AACT_HUMAN
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 03-AUG-2022, entry version 244.
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 BOCHUM-1 PRO-78 AND BONN-1
RP 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 ISEHARA-1 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 BONN-1 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";
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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; 148.
DR CORUM; P01011; -.
DR IntAct; P01011; 29.
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 GlyGen; P01011; 9 sites, 78 N-linked glycans (6 sites), 3 O-linked glycans (3 sites).
DR iPTMnet; P01011; -.
DR PhosphoSitePlus; P01011; -.
DR BioMuta; SERPINA3; -.
DR DMDM; 112874; -.
DR DOSAC-COBS-2DPAGE; P01011; -.
DR SWISS-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; P01011; -.
DR PeptideAtlas; P01011; -.
DR PRIDE; P01011; -.
DR ProteomicsDB; 51303; -. [P01011-1]
DR ProteomicsDB; 51304; -. [P01011-2]
DR ProteomicsDB; 51305; -. [P01011-3]
DR Antibodypedia; 765; 605 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 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 Orphanet; 93594; OBSOLETE: Alpha-1-antichymotrypsin deficiency.
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; PDEGRME; -.
DR OrthoDB; 131191at2759; -.
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; 10 hits in 1076 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 93 other tissues.
DR ExpressionAtlas; P01011; baseline and differential.
DR Genevisible; P01011; HS.
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:0010951; P:negative regulation of endopeptidase activity; IBA:GO_Central.
DR GO; GO:0019216; P:regulation of lipid metabolic process; NAS:UniProtKB.
DR Gene3D; 2.30.39.10; -; 1.
DR Gene3D; 3.30.497.10; -; 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; PTHR11461; 1.
DR Pfam; PF00079; Serpin; 1.
DR SMART; SM00093; SERPIN; 1.
DR SUPFAM; SSF56574; SSF56574; 1.
DR PROSITE; PS00284; SERPIN; 1.
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
