SERPINF2 serpin family F member 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SERPINF2provided by HGNC
Official Full Name: serpin family F member 2provided by HGNC
Primary source: HGNC:HGNC:9075
See related: Ensembl:ENSG00000167711 MIM:613168; AllianceGenome:HGNC:9075
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: AAP; API; PLI; A2AP; alpha2AP; ALPHA-2-PI
Summary: This gene encodes a member of the serpin family of serine protease inhibitors. The protein is a major inhibitor of plasmin, which degrades fibrin and various other proteins. Consequently, the proper function of this gene has a major role in regulating the blood clotting pathway. Mutations in this gene result in alpha-2-plasmin inhibitor deficiency, which is characterized by severe hemorrhagic diathesis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]
Expression: Biased expression in liver (RPKM 275.1) and kidney (RPKM 42.8) See more
Orthologs: mouse all
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Genomic context

Location:: 17p13.3

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (1742871..1755265)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (1632294..1643959)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (1646165..1658559)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Fibrinogen and Antifibrinolytic Proteins: Interactions and Future Therapeutics.
Title: Fibrinogen and Antifibrinolytic Proteins: Interactions and Future Therapeutics.
Decrease in matrix metalloproteinase3 activity in systemic sclerosis fibroblasts causes alpha2antiplasmin and extracellular matrix deposition, and contributes to fibrosis development.
Title: Decrease in matrix metalloproteinase‑3 activity in systemic sclerosis fibroblasts causes α2‑antiplasmin and extracellular matrix deposition, and contributes to fibrosis development.
Interaction of glycated and acetylated human alpha2-antiplasmin with fibrin clots.
Title: Interaction of glycated and acetylated human α2-antiplasmin with fibrin clots.
human alpha2-antiplasmin is glycated and acetylated at several sites, with the possible competition between acetylation and glycation at K-182 and K-448; finding suggests possibly relevant alterations to alpha2-antiplasmin function at high glycemia and during aspirin use
Title: Identification of glycated and acetylated lysine residues in human α2-antiplasmin.
Abnormal fibrinolysis recognized by thromboelastography in a case of severe bleeding with normal coagulation and platelet function, leads to detection of a novel SERPINF2 variant causing severe alpha-2-antiplasmin deficiency.
Title: Abnormal fibrinolysis recognized by thromboelastography in a case of severe bleeding with normal coagulation and platelet function, leads to detection of a novel SERPINF2 variant causing severe alpha-2-antiplasmin deficiency.
Data show that total free alpha-2-plasmin inhibitor (alpha2-PI) in human body fluids can be accurate and fast measured by new sandwich enzyme-linked immunosorbent assay (ELISA) method.
Title: A new ELISA method for the measurement of total α(2)-plasmin inhibitor level in human body fluids.
Studied sex hormone and serpin family F member 2 (SERPINF2) levels in preeclampsia and found a correlation between imbalanced steroid hormone levels and excessive SERPINF2 in early-onset preeclampsia patients.
Title: Association of imbalanced sex hormone production with excessive procoagulation factor SerpinF2 in preeclampsia.
findings suggest that the alpha2AP Arg407Lys polymorphism could be involved in the pathogenesis of cerebral ischemia and its outcomes
Title: Alpha-2-antiplasmin Arg407Lys polymorphism and cryptogenic ischemic cerebrovascular events: Association with neurological deficit.
Data suggest that protein aggregates interact with tissue-type plasminogen activator and plasminogen to efficiently generate plasmin; this aggregate-bound plasmin is shielded from inhibition by alpha-2-antiplasmin and degrades protein aggregates to release smaller, soluble but relatively hydrophobic peptide fragments; these fragments bind to and are cytotoxic to microglia (by not vascular endothelial cells).
Title: Amorphous protein aggregates stimulate plasminogen activation, leading to release of cytotoxic fragments that are clients for extracellular chaperones.
Higher plasma concentrations of a-2-AP and PAI-1 in patients with OSA indicated that these patients had increased prothrombotic activity. OSA increases the risk of cardiovascular complications as it enhances prothrombotic activity.
Title: Evaluation of Fibrinolytic Inhibitors: Alpha-2-Antiplasmin and Plasminogen Activator Inhibitor 1 in Patients with Obstructive Sleep Apnoea.

Submit: New GeneRIF Correction See all GeneRIFs (45)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Alpha-2-plasmin inhibitor deficiency MedGen: C2752081 OMIM: 262850 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Common variants in the calcium-sensing receptor gene are associated with total serum calcium levels. EBI GWAS Catalog EBI GWAS CatalogPubMed
Discovery and fine mapping of serum protein loci through transethnic meta-analysis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of genome-wide association studies identifies six new Loci for serum calcium concentrations. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D17S2100 (e-PCR)
- UniSTS:29520

RH68851 (e-PCR)
- UniSTS:26819

STS-T52007 (e-PCR)
- UniSTS:71921

GDB:177369 (e-PCR)
- UniSTS:154867

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables endopeptidase inhibitor activity	IDA Inferred from Direct Assay more info	PubMed
enables protease binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
enables serine-type endopeptidase inhibitor activity	IBA Inferred from Biological aspect of Ancestor more info
enables serine-type endopeptidase inhibitor activity	IDA Inferred from Direct Assay more info	PubMed
enables serine-type endopeptidase inhibitor activity	NAS Non-traceable Author Statement more info	PubMed
enables serine-type endopeptidase inhibitor activity	TAS Traceable Author Statement more info

Process	Evidence Code	Pubs
involved_in acute-phase response	IEA Inferred from Electronic Annotation more info
involved_in blood vessel morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in collagen fibril organization	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in fibrinolysis	TAS Traceable Author Statement more info
involved_in maintenance of blood vessel diameter homeostasis by renin-angiotensin	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of endopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of fibrinolysis	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of plasminogen activation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of ERK1 and ERK2 cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of JNK cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell-cell adhesion mediated by cadherin	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of collagen biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of smooth muscle cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of stress fiber assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transforming growth factor beta production	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in blood microparticle	HDA more info	PubMed
located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
located_in collagen-containing extracellular matrix	HDA more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	NAS Non-traceable Author Statement more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
part_of fibrinogen complex	IDA Inferred from Direct Assay more info	PubMed
located_in platelet alpha granule lumen	TAS Traceable Author Statement more info

General protein information

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Preferred Names: alpha-2-antiplasmin

Names: alpha-2-AP; alpha-2-plasmin inhibitor; plasmin inhibitor; serine (or cysteine) proteinase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derived factor), member 2; serpin F2; serpin peptidase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derived factor), member 2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_013215.1 RefSeqGene

Range

5001..17430

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_885

mRNA and Protein(s)

NM_000934.4 → NP_000925.2 alpha-2-antiplasmin isoform a precursor

See identical proteins and their annotated locations for NP_000925.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript. Both variants 1 and 2 encode the same isoform (a).

Source sequence(s)

BC031592, BX107460, J02654

Consensus CDS

CCDS11011.1

UniProtKB/Swiss-Prot

B4E1B7, P08697, Q8N5U7, Q9UCG2, Q9UCG3

UniProtKB/TrEMBL

A0A0G2JPA8

Related

ENSP00000402286.2, ENST00000453066.6

Conserved Domains (1) summary

cd02053
Location:82 → 433

alpha2AP; Alpha2-antiplasmin (alpha2AP) is the primary inhibitor of plasmin, a proteinase that digests fibrin, the main component of blood clots. Alpha2-Antiplasmin forms an inactive 1 : 1 stoichiometric complex with plasmin. It also rapidly crosslinks to fibrin ...
NM_001165920.1 → NP_001159392.1 alpha-2-antiplasmin isoform a precursor

See identical proteins and their annotated locations for NP_001159392.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) represents use of an alternate promoter and 5' UTR, compared to variant 1. Both variants 1 and 2 encode the same isoform (a).

Source sequence(s)

AL564784, BC031592, D00174

Consensus CDS

CCDS11011.1

UniProtKB/Swiss-Prot

B4E1B7, P08697, Q8N5U7, Q9UCG2, Q9UCG3

UniProtKB/TrEMBL

A0A0G2JPA8

Related

ENSP00000371493.4, ENST00000382061.5

Conserved Domains (1) summary

cd02053
Location:82 → 433

alpha2AP; Alpha2-antiplasmin (alpha2AP) is the primary inhibitor of plasmin, a proteinase that digests fibrin, the main component of blood clots. Alpha2-Antiplasmin forms an inactive 1 : 1 stoichiometric complex with plasmin. It also rapidly crosslinks to fibrin ...
NM_001165921.2 → NP_001159393.1 alpha-2-antiplasmin isoform b precursor

See identical proteins and their annotated locations for NP_001159393.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate splice site and lacks an alternate exon in the 5' coding region, compared to variant 1. The resulting isoform (b) lacks an internal segment, compared to isoform a.

Source sequence(s)

AK303763, AL564784, BC031592

Consensus CDS

CCDS54064.1

UniProtKB/TrEMBL

A0A0G2JPA8

Related

ENSP00000403877.2, ENST00000450523.6

Conserved Domains (1) summary

cd02053
Location:45 → 369

alpha2AP; Alpha2-antiplasmin (alpha2AP) is the primary inhibitor of plasmin, a proteinase that digests fibrin, the main component of blood clots. Alpha2-Antiplasmin forms an inactive 1 : 1 stoichiometric complex with plasmin. It also rapidly crosslinks to fibrin ...

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000017.11 Reference GRCh38.p14 Primary Assembly

Range

1742871..1755265

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047436303.1 → XP_047292259.1 alpha-2-antiplasmin isoform X1
XM_017024765.2 → XP_016880254.1 alpha-2-antiplasmin isoform X1

UniProtKB/TrEMBL

A0A0G2JPA8

Conserved Domains (1) summary

cd02053
Location:79 → 442

serpinF2_A2AP; serpin family F member 2, alpha2-antiplasmin inhibitor
XM_005256701.5 → XP_005256758.2 alpha-2-antiplasmin isoform X2

UniProtKB/TrEMBL

A0A0G2JPA8

Conserved Domains (1) summary

cd02053
Location:98 → 449

alpha2AP; Alpha2-antiplasmin (alpha2AP) is the primary inhibitor of plasmin, a proteinase that digests fibrin, the main component of blood clots. Alpha2-Antiplasmin forms an inactive 1 : 1 stoichiometric complex with plasmin. It also rapidly crosslinks to fibrin ...