Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Activin receptor type-1C

Gene

ACVR1C

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

Catalytic activityi

ATP + [receptor-protein] = ADP + [receptor-protein] phosphate.

Cofactori

Mg2+Curated, Mn2+Curated

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei222ATPPROSITE-ProRule annotationBy similarity1
Active sitei323Proton acceptorPROSITE-ProRule annotationBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi201 – 209ATPPROSITE-ProRule annotationBy similarity9

GO - Molecular functioni

  • activin receptor activity, type I Source: UniProtKB
  • ATP binding Source: UniProtKB-KW
  • growth factor binding Source: UniProtKB
  • metal ion binding Source: UniProtKB
  • nodal binding Source: BHF-UCL
  • protein serine/threonine kinase activity Source: Reactome
  • receptor signaling protein serine/threonine kinase activity Source: InterPro

GO - Biological processi

  • apoptotic nuclear changes Source: UniProtKB
  • cell differentiation Source: UniProtKB
  • lipid storage Source: Ensembl
  • negative regulation of chorionic trophoblast cell proliferation Source: BHF-UCL
  • negative regulation of insulin secretion Source: Ensembl
  • negative regulation of trophoblast cell migration Source: BHF-UCL
  • nodal signaling pathway Source: BHF-UCL
  • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: BHF-UCL
  • protein phosphorylation Source: UniProtKB
  • response to dietary excess Source: Ensembl
  • response to glucose Source: Ensembl
  • response to insulin Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis

Keywords - Ligandi

ATP-binding, Magnesium, Manganese, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS04680-MONOMER.
BRENDAi2.7.11.30. 2681.
ReactomeiR-HSA-1181150. Signaling by NODAL.
R-HSA-1433617. Regulation of signaling by NODAL.
R-HSA-1502540. Signaling by Activin.
SignaLinkiQ8NER5.
SIGNORiQ8NER5.

Names & Taxonomyi

Protein namesi
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 namesi
Name:ACVR1CImported
Synonyms:ALK71 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:18123. ACVR1C.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini22 – 113ExtracellularSequence analysisAdd BLAST92
Transmembranei114 – 134HelicalSequence analysisAdd BLAST21
Topological domaini135 – 493CytoplasmicSequence analysisAdd BLAST359

GO - Cellular componenti

  • activin receptor complex Source: UniProtKB
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi194T → D: Pro-apoptotic. 1 Publication1
Mutagenesisi222K → R: Loss of response to NODAL and SMAD2 phosphorylation. 2 Publications1

Organism-specific databases

DisGeNETi130399.
OpenTargetsiENSG00000123612.
PharmGKBiPA134908988.

Chemistry databases

ChEMBLiCHEMBL5642.

Polymorphism and mutation databases

BioMutaiACVR1C.
DMDMi74762565.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Sequence analysisAdd BLAST20
ChainiPRO_000004262821 – 493Activin receptor type-1CAdd BLAST473

Proteomic databases

MaxQBiQ8NER5.
PaxDbiQ8NER5.
PeptideAtlasiQ8NER5.
PRIDEiQ8NER5.

PTM databases

iPTMnetiQ8NER5.
PhosphoSitePlusiQ8NER5.

Expressioni

Tissue specificityi

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.2 Publications

Gene expression databases

BgeeiENSG00000123612.
CleanExiHS_ACVR1C.
GenevisibleiQ8NER5. HS.

Organism-specific databases

HPAiHPA007982.
HPA011933.

Interactioni

Subunit structurei

Binds the type 2 receptor protein ACVR2A.By similarity

GO - Molecular functioni

  • growth factor binding Source: UniProtKB
  • nodal binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi126232. 3 interactors.
IntActiQ8NER5. 3 interactors.
STRINGi9606.ENSP00000243349.

Structurei

3D structure databases

ProteinModelPortaliQ8NER5.
SMRiQ8NER5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini165 – 194GSPROSITE-ProRule annotationAdd BLAST30
Domaini195 – 485Protein kinasePROSITE-ProRule annotationAdd BLAST291

Sequence similaritiesi

Contains 1 GS domain.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2052. Eukaryota.
ENOG410XQT0. LUCA.
GeneTreeiENSGT00760000118876.
HOGENOMiHOG000230587.
HOVERGENiHBG054502.
InParanoidiQ8NER5.
KOiK13568.
OMAiAPKLGPM.
OrthoDBiEOG091G0BIU.
PhylomeDBiQ8NER5.
TreeFamiTF314724.

Family and domain databases

InterProiIPR003605. GS_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR000333. TGFB_receptor.
[Graphical view]
PANTHERiPTHR23255. PTHR23255. 1 hit.
PfamiPF07714. Pkinase_Tyr. 1 hit.
PF08515. TGF_beta_GS. 1 hit.
[Graphical view]
SMARTiSM00467. GS. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51256. GS. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 11 Publication (identifier: Q8NER5-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MTRALCSALR QALLLLAAAA ELSPGLKCVC LLCDSSNFTC QTEGACWASV
60 70 80 90 100
MLTNGKEQVI KSCVSLPELN AQVFCHSSNN VTKTECCFTD FCNNITLHLP
110 120 130 140 150
TASPNAPKLG PMELAIIITV PVCLLSIAAM LTVWACQGRQ CSYRKKKRPN
160 170 180 190 200
VEEPLSECNL VNAGKTLKDL IYDVTASGSG SGLPLLVQRT IARTIVLQEI
210 220 230 240 250
VGKGRFGEVW HGRWCGEDVA VKIFSSRDER SWFREAEIYQ TVMLRHENIL
260 270 280 290 300
GFIAADNKDN GTWTQLWLVS EYHEQGSLYD YLNRNIVTVA GMIKLALSIA
310 320 330 340 350
SGLAHLHMEI VGTQGKPAIA HRDIKSKNIL VKKCETCAIA DLGLAVKHDS
360 370 380 390 400
ILNTIDIPQN PKVGTKRYMA PEMLDDTMNV NIFESFKRAD IYSVGLVYWE
410 420 430 440 450
IARRCSVGGI VEEYQLPYYD MVPSDPSIEE MRKVVCDQKF RPSIPNQWQS
460 470 480 490
CEALRVMGRI MRECWYANGA ARLTALRIKK TISQLCVKED CKA
Length:493
Mass (Da):54,871
Last modified:October 1, 2002 - v1
Checksum:i5A10F259679204CB
GO
Isoform 21 Publication (identifier: Q8NER5-2) [UniParc]FASTAAdd to basket
Also known as: B1 Publication, soluble B1 Publication

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

Show »
Length:336
Mass (Da):37,461
Checksum:i9F2832F46C7E997C
GO
Isoform 31 Publication (identifier: Q8NER5-3) [UniParc]FASTAAdd to basket
Also known as: A1 Publication, soluble A1 Publication

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

Show »
Length:413
Mass (Da):46,357
Checksum:i1B34129E0CE1B2C2
GO
Isoform 41 Publication (identifier: Q8NER5-4) [UniParc]FASTAAdd to basket
Also known as: Truncated1 Publication

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

Show »
Length:443
Mass (Da):49,684
Checksum:iBB1AEE54E0187E02
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti231S → Y in AAH22530 (PubMed:15489334).Curated1
Sequence conflicti289V → M in AAH22530 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041407195I → T.1 PublicationCorresponds to variant rs56188432dbSNPEnsembl.1
Natural variantiVAR_041408216G → R.1 PublicationCorresponds to variant rs34742924dbSNPEnsembl.1
Natural variantiVAR_041409267W → R in a lung squamous cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_041410355I → V.1 PublicationCorresponds to variant rs35500979dbSNPEnsembl.1
Natural variantiVAR_041411482I → V.1 PublicationCorresponds to variant rs7594480dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0518401 – 50Missing in isoform 4. 1 PublicationAdd BLAST50
Alternative sequenceiVSP_051841102 – 258Missing in isoform 2. 1 PublicationAdd BLAST157
Alternative sequenceiVSP_051842102 – 181Missing in isoform 3. 1 PublicationAdd BLAST80

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS2205.1. [Q8NER5-1]
CCDS46432.1. [Q8NER5-2]
CCDS46433.1. [Q8NER5-3]
CCDS46434.1. [Q8NER5-4]
RefSeqiNP_001104501.1. NM_001111031.1. [Q8NER5-4]
NP_001104502.1. NM_001111032.1. [Q8NER5-3]
NP_001104503.1. NM_001111033.1. [Q8NER5-2]
NP_660302.2. NM_145259.2. [Q8NER5-1]
UniGeneiHs.562901.

Genome annotation databases

EnsembliENST00000243349; ENSP00000243349; ENSG00000123612. [Q8NER5-1]
ENST00000335450; ENSP00000335178; ENSG00000123612. [Q8NER5-3]
ENST00000348328; ENSP00000335139; ENSG00000123612. [Q8NER5-2]
ENST00000409680; ENSP00000387168; ENSG00000123612. [Q8NER5-4]
GeneIDi130399.
KEGGihsa:130399.
UCSCiuc002tzk.5. human. [Q8NER5-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS2205.1. [Q8NER5-1]
CCDS46432.1. [Q8NER5-2]
CCDS46433.1. [Q8NER5-3]
CCDS46434.1. [Q8NER5-4]
RefSeqiNP_001104501.1. NM_001111031.1. [Q8NER5-4]
NP_001104502.1. NM_001111032.1. [Q8NER5-3]
NP_001104503.1. NM_001111033.1. [Q8NER5-2]
NP_660302.2. NM_145259.2. [Q8NER5-1]
UniGeneiHs.562901.

3D structure databases

ProteinModelPortaliQ8NER5.
SMRiQ8NER5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi126232. 3 interactors.
IntActiQ8NER5. 3 interactors.
STRINGi9606.ENSP00000243349.

Chemistry databases

ChEMBLiCHEMBL5642.

PTM databases

iPTMnetiQ8NER5.
PhosphoSitePlusiQ8NER5.

Polymorphism and mutation databases

BioMutaiACVR1C.
DMDMi74762565.

Proteomic databases

MaxQBiQ8NER5.
PaxDbiQ8NER5.
PeptideAtlasiQ8NER5.
PRIDEiQ8NER5.

Protocols and materials databases

DNASUi130399.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000243349; ENSP00000243349; ENSG00000123612. [Q8NER5-1]
ENST00000335450; ENSP00000335178; ENSG00000123612. [Q8NER5-3]
ENST00000348328; ENSP00000335139; ENSG00000123612. [Q8NER5-2]
ENST00000409680; ENSP00000387168; ENSG00000123612. [Q8NER5-4]
GeneIDi130399.
KEGGihsa:130399.
UCSCiuc002tzk.5. human. [Q8NER5-1]

Organism-specific databases

CTDi130399.
DisGeNETi130399.
GeneCardsiACVR1C.
HGNCiHGNC:18123. ACVR1C.
HPAiHPA007982.
HPA011933.
MIMi608981. gene.
neXtProtiNX_Q8NER5.
OpenTargetsiENSG00000123612.
PharmGKBiPA134908988.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2052. Eukaryota.
ENOG410XQT0. LUCA.
GeneTreeiENSGT00760000118876.
HOGENOMiHOG000230587.
HOVERGENiHBG054502.
InParanoidiQ8NER5.
KOiK13568.
OMAiAPKLGPM.
OrthoDBiEOG091G0BIU.
PhylomeDBiQ8NER5.
TreeFamiTF314724.

Enzyme and pathway databases

BioCyciZFISH:HS04680-MONOMER.
BRENDAi2.7.11.30. 2681.
ReactomeiR-HSA-1181150. Signaling by NODAL.
R-HSA-1433617. Regulation of signaling by NODAL.
R-HSA-1502540. Signaling by Activin.
SignaLinkiQ8NER5.
SIGNORiQ8NER5.

Miscellaneous databases

ChiTaRSiACVR1C. human.
GeneWikiiACVR1C.
GenomeRNAii130399.
PROiQ8NER5.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000123612.
CleanExiHS_ACVR1C.
GenevisibleiQ8NER5. HS.

Family and domain databases

InterProiIPR003605. GS_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR000333. TGFB_receptor.
[Graphical view]
PANTHERiPTHR23255. PTHR23255. 1 hit.
PfamiPF07714. Pkinase_Tyr. 1 hit.
PF08515. TGF_beta_GS. 1 hit.
[Graphical view]
SMARTiSM00467. GS. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51256. GS. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiACV1C_HUMAN
AccessioniPrimary (citable) accession number: Q8NER5
Secondary accession number(s): Q4ZFZ8
, Q86UL1, Q86UL2, Q8TBG2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 25, 2005
Last sequence update: October 1, 2002
Last modified: November 2, 2016
This is version 140 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.