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

Gene ID: 92335, updated on 3-Apr-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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Location:
17q23.3
Exon count:
13
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (63702832..63741986, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (64573741..64612901, complement)
105.20220307 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. 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
  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. 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
  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 (45) 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
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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)

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

  • 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 IBA
Inferred from Biological aspect of Ancestor
more info
  
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_2023_10

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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