RGMC_HUMAN
ID RGMC_HUMAN Reviewed; 426 AA.
AC Q6ZVN8; B1ALI7; Q2PQ63; Q6IMF6; Q8NAH2; Q8WVJ5;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Hemojuvelin {ECO:0000305};
DE AltName: Full=Hemochromatosis type 2 protein;
DE AltName: Full=Hemojuvelin BMP coreceptor {ECO:0000305};
DE AltName: Full=RGM domain family member C;
DE Flags: Precursor;
GN Name=HJV {ECO:0000312|HGNC:HGNC:4887}; Synonyms=HFE2, RGMC;
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 A), ALTERNATIVE SPLICING, TISSUE
RP SPECIFICITY, AND VARIANTS HFE2A ASN-222 AND VAL-320.
RC TISSUE=Liver;
RX PubMed=14647275; DOI=10.1038/ng1274;
RA Papanikolaou G., Samuels M.E., Ludwig E.H., MacDonald M.L.E.,
RA Franchini P.L., Dube M.-P., Andres L., MacFarlane J., Sakellaropoulos N.,
RA Politou M., Nemeth E., Thompson J., Risler J.K., Zaborowska C.,
RA Babakaiff R., Radomski C.C., Pape T.D., Davidas O., Christakis J.,
RA Brissot P., Lockitch G., Ganz T., Hayden M.R., Goldberg Y.P.;
RT "Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile
RT hemochromatosis.";
RL Nat. Genet. 36:77-82(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS A AND B).
RC TISSUE=Liver, and Skeletal muscle;
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 [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
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] (ISOFORMS B AND C).
RC TISSUE=PNS, and Skeletal muscle;
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 INTERACTION WITH BMPR1B.
RX PubMed=16604073; DOI=10.1038/ng1777;
RA Babitt J.L., Huang F.W., Wrighting D.M., Xia Y., Sidis Y., Samad T.A.,
RA Campagna J.A., Chung R.T., Schneyer A.L., Woolf C.J., Andrews N.C.,
RA Lin H.Y.;
RT "Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin
RT expression.";
RL Nat. Genet. 38:531-539(2006).
RN [8]
RP FUNCTION, INTERACTION WITH TMPRSS6, AND PROTEOLYTIC PROCESSING.
RX PubMed=18976966; DOI=10.1016/j.cmet.2008.09.012;
RA Silvestri L., Pagani A., Nai A., De Domenico I., Kaplan J., Camaschella C.;
RT "The serine protease matriptase-2 (TMPRSS6) inhibits hepcidin activation by
RT cleaving membrane hemojuvelin.";
RL Cell Metab. 8:502-511(2008).
RN [9]
RP INTERACTION WITH TMPRSS6.
RX PubMed=19357398; DOI=10.1182/blood-2008-12-195594;
RA Silvestri L., Guillem F., Pagani A., Nai A., Oudin C., Silva M.,
RA Toutain F., Kannengiesser C., Beaumont C., Camaschella C., Grandchamp B.;
RT "Molecular mechanisms of the defective hepcidin inhibition in TMPRSS6
RT mutations associated with iron-refractory iron deficiency anemia.";
RL Blood 113:5605-5608(2009).
RN [10]
RP SUBCELLULAR LOCATION, AND PROTEOLYTIC PROCESSING.
RX PubMed=25156943; DOI=10.1002/humu.22632;
RA De Falco L., Silvestri L., Kannengiesser C., Moran E., Oudin C., Rausa M.,
RA Bruno M., Aranda J., Argiles B., Yenicesu I., Falcon-Rodriguez M.,
RA Yilmaz-Keskin E., Kocak U., Beaumont C., Camaschella C., Iolascon A.,
RA Grandchamp B., Sanchez M.;
RT "Functional and clinical impact of novel TMPRSS6 variants in iron-
RT refractory iron-deficiency anemia patients and genotype-phenotype
RT studies.";
RL Hum. Mutat. 35:1321-1329(2014).
RN [11]
RP VARIANTS HFE2A PRO-85; ARG-99; ASP-168; SER-170; GLU-172; CYS-191; ARG-205;
RP VAL-250; TRP-288 AND VAL-320.
RX PubMed=14982873; DOI=10.1182/blood-2004-01-0192;
RA Lanzara C., Roetto A., Daraio F., Rivard S., Ficarella R., Simard H.,
RA Cox T.M., Cazzola M., Piperno A., Gimenez-Roqueplo A.P., Grammatico P.,
RA Volinia S., Gasparini P., Camaschella C.;
RT "Spectrum of hemojuvelin gene mutations in 1q-linked juvenile
RT hemochromatosis.";
RL Blood 103:4317-4321(2004).
RN [12]
RP VARIANTS HFE2A ARG-80; PRO-101; ASN-222 AND VAL-320.
RX PubMed=14982867; DOI=10.1182/blood-2004-01-0072;
RA Lee P.L., Beutler E., Rao S.V., Barton J.C.;
RT "Genetic abnormalities and juvenile hemochromatosis: mutations of the HJV
RT gene encoding hemojuvelin.";
RL Blood 103:4669-4671(2004).
RN [13]
RP VARIANTS HFE2A VAL-320 AND TRP-321.
RX PubMed=15461631; DOI=10.1111/j.1365-2141.2004.05165.x;
RA Lee P.L., Barton J.C., Brandhagen D., Beutler E.;
RT "Hemojuvelin (HJV) mutations in persons of European, African-American and
RT Asian ancestry with adult onset haemochromatosis.";
RL Br. J. Haematol. 127:224-229(2004).
CC -!- FUNCTION: Acts as a bone morphogenetic protein (BMP) coreceptor
CC (PubMed:18976966). Through enhancement of BMP signaling regulates
CC hepcidin (HAMP) expression and regulates iron homeostasis
CC (PubMed:18976966). {ECO:0000269|PubMed:18976966}.
CC -!- SUBUNIT: Interacts with BMP2 and BMP4 (By similarity). Interacts with
CC BMP6 (By similarity). Interacts with BMPR1B (PubMed:16604073).
CC Interacts with TMPRSS6 (PubMed:18976966, PubMed:19357398).
CC {ECO:0000250|UniProtKB:Q7TQ32, ECO:0000269|PubMed:16604073,
CC ECO:0000269|PubMed:18976966, ECO:0000269|PubMed:19357398}.
CC -!- INTERACTION:
CC Q6ZVN8; P12643: BMP2; NbExp=2; IntAct=EBI-10900704, EBI-1029262;
CC Q6ZVN8; Q92859: NEO1; NbExp=3; IntAct=EBI-10900704, EBI-2829116;
CC Q6ZVN8; Q8IU80-4: TMPRSS6; NbExp=3; IntAct=EBI-10900704, EBI-11686560;
CC Q6ZVN8-1; P12643: BMP2; NbExp=2; IntAct=EBI-16155543, EBI-1029262;
CC Q6ZVN8-3; P55061: TMBIM6; NbExp=3; IntAct=EBI-12827977, EBI-1045825;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Lipid-anchor, GPI-
CC anchor {ECO:0000250}. Note=Also released in the extracellular space.
CC {ECO:0000269|PubMed:25156943}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=a;
CC IsoId=Q6ZVN8-1; Sequence=Displayed;
CC Name=b;
CC IsoId=Q6ZVN8-2; Sequence=VSP_011319;
CC Name=c;
CC IsoId=Q6ZVN8-3; Sequence=VSP_011320;
CC -!- TISSUE SPECIFICITY: Adult and fetal liver, heart, and skeletal muscle.
CC {ECO:0000269|PubMed:14647275}.
CC -!- PTM: Autocatalytically cleaved at low pH; the two chains remain linked
CC via two disulfide bonds (PubMed:25156943). Also proteolytically
CC processed by TMPRSS6, several fragments being released in the
CC extracellular space; regulates HJV activity in BMP signaling and
CC thefore iron homeostasis (PubMed:18976966, PubMed:25156943).
CC {ECO:0000269|PubMed:18976966, ECO:0000269|PubMed:25156943}.
CC -!- DISEASE: Hemochromatosis 2A (HFE2A) [MIM:602390]: A juvenile form of
CC hemochromatosis, a disorder of iron metabolism with excess deposition
CC of iron in a variety of organs leading to their failure, bronze skin
CC pigmentation, hepatic cirrhosis, arthropathy and diabetes. The most
CC common symptoms of juvenile hemochromatosis at presentation are
CC hypogonadism and cardiomyopathy. {ECO:0000269|PubMed:14647275,
CC ECO:0000269|PubMed:14982867, ECO:0000269|PubMed:14982873,
CC ECO:0000269|PubMed:15461631}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the repulsive guidance molecule (RGM) family.
CC {ECO:0000305}.
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DR EMBL; AY372521; AAR22390.1; -; mRNA.
DR EMBL; AK092682; BAC03944.1; -; mRNA.
DR EMBL; AK124273; BAC85823.1; -; mRNA.
DR EMBL; AK092692; BAC03947.1; -; mRNA.
DR EMBL; AK096905; BAC04890.1; -; mRNA.
DR EMBL; DQ309445; ABC40718.1; -; Genomic_DNA.
DR EMBL; AL355505; CAI22091.1; -; Genomic_DNA.
DR EMBL; AL138842; CAI22091.1; JOINED; Genomic_DNA.
DR EMBL; AL138842; CAI22349.1; -; Genomic_DNA.
DR EMBL; AL355505; CAI22349.1; JOINED; Genomic_DNA.
DR EMBL; CH471244; EAW71408.1; -; Genomic_DNA.
DR EMBL; BC017926; AAH17926.1; -; mRNA.
DR EMBL; BC085604; AAH85604.1; -; mRNA.
DR CCDS; CCDS72877.1; -. [Q6ZVN8-3]
DR CCDS; CCDS72878.1; -. [Q6ZVN8-2]
DR CCDS; CCDS72879.1; -. [Q6ZVN8-1]
DR RefSeq; NP_001303696.1; NM_001316767.1. [Q6ZVN8-3]
DR RefSeq; NP_660320.3; NM_145277.4. [Q6ZVN8-2]
DR RefSeq; NP_973733.1; NM_202004.3. [Q6ZVN8-3]
DR RefSeq; NP_998817.1; NM_213652.3. [Q6ZVN8-3]
DR RefSeq; NP_998818.1; NM_213653.3. [Q6ZVN8-1]
DR RefSeq; XP_005272989.1; XM_005272932.1.
DR PDB; 4UI1; X-ray; 2.35 A; C/D=35-145.
DR PDB; 6Z3L; X-ray; 2.51 A; B=36-145.
DR PDBsum; 4UI1; -.
DR PDBsum; 6Z3L; -.
DR AlphaFoldDB; Q6ZVN8; -.
DR SMR; Q6ZVN8; -.
DR BioGRID; 127164; 2.
DR DIP; DIP-61608N; -.
DR IntAct; Q6ZVN8; 5.
DR STRING; 9606.ENSP00000337014; -.
DR GlyGen; Q6ZVN8; 4 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q6ZVN8; -.
DR PhosphoSitePlus; Q6ZVN8; -.
DR BioMuta; HFE2; -.
DR DMDM; 51316254; -.
DR MassIVE; Q6ZVN8; -.
DR PaxDb; Q6ZVN8; -.
DR PeptideAtlas; Q6ZVN8; -.
DR PRIDE; Q6ZVN8; -.
DR ProteomicsDB; 68433; -. [Q6ZVN8-2]
DR Antibodypedia; 2609; 432 antibodies from 29 providers.
DR DNASU; 148738; -.
DR Ensembl; ENST00000336751.11; ENSP00000337014.5; ENSG00000168509.20. [Q6ZVN8-1]
DR Ensembl; ENST00000357836.5; ENSP00000350495.5; ENSG00000168509.20. [Q6ZVN8-2]
DR Ensembl; ENST00000475797.1; ENSP00000425716.1; ENSG00000168509.20. [Q6ZVN8-3]
DR Ensembl; ENST00000497365.5; ENSP00000421820.1; ENSG00000168509.20. [Q6ZVN8-3]
DR Ensembl; ENST00000636675.1; ENSP00000490072.1; ENSG00000168509.20. [Q6ZVN8-3]
DR GeneID; 148738; -.
DR KEGG; hsa:148738; -.
DR MANE-Select; ENST00000336751.11; ENSP00000337014.5; NM_213653.4; NP_998818.1.
DR UCSC; uc001eni.3; human. [Q6ZVN8-1]
DR CTD; 148738; -.
DR DisGeNET; 148738; -.
DR GeneCards; HJV; -.
DR GeneReviews; HJV; -.
DR HGNC; HGNC:4887; HJV.
DR HPA; ENSG00000168509; Group enriched (liver, skeletal muscle, tongue).
DR MalaCards; HJV; -.
DR MIM; 602390; phenotype.
DR MIM; 608374; gene.
DR neXtProt; NX_Q6ZVN8; -.
DR OpenTargets; ENSG00000168509; -.
DR Orphanet; 79230; Hemochromatosis type 2.
DR PharmGKB; PA29264; -.
DR VEuPathDB; HostDB:ENSG00000168509; -.
DR eggNOG; ENOG502QWAZ; Eukaryota.
DR GeneTree; ENSGT00950000183112; -.
DR HOGENOM; CLU_032775_1_1_1; -.
DR InParanoid; Q6ZVN8; -.
DR OMA; DYEGQFS; -.
DR PhylomeDB; Q6ZVN8; -.
DR TreeFam; TF329836; -.
DR PathwayCommons; Q6ZVN8; -.
DR Reactome; R-HSA-373752; Netrin-1 signaling.
DR SignaLink; Q6ZVN8; -.
DR BioGRID-ORCS; 148738; 28 hits in 1078 CRISPR screens.
DR ChiTaRS; HFE2; human.
DR GeneWiki; Hemojuvelin; -.
DR GenomeRNAi; 148738; -.
DR Pharos; Q6ZVN8; Tbio.
DR PRO; PR:Q6ZVN8; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q6ZVN8; protein.
DR Bgee; ENSG00000168509; Expressed in hindlimb stylopod muscle and 112 other tissues.
DR ExpressionAtlas; Q6ZVN8; baseline and differential.
DR Genevisible; Q6ZVN8; HS.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0070724; C:BMP receptor complex; IDA:BHF-UCL.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:1990712; C:HFE-transferrin receptor complex; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0098797; C:plasma membrane protein complex; IDA:BHF-UCL.
DR GO; GO:0036122; F:BMP binding; IPI:BHF-UCL.
DR GO; GO:0015026; F:coreceptor activity; IDA:BHF-UCL.
DR GO; GO:0005102; F:signaling receptor binding; IPI:BHF-UCL.
DR GO; GO:1990459; F:transferrin receptor binding; IPI:BHF-UCL.
DR GO; GO:0032924; P:activin receptor signaling pathway; IGI:BHF-UCL.
DR GO; GO:0030509; P:BMP signaling pathway; IMP:BHF-UCL.
DR GO; GO:0006879; P:cellular iron ion homeostasis; ISS:BHF-UCL.
DR GO; GO:0071773; P:cellular response to BMP stimulus; IMP:BHF-UCL.
DR GO; GO:0055072; P:iron ion homeostasis; IDA:MGI.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0016540; P:protein autoprocessing; IMP:BHF-UCL.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl.
DR DisProt; DP02661; -.
DR InterPro; IPR033606; Hemojuvelin.
DR InterPro; IPR040287; RGM.
DR InterPro; IPR009496; RGM_C.
DR InterPro; IPR010536; RGM_N.
DR PANTHER; PTHR31428; PTHR31428; 1.
DR PANTHER; PTHR31428:SF3; PTHR31428:SF3; 1.
DR Pfam; PF06534; RGM_C; 1.
DR Pfam; PF06535; RGM_N; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Autocatalytic cleavage; Cell membrane;
KW Disease variant; Disulfide bond; Glycoprotein; GPI-anchor; Lipoprotein;
KW Membrane; Phosphoprotein; Reference proteome; Signal.
FT SIGNAL 1..35
FT /evidence="ECO:0000255"
FT CHAIN 36..400
FT /note="Hemojuvelin"
FT /id="PRO_0000030398"
FT PROPEP 401..426
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000030399"
FT REGION 119..142
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 172..173
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250"
FT MOD_RES 46
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q7TQ32"
FT LIPID 400
FT /note="GPI-anchor amidated aspartate"
FT /evidence="ECO:0000255"
FT CARBOHYD 118
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 213
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 372
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 148..230
FT /evidence="ECO:0000250"
FT DISULFID 167..317
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..226
FT /note="Missing (in isoform c)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_011320"
FT VAR_SEQ 1..113
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_011319"
FT VARIANT 80
FT /note="C -> R (in HFE2A; dbSNP:rs28940586)"
FT /evidence="ECO:0000269|PubMed:14982867"
FT /id="VAR_019617"
FT VARIANT 85
FT /note="S -> P (in HFE2A; dbSNP:rs1553769752)"
FT /evidence="ECO:0000269|PubMed:14982873"
FT /id="VAR_019618"
FT VARIANT 99
FT /note="G -> R (in HFE2A; dbSNP:rs1553769745)"
FT /evidence="ECO:0000269|PubMed:14982873"
FT /id="VAR_019619"
FT VARIANT 101
FT /note="L -> P (in HFE2A; dbSNP:rs74315327)"
FT /evidence="ECO:0000269|PubMed:14982867"
FT /id="VAR_019620"
FT VARIANT 168
FT /note="A -> D (in HFE2A; dbSNP:rs782125244)"
FT /evidence="ECO:0000269|PubMed:14982873"
FT /id="VAR_019621"
FT VARIANT 170
FT /note="F -> S (in HFE2A; dbSNP:rs1553769659)"
FT /evidence="ECO:0000269|PubMed:14982873"
FT /id="VAR_019622"
FT VARIANT 172
FT /note="D -> E (in HFE2A; dbSNP:rs782708481)"
FT /evidence="ECO:0000269|PubMed:14982873"
FT /id="VAR_019623"
FT VARIANT 191
FT /note="W -> C (in HFE2A; dbSNP:rs1553769634)"
FT /evidence="ECO:0000269|PubMed:14982873"
FT /id="VAR_019624"
FT VARIANT 205
FT /note="S -> R (in HFE2A; dbSNP:rs1553769627)"
FT /evidence="ECO:0000269|PubMed:14982873"
FT /id="VAR_019625"
FT VARIANT 222
FT /note="I -> N (in HFE2A; dbSNP:rs74315325)"
FT /evidence="ECO:0000269|PubMed:14647275,
FT ECO:0000269|PubMed:14982867"
FT /id="VAR_019626"
FT VARIANT 250
FT /note="G -> V (in HFE2A; dbSNP:rs863224819)"
FT /evidence="ECO:0000269|PubMed:14982873"
FT /id="VAR_019627"
FT VARIANT 288
FT /note="R -> W (in HFE2A; dbSNP:rs782493762)"
FT /evidence="ECO:0000269|PubMed:14982873"
FT /id="VAR_019628"
FT VARIANT 310
FT /note="A -> G (in dbSNP:rs7540883)"
FT /id="VAR_053636"
FT VARIANT 320
FT /note="G -> V (in HFE2A; dbSNP:rs74315323)"
FT /evidence="ECO:0000269|PubMed:14647275,
FT ECO:0000269|PubMed:14982867, ECO:0000269|PubMed:14982873,
FT ECO:0000269|PubMed:15461631"
FT /id="VAR_019629"
FT VARIANT 321
FT /note="C -> W (in HFE2A; dbSNP:rs121434374)"
FT /evidence="ECO:0000269|PubMed:15461631"
FT /id="VAR_019927"
FT CONFLICT 69
FT /note="G -> GG (in Ref. 3; ABC40718)"
FT /evidence="ECO:0000305"
FT CONFLICT 299
FT /note="K -> E (in Ref. 2; BAC03944)"
FT /evidence="ECO:0000305"
FT HELIX 39..51
FT /evidence="ECO:0007829|PDB:4UI1"
FT HELIX 78..93
FT /evidence="ECO:0007829|PDB:4UI1"
FT HELIX 94..96
FT /evidence="ECO:0007829|PDB:4UI1"
FT HELIX 101..116
FT /evidence="ECO:0007829|PDB:4UI1"
SQ SEQUENCE 426 AA; 45080 MW; 031C835F9B6DC06C CRC64;
MGEPGQSPSP RSSHGSPPTL STLTLLLLLC GHAHSQCKIL RCNAEYVSST LSLRGGGSSG
ALRGGGGGGR GGGVGSGGLC RALRSYALCT RRTARTCRGD LAFHSAVHGI EDLMIQHNCS
RQGPTAPPPP RGPALPGAGS GLPAPDPCDY EGRFSRLHGR PPGFLHCASF GDPHVRSFHH
HFHTCRVQGA WPLLDNDFLF VQATSSPMAL GANATATRKL TIIFKNMQEC IDQKVYQAEV
DNLPVAFEDG SINGGDRPGG SSLSIQTANP GNHVEIQAAY IGTTIIIRQT AGQLSFSIKV
AEDVAMAFSA EQDLQLCVGG CPPSQRLSRS ERNRRGAITI DTARRLCKEG LPVEDAYFHS
CVFDVLISGD PNFTVAAQAA LEDARAFLPD LEKLHLFPSD AGVPLSSATL LAPLLSGLFV
LWLCIQ
