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HUMAN:KCNE2

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Species (Taxon ID) Homo sapiens (Human). (9606)
Gene Name(s) KCNE2
Protein Name(s) Potassium voltage-gated channel subfamily E member 2

MinK-related peptide 1 Minimum potassium ion channel-related peptide 1 Potassium channel subunit beta MiRP1

External Links
UniProt Q9Y6J6
EMBL AF071002
AF302095
DQ784804
CH471079
BC093892
BC112087
CCDS CCDS13635.1
RefSeq NP_751951.1
UniGene Hs.551521
Hs.736062
PDB 2M0Q
PDBsum 2M0Q
ProteinModelPortal Q9Y6J6
SMR Q9Y6J6
BioGrid 115313
STRING 9606.ENSP00000290310
PhosphoSite Q9Y6J6
DMDM 6685661
PRIDE Q9Y6J6
DNASU 9992
Ensembl ENST00000290310
GeneID 9992
KEGG hsa:9992
UCSC uc002ytt.1
CTD 9992
GeneCards GC21P035736
GeneReviews KCNE2
HGNC HGNC:6242
HPA CAB022640
MIM 603796
611493
613693
neXtProt NX_Q9Y6J6
Orphanet 334
101016
PharmGKB PA392
eggNOG NOG43841
GeneTree ENSGT00510000048894
HOGENOM HOG000113208
HOVERGEN HBG052227
InParanoid Q9Y6J6
KO K04896
OMA WRRNTTA
OrthoDB EOG7WDN4J
PhylomeDB Q9Y6J6
TreeFam TF336058
GeneWiki KCNE2
GenomeRNAi 9992
NextBio 37747
PRO PR:Q9Y6J6
Proteomes UP000005640
Bgee Q9Y6J6
CleanEx HS_KCNE2
ExpressionAtlas Q9Y6J6
Genevestigator Q9Y6J6
GO GO:0009986
GO:0005764
GO:0005886
GO:0008076
GO:0005251
GO:0005242
GO:0044325
GO:0015459
GO:1902282
GO:0007568
GO:0086002
GO:0034613
GO:0035690
GO:0086009
GO:0086011
GO:1901800
GO:0071435
GO:0010107
GO:0071805
GO:1902159
GO:1902259
GO:0086091
GO:1901979
GO:0060306
GO:1901379
GO:0060307
GO:0043586
GO:0086005
InterPro IPR000369
IPR005424
IPR005425
PANTHER PTHR17028
Pfam PF02060
PRINTS PR01605

Annotations

Qualifier GO ID GO term name Reference ECO ID ECO term name with/from Aspect Extension Notes Status
GO:0006811

ion transport

PMID:22880098[1]

ECO:0000247

UniProtKB:

P

Figure 4: Activation time constants for Ih in pyramidal cells were fast in both genotypes compared to those in VB neurons, Kcne2 deletion again increased time constants in pyramidal neurons Figure 6: he frequency of spontaneous EPSPs in layer 6 pyramidal neurons in the absence of 4-AP was increased by Kcne2 deletion, suggesting a possible alteration in glutamate release machinery.

complete
CACAO 10709

part_of

GO:0005886

plasma membrane

PMID:20533308[2]

ECO:0000314

direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

colocalizes_with

GO:0008076

voltage-gated potassium channel complex

PMID:19219384[3]

ECO:0000314

direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

part_of

GO:0005886

plasma membrane

PMID:19219384[3]

ECO:0000314

direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

enables

GO:0015459

potassium channel regulator activity

PMID:19219384[3]

ECO:0000314

direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

involved_in

GO:1902260

negative regulation of delayed rectifier potassium channel activity

PMID:19219384[3]

ECO:0000314

direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

involved_in

GO:0098915

membrane repolarization during ventricular cardiac muscle cell action potential

PMID:10219239[4]

ECO:0000315

mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

enables

GO:1902282

voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization

PMID:10219239[4]

ECO:0000315

mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

involved_in

GO:1902259

regulation of delayed rectifier potassium channel activity

PMID:10219239[4]

ECO:0000314

direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

involved_in

GO:1901979

regulation of inward rectifier potassium channel activity

PMID:10219239[4]

ECO:0000314

direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

involved_in

GO:1901800

positive regulation of proteasomal protein catabolic process

PMID:22180649[5]

ECO:0000314

direct assay evidence used in manual assertion

P

has_direct_input:(UniProtKB:Q12809)

Seeded From UniProt

complete

involved_in

GO:1901379

regulation of potassium ion transmembrane transport

PMID:10219239[4]

ECO:0000314

direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

involved_in

GO:0086091

regulation of heart rate by cardiac conduction

PMID:10219239[4]

ECO:0000315

mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

involved_in

GO:0086011

membrane repolarization during action potential

PMID:10219239[4]

ECO:0000315

mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

involved_in

GO:0086009

membrane repolarization

PMID:10219239[4]

ECO:0000314

direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

involved_in

GO:0086005

ventricular cardiac muscle cell action potential

PMID:10219239[4]

ECO:0000315

mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

involved_in

GO:0086002

cardiac muscle cell action potential involved in contraction

PMID:10219239[4]

ECO:0000315

mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

involved_in

GO:0071805

potassium ion transmembrane transport

PMID:10219239[4]

ECO:0000314

direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

involved_in

GO:0097623

potassium ion export across plasma membrane

PMID:10219239[4]

ECO:0000314

direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

involved_in

GO:0060307

regulation of ventricular cardiac muscle cell membrane repolarization

PMID:10219239[4]

ECO:0000315

mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

involved_in

GO:0060306

regulation of membrane repolarization

PMID:10219239[4]

ECO:0000314

direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

enables

GO:0044325

ion channel binding

PMID:10219239[4]

ECO:0000314

direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

involved_in

GO:0035690

cellular response to drug

PMID:10219239[4]

ECO:0000314

direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

enables

GO:0015459

potassium channel regulator activity

PMID:10219239[4]

ECO:0000314

direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

involved_in

GO:1990573

potassium ion import across plasma membrane

PMID:10219239[4]

ECO:0000315

mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

part_of

GO:0009986

cell surface

PMID:22180649[5]

ECO:0000314

direct assay evidence used in manual assertion

C

part_of:(CL:0000746)

Seeded From UniProt

complete

part_of

GO:0008076

voltage-gated potassium channel complex

PMID:10219239[4]

ECO:0000314

direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

contributes_to

GO:0005251

delayed rectifier potassium channel activity

PMID:10219239[4]

ECO:0000314

direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

contributes_to

GO:0005242

inward rectifier potassium channel activity

PMID:10219239[4]

ECO:0000314

direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

part_of

GO:0005886

plasma membrane

PMID:16780588[6]

ECO:0007005

high throughput direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

part_of

GO:0005764

lysosome

PMID:16780588[6]

ECO:0007005

high throughput direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

contributes_to

GO:1902282

voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization

PMID:21873635[7]

ECO:0000318

biological aspect of ancestor evidence used in manual assertion

PANTHER:PTN001445835
UniProtKB:P15382

F

Seeded From UniProt

complete

involved_in

GO:1902260

negative regulation of delayed rectifier potassium channel activity

PMID:21873635[7]

ECO:0000318

biological aspect of ancestor evidence used in manual assertion

PANTHER:PTN001445835
RGD:2956
RGD:621383
RGD:621384
UniProtKB:P15382
UniProtKB:Q9Y6H6
UniProtKB:Q9Y6J6

P

Seeded From UniProt

complete

involved_in

GO:0097623

potassium ion export across plasma membrane

PMID:21873635[7]

ECO:0000318

biological aspect of ancestor evidence used in manual assertion

PANTHER:PTN001445835
UniProtKB:Q9Y6J6

P

Seeded From UniProt

complete

involved_in

GO:0086091

regulation of heart rate by cardiac conduction

PMID:21873635[7]

ECO:0000318

biological aspect of ancestor evidence used in manual assertion

MGI:MGI:96673
PANTHER:PTN001445835
UniProtKB:P15382
UniProtKB:Q9UJ90
UniProtKB:Q9Y6H6
UniProtKB:Q9Y6J6

P

Seeded From UniProt

complete

involved_in

GO:0086011

membrane repolarization during action potential

PMID:21873635[7]

ECO:0000318

biological aspect of ancestor evidence used in manual assertion

PANTHER:PTN001445835
RGD:621383
UniProtKB:P15382
UniProtKB:Q9UJ90
UniProtKB:Q9Y6J6

P

Seeded From UniProt

complete

involved_in

GO:0086005

ventricular cardiac muscle cell action potential

PMID:21873635[7]

ECO:0000318

biological aspect of ancestor evidence used in manual assertion

MGI:MGI:1891123
PANTHER:PTN001445835
UniProtKB:P15382
UniProtKB:Q9UJ90
UniProtKB:Q9Y6J6

P

Seeded From UniProt

complete

involved_in

GO:0060307

regulation of ventricular cardiac muscle cell membrane repolarization

PMID:21873635[7]

ECO:0000318

biological aspect of ancestor evidence used in manual assertion

MGI:MGI:1891123
PANTHER:PTN001445835
UniProtKB:P15382
UniProtKB:Q9UJ90
UniProtKB:Q9Y6H6
UniProtKB:Q9Y6J6

P

Seeded From UniProt

complete

enables

GO:0044325

ion channel binding

PMID:21873635[7]

ECO:0000318

biological aspect of ancestor evidence used in manual assertion

PANTHER:PTN001445835
RGD:2956
RGD:621383
RGD:621384
UniProtKB:Q8WWG9
UniProtKB:Q9UJ90
UniProtKB:Q9Y6J6

F

Seeded From UniProt

complete

enables

GO:0015459

potassium channel regulator activity

PMID:21873635[7]

ECO:0000318

biological aspect of ancestor evidence used in manual assertion

MGI:MGI:96673
PANTHER:PTN001445835
RGD:2956
RGD:621383
RGD:621384
UniProtKB:P15382
UniProtKB:Q9UJ90
UniProtKB:Q9Y6H6
UniProtKB:Q9Y6J6

F

Seeded From UniProt

complete

colocalizes_with

GO:0008076

voltage-gated potassium channel complex

PMID:21873635[7]

ECO:0000318

biological aspect of ancestor evidence used in manual assertion

PANTHER:PTN001445835
RGD:2956
RGD:621383
RGD:621384
UniProtKB:P15382
UniProtKB:Q9Y6H6
UniProtKB:Q9Y6J6

C

Seeded From UniProt

complete

contributes_to

GO:0005251

delayed rectifier potassium channel activity

PMID:21873635[7]

ECO:0000318

biological aspect of ancestor evidence used in manual assertion

PANTHER:PTN001445835
RGD:621383
UniProtKB:P15382
UniProtKB:Q9Y6J6

F

Seeded From UniProt

complete

involved_in

GO:1990573

potassium ion import across plasma membrane

GO_REF:0000107

ECO:0000265

sequence orthology evidence used in automatic assertion

UniProtKB:P63161
ensembl:ENSRNOP00000045279

P

Seeded From UniProt

complete

involved_in

GO:1903817

negative regulation of voltage-gated potassium channel activity

GO_REF:0000107

ECO:0000265

sequence orthology evidence used in automatic assertion

UniProtKB:P63161
ensembl:ENSRNOP00000045279

P

Seeded From UniProt

complete

involved_in

GO:1902260

negative regulation of delayed rectifier potassium channel activity

GO_REF:0000107

ECO:0000265

sequence orthology evidence used in automatic assertion

UniProtKB:P63161
ensembl:ENSRNOP00000045279

P

Seeded From UniProt

complete

involved_in

GO:1902259

regulation of delayed rectifier potassium channel activity

GO_REF:0000107

ECO:0000265

sequence orthology evidence used in automatic assertion

UniProtKB:P63161
ensembl:ENSRNOP00000045279

P

Seeded From UniProt

complete

involved_in

GO:1902159

regulation of cyclic nucleotide-gated ion channel activity

GO_REF:0000107

ECO:0000265

sequence orthology evidence used in automatic assertion

UniProtKB:P63161
ensembl:ENSRNOP00000045279

P

Seeded From UniProt

complete

involved_in

GO:1901979

regulation of inward rectifier potassium channel activity

GO_REF:0000107

ECO:0000265

sequence orthology evidence used in automatic assertion

UniProtKB:P63161
ensembl:ENSRNOP00000045279

P

Seeded From UniProt

complete

involved_in

GO:1901387

positive regulation of voltage-gated calcium channel activity

GO_REF:0000107

ECO:0000265

sequence orthology evidence used in automatic assertion

UniProtKB:P63161
ensembl:ENSRNOP00000045279

P

Seeded From UniProt

complete

involved_in

GO:1901379

regulation of potassium ion transmembrane transport

GO_REF:0000107

ECO:0000265

sequence orthology evidence used in automatic assertion

UniProtKB:P63161
ensembl:ENSRNOP00000045279

P

Seeded From UniProt

complete

involved_in

GO:0097623

potassium ion export across plasma membrane

GO_REF:0000107

ECO:0000265

sequence orthology evidence used in automatic assertion

UniProtKB:P63161
ensembl:ENSRNOP00000045279

P

Seeded From UniProt

complete

involved_in

GO:0086011

membrane repolarization during action potential

GO_REF:0000107

ECO:0000265

sequence orthology evidence used in automatic assertion

UniProtKB:P63161
ensembl:ENSRNOP00000045279

P

Seeded From UniProt

complete

involved_in

GO:0086009

membrane repolarization

GO_REF:0000107

ECO:0000265

sequence orthology evidence used in automatic assertion

UniProtKB:P63161
ensembl:ENSRNOP00000045279

P

Seeded From UniProt

complete

involved_in

GO:0071805

potassium ion transmembrane transport

GO_REF:0000107

ECO:0000265

sequence orthology evidence used in automatic assertion

UniProtKB:P63161
ensembl:ENSRNOP00000045279

P

Seeded From UniProt

complete

involved_in

GO:0060306

regulation of membrane repolarization

GO_REF:0000107

ECO:0000265

sequence orthology evidence used in automatic assertion

UniProtKB:P63161
ensembl:ENSRNOP00000045279

P

Seeded From UniProt

complete

enables

GO:0044325

ion channel binding

GO_REF:0000107

ECO:0000265

sequence orthology evidence used in automatic assertion

UniProtKB:P63161
ensembl:ENSRNOP00000045279

F

Seeded From UniProt

complete

involved_in

GO:0043586

tongue development

GO_REF:0000107

ECO:0000265

sequence orthology evidence used in automatic assertion

UniProtKB:P63161
ensembl:ENSRNOP00000045279

P

Seeded From UniProt

complete

enables

GO:0042803

protein homodimerization activity

GO_REF:0000107

ECO:0000265

sequence orthology evidence used in automatic assertion

UniProtKB:P63161
ensembl:ENSRNOP00000045279

F

Seeded From UniProt

complete

involved_in

GO:0035690

cellular response to drug

GO_REF:0000107

ECO:0000265

sequence orthology evidence used in automatic assertion

UniProtKB:P63161
ensembl:ENSRNOP00000045279

P

Seeded From UniProt

complete

part_of

GO:0016021

integral component of membrane

GO_REF:0000107

ECO:0000265

sequence orthology evidence used in automatic assertion

UniProtKB:P63161
ensembl:ENSRNOP00000045279

C

Seeded From UniProt

complete

enables

GO:0015459

potassium channel regulator activity

GO_REF:0000107

ECO:0000265

sequence orthology evidence used in automatic assertion

UniProtKB:P63161
ensembl:ENSRNOP00000045279

F

Seeded From UniProt

complete

part_of

GO:0009986

cell surface

GO_REF:0000107

ECO:0000265

sequence orthology evidence used in automatic assertion

UniProtKB:P63161
ensembl:ENSRNOP00000045279

C

Seeded From UniProt

complete

part_of

GO:0008076

voltage-gated potassium channel complex

GO_REF:0000107

ECO:0000265

sequence orthology evidence used in automatic assertion

UniProtKB:P63161
ensembl:ENSRNOP00000045279

C

Seeded From UniProt

complete

involved_in

GO:0007568

aging

GO_REF:0000107

ECO:0000265

sequence orthology evidence used in automatic assertion

UniProtKB:P63161
ensembl:ENSRNOP00000045279

P

Seeded From UniProt

complete

part_of

GO:0005886

plasma membrane

GO_REF:0000107

ECO:0000265

sequence orthology evidence used in automatic assertion

UniProtKB:P63161
ensembl:ENSRNOP00000045279

C

Seeded From UniProt

complete

part_of

GO:0005794

Golgi apparatus

GO_REF:0000107

ECO:0000265

sequence orthology evidence used in automatic assertion

UniProtKB:P63161
ensembl:ENSRNOP00000045279

C

Seeded From UniProt

complete

part_of

GO:0005783

endoplasmic reticulum

GO_REF:0000107

ECO:0000265

sequence orthology evidence used in automatic assertion

UniProtKB:P63161
ensembl:ENSRNOP00000045279

C

Seeded From UniProt

complete

enables

GO:0005251

delayed rectifier potassium channel activity

GO_REF:0000107

ECO:0000265

sequence orthology evidence used in automatic assertion

UniProtKB:P63161
ensembl:ENSRNOP00000045279

F

Seeded From UniProt

complete

enables

GO:0005249

voltage-gated potassium channel activity

GO_REF:0000107

ECO:0000265

sequence orthology evidence used in automatic assertion

UniProtKB:P63161
ensembl:ENSRNOP00000045279

F

Seeded From UniProt

complete

enables

GO:0005242

inward rectifier potassium channel activity

GO_REF:0000107

ECO:0000265

sequence orthology evidence used in automatic assertion

UniProtKB:P63161
ensembl:ENSRNOP00000045279

F

Seeded From UniProt

complete

enables

GO:0005249

voltage-gated potassium channel activity

GO_REF:0000002

ECO:0000256

match to sequence model evidence used in automatic assertion

InterPro:IPR000369
InterPro:IPR005425

F

Seeded From UniProt

complete

involved_in

GO:0006811

ion transport

GO_REF:0000002

ECO:0000256

match to sequence model evidence used in automatic assertion

InterPro:IPR000369

P

Seeded From UniProt

complete

involved_in

GO:0006813

potassium ion transport

GO_REF:0000002

ECO:0000256

match to sequence model evidence used in automatic assertion

InterPro:IPR005425

P

Seeded From UniProt

complete

part_of

GO:0016020

membrane

GO_REF:0000002

ECO:0000256

match to sequence model evidence used in automatic assertion

InterPro:IPR000369
InterPro:IPR005425

C

Seeded From UniProt

complete

part_of

GO:0008076

voltage-gated potassium channel complex

PMID:10219239[4]

ECO:0000304

author statement supported by traceable reference used in manual assertion

C

Seeded From UniProt

complete

involved_in

GO:0061337

cardiac conduction

Reactome:R-HSA-5576893
Reactome:R-HSA-5576890

ECO:0000304

author statement supported by traceable reference used in manual assertion


P

Seeded From UniProt

complete

part_of

GO:0005886

plasma membrane

Reactome:R-HSA-5577237
Reactome:R-HSA-5577050

ECO:0000304

author statement supported by traceable reference used in manual assertion


C

Seeded From UniProt

complete

enables

GO:0005244

voltage-gated ion channel activity

GO_REF:0000037

ECO:0000322

imported manually asserted information used in automatic assertion

UniProtKB-KW:KW-0851

F

Seeded From UniProt

complete

part_of

GO:0005886

plasma membrane

GO_REF:0000037
GO_REF:0000039

ECO:0000322

imported manually asserted information used in automatic assertion

UniProtKB-KW:KW-1003
UniProtKB-SubCell:SL-0039

C

Seeded From UniProt

complete

involved_in

GO:0006811

ion transport

GO_REF:0000037

ECO:0000322

imported manually asserted information used in automatic assertion

UniProtKB-KW:KW-0406

P

Seeded From UniProt

complete

involved_in

GO:0034765

regulation of ion transmembrane transport

GO_REF:0000037

ECO:0000322

imported manually asserted information used in automatic assertion

UniProtKB-KW:KW-0851

P

Seeded From UniProt

complete

part_of

GO:0016021

integral component of membrane

GO_REF:0000037

ECO:0000322

imported manually asserted information used in automatic assertion

UniProtKB-KW:KW-0812

C

Seeded From UniProt

complete

involved_in

GO:0071805

potassium ion transmembrane transport

GO_REF:0000037

ECO:0000322

imported manually asserted information used in automatic assertion

UniProtKB-KW:KW-0631

P

Seeded From UniProt

complete

part_of

GO:0016020

membrane

GO_REF:0000037

ECO:0000322

imported manually asserted information used in automatic assertion

UniProtKB-KW:KW-0472

C

Seeded From UniProt

complete

enables

GO:0005267

potassium channel activity

GO_REF:0000037

ECO:0000322

imported manually asserted information used in automatic assertion

UniProtKB-KW:KW-0631

F

Seeded From UniProt

complete

involved_in

GO:0006813

potassium ion transport

GO_REF:0000037

ECO:0000322

imported manually asserted information used in automatic assertion

UniProtKB-KW:KW-0633

P

Seeded From UniProt

complete

Notes

References

See Help:References for how to manage references in GONUTS.

  1. Ying, SW et al. (2012) Targeted deletion of Kcne2 impairs HCN channel function in mouse thalamocortical circuits. PLoS ONE 7 e42756 PubMed GONUTS page
  2. Roura-Ferrer, M et al. (2010) Impact of KCNE subunits on KCNQ1 (Kv7.1) channel membrane surface targeting. J. Cell. Physiol. 225 692-700 PubMed GONUTS page
  3. 3.0 3.1 3.2 3.3 McCrossan, ZA et al. (2009) Regulation of the Kv2.1 potassium channel by MinK and MiRP1. J. Membr. Biol. 228 1-14 PubMed GONUTS page
  4. 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 4.13 4.14 4.15 4.16 4.17 4.18 4.19 4.20 4.21 Abbott, GW et al. (1999) MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. Cell 97 175-87 PubMed GONUTS page
  5. 5.0 5.1 Zhang, M et al. (2012) KCNE2 protein is more abundant in ventricles than in atria and can accelerate hERG protein degradation in a phosphorylation-dependent manner. Am. J. Physiol. Heart Circ. Physiol. 302 H910-22 PubMed GONUTS page
  6. 6.0 6.1 Hu, YH et al. (2006) Cell array-based intracellular localization screening reveals novel functional features of human chromosome 21 proteins. BMC Genomics 7 155 PubMed GONUTS page
  7. 7.00 7.01 7.02 7.03 7.04 7.05 7.06 7.07 7.08 7.09 7.10 Gaudet, P et al. (2011) Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Brief. Bioinformatics 12 449-62 PubMed GONUTS page