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    STRADA STE20 related adaptor alpha [ Homo sapiens (human) ]

    Gene ID: 92335, updated on 27-Nov-2024

    Summary

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    Official Symbol
    STRADAprovided by HGNC
    Official Full Name
    STE20 related adaptor alphaprovided by HGNC
    Primary source
    HGNC:HGNC:30172
    See related
    Ensembl:ENSG00000266173 MIM:608626; AllianceGenome:HGNC:30172
    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
    LYK5; PMSE; Stlk; STRAD; NY-BR-96; STRAD alpha
    Summary
    The protein encoded by this gene contains a STE20-like kinase domain, but lacks several residues that are critical for catalytic activity, so it is termed a 'pseudokinase'. The protein forms a heterotrimeric complex with serine/threonine kinase 11 (STK11, also known as LKB1) and the scaffolding protein calcium binding protein 39 (CAB39, also known as MO25). The protein activates STK11 leading to the phosphorylation of both proteins and excluding STK11 from the nucleus. The protein is necessary for STK11-induced G1 cell cycle arrest. A mutation in this gene has been shown to result in polyhydramnios, megalencephaly, and symptomatic epilepsy (PMSE) syndrome. Multiple transcript variants encoding different isoforms have been found for this gene. Additional transcript variants have been described but their full-length nature is not known. [provided by RefSeq, Sep 2009]
    Expression
    Broad expression in testis (RPKM 18.6), brain (RPKM 8.0) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See STRADA in Genome Data Viewer
    Location:
    17q23.3
    Exon count:
    13
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (63702832..63741986, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (64573741..64612901, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (61780192..61819346, complement)

    Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene mitogen-activated protein kinase kinase kinase 3 Neighboring gene uncharacterized LOC101927898 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12552 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12553 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12554 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:61771715-61772602 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12555 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12556 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12557 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12558 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8827 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8826 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:61777898-61778483 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:61778484-61779068 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8829 Neighboring gene uncharacterized LOC729683 Neighboring gene Sharpr-MPRA regulatory region 9817 Neighboring gene LIM domain containing 2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:61817285-61817784 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8830 Neighboring gene coiled-coil domain containing 47 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:61850832-61851416 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8831 Neighboring gene DEAD-box helicase 42

    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. Whole exome sequencing identifies the first STRADA point mutation in a patient with polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome (PMSE). Bi W, et al. Am J Med Genet A, 2016 Aug. PMID 27170158
    2. Two further cases of polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome, caused by a truncating variant in STRADA. Alsaif HS, et al. Am J Med Genet A, 2021 Feb. PMID 33247513
    3. Type II Binders Targeting the "GLR-Out" Conformation of the Pseudokinase STRADα. Smith RHB, et al. Biochemistry, 2021 Feb 2. PMID 33440120, Free PMC Article
    4. Novel splice isoforms of STRADalpha differentially affect LKB1 activity, complex assembly and subcellular localization. Marignani PA, et al. Cancer Biol Ther, 2007 Oct. PMID 17921699
    5. Crystal structure of MO25 alpha in complex with the C terminus of the pseudo kinase STE20-related adaptor. Milburn CC, et al. Nat Struct Mol Biol, 2004 Feb. PMID 14730349

    See all (49) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Two further cases of polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome, caused by a truncating variant in STRADA.
      Title: Two further cases of polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome, caused by a truncating variant in STRADA.
    2. Type II Binders Targeting the ""GLR-Out"" Conformation of the Pseudokinase STRADalpha.
      Title: Type II Binders Targeting the "GLR-Out" Conformation of the Pseudokinase STRADα.
    3. We identified for the first time a homozygous point mutation in STRADA causing PMSE. Additional bi-allelic mutations related to PMSE thus far have not been observed in Baylor approximately 6,000 consecutive clinical WES cases, supporting the rarity of this disorder.
      Title: Whole exome sequencing identifies the first STRADA point mutation in a patient with polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome (PMSE).
    4. aberrant nuclear accumulation of LKB1 caused by STRADalpha deficiency contributes to hyperactivation of mTORC1 signaling and disruption of neuronal lamination during corticogenesis
      Title: STRADalpha deficiency results in aberrant mTORC1 signaling during corticogenesis in humans and mice.
    5. study describes structure of the core heterotrimeric LKB1-STRADalpha-MO25alpha complex, revealing an unusual allosteric mechanism of LKB1 activation; structure also reveals how mutations in Peutz-Jeghers syndrome & sporadic cancers impair LKB1 function
      Title: Structure of the LKB1-STRAD-MO25 complex reveals an allosteric mechanism of kinase activation.
    6. ATP and MO25alpha cooperate to maintain STRADalpha in an "active" closed conformation required for LKB1 activation.
      Title: ATP and MO25alpha regulate the conformational state of the STRADalpha pseudokinase and activation of the LKB1 tumour suppressor.
    7. These data define a brush border induction pathway downstream of the Lkb1/Strad/Mo25 polarization complex, yet separate from other polarity events.
      Title: Mst4 and Ezrin induce brush borders downstream of the Lkb1/Strad/Mo25 polarization complex.
    8. STRADalpha.MO25alpha complexes containing LKB1 variants were equally effective at phosphorylating and activating AMPK, BRSK1, and BRSK2
      Title: C-terminal phosphorylation of LKB1 is not required for regulation of AMP-activated protein kinase, BRSK1, BRSK2, or cell cycle arrest.
    9. LKB1 deacetylation is regulated by SIRT1 and that this in turn influences its intracellular localization, association with STRAD, kinase activity, and ability to activate AMPK.
      Title: SIRT1 modulation of the acetylation status, cytosolic localization, and activity of LKB1. Possible role in AMP-activated protein kinase activation.
    10. identify a multifactored mechanism to control LKB1 localization, and they suggest that the STRADbeta-LKB1 complex might possess unique functions in the nucleus
      Title: STRADalpha regulates LKB1 localization by blocking access to importin-alpha, and by association with Crm1 and exportin-7.
    Submit: New GeneRIF Correction See all GeneRIFs (12)

    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
    Polyhydramnios, megalencephaly, and symptomatic epilepsy
    MedGen: C1970203 OMIM: 611087 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    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)

    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

    • FLJ90524

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables kinase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein kinase activator activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    NOT enables protein kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein serine/threonine kinase activator activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein serine/threonine kinase activator activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    acts_upstream_of_negative_effect G1 to G0 transition IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    involved_in activation of protein kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein export from nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein export from nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    NOT involved_in protein phosphorylation 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 cytoplasm ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    part_of intracellular protein-containing complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of serine/threonine protein kinase complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of serine/threonine protein kinase complex IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    part_of serine/threonine protein kinase complex ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  

    General protein information

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    Preferred Names
    STE20-related kinase adapter protein alpha
    Names
    STE20-like pseudokinase
    STE20-related kinase adaptor alpha
    protein kinase LYK5
    serologically defined breast cancer antigen NY-BR-96

    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_015817.1 RefSeqGene

      Range
      5172..44139
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001003786.3 → NP_001003786.1  STE20-related kinase adapter protein alpha isoform 2

      See identical proteins and their annotated locations for NP_001003786.1

      Status: REVIEWED

      Source sequence(s)
      AK074771, AY290821, BC043641, BQ682133, DA049174
      Consensus CDS
      CCDS86632.1
      UniProtKB/TrEMBL
      A0A1W2PQF1
      Related
      ENSP00000492578.1, ENST00000639835.1
      Conserved Domains (2) summary
      cd08227
      Location:33 → 359
      PK_STRAD_alpha; Pseudokinase domain of STE20-related kinase adapter protein alpha
      smart00220
      Location:32 → 342
      S_TKc; Serine/Threonine protein kinases, catalytic domain

    2. NM_001003787.4 → NP_001003787.1  STE20-related kinase adapter protein alpha isoform 1

      See identical proteins and their annotated locations for NP_001003787.1

      Status: REVIEWED

      Source sequence(s)
      AL832407, AY290821, BK001542, BQ682133
      Consensus CDS
      CCDS32703.1
      UniProtKB/Swiss-Prot
      B4DDE3, B4DW17, J3KTC9, Q5JPI2, Q7RTN6, Q7Z4K9, Q8NC31, Q8NCF1, Q9H272
      UniProtKB/TrEMBL
      A0A1W2PQF1
      Related
      ENSP00000336655.6, ENST00000336174.12
      Conserved Domains (2) summary
      cd08227
      Location:70 → 396
      PK_STRAD_alpha; Pseudokinase domain of STE20-related kinase adapter protein alpha
      smart00220
      Location:69 → 379
      S_TKc; Serine/Threonine protein kinases, catalytic domain

    3. NM_001003788.3 → NP_001003788.1  STE20-related kinase adapter protein alpha isoform 4

      See identical proteins and their annotated locations for NP_001003788.1

      Status: REVIEWED

      Source sequence(s)
      AL832407, AY290821, BK001542, BQ682133, DA049174
      Consensus CDS
      CCDS42367.1
      UniProtKB/TrEMBL
      A0A1W2PPM8
      Related
      ENSP00000365000.4, ENST00000375840.9
      Conserved Domains (1) summary
      cd08227
      Location:12 → 338
      PK_STRAD_alpha; Pseudokinase domain of STE20-related kinase adapter protein alpha

    4. NM_001165969.2 → NP_001159441.1  STE20-related kinase adapter protein alpha isoform 5

      See identical proteins and their annotated locations for NP_001159441.1

      Status: REVIEWED

      Source sequence(s)
      AK301331, AL832407, AY290821, BQ682133, DA049174
      Consensus CDS
      CCDS58585.1
      UniProtKB/TrEMBL
      A0A1W2PP78
      Related
      ENSP00000462922.1, ENST00000582137.6
      Conserved Domains (2) summary
      smart00220
      Location:40 → 279
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cl21453
      Location:41 → 312
      PKc_like; Protein Kinases, catalytic domain

    5. NM_001165970.2 → NP_001159442.1  STE20-related kinase adapter protein alpha isoform 6

      See identical proteins and their annotated locations for NP_001159442.1

      Status: REVIEWED

      Source sequence(s)
      AK293160, AL832407, AY290821, BQ682133, DA049174
      Consensus CDS
      CCDS54156.1
      UniProtKB/TrEMBL
      A0A1W2PP78
      Related
      ENSP00000398841.3, ENST00000447001.8
      Conserved Domains (2) summary
      smart00220
      Location:40 → 264
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cl21453
      Location:32 → 297
      PKc_like; Protein Kinases, catalytic domain

    6. NM_001363786.1 → NP_001350715.1  STE20-related kinase adapter protein alpha isoform 7

      Status: REVIEWED

      Source sequence(s)
      AC015651, AC046185
      UniProtKB/TrEMBL
      A0A1W2PQF1
      Conserved Domains (1) summary
      cd08227
      Location:62 → 388
      PK_STRAD_alpha; Pseudokinase domain of STE20-related kinase adapter protein alpha

    7. NM_001363787.1 → NP_001350716.1  STE20-related kinase adapter protein alpha isoform 8

      Status: REVIEWED

      Source sequence(s)
      AC015651, AC046185
      Consensus CDS
      CCDS86626.1
      UniProtKB/TrEMBL
      A0A1W2PPJ9, A0A1W2PQF1
      Related
      ENSP00000491580.1, ENST00000638708.1
      Conserved Domains (1) summary
      cd08227
      Location:41 → 367
      PK_STRAD_alpha; Pseudokinase domain of STE20-related kinase adapter protein alpha

    8. NM_001363788.1 → NP_001350717.1  STE20-related kinase adapter protein alpha isoform 9

      Status: REVIEWED

      Source sequence(s)
      AC015651, AC046185
      Consensus CDS
      CCDS86630.1
      UniProtKB/TrEMBL
      A0A1W2PP78, A0A1W2PPG2
      Related
      ENSP00000491528.1, ENST00000638888.1
      Conserved Domains (1) summary
      cl21453
      Location:70 → 341
      PKc_like; Protein Kinases, catalytic domain

    9. NM_001363789.1 → NP_001350718.1  STE20-related kinase adapter protein alpha isoform 10

      Status: REVIEWED

      Source sequence(s)
      AC015651, AC046185
      Consensus CDS
      CCDS86633.1
      UniProtKB/TrEMBL
      A0A1W2PQ00, A0A1W2PR00
      Related
      ENSP00000492238.1, ENST00000640086.1
      Conserved Domains (1) summary
      cl21453
      Location:33 → 304
      PKc_like; Protein Kinases, catalytic domain

    10. NM_001363790.1 → NP_001350719.1  STE20-related kinase adapter protein alpha isoform 11

      Status: REVIEWED

      Source sequence(s)
      AC015651, AC046185
      UniProtKB/TrEMBL
      A0A1W2PPM8
      Conserved Domains (1) summary
      cl21453
      Location:12 → 299
      PKc_like; Protein Kinases, catalytic domain

    11. NM_001363791.1 → NP_001350720.1  STE20-related kinase adapter protein alpha isoform 12

      Status: REVIEWED

      Source sequence(s)
      AC015651, AC046185
      Consensus CDS
      CCDS86625.1
      UniProtKB/TrEMBL
      A0A1W2PP78, A0A1W2PQE8
      Related
      ENSP00000491922.1, ENST00000638276.1
      Conserved Domains (1) summary
      cl21453
      Location:12 → 283
      PKc_like; Protein Kinases, catalytic domain

    12. NM_001411083.1 → NP_001398012.1  STE20-related kinase adapter protein alpha isoform 13

      Status: REVIEWED

      Source sequence(s)
      AC015651, AC046185
      Consensus CDS
      CCDS92380.1
      UniProtKB/TrEMBL
      A0A1W2PS04
      Related
      ENSP00000492877.1, ENST00000638309.1

    13. NM_001411084.1 → NP_001398013.1  STE20-related kinase adapter protein alpha isoform 14

      Status: REVIEWED

      Source sequence(s)
      AC015651, AC046185
      Consensus CDS
      CCDS92377.1
      UniProtKB/TrEMBL
      J3QS66
      Related
      ENSP00000464547.2, ENST00000578008.6

    14. NM_001411085.1 → NP_001398014.1  STE20-related kinase adapter protein alpha isoform 15

      Status: REVIEWED

      Source sequence(s)
      AC015651, AC046185
      Consensus CDS
      CCDS92378.1
      UniProtKB/TrEMBL
      J3QQS3
      Related
      ENSP00000463872.2, ENST00000578801.6

    15. NM_153335.6 → NP_699166.2  STE20-related kinase adapter protein alpha isoform 3

      See identical proteins and their annotated locations for NP_699166.2

      Status: REVIEWED

      Source sequence(s)
      AY290821, BQ682133, DA049174
      Consensus CDS
      CCDS11642.1
      UniProtKB/TrEMBL
      A0A1W2PPM8
      Related
      ENSP00000376677.4, ENST00000392950.9
      Conserved Domains (2) summary
      smart00220
      Location:32 → 331
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cl21453
      Location:33 → 330
      PKc_like; Protein Kinases, catalytic domain

    RNA

    1. NR_156741.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC015651, AC046185

    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_000017.11 Reference GRCh38.p14 Primary Assembly

      Range
      63702832..63741986 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060941.1 Alternate T2T-CHM13v2.0

      Range
      64573741..64612901 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q7RTN6.1 GenPept UniProtKB/Swiss-Prot:Q7RTN6

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