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Identification
HMDB Protein ID HMDBP08421
Secondary Accession Numbers
  • 14133
Name ADP-ribosylation factor-binding protein GGA2
Synonyms
  1. Gamma-adaptin-related protein 2
  2. Golgi-localized, gamma ear-containing, ARF-binding protein 2
  3. VHS domain and ear domain of gamma-adaptin
  4. Vear
Gene Name GGA2
Protein Type Unknown
Biological Properties
General Function Involved in protein binding
Specific 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
Pathways Not Available
Reactions Not Available
GO Classification
Component
membrane coat
golgi apparatus part
cell part
intracellular part
macromolecular complex
protein complex
cytoplasmic part
ap-type membrane coat adaptor complex
intracellular
clathrin adaptor complex
Function
binding
protein binding
Process
establishment of localization
transport
protein transport
intracellular protein transport
vesicle-mediated transport
Cellular Location
  1. Peripheral membrane protein
  2. Peripheral membrane protein
  3. Endosome membrane
  4. Golgi apparatus
  5. trans-Golgi network membrane
Gene Properties
Chromosome Location Chromosome:1
Locus 16p12
SNPs GGA2
Gene Sequence
>1842 bp
ATGGCGGCGACCGCGGTGGCGGCGGCTGTGGCGGGAACCGAGTCGGCCCAGGGTCCCCCG
GGCCCGGCAGCGTCGCTGGAGCTGTGGCTCAACAAAGCCACAGACCCAAGCATGTCGGAA
CAGGATTGGTCAGCTATCCAGAATTTCTGTGAGCAGGTGAACACTGACCCCAATGGCCCC
ACACATGCGCCCTGGCTACTGGCCCACAAGATCCAGTCTCCGCAAGAGAAGGAAGCTCTT
TATGCCTTAACGGTGCTGGAGATGTGCATGAACCACTGTGGGGAGAAGTTCCACAGCGAG
GTGGCCAAATTTCGTTTCCTGAACGAACTGATCAAAGTGTTGTCCCCAAAGTACCTGGGG
TCCTGGGCCACAGGAAAAGTTAAAGGAAGAGTCATTGAAATACTCTTCAGTTGGACAGTC
TGGTTTCCGGAAGACATCAAGATTCGAGACGCTTATCAGATGCTGAAGAAACAAGGAATT
ATAAAACAAGACCCTAAACTACCAGTGGATAAAATCTTACCCCCACCATCTCCCTGGCCC
AAGAGCTCCATCTTTGATGCTGATGAAGAAAAGTCCAAGCTTCTGACAAGGCTTCTAAAG
AGCAACCACCCCGAGGACCTTCAGGCTGCAAACCGGTTAATCAAGAATTTGGTCAAGGAG
GAACAAGAAAAATCGGAGAAGGTGTCCAAGAGGGTCAGTGCGGTGGAGGAAGTGCGAAGC
CATGTGAAGGTGCTGCAGGAGATGCTGAGCATGTACCGCAGGCCAGGGCAGGCCCCGCCC
GACCAGGAGGCCCTGCAGGTCGTGTATGAGAGGTGTGAAAAGCTGCGGCCCACGCTGTTC
CGGTTGGCGAGTGACACCACTGATGACGATGATGCACTCGCGGAAATTCTCCAGGCAAAT
GACCTCCTCACCCAAGGAGTTCTGCTGTACAAACAGGTGATGGAGGGCCGGGTCACCTTT
GGAAACAGAGTGACCAGCTCATTGGGAGACATCCCTGTCTCCAGAGTCTTTCAGAATCCA
GCAGGCTGCATGAAGACCTGCCCCCTGATTGACTTGGAGGTGGACAATGGACCTGCGCAG
ATGGGGACTGTGGTGCCATCTTTGCTTCATCAGGACCTGGCAGCCTTGGGAATCAGTGAT
GCTCCTGTTACAGGCATGGTTTCTGGTCAGAATTGCTGTGAGGAAAAGAGGAATCCCTCC
TCCAGCACGCTGCCAGGCGGTGGTGTTCAGAACCCTTCTGCAGACAGGAATTTGCTGGAC
CTCCTCTCAGCACAGCCAGCTCCGTGCCCTCTGAATTATGTTTCGCAGAAAAGTGTCCCC
AAGGAAGTGCCACCAGGTACTAAGTCCTCTCCAGGTTGGTCCTGGGAGGCTGGCCCGTTG
GCTCCTTCCCCATCTTCACAGAATACACCTCTGGCTCAAGTGTTTGTCCCTTTGGAGTCT
GTTAAGCCCAGCAGCCTGCCGCCTCTCATTGTGTATGACCGGAATGGATTCAGAATTCTG
CTCCACTTCTCCCAGACGGGAGCCCCTGGGCACCCAGAGGTACAGGTGCTGCTCTTGACC
ATGATGAGCACGGCTCCCCAGCCTGTCTGGGATATCATGTTTCAAGTGGCTGTGCCAAAG
TCAATGAGAGTGAAGCTGCAGCCGGCATCCAGCTCCAAGCTTCCTGCATTCAGTCCTTTG
ATGCCTCCAGCTGTGATATCTCAGATGCTGCTGCTTGACAATCCACACAAAGAACCTATC
CGCTTACGGTACAAGCTGACATTCAACCAAGGTGGACAGCCTTTCAGCGAAGTAGGAGAA
GTGAAAGACTTCCCAGACCTGGCTGTCTTGGGCGCAGCCTAA
Protein Properties
Number of Residues 613
Molecular Weight 67149.7
Theoretical pI 6.52
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>ADP-ribosylation factor-binding protein GGA2
MAATAVAAAVAGTESAQGPPGPAASLELWLNKATDPSMSEQDWSAIQNFCEQVNTDPNGP
THAPWLLAHKIQSPQEKEALYALTVLEMCMNHCGEKFHSEVAKFRFLNELIKVLSPKYLG
SWATGKVKGRVIEILFSWTVWFPEDIKIRDAYQMLKKQGIIKQDPKLPVDKILPPPSPWP
KSSIFDADEEKSKLLTRLLKSNHPEDLQAANRLIKNLVKEEQEKSEKVSKRVSAVEEVRS
HVKVLQEMLSMYRRPGQAPPDQEALQVVYERCEKLRPTLFRLASDTTDDDDALAEILQAN
DLLTQGVLLYKQVMEGRVTFGNRVTSSLGDIPVSRVFQNPAGCMKTCPLIDLEVDNGPAQ
MGTVVPSLLHQDLAALGISDAPVTGMVSGQNCCEEKRNPSSSTLPGGGVQNPSADRNLLD
LLSAQPAPCPLNYVSQKSVPKEVPPGTKSSPGWSWEAGPLAPSPSSQNTPLAQVFVPLES
VKPSSLPPLIVYDRNGFRILLHFSQTGAPGHPEVQVLLLTMMSTAPQPVWDIMFQVAVPK
SMRVKLQPASSSKLPAFSPLMPPAVISQMLLLDNPHKEPIRLRYKLTFNQGGQPFSEVGE
VKDFPDLAVLGAA
GenBank ID Protein 9558751
UniProtKB/Swiss-Prot ID Q9UJY4
UniProtKB/Swiss-Prot Entry Name GGA2_HUMAN
PDB IDs
GenBank Gene ID NM_015044.4
GeneCard ID GGA2
GenAtlas ID GGA2
HGNC ID HGNC:16064
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Loftus BJ, Kim UJ, Sneddon VP, Kalush F, Brandon R, Fuhrmann J, Mason T, Crosby ML, Barnstead M, Cronin L, Deslattes Mays A, Cao Y, Xu RX, Kang HL, Mitchell S, Eichler EE, Harris PC, Venter JC, Adams MD: Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q. Genomics. 1999 Sep 15;60(3):295-308. [PubMed:10493829 ]
  3. Kikuno R, Nagase T, Ishikawa K, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O: 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. DNA Res. 1999 Jun 30;6(3):197-205. [PubMed:10470851 ]
  4. Puertollano R, Aguilar RC, Gorshkova I, Crouch RJ, Bonifacino JS: Sorting of mannose 6-phosphate receptors mediated by the GGAs. Science. 2001 Jun 1;292(5522):1712-6. [PubMed:11387475 ]
  5. Doray B, Bruns K, Ghosh P, Kornfeld S: Interaction of the cation-dependent mannose 6-phosphate receptor with GGA proteins. J Biol Chem. 2002 May 24;277(21):18477-82. Epub 2002 Mar 8. [PubMed:11886874 ]
  6. He X, Zhu G, Koelsch G, Rodgers KK, Zhang XC, Tang J: Biochemical and structural characterization of the interaction of memapsin 2 (beta-secretase) cytosolic domain with the VHS domain of GGA proteins. Biochemistry. 2003 Oct 28;42(42):12174-80. [PubMed:14567678 ]
  7. Boman AL, Zhang Cj, Zhu X, Kahn RA: A family of ADP-ribosylation factor effectors that can alter membrane transport through the trans-Golgi. Mol Biol Cell. 2000 Apr;11(4):1241-55. [PubMed:10749927 ]
  8. Hirst J, Lui WW, Bright NA, Totty N, Seaman MN, Robinson MS: A family of proteins with gamma-adaptin and VHS domains that facilitate trafficking between the trans-Golgi network and the vacuole/lysosome. J Cell Biol. 2000 Apr 3;149(1):67-80. [PubMed:10747088 ]
  9. Takatsu H, Yoshino K, Nakayama K: Adaptor gamma ear homology domain conserved in gamma-adaptin and GGA proteins that interact with gamma-synergin. Biochem Biophys Res Commun. 2000 May 19;271(3):719-25. [PubMed:10814529 ]
  10. Puertollano R, Randazzo PA, Presley JF, Hartnell LM, Bonifacino JS: The GGAs promote ARF-dependent recruitment of clathrin to the TGN. Cell. 2001 Apr 6;105(1):93-102. [PubMed:11301005 ]
  11. Takatsu H, Katoh Y, Shiba Y, Nakayama K: 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. J Biol Chem. 2001 Jul 27;276(30):28541-5. Epub 2001 Jun 4. [PubMed:11390366 ]
  12. Takatsu H, Yoshino K, Toda K, Nakayama K: GGA proteins associate with Golgi membranes through interaction between their GGAH domains and ADP-ribosylation factors. Biochem J. 2002 Jul 15;365(Pt 2):369-78. [PubMed:11950392 ]
  13. Jacobsen L, Madsen P, Nielsen MS, Geraerts WP, Gliemann J, Smit AB, Petersen CM: The sorLA cytoplasmic domain interacts with GGA1 and -2 and defines minimum requirements for GGA binding. FEBS Lett. 2002 Jan 30;511(1-3):155-8. [PubMed:11821067 ]
  14. Mattera R, Arighi CN, Lodge R, Zerial M, Bonifacino JS: Divalent interaction of the GGAs with the Rabaptin-5-Rabex-5 complex. EMBO J. 2003 Jan 2;22(1):78-88. [PubMed:12505986 ]
  15. Ghosh P, Griffith J, Geuze HJ, Kornfeld S: Mammalian GGAs act together to sort mannose 6-phosphate receptors. J Cell Biol. 2003 Nov 24;163(4):755-66. [PubMed:14638859 ]
  16. Lui WW, Collins BM, Hirst J, Motley A, Millar C, Schu P, Owen DJ, Robinson MS: Binding partners for the COOH-terminal appendage domains of the GGAs and gamma-adaptin. Mol Biol Cell. 2003 Jun;14(6):2385-98. Epub 2003 Mar 20. [PubMed:12808037 ]
  17. Mattera R, Ritter B, Sidhu SS, McPherson PS, Bonifacino JS: Definition of the consensus motif recognized by gamma-adaptin ear domains. J Biol Chem. 2004 Feb 27;279(9):8018-28. Epub 2003 Dec 9. [PubMed:14665628 ]
  18. Puertollano R, Bonifacino JS: Interactions of GGA3 with the ubiquitin sorting machinery. Nat Cell Biol. 2004 Mar;6(3):244-51. Epub 2004 Feb 22. [PubMed:15039775 ]
  19. Poussu A, Lohi O, Lehto VP: Vear, a novel Golgi-associated protein with VHS and gamma-adaptin "ear" domains. J Biol Chem. 2000 Mar 10;275(10):7176-83. [PubMed:10702286 ]
  20. Nielsen MS, Madsen P, Christensen EI, Nykjaer A, Gliemann J, Kasper D, Pohlmann R, Petersen CM: The sortilin cytoplasmic tail conveys Golgi-endosome transport and binds the VHS domain of the GGA2 sorting protein. EMBO J. 2001 May 1;20(9):2180-90. [PubMed:11331584 ]
  21. Kalthoff C, Groos S, Kohl R, Mahrhold S, Ungewickell EJ: Clint: a novel clathrin-binding ENTH-domain protein at the Golgi. Mol Biol Cell. 2002 Nov;13(11):4060-73. [PubMed:12429846 ]
  22. Zhu G, He X, Zhai P, Terzyan S, Tang J, Zhang XC: Crystal structure of GGA2 VHS domain and its implication in plasticity in the ligand binding pocket. FEBS Lett. 2003 Feb 27;537(1-3):171-6. [PubMed:12606052 ]