| General information | | DisProt: | DP00520 | | Name: | Protein naked cuticle homolog 2 [Isoform 1] | | Synonym(s): | NKD2_HUMAN
Naked-2
hNkd2
Naked cuticle-2
Dvl-binding protein NKD2
| | First appeared in release: | Release 3.5 (12/22/2006) | | UniProt: | Q969F2-1 | | UniGene: | Hs.240951 | | SwissProt: | NKD2_HUMAN | | TrEMBL: | | | NCBI (GI): | 74716653 | | Source organism: | Homo sapiens (Human) | | Sequence length: | 451 | | Percent disordered: | 48% | | Homologues: | |
| Native sequence |
10 20 30 40 50 60
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MGKLQSKHAA AARKRRESPE GDSFVASAYA SGRKGAEEAE RRARDKQELP NGDPKEGPFR - 60
EDQCPLQVAL PAEKAEGREH PGQLLSADDG ERAANREGPR GPGGQRLNID ALQCDVSVEE - 120
DDRQEWTFTL YDFDNCGKVT REDMSSLMHT IYEVVDASVN HSSGSSKTLR VKLTVSPEPS - 180
SKRKEGPPAG QDREPTRCRM EGELAEEPRV ADRRLSAHVR RPSTDPQPCS ERGPYCVDEN - 240
TERRNHYLDL AGIENYTSRF GPGSPPVQAK QEPQGRASHL QARSRSQEPD THAVHHRRSQ - 300
VLVEHVVPAS EPAARALDTQ PRPKGPEKQF LKSPKGSGKP PGVPASSKSG KAFSYYLPAV - 360
LPPQAPQDGH HLPQPPPPPY GHKRYRQKGR EGHSPLKAPH AQPATVEHEV VRDLPPTPAG - 420
EGYAVPVIQR HEHHHHHEHH HHHHHHHFHP S
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| Functional narrative |
Canonical Wnt signaling has emerged as a critical regulator of both stem cells and cancer cells. Naked1 and Naked2 are two mammalian orthologs of Drosophila Naked Cuticle, which has been shown to negatively regulate canonical Wnt signaling through an interaction with Dishevelled. Both Naked1 and Naked2 have been proposed to interact with Dishevelled through their EF-hand like motif (residues 137-157). In addition, Naked2 has been reported to bind to Dishevelled through its TGF-alpha binding region. Naked1 has been shown to be highly upregulated in human colorectal cancers. Naked2, but not Naked1, interacts with the cytoplasmic C-terminal fragment of a Golgi-processed form of TGF-alpha, coats TGF-alpha containing exocytic vesicles and escorts them to the basolateral membrane of polarized epithelial cells. Myristoylation of the N-terminal glycine residue of Naked2 is required for fusion of Naked2-associated vesicles to the plasma membrane. The first 36 residues of Naked2 possibly contain an exocytic vesicle recognition motif. Naked2 binds to multiple proteins and may function as a switch protein through its several functional motifs. 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 and targeting of TGF-alpha to the basolateral membrane of polarized epithelial cells.
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| Map of ordered and disordered regions |
Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.
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| Region 1 | | Type: | Disordered | | Name: | N-terminal | | Location: | 1 - 217 | | Length: | 217 | | Region sequence: |
MGKLQSKHAAAARKRRESPEGDSFVASAYASGRKGAEEAERRARDKQELPNGDPKEGPFR
EDQCPLQVALPAEKAEGREHPGQLLSADDGERAANREGPRGPGGQRLNIDALQCDVSVEE
DDRQEWTFTLYDFDNCGKVTREDMSSLMHTIYEVVDASVNHSSGSSKTLRVKLTVSPEPS
SKRKEGPPAGQDREPTRCRMEGELAEEPRVADRRLSA | | Modification type: | Fragment
Native
| | PDB: | | | Structural/functional type: | Function arises from the disordered state
| | Functional classes: | Molecular assembly
| | Functional subclasses: | Fatty acylation (myristolation and palmitoylation)
Protein-protein binding
| Detection methods:
- Circular dichroism (CD) spectroscopy, far-UV (298 K; 1 mm path-length; PBS (buffer); protein (sample) 10 uM)
- Nuclear magnetic resonance (NMR) (292 K; pH: 7.5; NaCl (buffer) 0.3 M; protein (sample) 0.25 mM; Tris (buffer) 50 mM)
| References:
- Hu T, Krezel AM, Li C, Coffey RJ. "Structural studies of human Naked2: a biologically active intrinsically unstructured protein." Biochem Biophys Res Commun. 2006; 350(4): 911-5. PubMed: 17045239
| Comments:Structure prediction algorithms suggest very little secondary and/or tertiary
structure for Naked2. Full-length Naked2 was insoluble under all condition employed and
so were C-terminally deleted forms of Naked2. Full length Naked2 or even constructs
containing residues 1- 331 are insoluble and therefore not amenable to solution studies.
The 217 N-terminal residues constitute the largest soluble fragment of human Naked2
and it contains the conserved EF-hand motif, thought to be a key functional element.
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