Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q9NPB6 (PAR6A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Partitioning defective 6 homolog alpha

Short name=PAR-6
Short name=PAR-6 alpha
Short name=PAR-6A
Alternative name(s):
PAR6C
Tax interaction protein 40
Short name=TIP-40
Gene names
Name:PARD6A
Synonyms:PAR6A
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length346 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Adapter protein involved in asymmetrical cell division and cell polarization processes. Probably involved in the formation of epithelial tight junctions. Association with PARD3 may prevent the interaction of PARD3 with F11R/JAM1, thereby preventing tight junction assembly. The PARD6-PARD3 complex links GTP-bound Rho small GTPases to atypical protein kinase C proteins. Ref.2

Subunit structure

Interacts with MAP2K5 By similarity. Interacts with PARD3. Interacts with GTP-bound forms of CDC42, ARHQ/TC10 and RAC1. Interacts with the N-terminal part of PRKCI and PRKCZ. Part of a complex with PARD3, CDC42 or RAC1 and PRKCI or PRKCZ. Part of a complex with LLGL1 and PRKCI By similarity. Interacts with human T-cell leukemia virus type I TAX protein. Interacts with MPP5 and CRB3. Interacts with TGFBR1; involved in TGF-beta induced epithelial to mesenchymal transition. Interacts with ECT2 ('Thr-359' phosphorylated form) and PRKCI. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.14

Subcellular location

Cytoplasm. Cell membrane. Cell projectionruffle. Cell junctiontight junction. Note: Colocalizes with GTP-bound CDC42 or RAC1 at membrane ruffles and with PARD3 and PRKCI at epithelial tight junctions.

Tissue specificity

Expressed in pancreas, skeletal muscle, brain and heart. Weakly expressed in kidney and placenta.

Domain

The pseudo-CRIB domain together with the PDZ domain is required for the interaction with Rho small GTPases By similarity. Ref.9

The OPR domain mediates interactions with MAP2K5 By similarity. Ref.9

The PDZ domain mediates the interaction with CRB3. Ref.9

Post-translational modification

Phosphorylated by the TGF-beta receptor By similarity. Ref.11

Sequence similarities

Belongs to the PAR6 family.

Contains 1 OPR domain.

Contains 1 PDZ (DHR) domain.

Contains 1 pseudo-CRIB domain.

Ontologies

Keywords
   Biological processCell cycle
Cell division
   Cellular componentCell junction
Cell membrane
Cell projection
Cytoplasm
Membrane
Tight junction
   Coding sequence diversityAlternative splicing
Polymorphism
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell cycle

Inferred from electronic annotation. Source: UniProtKB-KW

cell division

Inferred from electronic annotation. Source: UniProtKB-KW

cell junction assembly

Traceable author statement. Source: Reactome

cell-cell junction maintenance

Inferred from sequence or structural similarity. Source: UniProtKB

cell-cell junction organization

Traceable author statement. Source: Reactome

tight junction assembly

Traceable author statement. Source: Reactome

transforming growth factor beta receptor signaling pathway

Traceable author statement. Source: Reactome

viral process

Traceable author statement Ref.7. Source: ProtInc

   Cellular_componentapical part of cell

Inferred from electronic annotation. Source: Ensembl

cell cortex

Inferred from electronic annotation. Source: Ensembl

cytosol

Traceable author statement. Source: Reactome

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Traceable author statement. Source: Reactome

protein complex

Inferred from electronic annotation. Source: Ensembl

ruffle

Inferred from electronic annotation. Source: UniProtKB-SubCell

tight junction

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionGTP-dependent protein binding

Inferred from sequence or structural similarity. Source: UniProtKB

Rho GTPase binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.1Ref.11Ref.14. Source: UniProtKB

transcription factor binding

Traceable author statement Ref.7. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9NPB6-1)

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: Q9NPB6-2)

The sequence of this isoform differs from the canonical sequence as follows:
     96-96: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 346346Partitioning defective 6 homolog alpha
PRO_0000112513

Regions

Domain15 – 9581OPR
Domain133 – 15018Pseudo-CRIB
Domain157 – 25094PDZ
Region1 – 116116Interaction with PRKCI and PRKCZ
Region126 – 253128Interaction with PARD3 and CDC42 By similarity

Amino acid modifications

Modified residue2781Phosphoserine Ref.12

Natural variations

Alternative sequence961Missing in isoform 2.
VSP_007459
Natural variant2861V → I.
Corresponds to variant rs35356834 [ dbSNP | Ensembl ].
VAR_050454

Experimental info

Mutagenesis191K → A: Loss of interaction with ECT2 and PRKCI. Ref.14 Ref.16
Mutagenesis281R → A: Slight decrease of interaction with PRKCI. Loss of interaction with PRKCI; when associated with A-89. Ref.16
Mutagenesis891R → A: Slight decrease of interaction with PRKCI. Loss of interaction with PRKCI; when associated with A-28. Ref.16

Secondary structure

.................. 346
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: 9241E0EDC3694AD4

FASTA34637,388
        10         20         30         40         50         60 
MARPQRTPAR SPDSIVEVKS KFDAEFRRFA LPRASVSGFQ EFSRLLRAVH QIPGLDVLLG 

        70         80         90        100        110        120 
YTDAHGDLLP LTNDDSLHRA LASGPPPLRL LVQKRAEADS SGLAFASNSL QRRKKGLLLR 

       130        140        150        160        170        180 
PVAPLRTRPP LLISLPQDFR QVSSVIDVDL LPETHRRVRL HKHGSDRPLG FYIRDGMSVR 

       190        200        210        220        230        240 
VAPQGLERVP GIFISRLVRG GLAESTGLLA VSDEILEVNG IEVAGKTLDQ VTDMMVANSH 

       250        260        270        280        290        300 
NLIVTVKPAN QRNNVVRGAS GRLTGPPSAG PGPAEPDSDD DSSDLVIENR QPPSSNGLSQ 

       310        320        330        340 
GPPCWDLHPG CRHPGTRSSL PSLDDQEQAS SGWGSRIRGD GSGFSL 

« Hide

Isoform 2 [UniParc].

Checksum: 035F9FA6BB62F085
Show »

FASTA34537,317

References

« Hide 'large scale' references
[1]"The mammalian homologue of the Caenorhabditis elegans polarity protein PAR-6 is a binding partner for the Rho GTPases Cdc42 and Rac1."
Johansson A.-S., Driessens M., Aspenstroem P.
J. Cell Sci. 113:3267-3275(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION, INTERACTION WITH PARD3; CDC42 AND RAC1.
Tissue: B-cell.
[2]"A human homolog of the Caenorhabditis elegans polarity determinant Par-6 links Rac and Cdc42 to PKC-zeta signaling and cell transformation."
Qiu R.-G., Abo A., Martin G.S.
Curr. Biol. 10:697-707(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, INTERACTION WITH CDC42; RAC1 AND PRKCZ.
Tissue: Cervix carcinoma.
[3]"The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42."
Joberty G., Petersen C., Gao L., Macara I.G.
Nat. Cell Biol. 2:531-539(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INTERACTION WITH ARHQ.
Tissue: Brain.
[4]"Atypical protein kinase C is involved in the evolutionarily conserved par protein complex and plays a critical role in establishing epithelia-specific junctional structures."
Suzuki A., Yamanaka T., Hirose T., Manabe N., Mizuno K., Shimizu M., Akimoto K., Izumi Y., Ohnishi T., Ohno S.
J. Cell Biol. 152:1183-1196(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBUNIT OF A COMPLEX CONTAINING PARD3 AND PRKCI.
Tissue: Kidney.
[5]"Human homologues of the Caenorhabditis elegans cell polarity protein PAR6 as an adaptor that links the small GTPases Rac and Cdc42 to atypical protein kinase C."
Noda Y., Takeya R., Ohno S., Naito S., Ito T., Sumimoto H.
Genes Cells 6:107-119(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INTERACTION WITH RAC1; CDC42; PRKCI AND PRKCZ.
Tissue: Neuroblastoma.
[6]"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).
Tissue: Eye.
[7]"The C-terminus of the HTLV-1 Tax oncoprotein mediates interaction with the PDZ domain of cellular proteins."
Rousset R., Fabre S., Desbois C., Bantignies F., Jalinot P.
Oncogene 16:643-654(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 115-345, INTERACTION WITH HTLV-1 TAX.
Tissue: Lymphocyte.
[8]"Direct interaction of two polarity complexes implicated in epithelial tight junction assembly."
Hurd T.W., Gao L., Roh M.H., Macara I.G., Margolis B.
Nat. Cell Biol. 5:137-142(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MPP5.
[9]"CRB3 binds directly to Par6 and regulates the morphogenesis of the tight junctions in mammalian epithelial cells."
Lemmers C., Michel D., Lane-Guermonprez L., Delgrossi M.-H., Medina E., Arsanto J.-P., Le Bivic A.
Mol. Biol. Cell 15:1324-1333(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CRB3, DOMAIN.
[10]"Nucleotide exchange factor ECT2 interacts with the polarity protein complex Par6/Par3/protein kinase Czeta (PKCzeta) and regulates PKCzeta activity."
Liu X.F., Ishida H., Raziuddin R., Miki T.
Mol. Cell. Biol. 24:6665-6675(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ECT2.
[11]"Regulation of the polarity protein Par6 by TGFbeta receptors controls epithelial cell plasticity."
Ozdamar B., Bose R., Barrios-Rodiles M., Wang H.R., Zhang Y., Wrana J.L.
Science 307:1603-1609(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TGFBR1, PHOSPHORYLATION BY TGF-BETA RECEPTOR.
[12]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-278, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[13]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[14]"Ect2 links the PKCiota-Par6alpha complex to Rac1 activation and cellular transformation."
Justilien V., Fields A.P.
Oncogene 28:3597-3607(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ECT2 AND PRKCI, MUTAGENESIS OF LYS-19.
[15]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[16]"Structure of a cell polarity regulator, a complex between atypical PKC and Par6 PB1 domains."
Hirano Y., Yoshinaga S., Takeya R., Suzuki N.N., Horiuchi M., Kohjima M., Sumimoto H., Inagaki F.
J. Biol. Chem. 280:9653-9661(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 14-95 IN COMPLEX WITH PRKCI, MUTAGENESIS OF LYS-19; ARG-28 AND ARG-89.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ277095 mRNA. Translation: CAB85490.1.
AF265565 mRNA. Translation: AAF75548.1.
AF252292 mRNA. Translation: AAF71529.1.
AB043634 mRNA. Translation: BAA96235.1.
AB041642 mRNA. Translation: BAB16105.1.
BC015626 mRNA. Translation: AAH15626.1.
AF028827 mRNA. Translation: AAB84252.1.
CCDSCCDS10843.1. [Q9NPB6-1]
CCDS45514.1. [Q9NPB6-2]
RefSeqNP_001032358.1. NM_001037281.1. [Q9NPB6-2]
NP_058644.1. NM_016948.2. [Q9NPB6-1]
UniGeneHs.112933.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1WMHX-ray1.50B14-95[»]
ProteinModelPortalQ9NPB6.
SMRQ9NPB6. Positions 14-95, 126-252.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid119157. 32 interactions.
IntActQ9NPB6. 20 interactions.
MINTMINT-191836.
STRING9606.ENSP00000219255.

PTM databases

PhosphoSiteQ9NPB6.

Polymorphism databases

DMDM30913215.

Proteomic databases

PaxDbQ9NPB6.
PRIDEQ9NPB6.

Protocols and materials databases

DNASU50855.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000219255; ENSP00000219255; ENSG00000102981. [Q9NPB6-1]
ENST00000458121; ENSP00000392388; ENSG00000102981. [Q9NPB6-2]
GeneID50855.
KEGGhsa:50855.
UCSCuc002ets.3. human. [Q9NPB6-2]
uc002ett.3. human. [Q9NPB6-1]

Organism-specific databases

CTD50855.
GeneCardsGC16P067696.
HGNCHGNC:15943. PARD6A.
HPACAB009733.
MIM607484. gene.
neXtProtNX_Q9NPB6.
PharmGKBPA32937.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG315424.
HOGENOMHOG000231716.
HOVERGENHBG053509.
InParanoidQ9NPB6.
KOK06093.
OMAPCWDLHP.
OrthoDBEOG73JKWB.
PhylomeDBQ9NPB6.
TreeFamTF312899.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_111155. Cell-Cell communication.
REACT_116125. Disease.
SignaLinkQ9NPB6.

Gene expression databases

BgeeQ9NPB6.
CleanExHS_PARD6A.
GenevestigatorQ9NPB6.

Family and domain databases

Gene3D2.30.42.10. 1 hit.
InterProIPR000270. OPR_PB1.
IPR001478. PDZ.
[Graphical view]
PfamPF00564. PB1. 1 hit.
PF00595. PDZ. 1 hit.
[Graphical view]
SMARTSM00666. PB1. 1 hit.
SM00228. PDZ. 1 hit.
[Graphical view]
SUPFAMSSF50156. SSF50156. 1 hit.
PROSITEPS50106. PDZ. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPARD6A. human.
EvolutionaryTraceQ9NPB6.
GeneWikiPARD6A.
GenomeRNAi50855.
NextBio53337.
PROQ9NPB6.
SOURCESearch...

Entry information

Entry namePAR6A_HUMAN
AccessionPrimary (citable) accession number: Q9NPB6
Secondary accession number(s): O14911, Q9NPJ7
Entry history
Integrated into UniProtKB/Swiss-Prot: May 16, 2003
Last sequence update: October 1, 2000
Last modified: July 9, 2014
This is version 122 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM