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ACAN aggrecan [ Homo sapiens (human) ]

Gene ID: 176, updated on 14-Nov-2024

Summary

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Official Symbol
ACANprovided by HGNC
Official Full Name
aggrecanprovided by HGNC
Primary source
HGNC:HGNC:319
See related
Ensembl:ENSG00000157766 MIM:155760; AllianceGenome:HGNC:319
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
AGC1; SEDK; AGCAN; CSPG1; MSK16; CSPGCP; SSOAOD
Summary
This gene is a member of the aggrecan/versican proteoglycan family. The encoded protein is an integral part of the extracellular matrix in cartilagenous tissue and it withstands compression in cartilage. Mutations in this gene may be involved in skeletal dysplasia and spinal degeneration. Multiple alternatively spliced transcript variants that encode different protein isoforms have been observed in this gene. [provided by RefSeq, Jul 2008]
Expression
Broad expression in testis (RPKM 1.8), urinary bladder (RPKM 1.4) and 17 other tissues See more
Orthologs
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Genomic context

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See ACAN in Genome Data Viewer
Location:
15q26.1
Exon count:
20
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (88803436..88875353)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (86558075..86629996)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (89346667..89418584)

Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr15:89156265-89156949 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:89163779-89164452 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:89164453-89165126 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr15:89166102-89167301 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:89169771-89170314 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10029 Neighboring gene microRNA 3529 Neighboring gene Sharpr-MPRA regulatory region 1748 Neighboring gene microRNA 7-2 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:89181184-89182162 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:89182163-89183141 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10033 Neighboring gene apoptosis enhancing nuclease Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:89191225-89191986 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10034 Neighboring gene interferon stimulated exonuclease gene 20 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10035 Neighboring gene uncharacterized LOC105370960 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:89390146-89390646 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:89390647-89391147 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:89391205-89391372 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:89421781-89422356 Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:89428493-89429204 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:89438001-89438612 Neighboring gene Sharpr-MPRA regulatory region 11373 Neighboring gene hyaluronan and proteoglycan link protein 3 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6792 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:89450127-89451112 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:89455820-89456351 Neighboring gene milk fat globule EGF and factor V/VIII domain containing

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. Identification of a locus for a form of spondyloepiphyseal dysplasia on chromosome 15q26.1: exclusion of aggrecan as a candidate gene. Eyre S, et al. J Med Genet, 2002 Sep. PMID 12205105, Free PMC Article
  2. Aggrecan turnover in human intervertebral disc as determined by the racemization of aspartic acid. Sivan SS, et al. J Biol Chem, 2006 May 12. PMID 16537531
  3. Short aggrecan gene repetitive alleles associated with lumbar degenerative disc disease in Turkish patients. Eser O, et al. Genet Mol Res, 2011 Aug 30. PMID 21948754
  4. The involvement of aggrecan polymorphism in degeneration of human intervertebral disc and articular cartilage. Roughley P, et al. Eur Cell Mater, 2006 Jan 18. PMID 16425147
  5. Genetic variability in the extracellular matrix protein as a determinant of risk for developing HTLV-I-associated neurological disease. Nobuhara Y, et al. Immunogenetics, 2006 Jan. PMID 16402214

See all (176) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Genotype and phenotype in patients with ACAN gene variants: Three cases and literature review.
    Title: Genotype and phenotype in patients with ACAN gene variants: Three cases and literature review.
  2. Brachyury positively regulates extracellular matrix synthesis via directly promoting aggrecan transcription in nucleus pulposus.
    Title: Brachyury positively regulates extracellular matrix synthesis via directly promoting aggrecan transcription in nucleus pulposus.
  3. The relationship between the aggrecan VNTR polymorphism and its content in lumbar intervertebral discs.
    Title: The relationship between the aggrecan VNTR polymorphism and its content in lumbar intervertebral discs.
  4. [Analysis of a Chinese pedigree affected with familial short stature due to 15q25.3q26.1 deletion involving the ACAN gene].
    Title: [Analysis of a Chinese pedigree affected with familial short stature due to 15q25.3q26.1 deletion involving the ACAN gene].
  5. Downregulation of ACAN is Associated with the Growth hormone pathway and Induces short stature.
    Title: Downregulation of ACAN is Associated with the Growth hormone pathway and Induces short stature.
  6. Identification of variants in ACAN and PAPSS2 leading to spondyloepi(meta)physeal dysplasias in four Chinese families.
    Title: Identification of variants in ACAN and PAPSS2 leading to spondyloepi(meta)physeal dysplasias in four Chinese families.
  7. Novel missense ACAN gene variants linked to familial osteochondritis dissecans cluster in the C-terminal globular domain of aggrecan.
    Title: Novel missense ACAN gene variants linked to familial osteochondritis dissecans cluster in the C-terminal globular domain of aggrecan.
  8. Identification of novel ACAN mutations in two Chinese families and genotype-phenotype correlation in patients with 74 pathogenic ACAN variations.
    Title: Identification of novel ACAN mutations in two Chinese families and genotype-phenotype correlation in patients with 74 pathogenic ACAN variations.
  9. Altered Expression of Aggrecan, FAM20B, B3GALT6, and EXTL2 in Patients with Osteoarthritis and Kashin-Beck Disease.
    Title: Altered Expression of Aggrecan, FAM20B, B3GALT6, and EXTL2 in Patients with Osteoarthritis and Kashin-Beck Disease.
  10. Blood and urine biomarkers in osteoarthritis - an update on cartilage associated type II collagen and aggrecan markers.
    Title: Blood and urine biomarkers in osteoarthritis - an update on cartilage associated type II collagen and aggrecan markers.
Submit: New GeneRIF Correction See all GeneRIFs (125)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans
MedGen: C3665488 OMIM: 165800 GeneReviews: Not available
not available
Spondyloepimetaphyseal dysplasia, aggrecan type
MedGen: C2748544 OMIM: 612813 GeneReviews: Not available
not available
Spondyloepiphyseal dysplasia, Kimberley type
MedGen: C1842149 OMIM: 608361 GeneReviews: Not available
not available

EBI GWAS Catalog

Description
A novel common variant in DCST2 is associated with length in early life and height in adulthood.
EBI GWAS Catalog
Genome-wide association analysis identifies 20 loci that influence adult height.
EBI GWAS Catalog
Genome-wide association studies and heritability estimates of body mass index related phenotypes in bangladeshi adults.
EBI GWAS Catalog
Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture.
EBI GWAS Catalog
Hundreds of variants clustered in genomic loci and biological pathways affect human height.
EBI GWAS Catalog
Identification, replication, and fine-mapping of Loci associated with adult height in individuals of african ancestry.
EBI GWAS Catalog
Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci.
EBI GWAS Catalog

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
Tat tat HIV-Tat peptide interferes with polyamine uptake via competition for proteoglycan binding sites rather than a putative downstream transporter in human carcinoma cells PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables carbohydrate binding IEA
Inferred from Electronic Annotation
more info
  
enables extracellular matrix structural constituent TAS
Traceable Author Statement
more info
 PubMed 
enables extracellular matrix structural constituent conferring compression resistance RCA
inferred from Reviewed Computational Analysis
more info
 PubMed 
enables hyaluronic acid binding IEA
Inferred from Electronic Annotation
more info
  
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in cell adhesion IEA
Inferred from Electronic Annotation
more info
  
involved_in central nervous system development IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in proteolysis NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in skeletal system development IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in skeletal system development NAS
Non-traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
located_in Golgi lumen TAS
Traceable Author Statement
more info
  
colocalizes_with collagen-containing extracellular matrix HDA PubMed 
located_in collagen-containing extracellular matrix HDA 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 lysosomal lumen TAS
Traceable Author Statement
more info
  
is_active_in perineuronal net IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_in synapse IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
aggrecan core protein
Names
cartilage-specific proteoglycan core protein
chondroitin sulfate proteoglycan core protein 1
large aggregating 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

  1. NG_012794.1 RefSeqGene

    Range
    4994..76911
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001135.4 → NP_001126.3  aggrecan core protein isoform 1 precursor

    See identical proteins and their annotated locations for NP_001126.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) lacks three alternate in-frame exons in the 3' CDS, compared to variant 3. It encodes isoform 1, which lacks two internal segments, and is shorter, compared to isoform 3.
    Source sequence(s)
    AC103982
    Consensus CDS
    CCDS53971.1
    UniProtKB/TrEMBL
    E7ENV9
    Related
    ENSP00000341615.7, ENST00000352105.11
    Conserved Domains (7) summary
    cd03588
    Location:2282 → 2405
    CLECT_CSPGs; C-type lectin-like domain (CTLD) of the type found in chondroitin sulfate proteoglycan core proteins
    PRK15387
    Location:1433 → 1614
    PRK15387; type III secretion system effector E3 ubiquitin transferase SspH2
    TIGR00864
    Location:2115 → 2403
    PCC; polycystin cation channel protein
    smart00409
    Location:36 → 150
    IG; Immunoglobulin
    PHA03307
    Location:716 → 975
    PHA03307; transcriptional regulator ICP4; Provisional
    cd03517
    Location:153 → 247
    Link_domain_CSPGs_modules_1_3; this extracellular link domain is found in the first and third link modules of the chondroitin sulfate proteoglycan core protein (CSPG) aggrecan. In addition, it is found in the first link module of three other CSPGs: versican, neurocan, and brevican. ...
    cd03520
    Location:254 → 349
    Link_domain_CSPGs_modules_2_4; this link domain is found in the second and fourth link modules of the chondroitin sulfate proteoglycan core protein (CSPG) aggrecan and, in the second link module of three other CSPGs: versican, neurocan, and brevican. The link domain is a hyaluronan ...

  2. NM_001369268.1 → NP_001356197.1  aggrecan core protein isoform 3 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) represents the longest transcript and encodes the longest isoform (3).
    Source sequence(s)
    AC103982
    Consensus CDS
    CCDS92054.1
    UniProtKB/TrEMBL
    H0YMF1
    Related
    ENSP00000453581.2, ENST00000560601.4
    Conserved Domains (8) summary
    cd05900
    Location:43 → 154
    Ig_Aggrecan; Immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), aggrecan
    cd00033
    Location:2485 → 2541
    CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system
    cd03588
    Location:2358 → 2481
    CLECT_CSPGs; C-type lectin-like domain (CTLD) of the type found in chondroitin sulfate proteoglycan core proteins
    PRK15387
    Location:1433 → 1614
    PRK15387; E3 ubiquitin-protein ligase SspH2; Provisional
    PHA03307
    Location:716 → 975
    PHA03307; transcriptional regulator ICP4; Provisional
    cd00054
    Location:2316 → 2352
    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 ...
    cd03517
    Location:153 → 247
    Link_domain_CSPGs_modules_1_3; this extracellular link domain is found in the first and third link modules of the chondroitin sulfate proteoglycan core protein (CSPG) aggrecan. In addition, it is found in the first link module of three other CSPGs: versican, neurocan, and brevican. ...
    cd03520
    Location:254 → 349
    Link_domain_CSPGs_modules_2_4; this link domain is found in the second and fourth link modules of the chondroitin sulfate proteoglycan core protein (CSPG) aggrecan and, in the second link module of three other CSPGs: versican, neurocan, and brevican. The link domain is a hyaluronan ...

  3. NM_001411096.1 → NP_001398025.1  aggrecan core protein isoform 4 precursor

    Status: REVIEWED

    Source sequence(s)
    AC103982
    Consensus CDS
    CCDS92056.1
    Related
    ENSP00000453499.1, ENST00000559004.5

  4. NM_001411097.1 → NP_001398026.1  aggrecan core protein isoform 5 precursor

    Status: REVIEWED

    Source sequence(s)
    AC103982
    Consensus CDS
    CCDS92055.1
    UniProtKB/TrEMBL
    A0A5K1VW97
    Related
    ENSP00000453342.3, ENST00000561243.7

  5. NM_013227.4 → NP_037359.3  aggrecan core protein isoform 2 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 3' CDS, compared to variant 3. It encodes isoform 2, which lacks an internal segment, and is shorter, compared to isoform 3.
    Source sequence(s)
    AC103982
    Consensus CDS
    CCDS53970.1
    UniProtKB/Swiss-Prot
    B9EK55, E7ENV9, E7EX88, H0YM81, P16112, Q13650, Q9UCD3, Q9UCP4, Q9UCP5, Q9UDE0
    Related
    ENSP00000387356.2, ENST00000439576.7
    Conserved Domains (8) summary
    cd05900
    Location:43 → 154
    Ig_Aggrecan; Immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), aggrecan
    cd00033
    Location:2447 → 2503
    CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system
    cd03588
    Location:2320 → 2443
    CLECT_CSPGs; C-type lectin-like domain (CTLD) of the type found in chondroitin sulfate proteoglycan core proteins
    cd00054
    Location:2283 → 2313
    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 ...
    cd03517
    Location:153 → 247
    Link_domain_CSPGs_modules_1_3; Link_domain_CSPGs_modules_1_3; this extracellular link domain is found in the first and third link modules of the chondroitin sulfate proteoglycan core protein (CSPG) aggrecan. In addition, it is found in the first link module of three other CSPGs: ...
    cd03520
    Location:254 → 349
    Link_domain_CSPGs_modules_2_4; Link_domain_CSPGs_modules_2_4; this link domain is found in the second and fourth link modules of the chondroitin sulfate proteoglycan core protein (CSPG) aggrecan and, in the second link module of three other CSPGs: versican, neurocan, and brevican. The ...
    cl26018
    Location:1433 → 1614
    NEL; C-terminal novel E3 ligase, LRR-interacting
    cl28033
    Location:716 → 975
    Herpes_ICP4_C; Herpesvirus ICP4-like protein C-terminal region

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

  1. NC_000015.10 Reference GRCh38.p14 Primary Assembly

    Range
    88803436..88875353
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047432214.1 → XP_047288170.1  aggrecan core protein isoform X1

  2. XM_047432216.1 → XP_047288172.1  aggrecan core protein isoform X3

  3. XM_047432215.1 → XP_047288171.1  aggrecan core protein isoform X2

  4. XM_047432217.1 → XP_047288173.1  aggrecan core protein isoform X3

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060939.1 Alternate T2T-CHM13v2.0

    Range
    86558075..86629996
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054377434.1 → XP_054233409.1  aggrecan core protein isoform X1

  2. XM_054377436.1 → XP_054233411.1  aggrecan core protein isoform X3

  3. XM_054377435.1 → XP_054233410.1  aggrecan core protein isoform X2

  4. XM_054377437.1 → XP_054233412.1  aggrecan core protein isoform X3

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P16112.3 GenPept UniProtKB/Swiss-Prot:P16112

Gene LinkOut

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