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SIK3 SIK family kinase 3 [ Homo sapiens (human) ]

Gene ID: 23387, updated on 3-Apr-2024

Summary

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Official Symbol
SIK3provided by HGNC
Official Full Name
SIK family kinase 3provided by HGNC
Primary source
HGNC:HGNC:29165
See related
Ensembl:ENSG00000160584 MIM:614776; AllianceGenome:HGNC:29165
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
L19; QSK; SEMDK; SIK-3
Summary
Enables ATP binding activity; magnesium ion binding activity; and protein serine/threonine kinase activity. Involved in positive regulation of TORC1 signaling; positive regulation of TORC2 signaling; and protein phosphorylation. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
Expression
Broad expression in testis (RPKM 19.2), brain (RPKM 13.9) and 25 other tissues See more
Orthologs
mouse all
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Genomic context

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Location:
11q23.3
Exon count:
34
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (116843402..117098428, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (116858511..117113691, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (116714118..116969144, complement)

Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:116700143-116701075 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3925 Neighboring gene APOA1 antisense RNA Neighboring gene apolipoprotein C3 Neighboring gene apolipoprotein A1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3926 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5557 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5558 Neighboring gene OCT4 hESC enhancer GRCh37_chr11:116766707-116767208 Neighboring gene MPRA-validated peak1483 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3927 Neighboring gene MPRA-validated peak1484 silencer Neighboring gene MPRA-validated peak1485 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5560 Neighboring gene H3K27ac hESC enhancer GRCh37_chr11:116881555-116882207 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5561 Neighboring gene RNY4 pseudogene 6 Neighboring gene ribosomal protein S27 pseudogene 19 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3928 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5562 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5563 Neighboring gene MPRA-validated peak1487 silencer Neighboring gene uncharacterized LOC124902763 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5564 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3929 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3930 Neighboring gene ReSE screen-validated silencer GRCh37_chr11:116979894-116980128 Neighboring gene cleavage and polyadenylation specificity factor subunit 5-like Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:117008445-117009330 Neighboring gene proprotein convertase subtilisin/kexin type 7 pseudogene

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. [Analysis of SIK3 gene variation in a boy with autism spectrum disorder complicated with epilepsy]. Jia X, et al. Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 2021 Dec 10. PMID 34839513
  2. Salt-Inducible Kinase 3 Haplotypes Associated with Noise-Induced Hearing Loss in Chinese Workers. Yin H, et al. Audiol Neurootol, 2020. PMID 32126566
  3. Critical role of SIK3 in mediating high salt and IL-17 synergy leading to breast cancer cell proliferation. Amara S, et al. PLoS One, 2017. PMID 28658303, Free PMC Article
  4. Identification of salt-inducible kinase 3 as a novel tumor antigen associated with tumorigenesis of ovarian cancer. Charoenfuprasert S, et al. Oncogene, 2011 Aug 18. PMID 21399663
  5. Faecal ribosomal protein L19 is a genetic prognostic factor for survival in colorectal cancer. Huang CJ, et al. J Cell Mol Med, 2008 Oct. PMID 18266979, Free PMC Article

See all (70) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. [Analysis of SIK3 gene variation in a boy with autism spectrum disorder complicated with epilepsy].
    Title: [Analysis of SIK3 gene variation in a boy with autism spectrum disorder complicated with epilepsy].
  2. High-Throughput Implementation of the NanoBRET Target Engagement Intracellular Kinase Assay to Reveal Differential Compound Engagement by SIK2/3 Isoforms.
    Title: High-Throughput Implementation of the NanoBRET Target Engagement Intracellular Kinase Assay to Reveal Differential Compound Engagement by SIK2/3 Isoforms.
  3. Salt-Inducible Kinase 3 Haplotypes Associated with Noise-Induced Hearing Loss in Chinese Workers.
    Title: Salt-Inducible Kinase 3 Haplotypes Associated with Noise-Induced Hearing Loss in Chinese Workers.
  4. Salt-inducible Kinases Are Critical Determinants of Female Fertility.
    Title: Salt-inducible Kinases Are Critical Determinants of Female Fertility.
  5. Salt-inducible kinases (SIKs) regulate TGFbeta-mediated transcriptional and apoptotic responses.
    Title: Salt-inducible kinases (SIKs) regulate TGFβ-mediated transcriptional and apoptotic responses.
  6. An LKB1-SIK Axis Suppresses Lung Tumor Growth and Controls Differentiation.
    Title: An LKB1-SIK Axis Suppresses Lung Tumor Growth and Controls Differentiation.
  7. Targeting of LKB1 or SIK3 diminishes histone acetylation at MEF2C-bound enhancers and deprives leukemia cells of the output of this essential TF.
    Title: LKB1, Salt-Inducible Kinases, and MEF2C Are Linked Dependencies in Acute Myeloid Leukemia.
  8. Data suggest that cAMP/protein kinase A-dependent phosphorylation of SIK1, SIK2, and SIK3 inhibits their catalytic activity by inducing 14-3-3 protein binding.
    Title: 14-3-3 proteins mediate inhibitory effects of cAMP on salt-inducible kinases (SIKs).
  9. role in mediating high salt and IL-17 synergy leading to breast cancer cell proliferation
    Title: Critical role of SIK3 in mediating high salt and IL-17 synergy leading to breast cancer cell proliferation.
  10. Data demonstrate that SIK2 and SIK3 mRNA are downregulated in adipose tissue from obese individuals and that the expression is regulated by weight change. SIK2 is also negatively associated with in vivo insulin resistance (HOMA-IR), independently of BMI and age.
    Title: Salt-inducible kinase 2 and -3 are downregulated in adipose tissue from obese or insulin-resistant individuals: implications for insulin signalling and glucose uptake in human adipocytes.
Submit: New GeneRIF Correction See all GeneRIFs (22)

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
Spondyloepimetaphyseal dysplasia, Krakow type
MedGen: C4748455 OMIM: 618162 GeneReviews: Not available
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EBI GWAS Catalog

Description
Amerindian-specific regions under positive selection harbour new lipid variants in Latinos.
EBI GWAS Catalog
Common variants near MBNL1 and NKX2-5 are associated with infantile hypertrophic pyloric stenosis.
EBI GWAS Catalog
Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women.
EBI GWAS Catalog
Genome-wide association study identifies three common variants associated with serologic response to vitamin E supplementation in men.
EBI GWAS Catalog
Genome-wide scan identifies variation in MLXIPL associated with plasma triglycerides.
EBI GWAS Catalog
Genomic study in Mexicans identifies a new locus for triglycerides and refines European lipid loci.
EBI GWAS Catalog
Novel association to the proprotein convertase PCSK7 gene locus revealed by analysing soluble transferrin receptor (sTfR) levels.
EBI GWAS Catalog
Salt-inducible kinase 3, SIK3, is a new gene associated with hearing.
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

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

  • FLJ12240, KIAA0999

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables magnesium ion binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein serine kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein serine/threonine kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables protein serine/threonine kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables tau-protein kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
Process Evidence Code Pubs
involved_in intracellular signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in microtubule cytoskeleton organization IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of TORC1 signaling IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of TORC2 signaling IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in protein phosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
serine/threonine-protein kinase SIK3
Names
salt-inducible kinase 3
serine/threonine-protein kinase QSK
NP_001268677.1
NP_001268678.1
NP_001353615.1
NP_001353616.1
NP_079440.3
XP_005271539.2
XP_005271541.2
XP_005271542.1
XP_011541024.1
XP_011541025.1
XP_011541026.1
XP_011541027.1
XP_011541028.1
XP_016872913.1
XP_016872914.1
XP_016872915.1
XP_047282627.1
XP_047282628.1
XP_047282629.1
XP_047282630.1
XP_047282631.1
XP_047282632.1
XP_054224194.1
XP_054224195.1
XP_054224196.1
XP_054224197.1
XP_054224198.1
XP_054224199.1
XP_054224200.1
XP_054224201.1
XP_054224202.1
XP_054224203.1
XP_054224204.1
XP_054224205.1
XP_054224206.1
XP_054224207.1
XP_054224208.1
XP_054224209.1
XP_054224210.1

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.

mRNA and Protein(s)

  1. NM_001281748.3 → NP_001268677.1  serine/threonine-protein kinase SIK3 isoform 2

    See identical proteins and their annotated locations for NP_001268677.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) uses an alternate exon in the 5' UTR and uses a downstream start codon compared to variant 1. It encodes isoform 2 which has a shorter N-terminus compared to isoform 1.
    Source sequence(s)
    AI369377, AP000936, AP006216, BC128511
    UniProtKB/TrEMBL
    A1A5A9, M5FMX3
    Conserved Domains (3) summary
    smart00220
    Location:1 → 158
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd14410
    Location:187 → 231
    UBA_SIK3; UBA domain found in salt-inducible kinase 3 (SIK3)
    cl21453
    Location:1 → 158
    PKc_like; Protein Kinases, catalytic domain

  2. NM_001281749.3 → NP_001268678.1  serine/threonine-protein kinase SIK3 isoform 3

    Status: VALIDATED

    Description
    Transcript Variant: This variant (3) has multiple differences in the coding region but maintains the reading frame, compared to variant 1. This results in a shorter isoform (3) compared to isoform 1.
    Source sequence(s)
    AI369377, AP000936, AP006216, BC128510
    Consensus CDS
    CCDS60974.1
    UniProtKB/TrEMBL
    M5FMX3
    Related
    ENSP00000390442.2, ENST00000446921.6
    Conserved Domains (1) summary
    cd14071
    Location:65 → 317
    STKc_SIK; Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases

  3. NM_001366686.3 → NP_001353615.1  serine/threonine-protein kinase SIK3 isoform 4

    Status: VALIDATED

    Source sequence(s)
    AP000936, AP003070, AP006216
    Consensus CDS
    CCDS91600.1
    UniProtKB/TrEMBL
    H0Y4E8, M5FMX3
    Related
    ENSP00000391295.2, ENST00000445177.6
    Conserved Domains (2) summary
    cd14410
    Location:346 → 390
    UBA_SIK3; UBA domain found in salt-inducible kinase 3 (SIK3)
    cd14071
    Location:65 → 317
    STKc_SIK; Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases

  4. NM_001366687.1 → NP_001353616.1  serine/threonine-protein kinase SIK3 isoform 5

    Status: VALIDATED

    Source sequence(s)
    AP000936, AP003070, BC121188
    UniProtKB/TrEMBL
    Q0IJ40
    Conserved Domains (1) summary
    cl21453
    Location:65 → 205
    PKc_like; Protein Kinases, catalytic domain

  5. NM_025164.6 → NP_079440.3  serine/threonine-protein kinase SIK3 isoform 1

    Status: VALIDATED

    Source sequence(s)
    AB023216, AI369377, AP000936, AP006216
    Consensus CDS
    CCDS8379.2
    UniProtKB/Swiss-Prot
    A1A5A8, H0Y494, J3KPC8, Q59FY2, Q5M9N1, Q6P3R6, Q8IYM8, Q9HA50, Q9Y2K2
    UniProtKB/TrEMBL
    M5FMX3
    Related
    ENSP00000364449.1, ENST00000375300.6
    Conserved Domains (2) summary
    cd14410
    Location:346 → 390
    UBA_SIK3; UBA domain found in salt-inducible kinase 3 (SIK3)
    cd14071
    Location:65 → 317
    STKc_SIK; Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases

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_000011.10 Reference GRCh38.p14 Primary Assembly

    Range
    116843402..117098428 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017017424.2 → XP_016872913.1  serine/threonine-protein kinase SIK3 isoform X6

    UniProtKB/TrEMBL
    M5FMX3

  2. XM_047426672.1 → XP_047282628.1  serine/threonine-protein kinase SIK3 isoform X4

  3. XM_005271482.5 → XP_005271539.2  serine/threonine-protein kinase SIK3 isoform X2

    UniProtKB/TrEMBL
    M5FMX3
    Conserved Domains (2) summary
    smart00220
    Location:66 → 317
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd14071
    Location:65 → 317
    STKc_SIK; Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases

  4. XM_005271484.4 → XP_005271541.2  serine/threonine-protein kinase SIK3 isoform X5

    UniProtKB/TrEMBL
    M5FMX3
    Conserved Domains (2) summary
    cd14410
    Location:346 → 390
    UBA_SIK3; UBA domain found in salt-inducible kinase 3 (SIK3)
    cd14071
    Location:65 → 317
    STKc_SIK; Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases

  5. XM_011542722.2 → XP_011541024.1  serine/threonine-protein kinase SIK3 isoform X3

    UniProtKB/TrEMBL
    M5FMX3
    Conserved Domains (2) summary
    cd14410
    Location:346 → 390
    UBA_SIK3; UBA domain found in salt-inducible kinase 3 (SIK3)
    cd14071
    Location:65 → 317
    STKc_SIK; Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases

  6. XM_011542725.3 → XP_011541027.1  serine/threonine-protein kinase SIK3 isoform X7

    See identical proteins and their annotated locations for XP_011541027.1

    UniProtKB/TrEMBL
    M5FMX3
    Conserved Domains (3) summary
    smart00220
    Location:1 → 158
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd14410
    Location:187 → 231
    UBA_SIK3; UBA domain found in salt-inducible kinase 3 (SIK3)
    cl21453
    Location:1 → 158
    PKc_like; Protein Kinases, catalytic domain

  7. XM_011542724.3 → XP_011541026.1  serine/threonine-protein kinase SIK3 isoform X7

    See identical proteins and their annotated locations for XP_011541026.1

    UniProtKB/TrEMBL
    M5FMX3
    Conserved Domains (3) summary
    smart00220
    Location:1 → 158
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd14410
    Location:187 → 231
    UBA_SIK3; UBA domain found in salt-inducible kinase 3 (SIK3)
    cl21453
    Location:1 → 158
    PKc_like; Protein Kinases, catalytic domain

  8. XM_011542723.3 → XP_011541025.1  serine/threonine-protein kinase SIK3 isoform X7

    See identical proteins and their annotated locations for XP_011541025.1

    UniProtKB/TrEMBL
    M5FMX3
    Conserved Domains (3) summary
    smart00220
    Location:1 → 158
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd14410
    Location:187 → 231
    UBA_SIK3; UBA domain found in salt-inducible kinase 3 (SIK3)
    cl21453
    Location:1 → 158
    PKc_like; Protein Kinases, catalytic domain

  9. XM_017017425.2 → XP_016872914.1  serine/threonine-protein kinase SIK3 isoform X7

    UniProtKB/TrEMBL
    M5FMX3
    Conserved Domains (3) summary
    smart00220
    Location:1 → 158
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd14410
    Location:187 → 231
    UBA_SIK3; UBA domain found in salt-inducible kinase 3 (SIK3)
    cl21453
    Location:1 → 158
    PKc_like; Protein Kinases, catalytic domain

  10. XM_017017426.2 → XP_016872915.1  serine/threonine-protein kinase SIK3 isoform X7

    UniProtKB/TrEMBL
    M5FMX3
    Conserved Domains (3) summary
    smart00220
    Location:1 → 158
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd14410
    Location:187 → 231
    UBA_SIK3; UBA domain found in salt-inducible kinase 3 (SIK3)
    cl21453
    Location:1 → 158
    PKc_like; Protein Kinases, catalytic domain

  11. XM_047426673.1 → XP_047282629.1  serine/threonine-protein kinase SIK3 isoform X9

    Related
    ENST00000488337.5

  12. XM_005271485.4 → XP_005271542.1  serine/threonine-protein kinase SIK3 isoform X8

    UniProtKB/TrEMBL
    B3KVE2

  13. XM_047426671.1 → XP_047282627.1  serine/threonine-protein kinase SIK3 isoform X1

    UniProtKB/TrEMBL
    H0Y4E8

  14. XM_011542726.2 → XP_011541028.1  serine/threonine-protein kinase SIK3 isoform X10

    Conserved Domains (2) summary
    cd14410
    Location:346 → 390
    UBA_SIK3; UBA domain found in salt-inducible kinase 3 (SIK3)
    cd14071
    Location:65 → 317
    STKc_SIK; Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases

  15. XM_047426674.1 → XP_047282630.1  serine/threonine-protein kinase SIK3 isoform X11

  16. XM_047426676.1 → XP_047282632.1  serine/threonine-protein kinase SIK3 isoform X13

  17. XM_047426675.1 → XP_047282631.1  serine/threonine-protein kinase SIK3 isoform X12

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060935.1 Alternate T2T-CHM13v2.0

    Range
    116858511..117113691 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054368224.1 → XP_054224199.1  serine/threonine-protein kinase SIK3 isoform X6

  2. XM_054368222.1 → XP_054224197.1  serine/threonine-protein kinase SIK3 isoform X4

  3. XM_054368220.1 → XP_054224195.1  serine/threonine-protein kinase SIK3 isoform X2

  4. XM_054368223.1 → XP_054224198.1  serine/threonine-protein kinase SIK3 isoform X5

  5. XM_054368221.1 → XP_054224196.1  serine/threonine-protein kinase SIK3 isoform X3

  6. XM_054368229.1 → XP_054224204.1  serine/threonine-protein kinase SIK3 isoform X7

  7. XM_054368227.1 → XP_054224202.1  serine/threonine-protein kinase SIK3 isoform X7

  8. XM_054368225.1 → XP_054224200.1  serine/threonine-protein kinase SIK3 isoform X7

  9. XM_054368226.1 → XP_054224201.1  serine/threonine-protein kinase SIK3 isoform X7

  10. XM_054368228.1 → XP_054224203.1  serine/threonine-protein kinase SIK3 isoform X7

  11. XM_054368231.1 → XP_054224206.1  serine/threonine-protein kinase SIK3 isoform X9

  12. XM_054368230.1 → XP_054224205.1  serine/threonine-protein kinase SIK3 isoform X8

  13. XM_054368219.1 → XP_054224194.1  serine/threonine-protein kinase SIK3 isoform X1

    UniProtKB/TrEMBL
    H0Y4E8

  14. XM_054368232.1 → XP_054224207.1  serine/threonine-protein kinase SIK3 isoform X10

  15. XM_054368233.1 → XP_054224208.1  serine/threonine-protein kinase SIK3 isoform X11

  16. XM_054368235.1 → XP_054224210.1  serine/threonine-protein kinase SIK3 isoform X13

  17. XM_054368234.1 → XP_054224209.1  serine/threonine-protein kinase SIK3 isoform X12

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9Y2K2.4 GenPept UniProtKB/Swiss-Prot:Q9Y2K2

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