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KHDRBS1 KH RNA binding domain containing, signal transduction associated 1 [ Homo sapiens (human) ]

Gene ID: 10657, updated on 11-Sep-2019

Summary

Official Symbol
KHDRBS1provided by HGNC
Official Full Name
KH RNA binding domain containing, signal transduction associated 1provided by HGNC
Primary source
HGNC:HGNC:18116
See related
Ensembl:ENSG00000121774 MIM:602489
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
p62; p68; Sam68
Summary
This gene encodes a member of the K homology domain-containing, RNA-binding, signal transduction-associated protein family. The encoded protein appears to have many functions and may be involved in a variety of cellular processes, including alternative splicing, cell cycle regulation, RNA 3'-end formation, tumorigenesis, and regulation of human immunodeficiency virus gene expression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]
Expression
Ubiquitous expression in ovary (RPKM 44.4), endometrium (RPKM 41.0) and 25 other tissues See more
Orthologs

Genomic context

See KHDRBS1 in Genome Data Viewer
Location:
1p35.2
Exon count:
11
Annotation release Status Assembly Chr Location
109.20190905 current GRCh38.p13 (GCF_000001405.39) 1 NC_000001.11 (32013868..32060850)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (32479295..32526460)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene protein tyrosine phosphatase 4A2 Neighboring gene PTP4A2-KHDRBS1 intergenic CAGE-defined high expression enhancer Neighboring gene VISTA enhancer hs645 Neighboring gene Sharpr-MPRA regulatory region 15509 Neighboring gene transmembrane protein 39B Neighboring gene microRNA 5585

Genomic regions, transcripts, and products

Expression

  • 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

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

HIV-1 interactions

Replication interactions

Interaction Pubs
Knockdown of KH domain containing, RNA binding, signal transduction associated 1 (KHDRBS1) by siRNA inhibits the early stages of HIV-1 replication in 293T cells infected with VSV-G pseudotyped HIV-1 PubMed

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env Sam68deltaC inhibits HIV-1 gp120 protein synthesis by altering the association of Rev-dependent RNA with PABP. N-terminal (residues 1-28) and C-terminal (residues 262-300) domain of Sam68deltaC are required for the inhibition PubMed
Envelope surface glycoprotein gp160, precursor env Sam68deltaC inhibits HIV-1 gp160 protein synthesis by altering the association of Rev-dependent RNA with PABP. N-terminal (residues 1-28) and C-terminal (residues 262-300) domain of Sam68deltaC are required for the inhibition PubMed
Nef nef Suppression of HIV-1 Nef expression by Sam68 mutant (delta410) requires the Sam68 domain between amino acids 269 and 321. Sam68 mutant delta410 interacts with the nef mRNA 3'UTR in stress granules PubMed
Rev rev In stable Sam68 knockdown HeLa cells, HIV-1 Rev activation of RRE-mediated gene expression and HIV-1 production are inhibited due to the failure of exporting unspliced HIV-1 mRNAs to the cytoplasm, indicating Rev requires Sam68 for proper function PubMed
rev Amino acid residues 269-321 of Sam68 are required for inhibition of HIV-1 Rev function and viral replication by Sam68 dominant negative mutants lacking the nuclear localization signals PubMed
rev The GSG domain (amino acids 97-255) of Sam68 is sufficient to enhance HIV-1 3' end cleavage and gene expression. The GSG domain-mediated effects requires HIV-1 Rev and RRE PubMed
rev down-modulation of Sam68 causes nuclear retention and co-localization of Rev and CRM1, suggesting Sam68 is directly involved in the CRM1-mediated Rev nuclear export pathway and is required for Rev function PubMed
rev Sam68 dominant negative mutants inhibit Rev function resulting in sequestration of unspliced HIV-1 mRNA at perinuclear bundles PubMed
rev Sam68 promotes Rev-mediated nuclear export of HIV-1 mRNA and synergizes with Rev during this function PubMed
rev amino acids 321-410 of Sam68 are directly involved in the binding of Sam68 to the Rev nuclear export signal (NES, amino acids 75-83) PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

  • Leptin signaling pathway, organism-specific biosystem (from WikiPathways)
    Leptin signaling pathway, organism-specific biosystemLeptin is a peptide hormone mainly synthesised and secreted from adipocytes. It is also expressed in other tissues including placenta, stomach and skeletal muscle. Leptin mediates its effects by bind...
  • PTK6 Regulates Proteins Involved in RNA Processing, organism-specific biosystem (from REACTOME)
    PTK6 Regulates Proteins Involved in RNA Processing, organism-specific biosystemPTK6 binds and phosphorylates several nuclear RNA-binding proteins, including SAM68 family members (KHDRSB1, KHDRSB2 and KHDRSB3) (Derry et al. 2000, Haegebarth et al. 2004, Lukong et al. 2005) and S...
  • Signal Transduction, organism-specific biosystem (from REACTOME)
    Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
  • Signaling by PTK6, organism-specific biosystem (from REACTOME)
    Signaling by PTK6, organism-specific biosystemPTK6 (BRK) is an oncogenic non-receptor tyrosine kinase that functions downstream of ERBB2 (HER2) (Xiang et al. 2008, Peng et al. 2015) and other receptor tyrosine kinases, such as EGFR (Kamalati et ...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • FLJ34027

Gene Ontology Provided by GOA

Function Evidence Code Pubs
DNA binding TAS
Traceable Author Statement
more info
PubMed 
RNA binding HDA PubMed 
RNA binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
RNA binding IDA
Inferred from Direct Assay
more info
PubMed 
SH3 domain binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
SH3/SH2 adaptor activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
SH3/SH2 adaptor activity IPI
Inferred from Physical Interaction
more info
PubMed 
identical protein binding IDA
Inferred from Direct Assay
more info
PubMed 
identical protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
poly(A) binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
poly(A) binding IDA
Inferred from Direct Assay
more info
PubMed 
poly(U) RNA binding IDA
Inferred from Direct Assay
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein domain specific binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein-containing complex binding IEA
Inferred from Electronic Annotation
more info
 
Process Evidence Code Pubs
G1/S transition of mitotic cell cycle TAS
Traceable Author Statement
more info
PubMed 
G2/M transition of mitotic cell cycle ISS
Inferred from Sequence or Structural Similarity
more info
 
cell surface receptor signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
mRNA processing IEA
Inferred from Electronic Annotation
more info
 
negative regulation of transcription, DNA-templated ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of RNA export from nucleus IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of signal transduction IEA
Inferred from Electronic Annotation
more info
 
positive regulation of translational initiation IDA
Inferred from Direct Assay
more info
PubMed 
protein complex oligomerization IDA
Inferred from Direct Assay
more info
PubMed 
regulation of RNA export from nucleus ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of alternative mRNA splicing, via spliceosome IDA
Inferred from Direct Assay
more info
PubMed 
regulation of mRNA splicing, via spliceosome IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
NOT regulation of protein stability IDA
Inferred from Direct Assay
more info
PubMed 
spermatogenesis IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
Grb2-Sos complex IEA
Inferred from Electronic Annotation
more info
 
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 
membrane HDA PubMed 
membrane IDA
Inferred from Direct Assay
more info
PubMed 
nucleoplasm IDA
Inferred from Direct Assay
more info
 
nucleoplasm TAS
Traceable Author Statement
more info
 
nucleus IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

Preferred Names
KH domain-containing, RNA-binding, signal transduction-associated protein 1
Names
GAP-associated tyrosine phosphoprotein p62 (Sam68)
KH domain containing, RNA binding, signal transduction associated 1
p21 Ras GTPase-activating protein-associated p62
src-associated in mitosis 68 kDa protein

NCBI Reference Sequences (RefSeq)

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_001271878.2NP_001258807.1  KH domain-containing, RNA-binding, signal transduction-associated protein 1 isoform 2

    See identical proteins and their annotated locations for NP_001258807.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an in-frame exon in the coding region, compared to variant 1. The encoded isoform (2, also known as SAM68DeltaKH) is shorter, compared to isoform 1. This isoform (with a truncated KH domain) is specifically expressed in growth-arrested cells and has an antagonistic role in cell cycle progression (PMID:9013542).
    Source sequence(s)
    CA442272, CN345570, M88108, U78971
    Consensus CDS
    CCDS60067.1
    UniProtKB/Swiss-Prot
    Q07666
    Related
    ENSP00000417731.1, ENST00000492989.1
    Conserved Domains (3) summary
    pfam16274
    Location:103153
    Qua1; Qua1 domain
    pfam16568
    Location:327376
    Sam68-YY; Tyrosine-rich domain of Sam68
    cl00098
    Location:157237
    KH-I; K homology RNA-binding domain, type I. KH binds single-stranded RNA or DNA. It is found in a wide variety of proteins including ribosomal proteins, transcription factors and post-transcriptional modifiers of mRNA. There are two different KH domains that ...
  2. NM_006559.3NP_006550.1  KH domain-containing, RNA-binding, signal transduction-associated protein 1 isoform 1

    See identical proteins and their annotated locations for NP_006550.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longer isoform (1).
    Source sequence(s)
    CA442272, CN345570, M88108
    Consensus CDS
    CCDS350.1
    UniProtKB/Swiss-Prot
    Q07666
    Related
    ENSP00000313829.7, ENST00000327300.12
    Conserved Domains (3) summary
    cd02395
    Location:157276
    SF1_like-KH; Splicing factor 1 (SF1) K homology RNA-binding domain (KH). Splicing factor 1 (SF1) specifically recognizes the intron branch point sequence (BPS) UACUAAC in the pre-mRNA transcripts during spliceosome assembly. We show that the KH-QUA2 region of SF1 ...
    pfam16274
    Location:103153
    Qua1; Qua1 domain
    pfam16568
    Location:366415
    Sam68-YY; Tyrosine-rich domain of Sam68

RNA

  1. NR_073498.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) uses an alternate splice site in an internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    BC010132, CA442272, CN345570
    Related
    ENST00000307714.12
  2. NR_073499.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) uses an alternate 3' exon structure, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AK091346, CN345570, DB365017, M88108
    Related
    ENST00000484270.2

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p13 Primary Assembly

    Range
    32013868..32060850
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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