.1; -; mRNA. DR CCDS; CCDS55933.1; -. [Q9UPI3-2] DR CCDS; CCDS9844.1; -. [Q9UPI3-1] DR RefSeq; NP_001182212.1; NM_001195283.1. [Q9UPI3-2] DR RefSeq; NP_060261.2; NM_017791.2. [Q9UPI3-1] DR AlphaFoldDB; Q9UPI3; -. DR SMR; Q9UPI3; -. DR BioGRID; 120777; 30. DR IntAct; Q9UPI3; 1. DR STRING; 9606.ENSP00000238667; -. DR TCDB; 2.A.1.28.4; the major facilitator superfamily (mfs). DR iPTMnet; Q9UPI3; -. DR PhosphoSitePlus; Q9UPI3; -. DR BioMuta; FLVCR2; -. DR DMDM; 46396034; -. DR jPOST; Q9UPI3; -. DR MassIVE; Q9UPI3; -. DR MaxQB; Q9UPI3; -. DR PaxDb; 9606-ENSP00000238667; -. DR PeptideAtlas; Q9UPI3; -. DR ProteomicsDB; 85372; -. [Q9UPI3-1] DR ProteomicsDB; 85373; -. [Q9UPI3-2] DR Antibodypedia; 51434; 149 antibodies from 22 providers. DR DNASU; 55640; -. DR Ensembl; ENST00000238667.9; ENSP00000238667.4; ENSG00000119686.10. [Q9UPI3-1] DR Ensembl; ENST00000539311.5; ENSP00000443439.1; ENSG00000119686.10. [Q9UPI3-2] DR GeneID; 55640; -. DR KEGG; hsa:55640; -. DR MANE-Select; ENST00000238667.9; ENSP00000238667.4; NM_017791.3; NP_060261.2. DR UCSC; uc001xrs.3; human. [Q9UPI3-1] DR AGR; HGNC:20105; -. DR CTD; 55640; -. DR DisGeNET; 55640; -. DR GeneCards; FLVCR2; -. DR HGNC; HGNC:20105; FLVCR2. DR HPA; ENSG00000119686; Tissue enhanced (choroid). DR MalaCards; FLVCR2; -. DR MIM; 225790; phenotype. DR MIM; 610865; gene. DR neXtProt; NX_Q9UPI3; -. DR OpenTargets; ENSG00000119686; -. DR Orphanet; 221126; Fowler vasculopathy. DR PharmGKB; PA162388720; -. DR VEuPathDB; HostDB:ENSG00000119686; -. DR eggNOG; KOG2563; Eukaryota. DR GeneTree; ENSGT01030000234625; -. DR HOGENOM; CLU_023132_0_1_1; -. DR InParanoid; Q9UPI3; -. DR OMA; STICWTG; -. DR OrthoDB; 1382276at2759; -. DR PhylomeDB; Q9UPI3; -. DR TreeFam; TF314292; -. DR PathwayCommons; Q9UPI3; -. DR SignaLink; Q9UPI3; -. DR BioGRID-ORCS; 55640; 30 hits in 1151 CRISPR screens. DR ChiTaRS; FLVCR2; human. DR GenomeRNAi; 55640; -. DR Pharos; Q9UPI3; Tbio. DR PRO; PR:Q9UPI3; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; Q9UPI3; Protein. DR Bgee; ENSG00000119686; Expressed in secondary oocyte and 136 other cell types or tissues. DR ExpressionAtlas; Q9UPI3; baseline and differential. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; IBA:GO_Central. DR GO; GO:0031966; C:mitochondrial membrane; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0020037; F:heme binding; IDA:UniProtKB. DR GO; GO:0015232; F:heme transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0097037; P:heme export; IBA:GO_Central. DR CDD; cd17456; MFS_FLVCR2; 1. DR Gene3D; 1.20.1250.20; MFS general substrate transporter like domains; 2. DR InterPro; IPR011701; MFS. DR InterPro; IPR020846; MFS_dom. DR InterPro; IPR036259; MFS_trans_sf. DR InterPro; IPR049680; SLC49-like. DR PANTHER; PTHR10924:SF3; FELINE LEUKEMIA VIRUS SUBGROUP C RECEPTOR-RELATED PROTEIN 2; 1. DR PANTHER; PTHR10924; MAJOR FACILITATOR SUPERFAMILY PROTEIN-RELATED; 1. DR Pfam; PF07690; MFS_1; 1. DR SUPFAM; SSF103473; MFS general substrate transporter; 1. DR PROSITE; PS50850; MFS; 1. DR Genevisible; Q9UPI3; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cell membrane; Disease variant; KW Endoplasmic reticulum; Membrane; Mitochondrion; Phosphoprotein; KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..526 FT /note="Heme transporter FLVCR2" FT /id="PRO_0000084846" FT TRANSMEM 103..123 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 125..145 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 152..172 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 176..196 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 217..237 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 252..272 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 310..330 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 349..369 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 386..406 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 407..427 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 436..456 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 471..491 FT /note="Helical" FT /evidence="ECO:0000255" FT REPEAT 25..30 FT /note="1" FT REPEAT 31..36 FT /note="2" FT REPEAT 37..42 FT /note="3" FT REPEAT 43..48 FT /note="4" FT REPEAT 49..54 FT /note="5" FT REPEAT 55..60 FT /note="6; approximate" FT REPEAT 61..66 FT /note="7; approximate" FT REPEAT 67..72 FT /note="8" FT REGION 1..70 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 25..72 FT /note="8 X 6 AA tandem repeats of P-S-[VS]-S-[VIAG]-[HNP]" FT REGION 500..526 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1..15 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 25..69 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 500..514 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 1..84 FT /ligand="heme b" FT /ligand_id="ChEBI:CHEBI:60344" FT /evidence="ECO:0000305|PubMed:32973183" FT MOD_RES 515 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q91X85" FT VAR_SEQ 1..18 FT /note="MVNEGPNQEESDDTPVPE -> MSADNSSTICVCRSVRQE (in isoform FT 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043048" FT VAR_SEQ 19..223 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043049" FT VARIANT 16 FT /note="V -> A (in dbSNP:rs2287015)" FT /evidence="ECO:0000269|PubMed:14702039" FT /id="VAR_018271" FT VARIANT 84 FT /note="R -> H (in PVHH)" FT /evidence="ECO:0000269|PubMed:20690116" FT /id="VAR_064410" FT VARIANT 110..112 FT /note="NIF -> I (in PVHH)" FT /evidence="ECO:0000269|PubMed:20518025" FT /id="VAR_064411" FT VARIANT 280 FT /note="P -> R (in PVHH; dbSNP:rs267606823)" FT /evidence="ECO:0000269|PubMed:20206334" FT /id="VAR_064043" FT VARIANT 326 FT /note="A -> V (in PVHH; dbSNP:rs267606824)" FT /evidence="ECO:0000269|PubMed:20518025" FT /id="VAR_064412" FT VARIANT 352 FT /note="T -> R (in PVHH)" FT /evidence="ECO:0000269|PubMed:20690116" FT /id="VAR_064413" FT VARIANT 398 FT /note="L -> V (in PVHH; dbSNP:rs267606822)" FT /evidence="ECO:0000269|PubMed:20206334, FT ECO:0000269|PubMed:20518025, ECO:0000269|PubMed:20690116" FT /id="VAR_064044" FT VARIANT 412 FT /note="G -> R (in PVHH)" FT /evidence="ECO:0000269|PubMed:20690116" FT /id="VAR_064414" FT VARIANT 430 FT /note="T -> M (in PVHH; dbSNP:rs267606825)" FT /evidence="ECO:0000269|PubMed:20690116" FT /id="VAR_064415" FT VARIANT 430 FT /note="T -> R (in PVHH; dbSNP:rs267606825)" FT /evidence="ECO:0000269|PubMed:20206334" FT /id="VAR_064045" FT VARIANT 481 FT /note="A -> T (in dbSNP:rs35126362)" FT /id="VAR_050299" FT MUTAGEN 30..66 FT /note="HPSVSVHPSVSINPSVSVHPSSSAHPSALAQPSGLAH->APSVSVAPSVSIN FT PSVSVAPSSSAAPSALAQPSGLAA: Loss of heme-binding activity." FT /evidence="ECO:0000269|PubMed:32973183" FT CONFLICT 419 FT /note="L -> H (in Ref. 3; BAB55381)" FT /evidence="ECO:0000305" FT CONFLICT 439 FT /note="S -> F (in Ref. 3; BAA91126)" FT /evidence="ECO:0000305" SQ SEQUENCE 526 AA; 57241 MW; D233C07350B17870 CRC64; MVNEGPNQEE SDDTPVPESA LQADPSVSVH PSVSVHPSVS INPSVSVHPS SSAHPSALAQ PSGLAHPSSS GPEDLSVIKV SRRRWAVVLV FSCYSMCNSF QWIQYGSINN IFMHFYGVSA FAIDWLSMCY MLTYIPLLLP VAWLLEKFGL RTIALTGSAL NCLGAWVKLG SLKPHLFPVT VVGQLICSVA QVFILGMPSR IASVWFGANE VSTACSVAVF GNQLGIAIGF LVPPVLVPNI EDRDELAYHI SIMFYIIGGV ATLLLILVII VFKEKPKYPP SRAQSLSYAL TSPDASYLGS IARLFKNLNF VLLVITYGLN AGAFYALSTL LNRMVIWHYP GEEVNAGRIG LTIVIAGMLG AVISGIWLDR SKTYKETTLV VYIMTLVGMV VYTFTLNLGH LWVVFITAGT MGFFMTGYLP LGFEFAVELT YPESEGISSG LLNISAQVFG IIFTISQGQI IDNYGTKPGN IFLCVFLTLG AALTAFIKAD LRRQKANKET LENKLQEEEE ESNTSKVPTA VSEDHL //