Reviewed, UniProtKB/Swiss-Prot P01011 (AACT_HUMAN)

Names and origin

Protein names

Recommended name:
    Alpha-1-antichymotrypsin
      Short name=ACT
Alternative name(s):
    Cell growth-inhibiting gene 24/25 protein
Cleaved into the following chain:
    1- Recommended name:
            Alpha-1-antichymotrypsin His-Pro-less

Gene names

Name:	SERPINA3
Synonyms:	AACT
ORF Names:	GIG24, GIG25

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	423 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Although its physiological function is unclear, it can inhibit neutrophil cathepsin G and mast cell chymase, both of which can convert angiotensin-1 to the active angiotensin-2.
Subunit structure	Interacts with DNAJC1.
Subcellular location	Secreted.
Tissue specificity	Plasma. Synthesized in the liver. Like the related alpha-1-antitrypsin, its concentration increases in the acute phase of inflammation or infection. Found in the myloid plaques from the hippocampus of Alzheimer's disease brains.
Domain	The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the carboxyl group of the serpin reactive site and the serine hydroxyl of the protease. The resulting inactive serpin-protease complex is highly stable.
Involvement in disease	Defects in SERPINA3 may be a cause of chronic obstructive pulmonary disease (COPD) [MIM:107280].
Miscellaneous	Alpha-1-antichymotrypsin can bind DNA.
Sequence similarities	Belongs to the serpin family.
Caution	It is uncertain whether Met-1 or Met-4 is the initiator.
Sequence caution	The sequence AAA51543.1 differs from that shown. Reason: Frameshift at positions 101, 106, 111, 117, 123, 129 and 421. The sequence AAT08029.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence AAT08029.1 differs from that shown. Reason: Frameshift at position 4.

Ontologies

Keywords
Biological process	Acute phase
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Signal
Molecular function	Protease inhibitor Serine protease inhibitor
PTM	Glycoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	acute-phase response Inferred from electronic annotation. Source: UniProtKB-KW regulation of lipid metabolic process Non-traceable author statement. Source: UniProtKB
Cellular component	extracellular region Ref.7 Non-traceable author statement. Source: UniProtKB nucleus Ref.17 Traceable author statement. Source: UniProtKB
Molecular function	DNA binding Ref.7 Ref.17 Traceable author statement. Source: UniProtKB chymotrypsin inhibitor activity Ref.7 Non-traceable author statement. Source: UniProtKB protein binding Ref.17 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P01011-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P01011-2)

The sequence of this isoform differs from the canonical sequence as follows:
     215-216: AK → ER
     217-423: Missing.

Notes: No experimental confirmation available.

Isoform 3 (identifier: P01011-3)

The sequence of this isoform differs from the canonical sequence as follows:
     64-95: LVLKAPDKNVIFSPLSISTALAFLSLGAHNTT → SPRWSIRLCLMYLRRAQKHLLPQQSKSPSFLH
     96-423: Missing.

Notes: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 23

23

Chain

24 – 423

400

Alpha-1-antichymotrypsin

PRO_0000032411

Chain

26 – 423

398

Alpha-1-antichymotrypsin His-Pro-less

PRO_0000032412

Regions

DNA binding

235 – 237

3

Region

369 – 394

26

RCL

Sites

Site

383 – 384

2

Reactive bond

Amino acid modifications

Glycosylation

33

1

N-linked (GlcNAc...)

Glycosylation

93

1

N-linked (GlcNAc...)

Glycosylation

106

1

N-linked (GlcNAc...)

Glycosylation

127

1

N-linked (GlcNAc...)

Glycosylation

186

1

N-linked (GlcNAc...)

Glycosylation

271

1

N-linked (GlcNAc...)

Natural variations

Alternative sequence

64 – 95

32

LVLKA…AHNTT → SPRWSIRLCLMYLRRAQKHL LPQQSKSPSFLH in isoform 3.

VSP_014225

Alternative sequence

96 – 423

328

Missing in isoform 3.

VSP_014226

Alternative sequence

215 – 216

2

AK → ER in isoform 2.

VSP_014227

Alternative sequence

217 – 423

207

Missing in isoform 2.

VSP_014228

Natural variant

9

1

A → T: dbSNP rs4934.

VAR_006973

Natural variant

78

1

L → P in COPD; Bochum-1. dbSNP rs1800463.

VAR_006974

Natural variant

167

1

A → G

VAR_006975

Natural variant

252

1

P → A in COPD; Bonn-1. dbSNP rs17473.

VAR_006976

Natural variant

267

1

K → R: dbSNP rs17853314.

VAR_037902

Natural variant

401

1

M → V Associated with occlusive-cerebrovascular disease; Isehara-1.

VAR_006977

Natural variant

407

1

D → G: dbSNP rs10956.

VAR_011742

Experimental info

Sequence conflict

55

1

D → S AA sequence Ref.11

Sequence conflict

69

1

P → L in AAA51543. Ref.1

Sequence conflict

101

1

K → R in BAD92297. Ref.4

Sequence conflict

106

1

N → Y in AAT08028. Ref.3

Sequence conflict

198

1

D → N in AAT08029. Ref.3

Sequence conflict

199

1

L → P in AAA51543. Ref.1

Sequence conflict

234

1

S → N in AAT08029. Ref.3

Sequence conflict

339

1

S → G in AAT08028. Ref.3

Sequence conflict

346

1

I → S in AAT08028. Ref.3

Sequence conflict

361 – 363

3

AVL → VVS in AAA51543. Ref.1

Secondary structure

1

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423

Helix Strand Turn

Details...

Helix

49 – 67

19

Beta strand

73 – 75

3

Helix

77 – 88

12

Helix

93 – 102

10

Turn

107 – 109

3

Helix

112 – 126

15

Beta strand

134 – 144

11

Helix

151 – 161

11

Beta strand

164 – 168

5

Helix

173 – 187

15

Turn

188 – 190

3

Beta strand

203 – 219

17

Helix

223 – 225

3

Beta strand

227 – 234

8

Beta strand

237 – 256

20

Turn

257 – 260

4

Beta strand

261 – 279

19

Helix

284 – 289

6

Helix

293 – 302

10

Beta strand

304 – 314

11

Beta strand

316 – 323

8

Helix

325 – 330

6

Helix

335 – 337

3

Helix

344 – 347

4

Beta strand

348 – 350

3

Beta strand

352 – 365

14

Beta strand

367 – 382

16

Beta strand

391 – 394

4

Beta strand

399 – 405

7

Beta strand

412 – 418

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified August 1, 1991. Version 2. Checksum: B002F946C86A8951	FASTA	423	47,651
	10 20 30 40 50 60 MERMLPLLAL GLLAAGFCPA VLCHPNSPLD EENLTQENQD RGTHVDLGLA SANVDFAFSL 70 80 90 100 110 120 YKQLVLKAPD KNVIFSPLSI STALAFLSLG AHNTTLTEIL KGLKFNLTET SEAEIHQSFQ 130 140 150 160 170 180 HLLRTLNQSS DELQLSMGNA MFVKEQLSLL DRFTEDAKRL YGSEAFATDF QDSAAAKKLI 190 200 210 220 230 240 NDYVKNGTRG KITDLIKDLD SQTMMVLVNY IFFKAKWEMP FDPQDTHQSR FYLSKKKWVM 250 260 270 280 290 300 VPMMSLHHLT IPYFRDEELS CTVVELKYTG NASALFILPD QDKMEEVEAM LLPETLKRWR 310 320 330 340 350 360 DSLEFREIGE LYLPKFSISR DYNLNDILLQ LGIEEAFTSK ADLSGITGAR NLAVSQVVHK 370 380 390 400 410 420 AVLDVFEEGT EASAATAVKI TLLSALVETR TIVRFNRPFL MIIVPTDTQN IFFMSKVTNP KQA
	Isoform 2 [UniParc]. Checksum: 49312EDF91439D4D		216	24,034
	10 20 30 40 50 60 MERMLPLLAL GLLAAGFCPA VLCHPNSPLD EENLTQENQD RGTHVDLGLA SANVDFAFSL 70 80 90 100 110 120 YKQLVLKAPD KNVIFSPLSI STALAFLSLG AHNTTLTEIL KGLKFNLTET SEAEIHQSFQ 130 140 150 160 170 180 HLLRTLNQSS DELQLSMGNA MFVKEQLSLL DRFTEDAKRL YGSEAFATDF QDSAAAKKLI 190 200 210 NDYVKNGTRG KITDLIKDLD SQTMMVLVNY IFFKER
	Isoform 3 [UniParc]. Checksum: 15B1759843F9809B		95	10,717
	10 20 30 40 50 60 MERMLPLLAL GLLAAGFCPA VLCHPNSPLD EENLTQENQD RGTHVDLGLA SANVDFAFSL 70 80 90 YKQSPRWSIR LCLMYLRRAQ KHLLPQQSKS PSFLH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence homology between human alpha 1-antichymotrypsin, alpha 1-antitrypsin, and antithrombin III." Chandra T., Stackhouse R., Kidd V.J., Robson K.J.H., Woo S.L.C. Biochemistry 22:5055-5061(1983) [PubMed: 6606438] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Liver.
[2]	"A leucine-to-proline substitution causes a defective alpha 1-antichymotrypsin allele associated with familial obstructive lung disease." Poller W., Faber J.-P., Weidinger S., Tief K., Scholz S., Fischer M., Olek K., Kirchgesser M., Heidtmann H.-H. Genomics 17:740-743(1993) [PubMed: 8244391] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], INVOLVEMENT IN COPD, VARIANTS BOCHUM-1 PRO-78 AND BONN-1 ALA-252.
[3]	"Identification of a human cell growth inhibiting gene." Kim J.W. Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT THR-9.
[4]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno F.R. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT THR-9. Tissue: Brain.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), VARIANTS THR-9 AND ARG-267. Tissue: Brain, Liver and Skin.
[6]	"Immunochemical identification of the serine protease inhibitor alpha 1-antichymotrypsin in the brain amyloid deposits of Alzheimer's disease." Abraham C.R., Selkoe D.J., Potter H. Cell 52:487-501(1988) [PubMed: 3257719] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-46, TISSUE SPECIFICITY. Tissue: Liver.
[7]	"Molecular studies define the primary structure of alpha1-antichymotrypsin (ACT) protease inhibitor in Alzheimer's disease brains. Comparison of act in hippocampus and liver." Hwang S.-R., Steineckert B., Kohn A., Palkovits M., Hook V.Y.H. J. Biol. Chem. 274:1821-1827(1999) [PubMed: 9880565] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 17-423 (ISOFORM 1), TISSUE SPECIFICITY. Tissue: Hippocampus.
[8]	Rubin H. Submitted (OCT-1989) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 22-86 AND 130-423 (ISOFORM 1).
[9]	"The microheterogeneity of desialylated alpha 1-antichymotrypsin: the occurrence of two amino-terminal isoforms, one lacking a His-Pro dipeptide." Lindmark B., Hilja H., Alan R., Eriksson S. Biochim. Biophys. Acta 997:90-95(1989) [