GDAP1_HUMAN
ID GDAP1_HUMAN Reviewed; 358 AA.
AC Q8TB36; A8K957; E7FJF3; E7FJF4;
DT 07-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 24-NOV-2009, sequence version 3.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Ganglioside-induced differentiation-associated protein 1;
DE Short=GDAP1;
GN Name=GDAP1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10217254; DOI=10.1046/j.1471-4159.1999.0721781.x;
RA Liu H., Nakagawa T., Kanematsu T., Uchida T., Tsuji S.;
RT "Isolation of 10 differentially expressed cDNAs in differentiated Neuro2a
RT cells induced through controlled expression of the GD3 synthase gene.";
RL J. Neurochem. 72:1781-1790(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT CMT2K SER-226.
RC TISSUE=Blood;
RX PubMed=20685671; DOI=10.1136/jmg.2010.077909;
RA Crimella C., Tonelli A., Airoldi G., Baschirotto C., D'Angelo M.G.,
RA Bonato S., Losito L., Trabacca A., Bresolin N., Bassi M.T.;
RT "The GST domain of GDAP1 is a frequent target of mutations in the dominant
RT form of axonal Charcot Marie Tooth type 2K.";
RL J. Med. Genet. 47:712-716(2010).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Melanoma;
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 [6]
RP DISEASE, AND TISSUE SPECIFICITY.
RX PubMed=11743580; DOI=10.1038/ng798;
RA Cuesta A., Pedrola L., Sevilla T., Garcia-Planells J., Chumillas M.J.,
RA Mayordomo F., LeGuern E., Marin I., Vilchez J.J., Palau F.;
RT "The gene encoding ganglioside-induced differentiation-associated protein 1
RT is mutated in axonal Charcot-Marie-Tooth type 4A disease.";
RL Nat. Genet. 30:22-25(2002).
RN [7]
RP SUBCELLULAR LOCATION, MUTAGENESIS OF THR-157, CHARACTERIZATION OF VARIANTS
RP CMT4A GLN-120 AND HIS-161, CHARACTERIZATION OF VARIANT CMTRIA CYS-282, AND
RP CHARACTERIZATION OF VARIANT CMT2K TRP-120.
RX PubMed=15772096; DOI=10.1093/hmg/ddi121;
RA Pedrola L., Espert A., Wu X., Claramunt R., Shy M.E., Palau F.;
RT "GDAP1, the protein causing Charcot-Marie-Tooth disease type 4A, is
RT expressed in neurons and is associated with mitochondria.";
RL Hum. Mol. Genet. 14:1087-1094(2005).
RN [8]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, TOPOLOGY, FUNCTION, MUTAGENESIS
RP OF MET-116, CHARACTERIZATION OF VARIANTS CMT4A GLN-120 AND HIS-161,
RP CHARACTERIZATION OF VARIANT CMT2RV GLN-310, AND CHARACTERIZATION OF VARIANT
RP CMTRIA CYS-282.
RX PubMed=16172208; DOI=10.1083/jcb.200507087;
RA Niemann A., Ruegg M., La Padula V., Schenone A., Suter U.;
RT "Ganglioside-induced differentiation associated protein 1 is a regulator of
RT the mitochondrial network: new implications for Charcot-Marie-Tooth
RT disease.";
RL J. Cell Biol. 170:1067-1078(2005).
RN [9]
RP SUBUNIT, SUBCELLULAR LOCATION, AND LACK OF GLUTATHIONE TRANSFERASE
RP ACTIVITY.
RX PubMed=16857173; DOI=10.1016/j.bbrc.2006.06.189;
RA Shield A.J., Murray T.P., Board P.G.;
RT "Functional characterisation of ganglioside-induced differentiation-
RT associated protein 1 as a glutathione transferase.";
RL Biochem. Biophys. Res. Commun. 347:859-866(2006).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-203, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [11]
RP UBIQUITINATION AT LYS-50; LYS-172; LYS-173; LYS-188; LYS-190; LYS-203;
RP LYS-206; LYS-207- AND LYS-214.
RX PubMed=25621951; DOI=10.1038/ncb3097;
RA Cunningham C.N., Baughman J.M., Phu L., Tea J.S., Yu C., Coons M.,
RA Kirkpatrick D.S., Bingol B., Corn J.E.;
RT "USP30 and parkin homeostatically regulate atypical ubiquitin chains on
RT mitochondria.";
RL Nat. Cell Biol. 17:160-169(2015).
RN [12]
RP VARIANT CMT4A HIS-161.
RX PubMed=11743579; DOI=10.1038/ng796;
RA Baxter R.V., Ben-Othmane K., Rochelle J.M., Stajich J.E., Hulette C.,
RA Dew-Knight S., Hentati F., Ben-Hamida M., Bel S., Stenger J.E.,
RA Gilbert J.R., Pericak-Vance M.A., Vance J.M.;
RT "Ganglioside-induced differentiation-associated protein-1 is mutant in
RT Charcot-Marie-Tooth disease type 4A/8q21.";
RL Nat. Genet. 30:21-22(2002).
RN [13]
RP INVOLVEMENT IN CMTRIA, AND VARIANT CMTRIA CYS-282.
RX PubMed=12499475; DOI=10.1212/01.wnl.0000036272.36047.54;
RA Nelis E., Erdem S., Van Den Bergh P.Y.K., Belpaire-Dethiou M.-C.,
RA Ceuterick C., Van Gerwen V., Cuesta A., Pedrola L., Palau F.,
RA Gabreels-Festen A.A.W.M., Verellen C., Tan E., Demirci M.,
RA Van Broeckhoven C., De Jonghe P., Topaloglu H., Timmerman V.;
RT "Mutations in GDAP1: autosomal recessive CMT with demyelination and
RT axonopathy.";
RL Neurology 59:1865-1872(2002).
RN [14]
RP VARIANT CMT2RV GLN-310.
RX PubMed=12868504; DOI=10.1016/s0960-8966(02)00281-x;
RA Azzedine H., Ruberg M., Ente D., Gilardeau C., Perie S., Wechsler B.,
RA Brice A., LeGuern E., Dubourg O.;
RT "Variability of disease progression in a family with autosomal recessive
RT CMT associated with a S194X and new R310Q mutation in the GDAP1 gene.";
RL Neuromuscul. Disord. 13:341-346(2003).
RN [15]
RP VARIANT CMT4A GLN-120.
RX PubMed=12601710; DOI=10.1002/ana.10505;
RA Boerkoel C.F., Takashima H., Nakagawa M., Izumo S., Armstrong D.,
RA Butler I., Mancias P., Papasozomenos S.C.H., Stern L.Z., Lupski J.R.;
RT "CMT4A: identification of a Hispanic GDAP1 founder mutation.";
RL Ann. Neurol. 53:400-405(2003).
RN [16]
RP INVOLVEMENT IN CMTRIA.
RX PubMed=12566285; DOI=10.1093/brain/awg068;
RA Senderek J., Bergmann C., Ramaekers V.T., Nelis E., Bernert G.,
RA Makowski A., Zuechner S., De Jonghe P., Rudnik-Schoeneborn S., Zerres K.,
RA Schroeder J.M.;
RT "Mutations in the ganglioside-induced differentiation-associated protein-1
RT (GDAP1) gene in intermediate type autosomal recessive Charcot-Marie-Tooth
RT neuropathy.";
RL Brain 126:642-649(2003).
RN [17]
RP VARIANTS CMT2K ARG-256 AND HIS-282.
RX PubMed=22206013; DOI=10.1371/journal.pone.0029393;
RA Lin K.P., Soong B.W., Yang C.C., Huang L.W., Chang M.H., Lee I.H.,
RA Antonellis A., Lee Y.C.;
RT "The mutational spectrum in a cohort of Charcot-Marie-Tooth disease type 2
RT among the Han Chinese in Taiwan.";
RL PLoS ONE 6:E29393-E29393(2011).
RN [18]
RP VARIANT ASN-39.
RX PubMed=24627108; DOI=10.1007/s00415-014-7289-8;
RA Schabhuettl M., Wieland T., Senderek J., Baets J., Timmerman V.,
RA De Jonghe P., Reilly M.M., Stieglbauer K., Laich E., Windhager R., Erwa W.,
RA Trajanoski S., Strom T.M., Auer-Grumbach M.;
RT "Whole-exome sequencing in patients with inherited neuropathies: outcome
RT and challenges.";
RL J. Neurol. 261:970-982(2014).
RN [19]
RP VARIANTS CMT2K GLY-120; TRP-120; ARG-123; GLU-218 AND SER-226.
RX PubMed=26525999; DOI=10.1016/j.nmd.2015.09.008;
RA Pezzini I., Geroldi A., Capponi S., Gulli R., Schenone A., Grandis M.,
RA Doria-Lamba L., La Piana C., Cremonte M., Pisciotta C., Nolano M.,
RA Manganelli F., Santoro L., Mandich P., Bellone E.;
RT "GDAP1 mutations in Italian axonal Charcot-Marie-Tooth patients: Phenotypic
RT features and clinical course.";
RL Neuromuscul. Disord. 26:26-32(2016).
RN [20]
RP VARIANTS CMT2K TRP-120; ARG-123; LYS-126; GLY-156; VAL-247 AND TRP-310.
RX PubMed=28244113; DOI=10.1111/cge.13002;
RA Yoshimura A., Yuan J.H., Hashiguchi A., Hiramatsu Y., Ando M., Higuchi Y.,
RA Nakamura T., Okamoto Y., Matsumura K., Hamano T., Sawaura N., Shimatani Y.,
RA Kumada S., Okumura Y., Miyahara J., Yamaguchi Y., Kitamura S., Haginoya K.,
RA Mitsui J., Ishiura H., Tsuji S., Takashima H.;
RT "Clinical and mutational spectrum of Japanese patients with Charcot-Marie-
RT Tooth disease caused by GDAP1 variants.";
RL Clin. Genet. 92:274-280(2017).
CC -!- FUNCTION: Regulates the mitochondrial network by promoting
CC mitochondrial fission. {ECO:0000269|PubMed:16172208}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:16857173}.
CC -!- INTERACTION:
CC Q8TB36; Q9H7C9: AAMDC; NbExp=3; IntAct=EBI-11110431, EBI-10308705;
CC Q8TB36; O95870: ABHD16A; NbExp=3; IntAct=EBI-11110431, EBI-348517;
CC Q8TB36; P05090: APOD; NbExp=3; IntAct=EBI-11110431, EBI-715495;
CC Q8TB36; P54252: ATXN3; NbExp=3; IntAct=EBI-11110431, EBI-946046;
CC Q8TB36; Q9UQB8-6: BAIAP2; NbExp=3; IntAct=EBI-11110431, EBI-9092016;
CC Q8TB36; O15392: BIRC5; NbExp=3; IntAct=EBI-11110431, EBI-518823;
CC Q8TB36; Q9UMX3: BOK; NbExp=3; IntAct=EBI-11110431, EBI-7105206;
CC Q8TB36; Q53EZ4: CEP55; NbExp=3; IntAct=EBI-11110431, EBI-747776;
CC Q8TB36; P51798: CLCN7; NbExp=3; IntAct=EBI-11110431, EBI-4402346;
CC Q8TB36; Q16740: CLPP; NbExp=3; IntAct=EBI-11110431, EBI-1056029;
CC Q8TB36; Q9NR90-2: DAZ3; NbExp=3; IntAct=EBI-11110431, EBI-25830216;
CC Q8TB36; Q96PD2-2: DCBLD2; NbExp=5; IntAct=EBI-11110431, EBI-12135455;
CC Q8TB36; Q9UHI6: DDX20; NbExp=3; IntAct=EBI-11110431, EBI-347658;
CC Q8TB36; Q9UI08-2: EVL; NbExp=3; IntAct=EBI-11110431, EBI-6448852;
CC Q8TB36; Q8IWE2: FAM114A1; NbExp=3; IntAct=EBI-11110431, EBI-2686288;
CC Q8TB36; Q6PIV2: FOXR1; NbExp=3; IntAct=EBI-11110431, EBI-10253815;
CC Q8TB36; P09017: HOXC4; NbExp=3; IntAct=EBI-11110431, EBI-3923226;
CC Q8TB36; Q6DN90-2: IQSEC1; NbExp=3; IntAct=EBI-11110431, EBI-21911304;
CC Q8TB36; Q8NA54: IQUB; NbExp=3; IntAct=EBI-11110431, EBI-10220600;
CC Q8TB36; Q8IUC2: KRTAP8-1; NbExp=3; IntAct=EBI-11110431, EBI-10261141;
CC Q8TB36; Q99683: MAP3K5; NbExp=3; IntAct=EBI-11110431, EBI-476263;
CC Q8TB36; Q8TDB4: MGARP; NbExp=3; IntAct=EBI-11110431, EBI-4397720;
CC Q8TB36; Q9Y605: MRFAP1; NbExp=3; IntAct=EBI-11110431, EBI-995714;
CC Q8TB36; O43196-2: MSH5; NbExp=3; IntAct=EBI-11110431, EBI-25844576;
CC Q8TB36; Q96CV9-2: OPTN; NbExp=3; IntAct=EBI-11110431, EBI-9091423;
CC Q8TB36; P27986-2: PIK3R1; NbExp=3; IntAct=EBI-11110431, EBI-9090282;
CC Q8TB36; P54315: PNLIPRP1; NbExp=3; IntAct=EBI-11110431, EBI-8652812;
CC Q8TB36; Q9BY12-3: SCAPER; NbExp=3; IntAct=EBI-11110431, EBI-25837959;
CC Q8TB36; Q16637-3: SMN2; NbExp=3; IntAct=EBI-11110431, EBI-395447;
CC Q8TB36; O60749: SNX2; NbExp=3; IntAct=EBI-11110431, EBI-1046690;
CC Q8TB36; Q05C28: SPACA3; NbExp=3; IntAct=EBI-11110431, EBI-25845337;
CC Q8TB36; Q7Z6I5: SPATA12; NbExp=3; IntAct=EBI-11110431, EBI-10696971;
CC Q8TB36; Q96DR4: STARD4; NbExp=3; IntAct=EBI-11110431, EBI-17217258;
CC Q8TB36; P37802: TAGLN2; NbExp=3; IntAct=EBI-11110431, EBI-1056740;
CC Q8TB36; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-11110431, EBI-8638294;
CC Q8TB36; A2RU14: TMEM218; NbExp=3; IntAct=EBI-11110431, EBI-10173151;
CC Q8TB36; Q8NEZ2: VPS37A; NbExp=3; IntAct=EBI-11110431, EBI-2850578;
CC Q8TB36; Q9GZS3: WDR61; NbExp=3; IntAct=EBI-11110431, EBI-358545;
CC Q8TB36; Q8IUH5: ZDHHC17; NbExp=3; IntAct=EBI-11110431, EBI-524753;
CC Q8TB36; Q14966-2: ZNF638; NbExp=3; IntAct=EBI-11110431, EBI-25845021;
CC Q8TB36; Q5TEC3: ZNF697; NbExp=3; IntAct=EBI-11110431, EBI-25845217;
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000269|PubMed:15772096, ECO:0000269|PubMed:16172208,
CC ECO:0000269|PubMed:16857173}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:16172208}. Cytoplasm
CC {ECO:0000250|UniProtKB:O88741}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8TB36-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8TB36-2; Sequence=VSP_038393;
CC -!- TISSUE SPECIFICITY: Highly expressed in whole brain and spinal cord.
CC Predominant expression in central tissues of the nervous system not
CC only in neurons but also in Schwann cells.
CC {ECO:0000269|PubMed:11743580, ECO:0000269|PubMed:16172208}.
CC -!- PTM: Ubiquitinated by PRKN during mitophagy, leading to its degradation
CC and enhancement of mitophagy. Deubiquitinated by USP30.
CC {ECO:0000269|PubMed:25621951}.
CC -!- DISEASE: Charcot-Marie-Tooth disease 4A (CMT4A) [MIM:214400]: A
CC recessive demyelinating form of Charcot-Marie-Tooth disease, a disorder
CC of the peripheral nervous system, characterized by progressive weakness
CC and atrophy, initially of the peroneal muscles and later of the distal
CC muscles of the arms. Charcot-Marie-Tooth disease is classified in two
CC main groups on the basis of electrophysiologic properties and
CC histopathology: primary peripheral demyelinating neuropathies
CC (designated CMT1 when they are dominantly inherited) and primary
CC peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are
CC characterized by severely reduced nerve conduction velocities (less
CC than 38 m/sec), segmental demyelination and remyelination with onion
CC bulb formations on nerve biopsy, slowly progressive distal muscle
CC atrophy and weakness, absent deep tendon reflexes, and hollow feet. By
CC convention autosomal recessive forms of demyelinating Charcot-Marie-
CC Tooth disease are designated CMT4. CMT4A is a severe form characterized
CC by early age of onset and rapid progression leading to inability to
CC walk in late childhood or adolescence. {ECO:0000269|PubMed:11743579,
CC ECO:0000269|PubMed:12601710, ECO:0000269|PubMed:15772096,
CC ECO:0000269|PubMed:16172208}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Charcot-Marie-Tooth disease, axonal, with vocal cord paresis,
CC autosomal recessive (CMT2RV) [MIM:607706]: A form of Charcot-Marie-
CC Tooth disease characterized by the association of axonal neuropathy
CC with vocal cord paresis. Charcot-Marie-Tooth disease is a disorder of
CC the peripheral nervous system, characterized by progressive weakness
CC and atrophy, initially of the peroneal muscles and later of the distal
CC muscles of the arms. {ECO:0000269|PubMed:12868504,
CC ECO:0000269|PubMed:16172208}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Charcot-Marie-Tooth disease 2K (CMT2K) [MIM:607831]: An axonal
CC form of Charcot-Marie-Tooth disease, a disorder of the peripheral
CC nervous system, characterized by progressive weakness and atrophy,
CC initially of the peroneal muscles and later of the distal muscles of
CC the arms. Charcot-Marie-Tooth disease is classified in two main groups
CC on the basis of electrophysiologic properties and histopathology:
CC primary peripheral demyelinating neuropathies (designated CMT1 when
CC they are dominantly inherited) and primary peripheral axonal
CC neuropathies (CMT2). Neuropathies of the CMT2 group are characterized
CC by signs of axonal degeneration in the absence of obvious myelin
CC alterations, normal or slightly reduced nerve conduction velocities,
CC and progressive distal muscle weakness and atrophy. Charcot-Marie-Tooth
CC disease type 2K onset is in early childhood (younger than 3 years).
CC This phenotype is characterized by foot deformities, kyphoscoliosis,
CC distal limb muscle weakness and atrophy, areflexia, and diminished
CC sensation in the lower limbs. Weakness in the upper limbs is observed
CC in the first decade, with clawing of the fingers. Inheritance can be
CC autosomal dominant or recessive. {ECO:0000269|PubMed:15772096,
CC ECO:0000269|PubMed:20685671, ECO:0000269|PubMed:22206013,
CC ECO:0000269|PubMed:26525999, ECO:0000269|PubMed:28244113}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Charcot-Marie-Tooth disease, recessive, intermediate type, A
CC (CMTRIA) [MIM:608340]: A form of Charcot-Marie-Tooth disease, a
CC disorder of the peripheral nervous system, characterized by progressive
CC weakness and atrophy, initially of the peroneal muscles and later of
CC the distal muscles of the arms. Recessive intermediate forms of
CC Charcot-Marie-Tooth disease are characterized by clinical and
CC pathologic features intermediate between demyelinating and axonal
CC peripheral neuropathies, and motor median nerve conduction velocities
CC ranging from 25 to 45 m/sec. {ECO:0000269|PubMed:12499475,
CC ECO:0000269|PubMed:12566285, ECO:0000269|PubMed:15772096,
CC ECO:0000269|PubMed:16172208}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the GST superfamily. {ECO:0000305}.
CC -!- CAUTION: While belonging to the GST superfamily, it lacks glutathione
CC transferase activity. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Inherited peripheral neuropathies mutation db;
CC URL="https://uantwerpen.vib.be/CMTMutations";
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DR EMBL; Y17849; CAA76892.1; -; mRNA.
DR EMBL; AB551556; BAJ65577.1; -; mRNA.
DR EMBL; AB551557; BAJ65578.1; -; mRNA.
DR EMBL; AK292572; BAF85261.1; -; mRNA.
DR EMBL; AC103952; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC024939; AAH24939.1; -; mRNA.
DR CCDS; CCDS34911.1; -. [Q8TB36-1]
DR CCDS; CCDS47877.1; -. [Q8TB36-2]
DR RefSeq; NP_001035808.1; NM_001040875.2. [Q8TB36-2]
DR RefSeq; NP_061845.2; NM_018972.2. [Q8TB36-1]
DR PDB; 7AIA; X-ray; 2.20 A; AAA/BBB=23-302.
DR PDB; 7ALM; X-ray; 2.80 A; A/B=23-302.
DR PDB; 7B2G; X-ray; 3.00 A; A=1-302.
DR PDBsum; 7AIA; -.
DR PDBsum; 7ALM; -.
DR PDBsum; 7B2G; -.
DR AlphaFoldDB; Q8TB36; -.
DR SASBDB; Q8TB36; -.
DR SMR; Q8TB36; -.
DR BioGRID; 119934; 46.
DR IntAct; Q8TB36; 46.
DR MINT; Q8TB36; -.
DR STRING; 9606.ENSP00000220822; -.
DR iPTMnet; Q8TB36; -.
DR PhosphoSitePlus; Q8TB36; -.
DR BioMuta; GDAP1; -.
DR DMDM; 269849682; -.
DR EPD; Q8TB36; -.
DR jPOST; Q8TB36; -.
DR MassIVE; Q8TB36; -.
DR MaxQB; Q8TB36; -.
DR PaxDb; Q8TB36; -.
DR PeptideAtlas; Q8TB36; -.
DR PRIDE; Q8TB36; -.
DR ProteomicsDB; 73956; -. [Q8TB36-1]
DR ProteomicsDB; 73957; -. [Q8TB36-2]
DR Antibodypedia; 2988; 126 antibodies from 23 providers.
DR DNASU; 54332; -.
DR Ensembl; ENST00000220822.12; ENSP00000220822.7; ENSG00000104381.14. [Q8TB36-1]
DR Ensembl; ENST00000674865.1; ENSP00000502437.1; ENSG00000104381.14. [Q8TB36-2]
DR Ensembl; ENST00000675944.1; ENSP00000502673.1; ENSG00000104381.14. [Q8TB36-2]
DR GeneID; 54332; -.
DR KEGG; hsa:54332; -.
DR MANE-Select; ENST00000220822.12; ENSP00000220822.7; NM_018972.4; NP_061845.2.
DR UCSC; uc003yah.4; human. [Q8TB36-1]
DR CTD; 54332; -.
DR DisGeNET; 54332; -.
DR GeneCards; GDAP1; -.
DR GeneReviews; GDAP1; -.
DR HGNC; HGNC:15968; GDAP1.
DR HPA; ENSG00000104381; Tissue enhanced (brain).
DR MalaCards; GDAP1; -.
DR MIM; 214400; phenotype.
DR MIM; 606598; gene.
DR MIM; 607706; phenotype.
DR MIM; 607831; phenotype.
DR MIM; 608340; phenotype.
DR neXtProt; NX_Q8TB36; -.
DR OpenTargets; ENSG00000104381; -.
DR Orphanet; 99944; Autosomal dominant Charcot-Marie-Tooth disease type 2K.
DR Orphanet; 101097; Autosomal recessive Charcot-Marie-Tooth disease with hoarseness.
DR Orphanet; 217055; Autosomal recessive intermediate Charcot-Marie-Tooth disease type A.
DR Orphanet; 101102; Charcot-Marie-Tooth disease type 2H.
DR Orphanet; 99948; Charcot-Marie-Tooth disease type 4A.
DR PharmGKB; PA28626; -.
DR VEuPathDB; HostDB:ENSG00000104381; -.
DR eggNOG; KOG4420; Eukaryota.
DR GeneTree; ENSGT00940000159124; -.
DR HOGENOM; CLU_049129_0_0_1; -.
DR InParanoid; Q8TB36; -.
DR OMA; LHCEEYD; -.
DR OrthoDB; 1011771at2759; -.
DR PhylomeDB; Q8TB36; -.
DR TreeFam; TF327072; -.
DR PathwayCommons; Q8TB36; -.
DR Reactome; R-HSA-9603798; Class I peroxisomal membrane protein import.
DR SignaLink; Q8TB36; -.
DR SIGNOR; Q8TB36; -.
DR BioGRID-ORCS; 54332; 11 hits in 1075 CRISPR screens.
DR ChiTaRS; GDAP1; human.
DR GeneWiki; GDAP1; -.
DR GenomeRNAi; 54332; -.
DR Pharos; Q8TB36; Tbio.
DR PRO; PR:Q8TB36; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q8TB36; protein.
DR Bgee; ENSG00000104381; Expressed in endothelial cell and 157 other tissues.
DR ExpressionAtlas; Q8TB36; baseline and differential.
DR Genevisible; Q8TB36; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0031307; C:integral component of mitochondrial outer membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0005778; C:peroxisomal membrane; TAS:Reactome.
DR GO; GO:0071305; P:cellular response to vitamin D; IEA:Ensembl.
DR GO; GO:0006749; P:glutathione metabolic process; IEA:InterPro.
DR GO; GO:0000266; P:mitochondrial fission; IDA:UniProtKB.
DR GO; GO:0008053; P:mitochondrial fusion; IMP:CACAO.
DR GO; GO:0006626; P:protein targeting to mitochondrion; IMP:UniProtKB.
DR GO; GO:0032526; P:response to retinoic acid; IEA:Ensembl.
DR InterPro; IPR034336; GDAP1.
DR InterPro; IPR010987; Glutathione-S-Trfase_C-like.
DR InterPro; IPR036282; Glutathione-S-Trfase_C_sf.
DR InterPro; IPR040079; Glutathione_S-Trfase.
DR InterPro; IPR004045; Glutathione_S-Trfase_N.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR PANTHER; PTHR44188:SF3; PTHR44188:SF3; 1.
DR Pfam; PF13417; GST_N_3; 1.
DR SFLD; SFLDS00019; Glutathione_Transferase_(cytos; 1.
DR SUPFAM; SSF47616; SSF47616; 1.
DR SUPFAM; SSF52833; SSF52833; 1.
DR PROSITE; PS50405; GST_CTER; 1.
DR PROSITE; PS50404; GST_NTER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing;
KW Charcot-Marie-Tooth disease; Coiled coil; Cytoplasm; Disease variant;
KW Isopeptide bond; Membrane; Mitochondrion; Mitochondrion outer membrane;
KW Neurodegeneration; Neuropathy; Reference proteome; Transmembrane;
KW Transmembrane helix; Ubl conjugation.
FT CHAIN 1..358
FT /note="Ganglioside-induced differentiation-associated
FT protein 1"
FT /id="PRO_0000186038"
FT TRANSMEM 292..312
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 320..340
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 24..105
FT /note="GST N-terminal"
FT DOMAIN 153..309
FT /note="GST C-terminal"
FT REGION 320..358
FT /note="Required for mitochondrial localization"
FT MOD_RES 203
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT CROSSLNK 50
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT CROSSLNK 172
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT CROSSLNK 173
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT CROSSLNK 188
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT CROSSLNK 190
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT CROSSLNK 203
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000269|PubMed:25621951"
FT CROSSLNK 206
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT CROSSLNK 207
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT CROSSLNK 214
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT VAR_SEQ 1..68
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_038393"
FT VARIANT 39
FT /note="K -> N (found in a patient with hereditary motor
FT neuropathy; unknown pathological significance;
FT dbSNP:rs1586794314)"
FT /evidence="ECO:0000269|PubMed:24627108"
FT /id="VAR_073297"
FT VARIANT 120
FT /note="R -> G (in CMT2K; dominant form; dbSNP:rs104894078)"
FT /evidence="ECO:0000269|PubMed:26525999"
FT /id="VAR_078265"
FT VARIANT 120
FT /note="R -> Q (in CMT4A; no effect on mitochondrial
FT localization but impairment in the ability to induce
FT mitochondrial fragmentation; dbSNP:rs1174933176)"
FT /evidence="ECO:0000269|PubMed:12601710,
FT ECO:0000269|PubMed:15772096, ECO:0000269|PubMed:16172208"
FT /id="VAR_017184"
FT VARIANT 120
FT /note="R -> W (in CMT2K; dominant form; no effect on
FT mitochondrial localization; dbSNP:rs104894078)"
FT /evidence="ECO:0000269|PubMed:15772096,
FT ECO:0000269|PubMed:26525999, ECO:0000269|PubMed:28244113"
FT /id="VAR_078266"
FT VARIANT 123
FT /note="H -> R (in CMT2K; dominant form;;
FT dbSNP:rs397515442)"
FT /evidence="ECO:0000269|PubMed:26525999,
FT ECO:0000269|PubMed:28244113"
FT /id="VAR_078267"
FT VARIANT 126
FT /note="E -> K (in CMT2K; dominant form; unknown
FT pathological significance; dbSNP:rs879254005)"
FT /evidence="ECO:0000269|PubMed:28244113"
FT /id="VAR_078268"
FT VARIANT 156
FT /note="A -> G (in CMT2K; dominant form; dbSNP:rs397515441)"
FT /evidence="ECO:0000269|PubMed:28244113"
FT /id="VAR_078269"
FT VARIANT 161
FT /note="R -> H (in CMT4A; no effect on mitochondrial
FT localization but abolishes mitochondrial fission;
FT dbSNP:rs104894076)"
FT /evidence="ECO:0000269|PubMed:11743579,
FT ECO:0000269|PubMed:15772096, ECO:0000269|PubMed:16172208"
FT /id="VAR_017185"
FT VARIANT 218
FT /note="Q -> E (in CMT2K; dominant form; unknown
FT pathological significance; dbSNP:rs121908113)"
FT /evidence="ECO:0000269|PubMed:26525999"
FT /id="VAR_078270"
FT VARIANT 226
FT /note="R -> S (in CMT2K; dominant form; unknown
FT pathological significance; dbSNP:rs267606842)"
FT /evidence="ECO:0000269|PubMed:26525999"
FT /id="VAR_078271"
FT VARIANT 247
FT /note="A -> V (in CMT2K; recessive form; unknown
FT pathological significance; dbSNP:rs1586807209)"
FT /evidence="ECO:0000269|PubMed:28244113"
FT /id="VAR_078272"
FT VARIANT 256
FT /note="H -> R (in CMT2K; recessive form;
FT dbSNP:rs1476856429)"
FT /evidence="ECO:0000269|PubMed:22206013"
FT /id="VAR_067086"
FT VARIANT 282
FT /note="R -> C (in CMTRIA; no effect on mitochondrial
FT localization but impairment in the ability to induce
FT mitochondrial fragmentation; dbSNP:rs28937906)"
FT /evidence="ECO:0000269|PubMed:12499475,
FT ECO:0000269|PubMed:12566285, ECO:0000269|PubMed:15772096,
FT ECO:0000269|PubMed:16172208"
FT /id="VAR_017186"
FT VARIANT 282
FT /note="R -> H (in CMT2K; recessive form;
FT dbSNP:rs375431837)"
FT /evidence="ECO:0000269|PubMed:22206013"
FT /id="VAR_067087"
FT VARIANT 310
FT /note="R -> Q (in CMT2RV; Abolishes mitochondrial fission;
FT dbSNP:rs1323153568)"
FT /evidence="ECO:0000269|PubMed:12868504,
FT ECO:0000269|PubMed:16172208"
FT /id="VAR_017187"
FT VARIANT 310
FT /note="R -> W (in CMT2K; recessive form;
FT dbSNP:rs538389475)"
FT /evidence="ECO:0000269|PubMed:28244113"
FT /id="VAR_078273"
FT MUTAGEN 116
FT /note="M->H: Impairment in the ability to induce
FT mitochondrial fragmentation."
FT /evidence="ECO:0000269|PubMed:16172208"
FT MUTAGEN 157
FT /note="T->P: No effect on mitochondrial localization."
FT /evidence="ECO:0000269|PubMed:15772096"
FT CONFLICT 3
FT /note="E -> R (in Ref. 1; CAA76892)"
FT /evidence="ECO:0000305"
FT CONFLICT 16..17
FT /note="AE -> GK (in Ref. 1; CAA76892)"
FT /evidence="ECO:0000305"
FT CONFLICT 34
FT /note="S -> C (in Ref. 2; BAJ65577)"
FT /evidence="ECO:0000305"
FT CONFLICT 53
FT /note="E -> G (in Ref. 1; CAA76892)"
FT /evidence="ECO:0000305"
FT CONFLICT 133
FT /note="M -> I (in Ref. 3; BAF85261)"
FT /evidence="ECO:0000305"
FT CONFLICT 351
FT /note="F -> L (in Ref. 1; CAA76892)"
FT /evidence="ECO:0000305"
FT STRAND 26..30
FT /evidence="ECO:0007829|PDB:7ALM"
FT HELIX 35..46
FT /evidence="ECO:0007829|PDB:7ALM"
FT STRAND 52..55
FT /evidence="ECO:0007829|PDB:7ALM"
FT HELIX 67..69
FT /evidence="ECO:0007829|PDB:7ALM"
FT TURN 70..73
FT /evidence="ECO:0007829|PDB:7B2G"
FT STRAND 79..82
FT /evidence="ECO:0007829|PDB:7ALM"
FT STRAND 85..89
FT /evidence="ECO:0007829|PDB:7ALM"
FT HELIX 90..100
FT /evidence="ECO:0007829|PDB:7ALM"
FT HELIX 118..129
FT /evidence="ECO:0007829|PDB:7ALM"
FT HELIX 133..141
FT /evidence="ECO:0007829|PDB:7ALM"
FT HELIX 144..146
FT /evidence="ECO:0007829|PDB:7ALM"
FT HELIX 155..159
FT /evidence="ECO:0007829|PDB:7ALM"
FT HELIX 188..229
FT /evidence="ECO:0007829|PDB:7ALM"
FT STRAND 232..234
FT /evidence="ECO:0007829|PDB:7ALM"
FT STRAND 239..243
FT /evidence="ECO:0007829|PDB:7ALM"
FT HELIX 246..260
FT /evidence="ECO:0007829|PDB:7ALM"
FT TURN 265..267
FT /evidence="ECO:0007829|PDB:7ALM"
FT HELIX 274..283
FT /evidence="ECO:0007829|PDB:7ALM"
FT HELIX 287..293
FT /evidence="ECO:0007829|PDB:7ALM"
FT TURN 294..297
FT /evidence="ECO:0007829|PDB:7ALM"
SQ SEQUENCE 358 AA; 41346 MW; B1A61EE71918A28F CRC64;
MAERQEEQRG SPPLRAEGKA DAEVKLILYH WTHSFSSQKV RLVIAEKALK CEEHDVSLPL
SEHNEPWFMR LNSTGEVPVL IHGENIICEA TQIIDYLEQT FLDERTPRLM PDKESMYYPR
VQHYRELLDS LPMDAYTHGC ILHPELTVDS MIPAYATTRI RSQIGNTESE LKKLAEENPD
LQEAYIAKQK RLKSKLLDHD NVKYLKKILD ELEKVLDQVE TELQRRNEET PEEGQQPWLC
GESFTLADVS LAVTLHRLKF LGFARRNWGN GKRPNLETYY ERVLKRKTFN KVLGHVNNIL
ISAVLPTAFR VAKKRAPKVL GTTLVVGLLA GVGYFAFMLF RKRLGSMILA FRPRPNYF
