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Protein

Zinc finger protein 746

Gene

ZNF746

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri453 – 47826C2H2-type 1; degeneratePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri510 – 53223C2H2-type 2PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri538 – 56023C2H2-type 3PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri566 – 58823C2H2-type 4PROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. metal ion binding Source: UniProtKB-KW
  2. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
  3. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription Source: NTNU_SB
  4. sequence-specific DNA binding transcription factor activity Source: ParkinsonsUK-UCL
  5. transcription regulatory region DNA binding Source: UniProtKB
  6. ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

  1. negative regulation of transcription, DNA-templated Source: UniProtKB
  2. negative regulation of transcription from RNA polymerase II promoter Source: ParkinsonsUK-UCL
  3. positive regulation of neuron death Source: UniProtKB
  4. positive regulation of transcription from RNA polymerase II promoter Source: ParkinsonsUK-UCL
Complete GO annotation...

Keywords - Molecular functioni

Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_12627. Generic Transcription Pathway.

Names & Taxonomyi

Protein namesi
Recommended name:
Zinc finger protein 746
Alternative name(s):
Parkin-interacting substrate
Short name:
PARIS
Gene namesi
Name:ZNF746
Synonyms:PARIS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 7

Organism-specific databases

HGNCiHGNC:21948. ZNF746.

Subcellular locationi

Cytoplasm 1 Publication. Nucleus 1 Publication
Note: Mainly localizes to the cytoplasm; probably translocates to the nucleus to repress selected genes.

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. nucleus Source: ParkinsonsUK-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi458 – 4581C → A: No effect. 1 Publication
Mutagenesisi471 – 4711H → A: No effect. 1 Publication
Mutagenesisi518 – 5181C → A: No effect. 1 Publication
Mutagenesisi528 – 5281H → A: No effect. 1 Publication
Mutagenesisi543 – 5431C → A: No effect. 1 Publication
Mutagenesisi560 – 5601H → A: No effect. 1 Publication
Mutagenesisi571 – 5711C → A: Impairs DNA-binding and ability to repress PGC-1-alpha (PPARGC1A). 1 Publication
Mutagenesisi584 – 5841H → A: No effect. 1 Publication

Organism-specific databases

PharmGKBiPA144596520.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 644644Zinc finger protein 746PRO_0000253728Add
BLAST

Post-translational modificationi

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.1 Publication

Keywords - PTMi

Ubl conjugation

Proteomic databases

MaxQBiQ6NUN9.
PaxDbiQ6NUN9.
PRIDEiQ6NUN9.

PTM databases

PhosphoSiteiQ6NUN9.

Expressioni

Gene expression databases

BgeeiQ6NUN9.
CleanExiHS_ZNF746.
ExpressionAtlasiQ6NUN9. baseline and differential.
GenevestigatoriQ6NUN9.

Organism-specific databases

HPAiHPA020272.

Interactioni

Subunit structurei

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

Binary interactionsi

WithEntry#Exp.IntActNotes
PARK2O602606EBI-3862525,EBI-716346

Protein-protein interaction databases

BioGridi127574. 16 interactions.
IntActiQ6NUN9. 13 interactions.
MINTiMINT-8247451.
STRINGi9606.ENSP00000345140.

Structurei

3D structure databases

ProteinModelPortaliQ6NUN9.
SMRiQ6NUN9. Positions 367-590.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini96 – 16772KRABPROSITE-ProRule annotationAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili16 – 9277Sequence AnalysisAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi476 – 51641Gly-richAdd
BLAST

Sequence similaritiesi

Contains 4 C2H2-type zinc fingers.PROSITE-ProRule annotation
Contains 1 KRAB domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri453 – 47826C2H2-type 1; degeneratePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri510 – 53223C2H2-type 2PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri538 – 56023C2H2-type 3PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri566 – 58823C2H2-type 4PROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Coiled coil, Repeat, Zinc-finger

Phylogenomic databases

eggNOGiCOG5048.
GeneTreeiENSGT00530000063032.
HOGENOMiHOG000013125.
HOVERGENiHBG062119.
InParanoidiQ6NUN9.
KOiK09228.
OMAiNPRTGPE.
OrthoDBiEOG73JKWC.
PhylomeDBiQ6NUN9.
TreeFamiTF337777.

Family and domain databases

Gene3Di3.30.160.60. 4 hits.
InterProiIPR022137. DUF3669_Znf.
IPR001909. Krueppel-associated_box.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PfamiPF12417. DUF3669. 1 hit.
PF01352. KRAB. 1 hit.
PF00096. zf-C2H2. 2 hits.
[Graphical view]
SMARTiSM00349. KRAB. 1 hit.
SM00355. ZnF_C2H2. 4 hits.
[Graphical view]
SUPFAMiSSF109640. SSF109640. 1 hit.
PROSITEiPS50805. KRAB. 1 hit.
PS00028. ZINC_FINGER_C2H2_1. 3 hits.
PS50157. ZINC_FINGER_C2H2_2. 4 hits.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q6NUN9-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAEAVAAPIS PWTMAATIQA MERKIESQAA RLLSLEGRTG MAEKKLADCE
60 70 80 90 100
KTAVEFGNQL EGKWAVLGTL LQEYGLLQRR LENVENLLRN RNFWILRLPP
110 120 130 140 150
GSKGESPKEW GKLEDWQKEL YKHVMRGNYE TLVSLDYAIS KPEVLSQIEQ
160 170 180 190 200
GKEPCNWRRP GPKIPDVPVD PSPGSGPPVP APDLLMQIKQ EGELQLQEQQ
210 220 230 240 250
ALGVEAWAAG QPDIGEEPWG LSQLDSGAGD ISTDATSGVH SNFSTTIPPT
260 270 280 290 300
SWQTDLPPHH PSSACSDGTL KLNTAASTED VKIVIKTEVQ EEEVVATPVH
310 320 330 340 350
PTDLEAHGTL FGPGQATRFF PSPAQEGAWE SQGSSFPSQD PVLGLREPAR
360 370 380 390 400
PERDMGELSP AVAQEETPPG DWLFGGVRWG WNFRCKPPVG LNPRTGPEGL
410 420 430 440 450
PYSSPDNGEA ILDPSQAPRP FNEPCKYPGR TKGFGHKPGL KKHPAAPPGG
460 470 480 490 500
RPFTCATCGK SFQLQVSLSA HQRSCGAPDG SGPGTGGGGS GSGGGGGGSG
510 520 530 540 550
GGSARDGSAL RCGECGRCFT RPAHLIRHRM LHTGERPFPC TECEKRFTER
560 570 580 590 600
SKLIDHYRTH TGVRPFTCTV CGKSFIRKDH LRKHQRNHAA GAKTPARGQP
610 620 630 640
LPTPPAPPDP FKSPASKGPL ASTDLVTDWT CGLSVLGPTD GGDM
Length:644
Mass (Da):69,136
Last modified:July 5, 2004 - v1
Checksum:i4F6723D2225D95AB
GO
Isoform 2 (identifier: Q6NUN9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     279-279: E → EA

Note: No experimental confirmation available.

Show »
Length:645
Mass (Da):69,207
Checksum:i0272268BB5F4112C
GO
Isoform 3 (identifier: Q6NUN9-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-185: Missing.

Note: No experimental confirmation available.

Show »
Length:459
Mass (Da):48,454
Checksum:iAFB17AD468480D23
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 185185Missing in isoform 3. 1 PublicationVSP_041052Add
BLAST
Alternative sequencei279 – 2791E → EA in isoform 2. 1 PublicationVSP_041053

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK128244 mRNA. Translation: BAC87351.1.
AK291814 mRNA. Translation: BAF84503.1.
AC073314 Genomic DNA. No translation available.
BC068505 mRNA. Translation: AAH68505.1.
CCDSiCCDS55180.1. [Q6NUN9-2]
CCDS5897.1. [Q6NUN9-1]
RefSeqiNP_001156946.1. NM_001163474.1. [Q6NUN9-2]
NP_689770.3. NM_152557.4. [Q6NUN9-1]
UniGeneiHs.24643.

Genome annotation databases

EnsembliENST00000340622; ENSP00000345140; ENSG00000181220. [Q6NUN9-1]
ENST00000458143; ENSP00000395007; ENSG00000181220. [Q6NUN9-2]
GeneIDi155061.
KEGGihsa:155061.
UCSCiuc003wfw.2. human. [Q6NUN9-1]
uc010lpi.2. human. [Q6NUN9-2]

Polymorphism databases

DMDMi74736828.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK128244 mRNA. Translation: BAC87351.1.
AK291814 mRNA. Translation: BAF84503.1.
AC073314 Genomic DNA. No translation available.
BC068505 mRNA. Translation: AAH68505.1.
CCDSiCCDS55180.1. [Q6NUN9-2]
CCDS5897.1. [Q6NUN9-1]
RefSeqiNP_001156946.1. NM_001163474.1. [Q6NUN9-2]
NP_689770.3. NM_152557.4. [Q6NUN9-1]
UniGeneiHs.24643.

3D structure databases

ProteinModelPortaliQ6NUN9.
SMRiQ6NUN9. Positions 367-590.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi127574. 16 interactions.
IntActiQ6NUN9. 13 interactions.
MINTiMINT-8247451.
STRINGi9606.ENSP00000345140.

PTM databases

PhosphoSiteiQ6NUN9.

Polymorphism databases

DMDMi74736828.

Proteomic databases

MaxQBiQ6NUN9.
PaxDbiQ6NUN9.
PRIDEiQ6NUN9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000340622; ENSP00000345140; ENSG00000181220. [Q6NUN9-1]
ENST00000458143; ENSP00000395007; ENSG00000181220. [Q6NUN9-2]
GeneIDi155061.
KEGGihsa:155061.
UCSCiuc003wfw.2. human. [Q6NUN9-1]
uc010lpi.2. human. [Q6NUN9-2]

Organism-specific databases

CTDi155061.
GeneCardsiGC07M149169.
HGNCiHGNC:21948. ZNF746.
HPAiHPA020272.
MIMi613914. gene.
neXtProtiNX_Q6NUN9.
PharmGKBiPA144596520.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG5048.
GeneTreeiENSGT00530000063032.
HOGENOMiHOG000013125.
HOVERGENiHBG062119.
InParanoidiQ6NUN9.
KOiK09228.
OMAiNPRTGPE.
OrthoDBiEOG73JKWC.
PhylomeDBiQ6NUN9.
TreeFamiTF337777.

Enzyme and pathway databases

ReactomeiREACT_12627. Generic Transcription Pathway.

Miscellaneous databases

ChiTaRSiZNF746. human.
GenomeRNAii155061.
NextBioi87371.
PROiQ6NUN9.
SOURCEiSearch...

Gene expression databases

BgeeiQ6NUN9.
CleanExiHS_ZNF746.
ExpressionAtlasiQ6NUN9. baseline and differential.
GenevestigatoriQ6NUN9.

Family and domain databases

Gene3Di3.30.160.60. 4 hits.
InterProiIPR022137. DUF3669_Znf.
IPR001909. Krueppel-associated_box.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PfamiPF12417. DUF3669. 1 hit.
PF01352. KRAB. 1 hit.
PF00096. zf-C2H2. 2 hits.
[Graphical view]
SMARTiSM00349. KRAB. 1 hit.
SM00355. ZnF_C2H2. 4 hits.
[Graphical view]
SUPFAMiSSF109640. SSF109640. 1 hit.
PROSITEiPS50805. KRAB. 1 hit.
PS00028. ZINC_FINGER_C2H2_1. 3 hits.
PS50157. ZINC_FINGER_C2H2_2. 4 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.

Entry informationi

Entry nameiZN746_HUMAN
AccessioniPrimary (citable) accession number: Q6NUN9
Secondary accession number(s): A8K6Z9, Q6ZRF9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 17, 2006
Last sequence update: July 5, 2004
Last modified: February 4, 2015
This is version 98 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

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.1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.