Reviewed, UniProtKB/Swiss-Prot Q8WXF7 (ATLA1_HUMAN)

Names and origin

Protein names

Recommended name:
    Atlastin-1
    EC=3.6.5.-
Alternative name(s):
    Spastic paraplegia 3A
    Guanine nucleotide-binding protein 3
    GTP-binding protein 3
      Short name=GBP-3
      Short name=hGBP3
    Brain-specific GTP-binding protein

Gene names

Name:	ATL1
Synonyms:	GBP3, SPG3A

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	558 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	GTPase tethering membranes through formation of trans-homooligomer and mediating homotypic fusion of endoplasmic reticulum membranes. Functions in endoplasmic reticulum tubular network biogenesis. May also regulate Golgi biogenesis. May regulate axonal development. Ref.8 Ref.11 Ref.12 Ref.14
Subunit structure	Homooligomer. Interacts (via N-terminal region) with MAP4K4 (via CNH regulatory domain). Interacts with REEP5, RTN3 and RTN4 (via the transmembrane region). Interacts with SPAST; interaction is direct. May interact with TMED2. Ref.8 Ref.11 Ref.14 Ref.2 Ref.9 Ref.10
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein. Golgi apparatus membrane; Multi-pass membrane protein. Cell projection › axon By similarity.
Tissue specificity	Expressed predominantly in the adult and fetal central nervous system. Measurable expression in all tissues examined, although expression in adult brain is at least 50-fold higher than in other tissues. Detected predominantly in pyramidal neurons in the cerebral cortex and the hippocampus of the brain. Expressed in upper and lower motor neurons (at protein level). Ref.8 Ref.11 Ref.12
Involvement in disease	Defects in ATL1 are the cause of spastic paraplegia autosomal dominant type 3 (SPG3) [MIM:182600]; also known as Strumpell-Lorrain syndrome. Spastic paraplegia is a degenerative spinal cord disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Ref.1 Ref.15 Ref.16
Sequence similarities	Belongs to the GBP family. Atlastin subfamily.

Ontologies

Keywords
Cellular component	Cell projection Endoplasmic reticulum Golgi apparatus Membrane
Disease	Disease mutation Hereditary spastic paraplegia Neurodegeneration
Domain	Coiled coil Transmembrane
Ligand	GTP-binding Nucleotide-binding
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	axonogenesis Inferred from sequence or structural similarity. Source: UniProtKB cell death Inferred from electronic annotation. Source: UniProtKB-KW endoplasmic reticulum organization Ref.14 Inferred from direct assay. Source: UniProtKB protein homooligomerization Ref.8 Inferred from direct assay. Source: UniProtKB
Cellular component	Golgi cis cisterna Inferred from sequence or structural similarity. Source: UniProtKB axon Inferred from electronic annotation. Source: UniProtKB-SubCell endoplasmic reticulum membrane Inferred from sequence or structural similarity. Source: UniProtKB integral to membrane Ref.8 Inferred from direct assay. Source: UniProtKB microsome Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	GTP binding Inferred from sequence or structural similarity. Source: UniProtKB GTPase activity Ref.8 Inferred from direct assay. Source: UniProtKB identical protein binding Ref.8 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Reep5	Q60870	1	EBI-2410266,EBI-2410304	From a different organism.
Rtn3	Q9ES97-3	1	EBI-2410266,EBI-1487798	From a different organism.
RTN4	Q9NQC3-1	1	EBI-2410266,EBI-715972
Rtn4	Q9JK11-3	1	EBI-2410266,EBI-920002	From a different organism.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 558	558	Atlastin-1		PRO_0000190971
Regions
	Topological domain	1 – 449	449	Cytoplasmic Ref.8
	Transmembrane	450 – 470	21	Potential
	Topological domain	471	1	Lumenal Potential
	Transmembrane	472 – 492	21	Potential
	Topological domain	493 – 558	66	Cytoplasmic Ref.8
	Nucleotide binding	74 – 81	8	GTP Potential
	Nucleotide binding	146 – 150	5	GTP Potential
	Region	448 – 558	111	Sufficient for membrane association
	Coiled coil	412 – 439	28	Potential
Amino acid modifications
	Modified residue	10	1	Phosphoserine By similarity
	Modified residue	18	1	Phosphothreonine By similarity
	Modified residue	22	1	Phosphoserine Ref.13
	Modified residue	23	1	Phosphoserine Ref.13
Natural variations
	Natural variant	43	1	D → E: dbSNP rs17850684. Ref.6		VAR_058963
	Natural variant	161	1	A → P in SPG3; affects endoplasmic reticulum and Golgi morphology. Ref.11 Ref.16		VAR_019446
	Natural variant	193	1	F → C: dbSNP rs17850683. Ref.6		VAR_058964
	Natural variant	217	1	R → Q in SPG3; alters endoplasmic reticulum morphology. Ref.12 Ref.15		VAR_017146
	Natural variant	239	1	R → C in SPG3; affects endoplasmic reticulum and Golgi morphology. Ref.11 Ref.1		VAR_017147
	Natural variant	247	1	H → P in SPG3. Ref.16		VAR_019447
	Natural variant	258	1	H → R in SPG3. Ref.1		VAR_017148
	Natural variant	259	1	S → Y in SPG3. Ref.1		VAR_017149
Experimental info
	Mutagenesis	80	1	K → A: Alters endoplasmic reticulum morphogenesis. Ref.12
	Mutagenesis	151	1	F → S: Affects endoplasmic reticulum and Golgi morphology. Ref.11
	Mutagenesis	162	1	T → P: Affects endoplasmic reticulum and Golgi morphology. Ref.11
	Mutagenesis	398	1	S → Y: Affects endoplasmic reticulum and Golgi morphology. Ref.11
	Mutagenesis	495	1	R → W: Affects endoplasmic reticulum and Golgi morphology. Ref.11

Sequences

	Sequence		Length	Mass (Da)
	Q8WXF7-1 [UniParc]. Last modified March 1, 2002. Version 1. Checksum: 68A33C39DD43504C	FASTA	558	63,544
	10 20 30 40 50 60 MAKNRRDRNS WGGFSEKTYE WSSEEEEPVK KAGPVQVLIV KDDHSFELDE TALNRILLSE 70 80 90 100 110 120 AVRDKEVVAV SVAGAFRKGK SFLMDFMLRY MYNQESVDWV GDYNEPLTGF SWRGGSERET 130 140 150 160 170 180 TGIQIWSEIF LINKPDGKKV AVLLMDTQGT FDSQSTLRDS ATVFALSTMI SSIQVYNLSQ 190 200 210 220 230 240 NVQEDDLQHL QLFTEYGRLA MEETFLKPFQ SLIFLVRDWS FPYEFSYGAD GGAKFLEKRL 250 260 270 280 290 300 KVSGNQHEEL QNVRKHIHSC FTNISCFLLP HPGLKVATNP NFDGKLKEID DEFIKNLKIL 310 320 330 340 350 360 IPWLLSPESL DIKEINGNKI TCRGLVEYFK AYIKIYQGEE LPHPKSMLQA TAEANNLAAV 370 380 390 400 410 420 ATAKDTYNKK MEEICGGDKP FLAPNDLQTK HLQLKEESVK LFRGVKKMGG EEFSRRYLQQ 430 440 450 460 470 480 LESEIDELYI QYIKHNDSKN IFHAARTPAT LFVVIFITYV IAGVTGFIGL DIIASLCNMI 490 500 510 520 530 540 MGLTLITLCT WAYIRYSGEY RELGAVIDQV AAALWDQGST NEALYKLYSA AATHRHLYHQ 550 AFPTPKSEST EQSEKKKM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mutations in a newly identified GTPase gene cause autosomal dominant hereditary spastic paraplegia." Zhao X., Alvarado D., Rainier S., Lemons R., Hedera P., Weber C.H., Tukel T., Apak M., Heiman-Patterson T., Ming L., Bui M., Fink J.K. Nat. Genet. 29:326-331(2001) [PubMed: 11685207] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS SPG3 CYS-239; ARG-258 AND TYR-259.
[2]	"A novel GTP-binding protein hGBP3 interacts with NIK/HGK." Luan Z., Zhang Y., Liu A., Man Y., Cheng L., Hu G. FEBS Lett. 530:233-238(2002) [PubMed: 12387898] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH MAP4K4.
[3]	"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]. Tissue: Thalamus.
[4]	"The DNA sequence and analysis of human chromosome 14." Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J. Nature 421:601-607(2003) [PubMed: 12508121] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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], VARIANTS GLU-43 AND CYS-193. Tissue: Eye.
[7]	Mei G., Yu W., Gibbs R.A. Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 80-558. Tissue: Brain.
[8]	"Cellular localization, oligomerization, and membrane association of the hereditary spastic paraplegia 3A (SPG3A) protein atlastin." Zhu P.-P., Patterson A., Lavoie B., Stadler J., Shoeb M., Patel R., Blackstone C. J. Biol. Chem. 278:49063-49071(2003) [PubMed: 14506257] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, REGION, TOPOLOGY, SUBUNIT.
[9]	"Spastin and atlastin, two proteins mutated in autosomal-dominant hereditary spastic paraplegia, are binding partners." Sanderson C.M., Connell J.W., Edwards T.L., Bright N.A., Duley S., Thompson A., Luzio J.P., Reid E. Hum. Mol. Genet. 15:307-318(2006) [PubMed: 16339213] [Abstract] Cited for: INTERACTION WITH SPAST, SUBCELLULAR LOCATION.
[10]	"Interaction of two hereditary spastic paraplegia gene products, spastin and atlastin, suggests a common pathway for axonal maintenance." Evans K.J., Keller C., Pavur K., Glasgow K., Conn B., Lauring B.P. Proc. Natl. Acad. Sci. U.S.A. 103:10666-10671(2006) [PubMed: 16815977] [Abstract] Cited for: INTERACTION WITH SPAST.
[11]	"Mutations in the SPG3A gene encoding the GTPase atlastin interfere with vesicle trafficking in the ER/Golgi interface and Golgi morphogenesis." Namekawa M., Muriel M.-P., Janer A., Latouche M., Dauphin A., Debeir T., Martin E., Duyckaerts C., Prigent A., Depienne C., Sittler A., Brice A., Ruberg M. Mol. Cell. Neurosci. 35:1-13(2007) [PubMed: 17321752] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS SPAG3 PRO-161 AND CYS-239, MUTAGENESIS OF PHE-151; THR-162; SER-398 AND ARG-495, INTERACTION WITH TMED2, TISSUE SPECIFICITY.
[12]	"Atlastin GTPases are required for Golgi apparatus and ER morphogenesis." Rismanchi N., Soderblom C., Stadler J., Zhu P.-P., Blackstone C. Hum. Mol. Genet. 17:1591-1604(2008) [PubMed: 18270207] [Abstract] Cited for: FUNCTION, CHARACTERIZATION OF VARIANT SPAG3 GLN-217, MUTAGENESIS OF LYS-80, TISSUE SPECIFICITY.
[13]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-22 AND SER-23, MASS SPECTROMETRY. Tissue: Platelet.
[14]	"A class of dynamin-like GTPases involved in the generation of the tubular ER network." Hu J., Shibata Y., Zhu P.-P., Voss C., Rismanchi N., Prinz W.A., Rapoport T.A., Blackstone C. Cell 138:549-561(2009) [PubMed: 19665976] [Abstract] Cited for: FUNCTION, INTERACTION WITH REEP5; RTN3 AND RTN4, SUBCELLULAR LOCATION.
[15]	"Further evidence that SPG3A gene mutations cause autosomal dominant hereditary spastic paraplegia." Muglia M., Magariello A., Nicoletti G., Patitucci A., Gabriele A.L., Conforti F.L., Mazzei R., Caracciolo M., Ardito B., Lastilla M., Tedeschi G., Quattrone A. Ann. Neurol. 51:794-795(2002) [PubMed: 12112092] [Abstract] Cited for: VARIANT SPG3 GLN-217.
[16]	"Novel mutations in the Atlastin gene (SPG3A) in families with autosomal dominant hereditary spastic paraplegia and evidence for late onset forms of HSP linked to the SPG3A locus." Sauter S.M., Engel W., Neumann L.M., Kunze J., Neesen J. Hum. Mutat. 23:98-98(2004) [PubMed: 14695538] [Abstract] Cited for: VARIANTS SPG3 PRO-161 AND PRO-247.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	AY032844 mRNA. Translation: AAK51160.1. Different initiation. AF444143 mRNA. Translation: AAL37898.1. AK290185 mRNA. Translation: BAF82874.1. AL118556 Genomic DNA. No translation available. AL606834 Genomic DNA. No translation available. CH471078 Genomic DNA. Translation: EAW65706.1. BC010708 mRNA. Translation: AAH10708.2. AF131801 mRNA. Translation: AAD20047.1. Different initiation.
IPI	IPI00103530.
RefSeq	NP_001121185.1. NP_056999.2. NP_853629.2.
UniGene	Hs.584905
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8WXF7. 4 interactions.
STRING	Q8WXF7.
PTM databases
PhosphoSite	Q8WXF7.
Proteomic databases
PRIDE	Q8WXF7.
Genome annotation databases
Ensembl	ENST00000358385; ENSP00000351155; ENSG00000198513; Homo sapiens. [Genome view]
GeneID	51062.
UCSC	uc001wyf.2. human.
Organism-specific databases
CTD	51062.
GeneCards	GC14P050097.
H-InvDB	HIX0011643.
HGNC	HGNC:11231. ATL1.
MIM	182600. phenotype. 606439. gene.
Orphanet	100984. Autosomal dominant spastic paraplegia, type 3.
PharmGKB	PA36061.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q8WXF7.
OMA	ATHRHLY
Gene expression databases
ArrayExpress	Q8WXF7.
Bgee	Q8WXF7.
CleanEx	HS_ATL1.
Genevestigator	Q8WXF7.
GermOnline	ENSG00000198513. Homo sapiens.
Family and domain databases
InterPro	IPR015900. Guanylate-bd-like_C. IPR015894. Guanylate-bd_N. [Graphical view]
Pfam	PF02263. GBP. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	53649.
SOURCE	Search...

Entry information

Entry name

ATLA1_HUMAN

Accession

Primary (citable) accession number: Q8WXF7
Secondary accession number(s): A8K2C0, O95890, Q96FK0

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 24, 2003
Last sequence update:	March 1, 2002
Last modified:	November 24, 2009
This is version 72 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.