A8K2U0 (A2ML1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1454 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Bait region Signal
Molecular function	Protease inhibitor Serine protease inhibitor
PTM	Disulfide bond Glycoprotein Thioester bond
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of endopeptidase activity Inferred from electronic annotation. Source: GOC
Cellular_component	extracellular space Inferred from direct assay Ref.5. Source: UniProtKB
Molecular_function	peptidase inhibitor activity Inferred from direct assay Ref.5. Source: UniProtKB serine-type endopeptidase inhibitor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 17	17	Potential
	Chain	18 – 1454	1437	Alpha-2-macroglobulin-like protein 1		PRO_0000318074
Regions
	Region	695 – 726	32	Bait region
Amino acid modifications
	Glycosylation	120	1	N-linked (GlcNAc...) Potential
	Glycosylation	281	1	N-linked (GlcNAc...) Potential
	Glycosylation	409	1	N-linked (GlcNAc...) Potential
	Glycosylation	857	1	N-linked (GlcNAc...) Potential
	Glycosylation	1020	1	N-linked (GlcNAc...) Potential
	Disulfide bond	40 ↔ 78		By similarity UniProtKB P01023
	Disulfide bond	241 ↔ 291		By similarity UniProtKB P01023
	Disulfide bond	259 ↔ 279		By similarity UniProtKB P01023
	Disulfide bond	464 ↔ 557		By similarity UniProtKB P01023
	Disulfide bond	589 ↔ 769		By similarity UniProtKB P01023
	Disulfide bond	819 ↔ 847		By similarity UniProtKB P01023
	Disulfide bond	845 ↔ 881		By similarity UniProtKB P01023
	Disulfide bond	919 ↔ 1307		By similarity UniProtKB P01023
	Disulfide bond	1075 ↔ 1123		By similarity UniProtKB P01023
	Disulfide bond	1338 ↔ 1453		By similarity UniProtKB P01023
	Cross-link	970 ↔ 973		Isoglutamyl cysteine thioester (Cys-Gln) By similarity UniProtKB P01023
Natural variations
	Natural variant	207	1	G → R. Corresponds to variant rs11047499 [ dbSNP | Ensembl ].		VAR_055463
	Natural variant	850	1	D → E. Ref.1 Ref.2 Corresponds to variant rs1860926 [ dbSNP | Ensembl ].		VAR_059083
	Natural variant	970	1	C → Y. Corresponds to variant rs1558526 [ dbSNP | Ensembl ].		VAR_055464
	Natural variant	1131	1	T → M. Corresponds to variant rs7959680 [ dbSNP | Ensembl ].		VAR_055465
	Natural variant	1229	1	H → R. Ref.1 Ref.2 Corresponds to variant rs10219561 [ dbSNP | Ensembl ].		VAR_059084
	Natural variant	1412	1	T → A. Corresponds to variant rs7315591 [ dbSNP | Ensembl ].		VAR_055466
Experimental info
	Sequence conflict	733	1	F → L in BAC85654. Ref.1
	Sequence conflict	733	1	F → L in BAF83044. Ref.1
	Sequence conflict	748	1	G → E in AL832139. Ref.2
	Sequence conflict	1122	1	R → W in BAC04793. Ref.1
	Sequence conflict	1122	1	R → W in BAC85653. Ref.1
	Sequence conflict	1122	1	R → W in BAC85654. Ref.1
	Sequence conflict	1122	1	R → W in BAF83044. Ref.1
	Sequence conflict	1122	1	R → W in AL832139. Ref.2
	Sequence conflict	1150	1	M → I in BAF83044. Ref.1
	Sequence conflict	1248	1	L → P in BAC85654. Ref.1
	Sequence conflict	1257	1	M → V in BAC04793. Ref.1
	Sequence conflict	1257	1	M → V in BAC85653. Ref.1
	Sequence conflict	1257	1	M → V in BAC85654. Ref.1
	Sequence conflict	1257	1	M → V in BAF83044. Ref.1
	Sequence conflict	1257	1	M → V in AL832139. Ref.2
	Sequence conflict	1452	1	P → L in AL832139. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	A8K2U0 [UniParc]. Last modified October 5, 2010. Version 3. Checksum: 15ED65D000834E33	FASTA	1,454	161,107
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
IPI	IPI00419215.
UniGene	Hs.620532.
3D structure databases
ProteinModelPortal	A8K2U0.
SMR	A8K2U0. Positions 21-1452.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000299698.
Protein family/group databases
MEROPS	I39.007.
PTM databases
PhosphoSite	A8K2U0.
Proteomic databases
PaxDb	A8K2U0.
PRIDE	A8K2U0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000299698; ENSP00000299698; ENSG00000166535.
UCSC	uc001quz.4. human.
Organism-specific databases
GeneCards	GC12P008975.
HGNC	HGNC:23336. A2ML1.
HPA	HPA038848.
MIM	610627. gene.
neXtProt	NX_A8K2U0.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG2373.
HOVERGEN	HBG000039.
OMA	PSLVIYA.
OrthoDB	EOG4FTVZQ.
Gene expression databases
ArrayExpress	A8K2U0.
Bgee	A8K2U0.
CleanEx	HS_A2ML1.
Genevestigator	A8K2U0.
Family and domain databases
Gene3D	2.60.40.690. 1 hit.
InterPro	IPR009048. A-macroglobulin_rcpt-bd. IPR011626. A2M_comp. IPR002890. A2M_N. IPR011625. A2M_N_2. IPR001599. Macroglobln_a2. IPR019742. MacrogloblnA2_CS. IPR019565. MacrogloblnA2_thiol-ester-bond. IPR008930. Terpenoid_cyclase/PrenylTrfase. [Graphical view]
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. [Graphical view]
SUPFAM	SSF49410. AM_receptor_bind. 1 hit. SSF48239. Terp_cyc_toroid. 1 hit.
PROSITE	PS00477. ALPHA_2_MACROGLOBULIN. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	A2ML1. human.
SOURCE	Search...

Entry information

Entry name

A2ML1_HUMAN

Accession

Primary (citable) accession number: A8K2U0
Secondary accession number(s): B5MDD1 , Q2M224, Q6ZW52, Q6ZW53, Q8N1M4, Q96LQ8

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 5, 2008
Last sequence update:	October 5, 2010
Last modified:	May 1, 2013
This is version 46 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.