ID A2ML1_HUMAN Reviewed; 1454 AA. AC A8K2U0; B5MDD1; B7Z7V4; D3DUV3; F5H2Z2; Q2M224; Q6ZW52; Q6ZW53; Q8N1M4; AC Q96LQ8; DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot. DT 05-OCT-2010, sequence version 3. DT 27-MAR-2024, entry version 125. DE RecName: Full=Alpha-2-macroglobulin-like protein 1; DE AltName: Full=C3 and PZP-like alpha-2-macroglobulin domain-containing protein 9; DE Flags: Precursor; GN Name=A2ML1 {ECO:0000312|EMBL:AAI12132.1}; GN Synonyms=CPAMD9 {ECO:0000312|HGNC:HGNC:23336}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] {ECO:0000312|EMBL:BAF83044.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANTS RP GLU-850; TRP-1122; ARG-1229; VAL-1257 AND MET-1312. RC TISSUE=Brain {ECO:0000312|EMBL:BAB71612.1}, Testis, and Tongue RC {ECO:0000312|EMBL:BAF83044.1}; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS GLU-850; RP TRP-1122; ARG-1229 AND VAL-1257. RC TISSUE=Cervix; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS GLU-850; RP TRP-1122; ARG-1229 AND VAL-1257. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1290-1454. RC TISSUE=Brain {ECO:0000312|EMBL:AAI12132.1}; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND RP DEVELOPMENTAL STAGE. RX PubMed=16298998; DOI=10.1074/jbc.m508017200; RA Galliano M.-F., Toulza E., Gallinaro H., Jonca N., Ishida-Yamamoto A., RA Serre G., Guerrin M.; RT "A novel protease inhibitor of the alpha2-macroglobulin family expressed in RT the human epidermis."; RL J. Biol. Chem. 281:5780-5789(2006). RN [7] RP INVOLVEMENT IN OM, AND VARIANTS 255-GLN--GLU-1454 DEL; ALA-296; ARG-356; RP 893-ARG--GLU-1454 DEL; 972-GLU--GLU-1454 DEL; TRP-1001 AND VAL-1431. RX PubMed=26121085; DOI=10.1038/ng.3347; RG University of Washington Center for Mendelian Genomics; RA Santos-Cortez R.L., Chiong C.M., Reyes-Quintos M.R., Tantoco M.L., Wang X., RA Acharya A., Abbe I., Giese A.P., Smith J.D., Allen E.K., Li B., RA Cutiongco-de la Paz E.M., Garcia M.C., Llanes E.G., Labra P.J., RA Gloria-Cruz T.L., Chan A.L., Wang G.T., Daly K.A., Shendure J., RA Bamshad M.J., Nickerson D.A., Patel J.A., Riazuddin S., Sale M.M., RA Chonmaitree T., Ahmed Z.M., Abes G.T., Leal S.M.; RT "Rare A2ML1 variants confer susceptibility to otitis media."; RL Nat. Genet. 47:917-920(2015). CC -!- FUNCTION: Is able to inhibit all four classes of proteinases by a CC unique 'trapping' mechanism. This protein has a peptide stretch, called CC the 'bait region' which contains specific cleavage sites for different CC proteinases. When a proteinase cleaves the bait region, a CC conformational change is induced in the protein which traps the CC proteinase. The entrapped enzyme remains active against low molecular CC weight substrates (activity against high molecular weight substrates is CC greatly reduced). Following cleavage in the bait region a thioester CC bond is hydrolyzed and mediates the covalent binding of the protein to CC the proteinase (By similarity). Displays inhibitory activity against CC chymotrypsin, papain, thermolysin, subtilisin A and, to a lesser CC extent, elastase but not trypsin. May play an important role during CC desquamation by inhibiting extracellular proteases. CC {ECO:0000250|UniProtKB:P01023, ECO:0000269|PubMed:16298998}. CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:16298998}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16298998}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=A8K2U0-1; Sequence=Displayed; CC Name=2; CC IsoId=A8K2U0-2; Sequence=VSP_057135; CC -!- TISSUE SPECIFICITY: In the epidermis, expressed predominantly in the CC granular layer at the apical edge of keratinocytes (at protein level). CC Also detected in placenta, testis and thymus but not in epithelia of CC kidney, lung, small intestine or colon. {ECO:0000269|PubMed:16298998}. CC -!- DEVELOPMENTAL STAGE: Up-regulated during keratinocyte differentiation. CC {ECO:0000269|PubMed:16298998}. CC -!- DISEASE: Otitis media (OM) [MIM:166760]: An inflammation of the middle CC ear resulting in earache, fever, hearing disturbance, and vertigo. CC {ECO:0000269|PubMed:26121085}. Note=Disease susceptibility is CC associated with variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the protease inhibitor I39 (alpha-2- CC macroglobulin) family. {ECO:0000255}. CC -!- SEQUENCE CAUTION: CC Sequence=BAB71612.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAC04793.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAC85653.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAC85654.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK057908; BAB71612.1; ALT_INIT; mRNA. DR EMBL; AK096448; BAC04793.1; ALT_INIT; mRNA. DR EMBL; AK123591; BAC85653.1; ALT_INIT; mRNA. DR EMBL; AK123592; BAC85654.1; ALT_INIT; mRNA. DR EMBL; AK290355; BAF83044.1; -; mRNA. DR EMBL; AK302555; BAH13740.1; -; mRNA. DR EMBL; AL832139; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AC006513; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC006581; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471116; EAW88603.1; -; Genomic_DNA. DR EMBL; CH471116; EAW88606.1; -; Genomic_DNA. DR EMBL; BC093840; AAH93840.2; -; mRNA. DR EMBL; BC112131; AAI12132.1; -; mRNA. DR CCDS; CCDS73439.1; -. [A8K2U0-2] DR CCDS; CCDS8596.2; -. [A8K2U0-1] DR RefSeq; NP_001269353.1; NM_001282424.2. [A8K2U0-2] DR RefSeq; XP_016874359.1; XM_017018870.1. [A8K2U0-1] DR PDB; 7Q1Y; X-ray; 4.40 A; A/B=19-1454. DR PDB; 7Q5Z; EM; 3.25 A; A=19-1454. DR PDB; 7Q60; EM; 3.13 A; A=19-1454. DR PDB; 7Q61; EM; 2.88 A; A=19-1454. DR PDB; 7Q62; EM; 3.18 A; A/B=19-1454. DR PDBsum; 7Q1Y; -. DR PDBsum; 7Q5Z; -. DR PDBsum; 7Q60; -. DR PDBsum; 7Q61; -. DR PDBsum; 7Q62; -. DR AlphaFoldDB; A8K2U0; -. DR EMDB; EMD-13847; -. DR EMDB; EMD-13848; -. DR EMDB; EMD-13849; -. DR EMDB; EMD-13850; -. DR SMR; A8K2U0; -. DR IntAct; A8K2U0; 28. DR MINT; A8K2U0; -. DR STRING; 9606.ENSP00000299698; -. DR MEROPS; I39.007; -. DR GlyConnect; 1003; 3 N-Linked glycans (4 sites). DR GlyCosmos; A8K2U0; 6 sites, 3 glycans. DR GlyGen; A8K2U0; 6 sites, 3 N-linked glycans (4 sites). DR iPTMnet; A8K2U0; -. DR PhosphoSitePlus; A8K2U0; -. DR BioMuta; A2ML1; -. DR EPD; A8K2U0; -. DR MassIVE; A8K2U0; -. DR MaxQB; A8K2U0; -. DR PaxDb; 9606-ENSP00000299698; -. DR PeptideAtlas; A8K2U0; -. DR PRIDE; A8K2U0; -. DR ProteomicsDB; 1852; -. [A8K2U0-1] DR ProteomicsDB; 26118; -. DR Antibodypedia; 23090; 137 antibodies from 18 providers. DR DNASU; 144568; -. DR Ensembl; ENST00000299698.12; ENSP00000299698.7; ENSG00000166535.20. [A8K2U0-1] DR Ensembl; ENST00000539547.5; ENSP00000438292.1; ENSG00000166535.20. [A8K2U0-2] DR GeneID; 144568; -. DR KEGG; hsa:144568; -. DR MANE-Select; ENST00000299698.12; ENSP00000299698.7; NM_144670.6; NP_653271.3. DR UCSC; uc001quz.6; human. [A8K2U0-1] DR AGR; HGNC:23336; -. DR CTD; 144568; -. DR DisGeNET; 144568; -. DR GeneCards; A2ML1; -. DR HGNC; HGNC:23336; A2ML1. DR HPA; ENSG00000166535; Tissue enhanced (esophagus, vagina). DR MalaCards; A2ML1; -. DR MIM; 166760; phenotype. DR MIM; 610627; gene. DR neXtProt; NX_A8K2U0; -. DR OpenTargets; ENSG00000166535; -. DR VEuPathDB; HostDB:ENSG00000166535; -. DR eggNOG; KOG1366; Eukaryota. DR GeneTree; ENSGT00940000163018; -. DR HOGENOM; CLU_001634_0_0_1; -. DR InParanoid; A8K2U0; -. DR OMA; YQNAYLH; -. DR OrthoDB; 2970602at2759; -. DR PhylomeDB; A8K2U0; -. DR TreeFam; TF313285; -. DR PathwayCommons; A8K2U0; -. DR SignaLink; A8K2U0; -. DR BioGRID-ORCS; 144568; 12 hits in 1146 CRISPR screens. DR ChiTaRS; A2ML1; human. DR GenomeRNAi; 144568; -. DR Pharos; A8K2U0; Tbio. DR PRO; PR:A8K2U0; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; A8K2U0; Protein. DR Bgee; ENSG00000166535; Expressed in lower esophagus mucosa and 116 other cell types or tissues. DR ExpressionAtlas; A8K2U0; baseline and differential. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0030414; F:peptidase inhibitor activity; IDA:UniProtKB. DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW. DR GO; GO:0052548; P:regulation of endopeptidase activity; IDA:UniProtKB. DR CDD; cd02897; A2M_2; 1. DR Gene3D; 1.50.10.20; -; 1. DR Gene3D; 2.20.130.20; -; 1. DR Gene3D; 2.60.120.1540; -; 1. DR Gene3D; 2.60.40.1930; -; 2. DR Gene3D; 2.60.40.1940; -; 1. DR Gene3D; 6.20.50.160; -; 1. DR Gene3D; 2.60.40.690; Alpha-macroglobulin, receptor-binding domain; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 2. DR InterPro; IPR009048; A-macroglobulin_rcpt-bd. DR InterPro; IPR036595; A-macroglobulin_rcpt-bd_sf. DR InterPro; IPR011625; A2M_N_BRD. DR InterPro; IPR041813; A2M_TED. DR InterPro; IPR047565; Alpha-macroglob_thiol-ester_cl. DR InterPro; IPR011626; Alpha-macroglobulin_TED. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR014756; Ig_E-set. DR InterPro; IPR001599; Macroglobln_a2. DR InterPro; IPR019742; MacrogloblnA2_CS. DR InterPro; IPR002890; MG2. DR InterPro; IPR041555; MG3. DR InterPro; IPR040839; MG4. DR InterPro; IPR008930; Terpenoid_cyclase/PrenylTrfase. DR PANTHER; PTHR11412:SF178; ALPHA-2-MACROGLOBULIN-LIKE PROTEIN 1; 1. DR PANTHER; PTHR11412; MACROGLOBULIN / COMPLEMENT; 1. DR Pfam; PF00207; A2M; 1. DR Pfam; PF07703; A2M_BRD; 1. DR Pfam; PF07677; A2M_recep; 1. DR Pfam; PF01835; MG2; 1. DR Pfam; PF17791; MG3; 1. DR Pfam; PF17789; MG4; 1. DR Pfam; PF07678; TED_complement; 1. DR SMART; SM01360; A2M; 1. DR SMART; SM01359; A2M_N_2; 1. DR SMART; SM01361; A2M_recep; 1. DR SMART; SM01419; Thiol-ester_cl; 1. DR SUPFAM; SSF49410; Alpha-macroglobulin receptor domain; 1. DR SUPFAM; SSF81296; E set domains; 1. DR SUPFAM; SSF48239; Terpenoid cyclases/Protein prenyltransferases; 1. DR PROSITE; PS00477; ALPHA_2_MACROGLOBULIN; 1. DR Genevisible; A8K2U0; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Bait region; Disulfide bond; KW Glycoprotein; Protease inhibitor; Reference proteome; Secreted; KW Serine protease inhibitor; Signal; Thioester bond. FT SIGNAL 1..17 FT /evidence="ECO:0000255" FT CHAIN 18..1454 FT /note="Alpha-2-macroglobulin-like protein 1" FT /evidence="ECO:0000255" FT /id="PRO_0000318074" FT REGION 695..726 FT /note="Bait region" FT /evidence="ECO:0000255" FT CARBOHYD 120 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 281 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 409 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 857 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1020 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 40..78 FT /evidence="ECO:0000250|UniProtKB:P01023" FT DISULFID 241..291 FT /evidence="ECO:0000250|UniProtKB:P01023" FT DISULFID 259..279 FT /evidence="ECO:0000250|UniProtKB:P01023" FT DISULFID 464..557 FT /evidence="ECO:0000250|UniProtKB:P01023" FT DISULFID 589..769 FT /evidence="ECO:0000250|UniProtKB:P01023" FT DISULFID 819..847 FT /evidence="ECO:0000250|UniProtKB:P01023" FT DISULFID 845..881 FT /evidence="ECO:0000250|UniProtKB:P01023" FT DISULFID 919..1307 FT /evidence="ECO:0000250|UniProtKB:P01023" FT DISULFID 1075..1123 FT /evidence="ECO:0000250|UniProtKB:P01023" FT DISULFID 1338..1453 FT /evidence="ECO:0000250|UniProtKB:P01023" FT CROSSLNK 970..973 FT /note="Isoglutamyl cysteine thioester (Cys-Gln)" FT /evidence="ECO:0000250|UniProtKB:P01023" FT VAR_SEQ 2..492 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_057135" FT VARIANT 207 FT /note="G -> R (in dbSNP:rs11047499)" FT /id="VAR_055463" FT VARIANT 255..1454 FT /note="Missing (risk factor for otitis media)" FT /evidence="ECO:0000269|PubMed:26121085" FT /id="VAR_081009" FT VARIANT 296 FT /note="V -> A (in dbSNP:rs192888493)" FT /evidence="ECO:0000269|PubMed:26121085" FT /id="VAR_081010" FT VARIANT 356 FT /note="P -> R (may be a risk factor for otitis media; FT dbSNP:rs863224953)" FT /evidence="ECO:0000269|PubMed:26121085" FT /id="VAR_081011" FT VARIANT 850 FT /note="D -> E (in dbSNP:rs1860926)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:17974005, ECO:0000269|Ref.4" FT /id="VAR_059083" FT VARIANT 893..1454 FT /note="Missing (risk factor for otitis media)" FT /evidence="ECO:0000269|PubMed:26121085" FT /id="VAR_081012" FT VARIANT 970 FT /note="C -> Y (in dbSNP:rs1558526)" FT /id="VAR_055464" FT VARIANT 972..1454 FT /note="Missing (risk factor for otitis media)" FT /evidence="ECO:0000269|PubMed:26121085" FT /id="VAR_081013" FT VARIANT 1001 FT /note="R -> W (may be a risk factor for otitis media; FT dbSNP:rs201725377)" FT /evidence="ECO:0000269|PubMed:26121085" FT /id="VAR_081014" FT VARIANT 1122 FT /note="R -> W (in dbSNP:rs1860967)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:17974005, ECO:0000269|Ref.4" FT /id="VAR_071854" FT VARIANT 1131 FT /note="T -> M (in dbSNP:rs7959680)" FT /id="VAR_055465" FT VARIANT 1229 FT /note="H -> R (in dbSNP:rs10219561)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:17974005, ECO:0000269|Ref.4" FT /id="VAR_059084" FT VARIANT 1257 FT /note="M -> V (in dbSNP:rs7308811)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:17974005, ECO:0000269|Ref.4" FT /id="VAR_071855" FT VARIANT 1312 FT /note="T -> M (in dbSNP:rs201083574)" FT /evidence="ECO:0000269|PubMed:14702039" FT /id="VAR_071856" FT VARIANT 1412 FT /note="T -> A (in dbSNP:rs7315591)" FT /id="VAR_055466" FT VARIANT 1431 FT /note="A -> V (in dbSNP:rs863224955)" FT /evidence="ECO:0000269|PubMed:26121085" FT /id="VAR_081015" FT CONFLICT 733 FT /note="F -> L (in Ref. 1; BAC85654/BAF83044)" FT /evidence="ECO:0000305" FT CONFLICT 748 FT /note="G -> E (in Ref. 2; AL832139)" FT /evidence="ECO:0000305" FT CONFLICT 1150 FT /note="M -> I (in Ref. 1; BAF83044)" FT /evidence="ECO:0000305" FT CONFLICT 1248 FT /note="L -> P (in Ref. 1; BAC85654)" FT /evidence="ECO:0000305" FT CONFLICT 1452 FT /note="P -> L (in Ref. 2; AL832139)" FT /evidence="ECO:0000305" FT STRAND 24..32 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 35..42 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 51..57 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 62..69 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 76..82 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 87..102 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 105..116 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 121..127 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 129..131 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 136..144 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 155..161 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 167..174 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 180..186 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 194..200 FT /evidence="ECO:0007829|PDB:7Q61" FT TURN 201..204 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 205..211 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 219..223 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 227..232 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 234..244 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 252..262 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 269..271 FT /evidence="ECO:0007829|PDB:7Q62" FT STRAND 278..285 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 291..297 FT /evidence="ECO:0007829|PDB:7Q61" FT HELIX 298..300 FT /evidence="ECO:0007829|PDB:7Q5Z" FT STRAND 306..320 FT /evidence="ECO:0007829|PDB:7Q61" FT TURN 321..323 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 326..336 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 338..347 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 349..351 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 357..364 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 366..368 FT /evidence="ECO:0007829|PDB:7Q60" FT STRAND 375..382 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 388..392 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 398..403 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 406..408 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 413..419 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 428..430 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 434..436 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 438..444 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 448..450 FT /evidence="ECO:0007829|PDB:7Q60" FT STRAND 452..455 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 466..475 FT /evidence="ECO:0007829|PDB:7Q61" FT TURN 479..481 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 483..485 FT /evidence="ECO:0007829|PDB:7Q5Z" FT STRAND 487..495 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 498..507 FT /evidence="ECO:0007829|PDB:7Q61" FT HELIX 509..511 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 516..523 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 526..528 FT /evidence="ECO:0007829|PDB:7Q60" FT STRAND 533..539 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 541..543 FT /evidence="ECO:0007829|PDB:7Q5Z" FT STRAND 545..551 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 563..571 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 575..582 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 588..595 FT /evidence="ECO:0007829|PDB:7Q61" FT HELIX 596..601 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 603..606 FT /evidence="ECO:0007829|PDB:7Q5Z" FT HELIX 609..614 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 625..627 FT /evidence="ECO:0007829|PDB:7Q61" FT HELIX 671..676 FT /evidence="ECO:0007829|PDB:7Q61" FT TURN 677..679 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 680..687 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 735..743 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 748..755 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 760..771 FT /evidence="ECO:0007829|PDB:7Q61" FT TURN 772..774 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 775..778 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 782..786 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 789..795 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 798..801 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 804..814 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 816..818 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 820..826 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 832..834 FT /evidence="ECO:0007829|PDB:7Q61" FT HELIX 838..840 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 841..846 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 850..860 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 864..874 FT /evidence="ECO:0007829|PDB:7Q61" FT HELIX 881..883 FT /evidence="ECO:0007829|PDB:7Q60" FT STRAND 890..892 FT /evidence="ECO:0007829|PDB:7Q60" FT STRAND 894..904 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 906..918 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 921..930 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 943..953 FT /evidence="ECO:0007829|PDB:7Q61" FT TURN 956..963 FT /evidence="ECO:0007829|PDB:7Q61" FT HELIX 971..973 FT /evidence="ECO:0007829|PDB:7Q61" FT HELIX 975..989 FT /evidence="ECO:0007829|PDB:7Q61" FT TURN 990..992 FT /evidence="ECO:0007829|PDB:7Q61" FT HELIX 996..1010 FT /evidence="ECO:0007829|PDB:7Q61" FT HELIX 1011..1013 FT /evidence="ECO:0007829|PDB:7Q62" FT HELIX 1014..1016 FT /evidence="ECO:0007829|PDB:7Q5Z" FT STRAND 1021..1023 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 1025..1028 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 1030..1032 FT /evidence="ECO:0007829|PDB:7Q61" FT HELIX 1035..1045 FT /evidence="ECO:0007829|PDB:7Q61" FT HELIX 1048..1050 FT /evidence="ECO:0007829|PDB:7Q61" FT HELIX 1057..1069 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 1072..1075 FT /evidence="ECO:0007829|PDB:7Q62" FT STRAND 1079..1081 FT /evidence="ECO:0007829|PDB:7Q5Z" FT STRAND 1083..1086 FT /evidence="ECO:0007829|PDB:7Q61" FT TURN 1087..1089 FT /evidence="ECO:0007829|PDB:7Q5Z" FT HELIX 1094..1105 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 1106..1109 FT /evidence="ECO:0007829|PDB:7Q61" FT HELIX 1115..1124 FT /evidence="ECO:0007829|PDB:7Q61" FT HELIX 1127..1130 FT /evidence="ECO:0007829|PDB:7Q61" FT HELIX 1135..1143 FT /evidence="ECO:0007829|PDB:7Q61" FT TURN 1144..1148 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 1150..1154 FT /evidence="ECO:0007829|PDB:7Q61" FT TURN 1155..1160 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 1163..1167 FT /evidence="ECO:0007829|PDB:7Q5Z" FT STRAND 1170..1173 FT /evidence="ECO:0007829|PDB:7Q5Z" FT HELIX 1192..1204 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 1205..1208 FT /evidence="ECO:0007829|PDB:7Q60" FT HELIX 1212..1225 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 1230..1234 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 1236..1239 FT /evidence="ECO:0007829|PDB:7Q61" FT HELIX 1240..1254 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 1260..1268 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 1269..1271 FT /evidence="ECO:0007829|PDB:7Q60" FT STRAND 1274..1278 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 1280..1282 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 1287..1290 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 1295..1306 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 1308..1318 FT /evidence="ECO:0007829|PDB:7Q61" FT STRAND 1325..1332 FT /evidence="ECO:0007829|PDB:7Q5Z" FT STRAND 1338..1340 FT /evidence="ECO:0007829|PDB:7Q5Z" FT STRAND 1347..1355 FT /evidence="ECO:0007829|PDB:7Q5Z" FT STRAND 1357..1361 FT /evidence="ECO:0007829|PDB:7Q5Z" FT STRAND 1365..1370 FT /evidence="ECO:0007829|PDB:7Q5Z" FT TURN 1378..1380 FT /evidence="ECO:0007829|PDB:7Q5Z" FT HELIX 1381..1386 FT /evidence="ECO:0007829|PDB:7Q5Z" FT STRAND 1393..1396 FT /evidence="ECO:0007829|PDB:7Q5Z" FT STRAND 1398..1406 FT /evidence="ECO:0007829|PDB:7Q5Z" FT STRAND 1413..1423 FT /evidence="ECO:0007829|PDB:7Q5Z" FT STRAND 1425..1427 FT /evidence="ECO:0007829|PDB:7Q5Z" FT STRAND 1431..1439 FT /evidence="ECO:0007829|PDB:7Q5Z" FT STRAND 1443..1449 FT /evidence="ECO:0007829|PDB:7Q5Z" SQ SEQUENCE 1454 AA; 161107 MW; 15ED65D000834E33 CRC64; MWAQLLLGML ALSPAIAEEL PNYLVTLPAR LNFPSVQKVC LDLSPGYSDV KFTVTLETKD KTQKLLEYSG LKKRHLHCIS FLVPPPAGGT EEVATIRVSG VGNNISFEEK KKVLIQRQGN GTFVQTDKPL YTPGQQVYFR IVTMDSNFVP VNDKYSMVEL QDPNSNRIAQ WLEVVPEQGI VDLSFQLAPE AMLGTYTVAV AEGKTFGTFS VEEYVLPKFK VEVVEPKELS TVQESFLVKI CCRYTYGKPM LGAVQVSVCQ KANTYWYREV EREQLPDKCR NLSGQTDKTG CFSAPVDMAT FDLIGYAYSH QINIVATVVE EGTGVEANAT QNIYISPQMG SMTFEDTSNF YHPNFPFSGK IRVRGHDDSF LKNHLVFLVI YGTNGTFNQT LVTDNNGLAP FTLETSGWNG TDVSLEGKFQ MEDLVYNPEQ VPRYYQNAYL HLRPFYSTTR SFLGIHRLNG PLKCGQPQEV LVDYYIDPAD ASPDQEISFS YYLIGKGSLV MEGQKHLNSK KKGLKASFSL SLTFTSRLAP DPSLVIYAIF PSGGVVADKI QFSVEMCFDN QVSLGFSPSQ QLPGAEVELQ LQAAPGSLCA LRAVDESVLL LRPDRELSNR SVYGMFPFWY GHYPYQVAEY DQCPVSGPWD FPQPLIDPMP QGHSSQRSII WRPSFSEGTD LFSFFRDVGL KILSNAKIKK PVDCSHRSPE YSTAMGAGGG HPEAFESSTP LHQAEDSQVR QYFPETWLWD LFPIGNSGKE AVHVTVPDAI TEWKAMSFCT SQSRGFGLSP TVGLTAFKPF FVDLTLPYSV VRGESFRLTA TIFNYLKDCI RVQTDLAKSH EYQLESWADS QTSSCLCADD AKTHHWNITA VKLGHINFTI STKILDSNEP CGGQKGFVPQ KGRSDTLIKP VLVKPEGVLV EKTHSSLLCP KGKVASESVS LELPVDIVPD STKAYVTVLG DIMGTALQNL DGLVQMPSGC GEQNMVLFAP IIYVLQYLEK AGLLTEEIRS RAVGFLEIGY QKELMYKHSN GSYSAFGERD GNGNTWLTAF VTKCFGQAQK FIFIDPKNIQ DALKWMAGNQ LPSGCYANVG NLLHTAMKGG VDDEVSLTAY VTAALLEMGK DVDDPMVSQG LRCLKNSATS TTNLYTQALL AYIFSLAGEM DIRNILLKQL DQQAIISGES IYWSQKPTPS SNASPWSEPA AVDVELTAYA LLAQLTKPSL TQKEIAKATS IVAWLAKQHN AYGGFSSTQD TVVALQALAK YATTAYMPSE EINLVVKSTE NFQRTFNIQS VNRLVFQQDT LPNVPGMYTL EASGQGCVYV QTVLRYNILP PTNMKTFSLS VEIGKARCEQ PTSPRSLTLT IHTSYVGSRS SSNMAIVEVK MLSGFSPMEG TNQLLLQQPL VKKVEFGTDT LNIYLDELIK NTQTYTFTIS QSVLVTNLKP ATIKVYDYYL PDEQATIQYS DPCE //