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PRRX2 Gene

protein-coding GIFtS: 50
GCID: GC09P132427

Paired Related Homeobox 2

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disease database

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, ¹⁰fRNAdb, ¹²H-InvDB, ¹³NCBI, ¹⁴NONCODE, and/or ¹⁵RNAdb)
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Aliases
Paired Related Homeobox 2¹ ²		PRX-2² ³
PRX2² ³ ⁵		Paired Mesoderm Homeobox Protein 2²
Paired-Related Homeobox Protein 2² ³		Paired-Like Homeodomain Protein PRX2²
PMX2² ³

External Ids:	HGNC: 21338¹	Entrez Gene: 51450²	Ensembl: ENSG00000167157⁷	OMIM: 604675⁵	UniProtKB: Q99811³

Export aliases for PRRX2 gene to outside databases

Previous GC identifers: GC09P127803 GC09P129507 GC09P131467 GC09P102027

(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for PRRX2 Gene:

The DNA-associated protein encoded by this gene is a member of the paired family of homeobox proteins. Expression

is localized to proliferating fetal fibroblasts and the developing dermal layer, with downregulated expression in

adult skin. Increases in expression of this gene during fetal but not adult wound healing suggest a possible role

in mechanisms that control mammalian dermal regeneration and prevent formation of scar response to wounding. The

expression patterns provide evidence consistent with a role in fetal skin development and a possible role in

cellular proliferation. (provided by RefSeq, Jul 2008)

GeneCards Summary for PRRX2 Gene:

PRRX2 (paired related homeobox 2) is a protein-coding gene. GO annotations related to this gene include sequence-specific DNA binding and sequence-specific DNA binding transcription factor activity. An important paralog of this gene is ALX1.

UniProtKB/Swiss-Prot: PRRX2_HUMAN, Q99811

Function: May play a role in the scarless healing of cutaneous wounds during the first two trimesters of

development

Gene Wiki entry for PRRX2 Gene

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:

NC_000009.11 NT_008470.20 NC_018920.2

Regulatory elements:

Regulatory transcription factor binding sites in the PRRX2 gene promoter:
HOXA9B SRF AML1a SRF (504 AA) FOXD3 Meis-1 Meis-1b
Other transcription factors

Browse SwitchGear Promoter luciferase reporter plasmids

Search Chromatin IP Primers for PRRX2

Epigenetics:

DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat PRRX2

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 9q34.1 Ensembl cytogenetic band: 9q34.11 HGNC cytogenetic band: 9q34.11

PRRX2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
PRRX2 gene location

GeneLoc information about chromosome 9 GeneLoc Exon Structure

GeneLoc location for GC09P132427: view genomic region (about GC identifiers)

Start:	132,427,920 bp from pter	End:	132,484,953 bp from pter
Size:	57,034 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, ²neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: PRRX2_HUMAN, Q99811 (See protein sequence)

Recommended Name: Paired mesoderm homeobox protein 2

Size: 253 amino acids; 27079 Da

Developmental stage: Higher expression in fetus than in adult

Secondary accessions: Q5SZB5 Q9UIB3

Explore the universe of human proteins at neXtProt for PRRX2: NX_Q99811

Explore proteomics data for PRRX2 at MOPED

Post-translational modifications:

Modification sites at neXtProt

Modification sites at PhosphoSitePlus

See PRRX2 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

REFSEQ proteins: NP_057391.1

ENSEMBL proteins:

ENSP00000361547

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(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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HGNC Gene Families:

PRD: Homeoboxes / PRD class

4 InterPro protein domains:

IPR003654 OAR_dom

IPR017970 Homeobox_CS

IPR001356 Homeobox_dom

IPR009057 Homeodomain-like

Graphical View of Domain Structure for InterPro Entry Q99811

ProtoNet protein and cluster: Q99811

2 Blocks protein domains:

IPB000047 Lambda and other repressor helix-turn-helix signature

IPB003654 Paired-like homeodomain protein

UniProtKB/Swiss-Prot: PRRX2_HUMAN, Q99811

Similarity: Belongs to the paired homeobox family

Similarity: Contains 1 homeobox DNA-binding domain

Find genes that share domains with PRRX2 About GenesLikeMe

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Molecular Function:

UniProtKB/Swiss-Prot Summary: PRRX2_HUMAN, Q99811

Function: May play a role in the scarless healing of cutaneous wounds during the first two trimesters of

development

Gene Ontology (GO): 3 molecular function terms: About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0003677	DNA binding	--	--
GO:0003700	sequence-specific DNA binding transcription factor activity	NAS	11063257
GO:0043565	sequence-specific DNA binding	IEA	--

Find genes that share ontologies with PRRX2 About GenesLikeMe

Phenotypes:
15 MGI mutant phenotypes (inferred from 2 alleles) (MGI details for Prrx2):

behavior/neurological	cardiovascular system	craniofacial	digestive/alimentary	embryogenesis
growth/size/body	hearing/vestibular/ear	homeostasis/metabolism	limbs/digits/tail	mortality/aging
nervous system	normal	respiratory system	skeleton	vision/eye

Find genes that share phenotypes with PRRX2 About GenesLikeMe

Animal Models:
MGI mouse knock-out Prrx2^tm1Mjk for PRRX2

genOway: Develop your customized and physiologically relevant rodent model for PRRX2

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In Situ Assay
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(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Subcellular locations from UniProtKB/Swiss-Prot

PRRX2_HUMAN, Q99811: Nucleus (By similarity)

Subcellular locations from COMPARTMENTS:

Compartment	Confidence
nucleus	5

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Gene Ontology (GO): 2 cellular component terms: About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000228	nuclear chromosome	--	--
GO:0005634	nucleus	IEA	--

Find genes that share ontologies with PRRX2 About GenesLikeMe

(SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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Custom Pathway & Disease-focused RT² Profiler PCR Arrays for PRRX2
Interactions:

Search GeneGlobe Interaction Network for PRRX2

STRING Interaction Network Preview (showing 4 interactants - click image to see more details)

4 Interacting proteins for PRRX2 (Q99811³ ENSP00000361547⁴) via UniProtKB, MINT, STRING, and/or I2D

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
SOX10	P56693³, ENSP00000354130⁴	I2D: score=1 STRING: ENSP00000354130
IFI16	ENSP00000357113⁴	STRING: ENSP00000357113
MNDA	ENSP00000357123⁴	STRING: ENSP00000357123
CHEK2	ENSP00000372023⁴	STRING: ENSP00000372023

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Gene Ontology (GO): Selected biological process terms (see all 10): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0002053	positive regulation of mesenchymal cell proliferation	IEA	--
GO:0006355	regulation of transcription, DNA-templated	NAS	9665387
GO:0030326	embryonic limb morphogenesis	IEA	--
GO:0042472	inner ear morphogenesis	IEA	--
GO:0042474	middle ear morphogenesis	IEA	--

Find genes that share ontologies with PRRX2 About GenesLikeMe

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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Browse Small Molecules at EMD Millipore

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Browse Tocris compounds for PRRX2

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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REFSEQ mRNAs for PRRX2 gene:

NM_016307.3

Unigene Cluster for PRRX2:

Paired related homeobox 2

Hs.660115 [show with all ESTs]

Unigene Representative Sequence: BM909706

1 Ensembl transcript including schematic representation, and UCSC links where relevant:

ENST00000372469(uc004byh.3)

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Additional mRNA sequence:

AF061970.1 BC014645.1 U81600.1

2 DOTS entries:

DT.203595 DT.121156198

Selected AceView cDNA sequences (see all 43):

BM694729 AI917607 BX097188 NM_016307 AI821507 BC014645 AI923085 BF939198

AI420043 AA548667 AI674514 BE645185 BU731241 BM716252 AI203915 AI751739

AI808278 AW167940 AI697307 BM800161 U81600 BG055248 BU624928 AI936570

GeneLoc Exon Structure

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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PRRX2 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>^2/3
CGAP TAG: GCCAACAGCA

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PRRX2 expression in embryonic tissues and stem cells About this table

Data from LifeMap, the Embryonic Development and Stem Cells Database
selected tissues (see all 17) fully expand


Fibroblasts (Uncategorized) fully expand to see all 10 entries
Human Dermal Fibroblasts-adult (HDF-a)

Dermis (Integumentary System) fully expand to see all 5 entries
Human Dermal Fibroblasts-adult (HDF-a)

Bone (Muscoskeletal System) fully expand to see all 4 entries
Mandibular Process
HyStem+BMP4-induced SK11 cells

Head Mesenchyme (Muscoskeletal System) fully expand to see all 4 entries
Dental Mesenchymal Cells Branchial Arch 1
Branchial Arch 1

Cartilage (Muscoskeletal System) fully expand to see all 3 entries
HyStem+BMP4-induced E15 cells

PRRX2 Protein expression data from MOPED¹, PaxDb² and MaxQB³:

About this image

PRRX2 Protein Expression

SOURCE GeneReport for Unigene cluster: Hs.660115

UniProtKB/Swiss-Prot: PRRX2_HUMAN, Q99811

Tissue specificity: In fetal skin, highest expression found in cells of mesodermal origin within the dermal

papilla of the developing hair shaft. Not detected in epidermis or dermis. In adult skin, weakly expressed within

the basal layers of the epidermis. Not expressed in dermis

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In Situ
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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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This gene was present in the common ancestor of animals.

Orthologs for PRRX2 gene from Selected species (see all 10) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Prrx2^{1 , 5}	paired related homeobox 2^{1, 5}	85.09(n)¹ 92.28(a)¹		2 (21.74 cM)⁵ 20204¹ NM_009116.2¹ NP_033142.2¹ 30834972⁵
chicken (Gallus gallus)	Aves	PRRX2¹	paired related homeobox 2	78.44(n) 86.24(a)		396314 XM_415476.4 XP_415476.3
tropical clawed frog (Xenopus tropicalis)	Amphibia	prrx2¹	paired related homeobox 2	67.28(n) 67.43(a)		100488907 XM_002940757.2 XP_002940803.1
zebrafish (Danio rerio)	Actinopterygii	phox2ba⁶	paired-like homeobox 2ba	36(a)	many ↔ many	1(17816221-17821852) ENSDARG00000075330
fruit fly (Drosophila melanogaster)	Insecta	CG9876⁶	--	29(a)	1 → many	2R(18977626-18981785)

ENSEMBL Gene Tree for PRRX2 (if available)
TreeFam Gene Tree for PRRX2 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
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Paralogs for PRRX2 gene

ALX1² PHOX2B² ARX² RAX² DRGX² SHOX2² PRRX1² PHOX2A²

ALX4² ISX² RAX2² ALX3² SHOX² OTP²

10 SIMAP similar genes for PRRX2 using alignment to 1 protein entry: PRRX2_HUMAN:

PRRX1 PHOX2A SHOX2 POU6F1 PHOX2B RAX

RAX2 PAX6 ARX OTP

Find genes that share paralogs with PRRX2 About GenesLikeMe

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, ⁴UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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SNP ID	Valid	Clinical significance	Chr 9 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs139917922^1,2	C	--	132425940(+)	`GTAGTA/GGCCCT`	1	--	us2k¹		0	--	--	--	--
rs7864717^1,2	C,F	--	132426059(+)	`ACTGGC/TGCCTC`	1	--	us2k¹		1		WA	118
rs149409904^1,2		--	132426160(+)	`CACCTA/GCACGG`	1	--	us2k¹		0	--	--	--	--
rs10739756^1,2	C,A,H	--	132426231(+)	`TATTTT/AATTTA`	1	--	us2k¹		9		NA WA CSA EA	371
rs181780915^1,2		--	132426242(+)	`ATTTAC/TATATA`	1	--	us2k¹		0	--	--	--	--
rs186163819^1,2		--	132426256(+)	`TTTGAA/GATGGA`	1	--	us2k¹		0	--	--	--	--
rs190930649^1,2		--	132426327(+)	`CGCCTC/TCCAGG`	1	--	us2k¹		0	--	--	--	--
rs147497339^1,2		--	132426382(+)	`CAGGCA/GCCTGC`	1	--	us2k¹		0	--	--	--	--
rs147854305^1,2		--	132426411(+)	`TTTTTA/TATTAT`	1	--	us2k¹		0	--	--	--	--
rs13291228^1,2	C,F	--	132426773(+)	`GGCCAA/GCATGG`	1	--	us2k¹		7		NA WA CSA EA	131

HapMap Linkage Disequilibrium report for PRRX2 (132427920 - 132484953 bp)

Structural Variations
Database of Genomic Variants (DGV) 8 variations for PRRX2: About this table

Variant ID	Type	Subtype	PubMed ID
nsv893919	CNV	Loss	21882294
nsv466589	CNV	Loss	19166990
nsv469901	CNV	Loss	18288195
nsv893924	CNV	Loss	21882294
nsv893909	CNV	Loss	21882294
nsv893927	CNV	Loss	21882294
nsv893925	CNV	Gain	21882294
nsv893926	CNV	Gain	21882294

Site Specific Mutation Identification with PCR Assays

SeqTarget long-range PCR primers for resequencing PRRX2

DNA2.0 Custom Variant and Variant Library Synthesis for PRRX2

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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OMIM gene information: 604675 OMIM disorders: --

Find genes that share disorders with PRRX2 About GenesLikeMe

Genetic Association Database (GAD): PRRX2
Human Genome Epidemiology (HuGE) Navigator: PRRX2 (1 document)

Export disorders for PRRX2 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
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PubMed articles for PRRX2 gene, integrated from 10 sources (see all 16):
(articles sorted by number of sources associating them with PRRX2)

Utopia: connect your pdf to the dynamic
world of online information

Human PRRX1 and PRRX2 genes: cloning, expression, genomic localization, and exclusion as disease genes for Nager syndrome. (PubMed id 11063257)^{1, 2, 3, 9} Norris R.A.... Kern M.J. (Mamm. Genome 2000)
Modulation of the human homeobox genes PRX-2 and HOXB13 in scarless fetal wounds. (PubMed id 9665387)^{1, 2, 9} Stelnicki E.J....Largman C. (J. Invest. Dermatol. 1998)
Web-based, participant-driven studies yield novel genetic associations for common traits. (PubMed id 20585627)^{1, 4} Eriksson N....Mountain J. (PLoS Genet. 2010)
Maternal genes and facial clefts in offspring: a comprehensive search for genetic associations in two population-based cleft studies from Scandinavia. (PubMed id 20634891)^{1, 4} Jugessur A....Murray J.C. (PLoS ONE 2010)
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)^{1, 2} Gerhard D.S.... Malek J. (Genome Res. 2004)
GeneChip microarrays facilitate identification of Protease Nexin-1 as a target gene of the Prx2 (S8) homeoprotein. (PubMed id 12713735)^{1, 9} Scott K.K....Kern M.J. (DNA Cell Biol. 2003)
Model for the exceptional reactivity of peroxiredoxins 2 and 3 with hydrogen peroxide: a kinetic and computational study. (PubMed id 21385867)¹ Nagy P....Winterbourn C.C. (J. Biol. Chem. 2011)
Oxidation of Prx2 and phosphorylation of GRP58 by angiotensin II in human coronary smooth muscle cells identified by 2D-DIGE analysis. (PubMed id 17964282)¹ Tokutomi Y....Kim-Mitsuyama S. (Biochem. Biophys. Res. Commun. 2007)
The high-mobility-group domain of Sox proteins interacts with DNA-binding domains of many transcription factors. (PubMed id 16582099)¹ WissmA1ller S....Wegner M. (Nucleic Acids Res. 2006)
A new translocation t(9;11)(q34;p15) fuses NUP98 to a novel homeobox partner gene, PRRX2, in a therapy-related acute myeloid leukemia. (PubMed id 15496970)¹ Gervais C.... Lessard M. (Leukemia 2005)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Free Text

Query String		PubMed OMIM NCBI Bookshelf
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(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 51450	HGNC: 21338	AceView: PRRX2	Ensembl:ENSG00000167157	euGenes: HUgn51450
ECgene: PRRX2	H-InvDB: PRRX2

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for PRRX2	Pharmacogenomics, SNPs, Pathways
ATLAS Chromosomes in Cancer entry for PRRX2	Genetics and Cytogenetics in Oncology and Haematology

Intellectual Property for PRRX2 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for PRRX2 gene:
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