Reviewed, UniProtKB/Swiss-Prot Q8NER5 (ACV1C_HUMAN)

Names and origin

Protein names

Recommended name:
    Activin receptor type-1C
    EC=2.7.11.30
Alternative name(s):
    ACTR-IC
    Activin receptor-like kinase 7
      Short name(s)=ALK-7

Gene names

Name:	ACVR1C
Synonyms:	ALK7

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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.
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.
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.
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
Ligand	ATP-binding Magnesium Manganese Metal-binding Nucleotide-binding
Molecular function	Kinase Receptor Serine/threonine-protein kinase Transferase
Gene Ontology (GO)
Biological process	cell differentiation Ref.5 Inferred from direct assay. Source: UniProtKB protein amino acid phosphorylation Ref.1 Inferred by curator. Source: UniProtKB regulation of apoptosis Ref.5 Inferred from direct assay. Source: UniProtKB
Cellular component	activin receptor complex Ref.5 Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Ref.1 Inferred by curator. Source: UniProtKB activin receptor activity, type I Ref.1 Inferred from direct assay. Source: UniProtKB metal ion binding Ref.1 Inferred by curator. Source: UniProtKB
Complete GO annotation...

Alternative products

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

Isoform 1 (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 (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 (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 (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
Molecule processing
	Signal peptide	1 – 20	20	Potential
	Chain	21 – 493	473	Activin receptor type-1C
Regions
	Topological domain	22 – 113	92	Extracellular Potential
	Transmembrane	114 – 134	21	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
Sites
	Active site	323	1	Proton acceptor By similarity
	Binding site	222	1	ATP By similarity
Natural variations
	Alternative sequence	1 – 50	50	Missing in isoform 4.
	Alternative sequence	102 – 258	157	Missing in isoform 2.
	Alternative sequence	102 – 181	80	Missing in isoform 3.
	Natural variant	195	1	I → T
	Natural variant	216	1	G → R
	Natural variant	267	1	W → R in a lung squamous cell carcinoma sample; somatic mutation.
	Natural variant	355	1	I → V
	Natural variant	482	1	I → V
Experimental info
	Mutagenesis	194	1	T → D: Pro-apoptotic
	Mutagenesis	222	1	K → R: Loss of response to NODAL and SMAD2 phosphorylation
	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		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		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		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: 12063393] [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: 12606401] [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: 15815621] [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: 15489334] [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: 15531507] [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: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-195; ARG-216; ARG-267; VAL-355 AND VAL-482.

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
RefSeq	NP_001104501.1. NP_001104502.1. NP_001104503.1. NP_660302.2.
UniGene	Hs.352338 Hs.541710 Hs.562901
3D structure databases
HSSP	HSSP built from PDB template 1IAS based on UniProtKB P36897.
SMR	Q8NER5. Positions 161-489.
ModBase	Search...
Genome annotation databases
Ensembl	ENSG00000123612. Homo sapiens. [Contig view]
GeneID	130399.
KEGG	hsa:130399.
Organism-specific databases
H-InvDB	HIX0002523.
HGNC	HGNC:18123. ACVR1C.
HPA	HPA007982. HPA011933.
MIM	608981. gene.
PharmGKB	PA134908988.
GenAtlas	Search...
GeneCards	Search...
GeneLynx	Search...
Phylogenomic databases
HOGENOM	Q8NER5.
HOVERGEN	Q8NER5.
Gene expression databases
ArrayExpress	Q8NER5.
CleanEx	HS_ACVR1C.
GermOnline	ENSG00000123612. Homo sapiens.
Family and domain databases
InterPro	IPR000472. Activin_rcpt. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_bd_CS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_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]
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00467. GS. 1 hit. [Graphical view]
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]
BLOCKS	Search...
Other Resources
SOURCE	Search...
ProtoNet	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:	July 22, 2008
This is version 54 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)