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    HYPK huntingtin interacting protein K [ Homo sapiens (human) ]

    Gene ID: 25764, updated on 6-May-2024

    Summary

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    Official Symbol
    HYPKprovided by HGNC
    Official Full Name
    huntingtin interacting protein Kprovided by HGNC
    Primary source
    HGNC:HGNC:18418
    See related
    Ensembl:ENSG00000242028 MIM:612784; AllianceGenome:HGNC:18418
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    HSPC136; C15orf63
    Summary
    Enables protein N-terminus binding activity. Involved in negative regulation of apoptotic process and protein stabilization. Located in cytoplasm; microtubule cytoskeleton; and nucleoplasm. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]
    Expression
    Ubiquitous expression in fat (RPKM 18.1), prostate (RPKM 18.1) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    15q15.3
    Exon count:
    4
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (43800421..43804427)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (41607784..41611789)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (44092619..44096625)

    Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene small EDRK-rich factor 2 Neighboring gene SERF2-C15orf63 readthrough Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:44085666-44086519 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:44087241-44087742 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:44087743-44088242 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:44091515-44092215 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:44092216-44092916 Neighboring gene microRNA 1282 Neighboring gene serine incorporator 4 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9329 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9330 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr15:44104820-44106019 Neighboring gene microfibril associated protein 1 Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:44116704-44117335 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6390 Neighboring gene WD repeat domain 76

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Molecular basis for N-terminal acetylation by human NatE and its modulation by HYPK. Deng S, et al. Nat Commun, 2020 Feb 10. PMID 32042062, Free PMC Article
    2. An IRES-dependent translation of HYPK mRNA generates a truncated isoform of the protein that lacks the nuclear localization and functional ability. Ghosh DK, et al. RNA Biol, 2019 Nov. PMID 31397627, Free PMC Article
    3. Metastable states of HYPK-UBA domain's seeds drive the dynamics of its own aggregation. Ghosh DK, et al. Biochim Biophys Acta Gen Subj, 2018 Dec. PMID 30251673
    4. Disordered Nanostructure in Huntingtin Interacting Protein K Acts as a Stabilizing Switch To Prevent Protein Aggregation. Ghosh DK, et al. Biochemistry, 2018 Apr 3. PMID 29381348
    5. Conserved C-terminal nascent peptide binding domain of HYPK facilitates its chaperone-like activity. Raychaudhuri S, et al. J Biosci, 2014 Sep. PMID 25116620

    See all (43) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. HYPK: A marginally disordered protein sensitive to charge decoration.
      Title: HYPK: A marginally disordered protein sensitive to charge decoration.
    2. HYPK coordinates degradation of polyneddylated proteins by autophagy.
      Title: HYPK coordinates degradation of polyneddylated proteins by autophagy.
    3. Phosphorylation of Arl4A/D promotes their binding by the HYPK chaperone for their stable recruitment to the plasma membrane.
      Title: Phosphorylation of Arl4A/D promotes their binding by the HYPK chaperone for their stable recruitment to the plasma membrane.
    4. Huntingtin interacting protein K (HYPK) forms a tetrameric complex with the human N-terminal acetyltransferase E (NatE). HYPK exhibits negative cooperative binding to NAA15 auxiliary subunit by inducing NAA15 shifts in opposing directions. HYPK inhibits NAA10 and NAA50 catalytic activities through structural alteration of the NAA10 and the NatE substrate-binding sites, respectively.
      Title: Molecular basis for N-terminal acetylation by human NatE and its modulation by HYPK.
    5. Results find the novel mode of internal ribosome entry site (IRES)-dependent translation initiation of HYPK mRNA, along with the determination of mechanism of the nuclear localization process of HYPK.
      Title: An IRES-dependent translation of HYPK mRNA generates a truncated isoform of the protein that lacks the nuclear localization and functional ability.
    6. this studu identified the metastable states in the seeds of the Ubiquitin associated (UBA) domain of Huntingtin Interacting Protein K (HYPK).
      Title: Metastable states of HYPK-UBA domain's seeds drive the dynamics of its own aggregation.
    7. Results find that HYPK harbors intrinsic hNatA-specific inhibitory activity through a bipartite structure: a ubiquitin-associated domain that binds a hNaa15 metazoan-specific region and an N-terminal loop-helix region that distorts the hNaa10 active site.
      Title: Structure of Human NatA and Its Regulation by the Huntingtin Interacting Protein HYPK.
    8. In combination with acetylation assays, the HypK N-terminal region is identified as a negative regulator of the NatA acetylation activity
      Title: Structural basis of HypK regulating N-terminal acetylation by the NatA complex.
    9. study provides evidence of the existence of disordered nanostructure in HYPK protein that mechanistically plays a decisive role in preventing both self and non-self protein aggregation.
      Title: Disordered Nanostructure in Huntingtin Interacting Protein K Acts as a Stabilizing Switch To Prevent Protein Aggregation.
    10. HYPK can act as negative regulator of heat shock response by repressing transcriptional activity of HSF1.
      Title: Huntingtin interacting protein HYPK is a negative regulator of heat shock response and is downregulated in models of Huntington's Disease.
    Submit: New GeneRIF Correction See all GeneRIFs (17)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein folding chaperone EXP
    Inferred from Experiment
    more info
    		 PubMed 
    enables protein folding chaperone IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in negative regulation of apoptotic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of apoptotic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein folding IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein stabilization IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein stabilization IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in microtubule cytoskeleton IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of protein-containing complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    huntingtin-interacting protein K
    Names
    huntingtin yeast partner K

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001199885.1 → NP_001186814.1  huntingtin-interacting protein K isoform 2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) lacks an alternate exon resulting in a frameshift in the 3' coding region, compared to variant 1. The encoded isoform (2) has a distinct and shorter C-terminus, compared to isoform 1.
      Source sequence(s)
      AC018512, BC019262, BQ478474, BQ772100
      UniProtKB/TrEMBL
      J3QT56

    2. NM_016400.4 → NP_057484.4  huntingtin-interacting protein K isoform 1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AC018512
      Consensus CDS
      CCDS10104.2
      UniProtKB/Swiss-Prot
      C9JKJ0, O75408, Q8WUW8, Q9NX55, Q9P024
      Related
      ENSP00000401155.3, ENST00000442995.4
      Conserved Domains (1) summary
      cd14361
      Location:80 → 120
      UBA_HYPK; UBA-like domain found in Huntingtin-interacting protein K (HYPK) and similar proteins

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000015.10 Reference GRCh38.p14 Primary Assembly

      Range
      43800421..43804427
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060939.1 Alternate T2T-CHM13v2.0

      Range
      41607784..41611789
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9NX55.3 GenPept UniProtKB/Swiss-Prot:Q9NX55

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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