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free fatty acid receptor 1

Summary

Gene Symbol

FFAR1

Organism

Homo sapiens (human)

External Links

NCBI Gene

2864

PubChem

2864

Alliance of Genome Resources

HGNC:4498

Annotation

Keyword

3D-structure
Cell membrane
Disulfide bond
G-protein coupled receptor
Glycoprotein
Lipid-binding
Reference proteome
Transmembrane helix

Proteins

Displaying 1 entry
UniProt	Protein Name
O14842	G-protein coupled receptor 40

Annotation information from UniProt.

Gene Ontology (GO)

Displaying entries **1 - 5** of 13 in total

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GO Term	Evidence Code	PMID
G protein-coupled receptor signaling pathway	IBA
phospholipase C-activating G protein-coupled receptor signaling pathway	IEA
positive regulation of cytosolic calcium ion concentration	IDA	24742677
positive regulation of cytosolic calcium ion concentration	IBA
insulin secretion	IEA

GO Hierarchy

biological process

cellular process [inference]

signal transduction [inference]

G protein-coupled receptor signaling pathway

ligand-gated ion channel signaling pathway

cellular localization [inference]

cellular macromolecule localization [inference]

protein localization [inference]

establishment of protein localization [inference]

protein transport [inference]

protein secretion [inference]

insulin secretion

establishment of protein localization to extracellular region [inference]

protein secretion [inference]

insulin secretion

protein localization to extracellular region [inference]

establishment of protein localization to extracellular region [inference]

protein secretion [inference]

insulin secretion

export from cell [inference]

secretion by cell [inference]

protein secretion [inference]

insulin secretion

signal release [inference]

hormone secretion [inference]

peptide hormone secretion [inference]

insulin secretion

homeostatic process [inference]

chemical homeostasis [inference]

carbohydrate homeostasis [inference]

glucose homeostasis

response to stimulus [inference]

response to chemical [inference]

response to organic substance [inference]

response to lipid [inference]

response to fatty acid

response to oxygen-containing compound [inference]

response to fatty acid

localization [inference]

macromolecule localization [inference]

cellular macromolecule localization [inference]

protein localization [inference]

establishment of protein localization [inference]

protein transport [inference]

protein secretion [inference]

insulin secretion

establishment of protein localization to extracellular region [inference]

protein secretion [inference]

insulin secretion

protein localization to extracellular region [inference]

establishment of protein localization to extracellular region [inference]

protein secretion [inference]

insulin secretion

establishment of localization [inference]

transport [inference]

hormone transport [inference]

hormone secretion [inference]

peptide hormone secretion [inference]

insulin secretion

secretion [inference]

peptide secretion [inference]

peptide hormone secretion [inference]

insulin secretion

secretion by cell [inference]

protein secretion [inference]

insulin secretion

signal release [inference]

hormone secretion [inference]

peptide hormone secretion [inference]

insulin secretion

organic substance transport [inference]

protein transport [inference]

protein secretion [inference]

insulin secretion

peptide transport [inference]

peptide secretion [inference]

peptide hormone secretion [inference]

insulin secretion

nitrogen compound transport [inference]

protein transport [inference]

protein secretion [inference]

insulin secretion

amide transport [inference]

peptide transport [inference]

peptide secretion [inference]

peptide hormone secretion [inference]

insulin secretion

export from cell [inference]

secretion by cell [inference]

protein secretion [inference]

insulin secretion

signal release [inference]

hormone secretion [inference]

peptide hormone secretion [inference]

insulin secretion

establishment of protein localization [inference]

protein transport [inference]

protein secretion [inference]

insulin secretion

establishment of protein localization to extracellular region [inference]

protein secretion [inference]

insulin secretion

cellular localization [inference]

cellular macromolecule localization [inference]

protein localization [inference]

establishment of protein localization [inference]

protein transport [inference]

protein secretion [inference]

insulin secretion

establishment of protein localization to extracellular region [inference]

protein secretion [inference]

insulin secretion

protein localization to extracellular region [inference]

establishment of protein localization to extracellular region [inference]

protein secretion [inference]

insulin secretion

biological regulation [inference]

regulation of biological process [inference]

regulation of metabolic process [inference]

regulation of biosynthetic process [inference]

negative regulation of biosynthetic process [inference]

negative regulation of cellular biosynthetic process [inference]

negative regulation of macromolecule biosynthetic process [inference]

negative regulation of gene expression [inference]

negative regulation of cytokine production [inference]

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

regulation of cellular biosynthetic process [inference]

regulation of macromolecule biosynthetic process [inference]

regulation of gene expression [inference]

regulation of cytokine production [inference]

negative regulation of cytokine production [inference]

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

regulation of interleukin-1 production [inference]

regulation of interleukin-1 beta production [inference]

negative regulation of interleukin-1 beta production

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

negative regulation of gene expression [inference]

negative regulation of cytokine production [inference]

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

negative regulation of macromolecule biosynthetic process [inference]

negative regulation of gene expression [inference]

negative regulation of cytokine production [inference]

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

negative regulation of cellular biosynthetic process [inference]

negative regulation of macromolecule biosynthetic process [inference]

negative regulation of gene expression [inference]

negative regulation of cytokine production [inference]

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

negative regulation of metabolic process [inference]

negative regulation of biosynthetic process [inference]

negative regulation of cellular biosynthetic process [inference]

negative regulation of macromolecule biosynthetic process [inference]

negative regulation of gene expression [inference]

negative regulation of cytokine production [inference]

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

negative regulation of macromolecule metabolic process [inference]

negative regulation of macromolecule biosynthetic process [inference]

negative regulation of gene expression [inference]

negative regulation of cytokine production [inference]

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

negative regulation of cellular metabolic process [inference]

negative regulation of cellular biosynthetic process [inference]

negative regulation of macromolecule biosynthetic process [inference]

negative regulation of gene expression [inference]

negative regulation of cytokine production [inference]

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

regulation of cellular metabolic process [inference]

negative regulation of cellular metabolic process [inference]

negative regulation of cellular biosynthetic process [inference]

negative regulation of macromolecule biosynthetic process [inference]

negative regulation of gene expression [inference]

negative regulation of cytokine production [inference]

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

regulation of cellular biosynthetic process [inference]

regulation of macromolecule biosynthetic process [inference]

regulation of gene expression [inference]

regulation of cytokine production [inference]

negative regulation of cytokine production [inference]

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

regulation of interleukin-1 production [inference]

regulation of interleukin-1 beta production [inference]

negative regulation of interleukin-1 beta production

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

negative regulation of gene expression [inference]

negative regulation of cytokine production [inference]

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

negative regulation of macromolecule biosynthetic process [inference]

negative regulation of gene expression [inference]

negative regulation of cytokine production [inference]

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

negative regulation of cellular biosynthetic process [inference]

negative regulation of macromolecule biosynthetic process [inference]

negative regulation of gene expression [inference]

negative regulation of cytokine production [inference]

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

regulation of macromolecule metabolic process [inference]

regulation of macromolecule biosynthetic process [inference]

regulation of gene expression [inference]

regulation of cytokine production [inference]

negative regulation of cytokine production [inference]

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

regulation of interleukin-1 production [inference]

regulation of interleukin-1 beta production [inference]

negative regulation of interleukin-1 beta production

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

negative regulation of gene expression [inference]

negative regulation of cytokine production [inference]

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

negative regulation of macromolecule biosynthetic process [inference]

negative regulation of gene expression [inference]

negative regulation of cytokine production [inference]

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

negative regulation of macromolecule metabolic process [inference]

negative regulation of macromolecule biosynthetic process [inference]

negative regulation of gene expression [inference]

negative regulation of cytokine production [inference]

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

regulation of signaling [inference]

positive regulation of signaling [inference]

positive regulation of hormone secretion [inference]

positive regulation of peptide hormone secretion [inference]

positive regulation of insulin secretion

regulation of hormone secretion [inference]

positive regulation of hormone secretion [inference]

positive regulation of peptide hormone secretion [inference]

positive regulation of insulin secretion

regulation of peptide hormone secretion [inference]

regulation of insulin secretion [inference]

positive regulation of insulin secretion

positive regulation of peptide hormone secretion [inference]

positive regulation of insulin secretion

regulation of localization [inference]

regulation of transport [inference]

regulation of monoatomic ion transport [inference]

regulation of metal ion transport [inference]

regulation of calcium ion transport [inference]

positive regulation of calcium ion transport

positive regulation of monoatomic ion transport [inference]

positive regulation of calcium ion transport

regulation of secretion [inference]

regulation of peptide secretion [inference]

positive regulation of peptide secretion [inference]

positive regulation of peptide hormone secretion [inference]

positive regulation of insulin secretion

regulation of peptide hormone secretion [inference]

regulation of insulin secretion [inference]

positive regulation of insulin secretion

positive regulation of peptide hormone secretion [inference]

positive regulation of insulin secretion

positive regulation of secretion [inference]

positive regulation of peptide secretion [inference]

positive regulation of peptide hormone secretion [inference]

positive regulation of insulin secretion

positive regulation of secretion by cell [inference]

positive regulation of hormone secretion [inference]

positive regulation of peptide hormone secretion [inference]

positive regulation of insulin secretion

positive regulation of protein secretion [inference]

positive regulation of insulin secretion

regulation of secretion by cell [inference]

regulation of hormone secretion [inference]

positive regulation of hormone secretion [inference]

positive regulation of peptide hormone secretion [inference]

positive regulation of insulin secretion

regulation of peptide hormone secretion [inference]

regulation of insulin secretion [inference]

positive regulation of insulin secretion

positive regulation of peptide hormone secretion [inference]

positive regulation of insulin secretion

regulation of protein secretion [inference]

positive regulation of protein secretion [inference]

positive regulation of insulin secretion

regulation of insulin secretion [inference]

positive regulation of insulin secretion

positive regulation of secretion by cell [inference]

positive regulation of hormone secretion [inference]

positive regulation of peptide hormone secretion [inference]

positive regulation of insulin secretion

positive regulation of protein secretion [inference]

positive regulation of insulin secretion

positive regulation of transport [inference]

positive regulation of monoatomic ion transport [inference]

positive regulation of calcium ion transport

positive regulation of secretion [inference]

positive regulation of peptide secretion [inference]

positive regulation of peptide hormone secretion [inference]

positive regulation of insulin secretion

positive regulation of secretion by cell [inference]

positive regulation of hormone secretion [inference]

positive regulation of peptide hormone secretion [inference]

positive regulation of insulin secretion

positive regulation of protein secretion [inference]

positive regulation of insulin secretion

positive regulation of protein transport [inference]

positive regulation of protein secretion [inference]

positive regulation of insulin secretion

regulation of protein transport [inference]

regulation of protein secretion [inference]

positive regulation of protein secretion [inference]

positive regulation of insulin secretion

regulation of insulin secretion [inference]

positive regulation of insulin secretion

positive regulation of protein transport [inference]

positive regulation of protein secretion [inference]

positive regulation of insulin secretion

regulation of peptide transport [inference]

regulation of peptide secretion [inference]

positive regulation of peptide secretion [inference]

positive regulation of peptide hormone secretion [inference]

positive regulation of insulin secretion

regulation of peptide hormone secretion [inference]

regulation of insulin secretion [inference]

positive regulation of insulin secretion

positive regulation of peptide hormone secretion [inference]

positive regulation of insulin secretion

regulation of cellular localization [inference]

regulation of protein localization [inference]

regulation of establishment of protein localization [inference]

regulation of protein transport [inference]

regulation of protein secretion [inference]

positive regulation of protein secretion [inference]

positive regulation of insulin secretion

regulation of insulin secretion [inference]

positive regulation of insulin secretion

positive regulation of protein transport [inference]

positive regulation of protein secretion [inference]

positive regulation of insulin secretion

positive regulation of establishment of protein localization [inference]

positive regulation of protein transport [inference]

positive regulation of protein secretion [inference]

positive regulation of insulin secretion

positive regulation of protein localization [inference]

positive regulation of establishment of protein localization [inference]

positive regulation of protein transport [inference]

positive regulation of protein secretion [inference]

positive regulation of insulin secretion

positive regulation of biological process [inference]

positive regulation of signaling [inference]

positive regulation of hormone secretion [inference]

positive regulation of peptide hormone secretion [inference]

positive regulation of insulin secretion

positive regulation of cellular process [inference]

positive regulation of cell communication [inference]

positive regulation of hormone secretion [inference]

positive regulation of peptide hormone secretion [inference]

positive regulation of insulin secretion

positive regulation of secretion by cell [inference]

positive regulation of hormone secretion [inference]

positive regulation of peptide hormone secretion [inference]

positive regulation of insulin secretion

positive regulation of protein secretion [inference]

positive regulation of insulin secretion

positive regulation of protein localization [inference]

positive regulation of establishment of protein localization [inference]

positive regulation of protein transport [inference]

positive regulation of protein secretion [inference]

positive regulation of insulin secretion

positive regulation of transport [inference]

positive regulation of monoatomic ion transport [inference]

positive regulation of calcium ion transport

positive regulation of secretion [inference]

positive regulation of peptide secretion [inference]

positive regulation of peptide hormone secretion [inference]

positive regulation of insulin secretion

positive regulation of secretion by cell [inference]

positive regulation of hormone secretion [inference]

positive regulation of peptide hormone secretion [inference]

positive regulation of insulin secretion

positive regulation of protein secretion [inference]

positive regulation of insulin secretion

positive regulation of protein transport [inference]

positive regulation of protein secretion [inference]

positive regulation of insulin secretion

negative regulation of biological process [inference]

negative regulation of metabolic process [inference]

negative regulation of biosynthetic process [inference]

negative regulation of cellular biosynthetic process [inference]

negative regulation of macromolecule biosynthetic process [inference]

negative regulation of gene expression [inference]

negative regulation of cytokine production [inference]

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

negative regulation of macromolecule metabolic process [inference]

negative regulation of macromolecule biosynthetic process [inference]

negative regulation of gene expression [inference]

negative regulation of cytokine production [inference]

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

negative regulation of cellular metabolic process [inference]

negative regulation of cellular biosynthetic process [inference]

negative regulation of macromolecule biosynthetic process [inference]

negative regulation of gene expression [inference]

negative regulation of cytokine production [inference]

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

negative regulation of cellular process [inference]

negative regulation of cellular metabolic process [inference]

negative regulation of cellular biosynthetic process [inference]

negative regulation of macromolecule biosynthetic process [inference]

negative regulation of gene expression [inference]

negative regulation of cytokine production [inference]

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

negative regulation of multicellular organismal process [inference]

negative regulation of cytokine production [inference]

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

regulation of cellular process [inference]

signal transduction [inference]

G protein-coupled receptor signaling pathway

ligand-gated ion channel signaling pathway

regulation of cell communication [inference]

positive regulation of cell communication [inference]

positive regulation of hormone secretion [inference]

positive regulation of peptide hormone secretion [inference]

positive regulation of insulin secretion

regulation of hormone secretion [inference]

positive regulation of hormone secretion [inference]

positive regulation of peptide hormone secretion [inference]

positive regulation of insulin secretion

regulation of peptide hormone secretion [inference]

regulation of insulin secretion [inference]

positive regulation of insulin secretion

positive regulation of peptide hormone secretion [inference]

positive regulation of insulin secretion

regulation of cellular metabolic process [inference]

negative regulation of cellular metabolic process [inference]

negative regulation of cellular biosynthetic process [inference]

negative regulation of macromolecule biosynthetic process [inference]

negative regulation of gene expression [inference]

negative regulation of cytokine production [inference]

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

regulation of cellular biosynthetic process [inference]

regulation of macromolecule biosynthetic process [inference]

regulation of gene expression [inference]

regulation of cytokine production [inference]

negative regulation of cytokine production [inference]

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

regulation of interleukin-1 production [inference]

regulation of interleukin-1 beta production [inference]

negative regulation of interleukin-1 beta production

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

negative regulation of gene expression [inference]

negative regulation of cytokine production [inference]

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

negative regulation of macromolecule biosynthetic process [inference]

negative regulation of gene expression [inference]

negative regulation of cytokine production [inference]

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

negative regulation of cellular biosynthetic process [inference]

negative regulation of macromolecule biosynthetic process [inference]

negative regulation of gene expression [inference]

negative regulation of cytokine production [inference]

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

positive regulation of cellular process [inference]

positive regulation of cell communication [inference]

positive regulation of hormone secretion [inference]

positive regulation of peptide hormone secretion [inference]

positive regulation of insulin secretion

positive regulation of secretion by cell [inference]

positive regulation of hormone secretion [inference]

positive regulation of peptide hormone secretion [inference]

positive regulation of insulin secretion

positive regulation of protein secretion [inference]

positive regulation of insulin secretion

positive regulation of protein localization [inference]

positive regulation of establishment of protein localization [inference]

positive regulation of protein transport [inference]

positive regulation of protein secretion [inference]

positive regulation of insulin secretion

negative regulation of cellular process [inference]

negative regulation of cellular metabolic process [inference]

negative regulation of cellular biosynthetic process [inference]

negative regulation of macromolecule biosynthetic process [inference]

negative regulation of gene expression [inference]

negative regulation of cytokine production [inference]

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

regulation of cellular localization [inference]

regulation of protein localization [inference]

regulation of establishment of protein localization [inference]

regulation of protein transport [inference]

regulation of protein secretion [inference]

positive regulation of protein secretion [inference]

positive regulation of insulin secretion

regulation of insulin secretion [inference]

positive regulation of insulin secretion

positive regulation of protein transport [inference]

positive regulation of protein secretion [inference]

positive regulation of insulin secretion

positive regulation of establishment of protein localization [inference]

positive regulation of protein transport [inference]

positive regulation of protein secretion [inference]

positive regulation of insulin secretion

positive regulation of protein localization [inference]

positive regulation of establishment of protein localization [inference]

positive regulation of protein transport [inference]

positive regulation of protein secretion [inference]

positive regulation of insulin secretion

regulation of secretion by cell [inference]

regulation of hormone secretion [inference]

positive regulation of hormone secretion [inference]

positive regulation of peptide hormone secretion [inference]

positive regulation of insulin secretion

regulation of peptide hormone secretion [inference]

regulation of insulin secretion [inference]

positive regulation of insulin secretion

positive regulation of peptide hormone secretion [inference]

positive regulation of insulin secretion

regulation of protein secretion [inference]

positive regulation of protein secretion [inference]

positive regulation of insulin secretion

regulation of insulin secretion [inference]

positive regulation of insulin secretion

positive regulation of secretion by cell [inference]

positive regulation of hormone secretion [inference]

positive regulation of peptide hormone secretion [inference]

positive regulation of insulin secretion

positive regulation of protein secretion [inference]

positive regulation of insulin secretion

regulation of multicellular organismal process [inference]

regulation of cytokine production [inference]

negative regulation of cytokine production [inference]

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

regulation of interleukin-1 production [inference]

regulation of interleukin-1 beta production [inference]

negative regulation of interleukin-1 beta production

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

negative regulation of multicellular organismal process [inference]

negative regulation of cytokine production [inference]

negative regulation of interleukin-1 production [inference]

negative regulation of interleukin-1 beta production

regulation of biological quality [inference]

positive regulation of cytosolic calcium ion concentration

regulation of hormone levels [inference]

hormone transport [inference]

hormone secretion [inference]

peptide hormone secretion [inference]

insulin secretion

regulation of hormone secretion [inference]

positive regulation of hormone secretion [inference]

positive regulation of peptide hormone secretion [inference]

positive regulation of insulin secretion

regulation of peptide hormone secretion [inference]

regulation of insulin secretion [inference]

positive regulation of insulin secretion

positive regulation of peptide hormone secretion [inference]

positive regulation of insulin secretion

Displaying **all 3** entries
GO Term	Evidence Code	PMID
plasma membrane	TAS
plasma membrane	IDA	24130766 25043059
plasma membrane	IBA

GO Hierarchy

cellular component

cellular anatomical entity [inference]

membrane [inference]

plasma membrane

Displaying **all 4** entries
GO Term	Evidence Code	PMID
G protein-coupled receptor activity	TAS	9344866
lipid binding	IEA
bioactive lipid receptor activity	IDA	24130766
bioactive lipid receptor activity	IBA

GO Hierarchy

molecular function

binding [inference]

lipid binding

molecular transducer activity [inference]

signaling receptor activity [inference]

transmembrane signaling receptor activity [inference]

G protein-coupled receptor activity

bioactive lipid receptor activity

Gene Ontology information from NCBI Gene and UniProt.

OrthoDB (Group)

Group level

Eukaryota

Group Name

free fatty acid receptor 1

Functional Category

E: Amino acid transport and metabolism
K: Transcription
M: Cell wall/membrane/envelope biogenesis

Displaying **all 4** entries
Gene Ontology
bioactive lipid receptor activity
positive regulation of cytosolic calcium ion concentration
positive regulation of insulin secretion
response to fatty acid

Displaying **all 4** entries
InterPro
G protein-coupled receptor 40-related receptor
G protein-coupled receptor, rhodopsin-like
GPCR, rhodopsin-like, 7TM
GPR40 receptor fatty acid

Disease

Disease Ontology

Displaying 1 entry
DO ID	Disease Name	Source
DOID:9352	type 2 diabetes mellitus	Alliance of Genome Resources

Ortholog

Displaying entries **1 - 10** of 50 in total

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Species	Gene ID	Alliance of Genome Resources	Orthologous MAtrix
Danio rerio	2864	ZFIN:ZDB-GENE-120215-191
Mus musculus	233081	ZFIN:ZDB-GENE-120215-191	MOUSE55836
Rattus norvegicus	266607	ZFIN:ZDB-GENE-120215-191	RATNO21314
Pan troglodytes	468836		PANTR17975
Canis lupus familiaris	612661		CANLF01210
Macaca mulatta	708620		MACMU18714
Callithrix jacchus	100410637		CALJA24315
Ailuropoda melanoleuca	100468088		AILME11057
Monodelphis domestica	100617163		MONDO25557
Loxodonta africana	100671890		LOXAF03427

GlyTouCan

GlyComb

GlycoPOST

UniCarb-DR

LM-GlycoRepo

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Annotation

OrthoDB (Group)

International Collaboration

Acknowledgements