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7  structures 521  species 0  interactions 7364  sequences 53  architectures

Family: PAX (PF00292)

Summary: 'Paired box' domain

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Pax genes". More...

Pax genes Edit Wikipedia article

Paired domain
PDB 1mdm EBI.jpg
PAX5 bound to DNA (PDB: 1mdm​).
Identifiers
SymbolPAX
PfamPF00292
InterProIPR001523
PROSITEPDOC00034
CATH1pdn
SCOP21pdn / SCOPe / SUPFAM
CDDcd00131

In evolutionary developmental biology, Paired box (Pax) genes are a family of genes coding for tissue specific transcription factors containing an N-terminal paired domain and usually a partial, or in the case of four family members (PAX3, PAX4, PAX6 and PAX7),[1] a complete homeodomain to the C-terminus. An octapeptide as well as a Pro-Ser-Thr-rich C terminus may also be present.[2] Pax proteins are important in early animal development for the specification of specific tissues, as well as during epimorphic limb regeneration in animals capable of such.

The paired domain was initially described in 1987 as the "paired box" in the Drosophila protein paired (prd; P06601).[3][4]

Groups

Within the mammalian family, there are four well defined groups of Pax genes.

  • Pax group 1 (Pax 1 and 9),
  • Pax group 2 (Pax 2, 5 and 8),
  • Pax group 3 (Pax 3 and 7) and
  • Pax group 4 (Pax 4 and 6).

Two more families, Pox-neuro and Pax-α/β, exist in basal bilaterian species.[5][6] Orthologous genes exist throughout the Metazoa, including extensive study of the ectopic expression in Drosophila using murine Pax6.[7] The two rounds of whole-genome duplications in vertebrate evolution is responsible for the creation of as many as 4 paralogs for each Pax protein.[8]

Members

  • PAX1 has been identified in mice with the development of vertebrate and embryo segmentation, and some evidence this is also true in humans. It transcribes a 440 amino acid protein from 4 exons and 1,323bps in humans.
  • PAX2 has been identified with kidney and optic nerve development. It transcribes a 417 amino acid protein from 11 exons and 4,261 bps in humans. Mutation of PAX2 in humans has been associated with renal-coloboma syndrome as well as oligomeganephronia.[9]
  • PAX3 has been identified with ear, eye and facial development. It transcribes a 479 amino acid protein in humans. Mutations in it can cause Waardenburg syndrome. PAX3 is frequently expressed in melanomas[10] and contributes to tumor cell survival.[11]
  • PAX4 has been identified with pancreatic islet beta cells. It transcribes a 350 amino acid protein from 9 exons and 2,010 bps in humans.
  • PAX5 has been identified with neural and spermatogenesis development and b-cell differentiation. It transcribes a 391 amino acid protein from 10 exons and 3,644bps in humans.
  • PAX6 (eyeless) is the most researched and appears throughout the literature as a "master control" gene for the development of eyes and sensory organs, certain neural and epidermal tissues as well as other homologous structures, usually derived from ectodermal tissues.
  • PAX7 has been possibly associated with myogenesis. It transcribes a protein of 520 amino acids from 8 exons and 2,260bps in humans. PAX7 directs postnatal renewal and propagation of myogenic satellite cells but not for the specification.[12]
  • PAX8 has been associated with thyroid specific expression. It transcribes a protein of 451 amino acids from 11 exons and 2,526bps in humans.
  • PAX9 has found to be associated with a number of organ and other skeletal developments, particularly teeth. It transcribes a protein of 341 amino acids from 4 exons and 1,644bps in humans.

See also

References

  1. ^ Chi, N; Epstein, JA (January 2002). "Getting your Pax straight: Pax proteins in development and disease". Trends in Genetics. 18 (1): 41–7. doi:10.1016/s0168-9525(01)02594-x. PMID 11750700.
  2. ^ Eberhard, D; Jiménez, G; Heavey, B; Busslinger, M (15 May 2000). "Transcriptional repression by Pax5 (BSAP) through interaction with corepressors of the Groucho family". The EMBO Journal. 19 (10): 2292–303. doi:10.1093/emboj/19.10.2292. PMC 384353. PMID 10811620.
  3. ^ Bopp, D; Burri, M; Baumgartner, S; Frigerio, G; Noll, M (26 December 1986). "Conservation of a large protein domain in the segmentation gene paired and in functionally related genes of Drosophila". Cell. 47 (6): 1033–40. doi:10.1016/0092-8674(86)90818-4. PMID 2877747. S2CID 21943167.
  4. ^ Baumgartner, S; Bopp, D; Burri, M; Noll, M (December 1987). "Structure of two genes at the gooseberry locus related to the paired gene and their spatial expression during Drosophila embryogenesis". Genes & Development. 1 (10): 1247–67. doi:10.1101/gad.1.10.1247. PMID 3123319.
  5. ^ Navet, S; Buresi, A; Baratte, S; Andouche, A; Bonnaud-Ponticelli, L; Bassaglia, Y (2017). "The Pax gene family: Highlights from cephalopods". PLOS ONE. 12 (3): e0172719. Bibcode:2017PLoSO..1272719N. doi:10.1371/journal.pone.0172719. PMC 5333810. PMID 28253300.
  6. ^ Franke, FA; Schumann, I; Hering, L; Mayer, G (2015). "Phylogenetic analysis and expression patterns of Pax genes in the onychophoran Euperipatoides rowelli reveal a novel bilaterian Pax subfamily". Evolution & Development. 17 (1): 3–20. doi:10.1111/ede.12110. PMID 25627710. S2CID 205095304.
  7. ^ Gehring WJ, Ikeo K (September 1999). "Pax 6: mastering eye morphogenesis and eye evolution". Trends in Genetics. 15 (9): 371–7. doi:10.1016/S0168-9525(99)01776-X. PMID 10461206.
  8. ^ Ravi V, Bhatia S, Gautier P, Loosli F, Tay BH, Tay A, Murdoch E, Coutinho P, van Heyningen V, Brenner S, Venkatesh B, Kleinjan DA (2013). "Sequencing of Pax6 loci from the elephant shark reveals a family of Pax6 genes in vertebrate genomes, forged by ancient duplications and divergences". PLOS Genetics. 9 (1): e1003177. doi:10.1371/journal.pgen.1003177. PMC 3554528. PMID 23359656.
  9. ^ Online Mendelian Inheritance in Man (OMIM): 167409
  10. ^ Medic S, Ziman M (April 2010). Soyer, H. Peter (ed.). "PAX3 Expression in Normal Skin Melanocytes and Melanocytic Lesions (Naevi and Melanomas)". PLOS ONE. 5 (4): e9977. Bibcode:2010PLoSO...5.9977M. doi:10.1371/journal.pone.0009977. PMC 2858648. PMID 20421967.
  11. ^ Scholl FA, Kamarashev J, Murmann OV, Geertsen R, Dummer R, Schäfer BW (Feb 2001). "PAX3 is expressed in human melanomas and contributes to tumor cell survival". Cancer Res. 61 (3): 823–6. PMID 11221862.
  12. ^ Oustanina, S; et al. (2004). "PAX7 directs postnatal renewal and propagation of myogenic satellite cells but not their specification". The EMBO Journal. 23 (16): 3430–3439. doi:10.1038/sj.emboj.7600346. PMC 514519. PMID 15282552.

Further reading

External links

This article incorporates text from the public domain Pfam and InterPro: IPR001523

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

'Paired box' domain Provide feedback

No Pfam abstract.

Literature references

  1. Dahl E, Koseki H, Balling R; , Bioessays 1997;19:755-765.: Pax genes and organogenesis. PUBMED:9297966 EPMC:9297966


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001523

The paired domain is an approximately 126 amino acid DNA-binding domain, which is found in eukaryotic transcription regulatory proteins involved in embryogenesis. The domain was originally described as the 'paired box' in the Drosophila protein paired (prd) [ PUBMED:2877747 , PUBMED:3123319 ]. The paired domain is generally located in the N-terminal part. An octapeptide [ PUBMED:10811620 ] and/or a homeodomain can occur C-terminal to the paired domain, as well as a Pro-Ser-Thr-rich C terminus.

Paired domain proteins can function as transcription repressors or activators. The paired domain contains three subdomains, which show functional differences in DNA-binding. The crystal structures of prd and Pax proteins show that the DNA-bound paired domain is bipartite, consisting of an N-terminal subdomain (PAI or NTD) and a C-terminal subdomain (RED or CTD), connected by a linker. PAI and RED each form a three-helical fold, with the most C-terminal helices comprising a helix-turn-helix (HTH) motif that binds the DNA major groove. In addition, the PAI subdomain encompasses an N-terminal beta-turn and beta-hairpin, also named 'wing', participating in DNA-binding. The linker can bind into the DNA minor groove. Different Pax proteins and their alternatively spliced isoforms use different (sub)domains for DNA-binding to mediate the specificity of sequence recognition [ PUBMED:11103953 , PUBMED:15148315 ].

Some proteins known to contain a paired domain:

  • Drosophila paired (prd), a segmentation pair-rule class protein.
  • Drosophila gooseberry proximal (gsb-p) and gooseberry distal (gsb-d), segmentation polarity class proteins.
  • Drosophila Pox-meso and Pox-neuro proteins.

The Pax proteins:

  • Mammalian protein Pax1, which may play a role in the formation of segmented structures in the embryo. In mouse, mutations in Pax1 produce the undulated phenotype, characterised by vertebral malformations along the entire rostro-caudal axis.
  • Mammalian protein Pax2, a probable transcription factor that may have a role in kidney cell differentiation.
  • Mammalian protein Pax3. Pax3 is expressed during early neurogenesis. In Man, defects in Pax3 are the cause of Waardenburg's syndrome (WS), an autosomal dominant combination of deafness and pigmentary disturbance.
  • Mammalian protein Pax5, also known as B-cell specific transcription factor (BSAP). Pax5 is involved in the regulation of the CD19 gene. It plays an important role in B-cell differentiation as well as neural development and spermatogenesis.
  • Mammalian protein Pax6 (oculorhombin). Pax6 is a transcription factor with important functions in eye and nasal development. In Man, defects in Pax6 are the cause of aniridia type II (AN2), an autosomal dominant disorder characterised by complete or partial absence of the iris.
  • Mammalian protein Pax8, required in thyroid development.
  • Mammalian protein Pax9. In man, defects in Pax9 cause oligodontia.
  • Zebrafish proteins Pax[Zf-a] and Pax[Zf-b].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan HTH (CL0123), which has the following description:

This family contains a diverse range of mostly DNA-binding domains that contain a helix-turn-helix motif.

The clan contains the following 381 members:

AbiEi_3_N AbiEi_4 ANAPC2 AphA_like AraR_C Arg_repressor ARID ArsR B-block_TFIIIC B5 Bac_DnaA_C Baculo_PEP_N BetR BHD_3 BLACT_WH Bot1p BrkDBD BrxA BsuBI_PstI_RE_N C_LFY_FLO CaiF_GrlA CarD_CdnL_TRCF CDC27 Cdc6_C Cdh1_DBD_1 CDT1 CDT1_C CENP-B_N Costars CPSase_L_D3 Cro Crp CSN4_RPN5_eIF3a CSN8_PSD8_EIF3K CtsR Cullin_Nedd8 CUT CUTL CvfB_WH DBD_HTH DDRGK DEP Dimerisation Dimerisation2 DNA_binding_1 DNA_meth_N DpnI_C DprA_WH DsrC DsrD DUF1016_N DUF1133 DUF1153 DUF1323 DUF134 DUF1376 DUF1441 DUF1492 DUF1495 DUF1670 DUF1804 DUF1836 DUF1870 DUF2089 DUF2250 DUF2316 DUF2513 DUF2551 DUF2582 DUF3116 DUF3161 DUF3253 DUF3489 DUF3853 DUF3860 DUF3895 DUF3908 DUF433 DUF434 DUF4364 DUF4373 DUF4423 DUF4447 DUF4777 DUF480 DUF4817 DUF5635 DUF573 DUF5805 DUF6088 DUF6262 DUF6362 DUF6432 DUF6462 DUF6471 DUF722 DUF739 DUF742 DUF937 DUF977 E2F_TDP EAP30 eIF-5_eIF-2B ELL ESCRT-II Ets EutK_C Exc F-112 FaeA Fe_dep_repr_C Fe_dep_repress FeoC FokI_D1 FokI_dom_2 Forkhead FtsK_gamma FUR GcrA GerE GntR GP3_package HARE-HTH HemN_C HNF-1_N Homeobox_KN Homeodomain Homez HPD HrcA_DNA-bdg HSF_DNA-bind HTH_1 HTH_10 HTH_11 HTH_12 HTH_13 HTH_15 HTH_16 HTH_17 HTH_18 HTH_19 HTH_20 HTH_21 HTH_22 HTH_23 HTH_24 HTH_25 HTH_26 HTH_27 HTH_28 HTH_29 HTH_3 HTH_30 HTH_31 HTH_32 HTH_33 HTH_34 HTH_35 HTH_36 HTH_37 HTH_38 HTH_39 HTH_40 HTH_41 HTH_42 HTH_43 HTH_45 HTH_46 HTH_47 HTH_48 HTH_49 HTH_5 HTH_50 HTH_51 HTH_52 HTH_53 HTH_54 HTH_55 HTH_56 HTH_57 HTH_58 HTH_59 HTH_6 HTH_60 HTH_61 HTH_7 HTH_8 HTH_9 HTH_ABP1_N HTH_AraC HTH_AsnC-type HTH_CodY HTH_Crp_2 HTH_DeoR HTH_IclR HTH_Mga HTH_micro HTH_OrfB_IS605 HTH_PafC HTH_ParB HTH_psq HTH_SUN2 HTH_Tnp_1 HTH_Tnp_1_2 HTH_Tnp_2 HTH_Tnp_4 HTH_Tnp_IS1 HTH_Tnp_IS630 HTH_Tnp_ISL3 HTH_Tnp_Mu_1 HTH_Tnp_Mu_2 HTH_Tnp_Tc3_1 HTH_Tnp_Tc3_2 HTH_Tnp_Tc5 HTH_WhiA HxlR IBD IF2_N IRF KicB KilA-N Kin17_mid KORA KorB La LacI LexA_DNA_bind Linker_histone LZ_Tnp_IS481 MADF_DNA_bdg MAGE MARF1_LOTUS MarR MarR_2 MC6 MC7 MC8 MerR MerR-DNA-bind MerR_1 MerR_2 Mga Mnd1 MogR_DNAbind Mor MotA_activ MqsA_antitoxin MRP-L20 Mrr_N MukE Myb_DNA-bind_2 Myb_DNA-bind_3 Myb_DNA-bind_4 Myb_DNA-bind_5 Myb_DNA-bind_6 Myb_DNA-bind_7 Myb_DNA-binding Neugrin NFRKB_winged NOD2_WH NUMOD1 ORC_WH_C OST-HTH P22_Cro PaaX PadR PapB PAX PCI Penicillinase_R Phage_AlpA Phage_antitermQ Phage_CI_repr Phage_CII Phage_NinH Phage_Nu1 Phage_rep_O Phage_rep_org_N Phage_terminase PheRS_DBD1 PheRS_DBD2 PheRS_DBD3 PhetRS_B1 Pou Pox_D5 PqqD PRC2_HTH_1 PUFD PuR_N Put_DNA-bind_N pXO2-72 Raf1_HTH Rap1-DNA-bind Rep_3 RepA_C RepA_N RepB RepC RepL Replic_Relax RFX_DNA_binding Ribosomal_S18 Ribosomal_S19e Ribosomal_S25 Rio2_N RNA_pol_Rpc34 RNA_pol_Rpc82 RNase_H2-Ydr279 ROQ_II ROXA-like_wH RP-C RPA RPA_C RPN6_C_helix RQC Rrf2 RTP RuvB_C S10_plectin SAC3_GANP SANT_DAMP1_like SatD SelB-wing_1 SelB-wing_2 SelB-wing_3 SgrR_N Sigma54_CBD Sigma54_DBD Sigma70_ECF Sigma70_ner Sigma70_r2 Sigma70_r3 Sigma70_r4 Sigma70_r4_2 SinI SKA1 Ski_Sno SLIDE Slx4 SMC_Nse1 SMC_ScpB SoPB_HTH SpoIIID SRP19 SRP_SPB STN1_2 Stn1_C Stork_head Sulfolobus_pRN Suv3_N Swi6_N SWIRM Tau95 TBPIP TEA Terminase_5 TetR_N TFA2_Winged_2 TFIIE_alpha TFIIE_beta TFIIF_alpha TFIIF_beta Tn7_Tnp_TnsA_C Tn916-Xis TraI_2_C Trans_reg_C TrfA TrmB tRNA_bind_2 tRNA_bind_3 Trp_repressor UPF0122 UPF0175 Vir_act_alpha_C XPA_C Xre-like-HTH YdaS_antitoxin YidB YjcQ YokU z-alpha

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(4)
Full
(7364)
Representative proteomes UniProt
(11939)
RP15
(1131)
RP35
(2480)
RP55
(5510)
RP75
(7524)
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PP/heatmap 1            

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(4)
Full
(7364)
Representative proteomes UniProt
(11939)
RP15
(1131)
RP35
(2480)
RP55
(5510)
RP75
(7524)
Alignment:
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Sequence:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(4)
Full
(7364)
Representative proteomes UniProt
(11939)
RP15
(1131)
RP35
(2480)
RP55
(5510)
RP75
(7524)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Prosite
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Finn RD
Number in seed: 4
Number in full: 7364
Average length of the domain: 119.30 aa
Average identity of full alignment: 67 %
Average coverage of the sequence by the domain: 30.02 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 22.0 22.0
Trusted cut-off 22.0 22.0
Noise cut-off 21.9 21.9
Model length: 125
Family (HMM) version: 21
Download: download the raw HMM for this family

Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

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Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the PAX domain has been found. There are 7 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A0R4IQL7 View 3D Structure Click here
A0A2R8PYI0 View 3D Structure Click here
A0JMA6 View 3D Structure Click here
C0M005 View 3D Structure Click here
D3ZRA8 View 3D Structure Click here
D4ACZ2 View 3D Structure Click here
F1LMV3 View 3D Structure Click here
F1M4W2 View 3D Structure Click here
F1Q9Q9 View 3D Structure Click here
F1Q9S0 View 3D Structure Click here
F1QGF8 View 3D Structure Click here
F1QRF4 View 3D Structure Click here
F1R139 View 3D Structure Click here
F1R840 View 3D Structure Click here
G5ED14 View 3D Structure Click here
G5ED66 View 3D Structure Click here
G5EDS1 View 3D Structure Click here
O01996 View 3D Structure Click here
O16117 View 3D Structure Click here
O18381 View 3D Structure Click here
O43316 View 3D Structure Click here
O57416 View 3D Structure Click here
O57418 View 3D Structure Click here
O73917 View 3D Structure Click here
O88436 View 3D Structure Click here
P06601 View 3D Structure Click here
P09082 View 3D Structure Click here
P09083 View 3D Structure Click here
P09084 View 3D Structure Click here
P15863 View 3D Structure Click here
P23757 View 3D Structure Click here
P23758 View 3D Structure Click here
P23759 View 3D Structure Click here
P23760 View 3D Structure Click here
P24610 View 3D Structure Click here
P26367 View 3D Structure Click here
P26630 View 3D Structure Click here
P32114 View 3D Structure Click here
P32115 View 3D Structure Click here
P47236 View 3D Structure Click here