SHC4 SHC adaptor protein 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SHC4provided by HGNC
Official Full Name: SHC adaptor protein 4provided by HGNC
Primary source: HGNC:HGNC:16743
See related: Ensembl:ENSG00000185634 MIM:617372; AllianceGenome:HGNC:16743
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: RaLP; SHCD
Summary: Predicted to enable receptor tyrosine kinase binding activity. Predicted to be involved in cell surface receptor protein tyrosine kinase signaling pathway. Predicted to act upstream of or within several processes, including apoptotic process; positive regulation of cell population proliferation; and stem cell differentiation. Predicted to be located in postsynaptic membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Nov 2024]
Expression: Biased expression in testis (RPKM 6.4), brain (RPKM 2.8) and 5 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 15q21.1

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	15	NC_000015.10 (48823741..48963919, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	15	NC_060939.1 (46631939..46772161, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	15	NC_000015.9 (49115938..49256116, complement)

Chromosome 15 - NC_000015.10 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?

SHC4 orchestrates beta-catenin pathway-mediated metastasis in triple-negative breast cancer by promoting Src kinase autophosphorylation.
Title: SHC4 orchestrates β-catenin pathway-mediated metastasis in triple-negative breast cancer by promoting Src kinase autophosphorylation.
Adaptor Protein ShcD/SHC4 Interacts with Tie2 Receptor to Synergistically Promote Glioma Cell Invasion.
Title: Adaptor Protein ShcD/SHC4 Interacts with Tie2 Receptor to Synergistically Promote Glioma Cell Invasion.
ShcD appears to possess several molecular permutations that actively govern the EGFR, which may have implications in development and disease.
Title: The ShcD phosphotyrosine adaptor subverts canonical EGF receptor trafficking.
ShcD binds to active Ret, TrkA, and TrkB neurotrophic factor receptors predominantly via its phosphotyrosine-binding (PTB) domain.
Title: Signaling adaptor ShcD suppresses extracellular signal-regulated kinase (Erk) phosphorylation distal to the Ret and Trk neurotrophic receptors.
The ShcD signaling adaptor facilitates ligand-independent phosphorylation of the EGF receptor.
Title: The ShcD signaling adaptor facilitates ligand-independent phosphorylation of the EGF receptor.
ShcD can exist within the nucleus, and its CH2 domain has a critical role in nuclear export of ShcD.
Title: A nuclear export signal and oxidative stress regulate ShcD subcellular localisation: a potential role for ShcD in the nucleus.
ShcD binds to TrkC in a kinase-activity-dependent manner through its PTB and SH2 domains.
Title: [ShcD interacts with TrkC through its PTB and SH2 domains].
ShcD interacts with TrkB in a kinase-activity-dependent manner.
Title: ShcD interacts with TrkB via its PTB and SH2 domains and regulates BDNF-induced MAPK activation.
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
A new member of the Shc family of docking proteins is characterised, which may mediate a specific aspect of signaling downstream of the MuSK receptor.
Title: Analysis of a Shc family adaptor protein, ShcD/Shc4, that associates with muscle-specific kinase.

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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

EBI GWAS Catalog

Description
Genome-wide association analysis of eating disorder-related symptoms, behaviors, and personality traits. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analysis of gender differences in major depressive disorder in the Netherlands NESDA and NTR population-based samples. 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

STS-N93791 (e-PCR)
- UniSTS:21760

SHGC-34647 (e-PCR)
- UniSTS:59960

SGC34499 (e-PCR)
- UniSTS:80985

RH123395 (e-PCR)
- UniSTS:135770

RH47286 (e-PCR)
- UniSTS:69240

RH66594 (e-PCR)
- UniSTS:90760

G27429 (e-PCR)
- UniSTS:77227

WI-10566 (e-PCR)
- UniSTS:30123

RH15715 (e-PCR)
- UniSTS:81582

RH118974 (e-PCR)
- UniSTS:138942

RH47316 (e-PCR)
- UniSTS:79815

STS-R92213 (e-PCR)
- UniSTS:46023

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein domain specific binding	IEA Inferred from Electronic Annotation more info
enables receptor tyrosine kinase binding	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in cell surface receptor protein tyrosine kinase signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in intracellular signal transduction	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cell population proliferation	IEA Inferred from Electronic Annotation more info
involved_in regulation of gene expression	IEA Inferred from Electronic Annotation more info
involved_in stem cell differentiation	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in postsynaptic membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: SHC-transforming protein 4

Names: SH2 domain protein C4; SHC (Src homology 2 domain containing) family, member 4; SHC-transforming protein D; hShcD; rai-like protein; src homology 2 domain-containing-transforming protein C4

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.

mRNA and Protein(s)

NM_203349.4 → NP_976224.3 SHC-transforming protein 4

See identical proteins and their annotated locations for NP_976224.3

Status: VALIDATED

Source sequence(s)

AC012379, AC091073, AY464565

Consensus CDS

CCDS10130.1

UniProtKB/Swiss-Prot

Q6S5L8, Q6UXQ3, Q8IYW3

Related

ENSP00000329668.4, ENST00000332408.9

Conserved Domains (2) summary

cd09925
Location:518 → 618

SH2_SHC; Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC)

cd01209
Location:176 → 347

PTB_Shc; Shc-like phosphotyrosine-binding (PTB) 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_000015.10 Reference GRCh38.p14 Primary Assembly

Range

48823741..48963919 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005254375.4 → XP_005254432.1 SHC-transforming protein 4 isoform X1

UniProtKB/TrEMBL

B3KWT2

Conserved Domains (2) summary

cd09925
Location:335 → 435

SH2_SHC; Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC)

cd01209
Location:13 → 164

PTB_Shc; Shc-like phosphotyrosine-binding (PTB) domain
XM_047432493.1 → XP_047288449.1 SHC-transforming protein 4 isoform X2

UniProtKB/TrEMBL

F5H5M1

Related

ENSP00000443300.1, ENST00000537958.5
XM_047432492.1 → XP_047288448.1 SHC-transforming protein 4 isoform X2

UniProtKB/TrEMBL

F5H5M1

Related

ENSP00000379786.3, ENST00000396535.7

Alternate T2T-CHM13v2.0

Genomic

NC_060939.1 Alternate T2T-CHM13v2.0

Range

46631939..46772161 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054377896.1 → XP_054233871.1 SHC-transforming protein 4 isoform X1
XM_054377897.1 → XP_054233872.1 SHC-transforming protein 4 isoform X2

UniProtKB/TrEMBL

F5H5M1