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KNL1 kinetochore scaffold 1 [ Homo sapiens (human) ]

Gene ID: 57082, updated on 27-Nov-2024

Summary

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Official Symbol
KNL1provided by HGNC
Official Full Name
kinetochore scaffold 1provided by HGNC
Primary source
HGNC:HGNC:24054
See related
Ensembl:ENSG00000137812 MIM:609173; AllianceGenome:HGNC:24054
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
D40; CT29; Spc7; CASC5; MCPH4; hKNL-1; AF15Q14; PPP1R55; hSpc105
Summary
The protein encoded by this gene is a component of the multiprotein assembly that is required for creation of kinetochore-microtubule attachments and chromosome segregation. The encoded protein functions as a scaffold for proteins that influence the spindle assembly checkpoint during the eukaryotic cell cycle and it interacts with at least five different kinetochore proteins and two checkpoint kinases. In adults, this gene is predominantly expressed in normal testes, various cancer cell lines and primary tumors from other tissues and is ubiquitously expressed in fetal tissues. This gene was originally identified as a fusion partner with the mixed-lineage leukemia (MLL) gene in t(11;15)(q23;q14). Mutations in this gene cause autosomal recessive primary microcephaly-4 (MCPH4). Alternative splicing results in multiple transcript variants encoding different isoforms. Additional splice variants have been described but their biological validity has not been confirmed. [provided by RefSeq, Jan 2013]
Expression
Biased expression in testis (RPKM 14.1), bone marrow (RPKM 2.9) and 6 other tissues See more
Orthologs
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Genomic context

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See KNL1 in Genome Data Viewer
Location:
15q15.1
Exon count:
27
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (40594249..40664342)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (38399974..38470044)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (40886447..40956540)

Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9251 Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:40861831-40862330 Neighboring gene RNA pseudouridine synthase domain containing 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9253 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6339 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9254 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9255 Neighboring gene tRNA-Ser (anticodon GCT) 4-2 Neighboring gene small nucleolar RNA U13 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:40903378-40903589 Neighboring gene RNA, 7SL, cytoplasmic 376, pseudogene Neighboring gene MPRA-validated peak2302 silencer Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:40986424-40987021 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9258 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:40987619-40988216 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:40988217-40988813 Neighboring gene RAD51 antisense RNA 1 Neighboring gene RAD51 recombinase Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:41032727-41033599 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6340 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:41046843-41047057 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9259 Neighboring gene regulator of microtubule dynamics 3

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Kinetochore scaffold 1 downregulation suppressed the development of non-small cell lung cancer by inactivating the phosphatidylinositol 3 kinase/protein kinase B (AKT)/nuclear factor-kappa B pathway.
    Title: Kinetochore scaffold 1 downregulation suppressed the development of non-small cell lung cancer by inactivating the phosphatidylinositol 3 kinase/protein kinase B (AKT)/nuclear factor-kappa B pathway.
  2. A novel KNL1 intronic splicing variant likely destabilizes the KMN complex, causing primary microcephaly.
    Title: A novel KNL1 intronic splicing variant likely destabilizes the KMN complex, causing primary microcephaly.
  3. LINC02418 promotes malignant behaviors in lung adenocarcinoma cells by sponging miR-4677-3p to upregulate KNL1 expression.
    Title: LINC02418 promotes malignant behaviors in lung adenocarcinoma cells by sponging miR-4677-3p to upregulate KNL1 expression.
  4. CASC5 is a potential tumour driving gene in lung adenocarcinoma.
    Title: CASC5 is a potential tumour driving gene in lung adenocarcinoma.
  5. [CASC5</I> Gene Expression Changes Correlate with Targeted Mutations in Leukemia].
    Title: [CASC5</I> Gene Expression Changes Correlate with Targeted Mutations in Leukemia].
  6. KNL1 protein expression was also significantly associated with poorer survival. Moreover, there was a significant correlation between KNL1 and BUB1 in colorectal cancer tissues. KNL1 plays an effective role in decreasing apoptosis and promoting the proliferation of colorectal cancer cells, suggesting that its inhibition may represent a promising therapeutic approach in patients with colorectal cancer.
    Title: Effect of KNL1 on the proliferation and apoptosis of colorectal cancer cells.
  7. KNL1 mutation is associated with Microcephaly.
    Title: Microcephaly Modeling of Kinetochore Mutation Reveals a Brain-Specific Phenotype.
  8. Data show how KNL1 binds both PP1 and microtubules. Unexpectedly, PP1 and microtubules bind KNL1 via overlapping binding sites. Co-sedimentation assays unequivocally demonstrated that microtubules and PP1 binding to KNL1 is mutually exclusive, with preferential formation of the KNL1:PP1 holoenzyme in the presence of PP1.
    Title: KNL1 Binding to PP1 and Microtubules Is Mutually Exclusive.
  9. Study demonstrates that KNL1 acts as a receptor of linear ubiquitin chains to anchor CENP-E at attached kinetochores. Thus, linear ubiquitin chains constitute a critical mechanism for chromosome congression and alignment by coupling the dynamic kinetochore microtubule motor CENP-E to the static one, the KMN network.
    Title: LUBAC controls chromosome alignment by targeting CENP-E to attached kinetochores.
  10. Mutations in the CASC5 gene were found to encode a kinetochore protein essential for mitotic cell division and to cause autosomal recessive primary microcephaly 4. (Review)
    Title: D40/KNL1/CASC5 and autosomal recessive primary microcephaly.
Submit: New GeneRIF Correction See all GeneRIFs (32)

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
Microcephaly 4, primary, autosomal recessive
MedGen: C1858516 OMIM: 604321 GeneReviews: Not available
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Variation

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See Variation Viewer (GRCh37.p13)

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

  • KIAA1570

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables microtubule binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in acrosome assembly NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in attachment of spindle microtubules to kinetochore IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in attachment of spindle microtubules to kinetochore IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cell division IEA
Inferred from Electronic Annotation
more info
  
involved_in homologous chromosome orientation in meiotic metaphase I ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in mitotic sister chromatid segregation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of meiosis I spindle assembly checkpoint ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in protein localization to kinetochore IBA
Inferred from Biological aspect of Ancestor
more info
  
acts_upstream_of_or_within protein localization to kinetochore IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of mitotic cell cycle spindle assembly checkpoint IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
part_of Knl1/Spc105 complex IDA
Inferred from Direct Assay
more info
 PubMed 
located_in acrosomal vesicle IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in kinetochore IDA
Inferred from Direct Assay
more info
 PubMed 
located_in kinetochore NAS
Non-traceable Author Statement
more info
 PubMed 
located_in nuclear body IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm TAS
Traceable Author Statement
more info
  
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
part_of outer kinetochore IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
kinetochore scaffold 1
Names
ALL1-fused gene from chromosome 15q14 protein
blinkin, bub-linking kinetochore protein
cancer susceptibility candidate 5
cancer susceptibility candidate gene 5 protein
cancer/testis antigen 29
kinetochore null 1 homolog
kinetochore-null protein 1
microcephaly, primary autosomal recessive 4
protein phosphatase 1, regulatory subunit 55

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_033114.1 RefSeqGene

    Range
    5001..75094
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_144508.5 → NP_653091.3  kinetochore scaffold 1 isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.
    Source sequence(s)
    AB046790, AC022405, AF461041, BC014306
    Consensus CDS
    CCDS42024.1
    UniProtKB/Swiss-Prot
    Q8NG31
    Related
    ENSP00000382576.3, ENST00000399668.7
    Conserved Domains (5) summary
    COG1196
    Location:1916 → 2104
    Smc; Chromosome segregation ATPase [Cell cycle control, cell division, chromosome partitioning]
    pfam19221
    Location:857 → 882
    MELT; MELT motif
    cd22817
    Location:2095 → 2205
    Knl1_RWD_N; Knl1 RWD (RING finger, WD repeat, DEAD-like helicase) N-terminal domain
    cd22892
    Location:2212 → 2310
    Knl1_RWD_C; Knl1 RWD (RING finger, WD repeat, DEAD-like helicase) C-terminal domain
    cd21853
    Location:20 → 75
    KNL1_NTD; N-terminal domain found in kinetochore scaffold 1 (KNL1) and similar proteins

  2. NM_170589.5 → NP_733468.3  kinetochore scaffold 1 isoform 1

    See identical proteins and their annotated locations for NP_733468.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AB046790, AC022405, AF173994, AF461041, BC014306
    Consensus CDS
    CCDS42023.1
    UniProtKB/Swiss-Prot
    Q8NG31, Q8NHE1, Q8WXA6, Q9HCK2, Q9NR92
    Related
    ENSP00000335463.6, ENST00000346991.9
    Conserved Domains (5) summary
    COG1196
    Location:1942 → 2130
    Smc; Chromosome segregation ATPase [Cell cycle control, cell division, chromosome partitioning]
    pfam19221
    Location:883 → 908
    MELT; MELT motif
    cd22817
    Location:2121 → 2231
    Knl1_RWD_N; Knl1 RWD (RING finger, WD repeat, DEAD-like helicase) N-terminal domain
    cd22892
    Location:2238 → 2336
    Knl1_RWD_C; Knl1 RWD (RING finger, WD repeat, DEAD-like helicase) C-terminal domain
    cd21853
    Location:20 → 75
    KNL1_NTD; N-terminal domain found in kinetochore scaffold 1 (KNL1) and similar proteins

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_000015.10 Reference GRCh38.p14 Primary Assembly

    Range
    40594249..40664342
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060939.1 Alternate T2T-CHM13v2.0

    Range
    38399974..38470044
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054378486.1 → XP_054234461.1  kinetochore scaffold 1 isoform X1

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_020380.2: Suppressed sequence

    Description
    NM_020380.2: This RefSeq record was removed by NCBI staff. Contact [email protected] for further information.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q8NG31.3 GenPept UniProtKB/Swiss-Prot:Q8NG31

Gene LinkOut

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