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Q6NUN9 (ZN746_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 89. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | 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:
Zinc finger protein 746
Alternative name(s):
Parkin-interacting substrate
Short name=PARIS
Gene names
Name:ZNF746
Synonyms:PARIS
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length644 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transcription repressor that specifically binds to the 5'-TATTTT[T/G]-3' consensus sequence on promoters and repress transcription of PGC-1-alpha (PPARGC1A), thereby playing a role in regulation of neuron death. Ref.4

Subunit structure

Interacts (via C2H2-type zinc fingers) with PARK2.

Subcellular location

Cytoplasm. Nucleus Probable. Note: Mainly localizes to the cytoplasm; probably translocates to the nucleus to repress selected genes. Ref.4

Post-translational modification

Ubiquitinated by PARK2. 'Lys-48'-linked polyubiquitination by PARK2 leads to degradation by the proteasome and may play a key role in regulation of neuron death. Ref.4

Miscellaneous

May act as a downstream effector of PARK2 and contribute to neurodegeneration in Parkinson disease cases caused by defects in PARK2: its accumulation due to the absence of PARK2, followed by up-regulation of PPARGC1A, could lead to the selective loss of dopamine neurons in the substantia nigra (Ref.4).

Sequence similarities

Belongs to the krueppel C2H2-type zinc-finger protein family.

Contains 4 C2H2-type zinc fingers.

Contains 1 KRAB domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PARK2O602606EBI-3862525,EBI-716346

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q6NUN9-1)

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: Q6NUN9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     279-279: E → EA
Note: No experimental confirmation available.
Isoform 3 (identifier: Q6NUN9-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-185: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 644644Zinc finger protein 746
PRO_0000253728

Regions

Domain96 – 16772KRAB
Zinc finger453 – 47826C2H2-type 1; degenerate
Zinc finger510 – 53223C2H2-type 2
Zinc finger538 – 56023C2H2-type 3
Zinc finger566 – 58823C2H2-type 4
Coiled coil16 – 9277 Potential
Compositional bias476 – 51641Gly-rich

Natural variations

Alternative sequence1 – 185185Missing in isoform 3.
VSP_041052
Alternative sequence2791E → EA in isoform 2.
VSP_041053

Experimental info

Mutagenesis4581C → A: No effect. Ref.4
Mutagenesis4711H → A: No effect. Ref.4
Mutagenesis5181C → A: No effect. Ref.4
Mutagenesis5281H → A: No effect. Ref.4
Mutagenesis5431C → A: No effect. Ref.4
Mutagenesis5601H → A: No effect. Ref.4
Mutagenesis5711C → A: Impairs DNA-binding and ability to repress PGC-1-alpha (PPARGC1A). Ref.4
Mutagenesis5841H → A: No effect. Ref.4

Sequences

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

Last modified July 5, 2004. Version 1.
Checksum: 4F6723D2225D95AB

FASTA64469,136
        10         20         30         40         50         60 
MAEAVAAPIS PWTMAATIQA MERKIESQAA RLLSLEGRTG MAEKKLADCE KTAVEFGNQL 

        70         80         90        100        110        120 
EGKWAVLGTL LQEYGLLQRR LENVENLLRN RNFWILRLPP GSKGESPKEW GKLEDWQKEL 

       130        140        150        160        170        180 
YKHVMRGNYE TLVSLDYAIS KPEVLSQIEQ GKEPCNWRRP GPKIPDVPVD PSPGSGPPVP 

       190        200        210        220        230        240 
APDLLMQIKQ EGELQLQEQQ ALGVEAWAAG QPDIGEEPWG LSQLDSGAGD ISTDATSGVH 

       250        260        270        280        290        300 
SNFSTTIPPT SWQTDLPPHH PSSACSDGTL KLNTAASTED VKIVIKTEVQ EEEVVATPVH 

       310        320        330        340        350        360 
PTDLEAHGTL FGPGQATRFF PSPAQEGAWE SQGSSFPSQD PVLGLREPAR PERDMGELSP 

       370        380        390        400        410        420 
AVAQEETPPG DWLFGGVRWG WNFRCKPPVG LNPRTGPEGL PYSSPDNGEA ILDPSQAPRP 

       430        440        450        460        470        480 
FNEPCKYPGR TKGFGHKPGL KKHPAAPPGG RPFTCATCGK SFQLQVSLSA HQRSCGAPDG 

       490        500        510        520        530        540 
SGPGTGGGGS GSGGGGGGSG GGSARDGSAL RCGECGRCFT RPAHLIRHRM LHTGERPFPC 

       550        560        570        580        590        600 
TECEKRFTER SKLIDHYRTH TGVRPFTCTV CGKSFIRKDH LRKHQRNHAA GAKTPARGQP 

       610        620        630        640 
LPTPPAPPDP FKSPASKGPL ASTDLVTDWT CGLSVLGPTD GGDM 

« Hide

Isoform 2 [UniParc].

Checksum: 0272268BB5F4112C
Show »

FASTA64569,207
Isoform 3 [UniParc].

Checksum: AFB17AD468480D23
Show »

FASTA45948,454

References

« Hide 'large scale' references
[1]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
Tissue: Prostate and Testis.
[2]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Placenta.
[4]"PARIS (ZNF746) repression of PGC-1alpha contributes to neurodegeneration in Parkinson's disease."
Shin J.H., Ko H.S., Kang H., Lee Y., Lee Y.I., Pletinkova O., Troconso J.C., Dawson V.L., Dawson T.M.
Cell 144:689-702(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, UBIQUITINATION, MUTAGENESIS OF CYS-458; HIS-471; CYS-518; HIS-528; CYS-543; HIS-560; CYS-571 AND HIS-584.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK128244 mRNA. Translation: BAC87351.1.
AK291814 mRNA. Translation: BAF84503.1.
AC073314 Genomic DNA. No translation available.
BC068505 mRNA. Translation: AAH68505.1.
RefSeqNP_001156946.1. NM_001163474.1.
NP_689770.3. NM_152557.4.
UniGeneHs.24643.

3D structure databases

ProteinModelPortalQ6NUN9.
SMRQ6NUN9. Positions 102-144, 383-590.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid127574. 15 interactions.
IntActQ6NUN9. 13 interactions.
MINTMINT-8247451.
STRING9606.ENSP00000345140.

PTM databases

PhosphoSiteQ6NUN9.

Polymorphism databases

DMDM74736828.

Proteomic databases

PaxDbQ6NUN9.
PRIDEQ6NUN9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000340622; ENSP00000345140; ENSG00000181220. [Q6NUN9-1]
ENST00000458143; ENSP00000395007; ENSG00000181220. [Q6NUN9-2]
GeneID155061.
KEGGhsa:155061.
UCSCuc003wfw.2. human. [Q6NUN9-1]
uc010lpi.2. human. [Q6NUN9-2]

Organism-specific databases

CTD155061.
GeneCardsGC07M149169.
HGNCHGNC:21948. ZNF746.
HPAHPA020272.
MIM613914. gene.
neXtProtNX_Q6NUN9.
PharmGKBPA144596520.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5048.
HOGENOMHOG000013125.
HOVERGENHBG062119.
InParanoidQ6NUN9.
KOK09228.
OMAFRCKPPV.
OrthoDBEOG73JKWC.
PhylomeDBQ6NUN9.
TreeFamTF337777.

Enzyme and pathway databases

ReactomeREACT_71. Gene Expression.

Gene expression databases

ArrayExpressQ6NUN9.
BgeeQ6NUN9.
CleanExHS_ZNF746.
GenevestigatorQ6NUN9.

Family and domain databases

Gene3D3.30.160.60. 4 hits.
InterProIPR022137. DUF3669_Znf.
IPR001909. Krueppel-associated_box.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PfamPF12417. DUF3669. 1 hit.
PF01352. KRAB. 1 hit.
PF00096. zf-C2H2. 2 hits.
[Graphical view]
SMARTSM00349. KRAB. 1 hit.
SM00355. ZnF_C2H2. 4 hits.
[Graphical view]
SUPFAMSSF109640. SSF109640. 1 hit.
PROSITEPS50805. KRAB. 1 hit.
PS00028. ZINC_FINGER_C2H2_1. 3 hits.
PS50157. ZINC_FINGER_C2H2_2. 4 hits.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi155061.
NextBio87371.
PROQ6NUN9.
SOURCESearch...

Entry information

Entry nameZN746_HUMAN
AccessionPrimary (citable) accession number: Q6NUN9
Secondary accession number(s): A8K6Z9, Q6ZRF9
Entry history
Integrated into UniProtKB/Swiss-Prot: October 17, 2006
Last sequence update: July 5, 2004
Last modified: April 16, 2014
This is version 89 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

MIM cross-references

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

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM