Q61288 (ACVL1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase receptor R3
Short name=SKR3
EC=2.7.11.30

Alternative name(s):
Activin receptor-like kinase 1
Short name=ALK-1
TGF-B superfamily receptor type I
Short name=TSR-I

Gene names

Name:	Acvrl1
Synonyms:	Acvrlk1, Alk-1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	502 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Type I receptor for TGF-beta family ligands BMP9/GDF2 and BMP10 and important regulator of normal blood vessel development. On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. May bind activin as well.
Catalytic activity	ATP + [receptor-protein] = ADP + [receptor-protein] phosphate.
Cofactor	Magnesium or manganese By similarity.
Subcellular location	Membrane; Single-pass type I membrane protein.
Sequence similarities	Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily. Contains 1 GS domain. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Angiogenesis
Cellular component	Membrane
Domain	Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Magnesium Manganese Metal-binding Nucleotide-binding
Molecular function	Kinase Receptor Serine/threonine-protein kinase Transferase
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	BMP signaling pathway Inferred from mutant phenotype PubMed 22783020. Source: MGI angiogenesis Inferred from mutant phenotype PubMed 10716993PubMed 11062473. Source: MGI artery development Inferred from mutant phenotype PubMed 19903896. Source: BHF-UCL blood vessel remodeling Inferred from mutant phenotype PubMed 19903896. Source: BHF-UCL cellular response to BMP stimulus Inferred from electronic annotation. Source: Compara endothelial cell activation Traceable author statement PubMed 20406889. Source: DFLAT endothelial tube morphogenesis Inferred from electronic annotation. Source: Compara in utero embryonic development Inferred from mutant phenotype PubMed 17911384. Source: MGI lymphangiogenesis Inferred from mutant phenotype PubMed 19903896. Source: BHF-UCL lymphatic endothelial cell differentiation Inferred from mutant phenotype PubMed 19903896. Source: BHF-UCL negative regulation of DNA biosynthetic process Inferred from electronic annotation. Source: Compara negative regulation of blood vessel endothelial cell migration Inferred from electronic annotation. Source: Compara negative regulation of cell growth Inferred from electronic annotation. Source: Compara negative regulation of endothelial cell differentiation Inferred from direct assay PubMed 20406889. Source: DFLAT negative regulation of endothelial cell proliferation Inferred from direct assay PubMed 20406889. Source: DFLAT negative regulation of focal adhesion assembly Inferred from electronic annotation. Source: Compara positive regulation of BMP signaling pathway Inferred from direct assay PubMed 20406889. Source: DFLAT positive regulation of endothelial cell differentiation Inferred from direct assay PubMed 20406889. Source: DFLAT positive regulation of endothelial cell proliferation Inferred from direct assay PubMed 20406889. Source: DFLAT positive regulation of pathway-restricted SMAD protein phosphorylation Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara positive regulation of transcription, DNA-dependent Inferred from mutant phenotype PubMed 20406889. Source: DFLAT protein heterooligomerization Inferred from electronic annotation. Source: Compara regulation of blood pressure Inferred from electronic annotation. Source: Compara retina vasculature development in camera-type eye Inferred from mutant phenotype PubMed 19903896. Source: BHF-UCL transforming growth factor beta receptor signaling pathway Inferred from direct assay PubMed 14580334. Source: MGI venous blood vessel development Inferred from mutant phenotype PubMed 19903896. Source: BHF-UCL wound healing, spreading of epidermal cells Inferred from electronic annotation. Source: Compara
Cellular_component	cell surface Inferred from electronic annotation. Source: Compara dendrite Inferred from electronic annotation. Source: Compara integral to plasma membrane Inferred from electronic annotation. Source: Compara neuronal cell body Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW receptor signaling protein serine/threonine kinase activity Inferred from electronic annotation. Source: Compara transforming growth factor beta receptor activity, type I Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 22	22	Potential
	Chain	23 – 502	480	Serine/threonine-protein kinase receptor R3		PRO_0000024421
Regions
	Topological domain	23 – 119	97	Extracellular Potential
	Transmembrane	120 – 140	21	Helical; Potential
	Topological domain	141 – 502	362	Cytoplasmic Potential
	Domain	171 – 200	30	GS
	Domain	201 – 502	302	Protein kinase
	Nucleotide binding	207 – 215	9	ATP By similarity
	Region	72 – 75	4	Mediates specificity for BMP ligand By similarity
Sites
	Active site	329	1	Proton acceptor By similarity
	Binding site	228	1	ATP By similarity
Amino acid modifications
	Modified residue	154	1	Phosphoserine Ref.6
	Glycosylation	32	1	N-linked (GlcNAc...) Potential
	Glycosylation	97	1	N-linked (GlcNAc...) Potential
	Disulfide bond	33 ↔ 50		By similarity
	Disulfide bond	35 ↔ 40		By similarity
	Disulfide bond	45 ↔ 68		By similarity
	Disulfide bond	76 ↔ 88		By similarity
	Disulfide bond	89 ↔ 94		By similarity
Experimental info
	Sequence conflict	17	1	F → L in CAA83484. Ref.2
	Sequence conflict	21	1	R → Q Ref.2
	Sequence conflict	23	1	D → R Ref.2
	Sequence conflict	25 – 26	2	AK → RR in AAB03642. Ref.1
	Sequence conflict	305	1	A → P in CAA83484. Ref.2
	Sequence conflict	358 – 359	2	SD → NE in CAA83484. Ref.2
	Sequence conflict	366	1	N → T in CAA83484. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q61288 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: 439510D3CC740D65	FASTA	502	56,519
	10 20 30 40 50 60 MTLGSFRRGL LMLSVAFGLT RGDLAKPSKL VNCTCESPHC KRPFCQGSWC TVVLVREQGR 70 80 90 100 110 120 HPQVYRGCGS LNQELCLGRP TEFLNHHCCY RSFCNHNVSL MLEATQTPSE EPEVDAHLPL 130 140 150 160 170 180 ILGPVLALPV LVALGALGLW RVRRRQEKQR DLHSDLGESS LILKASEQAD SMLGDFLDSD 190 200 210 220 230 240 CTTGSGSGLP FLVQRTVARQ VALVECVGKG RYGEVWRGSW HGESVAVKIF SSRDEQSWFR 250 260 270 280 290 300 ETEIYNTVLL RHDNILGFIA SDMTSRNSST QLWLITHYHE HGSLYDFLQR QTLEPQLALR 310 320 330 340 350 360 LAVSAACGLA HLHVEIFGTQ GKPAIAHRDL KSRNVLVKSN LQCCIADLGL AVMHSQSSDY 370 380 390 400 410 420 LDIGNNPRVG TKRYMAPEVL DEHIRTDCFE SYKWTDIWAF GLVLWEIARR TIINGIVEDY 430 440 450 460 470 480 RPPFYDMVPN DPSFEDMKKV VCVDQQTPTI PNRLAADPVL SGLAQMMREC WYPNPSARLT 490 500 ALRIKKTLQK LSHNPEKPKV IH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of the murine activin receptor like kinase-1 (ALK-1) homolog." Wu X., Robinson C.E., Fong H.W., Crabtree J.S., Rodriguez B.R., Roe B.A., Gimble J.M. Biochem. Biophys. Res. Commun. 216:78-83(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lung.
[2]	"Distinct spatial and temporal expression patterns of two type I receptors for bone morphogenetic proteins during mouse embryogenesis." Dewulf N., Verschueren K., Lonnoy O., Moren A., Grimsby S., Spiegle K., Miyazono K., Huylebroeck D., ten Dijke P. Endocrinology 136:2652-2663(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J and NOD.
[4]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: FVB/N. Tissue: Mammary tumor.
[6]	"The phagosomal proteome in interferon-gamma-activated macrophages." Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P. Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-154, MASS SPECTROMETRY. Tissue: Macrophage.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L48015 mRNA. Translation: AAB03642.1. Z31664 mRNA. Translation: CAA83484.1. AK160915 mRNA. Translation: BAE36089.1. AK170870 mRNA. Translation: BAE42083.1. CH466550 Genomic DNA. Translation: EDL04061.1. CH466550 Genomic DNA. Translation: EDL04063.1. BC015083 mRNA. Translation: AAH15083.1.
IPI	IPI00314843.
PIR	I48241. JC4337.
RefSeq	NP_033742.2. NM_009612.2.
UniGene	Mm.279542.
3D structure databases
ProteinModelPortal	Q61288.
SMR	Q61288. Positions 30-103, 169-491.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-4086807.
PTM databases
PhosphoSite	Q61288.
Proteomic databases
PaxDb	Q61288.
PRIDE	Q61288.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000000542; ENSMUSP00000000542; ENSMUSG00000000530. ENSMUST00000117984; ENSMUSP00000113505; ENSMUSG00000000530. ENSMUST00000119063; ENSMUSP00000113536; ENSMUSG00000000530. ENSMUST00000120028; ENSMUSP00000113297; ENSMUSG00000000530. ENSMUST00000120754; ENSMUSP00000112490; ENSMUSG00000000530. ENSMUST00000121718; ENSMUSP00000114027; ENSMUSG00000000530.
GeneID	11482.
KEGG	mmu:11482.
Organism-specific databases
CTD	94.
MGI	MGI:1338946. Acvrl1.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00670000098005.
HOGENOM	HOG000230587.
HOVERGEN	HBG054502.
InParanoid	Q91YR0.
KO	K13594.
OMA	WHVRRRQ.
OrthoDB	EOG4HDSTB.
Enzyme and pathway databases
BRENDA	2.7.10.2. 3474.
Gene expression databases
ArrayExpress	Q61288.
Bgee	Q61288.
CleanEx	MM_ACVRL1.
Genevestigator	Q61288.
GermOnline	ENSMUSG00000000530. Mus musculus.
Family and domain databases
InterPro	IPR000472. Activin_rcpt. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR008271. Ser/Thr_kinase_AS. IPR003605. TGF_beta_rcpt_GS. [Graphical view]
Pfam	PF01064. Activin_recp. 1 hit. PF00069. Pkinase. 1 hit. PF08515. TGF_beta_GS. 1 hit. [Graphical view]
SMART	SM00467. GS. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS51256. GS. 1 hit. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	278836.
SOURCE	Search...

Entry information

Entry name

ACVL1_MOUSE

Accession

Primary (citable) accession number: Q61288
Secondary accession number(s): Q61289, Q91YR0

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	July 27, 2011
Last modified:	April 3, 2013
This is version 124 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program