Q8NER5 (ACV1C_HUMAN) 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

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

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.5
Catalytic activity	ATP + [receptor-protein] = ADP + [receptor-protein] phosphate.
Cofactor	Magnesium or manganese.
Subunit structure	Binds the type 2 receptor protein ACVR2A By similarity.
Subcellular location	Membrane; Single-pass type I membrane protein Ref.2.
Tissue specificity	Present in pancreas, heart, colon, small intestine, ovary and the hippocampus, medulla oblongata and putamen of the brain. Isoform 1, isoform 2, isoform 3 and isoform 4 are all expressed in the placenta throughout pregnancy. Ref.1 Ref.2
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
Coding sequence diversity	Alternative splicing Polymorphism
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 Reference proteome
Gene Ontology (GO)
Biological_process	cell differentiation Inferred from direct assay Ref.5. Source: UniProtKB lipid storage Inferred from electronic annotation. Source: Compara negative regulation of chorionic trophoblast cell proliferation Inferred from mutant phenotype PubMed 15150278. Source: BHF-UCL negative regulation of insulin secretion Inferred from electronic annotation. Source: Compara negative regulation of trophoblast cell migration Inferred from direct assay PubMed 21356369. Source: BHF-UCL nodal signaling pathway Inferred from mutant phenotype PubMed 15150278. Source: BHF-UCL positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from mutant phenotype PubMed 15150278. Source: BHF-UCL response to dietary excess Inferred from electronic annotation. Source: Compara response to glucose stimulus Inferred from electronic annotation. Source: Compara response to insulin stimulus Inferred from electronic annotation. Source: Compara
Cellular_component	activin receptor complex Inferred from direct assay Ref.5. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW activin receptor activity, type I Inferred from direct assay Ref.1. Source: UniProtKB metal ion binding Inferred by curator Ref.1. Source: UniProtKB nodal binding Inferred from mutant phenotype PubMed 21356369. Source: BHF-UCL transforming growth factor beta-activated receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 Ref.2 (identifier: Q8NER5-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 Ref.2 (identifier: Q8NER5-2)

Also known as: B; soluble B;

The sequence of this isoform differs from the canonical sequence as follows:
     102-258: Missing.

Isoform 3 Ref.2 (identifier: Q8NER5-3)

Also known as: A; soluble A;

The sequence of this isoform differs from the canonical sequence as follows:
     102-181: Missing.

Isoform 4 Ref.2 (identifier: Q8NER5-4)

Also known as: Truncated;

The sequence of this isoform differs from the canonical sequence as follows:
     1-50: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 20	20	Potential
	Chain	21 – 493	473	Activin receptor type-1C		PRO_0000042628
Regions
	Topological domain	22 – 113	92	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
Natural variations
	Alternative sequence	1 – 50	50	Missing in isoform 4. Ref.2		VSP_051840
	Alternative sequence	102 – 258	157	Missing in isoform 2. Ref.2		VSP_051841
	Alternative sequence	102 – 181	80	Missing in isoform 3. Ref.2		VSP_051842
	Natural variant	195	1	I → T. Ref.6		VAR_041407
	Natural variant	216	1	G → R. Ref.6		VAR_041408
	Natural variant	267	1	W → R in a lung squamous cell carcinoma sample; somatic mutation. Ref.6		VAR_041409
	Natural variant	355	1	I → V. Ref.6		VAR_041410
	Natural variant	482	1	I → V. Ref.6 Corresponds to variant rs7594480 [ dbSNP | Ensembl ].		VAR_041411
Experimental info
	Mutagenesis	194	1	T → D: Pro-apoptotic. Ref.5
	Mutagenesis	222	1	K → R: Loss of response to NODAL and SMAD2 phosphorylation. Ref.1 Ref.5
	Sequence conflict	231	1	S → Y in AAH22530. Ref.4
	Sequence conflict	289	1	V → M in AAH22530. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2002. Version 1. Checksum: 5A10F259679204CB	FASTA	493	54,871
	10 20 30 40 50 60 MTRALCSALR QALLLLAAAA ELSPGLKCVC LLCDSSNFTC QTEGACWASV MLTNGKEQVI 70 80 90 100 110 120 KSCVSLPELN AQVFCHSSNN VTKTECCFTD FCNNITLHLP TASPNAPKLG PMELAIIITV 130 140 150 160 170 180 PVCLLSIAAM LTVWACQGRQ CSYRKKKRPN VEEPLSECNL VNAGKTLKDL IYDVTASGSG 190 200 210 220 230 240 SGLPLLVQRT IARTIVLQEI VGKGRFGEVW HGRWCGEDVA VKIFSSRDER SWFREAEIYQ 250 260 270 280 290 300 TVMLRHENIL GFIAADNKDN GTWTQLWLVS EYHEQGSLYD YLNRNIVTVA GMIKLALSIA 310 320 330 340 350 360 SGLAHLHMEI VGTQGKPAIA HRDIKSKNIL VKKCETCAIA DLGLAVKHDS ILNTIDIPQN 370 380 390 400 410 420 PKVGTKRYMA PEMLDDTMNV NIFESFKRAD IYSVGLVYWE IARRCSVGGI VEEYQLPYYD 430 440 450 460 470 480 MVPSDPSIEE MRKVVCDQKF RPSIPNQWQS CEALRVMGRI MRECWYANGA ARLTALRIKK 490 TISQLCVKED CKA
	Isoform 2 (B) (soluble B) [UniParc]. Checksum: 9F2832F46C7E997C	FASTA	336	37,461
	10 20 30 40 50 60 MTRALCSALR QALLLLAAAA ELSPGLKCVC LLCDSSNFTC QTEGACWASV MLTNGKEQVI 70 80 90 100 110 120 KSCVSLPELN AQVFCHSSNN VTKTECCFTD FCNNITLHLP TDNGTWTQLW LVSEYHEQGS 130 140 150 160 170 180 LYDYLNRNIV TVAGMIKLAL SIASGLAHLH MEIVGTQGKP AIAHRDIKSK NILVKKCETC 190 200 210 220 230 240 AIADLGLAVK HDSILNTIDI PQNPKVGTKR YMAPEMLDDT MNVNIFESFK RADIYSVGLV 250 260 270 280 290 300 YWEIARRCSV GGIVEEYQLP YYDMVPSDPS IEEMRKVVCD QKFRPSIPNQ WQSCEALRVM 310 320 330 GRIMRECWYA NGAARLTALR IKKTISQLCV KEDCKA
	Isoform 3 (A) (soluble A) [UniParc]. Checksum: 1B34129E0CE1B2C2	FASTA	413	46,357
	10 20 30 40 50 60 MTRALCSALR QALLLLAAAA ELSPGLKCVC LLCDSSNFTC QTEGACWASV MLTNGKEQVI 70 80 90 100 110 120 KSCVSLPELN AQVFCHSSNN VTKTECCFTD FCNNITLHLP TGLPLLVQRT IARTIVLQEI 130 140 150 160 170 180 VGKGRFGEVW HGRWCGEDVA VKIFSSRDER SWFREAEIYQ TVMLRHENIL GFIAADNKDN 190 200 210 220 230 240 GTWTQLWLVS EYHEQGSLYD YLNRNIVTVA GMIKLALSIA SGLAHLHMEI VGTQGKPAIA 250 260 270 280 290 300 HRDIKSKNIL VKKCETCAIA DLGLAVKHDS ILNTIDIPQN PKVGTKRYMA PEMLDDTMNV 310 320 330 340 350 360 NIFESFKRAD IYSVGLVYWE IARRCSVGGI VEEYQLPYYD MVPSDPSIEE MRKVVCDQKF 370 380 390 400 410 RPSIPNQWQS CEALRVMGRI MRECWYANGA ARLTALRIKK TISQLCVKED CKA
	Isoform 4 (Truncated) [UniParc]. Checksum: BB1AEE54E0187E02	FASTA	443	49,684
	10 20 30 40 50 60 MLTNGKEQVI KSCVSLPELN AQVFCHSSNN VTKTECCFTD FCNNITLHLP TASPNAPKLG 70 80 90 100 110 120 PMELAIIITV PVCLLSIAAM LTVWACQGRQ CSYRKKKRPN VEEPLSECNL VNAGKTLKDL 130 140 150 160 170 180 IYDVTASGSG SGLPLLVQRT IARTIVLQEI VGKGRFGEVW HGRWCGEDVA VKIFSSRDER 190 200 210 220 230 240 SWFREAEIYQ TVMLRHENIL GFIAADNKDN GTWTQLWLVS EYHEQGSLYD YLNRNIVTVA 250 260 270 280 290 300 GMIKLALSIA SGLAHLHMEI VGTQGKPAIA HRDIKSKNIL VKKCETCAIA DLGLAVKHDS 310 320 330 340 350 360 ILNTIDIPQN PKVGTKRYMA PEMLDDTMNV NIFESFKRAD IYSVGLVYWE IARRCSVGGI 370 380 390 400 410 420 VEEYQLPYYD MVPSDPSIEE MRKVVCDQKF RPSIPNQWQS CEALRVMGRI MRECWYANGA 430 440 ARLTALRIKK TISQLCVKED CKA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning, expression studies and chromosome mapping of human type I serine/threonine kinase receptor ALK7 (ACVR1C)." Bondestam J., Huotari M.-A., Moren A., Ustinov J., Kaivo-Oja N., Kallio J., Horelli-Kuitunen N., Aaltonen J., Fujii M., Moustakas A., Ten Dijke P., Otonkoski T., Ritvos O. Cytogenet. Cell Genet. 95:157-162(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, MUTAGENESIS OF LYS-222. Tissue: Brain.
[2]	"Identification of novel isoforms of activin receptor-like kinase 7 (ALK7) generated by alternative splicing and expression of ALK7 and its ligand, Nodal, in human placenta." Roberts H.J., Hu S., Qiu Q., Leung P.C.K., Caniggia I., Gruslin A., Tsang B., Peng C. Biol. Reprod. 68:1719-1726(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Placenta.
[3]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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] (ISOFORM 1). Tissue: Brain.
[5]	"Nodal induces apoptosis and inhibits proliferation in human epithelial ovarian cancer cells via activin receptor-like kinase 7." Xu G., Zhong Y., Munir S., Yang B.B., Tsang B.K., Peng C. J. Clin. Endocrinol. Metab. 89:5523-5534(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF THR-194 AND LYS-222.
[6]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-195; ARG-216; ARG-267; VAL-355 AND VAL-482.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY127050 mRNA. Translation: AAM93495.1. AF525679 mRNA. Translation: AAP21993.1. AF525680 mRNA. Translation: AAP21994.1. AF525681 mRNA. Translation: AAP21995.1. AC019186 Genomic DNA. No translation available. AC079750 Genomic DNA. Translation: AAX88951.1. BC022530 mRNA. Translation: AAH22530.1.
IPI	IPI00302552. IPI00384221. IPI00384222. IPI00654757.
RefSeq	NP_001104501.1. NM_001111031.1. NP_001104502.1. NM_001111032.1. NP_001104503.1. NM_001111033.1. NP_660302.2. NM_145259.2.
UniGene	Hs.562901.
3D structure databases
ProteinModelPortal	Q8NER5.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8NER5. 1 interaction.
STRING	9606.ENSP00000243349.
PTM databases
PhosphoSite	Q8NER5.
Polymorphism databases
DMDM	74762565.
Proteomic databases
PaxDb	Q8NER5.
PRIDE	Q8NER5.
Protocols and materials databases
DNASU	130399.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000243349; ENSP00000243349; ENSG00000123612. ENST00000335450; ENSP00000335178; ENSG00000123612. ENST00000348328; ENSP00000335139; ENSG00000123612. ENST00000409680; ENSP00000387168; ENSG00000123612.
GeneID	130399.
KEGG	hsa:130399.
UCSC	uc002tzk.4. human. uc002tzl.4. human. uc010fof.3. human.
Organism-specific databases
CTD	130399.
GeneCards	GC02M158352.
HGNC	HGNC:18123. ACVR1C.
HPA	HPA007982. HPA011933.
MIM	608981. gene.
neXtProt	NX_Q8NER5.
PharmGKB	PA134908988.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000230587.
HOVERGEN	HBG054502.
InParanoid	Q8NER5.
KO	K13568.
OMA	YRKKKRP.
OrthoDB	EOG4PVNZN.
PhylomeDB	Q8NER5.
Enzyme and pathway databases
BRENDA	2.7.11.30. 2681.
Reactome	REACT_111045. Developmental Biology. REACT_111102. Signal Transduction.
SignaLink	Q8NER5.
Gene expression databases
ArrayExpress	Q8NER5.
Bgee	Q8NER5.
CleanEx	HS_ACVR1C.
Genevestigator	Q8NER5.
GermOnline	ENSG00000123612. Homo sapiens.
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
ChEMBL	CHEMBL5642.
GenomeRNAi	130399.
NextBio	82739.
SOURCE	Search...

Entry information

Entry name

ACV1C_HUMAN

Accession

Primary (citable) accession number: Q8NER5
Secondary accession number(s): Q4ZFZ8 , Q86UL1, Q86UL2, Q8TBG2

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 25, 2005
Last sequence update:	October 1, 2002
Last modified:	May 29, 2013
This is version 106 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.