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A8K2U0 (A2ML1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 53. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Alpha-2-macroglobulin-like protein 1
Alternative name(s):
C3 and PZP-like alpha-2-macroglobulin domain-containing protein 9
Gene names
Name:A2ML1
Synonyms:CPAMD9
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1454 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.5 UniProtKB P01023

Subunit structure

Monomer. Ref.5

Subcellular location

Secreted Ref.5.

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. Ref.5

Developmental stage

Up-regulated during keratinocyte differentiation. Ref.5

Sequence similarities

Belongs to the protease inhibitor I39 (alpha-2-macroglobulin) family. [View classification]

Sequence caution

The sequence BAB71612.1 differs from that shown. Reason: Erroneous initiation.

The sequence BAC04793.1 differs from that shown. Reason: Erroneous initiation.

The sequence BAC85653.1 differs from that shown. Reason: Erroneous initiation.

The sequence BAC85654.1 differs from that shown. Reason: Erroneous initiation.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1717 Potential
Chain18 – 14541437Alpha-2-macroglobulin-like protein 1
PRO_0000318074

Regions

Region695 – 72632Bait region

Amino acid modifications

Glycosylation1201N-linked (GlcNAc...) Potential
Glycosylation2811N-linked (GlcNAc...) Potential
Glycosylation4091N-linked (GlcNAc...) Potential
Glycosylation8571N-linked (GlcNAc...) Potential
Glycosylation10201N-linked (GlcNAc...) Potential
Disulfide bond40 ↔ 78 By similarity UniProtKB P01023
Disulfide bond241 ↔ 291 By similarity UniProtKB P01023
Disulfide bond259 ↔ 279 By similarity UniProtKB P01023
Disulfide bond464 ↔ 557 By similarity UniProtKB P01023
Disulfide bond589 ↔ 769 By similarity UniProtKB P01023
Disulfide bond819 ↔ 847 By similarity UniProtKB P01023
Disulfide bond845 ↔ 881 By similarity UniProtKB P01023
Disulfide bond919 ↔ 1307 By similarity UniProtKB P01023
Disulfide bond1075 ↔ 1123 By similarity UniProtKB P01023
Disulfide bond1338 ↔ 1453 By similarity UniProtKB P01023
Cross-link970 ↔ 973Isoglutamyl cysteine thioester (Cys-Gln) By similarity UniProtKB P01023

Natural variations

Natural variant2071G → R.
Corresponds to variant rs11047499 [ dbSNP | Ensembl ].
VAR_055463
Natural variant8501D → E. Ref.1 Ref.2
Corresponds to variant rs1860926 [ dbSNP | Ensembl ].
VAR_059083
Natural variant9701C → Y.
Corresponds to variant rs1558526 [ dbSNP | Ensembl ].
VAR_055464
Natural variant11311T → M.
Corresponds to variant rs7959680 [ dbSNP | Ensembl ].
VAR_055465
Natural variant12291H → R. Ref.1 Ref.2
Corresponds to variant rs10219561 [ dbSNP | Ensembl ].
VAR_059084
Natural variant14121T → A.
Corresponds to variant rs7315591 [ dbSNP | Ensembl ].
VAR_055466

Experimental info

Sequence conflict7331F → L in BAC85654. Ref.1
Sequence conflict7331F → L in BAF83044. Ref.1
Sequence conflict7481G → E in AL832139. Ref.2
Sequence conflict11221R → W in BAC04793. Ref.1
Sequence conflict11221R → W in BAC85653. Ref.1
Sequence conflict11221R → W in BAC85654. Ref.1
Sequence conflict11221R → W in BAF83044. Ref.1
Sequence conflict11221R → W in AL832139. Ref.2
Sequence conflict11501M → I in BAF83044. Ref.1
Sequence conflict12481L → P in BAC85654. Ref.1
Sequence conflict12571M → V in BAC04793. Ref.1
Sequence conflict12571M → V in BAC85653. Ref.1
Sequence conflict12571M → V in BAC85654. Ref.1
Sequence conflict12571M → V in BAF83044. Ref.1
Sequence conflict12571M → V in AL832139. Ref.2
Sequence conflict14521P → L in AL832139. Ref.2

Sequences

Sequence LengthMass (Da)Tools
A8K2U0 [UniParc].

Last modified October 5, 2010. Version 3.
Checksum: 15ED65D000834E33

FASTA1,454161,107
        10         20         30         40         50         60 
MWAQLLLGML ALSPAIAEEL PNYLVTLPAR LNFPSVQKVC LDLSPGYSDV KFTVTLETKD 

        70         80         90        100        110        120 
KTQKLLEYSG LKKRHLHCIS FLVPPPAGGT EEVATIRVSG VGNNISFEEK KKVLIQRQGN 

       130        140        150        160        170        180 
GTFVQTDKPL YTPGQQVYFR IVTMDSNFVP VNDKYSMVEL QDPNSNRIAQ WLEVVPEQGI 

       190        200        210        220        230        240 
VDLSFQLAPE AMLGTYTVAV AEGKTFGTFS VEEYVLPKFK VEVVEPKELS TVQESFLVKI 

       250        260        270        280        290        300 
CCRYTYGKPM LGAVQVSVCQ KANTYWYREV EREQLPDKCR NLSGQTDKTG CFSAPVDMAT 

       310        320        330        340        350        360 
FDLIGYAYSH QINIVATVVE EGTGVEANAT QNIYISPQMG SMTFEDTSNF YHPNFPFSGK 

       370        380        390        400        410        420 
IRVRGHDDSF LKNHLVFLVI YGTNGTFNQT LVTDNNGLAP FTLETSGWNG TDVSLEGKFQ 

       430        440        450        460        470        480 
MEDLVYNPEQ VPRYYQNAYL HLRPFYSTTR SFLGIHRLNG PLKCGQPQEV LVDYYIDPAD 

       490        500        510        520        530        540 
ASPDQEISFS YYLIGKGSLV MEGQKHLNSK KKGLKASFSL SLTFTSRLAP DPSLVIYAIF 

       550        560        570        580        590        600 
PSGGVVADKI QFSVEMCFDN QVSLGFSPSQ QLPGAEVELQ LQAAPGSLCA LRAVDESVLL 

       610        620        630        640        650        660 
LRPDRELSNR SVYGMFPFWY GHYPYQVAEY DQCPVSGPWD FPQPLIDPMP QGHSSQRSII 

       670        680        690        700        710        720 
WRPSFSEGTD LFSFFRDVGL KILSNAKIKK PVDCSHRSPE YSTAMGAGGG HPEAFESSTP 

       730        740        750        760        770        780 
LHQAEDSQVR QYFPETWLWD LFPIGNSGKE AVHVTVPDAI TEWKAMSFCT SQSRGFGLSP 

       790        800        810        820        830        840 
TVGLTAFKPF FVDLTLPYSV VRGESFRLTA TIFNYLKDCI RVQTDLAKSH EYQLESWADS 

       850        860        870        880        890        900 
QTSSCLCADD AKTHHWNITA VKLGHINFTI STKILDSNEP CGGQKGFVPQ KGRSDTLIKP 

       910        920        930        940        950        960 
VLVKPEGVLV EKTHSSLLCP KGKVASESVS LELPVDIVPD STKAYVTVLG DIMGTALQNL 

       970        980        990       1000       1010       1020 
DGLVQMPSGC GEQNMVLFAP IIYVLQYLEK AGLLTEEIRS RAVGFLEIGY QKELMYKHSN 

      1030       1040       1050       1060       1070       1080 
GSYSAFGERD GNGNTWLTAF VTKCFGQAQK FIFIDPKNIQ DALKWMAGNQ LPSGCYANVG 

      1090       1100       1110       1120       1130       1140 
NLLHTAMKGG VDDEVSLTAY VTAALLEMGK DVDDPMVSQG LRCLKNSATS TTNLYTQALL 

      1150       1160       1170       1180       1190       1200 
AYIFSLAGEM DIRNILLKQL DQQAIISGES IYWSQKPTPS SNASPWSEPA AVDVELTAYA 

      1210       1220       1230       1240       1250       1260 
LLAQLTKPSL TQKEIAKATS IVAWLAKQHN AYGGFSSTQD TVVALQALAK YATTAYMPSE 

      1270       1280       1290       1300       1310       1320 
EINLVVKSTE NFQRTFNIQS VNRLVFQQDT LPNVPGMYTL EASGQGCVYV QTVLRYNILP 

      1330       1340       1350       1360       1370       1380 
PTNMKTFSLS VEIGKARCEQ PTSPRSLTLT IHTSYVGSRS SSNMAIVEVK MLSGFSPMEG 

      1390       1400       1410       1420       1430       1440 
TNQLLLQQPL VKKVEFGTDT LNIYLDELIK NTQTYTFTIS QSVLVTNLKP ATIKVYDYYL 

      1450 
PDEQATIQYS DPCE 

« Hide

References

« Hide 'large scale' references
[1]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS GLU-850 AND ARG-1229.
Tissue: Brain and Tongue.
[2]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS GLU-850 AND ARG-1229.
Tissue: Cervix.
[3]"The finished DNA sequence of human chromosome 12."
Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. expand/collapse author list , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1290-1454.
Tissue: Brain.
[5]"A novel protease inhibitor of the alpha2-macroglobulin family expressed in the human epidermis."
Galliano M.-F., Toulza E., Gallinaro H., Jonca N., Ishida-Yamamoto A., Serre G., Guerrin M.
J. Biol. Chem. 281:5780-5789(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
AL832139 mRNA. No translation available.
AC006513 Genomic DNA. No translation available.
AC006581 Genomic DNA. No translation available.
BC093840 mRNA. Translation: AAH93840.2.
BC112131 mRNA. Translation: AAI12132.1.
UniGeneHs.620532.

3D structure databases

ProteinModelPortalA8K2U0.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActA8K2U0. 1 interaction.
STRING9606.ENSP00000299698.

Protein family/group databases

MEROPSI39.007.

PTM databases

PhosphoSiteA8K2U0.

Proteomic databases

PaxDbA8K2U0.
PRIDEA8K2U0.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000299698; ENSP00000299698; ENSG00000166535.
UCSCuc001quz.5. human.

Organism-specific databases

GeneCardsGC12P008975.
HGNCHGNC:23336. A2ML1.
HPAHPA038847.
HPA038848.
MIM610627. gene.
neXtProtNX_A8K2U0.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2373.
HOVERGENHBG000039.
OMAATGIVAW.
OrthoDBEOG7DJSKB.
PhylomeDBA8K2U0.
TreeFamTF313285.

Gene expression databases

ArrayExpressA8K2U0.
BgeeA8K2U0.
CleanExHS_A2ML1.
GenevestigatorA8K2U0.

Family and domain databases

Gene3D1.50.10.20. 1 hit.
2.60.40.690. 1 hit.
InterProIPR009048. A-macroglobulin_rcpt-bd.
IPR011626. A2M_comp.
IPR002890. A2M_N.
IPR011625. A2M_N_2.
IPR014756. Ig_E-set.
IPR001599. Macroglobln_a2.
IPR019742. MacrogloblnA2_CS.
IPR019565. MacrogloblnA2_thiol-ester-bond.
IPR008930. Terpenoid_cyclase/PrenylTrfase.
[Graphical view]
PfamPF00207. 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.
[Graphical view]
SUPFAMSSF48239. SSF48239. 1 hit.
SSF49410. SSF49410. 1 hit.
SSF81296. SSF81296. 1 hit.
PROSITEPS00477. ALPHA_2_MACROGLOBULIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSA2ML1. human.
PROA8K2U0.
SOURCESearch...

Entry information

Entry nameA2ML1_HUMAN
AccessionPrimary (citable) accession number: A8K2U0
Secondary accession number(s): B5MDD1 expand/collapse secondary AC list , Q2M224, Q6ZW52, Q6ZW53, Q8N1M4, Q96LQ8
Entry history
Integrated into UniProtKB/Swiss-Prot: February 5, 2008
Last sequence update: October 5, 2010
Last modified: April 16, 2014
This is version 53 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM