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O95166

- GBRAP_HUMAN

UniProt

O95166 - GBRAP_HUMAN

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Protein

Gamma-aminobutyric acid receptor-associated protein

Gene

GABARAP

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

Ubiquitin-like modifier that plays a role in intracellular transport of GABA(A) receptors and its interaction with the cytoskeleton. Involved in apoptosis. Involved in autophagy. Whereas LC3s are involved in elongation of the phagophore membrane, the GABARAP/GATE-16 subfamily is essential for a later stage in autophagosome maturation.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei116 – 1172Cleavage; by ATG4B

GO - Molecular functioni

  1. beta-tubulin binding Source: UniProtKB
  2. GABA receptor binding Source: UniProtKB

GO - Biological processi

  1. autophagy Source: UniProtKB-KW
  2. extrinsic apoptotic signaling pathway via death domain receptors Source: UniProtKB
  3. microtubule cytoskeleton organization Source: Ensembl
  4. protein targeting Source: ProtInc
  5. synaptic transmission Source: ProtInc
Complete GO annotation...

Keywords - Biological processi

Apoptosis, Autophagy, Protein transport, Transport

Protein family/group databases

TCDBi1.A.9.5.2. the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Gamma-aminobutyric acid receptor-associated protein
Alternative name(s):
GABA(A) receptor-associated protein
MM46
Gene namesi
Name:GABARAP
Synonyms:FLC3B
ORF Names:HT004
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 17

Organism-specific databases

HGNCiHGNC:4067. GABARAP.

Subcellular locationi

Endomembrane system By similarity. Cytoplasmcytoskeleton By similarity. Golgi apparatus membrane By similarity. Cytoplasmic vesicleautophagosome 4 Publications
Note: Largely associated with intracellular membrane structures including the Golgi apparatus and postsynaptic cisternae. Colocalizes with microtubules (By similarity). Localizes also to discrete punctae along the ciliary axoneme (By similarity).By similarity

GO - Cellular componenti

  1. actin cytoskeleton Source: Ensembl
  2. autophagic vacuole Source: UniProtKB
  3. autophagic vacuole membrane Source: UniProtKB
  4. axoneme Source: UniProtKB
  5. cell body Source: Ensembl
  6. cytoplasmic vesicle Source: UniProtKB-KW
  7. Golgi apparatus Source: UniProtKB-KW
  8. lysosome Source: Ensembl
  9. microtubule Source: UniProtKB-KW
  10. microtubule associated complex Source: Ensembl
  11. perinuclear region of cytoplasm Source: Ensembl
  12. plasma membrane Source: ProtInc
  13. smooth endoplasmic reticulum Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoplasmic vesicle, Cytoskeleton, Golgi apparatus, Membrane, Microtubule

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi49 – 502YL → AA: Inhibits interaction with TECPR2. 1 Publication
Mutagenesisi67 – 671R → A: No effect on interaction with TECPR2. 1 Publication
Mutagenesisi116 – 1161G → A: Impairs localization at the autophagosomal membrane. 1 Publication

Organism-specific databases

PharmGKBiPA28480.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 116116Gamma-aminobutyric acid receptor-associated proteinPRO_0000212363Add
BLAST
Propeptidei117 – 1171Removed in mature formPRO_0000423065

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi116 – 1161Phosphatidylethanolamine amidated glycine1 Publication

Post-translational modificationi

The precursor molecule is cleaved by ATG4B to form the cytosolic form, GABARAP-I. This is activated by APG7L/ATG7, transferred to ATG3 and conjugated to phospholipid to form the membrane-bound form, GABARAP-II.1 Publication

Keywords - PTMi

Lipoprotein

Proteomic databases

MaxQBiO95166.
PaxDbiO95166.
PRIDEiO95166.

PTM databases

PhosphoSiteiO95166.

Miscellaneous databases

PMAP-CutDBO95166.

Expressioni

Tissue specificityi

Heart, brain, placenta, liver, skeletal muscle, kidney and pancreas.2 Publications

Gene expression databases

BgeeiO95166.
CleanExiHS_GABARAP.
ExpressionAtlasiO95166. baseline.
GenevestigatoriO95166.

Interactioni

Subunit structurei

Interacts with GPHN and NSF (By similarity). Interacts with ATG3, ATG7, ATG13, RB1CC1, GABRG2, beta-tubulin and ULK1. Interacts with CALR. Interacts with DDX47. Interacts with TP53INP1 and TP53INP2. Interacts with TBC1D25. Directly interacts with SQSTM1. Interacts with MAPK15. Interacts with TECPR2 and PCM1.By similarity17 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ATG2AQ2TAZ02EBI-712001,EBI-2514077
ATG3Q9NT625EBI-712001,EBI-988094
ATG4BQ9Y4P18EBI-712001,EBI-712014
ATG5Q9H1Y02EBI-712001,EBI-1047414
ATG7O953528EBI-712001,EBI-987834
Bnip3lQ9Z2F72EBI-712001,EBI-1774669From a different organism.
CALRP277974EBI-712001,EBI-1049597
DDX47Q9H0S43EBI-712001,EBI-2515241
DYX1C1Q8WXU24EBI-712001,EBI-2946907
FNBP1Q96RU32EBI-712001,EBI-1111248
FNIP1Q8TF405EBI-712001,EBI-2946919
FYCO1Q9BQS82EBI-712001,EBI-2869338
GBASO753235EBI-712001,EBI-307133
HADHAP409395EBI-712001,EBI-356720
IPO5O004106EBI-712001,EBI-356424
KBTBD6Q86V973EBI-712001,EBI-2514778
KBTBD7Q8WVZ92EBI-712001,EBI-473695
NBR1Q145965EBI-712001,EBI-742698
NCOA7Q8NI084EBI-712001,EBI-80799
NEDD4P469346EBI-712001,EBI-726944
NEK9Q8TD195EBI-712001,EBI-1044009
NSMAFQ926362EBI-712001,EBI-2947053
RASSF1Q9NS232EBI-712001,EBI-367363
RASSF5Q8WWW02EBI-712001,EBI-367390
SQSTM1Q1350110EBI-712001,EBI-307104
STBD1O952105EBI-712001,EBI-2947137
STK3Q131882EBI-712001,EBI-992580
STK4Q130432EBI-712001,EBI-367376
TBC1D15Q8TC075EBI-712001,EBI-1048247
TBC1D2BQ9UPU72EBI-712001,EBI-2947180
TECPR2O150402EBI-712001,EBI-2946991
UBA5Q9GZZ92EBI-712001,EBI-747805

Protein-protein interaction databases

BioGridi116465. 46 interactions.
DIPiDIP-35050N.
IntActiO95166. 474 interactions.
MINTiMINT-206256.
STRINGi9606.ENSP00000306866.

Structurei

Secondary structure

1
117
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi4 – 85
Helixi11 – 2414
Beta strandi28 – 358
Beta strandi47 – 526
Helixi57 – 6812
Beta strandi77 – 804
Beta strandi87 – 904
Helixi91 – 988
Beta strandi101 – 1033
Beta strandi105 – 1117

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1GNUX-ray1.75A1-117[»]
1KLVNMR-A1-117[»]
1KM7NMR-A1-117[»]
1KOTNMR-A1-117[»]
3D32X-ray1.30A/B1-117[»]
3DOWX-ray2.30A1-117[»]
3WIMX-ray2.60A1-117[»]
ProteinModelPortaliO95166.
SMRiO95166. Positions 1-116.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO95166.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 2222Interaction with beta-tubulinAdd
BLAST
Regioni36 – 11782Interaction with GPHNBy similarityAdd
BLAST
Regioni36 – 6833Interaction with GABRG2Sequence AnalysisAdd
BLAST

Sequence similaritiesi

Belongs to the ATG8 family.Curated

Phylogenomic databases

eggNOGiNOG263746.
HOGENOMiHOG000232034.
HOVERGENiHBG051706.
KOiK08341.
OMAiTTMGQLY.
OrthoDBiEOG70KGRK.
PhylomeDBiO95166.
TreeFamiTF314556.

Family and domain databases

InterProiIPR004241. Atg8_like.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PANTHERiPTHR10969. PTHR10969. 1 hit.
PfamiPF02991. Atg8. 1 hit.
[Graphical view]
SUPFAMiSSF54236. SSF54236. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O95166-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MKFVYKEEHP FEKRRSEGEK IRKKYPDRVP VIVEKAPKAR IGDLDKKKYL
60 70 80 90 100
VPSDLTVGQF YFLIRKRIHL RAEDALFFFV NNVIPPTSAT MGQLYQEHHE
110
EDFFLYIAYS DESVYGL
Length:117
Mass (Da):13,918
Last modified:May 1, 1999 - v1
Checksum:iBC0B84B8A51C1E32
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF161586 mRNA. Translation: AAD47641.1.
AB030711 mRNA. Translation: BAB21549.1.
AF044671 mRNA. Translation: AAD02337.1.
AF067171 mRNA. Translation: AAD32455.1.
AF183425 mRNA. Translation: AAG09694.1.
CCDSiCCDS11092.1.
RefSeqiNP_009209.1. NM_007278.1.
UniGeneiHs.647421.

Genome annotation databases

EnsembliENST00000302386; ENSP00000306866; ENSG00000170296.
GeneIDi11337.
KEGGihsa:11337.
UCSCiuc002gfb.3. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF161586 mRNA. Translation: AAD47641.1 .
AB030711 mRNA. Translation: BAB21549.1 .
AF044671 mRNA. Translation: AAD02337.1 .
AF067171 mRNA. Translation: AAD32455.1 .
AF183425 mRNA. Translation: AAG09694.1 .
CCDSi CCDS11092.1.
RefSeqi NP_009209.1. NM_007278.1.
UniGenei Hs.647421.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1GNU X-ray 1.75 A 1-117 [» ]
1KLV NMR - A 1-117 [» ]
1KM7 NMR - A 1-117 [» ]
1KOT NMR - A 1-117 [» ]
3D32 X-ray 1.30 A/B 1-117 [» ]
3DOW X-ray 2.30 A 1-117 [» ]
3WIM X-ray 2.60 A 1-117 [» ]
ProteinModelPortali O95166.
SMRi O95166. Positions 1-116.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 116465. 46 interactions.
DIPi DIP-35050N.
IntActi O95166. 474 interactions.
MINTi MINT-206256.
STRINGi 9606.ENSP00000306866.

Protein family/group databases

TCDBi 1.A.9.5.2. the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family.

PTM databases

PhosphoSitei O95166.

Proteomic databases

MaxQBi O95166.
PaxDbi O95166.
PRIDEi O95166.

Protocols and materials databases

DNASUi 11337.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000302386 ; ENSP00000306866 ; ENSG00000170296 .
GeneIDi 11337.
KEGGi hsa:11337.
UCSCi uc002gfb.3. human.

Organism-specific databases

CTDi 11337.
GeneCardsi GC17M007143.
HGNCi HGNC:4067. GABARAP.
MIMi 605125. gene.
neXtProti NX_O95166.
PharmGKBi PA28480.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG263746.
HOGENOMi HOG000232034.
HOVERGENi HBG051706.
KOi K08341.
OMAi TTMGQLY.
OrthoDBi EOG70KGRK.
PhylomeDBi O95166.
TreeFami TF314556.

Miscellaneous databases

ChiTaRSi GABARAP. human.
EvolutionaryTracei O95166.
GeneWikii GABARAP.
GenomeRNAii 11337.
NextBioi 43075.
PMAP-CutDB O95166.
PROi O95166.
SOURCEi Search...

Gene expression databases

Bgeei O95166.
CleanExi HS_GABARAP.
ExpressionAtlasi O95166. baseline.
Genevestigatori O95166.

Family and domain databases

InterProi IPR004241. Atg8_like.
IPR029071. Ubiquitin-rel_dom.
[Graphical view ]
PANTHERi PTHR10969. PTHR10969. 1 hit.
Pfami PF02991. Atg8. 1 hit.
[Graphical view ]
SUPFAMi SSF54236. SSF54236. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "GABA(A)-receptor-associated protein links GABA(A) receptors and the cytoskeleton."
    Wang H., Bedford F.K., Brandon N.J., Moss S.J., Olsen R.W.
    Nature 397:69-72(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INTERACTION WITH GABRG2 AND BETA-TUBULIN.
    Tissue: Brain.
  2. "Interaction of the Unc-51-like kinase and microtubule-associated protein light chain 3 related proteins in the brain: possible role of vesicular transport in axonal elongation."
    Okazaki N., Yan J., Yuasa S., Ueno T., Kominami E., Masuho Y., Koga H., Muramatsu M.-A.
    Brain Res. Mol. Brain Res. 85:1-12(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INTERACTION WITH ULK1.
    Tissue: Frontal cortex.
  3. Iijima M., Mitsui Y.
    Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  4. Ye M., Fu G., Wu J., Zhou J., Zhang Q., Shen Y., Kan L., He K., Gu B., Chen S., Mao M., Chen Z.
    Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Hypothalamus.
  6. "The human homolog of Saccharomyces cerevisiae Apg7p is a Protein-activating enzyme for multiple substrates including human Apg12p, GATE-16, GABARAP, and MAP-LC3."
    Tanida I., Tanida-Miyake E., Ueno T., Kominami E.
    J. Biol. Chem. 276:1701-1706(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ATG7.
  7. "Human Apg3p/Aut1p homologue is an authentic E2 enzyme for multiple substrates, GATE-16, GABARAP, and MAP-LC3, and facilitates the conjugation of hApg12p to hApg5p."
    Tanida I., Tanida-Miyake E., Komatsu M., Ueno T., Kominami E.
    J. Biol. Chem. 277:13739-13744(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ATG3.
  8. "GATE-16 and GABARAP are authentic modifiers mediated by Apg7 and Apg3."
    Tanida I., Komatsu M., Ueno T., Kominami E.
    Biochem. Biophys. Res. Commun. 300:637-644(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: LIPIDATION AT GLY-116, INTERACTION WITH ATG3 AND ATG7, SUBCELLULAR LOCATION.
  9. "LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation."
    Kabeya Y., Mizushima N., Yamamoto A., Oshitani-Okamoto S., Ohsumi Y., Yoshimori T.
    J. Cell Sci. 117:2805-2812(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: CLEAVAGE, SUBCELLULAR LOCATION, MUTAGENESIS OF GLY-116.
  10. "GABAA receptor-associated protein (GABARAP) induces apoptosis by interacting with DEAD (Asp-Glu-Ala-Asp/His) box polypeptide 47 (DDX 47)."
    Lee J.H., Rho S.B., Chun T.
    Biotechnol. Lett. 27:623-628(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH DDX47.
  11. "p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy."
    Pankiv S., Clausen T.H., Lamark T., Brech A., Bruun J.A., Outzen H., Overvatn A., Bjorkoy G., Johansen T.
    J. Biol. Chem. 282:24131-24145(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SQSTM1, SUBCELLULAR LOCATION.
  12. Cited for: SUBCELLULAR LOCATION, INTERACTION WITH TP53INP2.
  13. "Network organization of the human autophagy system."
    Behrends C., Sowa M.E., Gygi S.P., Harper J.W.
    Nature 466:68-76(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TECPR2, MUTAGENESIS OF 49-TYR-LEU-50 AND ARG-67.
  14. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  15. "OATL1, a novel autophagosome-resident Rab33B-GAP, regulates autophagosomal maturation."
    Itoh T., Kanno E., Uemura T., Waguri S., Fukuda M.
    J. Cell Biol. 192:839-853(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TBC1D25.
  16. Cited for: INTERACTION WITH MAPK15.
  17. "TP53INP1, a tumor suppressor, interacts with LC3 and ATG8-family proteins through the LC3-interacting region (LIR) and promotes autophagy-dependent cell death."
    Seillier M., Peuget S., Gayet O., Gauthier C., N'guessan P., Monte M., Carrier A., Iovanna J.L., Dusetti N.J.
    Cell Death Differ. 19:1525-1535(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TP53INP1.
  18. "ATG8 family proteins act as scaffolds for assembly of the ULK complex: sequence requirements for LC3-interacting region (LIR) motifs."
    Alemu E.A., Lamark T., Torgersen K.M., Birgisdottir A.B., Larsen K.B., Jain A., Olsvik H., Overvatn A., Kirkin V., Johansen T.
    J. Biol. Chem. 287:39275-39290(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ATG13; RB1CC1 AND ULK1.
  19. "DOR/Tp53inp2 and Tp53inp1 constitute a metazoan gene family encoding dual regulators of autophagy and transcription."
    Sancho A., Duran J., Garcia-Espana A., Mauvezin C., Alemu E.A., Lamark T., Macias M.J., Desalle R., Royo M., Sala D., Chicote J.U., Palacin M., Johansen T., Zorzano A.
    PLoS ONE 7:E34034-E34034(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TP53INP1 AND TP53INP2.
  20. "Autophagy promotes primary ciliogenesis by removing OFD1 from centriolar satellites."
    Tang Z., Lin M.G., Stowe T.R., Chen S., Zhu M., Stearns T., Franco B., Zhong Q.
    Nature 502:254-257(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION PCM1.
  21. "The X-ray crystal structure and putative ligand-derived peptide binding properties of gamma-aminobutyric acid receptor type A receptor-associated protein."
    Knight D., Harris R., McAlister M.S.B., Phelan J.P., Geddes S., Moss S.J., Driscoll P.C., Keep N.H.
    J. Biol. Chem. 277:5556-5561(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS), INTERACTION WITH GABRG2; TUBULIN ALPHA AND TUBULIN BETA.
  22. "Solution structure of human GABA(A) receptor-associated protein GABARAP: implications for biological function and its regulation."
    Stangler T., Mayr L.M., Willbold D.
    J. Biol. Chem. 277:13363-13366(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR.
  23. "1H, 13C and '5N resonance assignments of GABARAP, GABAA receptor associated protein."
    Kouno T., Miura K., Kanematsu T., Shirakawa M., Hirata M., Kawano K.
    J. Biomol. NMR 22:97-98(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR.
  24. Cited for: X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS).
  25. "Structural framework of the GABARAP-calreticulin interface --implications for substrate binding to endoplasmic reticulum chaperones."
    Thielmann Y., Weiergraber O.H., Mohrluder J., Willbold D.
    FEBS J. 276:1140-1152(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH CALR, INTERACTION WITH CALR.

Entry informationi

Entry nameiGBRAP_HUMAN
AccessioniPrimary (citable) accession number: O95166
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 1, 2004
Last sequence update: May 1, 1999
Last modified: October 29, 2014
This is version 121 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3