PROX1 prospero homeobox 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PROX1provided by HGNC
Official Full Name: prospero homeobox 1provided by HGNC
Primary source: HGNC:HGNC:9459
See related: Ensembl:ENSG00000117707 MIM:601546
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
Summary: The protein encoded by this gene is a member of the homeobox transcription factor family. Members of this family contain a homeobox domain that consists of a 60-amino acid helix-turn-helix structure that binds DNA and RNA. The protein encoded by this gene is conserved across vertebrates and may play an essential role during development. Altered levels of this protein have been reported in cancers of different organs, such as colon, brain, blood, breast, pancreas, liver and esophagus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]
Expression: Biased expression in liver (RPKM 20.2), adrenal (RPKM 5.1) and 13 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 1q32.3

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	1	NC_000001.11 (213983239..214041510)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (214161278..214214853)

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 FunctionsWhat's a GeneRIF?

data suggest that TERT promoter mutations can enhance the promoter activity in HCC cell lines expressing PROX1 but are not the predominant mechanism of TERT upregulation in B viral HCC patients, based on the inhibition of PROX1-dependent transcriptional activation by HBx
Title: Suppression of PROX1-mediated TERT expression in hepatitis B viral hepatocellular carcinoma.
Prox1 protein expression was significantly higher in Crohn's Disease than in normal tissues. Decreased expression of Prox1 is associated with Postoperative Recurrence in Crohn's Disease. Prox1 expression could be useful as a protective factor against recurrence in Crohn's Disease patients.
Title: Decreased Expression of Prox1 Is Associated With Postoperative Recurrence in Crohn's Disease.
PROX1 expression was detected in gastric cancer tissues at various levels. PROX1 expression levels were positively correlated with cancer stage, N factor, lymphatic vascular invasion, and vascular invasion in patients with gastric cancer.
Title: PROX1 Is Associated with Cancer Progression and Prognosis in Gastric Cancer.
The present data demonstrate that the endothelial-specific and lymph endothelial-specific transcription factors SOX18 and PROX1 contribute to lymph endothelial cells retraction.
Title: 12(S)-HETE induces lymph endothelial cell retraction in vitro by upregulation of SOX18.
Prox1 is a critical transcription factor for the differentiation of myoblasts via bi-directional crosstalk with Notch1.
Title: The transcription factor Prox1 is essential for satellite cell differentiation and muscle fibre-type regulation.
PROX1 is a new prognostic biomarker for 1p19q non-codeleted high-grade astrocytomas that have progressed from pre-existing low-grade tumors and harbor IDH mutations.
Title: PROX1 is a novel pathway-specific prognostic biomarker for high-grade astrocytomas; results from independent glioblastoma cohorts stratified by age and IDH mutation status.
ERbeta in both normal and cancerous colon epithelial cells upregulates miRNA-205, which subsequently reduces PROX1 through direct interaction with its 3'UTR
Title: Estrogen receptor beta reduces colon cancer metastasis through a novel miR-205 - PROX1 mechanism.
The aim of this study was to examine the association between HHEX (rs5015480) and PROX1 (rs340874) gene polymorphisms and Gestational diabetes mellitus (GDM) .Despite these associations, PROX1 gene variants were not previously examined in women with GDM; however, our results suggest a lack of such an association.
Title: Hematopoietically expressed homeobox (HHEX) gene polymorphism (rs5015480) is associated with increased risk of gestational diabetes mellitus.
PROX1 overexpression in DAB2IP-deficient prostate cancer cells could enhance the accumulation of HIF1alpha protein by inhibiting ubiquitin pathway and then consequently induce an epithelial-mesenchymal transition response.
Title: DAB2IP regulates EMT and metastasis of prostate cancer through targeting PROX1 transcription and destabilizing HIF1α protein.
crucial promoter of hepatocellular carcinoma angiogenesis
Title: Prospero-related homeobox 1 drives angiogenesis of hepatocellular carcinoma through selectively activating interleukin-8 expression.

Submit: New GeneRIF Correction See all GeneRIFs (103)

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

NHGRI GWAS Catalog

Description
A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Combined linkage and association analyses identify a novel locus for obesity near PROX1 in Asians. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Multistage genomewide association study identifies a locus at 1q41 associated with rate of HIV-1 disease progression to clinical AIDS. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. 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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Replication interactions

Interaction	Pubs
Knockdown of prospero homeobox 1 (PROX1) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells	PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

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Circadian rythm related genes, organism-specific biosystem (from WikiPathways)
Circadian rythm related genes, organism-specific biosystemThis is currently not a pathway but a list of circadian rhythm related genes and proteins. The source for this information is the gene ontology. The genes and proteins were filtered for "circadian rh...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-76345 (e-PCR)
- UniSTS:48903

SHGC-76335 (e-PCR)
- UniSTS:12571

D1S3515 (e-PCR)
- UniSTS:33852

RH78799 (e-PCR)
- UniSTS:80708

SHGC-76346 (e-PCR)
- UniSTS:21354

PROX1_8568 (e-PCR)
- UniSTS:467846

SHGC-31006 (e-PCR)
- UniSTS:19930

Homology

Homologs of the PROX1 gene: The PROX1 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 265 organisms have orthologs with human gene PROX1
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
DBD domain binding	IPI Inferred from Physical Interaction more info	PubMed
DNA binding	IMP Inferred from Mutant Phenotype more info	PubMed
DNA-binding transcription factor activity	IC Inferred by Curator more info	PubMed
DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
DNA-binding transcription factor activity, RNA polymerase II-specific	ISM Inferred from Sequence Model more info	PubMed
DNA-binding transcription factor activity, RNA polymerase II-specific	ISS Inferred from Sequence or Structural Similarity more info
DNA-binding transcription factor activity, RNA polymerase II-specific	NAS Non-traceable Author Statement more info	PubMed
DNA-binding transcription repressor activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
LBD domain binding	IPI Inferred from Physical Interaction more info	PubMed
RNA polymerase II proximal promoter sequence-specific DNA binding	ISS Inferred from Sequence or Structural Similarity more info
nuclear receptor binding	IPI Inferred from Physical Interaction more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
transcription regulatory region DNA binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
acinar cell differentiation	IEA Inferred from Electronic Annotation more info
aorta smooth muscle tissue morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
atrial cardiac muscle tissue morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
brain development	IEP Inferred from Expression Pattern more info	PubMed
branching involved in pancreas morphogenesis	IEA Inferred from Electronic Annotation more info
cell fate determination	IEA Inferred from Electronic Annotation more info
cerebellar granule cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
circadian rhythm	IEA Inferred from Electronic Annotation more info
dentate gyrus development	ISS Inferred from Sequence or Structural Similarity more info
dorsal spinal cord development	ISS Inferred from Sequence or Structural Similarity more info	PubMed
embryonic retina morphogenesis in camera-type eye	IEP Inferred from Expression Pattern more info	PubMed
endocardium formation	ISS Inferred from Sequence or Structural Similarity more info
hepatocyte cell migration	IEA Inferred from Electronic Annotation more info
hepatocyte differentiation	IEP Inferred from Expression Pattern more info	PubMed
hepatocyte proliferation	IEA Inferred from Electronic Annotation more info
kidney development	IEP Inferred from Expression Pattern more info	PubMed
lens development in camera-type eye	IEP Inferred from Expression Pattern more info	PubMed
lens fiber cell morphogenesis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
lens fiber cell morphogenesis	IEP Inferred from Expression Pattern more info	PubMed
liver development	IEP Inferred from Expression Pattern more info	PubMed
lung development	IEP Inferred from Expression Pattern more info	PubMed
lymphangiogenesis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
lymphangiogenesis	IDA Inferred from Direct Assay more info	PubMed
lymphatic endothelial cell differentiation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
lymphatic endothelial cell differentiation	IDA Inferred from Direct Assay more info	PubMed
negative regulation of DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
negative regulation of bile acid biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info	PubMed
negative regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
negative regulation of transcription, DNA-templated	IDA Inferred from Direct Assay more info	PubMed
negative regulation of transcription, DNA-templated	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of viral genome replication	IDA Inferred from Direct Assay more info	PubMed
neural tube development	ISS Inferred from Sequence or Structural Similarity more info	PubMed
neuronal stem cell population maintenance	ISS Inferred from Sequence or Structural Similarity more info
olfactory placode formation	ISS Inferred from Sequence or Structural Similarity more info	PubMed
optic placode formation involved in camera-type eye formation	ISS Inferred from Sequence or Structural Similarity more info	PubMed
otic placode formation	ISS Inferred from Sequence or Structural Similarity more info	PubMed
pancreas development	IEP Inferred from Expression Pattern more info	PubMed
positive regulation of cell cycle	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of cell cycle checkpoint	IEA Inferred from Electronic Annotation more info
positive regulation of cell proliferation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cyclin-dependent protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
positive regulation of endothelial cell migration	IDA Inferred from Direct Assay more info	PubMed
positive regulation of endothelial cell proliferation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of forebrain neuron differentiation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of heart growth	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of neural precursor cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of sarcomere organization	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of transcription, DNA-templated	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of circadian rhythm	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of gene expression	IDA Inferred from Direct Assay more info	PubMed
regulation of transcription involved in lymphatic endothelial cell fate commitment	IMP Inferred from Mutant Phenotype more info	PubMed
response to nutrient levels	IEA Inferred from Electronic Annotation more info
retina morphogenesis in camera-type eye	ISS Inferred from Sequence or Structural Similarity more info	PubMed
skeletal muscle thin filament assembly	ISS Inferred from Sequence or Structural Similarity more info
venous blood vessel morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
ventricular cardiac muscle tissue morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
ventricular cardiac myofibril assembly	ISS Inferred from Sequence or Structural Similarity more info
ventricular septum morphogenesis	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
nucleus	IDA Inferred from Direct Assay more info	PubMed
nucleus	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: prospero homeobox protein 1

Names: homeobox prospero-like protein PROX1; prospero-related homeobox 1

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_001270616.2 → NP_001257545.1 prospero homeobox protein 1

See identical proteins and their annotated locations for NP_001257545.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript. Both variants 1 and 2 encode the same protein.

Source sequence(s)

AC011700, AL606537

Consensus CDS

CCDS31021.1

UniProtKB/Swiss-Prot

Q92786

Related

ENSP00000355925.4, ENST00000366958.8

Conserved Domains (1) summary

pfam05044
Location:579 → 730

HPD; Homeo-prospero domain
NM_002763.4 → NP_002754.2 prospero homeobox protein 1

See identical proteins and their annotated locations for NP_002754.2

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Both variants 1 and 2 encode the same protein.

Source sequence(s)

AL606537, BC024201, DA743374

Consensus CDS

CCDS31021.1

UniProtKB/Swiss-Prot

Q92786

Related

ENSP00000400694.1, ENST00000435016.2

Conserved Domains (1) summary

pfam05044
Location:579 → 730

HPD; Homeo-prospero domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

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

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000001.11 Reference GRCh38.p12 Primary Assembly

Range

213983239..214041510

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011509773.2 → XP_011508075.1 prospero homeobox protein 1 isoform X1

See identical proteins and their annotated locations for XP_011508075.1

Conserved Domains (2) summary

pfam05044
Location:579 → 731

HPD; Homeo-prospero domain

pfam09805
Location:229 → 278

Nop25; Nucleolar protein 12 (25kDa)
XM_011509771.1 → XP_011508073.1 prospero homeobox protein 1 isoform X1

See identical proteins and their annotated locations for XP_011508073.1

Conserved Domains (2) summary

pfam05044
Location:579 → 731

HPD; Homeo-prospero domain

pfam09805
Location:229 → 278

Nop25; Nucleolar protein 12 (25kDa)
XM_005273194.2 → XP_005273251.1 prospero homeobox protein 1 isoform X1

See identical proteins and their annotated locations for XP_005273251.1

Conserved Domains (2) summary

pfam05044
Location:579 → 731

HPD; Homeo-prospero domain

pfam09805
Location:229 → 278

Nop25; Nucleolar protein 12 (25kDa)
XM_005273195.4 → XP_005273252.1 prospero homeobox protein 1 isoform X1

See identical proteins and their annotated locations for XP_005273252.1

Conserved Domains (2) summary

pfam05044
Location:579 → 731

HPD; Homeo-prospero domain

pfam09805
Location:229 → 278

Nop25; Nucleolar protein 12 (25kDa)
XM_017001833.1 → XP_016857322.1 prospero homeobox protein 1 isoform X2

UniProtKB/Swiss-Prot

Q92786

Conserved Domains (1) summary

pfam05044
Location:579 → 730

HPD; Homeo-prospero domain
XM_011509772.2 → XP_011508074.1 prospero homeobox protein 1 isoform X1

See identical proteins and their annotated locations for XP_011508074.1

Conserved Domains (2) summary

pfam05044
Location:579 → 731

HPD; Homeo-prospero domain

pfam09805
Location:229 → 278

Nop25; Nucleolar protein 12 (25kDa)
XM_017001832.1 → XP_016857321.1 prospero homeobox protein 1 isoform X1

Conserved Domains (2) summary

pfam05044
Location:579 → 731

HPD; Homeo-prospero domain

pfam09805
Location:229 → 278

Nop25; Nucleolar protein 12 (25kDa)