APBB1 amyloid beta precursor protein binding family B member 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: APBB1provided by HGNC
Official Full Name: amyloid beta precursor protein binding family B member 1provided by HGNC
Primary source: HGNC:HGNC:581
See related: Ensembl:ENSG00000166313 MIM:602709; AllianceGenome:HGNC:581
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: RIR; FE65; MGC:9072
Summary: The protein encoded by this gene is a member of the Fe65 protein family. It is an adaptor protein localized in the nucleus. It interacts with the Alzheimer's disease amyloid precursor protein (APP), transcription factor CP2/LSF/LBP1 and the low-density lipoprotein receptor-related protein. APP functions as a cytosolic anchoring site that can prevent the gene product's nuclear translocation. This encoded protein could play an important role in the pathogenesis of Alzheimer's disease. It is thought to regulate transcription. Also it is observed to block cell cycle progression by downregulating thymidylate synthase expression. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Mar 2012]
Expression: Broad expression in brain (RPKM 44.0), ovary (RPKM 11.7) and 17 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11p15.4

Exon count:: 19

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (6395124..6419453, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (6453583..6477913, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (6416354..6440683, complement)

Chromosome 11 - NC_000011.10 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
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?

Alpha-secretase dependent nuclear localization of the amyloid-beta precursor protein-binding protein Fe65 promotes DNA repair.
Title: Alpha-secretase dependent nuclear localization of the amyloid-β precursor protein-binding protein Fe65 promotes DNA repair.
Abeta40 Promotes the Osteoblastic Differentiation of Aortic Valve Interstitial Cells through the RAGE Pathway.
Title: Aβ40 Promotes the Osteoblastic Differentiation of Aortic Valve Interstitial Cells through the RAGE Pathway.
ARF6-Rac1 signaling-mediated neurite outgrowth is potentiated by the neuronal adaptor FE65 through orchestrating ARF6 and ELMO1.
Title: ARF6-Rac1 signaling-mediated neurite outgrowth is potentiated by the neuronal adaptor FE65 through orchestrating ARF6 and ELMO1.
The findings reveal a novel mechanism whereby GSK3beta stimulates amyloidogenic processing of APP by phosphorylation of FE65 at threonine 579.
Title: Phosphorylation of FE65 at threonine 579 by GSK3β stimulates amyloid precursor protein processing.
FE65 is found to activate ELMO1 by diminishing ELMO1 intramolecular autoinhibitory interaction and to promote the targeting of ELMO1 to the plasma membrane, where Rac1 is activated. We also show that FE65, ELMO1, and DOCK180 form a tripartite complex
Title: Neuronal adaptor FE65 stimulates Rac1-mediated neurite outgrowth by recruiting and activating ELMO1.
Fe65 is an adaptor protein involved in both processing and signaling of the Alzheimer-associated amyloid-beta precursor protein, APP. Here, the subcellular localization was further investigated using TAP-tagged Fe65 constructs expressed in human neuroblastoma cells. Our results indicate that PTB2 rather than the WW domain is important for the nuclear localization of Fe65.
Title: Nuclear localization of amyloid-β precursor protein-binding protein Fe65 is dependent on regulated intramembrane proteolysis.
Fe65 Ser289 phosphorylation did not affect the transcriptional activity of the Fe65-APP complex, in contrast to the previously described Ser228 site.
Title: Fe65 Is Phosphorylated on Ser289 after UV-Induced DNA Damage.
Our findings imply that APBB1 plays an important role in the maintenance of EMT-associated CSC-like properties and gamma-radiation resistance via activation of IGF1Rbeta/AKT/GSK3beta pathway in lung cancer cells, highlighting APBB1 as a potential target for therapeutic cancer treatment.
Title: APBB1 reinforces cancer stem cell and epithelial-to-mesenchymal transition by regulating the IGF1R signaling pathway in non-small-cell lung cancer cells.
Targeted enhancement of the signaling through the Fe65-cortactin pathway, by either HDAC6 inhibition or Tip60 activation, may lead to the development of new therapeutic drugs that are effective for patients with metastatic breast cancers.
Title: Fe65 Suppresses Breast Cancer Cell Migration and Invasion through Tip60 Mediated Cortactin Acetylation.
Jagged1 is a novel binding partner of Fe65, and Fe65 may act as a novel effector of Jagged1 signaling.
Title: Fe65 negatively regulates Jagged1 signaling by decreasing Jagged1 protein stability through the E3 ligase Neuralized-like 1.

Submit: New GeneRIF Correction See all GeneRIFs (51)

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

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

Apbb1 (e-PCR), detects polymorphism
- UniSTS:141099

GDB:197904 (e-PCR)
- UniSTS:155997

G63687 (e-PCR)
- UniSTS:140649

RH125131 (e-PCR)
- UniSTS:161953

A002D29 (e-PCR)
- UniSTS:17869

SMPD1 (e-PCR)
- UniSTS:48627

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables amyloid-beta binding	IBA Inferred from Biological aspect of Ancestor more info
enables chromatin binding	IDA Inferred from Direct Assay more info	PubMed
enables histone binding	IPI Inferred from Physical Interaction more info	PubMed
enables low-density lipoprotein particle receptor binding	TAS Traceable Author Statement more info	PubMed
enables molecular adaptor activity	IDA Inferred from Direct Assay more info	PubMed
enables proline-rich region binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables transcription coactivator activity	TAS Traceable Author Statement more info	PubMed
enables transcription factor binding	IBA Inferred from Biological aspect of Ancestor more info
enables ubiquitin protein ligase binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA damage response	IDA Inferred from Direct Assay more info	PubMed
involved_in apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in axonogenesis	NAS Non-traceable Author Statement more info	PubMed
involved_in chromatin organization	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cell cycle G1/S phase transition	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of transcription by RNA polymerase II	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of neuron projection development	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein secretion	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	TAS Traceable Author Statement more info	PubMed
involved_in regulation of DNA-templated transcription	IBA Inferred from Biological aspect of Ancestor more info
involved_in signal transduction	NAS Non-traceable Author Statement more info	PubMed
involved_in smooth muscle contraction	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info
located_in growth cone	IDA Inferred from Direct Assay more info	PubMed
located_in lamellipodium	IDA Inferred from Direct Assay more info	PubMed
located_in nuclear speck	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in synapse	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: amyloid beta precursor protein binding family B member 1

Names: adaptor protein FE65a2; amyloid beta (A4) precursor protein-binding, family B, member 1 (Fe65); stat-like protein

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_029615.1 RefSeqGene

Range

5321..29290

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001164.5 → NP_001155.1 amyloid beta precursor protein binding family B member 1 isoform a

See identical proteins and their annotated locations for NP_001155.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a, also known as E9). This isoform is exclusively expressed in neurons.

Source sequence(s)

BC010854, HY145957, L77864

Consensus CDS

CCDS66018.1

UniProtKB/Swiss-Prot

A1E379, A6NH82, A6NL69, B7Z1J5, B7Z1J6, B7Z2Y0, D3DQT2, O00213, Q7Z324, Q96A93, V9GYK0, V9GYT4

UniProtKB/TrEMBL

A0A075B7G8

Related

ENSP00000477213.1, ENST00000609360.6

Conserved Domains (3) summary

cd01271
Location:535 → 660

PTB2_Fe65; Fe65 C-terminal Phosphotyrosine-binding (PTB) domain

cd01272
Location:368 → 507

PTB1_Fe65; Fe65 N-terminal Phosphotyrosine-binding (PTB) domain

pfam00397
Location:255 → 283

WW; WW domain
NM_001257319.3 → NP_001244248.1 amyloid beta precursor protein binding family B member 1 isoform g

See identical proteins and their annotated locations for NP_001244248.1

Status: REVIEWED

Description

Transcript Variant: This variant (9) represents use of an alternate promoter and thus differs in the 5' UTR and 5' coding region compared to variant 1. These differences cause translation initiation at an alternate start codon and result in an isoform (g) with a shorter and distinct N-terminus, compared to isoform 1.

Source sequence(s)

BX538185, DC316489

Consensus CDS

CCDS66017.1

UniProtKB/TrEMBL

B7Z327, B7Z9K0

Related

ENSP00000476846.1, ENST00000608655.6

Conserved Domains (3) summary

cd01271
Location:315 → 440

PTB2_Fe65; Fe65 C-terminal Phosphotyrosine-binding (PTB) domain

cd01272
Location:148 → 287

PTB1_Fe65; Fe65 N-terminal Phosphotyrosine-binding (PTB) domain

pfam00397
Location:35 → 63

WW; WW domain
NM_001257320.2 → NP_001244249.1 amyloid beta precursor protein binding family B member 1 isoform d

See identical proteins and their annotated locations for NP_001244249.1

Status: REVIEWED

Description

Transcript Variant: This variant (6) represents use of an alternate promoter and thus differs in the 5' UTR and 5' coding region compared to variant 1. These differences cause translation initiation at a downstream start codon and result in an isoform (d) with a shorter N-terminus, compared to isoform 1. Variants 4, 5, and 6 all encode the same isoform (d).

Source sequence(s)

BM145723, EF103274, HY118301

Consensus CDS

CCDS66015.1

UniProtKB/TrEMBL

B7Z327, B7Z9K0

Related

ENSP00000476871.1, ENST00000608704.5

Conserved Domains (3) summary

cd01271
Location:276 → 401

PTB2_Fe65; Fe65 C-terminal Phosphotyrosine-binding (PTB) domain

cd01272
Location:109 → 248

PTB1_Fe65; Fe65 N-terminal Phosphotyrosine-binding (PTB) domain

pfam00397
Location:5 → 24

WW; WW domain
NM_001257321.2 → NP_001244250.1 amyloid beta precursor protein binding family B member 1 isoform d

See identical proteins and their annotated locations for NP_001244250.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) represents use of an alternate promoter and thus differs in the 5' UTR and 5' coding region compared to variant 1. These differences cause translation initiation at a downstream start codon and result in an isoform (d) with a shorter N-terminus, compared to isoform 1. Variants 4, 5, and 6 all encode the same isoform (d).

Source sequence(s)

AK297550, BM145723, EF103274

Consensus CDS

CCDS66015.1

UniProtKB/TrEMBL

B7Z327, B7Z9K0

Related

ENSP00000476442.1, ENST00000608394.5

Conserved Domains (3) summary

cd01271
Location:276 → 401

PTB2_Fe65; Fe65 C-terminal Phosphotyrosine-binding (PTB) domain

cd01272
Location:109 → 248

PTB1_Fe65; Fe65 N-terminal Phosphotyrosine-binding (PTB) domain

pfam00397
Location:5 → 24

WW; WW domain
NM_001257323.3 → NP_001244252.1 amyloid beta precursor protein binding family B member 1 isoform f

See identical proteins and their annotated locations for NP_001244252.1

Status: REVIEWED

Description

Transcript Variant: This variant (8) represents use of an alternate promoter and thus differs in the 5' UTR and 5' coding region, and lacks an alternate, in-frame exon in the coding region compared to variant 1. These differences cause translation initiation at an alternate start codon and result in an isoform (f) that is shorter with a distinct N-terminus, compared to isoform 1.

Source sequence(s)

AK295241, BC010854, DC316489

Consensus CDS

CCDS58114.1

UniProtKB/TrEMBL

B7Z327, B7Z9K0

Related

ENSP00000433338.1, ENST00000530885.5

Conserved Domains (3) summary

cd01271
Location:313 → 438

PTB2_Fe65; Fe65 C-terminal Phosphotyrosine-binding (PTB) domain

cd01272
Location:148 → 285

PTB1_Fe65; Fe65 N-terminal Phosphotyrosine-binding (PTB) domain

pfam00397
Location:35 → 63

WW; WW domain
NM_001257325.3 → NP_001244254.1 amyloid beta precursor protein binding family B member 1 isoform e

See identical proteins and their annotated locations for NP_001244254.1

Status: REVIEWED

Description

Transcript Variant: This variant (7) represents use of an alternate promoter and thus differs in the 5' UTR and 5' coding region compared to variant 1. These differences cause translation initiation at an alternate start codon and result in an isoform (e) with a shorter and distinct N-terminus, compared to isoform 1.

Source sequence(s)

AK293554, BC010854, DC306210, DC319935

Consensus CDS

CCDS66016.1

UniProtKB/TrEMBL

B7Z327, B7Z9K0

Related

ENSP00000477069.1, ENST00000609331.5

Conserved Domains (3) summary

cd01271
Location:300 → 425

PTB2_Fe65; Fe65 C-terminal Phosphotyrosine-binding (PTB) domain

cd01272
Location:133 → 272

PTB1_Fe65; Fe65 N-terminal Phosphotyrosine-binding (PTB) domain

pfam00397
Location:20 → 48

WW; WW domain
NM_001257326.2 → NP_001244255.1 amyloid beta precursor protein binding family B member 1 isoform d

See identical proteins and their annotated locations for NP_001244255.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) represents use of an alternate promoter and thus differs in the 5' UTR and 5' coding region compared to variant 1. These differences cause translation initiation at a downstream start codon and result in an isoform (d) with a shorter N-terminus, compared to isoform 1. Variants 4, 5, and 6 all encode the same isoform (d).

Source sequence(s)

AK293550, AK297550, BC010854, BM145723

Consensus CDS

CCDS66015.1

UniProtKB/TrEMBL

B7Z327, B7Z9K0

Related

ENSP00000476646.1, ENST00000608645.5

Conserved Domains (3) summary

cd01271
Location:276 → 401

PTB2_Fe65; Fe65 C-terminal Phosphotyrosine-binding (PTB) domain

cd01272
Location:109 → 248

PTB1_Fe65; Fe65 N-terminal Phosphotyrosine-binding (PTB) domain

pfam00397
Location:5 → 24

WW; WW domain
NM_145689.3 → NP_663722.1 amyloid beta precursor protein binding family B member 1 isoform b

See identical proteins and their annotated locations for NP_663722.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and lacks an alternate, in-frame exon in the coding region compared to variant 1. This results in a protein that maintains the reading frame but is a shorter isoform (b, also known as delta E9), compared to isoform a. This encoded isoform (b) is widely expressed in all non-neuronal cells but is not expressed in differentiated neurons.

Source sequence(s)

BC010854, HY138432

Consensus CDS

CCDS31410.1

UniProtKB/TrEMBL

A0A075B7G8

Related

ENSP00000311912.3, ENST00000311051.7

Conserved Domains (3) summary

cd01271
Location:533 → 658

PTB2_Fe65; Fe65 C-terminal Phosphotyrosine-binding (PTB) domain

cd01272
Location:368 → 505

PTB1_Fe65; Fe65 N-terminal Phosphotyrosine-binding (PTB) domain

pfam00397
Location:255 → 283

WW; WW domain

RNA

NR_047512.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (11) uses an alternate acceptor splice site in the 3' terminal exon compared to variant 1. The resulting open reading frame (ORF) has no stop codon, and no other ORF is supported. Therefore, this is likely to be a non-coding transcript and subject to degradation via the nonstop-mediated mRNA surveillance pathway.

Source sequence(s)

AF394214, BC010854, BM145723, HY145957

Related

ENST00000608435.5

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000011.10 Reference GRCh38.p14 Primary Assembly

Range

6395124..6419453 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060935.1 Alternate T2T-CHM13v2.0

Range

6453583..6477913 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_001257322.1: Suppressed sequence

Description

NM_001257322.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
NM_001257324.1: Suppressed sequence

Description

NM_001257324.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.