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    HHAT hedgehog acyltransferase [ Homo sapiens (human) ]

    Gene ID: 55733, updated on 10-Dec-2024

    Summary

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    Official Symbol
    HHATprovided by HGNC
    Official Full Name
    hedgehog acyltransferaseprovided by HGNC
    Primary source
    HGNC:HGNC:18270
    See related
    Ensembl:ENSG00000054392 MIM:605743; AllianceGenome:HGNC:18270
    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
    Skn; NNMS; SKI1; MART2
    Summary
    'Skinny hedgehog' (SKI1) encodes an enzyme that acts within the secretory pathway to catalyze amino-terminal palmitoylation of 'hedgehog' (see MIM 600725).[supplied by OMIM, Jul 2002]
    Expression
    Ubiquitous expression in thyroid (RPKM 3.0), gall bladder (RPKM 1.6) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See HHAT in Genome Data Viewer
    Location:
    1q32.2
    Exon count:
    16
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (210327328..210676290)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (209566001..209918121)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (210501596..210849632)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr1:210484426-210485625 Neighboring gene uncharacterized LOC124904502 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_3009 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1779 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2478 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_3018 Neighboring gene ribonuclease H1 pseudogene 3 Neighboring gene uncharacterized LOC124904503 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr1:210546392-210547304 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr1:210547305-210548216 Neighboring gene Sharpr-MPRA regulatory region 10816 Neighboring gene RNA, U5A small nuclear 8, pseudogene Neighboring gene BPNT2 pseudogene 1 Neighboring gene Sharpr-MPRA regulatory region 9170 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:210770524-210771385 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:210771386-210772246 Neighboring gene Sharpr-MPRA regulatory region 1701 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2479 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2480 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:210863521-210864021 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2481 Neighboring gene uncharacterized LOC105372901 Neighboring gene MPRA-validated peak678 silencer Neighboring gene MPRA-validated peak679 silencer Neighboring gene potassium voltage-gated channel subfamily H member 1 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_3130 Neighboring gene importin 8 pseudogene 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. Isolation of a new melanoma antigen, MART-2, containing a mutated epitope recognized by autologous tumor-infiltrating T lymphocytes. Kawakami Y, et al. J Immunol, 2001 Feb 15. PMID 11160356
    2. Hedgehog acyltransferase catalyzes a random sequential reaction and utilizes multiple fatty acyl-CoA substrates. Schonbrun AR, et al. J Biol Chem, 2022 Oct. PMID 36030053, Free PMC Article
    3. A Homozygous Missense Variant in Hedgehog Acyltransferase (HHAT) Gene Associated with 46,XY Gonadal Dysgenesis. Mazen I, et al. Sex Dev, 2022. PMID 35045414
    4. Structure, mechanism, and inhibition of Hedgehog acyltransferase. Coupland CE, et al. Mol Cell, 2021 Dec 16. PMID 34890564, Free PMC Article
    5. Hedgehog acyl-transferase-related multiple congenital anomalies: Report of an additional family and delineation of the syndrome. Pande S, et al. Am J Med Genet A, 2021 Sep. PMID 33749989, Free PMC Article

    See all (31) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Additional evidence for the role of chromosomal imbalances and SOX8, ZNRF3 and HHAT gene variants in early human testis development.
      Title: Additional evidence for the role of chromosomal imbalances and SOX8, ZNRF3 and HHAT gene variants in early human testis development.
    2. A Homozygous Missense Variant in Hedgehog Acyltransferase (HHAT) Gene Associated with 46,XY Gonadal Dysgenesis.
      Title: A Homozygous Missense Variant in Hedgehog Acyltransferase (HHAT) Gene Associated with 46,XY Gonadal Dysgenesis.
    3. Hedgehog acyltransferase catalyzes a random sequential reaction and utilizes multiple fatty acyl-CoA substrates.
      Title: Hedgehog acyltransferase catalyzes a random sequential reaction and utilizes multiple fatty acyl-CoA substrates.
    4. Structure, mechanism, and inhibition of Hedgehog acyltransferase.
      Title: Structure, mechanism, and inhibition of Hedgehog acyltransferase.
    5. Hedgehog acyl-transferase-related multiple congenital anomalies: Report of an additional family and delineation of the syndrome.
      Title: Hedgehog acyl-transferase-related multiple congenital anomalies: Report of an additional family and delineation of the syndrome.
    6. Substrate and product complexes reveal mechanisms of Hedgehog acylation by HHAT.
      Title: Substrate and product complexes reveal mechanisms of Hedgehog acylation by HHAT.
    7. we confirm that biallelic loss of function HHAT variant ( likely deleterious) cause microcephaly, skeletal dysplasia and cerebellar vermis hypoplasia.
      Title: Biallelic novel missense HHAT variant causes syndromic microcephaly and cerebellar-vermis hypoplasia.
    8. HHAT is regulated in SSc in a TGFbeta-dependent manner and in turn stimulates TGFbeta-induced long-range hedgehog signalling to promote fibroblast activation and tissue fibrosis. Targeting of HHAT might be a novel approach to more selectively interfere with the profibrotic effects of long-range hedgehog signalling.
      Title: Acyltransferase skinny hedgehog regulates TGFβ-dependent fibroblast activation in SSc.
    9. Hhat plays a critical role in ER positive, HER2 amplified, and hormone resistant breast cancer proliferation.
      Title: Hedgehog Acyltransferase as a target in estrogen receptor positive, HER2 amplified, and tamoxifen resistant breast cancer cells.
    10. Data suggest that substrate specificity of hedgehog acyltransferase (HHAT) in palmitoylation reaction extends to oligopeptide fragments of Sonic hedgehog protein (SHH).
      Title: Click chemistry armed enzyme-linked immunosorbent assay to measure palmitoylation by hedgehog acyltransferase.
    Submit: New GeneRIF Correction See all GeneRIFs (18)

    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
    Chondrodysplasia-pseudohermaphroditism syndrome
    MedGen: C1838654 OMIM: 600092 GeneReviews: Not available
    		not available

    EBI GWAS Catalog

    Description
    Whole-genome-wide association study in the Bulgarian population reveals HHAT as schizophrenia susceptibility gene.
    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)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ10724, FLJ34867

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables GTP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables O-acyltransferase activity TAS
    Traceable Author Statement
    more info
    		  
    enables palmitoyltransferase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in N-terminal peptidyl-L-cysteine N-palmitoylation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in smoothened signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in Golgi apparatus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in Golgi membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in endoplasmic reticulum IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in endoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in endoplasmic reticulum membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    protein-cysteine N-palmitoyltransferase HHAT
    Names
    melanoma antigen recognized by T-cells 2
    skinny hedgehog protein 1

    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_001122834.4 → NP_001116306.1  protein-cysteine N-palmitoyltransferase HHAT isoform 1

      See identical proteins and their annotated locations for NP_001116306.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 6 encode the same isoform (1).
      Source sequence(s)
      AC217414, AL034351, BC117130, DB080645
      Consensus CDS
      CCDS1495.1
      UniProtKB/Swiss-Prot
      B7Z4D5, B7Z5I1, B7Z868, B7ZA75, D3DT91, F5H444, Q17RZ7, Q4G0K3, Q5CZ95, Q5TGI2, Q5VTY9, Q9NVH9, Q9Y3N8
      UniProtKB/TrEMBL
      Q05BM0
      Related
      ENSP00000416845.2, ENST00000413764.6
      Conserved Domains (1) summary
      pfam03062
      Location:150 → 442
      MBOAT; membrane-bound O-acyltransferase family

    2. NM_001170564.3 → NP_001164035.1  protein-cysteine N-palmitoyltransferase HHAT isoform 2

      See identical proteins and their annotated locations for NP_001164035.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR and lacks two in-frame exons in the coding region, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
      Source sequence(s)
      AC217414, AK297193, DB080645
      Consensus CDS
      CCDS53473.1
      UniProtKB/Swiss-Prot
      Q5VTY9
      Related
      ENSP00000444995.1, ENST00000541565.5
      Conserved Domains (1) summary
      cl00738
      Location:99 → 305
      MBOAT; MBOAT, membrane-bound O-acyltransferase family

    3. NM_001170580.3 → NP_001164051.1  protein-cysteine N-palmitoyltransferase HHAT isoform 1

      See identical proteins and their annotated locations for NP_001164051.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (6) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 6 encode the same isoform (1).
      Source sequence(s)
      AC217414, AL034351, BC051191
      Consensus CDS
      CCDS1495.1
      UniProtKB/Swiss-Prot
      B7Z4D5, B7Z5I1, B7Z868, B7ZA75, D3DT91, F5H444, Q17RZ7, Q4G0K3, Q5CZ95, Q5TGI2, Q5VTY9, Q9NVH9, Q9Y3N8
      UniProtKB/TrEMBL
      Q05BM0
      Related
      ENSP00000355977.1, ENST00000367010.5
      Conserved Domains (1) summary
      pfam03062
      Location:150 → 442
      MBOAT; membrane-bound O-acyltransferase family

    4. NM_001170587.3 → NP_001164058.1  protein-cysteine N-palmitoyltransferase HHAT isoform 4

      Status: VALIDATED

      Description
      Transcript Variant: This variant (5) differs in the 5' UTR and 5' coding region and initiates translation at an upstream start codon, compared to variant 1. The encoded isoform (4) has a longer N-terminus, compared to isoform (1).
      Source sequence(s)
      AC217414, AK302955, AL034351, AL035414
      Consensus CDS
      CCDS53471.1
      UniProtKB/TrEMBL
      B7Z2U8
      Related
      ENSP00000438468.1, ENST00000545154.5
      Conserved Domains (1) summary
      pfam03062
      Location:151 → 443
      MBOAT; MBOAT, membrane-bound O-acyltransferase family

    5. NM_001170588.3 → NP_001164059.1  protein-cysteine N-palmitoyltransferase HHAT isoform 3

      See identical proteins and their annotated locations for NP_001164059.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (4) lacks an in-frame exon in the coding region compared to variant 1. The encoded isoform (3) is shorter than isoform 1.
      Source sequence(s)
      AC217414, AK298991, AL034351, AL035414
      Consensus CDS
      CCDS53472.1
      UniProtKB/TrEMBL
      Q05BM0
      Related
      ENSP00000442625.1, ENST00000537898.5
      Conserved Domains (1) summary
      pfam03062
      Location:91 → 377
      MBOAT; MBOAT, membrane-bound O-acyltransferase family

    6. NM_018194.6 → NP_060664.2  protein-cysteine N-palmitoyltransferase HHAT isoform 1

      See identical proteins and their annotated locations for NP_060664.2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes isoform (1). Variants 1, 2 and 6 encode the same isoform (1).
      Source sequence(s)
      AC217414, AK001586, AK299200, AL034351, AL035414, AL691441
      Consensus CDS
      CCDS1495.1
      UniProtKB/Swiss-Prot
      B7Z4D5, B7Z5I1, B7Z868, B7ZA75, D3DT91, F5H444, Q17RZ7, Q4G0K3, Q5CZ95, Q5TGI2, Q5VTY9, Q9NVH9, Q9Y3N8
      UniProtKB/TrEMBL
      Q05BM0
      Related
      ENSP00000261458.3, ENST00000261458.8
      Conserved Domains (1) summary
      pfam03062
      Location:150 → 442
      MBOAT; membrane-bound O-acyltransferase family

    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_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      210327328..210676290
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047424804.1 → XP_047280760.1  protein-cysteine N-palmitoyltransferase HHAT isoform X4

      UniProtKB/Swiss-Prot
      B7Z4D5, B7Z5I1, B7Z868, B7ZA75, D3DT91, F5H444, Q17RZ7, Q4G0K3, Q5CZ95, Q5TGI2, Q5VTY9, Q9NVH9, Q9Y3N8
      UniProtKB/TrEMBL
      Q05BM0

    2. XM_047424811.1 → XP_047280767.1  protein-cysteine N-palmitoyltransferase HHAT isoform X8

      UniProtKB/TrEMBL
      B7Z2U8

    3. XM_047424806.1 → XP_047280762.1  protein-cysteine N-palmitoyltransferase HHAT isoform X7

      UniProtKB/TrEMBL
      B7Z2U8

    4. XM_047424835.1 → XP_047280791.1  protein-cysteine N-palmitoyltransferase HHAT isoform X12

    5. XM_011509747.2 → XP_011508049.1  protein-cysteine N-palmitoyltransferase HHAT isoform X6

      See identical proteins and their annotated locations for XP_011508049.1

      UniProtKB/TrEMBL
      B7Z5N1
      Conserved Domains (1) summary
      pfam03062
      Location:87 → 379
      MBOAT; MBOAT, membrane-bound O-acyltransferase family

    6. XM_047424829.1 → XP_047280785.1  protein-cysteine N-palmitoyltransferase HHAT isoform X11

      UniProtKB/TrEMBL
      B7Z5N1

    7. XM_047424823.1 → XP_047280779.1  protein-cysteine N-palmitoyltransferase HHAT isoform X10

      UniProtKB/TrEMBL
      B7Z5N1

    8. XM_047424791.1 → XP_047280747.1  protein-cysteine N-palmitoyltransferase HHAT isoform X1

    9. XM_006711441.4 → XP_006711504.1  protein-cysteine N-palmitoyltransferase HHAT isoform X2

      See identical proteins and their annotated locations for XP_006711504.1

      UniProtKB/TrEMBL
      Q05BM0
      Conserved Domains (1) summary
      pfam03062
      Location:184 → 476
      MBOAT; MBOAT, membrane-bound O-acyltransferase family

    10. XM_047424805.1 → XP_047280761.1  protein-cysteine N-palmitoyltransferase HHAT isoform X5

      UniProtKB/TrEMBL
      Q05BM0

    11. XM_047424817.1 → XP_047280773.1  protein-cysteine N-palmitoyltransferase HHAT isoform X9

    12. XM_047424802.1 → XP_047280758.1  protein-cysteine N-palmitoyltransferase HHAT isoform X3

      UniProtKB/TrEMBL
      Q05BM0

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_011332687.1 Reference GRCh38.p14 PATCHES

      Range
      107070..459389
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054331653.1 → XP_054187628.1  protein-cysteine N-palmitoyltransferase HHAT isoform X4

      UniProtKB/Swiss-Prot
      B7Z4D5, B7Z5I1, B7Z868, B7ZA75, D3DT91, F5H444, Q17RZ7, Q4G0K3, Q5CZ95, Q5TGI2, Q5VTY9, Q9NVH9, Q9Y3N8
      UniProtKB/TrEMBL
      Q05BM0

    2. XM_054331657.1 → XP_054187632.1  protein-cysteine N-palmitoyltransferase HHAT isoform X8

      UniProtKB/TrEMBL
      B7Z2U8

    3. XM_054331656.1 → XP_054187631.1  protein-cysteine N-palmitoyltransferase HHAT isoform X7

      UniProtKB/TrEMBL
      B7Z2U8

    4. XM_054331661.1 → XP_054187636.1  protein-cysteine N-palmitoyltransferase HHAT isoform X12

    5. XM_054331655.1 → XP_054187630.1  protein-cysteine N-palmitoyltransferase HHAT isoform X6

      UniProtKB/TrEMBL
      B7Z5N1

    6. XM_054331660.1 → XP_054187635.1  protein-cysteine N-palmitoyltransferase HHAT isoform X11

      UniProtKB/TrEMBL
      B7Z5N1

    7. XM_054331659.1 → XP_054187634.1  protein-cysteine N-palmitoyltransferase HHAT isoform X10

      UniProtKB/TrEMBL
      B7Z5N1

    8. XM_054331650.1 → XP_054187625.1  protein-cysteine N-palmitoyltransferase HHAT isoform X1

    9. XM_054331651.1 → XP_054187626.1  protein-cysteine N-palmitoyltransferase HHAT isoform X2

      UniProtKB/TrEMBL
      Q05BM0

    10. XM_054331652.1 → XP_054187627.1  protein-cysteine N-palmitoyltransferase HHAT isoform X3

      UniProtKB/TrEMBL
      Q05BM0

    11. XM_054331654.1 → XP_054187629.1  protein-cysteine N-palmitoyltransferase HHAT isoform X13

      UniProtKB/TrEMBL
      Q05BM0

    12. XM_054331658.1 → XP_054187633.1  protein-cysteine N-palmitoyltransferase HHAT isoform X14

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      209566001..209918121
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054337578.1 → XP_054193553.1  protein-cysteine N-palmitoyltransferase HHAT isoform X4

      UniProtKB/Swiss-Prot
      B7Z4D5, B7Z5I1, B7Z868, B7ZA75, D3DT91, F5H444, Q17RZ7, Q4G0K3, Q5CZ95, Q5TGI2, Q5VTY9, Q9NVH9, Q9Y3N8
      UniProtKB/TrEMBL
      Q05BM0

    2. XM_054337582.1 → XP_054193557.1  protein-cysteine N-palmitoyltransferase HHAT isoform X8

      UniProtKB/TrEMBL
      B7Z2U8

    3. XM_054337581.1 → XP_054193556.1  protein-cysteine N-palmitoyltransferase HHAT isoform X7

      UniProtKB/TrEMBL
      B7Z2U8

    4. XM_054337586.1 → XP_054193561.1  protein-cysteine N-palmitoyltransferase HHAT isoform X12

    5. XM_054337580.1 → XP_054193555.1  protein-cysteine N-palmitoyltransferase HHAT isoform X6

      UniProtKB/TrEMBL
      B7Z5N1

    6. XM_054337585.1 → XP_054193560.1  protein-cysteine N-palmitoyltransferase HHAT isoform X11

      UniProtKB/TrEMBL
      B7Z5N1

    7. XM_054337584.1 → XP_054193559.1  protein-cysteine N-palmitoyltransferase HHAT isoform X10

      UniProtKB/TrEMBL
      B7Z5N1

    8. XM_054337575.1 → XP_054193550.1  protein-cysteine N-palmitoyltransferase HHAT isoform X1

    9. XM_054337576.1 → XP_054193551.1  protein-cysteine N-palmitoyltransferase HHAT isoform X2

      UniProtKB/TrEMBL
      Q05BM0

    10. XM_054337577.1 → XP_054193552.1  protein-cysteine N-palmitoyltransferase HHAT isoform X3

      UniProtKB/TrEMBL
      Q05BM0

    11. XM_054337579.1 → XP_054193554.1  protein-cysteine N-palmitoyltransferase HHAT isoform X13

      UniProtKB/TrEMBL
      Q05BM0

    12. XM_054337583.1 → XP_054193558.1  protein-cysteine N-palmitoyltransferase HHAT isoform X14

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q5VTY9.1 GenPept UniProtKB/Swiss-Prot:Q5VTY9

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