SERPIND1 serpin family D member 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SERPIND1provided by HGNC
Official Full Name: serpin family D member 1provided by HGNC
Primary source: HGNC:HGNC:4838
See related: Ensembl:ENSG00000099937 MIM:142360; AllianceGenome:HGNC:4838
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: HC2; LS2; HCF2; HCII; HLS2; THPH10; D22S673
Summary: This gene belongs to the serpin gene superfamily. Serpins play roles in many processes including inflammation, blood clotting, and cancer metastasis. Members of this family have highly conserved secondary structures with a reactive center loop that interacts with the protease active site to inhibit protease activity. This gene encodes a plasma serine protease that functions as a thrombin and chymotrypsin inhibitor. The protein is activated by heparin, dermatan sulfate, and glycosaminoglycans. Allelic variations in this gene are associated with heparin cofactor II deficiency. [provided by RefSeq, Jul 2015]
Expression: Restricted expression toward liver (RPKM 330.2) See more
Orthologs: mouse all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 22q11.21

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	22	NC_000022.11 (20774113..20787720)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	22	NC_060946.1 (21182821..21196428)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	22	NC_000022.10 (21128401..21142008)

Chromosome 22 - NC_000022.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: 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

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Plasma Heparin Cofactor II Activity Is Inversely Associated with Hepatic Fibrosis of Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus.
Title: Plasma Heparin Cofactor II Activity Is Inversely Associated with Hepatic Fibrosis of Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus.
Identification and characterization of a novel isoform of heparin cofactor II in human liver.
Title: Identification and characterization of a novel isoform of heparin cofactor II in human liver.
Loss of Heparin Cofactor is associated with insulin resistance .
Title: The Role of Heparin Cofactor Ⅱ in the Regulation of Insulin Sensitivity and Maintenance of Glucose Homeostasis in Humans and Mice.
The plasma level of alpha2M was found positively correlated, while HCII level was negatively correlated with higher vulnerability of carotid plaques. Both proteins were efficient in differentiating stable and vulnerable carotid plaques. These provide potential new targets for the research of carotid plaque vulnerability. Plasma alpha2M and HCII may be potential biomarkers for evaluation of the vulnerability of carotid ...
Title: Alpha-2-macroglobulin and heparin cofactor II and the vulnerability of carotid atherosclerotic plaques: An iTRAQ-based analysis.
We found that SERPIND1 may act as a potential oncogene in the development of ovarian cancer
Title: Analysis of the gene expression profile in response to human epididymis protein 4 in epithelial ovarian cancer cells.
Molecular modelling of HCII 1-75 predicted those portions of the acidic extension that had been previously visualized in crystal structures, and suggested that an alpha-helix found between residues 26 and 36 stabilizes one found between residues 61-67.
Title: The complete N-terminal extension of heparin cofactor II is required for maximal effectiveness as a thrombin exosite 1 ligand.
heparin co-factor II is a novel metastasis enhancer and may be used as a prognostic predictor for heparin treatment in non-small cell lung cancer
Title: Heparin co-factor II enhances cell motility and promotes metastasis in non-small cell lung cancer.
In this study, we demonstrate a previously unknown role for HCII in host defense.
Title: Proteolytic activation transforms heparin cofactor II into a host defense molecule.
HCII potentiates the activation of vascular endothelial cells and the promotion of angiogenesis in response to hindlimb ischemia via an AMPK-eNOS signaling pathway.
Title: Heparin cofactor II, a serine protease inhibitor, promotes angiogenesis via activation of the AMP-activated protein kinase-endothelial nitric-oxide synthase signaling pathway.
Plasma heparin cofactor II activity was independently and inversely associated with the development of cardiac remodeling, including cardiac concentric change, left atrial enlargement and left ventricular diastolic dysfunction.
Title: Plasma heparin cofactor II activity is inversely associated with left atrial volume and diastolic dysfunction in humans with cardiovascular risk factors.

Submit: New GeneRIF Correction See all GeneRIFs (26)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Heparin cofactor II deficiency MedGen: C0398626 OMIM: 612356 GeneReviews: Not available	Compare labs

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

D22S1026 (e-PCR)
- UniSTS:59669

STS-M12849 (e-PCR)
- UniSTS:9301

RH27825 (e-PCR)
- UniSTS:90510

D22S1540 (e-PCR)
- UniSTS:22953

WI-7024 (e-PCR)
- UniSTS:32751

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables endopeptidase inhibitor activity	TAS Traceable Author Statement more info	PubMed
enables heparin binding	IEA Inferred from Electronic Annotation more info
enables serine-type endopeptidase inhibitor activity	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in blood coagulation	IEA Inferred from Electronic Annotation more info
involved_in chemotaxis	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of endopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in endoplasmic reticulum lumen	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	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

General protein information

Go to the top of the page Help

Preferred Names: heparin cofactor 2

Names: leuserpin 2; protease inhibitor leuserpin-2; serine (or cysteine) proteinase inhibitor, clade D (heparin cofactor), member 1; serpin D1; serpin peptidase inhibitor, clade D (heparin cofactor), member 1

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

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_012076.2 RefSeqGene

Range

5019..18626

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_594

mRNA and Protein(s)

NM_000185.4 → NP_000176.2 heparin cofactor 2 precursor

See identical proteins and their annotated locations for NP_000176.2

Status: REVIEWED

Source sequence(s)

AC007308, BC035028

Consensus CDS

CCDS13783.1

UniProtKB/Swiss-Prot

B2RAI1, D3DX34, P05546, Q6IBZ5

UniProtKB/TrEMBL

Q8IVC0

Related

ENSP00000215727.5, ENST00000215727.10

Conserved Domains (1) summary

cd02047
Location:62 → 497

HCII; Heparin cofactor II (HCII) inhibits thrombin, the final protease of the coagulation cascade. HCII is allosterically activated by binding to cell surface glycosaminoglycans (GAGs). The specificity of HCII for thrombin is conferred by a highly acidic ...