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PDZK1IP1 (PDZK1 interacting protein 1)

Written2011-07Amancio Carnero
Instituto de Biomedicina de Sevilla, (IBIS/HUVR), Consejo Superior de Investigaciones Cientificas (CSIC), Edificio IBIS, Campus Hospital Universitario Virgen del Rocio, Avda, Manuel Siurot s/n, 41013, Sevilla, Spain

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)DD96
MAP17
SPAP
Other aliasRP1-18D14.5
HGNC (Hugo) PDZK1IP1
LocusID (NCBI) 10158
Atlas_Id 41268
Location 1p33  [Link to chromosome band 1p33]
Location_base_pair Starts at 47649261 and ends at 47655771 bp from pter ( according to hg19-Feb_2009)  [Mapping PDZK1IP1.png]
Fusion genes
(updated 2016)
CDK13 (7p14.1) / PDZK1IP1 (1p33)TESK2 (1p34.1) / PDZK1IP1 (1p33)

DNA/RNA

 
  Scheme of the PDZK1IP1/MAP17 locus and transcript.
Transcription Four coding exons produce a 600 bp transcript only expressed in proximal tubule kidney cells. PDZK1IP1/MAP17 mRNA is overexpressed in a great variety of human carcinomas and strongly correlates with tumoral progression (P<0.0001). Many tumor cells also express MAP17 and its expression does not correlate with expression of SCL (TAL1) a neighbor gene reported to be co-expressed in some hematopoietic cell lines. SCL neither is expressed in most MAP17 positive tumors, indicating the independent transcription of MAP17, at least in carcinomas. MAP17 promoter is activated by oncogenes.

Protein

 
  Scheme of the PDZK1IP1/MAP17 protein. Blue barrs indicate transmembrane regions. Pink barr indicates PDZ-binding domain.
Description MAP17 is a small, non-glycosylated membrane-associated protein of 17 kDa, which is located on the plasma membrane and the Golgi apparatus. The protein sequence possesses a hydrophobic amino-terminus containing 13 amino acids that encodes a PDZ-binding domain and two transmembrane regions. MAP17 binds several PDZ domain-containing proteins, including PDZK1, NHERF proteins, NaPiIIa and NHe3. Together with NHRF3 and NHRF4, overexpression of MAP17 in opossum kidney cells leads to internalization of NaPilla to the trans-Golgi network. In normal tissue MAP17 is only expressed in the proximal tubules of kidney cells. The physiological role of MAP17 in proximal tubules is not known, but it stimulates specific Na-dependent transport of mannose and glucose in Xenopus oocytes and some mammary cells.
Expression MAP17 protein is overexpressed in a great variety of human carcinomas. Immunohistochemical analysis of MAP17 during cancer progression shows, at least in prostate and ovarian carcinomas, that overexpression of the protein strongly correlates with tumoral progression (P<0.0001). Many tumor cells also express MAP17 protein.
Localisation Apical end of proximal tubule cells in kidney.
Function MAP17 binds several PDZ domain-containing proteins, including PDZK1, NHERF proteins, NaPiIIa and NHe3. Overexpression of MAP17 into opossum kidney cells participates, together with NHRF3 and NHRF4 in NaPiIIa internalization to the transgolgi network. The physiological role of MAP17 in proximal tubules is not known but it stimulates specific Na-dependent transport of mannose and glucose in Xenopus oocytes and in mammary cells.
Homology Higly conserved protein troughout the evolution.

Mutations

Note Described mutated in malignant mesothelioma tumors with a change of aminoacid (T to I). The functional effect of the change is not known.
Somatic c403t

Implicated in

Note
  
Entity Cancer
Disease Carcinomas of different origin, melanoma, etc.
Prognosis Expression levels increase with stage in most carcinomas.
 
Overexpression of MAP17 in colon carcinoma.
Oncogenesis MAP17 (PDZK1IP1, DD96) enhances tumorigenic properties of melanoma cells through ROS increase (Guijarro et al., 2007b). Tumor cells that overexpress MAP17 show an increased tumoral phenotype with enhanced proliferative capabilities both in presence or absence of contact inhibition, decreased apoptotic sensitivity and increased migration. MAP17-expressing clones also grow better in nude mice. The increased malignant cell behavior induced by MAP17 are associated with an increase in ROS production, and the treatment of MAP17-expressing cells with antioxidants results in a reduction in the tumorigenic properties of these cells. Treatment of melanoma cells with inhibitors of Na+-coupled co-transporters lead to an inhibition of ROS increase and a decrease in the malignant cell behavior in MAP17-expressing clones. Finally, we show that MAP17-dependent ROS increase and tumorigenesis are dependent on its PDZ-binding domain, since disruption of its sequence by point mutations abolish its ability to enhance ROS production and tumorigenesis.
At the molecular level MAP17 protects Rat1a fibroblasts from Myc-induced apoptosis through ROS-mediated activation of the PI3K/AKT signalling pathway (Guijarro et al., 2007d). A fraction of PTEN undergoes oxidation in MAP17-overexpressing cells. Furthermore, activation of AKT by MAP17 as measured by Thr308 phosphorylation was independent of PI3K activity. Importantly, modulation of ROS by antioxidant treatment prevented activation of AKT, restoring the level of apoptosis in serum starved Rat1/c-Myc fibroblasts (Guijarro et al., 2007d).
MAP17 is overexpressed in a great variety of human carcinomas (Guijarro et al., 2007c). Immunohistochemical analysis of MAP17 during cancer progression shows in prostatic and ovarian carcinomas that overexpression of the protein strongly correlates with tumoral progression (Guijarro et al., 2007c).
  
  
Entity Skin diseases
Disease Abnormal keratinocyte differentiation.
In the meta-analysis of public microarray databases for different skin diseases, Noh and cols (Noh et al., 2010) revealed that MAP17 is commonly up-regulated suggesting that may be potentially associated with the abnormal keratinocyte differentiation. MAP17 was significantly up-regulated in response to interferon-gamma, interleukin 4 (IL-4), IL-6, IL-17A or IL-22 in normal human epidermal keratinocytes (NHEK). Interestingly, the PDZK1 gene is localized within the atopic dermatitis-linked region on human chromosome 1q21. In an attempt to evaluate whether MAP17 regulates the expression of cornified envelope-associated genes at the 1q21 locus, such as filaggrin, loricrin and involucrin, these authors found that the over-expression of MAP17 in HaCaT keratinocytes significantly decreased the expression of filaggrin, a cornified envelope-associated gene. Taken together, the Th cell cytokine-induced up-regulation of MAP17 expression may be linked to the down-regulation of filaggrin, which may be associated with the abnormal epidermal differentiation observed in the dermatological diseases (Noh et al., 2010).
Prognosis .
  

Bibliography

Rat kidney MAP17 induces cotransport of Na-mannose and Na-glucose in Xenopus laevis oocytes.
Blasco T, Aramayona JJ, Alcalde AI, Catalan J, Sarasa M, Sorribas V.
Am J Physiol Renal Physiol. 2003 Oct;285(4):F799-810. Epub 2003 Jun 17.
PMID 12812916
 
MAP17 inhibits Myc-induced apoptosis through PI3K/AKT pathway activation.
Guijarro MV, Link W, Rosado A, Leal JF, Carnero A.
Carcinogenesis. 2007d Dec;28(12):2443-50. Epub 2007 Aug 3.
PMID 17675338
 
The membrane-associated protein pKe#192/MAP17 in human keratinocytes.
Jaeger C, Schaefer BM, Wallich R, Kramer MD.
J Invest Dermatol. 2000 Sep;115(3):375-80.
PMID 10951271
 
Identification and partial characterization of a novel membrane-associated protein (MAP17) up-regulated in human carcinomas and modulating cell replication and tumor growth.
Kocher O, Cheresh P, Lee SW.
Am J Pathol. 1996 Aug;149(2):493-500.
PMID 8701988
 
Interaction of MAP17 with NHERF3/4 induces translocation of the renal Na/Pi IIa transporter to the trans-Golgi.
Lanaspa MA, Giral H, Breusegem SY, Halaihel N, Baile G, Catalan J, Carrodeguas JA, Barry NP, Levi M, Sorribas V.
Am J Physiol Renal Physiol. 2007 Jan;292(1):F230-42. Epub 2006 Aug 22.
PMID 16926447
 
MAP17 is associated with the T-helper cell cytokine-induced down-regulation of filaggrin transcription in human keratinocytes.
Noh M, Yeo H, Ko J, Kim HK, Lee CH.
Exp Dermatol. 2010 Apr;19(4):355-62. Epub 2009 Jul 8.
PMID 19601982
 
Interactions of MAP17 with the NaPi-IIa/PDZK1 protein complex in renal proximal tubular cells.
Pribanic S, Gisler SM, Bacic D, Madjdpour C, Hernando N, Sorribas V, Gantenbein A, Biber J, Murer H.
Am J Physiol Renal Physiol. 2003 Oct;285(4):F784-91. Epub 2003 Jul 1.
PMID 12837682
 

Citation

This paper should be referenced as such :
PDZK1IP1 (PDZK1 interacting protein 1)
PDZK1IP1 (PDZK1 interacting protein 1)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(12):1050-1053.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/PDZK1IP1ID41268ch1p33.html


External links

Nomenclature
HGNC (Hugo)PDZK1IP1   16887
Cards
AtlasPDZK1IP1ID41268ch1p33
Entrez_Gene (NCBI)PDZK1IP1  10158  PDZK1 interacting protein 1
AliasesDD96; MAP17; SPAP
GeneCards (Weizmann)PDZK1IP1
Ensembl hg19 (Hinxton)ENSG00000162366 [Gene_View]  chr1:47649261-47655771 [Contig_View]  PDZK1IP1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000162366 [Gene_View]  chr1:47649261-47655771 [Contig_View]  PDZK1IP1 [Vega]
ICGC DataPortalENSG00000162366
TCGA cBioPortalPDZK1IP1
AceView (NCBI)PDZK1IP1
Genatlas (Paris)PDZK1IP1
WikiGenes10158
SOURCE (Princeton)PDZK1IP1
Genetics Home Reference (NIH)PDZK1IP1
Genomic and cartography
GoldenPath hg19 (UCSC)PDZK1IP1  -     chr1:47649261-47655771 -  1p33   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)PDZK1IP1  -     1p33   [Description]    (hg38-Dec_2013)
EnsemblPDZK1IP1 - 1p33 [CytoView hg19]  PDZK1IP1 - 1p33 [CytoView hg38]
Mapping of homologs : NCBIPDZK1IP1 [Mapview hg19]  PDZK1IP1 [Mapview hg38]
OMIM607178   
Gene and transcription
Genbank (Entrez)BC012303 BI763294 BM924665 CR450304 HQ448165
RefSeq transcript (Entrez)NM_005764
RefSeq genomic (Entrez)NC_000001 NC_018912 NT_032977 NW_004929290
Consensus coding sequences : CCDS (NCBI)PDZK1IP1
Cluster EST : UnigeneHs.431099 [ NCBI ]
CGAP (NCI)Hs.431099
Alternative Splicing GalleryENSG00000162366
Gene ExpressionPDZK1IP1 [ NCBI-GEO ]   PDZK1IP1 [ EBI - ARRAY_EXPRESS ]   PDZK1IP1 [ SEEK ]   PDZK1IP1 [ MEM ]
Gene Expression Viewer (FireBrowse)PDZK1IP1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)10158
GTEX Portal (Tissue expression)PDZK1IP1
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ13113   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ13113  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ13113
Splice isoforms : SwissVarQ13113
PhosPhoSitePlusQ13113
Domains : Interpro (EBI)PDZK-int_prot1    PDZK1IP1/SMIM24   
Domain families : Pfam (Sanger)MAP17 (PF15807)   
Domain families : Pfam (NCBI)pfam15807   
Conserved Domain (NCBI)PDZK1IP1
DMDM Disease mutations10158
Blocks (Seattle)PDZK1IP1
SuperfamilyQ13113
Human Protein AtlasENSG00000162366
Peptide AtlasQ13113
HPRD06211
IPIIPI00011858   
Protein Interaction databases
DIP (DOE-UCLA)Q13113
IntAct (EBI)Q13113
FunCoupENSG00000162366
BioGRIDPDZK1IP1
STRING (EMBL)PDZK1IP1
ZODIACPDZK1IP1
Ontologies - Pathways
QuickGOQ13113
Ontology : AmiGOintegral component of membrane  extracellular exosome  
Ontology : EGO-EBIintegral component of membrane  extracellular exosome  
NDEx NetworkPDZK1IP1
Atlas of Cancer Signalling NetworkPDZK1IP1
Wikipedia pathwaysPDZK1IP1
Orthology - Evolution
OrthoDB10158
GeneTree (enSembl)ENSG00000162366
Phylogenetic Trees/Animal Genes : TreeFamPDZK1IP1
HOVERGENQ13113
HOGENOMQ13113
Homologs : HomoloGenePDZK1IP1
Homology/Alignments : Family Browser (UCSC)PDZK1IP1
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPDZK1IP1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PDZK1IP1
dbVarPDZK1IP1
ClinVarPDZK1IP1
1000_GenomesPDZK1IP1 
Exome Variant ServerPDZK1IP1
ExAC (Exome Aggregation Consortium)PDZK1IP1 (select the gene name)
Genetic variants : HAPMAP10158
Genomic Variants (DGV)PDZK1IP1 [DGVbeta]
DECIPHER (Syndromes)1:47649261-47655771  ENSG00000162366
CONAN: Copy Number AnalysisPDZK1IP1 
Mutations
ICGC Data PortalPDZK1IP1 
TCGA Data PortalPDZK1IP1 
Broad Tumor PortalPDZK1IP1
OASIS PortalPDZK1IP1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPDZK1IP1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDPDZK1IP1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch PDZK1IP1
DgiDB (Drug Gene Interaction Database)PDZK1IP1
DoCM (Curated mutations)PDZK1IP1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)PDZK1IP1 (select a term)
intoGenPDZK1IP1
NCG5 (London)PDZK1IP1
Cancer3DPDZK1IP1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM607178   
Orphanet
MedgenPDZK1IP1
Genetic Testing Registry PDZK1IP1
NextProtQ13113 [Medical]
TSGene10158
GENETestsPDZK1IP1
Huge Navigator PDZK1IP1 [HugePedia]
snp3D : Map Gene to Disease10158
BioCentury BCIQPDZK1IP1
ClinGenPDZK1IP1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD10158
Chemical/Pharm GKB GenePA142671188
Clinical trialPDZK1IP1
Miscellaneous
canSAR (ICR)PDZK1IP1 (select the gene name)
Probes
Litterature
PubMed27 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMinePDZK1IP1
EVEXPDZK1IP1
GoPubMedPDZK1IP1
iHOPPDZK1IP1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Apr 12 11:37:09 CEST 2017

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