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SCUBE3 signal peptide, CUB domain and EGF like domain containing 3 [ Homo sapiens (human) ]

Gene ID: 222663, updated on 2-Nov-2024

Summary

Official Symbol
SCUBE3provided by HGNC
Official Full Name
signal peptide, CUB domain and EGF like domain containing 3provided by HGNC
Primary source
HGNC:HGNC:13655
See related
Ensembl:ENSG00000146197 MIM:614708; AllianceGenome:HGNC:13655
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
CEGF3; SSFSC2
Summary
This gene encodes a member of the signal peptide, complement subcomponents C1r/C1s, Uegf, bone morphogenetic protein-1 and epidermal growth factor-like domain containing protein family. Overexpression of this gene in human embryonic kidney cells results in secretion of a glycosylated form of the protein that forms oligomers and tethers to the cell surface. This gene is upregulated in lung cancer tumor tissue compared to healthy tissue and is associated with loss of the epithelial marker E-cadherin and with increased expression of vimentin, a mesenchymal marker. In addition, the protein encoded by this gene is a transforming growth factor beta receptor ligand, and when secreted by cancer cells, it can be cleaved in vitro to release the N-terminal epidermal growth factor-like repeat domain and the C-terminal complement subcomponents C1r/C1s domain. Both the full length protein and C-terminal fragment can bind to the transforming growth factor beta type II receptor to promote the epithelial-mesenchymal transition and tumor angiogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]
Expression
Biased expression in thyroid (RPKM 18.5), adrenal (RPKM 1.4) and 2 other tissues See more
Orthologs
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Genomic context

See SCUBE3 in Genome Data Viewer
Location:
6p21.31
Exon count:
24
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (35213956..35253079)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (35037034..35076159)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (35181733..35220856)

Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene t-complex 11 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr6:35115441-35116234 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr6:35116235-35117028 Neighboring gene MPRA-validated peak5764 silencer Neighboring gene ReSE screen-validated silencer GRCh37_chr6:35152333-35152714 Neighboring gene Sharpr-MPRA regulatory region 4993 Neighboring gene uncharacterized LOC112267955 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17084 Neighboring gene SCUBE3 antisense RNA 1 Neighboring gene Sharpr-MPRA regulatory region 1078 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17085 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr6:35211069-35212268 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24396 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17086 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17087 Neighboring gene zinc finger protein 76 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr6:35253595-35254794 Neighboring gene ReSE screen-validated silencer GRCh37_chr6:35263932-35264096 Neighboring gene Sharpr-MPRA regulatory region 9100 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24398 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:35280323-35280822 Neighboring gene DEF6 guanine nucleotide exchange factor

Genomic regions, transcripts, and products

Expression

  • 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

Related articles in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 2
MedGen: C5543057 OMIM: 619184 GeneReviews: Not available
not available

EBI GWAS Catalog

Description
Many sequence variants affecting diversity of adult human height.
EBI GWAS Catalog

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Clone Names

  • FLJ34743, DKFZp686B1223, DKFZp686B09105, DKFZp686D20108

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables BMP binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables BMP receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables calcium ion binding IEA
Inferred from Electronic Annotation
more info
 
enables identical protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
involved_in positive regulation of BMP signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in positive regulation of osteoblast differentiation IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
 
Component Evidence Code Pubs
is_active_in cell surface IBA
Inferred from Biological aspect of Ancestor
more info
 
located_in cell surface IDA
Inferred from Direct Assay
more info
PubMed 
is_active_in extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
 
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 
located_in plasma membrane TAS
Traceable Author Statement
more info
 

General protein information

Preferred Names
signal peptide, CUB and EGF-like domain-containing protein 3
Names
CUB domain and EGF-like repeat containing 3

NCBI Reference Sequences (RefSeq)

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

  1. NG_050574.1 RefSeqGene

    Range
    4910..44033
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001303136.2NP_001290065.1  signal peptide, CUB and EGF-like domain-containing protein 3 isoform 2 precursor

    See identical proteins and their annotated locations for NP_001290065.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate in-frame splice acceptor compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
    Source sequence(s)
    BC052263, CR936873, Z97832
    UniProtKB/Swiss-Prot
    Q8IX30
    Conserved Domains (6) summary
    smart00179
    Location:356397
    EGF_CA; Calcium-binding EGF-like domain
    cd00041
    Location:803914
    CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.
    pfam07699
    Location:695742
    GCC2_GCC3; GCC2 and GCC3
    pfam12947
    Location:3368
    EGF_3; EGF domain
    pfam14670
    Location:239274
    FXa_inhibition; Coagulation Factor Xa inhibitory site
    cl00057
    Location:312348
    vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...
  2. NM_152753.4NP_689966.2  signal peptide, CUB and EGF-like domain-containing protein 3 isoform 1 precursor

    See identical proteins and their annotated locations for NP_689966.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AF452494, BC052263, CR936873, Z97832
    Consensus CDS
    CCDS4800.1
    UniProtKB/Swiss-Prot
    A8K5A3, Q5CZB3, Q86UZ9, Q8IX30, Q8NAU9
    Related
    ENSP00000274938.7, ENST00000274938.8
    Conserved Domains (6) summary
    smart00179
    Location:357398
    EGF_CA; Calcium-binding EGF-like domain
    cd00041
    Location:804915
    CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.
    pfam07699
    Location:696743
    Ephrin_rec_like; Putative ephrin-receptor like
    pfam12947
    Location:3368
    EGF_3; EGF domain
    pfam14670
    Location:240275
    FXa_inhibition; Coagulation Factor Xa inhibitory site
    cl00057
    Location:313349
    vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...

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_000006.12 Reference GRCh38.p14 Primary Assembly

    Range
    35213956..35253079
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005248943.2XP_005249000.1  signal peptide, CUB and EGF-like domain-containing protein 3 isoform X1

    See identical proteins and their annotated locations for XP_005249000.1

    UniProtKB/Swiss-Prot
    Q8IX30
    Conserved Domains (6) summary
    smart00179
    Location:373414
    EGF_CA; Calcium-binding EGF-like domain
    cd00041
    Location:820931
    CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.
    pfam07699
    Location:712759
    GCC2_GCC3; GCC2 and GCC3
    pfam12947
    Location:3368
    EGF_3; EGF domain
    pfam14670
    Location:256291
    FXa_inhibition; Coagulation Factor Xa inhibitory site
    cl00057
    Location:329365
    vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...
  2. XM_005248947.2XP_005249004.1  signal peptide, CUB and EGF-like domain-containing protein 3 isoform X3

    Conserved Domains (6) summary
    smart00179
    Location:373414
    EGF_CA; Calcium-binding EGF-like domain
    cd00041
    Location:766877
    CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.
    pfam07699
    Location:658705
    GCC2_GCC3; GCC2 and GCC3
    pfam12947
    Location:3368
    EGF_3; EGF domain
    pfam14670
    Location:256291
    FXa_inhibition; Coagulation Factor Xa inhibitory site
    cl00057
    Location:329365
    vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...
  3. XM_047418383.1XP_047274339.1  signal peptide, CUB and EGF-like domain-containing protein 3 isoform X4

  4. XM_047418382.1XP_047274338.1  signal peptide, CUB and EGF-like domain-containing protein 3 isoform X2

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060930.1 Alternate T2T-CHM13v2.0

    Range
    35037034..35076159
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054354663.1XP_054210638.1  signal peptide, CUB and EGF-like domain-containing protein 3 isoform X1

  2. XM_054354665.1XP_054210640.1  signal peptide, CUB and EGF-like domain-containing protein 3 isoform X3

  3. XM_054354666.1XP_054210641.1  signal peptide, CUB and EGF-like domain-containing protein 3 isoform X4

  4. XM_054354664.1XP_054210639.1  signal peptide, CUB and EGF-like domain-containing protein 3 isoform X2