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

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: mouse all
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Genomic context

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_000006.12 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
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?

Biochemical study of ZNF76 rs10947540 and SCUBE3 rs1888822 single nucleotide polymorphisms in the Egyptian patients with systemic lupus Erythematosus.
Title: Biochemical study of ZNF76 rs10947540 and SCUBE3 rs1888822 single nucleotide polymorphisms in the Egyptian patients with systemic lupus Erythematosus.
CircSCUBE3 promoted ferroptosis to inhibit lung adenocarcinoma progression.
Title: CircSCUBE3 promoted ferroptosis to inhibit lung adenocarcinoma progression.
Epithelium-derived SCUBE3 promotes polarized odontoblastic differentiation of dental mesenchymal stem cells and pulp regeneration.
Title: Epithelium-derived SCUBE3 promotes polarized odontoblastic differentiation of dental mesenchymal stem cells and pulp regeneration.
DEPDC1B Promotes Melanoma Angiogenesis and Metastasis through Sequestration of Ubiquitin Ligase CDC16 to Stabilize Secreted SCUBE3.
Title: DEPDC1B Promotes Melanoma Angiogenesis and Metastasis through Sequestration of Ubiquitin Ligase CDC16 to Stabilize Secreted SCUBE3.
SCUBE3 Is Likely a Susceptibility Gene for Systemic Lupus Erythematosus for Chinese Populations.
Title: SCUBE3 Is Likely a Susceptibility Gene for Systemic Lupus Erythematosus for Chinese Populations.
SCUBE3 loss-of-function causes a recognizable recessive developmental disorder due to defective bone morphogenetic protein signaling.
Title: SCUBE3 loss-of-function causes a recognizable recessive developmental disorder due to defective bone morphogenetic protein signaling.
The relationship of serum SCUBE-1, -2 and -3 levels with clinical findings and ultrasonographic skin thickness in systemic sclerosis patients.
Title: The relationship of serum SCUBE-1, -2 and -3 levels with clinical findings and ultrasonographic skin thickness in systemic sclerosis patients.
Activation of TGF-beta1 Pathway by SCUBE3 Regulates TWIST1 Expression and Promotes Breast Cancer Progression.
Title: Activation of TGF-β1 Pathway by SCUBE3 Regulates TWIST1 Expression and Promotes Breast Cancer Progression.
The results of this pioneering study indicate that SCUBE protein family appears to have a probable role in the pathogenesis and angiogenesis development in psoriasis and SCUBE 1 and 3 may be novel markers of angiogenesis in psoriasis.
Title: Can signal peptide-CUB-EGF domain-containing protein (SCUBE) levels be a marker of angiogenesis in patients with psoriasis?
Elevated expression of SCUBE3 in osteosarcoma tissues correlated with poor prognosis of the osteosarcoma patients.
Title: The Expression of HSPD1, SCUBE3, CXCL14 and Its Relations with the Prognosis in Osteosarcoma.

Submit: New GeneRIF Correction See all GeneRIFs (16)

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
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 EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH46635 (e-PCR)
- UniSTS:313

RH69466 (e-PCR)
- UniSTS:80486

RH46803 (e-PCR)
- UniSTS:7298

D6S2187 (e-PCR)
- UniSTS:7299

SGC30588 (e-PCR)
- UniSTS:34284

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

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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)

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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_050574.1 RefSeqGene

Range

4910..44033

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001303136.2 → NP_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:356 → 397

EGF_CA; Calcium-binding EGF-like domain

cd00041
Location:803 → 914

CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.

pfam07699
Location:695 → 742

GCC2_GCC3; GCC2 and GCC3

pfam12947
Location:33 → 68

EGF_3; EGF domain

pfam14670
Location:239 → 274

FXa_inhibition; Coagulation Factor Xa inhibitory site

cl00057
Location:312 → 348

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 ...
NM_152753.4 → NP_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:357 → 398

EGF_CA; Calcium-binding EGF-like domain

cd00041
Location:804 → 915

CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.

pfam07699
Location:696 → 743

Ephrin_rec_like; Putative ephrin-receptor like

pfam12947
Location:33 → 68

EGF_3; EGF domain

pfam14670
Location:240 → 275

FXa_inhibition; Coagulation Factor Xa inhibitory site

cl00057
Location:313 → 349

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

NC_000006.12 Reference GRCh38.p14 Primary Assembly

Range

35213956..35253079

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005248943.2 → XP_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:373 → 414

EGF_CA; Calcium-binding EGF-like domain

cd00041
Location:820 → 931

CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.

pfam07699
Location:712 → 759

GCC2_GCC3; GCC2 and GCC3

pfam12947
Location:33 → 68

EGF_3; EGF domain

pfam14670
Location:256 → 291

FXa_inhibition; Coagulation Factor Xa inhibitory site

cl00057
Location:329 → 365

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 ...
XM_005248947.2 → XP_005249004.1 signal peptide, CUB and EGF-like domain-containing protein 3 isoform X3

Conserved Domains (6) summary

smart00179
Location:373 → 414

EGF_CA; Calcium-binding EGF-like domain

cd00041
Location:766 → 877

CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.

pfam07699
Location:658 → 705

GCC2_GCC3; GCC2 and GCC3

pfam12947
Location:33 → 68

EGF_3; EGF domain

pfam14670
Location:256 → 291

FXa_inhibition; Coagulation Factor Xa inhibitory site

cl00057
Location:329 → 365

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 ...
XM_047418383.1 → XP_047274339.1 signal peptide, CUB and EGF-like domain-containing protein 3 isoform X4
XM_047418382.1 → XP_047274338.1 signal peptide, CUB and EGF-like domain-containing protein 3 isoform X2

Alternate T2T-CHM13v2.0

Genomic

NC_060930.1 Alternate T2T-CHM13v2.0

Range

35037034..35076159

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054354663.1 → XP_054210638.1 signal peptide, CUB and EGF-like domain-containing protein 3 isoform X1
XM_054354665.1 → XP_054210640.1 signal peptide, CUB and EGF-like domain-containing protein 3 isoform X3
XM_054354666.1 → XP_054210641.1 signal peptide, CUB and EGF-like domain-containing protein 3 isoform X4
XM_054354664.1 → XP_054210639.1 signal peptide, CUB and EGF-like domain-containing protein 3 isoform X2