SMAP1 (stromal membrane-associated protein 1)

2008-03-01   Kenji Tanabe , Shunsuke Kon , Masanobu Satake 

Department of Molecular Immunology, Institute of Development, Aging,, Cancer, Tohoku University, Sendai, Japan

Identity

HGNC
LOCATION
6q13
LOCUSID
ALIAS
SMAP-1
FUSION GENES

DNA/RNA

Description

The gene spans an approximately 190 kb region, and is composed of 11 exons.

Transcription

There is only one transcription initiation site. However, due to alternative splicing, generated are two types of transcripts, isoforms A and B. The length of each transcript is either 3344 (isoform A) or 3263 nt (isoform B). The isoform A retains, and the isoform B lacks in-flame exon 5, respectively.

Proteins

Note

SMAP1 is a member in the ArfGAP protein family.
Atlas Image
GAP, an ArfGAP domain; K-rich, a lysine-rich region; CHC, a clathrin heavy chain-binding motif; CALM, a clathrin assembly protein (CALM)-binding domain.

Description

There are two isoform proteins. One translated from an isoform A transcript is constituted by 467, and the other from an isoform B is by 440 aa residues. A protein diagram shown above represents an isoform B type.

Expression

Both isoform transcripts are detected in various human tissues. Expression appears to be almost ubiquitous.

Localisation

SMAP1 protein is detected in the cytoplasm of cells, and appears to be highly concentrated near the plasma membrane.

Function

SMAP1 functions as a GTPase-activating protein for an Arf6 GTPase. Arf6 is a Ras-related, small GTPase, and regulates clathrin-dependent and -independent endocytosis as well as actin dynamics. SMAP1 is specifically involved in the Arf6-regulated, clathrin-dependent endocytosis. This is achieved by direct interaction of SMAP1 with clathrin heavy chain.

Homology

As a highly homologous gene to SMAP1, SMAP2 is identified on 1p34.1-35.3. SMAP1 and SMAP2 constitute a small subfamily in the ArfGAP family. SMAP2 protein is specifically involved in the early endosomes to trans-Golgi network transport.

Implicated in

Entity name
t(6;11)(q13;q23) in acute leukemia.
Note
Two cases have been reported so far.
Disease
One case is from an M4 subtype of acute myeloid leukemia. A type of leukemia is not described for the other case.
Hybrid gene
One leukemia patient possessed the 46, XX, t(6;11)(q13;q23) karyotype. In this patient, reciprocal translocation occured between intron 11 of MLL gene and intron 6 of SMAP1 gene. The chimeric 5-MLL-SMAP1-3 transcript encodes a chimeric MLL-SMAP1 protein.
Fusion protein
MLL-SMAP1
Atlas Image
Schematic illustration of chimeric MLL-SMAP1 protein. The authentic MLL and SMAP1 proteins are also shown.
AT hook, an AT-hook domain; NLS, a nuclear localization signal; MT, a methyltransferase domain; PHD, a plant homeodomain zinc finger; BROMO, a bromo domain; SET, a su(var)3-9, enhancer-of-zeste, trithorax domain. GAP, an ArfGAP domain; K-rich, a lysine-rich region; CHC, a clathrin heavy chain-binding motif; CALM, a clathrin assembly protein (CALM)-binding domain.

Bibliography

Pubmed IDLast YearTitleAuthors
95932861998Ten novel 11q23 chromosomal partner sites. European 11q23 Workshop participants.Harrison CJ et al
121191102002Cloning, characterization and chromosome mapping of the human SMAP1 gene.Marcos I et al
156267572005Diagnostic tool for the identification of MLL rearrangements including unknown partner genes.Meyer C et al
165716802006SMAP2, a novel ARF GTPase-activating protein, interacts with clathrin and clathrin assembly protein and functions on the AP-1-positive early endosome/trans-Golgi network.Natsume W et al
168058232006Involvement of a novel ADP-ribosylation factor GTPase-activating protein, SMAP, in membrane trafficking: implications in cancer cell biology.Tanabe K et al
156596522005A novel GTPase-activating protein for ARF6 directly interacts with clathrin and regulates clathrin-dependent endocytosis.Tanabe K et al

Other Information

Locus ID:

NCBI: 60682
MIM: 611372
HGNC: 19651
Ensembl: ENSG00000112305

Variants:

dbSNP: 60682
ClinVar: 60682
TCGA: ENSG00000112305
COSMIC: SMAP1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000112305ENST00000316999Q8IYB5
ENSG00000112305ENST00000370452Q8IYB5
ENSG00000112305ENST00000370455Q8IYB5
ENSG00000112305ENST00000439432H0Y5G0
ENSG00000112305ENST00000445046Q5T6I8
ENSG00000112305ENST00000619054A0A087X1X9

Expression (GTEx)

0
5
10
15
20
25

Pathways

PathwaySourceExternal ID
EndocytosisKEGGko04144
EndocytosisKEGGhsa04144

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
156596522005A novel GTPase-activating protein for ARF6 directly interacts with clathrin and regulates clathrin-dependent endocytosis.26
237521922014Involvement of small ArfGAP1 (SMAP1), a novel Arf6-specific GTPase-activating protein, in microsatellite instability oncogenesis.11
252815352014The Arf GTPase-activating protein SMAP1 promotes transferrin receptor endocytosis and interacts with SMAP2.5
280116742017Rare genetic variants in SMAP1, B3GAT2, and RIMS1 contribute to pediatric venous thromboembolism.2

Citation

Kenji Tanabe ; Shunsuke Kon ; Masanobu Satake

SMAP1 (stromal membrane-associated protein 1)

Atlas Genet Cytogenet Oncol Haematol. 2008-03-01

Online version: http://atlasgeneticsoncology.org/gene/42974/smap1