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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

A2ML1 Gene

protein-coding GIFtS: 47
GCID: GC12P008975

alpha-2-macroglobulin-like 1

(Previous names: C3 and PZP-like, alpha-2-macroglobulin domain containing...)
(Previous symbol: CPAMD9)

Explore 2 diseases affiliated with
A2ML1 via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Alpha-2-Macroglobulin-Like 1¹ ²
CPAMD9¹ ² ³
C3 And PZP-Like, Alpha-2-Macroglobulin Domain Containing 9¹ ²
FLJ25179¹
Alpha-2-Macroglobulin-Like Protein 1²
C3 And PZP-Like Alpha-2-Macroglobulin Domain-Containing Protein 9³

External Ids:	HGNC: 23336¹	Entrez Gene: 144568²	Ensembl: ENSG00000166535⁷	OMIM: 610627⁵	UniProtKB: A8K2U0³

Export aliases for A2ML1 gene to outside databases

Previous GC identifers: GC12P008867 GC12P008757

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

Entrez Gene summary for A2ML1:

This gene encodes a member of the alpha-macroglobulin superfamily. The encoded protein acts as an inhibitor for several

proteases, and has been reported as the p170 antigen recognized by autoantibodies in the autoimmune disease

paraneoplastic pemphigus (PNP; PMID: 20805888). Alternative splicing results in multiple transcript variants.

(provided by RefSeq, Feb 2012)

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 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000012.11 NC_018923.1 NT_009714.17

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the A2ML1 gene promoter:
SRF HOXA3 AP-1 SRF (504 AA) POU3F2 (N-Oct-5a) POU3F2 (N-Oct-5b) POU3F2 PPAR-alpha Pax-3 SRY
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: A2ML1 promoter sequence

Search SABiosciences Chromatin IP Primers for A2ML1

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat A2ML1

Genomic Location:
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)
A2ML1 gene location

GeneLoc information about chromosome 12 GeneLoc Exon Structure

GeneLoc location for GC12P008975: view genomic region (about GC identifiers)

Start:	8,975,068 bp from pter	End:	9,039,597 bp from pter
Size:	64,530 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
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; 161107 Da

Subunit: Monomer

Subcellular location: Secreted

Developmental stage: Up-regulated during keratinocyte differentiation

Sequence caution: Sequence=BAB71612.1; Type=Erroneous initiation; Sequence=BAC04793.1; Type=Erroneous initiation;

Sequence=BAC85653.1; Type=Erroneous initiation; Sequence=BAC85654.1; Type=Erroneous initiation;

Secondary accessions: B5MDD1 Q2M224 Q6ZW52 Q6ZW53 Q8N1M4 Q96LQ8

Explore the universe of human proteins at neXtProt for A2ML1: NX_A8K2U0

Post-translational modifications:

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_A8K2U0

A2ML1 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins: NP_653271.2

ENSEMBL proteins:

ENSP00000299698 ENSP00000443174 ENSP00000440662 ENSP00000438292 ENSP00000440057

ENSP00000445674

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Gene Ontology (GO): 1 cellular component term (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005615	extracellular space	IDA	16298998

A2ML1 for ontologies About GeneDecksing

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

A2ML1 for domains About GeneDecksing

5/8 InterPro domains/families (see all 8):

IPR019742 MacrogloblnA2_CS

IPR001599 Macroglobln_a2

IPR011626 A2M_comp

IPR002890 A2M_N

IPR011625 A2M_N_2

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 ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

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

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In Situ Assay
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Gene Ontology (GO): 3 molecular function terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0004866	endopeptidase inhibitor activity	--	--
GO:0004867	serine-type endopeptidase inhibitor activity	IEA	--
GO:0030414	peptidase inhibitor activity	IDA	16298998

A2ML1 for ontologies About GeneDecksing

1 GenomeRNAi human phenotype for A2ML1:

Synthetic lethal with Ras

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Interactions:

Search SABiosciences Gene Network Central^TM Interacting Genes and Proteins Networks for A2ML1

Gene Ontology (GO): 2 biological process terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0010466	negative regulation of peptidase activity	--	--
GO:0052548	regulation of endopeptidase activity	IDA	16298998

A2ML1 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for A2ML1
Search CenterWatch for drugs/clinical trials and news about A2ML1

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
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About This Section

REFSEQ mRNAs for A2ML1 gene:

NM_144670.4

Unigene Cluster for A2ML1:

Alpha-2-macroglobulin-like 1

Hs.620532 [show with all ESTs]

Unigene Representative Sequence: AL832139

9 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000299698(uc001quz.4 uc010sgm.2) ENST00000537546 ENST00000541459(uc001qva.1)

ENST00000536789 ENST00000539547 ENST00000545692 ENST00000540049 ENST00000545850

ENST00000537475(uc001qvb.1)

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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 NR_046256.1

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 AA316097 BX504185 AL832139 AK122624 AL700698 AL832750

BE151370 AK096448 AW862460 AK123592 AW860672 BU101571 AL833479 BX504184

BU101570 BX648231 AK123591 BX647674 AK123601 BG680886 BE144308 BF330285

GeneLoc Exon Structure

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

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:

ECgene alternative splicing isoforms for A2ML1

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

A2ML1 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: GTAAAACCCG

About this image

A2ML1 expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

2 LifeMap In Vivo Development Anatomical Compartments/Cells

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Ovary

Ovary

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

See A2ML1 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for A2ML1

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

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In Situ
Assay Products:

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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of animals.

Orthologs for A2ML1 gene from 4/12 species (see all 12) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	LOC100858010¹	alpha-2-macroglobulin-like protein 1-like	53.83(n) 45.25(a)		100858010 XM_003642785.1 XP_003642833.1
lizard (Anolis carolinensis)	Reptilia	-- --	--	39(a) 38(a)	possible ortholog possible ortholog	2(81010205-81073674) 2(81153137-81246353)
zebrafish (Danio rerio)	Actinopterygii	wu:fb68b01⁶ BX548078.2⁶ (see all 15)	--	44(a) 42(a) (see all 15)	1 ↔ many 1 ↔ many (see all 15)	15(20041521-20056443) 15(19920610-19938131)
honey bee (Apis mellifera)	Insecta	--	--	23(a)	1 → many	Group7.14(1063-10516)

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

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for A2ML1 gene

A2M² C5² C3² C4B² C4A² PZP² CPAMD8² CD109²

4 SIMAP similar genes for A2ML1 using alignment to 7 protein entries: A2ML1_HUMAN (see all proteins):

A2M DKFZp686C0338 PZP OVOS2

A2ML1 for paralogs About GeneDecksing

1 Pseudogenes.org Pseudogene for A2ML1
PGOHUM00000258659

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 12 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs4534635^1,2	C,	--	8973175(+)	`ggtggC/Tgggcg`	1	--	us2k¹		1		NA	2
rs4542461^1,2	C,F,	--	8973268(+)	`cgccaT/Ctgcac`	1	--	us2k¹		4		NA	8
rs2377591^1,2	C,A,	--	8973275(+)	`GCACTC/TCAGCC`	1	--	us2k¹		6		NA CSA	11
rs184211176^1,2		--	8973383(+)	`AATTGC/TTCCTG`	1	--	us2k¹		0	--	--	--	--
rs112105478^1,2	F	--	8973394(+)	`GGGATG/AACATC`	1	--	us2k¹		2		CSA	4
rs145976253^1,2		--	8973406(+)	`CTGCTA/GTAAAA`	1	--	us2k¹		0	--	--	--	--
rs188819682^1,2		--	8973418(+)	`CTAAGA/CTCAGT`	1	--	us2k¹		0	--	--	--	--
rs193015335^1,2		--	8973607(+)	`GCCCCG/TACCTG`	1	--	us2k¹		0	--	--	--	--
rs183522888^1,2		--	8973630(+)	`TAAAAA/TCTCTG`	1	--	us2k¹		0	--	--	--	--
rs139842122^1,2		--	8973672(+)	`TAAAAC/TTCCAG`	1	--	us2k¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for A2ML1 (8975068 - 9039597 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 10 variations for A2ML1
7 CNVs: 23452 38271 66135 101426 5654 86188 49153
3 Indels: 75932 75931 86189

SABiosciences Cancer Mutation PCR Assays

QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing A2ML1

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

A2ML1 for disorders           About GeneDecksing

OMIM gene information: 610627    OMIM disorders: --

2 diseases for A2ML1:    About MalaCards

pemphigus bullous pemphigoid

Human Genome Epidemiology (HuGE) Navigator: A2ML1 (1 document)

Export disorders for A2ML1 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for A2ML1 gene, integrated from 9 sources (see all 12):
(articles sorted by number of sources associating them with A2ML1)

Utopia: connect your pdf to the dynamic
world of online information

A novel protease inhibitor of the alpha2-macroglobulin family expressed in the human epidermis. (PubMed id 16298998)^{1, 2, 3} Galliano M.F....Guerrin M. (2006)
Complete sequencing and characterization of 21,243 full-length human cDNAs. (PubMed id 14702039)^{1, 2} Ota T.... Sugano S. (2004)
The protease inhibitor alpha-2-macroglobulin-like-1 i s the p170 antigen recognized by paraneoplastic pemphigus autoantibodies in hum an. (PubMed id 20805888)¹ Schepens I....Borradori L. (2010)
Transcriptomic and genetic studies identify IL-33 as a candidate gene for Alzheimer's disease. (PubMed id 19204726)¹ Chapuis J....Lambert J.C. (2009)
Binding of alpha2ML1 to the low density lipoprotein receptor-related protein 1 (LRP1) reveals a new role for LRP1 in the human epidermis. (PubMed id 18648652)¹ Galliano M.F....Guerrin M. (2008)
Large-scale identification of human genes implicated in epidermal barrier function. (PubMed id 17562024)¹ Toulza E.... Guerrin M. (2007)
The full-ORF clone resource of the German cDNA consortium. (PubMed id 17974005)² Bechtel S.... Schupp I. (2007)
Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. (PubMed id 16344560)¹ Kimura K.... Sugano S. (2006)
The finished DNA sequence of human chromosome 12. (PubMed id 16541075)² Scherer S.E.... Gibbs R.A. (2006)
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)² Gerhard D.S....Malek J. (2004)

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(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 144568	HGNC: 23336	AceView: FLJ25179	Ensembl:ENSG00000166535	euGenes: HUgn144568
ECgene: A2ML1	H-InvDB: A2ML1

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for A2ML1	Pharmacogenomics, SNPs, Pathways

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Patent Information for A2ML1 gene:
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alpha-2-macroglobulin-like 1

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