GAN_MOUSE
ID GAN_MOUSE Reviewed; 597 AA.
AC Q8CA72;
DT 16-DEC-2008, integrated into UniProtKB/Swiss-Prot.
DT 16-DEC-2008, sequence version 2.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Gigaxonin {ECO:0000312|MGI:MGI:1890619};
GN Name=Gan {ECO:0000312|MGI:MGI:1890619};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2] {ECO:0000305, ECO:0000312|EMBL:BAC30353.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2-597.
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAC30353.1};
RC TISSUE=Spinal cord {ECO:0000312|EMBL:BAC30353.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3] {ECO:0000305, ECO:0000312|EMBL:AAI12433.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2-597.
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4] {ECO:0000305}
RP INTERACTION WITH MAP1B, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=12147674; DOI=10.1083/jcb.200202055;
RA Ding J., Liu J.-J., Kowal A.S., Nardine T., Bhattacharya P., Lee A.,
RA Yang Y.;
RT "Microtubule-associated protein 1B: a neuronal binding partner for
RT gigaxonin.";
RL J. Cell Biol. 158:427-433(2002).
RN [5] {ECO:0000305}
RP FUNCTION.
RX PubMed=16227972; DOI=10.1038/nature04256;
RA Allen E., Ding J., Wang W., Pramanik S., Chou J., Yau V., Yang Y.;
RT "Gigaxonin-controlled degradation of MAP1B light chain is critical to
RT neuronal survival.";
RL Nature 438:224-228(2005).
RN [6] {ECO:0000305}
RP FUNCTION, INTERACTION WITH MAP1S, AND DISRUPTION PHENOTYPE.
RX PubMed=16565160; DOI=10.1093/hmg/ddl069;
RA Ding J., Allen E., Wang W., Valle A., Wu C., Nardine T., Cui B., Yi J.,
RA Taylor A., Jeon N.L., Chu S., So Y., Vogel H., Tolwani R., Mobley W.,
RA Yang Y.;
RT "Gene targeting of GAN in mouse causes a toxic accumulation of microtubule-
RT associated protein 8 and impaired retrograde axonal transport.";
RL Hum. Mol. Genet. 15:1451-1463(2006).
RN [7] {ECO:0000305}
RP DISRUPTION PHENOTYPE.
RX PubMed=18680552; DOI=10.1111/j.1471-4159.2008.05601.x;
RA Dequen F., Bomont P., Gowing G., Cleveland D.W., Julien J.-P.;
RT "Modest loss of peripheral axons, muscle atrophy and formation of brain
RT inclusions in mice with targeted deletion of gigaxonin exon 1.";
RL J. Neurochem. 107:253-264(2008).
CC -!- FUNCTION: Probable cytoskeletal component that directly or indirectly
CC plays an important role in neurofilament architecture. May act as a
CC substrate-specific adapter of an E3 ubiquitin-protein ligase complex
CC which mediates the ubiquitination and subsequent proteasomal
CC degradation of target proteins. Controls degradation of TBCB (By
CC similarity). Controls degradation of MAP1B and MAP1S, and is critical
CC for neuronal maintenance and survival. {ECO:0000250,
CC ECO:0000269|PubMed:16227972, ECO:0000269|PubMed:16565160}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q9H2C0}.
CC -!- SUBUNIT: Interacts with TBCB. Interacts with CUL3. Part of a complex
CC that contains CUL3, RBX1 and GAN. Interacts (via BTB domain) with UBA1
CC (By similarity). Interacts (via Kelch domains) with MAP1B (via C-
CC terminus) and MAP1S (via C-terminus). {ECO:0000250|UniProtKB:Q9H2C0,
CC ECO:0000269|PubMed:12147674, ECO:0000269|PubMed:16565160}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:12147674}.
CC -!- TISSUE SPECIFICITY: Expressed in brain, heart and muscle (at protein
CC level). {ECO:0000269|PubMed:12147674}.
CC -!- PTM: Ubiquitinated by E3 ubiquitin ligase complex formed by CUL3 and
CC RBX1 and probably targeted for proteasome-independent degradation.
CC {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice have a relatively normal life span. However,
CC they display deterioration in motor function with onset varying from 6
CC to 10 months as well as abnormalities in non-neuronal tissues. The
CC prominent pathological features include limb weakness, muscular
CC atrophy, axonal degeneration, neurofilament accumulation, an abnormal
CC microtubule network, mitochondrial swelling and thinned myelin sheaths.
CC {ECO:0000269|PubMed:16565160, ECO:0000269|PubMed:18680552}.
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DR EMBL; AC121116; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK039455; BAC30353.1; -; mRNA.
DR EMBL; BC112432; AAI12433.1; -; mRNA.
DR CCDS; CCDS40490.1; -.
DR RefSeq; NP_001074620.1; NM_001081151.1.
DR AlphaFoldDB; Q8CA72; -.
DR SMR; Q8CA72; -.
DR BioGRID; 229062; 9.
DR IntAct; Q8CA72; 1.
DR MINT; Q8CA72; -.
DR STRING; 10090.ENSMUSP00000124904; -.
DR iPTMnet; Q8CA72; -.
DR PhosphoSitePlus; Q8CA72; -.
DR MaxQB; Q8CA72; -.
DR PaxDb; Q8CA72; -.
DR PeptideAtlas; Q8CA72; -.
DR PRIDE; Q8CA72; -.
DR ProteomicsDB; 273026; -.
DR Antibodypedia; 71668; 135 antibodies from 24 providers.
DR DNASU; 209239; -.
DR Ensembl; ENSMUST00000064488; ENSMUSP00000070168; ENSMUSG00000052557.
DR GeneID; 209239; -.
DR KEGG; mmu:209239; -.
DR UCSC; uc009nox.1; mouse.
DR CTD; 8139; -.
DR MGI; MGI:1890619; Gan.
DR VEuPathDB; HostDB:ENSMUSG00000052557; -.
DR eggNOG; KOG4441; Eukaryota.
DR GeneTree; ENSGT00940000155273; -.
DR InParanoid; Q8CA72; -.
DR OMA; MCPLYDR; -.
DR OrthoDB; 925701at2759; -.
DR PhylomeDB; Q8CA72; -.
DR TreeFam; TF329218; -.
DR Reactome; R-MMU-8951664; Neddylation.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 209239; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Gan; mouse.
DR PRO; PR:Q8CA72; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q8CA72; protein.
DR Bgee; ENSMUSG00000052557; Expressed in lumbar dorsal root ganglion and 214 other tissues.
DR ExpressionAtlas; Q8CA72; baseline and differential.
DR Genevisible; Q8CA72; MM.
DR GO; GO:0031463; C:Cul3-RING ubiquitin ligase complex; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0007010; P:cytoskeleton organization; ISO:MGI.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR Gene3D; 2.120.10.80; -; 1.
DR Gene3D; 3.30.710.10; -; 1.
DR InterPro; IPR011705; BACK.
DR InterPro; IPR017096; BTB-kelch_protein.
DR InterPro; IPR000210; BTB/POZ_dom.
DR InterPro; IPR015915; Kelch-typ_b-propeller.
DR InterPro; IPR006652; Kelch_1.
DR InterPro; IPR030579; KLHL16.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR PANTHER; PTHR24412:SF232; PTHR24412:SF232; 1.
DR Pfam; PF07707; BACK; 1.
DR Pfam; PF00651; BTB; 1.
DR Pfam; PF01344; Kelch_1; 3.
DR PIRSF; PIRSF037037; Kelch-like_protein_gigaxonin; 1.
DR SMART; SM00875; BACK; 1.
DR SMART; SM00225; BTB; 1.
DR SMART; SM00612; Kelch; 5.
DR SUPFAM; SSF117281; SSF117281; 1.
DR SUPFAM; SSF54695; SSF54695; 1.
DR PROSITE; PS50097; BTB; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Cytoskeleton; Kelch repeat; Neurodegeneration;
KW Reference proteome; Repeat; Ubl conjugation; Ubl conjugation pathway.
FT CHAIN 1..597
FT /note="Gigaxonin"
FT /id="PRO_0000358592"
FT DOMAIN 30..99
FT /note="BTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT DOMAIN 134..236
FT /note="BACK"
FT /evidence="ECO:0000255"
FT REPEAT 274..326
FT /note="Kelch 1"
FT /evidence="ECO:0000255"
FT REPEAT 327..374
FT /note="Kelch 2"
FT /evidence="ECO:0000255"
FT REPEAT 376..421
FT /note="Kelch 3"
FT /evidence="ECO:0000255"
FT REPEAT 422..468
FT /note="Kelch 4"
FT /evidence="ECO:0000255"
FT REPEAT 470..522
FT /note="Kelch 5"
FT /evidence="ECO:0000255"
FT REPEAT 528..574
FT /note="Kelch 6"
FT /evidence="ECO:0000255"
SQ SEQUENCE 597 AA; 67671 MW; 6A7DE61945B64F98 CRC64;
MAEGSAVSDP QHAARLLRAL SSFREEARFC DAHLVLDGEE IPVQKNILAA ASPYIRTKLN
YNPPKDDGST YKIELEGISV MVMREILDYI FSGQIRLNED TIQDVVQAAD LLLLTDLKTL
CCEFLEGCIA AENCIGIRDF ALHYCLHHVH YLATEYLETH FRDVSSTEEF LELSPQKLKE
VISLEKLNVG NERYVFEAVI RWIAHDVEMR KVHMKDVMSA LWVSGLDSSY LREQMLNEPL
VREIVKECSN IPLSQPQQGE AMLASFKPRG YSECIVTIGG EERVSRKPTA AMRCMCPLYD
PNRQLWIELA PLSMPRINHG VLSAEGFLFV LGGQDENKQT LSSGEKYDPD ANTWTALPPM
HEARHNFGIV EIDGMLYILG GEDGDRELIS MECYDIYSKT WTKQPDLTMV RKIGCYAAMK
KKIYAMGGGS YGKLFESVEC YDPRTQQWTA ICPLKERRFG AVACGVAMEL YVFGGVRSRE
DIQGSEMVTC KSEFYHDEFK RWIYLNDQNL CIPASSSFVY GAVPIGASIY VIGDLDTGTN
YDYVREFKRS TGTWHHTKPL LPSDLRRTGC AALRIANCKL FRLQLQQGLF RIRVHSP
