LOCUS       NP_775960               1285 aa            linear   PRI 27-APR-2025
DEFINITION  protein crumbs homolog 2 precursor [Homo sapiens].
ACCESSION   NP_775960
VERSION     NP_775960.4
DBSOURCE    REFSEQ: accession NM_173689.7
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 1285)
  AUTHORS   Stehle,I.F., Imventarza,J.A., Woerz,F., Hoffmann,F., Boldt,K.,
            Beyer,T., Quinn,P.M. and Ueffing,M.
  TITLE     Human CRB1 and CRB2 form homo- and heteromeric protein complexes in
            the retina
  JOURNAL   Life Sci Alliance 7 (6), e202302440 (2024)
   PUBMED   38570189
  REMARK    GeneRIF: Human CRB1 and CRB2 form homo- and heteromeric protein
            complexes in the retina.
            Publication Status: Online-Only
REFERENCE   2  (residues 1 to 1285)
  AUTHORS   Tessier,A., Roux,N., Boutaud,L., Lunel,E., Hakkakian,L.,
            Parisot,M., Garfa-Traore,M., Ichkou,A., Elkhartoufi,N., Bole,C.,
            Nitschke,P., Amiel,J., Martinovic,J., Encha-Razavi,F.,
            Attie-Bitach,T. and Thomas,S.
  TITLE     Bi-allelic variations in CRB2, encoding the crumbs cell polarity
            complex component 2, lead to non-communicating hydrocephalus due to
            atresia of the aqueduct of sylvius and central canal of the medulla
  JOURNAL   Acta Neuropathol Commun 11 (1), 29 (2023)
   PUBMED   36803301
  REMARK    GeneRIF: Bi-allelic variations in CRB2, encoding the crumbs cell
            polarity complex component 2, lead to non-communicating
            hydrocephalus due to atresia of the aqueduct of sylvius and central
            canal of the medulla.
            Publication Status: Online-Only
REFERENCE   3  (residues 1 to 1285)
  AUTHORS   Moller-Kerutt,A., Schonhoff,B., Rellmann,Y., George,B., Braun,D.A.,
            Pavenstadt,H. and Weide,T.
  TITLE     Loss of surface transport is a main cellular pathomechanism of CRB2
            variants causing podocytopathies
  JOURNAL   Life Sci Alliance 6 (3), e202201649 (2022)
   PUBMED   36549870
  REMARK    GeneRIF: Loss of surface transport is a main cellular
            pathomechanism of CRB2 variants causing podocytopathies.
            Publication Status: Online-Only
REFERENCE   4  (residues 1 to 1285)
  AUTHORS   Simaab,A., Krishin,J., Alaradi,S.R., Haider,N., Shah,M., Ullah,A.,
            Abdullah,A., Ahmad,W., Hansen,T. and Basit,S.
  TITLE     Exome Sequencing Revealed a Novel Splice Site Variant in the CRB2
            Gene Underlying Nephrotic Syndrome
  JOURNAL   Medicina (Kaunas) 58 (12), 1784 (2022)
   PUBMED   36556986
  REMARK    GeneRIF: Exome Sequencing Revealed a Novel Splice Site Variant in
            the CRB2 Gene Underlying Nephrotic Syndrome.
            Publication Status: Online-Only
REFERENCE   5  (residues 1 to 1285)
  AUTHORS   Wang,Y., Bao,G., Zhang,M., Xiang,J., Zhou,H., Wahafu,A., Wu,W.,
            Ma,X., Huo,L., Bai,X., Xie,W., Liu,P. and Wang,M.
  TITLE     CRB2 enhances malignancy of glioblastoma via activation of the
            NF-kappaB pathway
  JOURNAL   Exp Cell Res 414 (1), 113077 (2022)
   PUBMED   35219647
  REMARK    GeneRIF: CRB2 enhances malignancy of glioblastoma via activation of
            the NF-kappaB pathway.
REFERENCE   6  (residues 1 to 1285)
  AUTHORS   Gosens,I., Sessa,A., den Hollander,A.I., Letteboer,S.J.,
            Belloni,V., Arends,M.L., Le Bivic,A., Cremers,F.P., Broccoli,V. and
            Roepman,R.
  TITLE     FERM protein EPB41L5 is a novel member of the mammalian CRB-MPP5
            polarity complex
  JOURNAL   Exp Cell Res 313 (19), 3959-3970 (2007)
   PUBMED   17920587
REFERENCE   7  (residues 1 to 1285)
  AUTHORS   Roni,V., Carpio,R. and Wissinger,B.
  TITLE     Mapping of transcription start sites of human retina expressed
            genes
  JOURNAL   BMC Genomics 8, 42 (2007)
   PUBMED   17286855
  REMARK    Publication Status: Online-Only
REFERENCE   8  (residues 1 to 1285)
  AUTHORS   Botuyan,M.V., Lee,J., Ward,I.M., Kim,J.E., Thompson,J.R., Chen,J.
            and Mer,G.
  TITLE     Structural basis for the methylation state-specific recognition of
            histone H4-K20 by 53BP1 and Crb2 in DNA repair
  JOURNAL   Cell 127 (7), 1361-1373 (2006)
   PUBMED   17190600
  REMARK    GeneRIF: Using X-ray crystallography and NMR spectroscopy, we show
            that, despite low amino acid sequence conservation, both 53BP1 and
            Crb2 contain tandem tudor domains that interact with histone H4
            specifically dimethylated at Lys20 (H4-K20me2).
REFERENCE   9  (residues 1 to 1285)
  AUTHORS   van den Hurk,J.A., Rashbass,P., Roepman,R., Davis,J.,
            Voesenek,K.E., Arends,M.L., Zonneveld,M.N., van Roekel,M.H.,
            Cameron,K., Rohrschneider,K., Heckenlively,J.R., Koenekoop,R.K.,
            Hoyng,C.B., Cremers,F.P. and den Hollander,A.I.
  TITLE     Characterization of the Crumbs homolog 2 (CRB2) gene and analysis
            of its role in retinitis pigmentosa and Leber congenital amaurosis
  JOURNAL   Mol Vis 11, 263-273 (2005)
   PUBMED   15851977
  REMARK    GeneRIF: This study shows that CRB2 sequence variants are not a
            common cause of autosomal recessive RP and LCA.
            Publication Status: Online-Only
REFERENCE   10 (residues 1 to 1285)
  AUTHORS   Katoh,M. and Katoh,M.
  TITLE     Identification and characterization of Crumbs homolog 2 gene at
            human chromosome 9q33.3
  JOURNAL   Int J Oncol 24 (3), 743-749 (2004)
   PUBMED   14767562
  REMARK    GeneRIF: Crumbs homolog 2 gene maps to human chromosome 9q33.3
            GeneRIF: The CRB2 gene encodes a transmembrane protein (1285 aa)
            and a secreted protein (1176 aa). The transmembrane isoform
            consists of 14 extracellular EGF-like domains, 3 extracellular
            laminin G-like domains, and a Crb cytoplasmic tail domain.
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DA240339.1, AL365504.33,
            AY720432.1, AL445489.10 and AK124819.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Aug 17, 2006 this sequence version replaced NP_775960.3.
            
            Summary: This gene encodes a member of a family of proteins that
            are components of the Crumbs cell polarity complex. In mammals,
            members of this family are thought to play a role in many cellular
            processes in early embryonic development. A similar protein in
            Drosophila determines apicobasal polarity in embryonic epithelial
            cells. Mutations in this gene are associated with focal segmental
            glomerulosclerosis 9, and with ventriculomegaly with cystic kidney
            disease. [provided by RefSeq, Aug 2016].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the supported protein.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AY720432.1, SRR14372080.4666007.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1970526, SAMEA2154665
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000373631.8/ ENSP00000362734.3
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..1285
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="9"
                     /map="9q33.3"
     Protein         1..1285
                     /product="protein crumbs homolog 2 precursor"
                     /note="crumbs-like protein 2; protein crumbs homolog 2;
                     crumbs family member 2; crumbs 2, cell polarity complex
                     component"
                     /calculated_mol_wt=131397
     Region          1..350
                     /region_name="Required for maximum inhibition of APP
                     amyloid-beta peptide secretion.
                     /evidence=ECO:0000269|PubMed:20299451"
                     /note="propagated from UniProtKB/Swiss-Prot (Q5IJ48.2)"
     sig_peptide     1..28
                     /note="/evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (Q5IJ48.2)"
                     /calculated_mol_wt=2887
     mat_peptide     29..1285
                     /product="Protein crumbs homolog 2. /evidence=ECO:0000255.
                     /id=PRO_0000007502"
                     /note="propagated from UniProtKB/Swiss-Prot (Q5IJ48.2)"
                     /calculated_mol_wt=131397
     Region          108..144
                     /region_name="EGF_CA"
                     /note="Calcium-binding EGF-like domain, present in a large
                     number of membrane-bound and extracellular (mostly animal)
                     proteins. Many of these proteins require calcium for their
                     biological function and calcium-binding sites have been
                     found to be located at the...; cd00054"
                     /db_xref="CDD:238011"
     Site            order(108,111,125)
                     /site_type="other"
                     /note="Ca2+ binding site [ion binding]"
                     /db_xref="CDD:238011"
     Region          147..182
                     /region_name="EGF_CA"
                     /note="Calcium-binding EGF-like domain, present in a large
                     number of membrane-bound and extracellular (mostly animal)
                     proteins. Many of these proteins require calcium for their
                     biological function and calcium-binding sites have been
                     found to be located at the...; cd00054"
                     /db_xref="CDD:238011"
     Region          184..221
                     /region_name="EGF_CA"
                     /note="Calcium-binding EGF-like domain, present in a large
                     number of membrane-bound and extracellular (mostly animal)
                     proteins. Many of these proteins require calcium for their
                     biological function and calcium-binding sites have been
                     found to be located at the...; cd00054"
                     /db_xref="CDD:238011"
     Site            order(184,187,201)
                     /site_type="other"
                     /note="Ca2+ binding site [ion binding]"
                     /db_xref="CDD:238011"
     Region          226..259
                     /region_name="EGF_CA"
                     /note="Calcium-binding EGF-like domain, present in a large
                     number of membrane-bound and extracellular (mostly animal)
                     proteins. Many of these proteins require calcium for their
                     biological function and calcium-binding sites have been
                     found to be located at the...; cd00054"
                     /db_xref="CDD:238011"
     Site            235
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (Q5IJ48.2)"
     Site            267
                     /site_type="glycosylation"
                     /note="O-linked (Glc...) serine.
                     /evidence=ECO:0000250|UniProtKB:Q80YA8; propagated from
                     UniProtKB/Swiss-Prot (Q5IJ48.2)"
     Region          321..356
                     /region_name="EGF_CA"
                     /note="Calcium-binding EGF-like domain, present in a large
                     number of membrane-bound and extracellular (mostly animal)
                     proteins. Many of these proteins require calcium for their
                     biological function and calcium-binding sites have been
                     found to be located at the...; cd00054"
                     /db_xref="CDD:238011"
     Region          358..393
                     /region_name="EGF_CA"
                     /note="Calcium-binding EGF-like domain, present in a large
                     number of membrane-bound and extracellular (mostly animal)
                     proteins. Many of these proteins require calcium for their
                     biological function and calcium-binding sites have been
                     found to be located at the...; cd00054"
                     /db_xref="CDD:238011"
     Site            order(358,361,375)
                     /site_type="other"
                     /note="Ca2+ binding site [ion binding]"
                     /db_xref="CDD:238011"
     Site            438
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (Q5IJ48.2)"
     Region          465..588
                     /region_name="Laminin_G_2"
                     /note="Laminin G domain; pfam02210"
                     /db_xref="CDD:460494"
     Site            478
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (Q5IJ48.2)"
     Region          <613..640
                     /region_name="EGF_CA"
                     /note="Calcium-binding EGF-like domain, present in a large
                     number of membrane-bound and extracellular (mostly animal)
                     proteins. Many of these proteins require calcium for their
                     biological function and calcium-binding sites have been
                     found to be located at the...; cd00054"
                     /db_xref="CDD:238011"
     Region          653..773
                     /region_name="LamG"
                     /note="Laminin G domain; Laminin G-like domains are
                     usually Ca++ mediated receptors that can have binding
                     sites for steroids, beta1 integrins, heparin, sulfatides,
                     fibulin-1, and alpha-dystroglycans. Proteins that contain
                     LamG domains serve a variety of...; cd00110"
                     /db_xref="CDD:238058"
     Site            669
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (Q5IJ48.2)"
     Site            690
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (Q5IJ48.2)"
     Site            786
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (Q5IJ48.2)"
     Site            800
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (Q5IJ48.2)"
     Region          811..841
                     /region_name="EGF"
                     /note="EGF-like domain; pfam00008"
                     /db_xref="CDD:394967"
     Site            836
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (Q5IJ48.2)"
     Site            886
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (Q5IJ48.2)"
     Region          900..1024
                     /region_name="LamG"
                     /note="Laminin G domain; Laminin G-like domains are
                     usually Ca++ mediated receptors that can have binding
                     sites for steroids, beta1 integrins, heparin, sulfatides,
                     fibulin-1, and alpha-dystroglycans. Proteins that contain
                     LamG domains serve a variety of...; cl22861"
                     /db_xref="CDD:473984"
     Site            926
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (Q5IJ48.2)"
     Site            1009
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (Q5IJ48.2)"
     Region          1060..1090
                     /region_name="EGF"
                     /note="EGF-like domain; pfam00008"
                     /db_xref="CDD:394967"
     Site            1141
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (Q5IJ48.2)"
     Site            1158
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (Q5IJ48.2)"
     Site            1225..1245
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q5IJ48.2)"
     Region          1249..1285
                     /region_name="Interaction with EPB41L5.
                     /evidence=ECO:0000269|PubMed:17920587"
                     /note="propagated from UniProtKB/Swiss-Prot (Q5IJ48.2)"
     CDS             1..1285
                     /gene="CRB2"
                     /gene_synonym="FSGS9; VMCKD"
                     /coded_by="NM_173689.7:65..3922"
                     /db_xref="CCDS:CCDS6852.2"
                     /db_xref="GeneID:286204"
                     /db_xref="HGNC:HGNC:18688"
                     /db_xref="MIM:609720"
ORIGIN      
        1 malarpgtpd pqalasvlll llwapalsll agtvpsepps acasdpcapg tecqatesgg
       61 ytcgpmeprg catqpchhga lcvpqgpdpt gfrcycvpgf qgprceldid ecasrpchhg
      121 atcrnladry echcplgyag vtcemevdec asapclhggs cldgvgsfrc vcapgyggtr
      181 cqldldecqs qpcahggtch dlvngfrcdc agtgyegthc erevlecasa pcehnascle
      241 glgsfrclcw pgysgelcev dedecasspc qhggrclqrs dpalyggvqa afpgafsfrh
      301 aagflchcpp gfegadcgve vdecasrpcl ngghcqdlpn gfqchcpdgy agptceedvd
      361 eclsdpclhg gtcsdtvagy icrcpetwgg rdcsvqltgc qghtcplaat cipifesgvh
      421 syvchcppgt hgpfcgqntt fsvmagspiq asvpaggplg lalrfrttlp agtlatrndt
      481 keslelalva atlqatlwsy sttvlvlrlp dlalndghwh qvevvlhlat lelrlwhegc
      541 parlcvasgp valastasat plpagissaq lgdatfagcl qdvrvdghll lpedlgenvl
      601 lgcerreqcr plpcvhggsc vdlwthfrcd carphrgptc adeipaatfg lggapssasf
      661 llqelpgpnl tvsfllrtre saglllqfan dsaagltvfl segriraevp gspavvlpgr
      721 wddglrhlvm lsfgpdqlqd lgqhvhvggr llaadsqpwg gpfrgclqdl rldgchlpff
      781 plpldnssqp selggrqswn ltagcvsedm cspdpcfngg tclvtwndfh ctcpanftgp
      841 tcaqqlwcpg qpclppatce evpdgfvcva eatfregppa afsghnassg rllgglslaf
      901 rtrdseawll raaagalegv wlavrngsla ggvrgghglp gavlpipgpr vadgawhrvr
      961 lamerpaatt srwllwldga atpvalrgla sdlgflqgpg avrillaenf tgclgrvalg
     1021 glplplarpr pgaapgareh faswpgtpap ilgcrgapvc apspclhdga crdlfdafac
     1081 acgpgwegpr ceahvdpchs apcargrcht hpdgrfecrc ppgfggprcr lpvpskecsl
     1141 nvtcldgspc eggspaancs cleglagqrc qvptlpcean pclnggtcra aggvsecicn
     1201 arfsgqfcev akglplplpf pllevavpaa cacllllllg llsgilaark rrqsegtysp
     1261 sqqevagarl emdsvlkvpp eerli
//
