RBCC Red Blood Cell Collection

BMP6 (VGR) [Confidence: low (only semi-automatic identification from reviews)]
Bone morphogenetic protein 6; BMP-6 (VG-1-related protein; VG-1-R; VGR-1; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)

UniProt P22004
ID BMP6_HUMAN Reviewed; 513 AA.
AC P22004; Q5TCP3;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-AUG-1991, sequence version 1.
DT 22-JAN-2014, entry version 136.
DE RecName: Full=Bone morphogenetic protein 6;
DE Short=BMP-6;
DE AltName: Full=VG-1-related protein;
DE Short=VG-1-R;
DE Short=VGR-1;
DE Flags: Precursor;
GN Name=BMP6; Synonyms=VGR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Bone;
RX PubMed=2263636; DOI=10.1073/pnas.87.24.9843;
RA Celeste A.J., Iannazzi J.A., Taylor R.C., Hewick R.M., Rosen V.,
RA Wang E.A., Wozney J.M.;
RT "Identification of transforming growth factor beta family members
RT present in bone-inductive protein purified from bovine bone.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:9843-9847(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [3]
RP VARIANTS [LARGE SCALE ANALYSIS] ASP-343 AND LEU-476.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.49 ANGSTROMS) OF 382-513.
RX PubMed=17924656; DOI=10.1021/bi700907k;
RA Allendorph G.P., Isaacs M.J., Kawakami Y., Izpisua Belmonte J.C.,
RA Choe S.;
RT "BMP-3 and BMP-6 structures illuminate the nature of binding
RT specificity with receptors.";
RL Biochemistry 46:12238-12247(2007).
CC -!- FUNCTION: Induces cartilage and bone formation.
CC -!- SUBUNIT: Interacts with SOSTDC1 (By similarity).
CC -!- SUBCELLULAR LOCATION: Secreted (By similarity).
CC -!- SIMILARITY: Belongs to the TGF-beta family.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Bone morphogenetic protein 6
CC entry;
CC URL="http://en.wikipedia.org/wiki/Bone_morphogenetic_protein_6";
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DR EMBL; M60315; AAA36737.1; -; mRNA.
DR EMBL; AL135778; CAI19426.1; -; Genomic_DNA.
DR EMBL; AL133541; CAI19426.1; JOINED; Genomic_DNA.
DR EMBL; AL133541; CAI19472.1; -; Genomic_DNA.
DR EMBL; AL135778; CAI19472.1; JOINED; Genomic_DNA.
DR PIR; B39263; BMHU6.
DR RefSeq; NP_001709.1; NM_001718.4.
DR UniGene; Hs.285671; -.
DR PDB; 2QCW; X-ray; 2.49 A; A/B=382-513.
DR PDB; 2R52; X-ray; 2.50 A; A/B=375-513.
DR PDB; 2R53; X-ray; 2.10 A; A/B=411-513.
DR PDBsum; 2QCW; -.
DR PDBsum; 2R52; -.
DR PDBsum; 2R53; -.
DR ProteinModelPortal; P22004; -.
DR SMR; P22004; 411-513.
DR DIP; DIP-5797N; -.
DR STRING; 9606.ENSP00000283147; -.
DR PhosphoSite; P22004; -.
DR DMDM; 115076; -.
DR PaxDb; P22004; -.
DR PRIDE; P22004; -.
DR DNASU; 654; -.
DR Ensembl; ENST00000283147; ENSP00000283147; ENSG00000153162.
DR GeneID; 654; -.
DR KEGG; hsa:654; -.
DR UCSC; uc003mxu.4; human.
DR CTD; 654; -.
DR GeneCards; GC06P007672; -.
DR HGNC; HGNC:1073; BMP6.
DR HPA; CAB002773; -.
DR MIM; 112266; gene.
DR neXtProt; NX_P22004; -.
DR PharmGKB; PA25383; -.
DR eggNOG; NOG272883; -.
DR HOGENOM; HOG000249476; -.
DR HOVERGEN; HBG004860; -.
DR InParanoid; P22004; -.
DR KO; K16620; -.
DR OMA; WWGLLCS; -.
DR OrthoDB; EOG7J9VPQ; -.
DR PhylomeDB; P22004; -.
DR SignaLink; P22004; -.
DR ChiTaRS; BMP6; human.
DR EvolutionaryTrace; P22004; -.
DR GeneWiki; Bone_morphogenetic_protein_6; -.
DR GenomeRNAi; 654; -.
DR NextBio; 2660; -.
DR PRO; PR:P22004; -.
DR ArrayExpress; P22004; -.
DR Bgee; P22004; -.
DR CleanEx; HS_BMP6; -.
DR Genevestigator; P22004; -.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR GO; GO:0031988; C:membrane-bounded vesicle; IEA:Ensembl.
DR GO; GO:0046982; F:protein heterodimerization activity; IDA:MGI.
DR GO; GO:0030509; P:BMP signaling pathway; IDA:BHF-UCL.
DR GO; GO:0051216; P:cartilage development; IEA:UniProtKB-KW.
DR GO; GO:0001958; P:endochondral ossification; IEA:Ensembl.
DR GO; GO:0001654; P:eye development; IEA:Ensembl.
DR GO; GO:0040007; P:growth; IEA:InterPro.
DR GO; GO:0006955; P:immune response; IMP:BHF-UCL.
DR GO; GO:0006954; P:inflammatory response; IEA:Ensembl.
DR GO; GO:0001822; P:kidney development; IEA:Ensembl.
DR GO; GO:0030539; P:male genitalia development; IEA:Ensembl.
DR GO; GO:0001649; P:osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0032349; P:positive regulation of aldosterone biosynthetic process; IDA:UniProtKB.
DR GO; GO:0030501; P:positive regulation of bone mineralization; IDA:BHF-UCL.
DR GO; GO:2000105; P:positive regulation of DNA-dependent DNA replication; NAS:BHF-UCL.
DR GO; GO:0045603; P:positive regulation of endothelial cell differentiation; IEA:Ensembl.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IEA:Ensembl.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IDA:BHF-UCL.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IDA:BHF-UCL.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0050714; P:positive regulation of protein secretion; NAS:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
DR GO; GO:0051384; P:response to glucocorticoid stimulus; IEA:Ensembl.
DR GO; GO:0032526; P:response to retinoic acid; IEA:Ensembl.
DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc.
DR GO; GO:0060395; P:SMAD protein signal transduction; IDA:UniProtKB.
DR GO; GO:0003323; P:type B pancreatic cell development; IDA:BHF-UCL.
DR InterPro; IPR001839; TGF-b_C.
DR InterPro; IPR001111; TGF-b_N.
DR InterPro; IPR015615; TGF-beta-rel.
DR InterPro; IPR017948; TGFb_CS.
DR PANTHER; PTHR11848; PTHR11848; 1.
DR Pfam; PF00019; TGF_beta; 1.
DR Pfam; PF00688; TGFb_propeptide; 1.
DR SMART; SM00204; TGFB; 1.
DR PROSITE; PS00250; TGF_BETA_1; 1.
DR PROSITE; PS51362; TGF_BETA_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Chondrogenesis; Cleavage on pair of basic residues;
KW Complete proteome; Cytokine; Developmental protein; Differentiation;
KW Disulfide bond; Glycoprotein; Growth factor; Osteogenesis;
KW Polymorphism; Reference proteome; Secreted; Signal.
FT SIGNAL 1 20 Potential.
FT PROPEP 21 374 Potential.
FT /FTId=PRO_0000033870.
FT CHAIN 375 513 Bone morphogenetic protein 6.
FT /FTId=PRO_0000033871.
FT CARBOHYD 241 241 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 269 269 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 386 386 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 404 404 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 454 454 N-linked (GlcNAc...) (Potential).
FT DISULFID 412 478 By similarity.
FT DISULFID 441 510 By similarity.
FT DISULFID 445 512 By similarity.
FT DISULFID 477 477 Interchain (By similarity).
FT VARIANT 257 257 R -> C (in dbSNP:rs10458105).
FT /FTId=VAR_047055.
FT VARIANT 343 343 A -> D (in a colorectal cancer sample;
FT somatic mutation).
FT /FTId=VAR_036200.
FT VARIANT 476 476 P -> L (in a colorectal cancer sample;
FT somatic mutation).
FT /FTId=VAR_036201.
FT STRAND 411 415
FT STRAND 418 420
FT TURN 421 425
FT TURN 427 429
FT STRAND 430 432
FT STRAND 434 437
FT STRAND 440 442
FT TURN 451 454
FT HELIX 457 468
FT TURN 470 472
FT STRAND 477 491
FT STRAND 497 513
SQ SEQUENCE 513 AA; 57226 MW; 3F19155B36049278 CRC64;
MPGLGRRAQW LCWWWGLLCS CCGPPPLRPP LPAAAAAAAG GQLLGDGGSP GRTEQPPPSP
QSSSGFLYRR LKTQEKREMQ KEILSVLGLP HRPRPLHGLQ QPQPPALRQQ EEQQQQQQLP
RGEPPPGRLK SAPLFMLDLY NALSADNDED GASEGERQQS WPHEAASSSQ RRQPPPGAAH
PLNRKSLLAP GSGSGGASPL TSAQDSAFLN DADMVMSFVN LVEYDKEFSP RQRHHKEFKF
NLSQIPEGEV VTAAEFRIYK DCVMGSFKNQ TFLISIYQVL QEHQHRDSDL FLLDTRVVWA
SEEGWLEFDI TATSNLWVVT PQHNMGLQLS VVTRDGVHVH PRAAGLVGRD GPYDKQPFMV
AFFKVSEVHV RTTRSASSRR RQQSRNRSTQ SQDVARVSSA SDYNSSELKT ACRKHELYVS
FQDLGWQDWI IAPKGYAANY CDGECSFPLN AHMNATNHAI VQTLVHLMNP EYVPKPCCAP
TKLNAISVLY FDDNSNVILK KYRNMVVRAC GCH
//

MIM 112266
*RECORD*
*FIELD* NO
112266
*FIELD* TI
*112266 BONE MORPHOGENETIC PROTEIN 6; BMP6
;;VG1-RELATED SEQUENCE; VGR1
*FIELD* TX
read more
DESCRIPTION

Bone morphogenetic proteins, such as BMP6, belong to the transforming
growth factor-beta (see TGFB1; 190180) superfamily of regulatory
molecules (Rickard et al., 1998).

CLONING

Using bovine Bmp6 to screen a U2-OS cell line cDNA library, followed by
screening placenta and brain cDNA libraries, Celeste et al. (1990)
cloned BMP6. The deduced full-length 513-amino acid protein contains a
hydrophobic leader sequence that terminates in a proline-rich region.
The leader sequence is followed by a proprotein region, which contains
an alanine repeat and a glutamine-rich sequence, and a 139-amino acid
mature domain, which contains 3 potential N-glycosylation sites.
Sequence comparison suggested that BMP2 (112261), BMP5 (112265), BMP6,
and BMP7 (112267) form a BMP subfamily. Northern blot analysis detected
BMP6 transcripts of about 4.3 and 2.6 kb in U2-OS cells.

GENE FUNCTION

Rickard et al. (1998) presented evidence that the skeletal effects of
estrogen on bone and cartilage may be mediated by increased production
of BMP6 by osteoblasts. They investigated the effect of estrogen on BMP
production in 2 estrogen-responsive, human immortalized cell lines that
display the mature osteoblast phenotype.

Cheng et al. (2003) measured the ability of 14 human BMPs to induce
osteogenic transformation in a mouse pluripotential stem cell line, a
mouse mesenchymal stem cell line, and a mature human osteoblastic cell
line. Osteogenic activity was determined by measuring the induction of
alkaline phosphatase (see 171760), osteocalcin (112260), and matrix
mineralization upon BMP stimulation. All BMPs except BMP3 (112263) and
BMP12 (604651) were able to stimulate alkaline phosphatase activity in
the mature osteoblasts; however, BMP6 was among the few able to induce
all markers of osteoblast differentiation in pluripotential and
mesenchymal stem cells.

Using RT-PCR, Lories et al. (2003) detected BMP transcripts,
predominantly BMP2 and BMP6, in synovial tissues. Western blot analysis
detected BMP2 and BMP6 precursor proteins in rheumatoid arthritis (RA)
and spondylarthropathy (SpA) synovial tissue extracts, but not in
extracts of noninflamed synovial tissue. Immunohistochemical analysis
found BMP2 and BMP6 in the hyperplastic lining and sublining layer of
synovium from RA and SpA patients, both in CD90 (THY1; 188230)-positive
fibroblast-like synoviocytes and in some CD68 (153634)-positive
macrophages. Proinflammatory cytokines, such as interleukin-1B (147720)
and TNF-alpha (191160), but not interferon-gamma (147570), enhanced the
expression of BMP2 and BMP6 transcripts in synoviocytes in vitro.
Neither BMP2 nor BMP6 affected synoviocyte proliferation. BMP2 promoted
synoviocyte apoptosis, whereas BMP6 protected against nitric
oxide-induced apoptosis. BMP2-positive apoptotic cells were found in
arthritic synovium. Lories et al. (2003) concluded that BMP2 and BMP6
modulate fibroblast-like synoviocyte cell populations in inflamed
synovium.

Hepcidin (HAMP; 606464) is a key regulator of intestinal iron absorption
whose expression is controlled by the BMP and SMAD (see 601595)
signaling pathway. Kautz et al. (2008) performed a genomic screen in
mice fed either an iron-enriched or iron-deficient diet, which
demonstrated that in contrast to other BMP genes, Bmp6 mRNA expression
was regulated by iron similar to Hamp mRNA expression, and suggested
that BMP6 has a preponderant role in the activation of the SMAD
signaling pathway leading to hepcidin synthesisin vivo.

Hemojuvelin (HJV; 608374) is a coreceptor for BMPs, and inhibition of
endogenous BMP signaling reduces hepcidin expression and increases serum
iron in mice (Babitt et al., 2006, 2007). Using a protein pull-down
assay, Andriopoulos et al. (2009) demonstrated a direct physical
interaction between recombinant soluble human HJV and BMP6.
Intraperitoneal injection of BMP6 in mice caused increased hepatic
hepcidin mRNA expression and reduced serum iron and transferrin (190000)
saturation in a dose-dependent manner. Conversely, inhibition of
endogenous Bmp6 in mice reduced hepcidin expression and increased serum
iron. Andriopoulos et al. (2009) concluded that BMP6 is an HJV ligand
and an endogenous regulator of hepcidin expression and iron metabolism.

BIOCHEMICAL FEATURES

Using x-ray diffraction and statistical analysis, Allendorph et al.
(2007) resolved the crystal structure of the mature domain of human BMP6
to 2.49-angstrom resolution. The first 28 N-terminal residues were
disordered, and the remainder exhibited the classic TGF-beta family
fold, with each monomer containing a cystine knot motif, 4 beta strands,
and the conserved alpha-helix H3. Covalently linked BMP6 dimers had an
overall butterfly shape, with the cystine knot forming the body.

GENE STRUCTURE

Tamada et al. (1998) found that the promoter region of the BMP6 gene
lacks a canonical TATA box, but has a GC-rich region with 2 SP1
(189906)-binding sites, an inverted CCAAT element, and a putative
tramtrack responsive element. Reporter gene assays suggested that the
BMP6 promoter has osteogenic cell specificity.

MAPPING

Hahn et al. (1992) mapped both BMP5 and BMP6 to human chromosome 6 by
study of human/rodent somatic cell hybrid lines with cDNA probes.

Olavesen et al. (1997) reported fine mapping of 39 ESTs on 6p25-p23.
Most of the ESTs (31 of 39) were positioned in the 6p24-p23 interval; of
these, 8 were located within a single PAC clone. BMP6 was 1 of the 8
loci on the PAC, between TFAP2 (107580) at the centromeric side and DSP
(125647) on the telomeric side.

The product of the VG1-related sequence, which was described by Lyons et
al. (1989), is a protein that belongs to the transforming growth
factor-beta (TGFB; 190180) superfamily. Dickinson et al. (1990) showed
that in the mouse Vgr1 is located on chromosome 13. Arguing from
homology of synteny, they suggested that the human cognate is on
chromosome 6.

ANIMAL MODEL

Kugimiya et al. (2005) noted that Bmp2 (112261) -/- mice die during an
early embryonic stage, and that Bmp6 -/- mice show no skeletal
abnormality except for a slight delay in ossification of the sternum.
They found that these BMPs were the main BMP subtypes expressed in
hypertrophic chondrocytes that induced endochondrial bone formation in
mice. Compound deficiency for these BMPs (Bmp2 +/- Bmp6 -/-) resulted in
moderate growth retardation compared with wildtype littermates. Both
fetal and adult Bmp2 +/- Bmp6 -/- mice showed reduced trabecular bone
volume with suppressed bone formation, but normal bone resorption.
Single-deficient Bmp2 +/- or Bmp6 -/- mice did not show these
phenotypes. Kugimiya et al. (2005) concluded that BMP2 and BMP6
cooperate in long bone formation.

Meynard et al. (2009) found that Bmp6 -/- mice were viable and fertile.
Although Bmp6 mutant embryos showed delayed ossification confined to the
developing sternum, newborn and adult Bmp6 mutants had skeletal elements
indistinguishable from wildtype animals. However, disruption of Bmp6
resulted in a phenotype similar to hemochromatosis in humans (see
602390), with iron accumulation in the liver, acinar cells of the
exocrine pancreas, the heart, and renal convoluted tubules. Despite
their severe iron overload, the livers of Bmp6 -/- mice had low levels
of phosphorylated Smad1, Smad5 (603110), and Smad8 (SMAD9; 603295),
which transmit BMP6-dependent signals; these Smads were not translocated
to the nucleus. The expression of several iron transporters was
elevated, but hepcidin synthesis was markedly reduced. Bmp6 -/- mice
retained their capacity to induce hepcidin in response to inflammation.
Meynard et al. (2009) concluded that BMP6 has an essential role in the
maintenance of iron homeostasis.

Andriopoulos et al. (2009) also found that Bmp6 -/- mice had a phenotype
resembling hereditary hemochromatosis, with reduced hepcidin expression
and tissue iron overload.

Lenoir et al. (2011) found that double knockout of Bmp6 and Tmprss6
(609862) in mice rescued the iron deficiency anemia observed in Tmprss6
-/- mice, although hepcidin expression was repressed to the same extent
as in Bmp6 -/- mice. Heterozygous loss of Bmp6 in Tmprss6 -/- mice
partly corrected systemic iron homeostasis by decreasing hepcidin gene
expression and increasing plasma and liver iron levels. Lenoir et al.
(2011) concluded that BMP6 is the physiologic ligand of HJV and that
regulation of HJV membrane expression by TMPRSS6 tightly controls BMP6
signaling.

*FIELD* RF
1. Allendorph, G. P.; Isaacs, M. J.; Kawakami, Y.; Belmonte, J. C.
I.; Choe, S.: BMP-3 and BMP-6 structures illuminate the nature of
binding specificity with receptors. Biochemistry 46: 12238-12247,
2007. Note: Erratum: Biochemistry 46: 12246 only, 2007.

2. Andriopoulos, B., Jr.; Corradini, E.; Xia, Y.; Faasse, S. A.; Chen,
S.; Grgurevic, L.; Knutson, M. D.; Pietrangelo, A.; Vukicevic, S.;
Lin, H. Y.; Babitt, J. L.: BMP6 is a key endogenous regulator of
hepcidin expression and iron metabolism. Nature Genet. 41: 482-487,
2009.

3. Babitt, J. L.; Huang, F. W.; Wrighting, D. M.; Xia, Y.; Sidis,
Y.; Samad, T. A.; Campagna, J. A.; Chung, R. T.; Schneyer, A. L.;
Woolf, C. J.; Andrews, N. C.; Lin, H. Y.: Bone morphogenetic protein
signaling by hemojuvelin regulates hepcidin expression. Nature Genet. 38:
531-539, 2006.

4. Babitt, J. L.; Huang, F. W.; Xia, Y.; Sidis, Y.; Andrews, N. C.;
Lin, H. Y.: Modulation of bone morphogenetic protein signaling in
vivo regulates systemic iron balance. J. Clin. Invest. 117: 1933-1939,
2007.

5. Celeste, A. J.; Iannazzi, J. A.; Taylor, R. C.; Hewick, R. M.;
Rosen, V.; Wang, E. A.; Wozney, J. M.: Identification of transforming
growth factor beta family members present in bone-inductive protein
purified from bovine bone. Proc. Nat. Acad. Sci. 87: 9843-9847,
1990.

6. Cheng, H.; Jiang, W.; Phillips, F. M.; Haydon, R. C.; Peng, Y.;
Zhou, L.; Luu, H. H.; An, N.; Breyer, B.; Vanichakarn, P.; Szatkowski,
J. P.; Park, J. Y.; He, T.-C.: Osteogenic activity of the fourteen
types of human bone morphogenetic proteins (BMPs). J. Bone Joint
Surg. Am. 85: 1544-1552, 2003. Note: Erratum: J. Bone Joint Surg.
Am. 86: 141 only, 2003.

7. Dickinson, M. E.; Kobrin, M. S.; Silan, C. M.; Kingsley, D. M.;
Justice, M. J.; Miller, D. A.; Ceci, J. D.; Lock, L. F.; Lee, A.;
Buchberg, A. M.; Siracusa, L. D.; Lyons, K. M.; Derynck, R.; Hogan,
B. L. M.; Copeland, N. G.; Jenkins, N. A.: Chromosomal localization
of seven members of the murine TGF-beta superfamily suggests close
linkage to several morphogenetic mutant loci. Genomics 6: 505-520,
1990.

8. Hahn, G. V.; Cohen, R. B.; Wozney, J. M.; Levitz, C. L.; Shore,
E. M.; Zasloff, M. A.; Kaplan, F. S.: A bone morphogenetic protein
subfamily: chromosomal localization of human genes for BMP5, BMP6,
and BMP7. Genomics 14: 759-762, 1992.

9. Kautz, L.; Meynard, D.; Monnier, A.; Darnaud, V.; Bouvet, R.; Wang,
R. H.; Deng, C.; Vaulont, S.; Mosser, J.; Coppin, H.; Roth, M. P.
: Iron regulates phosphorylation of Smad1/5/8 and gene expression
of Bmp6, Smad7, Id1, and Atoh8 in the mouse liver. Blood 112: 1503-1509,
2008.

10. Kugimiya, F.; Kawaguchi, H.; Kamekura, S.; Chikuda, H.; Ohba,
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*FIELD* CN
Patricia A. Hartz - updated: 8/2/2011
Patricia A. Hartz - updated: 11/20/2009
Patricia A. Hartz - updated: 11/3/2009
Patricia A. Hartz - updated: 9/21/2009
Patricia A. Hartz - updated: 4/23/2009
Patricia A. Hartz - updated: 5/26/2005
Patricia A. Hartz - updated: 3/24/2004
Victor A. McKusick - updated: 3/25/1998
Victor A. McKusick - updated: 2/4/1998

*FIELD* CD
Victor A. McKusick: 11/6/1992

*FIELD* ED
alopez: 03/11/2013
terry: 5/29/2012
mgross: 8/15/2011
terry: 8/2/2011
terry: 1/13/2011
mgross: 1/12/2010
terry: 11/20/2009
mgross: 11/5/2009
mgross: 11/4/2009
terry: 11/3/2009
carol: 10/28/2009
mgross: 10/6/2009
terry: 9/21/2009
alopez: 4/23/2009
wwang: 6/15/2005
wwang: 6/7/2005
terry: 5/26/2005
mgross: 4/12/2004
terry: 3/24/2004
alopez: 4/27/1999
carol: 4/23/1999
terry: 6/18/1998
alopez: 3/25/1998
terry: 3/19/1998
mark: 2/11/1998
terry: 2/4/1998
carol: 11/6/1992