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Aliases for A2ML1 Gene

Aliases for A2ML1 Gene

  • Alpha-2-Macroglobulin Like 1 2 3 5
  • C3 And PZP-Like, Alpha-2-Macroglobulin Domain Containing 9 2 3
  • CPAMD9 3 4
  • C3 And PZP-Like Alpha-2-Macroglobulin Domain-Containing Protein 9 4
  • Alpha-2-Macroglobulin-Like Protein 1 3
  • P170 3

External Ids for A2ML1 Gene

Previous HGNC Symbols for A2ML1 Gene

  • CPAMD9

Previous GeneCards Identifiers for A2ML1 Gene

  • GC12P008867
  • GC12P008975
  • GC12P008757

Summaries for A2ML1 Gene

Entrez Gene Summary for A2ML1 Gene

  • This gene encodes a member of the alpha-macroglobulin superfamily. The encoded protein is thought to be an N-glycosylated monomeric protein that acts as an inhibitor of several proteases. It has been shown to form covalent interactions with proteases, and has been reported as the p170 antigen recognized by autoantibodies in the autoimmune disease paraneoplastic pemphigus (PNP; PMID:20805888). Mutations in these gene have also been associated with some cases of Noonan syndrome (NS; PMID:24939586) as well as some cases of otitis media (PMID:26121085). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]

GeneCards Summary for A2ML1 Gene

A2ML1 (Alpha-2-Macroglobulin Like 1) is a Protein Coding gene. Diseases associated with A2ML1 include Noonan Syndrome 1 and Otitis Media. GO annotations related to this gene include serine-type endopeptidase inhibitor activity and peptidase inhibitor activity. An important paralog of this gene is A2M.

UniProtKB/Swiss-Prot for A2ML1 Gene

  • Is able to inhibit all four classes of proteinases by a unique trapping mechanism. This protein has a peptide stretch, called the bait region which contains specific cleavage sites for different proteinases. When a proteinase cleaves the bait region, a conformational change is induced in the protein which traps the proteinase. The entrapped enzyme remains active against low molecular weight substrates (activity against high molecular weight substrates is greatly reduced). Following cleavage in the bait region a thioester bond is hydrolyzed and mediates the covalent binding of the protein to the proteinase (By similarity). Displays inhibitory activity against chymotrypsin, papain, thermolysin, subtilisin A and, to a lesser extent, elastase but not trypsin. May play an important role during desquamation by inhibiting extracellular proteases.

No data available for CIViC summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for A2ML1 Gene

Genomics for A2ML1 Gene

Regulatory Elements for A2ML1 Gene

Enhancers for A2ML1 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH12G008909 1.8 FANTOM5 Ensembl ENCODE dbSUPER 9.7 +90.4 90390 7.1 HDGF HNRNPUL1 PKNOX1 ARNT ZFP64 ARID4B SIN3A DMAP1 FEZF1 ZNF2 PHC1 KLRG1 M6PR ENSG00000255829 MFAP5 FAM66C A2ML1 A2ML1-AS2 A2ML1-AS1
GH12G008617 1.4 FANTOM5 Ensembl ENCODE 10.2 -203.6 -203579 2.7 PKNOX1 BMI1 ZBTB40 GTF3C2 GATA2 RELB FOS IKZF2 CEBPB JUNB CLEC4E LOC642846 DDX12P M6PR LINC00612 ENSG00000255753 A2ML1-AS2 A2ML1 CLEC6A CLEC4A
GH12G008796 1.1 ENCODE 12.3 -25.2 -25244 0.6 PKNOX1 CREB3L1 ARID4B SIN3A DMAP1 FEZF1 ZNF2 YY1 ZNF143 ZNF207 A2ML1-AS2 A2ML1 ENSG00000249790
GH12G008643 1.1 Ensembl ENCODE 10.2 -177.4 -177364 2.4 TBP PKNOX1 TBL1XR1 BACH1 ASH2L BMI1 RELA ARID3A ELK1 POLR2A CLEC4E A2ML1 A2ML1-AS2 RNU6-275P RIMKLB HADHAP2 MFAP5
GH12G008609 1 Ensembl ENCODE 9.5 -213.1 -213072 0.8 CTCF WRNIP1 BMI1 RAD21 CBX5 POLR2A EED SCRT2 ZNF143 SMC3 CLEC4E A2ML1 A2ML1-AS2 KLRB1 AICDA ENSG00000252727
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around A2ML1 on UCSC Golden Path with GeneCards custom track

Genomic Location for A2ML1 Gene

Chromosome:
12
Start:
8,822,472 bp from pter
End:
8,887,001 bp from pter
Size:
64,530 bases
Orientation:
Plus strand

Genomic View for A2ML1 Gene

Genes around A2ML1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
A2ML1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for A2ML1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for A2ML1 Gene

Proteins for A2ML1 Gene

  • Protein details for A2ML1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    A8K2U0-A2ML1_HUMAN
    Recommended name:
    Alpha-2-macroglobulin-like protein 1
    Protein Accession:
    A8K2U0
    Secondary Accessions:
    • B5MDD1
    • B7Z7V4
    • D3DUV3
    • F5H2Z2
    • Q2M224
    • Q6ZW52
    • Q6ZW53
    • Q8N1M4
    • Q96LQ8

    Protein attributes for A2ML1 Gene

    Size:
    1454 amino acids
    Molecular mass:
    161107 Da
    Quaternary structure:
    • Monomer.
    SequenceCaution:
    • Sequence=BAB71612.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAC04793.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAC85653.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAC85654.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Alternative splice isoforms for A2ML1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for A2ML1 Gene

Post-translational modifications for A2ML1 Gene

  • Glycosylation at posLast=120120, posLast=281281, posLast=409409, posLast=857857, and posLast=10201020
  • Modification sites at PhosphoSitePlus

Antibody Products

  • Abcam antibodies for A2ML1
  • Cloud-Clone Corp. Antibodies for A2ML1
  • Santa Cruz Biotechnology (SCBT) Antibodies for A2ML1

No data available for DME Specific Peptides for A2ML1 Gene

Domains & Families for A2ML1 Gene

Suggested Antigen Peptide Sequences for A2ML1 Gene

Graphical View of Domain Structure for InterPro Entry

A8K2U0

UniProtKB/Swiss-Prot:

A2ML1_HUMAN :
  • Belongs to the protease inhibitor I39 (alpha-2-macroglobulin) family.
Family:
  • Belongs to the protease inhibitor I39 (alpha-2-macroglobulin) family.
genes like me logo Genes that share domains with A2ML1: view

Function for A2ML1 Gene

Molecular function for A2ML1 Gene

UniProtKB/Swiss-Prot Function:
Is able to inhibit all four classes of proteinases by a unique trapping mechanism. This protein has a peptide stretch, called the bait region which contains specific cleavage sites for different proteinases. When a proteinase cleaves the bait region, a conformational change is induced in the protein which traps the proteinase. The entrapped enzyme remains active against low molecular weight substrates (activity against high molecular weight substrates is greatly reduced). Following cleavage in the bait region a thioester bond is hydrolyzed and mediates the covalent binding of the protein to the proteinase (By similarity). Displays inhibitory activity against chymotrypsin, papain, thermolysin, subtilisin A and, to a lesser extent, elastase but not trypsin. May play an important role during desquamation by inhibiting extracellular proteases.

Gene Ontology (GO) - Molecular Function for A2ML1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004867 serine-type endopeptidase inhibitor activity IEA --
GO:0030414 peptidase inhibitor activity IEA,IDA 16298998
genes like me logo Genes that share ontologies with A2ML1: view
genes like me logo Genes that share phenotypes with A2ML1: view

Human Phenotype Ontology for A2ML1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

CRISPR Products

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targets and HOMER Transcription for A2ML1 Gene

Localization for A2ML1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for A2ML1 Gene

Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for A2ML1 gene
Compartment Confidence
extracellular 5
plasma membrane 2
cytoskeleton 1
nucleus 1
endoplasmic reticulum 1
cytosol 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for A2ML1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005615 extracellular space IEA,IDA 16298998
GO:0070062 extracellular exosome IDA 19199708
genes like me logo Genes that share ontologies with A2ML1: view

Pathways & Interactions for A2ML1 Gene

SuperPathways for A2ML1 Gene

No Data Available

Gene Ontology (GO) - Biological Process for A2ML1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0010466 negative regulation of peptidase activity IEA --
GO:0010951 negative regulation of endopeptidase activity IEA --
GO:0052548 regulation of endopeptidase activity IDA 16298998
genes like me logo Genes that share ontologies with A2ML1: view

No data available for Pathways by source and SIGNOR curated interactions for A2ML1 Gene

Transcripts for A2ML1 Gene

Unigene Clusters for A2ML1 Gene

Alpha-2-macroglobulin-like 1:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for A2ML1 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13a · 13b ^ 14a · 14b ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20 ^ 21 ^ 22 ^ 23 ^ 24 ^
SP1: -
SP2: -
SP3:
SP4:
SP5:
SP6: -
SP7:

ExUns: 25 ^ 26 ^ 27 ^ 28 ^ 29 ^ 30 ^ 31 ^ 32 ^ 33 ^ 34 ^ 35 ^ 36 ^ 37 ^ 38 ^ 39 ^ 40
SP1: -
SP2:
SP3: -
SP4:
SP5:
SP6:
SP7:

Relevant External Links for A2ML1 Gene

GeneLoc Exon Structure for
A2ML1
ECgene alternative splicing isoforms for
A2ML1

Expression for A2ML1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for A2ML1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for A2ML1 Gene

This gene is overexpressed in Esophagus - Mucosa (x27.2), Vagina (x8.8), Cervix - Ectocervix (x5.3), and Minor Salivary Gland (x5.2).

Protein differential expression in normal tissues from HIPED for A2ML1 Gene

This gene is overexpressed in Saliva (26.2), Cervix (21.0), and Esophagus (9.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for A2ML1 Gene



Protein tissue co-expression partners for A2ML1 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of A2ML1 Gene:

A2ML1

SOURCE GeneReport for Unigene cluster for A2ML1 Gene:

Hs.620532

mRNA Expression by UniProt/SwissProt for A2ML1 Gene:

A8K2U0-A2ML1_HUMAN
Tissue specificity: In the epidermis, expressed predominantly in the granular layer at the apical edge of keratinocytes (at protein level). Also detected in placenta, testis and thymus but not in epithelia of kidney, lung, small intestine or colon.

Evidence on tissue expression from TISSUES for A2ML1 Gene

  • Skin(3)

Phenotype-based relationships between genes and organs from Gene ORGANizer for A2ML1 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • immune
  • integumentary
  • lymphatic
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
  • skeleton
Organs:
Head and neck:
  • brain
  • cheek
  • chin
  • cranial nerve
  • ear
  • eye
  • eyelid
  • face
  • forehead
  • head
  • jaw
  • lip
  • mandible
  • maxilla
  • mouth
  • neck
  • nose
  • outer ear
  • scalp
  • skull
  • tooth
Thorax:
  • aorta
  • breast
  • chest wall
  • clavicle
  • heart
  • heart valve
  • lung
  • rib
  • rib cage
  • scapula
  • sternum
Abdomen:
  • abdominal wall
  • liver
  • spleen
Pelvis:
  • pelvis
  • placenta
  • testicle
  • uterus
Limb:
  • ankle
  • arm
  • digit
  • elbow
  • femur
  • fibula
  • finger
  • foot
  • forearm
  • hand
  • hip
  • humerus
  • knee
  • lower limb
  • nail
  • radius
  • shin
  • shoulder
  • thigh
  • tibia
  • toe
  • ulna
  • upper limb
  • wrist
General:
  • blood
  • blood vessel
  • bone marrow
  • coagulation system
  • hair
  • lymph node
  • lymph vessel
  • peripheral nervous system
  • skin
  • spinal column
  • spinal cord
  • vertebrae
  • white blood cell
genes like me logo Genes that share expression patterns with A2ML1: view

Primer Products

Orthologs for A2ML1 Gene

This gene was present in the common ancestor of chordates.

Orthologs for A2ML1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia A2ML1 34 35
  • 99.15 (n)
dog
(Canis familiaris)
Mammalia A2ML1 34 35
  • 85.88 (n)
cow
(Bos Taurus)
Mammalia A2ML1 34 35
  • 82.83 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia -- 35
  • 37 (a)
OneToMany
mouse
(Mus musculus)
Mammalia BC048546 35
  • 33 (a)
OneToOne
chicken
(Gallus gallus)
Aves A2ML4 34
  • 53.88 (n)
A2ML1 35
  • 42 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia -- 35
  • 39 (a)
OneToMany
-- 35
  • 38 (a)
OneToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia mug1 34
  • 54.42 (n)
Species where no ortholog for A2ML1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • oppossum (Monodelphis domestica)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rat (Rattus norvegicus)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)
  • zebrafish (Danio rerio)

Evolution for A2ML1 Gene

ENSEMBL:
Gene Tree for A2ML1 (if available)
TreeFam:
Gene Tree for A2ML1 (if available)

Paralogs for A2ML1 Gene

Paralogs for A2ML1 Gene

(4) SIMAP similar genes for A2ML1 Gene using alignment to 7 proteins:

genes like me logo Genes that share paralogs with A2ML1: view

Variants for A2ML1 Gene

Sequence variations from dbSNP and Humsavar for A2ML1 Gene

SNP ID Clin Chr 12 pos Sequence Context AA Info Type
rs863224951 Pathogenic 8,852,231(+) TAAAT(-/GGCTAAAT)CGCAT nc-transcript-variant, reference, frameshift-variant
rs138301233 Likely benign 8,848,913(+) TTTCC(A/G)GGTAG nc-transcript-variant, reference, missense
rs200188816 Likely benign 8,852,206(+) CCTCC(A/G)TAGGT intron-variant
rs200763256 Likely benign 8,852,306(+) AAACC(C/T)ACCAC nc-transcript-variant, reference, missense
rs200964353 Likely benign 8,860,885(+) GGGTG(A/G)TGTTG nc-transcript-variant, reference, missense

Structural Variations from Database of Genomic Variants (DGV) for A2ML1 Gene

Variant ID Type Subtype PubMed ID
dgv28e180 CNV deletion 20482838
dgv42n73 CNV deletion 24416366
dgv760n106 CNV deletion 24896259
esv1448345 CNV deletion 17803354
esv2603013 CNV deletion 19546169
esv2661025 CNV deletion 23128226
esv2745509 CNV deletion 23290073
esv2745510 CNV deletion 23290073
esv29462 CNV loss 19812545
esv3254162 CNV deletion 24192839
esv3548721 CNV deletion 23714750
esv3628482 CNV loss 21293372
esv3628483 CNV loss 21293372
esv3628484 CNV loss 21293372
nsv1049949 CNV gain 25217958
nsv1051530 CNV gain 25217958
nsv1068606 CNV deletion 25765185
nsv1127246 CNV deletion 24896259
nsv1152492 CNV deletion 26484159
nsv442254 CNV loss 18776908
nsv512254 CNV loss 21212237
nsv516260 CNV loss 19592680
nsv521922 CNV loss 19592680
nsv53517 CNV deletion 16902084

Variation tolerance for A2ML1 Gene

Residual Variation Intolerance Score: 98.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 18.32; 98.53% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for A2ML1 Gene

Human Gene Mutation Database (HGMD)
A2ML1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
A2ML1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for A2ML1 Gene

Disorders for A2ML1 Gene

MalaCards: The human disease database

(6) MalaCards diseases for A2ML1 Gene - From: Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
noonan syndrome 1
  • ns1
otitis media
  • otitis media, susceptibility to
paraneoplastic pemphigus
pemphigus
middle ear disease
  • disorder of middle ear
- elite association - COSMIC cancer census association via MalaCards
Search A2ML1 in MalaCards View complete list of genes associated with diseases

Relevant External Links for A2ML1

Genetic Association Database (GAD)
A2ML1
Human Genome Epidemiology (HuGE) Navigator
A2ML1
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
A2ML1
genes like me logo Genes that share disorders with A2ML1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for A2ML1 Gene

Publications for A2ML1 Gene

  1. A novel protease inhibitor of the alpha2-macroglobulin family expressed in the human epidermis. (PMID: 16298998) Galliano M.-F. … Guerrin M. (J. Biol. Chem. 2006) 2 3 4 64
  2. Transcriptomic and genetic studies identify IL-33 as a candidate gene for Alzheimer's disease. (PMID: 19204726) Chapuis J. … Lambert J.C. (Mol. Psychiatry 2009) 3 46 64
  3. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T. … Sugano S. (Nat. Genet. 2004) 3 4 64
  4. Middle ear microbiome differences in indigenous Filipinos with chronic otitis media due to a duplication in the A2ML1 gene. (PMID: 27799062) Santos-Cortez R.L. … Chiong C.M. (Infect Dis Poverty 2016) 3 64
  5. Proteomic analyses reveal distinct chromatin-associated and soluble transcription factor complexes. (PMID: 25609649) Li X. … Chen J. (Mol. Syst. Biol. 2015) 3 64

Products for A2ML1 Gene

Sources for A2ML1 Gene

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