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PANO1

January 01, 1970

PANO1 is a protein which in humans is encoded by the PANO1 gene. PANO1 is an apoptosis inducing protein that is able to regulate the function of tumor suppressor.[3] More specifically, P14ARF is a protein in which in humans is modulated by the PANO1 gene. P14ARF is known to function as a tumor suppressor.[4] When PANO1 is highly expressed in the cells, it is able to modulate p14ARF by stabilizing it and protecting it from degradation.[4] With a confidence level of 5 out of 5, PANO1 has been theorized to be expressed in the nucleolus of the cell.[5] PANO1 is an intron-less gene.[3] Intron-less genes only make up about 3% of the human genome.[6] A functional analysis of these types of genes revealed that they often have tissue-specific expression in tissues such as the nervous system and testis.[6] This kind of expression is commonly associated with neuropathies, disease, and cancer.[6] The tissue types that PANO1 has the highest expression in, are the cerebellum regions of the brain as well as pituitary and testis tissues.[7]

PANO1
Identifiers
AliasesPANO1, PANO, proapoptotic nucleolar protein 1
External IDsGeneCards: PANO1
Orthologs
SpeciesHumanMouse
Entrez

101927423

n/a

Ensembl

ENSG00000288675

n/a

UniProt

I0J062

n/a

RefSeq (mRNA)

NM_001293167

n/a

RefSeq (protein)

NP_001280096

n/a

Location (UCSC)Chr 11: 0.8 – 0.8 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

Gene edit

PANO1 is also known as Proapoptotic Nucleolar Protein 1, PANO, and Pre-mRNA-splicing Factor CW22-like. PANO1 is located on human chromosome 11 at positions 797,511-799,190 and is positioned on the + strand.[8] Its protein contains 1 exon and 215 amino acids.[3]

Transcripts and proteins edit

 
PANO1 protein model with motifs generated through IBS tool at Cuckoo Workgroup

PANO1 has one isoform, isoform 1, located in the PONAB and PANTR species.[3] These isoforms have proteins with 215 and 216 amino acids, respectively.[3] No isoforms for the human PANO1 protein could be identified. Human PANO1 protein has a molecular weight of 22.8 kb and a theoretical, isoelectric point of 12.21.[3] From an analysis of the PANO1 protein, it was observed that the protein contains a low amount of lysine and a very low amount of asparagine when compared to other human proteins.[9] The same analysis indicated that the protein does not contain any hydrophobic or transmembrane regions.[9] PANO1 contains 2 cAMP phosphorylation sites, 6 N-myristoylation sites, 4 protein kinase C phosphorylation sites, 3 bipartite nuclear localization signals as well as arginine-rich and proline-rich regions. Using PSORTII, 3 discrimination of nuclear localization signals were identified.[10] Pat4 (RRRR) at position 200, Pat7 (RRRR) at position 201 and a bipartite (RKGTPTARCLGQRTKEK) at position 35.[10] Nuclear localization signals allow proteins to be able to enter the nucleus, but many nuclear proteins possess their own.[10] PANO1 overlaps solute carrier family 25 member 22 (SLC25A22).[5] A causal link between this solute carrier, when upregulated, has been strongly associated with an osteosarcoma's ability to proliferate.[11] In addition to promoting proliferation, SLC25A22 when expressed in vitro, progressed the cell cycle and inhibited apoptosis.[11] It is curious that PANO1, an apoptosis inducer, and SLC25A22, an apoptosis inhibiter, overlap one another.

 
Predicted secondary structure of PANO1 protein generated from Phyre2 and annotated to show alpha helices as well as a beta strand

Structure edit

The structure of PANO1 is 82% disordered meaning the protein is able to move around easily.[12] The secondary structure reveals a beta strand at positions 3-9 as well as alpha helices incorporated throughout.[12]

Gene level regulation edit

Promoter edit

One promoter region was identified using Genomatix. It is located on the positive strand and is 1040 bp in length.[13] Its start site is located at 795633 and it ends at 796672.[13] It overlaps with the primary transcript which starts at 796633.[13] 440 transcription factors were identified within the promoter region.[13] To highlight some of relevance and importance to PANO1: Wilms tumor suppressor, spermatogenic zip 1 transcription factor, signal transducer and activator of transcription, pleomorphic adenoma gene, general transcription factor IIIA, stimulating protein 1, CCAAT/enhancer binding protein, GC box elements and HMG box-containing protein 1.

Expression edit

Like previously mentioned, PANO1 is detected to be most expressed in the cerebellum, pituitary and testis tissues.[7] Furthermore, NCBI Geo profiles indicated that PANO1 is highly expressed in B-lymphocytes, liposarcomas, and the testis cell lines.[14] It also appears that PANO1 is highly expressed in the androgen-sensitive LAPC-4 cell line with a rank of 97.  PANO1 is biased to being expressed in androgen sensitive cells compared to androgen insensitive cells.[14]

Transcript level regulation edit

 
Predicted 3' UTR DNA folding structure generated from Unafold program and annotated to be able to see stem loops.

A predicted 3' UTR structure was generated using Unafold and depicts predicted stem loop structures.[15] Two stem loop structures are zoomed in on.

Protein level regulation edit

A possible cleavage site was identified between amino acids 33 and 34 as depicted in the PANO1 protein model.[3] As mentioned previously, 6 N-myristoylation sites, 2 cAMP phosphorylation sites, and 4 protein kinase C phosphorylation sites are also present.[3]

Protein motif locations
Motif Location (aa)
N-myristoylation site 23-28
N-myristoylation site 33-38
N-myristoylation site 71-76
N-myristoylation site 111-116
N-myristoylation site 120-125
N-myristoylation site 186-191
cAMP phosphorylation site 35-38
cAMP phosphorylation site 136-139
protein kinase C phosphorylation site 34-36
protein kinase C phosphorylation site 40-42
protein kinase C phosphorylation site 57-59
protein kinase C phosphorylation site 191-193

Homology and evolutionary history edit

Orthologs and phylogenic tree edit

 
Phylogenic tree of PANO1 generated using date of divergence data.

PANO1 orthologs were only able to be traced back in divergence to birds. Much more closely related orthologs include primates, as well as marsupial and placental mammals.[16] Specific examples of orthologs can be seen in the table below.

Genus & species Common name Tax. group Date of divergence (MYA) Accession # Seq. length (aa) Seq. identity to HSA prot. (%) Seq. identity to HSA prot. (#/100) Seq. similarity to HSA prot. (%) n m
Homo sapiens Human human 0 XP_034607700.1 215 100 1 100 0 0
Pongo abelii Sumatran orangutan primate 15.76 XP_024111240.1 216 96.3 0.963 100 0.037 3.770186718
Sapajus apella tufted capuchin primate 43.2 XP_024111240.1 216 96.3 0.963 100 0.037 3.770186718
Hylobates moloch silvery gibbon primate 19.8 XP_032005218.1 175 95.43 0.9543 81 0.0457 4.677719156
Rhinopithecus roxellana golden monkey primate 28.21 XP_030773457.1 239 86.63 0.8663 86 0.1337 14.35240101
Callithrix jacchus white-tufted-eared marmoset primate 42.9 XP_009007032.2 268 72.5 0.725 91 0.275 32.15836241
Propithecus coquereli Coquerel's sifaka primate 74.1 XP_012507388.1 183 69.28 0.6928 71 0.3072 36.70139217
Phascolarctos cinereus koala marsupial 160 XP_020836186.1 205 28.5 0.285 0.715 125.5266099
Leptonychotes weddellii Weddell seal placental 96 XP_030893169.1 182 47.88 0.4788 70 0.5212 73.64723053
Phoca vitulina harbor seal placental 96 XP_032270736.1 264 54.55 0.5455 67 0.4545 60.60524737
Loxodonta africana African bush elephant placental 105 XP_010600675.1 204 39 0.39 85 0.61 94.16085399
Orcinus orca killer whale placental 96 XP_012391505.1 237 41.21 0.4121 91 0.5879 88.64892406
Felis catus house cat placental 96 XP_023096045.1 217 59.86 0.5986 0.4014 51.31616836
Ursus arctos horribilis grizzly bear placental 96 XP_026346196.1 290 60.34 0.6034 53 0.3966 50.51749523
Oxyura jamaicensis ruddy duck bird 312 XP_035173110.1 278 29.26 0.2926 0.7074 122.894879
Melopsittacus undulatus budgerigar bird 312 XP_033919672.1 228 28.73 0.2873 0.7127 124.7228313

Divergence edit

 
Date of divergence in millions of years vs. "m" (changes / 100 amino acids) graph comparing PANO1 to two different proteins, fibrinogen alpha as well as cytochrome c.

PANO1 was compared to two other genes, fibrinogen alpha chain as well as cytochrome C. The date of divergence as well as amino acid changes were tracked over many different species types to generate a divergence date vs. number of amino acids changes as seen to the right. PANO1 appears to diverge much more quickly than fibrinogen alpha and much more quickly than cytochrome c.

Interacting proteins edit

p14ARF is a protein that is a known tumor suppressor.[4] It does this by controlling cell proliferation and cell survival, however the mechanism for how this process is controlled/modulated remained unclear.[4] PANO1 has been identified to modulate and stabilize p14ARF by stabilizing it and protecting it from degradation in HeLa cells.[4] When PANO1 is over-expressed, as a direct result, p14ARF expression also increases.[4]

Clinical significance edit

When there is an abnormal expression of PANO1 in HeLa cells, scientists have seen a decrease in tumorigenicity in nude mice.[4] Additionally, other diseases that have been associated with PANO1 include hemochromatosis 2.[5]

References edit

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000288675 – Ensembl, May 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ a b c d e f g h "PANO1 - Proapoptotic nucleolar protein 1 - Homo sapiens (Human) - PANO1 gene & protein". www.uniprot.org. Retrieved 2021-08-01.
  4. ^ a b c d e f g Watari A, Li Y, Higashiyama S, Yutsudo M (February 2012). "A novel proapoptotic gene PANO encodes a post-translational modulator of the tumor suppressor p14ARF". Exp Cell Res. 318 (3): 187–95. doi:10.1016/j.yexcr.2011.10.019. PMID 22094112.
  5. ^ a b c "PANO1". www.genecards.org. Retrieved 2021-07-30.
  6. ^ a b c Grzybowska EA (July 2012). "Human intronless genes: functional groups, associated diseases, evolution, and mRNA processing in absence of splicing". Biochem Biophys Res Commun. 424 (1): 1–6. doi:10.1016/j.bbrc.2012.06.092. PMID 22732409.
  7. ^ a b "Human BLAT Search". genome.ucsc.edu. Retrieved 2021-08-01.
  8. ^ "GeneLoc Integrated Map for Chromosome 11: Search Results". genecards.weizmann.ac.il. Retrieved 2021-08-01.
  9. ^ a b "SAPS < Sequence Statistics < EMBL-EBI". www.ebi.ac.uk. Retrieved 2021-08-01.
  10. ^ a b c "PSORT II Prediction". psort.hgc.jp. Retrieved 2021-08-01.
  11. ^ a b Chen MW, Wu XJ (January 2018). "SLC25A22 Promotes Proliferation and Metastasis of Osteosarcoma Cells via the PTEN Signaling Pathway". Technol Cancer Res Treat. 17: 1533033818811143. doi:10.1177/1533033818811143. PMC 6259056. PMID 30482097.
  12. ^ a b "Phyre 2 Results for PANO1_phyre2". www.sbg.bio.ic.ac.uk. Retrieved 2021-08-01.
  13. ^ a b c d "Genomatix Software Suite". Genomatix.
  14. ^ a b "PANO1 - GEO Profiles - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2021-08-01.
  15. ^ "DNA folding results on 21Aug01-20-42-28 for 73.242.41.233". www.unafold.org. Retrieved 2021-08-01.
  16. ^ "Protein BLAST: search protein databases using a protein query". blast.ncbi.nlm.nih.gov. Retrieved 2021-08-01.

January 01, 1970
pano1, protein, which, humans, encoded, gene, apoptosis, inducing, protein, that, able, regulate, function, tumor, suppressor, more, specifically, p14arf, protein, which, humans, modulated, gene, p14arf, known, function, tumor, suppressor, when, highly, expres. PANO1 is a protein which in humans is encoded by the PANO1 gene PANO1 is an apoptosis inducing protein that is able to regulate the function of tumor suppressor 3 More specifically P14ARF is a protein in which in humans is modulated by the PANO1 gene P14ARF is known to function as a tumor suppressor 4 When PANO1 is highly expressed in the cells it is able to modulate p14ARF by stabilizing it and protecting it from degradation 4 With a confidence level of 5 out of 5 PANO1 has been theorized to be expressed in the nucleolus of the cell 5 PANO1 is an intron less gene 3 Intron less genes only make up about 3 of the human genome 6 A functional analysis of these types of genes revealed that they often have tissue specific expression in tissues such as the nervous system and testis 6 This kind of expression is commonly associated with neuropathies disease and cancer 6 The tissue types that PANO1 has the highest expression in are the cerebellum regions of the brain as well as pituitary and testis tissues 7 PANO1IdentifiersAliasesPANO1 PANO proapoptotic nucleolar protein 1External IDsGeneCards PANO1Gene location Human Chr Chromosome 11 human 1 Band11p15 5Start797 511 bp 1 End799 190 bp 1 RNA expression patternBgeeHumanMouse ortholog Top expressed instromal cell of endometriumpituitary glandbody of pancreasanterior pituitaryright lobe of liversuperior frontal gyrusprefrontal cortexganglionic eminencedorsolateral prefrontal cortexBrodmann area 9n aMore reference expression dataBioGPSn aOrthologsSpeciesHumanMouseEntrez101927423n aEnsemblENSG00000288675n aUniProtI0J062n aRefSeq mRNA NM 001293167n aRefSeq protein NP 001280096n aLocation UCSC Chr 11 0 8 0 8 Mbn aPubMed search 2 n aWikidataView Edit Human Contents 1 Gene 2 Transcripts and proteins 2 1 Structure 3 Gene level regulation 3 1 Promoter 3 2 Expression 4 Transcript level regulation 5 Protein level regulation 6 Homology and evolutionary history 6 1 Orthologs and phylogenic tree 6 2 Divergence 7 Interacting proteins 7 1 Clinical significance 8 ReferencesGene editPANO1 is also known as Proapoptotic Nucleolar Protein 1 PANO and Pre mRNA splicing Factor CW22 like PANO1 is located on human chromosome 11 at positions 797 511 799 190 and is positioned on the strand 8 Its protein contains 1 exon and 215 amino acids 3 Transcripts and proteins edit nbsp PANO1 protein model with motifs generated through IBS tool at Cuckoo Workgroup PANO1 has one isoform isoform 1 located in the PONAB and PANTR species 3 These isoforms have proteins with 215 and 216 amino acids respectively 3 No isoforms for the human PANO1 protein could be identified Human PANO1 protein has a molecular weight of 22 8 kb and a theoretical isoelectric point of 12 21 3 From an analysis of the PANO1 protein it was observed that the protein contains a low amount of lysine and a very low amount of asparagine when compared to other human proteins 9 The same analysis indicated that the protein does not contain any hydrophobic or transmembrane regions 9 PANO1 contains 2 cAMP phosphorylation sites 6 N myristoylation sites 4 protein kinase C phosphorylation sites 3 bipartite nuclear localization signals as well as arginine rich and proline rich regions Using PSORTII 3 discrimination of nuclear localization signals were identified 10 Pat4 RRRR at position 200 Pat7 RRRR at position 201 and a bipartite RKGTPTARCLGQRTKEK at position 35 10 Nuclear localization signals allow proteins to be able to enter the nucleus but many nuclear proteins possess their own 10 PANO1 overlaps solute carrier family 25 member 22 SLC25A22 5 A causal link between this solute carrier when upregulated has been strongly associated with an osteosarcoma s ability to proliferate 11 In addition to promoting proliferation SLC25A22 when expressed in vitro progressed the cell cycle and inhibited apoptosis 11 It is curious that PANO1 an apoptosis inducer and SLC25A22 an apoptosis inhibiter overlap one another nbsp Predicted secondary structure of PANO1 protein generated from Phyre2 and annotated to show alpha helices as well as a beta strand Structure edit The structure of PANO1 is 82 disordered meaning the protein is able to move around easily 12 The secondary structure reveals a beta strand at positions 3 9 as well as alpha helices incorporated throughout 12 Gene level regulation editPromoter edit One promoter region was identified using Genomatix It is located on the positive strand and is 1040 bp in length 13 Its start site is located at 795633 and it ends at 796672 13 It overlaps with the primary transcript which starts at 796633 13 440 transcription factors were identified within the promoter region 13 To highlight some of relevance and importance to PANO1 Wilms tumor suppressor spermatogenic zip 1 transcription factor signal transducer and activator of transcription pleomorphic adenoma gene general transcription factor IIIA stimulating protein 1 CCAAT enhancer binding protein GC box elements and HMG box containing protein 1 Expression edit Like previously mentioned PANO1 is detected to be most expressed in the cerebellum pituitary and testis tissues 7 Furthermore NCBI Geo profiles indicated that PANO1 is highly expressed in B lymphocytes liposarcomas and the testis cell lines 14 It also appears that PANO1 is highly expressed in the androgen sensitive LAPC 4 cell line with a rank of 97 PANO1 is biased to being expressed in androgen sensitive cells compared to androgen insensitive cells 14 Transcript level regulation edit nbsp Predicted 3 UTR DNA folding structure generated from Unafold program and annotated to be able to see stem loops A predicted 3 UTR structure was generated using Unafold and depicts predicted stem loop structures 15 Two stem loop structures are zoomed in on Protein level regulation editA possible cleavage site was identified between amino acids 33 and 34 as depicted in the PANO1 protein model 3 As mentioned previously 6 N myristoylation sites 2 cAMP phosphorylation sites and 4 protein kinase C phosphorylation sites are also present 3 Protein motif locations Motif Location aa N myristoylation site 23 28 N myristoylation site 33 38 N myristoylation site 71 76 N myristoylation site 111 116 N myristoylation site 120 125 N myristoylation site 186 191 cAMP phosphorylation site 35 38 cAMP phosphorylation site 136 139 protein kinase C phosphorylation site 34 36 protein kinase C phosphorylation site 40 42 protein kinase C phosphorylation site 57 59 protein kinase C phosphorylation site 191 193Homology and evolutionary history editOrthologs and phylogenic tree edit nbsp Phylogenic tree of PANO1 generated using date of divergence data PANO1 orthologs were only able to be traced back in divergence to birds Much more closely related orthologs include primates as well as marsupial and placental mammals 16 Specific examples of orthologs can be seen in the table below Genus amp species Common name Tax group Date of divergence MYA Accession Seq length aa Seq identity to HSA prot Seq identity to HSA prot 100 Seq similarity to HSA prot n m Homo sapiens Human human 0 XP 034607700 1 215 100 1 100 0 0 Pongo abelii Sumatran orangutan primate 15 76 XP 024111240 1 216 96 3 0 963 100 0 037 3 770186718 Sapajus apella tufted capuchin primate 43 2 XP 024111240 1 216 96 3 0 963 100 0 037 3 770186718 Hylobates moloch silvery gibbon primate 19 8 XP 032005218 1 175 95 43 0 9543 81 0 0457 4 677719156 Rhinopithecus roxellana golden monkey primate 28 21 XP 030773457 1 239 86 63 0 8663 86 0 1337 14 35240101 Callithrix jacchus white tufted eared marmoset primate 42 9 XP 009007032 2 268 72 5 0 725 91 0 275 32 15836241 Propithecus coquereli Coquerel s sifaka primate 74 1 XP 012507388 1 183 69 28 0 6928 71 0 3072 36 70139217 Phascolarctos cinereus koala marsupial 160 XP 020836186 1 205 28 5 0 285 0 715 125 5266099 Leptonychotes weddellii Weddell seal placental 96 XP 030893169 1 182 47 88 0 4788 70 0 5212 73 64723053 Phoca vitulina harbor seal placental 96 XP 032270736 1 264 54 55 0 5455 67 0 4545 60 60524737 Loxodonta africana African bush elephant placental 105 XP 010600675 1 204 39 0 39 85 0 61 94 16085399 Orcinus orca killer whale placental 96 XP 012391505 1 237 41 21 0 4121 91 0 5879 88 64892406 Felis catus house cat placental 96 XP 023096045 1 217 59 86 0 5986 0 4014 51 31616836 Ursus arctos horribilis grizzly bear placental 96 XP 026346196 1 290 60 34 0 6034 53 0 3966 50 51749523 Oxyura jamaicensis ruddy duck bird 312 XP 035173110 1 278 29 26 0 2926 0 7074 122 894879 Melopsittacus undulatus budgerigar bird 312 XP 033919672 1 228 28 73 0 2873 0 7127 124 7228313 Divergence edit nbsp Date of divergence in millions of years vs m changes 100 amino acids graph comparing PANO1 to two different proteins fibrinogen alpha as well as cytochrome c PANO1 was compared to two other genes fibrinogen alpha chain as well as cytochrome C The date of divergence as well as amino acid changes were tracked over many different species types to generate a divergence date vs number of amino acids changes as seen to the right PANO1 appears to diverge much more quickly than fibrinogen alpha and much more quickly than cytochrome c Interacting proteins editp14ARF is a protein that is a known tumor suppressor 4 It does this by controlling cell proliferation and cell survival however the mechanism for how this process is controlled modulated remained unclear 4 PANO1 has been identified to modulate and stabilize p14ARF by stabilizing it and protecting it from degradation in HeLa cells 4 When PANO1 is over expressed as a direct result p14ARF expression also increases 4 Clinical significance edit When there is an abnormal expression of PANO1 in HeLa cells scientists have seen a decrease in tumorigenicity in nude mice 4 Additionally other diseases that have been associated with PANO1 include hemochromatosis 2 5 References edit a b c GRCh38 Ensembl release 89 ENSG00000288675 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine a b c d e f g h PANO1 Proapoptotic nucleolar protein 1 Homo sapiens Human PANO1 gene amp protein www uniprot org Retrieved 2021 08 01 a b c d e f g Watari A Li Y Higashiyama S Yutsudo M February 2012 A novel proapoptotic gene PANO encodes a post translational modulator of the tumor suppressor p14ARF Exp Cell Res 318 3 187 95 doi 10 1016 j yexcr 2011 10 019 PMID 22094112 a b c PANO1 www genecards org Retrieved 2021 07 30 a b c Grzybowska EA July 2012 Human intronless genes functional groups associated diseases evolution and mRNA processing in absence of splicing Biochem Biophys Res Commun 424 1 1 6 doi 10 1016 j bbrc 2012 06 092 PMID 22732409 a b Human BLAT Search genome ucsc edu Retrieved 2021 08 01 GeneLoc Integrated Map for Chromosome 11 Search Results genecards weizmann ac il Retrieved 2021 08 01 a b SAPS lt Sequence Statistics lt EMBL EBI www ebi ac uk Retrieved 2021 08 01 a b c PSORT II Prediction psort hgc jp Retrieved 2021 08 01 a b Chen MW Wu XJ January 2018 SLC25A22 Promotes Proliferation and Metastasis of Osteosarcoma Cells via the PTEN Signaling Pathway Technol Cancer Res Treat 17 1533033818811143 doi 10 1177 1533033818811143 PMC 6259056 PMID 30482097 a b Phyre 2 Results for PANO1 phyre2 www sbg bio ic ac uk Retrieved 2021 08 01 a b c d Genomatix Software Suite Genomatix a b PANO1 GEO Profiles NCBI www ncbi nlm nih gov Retrieved 2021 08 01 DNA folding results on 21Aug01 20 42 28 for 73 242 41 233 www unafold org Retrieved 2021 08 01 Protein BLAST search protein databases using a protein query blast ncbi nlm nih gov Retrieved 2021 08 01 Retrieved from https en wikipedia org w index php title PANO1 amp oldid 1196313654, wikipedia, wiki, book, books, library,

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