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 27-MAR-2024, entry version 185. 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 -!- SUBUNIT: Interacts with TSC22D1/TSC-22. {ECO:0000250|UniProtKB:P37023}. 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}. 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; 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.ENSRNOP00000072526; -. DR GlyCosmos; P80203; 2 sites, No reported glycans. DR GlyGen; P80203; 2 sites. DR iPTMnet; P80203; -. DR PhosphoSitePlus; P80203; -. DR PaxDb; 10116-ENSRNOP00000008673; -. DR Ensembl; ENSRNOT00000008673.5; ENSRNOP00000008673.3; ENSRNOG00000028713.7. DR Ensembl; ENSRNOT00055049771; ENSRNOP00055040972; ENSRNOG00055028741. DR Ensembl; ENSRNOT00060026631; ENSRNOP00060021306; ENSRNOG00060015566. DR Ensembl; ENSRNOT00065038495; ENSRNOP00065031204; ENSRNOG00065022556. DR GeneID; 25237; -. DR KEGG; rno:25237; -. DR UCSC; RGD:2029; rat. DR AGR; RGD:2029; -. 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; TIHAENQ; -. DR OrthoDB; 3900892at2759; -. 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 cell types or tissues. 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:0043025; C:neuronal cell body; IDA:RGD. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. 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: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:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:RGD. DR GO; GO:1903348; P:positive regulation of bicellular tight junction assembly; ISO:RGD. DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; ISO:RGD. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; 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:0030858; P:positive regulation of epithelial cell differentiation; ISO:RGD. DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; ISO:RGD. DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; ISO:RGD. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD. DR GO; GO:0008217; P:regulation of blood pressure; ISO:RGD. DR GO; GO:0006355; P:regulation of DNA-templated transcription; 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 CDD; cd14142; STKc_ACVR1_ALK1; 1. DR Gene3D; 2.10.60.10; CD59; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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:SF66; SERINE_THREONINE-PROTEIN KINASE RECEPTOR R3; 1. DR PANTHER; PTHR23255; TRANSFORMING GROWTH FACTOR-BETA RECEPTOR TYPE I AND II; 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; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF57302; Snake toxin-like; 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. DR Genevisible; P80203; RN. 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 //