ACVL1_RAT
ID ACVL1_RAT Reviewed; 504 AA.
AC P80203; Q63559;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 13-APR-2004, sequence version 2.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Serine/threonine-protein kinase receptor R3;
DE Short=SKR3;
DE EC=2.7.11.30;
DE AltName: Full=TGF-B superfamily receptor type I;
DE Short=TSR-I;
DE Flags: Precursor;
GN Name=Acvrl1; Synonyms=Acvrlk1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Urogenital ridge;
RX PubMed=8395914; DOI=10.1002/aja.1001960207;
RA He W.-W., Gustafson M.L., Hirobe S., Donahoe P.K.;
RT "Developmental expression of four novel serine/threonine kinase receptors
RT homologous to the activin/transforming growth factor-beta type II receptor
RT family.";
RL Dev. Dyn. 196:133-142(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Lung;
RX PubMed=8928814; DOI=10.1152/ajplung.1996.270.4.l547;
RA Panchenko M.P., Williams M.C., Brody J.S., Yu Q.;
RT "Type I receptor serine-threonine kinase preferentially expressed in
RT pulmonary blood vessels.";
RL Am. J. Physiol. 270:L547-L558(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-156; SER-161 AND SER-162, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Type I receptor for TGF-beta family ligands BMP9/GDF2 and
CC BMP10 and important regulator of normal blood vessel development. On
CC ligand binding, forms a receptor complex consisting of two type II and
CC two type I transmembrane serine/threonine kinases. Type II receptors
CC phosphorylate and activate type I receptors which autophosphorylate,
CC then bind and activate SMAD transcriptional regulators. May bind
CC activin as well. {ECO:0000250|UniProtKB:P37023}.
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 -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P37023};
CC Single-pass type I membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Urogenital ridge, testis, ovary, brain and lung. In
CC lung, found exclusively in pulmonary vessels of all sizes. Also
CC expressed in aorta, vena cava and certain blood vessels of kidney,
CC spleen, heart and intestine. For most blood vessels, a higher level of
CC expression is found in endothelium than in adjacent smooth muscle.
CC {ECO:0000269|PubMed:8928814}.
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; L36088; AAC37705.1; -; mRNA.
DR EMBL; BC083173; AAH83173.1; -; mRNA.
DR RefSeq; NP_071886.1; NM_022441.2.
DR RefSeq; XP_006242365.1; XM_006242303.3.
DR RefSeq; XP_006242366.1; XM_006242304.3.
DR RefSeq; XP_006242367.1; XM_006242305.3.
DR RefSeq; XP_008763895.1; XM_008765673.2.
DR RefSeq; XP_017450156.1; XM_017594667.1.
DR RefSeq; XP_017450157.1; XM_017594668.1.
DR AlphaFoldDB; P80203; -.
DR SMR; P80203; -.
DR STRING; 10116.ENSRNOP00000008673; -.
DR GlyGen; P80203; 2 sites.
DR iPTMnet; P80203; -.
DR PhosphoSitePlus; P80203; -.
DR PaxDb; P80203; -.
DR Ensembl; ENSRNOT00000008673; ENSRNOP00000008673; ENSRNOG00000028713.
DR GeneID; 25237; -.
DR KEGG; rno:25237; -.
DR UCSC; RGD:2029; rat.
DR CTD; 94; -.
DR RGD; 2029; Acvrl1.
DR eggNOG; KOG2052; Eukaryota.
DR GeneTree; ENSGT00940000161446; -.
DR HOGENOM; CLU_000288_8_1_1; -.
DR InParanoid; P80203; -.
DR OMA; CQGTWCT; -.
DR OrthoDB; 776697at2759; -.
DR BRENDA; 2.7.10.2; 5301.
DR Reactome; R-RNO-201451; Signaling by BMP.
DR PRO; PR:P80203; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Bgee; ENSRNOG00000028713; Expressed in lung and 19 other tissues.
DR Genevisible; P80203; RN.
DR GO; GO:0070724; C:BMP receptor complex; IBA:GO_Central.
DR GO; GO:0009986; C:cell surface; IDA:RGD.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0048185; F:activin binding; ISO:RGD.
DR GO; GO:0016361; F:activin receptor activity, type I; ISO:RGD.
DR GO; GO:0005524; F:ATP binding; ISO:RGD.
DR GO; GO:0098821; F:BMP receptor activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:RGD.
DR GO; GO:0046332; F:SMAD binding; ISO:RGD.
DR GO; GO:0050431; F:transforming growth factor beta binding; ISO:RGD.
DR GO; GO:0005024; F:transforming growth factor beta receptor activity; ISO:RGD.
DR GO; GO:0005025; F:transforming growth factor beta receptor activity, type I; ISO:RGD.
DR GO; GO:0004675; F:transmembrane receptor protein serine/threonine kinase activity; TAS:RGD.
DR GO; GO:0001525; P:angiogenesis; ISO:RGD.
DR GO; GO:0060840; P:artery development; ISO:RGD.
DR GO; GO:0008015; P:blood circulation; ISO:RGD.
DR GO; GO:0048514; P:blood vessel morphogenesis; ISO:RGD.
DR GO; GO:0001974; P:blood vessel remodeling; ISO:RGD.
DR GO; GO:0030509; P:BMP signaling pathway; ISO:RGD.
DR GO; GO:0071773; P:cellular response to BMP stimulus; ISO:RGD.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IBA:GO_Central.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; ISO:RGD.
DR GO; GO:0035912; P:dorsal aorta morphogenesis; ISO:RGD.
DR GO; GO:0009953; P:dorsal/ventral pattern formation; IBA:GO_Central.
DR GO; GO:0003203; P:endocardial cushion morphogenesis; ISO:RGD.
DR GO; GO:0061154; P:endothelial tube morphogenesis; ISO:RGD.
DR GO; GO:0007507; P:heart development; IBA:GO_Central.
DR GO; GO:0001701; P:in utero embryonic development; ISO:RGD.
DR GO; GO:0001946; P:lymphangiogenesis; ISO:RGD.
DR GO; GO:0060836; P:lymphatic endothelial cell differentiation; ISO:RGD.
DR GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; ISO:RGD.
DR GO; GO:0007162; P:negative regulation of cell adhesion; ISO:RGD.
DR GO; GO:0030308; P:negative regulation of cell growth; ISO:RGD.
DR GO; GO:0030336; P:negative regulation of cell migration; ISO:RGD.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD.
DR GO; GO:2000279; P:negative regulation of DNA biosynthetic process; ISO:RGD.
DR GO; GO:0045602; P:negative regulation of endothelial cell differentiation; ISO:RGD.
DR GO; GO:0010596; P:negative regulation of endothelial cell migration; ISO:RGD.
DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; ISO:RGD.
DR GO; GO:0051895; P:negative regulation of focal adhesion assembly; ISO:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:RGD.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; ISO:RGD.
DR GO; GO:0045603; P:positive regulation of endothelial cell differentiation; ISO:RGD.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISO:RGD.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; ISO:RGD.
DR GO; GO:0008217; P:regulation of blood pressure; ISO:RGD.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0061298; P:retina vasculature development in camera-type eye; ISO:RGD.
DR GO; GO:0007165; P:signal transduction; ISO:RGD.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISO:RGD.
DR GO; GO:0060841; P:venous blood vessel development; ISO:RGD.
DR GO; GO:0035313; P:wound healing, spreading of epidermal cells; ISO:RGD.
DR Gene3D; 2.10.60.10; -; 1.
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; 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 Angiogenesis; ATP-binding; Cell membrane; Disulfide bond; Glycoprotein;
KW Kinase; Magnesium; Manganese; Membrane; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Receptor; Reference proteome;
KW Serine/threonine-protein kinase; Signal; Transferase; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..504
FT /note="Serine/threonine-protein kinase receptor R3"
FT /id="PRO_0000024422"
FT TOPO_DOM 21..121
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 122..142
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 143..504
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 173..202
FT /note="GS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00585"
FT DOMAIN 203..504
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 74..77
FT /note="Mediates specificity for BMP ligand"
FT /evidence="ECO:0000250"
FT ACT_SITE 331
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 209..217
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 230
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 156
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 161
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 162
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CARBOHYD 34
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 99
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 35..52
FT /evidence="ECO:0000250|UniProtKB:P37023"
FT DISULFID 37..42
FT /evidence="ECO:0000250|UniProtKB:P37023"
FT DISULFID 47..70
FT /evidence="ECO:0000250|UniProtKB:P37023"
FT DISULFID 78..90
FT /evidence="ECO:0000250|UniProtKB:P37023"
FT DISULFID 91..96
FT /evidence="ECO:0000250|UniProtKB:P37023"
FT CONFLICT 309
FT /note="C -> CA (in Ref. 1)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 504 AA; 56703 MW; B40EA30775223C8F CRC64;
MTLGIFRRVF LMLSVALGLT KGDLVKPSRG QLVNCTCENP HCKRPICQGA WCTVVLVREQ
GRHPQVYRGC GSLNQELCLG RPTEFVNHHC CYRSFCNHNV SLMLEATQTP SEEPEVDAHL
PLILGPVLAL LVLVALGTLG LWRVRRRQEK QRGLHSDLGE SSLILKASEQ GDSMLGDFLV
SDCTTGSGSG LPFLVQRTVA RQVALVECVG KGRYGEVWRG SWHGESVAVK IFSSRDEQSW
FRETEIYNTV LLRHDNILGF IASDMTSRNS STQLWLITHY HEHGSLYDFL QRQTLEPQLA
LRLAVSAACG LAHLHVEIFG TQGKPAIAHR DLKSRNVLVK SNLQCCIADL GLAVMHSQSS
DYLDIGNNPR VGTKRYMAPE VLDEQIRTDC FESYKWTDIW AFGLVLWEIA RRTIINGIVE
DYRPPFYDMV PNDPSFEDMK KVVCVDQQTP TIPNRLAADP VLSGLAQMMR ECWYPNPSAR
LTALRIKKTL QKLSQNPEKP KVIH
