Reviewed, UniProtKB/Swiss-Prot Q969F2 (NKD2_HUMAN)

Names and origin

Protein names

Recommended name:
    Protein naked cuticle homolog 2
      Short name=Naked-2
      Short name=hNkd2

Gene names

Name:

NKD2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	451 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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.
Subunit structure	Interacts with DVL1, DVL2, DVL3 and PPP2R3A By similarity. Interacts with TGFA.
Subcellular location	Cell membrane. Cytoplasm. Cytoplasmic vesicle. Ref.4 Ref.5
Tissue specificity	Expressed in kidney, lung, pancreas and spleen. Ref.2
Developmental stage	Expressed in fetal kidney and lung. Ref.2
Sequence similarities	Belongs to the NKD family. Contains 1 EF-hand domain.

Ontologies

Keywords
Biological process	Exocytosis Transport Wnt signaling pathway
Cellular component	Cell membrane Cytoplasm Cytoplasmic vesicle Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Calcium
PTM	Lipoprotein Myristate
Gene Ontology (GO)
Biological process	Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW exocytosis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasmic vesicle Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Ref.4 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
TGFA	P01135	2	EBI-1538629,EBI-1034374

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q969F2-1)

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.

Isoform 2 (identifier: Q969F2-2)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed
	Chain	2 – 451	450	Protein naked cuticle homolog 2		PRO_0000301993
Regions
	Domain	119 – 154	36	EF-hand
	Calcium binding	132 – 144	13	Potential
	Region	2 – 173	172	Targeting to the basolateral cell membrane
	Region	113 – 178	66	Interaction with DVL1, DVL2 and DVL3 By similarity
	Region	300 – 385	86	Interaction with TGFA
	Compositional bias	431 – 449	19	His-rich
Amino acid modifications
	Lipidation	2	1	N-myristoyl glycine
Natural variations
	Alternative sequence	265 – 311	47	PPVQA…VPASE → QLCEKRSSAPRTHSGDKARG VGLCRELWSQAGHPQWPGPF PSGLVAV in isoform 2.		VSP_027900
	Alternative sequence	312 – 451	140	Missing in isoform 2.		VSP_027901
	Natural variant	257	1	T → K: dbSNP rs35679233.		VAR_034934
Experimental info
	Mutagenesis	2	1	G → A: Abrogates myristoylation and membrane association and impairs delivery of TGFA to the cell surface. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: F27E708F9FAD1F2A	FASTA	451	50,055
	10 20 30 40 50 60 MGKLQSKHAA AARKRRESPE GDSFVASAYA SGRKGAEEAE RRARDKQELP NGDPKEGPFR 70 80 90 100 110 120 EDQCPLQVAL PAEKAEGREH PGQLLSADDG ERAANREGPR GPGGQRLNID ALQCDVSVEE 130 140 150 160 170 180 DDRQEWTFTL YDFDNCGKVT REDMSSLMHT IYEVVDASVN HSSGSSKTLR VKLTVSPEPS 190 200 210 220 230 240 SKRKEGPPAG QDREPTRCRM EGELAEEPRV ADRRLSAHVR RPSTDPQPCS ERGPYCVDEN 250 260 270 280 290 300 TERRNHYLDL AGIENYTSRF GPGSPPVQAK QEPQGRASHL QARSRSQEPD THAVHHRRSQ 310 320 330 340 350 360 VLVEHVVPAS EPAARALDTQ PRPKGPEKQF LKSPKGSGKP PGVPASSKSG KAFSYYLPAV 370 380 390 400 410 420 LPPQAPQDGH HLPQPPPPPY GHKRYRQKGR EGHSPLKAPH AQPATVEHEV VRDLPPTPAG 430 440 450 EGYAVPVIQR HEHHHHHEHH HHHHHHHFHP S
	Isoform 2. Checksum: E702F46F4DFBA4BF	FASTA	311	34,314
	10 20 30 40 50 60 MGKLQSKHAA AARKRRESPE GDSFVASAYA SGRKGAEEAE RRARDKQELP NGDPKEGPFR 70 80 90 100 110 120 EDQCPLQVAL PAEKAEGREH PGQLLSADDG ERAANREGPR GPGGQRLNID ALQCDVSVEE 130 140 150 160 170 180 DDRQEWTFTL YDFDNCGKVT REDMSSLMHT IYEVVDASVN HSSGSSKTLR VKLTVSPEPS 190 200 210 220 230 240 SKRKEGPPAG QDREPTRCRM EGELAEEPRV ADRRLSAHVR RPSTDPQPCS ERGPYCVDEN 250 260 270 280 290 300 TERRNHYLDL AGIENYTSRF GPGSQLCEKR SSAPRTHSGD KARGVGLCRE LWSQAGHPQW 310 PGPFPSGLVA V

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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: 11356022] [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: 11604995] [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: 15489334] [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: 15064403] [Abstract] Cited for: FUNCTION, INTERACTION WITH TGFA, SUBCELLULAR LOCATION, MYRISTOYLATION, MUTAGENESIS OF GLY-2.
[5]	"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: 17553928] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF358137 mRNA. Translation: AAK57486.1. AB062887 mRNA. Translation: BAB70501.1. BC004940 mRNA. Translation: AAH04940.1. BC012176 mRNA. Translation: AAH12176.1.
IPI	IPI00056319. IPI00061527.
RefSeq	NP_149111.1.
UniGene	Hs.240951
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q969F2. 1 interaction.
PTM databases
PhosphoSite	Q969F2.
Proteomic databases
PeptideAtlas	Q969F2.
PRIDE	Q969F2.
Genome annotation databases
Ensembl	ENSG00000145506. Homo sapiens. [Contig view]
GeneID	85409.
KEGG	hsa:85409.
Organism-specific databases
GeneCards	GC05P001062.
H-InvDB	HIX0004713.
HGNC	HGNC:17046. NKD2.
MIM	607852. gene.
PharmGKB	PA31638.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q969F2.
HOVERGEN	Q969F2.
OMA	Q969F2. RELWSQA.
Gene expression databases
ArrayExpress	Q969F2.
Bgee	Q969F2.
CleanEx	HS_NKD2.
Family and domain databases
InterPro	IPR011992. EF-Hand_type. IPR018247. EF_HAND_1. IPR018249. EF_HAND_2. [Graphical view]
Gene3D	G3DSA:1.10.238.10. EF-Hand_type. 1 hit.
PROSITE	PS00018. EF_HAND_1. False negative. PS50222. EF_HAND_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	75974.
SOURCE	Search...

Entry information

Entry name

NKD2_HUMAN

Accession

Primary (citable) accession number: Q969F2
Secondary accession number(s): Q96EK8, Q9BSN0

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 11, 2007
Last sequence update:	December 1, 2001
Last modified:	June 16, 2009
This is version 53 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)