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Q8NER5 (ACV1C_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 116. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length493 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 processApoptosis
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSignal
Transmembrane
Transmembrane helix
   LigandATP-binding
Magnesium
Manganese
Metal-binding
Nucleotide-binding
   Molecular functionKinase
Receptor
Serine/threonine-protein kinase
Transferase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic nuclear changes

Inferred from direct assay Ref.5. Source: UniProtKB

cell differentiation

Inferred from direct assay Ref.5. Source: UniProtKB

lipid storage

Inferred from electronic annotation. Source: Ensembl

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: Ensembl

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

protein phosphorylation

Inferred by curator Ref.1. Source: UniProtKB

response to dietary excess

Inferred from electronic annotation. Source: Ensembl

response to glucose

Inferred from electronic annotation. Source: Ensembl

response to insulin

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentactivin receptor complex

Inferred from direct assay Ref.5. Source: UniProtKB

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

activin receptor activity, type I

Inferred from direct assay Ref.1. Source: UniProtKB

growth factor binding

Inferred from physical interaction PubMed 21805089. Source: UniProt

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020 Potential
Chain21 – 493473Activin receptor type-1C
PRO_0000042628

Regions

Topological domain22 – 11392Extracellular Potential
Transmembrane114 – 13421Helical; Potential
Topological domain135 – 493359Cytoplasmic Potential
Domain165 – 19430GS
Domain195 – 485291Protein kinase
Nucleotide binding201 – 2099ATP By similarity UniProtKB Q04771

Sites

Active site3231Proton acceptor By similarity UniProtKB Q04771
Binding site2221ATP By similarity UniProtKB Q04771

Natural variations

Alternative sequence1 – 5050Missing in isoform 4. Ref.2
VSP_051840
Alternative sequence102 – 258157Missing in isoform 2. Ref.2
VSP_051841
Alternative sequence102 – 18180Missing in isoform 3. Ref.2
VSP_051842
Natural variant1951I → T. Ref.6
Corresponds to variant rs56188432 [ dbSNP | Ensembl ].
VAR_041407
Natural variant2161G → R. Ref.6
VAR_041408
Natural variant2671W → R in a lung squamous cell carcinoma sample; somatic mutation. Ref.6
VAR_041409
Natural variant3551I → V. Ref.6
Corresponds to variant rs35500979 [ dbSNP | Ensembl ].
VAR_041410
Natural variant4821I → V. Ref.6
Corresponds to variant rs7594480 [ dbSNP | Ensembl ].
VAR_041411

Experimental info

Mutagenesis1941T → D: Pro-apoptotic. Ref.5
Mutagenesis2221K → R: Loss of response to NODAL and SMAD2 phosphorylation. Ref.1 Ref.5
Sequence conflict2311S → Y in AAH22530. Ref.4
Sequence conflict2891V → M in AAH22530. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 2002. Version 1.
Checksum: 5A10F259679204CB

FASTA49354,871
        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 

« Hide

Isoform 2 (B) (soluble B) [UniParc].

Checksum: 9F2832F46C7E997C
Show »

FASTA33637,461
Isoform 3 (A) (soluble A) [UniParc].

Checksum: 1B34129E0CE1B2C2
Show »

FASTA41346,357
Isoform 4 (Truncated) [UniParc].

Checksum: BB1AEE54E0187E02
Show »

FASTA44349,684

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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.
RefSeqNP_001104501.1. NM_001111031.1.
NP_001104502.1. NM_001111032.1.
NP_001104503.1. NM_001111033.1.
NP_660302.2. NM_145259.2.
UniGeneHs.562901.

3D structure databases

ProteinModelPortalQ8NER5.
SMRQ8NER5. Positions 25-97, 190-485.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid126232. 2 interactions.
IntActQ8NER5. 1 interaction.
STRING9606.ENSP00000243349.

Chemistry

ChEMBLCHEMBL5642.

PTM databases

PhosphoSiteQ8NER5.

Polymorphism databases

DMDM74762565.

Proteomic databases

PaxDbQ8NER5.
PRIDEQ8NER5.

Protocols and materials databases

DNASU130399.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000243349; ENSP00000243349; ENSG00000123612. [Q8NER5-1]
ENST00000335450; ENSP00000335178; ENSG00000123612. [Q8NER5-3]
ENST00000348328; ENSP00000335139; ENSG00000123612. [Q8NER5-2]
ENST00000409680; ENSP00000387168; ENSG00000123612. [Q8NER5-4]
GeneID130399.
KEGGhsa:130399.
UCSCuc002tzk.4. human. [Q8NER5-1]
uc002tzl.4. human. [Q8NER5-3]
uc010fof.3. human. [Q8NER5-2]

Organism-specific databases

CTD130399.
GeneCardsGC02M158352.
HGNCHGNC:18123. ACVR1C.
HPAHPA007982.
HPA011933.
MIM608981. gene.
neXtProtNX_Q8NER5.
PharmGKBPA134908988.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000230587.
HOVERGENHBG054502.
InParanoidQ8NER5.
KOK13568.
OMAWACQGRQ.
OrthoDBEOG7Q8CN3.
PhylomeDBQ8NER5.
TreeFamTF314724.

Enzyme and pathway databases

BRENDA2.7.11.30. 2681.
ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
SignaLinkQ8NER5.

Gene expression databases

ArrayExpressQ8NER5.
BgeeQ8NER5.
CleanExHS_ACVR1C.
GenevestigatorQ8NER5.

Family and domain databases

InterProIPR000472. Activin_rcpt.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR003605. TGF_beta_rcpt_GS.
[Graphical view]
PfamPF01064. Activin_recp. 1 hit.
PF00069. Pkinase. 1 hit.
PF08515. TGF_beta_GS. 1 hit.
[Graphical view]
SMARTSM00467. GS. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS51256. GS. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiACVR1C.
GenomeRNAi130399.
NextBio82739.
PROQ8NER5.
SOURCESearch...

Entry information

Entry nameACV1C_HUMAN
AccessionPrimary (citable) accession number: Q8NER5
Secondary accession number(s): Q4ZFZ8 expand/collapse secondary AC list , Q86UL1, Q86UL2, Q8TBG2
Entry history
Integrated into UniProtKB/Swiss-Prot: October 25, 2005
Last sequence update: October 1, 2002
Last modified: April 16, 2014
This is version 116 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM