ID   RGMC_MOUSE              Reviewed;         420 AA.
AC   Q7TQ32; Q8CEU7; Q8K1D4; Q9D741;
DT   16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2003, sequence version 1.
DT   24-JAN-2024, entry version 144.
DE   RecName: Full=Hemojuvelin {ECO:0000305};
DE   AltName: Full=Hemochromatosis type 2 protein homolog;
DE   AltName: Full=Hemojuvelin BMP coreceptor {ECO:0000305};
DE   AltName: Full=RGM domain family member C;
DE   Flags: Precursor;
GN   Name=Hjv {ECO:0000250|UniProtKB:Q6ZVN8}; Synonyms=Hfe2, Rgmc;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), DEVELOPMENTAL STAGE, AND TISSUE
RP   SPECIFICITY.
RX   PubMed=14678836; DOI=10.1016/s1567-133x(03)00144-3;
RA   Schmidtmer J., Engelkamp D.;
RT   "Isolation and expression pattern of three mouse homologues of chick Rgm.";
RL   Gene Expr. Patterns 4:105-110(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   STRAIN=C57BL/6J; TISSUE=Head, and Tongue;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   STRAIN=FVB/N; TISSUE=Liver;
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   [4]
RP   FUNCTION, AND INTERACTION WITH BMP2 AND BMP4.
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   [5]
RP   FUNCTION, AND INTERACTION WITH BMP6.
RX   PubMed=19252486; DOI=10.1038/ng.335;
RA   Andriopoulos B. Jr., Corradini E., Xia Y., Faasse S.A., Chen S.,
RA   Grgurevic L., Knutson M.D., Pietrangelo A., Vukicevic S., Lin H.Y.,
RA   Babitt J.L.;
RT   "BMP6 is a key endogenous regulator of hepcidin expression and iron
RT   metabolism.";
RL   Nat. Genet. 41:482-487(2009).
RN   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-43, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brown adipose tissue;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
CC   -!- FUNCTION: Acts as a bone morphogenetic protein (BMP) coreceptor.
CC       Through enhancement of BMP signaling regulates hepcidin (HAMP)
CC       expression and regulates iron homeostasis.
CC       {ECO:0000269|PubMed:16604073, ECO:0000269|PubMed:19252486}.
CC   -!- SUBUNIT: Interacts with BMP2 and BMP4 (PubMed:16604073). Interacts with
CC       BMP6 (PubMed:19252486). Interacts with BMPR1B (By similarity).
CC       Interacts with TMPRSS6 (By similarity). {ECO:0000250|UniProtKB:Q6ZVN8,
CC       ECO:0000269|PubMed:16604073}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Lipid-anchor, GPI-
CC       anchor {ECO:0000250}. Note=Also released in the extracellular space.
CC       {ECO:0000250|UniProtKB:Q6ZVN8}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q7TQ32-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q7TQ32-2; Sequence=VSP_011321;
CC   -!- TISSUE SPECIFICITY: Muscle cell lineage. {ECO:0000269|PubMed:14678836}.
CC   -!- DEVELOPMENTAL STAGE: Expressed at low levels in somite derived
CC       structures. In the developing eye, marked the ocular musculature.
CC       Expressed in all differentiating muscles of the limb and the body wall,
CC       but not in migrating muscle precursor cells. Not detected in the
CC       nervous system, either at 9.5 dpc or at any stage later during
CC       development. {ECO:0000269|PubMed:14678836}.
CC   -!- PTM: Autocatalytically cleaved at low pH; the two chains remain linked
CC       via two disulfide bonds. Also proteolytically processed by TMPRSS6,
CC       several fragments being released in the extracellular space; regulates
CC       HJV activity in BMP signaling and thefore iron homeostasis.
CC       {ECO:0000250|UniProtKB:Q6ZVN8}.
CC   -!- SIMILARITY: Belongs to the repulsive guidance molecule (RGM) family.
CC       {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; AJ557515; CAD89720.1; -; mRNA.
DR   EMBL; AK009636; BAB26407.1; -; mRNA.
DR   EMBL; AK014082; BAC25423.1; -; mRNA.
DR   EMBL; BC022603; AAH22603.1; -; mRNA.
DR   CCDS; CCDS51003.1; -. [Q7TQ32-1]
DR   RefSeq; NP_081402.3; NM_027126.4. [Q7TQ32-1]
DR   RefSeq; XP_006502100.1; XM_006502037.3. [Q7TQ32-1]
DR   AlphaFoldDB; Q7TQ32; -.
DR   SMR; Q7TQ32; -.
DR   BioGRID; 213552; 1.
DR   STRING; 10090.ENSMUSP00000046659; -.
DR   GlyCosmos; Q7TQ32; 3 sites, No reported glycans.
DR   GlyGen; Q7TQ32; 3 sites.
DR   iPTMnet; Q7TQ32; -.
DR   PhosphoSitePlus; Q7TQ32; -.
DR   MaxQB; Q7TQ32; -.
DR   PaxDb; 10090-ENSMUSP00000046659; -.
DR   Antibodypedia; 2609; 479 antibodies from 29 providers.
DR   DNASU; 69585; -.
DR   Ensembl; ENSMUST00000049208.11; ENSMUSP00000046659.10; ENSMUSG00000038403.11. [Q7TQ32-1]
DR   GeneID; 69585; -.
DR   KEGG; mmu:69585; -.
DR   UCSC; uc008qna.2; mouse. [Q7TQ32-1]
DR   AGR; MGI:1916835; -.
DR   CTD; 148738; -.
DR   MGI; MGI:1916835; Hjv.
DR   VEuPathDB; HostDB:ENSMUSG00000038403; -.
DR   eggNOG; ENOG502QWAZ; Eukaryota.
DR   GeneTree; ENSGT00950000183112; -.
DR   HOGENOM; CLU_032775_1_1_1; -.
DR   InParanoid; Q7TQ32; -.
DR   OMA; SYQHCAA; -.
DR   OrthoDB; 4091162at2759; -.
DR   PhylomeDB; Q7TQ32; -.
DR   TreeFam; TF329836; -.
DR   BioGRID-ORCS; 69585; 1 hit in 77 CRISPR screens.
DR   PRO; PR:Q7TQ32; -.
DR   Proteomes; UP000000589; Chromosome 3.
DR   RNAct; Q7TQ32; Protein.
DR   Bgee; ENSMUSG00000038403; Expressed in interventricular septum and 84 other cell types or tissues.
DR   GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI.
DR   GO; GO:0070724; C:BMP receptor complex; ISO:MGI.
DR   GO; GO:0009986; C:cell surface; IDA:MGI.
DR   GO; GO:0005615; C:extracellular space; IDA:MGI.
DR   GO; GO:1990712; C:HFE-transferrin receptor complex; ISO:MGI.
DR   GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR   GO; GO:0098797; C:plasma membrane protein complex; ISO:MGI.
DR   GO; GO:0098552; C:side of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0036122; F:BMP binding; IDA:MGI.
DR   GO; GO:0098821; F:BMP receptor activity; IEA:Ensembl.
DR   GO; GO:0015026; F:coreceptor activity; IGI:MGI.
DR   GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR   GO; GO:1990459; F:transferrin receptor binding; ISO:MGI.
DR   GO; GO:0032924; P:activin receptor signaling pathway; ISO:MGI.
DR   GO; GO:0030509; P:BMP signaling pathway; IMP:MGI.
DR   GO; GO:0071773; P:cellular response to BMP stimulus; ISO:MGI.
DR   GO; GO:0006879; P:intracellular iron ion homeostasis; IMP:BHF-UCL.
DR   GO; GO:0060586; P:multicellular organismal-level iron ion homeostasis; IMP:MGI.
DR   GO; GO:0030514; P:negative regulation of BMP signaling pathway; IGI:MGI.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR   GO; GO:0016540; P:protein autoprocessing; ISO:MGI.
DR   GO; GO:0006366; P:transcription by RNA polymerase II; IDA:MGI.
DR   Gene3D; 3.40.1000.10; Mog1/PsbP, alpha/beta/alpha sandwich; 1.
DR   InterPro; IPR040287; RGM.
DR   InterPro; IPR009496; RGM_C.
DR   InterPro; IPR010536; RGM_N.
DR   PANTHER; PTHR31428:SF3; HEMOJUVELIN; 1.
DR   PANTHER; PTHR31428; RGM DOMAIN FAMILY MEMBER DRAG-1; 1.
DR   Pfam; PF06534; RGM_C; 1.
DR   Pfam; PF06535; RGM_N; 1.
DR   Genevisible; Q7TQ32; MM.
PE   1: Evidence at protein level;
KW   Alternative splicing; Autocatalytic cleavage; Cell membrane;
KW   Disulfide bond; Glycoprotein; GPI-anchor; Lipoprotein; Membrane;
KW   Phosphoprotein; Reference proteome; Signal.
FT   SIGNAL          1..32
FT                   /evidence="ECO:0000255"
FT   CHAIN           33..393
FT                   /note="Hemojuvelin"
FT                   /id="PRO_0000030400"
FT   PROPEP          394..420
FT                   /note="Removed in mature form"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000030401"
FT   REGION          113..135
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        119..135
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            165..166
FT                   /note="Cleavage; by autolysis"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         43
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   LIPID           393
FT                   /note="GPI-anchor amidated aspartate"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        111
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        206
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        365
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        141..223
FT                   /evidence="ECO:0000250"
FT   DISULFID        160..310
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         1..219
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334,
FT                   ECO:0000303|PubMed:16141072"
FT                   /id="VSP_011321"
FT   CONFLICT        264
FT                   /note="G -> W (in Ref. 2; BAC25423)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        379
FT                   /note="I -> V (in Ref. 3; AAH22603)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   420 AA;  44848 MW;  B336B0686EDFC938 CRC64;
     MGQSPSPRSP HGSPPTLSTL TLLLLLCGQA HSQCKILRCN AEYVSSTLSL RGGGSPDTPR
     GGGRGGLASG GLCRALRSYA LCTRRTARTC RGDLAFHSAV HGIEDLMIQH NCSRQGPTAP
     PPARGPALPG AGPAPLTPDP CDYEARFSRL HGRAPGFLHC ASFGDPHVRS FHNQFHTCRV
     QGAWPLLDND FLFVQATSSP VSSGANATTI RKITIIFKNM QECIDQKVYQ AEVDNLPAAF
     EDGSINGGDR PGGSSLSIQT ANLGSHVEIR AAYIGTTIII RQTAGQLSFS IRVAEDVARA
     FSAEQDLQLC VGGCPPSQRL SRSERNRRGA IAIDTARRLC KEGLPVEDAY FQSCVFDVSV
     SGDPNFTVAA QTALDDARIF LTDLENLHLF PSDAGPPLSP AICLVPLLSA LFVLWLCFSK
//