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A2ML1 Gene

protein-coding   GIFtS: 44

GC12P008867
alpha-2-macroglobulin-like 1
(Previous names: C3 and PZP-like, alpha-2-macroglobulin domain containing 9 )
Symbol approved by the HUGO Gene Nomenclature Committee (HGNC) database
(Previous symbol: CPAMD9)
Services    
(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc , and/or 7Ensembl, 8miRBase)
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Aliases
CPAMD9 2, 3
DKFZp686C1729 2
DKFZp686D2011 2
DKFZp686G1812 2
DKFZp686L1821 2
DKFZp686O1010 2
FLJ16045 2
FLJ25179 1, 2
FLJ39129 2
FLJ41597 2
FLJ41598 2
FLJ41607 2
OTTHUMP00000158614 2
Descriptions
C3 and PZP-like alpha-2-macroglobulin domain-containing
protein 9 3
C3 and PZP-like, alpha-2-macroglobulin domain containing 9 1, 2
alpha-2-macroglobulin-like 1 2
External Ids
HGNC: 233361
Entrez Gene: 1445682
UniProtKB: A8K2U03
Ensembl: ENSG000001665357
Search outside databases for aliases for A2ML1 gene

(According to Entrez Gene, Wikipedia's Gene Wiki,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

EntrezGene summary for A2ML1:
The alpha-macroglobulin (AM) superfamily of proteins contains both complement components and
protease inhibitors, including A2M (MIM 103950) and A2ML1. AM proteins display a unique trap
mechanism of inhibition, by which the AM inhibitor undergoes a major conformational change upon
its cleavage by a protease, thus trapping the protease and blocking it from subsequent substrate
binding (Galliano et al., 2006 [PubMed 16298998]).[supplied by OMIM]

UniProtKB/Swiss-Prot: A2ML1_HUMAN, A8K2U0
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

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 36),
and/or miRBase,
Genomic Views according to UCSC and Ensembl, Transcription factor binding sites according to SABiosciences)
About This Section

Genomic View:
UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 12p13.31   Ensembl cytogenetic band:  12p13.31   HGNC cytogenetic band: 12p13

A2ML1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)

GeneLoc gene densities for chromosome 12         GeneLoc Exon Structure

GeneLoc location for GC12P008867:     (about GC identifiers)

Start:
8,866,417 bp from pter
End:
8,920,646 bp from pter
Size:
54,230 bases
Orientation:
plus strand
RefSeq DNA sequence:
NC_000012.10  NT_009714.16  
(According to 1UniProtKB, and/or Ensembl, Phosphorylation sites according to 2Phosphosite, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from Invitrogen, Millipore, Sigma-Aldrich, R&D Systems, Enzo Life Sciences, Abnova, OriGene and/or, Abcam,
Biochemical Assays by Invitrogen, Millipore, R&D Systems, Cell Signaling Technology, and/or Enzo Life Sciences, Ontologies according to Gene Ontology Consortium 01 Apr 2009 and Entrez Gene, Antibodies by Invitrogen, Millipore, Sigma-Aldrich, R&D Systems, Cell Signaling Technology, Abcam, Abnova, and/or Novus Biologicals)
About This Section

UniProtKB/Swiss-Prot: A2ML1_HUMAN, A8K2U0 (See protein sequence)
Recommended Name: Alpha-2-macroglobulin-like protein 1 precursor  
Size: 1454 amino acids; 161104 Da
Subunit: Monomer
Subcellular location: Secreted
Developmental stage: Up-regulated during keratinocyte differentiation
Secondary accessions: Q2M224 Q6ZW52 Q6ZW53 Q8N1M4 Q96LQ8

REFSEQ proteins: NP_653271.2  

ENSEMBL proteins: 
ENSP00000299698 ENSP00000382304 ENSP00000311179 


Human Recombinant Proteins 
Browse Drug Discovery Central at Invitrogen for human recombinant proteins
Browse Purified and Recombinant Proteins at Millipore
Browse Human Recombinant Proteins at Sigma-Aldrich  
Browse R&D Systems for human recombinant proteins
Browse recombinant and purified proteins available from Enzo Life Sciences
Recombinant Proteins from Abcam (A2ML1)
Human Recombinant Proteins from Abnova (A2ML1)
                Browse Origene for full length recombinant human proteins expressed in human HEK293 cells 

2 Gene Ontology (GO) cellular component terms (links to tree view):

GO IDQualified GO termEvidencePubMed IDs
GO:0005576 extracellular region IEA--
GO:0005615 extracellular space IDA16298998
About this table

Antibodies for A2ML1: 
Browse Antibodies Central at Invitrogen
Browse Millipore's Extensive Line of Mono- and Polyclonal Antibodies
Browse Antibodies at Sigma-Aldrich
Browse R&D Systems for Antibodies
Antibodies from Abcam (A2ML1), each with their AbpromiseSM
Monoclonal and Polyclonal Antibodies from Abnova (A2ML1)
Novus Biologicals Antibodies for A2ML1

Assays for A2ML1: 
Browse Invitrogen for biochemical assays
Browse Kits and Assays available from Millipore
Browse R&D Systems for biochemical assays
Browse biochemical assays available from Enzo Life Sciences

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

5/7 InterPro domains/families (see all 7 ):
 IPR002890 A2M_N
 IPR011625 A2M_N_2
 IPR009048 A-macroglobulin_rcpt-bd
 IPR019742 MacrogloblnA2_CS
 IPR001599 MacrogloblnA2


   GeneDecks  A2ML1 for the domains selected above  
About GeneDecksing

Graphical View of Domain Structure for InterPro Entry A8K2U0

ProtoNet protein and cluster: A8K2U0

UniProtKB/Swiss-Prot: A2ML1_HUMAN, A8K2U0
Similarity: Belongs to the protease inhibitor I39 (alpha-2-macroglobulin) family

(According to MGI Jun 06 2009, UniProtKB, IUBMB,and/or Genatlas,
shRNA from OriGene, Sigma-Aldrich, RNAi from Sigma-Aldrich,
RNAi Products, Clones, and Q-PCR Products from Invitrogen, Millipore, OriGene, and/or Abnova, siRNAs from Applied Biosystems, SYBR primers from OriGene, Cell-based Assays from Millipore, Ontologies according to Gene Ontology Consortium 01 Apr 2009 via Entrez Gene.)
About This Section

Inhib.
RNA:
Invitrogen RNAi Products for gene knock-down (A2ML1)
Browse for Gene Knock-down Tools from Millipore
Browse Abnova for Chimera RNAi Products
              OriGene 29mer shRNA kit in GFP-retroviral vector: NM_144670

              Applied Biosystems Silencer® siRNAs for A2ML1

              Sigma-Aldrich siRNA for A2ML1  
                     Sigma-Aldrich shRNA for A2ML1  
                     Explore Sigma-Aldrich super-pooled esiRNAs  

Clones:Invitrogen Clones for A2ML1
Browse Clones for the Expression of Recombinant Proteins Available from Millipore
              OriGene GFP tagged cDNA clone in CMV expression vector: NM_144670
                                 Myc/DDK tagged cDNA clone in CMV expression vector: NM_144670
                                 untagged cDNA clone in CMV expression vector: NM_144670 

Primers: Browse Quantitative PCR Central at Invitrogen for Q-PCR LUX™ Primers
              OriGene genome-wide validated SYBR primer pairs: NM_144670

UniProtKB/Swiss-Prot: A2ML1_HUMAN, A8K2U0
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

2 Gene Ontology (GO) molecular function terms (links to tree view):

GO IDQualified GO termEvidencePubMed IDs
GO:0004867 serine-type endopeptidase inhibitor activity IEA--
GO:0005515 protein binding IEA--
About this table

(Pathways according to Invitrogen (maps by GeneGo), Millipore, Cell Signaling Technology, Sigma-Aldrich, KEGG and/or UniProtKB,
Sets of similar genes according to GeneDecks, Proteins Network according to SABiosciences, Interactions according to 1UniProtKB, 2MINT, and/or 3STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2009 via Entrez Gene.)
About This Section


  --

1 Gene Ontology (GO) biological process term (links to tree view):

GO IDQualified GO termEvidencePubMed IDs
GO:0052548 regulation of endopeptidase activity IDA16298998
About this table
(Chemical Compounds according to UniProtKB, Enzo Life Sciences, Sigma-Aldrich, Tocris Bioscience, and/or Novoseek and Drugs according to Enzo Life Sciences and/or PharmGKB)
About This Section

Browse drugs & compounds from Enzo Life Sciences
Browse Small Molecules at Sigma-Aldrich

Browse Tocris compounds for A2ML1

(GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 219 Homo sapiens; Jun 2 2009) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView,
non coding RNAs according to RNAdb,
ESTs according to GeneTide,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from Invitrogen, Millipore, and/or Abnova,
siRNAs from Applied Biosystems, Sigma-Aldrich,
shRNA from Sigma-Aldrich, OriGene,
Tagged/untagged cDNA clones from OriGene,
Expression Assays from Applied Biosystems)
About This Section

Inhib.
RNA:
Invitrogen RNAi Products for gene knock-down (A2ML1)
Browse for Gene Knock-down Tools from Millipore
Browse Abnova for Chimera RNAi Products
              OriGene 29mer shRNA kit in GFP-retroviral vector: NM_144670

              Sigma-Aldrich siRNA for A2ML1  
                     Sigma-Aldrich shRNA for A2ML1  
                     Explore Sigma-Aldrich super-pooled esiRNAs  

Applied Biosystems Silencer® siRNAs: 

NM_144670  

REFSEQ mRNAs for A2ML1 gene: 

NM_144670.3   

Applied Biosystems TaqMan ® Gene Expression Assays: 

NM_144670  

              OriGene GFP tagged cDNA clone in CMV expression vector: NM_144670
                                 Myc/DDK tagged cDNA clone in CMV expression vector: NM_144670
                                 untagged cDNA clone in CMV expression vector: NM_144670 

Additional cDNA sequence: 

AK057908.1 AK096448.1 AK123591.1 AK123592.1 AK123601.1 AK290355.1 AK302555.1 AL832139.1 
AL832750.1 AL833479.1 BC093840.1 BC112131.1 BX647674.1 BX648231.1 

6 DOTS entries:

DT.421412  DT.97822102  DT.95220277  DT.101981889  DT.121190124  DT.91979364 

24/46 AceView cDNA sequences (see all 46 ):

NM_144670 AK057908 AK096448 AK123592 BX504185 BX647674 BU101570 BX648231 
AL700698 AK123601 AK123591 AK122624 AL832139 BU101571 AW862460 AW860672 
BE151370 BX504184 AA316097 AL833479 AL832750 BF354179 AA307331 BE144308 

highest scoring ESTs for A2ML1:

AK057908 AK096448 AK123601 AL832139 AL833479 BC093840 BF350613 BF827869 BG680886 BX647674 

Unigene Cluster for A2ML1:

Alpha-2-macroglobulin-like 1
Hs.620532  [show with all ESTs]
Unigene Representative Sequence: AL832139


GeneLoc Exon Structure

5/7 Alternative Splicing Database (ASD) splice patterns (SP) for A2ML1 (see all 7 )

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:                                                                                                                                                            

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

About this scheme

ECgene alternative splicing isoforms for A2ML1

3 Ensembl transcripts including schematic representations:
ENST00000299698  ENST00000399370  ENST00000311537  
(Experimental results according to 1GeneNote and GNF BioGPS,
probe sets-to-genes annotations according to 2GeneAnnot , 3GeneTide , Sets of similar genes according to GeneDecks, Electronic Northern calculations according to data from UniGene (Build 219 Homo sapiens), SAGE tags according to CGAP, plus additional links to SOURCE, and/or GNF BioGPS, and/or EXPOLDB, and/or UniProtKB,
Expression Assays from Applied Biosystems )
About This Section

A2ML1 expression in normal and diseased human tissues

 Applied Biosystems TaqMan ® Gene Expression Assays for A2ML1

1 / 2 / 3

2 probe-sets matching A2ML1 gene


Affymetrix
probe-set
Array  GeneAnnot data GeneNote data GeneTide data
# genes Sensitivity Specificity Correlation Length Gb_Accession Consensus Uniqueness Score Rank

1564307_a_at2 U133Plus2 1 1.00 1.00 -- -- -- -- -- -- --

1553505_at2 U133Plus2 1 1.00 1.00 -- -- -- -- -- -- --
About this table
Data from (Publications) and GNF BioGPS
    About these images
About these images

CGAP SAGE TAG: GTAAAACCCG

SOURCE GeneReport for Unigene cluster: Hs.620532

UniProtKB/Swiss-Prot: A2ML1_HUMAN, A8K2U0
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

(Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD and/or 5MGI Jun 06 2009, with possible further links to Flybase and/or WormBase, Gene Trees according to Ensembl)
About This Section


Orthologs for A2ML1 gene from 4 species
Organism Gene Locus Description Human
Similarity
NCBI accessions
dog
(Canis familiaris)
A2ML11   -- alpha-2-macroglobulin-like 1 85.53(n)
82.14(a)
486697  XM_543824.2  XP_543824.2 
chimpanzee
(Pan troglodytes)
A2ML11   -- alpha-2-macroglobulin-like 1 99.15(n)
99.04(a)
465375  XM_520828.2  XP_520828.2 
chicken
(Gallus gallus)
A2ML11   -- alpha-2-macroglobulin-like 1 56.03(n)
46.49(a)
418254  XM_416480.2  XP_416480.2 
zebrafish
(Danio rerio)
LOC4076431   -- alpha-2 macroglobulin like-protein 51.36(n)
42.34(a)
407643  XM_001920709.1  XP_001920744.1 
About this table        Species with no ortholog for A2ML1

ENSEMBL Gene Tree for A2ML1
(Paralogs according to 1HomoloGene
and 2Ensembl, Pseudogenes according to 3Pseudogene.org)
About This Section

  --
(According to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, and UniProtKB, Linkage Disequilibrium by HapMap, Genotyping Reagents from Applied Biosystems)
About This Section


10/515 NCBI SNPs in A2ML1 are shown (see all 515 )
(Click for Applied Biosystems TaqMan ® Genotyping Assay)  (see all 138)
ABGenomic DataTranscription DataAllele Frequencies
SNP IDValidChr 12 posSequenceRecsAA
Chg
TypeMoreRecsAllele
freq
PopTotal
sample
More
------------
rs18609671,2
A,C,F,H,O8905022(+) GTCTAC/TGGTGT 1 R/W mis1 ese317Minor allele frequency- T:0.49MN EA NA EU WA 1652
rs48831941,2
A,C,F,H8920139(+) CATGGA/GCAGGG 1 -- ut31 ese311Minor allele frequency- G:0.45EU EA WA NA 966
--
rs110474321,2
A,C,F,H8866082(+) TTTACT/CGCTTT 1 -- ng51 tfbs33Minor allele frequency- C:0.41EU EA 300
rs107711511,2
A,C,F,H8920868(+) GTGATT/GGATTA 1 -- ng3115Minor allele frequency- G:0.47NA EU EA WA 1344
rs73088111,2
A,C,F,H8911756(+) CCTACG/ATGCCA 1 V/M mis1 ese34Minor allele frequency- A:0.18EU EA WA 416
rs15585261,2
A,C,F,H8901087(+) TGGCTG/ATGGCG 1 Y/C mis1 ese39Minor allele frequency- A:0.10MN EU EA WA 1022
rs73082091,2
A,C,F,H8920732(+) TCACAA/GTTTGG 1 -- ng3111Minor allele frequency- G:0.26EU EA WA NA 928
--
rs73083241,2
A,C,F8920845(+) AGCCCA/GCTACT 1 -- ng313Minor allele frequency- G:0.47NA 138
--
rs73155911,2
C,F,H8918300(+) AGAACA/GCTCAG 1 T/A mis19Minor allele frequency- G:0.03EU EA WA NA 916
rs110474991,2
C,F,H8879505(+) CCTTTG/CGTACT 1 R/G mis1 ese38Minor allele frequency- C:0.04EU EA WA 834
About this table

HapMap Linkage Disequilibrium images for A2ML1 (up to first 250kb)

(in which this Gene is Involved, According to OMIM, UniProtKB, PharmGKB, Genatlas, GeneTests, Blood group antigen gene mutations by BGMUT, HGMD, GAD, HuGE Navigator, BCGD, and/or TGDB.)
About This Section

OMIM: 610627

Human Genome Epidemiology Navigator: A2ML1 (1 document)

(Possibly Related Articles in Doctor's Guide)
About This Section

  --

(in PubMed. Associations of this gene to articles via 1Novoseek, 2HGNC, 3Entrez Gene, 4UniProtKB/Swiss-Prot, 5UniProtKB/TrEMBL, 6GAD, and/or 7PharmGKB)
About This Section

10 PubMed articles for A2ML1 gene:
(in PubMed, OMIM, and NCBI Bookshelf)
About This Section

 ANDOR
Aliases
Free Text  

  Query String
PubMed
OMIM
NCBI Bookshelf
  (Note: In FireFox, select the above section and copy using Ctrl-C)
(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, and/or H-InvDB)
About This Section

Entrez Gene: 144568 HGNC: 23336 AceView: FLJ25179 Ensembl:ENSG00000166535 euGenes: HUgn144568
ECgene: A2ML1 H-InvDB: A2ML1
(According to HUGE)
About This Section

  --
(According to ATLAS, HORDE, IMGT, MTDB, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

  --
(Available from WIS Yeda, Salk, Tufts)
About This Section

  --
(Reagents available from Applied Biosystems, Antibodies and assays by Cell Signaling Technology, Abcam, Novus Biologicals,
Sigma-Aldrich, R&D Systems, Millipore, Abnova, and/or Invitrogen, Clones available from OriGene,and/or Invitrogen, Drugs and/or compounds by Sigma-Aldrich,
Enzo Life Sciences, and/or Tocris Bioscience)
About This Section



Products for A2ML1:
 TaqMan ® Gene Expression Assays
 TaqMan ® Genotyping Assays
  Free SNP selection tool



  Invitrogen iPath Pathways  Invitrogen BLOCK-iT™ RNAi
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 Predesigned and custom siRNAs for A2ML1 Browse antibodies at Sigma-Aldrich
 Explore super-pooled esiRNAs Browse proteins at Sigma-Aldrich
 Lentivirus-delivered shRNAs for A2ML1 Browse small molecules at Sigma-Aldrich
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