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Protein

Alpha-2-macroglobulin-like protein 1

Gene

A2ML1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.By similarity1 Publication

GO - Molecular functioni

  • peptidase inhibitor activity Source: UniProtKB
  • serine-type endopeptidase inhibitor activity Source: UniProtKB-KW

GO - Biological processi

Keywordsi

Molecular functionProtease inhibitor, Serine protease inhibitor

Protein family/group databases

MEROPSiI39.007

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-2-macroglobulin-like protein 1
Alternative name(s):
C3 and PZP-like alpha-2-macroglobulin domain-containing protein 9
Gene namesi
Name:A2ML1Imported
Synonyms:CPAMD9Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000166535.19
HGNCiHGNC:23336 A2ML1
MIMi610627 gene
neXtProtiNX_A8K2U0

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Otitis media (OM)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionAn inflammation of the middle ear resulting in earache, fever, hearing disturbance, and vertigo.
See also OMIM:166760

Organism-specific databases

DisGeNETi144568
MalaCardsiA2ML1
MIMi166760 phenotype
OpenTargetsiENSG00000166535
Orphaneti648 Noonan syndrome

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 17Sequence analysisAdd BLAST17
ChainiPRO_000031807418 – 1454Alpha-2-macroglobulin-like protein 1Sequence analysisAdd BLAST1437

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi40 ↔ 78By similarity
Glycosylationi120N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi241 ↔ 291By similarity
Disulfide bondi259 ↔ 279By similarity
Glycosylationi281N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi409N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi464 ↔ 557By similarity
Disulfide bondi589 ↔ 769By similarity
Disulfide bondi819 ↔ 847By similarity
Disulfide bondi845 ↔ 881By similarity
Glycosylationi857N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi919 ↔ 1307By similarity
Cross-linki970 ↔ 973Isoglutamyl cysteine thioester (Cys-Gln)By similarity
Glycosylationi1020N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi1075 ↔ 1123By similarity
Disulfide bondi1338 ↔ 1453By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Thioester bond

Proteomic databases

EPDiA8K2U0
MaxQBiA8K2U0
PaxDbiA8K2U0
PRIDEiA8K2U0
ProteomicsDBi1852

PTM databases

GlyConnecti1003
iPTMnetiA8K2U0
PhosphoSitePlusiA8K2U0

Expressioni

Tissue specificityi

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.1 Publication

Developmental stagei

Up-regulated during keratinocyte differentiation.1 Publication

Gene expression databases

BgeeiENSG00000166535 Expressed in 112 organ(s), highest expression level in mouth mucosa
CleanExiHS_A2ML1
ExpressionAtlasiA8K2U0 baseline and differential
GenevisibleiA8K2U0 HS

Organism-specific databases

HPAiHPA038847
HPA038848

Interactioni

Subunit structurei

Monomer.1 Publication

Protein-protein interaction databases

IntActiA8K2U0, 5 interactors
MINTiA8K2U0
STRINGi9606.ENSP00000299698

Structurei

3D structure databases

ProteinModelPortaliA8K2U0
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni695 – 726Bait regionSequence analysisAdd BLAST32

Sequence similaritiesi

Keywords - Domaini

Bait region, Signal

Phylogenomic databases

eggNOGiKOG1366 Eukaryota
ENOG410XRED LUCA
GeneTreeiENSGT00760000118982
HOVERGENiHBG000039
InParanoidiA8K2U0
OMAiVSVCQKA
OrthoDBiEOG091G00HD
PhylomeDBiA8K2U0
TreeFamiTF313285

Family and domain databases

Gene3Di2.60.40.10, 2 hits
2.60.40.690, 1 hit
InterProiView protein in InterPro
IPR009048 A-macroglobulin_rcpt-bd
IPR036595 A-macroglobulin_rcpt-bd_sf
IPR011626 A2M_comp
IPR002890 A2M_N
IPR011625 A2M_N_2
IPR013783 Ig-like_fold
IPR014756 Ig_E-set
IPR001599 Macroglobln_a2
IPR019742 MacrogloblnA2_CS
IPR019565 MacrogloblnA2_thiol-ester-bond
IPR008930 Terpenoid_cyclase/PrenylTrfase
PfamiView protein in Pfam
PF00207 A2M, 1 hit
PF07678 A2M_comp, 1 hit
PF01835 A2M_N, 1 hit
PF07703 A2M_N_2, 1 hit
PF07677 A2M_recep, 1 hit
PF10569 Thiol-ester_cl, 1 hit
SMARTiView protein in SMART
SM01360 A2M, 1 hit
SM01359 A2M_N_2, 1 hit
SM01361 A2M_recep, 1 hit
SUPFAMiSSF48239 SSF48239, 1 hit
SSF49410 SSF49410, 1 hit
SSF81296 SSF81296, 1 hit
PROSITEiView protein in PROSITE
PS00477 ALPHA_2_MACROGLOBULIN, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: A8K2U0-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MWAQLLLGML ALSPAIAEEL PNYLVTLPAR LNFPSVQKVC LDLSPGYSDV
60 70 80 90 100
KFTVTLETKD KTQKLLEYSG LKKRHLHCIS FLVPPPAGGT EEVATIRVSG
110 120 130 140 150
VGNNISFEEK KKVLIQRQGN GTFVQTDKPL YTPGQQVYFR IVTMDSNFVP
160 170 180 190 200
VNDKYSMVEL QDPNSNRIAQ WLEVVPEQGI VDLSFQLAPE AMLGTYTVAV
210 220 230 240 250
AEGKTFGTFS VEEYVLPKFK VEVVEPKELS TVQESFLVKI CCRYTYGKPM
260 270 280 290 300
LGAVQVSVCQ KANTYWYREV EREQLPDKCR NLSGQTDKTG CFSAPVDMAT
310 320 330 340 350
FDLIGYAYSH QINIVATVVE EGTGVEANAT QNIYISPQMG SMTFEDTSNF
360 370 380 390 400
YHPNFPFSGK IRVRGHDDSF LKNHLVFLVI YGTNGTFNQT LVTDNNGLAP
410 420 430 440 450
FTLETSGWNG TDVSLEGKFQ MEDLVYNPEQ VPRYYQNAYL HLRPFYSTTR
460 470 480 490 500
SFLGIHRLNG PLKCGQPQEV LVDYYIDPAD ASPDQEISFS YYLIGKGSLV
510 520 530 540 550
MEGQKHLNSK KKGLKASFSL SLTFTSRLAP DPSLVIYAIF PSGGVVADKI
560 570 580 590 600
QFSVEMCFDN QVSLGFSPSQ QLPGAEVELQ LQAAPGSLCA LRAVDESVLL
610 620 630 640 650
LRPDRELSNR SVYGMFPFWY GHYPYQVAEY DQCPVSGPWD FPQPLIDPMP
660 670 680 690 700
QGHSSQRSII WRPSFSEGTD LFSFFRDVGL KILSNAKIKK PVDCSHRSPE
710 720 730 740 750
YSTAMGAGGG HPEAFESSTP LHQAEDSQVR QYFPETWLWD LFPIGNSGKE
760 770 780 790 800
AVHVTVPDAI TEWKAMSFCT SQSRGFGLSP TVGLTAFKPF FVDLTLPYSV
810 820 830 840 850
VRGESFRLTA TIFNYLKDCI RVQTDLAKSH EYQLESWADS QTSSCLCADD
860 870 880 890 900
AKTHHWNITA VKLGHINFTI STKILDSNEP CGGQKGFVPQ KGRSDTLIKP
910 920 930 940 950
VLVKPEGVLV EKTHSSLLCP KGKVASESVS LELPVDIVPD STKAYVTVLG
960 970 980 990 1000
DIMGTALQNL DGLVQMPSGC GEQNMVLFAP IIYVLQYLEK AGLLTEEIRS
1010 1020 1030 1040 1050
RAVGFLEIGY QKELMYKHSN GSYSAFGERD GNGNTWLTAF VTKCFGQAQK
1060 1070 1080 1090 1100
FIFIDPKNIQ DALKWMAGNQ LPSGCYANVG NLLHTAMKGG VDDEVSLTAY
1110 1120 1130 1140 1150
VTAALLEMGK DVDDPMVSQG LRCLKNSATS TTNLYTQALL AYIFSLAGEM
1160 1170 1180 1190 1200
DIRNILLKQL DQQAIISGES IYWSQKPTPS SNASPWSEPA AVDVELTAYA
1210 1220 1230 1240 1250
LLAQLTKPSL TQKEIAKATS IVAWLAKQHN AYGGFSSTQD TVVALQALAK
1260 1270 1280 1290 1300
YATTAYMPSE EINLVVKSTE NFQRTFNIQS VNRLVFQQDT LPNVPGMYTL
1310 1320 1330 1340 1350
EASGQGCVYV QTVLRYNILP PTNMKTFSLS VEIGKARCEQ PTSPRSLTLT
1360 1370 1380 1390 1400
IHTSYVGSRS SSNMAIVEVK MLSGFSPMEG TNQLLLQQPL VKKVEFGTDT
1410 1420 1430 1440 1450
LNIYLDELIK NTQTYTFTIS QSVLVTNLKP ATIKVYDYYL PDEQATIQYS

DPCE
Length:1,454
Mass (Da):161,107
Last modified:October 5, 2010 - v3
Checksum:i15ED65D000834E33
GO
Isoform 2 (identifier: A8K2U0-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     2-492: Missing.

Note: No experimental confirmation available.
Show »
Length:963
Mass (Da):105,968
Checksum:iF768614879F8E89C
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YGG5H0YGG5_HUMAN
Alpha-2-macroglobulin-like protein ...
A2ML1
1,004Annotation score:
H0YH14H0YH14_HUMAN
Alpha-2-macroglobulin-like protein ...
A2ML1
182Annotation score:
F5GXP1F5GXP1_HUMAN
Alpha-2-macroglobulin-like protein ...
A2ML1
183Annotation score:
F5GYG7F5GYG7_HUMAN
Alpha-2-macroglobulin-like protein ...
A2ML1
81Annotation score:

Sequence cautioni

The sequence BAB71612 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAC04793 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAC85653 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAC85654 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti733F → L in BAC85654 (PubMed:14702039).Curated1
Sequence conflicti733F → L in BAF83044 (PubMed:14702039).Curated1
Sequence conflicti748G → E in AL832139 (PubMed:17974005).Curated1
Sequence conflicti1150M → I in BAF83044 (PubMed:14702039).Curated1
Sequence conflicti1248L → P in BAC85654 (PubMed:14702039).Curated1
Sequence conflicti1452P → L in AL832139 (PubMed:17974005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_055463207G → R. Corresponds to variant dbSNP:rs11047499EnsemblClinVar.1
Natural variantiVAR_081009255 – 1454Missing Risk factor for otitis media. 1 PublicationAdd BLAST1200
Natural variantiVAR_081010296V → A1 Publication1
Natural variantiVAR_081011356P → R May be a risk factor for otitis media. 1 Publication1
Natural variantiVAR_059083850D → E3 PublicationsCorresponds to variant dbSNP:rs1860926Ensembl.1
Natural variantiVAR_081012893 – 1454Missing Risk factor for otitis media. 1 PublicationAdd BLAST562
Natural variantiVAR_055464970C → Y. Corresponds to variant dbSNP:rs1558526EnsemblClinVar.1
Natural variantiVAR_081013972 – 1454Missing Risk factor for otitis media. 1 PublicationAdd BLAST483
Natural variantiVAR_0810141001R → W May be a risk factor for otitis media. 1 Publication1
Natural variantiVAR_0718541122R → W3 PublicationsCorresponds to variant dbSNP:rs1860967EnsemblClinVar.1
Natural variantiVAR_0554651131T → M. Corresponds to variant dbSNP:rs7959680EnsemblClinVar.1
Natural variantiVAR_0590841229H → R3 PublicationsCorresponds to variant dbSNP:rs10219561Ensembl.1
Natural variantiVAR_0718551257M → V3 PublicationsCorresponds to variant dbSNP:rs7308811EnsemblClinVar.1
Natural variantiVAR_0718561312T → M1 PublicationCorresponds to variant dbSNP:rs201083574Ensembl.1
Natural variantiVAR_0554661412T → A. Corresponds to variant dbSNP:rs7315591EnsemblClinVar.1
Natural variantiVAR_0810151431A → V1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0571352 – 492Missing in isoform 2. 1 PublicationAdd BLAST491

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK057908 mRNA Translation: BAB71612.1 Different initiation.
AK096448 mRNA Translation: BAC04793.1 Different initiation.
AK123591 mRNA Translation: BAC85653.1 Different initiation.
AK123592 mRNA Translation: BAC85654.1 Different initiation.
AK290355 mRNA Translation: BAF83044.1
AK302555 mRNA Translation: BAH13740.1
AL832139 mRNA No translation available.
AC006513 Genomic DNA No translation available.
AC006581 Genomic DNA No translation available.
CH471116 Genomic DNA Translation: EAW88603.1
CH471116 Genomic DNA Translation: EAW88606.1
BC093840 mRNA Translation: AAH93840.2
BC112131 mRNA Translation: AAI12132.1
CCDSiCCDS73439.1 [A8K2U0-2]
CCDS8596.2 [A8K2U0-1]
RefSeqiNP_001269353.1, NM_001282424.2
XP_016874359.1, XM_017018870.1 [A8K2U0-1]
UniGeneiHs.620532

Genome annotation databases

EnsembliENST00000299698; ENSP00000299698; ENSG00000166535 [A8K2U0-1]
ENST00000539547; ENSP00000438292; ENSG00000166535 [A8K2U0-2]
GeneIDi144568
KEGGihsa:144568
UCSCiuc001quz.6 human [A8K2U0-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK057908 mRNA Translation: BAB71612.1 Different initiation.
AK096448 mRNA Translation: BAC04793.1 Different initiation.
AK123591 mRNA Translation: BAC85653.1 Different initiation.
AK123592 mRNA Translation: BAC85654.1 Different initiation.
AK290355 mRNA Translation: BAF83044.1
AK302555 mRNA Translation: BAH13740.1
AL832139 mRNA No translation available.
AC006513 Genomic DNA No translation available.
AC006581 Genomic DNA No translation available.
CH471116 Genomic DNA Translation: EAW88603.1
CH471116 Genomic DNA Translation: EAW88606.1
BC093840 mRNA Translation: AAH93840.2
BC112131 mRNA Translation: AAI12132.1
CCDSiCCDS73439.1 [A8K2U0-2]
CCDS8596.2 [A8K2U0-1]
RefSeqiNP_001269353.1, NM_001282424.2
XP_016874359.1, XM_017018870.1 [A8K2U0-1]
UniGeneiHs.620532

3D structure databases

ProteinModelPortaliA8K2U0
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiA8K2U0, 5 interactors
MINTiA8K2U0
STRINGi9606.ENSP00000299698

Protein family/group databases

MEROPSiI39.007

PTM databases

GlyConnecti1003
iPTMnetiA8K2U0
PhosphoSitePlusiA8K2U0

Proteomic databases

EPDiA8K2U0
MaxQBiA8K2U0
PaxDbiA8K2U0
PRIDEiA8K2U0
ProteomicsDBi1852

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000299698; ENSP00000299698; ENSG00000166535 [A8K2U0-1]
ENST00000539547; ENSP00000438292; ENSG00000166535 [A8K2U0-2]
GeneIDi144568
KEGGihsa:144568
UCSCiuc001quz.6 human [A8K2U0-1]

Organism-specific databases

CTDi144568
DisGeNETi144568
EuPathDBiHostDB:ENSG00000166535.19
GeneCardsiA2ML1
HGNCiHGNC:23336 A2ML1
HPAiHPA038847
HPA038848
MalaCardsiA2ML1
MIMi166760 phenotype
610627 gene
neXtProtiNX_A8K2U0
OpenTargetsiENSG00000166535
Orphaneti648 Noonan syndrome
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1366 Eukaryota
ENOG410XRED LUCA
GeneTreeiENSGT00760000118982
HOVERGENiHBG000039
InParanoidiA8K2U0
OMAiVSVCQKA
OrthoDBiEOG091G00HD
PhylomeDBiA8K2U0
TreeFamiTF313285

Miscellaneous databases

ChiTaRSiA2ML1 human
PROiPR:A8K2U0
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000166535 Expressed in 112 organ(s), highest expression level in mouth mucosa
CleanExiHS_A2ML1
ExpressionAtlasiA8K2U0 baseline and differential
GenevisibleiA8K2U0 HS

Family and domain databases

Gene3Di2.60.40.10, 2 hits
2.60.40.690, 1 hit
InterProiView protein in InterPro
IPR009048 A-macroglobulin_rcpt-bd
IPR036595 A-macroglobulin_rcpt-bd_sf
IPR011626 A2M_comp
IPR002890 A2M_N
IPR011625 A2M_N_2
IPR013783 Ig-like_fold
IPR014756 Ig_E-set
IPR001599 Macroglobln_a2
IPR019742 MacrogloblnA2_CS
IPR019565 MacrogloblnA2_thiol-ester-bond
IPR008930 Terpenoid_cyclase/PrenylTrfase
PfamiView protein in Pfam
PF00207 A2M, 1 hit
PF07678 A2M_comp, 1 hit
PF01835 A2M_N, 1 hit
PF07703 A2M_N_2, 1 hit
PF07677 A2M_recep, 1 hit
PF10569 Thiol-ester_cl, 1 hit
SMARTiView protein in SMART
SM01360 A2M, 1 hit
SM01359 A2M_N_2, 1 hit
SM01361 A2M_recep, 1 hit
SUPFAMiSSF48239 SSF48239, 1 hit
SSF49410 SSF49410, 1 hit
SSF81296 SSF81296, 1 hit
PROSITEiView protein in PROSITE
PS00477 ALPHA_2_MACROGLOBULIN, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiA2ML1_HUMAN
AccessioniPrimary (citable) accession number: A8K2U0
Secondary accession number(s): B5MDD1
, B7Z7V4, D3DUV3, F5H2Z2, Q2M224, Q6ZW52, Q6ZW53, Q8N1M4, Q96LQ8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 5, 2008
Last sequence update: October 5, 2010
Last modified: November 7, 2018
This is version 97 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
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