GlyCosmos Portal

Annotation

Keyword: 3D-structure ANK repeat Activator Cell membrane Developmental protein Differentiation Disease variant Disulfide bond EGF-like domain Glycoprotein Methylation Notch signaling pathway Nucleus Phosphoprotein Proteomics identification Receptor Reference proteome Repeat Signal Transcription regulation Transmembrane helix

Gene Ontology (GO)

Displaying entries **1 - 5** of 15 in total

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GO Term	Evidence Code	Reference
negative regulation of transcription by RNA polymerase II
Notch signaling pathway	IMP	PMID
Notch signaling pathway	IBA	GO_REF
Notch signaling pathway	IEA	GO_REF GO_REF GO_REF
axon guidance	IBA	GO_REF

GO Hierarchy

biological process

cellular process [inference]

signal transduction [inference]

cell surface receptor signaling pathway [inference]

Notch signaling pathway

cellular developmental process [inference]

cell differentiation [inference]

neuroblast differentiation

cell fate commitment [inference]

neuron fate commitment

cellular component organization or biogenesis [inference]

cellular component organization [inference]

cell projection organization [inference]

plasma membrane bounded cell projection organization [inference]

neuron projection development [inference]

neuron projection guidance [inference]

axon guidance

developmental process [inference]

anatomical structure morphogenesis [inference]

tube morphogenesis [inference]

blood vessel morphogenesis [inference]

artery morphogenesis

anatomical structure formation involved in morphogenesis [inference]

angiogenesis [inference]

glomerular capillary formation

anatomical structure development [inference]

animal gross anatomical part developmental process [inference]

forebrain development

cellular developmental process [inference]

cell differentiation [inference]

neuroblast differentiation

cell fate commitment [inference]

neuron fate commitment

biological regulation [inference]

regulation of biological process [inference]

positive regulation of biological process [inference]

positive regulation of cellular process [inference]

positive regulation of cell population proliferation [inference]

positive regulation of smooth muscle cell proliferation

positive regulation of metabolic process [inference]

positive regulation of biosynthetic process [inference]

positive regulation of macromolecule biosynthetic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of macromolecule metabolic process [inference]

positive regulation of macromolecule biosynthetic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of RNA metabolic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of miRNA metabolic process [inference]

positive regulation of miRNA transcription

negative regulation of biological process [inference]

negative regulation of cellular process [inference]

negative regulation of metabolic process [inference]

negative regulation of biosynthetic process [inference]

negative regulation of macromolecule biosynthetic process [inference]

negative regulation of RNA biosynthetic process [inference]

negative regulation of DNA-templated transcription [inference]

negative regulation of transcription by RNA polymerase II

negative regulation of macromolecule metabolic process [inference]

negative regulation of macromolecule biosynthetic process [inference]

negative regulation of RNA biosynthetic process [inference]

negative regulation of DNA-templated transcription [inference]

negative regulation of transcription by RNA polymerase II

negative regulation of RNA metabolic process [inference]

negative regulation of RNA biosynthetic process [inference]

negative regulation of DNA-templated transcription [inference]

negative regulation of transcription by RNA polymerase II

negative regulation of nucleobase-containing compound metabolic process [inference]

negative regulation of RNA metabolic process [inference]

negative regulation of RNA biosynthetic process [inference]

negative regulation of DNA-templated transcription [inference]

negative regulation of transcription by RNA polymerase II

negative regulation of cell differentiation [inference]

negative regulation of neuron differentiation

negative regulation of developmental process [inference]

negative regulation of cell differentiation [inference]

negative regulation of neuron differentiation

regulation of developmental process [inference]

regulation of cell differentiation [inference]

negative regulation of cell differentiation [inference]

negative regulation of neuron differentiation

regulation of neuron differentiation [inference]

negative regulation of neuron differentiation

negative regulation of developmental process [inference]

negative regulation of cell differentiation [inference]

negative regulation of neuron differentiation

regulation of cellular process [inference]

signal transduction [inference]

cell surface receptor signaling pathway [inference]

Notch signaling pathway

regulation of metabolic process [inference]

regulation of biosynthetic process [inference]

negative regulation of biosynthetic process [inference]

negative regulation of macromolecule biosynthetic process [inference]

negative regulation of RNA biosynthetic process [inference]

negative regulation of DNA-templated transcription [inference]

negative regulation of transcription by RNA polymerase II

positive regulation of biosynthetic process [inference]

positive regulation of macromolecule biosynthetic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

regulation of macromolecule biosynthetic process [inference]

regulation of gene expression [inference]

regulation of DNA-templated transcription [inference]

regulation of transcription by RNA polymerase II [inference]

negative regulation of DNA-templated transcription [inference]

negative regulation of transcription by RNA polymerase II

positive regulation of DNA-templated transcription [inference]

regulation of miRNA transcription [inference]

positive regulation of miRNA transcription

positive regulation of macromolecule biosynthetic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

negative regulation of macromolecule biosynthetic process [inference]

negative regulation of RNA biosynthetic process [inference]

negative regulation of DNA-templated transcription [inference]

negative regulation of transcription by RNA polymerase II

regulation of RNA biosynthetic process [inference]

regulation of DNA-templated transcription [inference]

regulation of transcription by RNA polymerase II [inference]

negative regulation of DNA-templated transcription [inference]

negative regulation of transcription by RNA polymerase II

positive regulation of DNA-templated transcription [inference]

regulation of miRNA transcription [inference]

positive regulation of miRNA transcription

negative regulation of RNA biosynthetic process [inference]

negative regulation of DNA-templated transcription [inference]

negative regulation of transcription by RNA polymerase II

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

negative regulation of metabolic process [inference]

negative regulation of biosynthetic process [inference]

negative regulation of macromolecule biosynthetic process [inference]

negative regulation of RNA biosynthetic process [inference]

negative regulation of DNA-templated transcription [inference]

negative regulation of transcription by RNA polymerase II

negative regulation of macromolecule metabolic process [inference]

negative regulation of macromolecule biosynthetic process [inference]

negative regulation of RNA biosynthetic process [inference]

negative regulation of DNA-templated transcription [inference]

negative regulation of transcription by RNA polymerase II

negative regulation of RNA metabolic process [inference]

negative regulation of RNA biosynthetic process [inference]

negative regulation of DNA-templated transcription [inference]

negative regulation of transcription by RNA polymerase II

negative regulation of nucleobase-containing compound metabolic process [inference]

negative regulation of RNA metabolic process [inference]

negative regulation of RNA biosynthetic process [inference]

negative regulation of DNA-templated transcription [inference]

negative regulation of transcription by RNA polymerase II

positive regulation of metabolic process [inference]

positive regulation of biosynthetic process [inference]

positive regulation of macromolecule biosynthetic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of macromolecule metabolic process [inference]

positive regulation of macromolecule biosynthetic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of RNA metabolic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of miRNA metabolic process [inference]

positive regulation of miRNA transcription

regulation of macromolecule metabolic process [inference]

regulation of macromolecule biosynthetic process [inference]

regulation of gene expression [inference]

regulation of DNA-templated transcription [inference]

regulation of transcription by RNA polymerase II [inference]

negative regulation of DNA-templated transcription [inference]

negative regulation of transcription by RNA polymerase II

positive regulation of DNA-templated transcription [inference]

regulation of miRNA transcription [inference]

positive regulation of miRNA transcription

positive regulation of macromolecule biosynthetic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

negative regulation of macromolecule biosynthetic process [inference]

negative regulation of RNA biosynthetic process [inference]

negative regulation of DNA-templated transcription [inference]

negative regulation of transcription by RNA polymerase II

regulation of RNA biosynthetic process [inference]

regulation of DNA-templated transcription [inference]

regulation of transcription by RNA polymerase II [inference]

negative regulation of DNA-templated transcription [inference]

negative regulation of transcription by RNA polymerase II

positive regulation of DNA-templated transcription [inference]

regulation of miRNA transcription [inference]

positive regulation of miRNA transcription

negative regulation of RNA biosynthetic process [inference]

negative regulation of DNA-templated transcription [inference]

negative regulation of transcription by RNA polymerase II

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of macromolecule metabolic process [inference]

positive regulation of macromolecule biosynthetic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of RNA metabolic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of miRNA metabolic process [inference]

positive regulation of miRNA transcription

negative regulation of macromolecule metabolic process [inference]

negative regulation of macromolecule biosynthetic process [inference]

negative regulation of RNA biosynthetic process [inference]

negative regulation of DNA-templated transcription [inference]

negative regulation of transcription by RNA polymerase II

negative regulation of RNA metabolic process [inference]

negative regulation of RNA biosynthetic process [inference]

negative regulation of DNA-templated transcription [inference]

negative regulation of transcription by RNA polymerase II

regulation of RNA metabolic process [inference]

negative regulation of RNA metabolic process [inference]

negative regulation of RNA biosynthetic process [inference]

negative regulation of DNA-templated transcription [inference]

negative regulation of transcription by RNA polymerase II

positive regulation of RNA metabolic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of miRNA metabolic process [inference]

positive regulation of miRNA transcription

regulation of miRNA metabolic process [inference]

regulation of miRNA transcription [inference]

positive regulation of miRNA transcription

positive regulation of miRNA metabolic process [inference]

positive regulation of miRNA transcription

regulation of RNA biosynthetic process [inference]

regulation of DNA-templated transcription [inference]

regulation of transcription by RNA polymerase II [inference]

negative regulation of DNA-templated transcription [inference]

negative regulation of transcription by RNA polymerase II

positive regulation of DNA-templated transcription [inference]

regulation of miRNA transcription [inference]

positive regulation of miRNA transcription

negative regulation of RNA biosynthetic process [inference]

negative regulation of DNA-templated transcription [inference]

negative regulation of transcription by RNA polymerase II

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

regulation of primary metabolic process [inference]

regulation of nucleobase-containing compound metabolic process [inference]

negative regulation of nucleobase-containing compound metabolic process [inference]

negative regulation of RNA metabolic process [inference]

negative regulation of RNA biosynthetic process [inference]

negative regulation of DNA-templated transcription [inference]

negative regulation of transcription by RNA polymerase II

regulation of RNA metabolic process [inference]

negative regulation of RNA metabolic process [inference]

negative regulation of RNA biosynthetic process [inference]

negative regulation of DNA-templated transcription [inference]

negative regulation of transcription by RNA polymerase II

positive regulation of RNA metabolic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of miRNA metabolic process [inference]

positive regulation of miRNA transcription

regulation of miRNA metabolic process [inference]

regulation of miRNA transcription [inference]

positive regulation of miRNA transcription

positive regulation of miRNA metabolic process [inference]

positive regulation of miRNA transcription

regulation of RNA biosynthetic process [inference]

regulation of DNA-templated transcription [inference]

regulation of transcription by RNA polymerase II [inference]

negative regulation of DNA-templated transcription [inference]

negative regulation of transcription by RNA polymerase II

positive regulation of DNA-templated transcription [inference]

regulation of miRNA transcription [inference]

positive regulation of miRNA transcription

negative regulation of RNA biosynthetic process [inference]

negative regulation of DNA-templated transcription [inference]

negative regulation of transcription by RNA polymerase II

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

regulation of cell population proliferation [inference]

positive regulation of cell population proliferation [inference]

positive regulation of smooth muscle cell proliferation

regulation of smooth muscle cell proliferation [inference]

positive regulation of smooth muscle cell proliferation

regulation of cell differentiation [inference]

negative regulation of cell differentiation [inference]

negative regulation of neuron differentiation

regulation of neuron differentiation [inference]

negative regulation of neuron differentiation

positive regulation of cellular process [inference]

positive regulation of cell population proliferation [inference]

positive regulation of smooth muscle cell proliferation

positive regulation of metabolic process [inference]

positive regulation of biosynthetic process [inference]

positive regulation of macromolecule biosynthetic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of macromolecule metabolic process [inference]

positive regulation of macromolecule biosynthetic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of RNA metabolic process [inference]

positive regulation of RNA biosynthetic process [inference]

positive regulation of DNA-templated transcription [inference]

positive regulation of miRNA metabolic process [inference]

positive regulation of miRNA transcription

negative regulation of cellular process [inference]

negative regulation of metabolic process [inference]

negative regulation of biosynthetic process [inference]

negative regulation of macromolecule biosynthetic process [inference]

negative regulation of RNA biosynthetic process [inference]

negative regulation of DNA-templated transcription [inference]

negative regulation of transcription by RNA polymerase II

negative regulation of macromolecule metabolic process [inference]

negative regulation of macromolecule biosynthetic process [inference]

negative regulation of RNA biosynthetic process [inference]

negative regulation of DNA-templated transcription [inference]

negative regulation of transcription by RNA polymerase II

negative regulation of RNA metabolic process [inference]

negative regulation of RNA biosynthetic process [inference]

negative regulation of DNA-templated transcription [inference]

negative regulation of transcription by RNA polymerase II

negative regulation of nucleobase-containing compound metabolic process [inference]

negative regulation of RNA metabolic process [inference]

negative regulation of RNA biosynthetic process [inference]

negative regulation of DNA-templated transcription [inference]

negative regulation of transcription by RNA polymerase II

negative regulation of cell differentiation [inference]

negative regulation of neuron differentiation

Displaying entries **1 - 5** of 19 in total

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GO Term	Evidence Code	Reference
Golgi membrane	TAS	Reactome Reactome
Golgi membrane	IEA	GO_REF
extracellular region	TAS	Reactome Reactome Reactome Reactome Reactome
extracellular region	IEA	GO_REF
nucleoplasm	TAS	Reactome Reactome Reactome Reactome Reactome

GO Hierarchy

cellular component

protein-containing complex [inference]

signaling receptor complex

cellular anatomical structure [inference]

membrane [inference]

plasma membrane

organelle membrane [inference]

endoplasmic reticulum membrane

bounding membrane of organelle [inference]

Golgi membrane

Displaying entries **1 - 5** of 6 in total

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GO Term	Evidence Code	Reference
calcium ion binding	IEA	GO_REF
enzyme binding	IEA	GO_REF
signaling receptor activity	IMP	PMID
signaling receptor activity	IEA	GO_REF GO_REF
identical protein binding	IPI	PMID

GO Hierarchy

molecular function

binding [inference]

protein binding [inference]

cell adhesion molecule binding [inference]

cadherin binding

small molecule binding [inference]

ion binding [inference]

cation binding [inference]

metal ion binding [inference]

calcium ion binding

molecular transducer activity [inference]

signaling receptor activity

Gene Ontology information from UniProt.

Annotation information from UniProt.

Sequence

MGPGARGRRRRRRPMSPPPPPPPVRALPLLLLLAGPGAAAPPCLDGSPCANGGRCTQLPSREAACLCPPGWVGERCQLEDPCHSGPCAGRGVCQSSVVAGTARFSCRCPRGFRGPDCSLPDPCLSSPCAHGARCSVGPDGRFLCSCPPGYQGRSCRSDVDECRVGEPCRHGGTCLNTPGSFRCQCPAGYTGPLCENPAVPCAPSPCRNGGTCRQSGDLTYDCACLPGFEGQNCEVNVDDCPGHRCLNGGTCVDGVNTYNCQCPPEWTGQFCTEDVDECQLQPNACHNGGTCFNTLGGHSCVCVNGWTGESCSQNIDDCATAVCFHGATCHDRVASFYCACPMGKTGLLCHLDDACVSNPCHEDAICDTNPVNGRAICTCPPGFTGGACDQDVDECSIGANPCEHLGRCVNTQGSFLCQCGRGYTGPRCETDVNECLSGPCRNQATCLDRIGQFTCICMAGFTGTYCEVDIDECQSSPCVNGGVCKDRVNGFSCTCPSGFSGSTCQLDVDECASTPCRNGAKCVDQPDGYECRCAEGFEGTLCDRNVDDCSPDPCHHGRCVDGIASFSCACAPGYTGTRCESQVDECRSQPCRHGGKCLDLVDKYLCRCPSGTTGVNCEVNIDDCASNPCTFGVCRDGINRYDCVCQPGFTGPLCNVEINECASSPCGEGGSCVDGENGFRCLCPPGSLPPLCLPPSHPCAHEPCSHGICYDAPGGFRCVCEPGWSGPRCSQSLARDACESQPCRAGGTCSSDGMGFHCTCPPGVQGRQCELLSPCTPNPCEHGGRCESAPGQLPVCSCPQGWQGPRCQQDVDECAGPAPCGPHGICTNLAGSFSCTCHGGYTGPSCDQDINDCDPNPCLNGGSCQDGVGSFSCSCLPGFAGPRCARDVDECLSNPCGPGTCTDHVASFTCTCPPGYGGFHCEQDLPDCSPSSCFNGGTCVDGVNSFSCLCRPGYTGAHCQHEADPCLSRPCLHGGVCSAAHPGFRCTCLESFTGPQCQTLVDWCSRQPCQNGGRCVQTGAYCLCPPGWSGRLCDIRSLPCREAAAQIGVRLEQLCQAGGQCVDEDSSHYCVCPEGRTGSHCEQEVDPCLAQPCQHGGTCRGYMGGYMCECLPGYNGDNCEDDVDECASQPCQHGGSCIDLVARYLCSCPPGTLGVLCEINEDDCGPGPPLDSGPRCLHNGTCVDLVGGFRCTCPPGYTGLRCEADINECRSGACHAAHTRDCLQDPGGGFRCLCHAGFSGPRCQTVLSPCESQPCQHGGQCRPSPGPGGGLTFTCHCAQPFWGPRCERVARSCRELQCPVGVPCQQTPRGPRCACPPGLSGPSCRSFPGSPPGASNASCAAAPCLHGGSCRPAPLAPFFRCACAQGWTGPRCEAPAAAPEVSEEPRCPRAACQAKRGDQRCDRECNSPGCGWDGGDCSLSVGDPWRQCEALQCWRLFNNSRCDPACSSPACLYDNFDCHAGGRERTCNPVYEKYCADHFADGRCDQGCNTEECGWDGLDCASEVPALLARGVLVLTVLLPPEELLRSSADFLQRLSAILRTSLRFRLDAHGQAMVFPYHRPSPGSEPRARRELAPEVIGSVVMLEIDNRLCLQSPENDHCFPDAQSAADYLGALSAVERLDFPYPLRDVRGEPLEPPEPSVPLLPLLVAGAVLLLVILVLGVMVARRKREHSTLWFPEGFSLHKDVASGHKGRREPVGQDALGMKNMAKGESLMGEVATDWMDTECPEAKRLKVEEPGMGAEEAVDCRQWTQHHLVAADIRVAPAMALTPPQGDADADGMDVNVRGPDGFTPLMLASFCGGALEPMPTEEDEADDTSASIISDLICQGAQLGARTDRTGETALHLAARYARADAAKRLLDAGADTNAQDHSGRTPLHTAVTADAQGVFQILIRNRSTDLDARMADGSTALILAARLAVEGMVEELIASHADVNAVDELGKSALHWAAAVNNVEATLALLKNGANKDMQDSKEETPLFLAAREGSYEAAKLLLDHFANREITDHLDRLPRDVAQERLHQDIVRLLDQPSGPRSPPGPHGLGPLLCPPGAFLPGLKAAQSGSKKSRRPPGKAGLGPQGPRGRGKKLTLACPGPLADSSVTLSPVDSLDSPRPFGGPPASPGGFPLEGPYAAATATAVSLAQLGGPGRAGLGRQPPGGCVLSLGLLNPVAVPLDWARLPPPAPPGPSFLLPLAPGPQLLNPGTPVSPQERPPPYLAVPGHGEEYPAAGAHSSPPKARFLRVPSEHPYLTPSPESPEHWASPSPPSLSDWSESTPSPATATGAMATTTGALPAQPLPLSVPSSLAQAQTQLGPQPEVTPKRQVLA

N : N-glycosylation Site
___ : Potential Sequon

Glycosylation Sites

Displaying entries **1 - 10** of 18 in total

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Position	Description	PubMed ID	GlyTouCan ID	Source
84		28657654 29351928 32574038 35254053 35289036 36067866 37217939 37340703 38665916	G49108TO	GlyGen The O-GlcNAc Database
190		28657654 29351928 32574038 35254053 35289036 36067866 37217939 37340703 38665916	G49108TO	The O-GlcNAc Database
384		28657654 29351928 32574038 35254053 35289036 36067866 37217939 37340703 38665916	G49108TO	The O-GlcNAc Database
424		28657654 29351928 32574038 35254053 35289036 36067866 37217939 37340703 38665916	G49108TO	The O-GlcNAc Database
575		28657654 29351928 32574038 35254053 35289036 36067866 37217939 37340703 38665916	G49108TO	The O-GlcNAc Database
725		28657654 29351928 32574038 35254053 35289036 36067866 37217939 37340703 38665916	G49108TO	GlyGen The O-GlcNAc Database
851		23090970		GlyGen
993		28657654 29351928 32574038 35254053 35289036 36067866 37217939 37340703 38665916	G49108TO	The O-GlcNAc Database
1029		28657654 29351928 32574038 35254053 35289036 36067866 37217939 37340703 38665916	G49108TO	The O-GlcNAc Database
1179	N-linked (GlcNAc...) asparagine	23090970 24190977 37074911	G45395BF G43223CG G27058EU G41071NU G02815KT	GlycoProtDB UniProt GlyGen

Feature

: Glycosylation Site from GlyGen
: Glycosylation Site from UniProt

Pathway

Displaying **all 8** entries
Pathway Name	Organism
Defective LFNG causes SCDO3	Homo sapiens
NOTCH3 Activation and Transmission of Signal to the Nucleus	Homo sapiens
NOTCH3 Intracellular Domain Regulates Transcription	Homo sapiens
Noncanonical activation of NOTCH3	Homo sapiens
Notch-HLH transcription pathway	Homo sapiens
Pre-NOTCH Processing in Golgi	Homo sapiens
Pre-NOTCH Processing in the Endoplasmic Reticulum	Homo sapiens
Pre-NOTCH Transcription and Translation	Homo sapiens

Human Protein Atlas

ENSG00000074181

Tissue with high expression from Human Protein Atlas. Tissues that are highly expressed are highlighted.

Data available from v23.0.proteinatlas.org. Image credit: Human Protein Atlas

Disease

Displaying **all 3** entries
DO ID	Disease Name	Source
DOID:0111035	autosomal dominant cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1	Alliance of Genome Resources
DOID:0111343	lateral meningocele syndrome	Alliance of Genome Resources
DOID:0080109	infantile myofibromatosis	Alliance of Genome Resources

GlyTouCan

GlyComb

GlycoPOST

UniCarb-DR

LM-GlycoRepo

All Resources

Other Information

Tools

Search Tools

Guidelines

Summary

External Links

Annotation

International Collaboration

Acknowledgements