KCTD15 (19q13.119 , Expr. . skin, endometrium +21.
https://www.ncbi.nlm.nih.gov/gene/79047
- Official
Symbol
- KCTD15
- Official
Full Name
- potassium channel tetramerization domain containing 15provided by HGNC
- Expression
- Broad expression in skin (RPKM 22.8), endometrium (RPKM 7.8) and 21 other tissues See more
- Orthologs
- mouse
all
- Preferred Names
- BTB/POZ domain-containing protein KCTD15
- Names
- potassium channel tetramerisation domain containing 15
- potassium channel tetramerization domain-containing protein 15
-
REFERENCE 1 (residues 1 to 283)
AUTHORS Smaldone G, Pirone L, Capolupo A, Vitagliano L, Monti MC, Di
Gaetano S and Pedone E.
TITLE The essential player in adipogenesis GRP78 is a novel KCTD15
interactor
JOURNAL Int. J. Biol. Macromol. 115, 469-475 (2018)
PUBMED 29665387 Abstract
KCTD15 is a member of the K+ Channel
Tetramerization Domain family, implicated in crucial physio-pathological
processes. Recent evidences suggest that KCTD15 is an obesity-linked
protein in humans and its Drosophila homologue is involved in food
uptake. KCTD15 molecular mechanism in these processes is still unknown.
To fill this gap, KCTD15 was biophysically characterized showing a
folded, pentameric region endowed with a remarkable thermal stability.
Notably, the C-terminal domain significantly contributes to the
stabilization of the BTB N-terminal domain. The availability of large
amount of stable recombinant protein also made possible a functional
proteomic approach in 3T3-L1 cells to search for novel KCTD15
interactors. These investigations led to the discovery that GRP78 is a
KCTD15 partner in all the adipogenesis phases. Our data clearly prove
the physical interaction of the two proteins and also indicate that
GRP78 plays an active role in the stabilization of KCTD15. Furthermore,
the presence in Drosophila of a GRP78 homologue corroborates the
physiological role played by the complex KCTD15-GRP78 in the
adipogenesis process and indicates that it is evolutionarily conserved.
Present results also suggest that KCTD15 may be a new target for obesity
control.
(GRP78 as a Master Regulator of the Unfolded Protein Response, UPR).
- Influence of TFAP2B and KCTD15 genetic variability on personality dimensions in anorexia and bulimia nervosa.
Gamero-Villarroel C, et al. Brain Behav, 2017 Sep. PMID 28948079, Free PMC Article
-
Genetic
variations in SEC16B, MC4R, MAP2K5 and KCTD15 were associated with
childhood obesity and interacted with dietary behaviors in Chinese
school-age population.
Lv D, et al. Gene, 2015 Apr 15. PMID 25637721
-
Obesity genotype score and cardiovascular risk in women with type 2 diabetes mellitus.
He M, et al. Arterioscler Thromb Vasc Biol, 2010 Feb. PMID 19910641, Free PMC Article
-
The BTB-containing protein Kctd15 is SUMOylated in vivo.
Zarelli VE, et al. PLoS One, 2013. PMID 24086424, Free PMC ArticleAbstract
Potassium Channel
Tetramerization Domain containing 15 (Kctd15) has a role in regulating
the neural crest (NC) domain in the embryo. Kctd15 inhibits NC induction
by antagonizing Wnt signaling and by interaction with the transcription
factor AP-2α activation domain blocking its activity. Here we
demonstrate that Kctd15 is SUMOylated by SUMO1 and SUMO2/3. Kctd15
contains a classical SUMO interacting motif, ψKxE, at the C-terminal
end, and variants of the motif within the molecule. Kctd15 SUMOylation
occurs exclusively in the C-terminal motif. Inability to be SUMOylated
did not affect Kctd15's subcellular localization, or its ability to
repress AP-2 transcriptional activity and to inhibit NC formation in
zebrafish embryos. In contrast, a fusion of Kctd15 and SUMO had little
effectiveness in AP-2 inhibition and in blocking of NC formation. These
data suggest that the non-SUMOylated form of Kctd15 functions in NC
development.
-
Sex-dependent
associations of genetic variants identified by GWAS with indices of
adiposity and obesity risk in a Chinese children population.
Xi B, et al. Clin Endocrinol (Oxf), 2013 Oct. PMID 23121087
What's a GeneRIF?
-
The
KCTD15 rs287103 T variant allele was associated with increased risk of
bulimia nervosa and with scores of psychopathological scales of these
patients.
-
SEC16B,
MC4R, MAP2K5 and KCTD15 (rs17782313, rs543874, rs2241423 and
rs11084753) polymorphisms are associated with the risk for children
obesity in China.
-
These data suggest that the non-SUMOylated form of Kctd15 functions in neural crest development.
-
Data
show the synthetic effect of SNPs on the indices of adiposity and risk
of obesity in Chinese girls, but failed to replicate the effect of five
separate variants of SEC16B rs10913469, SH2B1 rs4788102, PCSK1 rs6235,
KCTD15 rs29941 and BAT2 rs2844479.
-
results
indicate that Kctd15 acts in the embryo at least in part by
specifically binding to the activation domain of AP-2alpha, thereby
blocking the function of this critical factor in the neural crest
induction hierarchy.
-
Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
-
Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
-
Observational study of gene-disease association. (HuGE Navigator)
-
Observational study, meta-analysis, and genome-wide association study of gene-disease association. (HuGE Navigator)
LOCUS NP_001123466 283 aa linear PRI 02-JUN-2019
DEFINITION BTB/POZ domain-containing protein KCTD15 isoform 2 [Homo sapiens].
ACCESSION NP_001123466
VERSION NP_001123466.1
DBSOURCE REFSEQ: accession NM_001129994.2
KEYWORDS RefSeq; RefSeq Select.
SOURCE Homo sapiens (human)
ORGANISM Homo sapiens
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
REFERENCE 1 (residues 1 to 283)
AUTHORS Smaldone G, Pirone L, Capolupo A, Vitagliano L, Monti MC, Di
Gaetano S and Pedone E.
TITLE The essential player in adipogenesis GRP78 is a novel KCTD15
interactor
JOURNAL Int. J. Biol. Macromol. 115, 469-475 (2018)
PUBMED 29665387
REFERENCE 2 (residues 1 to 283)
AUTHORS Gamero-Villarroel C, Gonzalez LM, Rodriguez-Lopez R, Albuquerque D,
Carrillo JA, Garcia-Herraiz A, Flores I and Gervasini G.
TITLE Influence of TFAP2B and KCTD15 genetic variability on personality
dimensions in anorexia and bulimia nervosa
JOURNAL Brain Behav 7 (9), e00784 (2017)
PUBMED 28948079
REMARK GeneRIF: The KCTD15 rs287103 T variant allele was associated with
increased risk of bulimia nervosa and with scores of
psychopathological scales of these patients.
Publication Status: Online-Only
REFERENCE 3 (residues 1 to 283)
AUTHORS Smaldone G, Pirone L, Pedone E, Marlovits T, Vitagliano L and
Ciccarelli L.
TITLE The BTB domains of the potassium channel tetramerization domain
proteins prevalently assume pentameric states
JOURNAL FEBS Lett. 590 (11), 1663-1671 (2016)
PUBMED 27152988
REFERENCE 4 (residues 1 to 283)
AUTHORS Lv D, Zhang DD, Wang H, Zhang Y, Liang L, Fu JF, Xiong F, Liu GL,
Gong CX, Luo FH, Chen SK, Li ZL and Zhu YM.
TITLE Genetic variations in SEC16B, MC4R, MAP2K5 and KCTD15 were
associated with childhood obesity and interacted with dietary
behaviors in Chinese school-age population
JOURNAL Gene 560 (2), 149-155 (2015)
PUBMED 25637721
REMARK GeneRIF: SEC16B, MC4R, MAP2K5 and KCTD15 (rs17782313, rs543874,
rs2241423 and rs11084753) polymorphisms are associated with the
risk for children obesity in China.
REFERENCE 5 (residues 1 to 283)
AUTHORS Zarelli VE and Dawid IB.
TITLE The BTB-containing protein Kctd15 is SUMOylated in vivo
JOURNAL PLoS ONE 8 (9), e75016 (2013)
PUBMED 24086424
REMARK GeneRIF: These data suggest that the non-SUMOylated form of Kctd15
functions in neural crest development.
Publication Status: Online-Only
REFERENCE 6 (residues 1 to 283)
AUTHORS Bauer F, Elbers CC, Adan RA, Loos RJ, Onland-Moret NC, Grobbee DE,
van Vliet-Ostaptchouk JV, Wijmenga C and van der Schouw YT.
TITLE Obesity genes identified in genome-wide association studies are
associated with adiposity measures and potentially with
nutrient-specific food preference
JOURNAL Am. J. Clin. Nutr. 90 (4), 951-959 (2009)
PUBMED 19692490
REMARK GeneRIF: Observational study of gene-disease association. (HuGE
Navigator)
REFERENCE 7 (residues 1 to 283)
AUTHORS Renstrom F, Payne F, Nordstrom A, Brito EC, Rolandsson O, Hallmans
G, Barroso I, Nordstrom P and Franks PW.
CONSRTM GIANT Consortium
TITLE Replication and extension of genome-wide association study results
for obesity in 4923 adults from northern Sweden
JOURNAL Hum. Mol. Genet. 18 (8), 1489-1496 (2009)
PUBMED 19164386
REMARK GeneRIF: Observational study of gene-disease association. (HuGE
Navigator)
REFERENCE 8 (residues 1 to 283)
AUTHORS Willer CJ, Speliotes EK, Loos RJ, Li S, Lindgren CM, Heid IM,
Berndt SI, Elliott AL, Jackson AU, Lamina C, Lettre G, Lim N, Lyon
HN, McCarroll SA, Papadakis K, Qi L, Randall JC, Roccasecca RM,
Sanna S, Scheet P, Weedon MN, Wheeler E, Zhao JH, Jacobs LC,
Prokopenko I, Soranzo N, Tanaka T, Timpson NJ, Almgren P, Bennett
A, Bergman RN, Bingham SA, Bonnycastle LL, Brown M, Burtt NP,
Chines P, Coin L, Collins FS, Connell JM, Cooper C, Smith GD,
Dennison EM, Deodhar P, Elliott P, Erdos MR, Estrada K, Evans DM,
Gianniny L, Gieger C, Gillson CJ, Guiducci C, Hackett R, Hadley D,
Hall AS, Havulinna AS, Hebebrand J, Hofman A, Isomaa B, Jacobs KB,
Johnson T, Jousilahti P, Jovanovic Z, Khaw KT, Kraft P, Kuokkanen
M, Kuusisto J, Laitinen J, Lakatta EG, Luan J, Luben RN, Mangino M,
McArdle WL, Meitinger T, Mulas A, Munroe PB, Narisu N, Ness AR,
Northstone K, O'Rahilly S, Purmann C, Rees MG, Ridderstrale M, Ring
SM, Rivadeneira F, Ruokonen A, Sandhu MS, Saramies J, Scott LJ,
Scuteri A, Silander K, Sims MA, Song K, Stephens J, Stevens S,
Stringham HM, Tung YC, Valle TT, Van Duijn CM, Vimaleswaran KS,
Vollenweider P, Waeber G, Wallace C, Watanabe RM, Waterworth DM,
Watkins N, Witteman JC, Zeggini E, Zhai G, Zillikens MC, Altshuler
D, Caulfield MJ, Chanock SJ, Farooqi IS, Ferrucci L, Guralnik JM,
Hattersley AT, Hu FB, Jarvelin MR, Laakso M, Mooser V, Ong KK,
Ouwehand WH, Salomaa V, Samani NJ, Spector TD, Tuomi T, Tuomilehto
J, Uda M, Uitterlinden AG, Wareham NJ, Deloukas P, Frayling TM,
Groop LC, Hayes RB, Hunter DJ, Mohlke KL, Peltonen L, Schlessinger
D, Strachan DP, Wichmann HE, McCarthy MI, Boehnke M, Barroso I,
Abecasis GR and Hirschhorn JN.
CONSRTM Wellcome Trust Case Control Consortium; Genetic Investigation of
ANthropometric Traits Consortium
TITLE Six new loci associated with body mass index highlight a neuronal
influence on body weight regulation
JOURNAL Nat. Genet. 41 (1), 25-34 (2009)
PUBMED 19079261
REMARK GeneRIF: Observational study, meta-analysis, and genome-wide
association study of gene-disease association. (HuGE Navigator)
REFERENCE 9 (residues 1 to 283)
AUTHORS Thorleifsson G, Walters GB, Gudbjartsson DF, Steinthorsdottir V,
Sulem P, Helgadottir A, Styrkarsdottir U, Gretarsdottir S,
Thorlacius S, Jonsdottir I, Jonsdottir T, Olafsdottir EJ,
Olafsdottir GH, Jonsson T, Jonsson F, Borch-Johnsen K, Hansen T,
Andersen G, Jorgensen T, Lauritzen T, Aben KK, Verbeek AL,
Roeleveld N, Kampman E, Yanek LR, Becker LC, Tryggvadottir L,
Rafnar T, Becker DM, Gulcher J, Kiemeney LA, Pedersen O, Kong A,
Thorsteinsdottir U and Stefansson K.
TITLE Genome-wide association yields new sequence variants at seven loci
that associate with measures of obesity
JOURNAL Nat. Genet. 41 (1), 18-24 (2009)
PUBMED 19079260
REFERENCE 10 (residues 1 to 283)
AUTHORS Ballif BA, Villen J, Beausoleil SA, Schwartz D and Gygi SP.
TITLE Phosphoproteomic analysis of the developing mouse brain
JOURNAL Mol. Cell Proteomics 3 (11), 1093-1101 (2004)
PUBMED 15345747
COMMENT VALIDATED REFSEQ: This record has undergone validation or
preliminary review. The reference sequence was derived from
BP339379.1, AK027901.1, AK225793.1, AK025590.1, CX752088.1 and
AI741557.1.
Transcript Variant: This variant (2) uses a different splice site
in the 3' coding region, compared to variant 1, that results in a
frameshift. The resulting protein (isoform 2) has a longer and
distinct C-terminus compared to isoform 1. Variants 2 and 3 both
encode the same protein.
Publication Note: This RefSeq record includes a subset of the
publications that are available for this gene. Please see the Gene
record to access additional publications.
##Evidence-Data-START##
Transcript exon combination :: SRR1803615.41157.1,
SRR1660803.131822.1 [ECO:0000332]
RNAseq introns :: single sample supports all introns
SAMEA1965299, SAMEA1966682
[ECO:0000348]
##Evidence-Data-END##
##RefSeq-Attributes-START##
RefSeq Select criteria :: based on conservation, expression,
longest protein
##RefSeq-Attributes-END##
FEATURES Location/Qualifiers
source 1..283
/organism="Homo sapiens"
/db_xref="taxon:9606"
/chromosome="19"
/map="19q13.11"
Protein 1..283
/product="BTB/POZ domain-containing protein KCTD15 isoform
2"
/note="BTB/POZ domain-containing protein KCTD15; potassium
channel tetramerisation domain containing 15; potassium
channel tetramerization domain-containing protein 15"
/calculated_mol_wt=31811
Site 31
/site_type="phosphorylation"
/experiment="experimental evidence, no additional details
recorded"
/note="Phosphoserine. {ECO:0000244|PubMed:18669648};
propagated from UniProtKB/Swiss-Prot (Q96SI1.1)"
Site 35
/site_type="phosphorylation"
/experiment="experimental evidence, no additional details
recorded"
/note="Phosphoserine. {ECO:0000244|PubMed:18669648,
ECO:0000244|PubMed:19369195, ECO:0000244|PubMed:20068231,
ECO:0000244|PubMed:23186163}; propagated from
UniProtKB/Swiss-Prot (Q96SI1.1)"
Site 38
/site_type="phosphorylation"
/experiment="experimental evidence, no additional details
recorded"
/note="Phosphoserine. {ECO:0000244|PubMed:18669648,
ECO:0000244|PubMed:20068231}; propagated from
UniProtKB/Swiss-Prot (Q96SI1.1)"
Region 58..145
/region_name="BTB"
/note="BTB/POZ domain; cl02518"
/db_xref="CDD:321966"
CDS 1..283
/gene="KCTD15"
/coded_by="NM_001129994.2:245..1096"
/note="isoform 2 is encoded by transcript variant 2"
/db_xref="CCDS:CCDS46039.1"
/db_xref="GeneID:79047"
/db_xref="HGNC:HGNC:23297"
/db_xref="MIM:615240"
ORIGIN
1 mphrkerpsg sslhthgstg taeggnmsrl sltrspvspl aaqgiplpaq ltksnapvhi
61 dvgghmytss latltkypds risrlfngte pivldslkqh yfidrdgeif ryvlsflrts
121 klllpddfkd fsllyeeary yqlqpmvrel erwqqeqeqr rrsracdclv vrvtpdlger
181 ialsgekali eevfpetgdv mcnsvnagwn qdpthvirfp lngycrlnsv qvlerlfqrg
241 fsvaascggg vdssqfseyv lcreerrpqp tptavrikqe pld
//
