HSPG2 heparan sulfate proteoglycan 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: HSPG2provided by HGNC
Official Full Name: heparan sulfate proteoglycan 2provided by HGNC
Primary source: HGNC:HGNC:5273
See related: Ensembl:ENSG00000142798 MIM:142461; AllianceGenome:HGNC:5273
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: PLC; SJA; SJS; HSPG; SJS1; PRCAN
Summary: This gene encodes the perlecan protein, which consists of a core protein to which three long chains of glycosaminoglycans (heparan sulfate or chondroitin sulfate) are attached. The perlecan protein is a large multidomain proteoglycan that binds to and cross-links many extracellular matrix components and cell-surface molecules. It has been shown that this protein interacts with laminin, prolargin, collagen type IV, FGFBP1, FBLN2, FGF7 and transthyretin, etc., and it plays essential roles in multiple biological activities. Perlecan is a key component of the vascular extracellular matrix, where it helps to maintain the endothelial barrier function. It is a potent inhibitor of smooth muscle cell proliferation and is thus thought to help maintain vascular homeostasis. It can also promote growth factor (e.g., FGF2) activity and thus stimulate endothelial growth and re-generation. It is a major component of basement membranes, where it is involved in the stabilization of other molecules as well as being involved with glomerular permeability to macromolecules and cell adhesion. Mutations in this gene cause Schwartz-Jampel syndrome type 1, Silverman-Handmaker type of dyssegmental dysplasia, and tardive dyskinesia. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2014]
Expression: Broad expression in fat (RPKM 67.9), gall bladder (RPKM 21.5) and 21 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1p36.12

Exon count:: 103

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (21822244..21937310, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (21646052..21761123, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (22148737..22263803, complement)

Chromosome 1 - NC_000001.11 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?

Dyssegmental dysplasia Rolland-Desbuquois type is caused by pathogenic variants in HSPG2 - a founder haplotype shared in five patients.
Title: Dyssegmental dysplasia Rolland-Desbuquois type is caused by pathogenic variants in HSPG2 - a founder haplotype shared in five patients.
Perlecan (HSPG2) promotes structural, contractile, and metabolic development of human cardiomyocytes.
Title: Perlecan (HSPG2) promotes structural, contractile, and metabolic development of human cardiomyocytes.
Identification of B-cell-related HSPG2 and CDSN as susceptibility loci for Kawasaki disease.
Title: Identification of B-cell-related HSPG2 and CDSN as susceptibility loci for Kawasaki disease.
Perlecan: Roles in osteoarthritis and potential treating target.
Title: Perlecan: Roles in osteoarthritis and potential treating target.
DAL-1/4.1B promotes the uptake of exosomes in lung cancer cells via Heparan Sulfate Proteoglycan 2 (HSPG2).
Title: DAL-1/4.1B promotes the uptake of exosomes in lung cancer cells via Heparan Sulfate Proteoglycan 2 (HSPG2).
Replicative verification of susceptibility genes previously identified from families with segregating developmental dysplasia of the hip.
Title: Replicative verification of susceptibility genes previously identified from families with segregating developmental dysplasia of the hip.
Perlecan, a modular instructive proteoglycan with diverse functional properties.
Title: Perlecan, a modular instructive proteoglycan with diverse functional properties.
Expression and Circulating Levels of Perlecan in Breast Cancer - Implications for Oestrogen Dependent Stromal Remodeling.
Title: Expression and Circulating Levels of Perlecan in Breast Cancer - Implications for Oestrogen Dependent Stromal Remodeling.
Perlecan in Pericellular Mechanosensory Cell-Matrix Communication, Extracellular Matrix Stabilisation and Mechanoregulation of Load-Bearing Connective Tissues.
Title: Perlecan in Pericellular Mechanosensory Cell-Matrix Communication, Extracellular Matrix Stabilisation and Mechanoregulation of Load-Bearing Connective Tissues.
HSPG2 overexpression independently predicts poor survival in patients with acute myeloid leukemia.
Title: HSPG2 overexpression independently predicts poor survival in patients with acute myeloid leukemia.

Submit: New GeneRIF Correction See all GeneRIFs (105)

Phenotypes

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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
Lethal Kniest-like syndrome MedGen: C1857100 OMIM: 224410 GeneReviews: Not available	Compare labs
Schwartz-Jampel syndrome type 1 MedGen: C4551479 OMIM: 255800 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 SF33 Env (gp120) binds to HSPG2 in polarized infant tonsil cells as shown through immunoprecipitation	PubMed
	env	HSPG interacts strongly with positively charged-V3 loop of X4-tropic gp120, but weakly with less positively charged-V3 loop of R5-tropic gp120 on epithelial cells	PubMed
Tat	tat	Perlecan mediates Tat uptake and is required for HIV-1 LTR-directed transactivation in the human colon carcinoma cell line, WiDr.	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

STS-M85289 (e-PCR)
- UniSTS:38420

G15904 (e-PCR)
- UniSTS:13364

D10S16 (e-PCR)
- UniSTS:155756

D1S1432 (e-PCR)
- UniSTS:149628

GDB:549190 (e-PCR)
- UniSTS:157627

SHGC-74354 (e-PCR)
- UniSTS:12496

RH79675 (e-PCR)
- UniSTS:91104

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables amyloid-beta binding	IC Inferred by Curator more info	PubMed
enables calcium ion binding	IEA Inferred from Electronic Annotation more info
enables collagen V binding	IEA Inferred from Electronic Annotation more info
enables extracellular matrix structural constituent conferring compression resistance	RCA inferred from Reviewed Computational Analysis more info	PubMed
enables integrin binding	TAS Traceable Author Statement more info	PubMed
enables low-density lipoprotein particle receptor binding	TAS Traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in angiogenesis	IEA Inferred from Electronic Annotation more info
involved_in animal organ regeneration	IEA Inferred from Electronic Annotation more info
involved_in brain development	TAS Traceable Author Statement more info	PubMed
involved_in cell differentiation	TAS Traceable Author Statement more info	PubMed
involved_in circulatory system development	TAS Traceable Author Statement more info	PubMed
involved_in embryo implantation	IEA Inferred from Electronic Annotation more info
involved_in inflammatory response	TAS Traceable Author Statement more info	PubMed
involved_in lipid metabolic process	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of amyloid fibril formation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of angiogenesis	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of cell adhesion	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cell population proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of endothelial cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in receptor-mediated endocytosis	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to hypoxia	IEA Inferred from Electronic Annotation more info
involved_in response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info
involved_in smoothened signaling pathway	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in Golgi lumen	TAS Traceable Author Statement more info
located_in basement membrane	TAS Traceable Author Statement more info	PubMed
colocalizes_with collagen-containing extracellular matrix	HDA 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	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in extracellular space	HDA more info	PubMed
located_in focal adhesion	HDA more info	PubMed
located_in lysosomal lumen	TAS Traceable Author Statement more info
located_in plasma membrane	TAS Traceable Author Statement more info
part_of plasma membrane protein complex	TAS Traceable Author Statement more info	PubMed

General protein information

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Preferred Names: basement membrane-specific heparan sulfate proteoglycan core protein

Names: endorepellin (domain V region); perlecan proteoglycan

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_016740.1 RefSeqGene

Range

4948..120014

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001291860.2 → NP_001278789.1 basement membrane-specific heparan sulfate proteoglycan core protein isoform a precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (a).

Source sequence(s)

AA450342, AL590103, AL590556, BC033152, BE273742, M85289, X62515

Conserved Domains (18) summary

cd00096
Location:3131 → 3200

Ig; Immunoglobulin domain

cd05743
Location:421 → 498

Ig_Perlecan_D2_like; Immunoglobulin (Ig)-like domain II (D2) of the human basement membrane heparan sulfate proteoglycan perlecan, also known as HSPG2

cd05754
Location:1772 → 1857

Ig3_Perlecan_like; Third immunoglobulin (Ig)-like domain found in Perlecan and similar proteins

smart00408
Location:1971 → 2033

IGc2; Immunoglobulin C-2 Type

smart00200
Location:80 → 194

SEA; Domain found in sea urchin sperm protein, enterokinase, agrin

smart00281
Location:986 → 1113

LamB; Laminin B domain

smart00409
Location:414 → 490

IG; Immunoglobulin

smart00410
Location:2058 → 2135

IG_like; Immunoglobulin like

cd00054
Location:3853 → 3882

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

cd00055
Location:1159 → 1208

EGF_Lam; Laminin-type epidermal growth factor-like domain; laminins are the major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation; the laminin-type epidermal growth factor-like module occurs in ...

cd00110
Location:4204 → 4363

LamG; Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of ...

cd00112
Location:285 → 319

LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...

pfam07679
Location:3582 → 3659

I-set; Immunoglobulin I-set domain

pfam00008
Location:4109 → 4139

EGF; EGF-like domain

pfam00047
Location:3027 → 3107

ig; Immunoglobulin domain

pfam00053
Location:1276 → 1323

Laminin_EGF; Laminin EGF domain

pfam13895
Location:2930 → 3010

Ig_2; Immunoglobulin domain

cl11960
Location:3597 → 3652

Ig; Immunoglobulin domain
NM_005529.7 → NP_005520.4 basement membrane-specific heparan sulfate proteoglycan core protein isoform b precursor

See identical proteins and their annotated locations for NP_005520.4

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 5' coding region, compared to variant 1, resulting in an isoform (b) that is 1 aa shorter than isoform a.

Source sequence(s)

AA450342, AL590103, AL590556, BC033152, BE273742, M85289, X62515

Consensus CDS

CCDS30625.1

UniProtKB/Swiss-Prot

P98160, Q16287, Q5SZI3, Q9H3V5

Related

ENSP00000363827.3, ENST00000374695.8

Conserved Domains (18) summary

cd00096
Location:3130 → 3199

Ig; Immunoglobulin domain

cd05743
Location:421 → 498

Ig_Perlecan_D2_like; Immunoglobulin (Ig)-like domain II (D2) of the human basement membrane heparan sulfate proteoglycan perlecan, also known as HSPG2

cd05754
Location:1771 → 1856

Ig3_Perlecan_like; Third immunoglobulin (Ig)-like domain found in Perlecan and similar proteins

smart00408
Location:1970 → 2032

IGc2; Immunoglobulin C-2 Type

smart00200
Location:80 → 194

SEA; Domain found in sea urchin sperm protein, enterokinase, agrin

smart00281
Location:985 → 1112

LamB; Laminin B domain

smart00409
Location:414 → 490

IG; Immunoglobulin

smart00410
Location:2057 → 2134

IG_like; Immunoglobulin like

cd00054
Location:3852 → 3881

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

cd00055
Location:1158 → 1207

EGF_Lam; Laminin-type epidermal growth factor-like domain; laminins are the major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation; the laminin-type epidermal growth factor-like module occurs in ...

cd00110
Location:4203 → 4362

LamG; Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of ...

cd00112
Location:285 → 319

LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...

pfam07679
Location:3581 → 3658

I-set; Immunoglobulin I-set domain

pfam00008
Location:4108 → 4138

EGF; EGF-like domain

pfam00047
Location:3026 → 3106

ig; Immunoglobulin domain

pfam00053
Location:1275 → 1322

Laminin_EGF; Laminin EGF domain

pfam13895
Location:2929 → 3009

Ig_2; Immunoglobulin domain

cl11960
Location:3596 → 3651

Ig; Immunoglobulin domain

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_000001.11 Reference GRCh38.p14 Primary Assembly

Range

21822244..21937310 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047419090.1 → XP_047275046.1 basement membrane-specific heparan sulfate proteoglycan core protein isoform X3
XM_047419080.1 → XP_047275036.1 basement membrane-specific heparan sulfate proteoglycan core protein isoform X2
XM_011541318.3 → XP_011539620.1 basement membrane-specific heparan sulfate proteoglycan core protein isoform X1

Conserved Domains (18) summary

cd00096
Location:3313 → 3382

Ig; Immunoglobulin domain

cd05743
Location:438 → 515

Ig_Perlecan_D2_like; Immunoglobulin (Ig)-like domain II (D2) of the human basement membrane heparan sulfate proteoglycan perlecan, also known as HSPG2

cd05754
Location:1954 → 2039

Ig3_Perlecan_like; Third immunoglobulin (Ig)-like domain found in Perlecan and similar proteins

smart00408
Location:2153 → 2215

IGc2; Immunoglobulin C-2 Type

smart00200
Location:80 → 193

SEA; Domain found in sea urchin sperm protein, enterokinase, agrin

smart00281
Location:1003 → 1130

LamB; Laminin B domain

smart00409
Location:431 → 507

IG; Immunoglobulin

smart00410
Location:2240 → 2317

IG_like; Immunoglobulin like

cd00054
Location:4035 → 4064

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

cd00055
Location:1176 → 1225

EGF_Lam; Laminin-type epidermal growth factor-like domain; laminins are the major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation; the laminin-type epidermal growth factor-like module occurs in ...

cd00110
Location:4386 → 4545

LamG; Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of ...

cd00112
Location:302 → 336

LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...

pfam07679
Location:3764 → 3841

I-set; Immunoglobulin I-set domain

pfam00008
Location:4291 → 4321

EGF; EGF-like domain

pfam00047
Location:3209 → 3289

ig; Immunoglobulin domain

pfam00053
Location:1293 → 1340

Laminin_EGF; Laminin EGF domain

pfam13895
Location:3112 → 3192

Ig_2; Immunoglobulin domain

cl11960
Location:3779 → 3834

Ig; Immunoglobulin domain
XM_017001122.1 → XP_016856611.1 basement membrane-specific heparan sulfate proteoglycan core protein isoform X7
XM_017001121.1 → XP_016856610.1 basement membrane-specific heparan sulfate proteoglycan core protein isoform X6
XM_047419091.1 → XP_047275047.1 basement membrane-specific heparan sulfate proteoglycan core protein isoform X5
XM_017001120.1 → XP_016856609.1 basement membrane-specific heparan sulfate proteoglycan core protein isoform X4

Alternate T2T-CHM13v2.0

Genomic

NC_060925.1 Alternate T2T-CHM13v2.0

Range

21646052..21761123 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054336237.1 → XP_054192212.1 basement membrane-specific heparan sulfate proteoglycan core protein isoform X3
XM_054336236.1 → XP_054192211.1 basement membrane-specific heparan sulfate proteoglycan core protein isoform X2
XM_054336235.1 → XP_054192210.1 basement membrane-specific heparan sulfate proteoglycan core protein isoform X1
XM_054336241.1 → XP_054192216.1 basement membrane-specific heparan sulfate proteoglycan core protein isoform X7
XM_054336240.1 → XP_054192215.1 basement membrane-specific heparan sulfate proteoglycan core protein isoform X6
XM_054336239.1 → XP_054192214.1 basement membrane-specific heparan sulfate proteoglycan core protein isoform X5
XM_054336238.1 → XP_054192213.1 basement membrane-specific heparan sulfate proteoglycan core protein isoform X4