A2ML1_HUMAN
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 03-AUG-2022, entry version 117.
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
RC Tongue {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};
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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 AlphaFoldDB; A8K2U0; -.
DR SMR; A8K2U0; -.
DR IntAct; A8K2U0; 27.
DR MINT; A8K2U0; -.
DR STRING; 9606.ENSP00000299698; -.
DR MEROPS; I39.007; -.
DR GlyConnect; 1003; 3 N-Linked glycans (4 sites).
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; A8K2U0; -.
DR PeptideAtlas; A8K2U0; -.
DR PRIDE; A8K2U0; -.
DR ProteomicsDB; 1852; -. [A8K2U0-1]
DR ProteomicsDB; 26118; -.
DR Antibodypedia; 23090; 121 antibodies from 17 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 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; VSVCQKA; -.
DR OrthoDB; 354230at2759; -.
DR PhylomeDB; A8K2U0; -.
DR TreeFam; TF313285; -.
DR PathwayCommons; A8K2U0; -.
DR SignaLink; A8K2U0; -.
DR BioGRID-ORCS; 144568; 11 hits in 1070 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 114 other tissues.
DR ExpressionAtlas; A8K2U0; baseline and differential.
DR Genevisible; A8K2U0; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; IBA:GO_Central.
DR GO; GO:0030414; F:peptidase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0002020; F:protease binding; IBA:GO_Central.
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; 2.60.40.10; -; 2.
DR Gene3D; 2.60.40.690; -; 1.
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; 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 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 SUPFAM; SSF48239; SSF48239; 1.
DR SUPFAM; SSF49410; SSF49410; 1.
DR SUPFAM; SSF81296; SSF81296; 1.
DR PROSITE; PS00477; ALPHA_2_MACROGLOBULIN; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Bait region; Disulfide bond; Glycoprotein;
KW 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"
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
