Q6NUN9 (ZN746_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Zinc finger protein 746

Alternative name(s):
Parkin-interacting substrate
Short name=PARIS

Gene names

Name:	ZNF746
Synonyms:	PARIS

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	644 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Domain	Coiled coil Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Repressor
PTM	Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of transcription, DNA-dependent Inferred from direct assay Ref.4. Source: UniProtKB neuron death Inferred from direct assay Ref.4. Source: UniProtKB regulation of cell death Inferred from direct assay Ref.4. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from direct assay Ref.4. Source: UniProtKB nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	transcription regulatory region DNA binding Inferred from direct assay Ref.4. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PARK2	O60260	6	EBI-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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 644	644	Zinc finger protein 746		PRO_0000253728
Regions
	Domain	96 – 167	72	KRAB
	Zinc finger	453 – 478	26	C2H2-type 1; degenerate
	Zinc finger	510 – 532	23	C2H2-type 2
	Zinc finger	538 – 560	23	C2H2-type 3
	Zinc finger	566 – 588	23	C2H2-type 4
	Coiled coil	16 – 92	77	Potential
	Compositional bias	476 – 516	41	Gly-rich
Natural variations
	Alternative sequence	1 – 185	185	Missing in isoform 3.		VSP_041052
	Alternative sequence	279	1	E → EA in isoform 2.		VSP_041053
Experimental info
	Mutagenesis	458	1	C → A: No effect. Ref.4
	Mutagenesis	471	1	H → A: No effect. Ref.4
	Mutagenesis	518	1	C → A: No effect. Ref.4
	Mutagenesis	528	1	H → A: No effect. Ref.4
	Mutagenesis	543	1	C → A: No effect. Ref.4
	Mutagenesis	560	1	H → A: No effect. Ref.4
	Mutagenesis	571	1	C → A: Impairs DNA-binding and ability to repress PGC-1-alpha (PPARGC1A). Ref.4
	Mutagenesis	584	1	H → A: No effect. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: 4F6723D2225D95AB	FASTA	644	69,136
	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
	Isoform 2 [UniParc]. Checksum: 0272268BB5F4112C	FASTA	645	69,207
	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 KLNTAASTEA DVKIVIKTEV QEEEVVATPV 310 320 330 340 350 360 HPTDLEAHGT LFGPGQATRF FPSPAQEGAW ESQGSSFPSQ DPVLGLREPA RPERDMGELS 370 380 390 400 410 420 PAVAQEETPP GDWLFGGVRW GWNFRCKPPV GLNPRTGPEG LPYSSPDNGE AILDPSQAPR 430 440 450 460 470 480 PFNEPCKYPG RTKGFGHKPG LKKHPAAPPG GRPFTCATCG KSFQLQVSLS AHQRSCGAPD 490 500 510 520 530 540 GSGPGTGGGG SGSGGGGGGS GGGSARDGSA LRCGECGRCF TRPAHLIRHR MLHTGERPFP 550 560 570 580 590 600 CTECEKRFTE RSKLIDHYRT HTGVRPFTCT VCGKSFIRKD HLRKHQRNHA AGAKTPARGQ 610 620 630 640 PLPTPPAPPD PFKSPASKGP LASTDLVTDW TCGLSVLGPT DGGDM
	Isoform 3 [UniParc]. Checksum: AFB17AD468480D23	FASTA	459	48,454
	10 20 30 40 50 60 MQIKQEGELQ LQEQQALGVE AWAAGQPDIG EEPWGLSQLD SGAGDISTDA TSGVHSNFST 70 80 90 100 110 120 TIPPTSWQTD LPPHHPSSAC SDGTLKLNTA ASTEDVKIVI KTEVQEEEVV ATPVHPTDLE 130 140 150 160 170 180 AHGTLFGPGQ ATRFFPSPAQ EGAWESQGSS FPSQDPVLGL REPARPERDM GELSPAVAQE 190 200 210 220 230 240 ETPPGDWLFG GVRWGWNFRC KPPVGLNPRT GPEGLPYSSP DNGEAILDPS QAPRPFNEPC 250 260 270 280 290 300 KYPGRTKGFG HKPGLKKHPA APPGGRPFTC ATCGKSFQLQ VSLSAHQRSC GAPDGSGPGT 310 320 330 340 350 360 GGGGSGSGGG GGGSGGGSAR DGSALRCGEC GRCFTRPAHL IRHRMLHTGE RPFPCTECEK 370 380 390 400 410 420 RFTERSKLID HYRTHTGVRP FTCTVCGKSF IRKDHLRKHQ RNHAAGAKTP ARGQPLPTPP 430 440 450 APPDPFKSPA SKGPLASTDL VTDWTCGLSV LGPTDGGDM

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
IPI	IPI00071929. IPI00940207. IPI01011016.
RefSeq	NP_001156946.1. NM_001163474.1. NP_689770.3. NM_152557.4.
UniGene	Hs.24643.
3D structure databases
HSSP	HSSP built from PDB template 1U86 based on UniProtKB Q60980.
ProteinModelPortal	Q6NUN9.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q6NUN9. 1 interaction.
STRING	9606.ENSP00000345140.
PTM databases
PhosphoSite	Q6NUN9.
Polymorphism databases
DMDM	74736828.
Proteomic databases
PaxDb	Q6NUN9.
PRIDE	Q6NUN9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000340622; ENSP00000345140; ENSG00000181220. ENST00000458143; ENSP00000395007; ENSG00000181220.
GeneID	155061.
KEGG	hsa:155061.
UCSC	uc003wfw.2. human. uc010lpi.2. human.
Organism-specific databases
CTD	155061.
GeneCards	GC07M149169.
HGNC	HGNC:21948. ZNF746.
HPA	HPA020272.
MIM	613914. gene.
neXtProt	NX_Q6NUN9.
PharmGKB	PA144596520.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5048.
HOGENOM	HOG000013125.
HOVERGEN	HBG062119.
InParanoid	Q6NUN9.
KO	K09228.
OMA	FKSPASK.
OrthoDB	EOG4SQWWD.
PhylomeDB	Q6NUN9.
Enzyme and pathway databases
Reactome	REACT_71. Gene Expression.
Gene expression databases
ArrayExpress	Q6NUN9.
Bgee	Q6NUN9.
CleanEx	HS_ZNF746.
Genevestigator	Q6NUN9.
GermOnline	ENSG00000181220. Homo sapiens.
Family and domain databases
Gene3D	3.30.160.60. 4 hits.
InterPro	IPR022137. DUF3669_Znf. IPR001909. Krueppel-associated_box. IPR007087. Znf_C2H2. IPR015880. Znf_C2H2-like. IPR013087. Znf_C2H2/integrase_DNA-bd. [Graphical view]
Pfam	PF12417. DUF3669. 1 hit. PF01352. KRAB. 1 hit. PF00096. zf-C2H2. 2 hits. [Graphical view]
SMART	SM00349. KRAB. 1 hit. SM00355. ZnF_C2H2. 4 hits. [Graphical view]
SUPFAM	SSF109640. Krueppel-associated_box. 1 hit.
PROSITE	PS50805. KRAB. 1 hit. PS00028. ZINC_FINGER_C2H2_1. 3 hits. PS50157. ZINC_FINGER_C2H2_2. 4 hits. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	155061.
NextBio	87371.
SOURCE	Search...

Entry information

Entry name

ZN746_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 81 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.