Q9NZD8 (SPG21_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Maspardin

Alternative name(s):
Acid cluster protein 33
Spastic paraplegia 21 autosomal recessive Mast syndrome protein
Spastic paraplegia 21 protein

Gene names

Name:	SPG21
Synonyms:	ACP33
ORF Names:	BM-019, GL010

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	308 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May play a role as a negative regulatory factor in CD4-dependent T-cell activation. Ref.1
Subunit structure	Interacts with CD4. Interacts with ALDH16A1. Ref.1 Ref.10
Subcellular location	Cytoplasm › cytosol. Membrane; Peripheral membrane protein. Endosome membrane; Peripheral membrane protein. Golgi apparatus › trans-Golgi network membrane; Peripheral membrane protein. Note: Partially localized in the cytosol but also accumulated on an intracellular vesicular compartment. Colocalizes with CD4 on endosomal/trans-Golgi network. Ref.1
Tissue specificity	Expressed in all tissues tested, including heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Expressed in JCaM1.6, HUT 78 and HeLa cell lines (at protein level). Ref.1
Involvement in disease	Defects in SPG21 are the cause of spastic paraplegia autosomal recessive type 21 (SPG21) [MIM:248900]; also known as Mast syndrome. Spastic paraplegia is 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. Ref.8
Sequence similarities	Belongs to the AB hydrolase superfamily.

Ontologies

Keywords
Cellular component	Cytoplasm Endosome Golgi apparatus Membrane
Coding sequence diversity	Alternative splicing
Disease	Hereditary spastic paraplegia Neurodegeneration
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	antigen receptor-mediated signaling pathway Inferred by curator Ref.1. Source: UniProtKB cell death Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Inferred from direct assay Ref.1. Source: UniProtKB endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from direct assay. Source: HPA trans-Golgi network transport vesicle Inferred from direct assay Ref.1. Source: UniProtKB
Molecular function	CD4 receptor binding Inferred from physical interaction Ref.1. Source: UniProtKB
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q9NZD8-1)

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: Q9NZD8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     76-102: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 308	308	Maspardin		PRO_0000227980
Amino acid modifications
	Modified residue	304	1	Phosphoserine Ref.9
Natural variations
	Alternative sequence	76 – 102	27	Missing in isoform 2.		VSP_041512
Experimental info
	Mutagenesis	109	1	S → A: Abolishes interaction with CD4. Ref.1
	Sequence conflict	40	1	R → Q in BAG62906. Ref.4
	Sequence conflict	58	1	V → A in BAG62906. Ref.4
	Sequence conflict	210	1	E → V in BAD18813. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 83C4F7B4B3EDEC7C	FASTA	308	34,960
	10 20 30 40 50 60 MGEIKVSPDY NWFRGTVPLK KIIVDDDDSK IWSLYDAGPR SIRCPLIFLP PVSGTADVFF 70 80 90 100 110 120 RQILALTGWG YRVIALQYPV YWDHLEFCDG FRKLLDHLQL DKVHLFGASL GGFLAQKFAE 130 140 150 160 170 180 YTHKSPRVHS LILCNSFSDT SIFNQTWTAN SFWLMPAFML KKIVLGNFSS GPVDPMMADA 190 200 210 220 230 240 IDFMVDRLES LGQSELASRL TLNCQNSYVE PHKIRDIPVT IMDVFDQSAL STEAKEEMYK 250 260 270 280 290 300 LYPNARRAHL KTGGNFPYLC RSAEVNLYVQ IHLLQFHGTK YAAIDPSMVS AEELEVQKGS LGISQEEQ
	Isoform 2 [UniParc]. Checksum: 90AD940048A485DE	FASTA	281	31,585
	10 20 30 40 50 60 MGEIKVSPDY NWFRGTVPLK KIIVDDDDSK IWSLYDAGPR SIRCPLIFLP PVSGTADVFF 70 80 90 100 110 120 RQILALTGWG YRVIAVHLFG ASLGGFLAQK FAEYTHKSPR VHSLILCNSF SDTSIFNQTW 130 140 150 160 170 180 TANSFWLMPA FMLKKIVLGN FSSGPVDPMM ADAIDFMVDR LESLGQSELA SRLTLNCQNS 190 200 210 220 230 240 YVEPHKIRDI PVTIMDVFDQ SALSTEAKEE MYKLYPNARR AHLKTGGNFP YLCRSAEVNL 250 260 270 280 YVQIHLLQFH GTKYAAIDPS MVSAEELEVQ KGSLGISQEE Q

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of ACP33 as a novel intracellular ligand of CD4." Zeitlmann L., Sirim P., Kremmer E., Kolanus W. J. Biol. Chem. 276:9123-9132(2001) [PubMed: 11113139] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INTERACTION WITH CD4, MUTAGENESIS OF SER-109.
[2]	"A novel gene expressed in human bone marrow." Zhao M., Song H., Li N., Peng Y., Han Z., Chen Z. Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Bone marrow.
[3]	"A novel gene expressed in human liver non-tumor tissues." Li Y., Wu T., Xu S., Ren S., Chen Z., Han Z. Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Liver.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." 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. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Synovium.
[5]	"Analysis of the DNA sequence and duplication history of human chromosome 15." 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. Nature 440:671-675(2006) [PubMed: 16572171] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	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 Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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 1). Tissue: Eye.
[8]	"Maspardin is mutated in Mast syndrome, a complicated form of hereditary spastic paraplegia associated with dementia." Simpson M.A., Cross H., Proukakis C., Pryde A., Hershberger R., Chatonnet A., Patton M.A., Crosby A.H. Am. J. Hum. Genet. 73:1147-1156(2003) [PubMed: 14564668] [Abstract] Cited for: INVOLVEMENT IN SPG21.
[9]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-304, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[10]	"Interaction of the SPG21 protein ACP33/maspardin with the aldehyde dehydrogenase ALDH16A1." Hanna M.C., Blackstone C. Neurogenetics 10:217-228(2009) [PubMed: 19184135] [Abstract] Cited for: INTERACTION WITH ALDH16A1.
[11]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF208861 mRNA. Translation: AAF64275.1. AF212231 mRNA. Translation: AAK14917.1. AK172849 mRNA. Translation: BAD18813.1. AK301362 mRNA. Translation: BAG62906.1. AC069368 Genomic DNA. No translation available. AC103691 Genomic DNA. No translation available. CH471082 Genomic DNA. Translation: EAW77704.1. BC000244 mRNA. Translation: AAH00244.1.
IPI	IPI00010248. IPI00895915.
RefSeq	NP_001121361.1. NM_001127889.1. NP_001121362.1. NM_001127890.1. NP_057714.1. NM_016630.3.
UniGene	Hs.242458.
3D structure databases
ProteinModelPortal	Q9NZD8.
SMR	Q9NZD8. Positions 37-139.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NZD8. 11 interactions.
MINT	MINT-1443026.
STRING	Q9NZD8.
PTM databases
PhosphoSite	Q9NZD8.
Polymorphism databases
DMDM	74734726.
Proteomic databases
PRIDE	Q9NZD8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000204566; ENSP00000204566; ENSG00000090487. ENST00000433215; ENSP00000404111; ENSG00000090487.
GeneID	51324.
KEGG	hsa:51324.
UCSC	uc002aod.1. human.
Organism-specific databases
CTD	51324.
GeneCards	GC15M065255.
H-InvDB	HIX0012344.
HGNC	HGNC:20373. SPG21.
HPA	HPA040436.
MIM	248900. phenotype. 608181. gene.
neXtProt	NX_Q9NZD8.
Orphanet	101001. Autosomal recessive spastic paraplegia type 21.
PharmGKB	PA134921126.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG13789.
GeneTree	ENSGT00390000007857.
HOGENOM	HBG446721.
HOVERGEN	HBG080704.
InParanoid	Q9NZD8.
OMA	EVNLYIQ.
OrthoDB	EOG4640CF.
PhylomeDB	Q9NZD8.
Gene expression databases
ArrayExpress	Q9NZD8.
Bgee	Q9NZD8.
CleanEx	HS_SPG21.
Genevestigator	Q9NZD8.
GermOnline	ENSG00000090487. Homo sapiens.
Family and domain databases
ProtoNet	Search...
Other
NextBio	54722.
SOURCE	Search...

Entry information

Entry name

SPG21_HUMAN

Accession

Primary (citable) accession number: Q9NZD8
Secondary accession number(s): B4DW44, Q6ZMB6

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 21, 2006
Last sequence update:	October 1, 2000
Last modified:	January 25, 2012
This is version 88 of the entry and version 1 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.