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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

NECAB3 Gene

protein-coding GIFtS: 50
GCID: GC20M032244

N-terminal EF-hand calcium binding protein 3

(Previous names: amyloid beta (A4) precursor protein-binding, family A,...)
(Previous symbols: SYTIP2, APBA2BP)

Explore 7 diseases affiliated with
NECAB3 via

MalaCards

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Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
N-Terminal EF-Hand Calcium Binding Protein 3¹ ²		Neuronal Calcium-Binding Protein 3² ³
APBA2BP¹ ² ³ ⁵		Nek2-Interacting Protein 1² ³
NIP1¹ ² ³ ⁵		X11L-Binding Protein 51² ³
XB51¹ ² ³ ⁵		STIP3² ⁵
SYTIP2¹ ² ³		EF-Hand Calcium Binding Protein 3²
EFCBP3¹ ² ⁵		N-Terminal EF-Hand Calcium-Binding Protein 3²
Amyloid Beta (A4) Precursor Protein-Binding, Family A, Member 2 Binding Protein¹ ²		Neuronal Calcium-Binding Protein NECAB3²
DJ63M2.4¹		Synaptotagmin Interacting Protein 2²
DJ63M2.5¹		Synaptotagmin Interacting Protein STIP3²
Amyloid Beta A4 Protein-Binding Family A Member 2-Binding Protein² ³

External Ids:	HGNC: 15851¹	Entrez Gene: 63941²	Ensembl: ENSG00000125967⁷	OMIM: 612478⁵	UniProtKB: Q96P71³

Export aliases for NECAB3 gene to outside databases

Previous GC identifers: GC20M031709 GC20M029030

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for NECAB3:

The protein encoded by this gene interacts with the amino-terminal domain of the neuron-specific X11-like protein

(X11L), inhibits the association of X11L with amyloid precursor protein through a non-competitive mechanism, and

abolishes the suppression of beta-amyloid production by X11L. This protein, together with X11L, may play an important

role in the regulatory system of amyloid precursor protein metabolism and beta-amyloid generation. The protein is

phosphorylated by NIMA-related expressed kinase 2, and localizes to the Golgi apparatus. Multiple transcript variants

encoding different isoforms have been found for this gene. (provided by RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: NECA3_HUMAN, Q96P71

Function: Inhibits the interaction of APBA2 with beta-amyloid precursor protein (APP), and hence allows formation of

beta-amyloid

Gene Wiki entry for NECAB3 (APBA2BP)

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000020.10 NC_018931.1 NT_011362.10

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the NECAB3 gene promoter:
Sp1 GCNF GCNF-1 GCNF-2
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: NECAB3 promoter sequence

Search SABiosciences Chromatin IP Primers for NECAB3

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat NECAB3

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 20q11.22 Ensembl cytogenetic band: 20q11.22 HGNC cytogenetic band: 20q11.21

NECAB3 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
NECAB3 gene location

GeneLoc information about chromosome 20 GeneLoc Exon Structure

GeneLoc location for GC20M032244: view genomic region (about GC identifiers)

Start:	32,244,893 bp from pter	End:	32,262,269 bp from pter
Size:	17,377 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: NECA3_HUMAN, Q96P71 (See protein sequence)

Recommended Name: N-terminal EF-hand calcium-binding protein 3

Size: 396 amino acids; 44350 Da

Subunit: Interacts with the N-terminal domain of APBA2. Interacts with NEK2

Subcellular location: Golgi apparatus

Sequence caution: Sequence=BAB14649.1; Type=Frameshift; Positions=56; Sequence=BAB16413.1; Type=Erroneous initiation;

Secondary accessions: A8K780 E1P5N2 Q5JWF5 Q5JWF6 Q5JWF7 Q86VV1 Q9H433 Q9H8G8 Q9HBW7 Q9HCQ9

Alternative splicing: 3 isoforms: Q96P71-1 Q96P71-2 Q96P71-3 (May result from the retention of an intron in the cDNA)

Explore the universe of human proteins at neXtProt for NECAB3: NX_Q96P71

Post-translational modifications:

Phosphorylated by NEK2¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_Q96P71

NECAB3 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (2 alternative transcripts):

NP_112508.3 NP_112509.3

ENSEMBL proteins:

ENSP00000364386 ENSP00000246190 ENSP00000392064

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Gene Ontology (GO): 5 cellular component terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000137	Golgi cis cisterna	IDA	10833507
GO:0005634	nucleus	NAS	10833507
GO:0005737	cytoplasm	IDA	10833507
GO:0005783	endoplasmic reticulum	--	--
GO:0005789	endoplasmic reticulum membrane	IDA	10833507

NECAB3 for ontologies About GeneDecksing

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(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

NECAB3 for domains About GeneDecksing

5 InterPro domains/families:

IPR018247 EF_Hand_1_Ca_BS

IPR011992 EF-hand-like_dom

IPR002048 EF_hand_Ca-bd

IPR007138 Antibiotic_mOase

IPR011008 Dimeric_a/b-barrel

Graphical View of Domain Structure for InterPro Entry Q96P71

ProtoNet protein and cluster: Q96P71

1 Blocks protein family: IPB007138 Antibiotic biosynthesis monooxygenase

UniProtKB/Swiss-Prot: NECA3_HUMAN, Q96P71

Similarity: Contains 1 ABM domain

Similarity: Contains 1 EF-hand domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, Sirion Biotech, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, Sirion Biotech, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Molecular Function:

UniProtKB/Swiss-Prot Summary: NECA3_HUMAN, Q96P71

Function: Inhibits the interaction of APBA2 with beta-amyloid precursor protein (APP), and hence allows formation of

beta-amyloid

Gene Ontology (GO): 2 molecular function terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005509	calcium ion binding	IEA	--
GO:0005515	protein binding	IPI	10833507

NECAB3 for ontologies About GeneDecksing

Animal Models:

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(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for NECAB3

STRING Interaction Network Preview (showing 5 interactants - click image to see 7)

5/8 Interacting proteins for NECAB3 (Q96P71³ ENSP00000246190⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 8)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
APP	P05067³, ENSP00000284981⁴	I2D: score=1 STRING: ENSP00000284981
IKBKG	Q9Y6K9³, ENSP00000358622⁴	I2D: score=1 STRING: ENSP00000358622
APBA2	Q99767³	I2D: score=3
SF3A2	ENSP00000221494⁴	STRING: ENSP00000221494
NCBP1	ENSP00000364289⁴	STRING: ENSP00000364289

About this table

Gene Ontology (GO): 3 biological process terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0009306	protein secretion	NAS	12780348
GO:0019538	protein metabolic process	IDA	12780348
GO:0042984	regulation of amyloid precursor protein biosynthetic process	IDA	10833507

NECAB3 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

Browse Small Molecules at EMD Millipore

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(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
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About This Section

REFSEQ mRNAs for NECAB3 gene (2 alternative transcripts):

NM_031231.3 NM_031232.3

Unigene Cluster for NECAB3:

N-terminal EF-hand calcium binding protein 3

Hs.516986 [show with all ESTs]

Unigene Representative Sequence: NM_031232

16 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000477778 ENST00000375238(uc002wzl.3 uc002wzm.4) ENST00000246190(uc002wzn.4)

ENST00000488489(uc002wzo.4) ENST00000483813 ENST00000485399 ENST00000485976

ENST00000478237 ENST00000494174 ENST00000463246 ENST00000480994 ENST00000439478

ENST00000498353 ENST00000493590 ENST00000473892 ENST00000484824

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Additional cDNA sequence:

AB039947.1 AF193759.1 AF409141.1 AK124388.1 AK291895.1 BC023270.1 BC047673.1

22 DOTS entries:

DT.442829 DT.100792217 DT.91943655 DT.100792213 DT.95079738 DT.101982010 DT.95113107 DT.120827151

DT.92428753 DT.100792214 DT.120827146 DT.120827154 DT.92428755 DT.97848827 DT.100662363 DT.100774865

DT.100792212 DT.444073 DT.91985746 DT.92428756 DT.95113115 DT.97848828

24/181 AceView cDNA sequences (see all 181):

BQ067649 CR617645 NM_031231 BI820266 AA025666 AW444512 CR624229 AI918962

CB216810 CR610365 BM806357 CR603836 CR626345 CK904035 BI966137 BM847196

AI336556 BU616700 NM_031232 CR614917 AA609873 BF981126 BI965982 BF514598

GeneLoc Exon Structure

5/9 Alternative Splicing Database (ASD) splice patterns (SP) for NECAB3 (see all 9) About this scheme

ExUns:	1	^	2	^	3a	·	3b	^	4	^	5a	·	5b	^	6a	·	6b	^	7a	·	7b	^	8	^	9	^	10	^	11	^	12a	·	12b
SP1:									-						-						-
SP2:									-						-
SP3:									-												-
SP4:															-						-		-
SP5:									-												-

ECgene alternative splicing isoforms for NECAB3

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

NECAB3 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: --

About this image

NECAB3 expression in embryonic tissues and stem cells
Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

1 LifeMap In Vivo Development Anatomical Compartment/Cell

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Eye

Inner Nuclear Layer

AII Amacrine Cells

Amacrine, Retina

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

See NECAB3 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for NECAB3

SOURCE GeneReport for Unigene cluster: Hs.516986

UniProtKB/Swiss-Prot: NECA3_HUMAN, Q96P71

Tissue specificity: Strongly expressed in heart and skeletal muscle, moderately in brain and pancreas

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In Situ
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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of chordates.

Orthologs for NECAB3 gene from 3/12 species (see all 12) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	NECAB3¹	N-terminal EF-hand calcium binding protein 3	67.53(n) 61.03(a)		419154 NM_001030850.1 NP_001026021.1
lizard (Anolis carolinensis)	Reptilia	NECAB3⁶	--	56(a)	1 ↔ 1	4(136566235-136614268)
zebrafish (Danio rerio)	Actinopterygii	CU929339.1⁶	--	47(a)	1 ↔ 1	6(57533945-57570205)

ENSEMBL Gene Tree for NECAB3 (if available)
TreeFam Gene Tree for NECAB3 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for NECAB3 gene

NECAB1² NECAB2²

3 SIMAP similar genes for NECAB3 using alignment to 1 protein entry: NECA3_HUMAN:

APBA2BP NECAB1 NECAB2

NECAB3 for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 20 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs4911355^1,2	C,F,A,H	--	32244414(+)	`CAGGGG/ACCTCC`	2	--	ds500¹		8		EA NS NA	904
rs55893601^1,2	C	--	32244519(+)	`AGGACT/GGACTC`	2	--	ds500¹		2		WA	120
rs73259853^1,2	C	--	32244584(+)	`TGGTGG/AGGACA`	2	--	ds500¹		1		WA	2
rs150926750^1,2		--	32244665(+)	`CTGCAA/GAGACA`	2	--	ds500¹		0	--	--	--	--
rs6119395^1,2	C,F,A,H	--	32244711(+)	`GGTGTG/TTCAGG`	2	--	ds500¹		13		NS EA NA WA CSA	740
rs184396988^1,2		--	32244815(+)	`CAAGAA/GAGGTG`	2	--	ds500¹		0	--	--	--	--
rs115956772^1,2	C,F	--	32244865(+)	`CACAGC/TCCAGA`	2	--	ds500¹		1		WA	118
rs6088272^1,2	H	--	32244872(+)	`CAGACC/TTGCGA`	2	--	ds500¹		3		NS EA	298
rs149773976^1,2		--	32244946(+)	`GGTTC-/AAGAGG`	2	--	ut3¹		0	--	--	--	--
rs115239109^1,2	F	--	32244959(+)	`TCTGGG/AGGCAA`	2	--	ut3¹		1		WA	118

HapMap Linkage Disequilibrium report for NECAB3 (32244893 - 32262269 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 2 variations for NECAB3
1 CNV: 79180
1 Indel: 79181

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

NECAB3 for disorders           About GeneDecksing

OMIM gene information: 612478    OMIM disorders: --

7 diseases for NECAB3:    About MalaCards

neuronitis chronic lymphocytic leukemia lymphocytic leukemia hepatitis b

alzheimer's disease leukemia hepatitis

Human Genome Epidemiology (HuGE) Navigator: NECAB3 (2 documents)

Export disorders for NECAB3 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
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PubMed articles for NECAB3 gene, integrated from 9 sources (see all 17):
(articles sorted by number of sources associating them with NECAB3)

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Regulation of X11L-dependent amyloid precursor protein metabolism by XB51, a novel X11L-binding protein. (PubMed id 10833507)^{1, 2, 3, 9} Lee D.-S.... Suzuki T. (2000)
NIP1/XB51/NECAB3 is a potential substrate of Nek2, suggesting specific roles of Nek2 in Golgi. (PubMed id 14697346)^{1, 2} Yoo J.C....Rhee K. (2004)
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)^{1, 2} Gerhard D.S....Malek J. (2004)
Complete sequencing and characterization of 21,243 full-length human cDNAs. (PubMed id 14702039)^{1, 2} Ota T.... Sugano S. (2004)
NECABs: a family of neuronal Ca(2+)-binding proteins with an unusual domain structure and a restricted expression pattern. (PubMed id 12044471)^{1, 2} Sugita S.... Suedhof T.C. (2002)
The DNA sequence and comparative analysis of human chromosome 20. (PubMed id 11780052)^{1, 2} Deloukas P....Rogers J. (2001)
XB51 isoforms mediate Alzheimer's beta-amyloid peptide production by X11L (X11-like protein)-dependent and -independent mechanisms. (PubMed id 12780348)^{1, 9} Sumioka A....Suzuki T. (2003)
Functional genomics identifies therapeutic targets for MYC-driven cancer. (PubMed id 22623531)¹ Toyoshima M....Grandori C. (2012)
Systematic and quantitative assessment of the ubiquiti n-modified proteome. (PubMed id 21906983)¹ Kim W....Gygi S.P. (2011)
Interactions of pathological hallmark proteins: tubul in polymerization promoting protein/p25, beta-amyloid, and alpha-synuclein. (PubMed id 21832049)¹ OlA!h J....OvA!di J. (2011)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Free Text

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(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 63941	HGNC: 15851	AceView: APBA2BP	Ensembl:ENSG00000125967	euGenes: HUgn63941
ECgene: NECAB3	H-InvDB: NECAB3

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for NECAB3	Pharmacogenomics, SNPs, Pathways

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NECAB3 Gene

N-terminal EF-hand calcium binding protein 3

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NECAB3 (Gene Symbol)
N-Terminal EF-Hand Calcium Binding Protein 3
APBA2BP
NIP1
XB51
SYTIP2
EFCBP3
Amyloid Beta (A4) Precursor Protein-Binding, Family A, Member 2 Binding Protein
DJ63M2.4
DJ63M2.5
Amyloid Beta A4 Protein-Binding Family A Member 2-Binding Protein
Neuronal Calcium-Binding Protein 3
Nek2-Interacting Protein 1
X11L-Binding Protein 51
STIP3
EF-Hand Calcium Binding Protein 3
N-Terminal EF-Hand Calcium-Binding Protein 3
Neuronal Calcium-Binding Protein NECAB3
Synaptotagmin Interacting Protein 2
Synaptotagmin Interacting Protein STIP3

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NECAB3 Gene

N-terminal EF-hand calcium binding protein 3

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