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Maspardin (Acid cluster protein 33) (Spastic paraplegia 21 autosomal recessive Mast syndrome protein) (Spastic paraplegia 21 protein)

 SPG21_HUMAN             Reviewed;         308 AA.
Q9NZD8; B4DW44; Q6ZMB6;
21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
01-OCT-2000, sequence version 1.
25-APR-2018, entry version 140.
RecName: Full=Maspardin;
AltName: Full=Acid cluster protein 33;
AltName: Full=Spastic paraplegia 21 autosomal recessive Mast syndrome protein;
AltName: Full=Spastic paraplegia 21 protein;
Name=SPG21; Synonyms=ACP33; ORFNames=BM-019, GL010;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY,
SUBCELLULAR LOCATION, INTERACTION WITH CD4, AND MUTAGENESIS OF
SER-109.
PubMed=11113139; DOI=10.1074/jbc.M009270200;
Zeitlmann L., Sirim P., Kremmer E., Kolanus W.;
"Cloning of ACP33 as a novel intracellular ligand of CD4.";
J. Biol. Chem. 276:9123-9132(2001).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Bone marrow;
Zhao M., Song H., Li N., Peng Y., Han Z., Chen Z.;
"A novel gene expressed in human bone marrow.";
Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Liver;
Li Y., Wu T., Xu S., Ren S., Chen Z., Han Z.;
"A novel gene expressed in human liver non-tumor tissues.";
Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
TISSUE=Synovium;
PubMed=14702039; DOI=10.1038/ng1285;
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=16572171; DOI=10.1038/nature04601;
Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R.,
Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G.,
Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A.,
Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W.,
Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X.,
Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K.,
Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S.,
Nusbaum C.;
"Analysis of the DNA sequence and duplication history of human
chromosome 15.";
Nature 440:671-675(2006).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
Venter J.C.;
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Eye;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[8]
INVOLVEMENT IN SPG21.
PubMed=14564668; DOI=10.1086/379522;
Simpson M.A., Cross H., Proukakis C., Pryde A., Hershberger R.,
Chatonnet A., Patton M.A., Crosby A.H.;
"Maspardin is mutated in Mast syndrome, a complicated form of
hereditary spastic paraplegia associated with dementia.";
Am. J. Hum. Genet. 73:1147-1156(2003).
[9]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=19413330; DOI=10.1021/ac9004309;
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
Mohammed S.;
"Lys-N and trypsin cover complementary parts of the phosphoproteome in
a refined SCX-based approach.";
Anal. Chem. 81:4493-4501(2009).
[10]
INTERACTION WITH ALDH16A1.
PubMed=19184135; DOI=10.1007/s10048-009-0172-6;
Hanna M.C., Blackstone C.;
"Interaction of the SPG21 protein ACP33/maspardin with the aldehyde
dehydrogenase ALDH16A1.";
Neurogenetics 10:217-228(2009).
[11]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-304, AND IDENTIFICATION
BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma;
PubMed=20068231; DOI=10.1126/scisignal.2000475;
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
Mann M.;
"Quantitative phosphoproteomics reveals widespread full
phosphorylation site occupancy during mitosis.";
Sci. Signal. 3:RA3-RA3(2010).
[12]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=21269460; DOI=10.1186/1752-0509-5-17;
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
"Initial characterization of the human central proteome.";
BMC Syst. Biol. 5:17-17(2011).
-!- FUNCTION: May play a role as a negative regulatory factor in CD4-
dependent T-cell activation. {ECO:0000269|PubMed:11113139}.
-!- SUBUNIT: Interacts with CD4. Interacts with ALDH16A1.
{ECO:0000269|PubMed:11113139, ECO:0000269|PubMed:19184135}.
-!- INTERACTION:
Q6RW13:AGTRAP; NbExp=4; IntAct=EBI-742688, EBI-741181;
Q53H80:AKIRIN2; NbExp=5; IntAct=EBI-742688, EBI-742928;
Q15041:ARL6IP1; NbExp=5; IntAct=EBI-742688, EBI-714543;
Q8N5M1:ATPAF2; NbExp=13; IntAct=EBI-742688, EBI-1166928;
Q68D86:CCDC102B; NbExp=3; IntAct=EBI-742688, EBI-10171570;
P42772:CDKN2B; NbExp=4; IntAct=EBI-742688, EBI-711280;
Q9Y6K0:CEPT1; NbExp=4; IntAct=EBI-742688, EBI-1237183;
Q96DZ9:CMTM5; NbExp=3; IntAct=EBI-742688, EBI-2548702;
Q96JB2-2:COG3; NbExp=4; IntAct=EBI-742688, EBI-9091495;
P02489:CRYAA; NbExp=5; IntAct=EBI-742688, EBI-6875961;
Q9NRF8:CTPS2; NbExp=4; IntAct=EBI-742688, EBI-740874;
Q9NTM9:CUTC; NbExp=5; IntAct=EBI-742688, EBI-714918;
Q86UW9:DTX2; NbExp=6; IntAct=EBI-742688, EBI-740376;
Q8TDB6:DTX3L; NbExp=5; IntAct=EBI-742688, EBI-2340392;
Q5JST6:EFHC2; NbExp=5; IntAct=EBI-742688, EBI-2349927;
Q8IWE2:FAM114A1; NbExp=5; IntAct=EBI-742688, EBI-2686288;
Q9UJY4:GGA2; NbExp=3; IntAct=EBI-742688, EBI-447646;
Q08379:GOLGA2; NbExp=4; IntAct=EBI-742688, EBI-618309;
Q9UKT9:IKZF3; NbExp=5; IntAct=EBI-742688, EBI-747204;
Q0VD86:INCA1; NbExp=5; IntAct=EBI-742688, EBI-6509505;
P19012:KRT15; NbExp=3; IntAct=EBI-742688, EBI-739566;
Q9UJV3-2:MID2; NbExp=5; IntAct=EBI-742688, EBI-10172526;
Q15742:NAB2; NbExp=4; IntAct=EBI-742688, EBI-8641936;
P60891:PRPS1; NbExp=6; IntAct=EBI-742688, EBI-749195;
Q9UI14:RABAC1; NbExp=6; IntAct=EBI-742688, EBI-712367;
Q96HR9:REEP6; NbExp=3; IntAct=EBI-742688, EBI-750345;
P04271:S100B; NbExp=5; IntAct=EBI-742688, EBI-458391;
Q7Z698:SPRED2; NbExp=7; IntAct=EBI-742688, EBI-7082156;
P03410:tax (xeno); NbExp=3; IntAct=EBI-742688, EBI-9676218;
Q99081:TCF12; NbExp=3; IntAct=EBI-742688, EBI-722877;
P15884:TCF4; NbExp=3; IntAct=EBI-742688, EBI-533224;
Q8WW24:TEKT4; NbExp=4; IntAct=EBI-742688, EBI-750487;
Q92734:TFG; NbExp=5; IntAct=EBI-742688, EBI-357061;
Q13077:TRAF1; NbExp=5; IntAct=EBI-742688, EBI-359224;
Q12933:TRAF2; NbExp=6; IntAct=EBI-742688, EBI-355744;
P36406:TRIM23; NbExp=3; IntAct=EBI-742688, EBI-740098;
Q9BYV2:TRIM54; NbExp=5; IntAct=EBI-742688, EBI-2130429;
Q9C026:TRIM9; NbExp=5; IntAct=EBI-742688, EBI-720828;
Q2TAA8:TSNAXIP1; NbExp=4; IntAct=EBI-742688, EBI-6872498;
Q6PF05:TTC23L; NbExp=4; IntAct=EBI-742688, EBI-8656864;
P10599:TXN; NbExp=4; IntAct=EBI-742688, EBI-594644;
-!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
{ECO:0000269|PubMed:11113139}. Membrane
{ECO:0000269|PubMed:11113139}; Peripheral membrane protein
{ECO:0000269|PubMed:11113139}. Endosome membrane
{ECO:0000269|PubMed:11113139}; Peripheral membrane protein
{ECO:0000269|PubMed:11113139}. Golgi apparatus, trans-Golgi
network membrane {ECO:0000269|PubMed:11113139}; Peripheral
membrane protein {ECO:0000269|PubMed:11113139}. Note=Partially
localized in the cytosol but also accumulated on an intracellular
vesicular compartment. Colocalizes with CD4 on endosomal/trans-
Golgi network.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=Q9NZD8-1; Sequence=Displayed;
Name=2;
IsoId=Q9NZD8-2; Sequence=VSP_041512;
Note=No experimental confirmation available.;
-!- TISSUE SPECIFICITY: Expressed in all tissues tested, including
heart, brain, placenta, lung, liver, skeletal muscle, kidney and
pancreas. Expressed in J.CaM1.6, HuT 78 and HeLa cell lines (at
protein level). {ECO:0000269|PubMed:11113139}.
-!- DISEASE: Spastic paraplegia 21, autosomal recessive (SPG21)
[MIM:248900]: A form of spastic paraplegia, a neurodegenerative
disorder characterized by a slow, gradual, progressive weakness
and spasticity of the lower limbs. Rate of progression and the
severity of symptoms are quite variable. Initial symptoms may
include difficulty with balance, weakness and stiffness in the
legs, muscle spasms, and dragging the toes when walking. In some
forms of the disorder, bladder symptoms (such as incontinence) may
appear, or the weakness and stiffness may spread to other parts of
the body. SPG21 is associated with dementia and other central
nervous system abnormalities. Subtle childhood abnormalities may
be present, but the main features develop in early adulthood. The
disease is slowly progressive, and cerebellar and extrapyramidal
signs are also found in patients with advanced disease. Patients
have a thin corpus callosum and white-matter abnormalities.
{ECO:0000269|PubMed:14564668}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
-!- SIMILARITY: Belongs to the AB hydrolase superfamily.
{ECO:0000305}.
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EMBL; AF208861; AAF64275.1; -; mRNA.
EMBL; AF212231; AAK14917.1; -; mRNA.
EMBL; AK172849; BAD18813.1; -; mRNA.
EMBL; AK301362; BAG62906.1; -; mRNA.
EMBL; AC069368; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AC103691; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; CH471082; EAW77704.1; -; Genomic_DNA.
EMBL; BC000244; AAH00244.1; -; mRNA.
CCDS; CCDS10198.1; -. [Q9NZD8-1]
CCDS; CCDS45279.1; -. [Q9NZD8-2]
RefSeq; NP_001121361.1; NM_001127889.4. [Q9NZD8-1]
RefSeq; NP_001121362.1; NM_001127890.4. [Q9NZD8-2]
RefSeq; NP_057714.1; NM_016630.6. [Q9NZD8-1]
RefSeq; XP_005254494.1; XM_005254437.4. [Q9NZD8-1]
RefSeq; XP_016877786.1; XM_017022297.1. [Q9NZD8-1]
RefSeq; XP_016877787.1; XM_017022298.1. [Q9NZD8-1]
UniGene; Hs.242458; -.
ProteinModelPortal; Q9NZD8; -.
SMR; Q9NZD8; -.
BioGrid; 119474; 44.
IntAct; Q9NZD8; 140.
MINT; Q9NZD8; -.
STRING; 9606.ENSP00000204566; -.
ESTHER; human-SPG21; Maspardin-ACP33-SPG21_like.
iPTMnet; Q9NZD8; -.
PhosphoSitePlus; Q9NZD8; -.
DMDM; 74734726; -.
EPD; Q9NZD8; -.
MaxQB; Q9NZD8; -.
PaxDb; Q9NZD8; -.
PeptideAtlas; Q9NZD8; -.
PRIDE; Q9NZD8; -.
DNASU; 51324; -.
Ensembl; ENST00000204566; ENSP00000204566; ENSG00000090487. [Q9NZD8-1]
Ensembl; ENST00000416889; ENSP00000394846; ENSG00000090487. [Q9NZD8-2]
Ensembl; ENST00000433215; ENSP00000404111; ENSG00000090487. [Q9NZD8-1]
GeneID; 51324; -.
KEGG; hsa:51324; -.
UCSC; uc002aod.5; human. [Q9NZD8-1]
CTD; 51324; -.
DisGeNET; 51324; -.
EuPathDB; HostDB:ENSG00000090487.10; -.
GeneCards; SPG21; -.
HGNC; HGNC:20373; SPG21.
HPA; HPA040407; -.
HPA; HPA040436; -.
MalaCards; SPG21; -.
MIM; 248900; phenotype.
MIM; 608181; gene.
neXtProt; NX_Q9NZD8; -.
OpenTargets; ENSG00000090487; -.
Orphanet; 101001; Autosomal recessive spastic paraplegia type 21.
PharmGKB; PA134921126; -.
eggNOG; ENOG410IETY; Eukaryota.
eggNOG; ENOG410XPCG; LUCA.
GeneTree; ENSGT00390000007857; -.
HOGENOM; HOG000236323; -.
HOVERGEN; HBG080704; -.
InParanoid; Q9NZD8; -.
KO; K19367; -.
OMA; GIDFMVD; -.
OrthoDB; EOG091G0GY0; -.
PhylomeDB; Q9NZD8; -.
TreeFam; TF105253; -.
ChiTaRS; SPG21; human.
GeneWiki; SPG21; -.
GenomeRNAi; 51324; -.
PRO; PR:Q9NZD8; -.
Proteomes; UP000005640; Chromosome 15.
Bgee; ENSG00000090487; -.
CleanEx; HS_SPG21; -.
ExpressionAtlas; Q9NZD8; baseline and differential.
Genevisible; Q9NZD8; HS.
GO; GO:0005829; C:cytosol; IDA:UniProtKB.
GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
GO; GO:0030140; C:trans-Golgi network transport vesicle; IDA:UniProtKB.
GO; GO:0042609; F:CD4 receptor binding; IPI:UniProtKB.
GO; GO:0050851; P:antigen receptor-mediated signaling pathway; IC:UniProtKB.
Gene3D; 3.40.50.1820; -; 1.
InterPro; IPR029058; AB_hydrolase.
InterPro; IPR000073; AB_hydrolase_1.
InterPro; IPR026151; Maspardin.
PANTHER; PTHR15913; PTHR15913; 1.
Pfam; PF00561; Abhydrolase_1; 1.
SUPFAM; SSF53474; SSF53474; 1.
1: Evidence at protein level;
Alternative splicing; Complete proteome; Cytoplasm; Endosome;
Golgi apparatus; Hereditary spastic paraplegia; Membrane;
Neurodegeneration; Phosphoprotein; Reference proteome.
CHAIN 1 308 Maspardin.
/FTId=PRO_0000227980.
DOMAIN 87 159 AB hydrolase-1. {ECO:0000255}.
MOD_RES 304 304 Phosphoserine.
{ECO:0000244|PubMed:20068231}.
VAR_SEQ 76 102 Missing (in isoform 2).
{ECO:0000303|PubMed:14702039}.
/FTId=VSP_041512.
MUTAGEN 109 109 S->A: Abolishes interaction with CD4.
{ECO:0000269|PubMed:11113139}.
CONFLICT 40 40 R -> Q (in Ref. 4; BAG62906).
{ECO:0000305}.
CONFLICT 58 58 V -> A (in Ref. 4; BAG62906).
{ECO:0000305}.
CONFLICT 210 210 E -> V (in Ref. 4; BAD18813).
{ECO:0000305}.
SEQUENCE 308 AA; 34960 MW; 83C4F7B4B3EDEC7C CRC64;
MGEIKVSPDY NWFRGTVPLK KIIVDDDDSK IWSLYDAGPR SIRCPLIFLP PVSGTADVFF
RQILALTGWG YRVIALQYPV YWDHLEFCDG FRKLLDHLQL DKVHLFGASL GGFLAQKFAE
YTHKSPRVHS LILCNSFSDT SIFNQTWTAN SFWLMPAFML KKIVLGNFSS GPVDPMMADA
IDFMVDRLES LGQSELASRL TLNCQNSYVE PHKIRDIPVT IMDVFDQSAL STEAKEEMYK
LYPNARRAHL KTGGNFPYLC RSAEVNLYVQ IHLLQFHGTK YAAIDPSMVS AEELEVQKGS
LGISQEEQ


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SPG27 SPG27 Gene spastic paraplegia 27 (autosomal recessive)
SPG30 SPG30 Gene spastic paraplegia 30 (autosomal recessive)
SPG11 SPG11 Gene spastic paraplegia 11 (autosomal recessive)
SPG45 SPG45 Gene spastic paraplegia 45 (autosomal recessive)
SPG23 SPG23 Gene spastic paraplegia 23 (autosomal recessive)


 

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