P17900 (SAP3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ganglioside GM2 activator

Alternative name(s):
Cerebroside sulfate activator protein
GM2-AP
Shingolipid activator protein 3
Short name=SAP-3

Cleaved into the following chain:

1. Ganglioside GM2 activator isoform short

Gene names

Name:

GM2A

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	193 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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	Defects in GM2A are the cause of GM2-gangliosidosis type AB (GM2GAB) [MIM:272750]; also known as Tay-Sachs disease AB variant. GM2-gangliosidosis is an autosomal recessive lysosomal storage disease marked by the accumulation of GM2 gangliosides in the neuronal cells. GM2GAB is characterized by GM2 gangliosides accumulation in the presence of both hexosaminidase A and B. Ref.11 Ref.12 Ref.13
Sequence caution	The sequence CAA43408.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Lipid metabolism Sphingolipid metabolism
Cellular component	Lysosome
Coding sequence diversity	Polymorphism
Disease	Disease mutation Gangliosidosis
Domain	Signal
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Cellular component	lysosome Non-traceable author statement. Source: UniProtKB nucleolus Inferred from direct assay. Source: HPA
Molecular function	sphingolipid activator protein activity Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 23

23

Potential

Propeptide

24 – 31

8

PRO_0000031639

Chain

32 – 193

162

Ganglioside GM2 activator

PRO_0000031640

Chain

34 – 193

160

Ganglioside GM2 activator isoform short

PRO_0000031641

Amino acid modifications

Glycosylation

63

1

N-linked (GlcNAc...)

Disulfide bond

39 ↔ 183

Disulfide bond

99 ↔ 106

Disulfide bond

112 ↔ 138

Disulfide bond

125 ↔ 136

Natural variations

Natural variant

19

1

A → T. Ref.2 Ref.4 Ref.5 Ref.8
Corresponds to variant rs1048719 [ dbSNP | Ensembl ].

VAR_013830

Natural variant

59

1

I → V. Ref.1 Ref.2 Ref.4 Ref.5 Ref.7 Ref.8
Corresponds to variant rs153477 [ dbSNP | Ensembl ].

VAR_036892

Natural variant

69

1

M → V. Ref.1 Ref.2 Ref.4 Ref.5 Ref.7 Ref.8
Corresponds to variant rs153478 [ dbSNP | Ensembl ].

VAR_036893

Natural variant

88

1

Missing in GM2GAB.

VAR_011697

Natural variant

138

1

C → R in GM2GAB. Ref.11

VAR_006947

Natural variant

169

1

R → P in GM2GAB. Ref.12

VAR_011698

Secondary structure

1

.

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193

Helix Strand Turn

Details...

Beta strand

35 – 40

6

Turn

41 – 43

3

Beta strand

45 – 74

30

Beta strand

81 – 90

10

Beta strand

93 – 97

5

Beta strand

103 – 105

3

Helix

111 – 118

8

Turn

127 – 133

7

Beta strand

142 – 153

12

Helix

161 – 164

4

Beta strand

166 – 176

11

Beta strand

179 – 192

14

Sequences

	Sequence		Length	Mass (Da)
	P17900 [UniParc]. Last modified November 13, 2007. Version 4. Checksum: 4EB1119945365F7E	FASTA	193	20,838
	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

References

	« Hide 'large scale' referencesShow '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: 2059210] [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: 1915857] [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: 1554364] [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: 1427911] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS THR-19; VAL-59 AND VAL-69.
[5]	"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: 10364519] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-19; VAL-59 AND VAL-69.
[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 (SEP-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], VARIANTS VAL-59 AND VAL-69. Tissue: Uterus.
[8]	"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: 2753159] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 15-193, VARIANTS THR-19; VAL-59 AND VAL-69.
[9]	"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: 2209618] [Abstract] Cited for: PROTEIN SEQUENCE OF 32-193. Tissue: Kidney.
[10]	"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: 11090283] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
[11]	"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: 1915858] [Abstract] Cited for: VARIANT GM2GAB ARG-138.
[12]	"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: 8244332] [Abstract] Cited for: VARIANT GM2GAB PRO-169.
[13]	"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: 8900233] [Abstract] Cited for: VARIANT GM2GAB LYS-88 DEL.
+	Additional computationally mapped references.

Web resources

GM2Adb

GM2A mutation database

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M76477 mRNA. Translation: AAA35907.1.
X62078 mRNA. Translation: CAA43993.1.
X61095 mRNA. Translation: CAA43408.1. Different initiation.
L01439 mRNA. Translation: AAA52767.1.
AF124719, AF124717, AF124718 Genomic DNA. Translation: AAD25741.1.
CH471062 Genomic DNA. Translation: EAW61680.1.
CH471062 Genomic DNA. Translation: EAW61681.1.
BC009273 mRNA. Translation: AAH09273.1.
X16087 mRNA. Translation: CAA34215.1.

IPI

IPI00018236.

PIR

I54178.
S13195.
S22411.

RefSeq

NP_000396.2. NM_000405.4.

UniGene

Hs.483873.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1G13	X-ray	2.00	A/B/C	32-193	[»]
1PU5	X-ray	1.90	A/B/C	32-193	[»]
1PUB	X-ray	2.51	A	32-193	[»]
1TJJ	X-ray	2.00	A/B/C	32-192	[»]
2AF9	X-ray	2.00	A	32-193	[»]
2AG2	X-ray	2.00	A/B/C	32-193	[»]
2AG4	X-ray	1.80	A/B	32-193	[»]
2AG9	X-ray	2.20	A/B	32-193	[»]

ProteinModelPortal

P17900.

SMR

P17900. Positions 32-193.

ModBase

Search...

Protein-protein interaction databases

IntAct

P17900. 1 interaction.

STRING

P17900.

Polymorphism databases

DMDM

160331912.

Proteomic databases

PRIDE

P17900.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000357164; ENSP00000349687; ENSG00000196743.

GeneID

2760.

KEGG

hsa:2760.

UCSC

uc003ltr.2. human.

Organism-specific databases

CTD

2760.

GeneCards

GC05P150612.

HGNC

HGNC:4367. GM2A.

HPA

HPA008063.

MIM

272750. phenotype.
613109. gene.

neXtProt

NX_P17900.

Orphanet

845. Tay-Sachs disease.

PharmGKB

PA28752.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG18882.

HOGENOM

HBG268089.

HOVERGEN

HBG000260.

InParanoid

P17900.

OMA

HCPFKEG.

OrthoDB

EOG48PMMH.

PhylomeDB

P17900.

Gene expression databases

ArrayExpress

P17900.

Bgee

P17900.

CleanEx

HS_GM2A.

Genevestigator

P17900.

GermOnline

ENSG00000196743. Homo sapiens.

Family and domain databases

InterPro

IPR003172. MD-2_lipid-recog.
[Graphical view]

KO

K12383.

SMART

SM00737. ML. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

10860.

SOURCE

Search...

Entry information

Entry name

SAP3_HUMAN

Accession

Primary (citable) accession number: P17900
Secondary accession number(s): D3DQH6, Q14426, Q14428

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	November 13, 2007
Last modified:	January 25, 2012
This is version 125 of the entry and version 4 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.