human-SPG21

 
Homo sapiens (Human) Maspardin spg21 acid cluster protein 33 ACP33 sbm-019 (gl010)flj24010 Maspardin

Comment
Maspardin-ACP33-SPG21 is mutated in Mast syndrome (Cross and McKusick 1967, Simpson et al 2003); In an Ohio Amish isolate, Cross and McKusick (1967) found 20 cases of a recessively inherited form of presenile dementia, which they termed Mast syndrome: Onset in the late teens or twenties and slow progression, an autosomal recessive, complicated form of hereditary spastic paraplegia with dementia. A 1-bp insertion (601insA) in the ACP33 gene, causing a frameshift and premature termination of the protein was found (Simpson et al 2003). Ishiura et al. (2014) reported 2 Japanese brothers with autosomal recessive SPG21. The patients had onset of gait disturbances in their fifties and sixties, much later than that reported by Cross and McKusick (1967) The mutation was A108P substitution. ACP33 binds the intracellular domain of CD4. Mutation S109A abolishes the interraction. S109 is in similar position as active site serine of a/b hydrolase (Zeitlmann 2001). Maspardin interacts with the aldehyde dehydrogenase ALDH16A1 (Hanna 2009)


Relationship
Block X
Homo sapiens position in NCBI Life Tree :
N link to NCBI taxonomic web page and E link to ESTHER gene locus found in this strain.
> cellular organisms: N E > Eukaryota: N E > Opisthokonta: N E > Metazoa: N E > Eumetazoa: N E > Bilateria: N E > Deuterostomia: N E > Chordata: N E > Craniata: N E > Vertebrata: N E > Gnathostomata: N E > Teleostomi: N E > Euteleostomi: N E > Sarcopterygii: N E > Dipnotetrapodomorpha: N E > Tetrapoda: N E > Amniota: N E > Mammalia: N E > Theria: N E > Eutheria: N E > Boreoeutheria: N E > Euarchontoglires: N E > Primates: N E > Haplorrhini: N E > Simiiformes: N E > Catarrhini: N E > Hominoidea: N E > Hominidae: N E > Homininae: N E > Homo: N E > Homo sapiens: N E

Molecular evidence
Database
7 mutations: Table (ordered Natural and SD mutagenesis) (e.g. : T201NfsX11_human-SPG21, A108P_human-SPG21, F40EfsX27_human-SPG21 ... more)
No structure
No kinetic
Disease: Mast Syndrome -


>3 Genbank links 6 more: NM_016630, AF208861, AF212231
3 UniProt : Q9NZD8, H0YKB0, A0A024R5Y1
1 Ncbi-nid : 13699804
1 Ncbi-pid : 7706174
>3 UniProtTrembl links 6 more: Q9NZD8, H0YKB0, H3BRR0
>3 Interpro links 6 more: Q9NZD8, H0YKB0, H3BRR0
>3 Prodom links 6 more: Q9NZD8, H0YKB0, H3BRR0
>3 Pfam links 6 more: Q9NZD8, H0YKB0, H3BRR0
>3 PIRSF links 6 more: Q9NZD8, H0YKB0, H3BRR0
>3 SUPERFAM links 6 more: Q9NZD8, H0YKB0, H3BRR0
>3 QuickSwissBlast links 6 more: Q9NZD8, H0YKB0, H3BRR0
1 EntrezGene : 51324
1 SNP : 51324
1 UniGene : 242458
1 HUGO HGNC : 20373
2 OMIM : 248900, 608181
1 Ensembl : ENSG00000090487
 
Sequence
Graphical view for this peptide sequence: human-SPG21
Colored MSA for Maspardin-ACP33-SPG21_like (raw)
MGEIKVSPDYNWFRGTVPLKKIIVDDDDSKIWSLYDAGPRSIRCPLIFLP
PVSGTADVFFRQILALTGWGYRVIALQYPVYWDHLEFCDGFRKLLDHLQL
DKVHLFGASLGGFLAQKFAEYTHKSPRVHSLILCNSFSDTSIFNQTWTAN
SFWLMPAFMLKKIVLGNFSSGPVDPMMADAIDFMVDRLESLGQSELASRL
TLNCQNSYVEPHKIRDIPVTIMDVFDQSALSTEAKEEMYKLYPNARRAHL
KTGGNFPYLCRSAEVNLYVQIHLLQFHGTKYAAIDPSMVSAEELEVQKGS
LGISQEEQ
Legend This sequence has been compared to family alignement (MSA)
red => minority aminoacid
blue => majority aminoacid
color intensity => conservation rate
title => sequence position(MSA position)aminoacid rate
Catalytic site
Catalytic site in the MSA

MGEIKVSPDYNWFRGTVPLKKIIVDDDDSKIWSLYDAGPRSIRCPLIFLP
PVSGTADVFFRQILALTGWGYRVIALQYPVYWDHLEFCDGFRKLLDHLQL
DKVHLFGASLGGFLAQKFAEYTHKSPRVHSLILCNSFSDTSIFNQTWTAN
SFWLMPAFMLKKIVLGNFSSGPVDPMMADAIDFMVDRLESLGQSELASRL
TLNCQNSYVEPHKIRDIPVTIMDVFDQSALSTEAKEEMYKLYPNARRAHL
KTGGNFPYLCRSAEVNLYVQIHLLQFHGTKYAAIDPSMVSAEELEVQKGS
LGISQEEQ

Graphical view for this nucleotide DNA sequence (959 bp): human-SPG21



References
12 more
    Title: Targeted disruption of the Mast syndrome gene SPG21 in mice impairs hind limb function and alters axon branching in cultured cortical neurons
    Soderblom C, Stadler J, Jupille H, Blackstone C, Shupliakov O, Hanna MC
    Ref: Neurogenetics, 11:369, 2010 : PubMed

            

    Title: Maspardin is mutated in mast syndrome, a complicated form of hereditary spastic paraplegia associated with dementia
    Simpson MA, Cross H, Proukakis C, Pryde A, Hershberger R, Chatonnet A, Patton MA, Crosby AH
    Ref: American Journal of Human Genetics, 73:1147, 2003 : PubMed

            

    Title: Cloning of ACP33 as a novel intracellular ligand of CD4
    Zeitlmann L, Sirim P, Kremmer E, Kolanus W
    Ref: Journal of Biological Chemistry, 276:9123, 2001 : PubMed

            


Other Papers


Send your questions or comments to :
Mail to: Nicolas Lenfant, Thierry Hotelier, Yves Bourne, Pascale Marchot and Arnaud Chatonnet.
Please cite: Lenfant 2013 Nucleic.Acids.Res. or Marchot Chatonnet 2012 Prot.Pept Lett.
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