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Protein

Ganglioside-induced differentiation-associated protein 1

Gene

GDAP1

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

Functioni

Regulates the mitochondrial network by promoting mitochondrial fission.1 Publication

GO - Molecular functioni

GO - Biological processi

  • glutathione metabolic process Source: GO_Central
  • mitochondrial fission Source: UniProtKB
  • mitochondrial fusion Source: CACAO
  • protein targeting to mitochondrion Source: UniProtKB
  • response to retinoic acid Source: Ensembl
Complete GO annotation...

Enzyme and pathway databases

BioCyciZFISH:ENSG00000104381-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Ganglioside-induced differentiation-associated protein 1
Short name:
GDAP1
Gene namesi
Name:GDAP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:15968. GDAP1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei292 – 312HelicalSequence analysisAdd BLAST21
Transmembranei320 – 340HelicalSequence analysisAdd BLAST21

GO - Cellular componenti

  • cytoplasm Source: HPA
  • integral component of mitochondrial outer membrane Source: UniProtKB
  • membrane Source: UniProtKB
  • mitochondrion Source: HPA
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Mitochondrion, Mitochondrion outer membrane

Pathology & Biotechi

Involvement in diseasei

Charcot-Marie-Tooth disease 4A (CMT4A)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA recessive demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating 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. By convention autosomal recessive forms of demyelinating Charcot-Marie-Tooth disease are 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.
See also OMIM:214400
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_017184120R → Q in CMT4A; no effect on mitochondrial localization but impairment in the ability to induce mitochodrial fragmentation. 3 Publications1
Natural variantiVAR_017185161R → H in CMT4A; no effect on mitochondrial localization but abolishes mitochondrial fission. 3 PublicationsCorresponds to variant rs104894076dbSNPEnsembl.1
Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, autosomal recessive (CMT2RV)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of Charcot-Marie-Tooth disease characterized by the association of axonal neuropathy with vocal cord paresis. Charcot-Marie-Tooth disease is a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms.
See also OMIM:607706
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_017187310R → Q in CMT2RV; Abolishes mitochondrial fission. 2 Publications1
Charcot-Marie-Tooth disease 2K (CMT2K)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. Nerve conduction velocities are normal or slightly reduced. Charcot-Marie-Tooth disease type 2K 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.
See also OMIM:607831
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_067086256H → R in CMT2K; recessive form. 1 Publication1
Natural variantiVAR_067087282R → H in CMT2K; recessive form. 1 PublicationCorresponds to variant rs375431837dbSNPEnsembl.1
Charcot-Marie-Tooth disease, recessive, intermediate type, A (CMTRIA)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Recessive intermediate forms of Charcot-Marie-Tooth disease are 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.
See also OMIM:608340
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_017186282R → C in CMTRIA; no effect on mitochondrial localization but impairment in the ability to induce mitochodrial fragmentation. 4 PublicationsCorresponds to variant rs28937906dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi116M → H: Impairment in the ability to induce mitochodrial fragmentation. 1 Publication1
Mutagenesisi120R → W: No effect on mitochondrial localization. 1 Publication1
Mutagenesisi157T → P: No effect on mitochondrial localization. 1 Publication1

Keywords - Diseasei

Charcot-Marie-Tooth disease, Disease mutation, Neurodegeneration, Neuropathy

Organism-specific databases

DisGeNETi54332.
MalaCardsiGDAP1.
MIMi214400. phenotype.
607706. phenotype.
607831. phenotype.
608340. phenotype.
OpenTargetsiENSG00000104381.
Orphaneti99944. 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.
PharmGKBiPA28626.

Polymorphism and mutation databases

BioMutaiGDAP1.
DMDMi269849682.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001860381 – 358Ganglioside-induced differentiation-associated protein 1Add BLAST358

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki50Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki172Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki173Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki188Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki190Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei203N6-acetyllysine; alternateCombined sources1
Cross-linki203Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate1 Publication
Cross-linki206Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki207Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki214Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication

Post-translational modificationi

Ubiquitinated by PARK2 during mitophagy, leading to its degradation and enhancement of mitophagy. Deubiquitinated by USP30.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Ubl conjugation

Proteomic databases

EPDiQ8TB36.
MaxQBiQ8TB36.
PaxDbiQ8TB36.
PeptideAtlasiQ8TB36.
PRIDEiQ8TB36.

PTM databases

iPTMnetiQ8TB36.
PhosphoSitePlusiQ8TB36.

Expressioni

Tissue specificityi

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.2 Publications

Gene expression databases

BgeeiENSG00000104381.
CleanExiHS_GDAP1.
ExpressionAtlasiQ8TB36. baseline and differential.
GenevisibleiQ8TB36. HS.

Organism-specific databases

HPAiHPA014266.
HPA024334.

Interactioni

Subunit structurei

Homodimer.1 Publication

Protein-protein interaction databases

BioGridi119934. 12 interactors.
IntActiQ8TB36. 4 interactors.
STRINGi9606.ENSP00000220822.

Structurei

3D structure databases

ProteinModelPortaliQ8TB36.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini24 – 105GST N-terminalAdd BLAST82
Domaini153 – 309GST C-terminalAdd BLAST157

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni320 – 358Required for mitochondrial localizationAdd BLAST39

Sequence similaritiesi

Belongs to the GST superfamily.Curated
Contains 1 GST C-terminal domain.Curated
Contains 1 GST N-terminal domain.Curated

Keywords - Domaini

Coiled coil, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4420. Eukaryota.
ENOG410YE2J. LUCA.
GeneTreeiENSGT00510000046788.
HOGENOMiHOG000231002.
HOVERGENiHBG051717.
InParanoidiQ8TB36.
OMAiWAFGKLP.
OrthoDBiEOG091G0BAC.
PhylomeDBiQ8TB36.
TreeFamiTF327072.

Family and domain databases

Gene3Di1.20.1050.10. 1 hit.
3.40.30.10. 1 hit.
InterProiIPR010987. Glutathione-S-Trfase_C-like.
IPR004045. Glutathione_S-Trfase_N.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PfamiPF13417. GST_N_3. 1 hit.
[Graphical view]
SUPFAMiSSF47616. SSF47616. 1 hit.
SSF52833. SSF52833. 1 hit.
PROSITEiPS50405. GST_CTER. 1 hit.
PS50404. GST_NTER. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8TB36-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAERQEEQRG SPPLRAEGKA DAEVKLILYH WTHSFSSQKV RLVIAEKALK
60 70 80 90 100
CEEHDVSLPL SEHNEPWFMR LNSTGEVPVL IHGENIICEA TQIIDYLEQT
110 120 130 140 150
FLDERTPRLM PDKESMYYPR VQHYRELLDS LPMDAYTHGC ILHPELTVDS
160 170 180 190 200
MIPAYATTRI RSQIGNTESE LKKLAEENPD LQEAYIAKQK RLKSKLLDHD
210 220 230 240 250
NVKYLKKILD ELEKVLDQVE TELQRRNEET PEEGQQPWLC GESFTLADVS
260 270 280 290 300
LAVTLHRLKF LGFARRNWGN GKRPNLETYY ERVLKRKTFN KVLGHVNNIL
310 320 330 340 350
ISAVLPTAFR VAKKRAPKVL GTTLVVGLLA GVGYFAFMLF RKRLGSMILA

FRPRPNYF
Length:358
Mass (Da):41,346
Last modified:November 24, 2009 - v3
Checksum:iB1A61EE71918A28F
GO
Isoform 2 (identifier: Q8TB36-2) [UniParc]FASTAAdd to basket

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

Show »
Length:290
Mass (Da):33,480
Checksum:i904C89ADCE6841D2
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti3E → R in CAA76892 (PubMed:10217254).Curated1
Sequence conflicti16 – 17AE → GK in CAA76892 (PubMed:10217254).Curated2
Sequence conflicti34S → C in BAJ65577 (PubMed:20685671).Curated1
Sequence conflicti53E → G in CAA76892 (PubMed:10217254).Curated1
Sequence conflicti133M → I in BAF85261 (PubMed:14702039).Curated1
Sequence conflicti226R → S in BAJ65578 (PubMed:20685671).Curated1
Sequence conflicti351F → L in CAA76892 (PubMed:10217254).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07329739K → N Found in a patient with hereditary motor neuropathy; unknown pathological significance. 1 Publication1
Natural variantiVAR_017184120R → Q in CMT4A; no effect on mitochondrial localization but impairment in the ability to induce mitochodrial fragmentation. 3 Publications1
Natural variantiVAR_017185161R → H in CMT4A; no effect on mitochondrial localization but abolishes mitochondrial fission. 3 PublicationsCorresponds to variant rs104894076dbSNPEnsembl.1
Natural variantiVAR_067086256H → R in CMT2K; recessive form. 1 Publication1
Natural variantiVAR_017186282R → C in CMTRIA; no effect on mitochondrial localization but impairment in the ability to induce mitochodrial fragmentation. 4 PublicationsCorresponds to variant rs28937906dbSNPEnsembl.1
Natural variantiVAR_067087282R → H in CMT2K; recessive form. 1 PublicationCorresponds to variant rs375431837dbSNPEnsembl.1
Natural variantiVAR_017187310R → Q in CMT2RV; Abolishes mitochondrial fission. 2 Publications1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0383931 – 68Missing in isoform 2. 1 PublicationAdd BLAST68

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y17849 mRNA. Translation: CAA76892.1.
AB551556 mRNA. Translation: BAJ65577.1.
AB551557 mRNA. Translation: BAJ65578.1.
AK292572 mRNA. Translation: BAF85261.1.
AC103952 Genomic DNA. No translation available.
BC024939 mRNA. Translation: AAH24939.1.
CCDSiCCDS34911.1. [Q8TB36-1]
CCDS47877.1. [Q8TB36-2]
RefSeqiNP_001035808.1. NM_001040875.2. [Q8TB36-2]
NP_061845.2. NM_018972.2. [Q8TB36-1]
UniGeneiHs.168950.

Genome annotation databases

EnsembliENST00000220822; ENSP00000220822; ENSG00000104381. [Q8TB36-1]
ENST00000434412; ENSP00000417006; ENSG00000104381. [Q8TB36-2]
GeneIDi54332.
KEGGihsa:54332.
UCSCiuc003yah.4. human. [Q8TB36-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Inherited peripheral neuropathies mutation db

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y17849 mRNA. Translation: CAA76892.1.
AB551556 mRNA. Translation: BAJ65577.1.
AB551557 mRNA. Translation: BAJ65578.1.
AK292572 mRNA. Translation: BAF85261.1.
AC103952 Genomic DNA. No translation available.
BC024939 mRNA. Translation: AAH24939.1.
CCDSiCCDS34911.1. [Q8TB36-1]
CCDS47877.1. [Q8TB36-2]
RefSeqiNP_001035808.1. NM_001040875.2. [Q8TB36-2]
NP_061845.2. NM_018972.2. [Q8TB36-1]
UniGeneiHs.168950.

3D structure databases

ProteinModelPortaliQ8TB36.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119934. 12 interactors.
IntActiQ8TB36. 4 interactors.
STRINGi9606.ENSP00000220822.

PTM databases

iPTMnetiQ8TB36.
PhosphoSitePlusiQ8TB36.

Polymorphism and mutation databases

BioMutaiGDAP1.
DMDMi269849682.

Proteomic databases

EPDiQ8TB36.
MaxQBiQ8TB36.
PaxDbiQ8TB36.
PeptideAtlasiQ8TB36.
PRIDEiQ8TB36.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000220822; ENSP00000220822; ENSG00000104381. [Q8TB36-1]
ENST00000434412; ENSP00000417006; ENSG00000104381. [Q8TB36-2]
GeneIDi54332.
KEGGihsa:54332.
UCSCiuc003yah.4. human. [Q8TB36-1]

Organism-specific databases

CTDi54332.
DisGeNETi54332.
GeneCardsiGDAP1.
GeneReviewsiGDAP1.
HGNCiHGNC:15968. GDAP1.
HPAiHPA014266.
HPA024334.
MalaCardsiGDAP1.
MIMi214400. phenotype.
606598. gene.
607706. phenotype.
607831. phenotype.
608340. phenotype.
neXtProtiNX_Q8TB36.
OpenTargetsiENSG00000104381.
Orphaneti99944. 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.
PharmGKBiPA28626.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4420. Eukaryota.
ENOG410YE2J. LUCA.
GeneTreeiENSGT00510000046788.
HOGENOMiHOG000231002.
HOVERGENiHBG051717.
InParanoidiQ8TB36.
OMAiWAFGKLP.
OrthoDBiEOG091G0BAC.
PhylomeDBiQ8TB36.
TreeFamiTF327072.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000104381-MONOMER.

Miscellaneous databases

GeneWikiiGDAP1.
GenomeRNAii54332.
PROiQ8TB36.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000104381.
CleanExiHS_GDAP1.
ExpressionAtlasiQ8TB36. baseline and differential.
GenevisibleiQ8TB36. HS.

Family and domain databases

Gene3Di1.20.1050.10. 1 hit.
3.40.30.10. 1 hit.
InterProiIPR010987. Glutathione-S-Trfase_C-like.
IPR004045. Glutathione_S-Trfase_N.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PfamiPF13417. GST_N_3. 1 hit.
[Graphical view]
SUPFAMiSSF47616. SSF47616. 1 hit.
SSF52833. SSF52833. 1 hit.
PROSITEiPS50405. GST_CTER. 1 hit.
PS50404. GST_NTER. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiGDAP1_HUMAN
AccessioniPrimary (citable) accession number: Q8TB36
Secondary accession number(s): A8K957, E7FJF3, E7FJF4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 7, 2003
Last sequence update: November 24, 2009
Last modified: November 30, 2016
This is version 140 of the entry and version 3 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

Caution

While belonging to the GST superfamily, it lacks glutathione transferase activity.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: 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. 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.