Q9NPB6 (PAR6A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	346 AA.
Sequence status	Complete.
Protein existence	Evidence 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 projection › ruffle. Cell junction › tight 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 process	Cell cycle Cell division
Cellular component	Cell junction Cell membrane Cell projection Cytoplasm Membrane Tight junction
Coding sequence diversity	Alternative splicing Polymorphism
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW cell division Inferred from electronic annotation. Source: UniProtKB-KW cell-cell junction maintenance Inferred from sequence or structural similarity. Source: UniProtKB tight junction assembly Traceable author statement. Source: Reactome transforming growth factor beta receptor signaling pathway Traceable author statement. Source: Reactome viral reproduction Traceable author statement Ref.7. Source: ProtInc
Cellular_component	apical part of cell Inferred from electronic annotation. Source: Compara cell cortex Inferred from electronic annotation. Source: Compara 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: Compara ruffle Inferred from electronic annotation. Source: UniProtKB-SubCell tight junction Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	GTP-dependent protein binding Inferred from sequence or structural similarity. Source: UniProtKB Rho GTPase binding Inferred from sequence or structural similarity. Source: UniProtKB transcription factor binding Traceable author statement Ref.7. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDC42	P60953	7	EBI-81876,EBI-81752
PARD3	Q8TEW0	7	EBI-81876,EBI-81968
PNMA1	Q8ND90	2	EBI-81876,EBI-302345
PRKCI	P41743	9	EBI-81876,EBI-286199
PRKCZ	Q05513	3	EBI-81876,EBI-295351
RAC1	P63000	2	EBI-81876,EBI-413628
YWHAH	Q04917	2	EBI-81876,EBI-306940

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 346

346

Partitioning defective 6 homolog alpha

PRO_0000112513

Regions

Domain

15 – 95

81

OPR

Domain

133 – 150

18

Pseudo-CRIB

Domain

157 – 250

94

PDZ

Region

1 – 116

116

Interaction with PRKCI and PRKCZ

Region

126 – 253

128

Interaction with PARD3 and CDC42 By similarity

Amino acid modifications

Modified residue

278

1

Phosphoserine Ref.12

Natural variations

Alternative sequence

96

1

Missing in isoform 2.

VSP_007459

Natural variant

286

1

V → I.
Corresponds to variant rs35356834 [ dbSNP | Ensembl ].

VAR_050454

Experimental info

Mutagenesis

19

1

K → A: Loss of interaction with ECT2 and PRKCI. Ref.14 Ref.16

Mutagenesis

28

1

R → A: Slight decrease of interaction with PRKCI. Loss of interaction with PRKCI; when associated with A-89. Ref.16

Mutagenesis

89

1

R → A: Slight decrease of interaction with PRKCI. Loss of interaction with PRKCI; when associated with A-28. Ref.16

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

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346

Helix Strand Turn

Details...

Beta strand

15 – 22

8

Beta strand

25 – 32

8

Helix

33 – 35

3

Helix

39 – 49

11

Beta strand

58 – 62

5

Beta strand

68 – 70

3

Helix

74 – 80

7

Beta strand

83 – 86

4

Beta strand

88 – 93

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 9241E0EDC3694AD4	FASTA	346	37,388
	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
	Isoform 2 [UniParc]. Checksum: 035F9FA6BB62F085	FASTA	345	37,317
	10 20 30 40 50 60 MARPQRTPAR SPDSIVEVKS KFDAEFRRFA LPRASVSGFQ EFSRLLRAVH QIPGLDVLLG 70 80 90 100 110 120 YTDAHGDLLP LTNDDSLHRA LASGPPPLRL LVQKREADSS GLAFASNSLQ RRKKGLLLRP 130 140 150 160 170 180 VAPLRTRPPL LISLPQDFRQ VSSVIDVDLL PETHRRVRLH KHGSDRPLGF YIRDGMSVRV 190 200 210 220 230 240 APQGLERVPG IFISRLVRGG LAESTGLLAV SDEILEVNGI EVAGKTLDQV TDMMVANSHN 250 260 270 280 290 300 LIVTVKPANQ RNNVVRGASG RLTGPPSAGP GPAEPDSDDD SSDLVIENRQ PPSSNGLSQG 310 320 330 340 PPCWDLHPGC RHPGTRSSLP SLDDQEQASS GWGSRIRGDG SGFSL

References

	« Hide 'large scale' referencesShow '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, MASS SPECTROMETRY. 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.

IPI

IPI00027217.
IPI00295048.

RefSeq

NP_001032358.1. NM_001037281.1.
NP_058644.1. NM_016948.2.

UniGene

Hs.112933.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WMH	X-ray	1.50	B	14-95	[»]

ProteinModelPortal

Q9NPB6.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9NPB6. 18 interactions.

MINT

MINT-191836.

STRING

9606.ENSP00000219255.

PTM databases

PhosphoSite

Q9NPB6.

Polymorphism databases

DMDM

30913215.

Proteomic databases

PaxDb

Q9NPB6.

PRIDE

Q9NPB6.

Protocols and materials databases

DNASU

50855.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000219255; ENSP00000219255; ENSG00000102981.
ENST00000458121; ENSP00000392388; ENSG00000102981.

GeneID

50855.

KEGG

hsa:50855.

UCSC

uc002ets.3. human.
uc002ett.3. human.

Organism-specific databases

CTD

50855.

GeneCards

GC16P067696.

HGNC

HGNC:15943. PARD6A.

HPA

CAB009733.

MIM

607484. gene.

neXtProt

NX_Q9NPB6.

PharmGKB

PA32937.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG315424.

HOGENOM

HOG000231716.

HOVERGEN

HBG053509.

InParanoid

Q9NPB6.

KO

K06093.

OMA

PCWDLHP.

OrthoDB

EOG46HGB2.

PhylomeDB

Q9NPB6.

Enzyme and pathway databases

Pathway_Interaction_DB

tgfbrpathway. TGF-beta receptor signaling.

Reactome

REACT_111102. Signal Transduction.
REACT_111155. Cell-Cell communication.

Gene expression databases

Bgee

Q9NPB6.

CleanEx

HS_PARD6A.

Genevestigator

Q9NPB6.

GermOnline

ENSG00000102981. Homo sapiens.

Family and domain databases

InterPro

IPR000270. OPR_PB1.
IPR001478. PDZ.
[Graphical view]

Pfam

PF00564. PB1. 1 hit.
PF00595. PDZ. 1 hit.
[Graphical view]

SMART

SM00666. PB1. 1 hit.
SM00228. PDZ. 1 hit.
[Graphical view]

SUPFAM

SSF50156. PDZ. 1 hit.

PROSITE

PS50106. PDZ. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

PARD6A. human.

EvolutionaryTrace

Q9NPB6.

GenomeRNAi

50855.

NextBio

53337.

SOURCE

Search...

Entry information

Entry name

PAR6A_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 110 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.