ID HFE_HUMAN Reviewed; 348 AA. AC Q30201; B2CKL0; O75929; O75930; O75931; Q17RT0; Q96KU5; Q96KU6; Q96KU7; AC Q96KU8; Q9HC64; Q9HC68; Q9HC70; Q9HC83; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 1. DT 27-MAR-2024, entry version 233. DE RecName: Full=Hereditary hemochromatosis protein; DE AltName: Full=HLA-H; DE Flags: Precursor; GN Name=HFE; Synonyms=HLAH; 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), VARIANT HFE1 TYR-282, AND VARIANT RP ASP-63. RX PubMed=8696333; DOI=10.1038/ng0896-399; RA Feder J.N., Gnirke A., Thomas W., Tsuchihashi Z., Ruddy D.A., Basava A., RA Dormishian F., Domingo R. Jr., Ellis M.C. Jr., Fullan A., Hinton L.M., RA Jones N.L., Kimmel B.E., Kronmal G.S., Lauer P., Lee V.K., Loeb D.B., RA Mapa F.A., McClelland E., Meyer N.C., Mintier G.A., Moeller N., Moore T., RA Morikang E., Prass C.E., Quintana L., Starnes S.M., Schatzman R.C., RA Brunke K.J., Drayna D.T., Risch N.J., Bacon B.R., Wolff R.K.; RT "A novel MHC class I-like gene is mutated in patients with hereditary RT haemochromatosis."; RL Nat. Genet. 13:399-409(1996). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1). RX PubMed=9149941; DOI=10.1101/gr.7.5.441; RA Ruddy D.A., Kronmal G.S., Lee V.K., Mintier G.A., Quintana L., RA Domingo R. Jr., Meyer N.C., Irrinki A., McClelland E.E., Fullan A., RA Mapa F.A., Moore T., Thomas W., Loeb D.B., Harmon C., Tsuchihashi Z., RA Wolff R.K., Schatzman R.C., Feder J.N.; RT "A 1.1-Mb transcript map of the hereditary hemochromatosis locus."; RL Genome Res. 7:441-456(1997). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). RX PubMed=9548560; RX DOI=10.1002/(sici)1097-4644(19980501)69:2<117::aid-jcb3>3.0.co;2-v; RA Albig W., Drabent B., Burmester N., Bode C., Doenecke D.; RT "The haemochromatosis candidate gene HFE (HLA-H) of man and mouse is RT located in syntenic regions within the histone gene."; RL J. Cell. Biochem. 69:117-126(1998). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). RA Gasparini P.; RT "Hereditary hemochromatosis genomic structure and organization of HLA-H RT gene."; RL Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4). RX PubMed=10079302; DOI=10.1007/s002510050505; RA Rhodes D.A., Trowsdale J.; RT "Alternate splice variants of the hemochromatosis gene Hfe."; RL Immunogenetics 49:357-359(1999). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 7; 8; 9 AND 10). RX PubMed=11001625; DOI=10.1006/bcmd.2000.0291; RA Thenie A., Orhant M., Gicquel I., Fergelot P., Le Gall J.-Y., David V., RA Mosser J.; RT "The HFE gene undergoes alternate splicing processes."; RL Blood Cells Mol. Dis. 26:155-162(2000). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 5; 6; 7 AND 11). RX PubMed=11358357; DOI=10.1006/bcmd.2000.0346; RA Sanchez M., Bruguera M., Rodos J., Oliva R.; RT "Complete characterization of the 3' region of the human and mouse RT hereditary hemochromatosis HFE gene and detection of novel splicing RT forms."; RL Blood Cells Mol. Dis. 27:35-43(2001). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS MET-53; ASP-63; GLN-224 AND RP TYR-282. RG NIEHS SNPs program; RL Submitted (FEB-2008) to the EMBL/GenBank/DDBJ databases. RN [9] 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 [10] 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 [11] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=9465039; DOI=10.1073/pnas.95.4.1472; RA Feder J.N., Penny D.M., Irrinki A., Lee V.K., Lebron J.A., Watson N., RA Tsuchihashi Z., Sigal E., Bjorkman P.J., Schatzman R.C.; RT "The hemochromatosis gene product complexes with the transferrin receptor RT and lowers its affinity for ligand binding."; RL Proc. Natl. Acad. Sci. U.S.A. 95:1472-1477(1998). RN [12] RP POLYMORPHISM. RX PubMed=19084217; DOI=10.1016/j.ajhg.2008.11.011; RA Benyamin B., McRae A.F., Zhu G., Gordon S., Henders A.K., Palotie A., RA Peltonen L., Martin N.G., Montgomery G.W., Whitfield J.B., Visscher P.M.; RT "Variants in TF and HFE explain approximately 40% of genetic variation in RT serum-transferrin levels."; RL Am. J. Hum. Genet. 84:60-65(2009). RN [13] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 23-297 IN COMPLEX WITH TFR. RX PubMed=9546397; DOI=10.1016/s0092-8674(00)81151-4; RA Lebron J.A., Bennett M.J., Vaughn D.E., Chirino A.J., Snow P.M., RA Mintier G.A., Feder J.N., Bjorkman P.J.; RT "Crystal structure of the hemochromatosis protein HFE and characterization RT of its interaction with transferrin receptor."; RL Cell 93:111-123(1998). RN [14] RP 3D-STRUCTURE MODELING OF 26-293 IN COMPLEX WITH B2MG. RX PubMed=11018711; DOI=10.1016/s0167-4838(00)00126-6; RA Dupradeau F., Altenberg-Greulich B., Warin R., Fuentes V., Monti J., RA Rochette J.; RT "A 3-dimensional model building by homology of the HFE protein: molecular RT consequences and application to antibody development."; RL Biochim. Biophys. Acta 1481:213-221(2000). RN [15] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 26-297 IN COMPLEX WITH TFR. RX PubMed=10638746; DOI=10.1038/47417; RA Bennett M.J., Lebron J.A., Bjorkman P.J.; RT "Crystal structure of the hereditary haemochromatosis protein HFE complexed RT with transferrin receptor."; RL Nature 403:46-53(2000). RN [16] RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S). RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8; RA Hillman R.T., Green R.E., Brenner S.E.; RT "An unappreciated role for RNA surveillance."; RL Genome Biol. 5:R8.1-R8.16(2004). RN [17] RP VARIANTS HFE1 ASP-63 AND TYR-282. RX PubMed=9106528; RA Carella M., D'Ambrosio L., Totaro A., Grifa A., Valentino M.A., Piperno A., RA Girelli D., Roetto A., Franco B., Gasparini P., Camaschella C.; RT "Mutation analysis of the HLA-H gene in Italian hemochromatosis patients."; RL Am. J. Hum. Genet. 60:828-832(1997). RN [18] RP VARIANT HFE1 TYR-282, AND ASSOCIATION WITH PORPHYRIA CUTANEA TARDA. RX PubMed=9024376; DOI=10.1016/s0140-6736(96)09436-6; RA Roberts A.G., Whatley S.D., Morgan R.R., Worwood M., Elder G.H.; RT "Increased frequency of the haemochromatosis Cys282Tyr mutation in sporadic RT porphyria cutanea tarda."; RL Lancet 349:321-323(1997). RN [19] RP VARIANT ASP-63. RX PubMed=9425935; DOI=10.1002/hep.510270128; RA Sampietro M., Piperno A., Lupica L., Arosio C., Vergani A., Corbetta N., RA Malosio I., Mattioli M., Fracanzani A.L., Cappellini M.D., Fiorelli G., RA Fargion S.; RT "High prevalence of the His63Asp HFE mutation in Italian patients with RT porphyria cutanea tarda."; RL Hepatology 27:181-184(1998). RN [20] RP VARIANTS HFE1 ASP-63 AND TYR-282. RX PubMed=9620340; DOI=10.1002/hep.510270627; RA Bonkovsky H.L., Poh-Fitzpatrick M., Pimstone N., Obando J., RA Di Bisceglie A., Tattrie C., Tortorelli K., LeClair P., Mercurio M.G., RA Lambrecht R.W.; RT "Porphyria cutanea tarda, hepatitis C, and HFE gene mutations in North RT America."; RL Hepatology 27:1661-1669(1998). RN [21] RP VARIANTS HFE1 ASP-63; CYS-65 AND TYR-282. RX PubMed=10194428; RA Mura C., Raguenes O., Ferec C.; RT "HFE mutations analysis in 711 hemochromatosis probands: evidence for S65C RT implication in mild form of hemochromatosis."; RL Blood 93:2502-2505(1999). RN [22] RP VARIANTS HFE1 CYS-65; ARG-93 AND THR-105. RX PubMed=10575540; DOI=10.1006/bcmd.1999.0240; RA Barton J.C., Sawada-Hirai R., Rothenberg B.E., Acton R.T.; RT "Two novel missense mutations of the HFE gene (I105T and G93R) and RT identification of the S65C mutation in Alabama hemochromatosis probands."; RL Blood Cells Mol. Dis. 25:147-155(1999). RN [23] RP VARIANTS HFE1 ASP-63; HIS-127 AND MET-330, AND VARIANTS MET-53 AND MET-59. RX PubMed=10401000; DOI=10.1093/hmg/8.8.1517; RA de Villiers J.N.P., Hillermann R., Loubser L., Kotze M.J.; RT "Spectrum of mutations in the HFE gene implicated in haemochromatosis and RT porphyria."; RL Hum. Mol. Genet. 8:1517-1522(1999). RN [24] RP VARIANTS HFE1 ASP-63 AND TYR-282. RX PubMed=10094552; RX DOI=10.1002/(sici)1098-1004(1999)13:2<154::aid-humu8>3.0.co;2-e; RA Merryweather-Clarke A.T., Simonsen H., Shearman J.D., Pointon J.J., RA Norgaard-Pedersen B., Robson K.J.H.; RT "A retrospective anonymous pilot study in screening newborns for HFE RT mutations in Scandinavian populations."; RL Hum. Mutat. 13:154-159(1999). RN [25] RP VARIANT HFE1 CYS-65. RA Fagan E., Payne S.J.; RT "A novel missense mutation S65C in the HFE gene with a possible role in RT hereditary haemochromatosis."; RL Hum. Mutat. 13:507-508(1999). RN [26] RP VARIANT LYS-277. RX PubMed=10612845; RX DOI=10.1002/(sici)1098-1004(200001)15:1<120::aid-humu32>3.0.co;2-b; RA Bradbury R., Fagan E., Payne S.J.; RT "Two novel polymorphisms (E277K and V212V) in the haemochromatosis gene RT HFE."; RL Hum. Mutat. 15:120-120(2000). RN [27] RP VARIANTS ASP-63 AND TYR-282. RX PubMed=11069625; DOI=10.1046/j.1523-1747.2000.00148.x; RA Brady J.J., Jackson H.A., Roberts A.G., Morgan R.R., Whatley S.D., RA Rowlands G.L., Darby C., Shudell E., Watson R., Paiker J., Worwood M.W., RA Elder G.H.; RT "Co-inheritance of mutations in the uroporphyrinogen decarboxylase and RT hemochromatosis genes accelerates the onset of porphyria cutanea tarda."; RL J. Invest. Dermatol. 115:868-874(2000). RN [28] RP VARIANTS HFE1 ASP-63 AND TYR-282, AND ASSOCIATION WITH DIABETIC NEPHROPATHY RP SUSCEPTIBILITY. RX PubMed=11423500; DOI=10.2337/diacare.24.7.1187; RA Moczulski D.K., Grzeszczak W., Gawlik B.; RT "Role of hemochromatosis C282Y and H63D mutations in HFE gene in RT development of type 2 diabetes and diabetic nephropathy."; RL Diabetes Care 24:1187-1191(2001). RN [29] RP VARIANT HFE1 VAL-176. RX PubMed=11446670; DOI=10.2169/internalmedicine.40.479; RA Imanishi H., Liu W., Cheng J., Ikeda N., Amuro Y., Hada T.; RT "Idiopathic hemochromatosis with the mutation of Ala176Val heterozygous for RT HFE gene."; RL Intern. Med. 40:479-483(2001). RN [30] RP VARIANTS HFE1 CYS-65; TYR-282 AND ALA-295. RX PubMed=12542741; DOI=10.1034/j.1399-0039.2002.600603.x; RA Jones D.C., Young N.T., Pigott C., Fuggle S.V., Barnardo M.C.N.M., RA Marshall S.E., Bunce M.; RT "Comprehensive hereditary hemochromatosis genotyping."; RL Tissue Antigens 60:481-488(2002). RN [31] RP VARIANT HFE1 PRO-283, AND CHARACTERIZATION OF VARIANT HFE1 PRO-283. RX PubMed=12737937; DOI=10.1016/s1079-9796(03)00036-6; RA Le Gac G., Dupradeau F.-Y., Mura C., Jacolot S., Scotet V., Esnault G., RA Mercier A.-Y., Rochette J., Ferec C.; RT "Phenotypic expression of the C282Y/Q283P compound heterozygosity in HFE RT and molecular modeling of the Q283P mutation effect."; RL Blood Cells Mol. Dis. 30:231-237(2003). RN [32] RP VARIANTS HFE1 CYS-65; CYS-66; GLY-224 AND TYR-282. RX PubMed=14633868; DOI=10.1373/clinchem.2003.023440; RA Biasiotto G., Belloli S., Ruggeri G., Zanella I., Gerardi G., Corrado M., RA Gobbi E., Albertini A., Arosio P.; RT "Identification of new mutations of the HFE, hepcidin, and transferrin RT receptor 2 genes by denaturing HPLC analysis of individuals with RT biochemical indications of iron overload."; RL Clin. Chem. 49:1981-1988(2003). RN [33] RP VARIANT HFE1 SER-6. RX PubMed=12584229; DOI=10.1136/gut.52.3.433; RA Wigg A.J., Harley H., Casey G.; RT "Heterozygous recipient and donor HFE mutations associated with a RT hereditary haemochromatosis phenotype after liver transplantation."; RL Gut 52:433-435(2003). RN [34] RP VARIANT HFE1 ALA-295. RX PubMed=15046077; RA Bento M.C., Ribeiro M.L., Relvas L.; RT "Gene symbol: HFE. Disease: haemochromatosis."; RL Hum. Genet. 114:405-405(2004). RN [35] RP CHARACTERIZATION OF VARIANT HFE1 PRO-283. RX PubMed=15965644; DOI=10.1007/s00439-005-1307-y; RA Ka C., Le Gac G., Dupradeau F.-Y., Rochette J., Ferec C.; RT "The Q283P amino-acid change in HFE leads to structural and functional RT consequences similar to those described for the mutated 282Y HFE protein."; RL Hum. Genet. 117:467-475(2005). RN [36] RP VARIANTS HFE1 ASP-43; ASP-63 AND TYR-282. RX PubMed=18157833; DOI=10.1002/humu.9517; RA Dupradeau F.-Y., Pissard S., Coulhon M.-P., Cadet E., Foulon K., RA Fourcade C., Goossens M., Case D.A., Rochette J.; RT "An unusual case of hemochromatosis due to a new compound heterozygosity in RT HFE (p.[Gly43Asp;His63Asp]+[Cys282Tyr]): structural implications with RT respect to binding with transferrin receptor 1."; RL Hum. Mutat. 29:206-206(2008). CC -!- FUNCTION: Binds to transferrin receptor (TFR) and reduces its affinity CC for iron-loaded transferrin. {ECO:0000269|PubMed:9465039}. CC -!- SUBUNIT: Binds TFR through the extracellular domain in a pH-dependent CC manner. {ECO:0000269|PubMed:10638746, ECO:0000269|PubMed:9546397}. CC -!- INTERACTION: CC Q30201; P61769: B2M; NbExp=4; IntAct=EBI-1028850, EBI-714718; CC Q30201; P02786: TFRC; NbExp=3; IntAct=EBI-1028850, EBI-355727; CC Q30201-1; P02786: TFRC; NbExp=3; IntAct=EBI-15489346, EBI-355727; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:9465039}; CC Single-pass type I membrane protein {ECO:0000305|PubMed:8696333}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=11; CC Comment=Additional isoforms seem to exist.; CC Name=1; CC IsoId=Q30201-1; Sequence=Displayed; CC Name=2; Synonyms=delE2; CC IsoId=Q30201-2; Sequence=VSP_003218; CC Name=3; Synonyms=del14E4; CC IsoId=Q30201-3; Sequence=VSP_003225; CC Name=4; Synonyms=delE214E4; CC IsoId=Q30201-4; Sequence=VSP_003218, VSP_003225; CC Name=5; CC IsoId=Q30201-5; Sequence=VSP_003219; CC Name=6; CC IsoId=Q30201-6; Sequence=VSP_047336, VSP_003220; CC Name=7; Synonyms=delE3; CC IsoId=Q30201-7; Sequence=VSP_003221; CC Name=8; Synonyms=1043-2283del,intron6ins; CC IsoId=Q30201-8; Sequence=VSP_003226, VSP_003227; CC Name=9; Synonyms=delE3-7; CC IsoId=Q30201-9; Sequence=VSP_003223, VSP_003224; CC Name=10; Synonyms=562-878del; CC IsoId=Q30201-10; Sequence=VSP_003222; CC Name=11; CC IsoId=Q30201-11; Sequence=VSP_043477, VSP_043478; CC -!- TISSUE SPECIFICITY: Expressed in all tissues tested except brain. CC -!- POLYMORPHISM: Genetic variations in HFE may influence the transferrin CC serum levels. Iron is essential for biochemical functions such as CC oxygen transport and oxidative phosphorylation. Excessive iron can CC cause iron-overload-related liver diseases, whereas iron deficiency can CC lead to anemia. Iron status can be assessed by measuring the levels of CC serum iron, serum transferrin, transferrin saturation with iron, and CC serum ferritin. {ECO:0000269|PubMed:19084217}. CC -!- DISEASE: Hemochromatosis 1 (HFE1) [MIM:235200]: A disorder of iron CC metabolism characterized by iron overload. Excess iron is deposited in CC a variety of organs leading to their failure, and resulting in serious CC illnesses including cirrhosis, hepatomas, diabetes, cardiomyopathy, CC arthritis, and hypogonadotropic hypogonadism. Severe effects of the CC disease usually do not appear until after decades of progressive iron CC loading. {ECO:0000269|PubMed:10094552, ECO:0000269|PubMed:10194428, CC ECO:0000269|PubMed:10401000, ECO:0000269|PubMed:10575540, CC ECO:0000269|PubMed:11423500, ECO:0000269|PubMed:11446670, CC ECO:0000269|PubMed:12542741, ECO:0000269|PubMed:12584229, CC ECO:0000269|PubMed:12737937, ECO:0000269|PubMed:14633868, CC ECO:0000269|PubMed:15046077, ECO:0000269|PubMed:15965644, CC ECO:0000269|PubMed:18157833, ECO:0000269|PubMed:8696333, CC ECO:0000269|PubMed:9024376, ECO:0000269|PubMed:9106528, CC ECO:0000269|PubMed:9620340, ECO:0000269|Ref.25}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform 1]: May be produced at very low levels due to a CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA CC decay. CC -!- SIMILARITY: Belongs to the MHC class I family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/44099/HFE"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/hfe/"; 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; U60319; AAC51823.1; -; mRNA. DR EMBL; U91328; AAB82083.1; -; Genomic_DNA. DR EMBL; Z92910; CAB07442.1; -; Genomic_DNA. DR EMBL; Y09801; CAA70934.1; -; Genomic_DNA. DR EMBL; Y09800; CAA70934.1; JOINED; Genomic_DNA. DR EMBL; Y09803; CAA70934.1; JOINED; Genomic_DNA. DR EMBL; Y09799; CAA70934.1; JOINED; Genomic_DNA. DR EMBL; AF079407; AAC62646.1; -; mRNA. DR EMBL; AF079408; AAC62647.1; -; mRNA. DR EMBL; AF079409; AAC62648.1; -; mRNA. DR EMBL; AF115264; AAG29571.1; -; mRNA. DR EMBL; AF115265; AAG29572.1; -; mRNA. DR EMBL; AF144240; AAG29575.1; -; mRNA. DR EMBL; AF144242; AAG29577.1; -; mRNA. DR EMBL; AF149804; AAG29342.1; -; mRNA. DR EMBL; AJ249335; CAC67792.1; -; mRNA. DR EMBL; AJ249336; CAC67793.1; -; mRNA. DR EMBL; AJ249337; CAC67794.1; -; mRNA. DR EMBL; AJ249338; CAC67795.1; -; mRNA. DR EMBL; AJ250635; CAC80805.1; -; mRNA. DR EMBL; EU523119; ACB21042.1; -; Genomic_DNA. DR EMBL; CH471087; EAW55524.1; -; Genomic_DNA. DR EMBL; CH471087; EAW55526.1; -; Genomic_DNA. DR EMBL; BC117201; AAI17202.1; -; mRNA. DR EMBL; BC117203; AAI17204.1; -; mRNA. DR CCDS; CCDS4578.1; -. [Q30201-1] DR CCDS; CCDS4579.1; -. [Q30201-7] DR CCDS; CCDS4580.1; -. [Q30201-2] DR CCDS; CCDS4581.1; -. [Q30201-6] DR CCDS; CCDS4582.1; -. [Q30201-11] DR CCDS; CCDS47386.1; -. [Q30201-10] DR CCDS; CCDS47387.1; -. [Q30201-5] DR CCDS; CCDS54974.1; -. [Q30201-3] DR CCDS; CCDS54975.1; -. [Q30201-4] DR RefSeq; NP_000401.1; NM_000410.3. [Q30201-1] DR RefSeq; NP_001287678.1; NM_001300749.1. DR RefSeq; NP_620572.1; NM_139003.2. [Q30201-10] DR RefSeq; NP_620573.1; NM_139004.2. [Q30201-7] DR RefSeq; NP_620575.1; NM_139006.2. [Q30201-3] DR RefSeq; NP_620576.1; NM_139007.2. [Q30201-2] DR RefSeq; NP_620577.1; NM_139008.2. [Q30201-4] DR RefSeq; NP_620578.1; NM_139009.2. [Q30201-5] DR RefSeq; NP_620579.1; NM_139010.2. [Q30201-6] DR RefSeq; NP_620580.1; NM_139011.2. [Q30201-11] DR PDB; 1A6Z; X-ray; 2.60 A; A/C=23-297. DR PDB; 1DE4; X-ray; 2.80 A; A/D/G=23-297. DR PDBsum; 1A6Z; -. DR PDBsum; 1DE4; -. DR AlphaFoldDB; Q30201; -. DR SMR; Q30201; -. DR BioGRID; 109325; 174. DR DIP; DIP-2737N; -. DR IntAct; Q30201; 10. DR MINT; Q30201; -. DR STRING; 9606.ENSP00000417404; -. DR GlyCosmos; Q30201; 3 sites, No reported glycans. DR GlyGen; Q30201; 4 sites, 1 O-linked glycan (1 site). DR iPTMnet; Q30201; -. DR PhosphoSitePlus; Q30201; -. DR BioMuta; HFE; -. DR DMDM; 2497915; -. DR EPD; Q30201; -. DR jPOST; Q30201; -. DR MassIVE; Q30201; -. DR MaxQB; Q30201; -. DR PaxDb; 9606-ENSP00000417404; -. DR PeptideAtlas; Q30201; -. DR ProteomicsDB; 61558; -. [Q30201-1] DR ProteomicsDB; 61559; -. [Q30201-10] DR ProteomicsDB; 61560; -. [Q30201-11] DR ProteomicsDB; 61561; -. [Q30201-2] DR ProteomicsDB; 61562; -. [Q30201-3] DR ProteomicsDB; 61563; -. [Q30201-4] DR ProteomicsDB; 61564; -. [Q30201-5] DR ProteomicsDB; 61565; -. [Q30201-6] DR ProteomicsDB; 61566; -. [Q30201-7] DR ProteomicsDB; 61567; -. [Q30201-8] DR ProteomicsDB; 61568; -. [Q30201-9] DR Pumba; Q30201; -. DR TopDownProteomics; Q30201-1; -. [Q30201-1] DR Antibodypedia; 2221; 396 antibodies from 32 providers. DR DNASU; 3077; -. DR Ensembl; ENST00000317896.11; ENSP00000313776.7; ENSG00000010704.19. [Q30201-7] DR Ensembl; ENST00000336625.12; ENSP00000337819.8; ENSG00000010704.19. [Q30201-10] DR Ensembl; ENST00000349999.8; ENSP00000259699.6; ENSG00000010704.19. [Q30201-2] DR Ensembl; ENST00000352392.8; ENSP00000315936.4; ENSG00000010704.19. [Q30201-11] DR Ensembl; ENST00000353147.9; ENSP00000312342.5; ENSG00000010704.19. [Q30201-6] DR Ensembl; ENST00000357618.10; ENSP00000417404.1; ENSG00000010704.19. [Q30201-1] DR Ensembl; ENST00000397022.7; ENSP00000380217.3; ENSG00000010704.19. [Q30201-5] DR Ensembl; ENST00000461397.5; ENSP00000420802.1; ENSG00000010704.19. [Q30201-3] DR Ensembl; ENST00000488199.5; ENSP00000420559.1; ENSG00000010704.19. [Q30201-4] DR GeneID; 3077; -. DR KEGG; hsa:3077; -. DR MANE-Select; ENST00000357618.10; ENSP00000417404.1; NM_000410.4; NP_000401.1. DR UCSC; uc003nfx.2; human. [Q30201-1] DR AGR; HGNC:4886; -. DR CTD; 3077; -. DR DisGeNET; 3077; -. DR GeneCards; HFE; -. DR GeneReviews; HFE; -. DR HGNC; HGNC:4886; HFE. DR HPA; ENSG00000010704; Low tissue specificity. DR MalaCards; HFE; -. DR MIM; 235200; phenotype. DR MIM; 613609; gene. DR neXtProt; NX_Q30201; -. DR OpenTargets; ENSG00000010704; -. DR Orphanet; 586; Cystic fibrosis. DR Orphanet; 648581; Digenic hemochromatosis. DR Orphanet; 443062; Familial porphyria cutanea tarda. DR Orphanet; 139498; NON RARE IN EUROPE: Hemochromatosis type 1. DR Orphanet; 443057; Sporadic porphyria cutanea tarda. DR Orphanet; 465508; Symptomatic form of HFE-related hemochromatosis. DR PharmGKB; PA29263; -. DR VEuPathDB; HostDB:ENSG00000010704; -. DR eggNOG; KOG1745; Eukaryota. DR GeneTree; ENSGT01100000263517; -. DR HOGENOM; CLU_047501_10_1_1; -. DR InParanoid; Q30201; -. DR OMA; KGWEHMF; -. DR OrthoDB; 3840485at2759; -. DR PhylomeDB; Q30201; -. DR TreeFam; TF336617; -. DR PathwayCommons; Q30201; -. DR Reactome; R-HSA-917977; Transferrin endocytosis and recycling. DR SignaLink; Q30201; -. DR BioGRID-ORCS; 3077; 14 hits in 1151 CRISPR screens. DR EvolutionaryTrace; Q30201; -. DR GeneWiki; HFE_(gene); -. DR GenomeRNAi; 3077; -. DR Pharos; Q30201; Tbio. DR PRO; PR:Q30201; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; Q30201; Protein. DR Bgee; ENSG00000010704; Expressed in stromal cell of endometrium and 183 other cell types or tissues. DR ExpressionAtlas; Q30201; baseline and differential. DR GO; GO:0045177; C:apical part of cell; IDA:UniProtKB. DR GO; GO:0045178; C:basal part of cell; IDA:UniProtKB. DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB. DR GO; GO:0005769; C:early endosome; IDA:UniProtKB. DR GO; GO:0009897; C:external side of plasma membrane; IDA:BHF-UCL. DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL. DR GO; GO:1990712; C:HFE-transferrin receptor complex; IDA:BHF-UCL. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0055037; C:recycling endosome; IDA:UniProtKB. DR GO; GO:0030881; F:beta-2-microglobulin binding; IPI:BHF-UCL. DR GO; GO:0039706; F:co-receptor binding; IPI:BHF-UCL. DR GO; GO:0005102; F:signaling receptor binding; IPI:UniProtKB. DR GO; GO:1990459; F:transferrin receptor binding; IPI:BHF-UCL. DR GO; GO:0002486; P:antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent; IBA:GO_Central. DR GO; GO:0002476; P:antigen processing and presentation of endogenous peptide antigen via MHC class Ib; IBA:GO_Central. DR GO; GO:0030509; P:BMP signaling pathway; IDA:BHF-UCL. DR GO; GO:0071281; P:cellular response to iron ion; IGI:BHF-UCL. DR GO; GO:0042446; P:hormone biosynthetic process; IEA:Ensembl. DR GO; GO:0006879; P:intracellular iron ion homeostasis; IDA:UniProtKB. DR GO; GO:0006826; P:iron ion transport; IEA:UniProtKB-KW. DR GO; GO:0060586; P:multicellular organismal-level iron ion homeostasis; IMP:BHF-UCL. DR GO; GO:1904283; P:negative regulation of antigen processing and presentation of endogenous peptide antigen via MHC class I; IGI:BHF-UCL. DR GO; GO:2001186; P:negative regulation of CD8-positive, alpha-beta T cell activation; IGI:BHF-UCL. DR GO; GO:0032435; P:negative regulation of proteasomal ubiquitin-dependent protein catabolic process; IDA:BHF-UCL. DR GO; GO:1900121; P:negative regulation of receptor binding; IDA:BHF-UCL. DR GO; GO:2000272; P:negative regulation of signaling receptor activity; IDA:BHF-UCL. DR GO; GO:0002725; P:negative regulation of T cell cytokine production; IGI:BHF-UCL. DR GO; GO:2000059; P:negative regulation of ubiquitin-dependent protein catabolic process; IDA:BHF-UCL. DR GO; GO:1904434; P:positive regulation of ferrous iron binding; IGI:BHF-UCL. DR GO; GO:0010628; P:positive regulation of gene expression; ISS:BHF-UCL. DR GO; GO:0090277; P:positive regulation of peptide hormone secretion; IMP:BHF-UCL. DR GO; GO:0032092; P:positive regulation of protein binding; IGI:BHF-UCL. DR GO; GO:1900122; P:positive regulation of receptor binding; IGI:BHF-UCL. DR GO; GO:0048260; P:positive regulation of receptor-mediated endocytosis; IGI:BHF-UCL. DR GO; GO:2000273; P:positive regulation of signaling receptor activity; IGI:BHF-UCL. DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; IDA:BHF-UCL. DR GO; GO:0001916; P:positive regulation of T cell mediated cytotoxicity; IBA:GO_Central. DR GO; GO:1904437; P:positive regulation of transferrin receptor binding; IGI:BHF-UCL. DR GO; GO:0065003; P:protein-containing complex assembly; TAS:ProtInc. DR GO; GO:0034756; P:regulation of iron ion transport; IGI:BHF-UCL. DR GO; GO:2000008; P:regulation of protein localization to cell surface; IMP:BHF-UCL. DR GO; GO:0010039; P:response to iron ion; IMP:BHF-UCL. DR GO; GO:1990641; P:response to iron ion starvation; IBA:GO_Central. DR CDD; cd21021; IgC1_MHC_Ib_HLA-H; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 1. DR Gene3D; 3.30.500.10; MHC class I-like antigen recognition-like; 1. DR InterPro; IPR007110; Ig-like_dom. DR InterPro; IPR036179; Ig-like_dom_sf. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR003006; Ig/MHC_CS. DR InterPro; IPR003597; Ig_C1-set. DR InterPro; IPR011161; MHC_I-like_Ag-recog. DR InterPro; IPR037055; MHC_I-like_Ag-recog_sf. DR InterPro; IPR011162; MHC_I/II-like_Ag-recog. DR InterPro; IPR001039; MHC_I_a_a1/a2. DR PANTHER; PTHR16675:SF172; HEREDITARY HEMOCHROMATOSIS PROTEIN; 1. DR PANTHER; PTHR16675; MHC CLASS I-RELATED; 1. DR Pfam; PF07654; C1-set; 1. DR Pfam; PF00129; MHC_I; 1. DR PRINTS; PR01638; MHCCLASSI. DR SMART; SM00407; IGc1; 1. DR SUPFAM; SSF48726; Immunoglobulin; 1. DR SUPFAM; SSF54452; MHC antigen-recognition domain; 1. DR PROSITE; PS50835; IG_LIKE; 1. DR PROSITE; PS00290; IG_MHC; 1. DR Genevisible; Q30201; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Disease variant; KW Disulfide bond; Glycoprotein; Ion transport; Iron; Iron transport; KW Membrane; Reference proteome; Signal; Transmembrane; Transmembrane helix; KW Transport. FT SIGNAL 1..22 FT CHAIN 23..348 FT /note="Hereditary hemochromatosis protein" FT /id="PRO_0000018892" FT TOPO_DOM 23..306 FT /note="Extracellular" FT /evidence="ECO:0000305|PubMed:9465039" FT TRANSMEM 307..330 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 331..348 FT /note="Cytoplasmic" FT /evidence="ECO:0000305|PubMed:9465039" FT DOMAIN 207..298 FT /note="Ig-like C1-type" FT REGION 23..114 FT /note="Alpha-1" FT REGION 115..205 FT /note="Alpha-2" FT REGION 206..297 FT /note="Alpha-3" FT REGION 298..306 FT /note="Connecting peptide" FT CARBOHYD 110 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 130 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 234 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 124..187 FT DISULFID 225..282 FT VAR_SEQ 26..114 FT /note="RSHSLHYLFMGASEQDLGLSLFEALGYVDDQLFVFYDHESRRVEPRTPWVSS FT RISSQMWLQLSQSLKGWDHMFTVDFWTIMENHNHSKE -> Q (in isoform 2 FT and isoform 4)" FT /evidence="ECO:0000303|PubMed:10079302, FT ECO:0000303|PubMed:11358357" FT /id="VSP_003218" FT VAR_SEQ 26..49 FT /note="RSHSLHYLFMGASEQDLGLSLFEA -> P (in isoform 5)" FT /evidence="ECO:0000303|PubMed:11358357" FT /id="VSP_003219" FT VAR_SEQ 26 FT /note="R -> Q (in isoform 11)" FT /evidence="ECO:0000303|PubMed:11358357" FT /id="VSP_043477" FT VAR_SEQ 26 FT /note="R -> L (in isoform 6)" FT /evidence="ECO:0000303|PubMed:11358357" FT /id="VSP_047336" FT VAR_SEQ 27..298 FT /note="Missing (in isoform 11)" FT /evidence="ECO:0000303|PubMed:11358357" FT /id="VSP_043478" FT VAR_SEQ 27..206 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000303|PubMed:11358357" FT /id="VSP_003220" FT VAR_SEQ 114..219 FT /note="Missing (in isoform 10)" FT /evidence="ECO:0000303|PubMed:11001625" FT /id="VSP_003222" FT VAR_SEQ 114..205 FT /note="Missing (in isoform 7)" FT /evidence="ECO:0000303|PubMed:11001625, FT ECO:0000303|PubMed:11358357" FT /id="VSP_003221" FT VAR_SEQ 144..161 FT /note="DHLEFCPDTLDWRAAEPR -> VLQDTIYSSEVSSLGIKF (in isoform FT 9)" FT /evidence="ECO:0000303|PubMed:11001625" FT /id="VSP_003223" FT VAR_SEQ 162..348 FT /note="Missing (in isoform 9)" FT /evidence="ECO:0000303|PubMed:11001625" FT /id="VSP_003224" FT VAR_SEQ 207..220 FT /note="Missing (in isoform 3 and isoform 4)" FT /evidence="ECO:0000303|PubMed:10079302" FT /id="VSP_003225" FT VAR_SEQ 275..276 FT /note="GE -> KY (in isoform 8)" FT /evidence="ECO:0000303|PubMed:11001625" FT /id="VSP_003226" FT VAR_SEQ 277..348 FT /note="Missing (in isoform 8)" FT /evidence="ECO:0000303|PubMed:11001625" FT /id="VSP_003227" FT VARIANT 6 FT /note="R -> S (in HFE1; uncertain significance; FT dbSNP:rs149342416)" FT /evidence="ECO:0000269|PubMed:12584229" FT /id="VAR_042506" FT VARIANT 43 FT /note="G -> D (in HFE1; associated in cis with D-63 in one FT patient)" FT /evidence="ECO:0000269|PubMed:18157833" FT /id="VAR_042507" FT VARIANT 53 FT /note="V -> M (in dbSNP:rs28934889)" FT /evidence="ECO:0000269|PubMed:10401000, ECO:0000269|Ref.8" FT /id="VAR_008111" FT VARIANT 59 FT /note="V -> M (in dbSNP:rs111033557)" FT /evidence="ECO:0000269|PubMed:10401000" FT /id="VAR_008112" FT VARIANT 63 FT /note="H -> D (in HFE1; associated in cis with D-43 in one FT patient; also found in individuals with variegate FT porphyria; increased frequency among patients with diabetic FT nephropathy; low penetrance variant; dbSNP:rs1799945)" FT /evidence="ECO:0000269|PubMed:10094552, FT ECO:0000269|PubMed:10194428, ECO:0000269|PubMed:10401000, FT ECO:0000269|PubMed:11069625, ECO:0000269|PubMed:11423500, FT ECO:0000269|PubMed:18157833, ECO:0000269|PubMed:8696333, FT ECO:0000269|PubMed:9106528, ECO:0000269|PubMed:9425935, FT ECO:0000269|PubMed:9620340, ECO:0000269|Ref.8" FT /id="VAR_004396" FT VARIANT 65 FT /note="S -> C (in HFE1; mild form; dbSNP:rs1800730)" FT /evidence="ECO:0000269|PubMed:10194428, FT ECO:0000269|PubMed:10575540, ECO:0000269|PubMed:12542741, FT ECO:0000269|PubMed:14633868, ECO:0000269|Ref.25" FT /id="VAR_004397" FT VARIANT 66 FT /note="R -> C (in HFE1; dbSNP:rs747739169)" FT /evidence="ECO:0000269|PubMed:14633868" FT /id="VAR_042508" FT VARIANT 93 FT /note="G -> R (in HFE1; dbSNP:rs28934597)" FT /evidence="ECO:0000269|PubMed:10575540" FT /id="VAR_008729" FT VARIANT 105 FT /note="I -> T (in HFE1; dbSNP:rs28934596)" FT /evidence="ECO:0000269|PubMed:10575540" FT /id="VAR_008730" FT VARIANT 127 FT /note="Q -> H (in HFE1; dbSNP:rs28934595)" FT /evidence="ECO:0000269|PubMed:10401000" FT /id="VAR_008113" FT VARIANT 176 FT /note="A -> V (in HFE1; uncertain significance)" FT /evidence="ECO:0000269|PubMed:11446670" FT /id="VAR_042509" FT VARIANT 217 FT /note="T -> I (in dbSNP:rs4986950)" FT /id="VAR_020270" FT VARIANT 224 FT /note="R -> G (in HFE1)" FT /evidence="ECO:0000269|PubMed:14633868" FT /id="VAR_042510" FT VARIANT 224 FT /note="R -> Q (in dbSNP:rs62625346)" FT /evidence="ECO:0000269|Ref.8" FT /id="VAR_062279" FT VARIANT 277 FT /note="E -> K (in dbSNP:rs140080192)" FT /evidence="ECO:0000269|PubMed:10612845" FT /id="VAR_008731" FT VARIANT 282 FT /note="C -> Y (in HFE1; probable risk factor for porphyria FT cutanea tarda; correlated with increased serum transferrin FT levels; higher frequency in patients with type 2 diabetes FT than in controls; dbSNP:rs1800562)" FT /evidence="ECO:0000269|PubMed:10094552, FT ECO:0000269|PubMed:10194428, ECO:0000269|PubMed:11069625, FT ECO:0000269|PubMed:11423500, ECO:0000269|PubMed:12542741, FT ECO:0000269|PubMed:14633868, ECO:0000269|PubMed:18157833, FT ECO:0000269|PubMed:8696333, ECO:0000269|PubMed:9024376, FT ECO:0000269|PubMed:9106528, ECO:0000269|PubMed:9620340, FT ECO:0000269|Ref.8" FT /id="VAR_004398" FT VARIANT 283 FT /note="Q -> P (in HFE1; destabilizing effect on the FT tertiary structure of the protein; prevents the normal FT interaction between HFE and B2M and between HFE and TFRC; FT decreases the capacity of HFE to reduce FT transferrin-mediated iron uptake; dbSNP:rs111033563)" FT /evidence="ECO:0000269|PubMed:12737937, FT ECO:0000269|PubMed:15965644" FT /id="VAR_037304" FT VARIANT 295 FT /note="V -> A (in HFE1; dbSNP:rs143175221)" FT /evidence="ECO:0000269|PubMed:12542741, FT ECO:0000269|PubMed:15046077" FT /id="VAR_042511" FT VARIANT 330 FT /note="R -> M (in HFE1; dbSNP:rs111033558)" FT /evidence="ECO:0000269|PubMed:10401000" FT /id="VAR_008114" FT CONFLICT 230 FT /note="Y -> H (in Ref. 7; AAG29342)" FT /evidence="ECO:0000305" FT CONFLICT 248 FT /note="A -> T (in Ref. 7; AAG29575)" FT /evidence="ECO:0000305" FT CONFLICT 256 FT /note="V -> A (in Ref. 7; AAG29577)" FT /evidence="ECO:0000305" FT CONFLICT 275 FT /note="G -> E (in Ref. 7; AAG29342)" FT /evidence="ECO:0000305" FT CONFLICT 311 FT /note="S -> R (in Ref. 7; AAG29342)" FT /evidence="ECO:0000305" FT CONFLICT 339 FT /note="M -> V (in Ref. 7; AAG29577)" FT /evidence="ECO:0000305" FT STRAND 28..38 FT /evidence="ECO:0007829|PDB:1A6Z" FT STRAND 43..45 FT /evidence="ECO:0007829|PDB:1A6Z" FT STRAND 48..53 FT /evidence="ECO:0007829|PDB:1A6Z" FT STRAND 56..65 FT /evidence="ECO:0007829|PDB:1A6Z" FT STRAND 68..70 FT /evidence="ECO:0007829|PDB:1A6Z" FT HELIX 75..78 FT /evidence="ECO:0007829|PDB:1DE4" FT TURN 79..82 FT /evidence="ECO:0007829|PDB:1A6Z" FT HELIX 83..107 FT /evidence="ECO:0007829|PDB:1A6Z" FT TURN 108..110 FT /evidence="ECO:0007829|PDB:1A6Z" FT STRAND 112..114 FT /evidence="ECO:0007829|PDB:1A6Z" FT STRAND 117..126 FT /evidence="ECO:0007829|PDB:1A6Z" FT STRAND 132..140 FT /evidence="ECO:0007829|PDB:1A6Z" FT STRAND 143..149 FT /evidence="ECO:0007829|PDB:1A6Z" FT HELIX 150..152 FT /evidence="ECO:0007829|PDB:1A6Z" FT STRAND 154..159 FT /evidence="ECO:0007829|PDB:1A6Z" FT HELIX 160..162 FT /evidence="ECO:0007829|PDB:1A6Z" FT HELIX 163..170 FT /evidence="ECO:0007829|PDB:1A6Z" FT HELIX 174..184 FT /evidence="ECO:0007829|PDB:1A6Z" FT HELIX 186..198 FT /evidence="ECO:0007829|PDB:1A6Z" FT TURN 199..201 FT /evidence="ECO:0007829|PDB:1A6Z" FT STRAND 209..216 FT /evidence="ECO:0007829|PDB:1A6Z" FT STRAND 221..233 FT /evidence="ECO:0007829|PDB:1A6Z" FT STRAND 236..241 FT /evidence="ECO:0007829|PDB:1A6Z" FT HELIX 248..250 FT /evidence="ECO:0007829|PDB:1A6Z" FT STRAND 255..258 FT /evidence="ECO:0007829|PDB:1A6Z" FT STRAND 264..272 FT /evidence="ECO:0007829|PDB:1A6Z" FT HELIX 276..279 FT /evidence="ECO:0007829|PDB:1A6Z" FT STRAND 280..285 FT /evidence="ECO:0007829|PDB:1A6Z" FT STRAND 289..291 FT /evidence="ECO:0007829|PDB:1A6Z" FT STRAND 293..296 FT /evidence="ECO:0007829|PDB:1A6Z" SQ SEQUENCE 348 AA; 40108 MW; 432EB9A314A55BEA CRC64; MGPRARPALL LLMLLQTAVL QGRLLRSHSL HYLFMGASEQ DLGLSLFEAL GYVDDQLFVF YDHESRRVEP RTPWVSSRIS SQMWLQLSQS LKGWDHMFTV DFWTIMENHN HSKESHTLQV ILGCEMQEDN STEGYWKYGY DGQDHLEFCP DTLDWRAAEP RAWPTKLEWE RHKIRARQNR AYLERDCPAQ LQQLLELGRG VLDQQVPPLV KVTHHVTSSV TTLRCRALNY YPQNITMKWL KDKQPMDAKE FEPKDVLPNG DGTYQGWITL AVPPGEEQRY TCQVEHPGLD QPLIVIWEPS PSGTLVIGVI SGIAVFVVIL FIGILFIILR KRQGSRGAMG HYVLAERE //