NKD1_MOUSE
ID NKD1_MOUSE Reviewed; 471 AA.
AC Q99MH6; Q3TLD6; Q8K200; Q91Y46;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Protein naked cuticle homolog 1;
DE Short=Naked-1;
DE Short=mNkd;
DE Short=mNkd1;
GN Name=Nkd1;
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], FUNCTION, INTERACTION WITH DVL1; DVL2 AND DVL3,
RP 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 [MRNA], FUNCTION, INTERACTION WITH DVL3, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION, AND MUTAGENESIS OF
RP 138-TRP--ILE-163; ASP-144; ASP-146 AND GLY-149.
RX PubMed=11274398; DOI=10.1073/pnas.071041898;
RA Yan D., Wallingford J.B., Sun T.-Q., Nelson A.M., Sakanaka C., Reinhard C.,
RA Harland R.M., Fantl W.J., Williams L.T.;
RT "Cell autonomous regulation of multiple Dishevelled-dependent pathways by
RT mammalian Nkd.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:3802-3807(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Mammary gland;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-326.
RC STRAIN=C57BL/6J;
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 [5]
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 [6]
RP INTERACTION WITH PPP2R3A.
RX PubMed=15687260; DOI=10.1101/gad.328905;
RA Creyghton M.P., Roeel G., Eichhorn P.J.A., Hijmans E.M., Maurer I.,
RA Destree O., Bernards R.;
RT "PR72, a novel regulator of Wnt signaling required for Naked cuticle
RT function.";
RL Genes Dev. 19:376-386(2005).
RN [7]
RP FUNCTION, AND 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 [8]
RP INDUCTION.
RX PubMed=16488995; DOI=10.1158/0008-5472.can-05-3493;
RA Boerboom D., White L.D., Dalle S., Courty J., Richards J.S.;
RT "Dominant-stable beta-catenin expression causes cell fate alterations and
RT Wnt signaling antagonist expression in a murine granulosa cell tumor
RT model.";
RL Cancer Res. 66:1964-1973(2006).
RN [9]
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 spermatogenesis.
CC {ECO:0000269|PubMed:11274398, ECO:0000269|PubMed:11356022,
CC ECO:0000269|PubMed:15546883}.
CC -!- SUBUNIT: Interacts with DVL1, DVL2, DVL3 and PPP2R3A.
CC {ECO:0000269|PubMed:11274398, ECO:0000269|PubMed:11356022,
CC ECO:0000269|PubMed:15687260}.
CC -!- INTERACTION:
CC Q99MH6; P51140: dsh; Xeno; NbExp=2; IntAct=EBI-1538321, EBI-499383;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}. Cytoplasm
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Highly expressed in lung. Also expressed in brain,
CC heart, kidney, liver, skin, stomach and testis. Within the testis
CC expression is found in the seminiferous epithelium and round and
CC elongating spermatids. {ECO:0000269|PubMed:11274398,
CC ECO:0000269|PubMed:11356022, ECO:0000269|PubMed:15546883}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout embryonic development.
CC Expressed in the presomitic mesoderm (PSM) and the neural folds along
CC the entire rostrocaudal axis at 8.5 days post-coitum (dpc). Expressed
CC in the forelimb buds, the branchial arches, and at the anterior and
CC posterior of each somite boundary at 9.5 dpc. Expressed in the neural
CC tube, the PSM, somites and the dorsal limb bud mesenchyme at 10.5 dpc.
CC At 11.5 dpc three distinct phases of expression can be seen; expression
CC is initially low in the tailbud, rises in the PSM and then shifts
CC anteriorly. These oscillations require the activity of HES7.
CC {ECO:0000269|PubMed:11274398, ECO:0000269|PubMed:11356022,
CC ECO:0000269|PubMed:15511637, ECO:0000269|PubMed:17438140}.
CC -!- INDUCTION: Expression is induced by activation of the Wnt signaling
CC pathway. {ECO:0000269|PubMed:11274398, ECO:0000269|PubMed:16488995}.
CC -!- SIMILARITY: Belongs to the NKD family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAE38856.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF358134; AAK57483.1; -; mRNA.
DR EMBL; AF343352; AAK27485.1; -; mRNA.
DR EMBL; BC034838; AAH34838.1; -; mRNA.
DR EMBL; AK166564; BAE38856.1; ALT_FRAME; mRNA.
DR CCDS; CCDS22511.1; -.
DR RefSeq; NP_081556.3; NM_027280.3.
DR AlphaFoldDB; Q99MH6; -.
DR IntAct; Q99MH6; 5.
DR STRING; 10090.ENSMUSP00000034086; -.
DR iPTMnet; Q99MH6; -.
DR PhosphoSitePlus; Q99MH6; -.
DR MaxQB; Q99MH6; -.
DR PaxDb; Q99MH6; -.
DR PRIDE; Q99MH6; -.
DR ProteomicsDB; 293666; -.
DR Antibodypedia; 14551; 156 antibodies from 24 providers.
DR Ensembl; ENSMUST00000034086; ENSMUSP00000034086; ENSMUSG00000031661.
DR GeneID; 93960; -.
DR KEGG; mmu:93960; -.
DR UCSC; uc009mro.2; mouse.
DR CTD; 85407; -.
DR MGI; MGI:2135954; Nkd1.
DR VEuPathDB; HostDB:ENSMUSG00000031661; -.
DR eggNOG; ENOG502QT1X; Eukaryota.
DR GeneTree; ENSGT00440000033589; -.
DR HOGENOM; CLU_035610_1_1_1; -.
DR InParanoid; Q99MH6; -.
DR OMA; SWERKQR; -.
DR OrthoDB; 540161at2759; -.
DR PhylomeDB; Q99MH6; -.
DR TreeFam; TF328786; -.
DR BioGRID-ORCS; 93960; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Nkd1; mouse.
DR PRO; PR:Q99MH6; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q99MH6; protein.
DR Bgee; ENSMUSG00000031661; Expressed in animal zygote and 215 other tissues.
DR ExpressionAtlas; Q99MH6; baseline and differential.
DR Genevisible; Q99MH6; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000159; C:protein phosphatase type 2A complex; ISO:MGI.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0030165; F:PDZ domain binding; IPI:BHF-UCL.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:BHF-UCL.
DR GO; GO:1901233; P:negative regulation of convergent extension involved in axis elongation; IMP:BHF-UCL.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IGI:BHF-UCL.
DR GO; GO:1901231; P:positive regulation of non-canonical Wnt signaling pathway via JNK cascade; IDA:BHF-UCL.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; ISO:MGI.
DR GO; GO:2000096; P:positive regulation of Wnt signaling pathway, planar cell polarity pathway; IDA:BHF-UCL.
DR GO; GO:0007283; P:spermatogenesis; IEA:UniProtKB-KW.
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 Calcium; Cell membrane; Cytoplasm; Developmental protein; Differentiation;
KW Lipoprotein; Membrane; Metal-binding; Myristate; Reference proteome;
KW Spermatogenesis; Wnt signaling pathway.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..471
FT /note="Protein naked cuticle homolog 1"
FT /id="PRO_0000301991"
FT DOMAIN 131..166
FT /note="EF-hand"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 41..82
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 125..190
FT /note="Interaction with DVL1, DVL2 and DVL3"
FT /evidence="ECO:0000269|PubMed:11356022"
FT REGION 273..314
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 336..382
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 448..471
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 273..293
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 294..308
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 452..471
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 148
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 150
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 155
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 MUTAGEN 138..163
FT /note="Missing: Impairs inhibition of the Wnt signaling
FT pathway."
FT /evidence="ECO:0000269|PubMed:11274398"
FT MUTAGEN 144
FT /note="D->V: Impairs inhibition of the Wnt signaling
FT pathway; when associated with V-146."
FT /evidence="ECO:0000269|PubMed:11274398"
FT MUTAGEN 146
FT /note="D->V: Impairs inhibition of the Wnt signaling
FT pathway; when associated with V-144."
FT /evidence="ECO:0000269|PubMed:11274398"
FT MUTAGEN 149
FT /note="G->W: Impairs inhibition of the Wnt signaling
FT pathway."
FT /evidence="ECO:0000269|PubMed:11274398"
FT CONFLICT 104
FT /note="R -> G (in Ref. 4; BAE38856)"
FT /evidence="ECO:0000305"
FT CONFLICT 186
FT /note="T -> A (in Ref. 4; BAE38856)"
FT /evidence="ECO:0000305"
FT CONFLICT 305
FT /note="I -> V (in Ref. 3; AAH34838)"
FT /evidence="ECO:0000305"
FT CONFLICT 326
FT /note="A -> V (in Ref. 4; BAE38856)"
FT /evidence="ECO:0000305"
FT CONFLICT 440
FT /note="V -> M (in Ref. 1; AAK57483)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 471 AA; 52391 MW; 3E85E77B382F5C3B CRC64;
MGKLHSKPAA VCKRRESPEG DSFAVSAAWA RKGIEEWIGR QRCPGSVSGP RQLRLAGTVG
RGTRELVGDT SREALGEEDE DDFPLEVALP PEKIDSLGSG DEKRMERLSE PGQASKKQLK
FEELQCDVSV EEDSRQEWTF TLYDFDNNGK VTREDITSLL HTIYEVVDSS VNHSPTSSKT
LRVKLTVAPD GSQSKRSVLF NHTDLQSTRP RADTKPAEEL RGWEKKQRAP LRFQGDSHLE
QPDCYHHCVD ENIERRNHYL DLAGIENYTS QFGPGSPSVA QKSELPPRIS NPTRSRSHEP
EAAHIPHRRP QGVDPGSFHL LDTPFAKASE LQQRLRGTQD GSKHFVRSPK AQGKNMGMGH
GARGARSKPP LVPTTHTVSP SAHLATSPAL LPTLAPLGHK KHKHRAKESQ ASCRGLQGPL
AAGGSTVMGR EQVRELPAVV VYESQAGQAV QRHEHHHHHE HHHHYHHFYQ P
