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AAMP (angio-associated, migratory cell protein)

Written2011-09Marie E Beckner
Department of Pathology, Louisiana State University Health Sciences Center - Shreveport, USA

(Note : for Links provided by Atlas : click)

Identity

Other alias
HGNC (Hugo) AAMP
LocusID (NCBI) 14
Atlas_Id 533
Location 2q35  [Link to chromosome band 2q35]
Location_base_pair Starts at 218264129 and ends at 218270209 bp from pter ( according to hg19-Feb_2009)  [Mapping AAMP.png]
Fusion genes
(updated 2016)
AAMP (2q35) / ARPC2 (2q35)AAMP (2q35) / MARCH4 (2q35)ERCC3 (2q14.3) / AAMP (2q35)

DNA/RNA

Note The NCBI RefSeq (Aug-2011) consensus sequence for AAMP differs at the 5-prime end from the manually sequenced version published initially. A diagram of the NCBI ReqfSeq (Aug-2011) version for rAAMP is shown here.
 
  rAAMP encoding a 434 aa protein in normal cells. The codon for AAMP's initiating methionine, the stop codon, and the poly-adenylation sites are indicated at 85-87, 1387-1389, and 1774-1779, respectively. Untranslated sequence is indicated in the hatched regions at the 3' end of exon 1 and the 5' end of exon 11. The poly-adenosine tail, 1793-1859, is included.
Description The AAMP gene (NCBI RefSeq, Aug-2011) encompasses 6042 bp; 11 exons.
Transcription 1859 bp mRNA (NCBI RefSeq, Aug-2011).
Pseudogene None are known.

Protein

Note The NCBI RefSeq (Aug-2011) consensus sequence for AAMP (434 aa) is shorter than initially reported (452 aa, 52 kDa).
 
  The bulk of AAMP's sequence is constituted by WD40 domains that are known to commonly fold to form a platform for active portions of a protein. Thus the stretch of contiguous glutamic acid residues should be available for interactions with other proteins. Also, binding of other proteins may occur to regions of these repeats. The WD40 repeats are known to mediate aggregation of subunits to form complex, multi-protein structures. Two immunoglobulin-type domains are designated by pairs of cysteines, (C96 - C130) and (C216 - C265). AAMP may play a negative role in Nod2-mediated NF-kB activation via a physical interaction in the region indicated. A physical interaction between AAMP and thromboxane A2 receptors (TPalpha and TPbeta) has been suggested to occur via multiple sites with no particular domain identified in localization studies.
Description 434 amino acids, 49 kDa protein (NCBI RefSeq, Aug-2011).
Expression AAMP is widely expressed among many types of mammalian cells and has been conserved in evolution.
Localisation AAMP was initially detected in the cytoplasm of many types of nucleated mammalian cells and was strongly expressed in endothelial cells, cytotrophoblasts, and poorly differentiated colon adenocarcinoma cells in lymphatics. AAMP has been observed at the luminal edges of endometrial cells and has been found in the extracellular environment of vascular-associated mesenchymal cells.
Function Functional studies and associations suggest roles for AAMP in angiogenesis, including endothelial tube formation, migration of endothelial and smooth muscle cells, neointima formation, and thromboxane A receptor interactions. In immune cells AAMP may be involved in the regulation of NF-kappaB activation mediated by Nod2. The common occurrence of WD40 domains in signaling proteins supports a signaling function as a possibility for AAMP. The epitope, ESESES, that AAMP shares with alpha-actinin and a smaller protein specific for fast skeletal muscle, suggests that it may have cytoskeletal interactions. Although AAMP was described as having heparin-binding capacity in melanoma cells, the NCBI RefSeq (Aug-2011) version of AAMP does not include the heparin-binding sequence (encodes RRLRR) in the coding sequence. The RefSeq version of AAMP identifies the initiating methionine (85-87) as being 3' to the sequence encoding RRLRR (70-84).
Homology AAMP shares homology with the other members of the WD40 repeat superfamily. Several of the WD40 repeat proteins also contain an amino terminal run of glutamic acid residues outside of their WD repeats. The two immunoglobulin-type domains in AAMP resemble those of the immunoglobulin superfamily members, including domains of NCAM, DCC, NgCAM, etc.

Mutations

Note AAMP was initially cloned and sequenced as a transcript for a 452 aa, 52 kDa protein. It was obtained from an expression library derived from melanoma cells of a brain metastasis. However the amino terminus was missing from the library clone. AAMP's amino terminus was determined by 5' RACE from human brain mRNA. Two versions were obtained and both differed from the NCBI RefSeq (Aug-2011) version of AAMP. The one shown contains coding sequence upstream from the initiating methionine in the RefSeq version. This alternative form may represent a fusion protein due to an in-frame insertion or a chromosomal rearrangement. AAMP potentially gains heparin binding functionality when sequence upstream from AUG at nucleotides 85-87 is preceded by an alternative initiating methionine codon that enables translation of the codons for RRLRR.
 
  rAAMP encoding a 452 aa protein (alternative form). An alternative AUG was detected when the amino terminus was manually sequenced with 5' RACE using brain mRNA. It is shown in red. Its upstream location permits 17 codons to encode amino acids, including 5 codons for RRLRR, a heparin-binding site. Sequences of the alternative forms described for AAMP are the same as the NCBI RefSeq (Aug-2011) version of AAMP for nucleotides 34-1792 and the first 25 adenosines in the poly-A tail.
Germinal None are known.
Somatic Chromosomal rearrangements or insertions that place an initiating methionine codon further upstream than the methionine at 85-87 permit AAMP to gain heparin binding function when nucleotides 70-84 are translated.

Implicated in

Note
  
Entity Gastrointestinal stromal tumor (GIST)
Note GISTs are the most common mesenchymal tumors of the digestive tract and are believed to arise from the interstitial cells of Cajal. They respond to imitanib, a tyrosine kinase inhibitor, which is also used to treat myeloid leukemia. Expression of AAMP was found to be increased in GISTs with mutated KIT. Expression of AAMP among various soft tissue sarcomas and normal tissues was highest in the GISTs. AAMP ranks high among the upregulated genes in GISTs.
  
  
Entity Myeloid leukemia (chronic (CML) form
Note AAMP is expressed in myeloid leukemia cell lines and its expression is repressed by imitanib (mainline treatment drug for chronic myeloid leukemia), deferasirox (iron chelator that decreases cell proliferation), and anisomycin, an inducer of apoptosis.
  
  
Entity Myeloid leukemia acute (AML) form
Note AAMP is expressed in myeloid leukemia cell lines and its expression is repressed by imitanib (mainline treatment drug for chronic myeloid leukemia), deferasirox (iron chelator that decreases cell proliferation), and anisomycin, an inducer of apoptosis.
  
  
Entity Lymphoma (B and T cell origins, non-Hodgkins and Hodgkins types)
Note AAMP is expressed in activated T lymphocytes, monocytes, and lymphoma cells. Compared to normal B cells, AAMP is increased in non-Hodgkins lymphomas and in classical Hodgkins lymphoma.
  
  
Entity Melanoma (melanocyte origin, usually skin)
Note In lysates of a melanoma cell line obtained from a brain metastasis, the size of the protein that reacted with anti-AAMP was 52 kDa, thus corresponding to the size predicted by an alternative transcript. The alternative version of AAMP could have resulted from a chromosomal rearrangement due to 2q35 breakage in the amino terminal region of AAMP. Placement of AUG at the 5' end of nucleotide 34 to serve as an alternative initiating methionine codon permits expression of the heparin binding site, RRLRR (nucleotides 70-84 in the NCBI ReqSeq (Aug-2011) version of AAMP) as a gain of function.
  
  
Entity Breast cancer (ductal cell origin most common)
Note Expression profiling of human breast cancer cells versus mammary epithelial cells revealed higher expression of AAMP in the tumor cells. AAMP expression is higher in ductal carcinoma in situ (DCIS) with necrosis compared to DCIS without necrosis. However, expression profiling of DCIS and invasive ductal carcinoma (IDC) paired specimens from the same patients revealed decreased AAMP in IDC. AAMP expression may be relevant for the development of DCIS.
  
  
Entity Glial brain tumors (neuroectodermal cell origin)
Note When compared with normal, glioblastomas (Grade IV astrocytomas) and oligodendrogliomas (Grades II - III) demonstrated slightly elevated levels of AAMP expression. Expression of AAMP was increased in drug resistant glioblastomas, primary and recurrent.
  
  
Entity Colon neoplasia (benign adenomas and carcinoma arise from glandular cells of the mucosa in the gastrointestinal tract)
Note Expression profiling of normal mucosa and colorectal adenomas from the same patients showed that AAMP was slightly increased in the adenomas. However, a small dataset of colon tubular adenomas harboring focal adenocarcinomas, with microdissections of paired samples from each, showed that AAMP may become decreased in the incipient carcinomas. Although AAMP may play a role in the development of colonic neoplasia, it has not been shown to be positively involved in progression of adenomas to malignancy.
  
  
Entity Epidermoid carcinoma (keratinocyte origin if arises in skin)
Note AAMP is expressed in squamous carcinoma cell lines. In one cell line studied with PTEN knocked down, the expression of AAMP also fell significantly. Also, for tumors from a radiosensitive cell line, AAMP expression fell significantly in radioresistant tumors derived from the sensitive cell line.
  
  
Entity Cervical cancer (usually arises from squamous type cells)
Note In a study of cervical carcinoma HeLa cells treated with epidermal growth factor in a time course, expression of AAMP was increased at 2-8 hours.
  
  
Entity Ovarian cancer (often arises from serous cells)
Note Cancer cells prepared from primary cultures of ovarian papillary serous adenocarcinomas revealed increased AAMP expression in 2 of 3 carboplatin resistant tumors whereas none of the tumors from 3 patients with sensitivity to carboplatin demonstrated comparable levels.
  
  
Entity Papillary thyroid carcinoma (arises from cells in thyroid follicles)
Note Analysis of papillary thyroid carcinoma tumors matched with normal thyroid from nine patients found that AAMP expression fell slightly in the tumors.
  
  
Entity Pulmonary carcinoma (multiple types of cells can be the origin)
Note AAMP's expression in a lung alveolar adenocarcinoma cell line was down-regulated by TGF-beta that was added to induce an epithelial-mesenchymal transition.
  
  
Entity Chromosomal rearrangements at 2q35
Note The location of AAMP at 2q35 imparts susceptibility to chromosomal rearrangements involving the terminal region of chromosome 2's long arm, q. Terminal regions are more susceptible to rearrangements than the midregions of chromosomes. Fusion transcripts and proteins result from breakage and rearrangements that occur in unstable genomes. Several fusion proteins resulting from rearrangements involving other genes in this region have been reported in association with malignancy. Rearrangements that place in-frame coding sequence upstream from nucleotides 70-84 in the NCBI ReqSeq (Aug-2011) version of AAMP permit a gain of function, i.e. heparin-binding, to occur.
  

Breakpoints

Note Clones obtained in 5' RACE studies of AAMP's amino terminus revealed a breakpoint between nucleotides 30 and 31 with inclusion of upstream sequence that did not match the NCBI RefSeq (Aug-2011) form of AAMP and also another version with a breakpoint between nucleotides 33 and 34 and introduction of an alternative AUG. A schematic of the latter alternative form was shown earlier. The location of AAMP at 2q35 places it in a region near the end region of the chromosomal arm where breakpoints are more likely compared to the centromeric region. Importantly, in the sequences of the consensus and variant forms, in-frame codons are present for a heparin binding region that can be translated if an alternative initiating methionine is introduced upstream.

Bibliography

Analysis of gene expression in ductal carcinoma in situ of the breast.
Adeyinka A, Emberley E, Niu Y, Snell L, Murphy LC, Sowter H, Wykoff CC, Harris AL, Watson PH.
Clin Cancer Res. 2002 Dec;8(12):3788-95.
PMID 12473591
 
Gastrointestinal stromal tumors with KIT mutations exhibit a remarkably homogeneous gene expression profile.
Allander SV, Nupponen NN, Ringner M, Hostetter G, Maher GW, Goldberger N, Chen Y, Carpten J, Elkahloun AG, Meltzer PS.
Cancer Res. 2001 Dec 15;61(24):8624-8.
PMID 11751374
 
Extracellular angio-associated migratory cell protein plays a positive role in angiogenesis and is regulated by astrocytes in coculture.
Beckner ME, Jagannathan S, Peterson VA.
Microvasc Res. 2002 May;63(3):259-69.
PMID 11969303
 
A function for AAMP in Nod2-mediated NF-kappaB activation.
Bielig H, Zurek B, Kutsch A, Menning M, Philpott DJ, Sansonetti PJ, Kufer TA.
Mol Immunol. 2009 Aug;46(13):2647-54. Epub 2009 Jun 16.
PMID 19535145
 
Characterization of differential gene expression in quiescent and invasive human arterial smooth muscle cells.
Blindt R, Vogt F, Lamby D, Zeiffer U, Krott N, Hilger-Eversheim K, Hanrath P, vom Dahl J, Bosserhoff AK.
J Vasc Res. 2002 Jul-Aug;39(4):340-52.
PMID 12187124
 
Diagnostic and prognostic gene expression signatures in 177 soft tissue sarcomas: hypoxia-induced transcription profile signifies metastatic potential.
Francis P, Namlos HM, Muller C, Eden P, Fernebro J, Berner JM, Bjerkehagen B, Akerman M, Bendahl PO, Isinger A, Rydholm A, Myklebost O, Nilbert M.
BMC Genomics. 2007 Mar 14;8:73.
PMID 17359542
 
Angio-associated migratory cell protein and smooth muscle cell migration in development of restenosis and atherosclerosis.
Holvoet P, Sinnaeve P.
J Am Coll Cardiol. 2008 Jul 22;52(4):312-4.
PMID 18634988
 
Interaction of angio-associated migratory cell protein with the TPalpha and TPbeta isoforms of the human thromboxane Av(2) receptor.
Reid HM, Wikstrom K, Kavanagh DJ, Mulvaney EP, Kinsella BT.
Cell Signal. 2011 Apr;23(4):700-17. Epub 2010 Dec 21.
PMID 21172430
 
Blockade of angio-associated migratory cell protein inhibits smooth muscle cell migration and neointima formation in accelerated atherosclerosis.
Vogt F, Zernecke A, Beckner M, Krott N, Bosserhoff AK, Hoffmann R, Zandvoort MA, Jahnke T, Kelm M, Weber C, Blindt R.
J Am Coll Cardiol. 2008 Jul 22;52(4):302-11.
PMID 18634987
 

Citation

This paper should be referenced as such :
Beckner, ME
AAMP (angio-associated, migratory cell protein)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(2):111-114.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/AAMPID533ch2q35.html


External links

Nomenclature
HGNC (Hugo)AAMP   18
Cards
AtlasAAMPID533ch2q35
Entrez_Gene (NCBI)AAMP  14  angio associated migratory cell protein
Aliases
GeneCards (Weizmann)AAMP
Ensembl hg19 (Hinxton)ENSG00000127837 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000127837 [Gene_View]  chr2:218264129-218270209 [Contig_View]  AAMP [Vega]
ICGC DataPortalENSG00000127837
TCGA cBioPortalAAMP
AceView (NCBI)AAMP
Genatlas (Paris)AAMP
WikiGenes14
SOURCE (Princeton)AAMP
Genetics Home Reference (NIH)AAMP
Genomic and cartography
GoldenPath hg38 (UCSC)AAMP  -     chr2:218264129-218270209 -  2q35   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)AAMP  -     2q35   [Description]    (hg19-Feb_2009)
EnsemblAAMP - 2q35 [CytoView hg19]  AAMP - 2q35 [CytoView hg38]
Mapping of homologs : NCBIAAMP [Mapview hg19]  AAMP [Mapview hg38]
OMIM603488   
Gene and transcription
Genbank (Entrez)AB209790 AK131047 AK225078 BC008809 BC014122
RefSeq transcript (Entrez)NM_001087 NM_001302545
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)AAMP
Cluster EST : UnigeneHs.83347 [ NCBI ]
CGAP (NCI)Hs.83347
Alternative Splicing GalleryENSG00000127837
Gene ExpressionAAMP [ NCBI-GEO ]   AAMP [ EBI - ARRAY_EXPRESS ]   AAMP [ SEEK ]   AAMP [ MEM ]
Gene Expression Viewer (FireBrowse)AAMP [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)14
GTEX Portal (Tissue expression)AAMP
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ13685   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ13685  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ13685
Splice isoforms : SwissVarQ13685
PhosPhoSitePlusQ13685
Domaine pattern : Prosite (Expaxy)WD_REPEATS_1 (PS00678)    WD_REPEATS_2 (PS50082)    WD_REPEATS_REGION (PS50294)   
Domains : Interpro (EBI)WD40/YVTN_repeat-like_dom    WD40_repeat    WD40_repeat_CS    WD40_repeat_dom   
Domain families : Pfam (Sanger)WD40 (PF00400)   
Domain families : Pfam (NCBI)pfam00400   
Domain families : Smart (EMBL)WD40 (SM00320)  
Conserved Domain (NCBI)AAMP
DMDM Disease mutations14
Blocks (Seattle)AAMP
SuperfamilyQ13685
Human Protein AtlasENSG00000127837
Peptide AtlasQ13685
HPRD04600
IPIIPI00014481   IPI00927731   IPI00924477   IPI00924705   IPI00925243   
Protein Interaction databases
DIP (DOE-UCLA)Q13685
IntAct (EBI)Q13685
FunCoupENSG00000127837
BioGRIDAAMP
STRING (EMBL)AAMP
ZODIACAAMP
Ontologies - Pathways
QuickGOQ13685
Ontology : AmiGOangiogenesis  cytosol  plasma membrane  heparin binding  cell surface  positive regulation of endothelial cell migration  smooth muscle cell migration  microtubule cytoskeleton  cell differentiation  preribosome, large subunit precursor  ribosomal large subunit biogenesis  intercellular bridge  unfolded protein binding  
Ontology : EGO-EBIangiogenesis  cytosol  plasma membrane  heparin binding  cell surface  positive regulation of endothelial cell migration  smooth muscle cell migration  microtubule cytoskeleton  cell differentiation  preribosome, large subunit precursor  ribosomal large subunit biogenesis  intercellular bridge  unfolded protein binding  
NDEx NetworkAAMP
Atlas of Cancer Signalling NetworkAAMP
Wikipedia pathwaysAAMP
Orthology - Evolution
OrthoDB14
GeneTree (enSembl)ENSG00000127837
Phylogenetic Trees/Animal Genes : TreeFamAAMP
HOVERGENQ13685
HOGENOMQ13685
Homologs : HomoloGeneAAMP
Homology/Alignments : Family Browser (UCSC)AAMP
Gene fusions - Rearrangements
Fusion: TCGAAAMP 2q35 MARCH4 2q35 LUSC
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerAAMP [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)AAMP
dbVarAAMP
ClinVarAAMP
1000_GenomesAAMP 
Exome Variant ServerAAMP
ExAC (Exome Aggregation Consortium)AAMP (select the gene name)
Genetic variants : HAPMAP14
Genomic Variants (DGV)AAMP [DGVbeta]
DECIPHERAAMP [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisAAMP 
Mutations
ICGC Data PortalAAMP 
TCGA Data PortalAAMP 
Broad Tumor PortalAAMP
OASIS PortalAAMP [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICAAMP  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDAAMP
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch AAMP
DgiDB (Drug Gene Interaction Database)AAMP
DoCM (Curated mutations)AAMP (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)AAMP (select a term)
intoGenAAMP
NCG5 (London)AAMP
Cancer3DAAMP(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM603488   
Orphanet
MedgenAAMP
Genetic Testing Registry AAMP
NextProtQ13685 [Medical]
TSGene14
GENETestsAAMP
Target ValidationAAMP
Huge Navigator AAMP [HugePedia]
snp3D : Map Gene to Disease14
BioCentury BCIQAAMP
ClinGenAAMP
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD14
Chemical/Pharm GKB GenePA24365
Clinical trialAAMP
Miscellaneous
canSAR (ICR)AAMP (select the gene name)
Other databaseGEO Profiles
Probes
Litterature
PubMed30 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineAAMP
EVEXAAMP
GoPubMedAAMP
iHOPAAMP
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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