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P17900 (SAP3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 149. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ganglioside GM2 activator
Alternative name(s):
Cerebroside sulfate activator protein
GM2-AP
Sphingolipid activator protein 3
Short name=SAP-3

Cleaved into the following chain:

  1. Ganglioside GM2 activator isoform short
Gene names
Name:GM2A
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length193 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

The large binding pocket can accommodate several single chain phospholipids and fatty acids, GM2A also exhibits some calcium-independent phospholipase activity By similarity. Binds gangliosides and stimulates ganglioside GM2 degradation. It stimulates only the breakdown of ganglioside GM2 and glycolipid GA2 by beta-hexosaminidase A. It extracts single GM2 molecules from membranes and presents them in soluble form to beta-hexosaminidase A for cleavage of N-acetyl-D-galactosamine and conversion to GM3.

Subcellular location

Lysosome.

Post-translational modification

The serines in positions 32 and 33 are absent in 80% of the sequenced protein.

Involvement in disease

GM2-gangliosidosis AB (GM2GAB) [MIM:272750]: An autosomal recessive lysosomal storage disease marked by the accumulation of GM2 gangliosides in the neuronal cells. It is characterized by GM2 gangliosides accumulation in the presence of both normal hexosaminidase A and B.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13 Ref.14 Ref.15

Sequence caution

The sequence CAA43408.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

The sequence CAA43994.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Biological processLipid metabolism
Sphingolipid metabolism
   Cellular componentLysosome
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Gangliosidosis
   DomainSignal
   Molecular functionHydrolase
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processganglioside catabolic process

Inferred from electronic annotation. Source: Ensembl

glycosphingolipid metabolic process

Traceable author statement. Source: Reactome

learning or memory

Inferred from electronic annotation. Source: Ensembl

lipid storage

Inferred from electronic annotation. Source: Ensembl

neuromuscular process controlling balance

Inferred from electronic annotation. Source: Ensembl

oligosaccharide catabolic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of hydrolase activity

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

sphingolipid metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentapical cortex

Inferred from electronic annotation. Source: Ensembl

cytoplasmic side of plasma membrane

Inferred from electronic annotation. Source: Ensembl

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 23376485. Source: UniProt

lysosomal lumen

Traceable author statement. Source: Reactome

mitochondrion

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionbeta-N-acetylhexosaminidase activity

Inferred from electronic annotation. Source: Ensembl

lipid transporter activity

Inferred from electronic annotation. Source: Ensembl

phospholipase activator activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Potential
Propeptide24 – 318
PRO_0000031639
Chain32 – 193162Ganglioside GM2 activator
PRO_0000031640
Chain34 – 193160Ganglioside GM2 activator isoform short
PRO_0000031641

Amino acid modifications

Glycosylation631N-linked (GlcNAc...)
Disulfide bond39 ↔ 183
Disulfide bond99 ↔ 106
Disulfide bond112 ↔ 138
Disulfide bond125 ↔ 136

Natural variations

Natural variant191A → T. Ref.2 Ref.4 Ref.5 Ref.7 Ref.10
Corresponds to variant rs1048719 [ dbSNP | Ensembl ].
VAR_013830
Natural variant591I → V. Ref.1 Ref.2 Ref.4 Ref.7 Ref.9 Ref.10
Corresponds to variant rs153477 [ dbSNP | Ensembl ].
VAR_036892
Natural variant691M → V. Ref.1 Ref.2 Ref.4 Ref.5 Ref.7 Ref.9 Ref.10
Corresponds to variant rs153478 [ dbSNP | Ensembl ].
VAR_036893
Natural variant881Missing in GM2GAB. Ref.15
VAR_011697
Natural variant1381C → R in GM2GAB. Ref.13
VAR_006947
Natural variant1691R → P in GM2GAB. Ref.14
VAR_011698

Experimental info

Sequence conflict391C → R in BAG35396. Ref.5

Secondary structure

............................. 193
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P17900 [UniParc].

Last modified November 13, 2007. Version 4.
Checksum: 4EB1119945365F7E

FASTA19320,838
        10         20         30         40         50         60 
MQSLMQAPLL IALGLLLAAP AQAHLKKPSQ LSSFSWDNCD EGKDPAVIRS LTLEPDPIIV 

        70         80         90        100        110        120 
PGNVTLSVMG STSVPLSSPL KVDLVLEKEV AGLWIKIPCT DYIGSCTFEH FCDVLDMLIP 

       130        140        150        160        170        180 
TGEPCPEPLR TYGLPCHCPF KEGTYSLPKS EFVVPDLELP SWLTTGNYRI ESVLSSSGKR 

       190 
LGCIKIAASL KGI 

« Hide

References

« Hide 'large scale' references
[1]"Isolation and expression of a full-length cDNA encoding the human G-M2 activator protein."
Xie B., McInnes B., Neote K., Lamhonwah A.-M., Mahuran D.
Biochem. Biophys. Res. Commun. 177:1217-1223(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS VAL-59 AND VAL-69.
[2]"Characterization of full-length cDNAs and the gene coding for the human GM2 activator protein."
Klima H., Tanaka A., Schnabel D., Nakano T., Schroeder M., Suzuki K., Sandhoff K.
FEBS Lett. 289:260-264(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS THR-19; VAL-59 AND VAL-69.
[3]"Evidence for two cDNAs encoding human GM2-activator protein."
Nagarajan S., Chen H.C., Li S.C., Li Y.T., Lockyer J.
Biochem. J. 282:807-813(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Placenta.
[4]"Identification of a processed pseudogene related to the functional gene encoding the GM2 activator protein: localization of the pseudogene to human chromosome 3 and the functional gene to human chromosome 5."
Xie B., Kennedy J.L., McInnes B., Auger D., Mahuran D.J.
Genomics 14:796-798(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS THR-19; VAL-59 AND VAL-69.
[5]"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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS THR-19 AND VAL-69.
Tissue: Substantia nigra.
[6]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"Structure of the GM2A gene: identification of an exon 2 nonsense mutation and a naturally occurring transcript with an in-frame deletion of exon 2."
Chen B., Rigat B., Curry C., Mahuran D.J.
Am. J. Hum. Genet. 65:77-87(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-19; VAL-59 AND VAL-69.
[8]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. expand/collapse author list , 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].
[9]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS VAL-59 AND VAL-69.
Tissue: Uterus.
[10]"Isolation of a cDNA encoding the human GM2 activator protein."
Schroeder M., Klima H., Nakano T., Kwon H., Quintern L.E., Gaertner S., Suzuki K., Sandhoff K.
FEBS Lett. 251:197-200(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 15-193, VARIANTS THR-19; VAL-59 AND VAL-69.
[11]"The complete amino-acid sequences of human ganglioside GM2 activator protein and cerebroside sulfate activator protein."
Furst W., Schubert J., Machleidt W., Meyer H.E., Sandhoff K.
Eur. J. Biochem. 192:709-714(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 32-193.
Tissue: Kidney.
[12]"Crystal structure of human GM2-activator protein with a novel beta-cup topology."
Wright C.S., Li S.-C., Rastinejad F.
J. Mol. Biol. 304:411-422(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
[13]"A mutation in the gene of a glycolipid-binding protein (GM2 activator) that causes GM2-gangliosidosis variant AB."
Schroeder M., Schnabel D., Suzuki K., Sandhoff K.
FEBS Lett. 290:1-3(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GM2GAB ARG-138.
[14]"Molecular genetics of GM2-gangliosidosis AB variant: a novel mutation and expression in BHK cells."
Schroder M., Schnabel D., Hurwitz R., Young E., Suzuki K., Sandhoff K.
Hum. Genet. 92:437-440(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GM2GAB PRO-169.
[15]"Molecular analysis of a GM2-activator deficiency in two patients with GM2-gangliosidosis AB variant."
Schepers U., Glombitza G., Lemm T., Hoffmann A., Chabas A., Ozand P., Sandhoff K.
Am. J. Hum. Genet. 59:1048-1056(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GM2GAB LYS-88 DEL.
+Additional computationally mapped references.

Web resources

GM2Adb

GM2A mutation database

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M76477 mRNA. Translation: AAA35907.1.
X62078 mRNA. Translation: CAA43993.1.
X62078 mRNA. Translation: CAA43994.1. Different initiation.
X61095 mRNA. Translation: CAA43408.1. Different initiation.
L01439 mRNA. Translation: AAA52767.1.
AF124719, AF124717, AF124718 Genomic DNA. Translation: AAD25741.1.
AK312494 mRNA. Translation: BAG35396.1.
AC008385 Genomic DNA. No translation available.
CH471062 Genomic DNA. Translation: EAW61680.1.
CH471062 Genomic DNA. Translation: EAW61681.1.
BC009273 mRNA. Translation: AAH09273.1.
X16087 mRNA. Translation: CAA34215.1.
CCDSCCDS4313.1.
PIRI54178.
S13195.
S22411.
RefSeqNP_000396.2. NM_000405.4.
UniGeneHs.483873.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1G13X-ray2.00A/B/C32-193[»]
1PU5X-ray1.90A/B/C32-193[»]
1PUBX-ray2.51A32-193[»]
1TJJX-ray2.00A/B/C32-193[»]
2AF9X-ray2.00A32-193[»]
2AG2X-ray2.00A/B/C32-193[»]
2AG4X-ray1.80A/B32-193[»]
2AG9X-ray2.20A/B32-193[»]
ProteinModelPortalP17900.
SMRP17900. Positions 32-193.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109022. 3 interactions.
IntActP17900. 1 interaction.
STRING9606.ENSP00000349687.

Polymorphism databases

DMDM160331912.

Proteomic databases

MaxQBP17900.
PaxDbP17900.
PRIDEP17900.

Protocols and materials databases

DNASU2760.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000357164; ENSP00000349687; ENSG00000196743.
GeneID2760.
KEGGhsa:2760.
UCSCuc003ltr.4. human.

Organism-specific databases

CTD2760.
GeneCardsGC05P150612.
H-InvDBHIX0005327.
HGNCHGNC:4367. GM2A.
HPAHPA008063.
MIM272750. phenotype.
613109. gene.
neXtProtNX_P17900.
Orphanet309246. GM2-gangliosidosis, AB variant.
PharmGKBPA28752.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG47814.
HOGENOMHOG000031350.
HOVERGENHBG000260.
InParanoidP17900.
KOK12383.
OMAFSWENCD.
PhylomeDBP17900.
TreeFamTF353575.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressP17900.
BgeeP17900.
CleanExHS_GM2A.
GenevestigatorP17900.

Family and domain databases

InterProIPR028996. GM2-AP.
IPR003172. ML_dom.
[Graphical view]
PANTHERPTHR17357. PTHR17357. 1 hit.
PfamPF02221. E1_DerP2_DerF2. 1 hit.
[Graphical view]
SMARTSM00737. ML. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSGM2A. human.
EvolutionaryTraceP17900.
GeneWikiGM2A.
GenomeRNAi2760.
NextBio10860.
PROP17900.
SOURCESearch...

Entry information

Entry nameSAP3_HUMAN
AccessionPrimary (citable) accession number: P17900
Secondary accession number(s): B2R699 expand/collapse secondary AC list , D3DQH6, Q14426, Q14428, Q6LBL5
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: November 13, 2007
Last modified: July 9, 2014
This is version 149 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM