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Q6NUN9

- ZN746_HUMAN

UniProt

Q6NUN9 - ZN746_HUMAN

Protein

Zinc finger protein 746

Gene

ZNF746

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 94 (01 Oct 2014)
      Sequence version 1 (05 Jul 2004)
      Previous versions | rss
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    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. protein binding Source: IntAct
    3. sequence-specific DNA binding transcription factor activity Source: ParkinsonsUK-UCL
    4. transcription regulatory region DNA binding Source: UniProtKB
    5. 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. neuron death Source: UniProtKB
    4. positive regulation of transcription from RNA polymerase II promoter Source: ParkinsonsUK-UCL
    5. regulation of cell death Source: UniProtKB
    6. transcription, DNA-templated Source: UniProtKB-KW

    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: UniProtKB-SubCell

    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

    ArrayExpressiQ6NUN9.
    BgeeiQ6NUN9.
    CleanExiHS_ZNF746.
    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. 15 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.
    HOGENOMiHOG000013125.
    HOVERGENiHBG062119.
    InParanoidiQ6NUN9.
    KOiK09228.
    OMAiFRCKPPV.
    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. Align

    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

    MAEAVAAPIS PWTMAATIQA MERKIESQAA RLLSLEGRTG MAEKKLADCE    50
    KTAVEFGNQL EGKWAVLGTL LQEYGLLQRR LENVENLLRN RNFWILRLPP 100
    GSKGESPKEW GKLEDWQKEL YKHVMRGNYE TLVSLDYAIS KPEVLSQIEQ 150
    GKEPCNWRRP GPKIPDVPVD PSPGSGPPVP APDLLMQIKQ EGELQLQEQQ 200
    ALGVEAWAAG QPDIGEEPWG LSQLDSGAGD ISTDATSGVH SNFSTTIPPT 250
    SWQTDLPPHH PSSACSDGTL KLNTAASTED VKIVIKTEVQ EEEVVATPVH 300
    PTDLEAHGTL FGPGQATRFF PSPAQEGAWE SQGSSFPSQD PVLGLREPAR 350
    PERDMGELSP AVAQEETPPG DWLFGGVRWG WNFRCKPPVG LNPRTGPEGL 400
    PYSSPDNGEA ILDPSQAPRP FNEPCKYPGR TKGFGHKPGL KKHPAAPPGG 450
    RPFTCATCGK SFQLQVSLSA HQRSCGAPDG SGPGTGGGGS GSGGGGGGSG 500
    GGSARDGSAL RCGECGRCFT RPAHLIRHRM LHTGERPFPC TECEKRFTER 550
    SKLIDHYRTH TGVRPFTCTV CGKSFIRKDH LRKHQRNHAA GAKTPARGQP 600
    LPTPPAPPDP FKSPASKGPL ASTDLVTDWT CGLSVLGPTD GGDM 644
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AK128244 mRNA. Translation: BAC87351.1 .
    AK291814 mRNA. Translation: BAF84503.1 .
    AC073314 Genomic DNA. No translation available.
    BC068505 mRNA. Translation: AAH68505.1 .
    CCDSi CCDS55180.1. [Q6NUN9-2 ]
    CCDS5897.1. [Q6NUN9-1 ]
    RefSeqi NP_001156946.1. NM_001163474.1. [Q6NUN9-2 ]
    NP_689770.3. NM_152557.4. [Q6NUN9-1 ]
    UniGenei Hs.24643.

    3D structure databases

    ProteinModelPortali Q6NUN9.
    SMRi Q6NUN9. Positions 367-590.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 127574. 15 interactions.
    IntActi Q6NUN9. 13 interactions.
    MINTi MINT-8247451.
    STRINGi 9606.ENSP00000345140.

    PTM databases

    PhosphoSitei Q6NUN9.

    Polymorphism databases

    DMDMi 74736828.

    Proteomic databases

    MaxQBi Q6NUN9.
    PaxDbi Q6NUN9.
    PRIDEi Q6NUN9.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000340622 ; ENSP00000345140 ; ENSG00000181220 . [Q6NUN9-1 ]
    ENST00000458143 ; ENSP00000395007 ; ENSG00000181220 . [Q6NUN9-2 ]
    GeneIDi 155061.
    KEGGi hsa:155061.
    UCSCi uc003wfw.2. human. [Q6NUN9-1 ]
    uc010lpi.2. human. [Q6NUN9-2 ]

    Organism-specific databases

    CTDi 155061.
    GeneCardsi GC07M149169.
    HGNCi HGNC:21948. ZNF746.
    HPAi HPA020272.
    MIMi 613914. gene.
    neXtProti NX_Q6NUN9.
    PharmGKBi PA144596520.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG5048.
    HOGENOMi HOG000013125.
    HOVERGENi HBG062119.
    InParanoidi Q6NUN9.
    KOi K09228.
    OMAi FRCKPPV.
    OrthoDBi EOG73JKWC.
    PhylomeDBi Q6NUN9.
    TreeFami TF337777.

    Enzyme and pathway databases

    Reactomei REACT_12627. Generic Transcription Pathway.

    Miscellaneous databases

    GenomeRNAii 155061.
    NextBioi 87371.
    PROi Q6NUN9.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q6NUN9.
    Bgeei Q6NUN9.
    CleanExi HS_ZNF746.
    Genevestigatori Q6NUN9.

    Family and domain databases

    Gene3Di 3.30.160.60. 4 hits.
    InterProi IPR022137. DUF3669_Znf.
    IPR001909. Krueppel-associated_box.
    IPR007087. Znf_C2H2.
    IPR015880. Znf_C2H2-like.
    IPR013087. Znf_C2H2/integrase_DNA-bd.
    [Graphical view ]
    Pfami PF12417. DUF3669. 1 hit.
    PF01352. KRAB. 1 hit.
    PF00096. zf-C2H2. 2 hits.
    [Graphical view ]
    SMARTi SM00349. KRAB. 1 hit.
    SM00355. ZnF_C2H2. 4 hits.
    [Graphical view ]
    SUPFAMi SSF109640. SSF109640. 1 hit.
    PROSITEi PS50805. KRAB. 1 hit.
    PS00028. ZINC_FINGER_C2H2_1. 3 hits.
    PS50157. ZINC_FINGER_C2H2_2. 4 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 94 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