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

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; AllianceGenome:HGNC:18116
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: mouse all
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Genomic context

Location:: 1p35.2

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (32013868..32060850)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (31871794..31918779)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (32479469..32526451)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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?

Sam68 is a druggable vulnerability point in cancer stem cells.
Title: Sam68 is a druggable vulnerability point in cancer stem cells.
Cdk1-mediated threonine phosphorylation of Sam68 modulates its RNA binding, alternative splicing activity and cellular functions.
Title: Cdk1-mediated threonine phosphorylation of Sam68 modulates its RNA binding, alternative splicing activity and cellular functions.
The transcriptional terminator XRN2 and the RNA-binding protein Sam68 link alternative polyadenylation to cell cycle progression in prostate cancer.
Title: The transcriptional terminator XRN2 and the RNA-binding protein Sam68 link alternative polyadenylation to cell cycle progression in prostate cancer.
Decreased Expression of Sam68 Is Associated with Insulin Resistance in Granulosa Cells from PCOS Patients.
Title: Decreased Expression of Sam68 Is Associated with Insulin Resistance in Granulosa Cells from PCOS Patients.
High expression of Sam68 contributes to metastasis by regulating vimentin expression and a motile phenotype in oral squamous cell carcinoma.
Title: High expression of Sam68 contributes to metastasis by regulating vimentin expression and a motile phenotype in oral squamous cell carcinoma.
Effective targeting of breast cancer stem cells by combined inhibition of Sam68 and Rad51.
Title: Effective targeting of breast cancer stem cells by combined inhibition of Sam68 and Rad51.
Distinct RNA polymerase transcripts direct the assembly of phase-separated DBC1 nuclear bodies in different cell lines.
Title: Distinct RNA polymerase transcripts direct the assembly of phase-separated DBC1 nuclear bodies in different cell lines.
Sam68 contributes to intestinal inflammation in experimental and human colitis.
Title: Sam68 contributes to intestinal inflammation in experimental and human colitis.
Differential regulation of a placental SAM68 and sFLT1 gene pathway and the relevance to maternal vitamin D sufficiency.
Title: Differential regulation of a placental SAM68 and sFLT1 gene pathway and the relevance to maternal vitamin D sufficiency.
Antibody-based biosensor to detect oncogenic splicing factor Sam68 for the diagnosis of lung cancer.
Title: Antibody-based biosensor to detect oncogenic splicing factor Sam68 for the diagnosis of lung cancer.

Submit: New GeneRIF Correction See all GeneRIFs (98)

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

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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

SHGC-74493 (e-PCR)
- UniSTS:66903

AL009822 (e-PCR)
- UniSTS:3502

KHDRBS1_903 (e-PCR)
- UniSTS:277437

KHDRBS1_V189 (e-PCR)
- UniSTS:277437

D1S3208 (e-PCR)
- UniSTS:76798

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA binding	TAS Traceable Author Statement more info	PubMed
enables RNA binding	HDA more info	PubMed
enables RNA binding	IDA Inferred from Direct Assay more info	PubMed
enables SH2 domain binding	IDA Inferred from Direct Assay more info	PubMed
enables SH3 domain binding	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables mRNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables poly(A) binding	IBA Inferred from Biological aspect of Ancestor more info
enables poly(A) binding	IDA Inferred from Direct Assay more info	PubMed
enables poly(U) RNA binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein domain specific binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein tyrosine kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-containing complex binding	IEA Inferred from Electronic Annotation more info
enables signaling adaptor activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in G1/S transition of mitotic cell cycle	TAS Traceable Author Statement more info	PubMed
involved_in G2/M transition of mitotic cell cycle	ISS Inferred from Sequence or Structural Similarity more info
involved_in T cell receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in mRNA processing	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of DNA-templated transcription	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of RNA export from nucleus	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of translational initiation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of RNA export from nucleus	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of alternative mRNA splicing, via spliceosome	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of alternative mRNA splicing, via spliceosome	IDA Inferred from Direct Assay more info	PubMed
NOT involved_in regulation of protein stability	IDA Inferred from Direct Assay more info	PubMed
involved_in spermatogenesis	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
part_of Grb2-Sos complex	IEA Inferred from Electronic Annotation more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in membrane	HDA more info	PubMed
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
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 protein-containing complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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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)

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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)

NM_001271878.2 → NP_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/TrEMBL

B2R7B5

Related

ENSP00000417731.1, ENST00000492989.1

Conserved Domains (3) summary

pfam16274
Location:102 → 153

Qua1; Qua1 domain

pfam16568
Location:327 → 376

Sam68-YY; Tyrosine-rich domain of Sam68

cl00098
Location:152 → 218

KH-I; K homology (KH) RNA-binding domain, type I
NM_006559.3 → NP_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

D3DPP3, Q07666, Q6PJX7, Q8NB97, Q99760

UniProtKB/TrEMBL

B2R7B5

Related

ENSP00000313829.7, ENST00000327300.12

Conserved Domains (3) summary

pfam16274
Location:102 → 153

Qua1; Qua1 domain

pfam16568
Location:366 → 415

Sam68-YY; Tyrosine-rich domain of Sam68

cd22468
Location:152 → 257

KH-I_KHDRBS1; type I K homology (KH) RNA-binding domain found in KH domain-containing, RNA-binding, signal transduction-associated protein 1 (KHDRBS1) and similar proteins

RNA

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
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