NKD2_MOUSE
ID NKD2_MOUSE Reviewed; 461 AA.
AC Q8VE28; Q3TYU5; Q3UM34; Q8C4J8; Q91Y45; Q9D7U9;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-SEP-2007, sequence version 2.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Protein naked cuticle homolog 2;
DE Short=Naked-2;
DE Short=mNkd2;
GN Name=Nkd2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH DVL1; DVL2 AND
RP DVL3, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC STRAIN=C57BL/6 X CBA; TISSUE=Lung;
RX PubMed=11356022; DOI=10.1006/dbio.2001.0238;
RA Wharton K.A. Jr., Zimmermann G., Rousset R., Scott M.P.;
RT "Vertebrate proteins related to Drosophila Naked Cuticle bind Dishevelled
RT and antagonize Wnt signaling.";
RL Dev. Biol. 234:93-106(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J;
RC TISSUE=Amnion, Head, Inner ear, Mammary gland, and Stomach;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=Czech II; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP DEVELOPMENTAL STAGE.
RX PubMed=15511637; DOI=10.1016/j.mod.2004.08.003;
RA Ishikawa A., Kitajima S., Takahashi Y., Kokubo H., Kanno J., Inoue T.,
RA Saga Y.;
RT "Mouse Nkd1, a Wnt antagonist, exhibits oscillatory gene expression in the
RT PSM under the control of Notch signaling.";
RL Mech. Dev. 121:1443-1453(2004).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=15064403; DOI=10.1073/pnas.0401294101;
RA Li C., Franklin J.L., Graves-Deal R., Jerome W.G., Cao Z., Coffey R.J.;
RT "Myristoylated Naked2 escorts transforming growth factor alpha to the
RT basolateral plasma membrane of polarized epithelial cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:5571-5576(2004).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=15546883; DOI=10.1074/jbc.m405680200;
RA Li Q., Ishikawa T.O., Miyoshi H., Oshima M., Taketo M.M.;
RT "A targeted mutation of Nkd1 impairs mouse spermatogenesis.";
RL J. Biol. Chem. 280:2831-2839(2005).
RN [7]
RP DEVELOPMENTAL STAGE.
RX PubMed=17362910; DOI=10.1016/j.ydbio.2007.02.007;
RA William D.A., Saitta B., Gibson J.D., Traas J., Markov V., Gonzalez D.M.,
RA Sewell W., Anderson D.M., Pratt S.C., Rappaport E.F., Kusumi K.;
RT "Identification of oscillatory genes in somitogenesis from functional
RT genomic analysis of a human mesenchymal stem cell model.";
RL Dev. Biol. 305:172-186(2007).
RN [8]
RP DEVELOPMENTAL STAGE.
RX PubMed=17438140; DOI=10.1128/mcb.00133-07;
RA Zhang S., Cagatay T., Amanai M., Zhang M., Kline J., Castrillon D.H.,
RA Ashfaq R., Oez O.K., Wharton K.A. Jr.;
RT "Viable mice with compound mutations in the Wnt/Dvl pathway antagonists
RT nkd1 and nkd2.";
RL Mol. Cell. Biol. 27:4454-4464(2007).
CC -!- FUNCTION: Cell autonomous antagonist of the canonical Wnt signaling
CC pathway. May activate a second Wnt signaling pathway that controls
CC planar cell polarity. Required for processing of TGFA and for targeting
CC of TGFA to the basolateral membrane of polarized epithelial cells (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with RNF25, TGFA (via cytoplasmic domain), and
CC PPP2R3A (By similarity). Interacts with DVL1, DVL2 and DVL3.
CC {ECO:0000250, ECO:0000269|PubMed:11356022}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q969F2}.
CC Cytoplasm {ECO:0000250|UniProtKB:Q969F2}. Cytoplasmic vesicle
CC {ECO:0000250|UniProtKB:Q969F2}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8VE28-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8VE28-2; Sequence=VSP_027902;
CC -!- TISSUE SPECIFICITY: Expressed in the cecum, colon, esophagus, ileum,
CC jejunum, skin and stomach. {ECO:0000269|PubMed:11356022,
CC ECO:0000269|PubMed:15064403, ECO:0000269|PubMed:15546883}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the forelimb buds, the branchial
CC arches, the caudal presomitic mesoderm (PSM) and at the anterior and
CC posterior of each somite boundary at 9.5 days postcoitum (dpc). Also
CC expressed in the tailbud. {ECO:0000269|PubMed:11356022,
CC ECO:0000269|PubMed:15511637, ECO:0000269|PubMed:17362910,
CC ECO:0000269|PubMed:17438140}.
CC -!- DOMAIN: The N-terminal domain comprising the first 224 amino acid
CC residues is mostly unstructured. {ECO:0000250}.
CC -!- PTM: Ubiquitinated, leading to rapid proteasomal degradation.
CC Interaction with TGFA interferes with RNF25 binding and protects
CC against ubiquitination mediated by RNF25 (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the NKD family. {ECO:0000305}.
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DR EMBL; AF358136; AAK57485.1; -; mRNA.
DR EMBL; AK008814; BAB25908.1; -; mRNA.
DR EMBL; AK081904; BAC38367.1; -; mRNA.
DR EMBL; AK145155; BAE26264.1; -; mRNA.
DR EMBL; AK146667; BAE27345.1; -; mRNA.
DR EMBL; AK158350; BAE34467.1; -; mRNA.
DR EMBL; BC019952; AAH19952.1; -; mRNA.
DR CCDS; CCDS26636.1; -. [Q8VE28-1]
DR CCDS; CCDS84036.1; -. [Q8VE28-2]
DR RefSeq; NP_001334464.1; NM_001347535.1. [Q8VE28-2]
DR RefSeq; NP_082462.3; NM_028186.5. [Q8VE28-1]
DR AlphaFoldDB; Q8VE28; -.
DR BioGRID; 215287; 5.
DR IntAct; Q8VE28; 9.
DR STRING; 10090.ENSMUSP00000022051; -.
DR iPTMnet; Q8VE28; -.
DR PhosphoSitePlus; Q8VE28; -.
DR PaxDb; Q8VE28; -.
DR PRIDE; Q8VE28; -.
DR ProteomicsDB; 287426; -. [Q8VE28-1]
DR ProteomicsDB; 287427; -. [Q8VE28-2]
DR Antibodypedia; 22295; 155 antibodies from 29 providers.
DR Ensembl; ENSMUST00000022051; ENSMUSP00000022051; ENSMUSG00000021567. [Q8VE28-1]
DR Ensembl; ENSMUST00000118096; ENSMUSP00000113794; ENSMUSG00000021567. [Q8VE28-2]
DR GeneID; 72293; -.
DR KEGG; mmu:72293; -.
DR UCSC; uc007ref.2; mouse. [Q8VE28-1]
DR UCSC; uc007reg.2; mouse. [Q8VE28-2]
DR CTD; 85409; -.
DR MGI; MGI:1919543; Nkd2.
DR VEuPathDB; HostDB:ENSMUSG00000021567; -.
DR eggNOG; ENOG502QT1X; Eukaryota.
DR GeneTree; ENSGT00440000033589; -.
DR HOGENOM; CLU_035610_1_0_1; -.
DR InParanoid; Q8VE28; -.
DR OMA; PMVQRHE; -.
DR OrthoDB; 540161at2759; -.
DR PhylomeDB; Q8VE28; -.
DR TreeFam; TF328786; -.
DR BioGRID-ORCS; 72293; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Nkd2; mouse.
DR PRO; PR:Q8VE28; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; Q8VE28; protein.
DR Bgee; ENSMUSG00000021567; Expressed in embryonic post-anal tail and 161 other tissues.
DR ExpressionAtlas; Q8VE28; baseline and differential.
DR Genevisible; Q8VE28; MM.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI.
DR GO; GO:0071944; C:cell periphery; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:MGI.
DR GO; GO:0070382; C:exocytic vesicle; ISO:MGI.
DR GO; GO:0016328; C:lateral plasma membrane; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0051117; F:ATPase binding; ISO:MGI.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0019838; F:growth factor binding; ISO:MGI.
DR GO; GO:0032036; F:myosin heavy chain binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0006887; P:exocytosis; IEA:UniProtKB-KW.
DR GO; GO:0048210; P:Golgi vesicle fusion to target membrane; ISO:MGI.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISO:MGI.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IBA:GO_Central.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; ISO:MGI.
DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; ISO:MGI.
DR GO; GO:0010954; P:positive regulation of protein processing; ISO:MGI.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISO:MGI.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR040140; Nkd-like.
DR PANTHER; PTHR22611; PTHR22611; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS00018; EF_HAND_1; 1.
DR PROSITE; PS50222; EF_HAND_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Cell membrane; Cytoplasm;
KW Cytoplasmic vesicle; Exocytosis; Lipoprotein; Membrane; Metal-binding;
KW Myristate; Reference proteome; Transport; Ubl conjugation;
KW Wnt signaling pathway.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..461
FT /note="Protein naked cuticle homolog 2"
FT /id="PRO_0000301994"
FT DOMAIN 127..162
FT /note="EF-hand"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 1..106
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 121..186
FT /note="Interaction with DVL1, DVL2 and DVL3"
FT /evidence="ECO:0000269|PubMed:11356022"
FT REGION 176..205
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 263..302
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 307..396
FT /note="Interaction with TGFA"
FT /evidence="ECO:0000250"
FT REGION 321..359
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 372..414
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 441..461
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 34..82
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 276..302
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 377..391
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 140
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 142
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 144
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 146
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 151
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250"
FT VAR_SEQ 9..20
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_027902"
FT CONFLICT 77
FT /note="V -> A (in Ref. 2; BAE26264 and 3; AAH19952)"
FT /evidence="ECO:0000305"
FT CONFLICT 217
FT /note="V -> A (in Ref. 3; AAH19952)"
FT /evidence="ECO:0000305"
FT CONFLICT 317
FT /note="N -> S (in Ref. 2; BAB25908)"
FT /evidence="ECO:0000305"
FT CONFLICT 330
FT /note="I -> L (in Ref. 2; BAE26264/BAE34467 and 3;
FT AAH19952)"
FT /evidence="ECO:0000305"
FT CONFLICT 372
FT /note="S -> G (in Ref. 2; BAE26264/BAE34467 and 3;
FT AAH19952)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 461 AA; 51501 MW; 7C3B550024E87D27 CRC64;
MGKFQSKHAA AACKRRESPE GDSFVVPAYG SGRRGAEETD RRAGSGVEHR SRDKQELLNG
DPKEGPFWDD KGSLEVVLPP EKSEGHEGQG QLFSTDDGEK AASREGPLRL SKKHLNIDAL
QCDVSVEEDN RQEWTFTLYD FDNSGKVTRE DMSSLMHTIY EVVDASVNHS SGSSKTLRVK
LTVSPEPSSK KECPLTGQDR EPTRGRTEIE LTDEPRVADR RLSAYSRKPN ADPQPCSVRV
PYCVDENTER RNHYLDLAGI ENYTSKFGPG SPPEQARQEH HGRATHIPSR SRSQESDAHA
IHHRRSQVLA EHVIPANEPA TRALAAQPRI KGQEKQFLRS PKGPGKPLGT PGSGKPGKAL
SYCLQAVPLP QSAQDGHHLP QPPPQPPPQP YGHKRYRQKA REGHSPLKGH GQPTMVEHEV
VRDLPPMLGP EGYVMPVVQR HEHHHHHEHH HHHHHHHFHP S
