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Protein

Protein skinhead-1

Gene

skn-1

Organism
Caenorhabditis elegans
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transcription factor required to specify the fate of ventral blastomeres in the early embryo, and postembryonically for the development of the intestine. Directly regulates expression of zygotically expressed med-1 and med-2 to direct mesendoderm development (PubMed:1547503, PubMed:11463373). Required for stl-1 mRNA up-regulation in response to oxidative stress and anoxia. Required for the up-regulation of gcs-1 and several glutathione-S-transferase mRNAs in response to oxidative stress generated during pathogenic bacterial infection (PubMed:22216003). In neurons, involved in mitochondrial fusion and behavioral recovery during reoxygenation (PubMed:24385935). Required for riok-1 mRNA expression in the intestine (PubMed:25688864). Downstream of the let-60/Ras, mek-2 and pmk-1 pathway, positively regulates lifespan probably by preventing transcription of insulin-like peptides such as ins-39 (PubMed:20624915).6 Publications

GO - Molecular functioni

  • Hsp70 protein binding Source: WormBase
  • RNA polymerase II regulatory region sequence-specific DNA binding Source: WormBase
  • sequence-specific DNA binding Source: WormBase
  • transcription factor activity, sequence-specific DNA binding Source: UniProtKB

GO - Biological processi

  • cell fate specification Source: WormBase
  • determination of adult lifespan Source: WormBase
  • embryonic pattern specification Source: WormBase
  • endodermal cell fate specification Source: WormBase
  • mesendoderm development Source: WormBase
  • multicellular organism development Source: UniProtKB
  • positive regulation of cellular response to oxidative stress Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: WormBase
  • positive regulation of transcription from RNA polymerase II promoter in response to heat stress Source: WormBase
  • positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response Source: WormBase
  • regulation of translation Source: UniProtKB-KW
  • response to heat Source: WormBase
  • response to oxidative stress Source: WormBase
  • response to superoxide Source: WormBase
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator, Developmental protein

Keywords - Biological processi

Stress response, Transcription, Transcription regulation, Translation regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

SignaLinkiP34707.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein skinhead-1
Gene namesi
Name:skn-1
ORF Names:T19E7.2
OrganismiCaenorhabditis elegans
Taxonomic identifieri6239 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaNematodaChromadoreaRhabditidaRhabditoideaRhabditidaePeloderinaeCaenorhabditis
Proteomesi
  • UP000001940 Componenti: Chromosome IV

Organism-specific databases

WormBaseiT19E7.2a; CE27591; WBGene00004804; skn-1.
T19E7.2b; CE31238; WBGene00004804; skn-1.
T19E7.2c; CE31239; WBGene00004804; skn-1.

Subcellular locationi

GO - Cellular componenti

  • endoplasmic reticulum Source: WormBase
  • mitochondrion Source: WormBase
  • nucleus Source: WormBase
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

RNAi-mediated knockdown results in a severe reduction in transcription of gst-4, gst-5, gst-7 and gcs-1 mRNAs during infection by P.aeruginosa or P.faecalis (PubMed:22216003). Susceptibility to P.aeruginosa and P.faecalis is characterized by a decrease in survival rate (PubMed:22216003). Also causes a loss of transcription of riok-1 mRNA in intestine (PubMed:25688864). Reduces life span (PubMed:20624915). Moderate increase in transcription of ins-39 mRNA (PubMed:20624915).3 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi164 – 1641S → A: Abolishes phosphorylation by pmk-1. Loss of nuclear translocation and increased susceptibility in response to arsenite treatment; when associated with A-340. 1 Publication
Mutagenesisi430 – 4301S → A: Abolishes phosphorylation by pmk-1. Loss of nuclear translocation and increased susceptibility in response to arsenite treatment; when associated with A-74. 1 Publication

Chemistry

ChEMBLiCHEMBL2146298.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 623623Protein skinhead-1PRO_0000076639Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei164 – 1641Phosphoserine; by pmk-11 Publication
Modified residuei430 – 4301Phosphoserine; by pmk-11 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP34707.
PRIDEiP34707.

PTM databases

iPTMnetiP34707.

Expressioni

Tissue specificityi

Postembryonic intestinal cells.1 Publication

Developmental stagei

Expressed both maternally and zygotically.1 Publication

Gene expression databases

ExpressionAtlasiP34707. baseline.

Interactioni

Subunit structurei

Monomer.1 Publication

GO - Molecular functioni

  • Hsp70 protein binding Source: WormBase

Protein-protein interaction databases

BioGridi42465. 5 interactions.
IntActiP34707. 5 interactions.
MINTiMINT-1094083.
STRINGi6239.T19E7.2a.2.

Chemistry

BindingDBiP34707.

Structurei

Secondary structure

1
623
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi550 – 5578Combined sources
Helixi564 – 5696Combined sources
Helixi572 – 58110Combined sources
Helixi586 – 61530Combined sources
Turni616 – 6183Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1SKNX-ray2.50P540-623[»]
ProteinModelPortaliP34707.
SMRiP34707. Positions 546-619.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP34707.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni540 – 62384Basic motifBy similarityAdd
BLAST

Domaini

Alternative DNA-binding strategy due to lack of a leucine zipper dimerization segment: DNA binding domain binds to its cognate half-site, an N-terminal arm recognizes adjacent 5' AT-rich sequences in the minor groove and the intervening residues stabilize interactions of these two subdomains with DNA.1 Publication

Sequence similaritiesi

Belongs to the bZIP family. Skn1 subfamily.Curated

Phylogenomic databases

eggNOGiKOG3863. Eukaryota.
ENOG410ZGMS. LUCA.
GeneTreeiENSGT00510000052725.
HOGENOMiHOG000021747.
InParanoidiP34707.
KOiK05638.
OMAiCNQVNIT.

Family and domain databases

Gene3Di1.10.880.10. 1 hit.
InterProiIPR004827. bZIP.
IPR004826. bZIP_Maf.
IPR008917. TF_DNA-bd.
[Graphical view]
PfamiPF03131. bZIP_Maf. 1 hit.
[Graphical view]
SUPFAMiSSF47454. SSF47454. 1 hit.
PROSITEiPS00036. BZIP_BASIC. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform a (identifier: P34707-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGGSSRRQRS TSATRRDDKR RRRQCFSSVA DDEEETTSIY GVSSIFIWIL
60 70 80 90 100
ATSSLILVIS SPSSNTSIQS SSYDRITTKH LLDNISPTFK MYTDSNNRNF
110 120 130 140 150
DEVNHQHQQE QDFNGQSKYD YPQFNRPMGL RWRDDQRMME YFMSNGPVET
160 170 180 190 200
VPVMPILTEH PPASPFGRGP STERPTTSSR YEYSSPSLED IDLIDVLWRS
210 220 230 240 250
DIAGEKGTRQ VAPADQYECD LQTLTEKSTV APLTAEENAR YEDLSKGFYN
260 270 280 290 300
GFFESFNNNQ YQQKHQQQQR EQIKTPTLEH PTQKAELEDD LFDEDLAQLF
310 320 330 340 350
EDVSREEGQL NQLFDNKQQH PVINNVSLSE GIVYNQANLT EMQEMRDSCN
360 370 380 390 400
QVSISTIPTT STAQPETLFN VTDSQTVEQW LPTEVVPNDV FPTSNYAYIG
410 420 430 440 450
MQNDSLQAVV SNGQIDYDHS YQSTGQTPLS PLIIGSSGRQ QQTQTSPGSV
460 470 480 490 500
TVTATATQSL FDPYHSQRHS FSDCTTDSSS TCSRLSSESP RYTSESSTGT
510 520 530 540 550
HESRFYGKLA PSSGSRYQRS SSPRSSQSSI KIARVVPLAS GQRKRGRQSK
560 570 580 590 600
DEQLASDNEL PVSAFQISEM SLSELQQVLK NESLSEYQRQ LIRKIRRRGK
610 620
NKVAARTCRQ RRTDRHDKMS HYI
Length:623
Mass (Da):70,709
Last modified:May 27, 2002 - v2
Checksum:i31A70303AB7CC691
GO
Isoform b (identifier: P34707-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-313: Missing.
     314-389: FDNKQQHPVI...WLPTEVVPND → MSLPSDFASS...YSGVSSTFDR

Note: No experimental confirmation available.
Show »
Length:310
Mass (Da):34,588
Checksum:i21BD8A6536EE72B5
GO
Isoform c (identifier: P34707-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-90: Missing.

Note: No experimental confirmation available.
Show »
Length:533
Mass (Da):60,634
Checksum:iA911F45723ADCB13
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 313313Missing in isoform b. CuratedVSP_011488Add
BLAST
Alternative sequencei1 – 9090Missing in isoform c. CuratedVSP_011487Add
BLAST
Alternative sequencei314 – 38976FDNKQ…VVPND → MSLPSDFASSLLASSTTTNT TNTAPAAVNSFDEQEEESKK ILNMYLQMFNQQQVDQHGHH HQHPYAYSGVSSTFDR in isoform b. CuratedVSP_011489Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
FO080233 Genomic DNA. Translation: CCD62212.1.
FO080233 Genomic DNA. Translation: CCD62213.1.
FO080233 Genomic DNA. Translation: CCD62214.1.
M84359 Genomic DNA. No translation available.
PIRiA42143.
F88694.
RefSeqiNP_741404.1. NM_171345.4. [P34707-1]
NP_741405.1. NM_171346.3. [P34707-3]
NP_741406.1. NM_171347.5. [P34707-2]
UniGeneiCel.23037.

Genome annotation databases

EnsemblMetazoaiT19E7.2a; T19E7.2a; WBGene00004804. [P34707-1]
GeneIDi177343.
KEGGicel:CELE_T19E7.2.
UCSCiT19E7.2b. c. elegans. [P34707-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
FO080233 Genomic DNA. Translation: CCD62212.1.
FO080233 Genomic DNA. Translation: CCD62213.1.
FO080233 Genomic DNA. Translation: CCD62214.1.
M84359 Genomic DNA. No translation available.
PIRiA42143.
F88694.
RefSeqiNP_741404.1. NM_171345.4. [P34707-1]
NP_741405.1. NM_171346.3. [P34707-3]
NP_741406.1. NM_171347.5. [P34707-2]
UniGeneiCel.23037.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1SKNX-ray2.50P540-623[»]
ProteinModelPortaliP34707.
SMRiP34707. Positions 546-619.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi42465. 5 interactions.
IntActiP34707. 5 interactions.
MINTiMINT-1094083.
STRINGi6239.T19E7.2a.2.

Chemistry

BindingDBiP34707.
ChEMBLiCHEMBL2146298.

PTM databases

iPTMnetiP34707.

Proteomic databases

PaxDbiP34707.
PRIDEiP34707.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaiT19E7.2a; T19E7.2a; WBGene00004804. [P34707-1]
GeneIDi177343.
KEGGicel:CELE_T19E7.2.
UCSCiT19E7.2b. c. elegans. [P34707-1]

Organism-specific databases

CTDi177343.
WormBaseiT19E7.2a; CE27591; WBGene00004804; skn-1.
T19E7.2b; CE31238; WBGene00004804; skn-1.
T19E7.2c; CE31239; WBGene00004804; skn-1.

Phylogenomic databases

eggNOGiKOG3863. Eukaryota.
ENOG410ZGMS. LUCA.
GeneTreeiENSGT00510000052725.
HOGENOMiHOG000021747.
InParanoidiP34707.
KOiK05638.
OMAiCNQVNIT.

Enzyme and pathway databases

SignaLinkiP34707.

Miscellaneous databases

EvolutionaryTraceiP34707.
PROiP34707.

Gene expression databases

ExpressionAtlasiP34707. baseline.

Family and domain databases

Gene3Di1.10.880.10. 1 hit.
InterProiIPR004827. bZIP.
IPR004826. bZIP_Maf.
IPR008917. TF_DNA-bd.
[Graphical view]
PfamiPF03131. bZIP_Maf. 1 hit.
[Graphical view]
SUPFAMiSSF47454. SSF47454. 1 hit.
PROSITEiPS00036. BZIP_BASIC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Genome sequence of the nematode C. elegans: a platform for investigating biology."
    The C. elegans sequencing consortium
    Science 282:2012-2018(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], ALTERNATIVE SPLICING.
    Strain: Bristol N2.
  2. "skn-1, a maternally expressed gene required to specify the fate of ventral blastomeres in the early C. elegans embryo."
    Bowerman B., Eaton B.A., Priess J.R.
    Cell 68:1061-1075(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 49-623 (ISOFORM A), FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
    Strain: Bristol N2.
  3. "Formation of a monomeric DNA binding domain by Skn-1 bZIP and homeodomain elements."
    Blackwell T.K., Bowerman B., Priess J.R., Weintraub H.
    Science 266:621-628(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT, SUBCELLULAR LOCATION, DNA-BINDING.
  4. "Restriction of mesendoderm to a single blastomere by the combined action of SKN-1 and a GSK-3beta homolog is mediated by MED-1 and -2 in C. elegans."
    Maduro M.F., Meneghini M.D., Bowerman B., Broitman-Maduro G., Rothman J.H.
    Mol. Cell 7:475-485(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  5. "The C. elegans p38 MAPK pathway regulates nuclear localization of the transcription factor SKN-1 in oxidative stress response."
    Inoue H., Hisamoto N., An J.H., Oliveira R.P., Nishida E., Blackwell T.K., Matsumoto K.
    Genes Dev. 19:2278-2283(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-164 AND SER-430, MUTAGENESIS OF SER-164 AND SER-430.
  6. "The ERK-MAPK pathway regulates longevity through SKN-1 and insulin-like signaling in Caenorhabditis elegans."
    Okuyama T., Inoue H., Ookuma S., Satoh T., Kano K., Honjoh S., Hisamoto N., Matsumoto K., Nishida E.
    J. Biol. Chem. 285:30274-30281(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  7. "Ce-Duox1/BLI-3 generated reactive oxygen species trigger protective SKN-1 activity via p38 MAPK signaling during infection in C. elegans."
    Hoeven R.V., McCallum K.C., Cruz M.R., Garsin D.A.
    PLoS Pathog. 7:E1002453-E1002453(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE.
  8. "Anoxia-reoxygenation regulates mitochondrial dynamics through the hypoxia response pathway, SKN-1/Nrf, and stomatin-like protein STL-1/SLP-2."
    Ghose P., Park E.C., Tabakin A., Salazar-Vasquez N., Rongo C.
    PLoS Genet. 9:E1004063-E1004063(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  10. "A new DNA-binding motif in the Skn-1 binding domain-DNA complex."
    Rupert P.B., Daughdrill G.W., Bowerman B., Matthews B.W.
    Nat. Struct. Biol. 5:484-491(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 540-623.

Entry informationi

Entry nameiSKN1_CAEEL
AccessioniPrimary (citable) accession number: P34707
Secondary accession number(s): Q8MPW2, Q8MPW3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: May 27, 2002
Last modified: June 8, 2016
This is version 152 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programCaenorhabditis annotation project

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Caenorhabditis elegans
    Caenorhabditis elegans: entries, gene names and cross-references to WormBase
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.