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Protein

Alpha-1-antichymotrypsin

Gene

SERPINA3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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-2.1 Publication

Miscellaneous

Alpha-1-antichymotrypsin can bind DNA.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei383 – 384Reactive bond2

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi235 – 2373

GO - Molecular functioni

  • DNA binding Source: UniProtKB
  • serine-type endopeptidase inhibitor activity Source: UniProtKB

GO - Biological processi

  • acute-phase response Source: UniProtKB-KW
  • inflammatory response Source: UniProtKB
  • maintenance of gastrointestinal epithelium Source: UniProtKB
  • neutrophil degranulation Source: Reactome
  • platelet degranulation Source: Reactome
  • regulation of lipid metabolic process Source: UniProtKB

Keywordsi

Molecular functionProtease inhibitor, Serine protease inhibitor
Biological processAcute phase

Enzyme and pathway databases

ReactomeiR-HSA-114608. Platelet degranulation.
R-HSA-6798695. Neutrophil degranulation.

Protein family/group databases

MEROPSiI04.002.

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-1-antichymotrypsin
Short name:
ACT
Alternative name(s):
Cell growth-inhibiting gene 24/25 protein
Serpin A3
Cleaved into the following chain:
Gene namesi
Name:SERPINA3
Synonyms:AACT
ORF Names:GIG24, GIG25
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000196136.16.
HGNCiHGNC:16. SERPINA3.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi12.
OpenTargetsiENSG00000196136.
Orphaneti93594. Alpha-1-antichymotrypsin deficiency.
PharmGKBiPA35020.

Chemistry databases

ChEMBLiCHEMBL5960.

Polymorphism and mutation databases

BioMutaiSERPINA3.
DMDMi112874.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 231 PublicationAdd BLAST23
ChainiPRO_000003241124 – 423Alpha-1-antichymotrypsinAdd BLAST400
ChainiPRO_000003241226 – 423Alpha-1-antichymotrypsin His-Pro-lessAdd BLAST398

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi33N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi93N-linked (GlcNAc...) asparagine4 Publications1
Glycosylationi106N-linked (GlcNAc...) asparagine3 Publications1
Glycosylationi127N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi186N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi271N-linked (GlcNAc...) asparagine2 Publications1

Post-translational modificationi

N- and O-glycosylated.5 Publications

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiP01011.
MaxQBiP01011.
PaxDbiP01011.
PeptideAtlasiP01011.
PRIDEiP01011.

2D gel databases

DOSAC-COBS-2DPAGEiP01011.
SWISS-2DPAGEiP01011.

PTM databases

iPTMnetiP01011.
PhosphoSitePlusiP01011.
UniCarbKBiP01011.

Miscellaneous databases

PMAP-CutDBiP01011.

Expressioni

Tissue specificityi

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 amyloid plaques from the hippocampus of Alzheimer disease brains.2 Publications

Gene expression databases

BgeeiENSG00000196136.
ExpressionAtlasiP01011. baseline and differential.
GenevisibleiP01011. HS.

Organism-specific databases

HPAiCAB016647.
HPA000893.
HPA002560.

Interactioni

Subunit structurei

Interacts with DNAJC1.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
DNAJC1Q96KC83EBI-296557,EBI-296550

Protein-protein interaction databases

BioGridi106530. 28 interactors.
CORUMiP01011.
IntActiP01011. 10 interactors.
STRINGi9606.ENSP00000376793.

Structurei

Secondary structure

1423
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi49 – 67Combined sources19
Beta strandi69 – 71Combined sources3
Beta strandi73 – 75Combined sources3
Helixi77 – 88Combined sources12
Helixi93 – 102Combined sources10
Turni107 – 109Combined sources3
Helixi112 – 126Combined sources15
Beta strandi130 – 132Combined sources3
Beta strandi134 – 144Combined sources11
Helixi151 – 161Combined sources11
Beta strandi164 – 168Combined sources5
Helixi170 – 172Combined sources3
Helixi173 – 187Combined sources15
Turni188 – 190Combined sources3
Beta strandi203 – 219Combined sources17
Helixi223 – 225Combined sources3
Beta strandi227 – 234Combined sources8
Beta strandi237 – 256Combined sources20
Turni257 – 260Combined sources4
Beta strandi261 – 279Combined sources19
Turni281 – 283Combined sources3
Helixi284 – 289Combined sources6
Helixi293 – 302Combined sources10
Beta strandi304 – 314Combined sources11
Beta strandi316 – 323Combined sources8
Helixi325 – 330Combined sources6
Helixi335 – 337Combined sources3
Helixi344 – 347Combined sources4
Beta strandi348 – 350Combined sources3
Beta strandi352 – 365Combined sources14
Beta strandi367 – 382Combined sources16
Beta strandi391 – 394Combined sources4
Beta strandi399 – 405Combined sources7
Beta strandi412 – 418Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AS4X-ray2.10A43-383[»]
B387-423[»]
1QMNX-ray2.27A26-423[»]
2ACHX-ray2.70A24-383[»]
B384-423[»]
3CAAX-ray2.40A43-383[»]
B387-423[»]
3DLWX-ray2.70A25-423[»]
4CAAX-ray2.90A43-383[»]
B387-423[»]
ProteinModelPortaliP01011.
SMRiP01011.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01011.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni369 – 394RCLAdd BLAST26
Regioni381 – 389O-glycosylated at one site9

Domaini

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.

Sequence similaritiesi

Belongs to the serpin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG2392. Eukaryota.
COG4826. LUCA.
GeneTreeiENSGT00760000118839.
HOVERGENiHBG005957.
InParanoidiP01011.
KOiK04525.
OMAiFLMIIVP.
OrthoDBiEOG091G0ION.
PhylomeDBiP01011.
TreeFamiTF343201.

Family and domain databases

InterProiView protein in InterPro
IPR023795. Serpin_CS.
IPR023796. Serpin_dom.
IPR000215. Serpin_fam.
IPR036186. Serpin_sf.
PANTHERiPTHR11461. PTHR11461. 1 hit.
PfamiView protein in Pfam
PF00079. Serpin. 1 hit.
SMARTiView protein in SMART
SM00093. SERPIN. 1 hit.
SUPFAMiSSF56574. SSF56574. 1 hit.
PROSITEiView protein in PROSITE
PS00284. SERPIN. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P01011-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MERMLPLLAL GLLAAGFCPA VLCHPNSPLD EENLTQENQD RGTHVDLGLA
60 70 80 90 100
SANVDFAFSL YKQLVLKAPD KNVIFSPLSI STALAFLSLG AHNTTLTEIL
110 120 130 140 150
KGLKFNLTET SEAEIHQSFQ HLLRTLNQSS DELQLSMGNA MFVKEQLSLL
160 170 180 190 200
DRFTEDAKRL YGSEAFATDF QDSAAAKKLI NDYVKNGTRG KITDLIKDLD
210 220 230 240 250
SQTMMVLVNY IFFKAKWEMP FDPQDTHQSR FYLSKKKWVM VPMMSLHHLT
260 270 280 290 300
IPYFRDEELS CTVVELKYTG NASALFILPD QDKMEEVEAM LLPETLKRWR
310 320 330 340 350
DSLEFREIGE LYLPKFSISR DYNLNDILLQ LGIEEAFTSK ADLSGITGAR
360 370 380 390 400
NLAVSQVVHK AVLDVFEEGT EASAATAVKI TLLSALVETR TIVRFNRPFL
410 420
MIIVPTDTQN IFFMSKVTNP KQA
Length:423
Mass (Da):47,651
Last modified:August 1, 1991 - v2
Checksum:iB002F946C86A8951
GO
Isoform 2 (identifier: P01011-2) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:216
Mass (Da):24,034
Checksum:i49312EDF91439D4D
GO
Isoform 3 (identifier: P01011-3) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:95
Mass (Da):10,717
Checksum:i15B1759843F9809B
GO

Sequence cautioni

The sequence AAA51543 differs from that shown. Reason: Frameshift at positions 101, 106, 111, 117, 123, 129 and 421.Curated
The sequence AAT08029 differs from that shown. Reason: Frameshift at position 4.Curated
The sequence AAT08029 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence BAD92297 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence CAA48671 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti55D → S AA sequence (PubMed:6687683).Curated1
Sequence conflicti69P → L in AAA51543 (PubMed:6606438).Curated1
Sequence conflicti101K → R in BAD92297 (Ref. 5) Curated1
Sequence conflicti106N → Y in AAT08028 (Ref. 3) Curated1
Sequence conflicti198D → N in AAT08029 (Ref. 3) Curated1
Sequence conflicti199L → P in AAA51543 (PubMed:6606438).Curated1
Sequence conflicti234S → N in AAT08029 (Ref. 3) Curated1
Sequence conflicti339S → G in AAT08028 (Ref. 3) Curated1
Sequence conflicti346I → S in AAT08028 (Ref. 3) Curated1
Sequence conflicti361 – 363AVL → VVS in AAA51543 (PubMed:6606438).Curated3

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0069739A → T4 PublicationsCorresponds to variant dbSNP:rs4934Ensembl.1
Natural variantiVAR_00697478L → P in Bochum-1. 1 PublicationCorresponds to variant dbSNP:rs1800463Ensembl.1
Natural variantiVAR_006975167A → G. 1
Natural variantiVAR_006976252P → A in Bonn-1. 2 PublicationsCorresponds to variant dbSNP:rs17473Ensembl.1
Natural variantiVAR_037902267K → R1 PublicationCorresponds to variant dbSNP:rs17853314Ensembl.1
Natural variantiVAR_006977401M → V Associated with occlusive-cerebrovascular disease; Isehara-1. 2 Publications1
Natural variantiVAR_011742407D → G. Corresponds to variant dbSNP:rs10956Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_01422564 – 95LVLKA…AHNTT → SPRWSIRLCLMYLRRAQKHL LPQQSKSPSFLH in isoform 3. 1 PublicationAdd BLAST32
Alternative sequenceiVSP_01422696 – 423Missing in isoform 3. 1 PublicationAdd BLAST328
Alternative sequenceiVSP_014227215 – 216AK → ER in isoform 2. 1 Publication2
Alternative sequenceiVSP_014228217 – 423Missing in isoform 2. 1 PublicationAdd BLAST207

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K01500 mRNA. Translation: AAA51543.1. Frameshift.
X68733
, X68734, X68735, X68736, X68737 Genomic DNA. Translation: CAA48671.1. Different initiation.
AY513275 mRNA. Translation: AAT08028.1.
AY513276 mRNA. Translation: AAT08029.1. Sequence problems.
AK123091 mRNA. Translation: BAG53869.1.
AB209060 mRNA. Translation: BAD92297.1. Different initiation.
BC003559 mRNA. Translation: AAH03559.3.
BC010530 mRNA. Translation: AAH10530.1.
BC013189 mRNA. Translation: AAH13189.1.
BC034554 mRNA. Translation: AAH34554.1.
BC070265 mRNA. Translation: AAH70265.1.
M18906 mRNA. Translation: AAA51559.1.
AF089747 mRNA. Translation: AAD08810.1.
J05176 mRNA. Translation: AAA51560.1.
X00947 Genomic DNA. Translation: CAA25459.1.
CCDSiCCDS32150.1. [P01011-1]
PIRiA90475. ITHUC.
S62374.
RefSeqiNP_001076.2. NM_001085.4. [P01011-1]
UniGeneiHs.534293.
Hs.710488.

Genome annotation databases

EnsembliENST00000393078; ENSP00000376793; ENSG00000196136. [P01011-1]
ENST00000393080; ENSP00000376795; ENSG00000196136. [P01011-1]
ENST00000467132; ENSP00000450540; ENSG00000196136. [P01011-1]
ENST00000556968; ENSP00000452476; ENSG00000196136. [P01011-2]
GeneIDi12.
KEGGihsa:12.
UCSCiuc001ydp.4. human. [P01011-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiAACT_HUMAN
AccessioniPrimary (citable) accession number: P01011
Secondary accession number(s): B3KVQ7
, Q13703, Q2TU87, Q2TU88, Q59GP9, Q6LBY8, Q6LDT7, Q6NSC9, Q8N177, Q96DW8, Q9UC47, Q9UNU9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: August 1, 1991
Last modified: October 25, 2017
This is version 213 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Caution

It is uncertain whether Met-1 or Met-4 is the initiator.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families