SF3B4 splicing factor 3b subunit 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SF3B4provided by HGNC
Official Full Name: splicing factor 3b subunit 4provided by HGNC
Primary source: HGNC:HGNC:10771
See related: Ensembl:ENSG00000143368 MIM:605593
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: AFD1; Hsh49; SAP49; SF3b49
Summary: This gene encodes one of four subunits of the splicing factor 3B. The protein encoded by this gene cross-links to a region in the pre-mRNA immediately upstream of the branchpoint sequence in pre-mRNA in the prespliceosomal complex A. It also may be involved in the assembly of the B, C and E spliceosomal complexes. In addition to RNA-binding activity, this protein interacts directly and highly specifically with subunit 2 of the splicing factor 3B. This protein contains two N-terminal RNA-recognition motifs (RRMs), consistent with the observation that it binds directly to pre-mRNA. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in testis (RPKM 26.0), bone marrow (RPKM 20.1) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 1q21.2

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	1	NC_000001.11 (149923317..149928252, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (149895209..149901449, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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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 FunctionsWhat's a GeneRIF?

SF3B4 indicates early-stage hepatocellular carcinoma in precancerous lesions, and also functions as an early-stage driver in the development of liver cancer.
Title: SF3B4 as an early-stage diagnostic marker and driver of hepatocellular carcinoma.
We identified two heterozygous frameshift mutations in the SF3B4 gene in three of the four fetuses investigated. The observed mutation was apparently de novo in one fetus for whom parental DNA was available. Thus, Acrofacial dysostosis syndrome of Rodriguez is an autosomal dominant condition and the recurrences identified in the initial report were likely due to gonadal mosaicism.
Title: Rodriguez acrofacial dysostosis is caused by apparently de novo heterozygous mutations in the SF3B4 gene.
A novel synonymous variant within exon 3 of the SF3B4 gene was identified in three members of a family affected by Nager syndrome.
Title: A synonymous splicing mutation in the SF3B4 gene segregates in a family with highly variable Nager syndrome.
Chemical shift mapping showed that the SF3b145 fragment spanning residues 598-631 interacts with SF3b49 RRM1, which adopts a canonical RRM fold with a topology of beta1-alpha1-beta2-beta3-alpha2-beta4.
Title: Solution structure of the first RNA recognition motif domain of human spliceosomal protein SF3b49 and its mode of interaction with a SF3b145 fragment.
SF3B4 mutations identified in Rodriguez Acrofacial Dysostosis patients disrupted mRNA splicing and reduced expression of DLX5, DLX6, SOX9, and SOX6 in cultured chondrocytes.
Title: Altered mRNA Splicing, Chondrocyte Gene Expression and Abnormal Skeletal Development due to SF3B4 Mutations in Rodriguez Acrofacial Dysostosis.
splicing factor 3b subunit 4 was found to inhibit the activity of signal transducer and activator of transcription 3 signaling via downregulating the phosphorylation of signal transducer and activator of transcription 3 on a tyrosine residue at position 705.
Title: SF3B4 is decreased in pancreatic cancer and inhibits the growth and migration of cancer cells.
Overexpression of SF3B4, that is due to DNA copy number increase, is suggested to play a role in progression of HCC
Title: Increased Copy Number of the Gene Encoding SF3B4 Indicates Poor Prognosis in Hepatocellular Carcinoma.
High SF3B4 expression is associated with hepatocellular carcinoma.
Title: Meta-analysis of gene expression profiles indicates genes in spliceosome pathway are up-regulated in hepatocellular carcinoma (HCC).
SF3B4 haploinsufficiency confirmed as the major cause of Nager syndrome.
Title: Nager syndrome: confirmation of SF3B4 haploinsufficiency as the major cause.
SF3B4 mutation is associated with Nager syndrome.
Title: Clinical and mutation data in 12 patients with the clinical diagnosis of Nager syndrome.

Submit: New GeneRIF Correction See all GeneRIFs (15)

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
Nager syndrome MedGen: C0265245 OMIM: 154400 GeneReviews: Not available	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated (2014-07-17) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated (2014-07-17) ClinGen Genome Curation PagePubMed

NHGRI GWAS Catalog

Description
A novel common variant in DCST2 is associated with length in early life and height in adulthood. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Hundreds of variants clustered in genomic loci and biological pathways affect human height. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Many sequence variants affecting diversity of adult human height. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

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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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Tandem affinity purification and mass spectrometry analysis identify 49kDa subunit 4 of splicing factor 3b (SF3B4), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
Gag-Pol	gag-pol	Tandem affinity purification and mass spectrometry analysis identify 49kDa subunit 4 of splicing factor 3b (SF3B4), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
Nef	nef	Tandem affinity purification and mass spectrometry analysis identify 49kDa subunit 4 of splicing factor 3b (SF3B4), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
Pr55(Gag)	gag	Tandem affinity purification and mass spectrometry analysis identify 49kDa subunit 4 of splicing factor 3b (SF3B4), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
Vpr	vpr	Interaction of HIV-1 Vpr with SAP145 inhibits SAP145-SAP49 complex formation	PubMed
	vpr	HIV-1 Vpr induces checkpoint activation and G2 arrest by binding to the CUS1 domain of SAP145 and interfering with the functions of the SAP145 and SAP49 proteins, two subunits of the multimeric splicing factor 3b (SF3b)	PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

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Gene Expression, organism-specific biosystem (from REACTOME)
Gene Expression, organism-specific biosystemGene Expression covers the pathways by which genomic DNA is transcribed to yield RNA, the regulation of these transcription processes, and the pathways by which newly-made RNA Transcripts are process...
Processing of Capped Intron-Containing Pre-mRNA, organism-specific biosystem (from REACTOME)
Processing of Capped Intron-Containing Pre-mRNA, organism-specific biosystemCo-transcriptional pre-mRNA splicing is not obligatory. Pre-mRNA splicing begins co-transcriptionally and often continues post-transcriptionally. Human genes contain an average of nine introns per ge...
Spliceosome, organism-specific biosystem (from KEGG)
Spliceosome, organism-specific biosystemAfter transcription, eukaryotic mRNA precursors contain protein-coding exons and noncoding introns. In the following splicing, introns are excised and exons are joined by a macromolecular complex, th...
Spliceosome, conserved biosystem (from KEGG)
Spliceosome, conserved biosystemAfter transcription, eukaryotic mRNA precursors contain protein-coding exons and noncoding introns. In the following splicing, introns are excised and exons are joined by a macromolecular complex, th...
Spliceosome, U2-snRNP, organism-specific biosystem (from KEGG)
Spliceosome, U2-snRNP, organism-specific biosystemStructural complex; Genetic information processing; Spliceosome
Spliceosome, U2-snRNP, conserved biosystem (from KEGG)
Spliceosome, U2-snRNP, conserved biosystemStructural complex; Genetic information processing; Spliceosome
mRNA Processing, organism-specific biosystem (from WikiPathways)
mRNA Processing, organism-specific biosystemThis process describes the conversion of precursor messenger RNA into mature messenger RNA (mRNA). The pre-mRNA molecule undergoes three main modifications. These modifications are 5' capping, 3' po...
mRNA Splicing, organism-specific biosystem (from REACTOME)
mRNA Splicing, organism-specific biosystemThe process in which excision of introns from the primary transcript of messenger RNA (mRNA) is followed by ligation of the two exon termini exposed by removal of each intron, is called mRNA splicing...
mRNA Splicing - Major Pathway, organism-specific biosystem (from REACTOME)
mRNA Splicing - Major Pathway, organism-specific biosystemThe splicing of pre-mRNA occurs within a large, very dynamic complex, designated the 'spliceosome'. The 50-60S spliceosomes are estimated to be 40-60 nm in diameter, and have molecular weights in the...
mRNA Splicing - Minor Pathway, organism-specific biosystem (from REACTOME)
mRNA Splicing - Minor Pathway, organism-specific biosystemThe splicing of a subset of pre-mRNA introns occurs by a second pathway, designated the AT-AC or U12-dependent splicing pathway. AT-AC introns have highly conserved, non-canonical splice sites that ...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH36569 (e-PCR)
- UniSTS:34638

PMC193924P1 (e-PCR)
- UniSTS:271763

RH69043 (e-PCR)
- UniSTS:76998

Homology

Homologs of the SF3B4 gene: The SF3B4 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, and zebrafish.
Orthologs from Annotation Pipeline: 230 organisms have orthologs with human gene SF3B4
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
RNA binding	HDA more info	PubMed
RNA binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
RNA splicing	TAS Traceable Author Statement more info	PubMed
RNA splicing, via transesterification reactions	TAS Traceable Author Statement more info	PubMed
mRNA processing	TAS Traceable Author Statement more info	PubMed
mRNA splicing, via spliceosome	IC Inferred by Curator more info	PubMed
mRNA splicing, via spliceosome	IDA Inferred from Direct Assay more info	PubMed
mRNA splicing, via spliceosome	TAS Traceable Author Statement more info
positive regulation of mRNA splicing, via spliceosome	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Component	Evidence Code	Pubs
U12-type spliceosomal complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed
U12-type spliceosomal complex	IDA Inferred from Direct Assay more info	PubMed
U2-type precatalytic spliceosome	IDA Inferred from Direct Assay more info	PubMed
nucleolus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
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
ribonucleoprotein complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed
spliceosomal complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed
spliceosomal complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: splicing factor 3B subunit 4

Names: SAP 49; SF3b50; pre-mRNA-splicing factor SF3b 49 kDa subunit; spliceosomal protein; spliceosome-associated protein (U2 snRNP); spliceosome-associated protein 49; splicing factor 3b, subunit 4, 49kD; splicing factor 3b, subunit 4, 49kDa

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

NG_032777.1 RefSeqGene

Range

5001..9936

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_005850.5 → NP_005841.1 splicing factor 3B subunit 4

See identical proteins and their annotated locations for NP_005841.1

Status: REVIEWED

Source sequence(s)

AI925089, BC004273, DA535996

Consensus CDS

CCDS72900.1

UniProtKB/Swiss-Prot

Q15427

UniProtKB/TrEMBL

B3KUJ0

Related

ENSP00000271628.8, ENST00000271628.8

Conserved Domains (2) summary

cd12334
Location:15 → 88

RRM1_SF3B4; RNA recognition motif 1 in splicing factor 3B subunit 4 (SF3B4) and similar proteins

cd12335
Location:99 → 181

RRM2_SF3B4; RNA recognition motif 2 in splicing factor 3B subunit 4 (SF3B4) and similar proteins