Q8TB36 (GDAP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ganglioside-induced differentiation-associated protein 1
Short name=GDAP1

Gene names

Name:

GDAP1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	358 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May function in a signal transduction pathway responsible for ganglioside-induced neurite differentiation. May also have a role in protecting myelin membranes against free radical-mediated damage.
Subcellular location	Cytoplasm By similarity.
Tissue specificity	Highly expressed in whole brain and spinal cord. Predominant expression in central tissues of the nervous system not only in neurons but also in Schwann cells. Ref.4
Involvement in disease	Defects in GDAP1 are the cause of Charcot-Marie-Tooth disease type 4A (CMT4A) [MIM:214400]. CMT4A is a form of Charcot-Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathy or CMT1, and primary peripheral axonal neuropathy or CMT2. Demyelinating CMT neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. Autosomal recessive forms of demyelinating Charcot-Marie-Tooth disease are by convention designated CMT4. CMT4A is a severe form characterized by early age of onset and rapid progression leading to inability to walk in late childhood or adolescence. Ref.4 Ref.6 Ref.7 Ref.9 Ref.10 Defects in GDAP1 are the cause of Charcot-Marie-Tooth disease axonal recessive with vocal cord paresis (CMT2RV) [MIM:607706]. CMT2RV is a form of Charcot-Marie-Tooth disease characterized by the association of axonal neuropathy with vocal cord paresis. Defects in GDAP1 are the cause of Charcot-Marie-Tooth disease type 2K (CMT2K) [MIM:607831]. CMT2K is an axonal form of Charcot-Marie-Tooth disease. Axonal CMT neuropathies are characterized by signs of axonal regeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2K onset is in early childhood (younger than 3 years). This phenotype is characterized by foot deformities, kyphoscoliosis, distal limb muscle weakness and atrophy, areflexia, and diminished sensation in the lower limbs. Weakness in the upper limbs is observed in the first decade, with clawing of the fingers. Inheritance can be autosomal dominant or recessive. Defects in GDAP1 are the cause of Charcot-Marie-Tooth disease recessive intermediate type A (CMTRIA) [MIM:608340]. CMTRIA is a form of Charcot-Marie-Tooth disease characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec.
Sequence similarities	Belongs to the GST superfamily. Contains 1 GST C-terminal domain. Contains 1 GST N-terminal domain.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Disease	Charcot-Marie-Tooth disease Disease mutation Neuropathy
Domain	Coiled coil
PTM	Acetylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8TB36-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q8TB36-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-68: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 358	358	Ganglioside-induced differentiation-associated protein 1		PRO_0000186038
Regions
	Domain	24 – 105	82	GST N-terminal
	Domain	153 – 309	157	GST C-terminal
Amino acid modifications
	Modified residue	203	1	N6-acetyllysine Ref.5
Natural variations
	Alternative sequence	1 – 68	68	Missing in isoform 2.		VSP_038393
	Natural variant	120	1	R → Q in CMT4A. Ref.9		VAR_017184
	Natural variant	161	1	R → H in CMT4A. Ref.6		VAR_017185
	Natural variant	282	1	R → C in CMT4A. Ref.7 Ref.10 Corresponds to variant rs28937906 [ dbSNP | Ensembl ].		VAR_017186
	Natural variant	310	1	R → Q in CMT2RV. Ref.8		VAR_017187
Experimental info
	Sequence conflict	3	1	E → R in CAA76892. Ref.1
	Sequence conflict	16 – 17	2	AE → GK in CAA76892. Ref.1
	Sequence conflict	53	1	E → G in CAA76892. Ref.1
	Sequence conflict	351	1	F → L in CAA76892. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 24, 2009. Version 3. Checksum: B1A61EE71918A28F	FASTA	358	41,346
	10 20 30 40 50 60 MAERQEEQRG SPPLRAEGKA DAEVKLILYH WTHSFSSQKV RLVIAEKALK CEEHDVSLPL 70 80 90 100 110 120 SEHNEPWFMR LNSTGEVPVL IHGENIICEA TQIIDYLEQT FLDERTPRLM PDKESMYYPR 130 140 150 160 170 180 VQHYRELLDS LPMDAYTHGC ILHPELTVDS MIPAYATTRI RSQIGNTESE LKKLAEENPD 190 200 210 220 230 240 LQEAYIAKQK RLKSKLLDHD NVKYLKKILD ELEKVLDQVE TELQRRNEET PEEGQQPWLC 250 260 270 280 290 300 GESFTLADVS LAVTLHRLKF LGFARRNWGN GKRPNLETYY ERVLKRKTFN KVLGHVNNIL 310 320 330 340 350 ISAVLPTAFR VAKKRAPKVL GTTLVVGLLA GVGYFAFMLF RKRLGSMILA FRPRPNYF
	Isoform 2 [UniParc]. Checksum: 904C89ADCE6841D2	FASTA	290	33,480
	10 20 30 40 50 60 MRLNSTGEVP VLIHGENIIC EATQIIDYLE QTFLDERTPR LMPDKESMYY PRVQHYRELL 70 80 90 100 110 120 DSLPMDAYTH GCILHPELTV DSMIPAYATT RIRSQIGNTE SELKKLAEEN PDLQEAYIAK 130 140 150 160 170 180 QKRLKSKLLD HDNVKYLKKI LDELEKVLDQ VETELQRRNE ETPEEGQQPW LCGESFTLAD 190 200 210 220 230 240 VSLAVTLHRL KFLGFARRNW GNGKRPNLET YYERVLKRKT FNKVLGHVNN ILISAVLPTA 250 260 270 280 290 FRVAKKRAPK VLGTTLVVGL LAGVGYFAFM LFRKRLGSMI LAFRPRPNYF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation of 10 differentially expressed cDNAs in differentiated Neuro2a cells induced through controlled expression of the GD3 synthase gene." Liu H., Nakagawa T., Kanematsu T., Uchida T., Tsuji S. J. Neurochem. 72:1781-1790(1999) [PubMed: 10217254] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain.
[2]	"DNA sequence and analysis of human chromosome 8." Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S. Nature 439:331-335(2006) [PubMed: 16421571] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Melanoma.
[4]	"The gene encoding ganglioside-induced differentiation-associated protein 1 is mutated in axonal Charcot-Marie-Tooth type 4A disease." Cuesta A., Pedrola L., Sevilla T., Garcia-Planells J., Chumillas M.J., Mayordomo F., LeGuern E., Marin I., Vilchez J.J., Palau F. Nat. Genet. 30:22-25(2002) [PubMed: 11743580] [Abstract] Cited for: DISEASE, TISSUE SPECIFICITY.
[5]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-203, MASS SPECTROMETRY.
[6]	"Ganglioside-induced differentiation-associated protein-1 is mutant in Charcot-Marie-Tooth disease type 4A/8q21." Baxter R.V., Ben-Othmane K., Rochelle J.M., Stajich J.E., Hulette C., Dew-Knight S., Hentati F., Ben-Hamida M., Bel S., Stenger J.E., Gilbert J.R., Pericak-Vance M.A., Vance J.M. Nat. Genet. 30:21-22(2002) [PubMed: 11743579] [Abstract] Cited for: VARIANT CMT4A HIS-161.
[7]	"Mutations in GDAP1: autosomal recessive CMT with demyelination and axonopathy." Nelis E., Erdem S., Van Den Bergh P.Y.K., Belpaire-Dethiou M.-C., Ceuterick C., Van Gerwen V., Cuesta A., Pedrola L., Palau F., Gabreels-Festen A.A.W.M., Verellen C., Tan E., Demirci M., Van Broeckhoven C., De Jonghe P., Topaloglu H., Timmerman V. Neurology 59:1865-1872(2002) [PubMed: 12499475] [Abstract] Cited for: VARIANT CMT4A CYS-282.
[8]	"Variability of disease progression in a family with autosomal recessive CMT associated with a S194X and new R310Q mutation in the GDAP1 gene." Azzedine H., Ruberg M., Ente D., Gilardeau C., Perie S., Wechsler B., Brice A., LeGuern E., Dubourg O. Neuromuscul. Disord. 13:341-346(2003) [PubMed: 12868504] [Abstract] Cited for: VARIANT CMT2RV GLN-310.
[9]	"CMT4A: identification of a Hispanic GDAP1 founder mutation." Boerkoel C.F., Takashima H., Nakagawa M., Izumo S., Armstrong D., Butler I., Mancias P., Papasozomenos S.C.H., Stern L.Z., Lupski J.R. Ann. Neurol. 53:400-405(2003) [PubMed: 12601710] [Abstract] Cited for: VARIANT CMT4A GLN-120.
[10]	"Mutations in the ganglioside-induced differentiation-associated protein-1 (GDAP1) gene in intermediate type autosomal recessive Charcot-Marie-Tooth neuropathy." Senderek J., Bergmann C., Ramaekers V.T., Nelis E., Bernert G., Makowski A., Zuechner S., De Jonghe P., Rudnik-Schoeneborn S., Zerres K., Schroeder J.M. Brain 126:642-649(2003) [PubMed: 12566285] [Abstract] Cited for: VARIANT CMT4A CYS-282.
+	Additional computationally mapped references.

Web resources

Inherited peripheral neuropathies mutation db

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	Y17849 mRNA. Translation: CAA76892.1. AC103952 Genomic DNA. No translation available. BC024939 mRNA. Translation: AAH24939.1.
IPI	IPI00290544. IPI00877014.
RefSeq	NP_001035808.1. NM_001040875.1. NP_061845.2. NM_018972.2.
UniGene	Hs.168950.
3D structure databases
ProteinModelPortal	Q8TB36.
SMR	Q8TB36. Positions 25-295.
ModBase	Search...
Protein-protein interaction databases
STRING	Q8TB36.
PTM databases
PhosphoSite	Q8TB36.
Polymorphism databases
DMDM	269849682.
Proteomic databases
PRIDE	Q8TB36.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000220822; ENSP00000220822; ENSG00000104381.
GeneID	54332.
KEGG	hsa:54332.
Organism-specific databases
CTD	54332.
GeneCards	GC08P075276.
HGNC	HGNC:15968. GDAP1.
HPA	HPA014266. HPA024334.
MIM	214400. phenotype. 606598. gene. 607706. phenotype. 607831. phenotype. 608340. phenotype.
neXtProt	NX_Q8TB36.
Orphanet	99944. Autosomal dominant Charcot-Marie-Tooth disease type 2K. 101097. Autosomal recessive Charcot-Marie-Tooth disease with hoarseness. 217055. Autosomal recessive intermediate Charcot-Marie-Tooth disease type A. 101102. Charcot-Marie-Tooth disease type 2H. 99948. Charcot-Marie-Tooth disease type 4A.
PharmGKB	PA28626.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG13098.
GeneTree	ENSGT00510000046788.
HOGENOM	HBG445548.
HOVERGEN	HBG051717.
InParanoid	Q8TB36.
OMA	PEEGRQP.
OrthoDB	EOG4CZBGC.
PhylomeDB	Q8TB36.
Gene expression databases
ArrayExpress	Q8TB36.
Bgee	Q8TB36.
CleanEx	HS_GDAP1.
Genevestigator	Q8TB36.
GermOnline	ENSG00000104381. Homo sapiens.
Family and domain databases
InterPro	IPR010987. Glutathione-S-Trfase_C-like. IPR004045. Glutathione_S-Trfase_N. IPR017933. Glutathione_S_Trfase/Cl_chnl_C. IPR004046. GST_C. IPR012336. Thioredoxin-like_fold. [Graphical view]
Gene3D	G3DSA:1.20.1050.10. GST_C_like. 1 hit. G3DSA:3.40.30.10. Thioredoxin_fold. 1 hit.
Pfam	PF00043. GST_C. 1 hit. PF02798. GST_N. 1 hit. [Graphical view]
SUPFAM	SSF47616. GST_C_like. 1 hit. SSF52833. Thiordxn-like_fd. 1 hit.
PROSITE	PS50405. GST_CTER. 1 hit. PS50404. GST_NTER. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	56575.
SOURCE	Search...

Entry information

Entry name

GDAP1_HUMAN

Accession

Primary (citable) accession number: Q8TB36

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 7, 2003
Last sequence update:	November 24, 2009
Last modified:	January 25, 2012
This is version 92 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.