RGMC_MOUSE
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 03-AUG-2022, entry version 136.
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}.
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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 GlyGen; Q7TQ32; 3 sites.
DR iPTMnet; Q7TQ32; -.
DR PhosphoSitePlus; Q7TQ32; -.
DR MaxQB; Q7TQ32; -.
DR PaxDb; Q7TQ32; -.
DR PRIDE; Q7TQ32; -.
DR ProteomicsDB; 255250; -. [Q7TQ32-1]
DR ProteomicsDB; 255251; -. [Q7TQ32-2]
DR Antibodypedia; 2609; 432 antibodies from 29 providers.
DR DNASU; 69585; -.
DR Ensembl; ENSMUST00000049208; ENSMUSP00000046659; ENSMUSG00000038403. [Q7TQ32-1]
DR GeneID; 69585; -.
DR KEGG; mmu:69585; -.
DR UCSC; uc008qna.2; mouse. [Q7TQ32-1]
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; NDYLYVQ; -.
DR OrthoDB; 1300661at2759; -.
DR PhylomeDB; Q7TQ32; -.
DR TreeFam; TF329836; -.
DR BioGRID-ORCS; 69585; 0 hits in 72 CRISPR screens.
DR PRO; PR:Q7TQ32; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q7TQ32; protein.
DR Bgee; ENSMUSG00000038403; Expressed in interventricular septum and 82 other tissues.
DR Genevisible; Q7TQ32; MM.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
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:0036122; F:BMP binding; IDA:MGI.
DR GO; GO:0098821; F:BMP receptor activity; ISO:MGI.
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:0006879; P:cellular iron ion homeostasis; IMP:BHF-UCL.
DR GO; GO:0071773; P:cellular response to BMP stimulus; ISO:MGI.
DR GO; GO:0055072; P: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 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 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
