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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

Miscellaneous

May act as a downstream effector of PRKN and contribute to neurodegeneration in Parkinson disease cases caused by defects in PRKN: its accumulation due to the absence of PRKN, followed by up-regulation of PPARGC1A, could lead to the selective loss of dopamine neurons in the substantia nigra.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri453 – 478C2H2-type 1; degeneratePROSITE-ProRule annotationAdd BLAST26
Zinc fingeri510 – 532C2H2-type 2PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri538 – 560C2H2-type 3PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri566 – 588C2H2-type 4PROSITE-ProRule annotationAdd BLAST23

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
  • transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: NTNU_SB
  • transcription factor activity, sequence-specific DNA binding Source: ParkinsonsUK-UCL
  • transcription regulatory region DNA binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: ParkinsonsUK-UCL
  • positive regulation of neuron death Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: ParkinsonsUK-UCL
  • transcription, DNA-templated Source: UniProtKB-KW

Keywordsi

Molecular functionDNA-binding, Repressor
Biological processTranscription, Transcription regulation
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-212436. 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
Proteomesi
  • UP000005640 Componenti: 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

  • cytoplasm Source: UniProtKB
  • nucleus Source: ParkinsonsUK-UCL

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi458C → A: No effect. 1 Publication1
Mutagenesisi471H → A: No effect. 1 Publication1
Mutagenesisi518C → A: No effect. 1 Publication1
Mutagenesisi528H → A: No effect. 1 Publication1
Mutagenesisi543C → A: No effect. 1 Publication1
Mutagenesisi560H → A: No effect. 1 Publication1
Mutagenesisi571C → A: Impairs DNA-binding and ability to repress PGC-1-alpha (PPARGC1A). 1 Publication1
Mutagenesisi584H → A: No effect. 1 Publication1

Organism-specific databases

OpenTargetsiENSG00000181220.
PharmGKBiPA144596520.

Polymorphism and mutation databases

BioMutaiZNF746.
DMDMi74736828.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002537281 – 644Zinc finger protein 746Add BLAST644

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki282Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki286Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

Post-translational modificationi

Ubiquitinated by PRKN. 'Lys-48'-linked polyubiquitination by PRKN leads to degradation by the proteasome and may play a key role in regulation of neuron death.1 Publication

Keywords - PTMi

Isopeptide bond, Ubl conjugation

Proteomic databases

EPDiQ6NUN9.
MaxQBiQ6NUN9.
PaxDbiQ6NUN9.
PeptideAtlasiQ6NUN9.
PRIDEiQ6NUN9.

PTM databases

iPTMnetiQ6NUN9.
PhosphoSitePlusiQ6NUN9.

Expressioni

Gene expression databases

BgeeiENSG00000181220.
CleanExiHS_ZNF746.
ExpressionAtlasiQ6NUN9. baseline and differential.
GenevisibleiQ6NUN9. HS.

Organism-specific databases

HPAiHPA020272.

Interactioni

Subunit structurei

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

Binary interactionsi

WithEntry#Exp.IntActNotes
PRKNO602606EBI-3862525,EBI-716346

GO - Molecular functioni

  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi127574. 290 interactors.
IntActiQ6NUN9. 13 interactors.
MINTiMINT-8247451.
STRINGi9606.ENSP00000395007.

Structurei

3D structure databases

ProteinModelPortaliQ6NUN9.
SMRiQ6NUN9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini96 – 167KRABPROSITE-ProRule annotationAdd BLAST72

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili16 – 92Sequence analysisAdd BLAST77

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi476 – 516Gly-richAdd BLAST41

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri453 – 478C2H2-type 1; degeneratePROSITE-ProRule annotationAdd BLAST26
Zinc fingeri510 – 532C2H2-type 2PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri538 – 560C2H2-type 3PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri566 – 588C2H2-type 4PROSITE-ProRule annotationAdd BLAST23

Keywords - Domaini

Coiled coil, Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1721. Eukaryota.
ENOG41112U5. LUCA.
GeneTreeiENSGT00530000063032.
HOGENOMiHOG000013125.
HOVERGENiHBG062119.
InParanoidiQ6NUN9.
KOiK09228.
OMAiKYPGRTK.
OrthoDBiEOG091G0P6J.
PhylomeDBiQ6NUN9.
TreeFamiTF337777.

Family and domain databases

CDDicd07765. KRAB_A-box. 1 hit.
Gene3Di3.30.40.10. 1 hit.
InterProiView protein in InterPro
IPR022137. DUF3669_Znf.
IPR001909. KRAB.
IPR013087. Znf_C2H2_type.
IPR013083. Znf_RING/FYVE/PHD.
PfamiView protein in Pfam
PF12417. DUF3669. 1 hit.
PF01352. KRAB. 1 hit.
SMARTiView protein in SMART
SM00349. KRAB. 1 hit.
SM00355. ZnF_C2H2. 4 hits.
SUPFAMiSSF109640. SSF109640. 1 hit.
SSF57667. SSF57667. 3 hits.
PROSITEiView protein in PROSITE
PS50805. KRAB. 1 hit.
PS00028. ZINC_FINGER_C2H2_1. 3 hits.
PS50157. ZINC_FINGER_C2H2_2. 4 hits.

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)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0410521 – 185Missing in isoform 3. 1 PublicationAdd BLAST185
Alternative sequenceiVSP_041053279E → EA in isoform 2. 1 Publication1

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.3. human. [Q6NUN9-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiZN746_HUMAN
AccessioniPrimary (citable) accession number: Q6NUN9
Secondary accession number(s): A8K6Z9, Q6ZRF9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 17, 2006
Last sequence update: July 5, 2004
Last modified: August 30, 2017
This is version 120 of the entry and version 1 of the sequence. See 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

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