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    HACE1 HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 [ Homo sapiens (human) ]

    Gene ID: 57531, updated on 2-Nov-2024

    Summary

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    Official Symbol
    HACE1provided by HGNC
    Official Full Name
    HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1provided by HGNC
    Primary source
    HGNC:HGNC:21033
    See related
    Ensembl:ENSG00000085382 MIM:610876; AllianceGenome:HGNC:21033
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    SPPRS
    Summary
    This gene encodes a HECT domain and ankyrin repeat-containing ubiquitin ligase. The encoded protein is involved in specific tagging of target proteins, leading to their subcellular localization or proteasomal degradation. The protein is a potential tumor suppressor and is involved in the pathophysiology of several tumors, including Wilm's tumor. [provided by RefSeq, Mar 2016]
    Expression
    Broad expression in placenta (RPKM 13.5), testis (RPKM 6.0) and 22 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See HACE1 in Genome Data Viewer
    Location:
    6q16.3
    Exon count:
    27
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (104728094..104859919, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (105904367..106035941, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (105175969..105307794, complement)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC102724443 Neighboring gene Sharpr-MPRA regulatory region 11207 Neighboring gene uncharacterized LOC105377918 Neighboring gene MPRA-validated peak5987 silencer Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:104919911-104920484 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:104937517-104938123 Neighboring gene VISTA enhancer hs1452 Neighboring gene Sharpr-MPRA regulatory region 1651 Neighboring gene MPRA-validated peak5988 silencer Neighboring gene RNA, U6 small nuclear 897, pseudogene Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:105307475-105307974 Neighboring gene poly(A) binding protein cytoplasmic 4 pseudogene Neighboring gene MPRA-validated peak5989 silencer Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:105384704-105385204 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:105385205-105385705 Neighboring gene LIN28B antisense RNA 1 Neighboring gene lin-28 homolog B

    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 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. Lack of evidence that HACE1 is not a tumor suppressor gene in NKTCL: to the editor-in-chief. Authors' reply. Schmitt C, et al. Am J Pathol, 2015 Apr. PMID 25794711
    2. HACE1 is a potential tumor suppressor in osteosarcoma. El-Naggar AM, et al. Cell Death Dis, 2019 Jan 8. PMID 30622235, Free PMC Article
    3. Overexpression of HACE1 in gastric cancer inhibits tumor aggressiveness by impeding cell proliferation and migration. Chen YL, et al. Cancer Med, 2018 Jun. PMID 29673126, Free PMC Article
    4. Uncovering and deciphering the pro-invasive role of HACE1 in melanoma cells. El-Hachem N, et al. Cell Death Differ, 2018 Nov. PMID 29515254, Free PMC Article
    5. Association Between HACE1 Gene Polymorphisms and Wilms' Tumor Risk in a Chinese Population. Jia W, et al. Cancer Invest, 2017 Nov 26. PMID 29243987

    See all (78) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. A Missense Variant in HACE1 Is Associated with Intellectual Disability, Epilepsy, Spasticity, and Psychomotor Impairment in a Pakistani Kindred.
      Title: A Missense Variant in HACE1 Is Associated with Intellectual Disability, Epilepsy, Spasticity, and Psychomotor Impairment in a Pakistani Kindred.
    2. Emerging role and mechanism of HACE1 in the pathogenesis of neurodegenerative diseases: A promising target.
      Title: Emerging role and mechanism of HACE1 in the pathogenesis of neurodegenerative diseases: A promising target.
    3. HACE1 expression in heart failure patients might promote mitochondrial oxidative stress and ferroptosis by targeting NRF2.
      Title: HACE1 expression in heart failure patients might promote mitochondrial oxidative stress and ferroptosis by targeting NRF2.
    4. Structural Basis for the Enzymatic Activity of the HACE1 HECT-Type E3 Ligase Through N-Terminal Helix Dimerization.
      Title: Structural Basis for the Enzymatic Activity of the HACE1 HECT-Type E3 Ligase Through N-Terminal Helix Dimerization.
    5. HACE1-mediated NRF2 activation causes enhanced malignant phenotypes and decreased radiosensitivity of glioma cells.
      Title: HACE1-mediated NRF2 activation causes enhanced malignant phenotypes and decreased radiosensitivity of glioma cells.
    6. HACE1 negatively regulates neuroinflammation through ubiquitylating and degrading Rac1 in Parkinson's disease models.
      Title: HACE1 negatively regulates neuroinflammation through ubiquitylating and degrading Rac1 in Parkinson's disease models.
    7. HACE1 blocks HIF1alpha accumulation under hypoxia in a RAC1 dependent manner.
      Title: HACE1 blocks HIF1α accumulation under hypoxia in a RAC1 dependent manner.
    8. Correlations of HACE1 expression with pathological stages, CT features and prognosis of hepatocellular carcinoma patients.
      Title: Correlations of HACE1 expression with pathological stages, CT features and prognosis of hepatocellular carcinoma patients.
    9. meQTL and ncRNA functional analyses of 102 GWAS-SNPs associated with depression implicate HACE1 and SHANK2 genes.
      Title: meQTL and ncRNA functional analyses of 102 GWAS-SNPs associated with depression implicate HACE1 and SHANK2 genes.
    10. Ubiquitin-independent proteasomal degradation of Spindlin-1 by the E3 ligase HACE1 contributes to cell-cell adhesion.
      Title: Ubiquitin-independent proteasomal degradation of Spindlin-1 by the E3 ligase HACE1 contributes to cell-cell adhesion.
    Submit: New GeneRIF Correction See all GeneRIFs (43)

    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

    Associated conditions

    Description Tests
    Spastic paraplegia-severe developmental delay-epilepsy syndrome
    MedGen: C4225215 OMIM: 616756 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    A genome-wide association for kidney function and endocrine-related traits in the NHLBI's Framingham Heart Study.
    EBI GWAS Catalog
    A genome-wide association study of brain lesion distribution in multiple sclerosis.
    EBI GWAS Catalog
    Common variation at 6q16 within HACE1 and LIN28B influences susceptibility to neuroblastoma.
    EBI GWAS Catalog
    Genome-wide association study identifies sequence variants on 6q21 associated with age at menarche.
    EBI GWAS Catalog
    Genome-wide association study of obsessive-compulsive disorder.
    EBI GWAS Catalog
    Many sequence variants affecting diversity of adult human height.
    EBI GWAS Catalog

    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

    Clone Names

    • FLJ42274

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables small GTPase binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables small GTPase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables ubiquitin protein ligase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables ubiquitin-protein transferase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in Golgi organization IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in Golgi organization IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in Rac protein signal transduction TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in membrane fusion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in membrane fusion IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in protein K48-linked ubiquitination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein ubiquitination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of cell migration IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in ubiquitin-dependent protein catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in ubiquitin-dependent protein catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in Golgi cisterna membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in Golgi membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in Golgi membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in endoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nuclear body IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    E3 ubiquitin-protein ligase HACE1
    Names
    HECT-type E3 ubiquitin transferase HACE1
    NP_001308009.1
    NP_001308012.1
    NP_001308013.1
    NP_001337483.1
    NP_001337484.1
    NP_001337485.1
    NP_001337486.1
    NP_001337487.1
    NP_001337488.1
    NP_001337489.1
    NP_065822.2

    NCBI Reference Sequences (RefSeq)

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    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.

    Genomic

    1. NG_046782.1 RefSeqGene

      Range
      5001..136826
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001321080.2 → NP_001308009.1  E3 ubiquitin-protein ligase HACE1 isoform b

      Status: REVIEWED

      Source sequence(s)
      AK131207, AL513472, AL590402, BC034982
      UniProtKB/Swiss-Prot
      Q8IYU2
      Conserved Domains (4) summary
      cd00078
      Location:510 → 859
      HECTc; HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ...
      sd00045
      Location:66 → 95
      ANK; ANK repeat [structural motif]
      pfam12796
      Location:69 → 179
      Ank_2; Ankyrin repeats (3 copies)
      cl39094
      Location:157 → 207
      Ank_2; Ankyrin repeats (3 copies)

    2. NM_001321083.2 → NP_001308012.1  E3 ubiquitin-protein ligase HACE1 isoform c

      Status: REVIEWED

      Source sequence(s)
      AL513472, AL590402, BC034982, CN288032, DB094058
      UniProtKB/Swiss-Prot
      Q8IYU2
      Conserved Domains (5) summary
      cd00078
      Location:520 → 869
      HECTc; HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ...
      cd00204
      Location:58 → 183
      ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...
      sd00045
      Location:63 → 94
      ANK; ANK repeat [structural motif]
      pfam12796
      Location:4 → 92
      Ank_2; Ankyrin repeats (3 copies)
      pfam13637
      Location:165 → 215
      Ank_4; Ankyrin repeats (many copies)

    3. NM_001321084.2 → NP_001308013.1  E3 ubiquitin-protein ligase HACE1 isoform d

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5), as well as variants 9 and 10, encodes isoform d.
      Source sequence(s)
      AL513472, AL590402, BC034982, DB094058
      UniProtKB/Swiss-Prot
      Q8IYU2
      Conserved Domains (2) summary
      cd00078
      Location:386 → 735
      HECTc; HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ...
      cl39094
      Location:38 → 83
      Ank_2; Ankyrin repeats (3 copies)

    4. NM_001350554.2 → NP_001337483.1  E3 ubiquitin-protein ligase HACE1 isoform e

      Status: REVIEWED

      Source sequence(s)
      AL357315, AL513472, AL590402
      Conserved Domains (4) summary
      cd00078
      Location:476 → 825
      HECTc; HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ...
      sd00045
      Location:32 → 61
      ANK; ANK repeat [structural motif]
      pfam12796
      Location:35 → 145
      Ank_2; Ankyrin repeats (3 copies)
      cl39094
      Location:123 → 173
      Ank_2; Ankyrin repeats (3 copies)

    5. NM_001350555.2 → NP_001337484.1  E3 ubiquitin-protein ligase HACE1 isoform f

      Status: REVIEWED

      Source sequence(s)
      AL357315, AL513472, AL590402
      Conserved Domains (3) summary
      cd00078
      Location:457 → 806
      HECTc; HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ...
      cd00204
      Location:25 → 152
      ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...
      sd00045
      Location:66 → 95
      ANK; ANK repeat [structural motif]

    6. NM_001350556.2 → NP_001337485.1  E3 ubiquitin-protein ligase HACE1 isoform g

      Status: REVIEWED

      Source sequence(s)
      AL357315, AL513472, AL590402
      Conserved Domains (3) summary
      cd00078
      Location:392 → 741
      HECTc; HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ...
      sd00045
      Location:1 → 32
      ANK; ANK repeat [structural motif]
      pfam12796
      Location:6 → 89
      Ank_2; Ankyrin repeats (3 copies)

    7. NM_001350557.2 → NP_001337486.1  E3 ubiquitin-protein ligase HACE1 isoform d

      Status: REVIEWED

      Description
      Transcript Variant: This variant (9), as well as variants 5 and 10, encodes isoform d.
      Source sequence(s)
      AL357315, AL513472, AL590402
      Conserved Domains (2) summary
      cd00078
      Location:386 → 735
      HECTc; HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ...
      cl39094
      Location:38 → 83
      Ank_2; Ankyrin repeats (3 copies)

    8. NM_001350558.2 → NP_001337487.1  E3 ubiquitin-protein ligase HACE1 isoform d

      Status: REVIEWED

      Description
      Transcript Variant: This variant (10), as well as variants 5 and 9, encodes isoform d.
      Source sequence(s)
      AL357315, AL513472, AL590402
      Conserved Domains (2) summary
      cd00078
      Location:386 → 735
      HECTc; HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ...
      cl39094
      Location:38 → 83
      Ank_2; Ankyrin repeats (3 copies)

    9. NM_001350559.2 → NP_001337488.1  E3 ubiquitin-protein ligase HACE1 isoform h

      Status: REVIEWED

      Source sequence(s)
      AL357315, AL513472, AL590402
      Conserved Domains (2) summary
      cd00078
      Location:360 → 709
      HECTc; HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ...
      cd00204
      Location:12 → 58
      ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

    10. NM_001350560.2 → NP_001337489.1  E3 ubiquitin-protein ligase HACE1 isoform i

      Status: REVIEWED

      Source sequence(s)
      AL357315, AL513472, AL590402
      Conserved Domains (1) summary
      cd00078
      Location:293 → 642
      HECTc; HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ...

    11. NM_020771.4 → NP_065822.2  E3 ubiquitin-protein ligase HACE1 isoform a

      See identical proteins and their annotated locations for NP_065822.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (a).
      Source sequence(s)
      AJ420474, AK131207, BC034982, BC038119
      Consensus CDS
      CCDS5050.1
      UniProtKB/Swiss-Prot
      A8K6U5, B3KY89, B4DFM6, B4DTQ4, B7Z9X6, E9PGP0, Q5VU99, Q5VUA0, Q8IYU2, Q8ND12, Q9P2M6
      Related
      ENSP00000262903.4, ENST00000262903.9
      Conserved Domains (4) summary
      cd00078
      Location:554 → 903
      HECTc; HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ...
      cd00204
      Location:92 → 217
      ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...
      sd00045
      Location:97 → 128
      ANK; ANK repeat [structural motif]
      cl26073
      Location:27 → 283
      Ank_2; Ankyrin repeats (3 copies)

    RNA

    1. NR_104424.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) includes an additional exon in both the 5' and central regions, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      BC034982, BC038119, DA651352
      Related
      ENST00000416605.6

    2. NR_146787.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL357315, AL513472, AL590402

    3. NR_146788.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL357315, AL513472, AL590402

    4. NR_146789.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL357315, AL513472, AL590402

    5. NR_146790.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL357315, AL513472, AL590402

    6. NR_146791.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL357315, AL513472, AL590402

    7. NR_146792.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL357315, AL513472, AL590402

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      104728094..104859919 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      105904367..106035941 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8IYU2.2 GenPept UniProtKB/Swiss-Prot:Q8IYU2

    Gene LinkOut

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

    Chemical Information
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