Reviewed, UniProtKB/Swiss-Prot Q9UJY4 (GGA2_HUMAN)

Names and origin

Protein names

Recommended name:
    ADP-ribosylation factor-binding protein GGA2
Alternative name(s):
    Golgi-localized, gamma ear-containing, ARF-binding protein 2
    Gamma-adaptin-related protein 2
    VHS domain and ear domain of gamma-adaptin
      Short name=Vear

Gene names

Name:	GGA2
Synonyms:	KIAA1080

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	613 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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.
Subunit structure	Monomeric. Interacts with NECAP1, TSG101, UBC and AFTPH/aftiphilin By similarity. Interacts with GGA1 and GGA3. Binds to clathrin and activated ARFs. Binds RABEP1 and RABGEF1. Interacts with the type-I membrane proteins SORT1, SORL1, LRP3, M6PR/CD-MPR, IGF2R/CI-MPR and BACE1. Binds the accessory proteins CCDC91, P200, AP1GBP1, EPN4 and NECAP2.
Subcellular location	Golgi apparatus › trans-Golgi network membrane; Peripheral membrane protein. Endosome membrane; Peripheral membrane protein. Ref.21
Tissue specificity	Ubiquitously expressed.
Domain	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.
Post-translational modification	Ubiquitinated By similarity.
Sequence similarities	Belongs to the GGA protein family. Contains 1 GAE domain. Contains 1 GAT domain. Contains 1 VHS domain.
Sequence caution	The sequence AAK38634.1 differs from that shown. Reason: Frameshift at position 193.

Ontologies

Keywords
Biological process	Protein transport Transport
Cellular component	Endosome Golgi apparatus Membrane
Coding sequence diversity	Polymorphism
PTM	Ubl conjugation
Technical term	3D-structure
Gene Ontology (GO)
Biological process	intracellular protein transport Ref.1 Non-traceable author statement. Source: UniProtKB vesicle-mediated transport Inferred from electronic annotation. Source: InterPro
Cellular component	clathrin adaptor complex Inferred from electronic annotation. Source: InterPro endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell trans-Golgi network Ref.1 Inferred from direct assay. Source: UniProtKB
Molecular function	ADP-ribosylation factor binding Ref.1 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CLTC	P49951	1	EBI-447646,EBI-448355	From a different organism.
RABEP1	Q15276	2	EBI-447646,EBI-447043
RABGEF1	O18973	1	EBI-447646,EBI-447376	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 613

613

ADP-ribosylation factor-binding protein GGA2

PRO_0000212682

Regions

Domain

33 – 163

131

VHS

Domain

188 – 315

128

GAT

Domain

484 – 605

122

GAE

Region

316 – 483

168

Unstructured hinge

Natural variations

Natural variant

424

1

A → P: dbSNP rs1135045. Ref.1 Ref.2 Ref.5 Ref.6

VAR_028275

Experimental info

Mutagenesis

349 – 353

5

LIDLE → AADAA: Partial loss of clathrin-binding. Ref.9

Sequence conflict

281

1

R → W in AAF05708. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

613

Helix Strand Turn

Details...

Helix

26 – 34

9

Helix

43 – 55

13

Helix

58 – 71

14

Helix

76 – 92

17

Helix

95 – 101

7

Helix

104 – 112

9

Helix

125 – 141

17

Helix

146 – 157

12

Sequences

	Sequence		Length	Mass (Da)
	Q9UJY4-1 [UniParc]. Last modified April 3, 2007. Version 3. Checksum: 4B627ABA474A069C	FASTA	613	67,150
	10 20 30 40 50 60 MAATAVAAAV AGTESAQGPP GPAASLELWL NKATDPSMSE QDWSAIQNFC EQVNTDPNGP 70 80 90 100 110 120 THAPWLLAHK IQSPQEKEAL YALTVLEMCM NHCGEKFHSE VAKFRFLNEL IKVLSPKYLG 130 140 150 160 170 180 SWATGKVKGR VIEILFSWTV WFPEDIKIRD AYQMLKKQGI IKQDPKLPVD KILPPPSPWP 190 200 210 220 230 240 KSSIFDADEE KSKLLTRLLK SNHPEDLQAA NRLIKNLVKE EQEKSEKVSK RVSAVEEVRS 250 260 270 280 290 300 HVKVLQEMLS MYRRPGQAPP DQEALQVVYE RCEKLRPTLF RLASDTTDDD DALAEILQAN 310 320 330 340 350 360 DLLTQGVLLY KQVMEGRVTF GNRVTSSLGD IPVSRVFQNP AGCMKTCPLI DLEVDNGPAQ 370 380 390 400 410 420 MGTVVPSLLH QDLAALGISD APVTGMVSGQ NCCEEKRNPS SSTLPGGGVQ NPSADRNLLD 430 440 450 460 470 480 LLSAQPAPCP LNYVSQKSVP KEVPPGTKSS PGWSWEAGPL APSPSSQNTP LAQVFVPLES 490 500 510 520 530 540 VKPSSLPPLI VYDRNGFRIL LHFSQTGAPG HPEVQVLLLT MMSTAPQPVW DIMFQVAVPK 550 560 570 580 590 600 SMRVKLQPAS SSKLPAFSPL MPPAVISQML LLDNPHKEPI RLRYKLTFNQ GGQPFSEVGE 610 VKDFPDLAVL GAA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A family of ADP-ribosylation factor effectors that can alter transport through the trans-Golgi." Boman A.L., Zhang C.-J., Zhu X., Kahn R.A. Mol. Biol. Cell 11:1241-1255(2000) [PubMed: 10749927] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT PRO-424.
[2]	"A family of proteins with gamma-adaptin and VHS domains that facilitate trafficking between the trans-Golgi network and the vacuole/lysosome." Hirst J., Lui W.W.Y., Bright N.A., Totty N., Seaman M.N.J., Robinson M.S. J. Cell Biol. 149:67-80(2000) [PubMed: 10747088] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT PRO-424.
[3]	"Vear, a novel Golgi-associated protein with VHS and gamma-adaptin 'ear' domains." Poussu A., Lohi O., Lehto V.-P. J. Biol. Chem. 275:7176-7183(2000) [PubMed: 10702286] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q." Loftus B.J., Kim U.-J., Sneddon V.P., Kalush F., Brandon R., Fuhrmann J., Mason T., Crosby M.L., Barnstead M., Cronin L., Mays A.D., Cao Y., Xu R.X., Kang H.-L., Mitchell S., Eichler E.E., Harris P.C., Venter J.C., Adams M.D. Genomics 60:295-308(1999) [PubMed: 10493829] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT PRO-424. Tissue: Eye.
[6]	"The sortilin cytoplasmic tail conveys Golgi-endosome transport and binds the VHS domain of the GGA2 sorting protein." Nielsen M.S., Madsen P., Christensen E.I., Nykjaer A., Gliemann J., Kasper D., Pohlmann R., Petersen C.M. EMBO J. 20:2180-2190(2001) [PubMed: 11331584] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-455, VARIANT PRO-424, INTERACTION WITH SORT1. Tissue: Mammary gland.
[7]	"Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 6:197-205(1999) [PubMed: 10470851] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 97-613. Tissue: Brain.
[8]	"Adaptor gamma ear homology domain conserved in gamma-adaptin and GGA proteins that interact with gamma-synergin." Takatsu H., Yoshino K., Nakayama K. Biochem. Biophys. Res. Commun. 271:719-725(2000) [PubMed: 10814529] [Abstract] Cited for: INTERACTION WITH AP1GBP1.
[9]	"The GGAs promote ARF-dependent recruitment of clathrin to the TGN." Puertollano R., Randazzo P.A., Presley J.F., Hartnell L.M., Bonifacino J.S. Cell 105:93-102(2001) [PubMed: 11301005] [Abstract] Cited for: INTERACTION WITH CLATHRIN, MUTAGENESIS OF 349-LEU--GLU-353.
[10]	"Golgi-localizing, gamma-adaptin ear homology domain, ADP-ribosylation factor-binding (GGA) proteins interact with acidic dileucine sequences within the cytoplasmic domains of sorting receptors through their Vps27p/Hrs/STAM (VHS) domains." Takatsu H., Katoh Y., Shiba Y., Nakayama K. J. Biol. Chem. 276:28541-28545(2001) [PubMed: 11390366] [Abstract] Cited for: INTERACTION WITH SORT; LRP3 AND IGF2R.
[11]	"Sorting of mannose 6-phosphate receptors mediated by the GGAs." Puertollano R., Aguilar R.C., Gorshkova I., Crouch R.J., Bonifacino J.S. Science 292:1712-1716(2001) [PubMed: 11387475] [Abstract] Cited for: INTERACTION WITH IGF2R.
[12]	"GGA proteins associate with Golgi membranes through interaction between their GGAH domains and ADP-ribosylation factors." Takatsu H., Yoshino K., Toda K., Nakayama K. Biochem. J. 365:369-378(2002) [PubMed: 11950392] [Abstract] Cited for: INTERACTION WITH ARF1; ARF5 AND ARF6.
[13]	"The sorLA cytoplasmic domain interacts with GGA1 and -2 and defines minimum requirements for GGA binding." Jacobsen L., Madsen P., Nielsen M.S., Geraerts W.P.M., Gliemann J., Smit A.B., Petersen C.M. FEBS Lett. 511:155-158(2002) [PubMed: 11821067] [Abstract] Cited for: INTERACTION WITH SORL1.
[14]	"Interaction of the cation-dependent mannose 6-phosphate receptor with GGA proteins." Doray B., Bruns K., Ghosh P., Kornfeld S. J. Biol. Chem. 277:18477-18482(2002) [PubMed: 11886874] [Abstract] Cited for: INTERACTION WITH M6PR AND IGF2R.
[15]	"Clint: a novel clathrin-binding ENTH-domain protein at the Golgi." Kalthoff C., Groos S., Kohl R., Mahrhold S., Ungewickell E.J. Mol. Biol. Cell 13:4060-4073(2002) [PubMed: 12429846] [Abstract] Cited for: INTERACTION WITH EPN4.
[16]	"Biochemical and structural characterization of the interaction of memapsin 2 (beta-secretase) cytosolic domain with the VHS domain of GGA proteins." He X., Zhu G., Koelsch G., Rodgers K.K., Zhang X.C., Tang J. Biochemistry 42:12174-12180(2003) [PubMed: 14567678] [Abstract] Cited for: INTERACTION WITH BACE1.
[17]	"Divalent interaction of the GGAs with the Rabaptin-5-Rabex-5 complex." Mattera R., Arighi C.N., Lodge R., Zerial M., Bonifacino J.S. EMBO J. 22:78-88(2003) [PubMed: 12505986] [Abstract] Cited for: INTERACTION WITH RABEP1 AND RABGEF1.
[18]	"Binding partners for the COOH-terminal appendage domains of the GGAs and gamma-adaptin." Lui W.W.Y., Collins B.M., Hirst J., Motley A., Millar C., Schu P., Owen D.J., Robinson M.S. Mol. Biol. Cell 14:2385-2398(2003) [PubMed: 12808037] [Abstract] Cited for: INTERACTION WITH CCDC91; P200 AND AP1GBP1.
[19]	"Mammalian GGAs act together to sort mannose 6-phosphate receptors." Ghosh P., Griffith J., Geuze H.J., Kornfeld S. J. Cell Biol. 163:755-766(2003) [PubMed: 14638859] [Abstract] Cited for: INTERACTION WITH GGA1 AND GGA3.
[20]	"Definition of the consensus motif recognized by gamma-adaptin ear domains." Mattera R., Ritter B., Sidhu S.S., McPherson P.S., Bonifacino J.S. J. Biol. Chem. 279:8018-8028(2004) [PubMed: 14665628] [Abstract] Cited for: INTERACTION WITH NECAP2.
[21]	"Interactions of GGA3 with the ubiquitin sorting machinery." Puertollano R., Bonifacino J.S. Nat. Cell Biol. 6:244-251(2004) [PubMed: 15039775] [Abstract] Cited for: SUBCELLULAR LOCATION.
[22]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[23]	"Crystal structure of GGA2 VHS domain and its implication in plasticity in the ligand binding pocket." Zhu G., He X., Zhai P., Terzyan S., Tang J., Zhang X.C. FEBS Lett. 537:171-176(2003) [PubMed: 12606052] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 25-167.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF190863 mRNA. Translation: AAF05708.1.
AF233522 mRNA. Translation: AAF35394.1.
AF165531 mRNA. Translation: AAF42806.1.
AC002400 Genomic DNA. Translation: AAC05813.1.
BC000284 mRNA. Translation: AAH00284.1.
AF323754 mRNA. Translation: AAK38634.1. Frameshift.
AB029003 mRNA. Translation: BAA83032.1.

IPI

IPI00296772.

PIR

T00744.

RefSeq

NP_055859.1.

UniGene

Hs.460336

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1MHQ	X-ray	2.20	A/B	25-172	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9UJY4. 6 interactions.

PTM databases

PhosphoSite

Q9UJY4.

Genome annotation databases

Ensembl

ENSG00000103365. Homo sapiens. [Contig view]

GeneID

23062.

KEGG

hsa:23062.

Organism-specific databases

GeneCards

GC16M023383.

H-InvDB

HIX0012891.

HGNC

HGNC:16064. GGA2.

MIM

606005. gene.

PharmGKB

PA28658.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q9UJY4.

HOVERGEN

Q9UJY4.

OMA

Q9UJY4. KATDPSV.

Gene expression databases

ArrayExpress

Q9UJY4.

Bgee

Q9UJY4.

CleanEx

HS_GGA2.

GermOnline

ENSG00000103365. Homo sapiens.

Family and domain databases

InterPro

IPR008152. Clathrin_a/b/g-adaptin_app_Ig.
IPR008153. Clathrin_g-adaptin_app.
IPR008942. ENTH_VHS.
IPR004152. GAT.
IPR002014. VHS.
IPR018205. VHS_subgroup.
[Graphical view]

Gene3D

G3DSA:2.60.40.1230. Clathrin_g-adaptin_app. 1 hit.
G3DSA:1.25.40.90. ENTH_VHS. 1 hit.

Pfam

PF02883. Alpha_adaptinC2. 1 hit.
PF03127. GAT. 1 hit.
PF00790. VHS. 1 hit.
[Graphical view]

ProDom

PD021457. Gamma_adaptin_C. 1 hit.
PD003686. VHS. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00809. Alpha_adaptinC2. 1 hit.
SM00288. VHS. 1 hit.
[Graphical view]

PROSITE

PS50180. GAE. 1 hit.
PS50909. GAT. 1 hit.
PS50179. VHS. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

44137.

SOURCE

Search...

Entry information

Entry name

GGA2_HUMAN

Accession

Primary (citable) accession number: Q9UJY4
Secondary accession number(s): O14564, Q9NYN2, Q9UPS2

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 20, 2001
Last sequence update:	April 3, 2007
Last modified:	June 16, 2009
This is version 94 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)