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Protein

Gigaxonin

Gene

GAN

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

Functioni

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.4 Publications

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

BioCyciZFISH:ENSG00000127688-MONOMER.
ReactomeiR-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Gigaxonin
Alternative name(s):
Kelch-like protein 16
Gene namesi
Name:GAN
Synonyms:GAN1, KLHL16
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:4137. GAN.

Subcellular locationi

GO - Cellular componenti

  • Cul3-RING ubiquitin ligase complex Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • cytoskeleton Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton

Pathology & Biotechi

Involvement in diseasei

Giant axonal neuropathy 1, autosomal recessive (GAN1)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA severe autosomal recessive sensorimotor neuropathy affecting both the peripheral nerves and the central nervous system. Axonal loss and the presence of giant axonal swellings filled with neurofilaments on nerve biopsies are the hallmarks of this neurodegenerative disorder.
See also OMIM:256850
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01075915R → S in GAN1; no effect on binding to TBCB. 2 PublicationsCorresponds to variant rs119485093dbSNPEnsembl.1
Natural variantiVAR_05411351A → P in GAN1. 1 PublicationCorresponds to variant rs750258209dbSNPEnsembl.1
Natural variantiVAR_01076052S → G in GAN1. 1 Publication1
Natural variantiVAR_01076179S → L in GAN1. 1 Publication1
Natural variantiVAR_01076282V → F in GAN1; no effect on binding to TBCB. 2 Publications1
Natural variantiVAR_01568086I → F in GAN1. 1 Publication1
Natural variantiVAR_05411489Y → C in GAN1. 1 Publication1
Natural variantiVAR_010763138R → H in GAN1. 1 PublicationCorresponds to variant rs119485092dbSNPEnsembl.1
Natural variantiVAR_054115195V → F in GAN1. 1 Publication1
Natural variantiVAR_010764269R → Q in GAN1. 2 PublicationsCorresponds to variant rs759581558dbSNPEnsembl.1
Natural variantiVAR_010765309L → R in GAN1. 1 Publication1
Natural variantiVAR_054116315P → L in GAN1. 1 PublicationCorresponds to variant rs144486241dbSNPEnsembl.1
Natural variantiVAR_015681368G → R in GAN1. 2 PublicationsCorresponds to variant rs758756818dbSNPEnsembl.1
Natural variantiVAR_015560423I → T in GAN1. 2 PublicationsCorresponds to variant rs119485091dbSNPEnsembl.1
Natural variantiVAR_054117474G → R in GAN1. 1 Publication1
Natural variantiVAR_010757486E → K in GAN1. 1 PublicationCorresponds to variant rs119485088dbSNPEnsembl.1
Natural variantiVAR_010766545R → C in GAN1; complete loss of binding to TBCB. 2 PublicationsCorresponds to variant rs112201678dbSNPEnsembl.1
Natural variantiVAR_054118545R → H in GAN1. 1 PublicationCorresponds to variant rs746486469dbSNPEnsembl.1
Natural variantiVAR_010767570C → Y in GAN1. 1 Publication1

Keywords - Diseasei

Disease mutation, Neurodegeneration, Neuropathy

Organism-specific databases

DisGeNETi8139.
MalaCardsiGAN.
MIMi256850. phenotype.
OpenTargetsiENSG00000261609.
Orphaneti643. Giant axonal neuropathy.
PharmGKBiPA28550.

Polymorphism and mutation databases

BioMutaiGAN.
DMDMi13626745.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001190701 – 597GigaxoninAdd BLAST597

Post-translational modificationi

Ubiquitinated by E3 ubiquitin ligase complex formed by CUL3 and RBX1 and probably targeted for proteasome-independent degradation.1 Publication

Keywords - PTMi

Ubl conjugation

Proteomic databases

EPDiQ9H2C0.
MaxQBiQ9H2C0.
PaxDbiQ9H2C0.
PeptideAtlasiQ9H2C0.
PRIDEiQ9H2C0.

PTM databases

iPTMnetiQ9H2C0.
PhosphoSitePlusiQ9H2C0.

Expressioni

Tissue specificityi

Expressed in brain, heart and muscle.1 Publication

Gene expression databases

BgeeiENSG00000261609.
CleanExiHS_GAN.
ExpressionAtlasiQ9H2C0. baseline and differential.
GenevisibleiQ9H2C0. HS.

Organism-specific databases

HPAiCAB011825.
HPA049473.

Interactioni

Subunit structurei

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).5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MAP1BP468213EBI-764342,EBI-764611
TBCBQ994263EBI-764342,EBI-764356
UBA1P223145EBI-764342,EBI-709688

Protein-protein interaction databases

BioGridi113800. 207 interactors.
IntActiQ9H2C0. 10 interactors.
MINTiMINT-243055.
STRINGi9606.ENSP00000248272.

Structurei

Secondary structure

1597
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi12 – 22Combined sources11
Beta strandi32 – 36Combined sources5
Beta strandi39 – 43Combined sources5
Helixi45 – 51Combined sources7
Helixi53 – 61Combined sources9
Beta strandi72 – 74Combined sources3
Helixi80 – 90Combined sources11
Turni99 – 101Combined sources3
Helixi102 – 111Combined sources10
Helixi115 – 122Combined sources8
Helixi135 – 143Combined sources9
Helixi147 – 164Combined sources18
Helixi168 – 171Combined sources4
Helixi175 – 183Combined sources9
Helixi196 – 199Combined sources4
Turni200 – 202Combined sources3
Turni211 – 213Combined sources3
Helixi214 – 224Combined sources11
Helixi231 – 236Combined sources6
Helixi241 – 245Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2PPIX-ray2.40A6-126[»]
3HVEX-ray2.80A/B1-254[»]
ProteinModelPortaliQ9H2C0.
SMRiQ9H2C0.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9H2C0.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini30 – 99BTBPROSITE-ProRule annotationAdd BLAST70
Domaini134 – 236BACKAdd BLAST103
Repeati274 – 326Kelch 1Add BLAST53
Repeati327 – 374Kelch 2Add BLAST48
Repeati376 – 421Kelch 3Add BLAST46
Repeati422 – 468Kelch 4Add BLAST47
Repeati470 – 522Kelch 5Add BLAST53
Repeati528 – 574Kelch 6Add BLAST47

Sequence similaritiesi

Contains 1 BTB (POZ) domain.PROSITE-ProRule annotation
Contains 6 Kelch repeats.Curated

Keywords - Domaini

Kelch repeat, Repeat

Phylogenomic databases

eggNOGiKOG4441. Eukaryota.
ENOG410XNX8. LUCA.
GeneTreeiENSGT00760000119153.
HOGENOMiHOG000290709.
HOVERGENiHBG005802.
InParanoidiQ9H2C0.
KOiK10453.
OMAiWIELAPM.
OrthoDBiEOG091G0FDQ.
PhylomeDBiQ9H2C0.
TreeFamiTF329218.

Family and domain databases

Gene3Di2.120.10.80. 1 hit.
InterProiIPR011705. BACK.
IPR017096. BTB-kelch_protein.
IPR000210. BTB/POZ_dom.
IPR015915. Kelch-typ_b-propeller.
IPR006652. Kelch_1.
IPR030579. KLHL16.
IPR011333. SKP1/BTB/POZ.
[Graphical view]
PANTHERiPTHR24412:SF232. PTHR24412:SF232. 1 hit.
PfamiPF07707. BACK. 1 hit.
PF00651. BTB. 1 hit.
PF01344. Kelch_1. 3 hits.
[Graphical view]
PIRSFiPIRSF037037. Kelch-like_protein_gigaxonin. 1 hit.
SMARTiSM00875. BACK. 1 hit.
SM00225. BTB. 1 hit.
SM00612. Kelch. 5 hits.
[Graphical view]
SUPFAMiSSF54695. SSF54695. 1 hit.
PROSITEiPS50097. BTB. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9H2C0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAEGSAVSDP QHAARLLRAL SSFREESRFC DAHLVLDGEE IPVQKNILAA
60 70 80 90 100
ASPYIRTKLN YNPPKDDGST YKIELEGISV MVMREILDYI FSGQIRLNED
110 120 130 140 150
TIQDVVQAAD LLLLTDLKTL CCEFLEGCIA AENCIGIRDF ALHYCLHHVH
160 170 180 190 200
YLATEYLETH FRDVSSTEEF LELSPQKLKE VISLEKLNVG NERYVFEAVI
210 220 230 240 250
RWIAHDTEIR KVHMKDVMSA LWVSGLDSSY LREQMLNEPL VREIVKECSN
260 270 280 290 300
IPLSQPQQGE AMLANFKPRG YSECIVTVGG EERVSRKPTA AMRCMCPLYD
310 320 330 340 350
PNRQLWIELA PLSMPRINHG VLSAEGFLFV FGGQDENKQT LSSGEKYDPD
360 370 380 390 400
ANTWTALPPM NEARHNFGIV EIDGMLYILG GEDGEKELIS MECYDIYSKT
410 420 430 440 450
WTKQPDLTMV RKIGCYAAMK KKIYAMGGGS YGKLFESVEC YDPRTQQWTA
460 470 480 490 500
ICPLKERRFG AVACGVAMEL YVFGGVRSRE DAQGSEMVTC KSEFYHDEFK
510 520 530 540 550
RWIYLNDQNL CIPASSSFVY GAVPIGASIY VIGDLDTGTN YDYVREFKRS
560 570 580 590
TGTWHHTKPL LPSDLRRTGC AALRIANCKL FRLQLQQGLF RIRVHSP
Length:597
Mass (Da):67,638
Last modified:March 1, 2001 - v1
Checksum:i4B6ECFA6849880C7
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01075915R → S in GAN1; no effect on binding to TBCB. 2 PublicationsCorresponds to variant rs119485093dbSNPEnsembl.1
Natural variantiVAR_05411351A → P in GAN1. 1 PublicationCorresponds to variant rs750258209dbSNPEnsembl.1
Natural variantiVAR_01076052S → G in GAN1. 1 Publication1
Natural variantiVAR_01076179S → L in GAN1. 1 Publication1
Natural variantiVAR_01076282V → F in GAN1; no effect on binding to TBCB. 2 Publications1
Natural variantiVAR_01568086I → F in GAN1. 1 Publication1
Natural variantiVAR_05411489Y → C in GAN1. 1 Publication1
Natural variantiVAR_073289102I → T Probable disease-associated mutation found in hereditary motor and sensory neuropathy. 1 Publication1
Natural variantiVAR_010763138R → H in GAN1. 1 PublicationCorresponds to variant rs119485092dbSNPEnsembl.1
Natural variantiVAR_054115195V → F in GAN1. 1 Publication1
Natural variantiVAR_010764269R → Q in GAN1. 2 PublicationsCorresponds to variant rs759581558dbSNPEnsembl.1
Natural variantiVAR_010765309L → R in GAN1. 1 Publication1
Natural variantiVAR_054116315P → L in GAN1. 1 PublicationCorresponds to variant rs144486241dbSNPEnsembl.1
Natural variantiVAR_015681368G → R in GAN1. 2 PublicationsCorresponds to variant rs758756818dbSNPEnsembl.1
Natural variantiVAR_015560423I → T in GAN1. 2 PublicationsCorresponds to variant rs119485091dbSNPEnsembl.1
Natural variantiVAR_073290438V → I Probable disease-associated mutation found in hereditary motor and sensory neuropathy. 1 Publication1
Natural variantiVAR_054117474G → R in GAN1. 1 Publication1
Natural variantiVAR_010757486E → K in GAN1. 1 PublicationCorresponds to variant rs119485088dbSNPEnsembl.1
Natural variantiVAR_010766545R → C in GAN1; complete loss of binding to TBCB. 2 PublicationsCorresponds to variant rs112201678dbSNPEnsembl.1
Natural variantiVAR_054118545R → H in GAN1. 1 PublicationCorresponds to variant rs746486469dbSNPEnsembl.1
Natural variantiVAR_010767570C → Y in GAN1. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF291673 mRNA. Translation: AAG35311.1.
BC044840 mRNA. Translation: AAH44840.1.
CCDSiCCDS10935.1.
RefSeqiNP_071324.1. NM_022041.3.
UniGeneiHs.112569.

Genome annotation databases

EnsembliENST00000568107; ENSP00000476795; ENSG00000261609.
GeneIDi8139.
KEGGihsa:8139.
UCSCiuc002fgo.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Inherited peripheral neuropathies mutation db

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF291673 mRNA. Translation: AAG35311.1.
BC044840 mRNA. Translation: AAH44840.1.
CCDSiCCDS10935.1.
RefSeqiNP_071324.1. NM_022041.3.
UniGeneiHs.112569.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2PPIX-ray2.40A6-126[»]
3HVEX-ray2.80A/B1-254[»]
ProteinModelPortaliQ9H2C0.
SMRiQ9H2C0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113800. 207 interactors.
IntActiQ9H2C0. 10 interactors.
MINTiMINT-243055.
STRINGi9606.ENSP00000248272.

PTM databases

iPTMnetiQ9H2C0.
PhosphoSitePlusiQ9H2C0.

Polymorphism and mutation databases

BioMutaiGAN.
DMDMi13626745.

Proteomic databases

EPDiQ9H2C0.
MaxQBiQ9H2C0.
PaxDbiQ9H2C0.
PeptideAtlasiQ9H2C0.
PRIDEiQ9H2C0.

Protocols and materials databases

DNASUi8139.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000568107; ENSP00000476795; ENSG00000261609.
GeneIDi8139.
KEGGihsa:8139.
UCSCiuc002fgo.4. human.

Organism-specific databases

CTDi8139.
DisGeNETi8139.
GeneCardsiGAN.
GeneReviewsiGAN.
HGNCiHGNC:4137. GAN.
HPAiCAB011825.
HPA049473.
MalaCardsiGAN.
MIMi256850. phenotype.
605379. gene.
neXtProtiNX_Q9H2C0.
OpenTargetsiENSG00000261609.
Orphaneti643. Giant axonal neuropathy.
PharmGKBiPA28550.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4441. Eukaryota.
ENOG410XNX8. LUCA.
GeneTreeiENSGT00760000119153.
HOGENOMiHOG000290709.
HOVERGENiHBG005802.
InParanoidiQ9H2C0.
KOiK10453.
OMAiWIELAPM.
OrthoDBiEOG091G0FDQ.
PhylomeDBiQ9H2C0.
TreeFamiTF329218.

Enzyme and pathway databases

UniPathwayiUPA00143.
BioCyciZFISH:ENSG00000127688-MONOMER.
ReactomeiR-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.

Miscellaneous databases

ChiTaRSiGAN. human.
EvolutionaryTraceiQ9H2C0.
GeneWikiiGigaxonin.
GenomeRNAii8139.
PROiQ9H2C0.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000261609.
CleanExiHS_GAN.
ExpressionAtlasiQ9H2C0. baseline and differential.
GenevisibleiQ9H2C0. HS.

Family and domain databases

Gene3Di2.120.10.80. 1 hit.
InterProiIPR011705. BACK.
IPR017096. BTB-kelch_protein.
IPR000210. BTB/POZ_dom.
IPR015915. Kelch-typ_b-propeller.
IPR006652. Kelch_1.
IPR030579. KLHL16.
IPR011333. SKP1/BTB/POZ.
[Graphical view]
PANTHERiPTHR24412:SF232. PTHR24412:SF232. 1 hit.
PfamiPF07707. BACK. 1 hit.
PF00651. BTB. 1 hit.
PF01344. Kelch_1. 3 hits.
[Graphical view]
PIRSFiPIRSF037037. Kelch-like_protein_gigaxonin. 1 hit.
SMARTiSM00875. BACK. 1 hit.
SM00225. BTB. 1 hit.
SM00612. Kelch. 5 hits.
[Graphical view]
SUPFAMiSSF54695. SSF54695. 1 hit.
PROSITEiPS50097. BTB. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiGAN_HUMAN
AccessioniPrimary (citable) accession number: Q9H2C0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: March 1, 2001
Last modified: November 30, 2016
This is version 159 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 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.