BMR1A_MOUSE
ID BMR1A_MOUSE Reviewed; 532 AA.
AC P36895;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=Bone morphogenetic protein receptor type-1A;
DE Short=BMP type-1A receptor;
DE Short=BMPR-1A;
DE EC=2.7.11.30;
DE AltName: Full=Activin receptor-like kinase 3;
DE Short=ALK-3;
DE AltName: Full=BMP-2/BMP-4 receptor;
DE AltName: Full=Serine/threonine-protein kinase receptor R5;
DE Short=SKR5;
DE AltName: CD_antigen=CD292;
DE Flags: Precursor;
GN Name=Bmpr1a; Synonyms=Acvrlk3, Bmpr;
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].
RC STRAIN=SWR/J; TISSUE=Embryo;
RX PubMed=7750489; DOI=10.1210/endo.136.6.7750489;
RA Dewulf N., Verschueren K., Lonnoy O., Moren A., Grimsby S., Spiegle K.,
RA Miyazono K., Huylebroeck D., ten Dijke P.;
RT "Distinct spatial and temporal expression patterns of two type I receptors
RT for bone morphogenetic proteins during mouse embryogenesis.";
RL Endocrinology 136:2652-2663(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=7937936; DOI=10.1073/pnas.91.22.10255;
RA Suzuki A., Thies R.S., Yamaji N., Song J.J., Wozney J., Murakami K.,
RA Kung H.;
RT "A truncated bone morphogenetic protein receptor affects dorsal-ventral
RT patterning in the early Xenopus embryo.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:10255-10259(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8065329; DOI=10.1128/mcb.14.9.5961;
RA Koenig B.B., Cook J.S., Wolsing D.H., Ting J., Tiesman J.P., Correa P.E.,
RA Olson C.A., Pecquet A.L., Ventura F., Grant R.A., Chen G., Wrana J.L.,
RA Massague J., Rosenbaum J.S.;
RT "Characterization and cloning of a receptor for BMP-2 and BMP-4 from NIH
RT 3T3 cells.";
RL Mol. Cell. Biol. 14:5961-5974(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Retina;
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 [5]
RP FUNCTION.
RX PubMed=23527555; DOI=10.1111/febs.12256;
RA Wang S.S., Huang H.Y., Chen S.Z., Li X., Zhang W.T., Tang Q.Q.;
RT "Gdf6 induces commitment of pluripotent mesenchymal C3H10T1/2 cells to the
RT adipocyte lineage.";
RL FEBS J. 280:2644-2651(2013).
RN [6]
RP FUNCTION.
RX PubMed=24098149; DOI=10.1371/journal.pgen.1003846;
RA Degenkolbe E., Konig J., Zimmer J., Walther M., Reissner C., Nickel J.,
RA Ploger F., Raspopovic J., Sharpe J., Dathe K., Hecht J.T., Mundlos S.,
RA Doelken S.C., Seemann P.;
RT "A GDF5 point mutation strikes twice--causing BDA1 and SYNS2.";
RL PLoS Genet. 9:E1003846-E1003846(2013).
RN [7]
RP GLYCOSYLATION, MUTAGENESIS OF ASN-73; ASN-314 AND ASN-373, AND SUBCELLULAR
RP LOCATION.
RX PubMed=29415997; DOI=10.1038/s41419-017-0239-5;
RA Li S.F., Zhu C.S., Wang Y.M., Xie X.X., Xiao L.L., Zhang Z.C., Tang Q.Q.,
RA Li X.;
RT "Downregulation of beta1,4-galactosyltransferase 5 improves insulin
RT resistance by promoting adipocyte commitment and reducing inflammation.";
RL Cell Death Dis. 9:196-196(2018).
CC -!- FUNCTION: On ligand binding, forms a receptor complex consisting of two
CC type II and two type I transmembrane serine/threonine kinases. Type II
CC receptors phosphorylate and activate type I receptors which
CC autophosphorylate, then bind and activate SMAD transcriptional
CC regulators. Receptor for BMP2, BMP4, GDF5 and GDF6. Positively
CC regulates chondrocyte differentiation through GDF5 interaction
CC (PubMed:24098149). Mediates induction of adipogenesis by GDF6
CC (PubMed:23527555). {ECO:0000269|PubMed:23527555,
CC ECO:0000269|PubMed:24098149}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[receptor-protein] = ADP + H(+) + O-phospho-
CC L-threonyl-[receptor-protein]; Xref=Rhea:RHEA:44880, Rhea:RHEA-
CC COMP:11024, Rhea:RHEA-COMP:11025, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977,
CC ChEBI:CHEBI:456216; EC=2.7.11.30;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[receptor-protein] = ADP + H(+) + O-phospho-L-
CC seryl-[receptor-protein]; Xref=Rhea:RHEA:18673, Rhea:RHEA-COMP:11022,
CC Rhea:RHEA-COMP:11023, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216;
CC EC=2.7.11.30;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC -!- SUBUNIT: Interacts with BMP2. Interacts with low affinity with GDF5;
CC positively regulates chondrocyte differentiation. Interacts with BMP4.
CC Interacts with SCUBE3. {ECO:0000250|UniProtKB:P36894}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P36898};
CC Single-pass type I membrane protein {ECO:0000255}. Cell surface
CC {ECO:0000269|PubMed:29415997}.
CC -!- TISSUE SPECIFICITY: Widely expressed.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:29415997}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC protein kinase family. TGFB receptor subfamily. {ECO:0000305}.
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DR EMBL; Z23154; CAA80678.1; -; mRNA.
DR EMBL; D16250; BAA03769.1; -; mRNA.
DR EMBL; U04672; AAA21514.1; -; mRNA.
DR EMBL; BC042611; AAH42611.1; -; mRNA.
DR CCDS; CCDS26938.1; -.
DR PIR; A56238; A56238.
DR RefSeq; NP_033888.2; NM_009758.4.
DR RefSeq; XP_006518532.1; XM_006518469.3.
DR RefSeq; XP_006518533.1; XM_006518470.3.
DR RefSeq; XP_017171295.1; XM_017315806.1.
DR AlphaFoldDB; P36895; -.
DR BMRB; P36895; -.
DR SMR; P36895; -.
DR BioGRID; 198371; 140.
DR DIP; DIP-5796N; -.
DR IntAct; P36895; 137.
DR STRING; 10090.ENSMUSP00000035900; -.
DR BindingDB; P36895; -.
DR GlyGen; P36895; 1 site.
DR iPTMnet; P36895; -.
DR PhosphoSitePlus; P36895; -.
DR SwissPalm; P36895; -.
DR PaxDb; P36895; -.
DR PeptideAtlas; P36895; -.
DR PRIDE; P36895; -.
DR ProteomicsDB; 281699; -.
DR Antibodypedia; 4524; 791 antibodies from 39 providers.
DR DNASU; 12166; -.
DR Ensembl; ENSMUST00000049005; ENSMUSP00000035900; ENSMUSG00000021796.
DR GeneID; 12166; -.
DR KEGG; mmu:12166; -.
DR UCSC; uc007taw.1; mouse.
DR CTD; 657; -.
DR MGI; MGI:1338938; Bmpr1a.
DR VEuPathDB; HostDB:ENSMUSG00000021796; -.
DR eggNOG; KOG2052; Eukaryota.
DR GeneTree; ENSGT00940000156225; -.
DR HOGENOM; CLU_000288_8_1_1; -.
DR InParanoid; P36895; -.
DR OMA; VMGPFFD; -.
DR OrthoDB; 776697at2759; -.
DR PhylomeDB; P36895; -.
DR TreeFam; TF314724; -.
DR BRENDA; 2.7.10.2; 3474.
DR Reactome; R-MMU-201451; Signaling by BMP.
DR BioGRID-ORCS; 12166; 7 hits in 75 CRISPR screens.
DR ChiTaRS; Bmpr1a; mouse.
DR PRO; PR:P36895; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; P36895; protein.
DR Bgee; ENSMUSG00000021796; Expressed in ascending aorta and 297 other tissues.
DR ExpressionAtlas; P36895; baseline and differential.
DR Genevisible; P36895; MM.
DR GO; GO:0005901; C:caveola; ISO:MGI.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; ISO:MGI.
DR GO; GO:0036122; F:BMP binding; IDA:MGI.
DR GO; GO:0098821; F:BMP receptor activity; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019211; F:phosphatase activator activity; IDA:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; IDA:MGI.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:MGI.
DR GO; GO:0046332; F:SMAD binding; ISO:MGI.
DR GO; GO:0005025; F:transforming growth factor beta receptor activity, type I; IBA:GO_Central.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IMP:MGI.
DR GO; GO:0060928; P:atrioventricular node cell development; IMP:BHF-UCL.
DR GO; GO:0003171; P:atrioventricular valve development; IMP:BHF-UCL.
DR GO; GO:0030509; P:BMP signaling pathway; IDA:MGI.
DR GO; GO:0061312; P:BMP signaling pathway involved in heart development; IMP:BHF-UCL.
DR GO; GO:0003161; P:cardiac conduction system development; IMP:BHF-UCL.
DR GO; GO:0003215; P:cardiac right ventricle morphogenesis; IMP:BHF-UCL.
DR GO; GO:0051216; P:cartilage development; IMP:MGI.
DR GO; GO:0071773; P:cellular response to BMP stimulus; ISO:MGI.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IBA:GO_Central.
DR GO; GO:0021953; P:central nervous system neuron differentiation; IGI:MGI.
DR GO; GO:0002062; P:chondrocyte differentiation; IDA:UniProtKB.
DR GO; GO:0048589; P:developmental growth; IMP:MGI.
DR GO; GO:0035912; P:dorsal aorta morphogenesis; IMP:BHF-UCL.
DR GO; GO:0009950; P:dorsal/ventral axis specification; IMP:MGI.
DR GO; GO:0009953; P:dorsal/ventral pattern formation; IGI:MGI.
DR GO; GO:0007398; P:ectoderm development; IMP:MGI.
DR GO; GO:0042733; P:embryonic digit morphogenesis; IGI:MGI.
DR GO; GO:0048598; P:embryonic morphogenesis; IMP:MGI.
DR GO; GO:0048568; P:embryonic organ development; IMP:BHF-UCL.
DR GO; GO:0003272; P:endocardial cushion formation; IMP:MGI.
DR GO; GO:0003203; P:endocardial cushion morphogenesis; IMP:BHF-UCL.
DR GO; GO:0007492; P:endoderm development; IMP:MGI.
DR GO; GO:0050673; P:epithelial cell proliferation; IMP:MGI.
DR GO; GO:1905285; P:fibrous ring of heart morphogenesis; IMP:BHF-UCL.
DR GO; GO:0007507; P:heart development; IMP:MGI.
DR GO; GO:0060914; P:heart formation; IMP:MGI.
DR GO; GO:0003007; P:heart morphogenesis; IMP:MGI.
DR GO; GO:0035137; P:hindlimb morphogenesis; IMP:MGI.
DR GO; GO:0006955; P:immune response; ISO:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR GO; GO:0048368; P:lateral mesoderm development; IMP:MGI.
DR GO; GO:0030324; P:lung development; IMP:MGI.
DR GO; GO:0048382; P:mesendoderm development; IMP:MGI.
DR GO; GO:0001707; P:mesoderm formation; IMP:MGI.
DR GO; GO:0003183; P:mitral valve morphogenesis; IMP:BHF-UCL.
DR GO; GO:0001880; P:Mullerian duct regression; IMP:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:BHF-UCL.
DR GO; GO:0051148; P:negative regulation of muscle cell differentiation; IMP:MGI.
DR GO; GO:0050768; P:negative regulation of neurogenesis; IMP:MGI.
DR GO; GO:0014912; P:negative regulation of smooth muscle cell migration; ISO:MGI.
DR GO; GO:0007399; P:nervous system development; IMP:MGI.
DR GO; GO:0014032; P:neural crest cell development; IMP:MGI.
DR GO; GO:0021998; P:neural plate mediolateral regionalization; IMP:MGI.
DR GO; GO:0060896; P:neural plate pattern specification; IMP:MGI.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IMP:MGI.
DR GO; GO:0001649; P:osteoblast differentiation; IDA:MGI.
DR GO; GO:0003151; P:outflow tract morphogenesis; IMP:BHF-UCL.
DR GO; GO:0003148; P:outflow tract septum morphogenesis; IMP:BHF-UCL.
DR GO; GO:0048339; P:paraxial mesoderm development; IMP:MGI.
DR GO; GO:0048352; P:paraxial mesoderm structural organization; IMP:MGI.
DR GO; GO:0007389; P:pattern specification process; IMP:MGI.
DR GO; GO:0061626; P:pharyngeal arch artery morphogenesis; IMP:BHF-UCL.
DR GO; GO:0021983; P:pituitary gland development; IMP:MGI.
DR GO; GO:0030501; P:positive regulation of bone mineralization; ISO:MGI.
DR GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; IMP:BHF-UCL.
DR GO; GO:1904414; P:positive regulation of cardiac ventricle development; IMP:BHF-UCL.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IMP:MGI.
DR GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; IMP:MGI.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; IDA:BHF-UCL.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISO:MGI.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; ISO:MGI.
DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0032915; P:positive regulation of transforming growth factor beta2 production; IMP:BHF-UCL.
DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IMP:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; ISO:MGI.
DR GO; GO:0060043; P:regulation of cardiac muscle cell proliferation; IMP:BHF-UCL.
DR GO; GO:2000772; P:regulation of cellular senescence; IGI:MGI.
DR GO; GO:0048378; P:regulation of lateral mesodermal cell fate specification; IGI:MGI.
DR GO; GO:0060021; P:roof of mouth development; IMP:MGI.
DR GO; GO:0035019; P:somatic stem cell population maintenance; IMP:MGI.
DR GO; GO:0001756; P:somitogenesis; IMP:MGI.
DR GO; GO:0003186; P:tricuspid valve morphogenesis; IMP:BHF-UCL.
DR GO; GO:0003223; P:ventricular compact myocardium morphogenesis; IMP:BHF-UCL.
DR GO; GO:0060412; P:ventricular septum morphogenesis; IMP:BHF-UCL.
DR GO; GO:0003222; P:ventricular trabecula myocardium morphogenesis; IMP:BHF-UCL.
DR Gene3D; 2.10.60.10; -; 1.
DR InterPro; IPR000472; Activin_recp.
DR InterPro; IPR003605; GS_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR045860; Snake_toxin-like_sf.
DR InterPro; IPR000333; TGFB_receptor.
DR PANTHER; PTHR23255; PTHR23255; 1.
DR Pfam; PF01064; Activin_recp; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF08515; TGF_beta_GS; 1.
DR SMART; SM00467; GS; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57302; SSF57302; 1.
DR PROSITE; PS51256; GS; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell membrane; Disulfide bond; Glycoprotein; Kinase;
KW Magnesium; Manganese; Membrane; Metal-binding; Nucleotide-binding;
KW Receptor; Reference proteome; Serine/threonine-protein kinase; Signal;
KW Transferase; Transmembrane; Transmembrane helix.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..532
FT /note="Bone morphogenetic protein receptor type-1A"
FT /id="PRO_0000024411"
FT TOPO_DOM 24..152
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 153..176
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 177..532
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 204..233
FT /note="GS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00585"
FT DOMAIN 234..525
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 107..109
FT /note="Mediates specificity for BMP ligand"
FT /evidence="ECO:0000250"
FT ACT_SITE 362
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 240..248
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 261
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT CARBOHYD 73
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 61..82
FT /evidence="ECO:0000250|UniProtKB:P36894"
FT DISULFID 63..67
FT /evidence="ECO:0000250|UniProtKB:P36894"
FT DISULFID 76..100
FT /evidence="ECO:0000250|UniProtKB:P36894"
FT DISULFID 110..124
FT /evidence="ECO:0000250|UniProtKB:P36894"
FT DISULFID 125..130
FT /evidence="ECO:0000250|UniProtKB:P36894"
FT MUTAGEN 73
FT /note="N->Q: Reduced glycosylation and increased protein
FT stability; when associated with Q-314 and Q-373."
FT /evidence="ECO:0000269|PubMed:29415997"
FT MUTAGEN 314
FT /note="N->Q: Reduced glycosylation and increased protein
FT stability; when associated with Q-373 and Q-373."
FT /evidence="ECO:0000269|PubMed:29415997"
FT MUTAGEN 373
FT /note="N->Q: Reduced glycosylation and increased protein
FT stability; when associated with Q-73 and Q-314."
FT /evidence="ECO:0000269|PubMed:29415997"
SQ SEQUENCE 532 AA; 60063 MW; 70CC83CFB07CE9D5 CRC64;
MTQLYTYIRL LGACLFIISH VQGQNLDSML HGTGMKSDLD QKKPENGVTL APEDTLPFLK
CYCSGHCPDD AINNTCITNG HCFAIIEEDD QGETTLTSGC MKYEGSDFQC KDSPKAQLRR
TIECCRTNLC NQYLQPTLPP VVIGPFFDGS IRWLVVLISM AVCIVAMIIF SSCFCYKHYC
KSISSRGRYN RDLEQDEAFI PVGESLKDLI DQSQSSGSGS GLPLLVQRTI AKQIQMVRQV
GKGRYGEVWM GKWRGEKVAV KVFFTTEEAS WFRETEIYQT VLMRHENILG FIAADIKGTG
SWTQLYLITD YHENGSLYDF LKCATLDTRA LLKLAYSAAC GLCHLHTEIY GTQGKPAIAH
RDLKSKNILI KKNGSCCIAD LGLAVKFNSD TNEVDIPLNT RVGTKRYMAP EVLDESLNKN
HFQPYIMADI YSFGLIIWEM ARRCITGGIV EEYQLPYYNM VPSDPSYEDM REVVCVKRLR
PIVSNRWNSD ECLRAVLKLM SECWAHNPAS RLTALRIKKT LAKMVESQDV KI
