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Q9H2C0 (GAN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 136. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Gigaxonin
Alternative name(s):
Kelch-like protein 16
Gene names
Name:GAN
Synonyms:GAN1, KLHL16
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length597 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Probable cytoskeletal component that directly or indirectly plays an important role in neurofilament architecture. May act as a substrate-specific adapter of an E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Controls degradation of TBCB. Controls degradation of MAP1B and MAP1S, and is critical for neuronal maintenance and survival. Ref.3 Ref.5 Ref.6 Ref.7

Pathway

Protein modification; protein ubiquitination.

Subunit structure

Interacts with TBCB. Interacts with CUL3. Part of a complex that contains CUL3, RBX1 and GAN. Interacts (via BTB domain) with UBA1. Interacts (via Kelch domains) with MAP1B (via C-terminus) and MAP1S (via C-terminus). Ref.3 Ref.4 Ref.5 Ref.6 Ref.7

Subcellular location

Cytoplasm. Cytoplasmcytoskeleton Ref.3 Ref.8.

Tissue specificity

Expressed in brain, heart and muscle. Ref.3

Post-translational modification

Ubiquitinated by E3 ubiquitin ligase complex formed by CUL3 and RBX1 and probably targeted for proteasome-independent degradation. Ref.6

Involvement in disease

Giant axonal neuropathy (GAN) [MIM:256850]: Severe autosomal recessive sensorimotor neuropathy affecting both the peripheral nerves and the central nervous system. It is characterized by neurofilament accumulation, leading to segmental distention of axons.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.5 Ref.11 Ref.13 Ref.14 Ref.15

Sequence similarities

Contains 1 BACK (BTB/Kelch associated) domain.

Contains 1 BTB (POZ) domain.

Contains 6 Kelch repeats.

Ontologies

Keywords
   Biological processUbl conjugation pathway
   Cellular componentCytoplasm
Cytoskeleton
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Neurodegeneration
   DomainKelch repeat
Repeat
   PTMUbl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell death

Inferred from electronic annotation. Source: UniProtKB-KW

protein ubiquitination

Inferred from direct assay Ref.6. Source: UniProtKB

   Cellular_componentCul3-RING ubiquitin ligase complex

Inferred from direct assay Ref.6. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.8. Source: UniProtKB

cytoskeleton

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionprotein binding

Inferred from physical interaction Ref.3Ref.7Ref.5. Source: IntAct

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 597597Gigaxonin
PRO_0000119070

Regions

Domain30 – 9970BTB
Domain134 – 236103BACK
Repeat274 – 32653Kelch 1
Repeat327 – 37448Kelch 2
Repeat376 – 42146Kelch 3
Repeat422 – 46847Kelch 4
Repeat470 – 52253Kelch 5
Repeat528 – 57447Kelch 6

Natural variations

Natural variant151R → S in GAN; no effect on binding to TBCB. Ref.1 Ref.5
VAR_010759
Natural variant511A → P in GAN. Ref.14
VAR_054113
Natural variant521S → G in GAN. Ref.1
VAR_010760
Natural variant791S → L in GAN. Ref.1
VAR_010761
Natural variant821V → F in GAN; no effect on binding to TBCB. Ref.1 Ref.5
VAR_010762
Natural variant861I → F in GAN. Ref.13
VAR_015680
Natural variant891Y → C in GAN. Ref.15
VAR_054114
Natural variant1381R → H in GAN. Ref.1
VAR_010763
Natural variant1951V → F in GAN. Ref.15
VAR_054115
Natural variant2691R → Q in GAN. Ref.1 Ref.13
VAR_010764
Natural variant3091L → R in GAN. Ref.1
VAR_010765
Natural variant3151P → L in GAN. Ref.14
Corresponds to variant rs144486241 [ dbSNP | Ensembl ].
VAR_054116
Natural variant3681G → R in GAN. Ref.13 Ref.15
VAR_015681
Natural variant4231I → T in GAN. Ref.11 Ref.15
VAR_015560
Natural variant4741G → R in GAN. Ref.15
VAR_054117
Natural variant4861E → K in GAN. Ref.1
VAR_010757
Natural variant5451R → C in GAN; complete loss of binding to TBCB. Ref.1 Ref.5
VAR_010766
Natural variant5451R → H in GAN. Ref.15
VAR_054118
Natural variant5701C → Y in GAN. Ref.1
VAR_010767

Secondary structure

...................................... 597
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9H2C0 [UniParc].

Last modified March 1, 2001. Version 1.
Checksum: 4B6ECFA6849880C7

FASTA59767,638
        10         20         30         40         50         60 
MAEGSAVSDP QHAARLLRAL SSFREESRFC DAHLVLDGEE IPVQKNILAA ASPYIRTKLN 

        70         80         90        100        110        120 
YNPPKDDGST YKIELEGISV MVMREILDYI FSGQIRLNED TIQDVVQAAD LLLLTDLKTL 

       130        140        150        160        170        180 
CCEFLEGCIA AENCIGIRDF ALHYCLHHVH YLATEYLETH FRDVSSTEEF LELSPQKLKE 

       190        200        210        220        230        240 
VISLEKLNVG NERYVFEAVI RWIAHDTEIR KVHMKDVMSA LWVSGLDSSY LREQMLNEPL 

       250        260        270        280        290        300 
VREIVKECSN IPLSQPQQGE AMLANFKPRG YSECIVTVGG EERVSRKPTA AMRCMCPLYD 

       310        320        330        340        350        360 
PNRQLWIELA PLSMPRINHG VLSAEGFLFV FGGQDENKQT LSSGEKYDPD ANTWTALPPM 

       370        380        390        400        410        420 
NEARHNFGIV EIDGMLYILG GEDGEKELIS MECYDIYSKT WTKQPDLTMV RKIGCYAAMK 

       430        440        450        460        470        480 
KKIYAMGGGS YGKLFESVEC YDPRTQQWTA ICPLKERRFG AVACGVAMEL YVFGGVRSRE 

       490        500        510        520        530        540 
DAQGSEMVTC KSEFYHDEFK RWIYLNDQNL CIPASSSFVY GAVPIGASIY VIGDLDTGTN 

       550        560        570        580        590 
YDYVREFKRS TGTWHHTKPL LPSDLRRTGC AALRIANCKL FRLQLQQGLF RIRVHSP 

« Hide

References

« Hide 'large scale' references
[1]"The gene encoding gigaxonin, a new member of the cytoskeletal BTB/kelch repeat family, is mutated in giant axonal neuropathy."
Bomont P., Cavalier L., Blondeau F., Ben-Hamida C., Belal S., Tazir M., Demir E., Topaloglu H., Korinthenberg R., Tueysuez B., Landrieu P., Hentati F., Koenig M.
Nat. Genet. 26:370-374(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS GAN SER-15; GLY-52; LEU-79; PHE-82; HIS-138; GLN-269; ARG-309; LYS-486; CYS-545 AND TYR-570.
Tissue: Brain.
[2]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Placenta.
[3]"Microtubule-associated protein 1B: a neuronal binding partner for gigaxonin."
Ding J., Liu J.-J., Kowal A.S., Nardine T., Bhattacharya P., Lee A., Yang Y.
J. Cell Biol. 158:427-433(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH MAP1B, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[4]"Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases."
Furukawa M., He Y.J., Borchers C., Xiong Y.
Nat. Cell Biol. 5:1001-1007(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CUL3.
[5]"Gigaxonin interacts with tubulin folding cofactor B and controls its degradation through the ubiquitin-proteasome pathway."
Wang W., Ding J., Allen E., Zhu P., Zhang L., Vogel H., Yang Y.
Curr. Biol. 15:2050-2055(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH TBCB, CHARACTERIZATION OF VARIANTS GAN SER-15; PHE-82 AND CYS-545.
[6]"Ubiquitination of Keap1, a BTB-Kelch substrate adaptor protein for Cul3, targets Keap1 for degradation by a proteasome-independent pathway."
Zhang D.D., Lo S.C., Sun Z., Habib G.M., Lieberman M.W., Hannink M.
J. Biol. Chem. 280:30091-30099(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION IN A COMPLEX WITH CUL3 AND RBX1, UBIQUITINATION.
[7]"Gigaxonin-controlled degradation of MAP1B light chain is critical to neuronal survival."
Allen E., Ding J., Wang W., Pramanik S., Chou J., Yau V., Yang Y.
Nature 438:224-228(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH UBA1 AND MAP1B.
[8]"Ectodermal-neural cortex 1 down-regulates Nrf2 at the translational level."
Wang X.J., Zhang D.D.
PLoS ONE 4:E5492-E5492(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[9]"Structures of SPOP-substrate complexes: insights into molecular architectures of BTB-Cul3 ubiquitin ligases."
Zhuang M., Calabrese M.F., Liu J., Waddell M.B., Nourse A., Hammel M., Miller D.J., Walden H., Duda D.M., Seyedin S.N., Hoggard T., Harper J.W., White K.P., Schulman B.A.
Mol. Cell 36:39-50(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-254.
[10]"Structure of the BTB (tramtrack and bric a brac) domain of human gigaxonin."
Structural genomics consortium (SGC)
Submitted (JUL-2011) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 6-126.
[11]"Giant axonal neuropathy (GAN): case report and two novel mutations in the gigaxonin gene."
Kuhlenbaumer G., Young P., Oberwittler C., Hunermund G., Schirmacher A., Domschke K., Ringelstein B., Stogbauer F.
Neurology 58:1273-1276(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GAN THR-423.
[12]Erratum
Kuhlenbaumer G., Young P., Oberwittler C., Hunermund G., Schirmacher A., Domschke K., Ringelstein B., Stogbauer F.
Neurology 58:1444-1444(2002)
[13]"Identification of seven novel mutations in the GAN gene."
Bomont P., Ioos C., Yalcinkaya C., Korinthenberg R., Vallat J.-M., Assami S., Munnich A., Chabrol B., Kurlemann G., Tazir M., Koenig M.
Hum. Mutat. 21:446-446(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GAN PHE-86; GLN-269 AND ARG-368.
[14]"New mutations, genotype phenotype studies and manifesting carriers in giant axonal neuropathy."
Houlden H., Groves M., Miedzybrodzka Z., Roper H., Willis T., Winer J., Cole G., Reilly M.M.
J. Neurol. Neurosurg. Psych. 78:1267-1270(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GAN PRO-51 AND LEU-315.
[15]"Genotype-phenotype analysis in patients with giant axonal neuropathy (GAN)."
Koop O., Schirmacher A., Nelis E., Timmerman V., De Jonghe P., Ringelstein B., Rasic V.M., Evrard P., Gaertner J., Claeys K.G., Appenzeller S., Rautenstrauss B., Huehne K., Ramos-Arroyo M.A., Woerle H., Moilanen J.S., Hammans S., Kuhlenbaeumer G.
Neuromuscul. Disord. 17:624-630(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GAN CYS-89; PHE-195; ARG-368; THR-423; ARG-474 AND HIS-545.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF291673 mRNA. Translation: AAG35311.1.
BC044840 mRNA. Translation: AAH44840.1.
CCDSCCDS10935.1.
RefSeqNP_071324.1. NM_022041.3.
UniGeneHs.112569.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2PPIX-ray2.40A6-126[»]
3HVEX-ray2.80A/B1-254[»]
ProteinModelPortalQ9H2C0.
SMRQ9H2C0. Positions 3-581.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113800. 9 interactions.
IntActQ9H2C0. 7 interactions.
MINTMINT-243055.
STRING9606.ENSP00000248272.

PTM databases

PhosphoSiteQ9H2C0.

Polymorphism databases

DMDM13626745.

Proteomic databases

MaxQBQ9H2C0.
PaxDbQ9H2C0.
PRIDEQ9H2C0.

Protocols and materials databases

DNASU8139.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000568107; ENSP00000476795; ENSG00000261609.
GeneID8139.
KEGGhsa:8139.
UCSCuc002fgo.3. human.

Organism-specific databases

CTD8139.
GeneCardsGC16P081348.
GeneReviewsGAN.
HGNCHGNC:4137. GAN.
HPACAB011825.
HPA049473.
MIM256850. phenotype.
605379. gene.
neXtProtNX_Q9H2C0.
Orphanet643. Giant axonal neuropathy.
PharmGKBPA28550.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG274392.
HOGENOMHOG000290709.
HOVERGENHBG005802.
InParanoidQ9H2C0.
KOK10453.
OMAIQGSEMV.
OrthoDBEOG7P2XRJ.
PhylomeDBQ9H2C0.
TreeFamTF329218.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.
UniPathwayUPA00143.

Gene expression databases

BgeeQ9H2C0.
CleanExHS_GAN.
GenevestigatorQ9H2C0.

Family and domain databases

Gene3D2.120.10.80. 1 hit.
3.30.710.10. 1 hit.
InterProIPR011705. BACK.
IPR000210. BTB/POZ-like.
IPR011333. BTB/POZ_fold.
IPR013069. BTB_POZ.
IPR017096. Kelch-like_gigaxonin-typ.
IPR015915. Kelch-typ_b-propeller.
IPR006652. Kelch_1.
[Graphical view]
PfamPF07707. BACK. 1 hit.
PF00651. BTB. 1 hit.
PF01344. Kelch_1. 3 hits.
[Graphical view]
PIRSFPIRSF037037. Kelch-like_protein_gigaxonin. 1 hit.
SMARTSM00875. BACK. 1 hit.
SM00225. BTB. 1 hit.
SM00612. Kelch. 5 hits.
[Graphical view]
SUPFAMSSF54695. SSF54695. 1 hit.
PROSITEPS50097. BTB. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSGAN. human.
EvolutionaryTraceQ9H2C0.
GeneWikiGigaxonin.
GenomeRNAi8139.
NextBio30807.
PROQ9H2C0.
SOURCESearch...

Entry information

Entry nameGAN_HUMAN
AccessionPrimary (citable) accession number: Q9H2C0
Entry history
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: March 1, 2001
Last modified: July 9, 2014
This is version 136 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM