HSPG2

Protein identityUniProt · HPA

UniProt accession

P98160

Gene

HSPG2

Ensembl

ENSG00000142798

Chromosome

1

Canonical length

4391 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted secreted proteins

Secretome location

Secreted to extracellular matrix

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

4391 residues, UniProt reviewed canonical sequence.

>P98160|HSPG2
     1  MGWRAAGALL LALLLHGRLL AVTHGLRAYD GLSLPEDIET VTASQMRWTH SYLSDDEDML
    61  ADSISGDDLG SGDLGSGDFQ MVYFRALVNF TRSIEYSPQL EDAGSREFRE VSEAVVDTLE
   121  SEYLKIPGDQ VVSVVFIKEL DGWVFVELDV GSEGNADGAQ IQEMLLRVIS SGSVASYVTS
   181  PQGFQFRRLG TVPQFPRACT EAEFACHSYN ECVALEYRCD RRPDCRDMSD ELNCEEPVLG
   241  ISPTFSLLVE TTSLPPRPET TIMRQPPVTH APQPLLPGSV RPLPCGPQEA ACRNGHCIPR
   301  DYLCDGQEDC EDGSDELDCG PPPPCEPNEF PCGNGHCALK LWRCDGDFDC EDRTDEANCP
   361  TKRPEEVCGP TQFRCVSTNM CIPASFHCDE ESDCPDRSDE FGCMPPQVVT PPRESIQASR
   421  GQTVTFTCVA IGVPTPIINW RLNWGHIPSH PRVTVTSEGG RGTLIIRDVK ESDQGAYTCE
   481  AMNARGMVFG IPDGVLELVP QRGPCPDGHF YLEHSAACLP CFCFGITSVC QSTRRFRDQI
   541  RLRFDQPDDF KGVNVTMPAQ PGTPPLSSTQ LQIDPSLHEF QLVDLSRRFL VHDSFWALPE
   601  QFLGNKVDSY GGSLRYNVRY ELARGMLEPV QRPDVVLMGA GYRLLSRGHT PTQPGALNQR
   661  QVQFSEEHWV HESGRPVQRA ELLQVLQSLE AVLIQTVYNT KMASVGLSDI AMDTTVTHAT
   721  SHGRAHSVEE CRCPIGYSGL SCESCDAHFT RVPGGPYLGT CSGCNCNGHA SSCDPVYGHC
   781  LNCQHNTEGP QCNKCKAGFF GDAMKATATS CRPCPCPYID ASRRFSDTCF LDTDGQATCD
   841  ACAPGYTGRR CESCAPGYEG NPIQPGGKCR PVNQEIVRCD ERGSMGTSGE ACRCKNNVVG
   901  RLCNECADGS FHLSTRNPDG CLKCFCMGVS RHCTSSSWSR AQLHGASEEP GHFSLTNAAS
   961  THTTNEGIFS PTPGELGFSS FHRLLSGPYF WSLPSRFLGD KVTSYGGELR FTVTQRSQPG
  1021  STPLHGQPLV VLQGNNIILE HHVAQEPSPG QPSTFIVPFR EQAWQRPDGQ PATREHLLMA
  1081  LAGIDTLLIR ASYAQQPAES RVSGISMDVA VPEETGQDPA LEVEQCSCPP GYRGPSCQDC
  1141  DTGYTRTPSG LYLGTCERCS CHGHSEACEP ETGACQGCQH HTEGPRCEQC QPGYYGDAQR
  1201  GTPQDCQLCP CYGDPAAGQA AHTCFLDTDG HPTCDACSPG HSGRHCERCA PGYYGNPSQG
  1261  QPCQRDSQVP GPIGCNCDPQ GSVSSQCDAA GQCQCKAQVE GLTCSHCRPH HFHLSASNPD
  1321  GCLPCFCMGI TQQCASSAYT RHLISTHFAP GDFQGFALVN PQRNSRLTGE FTVEPVPEGA
  1381  QLSFGNFAQL GHESFYWQLP ETYQGDKVAA YGGKLRYTLS YTAGPQGSPL SDPDVQITGN
  1441  NIMLVASQPA LQGPERRSYE IMFREEFWRR PDGQPATREH LLMALADLDE LLIRATFSSV
  1501  PLAASISAVS LEVAQPGPSN RPRALEVEEC RCPPGYIGLS CQDCAPGYTR TGSGLYLGHC
  1561  ELCECNGHSD LCHPETGACS QCQHNAAGEF CELCAPGYYG DATAGTPEDC QPCACPLTNP
  1621  ENMFSRTCES LGAGGYRCTA CEPGYTGQYC EQCGPGYVGN PSVQGGQCLP ETNQAPLVVE
  1681  VHPARSIVPQ GGSHSLRCQV SGSPPHYFYW SREDGRPVPS GTQQRHQGSE LHFPSVQPSD
  1741  AGVYICTCRN LHQSNTSRAE LLVTEAPSKP ITVTVEEQRS QSVRPGADVT FICTAKSKSP
  1801  AYTLVWTRLH NGKLPTRAMD FNGILTIRNV QLSDAGTYVC TGSNMFAMDQ GTATLHVQAS
  1861  GTLSAPVVSI HPPQLTVQPG QLAEFRCSAT GSPTPTLEWT GGPGGQLPAK AQIHGGILRL
  1921  PAVEPTDQAQ YLCRAHSSAG QQVARAVLHV HGGGGPRVQV SPERTQVHAG RTVRLYCRAA
  1981  GVPSATITWR KEGGSLPPQA RSERTDIATL LIPAITTADA GFYLCVATSP AGTAQARIQV
  2041  VVLSASDASP PPVKIESSSP SVTEGQTLDL NCVVAGSAHA QVTWYRRGGS LPPHTQVHGS
  2101  RLRLPQVSPA DSGEYVCRVE NGSGPKEASI TVSVLHGTHS GPSYTPVPGS TRPIRIEPSS
  2161  SHVAEGQTLD LNCVVPGQAH AQVTWHKRGG SLPARHQTHG SLLRLHQVTP ADSGEYVCHV
  2221  VGTSGPLEAS VLVTIEASVI PGPIPPVRIE SSSSTVAEGQ TLDLSCVVAG QAHAQVTWYK
  2281  RGGSLPARHQ VRGSRLYIFQ ASPADAGQYV CRASNGMEAS ITVTVTGTQG ANLAYPAGST
  2341  QPIRIEPSSS QVAEGQTLDL NCVVPGQSHA QVTWHKRGGS LPVRHQTHGS LLRLYQASPA
  2401  DSGEYVCRVL GSSVPLEASV LVTIEPAGSV PALGVTPTVR IESSSSQVAE GQTLDLNCLV
  2461  AGQAHAQVTW HKRGGSLPAR HQVHGSRLRL LQVTPADSGE YVCRVVGSSG TQEASVLVTI
  2521  QQRLSGSHSQ GVAYPVRIES SSASLANGHT LDLNCLVASQ APHTITWYKR GGSLPSRHQI
  2581  VGSRLRIPQV TPADSGEYVC HVSNGAGSRE TSLIVTIQGS GSSHVPSVSP PIRIESSSPT
  2641  VVEGQTLDLN CVVARQPQAI ITWYKRGGSL PSRHQTHGSH LRLHQMSVAD SGEYVCRANN
  2701  NIDALEASIV ISVSPSAGSP SAPGSSMPIR IESSSSHVAE GETLDLNCVV PGQAHAQVTW
  2761  HKRGGSLPSH HQTRGSRLRL HHVSPADSGE YVCRVMGSSG PLEASVLVTI EASGSSAVHV
  2821  PAPGGAPPIR IEPSSSRVAE GQTLDLKCVV PGQAHAQVTW HKRGGNLPAR HQVHGPLLRL
  2881  NQVSPADSGE YSCQVTGSSG TLEASVLVTI EPSSPGPIPA PGLAQPIYIE ASSSHVTEGQ
  2941  TLDLNCVVPG QAHAQVTWYK RGGSLPARHQ THGSQLRLHL VSPADSGEYV CRAASGPGPE
  3001  QEASFTVTVP PSEGSSYRLR SPVISIDPPS STVQQGQDAS FKCLIHDGAA PISLEWKTRN
  3061  QELEDNVHIS PNGSIITIVG TRPSNHGTYR CVASNAYGVA QSVVNLSVHG PPTVSVLPEG
  3121  PVWVKVGKAV TLECVSAGEP RSSARWTRIS STPAKLEQRT YGLMDSHAVL QISSAKPSDA
  3181  GTYVCLAQNA LGTAQKQVEV IVDTGAMAPG APQVQAEEAE LTVEAGHTAT LRCSATGSPA
  3241  PTIHWSKLRS PLPWQHRLEG DTLIIPRVAQ QDSGQYICNA TSPAGHAEAT IILHVESPPY
  3301  ATTVPEHASV QAGETVQLQC LAHGTPPLTF QWSRVGSSLP GRATARNELL HFERAAPEDS
  3361  GRYRCRVTNK VGSAEAFAQL LVQGPPGSLP ATSIPAGSTP TVQVTPQLET KSIGASVEFH
  3421  CAVPSDRGTQ LRWFKEGGQL PPGHSVQDGV LRIQNLDQSC QGTYICQAHG PWGKAQASAQ
  3481  LVIQALPSVL INIRTSVQTV VVGHAVEFEC LALGDPKPQV TWSKVGGHLR PGIVQSGGVV
  3541  RIAHVELADA GQYRCTATNA AGTTQSHVLL LVQALPQISM PQEVRVPAGS AAVFPCIASG
  3601  YPTPDISWSK LDGSLPPDSR LENNMLMLPS VRPQDAGTYV CTATNRQGKV KAFAHLQVPE
  3661  RVVPYFTQTP YSFLPLPTIK DAYRKFEIKI TFRPDSADGM LLYNGQKRVP GSPTNLANRQ
  3721  PDFISFGLVG GRPEFRFDAG SGMATIRHPT PLALGHFHTV TLLRSLTQGS LIVGDLAPVN
  3781  GTSQGKFQGL DLNEELYLGG YPDYGAIPKA GLSSGFIGCV RELRIQGEEI VFHDLNLTAH
  3841  GISHCPTCRD RPCQNGGQCH DSESSSYVCV CPAGFTGSRC EHSQALHCHP EACGPDATCV
  3901  NRPDGRGYTC RCHLGRSGLR CEEGVTVTTP SLSGAGSYLA LPALTNTHHE LRLDVEFKPL
  3961  APDGVLLFSG GKSGPVEDFV SLAMVGGHLE FRYELGSGLA VLRSAEPLAL GRWHRVSAER
  4021  LNKDGSLRVN GGRPVLRSSP GKSQGLNLHT LLYLGGVEPS VPLSPATNMS AHFRGCVGEV
  4081  SVNGKRLDLT YSFLGSQGIG QCYDSSPCER QPCQHGATCM PAGEYEFQCL CRDGFKGDLC
  4141  EHEENPCQLR EPCLHGGTCQ GTRCLCLPGF SGPRCQQGSG HGIAESDWHL EGSGGNDAPG
  4201  QYGAYFHDDG FLAFPGHVFS RSLPEVPETI ELEVRTSTAS GLLLWQGVEV GEAGQGKDFI
  4261  SLGLQDGHLV FRYQLGSGEA RLVSEDPIND GEWHRVTALR EGRRGSIQVD GEELVSGRSP
  4321  GPNVAVNAKG SVYIGGAPDV ATLTGGRFSS GITGCVKNLV LHSARPGAPP PQPLDLQHRA
  4381  QAGANTRPCP S

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HSPG2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0

Highest tissue expression

246 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HSPG2.

Disease | AllUniProt

Conditions HSPG2 is implicated in, by any mechanism.

• Schwartz-Jampel syndrome (SJS1) MIM:255800
• Dyssegmental dysplasia Silverman-Handmaker type (DDSH) MIM:224410

Disease | GeneticClinVar

118 pathogenic / likely-pathogenic of 3,522 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Schwartz-Jampel syndrome type 1
• Lethal Kniest-like syndrome
• Schwartz-Jampel syndrome
• HSPG2-related disorder
• Malignant tumor of urinary bladder

ReferencesPubMed · IEDB

Publications for HSPG2 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.41

gnomAD pLI

0

gnomAD missense Z

1.14

DepMap mean gene effect

-0.07

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• angiogenesis
• animal organ regeneration
• brain development
• cell differentiation
• circulatory system development
• embryo implantation
• inflammatory response
• lipid metabolic process
• negative regulation of angiogenesis
• negative regulation of cell adhesion
• negative regulation of cell population proliferation
• negative regulation of synaptic transmission, cholinergic
• positive regulation of endothelial cell proliferation
• protein localization to synapse
• receptor-mediated endocytosis
• response to hypoxia
• response to xenobiotic stimulus
• smoothened signaling pathway

Molecular functions

• amyloid-beta binding
• calcium ion binding
• collagen V binding
• extracellular matrix structural constituent conferring compression resistance
• low-density lipoprotein particle receptor binding
• molecular adaptor activity

Cellular components

• basement membrane
• extracellular exosome
• extracellular matrix
• extracellular region
• extracellular space
• focal adhesion
• Golgi lumen
• lysosomal lumen
• neuromuscular junction
• neuron projection
• plasma membrane
• plasma membrane protein complex

Protein domainsUniProt · Pfam · InterPro

• Laminin IV
• SEA domain
• EGF-like domain
• Laminin G domain
• EGF-like calcium-binding domain
• Laminin-type EGF domain
• Low-density lipoprotein (LDL) receptor class A repeat
• Immunoglobulin subtype 2
• Immunoglobulin domain subtype
• Immunoglobulin-like domain
• Immunoglobulin I-set
• Immunoglobulin V-set domain
• Concanavalin A-like lectin/glucanase domain superfamily
• Immunoglobulin-like fold
• Low-density lipoprotein (LDL) receptor class A, conserved site
• LDL receptor-like superfamily
• Immunoglobulin-like domain superfamily
• Neural and epithelial cell adhesion domain-containing protein
• Laminin/attractin/netrin-like, EGF domain
• EGF-like domain
• Laminin B (Domain IV)
• Laminin EGF domain
• Laminin G domain
• Low-density lipoprotein receptor domain class A
• Immunoglobulin I-set domain
• Immunoglobulin domain
• Immunoglobulin domain
• Laminin/attractin EGF domain

KeywordsUniProt

• Angiogenesis
• Basement membrane
• Calcium
• Disulfide bond
• EGF-like domain
• Extracellular matrix
• Glycoprotein
• Heparan sulfate
• Immunoglobulin domain
• Laminin EGF-like domain
• Metal-binding
• Proteoglycan
• Repeat
• Secreted
• Signal

InteractionsUniProt · HPA

Protein binding partners of HSPG2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• COL13A1
• FGFBP1
• SVEP1
• VWA1
• COLQ
• DAG1
• COL18A1
• FBXO6