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

Protein naked cuticle homolog 2

Gene

NKD2

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

Functioni

Cell autonomous antagonist of the canonical Wnt signaling pathway. May activate a second Wnt signaling pathway that controls planar cell polarity (By similarity). Required for processing of TGFA and for targeting of TGFA to the basolateral membrane of polarized epithelial cells.By similarity2 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Calcium bindingi132 – 14413PROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • calcium ion binding Source: InterPro
  • growth factor binding Source: BHF-UCL
  • ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

  • exocytosis Source: UniProtKB-KW
  • Golgi vesicle fusion to target membrane Source: BHF-UCL
  • negative regulation of canonical Wnt signaling pathway Source: BHF-UCL
  • positive regulation of establishment of protein localization to plasma membrane Source: BHF-UCL
  • positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: BHF-UCL
  • positive regulation of protein processing Source: BHF-UCL
  • protein targeting to plasma membrane Source: BHF-UCL
  • Wnt signaling pathway Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Exocytosis, Transport, Wnt signaling pathway

Keywords - Ligandi

Calcium, Metal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Protein naked cuticle homolog 2
Short name:
Naked-2
Short name:
hNkd2
Gene namesi
Name:NKD2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:17046. NKD2.

Subcellular locationi

GO - Cellular componenti

  • basolateral plasma membrane Source: BHF-UCL
  • cell periphery Source: BHF-UCL
  • cytoplasmic, membrane-bounded vesicle Source: UniProtKB-SubCell
  • cytoplasmic vesicle Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoplasmic vesicle, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi2 – 21G → A: Abrogates myristoylation and membrane association and impairs delivery of TGFA to the cell surface. 1 Publication

Organism-specific databases

PharmGKBiPA31638.

Polymorphism and mutation databases

DMDMi74716653.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemoved
Chaini2 – 451450Protein naked cuticle homolog 2PRO_0000301993Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycine1 Publication

Post-translational modificationi

Ubiquitinated, leading to rapid proteasomal degradation. Interaction with TGFA interferes with RNF25 binding and protects against ubiquitination mediated by RNF25.1 Publication

Keywords - PTMi

Lipoprotein, Myristate, Ubl conjugation

Proteomic databases

EPDiQ969F2.
PaxDbiQ969F2.
PeptideAtlasiQ969F2.
PRIDEiQ969F2.

PTM databases

PhosphoSiteiQ969F2.

Expressioni

Tissue specificityi

Expressed in kidney, lung, pancreas and spleen.1 Publication

Developmental stagei

Expressed in fetal kidney and lung.1 Publication

Gene expression databases

BgeeiQ969F2.
CleanExiHS_NKD2.
GenevisibleiQ969F2. HS.

Organism-specific databases

HPAiHPA049463.

Interactioni

Subunit structurei

Interacts with DVL1, DVL2, DVL3 and PPP2R3A (By similarity). Interacts with RNF25 and TGFA (via cytoplasmic domain).By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
RCHY1Q96PM52EBI-1538629,EBI-947779

GO - Molecular functioni

  • growth factor binding Source: BHF-UCL
  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi124517. 21 interactions.
DIPiDIP-38642N.
IntActiQ969F2. 10 interactions.
STRINGi9606.ENSP00000296849.

Structurei

3D structure databases

DisProtiDP00520.
ProteinModelPortaliQ969F2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini119 – 15436EF-handPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni2 – 173172Targeting to the basolateral cell membraneAdd
BLAST
Regioni113 – 17866Interaction with DVL1, DVL2 and DVL3By similarityAdd
BLAST
Regioni300 – 38586Interaction with TGFAAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi431 – 44919His-richAdd
BLAST

Domaini

The N-terminal domain comprising the first 217 amino acid residues is mostly unstructured.1 Publication

Sequence similaritiesi

Belongs to the NKD family.Curated
Contains 1 EF-hand domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410IFZW. Eukaryota.
ENOG41114G9. LUCA.
GeneTreeiENSGT00440000033589.
HOGENOMiHOG000005649.
HOVERGENiHBG099718.
InParanoidiQ969F2.
KOiK03213.
OMAiYNPTESR.
OrthoDBiEOG75F4D6.
PhylomeDBiQ969F2.
TreeFamiTF328786.

Family and domain databases

Gene3Di1.10.238.10. 1 hit.
InterProiIPR011992. EF-hand-dom_pair.
IPR002048. EF_hand_dom.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
PROSITEiPS50222. EF_HAND_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q969F2-1) [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
MGKLQSKHAA AARKRRESPE GDSFVASAYA SGRKGAEEAE RRARDKQELP
60 70 80 90 100
NGDPKEGPFR EDQCPLQVAL PAEKAEGREH PGQLLSADDG ERAANREGPR
110 120 130 140 150
GPGGQRLNID ALQCDVSVEE DDRQEWTFTL YDFDNCGKVT REDMSSLMHT
160 170 180 190 200
IYEVVDASVN HSSGSSKTLR VKLTVSPEPS SKRKEGPPAG QDREPTRCRM
210 220 230 240 250
EGELAEEPRV ADRRLSAHVR RPSTDPQPCS ERGPYCVDEN TERRNHYLDL
260 270 280 290 300
AGIENYTSRF GPGSPPVQAK QEPQGRASHL QARSRSQEPD THAVHHRRSQ
310 320 330 340 350
VLVEHVVPAS EPAARALDTQ PRPKGPEKQF LKSPKGSGKP PGVPASSKSG
360 370 380 390 400
KAFSYYLPAV LPPQAPQDGH HLPQPPPPPY GHKRYRQKGR EGHSPLKAPH
410 420 430 440 450
AQPATVEHEV VRDLPPTPAG EGYAVPVIQR HEHHHHHEHH HHHHHHHFHP

S
Length:451
Mass (Da):50,055
Last modified:December 1, 2001 - v1
Checksum:iF27E708F9FAD1F2A
GO
Isoform 2 (identifier: Q969F2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     265-311: PPVQAKQEPQ...LVEHVVPASE → QLCEKRSSAP...GPFPSGLVAV
     312-451: Missing.

Show »
Length:311
Mass (Da):34,314
Checksum:iE702F46F4DFBA4BF
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti257 – 2571T → K.
Corresponds to variant rs35679233 [ dbSNP | Ensembl ].
VAR_034934

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei265 – 31147PPVQA…VPASE → QLCEKRSSAPRTHSGDKARG VGLCRELWSQAGHPQWPGPF PSGLVAV in isoform 2. 1 PublicationVSP_027900Add
BLAST
Alternative sequencei312 – 451140Missing in isoform 2. 1 PublicationVSP_027901Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF358137 mRNA. Translation: AAK57486.1.
AB062887 mRNA. Translation: BAB70501.1.
BC004940 mRNA. Translation: AAH04940.1.
BC012176 mRNA. Translation: AAH12176.1.
CCDSiCCDS3859.1. [Q969F2-1]
CCDS59486.1. [Q969F2-2]
RefSeqiNP_001258011.1. NM_001271082.1. [Q969F2-2]
NP_149111.1. NM_033120.3. [Q969F2-1]
UniGeneiHs.240951.

Genome annotation databases

EnsembliENST00000274150; ENSP00000274150; ENSG00000145506. [Q969F2-2]
ENST00000296849; ENSP00000296849; ENSG00000145506. [Q969F2-1]
ENST00000610777; ENSP00000482896; ENSG00000276920. [Q969F2-2]
ENST00000616539; ENSP00000479003; ENSG00000276920. [Q969F2-1]
GeneIDi85409.
KEGGihsa:85409.
UCSCiuc003jbt.3. human. [Q969F2-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF358137 mRNA. Translation: AAK57486.1.
AB062887 mRNA. Translation: BAB70501.1.
BC004940 mRNA. Translation: AAH04940.1.
BC012176 mRNA. Translation: AAH12176.1.
CCDSiCCDS3859.1. [Q969F2-1]
CCDS59486.1. [Q969F2-2]
RefSeqiNP_001258011.1. NM_001271082.1. [Q969F2-2]
NP_149111.1. NM_033120.3. [Q969F2-1]
UniGeneiHs.240951.

3D structure databases

DisProtiDP00520.
ProteinModelPortaliQ969F2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124517. 21 interactions.
DIPiDIP-38642N.
IntActiQ969F2. 10 interactions.
STRINGi9606.ENSP00000296849.

PTM databases

PhosphoSiteiQ969F2.

Polymorphism and mutation databases

DMDMi74716653.

Proteomic databases

EPDiQ969F2.
PaxDbiQ969F2.
PeptideAtlasiQ969F2.
PRIDEiQ969F2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000274150; ENSP00000274150; ENSG00000145506. [Q969F2-2]
ENST00000296849; ENSP00000296849; ENSG00000145506. [Q969F2-1]
ENST00000610777; ENSP00000482896; ENSG00000276920. [Q969F2-2]
ENST00000616539; ENSP00000479003; ENSG00000276920. [Q969F2-1]
GeneIDi85409.
KEGGihsa:85409.
UCSCiuc003jbt.3. human. [Q969F2-1]

Organism-specific databases

CTDi85409.
GeneCardsiNKD2.
H-InvDBHIX0004713.
HGNCiHGNC:17046. NKD2.
HPAiHPA049463.
MIMi607852. gene.
neXtProtiNX_Q969F2.
PharmGKBiPA31638.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IFZW. Eukaryota.
ENOG41114G9. LUCA.
GeneTreeiENSGT00440000033589.
HOGENOMiHOG000005649.
HOVERGENiHBG099718.
InParanoidiQ969F2.
KOiK03213.
OMAiYNPTESR.
OrthoDBiEOG75F4D6.
PhylomeDBiQ969F2.
TreeFamiTF328786.

Miscellaneous databases

GenomeRNAii85409.
NextBioi75974.
PROiQ969F2.
SOURCEiSearch...

Gene expression databases

BgeeiQ969F2.
CleanExiHS_NKD2.
GenevisibleiQ969F2. HS.

Family and domain databases

Gene3Di1.10.238.10. 1 hit.
InterProiIPR011992. EF-hand-dom_pair.
IPR002048. EF_hand_dom.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
PROSITEiPS50222. EF_HAND_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Vertebrate proteins related to Drosophila Naked Cuticle bind Dishevelled and antagonize Wnt signaling."
    Wharton K.A. Jr., Zimmermann G., Rousset R., Scott M.P.
    Dev. Biol. 234:93-106(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  2. "Molecular cloning, gene structure, and expression analyses of NKD1 and NKD2."
    Katoh M.
    Int. J. Oncol. 19:963-969(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
    Tissue: Fetus.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 127-451 (ISOFORM 1).
    Tissue: Placenta and Uterus.
  4. "Myristoylated Naked2 escorts transforming growth factor alpha to the basolateral plasma membrane of polarized epithelial cells."
    Li C., Franklin J.L., Graves-Deal R., Jerome W.G., Cao Z., Coffey R.J.
    Proc. Natl. Acad. Sci. U.S.A. 101:5571-5576(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH TGFA, SUBCELLULAR LOCATION, MYRISTOYLATION, MUTAGENESIS OF GLY-2.
  5. "Structural studies of human Naked2: a biologically active intrinsically unstructured protein."
    Hu T., Krezel A.M., Li C., Coffey R.J.
    Biochem. Biophys. Res. Commun. 350:911-915(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: DOMAIN, STRUCTURE BY NMR, CIRCULAR DICHROISM.
  6. "Naked2 acts as a cargo recognition and targeting protein to ensure proper delivery and fusion of TGF-{alpha} containing exocytic vesicles at the lower lateral membrane of polarized MDCK cells."
    Li C., Hao M., Cao Z., Ding W., Graves-Deal R., Hu J., Piston D.W., Coffey R.J.
    Mol. Biol. Cell 18:3081-3093(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  7. "EGF receptor-independent action of TGF-alpha protects Naked2 from AO7-mediated ubiquitylation and proteasomal degradation."
    Ding W., Li C., Hu T., Graves-Deal R., Fotia A.B., Weissman A.M., Coffey R.J.
    Proc. Natl. Acad. Sci. U.S.A. 105:13433-13438(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: UBIQUITINATION, INTERACTION WITH TGFA AND RNF25.

Entry informationi

Entry nameiNKD2_HUMAN
AccessioniPrimary (citable) accession number: Q969F2
Secondary accession number(s): Q96EK8, Q9BSN0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 11, 2007
Last sequence update: December 1, 2001
Last modified: March 16, 2016
This is version 112 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 5
    Human chromosome 5: 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. 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.