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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

CRB2 Gene

protein-coding GIFtS: 49
GCID: GC09P126118

crumbs homolog 2 (Drosophila)

Explore 6 diseases affiliated with
CRB2 via

MalaCards

our new
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
Crumbs Homolog 2 (Drosophila)¹ ²
Crumbs-Like Protein 2² ³
FLJ16786¹
FLJ38464¹
Protein Crumbs Homolog 2²

External Ids:	HGNC: 18688¹	Entrez Gene: 286204²	Ensembl: ENSG00000148204⁷	OMIM: 609720⁵	UniProtKB: Q5IJ48³

Export aliases for CRB2 gene to outside databases

Previous GC identifers: GC09P121513 GC09P123198 GC09P125158 GC09P095733

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

UniProtKB/Swiss-Prot: CRUM2_HUMAN, Q5IJ48

Function: May play a role in polarized cells morphogenesis

(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_000009.11 NC_018920.1 NT_008470.19

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the CRB2 gene promoter:
Max1 RFX1 Egr-1 Lmo2 POU6F1 (c2) C/EBPalpha MEF-2A c-Myb aMEF-2 c-Myc
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): CRB2 promoter sequence

Search SABiosciences Chromatin IP Primers for CRB2

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat CRB2

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

Entrez Gene cytogenetic band: 9q33.3 Ensembl cytogenetic band: 9q33.3 HGNC cytogenetic band: 9q33.2

CRB2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
CRB2 gene location

GeneLoc information about chromosome 9 GeneLoc Exon Structure

GeneLoc location for GC09P126118: view genomic region (about GC identifiers)

Start:	126,118,448 bp from pter	End:	126,142,603 bp from pter
Size:	24,156 bases	Orientation:	plus 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: CRUM2_HUMAN, Q5IJ48 (See protein sequence)

Recommended Name: Protein crumbs homolog 2 precursor

Size: 1285 amino acids; 134265 Da

Subcellular location: Isoform 1: Cell membrane; Single-pass type I membrane protein

Subcellular location: Isoform 2: Secreted

1 PDB 3D structure from and Proteopedia for CRB2:

2WO6 (3D)

Secondary accessions: A2A3N4 Q0QD46 Q5JS41 Q5JS43 Q6ZTA9 Q6ZWI6

Alternative splicing: 3 isoforms: Q5IJ48-1 Q5IJ48-2 Q5IJ48-3 (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for CRB2: NX_Q5IJ48

Post-translational modifications:

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_Q5IJ48

CRB2 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins: NP_775960.4

ENSEMBL proteins:

ENSP00000353092 ENSP00000362734 ENSP00000435279 ENSP00000362732

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	Uscn Proteins for CRB2

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

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005576	extracellular region	IEA	--
GO:0005886	plasma membrane	IEA	--
GO:0016021	integral to membrane	IEA	--

CRB2 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

CRB2 for domains About GeneDecksing

5/8 InterPro domains/families (see all 8):

IPR000742 EG-like_dom

IPR013320 ConA-like_subgrp

IPR001791 Laminin_G

IPR000152 EGF-type_Asp/Asn_hydroxyl_site

IPR018097 EGF_Ca-bd_CS

Graphical View of Domain Structure for InterPro Entry Q5IJ48

ProtoNet protein and cluster: Q5IJ48

1 Blocks protein family: IPB001791 Laminin G

UniProtKB/Swiss-Prot: CRUM2_HUMAN, Q5IJ48

Similarity: Belongs to the Crumbs protein family

Similarity: Contains 15 EGF-like domains

Similarity: Contains 3 laminin G-like domains

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

Function Summary:

UniProtKB/Swiss-Prot: CRUM2_HUMAN, Q5IJ48

Function: May play a role in polarized cells morphogenesis

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		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat CRB2
		8/23 QIAGEN miScript miRNA Assays for microRNAs that regulate CRB2 (see all 23):
		hsa-miR-4254 hsa-miR-125a-5p hsa-miR-3194-5p hsa-let-7d hsa-miR-202 hsa-let-7c hsa-miR-766 hsa-let-7g

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In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for CRB2

Gene Ontology (GO): 1 molecular function term (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005509	calcium ion binding	IEA	--

CRB2 for ontologies About GeneDecksing

Animal Models:
9 MGI mutant phenotypes (inferred from 2 alleles) (MGI details for Crb2):

cardiovascular system	digestive/alimentary	embryogenesis	growth/size	mortality/aging
nervous system	normal	pigmentation	vision/eye

CRB2 for phenotypes About GeneDecksing

(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:

Search SABiosciences Gene Network Central^TM Interacting Genes and Proteins Networks for CRB2

STRING Interaction Network Preview (showing 4 interactants - click image to see more details)

5/17 Interacting proteins for CRB2 (Q5IJ48³ ENSP00000362734⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 17)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
HIST1H4A	P62805³, ENSP00000352980⁴	I2D: score=1 STRING: ENSP00000352980
HIST1H4B	P62805³	I2D: score=1
HIST1H4C	P62805³	I2D: score=1
HIST1H4D	P62805³	I2D: score=1
HIST1H4E	P62805³	I2D: score=1

About this table

(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

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for CRB2

1 DrugBank Compound for CRB2 About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
N-(5-{[(2S)-4-amino-2-(3-chlorophenyl)butanoyl]amino}-1H-indazol-3-yl)benzamide	--	--	target	--	10592235

Search CenterWatch for drugs/clinical trials and news about CRB2 / CRUM2

(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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Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for CRB2 gene:

NM_173689.5

Unigene Cluster for CRB2:

Crumbs homolog 2 (Drosophila)

Hs.710092 [show with all ESTs]

Unigene Representative Sequence: NM_173689

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

ENST00000359999(uc004bnw.1) ENST00000373631(uc004bnx.1) ENST00000460253

ENST00000373629

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		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat CRB2
		8/23 QIAGEN miScript miRNA Assays for microRNAs that regulate CRB2 (see all 23):
		hsa-miR-4254 hsa-miR-125a-5p hsa-miR-3194-5p hsa-let-7d hsa-miR-202 hsa-let-7c hsa-miR-766 hsa-let-7g

		SwitchGear 3'UTR luciferase reporter plasmid: CRB2 3' UTR sequence

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		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for CRB2 (see all 4) OriGene shRNA RFP: CRB2 OriGene siRNA: CRB2
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Additional cDNA sequence:

AK095783.1 AK123000.1 AK124819.1 AK126775.1 AY720432.1

2 DOTS entries:

DT.97775951 DT.91974994

24/32 AceView cDNA sequences (see all 32):

AA586428 BI063722 AK124819 AK095783 AA927420 AA931641 AW026530 AA721043

BF726291 NM_173689 AI880330 BQ184081 BE396243 AK126775 AA349362 BQ695408

AW008664 BF344465 AK123000 AA349361 BF726292 BF341621 BE392023 BF432706

GeneLoc Exon Structure

(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

CRB2 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: TGCAGCAGTG

About this image

CRB2 expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

Stem Cell Differentiation: 1 LifeMap Cell

Name

Category

Posterior foregut-like cells (A scalable, suspensi...)

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

See CRB2 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for CRB2

SOURCE GeneReport for Unigene cluster: Hs.710092

UniProtKB/Swiss-Prot: CRUM2_HUMAN, Q5IJ48

Tissue specificity: Expressed in retina, fetal eye and brain. Also expressed in kidney, ARPE-19 and RPE/choroid cell

lines, and at low levels in lung, placenta, and heart

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In Situ
Assay Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for CRB2

(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 CRB2 gene from 2/15 species (see all 15) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	CRB2¹	crumbs homolog 2 (Drosophila)	54.67(n) 48.39(a)		417104 XM_415389.3 XP_415389.3
zebrafish (Danio rerio)	Actinopterygii	crb2a¹	crumbs homolog 2a	49.71(n) 43.98(a)		723994 NM_001045299.1 NP_001038764.1

ENSEMBL Gene Tree for CRB2 (if available)
TreeFam Gene Tree for CRB2 (if available)

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

Paralogs for CRB2 gene

NOTCH4² SNED1² NOTCH1² NOTCH3² DLL3² DLL4² JAG2² NOTCH2²

JAG1² DNER² CRB1² DLL1²

5 SIMAP similar genes for CRB2 using alignment to 1 protein entry: CRUM2_HUMAN:

CNTNAP2 F9 CRB3 NOTCH2NL NOTCH4

CRB2 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 9 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs115433747^1,2	F,	--	126116570(+)	`GGAGAC/GTGGAC`	1	--	us2k¹		1		WA	118
rs188264315^1,2		--	126116573(+)	`GACTGC/GACCTG`	1	--	us2k¹		0	--	--	--	--
rs62579935^1,2	C,F,	--	126116581(+)	`CTGCGC/ACGGGT`	1	--	us2k¹		6		NA WA EA	364
rs141388764^1,2		--	126116607(+)	`TGAAA-/GTGTG GGAGTTTGTGTC`	1	--	us2k¹		0	--	--	--	--
rs192803616^1,2		--	126116613(+)	`TGTGGA/GAGTTT`	1	--	us2k¹		0	--	--	--	--
rs145636290^1,2		--	126116695(+)	`TGCCTA/GGGTCT`	1	--	us2k¹		0	--	--	--	--
rs140450598^1,2		--	126116787(+)	`AGACTG/TAGGCC`	1	--	us2k¹		0	--	--	--	--
rs4838051^1,2	C,F,A,H,	--	126116865(+)	`TCTTAC/TGCTGT`	1	--	us2k¹		24		NA NS EA WA	2782
rs111466461^1,2		--	126116938(+)	`TTGTAC/TTGGAG`	1	--	us2k¹		1		CSA	2
rs77273674^1,2		--	126117069(+)	`CTACCC/TAGGCC`	1	--	us2k¹		1		EA	120

HapMap Linkage Disequilibrium report for CRB2 (126118448 - 126142603 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV) variations for CRB2: --

SABiosciences Cancer Mutation PCR Assays

QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing CRB2

DNA2.0 Custom Variant and Variant Library Synthesis for CRB2

(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

CRB2 for disorders           About GeneDecksing

OMIM gene information: 609720    OMIM disorders: --

6 diseases for CRB2:    About MalaCards

cleft lip/palate leber congenital amaurosis cleft lip retinitis pigmentosa

choroiditis retinitis

2 diseases from the University of Copenhagen DISEASES database for CRB2:

Leber congenital amaurosis Retinitis pigmentosa

Human Genome Epidemiology (HuGE) Navigator: CRB2 (2 documents)

Export disorders for CRB2 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)
About This Section

PubMed articles for CRB2 gene, integrated from 9 sources (see all 11):
(articles sorted by number of sources associating them with CRB2)

Utopia: connect your pdf to the dynamic
world of online information

Characterization of the crumbs homolog 2 (CRB2) gene and analysis of its role in retinitis pigmentosa and Leber congenital amaurosis. (PubMed id 15851977)^{1, 2, 9} van den Hurk J.A.J.M.... den Hollander A.I. (2005)
Identification and characterization of Crumbs homolog 2 gene at human chromosome 9q33.3. (PubMed id 14767562)^{1, 3, 9} Katoh M. and Katoh M. (2004)
Complete sequencing and characterization of 21,243 full-length human cDNAs. (PubMed id 14702039)^{1, 2} Ota T.... Sugano S. (2004)
DNA sequence and analysis of human chromosome 9. (PubMed id 15164053)^{1, 2} Humphray S.J.... Dunham I. (2004)
Follow-up association studies of chromosome region 9q and nonsyndromic cleft lip/palate. (PubMed id 20583170)¹ Letra A....Vieira A.R. (2010)
Human CRB2 inhibits gamma-secretase cleavage of amylo id precursor protein by binding to the presenilin complex. (PubMed id 20299451)¹ Mitsuishi Y....Nishimura M. (2010)
Overexpression of human CRB1 or related isoforms, CRB2 and CRB3, does not regulate the human presenilin complex in culture cells. (PubMed id 17988153)¹ Pardossi-Piquard R....Fraser P.E. (2007)
Structural basis for the methylation state-specific recognition of histone H4-K20 by 53BP1 and Crb2 in DNA repair. (PubMed id 17190600)¹ Botuyan M.V....Mer G. (2006)
Hepatocyte Growth Factor/scatter factor-induces phosphorylation of cortactin in A431 cells in a Src kinase-independent manner. (PubMed id 11439336)¹ Crostella L....Skouteris G.G. (2001)
The Protein Data Bank. (PubMed id 10592235)⁷ Berman H.M....Bourne P.E. (2000)

(in PubMed, OMIM, and NCBI Bookshelf)
About This Section

		AND	OR
Aliases
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
About This Section

Entrez Gene: 286204	HGNC: 18688	AceView: CRB2	Ensembl:ENSG00000148204	euGenes: HUgn286204
ECgene: CRB2	H-InvDB: CRB2

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for CRB2	Pharmacogenomics, SNPs, Pathways

Intellectual Property for CRB2 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

About This Section

Patent Information for CRB2 gene:
Search GeneIP for patents involving CRB2

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

(Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, SABiosciences, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Uscn, Thermo Fisher Scientific, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript and LifeMap BioReagents, PCR Arrays from SABiosciences, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, and/or Enzo Life Sciences),
In Situ Hybridization Assays from
Advanced Cell Diagnostics
About This Section


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	QIAGEN Custom miScript Target Protector blocks miRNA-binding site of in human, mouse, rat CRB2
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GeneCards Homepage - Last full update: 19 Mar 2013 - Incrementals: 21 Mar 2013 , 15 Apr 2013 , 26 Apr 2013

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Category			VWF (GIFTS: 73) von Willebrand factor
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The GeneCards human gene database gene index: 1 3 5 6 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

The GeneCards Human Gene Database

Developed at the Crown Human Genome Center, Department of Molecular Genetics, the Weizmann Institute of Science

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CRB2 Gene

crumbs homolog 2 (Drosophila)

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CRB2 Gene

crumbs homolog 2 (Drosophila)

Aliasesfor CRB2 gene

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Protein Domains /Familiesfor CRB2 gene

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