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FLASH GENE

Symbol

GABARAP

contributors: mct - updated : 28-03-2020

HGNC name	GABA(A) receptor-associated protein
HGNC id	4067

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	2.02 kb     4 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_007278 4 - 924 NP_009209 - 117 - 2009 19154346

EXPRESSION

Type	ubiquitous

expressed in

(based on citations)

organ(s)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       highly Endocrine neuroendocrine pituitary     highly Homo sapiens   pancreas       highly Homo sapiens   thyroid       highly Homo sapiens Nervous brain limbic system hippocampus     Homo sapiens   brain hindbrain cerebellum     Homo sapiens Reproductive male system prostate     highly Respiratory lung

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow       Connective bone       Muscular striatum skeletal

cells

System Cell Pubmed Species Stage Rna symbol Nervous mitral cell Nervous neuron Homo sapiens Nervous Purkinje cell Homo sapiens Nervous pyramidal cell Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text

placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

putative tubulin binding motif

HOMOLOGY

interspecies	homolog to murine Gabarap (100.00pc)
	ortholog to yeast Atg8
	homolog to rattus Gabarap (100.00pc)

intraspecies	homolog to GABARAPL1
	homolog to microtubule associated proteins 1A and 1B
	homolog to ganglioside expression factor homolog 2

Homologene

FAMILY	MAP1LC3 family
	ATG8 family LC3/GABARAP proteins

CATEGORY

receptor membrane

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,organelle,lysosome
	intracellular,cytoplasm,cytosolic,vesicle
	intracellular,cytoplasm,cytoskeleton,microtubule
text	perinuclear vesicles
	ULK1 and the GABARAP proteins co-localized to many kind of neurons such as pyramidal cells of the hippocampus, mitral cells of the olfactory bulb, and Purkinje cells of the cerebellum
	colocalizes with microtubules
	is enriched in the axonal initial segments (AIS, in addition to the cell bodies and dendrites, of these hippocampal pyramidal neurons and cerebellar Purkinje cells
	GABARAP is on the pericentriolar matrix

basic FUNCTION	acting as a neurotransmitter receptor by mediating interactions with the cytoskeleton
	may play a role in intracellular transport of GABA(A)receptors and its interaction with the cytoskeleton
	ligand-gated chloride channel mediating inhibitory neurotransmission
	involved in intracellular trafficking of the GABA(A) receptor, as a binding partner for AGTR1A
	GABARAP/GABARAPL2 subfamily is essential for a later stage in autophagosome maturation
	MAP1LC3A and MAP1LC3B and GABARAPs are essential for autophagosome formation and therefore suggest a dual role for individual members of this protein family
	important role of ATG8 homologues may be to act as a scaffold for the assembly of autophagy complexes
	functions in the immune system, and is involved in mitochondrial quality control in macrophages, thus influencing NLRP3 inflammasome-dependent inflammatory response
	PLCL1 and GABARAP function in a complex to regulate KIF5B-mediated insulin secretion, providing new insights into insulin exocytic mechanisms
	macroautophagic sequestration did not require the MAP1LC3 subfamily, but, intriguingly, GABARAP, GABARAPL1, GABARAPL2 are essential
	GABARAP is on the pericentriolar matrix, and this dynamic pool contributes to autophagosome formation
	unique non-hierarchical role for GABARAP in starvation-induced activation of autophagy
	potential involvement of GABARAP in tumorigenesis by delaying cell death and its associated immune-related response
	MAP1LC3B, GABARAPL2 and GABARAP might play specific roles in different autophagic processes
	GABARAP, GABARAPL1, GABARAPL2, MAP1LC3A, MAP1LC3B, are not essential for autophagosome formation but are critical for autophagosome-lysosome fusion
	essential for the formation of autophagosomes during macroautophagy/autophagy, and the sequestration of cargo during selective autophagy

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

GABARAP/GABARAPL2 subfamily is essential for a later stage in autophagosome maturation

INTERACTION

DNA

RNA

small molecule

protein	binding GABA-A receptor gamma 2 subunit and linking the receptors to the cytoskeleton
	TFRC
	interacts with GPHN and NSF
	interacts with beta-tubulin and ULK1 (important to vesicle transport and axonal elongation in mammalian neurons)
	interaction between RAB24 and two proteins, cyclophilin A (PPIA) and gamma-aminobutyric acid type A receptor-associated protein (GABARAP) (Pubmed 16596256)
	binds to and promotes trafficking of the AGTR1A to the plasma membrane
	binding to BNIP3L
	binding to CALR
	binding to CLTC
	MAP1LC3B, GABARAP and GABARAPL1 are novel interactors of MAPK15, a MAP kinase involved in cell proliferation and transformation
	ULK1 interacted most strongly with GABARAP and GABARAPL1, but it also interacted with GABARAPL2, MAP1LC3A, and MAP1LC3C
	presence of an acidic residue adjacent to the core motif is crucial for the ability of ULK1 and ATG13 to interact with GABARAP
	BCL2 directly binds to the phagophore-associated protein GABARAP
	FLCN-GABARAP association is modulated by the presence of either folliculin-interacting protein FNIP1 or FNIP2 and further regulated by ULK1
	MUL1 is involved in multiple biological pathways, and the interaction of GABARAP with MUL1-UBE2E3 supports the role of MUL1 as an important regulator of mitophagy and provides a plausible mechanism for its function in this process
	WAC and GOLGA2 interact with the ATG8 homolog GABARAP and regulate its subcellular localization
	GABARAP subfamily members, GABARAP, GABARAPL1, GABARAPL2, MAP1LC3A, MAP1LC3B, are primary contributors to PINK1/Parkin mitophagy and starvation autophagy
	key driver of starvation-induced autophagy and PINK1-PARK2-dependent mitophagy
	RIPOR2 interacts with GABARAP, a key macroautophagy/autophagy pathway protein

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

DEL17P131

Susceptibility

to nicotinic dependence

Variant & Polymorphism other	variants increasing nicotinic dependence

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

knockdown of Gabarap resulted in dwarfism of the entire zebrafish body, as well as a severely hypoplastic head and mandible. The findings suggested that the Gabarap gene plays a role in brain development in zebrafish (Komoike 2010)