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FLASH GENE

Symbol

SERPINA1

contributors: mct/npt/pgu - updated : 10-01-2013

HGNC name	serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1
HGNC id	8941

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	COPD1 pulmonary disease, chronic obstructive, 1
Location	14q32.13      Physical location : 94.843.084 - 94.857.029
Synonym name	protease inhibitor (alpha-1-antitrypsin)
	protease inhibitor 1 (anti-elastase), alpha-1-antitrypsin
	serine (or cysteine) proteinase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1
Synonym symbol(s)	AAT, PI, PI1, A1AT, A1A, alpha-1-antitrypsin, MGC23330, MGC9222, PRO2275
EC.number	5.3.1.1

DNA

TYPE	functioning gene
SPECIAL FEATURE	component of a cluster
STRUCTURE	13.95 kb     7 Exon(s)

10 Kb 5' upstream gene genomic sequence study

text structure	a 5' matrix attachment region (MAR)
	4 exons coding

MAPPING

cloned

Y

linked

Y

status

confirmed

Map	cen - SERPINA6 - SERPINA2 - SERPINA1 - SERPINA4 - SERPINA5 - SERPINA3 - qter

Physical map

RNA

TRANSCRIPTS	type	messenger

text	all transcripts encode the same protein

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000295 5 - 3220 NP_000286 44 418 - 1992 1406456 NM_001002235 5 - 3199 NP_001002235 44 418 - 1992 1406456 NM_001002236 7 - 3513 NP_001002236 44 418 - 1992 1406456 NM_001127700 5 - 3236 NP_001121172 44 418 - 1992 1406456 NM_001127701 7 - 3532 NP_001121173 44 418 - 1992 1406456 NM_001127702 6 - 3340 NP_001121174 44 418 - 1992 1406456 NM_001127703 7 - 3495 NP_001121175 44 418 - 1992 1406456 NM_001127704 7 - 3492 NP_001121176 44 418 - 1992 1406456 NM_001127705 7 - 3510 NP_001121177 44 418 - 1992 1406456 NM_001127706 6 - 3303 NP_001121178 44 418 - 1992 1406456 NM_001127707 6 - 3300 NP_001121179 44 418 - 1992 1406456

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive liver       predominantly Lymphoid/Immune spleen       highly   thymus       highly Visual eye anterior segment cornea

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow       Homo sapiens Epithelial       highly

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic neutrophil Homo sapiens Lymphoid/Immune macrophage

cell lineage
cell lines	hepatoma cells
fluid/secretion

at STAGE

physiological period

embryo, fetal

Text

liver

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

attachment sites for N-linked oligosaccharides

conjugated

GlycoP

HOMOLOGY

Homologene

FAMILY

serpin family

CATEGORY

enzyme , regulatory

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,cytosolic,granule
	intracellular,nucleus,nucleolus
text	associated with azurophile granules in neutrophils indicative of SERPINA1 expression being restricted to the promyelocyte stage

basic FUNCTION	serine protease inhibitor
	inhibiting elastase
	involved in the regulation of gene activity and chromatin structure by the complex HNF1A - HNF4
	entry and cell association of SERPINA1 is dependent on lipid raft cholesterol and SERPINA1 depletes lipid raft cholesterol
	regulates human neutrophil chemotaxis induced by soluble immune complexes and IL8
	provides an antiprotease protective screen throughout the body
	protective of tissue damage induced by enzymes of inflammatory cell source
	contributes to the pathogenesis of ankylosing spondylitis by up-regulating the gene expression in the synovial tissues

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	interacting with LMAN1 (intracellular transport receptor of alpha1-antitrypsin)
	important inhibitor of neutrophil proteases including elastase, cathepsin G, and proteinase 3

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

COPD1

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional       loss of function AAT activity was decreased in amnions from cases with premature rupture of the membranes, regardless of gestational age constitutional     --over   in synovial membranes of patients with ankylosing spondylitis constitutional     --low   in preterm premature rupture of membrane (PPROM)

Susceptibility

to Wegener granulomatosis to chronic obstructive pulmonary disease to liver cancer to liver disease

Variant & Polymorphism SNP , other	linkage desequilibrium
	SNP increasing the risk of chronic obstructive pulmonary disease
	AAT deficiency variants, besides increasing the risk of lung disease, may predispose to liver disease, particularly if associated with the common Z variant

Candidate gene
Marker	SERPINA1 and autoantibodies against SERPINA1 may be useful serum biomarkers for early-stage breast cancer screening and diagnosis
Therapy target

ANIMAL & CELL MODELS