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Protein

ADP-ribosylation factor-binding protein GGA1

Gene

GGA1

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

Functioni

Plays a role in protein sorting and trafficking between the trans-Golgi network (TGN) and endosomes. Mediates the ARF-dependent recruitment of clathrin to the TGN and binds ubiquitinated proteins and membrane cargo molecules with a cytosolic acidic cluster-dileucine (AC-LL) motif.1 Publication

Caution

It is uncertain whether Met-1 or Met-5 is the initiator.Curated

GO - Molecular functioni

  • ADP-ribosylation factor binding Source: CAFA
  • protein heterodimerization activity Source: CAFA

GO - Biological processi

Keywordsi

Biological processProtein transport, Transport

Enzyme and pathway databases

ReactomeiR-HSA-8854214 TBC/RABGAPs
R-HSA-977225 Amyloid fiber formation

Names & Taxonomyi

Protein namesi
Recommended name:
ADP-ribosylation factor-binding protein GGA1
Alternative name(s):
Gamma-adaptin-related protein 1
Golgi-localized, gamma ear-containing, ARF-binding protein 1
Gene namesi
Name:GGA1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

EuPathDBiHostDB:ENSG00000100083.18
HGNCiHGNC:17842 GGA1
MIMi606004 gene
neXtProtiNX_Q9UJY5

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Endosome, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi92N → A: Abolishes interaction with IGF2R. 1 Publication1
Mutagenesisi182L → A: Abolishes interaction with ARF1, UBC and TSG101. 1 Publication1
Mutagenesisi194N → A: Abolishes interaction with ARF1 and RABEP1. 1 Publication1
Mutagenesisi197I → A: Abolishes interaction with ARF1, UBC and TSG101. 1 Publication1
Mutagenesisi198K → A: Abolishes interaction with ARF1. 1 Publication1
Mutagenesisi200M → A: Abolishes interaction with ARF1. 1 Publication1
Mutagenesisi204D → A: Abolishes interaction with ARF1. 1 Publication1
Mutagenesisi259M → K: Abolishes interaction with RABEP1. 1
Mutagenesisi260R → A: No effect on interaction with RABEP1. 1 Publication1
Mutagenesisi260R → E: Abolishes interaction with RABEP1 and UBC. 1 Publication1
Mutagenesisi264F → A: Abolishes interaction with RABEP1. 1 Publication1
Mutagenesisi267A → D: Abolishes interaction with RABEP1 and UBC. 1 Publication1
Mutagenesisi277L → A: Abolishes interaction with RABEP1, UBC and TSG101. 1 Publication1
Mutagenesisi281L → A: Abolishes interaction with RABEP1. 1 Publication1
Mutagenesisi284N → A: Abolishes interaction with RABEP1. 1 Publication1
Mutagenesisi284N → S: Abolishes interaction with RABEP1. 1 Publication1
Mutagenesisi355S → A: Increased interaction with IGF2R. Reduced phosphorylation. 1 Publication1
Mutagenesisi355S → D: Abolishes interaction with IGF2R. 1 Publication1
Mutagenesisi356 – 360LLDDE → AADAA: Partial loss of clathrin-binding. 1 Publication5
Mutagenesisi358D → A: Increased interaction with IGF2R. 1 Publication1
Mutagenesisi361 – 362LM → AA: Increased interaction with IGF2R. 1 Publication2
Mutagenesisi563A → D: Abolishes interaction with CCDC91. 1 Publication1
Mutagenesisi564V → D: Abolishes interaction with CCDC91. 1 Publication1
Mutagenesisi570V → E: Abolishes interaction with CCDC91. 1 Publication1
Mutagenesisi572L → E: Abolishes interaction with CCDC91. 1 Publication1

Organism-specific databases

DisGeNETi26088
OpenTargetsiENSG00000100083
PharmGKBiPA28657

Polymorphism and mutation databases

BioMutaiGGA1
DMDMi14548066

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002126801 – 639ADP-ribosylation factor-binding protein GGA1Add BLAST639

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei185PhosphoserineCombined sources1
Modified residuei355Phosphoserine; by CK21 Publication1
Modified residuei418PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated by CK2 and dephosphorylated by PP2A. Phosphorylation of GGA1 allows the internal AC-LL motif to bind the VHS domain and to inhibit the recognition of cargo signals.1 Publication
Ubiquitinated.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9UJY5
PaxDbiQ9UJY5
PeptideAtlasiQ9UJY5
PRIDEiQ9UJY5

PTM databases

iPTMnetiQ9UJY5
PhosphoSitePlusiQ9UJY5

Expressioni

Tissue specificityi

Ubiquitously expressed.

Gene expression databases

BgeeiENSG00000100083
CleanExiHS_GGA1
ExpressionAtlasiQ9UJY5 baseline and differential
GenevisibleiQ9UJY5 HS

Organism-specific databases

HPAiHPA048280
HPA051016

Interactioni

Subunit structurei

Monomer. Interacts with NECAP1. Interacts with CNST (By similarity). Interacts with GGA2 and GGA3. Binds to clathrin and activated ARFs, including ARF1 and ARF6. Interacts with RABEP1 and RABGEF1. Interacts with the type-I membrane proteins SORT1, SORL1, LRP3, M6PR/CD-MPR, IGF2R/CI-MPR and BACE1. Binds CCDC91, P200, SYNRG, EPN4, NECAP2 and AFTPH/aftiphilin. Interacts with TSG101 and UBC. Interacts with RNF11.By similarity19 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • ADP-ribosylation factor binding Source: CAFA
  • protein heterodimerization activity Source: CAFA

Protein-protein interaction databases

BioGridi117540, 76 interactors
ELMiQ9UJY5
IntActiQ9UJY5, 38 interactors
MINTiQ9UJY5
STRINGi9606.ENSP00000341344

Structurei

Secondary structure

1639
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi3 – 5Combined sources3
Helixi10 – 17Combined sources8
Helixi27 – 36Combined sources10
Helixi37 – 39Combined sources3
Beta strandi40 – 42Combined sources3
Helixi43 – 55Combined sources13
Helixi60 – 76Combined sources17
Helixi79 – 85Combined sources7
Helixi88 – 98Combined sources11
Turni100 – 103Combined sources4
Helixi104 – 106Combined sources3
Helixi109 – 125Combined sources17
Helixi130 – 141Combined sources12
Helixi172 – 182Combined sources11
Helixi187 – 205Combined sources19
Helixi212 – 233Combined sources22
Turni235 – 238Combined sources4
Helixi243 – 267Combined sources25
Helixi274 – 298Combined sources25
Helixi494 – 497Combined sources4
Helixi504 – 506Combined sources3
Beta strandi515 – 520Combined sources6
Beta strandi523 – 531Combined sources9
Beta strandi533 – 535Combined sources3
Beta strandi540 – 549Combined sources10
Beta strandi555 – 563Combined sources9
Beta strandi568 – 572Combined sources5
Beta strandi592 – 599Combined sources8
Beta strandi608 – 616Combined sources9
Beta strandi619 – 627Combined sources9
Turni633 – 635Combined sources3
Helixi636 – 638Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1J2JX-ray1.60B166-210[»]
1JWFX-ray2.10A1-147[»]
1JWGX-ray2.00A/B1-147[»]
1NA8X-ray2.30A/B494-639[»]
1NAFX-ray2.80A165-314[»]
1NWMX-ray2.40X166-302[»]
1O3XX-ray2.10A166-305[»]
1OM9X-ray2.50A/B494-639[»]
1OXZX-ray2.80A141-326[»]
1PY1X-ray2.60A/B/C/D2-157[»]
1UJJX-ray2.60A/B1-147[»]
1UJKX-ray1.90A/B1-147[»]
1X79X-ray2.41A210-302[»]
2DWXX-ray2.55A/B/C/D507-639[»]
P/Q376-388[»]
2DWYX-ray2.30A/B/C/D507-639[»]
3G2SX-ray1.70A/B1-147[»]
3G2TX-ray2.00A/B1-147[»]
3G2UX-ray2.30A/B1-147[»]
3G2VX-ray2.10A/B1-147[»]
3G2WX-ray2.40A/B1-147[»]
C/D351-364[»]
DisProtiDP00314
ProteinModelPortaliQ9UJY5
SMRiQ9UJY5
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UJY5

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini17 – 147VHSPROSITE-ProRule annotationAdd BLAST131
Domaini171 – 299GATPROSITE-ProRule annotationAdd BLAST129
Domaini510 – 631GAEPROSITE-ProRule annotationAdd BLAST122

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni114 – 274Interaction with ARF3Add BLAST161
Regioni300 – 509Unstructured hingeAdd BLAST210

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi358 – 362Autoinhibitory5

Domaini

The VHS domain functions as a recognition module for sorting signals composed of an acidic cluster followed by two leucines (AC-LL motif).
The GAT domain is responsible for interaction with ARF-GTP, UBC and RABEP1. Required for recruitment to the TGN it prevents ARF-GTP hydrolysis.
The unstructured hinge region contains clathrin-binding but no autoinhibitory (AC-LL) motifs.
The GAE domain binds accessory proteins regulating GGAs function.

Sequence similaritiesi

Belongs to the GGA protein family.Curated

Phylogenomic databases

eggNOGiKOG1087 Eukaryota
ENOG410Y26G LUCA
GeneTreeiENSGT00870000136446
HOGENOMiHOG000231169
HOVERGENiHBG015945
InParanoidiQ9UJY5
KOiK12404
OMAiYKLTFTM
OrthoDBiEOG091G0BQK
PhylomeDBiQ9UJY5
TreeFamiTF318574

Family and domain databases

Gene3Di1.20.58.160, 1 hit
1.25.40.90, 1 hit
InterProiView protein in InterPro
IPR008152 Clathrin_a/b/g-adaptin_app_Ig
IPR013041 Clathrin_app_Ig-like_sf
IPR008942 ENTH_VHS
IPR008153 GAE_dom
IPR004152 GAT_dom
IPR038425 GAT_sf
IPR002014 VHS_dom
PfamiView protein in Pfam
PF02883 Alpha_adaptinC2, 1 hit
PF03127 GAT, 1 hit
PF00790 VHS, 1 hit
SMARTiView protein in SMART
SM00809 Alpha_adaptinC2, 1 hit
SM00288 VHS, 1 hit
SUPFAMiSSF48464 SSF48464, 1 hit
SSF49348 SSF49348, 1 hit
PROSITEiView protein in PROSITE
PS50180 GAE, 1 hit
PS50909 GAT, 1 hit
PS50179 VHS, 1 hit

Sequences (6)i

Sequence statusi: Complete.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9UJY5-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEPAMEPETL EARINRATNP LNKELDWASI NGFCEQLNED FEGPPLATRL
60 70 80 90 100
LAHKIQSPQE WEAIQALTVL ETCMKSCGKR FHDEVGKFRF LNELIKVVSP
110 120 130 140 150
KYLGSRTSEK VKNKILELLY SWTVGLPEEV KIAEAYQMLK KQGIVKSDPK
160 170 180 190 200
LPDDTTFPLP PPRPKNVIFE DEEKSKMLAR LLKSSHPEDL RAANKLIKEM
210 220 230 240 250
VQEDQKRMEK ISKRVNAIEE VNNNVKLLTE MVMSHSQGGA AAGSSEDLMK
260 270 280 290 300
ELYQRCERMR PTLFRLASDT EDNDEALAEI LQANDNLTQV INLYKQLVRG
310 320 330 340 350
EEVNGDATAG SIPGSTSALL DLSGLDLPPA GTTYPAMPTR PGEQASPEQP
360 370 380 390 400
SASVSLLDDE LMSLGLSDPT PPSGPSLDGT GWNSFQSSDA TEPPAPALAQ
410 420 430 440 450
APSMESRPPA QTSLPASSGL DDLDLLGKTL LQQSLPPESQ QVRWEKQQPT
460 470 480 490 500
PRLTLRDLQN KSSSCSSPSS SATSLLHTVS PEPPRPPQQP VPTELSLASI
510 520 530 540 550
TVPLESIKPS NILPVTVYDQ HGFRILFHFA RDPLPGRSDV LVVVVSMLST
560 570 580 590 600
APQPIRNIVF QSAVPKVMKV KLQPPSGTEL PAFNPIVHPS AITQVLLLAN
610 620 630
PQKEKVRLRY KLTFTMGDQT YNEMGDVDQF PPPETWGSL
Length:639
Mass (Da):70,384
Last modified:May 1, 2000 - v1
Checksum:iB0B6F089FA0F7DD5
GO
Isoform 2 (identifier: Q9UJY5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     69-101: Missing.

Note: No experimental confirmation available.
Show »
Length:606
Mass (Da):66,563
Checksum:i6231A20CC57997B1
GO
Isoform 3 (identifier: Q9UJY5-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-73: Missing.

Show »
Length:566
Mass (Da):62,138
Checksum:iF96825C24B633E03
GO
Isoform 4 (identifier: Q9UJY5-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     277-363: Missing.

Show »
Length:552
Mass (Da):61,379
Checksum:iAC507C9F975A32C3
GO
Isoform 5 (identifier: Q9UJY5-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     70-89: LETCMKSCGKRFHDEVGKFR → RRGEATIRPPPCDDTKGGQD
     90-639: Missing.

Show »
Length:89
Mass (Da):9,969
Checksum:iF209D7D764D4CA7E
GO
Isoform 6 (identifier: Q9UJY5-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     68-68: T → TVRRGEATIRPPPCDDTK

Note: No experimental confirmation available.
Show »
Length:656
Mass (Da):72,277
Checksum:i60EE957099B4847C
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_036522239G → S in a breast cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs765255006Ensembl.1
Natural variantiVAR_036523484P → A in a breast cancer sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0428061 – 73Missing in isoform 3. 1 PublicationAdd BLAST73
Alternative sequenceiVSP_05735268T → TVRRGEATIRPPPCDDTK in isoform 6. 1 Publication1
Alternative sequenceiVSP_00174469 – 101Missing in isoform 2. CuratedAdd BLAST33
Alternative sequenceiVSP_04280770 – 89LETCM…VGKFR → RRGEATIRPPPCDDTKGGQD in isoform 5. 1 PublicationAdd BLAST20
Alternative sequenceiVSP_04280890 – 639Missing in isoform 5. 1 PublicationAdd BLAST550
Alternative sequenceiVSP_042809277 – 363Missing in isoform 4. 1 PublicationAdd BLAST87

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF190862 mRNA Translation: AAF05707.1
AF218584 mRNA Translation: AAF42847.1
AF233521 mRNA Translation: AAF35393.1
CR456493 mRNA Translation: CAG30379.1
AK075256 mRNA Translation: BAC11501.1
AK122898 mRNA Translation: BAG53788.1
AK290548 mRNA Translation: BAF83237.1
AL035496 Genomic DNA No translation available.
Z83844 Genomic DNA No translation available.
CH471095 Genomic DNA Translation: EAW60169.1
BC000538 mRNA Translation: AAH00538.2
BC010917 mRNA Translation: AAH10917.1
BC029388 mRNA Translation: AAH29388.1
BC044629 mRNA Translation: AAH44629.1
AL110219 mRNA Translation: CAB53679.1
CCDSiCCDS13951.1 [Q9UJY5-1]
CCDS33643.1 [Q9UJY5-4]
CCDS54526.1 [Q9UJY5-3]
PIRiT14759
RefSeqiNP_001001560.1, NM_001001560.2 [Q9UJY5-4]
NP_001166158.1, NM_001172687.1
NP_001166159.1, NM_001172688.1 [Q9UJY5-3]
NP_037497.1, NM_013365.4 [Q9UJY5-1]
XP_005261574.1, XM_005261517.3 [Q9UJY5-6]
XP_005261577.1, XM_005261520.1 [Q9UJY5-3]
XP_006724292.1, XM_006724229.1 [Q9UJY5-3]
XP_011528424.1, XM_011530122.1 [Q9UJY5-6]
XP_016884249.1, XM_017028760.1 [Q9UJY5-1]
XP_016884250.1, XM_017028761.1 [Q9UJY5-3]
XP_016884251.1, XM_017028762.1 [Q9UJY5-4]
UniGeneiHs.499158

Genome annotation databases

EnsembliENST00000325180; ENSP00000321288; ENSG00000100083 [Q9UJY5-4]
ENST00000343632; ENSP00000341344; ENSG00000100083 [Q9UJY5-1]
ENST00000381756; ENSP00000371175; ENSG00000100083 [Q9UJY5-6]
ENST00000406772; ENSP00000385287; ENSG00000100083 [Q9UJY5-3]
GeneIDi26088
KEGGihsa:26088
UCSCiuc003atc.4 human [Q9UJY5-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiGGA1_HUMAN
AccessioniPrimary (citable) accession number: Q9UJY5
Secondary accession number(s): A8K3D3
, B0QYR7, Q5R3N1, Q5TG07, Q6IC75, Q86YA9, Q8NCS6, Q9BW94, Q9UG00, Q9UGW0, Q9UGW1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: May 1, 2000
Last modified: May 23, 2018
This is version 193 of the entry and version 1 of the sequence. See 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

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