ID AACT_HUMAN Reviewed; 423 AA. AC P01011; B3KVQ7; Q13703; Q2TU87; Q2TU88; Q59GP9; Q6LBY8; Q6LDT7; Q6NSC9; AC Q8N177; Q96DW8; Q9UC47; Q9UNU9; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1991, sequence version 2. DT 27-MAR-2024, entry version 253. DE RecName: Full=Alpha-1-antichymotrypsin; DE Short=ACT; DE AltName: Full=Cell growth-inhibiting gene 24/25 protein; DE AltName: Full=Serpin A3; DE Contains: DE RecName: Full=Alpha-1-antichymotrypsin His-Pro-less; DE Flags: Precursor; GN Name=SERPINA3; Synonyms=AACT; ORFNames=GIG24, GIG25; 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] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Liver; RX PubMed=6606438; DOI=10.1021/bi00291a001; RA Chandra T., Stackhouse R., Kidd V.J., Robson K.J.H., Woo S.L.C.; RT "Sequence homology between human alpha 1-antichymotrypsin, alpha 1- RT antitrypsin, and antithrombin III."; RL Biochemistry 22:5055-5061(1983). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS PRO-78 AND ALA-252. RX PubMed=8244391; DOI=10.1006/geno.1993.1396; RA Poller W., Faber J.-P., Weidinger S., Tief K., Scholz S., Fischer M., RA Olek K., Kirchgesser M., Heidtmann H.-H.; RT "A leucine-to-proline substitution causes a defective alpha 1- RT antichymotrypsin allele associated with familial obstructive lung RT disease."; RL Genomics 17:740-743(1993). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT THR-9. RA Kim J.W.; RT "Identification of a human cell growth inhibiting gene."; RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT THR-9. RC TISSUE=Urinary bladder; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT THR-9. RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANTS RP THR-9 AND ARG-267. RC TISSUE=Brain, Liver, and Skin; 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 [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-46, AND TISSUE SPECIFICITY. RC TISSUE=Liver; RX PubMed=3257719; DOI=10.1016/0092-8674(88)90462-x; RA Abraham C.R., Selkoe D.J., Potter H.; RT "Immunochemical identification of the serine protease inhibitor alpha 1- RT antichymotrypsin in the brain amyloid deposits of Alzheimer's disease."; RL Cell 52:487-501(1988). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 17-423 (ISOFORM 1), AND TISSUE SPECIFICITY. RC TISSUE=Hippocampus; RX PubMed=9880565; DOI=10.1074/jbc.274.3.1821; RA Hwang S.-R., Steineckert B., Kohn A., Palkovits M., Hook V.Y.H.; RT "Molecular studies define the primary structure of alpha1-antichymotrypsin RT (ACT) protease inhibitor in Alzheimer's disease brains. Comparison of act RT in hippocampus and liver."; RL J. Biol. Chem. 274:1821-1827(1999). RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 22-86 AND 130-423 (ISOFORM 1). RA Rubin H.; RL Submitted (OCT-1989) to the EMBL/GenBank/DDBJ databases. RN [10] RP PROTEIN SEQUENCE OF 24-34. RX PubMed=2787670; DOI=10.1016/0167-4838(89)90139-8; RA Lindmark B., Hilja H., Alan R., Eriksson S.; RT "The microheterogeneity of desialylated alpha 1-antichymotrypsin: the RT occurrence of two amino-terminal isoforms, one lacking a His-Pro RT dipeptide."; RL Biochim. Biophys. Acta 997:90-95(1989). RN [11] RP NUCLEOTIDE SEQUENCE [MRNA] OF 36-45. RX PubMed=7521171; DOI=10.1515/bchm3.1994.375.5.335; RA Korzus E., Luisetti M., Travis J.; RT "Interactions of alpha-1-antichymotrypsin, alpha-1-proteinase inhibitor, RT and alpha-2-macroglobulin with the fungal enzyme, seaprose."; RL Biol. Chem. Hoppe-Seyler 375:335-341(1994). RN [12] RP PROTEIN SEQUENCE OF 41-60. RX PubMed=6687683; DOI=10.1016/0006-291x(83)90325-x; RA Morii M., Travis J.; RT "Structural alterations in alpha 1-antichymotrypsin from normal and acute RT phase human plasma."; RL Biochem. Biophys. Res. Commun. 111:438-443(1983). RN [13] RP PROTEIN SEQUENCE OF 48-68 (ISOFORMS 1/2). RX PubMed=8647626; RX DOI=10.1002/(sici)1097-0215(19960529)66:5<636::aid-ijc10>3.0.co;2-2; RA Pinczower G.D., Williams R.P.W., Gianello R.D., Robinson H.C., RA Preston B.N., Linnane A.W.; RT "Characterisation of the tumour-associated carbohydrate epitope recognised RT by monoclonal antibody 4D3."; RL Int. J. Cancer 66:636-644(1996). RN [14] RP NUCLEOTIDE SEQUENCE [MRNA] OF 87-129 (ISOFORMS 1/2), AND FUNCTION. RC TISSUE=Liver; RX PubMed=2404007; DOI=10.1016/s0021-9258(19)40178-6; RA Rubin H., Wang Z., Nickbarg E.B., McLarney S., Naidoo N., RA Schoenberger O.L., Johnson J.L., Cooperman B.S.; RT "Cloning, expression, purification, and biological activity of recombinant RT native and variant human alpha 1-antichymotrypsins."; RL J. Biol. Chem. 265:1199-1207(1990). RN [15] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 205-423. RX PubMed=6547997; DOI=10.1038/311175a0; RA Hill R.E., Shaw P.H., Boyd P.A., Baumann H., Hastie N.D.; RT "Plasma protease inhibitors in mouse and man: divergence within the RT reactive centre regions."; RL Nature 311:175-177(1984). RN [16] RP REACTIVE SITE. RX PubMed=6556193; DOI=10.1016/s0021-9258(17)44026-9; RA Morii M., Travis J.; RT "Amino acid sequence at the reactive site of human alpha 1- RT antichymotrypsin."; RL J. Biol. Chem. 258:12749-12752(1983). RN [17] RP GLYCOSYLATION AT ASN-93 AND ASN-106. RX PubMed=12754519; DOI=10.1038/nbt827; RA Zhang H., Li X.-J., Martin D.B., Aebersold R.; RT "Identification and quantification of N-linked glycoproteins using RT hydrazide chemistry, stable isotope labeling and mass spectrometry."; RL Nat. Biotechnol. 21:660-666(2003). RN [18] RP INTERACTION WITH DNAJC1. RX PubMed=14668352; DOI=10.1074/jbc.m310903200; RA Kroczynska B., Evangelista C.M., Samant S.S., Elguindi E.C., Blond S.Y.; RT "The SANT2 domain of the murine tumor cell DnaJ-like protein 1 human RT homologue interacts with alpha1-antichymotrypsin and kinetically interferes RT with its serpin inhibitory activity."; RL J. Biol. Chem. 279:11432-11443(2004). RN [19] RP REGION RCL. RX PubMed=15638460; DOI=10.1007/s00239-004-2640-9; RA Horvath A.J., Forsyth S.L., Coughlin P.B.; RT "Expression patterns of murine antichymotrypsin-like genes reflect RT evolutionary divergence at the Serpina3 locus."; RL J. Mol. Evol. 59:488-497(2004). RN [20] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-93. RC TISSUE=Plasma; RX PubMed=14760718; DOI=10.1002/pmic.200300556; RA Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.; RT "Screening for N-glycosylated proteins by liquid chromatography mass RT spectrometry."; RL Proteomics 4:454-465(2004). RN [21] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-33; ASN-93; ASN-106; ASN-127; RP ASN-186 AND ASN-271. RC TISSUE=Plasma; RX PubMed=16335952; DOI=10.1021/pr0502065; RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., RA Smith R.D.; RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, RT hydrazide chemistry, and mass spectrometry."; RL J. Proteome Res. 4:2070-2080(2005). RN [22] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-93; ASN-106; ASN-127 AND RP ASN-271. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of multiple RT enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [23] RP GLYCOSYLATION, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=23234360; DOI=10.1021/pr300963h; RA Halim A., Ruetschi U., Larson G., Nilsson J.; RT "LC-MS/MS characterization of O-glycosylation sites and glycan structures RT of human cerebrospinal fluid glycoproteins."; RL J. Proteome Res. 12:573-584(2013). RN [24] RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 24-423. RX PubMed=2016749; DOI=10.1016/0022-2836(91)90704-a; RA Baumann U., Huber R., Bode W., Grosse D., Lesjak M., Laurell C.-B.; RT "Crystal structure of cleaved human alpha 1-antichymotrypsin at 2.7-A RT resolution and its comparison with other serpins."; RL J. Mol. Biol. 218:595-606(1991). RN [25] RP X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) OF 43-423 OF MUTANTS ARG-370 AND RP ARG-372. RX PubMed=8836107; DOI=10.1038/nsb1096-888; RA Lukacs C.M., Zhong J.Q., Plotnick M.I., Rubin H., Cooperman B.S., RA Christianson D.W.; RT "Arginine substitutions in the hinge region of antichymotrypsin affect RT serpin beta-sheet rearrangement."; RL Nat. Struct. Biol. 3:888-893(1996). RN [26] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 43-423 OF MUTANTS ARG-370; ARG-372 RP AND ARG-374. RX PubMed=9521649; DOI=10.1021/bi972359e; RA Lukacs C.M., Rubin H., Christianson D.W.; RT "Engineering an anion-binding cavity in antichymotrypsin modulates the RT 'spring-loaded' serpin-protease interaction."; RL Biochemistry 37:3297-3304(1998). RN [27] RP X-RAY CRYSTALLOGRAPHY (2.27 ANGSTROMS) OF 26-423. RX PubMed=10618372; DOI=10.1073/pnas.97.1.67; RA Gooptu B., Hazes B., Chang W.-S.W., Dafforn T.R., Carrell R.W., Read R.J., RA Lomas D.A.; RT "Inactive conformation of the serpin alpha(1)-antichymotrypsin indicates RT two-stage insertion of the reactive loop: implications for inhibitory RT function and conformational disease."; RL Proc. Natl. Acad. Sci. U.S.A. 97:67-72(2000). RN [28] RP VARIANT VAL-401. RX PubMed=1618300; DOI=10.1016/0014-5793(92)80590-d; RA Tsuda M., Sei Y., Yamamura M., Yamamoto M., Shinohara Y.; RT "Detection of a new mutant alpha-1-antichymotrypsin in patients with RT occlusive-cerebrovascular disease."; RL FEBS Lett. 304:66-68(1992). RN [29] RP VARIANT ALA-252. RX PubMed=1351206; DOI=10.1016/0140-6736(92)91301-n; RA Poller W., Faber J.-P., Scholz S., Weindinger S., Bartholome K., Olek K., RA Eriksson S.; RT "Mis-sense mutation of alpha 1-antichymotrypsin gene associated with RT chronic lung disease."; RL Lancet 339:1538-1538(1992). RN [30] RP VARIANT VAL-401. RX PubMed=11289720; DOI=10.1007/s100380170125; RA Tachikawa H., Tsuda M., Onoe K., Ueno M., Takagi S., Shinohara Y.; RT "Alpha-1-antichymotrypsin gene A1252G variant (ACT Isehara-1) is associated RT with a lacunar type of ischemic cerebrovascular disease."; RL J. Hum. Genet. 46:45-47(2001). CC -!- FUNCTION: Although its physiological function is unclear, it can CC inhibit neutrophil cathepsin G and mast cell chymase, both of which can CC convert angiotensin-1 to the active angiotensin-2. CC {ECO:0000269|PubMed:2404007}. CC -!- SUBUNIT: Interacts with DNAJC1. {ECO:0000269|PubMed:14668352}. CC -!- INTERACTION: CC P01011; P05067: APP; NbExp=3; IntAct=EBI-296557, EBI-77613; CC P01011; P55212: CASP6; NbExp=3; IntAct=EBI-296557, EBI-718729; CC P01011; Q96KC8: DNAJC1; NbExp=3; IntAct=EBI-296557, EBI-296550; CC P01011; P13473-2: LAMP2; NbExp=3; IntAct=EBI-296557, EBI-21591415; CC P01011; Q9Y371: SH3GLB1; NbExp=3; IntAct=EBI-296557, EBI-2623095; CC P01011; Q9UNE7: STUB1; NbExp=3; IntAct=EBI-296557, EBI-357085; CC P01011; Q9UBQ0-2: VPS29; NbExp=3; IntAct=EBI-296557, EBI-11141397; CC P01011; Q96AX1: VPS33A; NbExp=3; IntAct=EBI-296557, EBI-2527283; CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P01011-1; Sequence=Displayed; CC Name=2; CC IsoId=P01011-2; Sequence=VSP_014227, VSP_014228; CC Name=3; CC IsoId=P01011-3; Sequence=VSP_014225, VSP_014226; CC -!- TISSUE SPECIFICITY: Plasma. Synthesized in the liver. Like the related CC alpha-1-antitrypsin, its concentration increases in the acute phase of CC inflammation or infection. Found in the amyloid plaques from the CC hippocampus of Alzheimer disease brains. {ECO:0000269|PubMed:3257719, CC ECO:0000269|PubMed:9880565}. CC -!- DOMAIN: The reactive center loop (RCL) extends out from the body of the CC protein and directs binding to the target protease. The protease CC cleaves the serpin at the reactive site within the RCL, establishing a CC covalent linkage between the carboxyl group of the serpin reactive site CC and the serine hydroxyl of the protease. The resulting inactive serpin- CC protease complex is highly stable. CC -!- PTM: N- and O-glycosylated. {ECO:0000269|PubMed:12754519, CC ECO:0000269|PubMed:14760718, ECO:0000269|PubMed:16335952, CC ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:23234360}. CC -!- MISCELLANEOUS: Alpha-1-antichymotrypsin can bind DNA. CC -!- SIMILARITY: Belongs to the serpin family. {ECO:0000305}. CC -!- CAUTION: It is uncertain whether Met-1 or Met-4 is the initiator. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA51543.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=AAT08029.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAT08029.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=BAD92297.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=CAA48671.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Alpha-1 antichymotrypsin entry; CC URL="https://en.wikipedia.org/wiki/Alpha_1-antichymotrypsin"; 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; K01500; AAA51543.1; ALT_FRAME; mRNA. DR EMBL; X68733; CAA48671.1; ALT_INIT; Genomic_DNA. DR EMBL; X68734; CAA48671.1; JOINED; Genomic_DNA. DR EMBL; X68735; CAA48671.1; JOINED; Genomic_DNA. DR EMBL; X68736; CAA48671.1; JOINED; Genomic_DNA. DR EMBL; X68737; CAA48671.1; JOINED; Genomic_DNA. DR EMBL; AY513275; AAT08028.1; -; mRNA. DR EMBL; AY513276; AAT08029.1; ALT_SEQ; mRNA. DR EMBL; AK123091; BAG53869.1; -; mRNA. DR EMBL; AB209060; BAD92297.1; ALT_INIT; mRNA. DR EMBL; BC003559; AAH03559.3; -; mRNA. DR EMBL; BC010530; AAH10530.1; -; mRNA. DR EMBL; BC013189; AAH13189.1; -; mRNA. DR EMBL; BC034554; AAH34554.1; -; mRNA. DR EMBL; BC070265; AAH70265.1; -; mRNA. DR EMBL; M18906; AAA51559.1; -; mRNA. DR EMBL; AF089747; AAD08810.1; -; mRNA. DR EMBL; J05176; AAA51560.1; -; mRNA. DR EMBL; X00947; CAA25459.1; -; Genomic_DNA. DR CCDS; CCDS32150.1; -. [P01011-1] DR PIR; A90475; ITHUC. DR PIR; S62374; S62374. DR RefSeq; NP_001076.2; NM_001085.4. [P01011-1] DR PDB; 1AS4; X-ray; 2.10 A; A=43-383, B=387-423. DR PDB; 1QMN; X-ray; 2.27 A; A=26-423. DR PDB; 2ACH; X-ray; 2.70 A; A=24-383, B=384-423. DR PDB; 3CAA; X-ray; 2.40 A; A=43-383, B=387-423. DR PDB; 3DLW; X-ray; 2.70 A; A=25-423. DR PDB; 4CAA; X-ray; 2.90 A; A=43-383, B=387-423. DR PDB; 6HGE; X-ray; 2.80 A; A/B/C/D=26-423. DR PDBsum; 1AS4; -. DR PDBsum; 1QMN; -. DR PDBsum; 2ACH; -. DR PDBsum; 3CAA; -. DR PDBsum; 3DLW; -. DR PDBsum; 4CAA; -. DR PDBsum; 6HGE; -. DR AlphaFoldDB; P01011; -. DR SMR; P01011; -. DR BioGRID; 106530; 152. DR CORUM; P01011; -. DR IntAct; P01011; 30. DR MINT; P01011; -. DR STRING; 9606.ENSP00000450540; -. DR ChEMBL; CHEMBL5960; -. DR DrugBank; DB01593; Zinc. DR DrugBank; DB14487; Zinc acetate. DR DrugBank; DB14533; Zinc chloride. DR DrugBank; DB14548; Zinc sulfate, unspecified form. DR MEROPS; I04.002; -. DR CarbonylDB; P01011; -. DR GlyConnect; 19; 77 N-Linked glycans (5 sites). DR GlyCosmos; P01011; 8 sites, 79 glycans. DR GlyGen; P01011; 12 sites, 85 N-linked glycans (6 sites), 4 O-linked glycans (6 sites). DR iPTMnet; P01011; -. DR PhosphoSitePlus; P01011; -. DR BioMuta; SERPINA3; -. DR DMDM; 112874; -. DR DOSAC-COBS-2DPAGE; P01011; -. DR CPTAC; non-CPTAC-1061; -. DR CPTAC; non-CPTAC-1062; -. DR EPD; P01011; -. DR jPOST; P01011; -. DR MassIVE; P01011; -. DR MaxQB; P01011; -. DR PaxDb; 9606-ENSP00000376793; -. DR PeptideAtlas; P01011; -. DR PRIDE; P01011; -. DR ProteomicsDB; 51303; -. [P01011-1] DR ProteomicsDB; 51304; -. [P01011-2] DR ProteomicsDB; 51305; -. [P01011-3] DR Antibodypedia; 765; 705 antibodies from 39 providers. DR DNASU; 12; -. DR Ensembl; ENST00000393078.5; ENSP00000376793.3; ENSG00000196136.18. [P01011-1] DR Ensembl; ENST00000393080.8; ENSP00000376795.4; ENSG00000196136.18. [P01011-1] DR Ensembl; ENST00000467132.5; ENSP00000450540.1; ENSG00000196136.18. [P01011-1] DR Ensembl; ENST00000556968.2; ENSP00000452476.1; ENSG00000196136.18. [P01011-2] DR GeneID; 12; -. DR KEGG; hsa:12; -. DR MANE-Select; ENST00000393078.5; ENSP00000376793.3; NM_001085.5; NP_001076.2. DR UCSC; uc001ydp.4; human. [P01011-1] DR AGR; HGNC:16; -. DR CTD; 12; -. DR DisGeNET; 12; -. DR GeneCards; SERPINA3; -. DR HGNC; HGNC:16; SERPINA3. DR HPA; ENSG00000196136; Group enriched (liver, pancreas). DR MIM; 107280; gene. DR neXtProt; NX_P01011; -. DR OpenTargets; ENSG00000196136; -. DR PharmGKB; PA35020; -. DR VEuPathDB; HostDB:ENSG00000196136; -. DR eggNOG; KOG2392; Eukaryota. DR GeneTree; ENSGT00940000154392; -. DR HOGENOM; CLU_023330_2_1_1; -. DR InParanoid; P01011; -. DR OMA; MFVEEQL; -. DR OrthoDB; 3218836at2759; -. DR PhylomeDB; P01011; -. DR TreeFam; TF343201; -. DR PathwayCommons; P01011; -. DR Reactome; R-HSA-114608; Platelet degranulation. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR SignaLink; P01011; -. DR SIGNOR; P01011; -. DR BioGRID-ORCS; 12; 11 hits in 1160 CRISPR screens. DR ChiTaRS; SERPINA3; human. DR EvolutionaryTrace; P01011; -. DR GeneWiki; Alpha_1-antichymotrypsin; -. DR GenomeRNAi; 12; -. DR Pharos; P01011; Tbio. DR PRO; PR:P01011; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; P01011; Protein. DR Bgee; ENSG00000196136; Expressed in right lobe of liver and 95 other cell types or tissues. DR ExpressionAtlas; P01011; baseline and differential. DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome. DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB. DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; TAS:UniProtKB. DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome. DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome. DR GO; GO:0003677; F:DNA binding; TAS:UniProtKB. DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IBA:GO_Central. DR GO; GO:0006953; P:acute-phase response; IEA:UniProtKB-KW. DR GO; GO:0006954; P:inflammatory response; NAS:UniProtKB. DR GO; GO:0030277; P:maintenance of gastrointestinal epithelium; NAS:UniProtKB. DR GO; GO:0019216; P:regulation of lipid metabolic process; NAS:UniProtKB. DR CDD; cd19551; serpinA3_A1AC; 1. DR Gene3D; 2.30.39.10; Alpha-1-antitrypsin, domain 1; 1. DR Gene3D; 3.30.497.10; Antithrombin, subunit I, domain 2; 1. DR InterPro; IPR023795; Serpin_CS. DR InterPro; IPR023796; Serpin_dom. DR InterPro; IPR000215; Serpin_fam. DR InterPro; IPR036186; Serpin_sf. DR InterPro; IPR042178; Serpin_sf_1. DR InterPro; IPR042185; Serpin_sf_2. DR PANTHER; PTHR11461:SF145; ALPHA-1-ANTICHYMOTRYPSIN; 1. DR PANTHER; PTHR11461; SERINE PROTEASE INHIBITOR, SERPIN; 1. DR Pfam; PF00079; Serpin; 1. DR SMART; SM00093; SERPIN; 1. DR SUPFAM; SSF56574; Serpins; 1. DR PROSITE; PS00284; SERPIN; 1. DR SWISS-2DPAGE; P01011; -. DR Genevisible; P01011; HS. PE 1: Evidence at protein level; KW 3D-structure; Acute phase; Alternative splicing; Direct protein sequencing; KW Disease variant; Glycoprotein; Protease inhibitor; Reference proteome; KW Secreted; Serine protease inhibitor; Signal. FT SIGNAL 1..23 FT /evidence="ECO:0000269|PubMed:2787670" FT CHAIN 24..423 FT /note="Alpha-1-antichymotrypsin" FT /id="PRO_0000032411" FT CHAIN 26..423 FT /note="Alpha-1-antichymotrypsin His-Pro-less" FT /id="PRO_0000032412" FT DNA_BIND 235..237 FT REGION 369..394 FT /note="RCL" FT REGION 381..389 FT /note="O-glycosylated at one site" FT SITE 383..384 FT /note="Reactive bond" FT CARBOHYD 33 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:16335952" FT CARBOHYD 93 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12754519, FT ECO:0000269|PubMed:14760718, ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:19159218" FT CARBOHYD 106 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12754519, FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218" FT CARBOHYD 127 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:19159218" FT CARBOHYD 186 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:16335952" FT CARBOHYD 271 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:19159218" FT VAR_SEQ 64..95 FT /note="LVLKAPDKNVIFSPLSISTALAFLSLGAHNTT -> SPRWSIRLCLMYLRRA FT QKHLLPQQSKSPSFLH (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_014225" FT VAR_SEQ 96..423 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_014226" FT VAR_SEQ 215..216 FT /note="AK -> ER (in isoform 2)" FT /evidence="ECO:0000303|Ref.5" FT /id="VSP_014227" FT VAR_SEQ 217..423 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.5" FT /id="VSP_014228" FT VARIANT 9 FT /note="A -> T (in dbSNP:rs4934)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.3, FT ECO:0000269|Ref.5" FT /id="VAR_006973" FT VARIANT 78 FT /note="L -> P (in Bochum-1; dbSNP:rs1800463)" FT /evidence="ECO:0000269|PubMed:8244391" FT /id="VAR_006974" FT VARIANT 167 FT /note="A -> G" FT /id="VAR_006975" FT VARIANT 252 FT /note="P -> A (in Bonn-1; dbSNP:rs17473)" FT /evidence="ECO:0000269|PubMed:1351206, FT ECO:0000269|PubMed:8244391" FT /id="VAR_006976" FT VARIANT 267 FT /note="K -> R (in dbSNP:rs17853314)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_037902" FT VARIANT 401 FT /note="M -> V (associated with occlusive-cerebrovascular FT disease; Isehara-1; dbSNP:rs755521612)" FT /evidence="ECO:0000269|PubMed:11289720, FT ECO:0000269|PubMed:1618300" FT /id="VAR_006977" FT VARIANT 407 FT /note="D -> G (in dbSNP:rs10956)" FT /id="VAR_011742" FT CONFLICT 55 FT /note="D -> S (in Ref. 12; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 69 FT /note="P -> L (in Ref. 1; AAA51543)" FT /evidence="ECO:0000305" FT CONFLICT 101 FT /note="K -> R (in Ref. 5; BAD92297)" FT /evidence="ECO:0000305" FT CONFLICT 106 FT /note="N -> Y (in Ref. 3; AAT08028)" FT /evidence="ECO:0000305" FT CONFLICT 198 FT /note="D -> N (in Ref. 3; AAT08029)" FT /evidence="ECO:0000305" FT CONFLICT 199 FT /note="L -> P (in Ref. 1; AAA51543)" FT /evidence="ECO:0000305" FT CONFLICT 234 FT /note="S -> N (in Ref. 3; AAT08029)" FT /evidence="ECO:0000305" FT CONFLICT 339 FT /note="S -> G (in Ref. 3; AAT08028)" FT /evidence="ECO:0000305" FT CONFLICT 346 FT /note="I -> S (in Ref. 3; AAT08028)" FT /evidence="ECO:0000305" FT CONFLICT 361..363 FT /note="AVL -> VVS (in Ref. 1; AAA51543)" FT /evidence="ECO:0000305" FT HELIX 49..67 FT /evidence="ECO:0007829|PDB:1AS4" FT STRAND 69..71 FT /evidence="ECO:0007829|PDB:1QMN" FT STRAND 73..75 FT /evidence="ECO:0007829|PDB:1AS4" FT HELIX 77..88 FT /evidence="ECO:0007829|PDB:1AS4" FT HELIX 93..102 FT /evidence="ECO:0007829|PDB:1AS4" FT TURN 107..109 FT /evidence="ECO:0007829|PDB:1AS4" FT HELIX 112..126 FT /evidence="ECO:0007829|PDB:1AS4" FT STRAND 130..132 FT /evidence="ECO:0007829|PDB:1QMN" FT STRAND 134..144 FT /evidence="ECO:0007829|PDB:1AS4" FT HELIX 151..161 FT /evidence="ECO:0007829|PDB:1AS4" FT STRAND 164..168 FT /evidence="ECO:0007829|PDB:1AS4" FT HELIX 170..172 FT /evidence="ECO:0007829|PDB:1QMN" FT HELIX 173..187 FT /evidence="ECO:0007829|PDB:1AS4" FT TURN 188..190 FT /evidence="ECO:0007829|PDB:1AS4" FT STRAND 203..219 FT /evidence="ECO:0007829|PDB:1AS4" FT HELIX 223..225 FT /evidence="ECO:0007829|PDB:1AS4" FT STRAND 227..234 FT /evidence="ECO:0007829|PDB:1AS4" FT STRAND 237..256 FT /evidence="ECO:0007829|PDB:1AS4" FT TURN 257..260 FT /evidence="ECO:0007829|PDB:1AS4" FT STRAND 261..279 FT /evidence="ECO:0007829|PDB:1AS4" FT TURN 281..283 FT /evidence="ECO:0007829|PDB:2ACH" FT HELIX 284..289 FT /evidence="ECO:0007829|PDB:1AS4" FT HELIX 293..302 FT /evidence="ECO:0007829|PDB:1AS4" FT STRAND 304..314 FT /evidence="ECO:0007829|PDB:1AS4" FT STRAND 316..323 FT /evidence="ECO:0007829|PDB:1AS4" FT HELIX 325..330 FT /evidence="ECO:0007829|PDB:1AS4" FT HELIX 335..337 FT /evidence="ECO:0007829|PDB:1AS4" FT HELIX 344..347 FT /evidence="ECO:0007829|PDB:1AS4" FT STRAND 348..350 FT /evidence="ECO:0007829|PDB:1AS4" FT STRAND 352..365 FT /evidence="ECO:0007829|PDB:1AS4" FT STRAND 367..382 FT /evidence="ECO:0007829|PDB:1AS4" FT STRAND 391..394 FT /evidence="ECO:0007829|PDB:1AS4" FT STRAND 399..405 FT /evidence="ECO:0007829|PDB:1AS4" FT TURN 406..408 FT /evidence="ECO:0007829|PDB:6HGE" FT STRAND 412..418 FT /evidence="ECO:0007829|PDB:1AS4" SQ SEQUENCE 423 AA; 47651 MW; B002F946C86A8951 CRC64; MERMLPLLAL GLLAAGFCPA VLCHPNSPLD EENLTQENQD RGTHVDLGLA SANVDFAFSL YKQLVLKAPD KNVIFSPLSI STALAFLSLG AHNTTLTEIL KGLKFNLTET SEAEIHQSFQ HLLRTLNQSS DELQLSMGNA MFVKEQLSLL DRFTEDAKRL YGSEAFATDF QDSAAAKKLI NDYVKNGTRG KITDLIKDLD SQTMMVLVNY IFFKAKWEMP FDPQDTHQSR FYLSKKKWVM VPMMSLHHLT IPYFRDEELS CTVVELKYTG NASALFILPD QDKMEEVEAM LLPETLKRWR DSLEFREIGE LYLPKFSISR DYNLNDILLQ LGIEEAFTSK ADLSGITGAR NLAVSQVVHK AVLDVFEEGT EASAATAVKI TLLSALVETR TIVRFNRPFL MIIVPTDTQN IFFMSKVTNP KQA //