P70539 (ACV1C_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Activin receptor type-1C
EC=2.7.11.30

Alternative name(s):
Activin receptor type IC
Short name=ACTR-IC
Activin receptor-like kinase 7
Short name=ALK-7

Gene names

Name:	Acvr1c
Synonyms:	Alk7

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [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 › Rattus

Protein attributes

Sequence length	493 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	Serine/threonine protein kinase which forms a receptor complex on ligand binding. The receptor complex consisting of 2 type II and 2 type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators, SMAD2 and SMAD3. Receptor for activin AB, activin B and NODAL. Plays a role in cell differentiation, growth arrest and apoptosis. Ref.1 Ref.3 Ref.4 Ref.5
Catalytic activity	ATP + [receptor-protein] = ADP + [receptor-protein] phosphate.
Cofactor	Magnesium or manganese.
Subunit structure	Binds the type 2 receptor protein ACVR2A.
Subcellular location	Membrane; Single-pass type I membrane protein Ref.3.
Tissue specificity	Expressed in brain, kidney, lung, liver, testis, ovary, adrenal gland, heart, prostate, gastrointestinal tract, and spleen. Distributed throughout both adult and embryonic central nervous system and pancreatic islet cells. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5
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	Apoptosis
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
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW cell differentiation Inferred from direct assay Ref.5. Source: UniProtKB cerebellum development Inferred from expression pattern Ref.2. Source: RGD hippocampus development Inferred from expression pattern Ref.2. Source: RGD midbrain development Inferred from expression pattern Ref.2. Source: RGD ovarian follicle development Inferred from expression pattern PubMed 16709598. Source: RGD regulation of apoptotic process Inferred from direct assay Ref.5. Source: UniProtKB response to drug Inferred from expression pattern Ref.2. Source: RGD response to glucose stimulus Inferred from expression pattern PubMed 16440210. Source: RGD response to lipid Inferred from expression pattern PubMed 16440210. Source: RGD response to organic cyclic compound Inferred from expression pattern PubMed 8934566. Source: RGD transforming growth factor beta receptor complex assembly Inferred from direct assay Ref.2. Source: RGD
Cellular_component	activin receptor complex Inferred from direct assay Ref.3. Source: UniProtKB cell surface Inferred from direct assay Ref.2. Source: RGD cytoplasm Inferred from direct assay PubMed 16440210. Source: RGD
Molecular_function	ATP binding Inferred from direct assay PubMed 12065756. Source: HGNC BMP receptor binding Inferred from direct assay Ref.2. Source: RGD SMAD binding Inferred from direct assay PubMed 12065756. Source: HGNC activin binding Inferred from direct assay Ref.3. Source: MGI activin receptor activity, type I Inferred from direct assay Ref.1. Source: UniProtKB metal ion binding Inferred by curator Ref.1. Source: UniProtKB transforming growth factor beta-activated receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 25	25	Potential
	Chain	26 – 493	468	Activin receptor type-1C		PRO_0000042630
Regions
	Topological domain	26 – 113	88	Extracellular Potential
	Transmembrane	114 – 134	21	Helical; Potential
	Topological domain	135 – 493	359	Cytoplasmic Potential
	Domain	165 – 194	30	GS
	Domain	195 – 485	291	Protein kinase
	Nucleotide binding	201 – 209	9	ATP By similarity UniProtKB Q04771
Sites
	Active site	323	1	Proton acceptor By similarity UniProtKB Q04771
	Binding site	222	1	ATP By similarity UniProtKB Q04771
Experimental info
	Mutagenesis	194	1	T → D: Constitutively activates downstream transcription factor function. Ref.1 Ref.4
	Mutagenesis	222	1	K → R: Fails to activate downstream transcription factor function. Ref.1
	Sequence conflict	5	1	R → S in AAC52919. Ref.2
	Sequence conflict	60	1	S → I in AAC52919. Ref.2
	Sequence conflict	97	1	Q → L in AAC52919. Ref.2
	Sequence conflict	183	1	P → L in AAC52919. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P70539 [UniParc]. Last modified February 1, 1997. Version 1. Checksum: FB2BB3C2A026BCC3	FASTA	493	54,842
	10 20 30 40 50 60 MTPARRSALS LALLLVALAS DLAAGLKCVC LLCDSSNFTC QTEGACWASV MLTNGKEQVS 70 80 90 100 110 120 KSCVSLPELN AQVFCHSSNN VTKTECCFTD FCNNITQHLP TASPDAPRLG PTELTVVITV 130 140 150 160 170 180 PVCLLSIAAM LTIWACQDRQ CTYRKTKRHN VEEPLAEYSL VNAGKTLKDL IYDATASGSG 190 200 210 220 230 240 SGPPLLVQRT IARTIVLQEI VGKGRFGEVW HGRWCGEDVA VKIFSSRDER SWFREAEIYQ 250 260 270 280 290 300 TVMLRHENIL GFIAADNKDN GTWTQLWLVS EYHEQGSLYD YLNRNIVTVA GMVKLALSIA 310 320 330 340 350 360 SGLAHLHMEI VGTQGKPAIA HRDIKSKNIL VKKCDTCAIA DLGLAVKHDS IMNTIDIPQN 370 380 390 400 410 420 PKVGTKRYMA PEMLDDTMNV NIFESFKRAD IYSVGLVYWE IARRCSVGGL VEEYQLPYYD 430 440 450 460 470 480 MVPSDPSIEE MRKVVCDQKL RPNLPNQWQS CEALRVMGRI MRECWYANGA ARLTALRVKK 490 TISQLCVKED CKA

References

[1]	"Molecular cloning of a novel type I receptor serine/threonine kinase for the TGF beta superfamily from rat brain." Tsuchida K., Sawchenko P.E., Nishikawa S., Vale W.W. Mol. Cell. Neurosci. 7:467-478(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, MUTAGENESIS OF THR-194 AND LYS-222. Strain: Sprague-Dawley. Tissue: Brain.
[2]	"A novel type I receptor serine-threonine kinase predominantly expressed in the adult central nervous system." Ryden M., Imamura T., Joernvall H., Belluardo N., Neveu I., Trupp M., Okadome T., ten Dijke P., Ibanez C.F. J. Biol. Chem. 271:30603-30609(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Brain.
[3]	"Activin isoforms signal through type I receptor serine/threonine kinase ALK7." Tsuchida K., Nakatani M., Yamakawa N., Hashimoto O., Hasegawa Y., Sugino H. Mol. Cell. Endocrinol. 220:59-65(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 139-159, FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INTERACTION WITH ACVR2A; ACTIVIN AB AND B.
[4]	"The MH1 domains of smad2 and smad3 are involved in the regulation of the ALK7 signals." Watanabe R., Yamada Y., Ihara Y., Someya Y., Kubota A., Kagimoto S., Kuroe A., Iwakura T., Shen Z.-P., Inada A., Adachi T., Ban N., Miyawaki K., Sunaga Y., Tsuda K., Seino Y. Biochem. Biophys. Res. Commun. 254:707-712(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, MUTAGENESIS OF THR-194.
[5]	"The orphan receptor serine/threonine kinase ALK7 signals arrest of proliferation and morphological differentiation in a neuronal cell line." Joernvall H., Blokzijl A., ten Dijke P., Ibanez C.F. J. Biol. Chem. 276:5140-5146(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U35025 mRNA. Translation: AAC52803.1. U69702 mRNA. Translation: AAC52919.1.
IPI	IPI00190491.
RefSeq	NP_620790.1. NM_139090.1.
UniGene	Rn.10580.
3D structure databases
ProteinModelPortal	P70539.
SMR	P70539. Positions 161-489.
ModBase	Search...
Proteomic databases
PaxDb	P70539.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	245921.
KEGG	rno:245921.
UCSC	RGD:621789. rat.
Organism-specific databases
CTD	130399.
RGD	621789. Acvr1c.
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000230587.
HOVERGEN	HBG054502.
InParanoid	P70539.
KO	K13568.
Gene expression databases
ArrayExpress	P70539.
Genevestigator	P70539.
GermOnline	ENSRNOG00000004828. Rattus norvegicus.
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	623170.

Entry information

Entry name

ACV1C_RAT

Accession

Primary (citable) accession number: P70539
Secondary accession number(s): P70603

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 25, 2005
Last sequence update:	February 1, 1997
Last modified:	April 3, 2013
This is version 96 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program