NKD1_HUMAN
ID NKD1_HUMAN Reviewed; 470 AA.
AC Q969G9; B2RC39; Q8WZ08;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Protein naked cuticle homolog 1;
DE Short=Naked-1;
DE Short=hNkd;
DE Short=hNkd1;
GN Name=NKD1; Synonyms=NKD; ORFNames=PP7246;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
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], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC TISSUE=Fetus;
RX PubMed=11604995;
RA Katoh M.;
RT "Molecular cloning, gene structure, and expression analyses of NKD1 and
RT NKD2.";
RL Int. J. Oncol. 19:963-969(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND INDUCTION.
RX PubMed=11752446; DOI=10.1073/pnas.261574498;
RA Yan D., Wiesmann M., Rohan M., Chan V., Jefferson A.B., Guo L.,
RA Sakamoto D., Caothien R.H., Fuller J.H., Reinhard C., Garcia P.D.,
RA Randazzo F.M., Escobedo J., Fantl W.J., Williams L.T.;
RT "Elevated expression of axin2 and hnkd mRNA provides evidence that
RT Wnt/beta-catenin signaling is activated in human colon tumors.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:14973-14978(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15498874; DOI=10.1073/pnas.0404089101;
RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X.,
RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X.,
RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.;
RT "Large-scale cDNA transfection screening for genes related to cancer
RT development and progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thalamus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
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 [8]
RP FUNCTION, AND 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 [9]
RP FUNCTION, AND INTERACTION WITH DVL1; DVL2; DVL3 AND PPP2R3A.
RX PubMed=16567647; DOI=10.1073/pnas.0507237103;
RA Creyghton M.P., Roeel G., Eichhorn P.J.A., Vredeveld L.C., Destree O.,
RA Bernards R.;
RT "PR130 is a modulator of the Wnt-signaling cascade that counters repression
RT of the antagonist Naked cuticle.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:5397-5402(2006).
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. {ECO:0000269|PubMed:11752446,
CC ECO:0000269|PubMed:15687260, ECO:0000269|PubMed:16567647}.
CC -!- SUBUNIT: Interacts with DVL1, DVL2, DVL3 and PPP2R3A.
CC {ECO:0000269|PubMed:15687260, ECO:0000269|PubMed:16567647}.
CC -!- INTERACTION:
CC Q969G9; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-1538217, EBI-3867333;
CC Q969G9; Q92997: DVL3; NbExp=3; IntAct=EBI-1538217, EBI-739789;
CC Q969G9; P60371: KRTAP10-6; NbExp=3; IntAct=EBI-1538217, EBI-12012928;
CC Q969G9; P60409: KRTAP10-7; NbExp=5; IntAct=EBI-1538217, EBI-10172290;
CC Q969G9; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-1538217, EBI-10171774;
CC Q969G9; P60411: KRTAP10-9; NbExp=3; IntAct=EBI-1538217, EBI-10172052;
CC Q969G9; P60328: KRTAP12-3; NbExp=3; IntAct=EBI-1538217, EBI-11953334;
CC Q969G9; Q9BYR9: KRTAP2-4; NbExp=3; IntAct=EBI-1538217, EBI-14065470;
CC Q969G9; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-1538217, EBI-3958099;
CC Q969G9; Q9BYQ0: KRTAP9-8; NbExp=3; IntAct=EBI-1538217, EBI-11958364;
CC Q969G9; Q99750: MDFI; NbExp=3; IntAct=EBI-1538217, EBI-724076;
CC Q969G9; Q9UBU8-2: MORF4L1; NbExp=3; IntAct=EBI-1538217, EBI-10288852;
CC Q969G9; Q06190-1: PPP2R3A; NbExp=4; IntAct=EBI-1538217, EBI-949204;
CC Q969G9; Q06190-2: PPP2R3A; NbExp=3; IntAct=EBI-1538217, EBI-949210;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}. Cytoplasm
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in colon, heart, kidney, leukocyte,
CC liver, lung, ovary, pancreas, placenta, prostate, skeletal muscle,
CC small intestine and spleen. {ECO:0000269|PubMed:11604995}.
CC -!- DEVELOPMENTAL STAGE: Expressed in fetal brain, kidney, liver and lung.
CC {ECO:0000269|PubMed:11604995}.
CC -!- INDUCTION: Expression is induced by activation of the Wnt signaling
CC pathway. {ECO:0000269|PubMed:11752446}.
CC -!- SIMILARITY: Belongs to the NKD family. {ECO:0000305}.
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DR EMBL; AF358135; AAK57484.1; -; mRNA.
DR EMBL; AB062886; BAB70500.1; -; mRNA.
DR EMBL; AY061883; AAL32374.1; -; mRNA.
DR EMBL; AF289584; AAL55768.1; -; mRNA.
DR EMBL; AK314930; BAG37436.1; -; mRNA.
DR EMBL; CH471092; EAW82761.1; -; Genomic_DNA.
DR EMBL; BC051288; AAH51288.1; -; mRNA.
DR CCDS; CCDS10743.1; -.
DR RefSeq; NP_149110.1; NM_033119.4.
DR AlphaFoldDB; Q969G9; -.
DR BioGRID; 124516; 16.
DR DIP; DIP-38248N; -.
DR IntAct; Q969G9; 16.
DR STRING; 9606.ENSP00000268459; -.
DR iPTMnet; Q969G9; -.
DR PhosphoSitePlus; Q969G9; -.
DR BioMuta; NKD1; -.
DR DMDM; 74731040; -.
DR jPOST; Q969G9; -.
DR MassIVE; Q969G9; -.
DR MaxQB; Q969G9; -.
DR PaxDb; Q969G9; -.
DR PeptideAtlas; Q969G9; -.
DR PRIDE; Q969G9; -.
DR ProteomicsDB; 75758; -.
DR Antibodypedia; 14551; 156 antibodies from 24 providers.
DR DNASU; 85407; -.
DR Ensembl; ENST00000268459.6; ENSP00000268459.3; ENSG00000140807.7.
DR GeneID; 85407; -.
DR KEGG; hsa:85407; -.
DR MANE-Select; ENST00000268459.6; ENSP00000268459.3; NM_033119.5; NP_149110.1.
DR UCSC; uc002egg.3; human.
DR CTD; 85407; -.
DR DisGeNET; 85407; -.
DR GeneCards; NKD1; -.
DR HGNC; HGNC:17045; NKD1.
DR HPA; ENSG00000140807; Tissue enhanced (brain).
DR MIM; 607851; gene.
DR neXtProt; NX_Q969G9; -.
DR OpenTargets; ENSG00000140807; -.
DR PharmGKB; PA31637; -.
DR VEuPathDB; HostDB:ENSG00000140807; -.
DR eggNOG; ENOG502QT1X; Eukaryota.
DR GeneTree; ENSGT00440000033589; -.
DR HOGENOM; CLU_035610_1_1_1; -.
DR InParanoid; Q969G9; -.
DR OMA; SWERKQR; -.
DR OrthoDB; 540161at2759; -.
DR PhylomeDB; Q969G9; -.
DR TreeFam; TF328786; -.
DR PathwayCommons; Q969G9; -.
DR SignaLink; Q969G9; -.
DR SIGNOR; Q969G9; -.
DR BioGRID-ORCS; 85407; 10 hits in 1061 CRISPR screens.
DR ChiTaRS; NKD1; human.
DR GenomeRNAi; 85407; -.
DR Pharos; Q969G9; Tbio.
DR PRO; PR:Q969G9; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q969G9; protein.
DR Bgee; ENSG00000140807; Expressed in right lung and 137 other tissues.
DR Genevisible; Q969G9; HS.
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; IDA:BHF-UCL.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0030165; F:PDZ domain binding; IEA:Ensembl.
DR GO; GO:0001754; P:eye photoreceptor cell differentiation; ISS:BHF-UCL.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:BHF-UCL.
DR GO; GO:1901233; P:negative regulation of convergent extension involved in axis elongation; ISS:BHF-UCL.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IBA:GO_Central.
DR GO; GO:1901231; P:positive regulation of non-canonical Wnt signaling pathway via JNK cascade; ISS:BHF-UCL.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IMP:BHF-UCL.
DR GO; GO:2000096; P:positive regulation of Wnt signaling pathway, planar cell polarity pathway; ISS:BHF-UCL.
DR GO; GO:0090249; P:regulation of cell migration involved in somitogenic axis elongation; ISS:BHF-UCL.
DR GO; GO:0007525; P:somatic muscle development; ISS:BHF-UCL.
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; Lipoprotein; Membrane; Metal-binding;
KW Myristate; Reference proteome; Wnt signaling pathway.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..470
FT /note="Protein naked cuticle homolog 1"
FT /id="PRO_0000301990"
FT DOMAIN 131..166
FT /note="EF-hand"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 90..114
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:0000250"
FT REGION 192..228
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 271..314
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 337..357
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 446..470
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 96..114
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 192..208
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 211..228
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 271..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 451..470
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 CONFLICT 9..10
FT /note="AA -> VD (in Ref. 4; AAL55768)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 470 AA; 52285 MW; E50E528042662CDE CRC64;
MGKLHSKPAA VCKRRESPEG DSFAVSAAWA RKGIEEWIGR QRCPGGVSGP RQLRLAGTIG
RSTRELVGDV LRDTLSEEEE DDFRLEVALP PEKTDGLGSG DEKKMERVSE PCPGSKKQLK
FEELQCDVSM EEDSRQEWTF TLYDFDNNGK VTREDITSLL HTIYEVVDSS VNHSPTSSKM
LRVKLTVAPD GSQSKRSVLV NQADLQSARP RAETKPTEDL RSWEKKQRAP LRFQGDSRLE
QSGCYHHCVD ENIERRNHYL DLAGIENYTS QFGPGSPSVA QKSELPPRTS NPTRSRSHEP
EAIHIPHRKP QGVDPASFHF LDTPIAKVSE LQQRLRGTQD GSKHFVRSPK AQGKSVGVGH
VARGARNKPP LGPAIPAVSP SAHLAASPAL LPSLAPLGHK KHKHRAKESQ QGCRGLQAPL
ASGGPVLGRE HLRELPALVV YESQAGQPVQ RHEHHHHHEH HHHYHHFYQT
