CRUM3_HUMAN
ID CRUM3_HUMAN Reviewed; 120 AA.
AC Q9BUF7; A8KA91; D6W643; Q8N0V8; Q8WVA0;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2005, sequence version 3.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Protein crumbs homolog 3;
DE Flags: Precursor;
GN Name=CRB3 {ECO:0000312|HGNC:HGNC:20237}; ORFNames=UNQ588/PRO1158;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH PALS1, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, GLYCOSYLATION AT ASN-36, AND MUTAGENESIS OF
RP ASN-36.
RC TISSUE=Retina;
RX PubMed=12527193; DOI=10.1016/s0378111902010843;
RA Makarova O., Roh M.H., Liu C.-J., Laurinec S., Margolis B.;
RT "Mammalian Crumbs3 is a small transmembrane protein linked to protein
RT associated with Lin-7 (Pals1).";
RL Gene 302:21-29(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Pancreas;
RA Guo J.H., Yu L.;
RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Ovary, and Pancreas;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION, INTERACTION WITH PALS1, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP 117-GLU--ILE-120.
RX PubMed=12771187; DOI=10.1242/jcs.00500;
RA Roh M.H., Fan S., Liu C.-J., Margolis B.;
RT "The Crumbs3-Pals1 complex participates in the establishment of polarity in
RT mammalian epithelial cells.";
RL J. Cell Sci. 116:2895-2906(2003).
RN [8]
RP FUNCTION, INTERACTION WITH PARD6A, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND MUTAGENESIS OF 117-GLU--ILE-120.
RX PubMed=14718572; DOI=10.1091/mbc.e03-04-0235;
RA Lemmers C., Michel D., Lane-Guermonprez L., Delgrossi M.-H., Medina E.,
RA Arsanto J.-P., Le Bivic A.;
RT "CRB3 binds directly to Par6 and regulates the morphogenesis of the tight
RT junctions in mammalian epithelial cells.";
RL Mol. Biol. Cell 15:1324-1333(2004).
RN [9]
RP INTERACTION WITH EPB41L5, AND MUTAGENESIS OF 117-GLU--ILE-120.
RX PubMed=17920587; DOI=10.1016/j.yexcr.2007.08.025;
RA Gosens I., Sessa A., den Hollander A.I., Letteboer S.J.F., Belloni V.,
RA Arends M.L., Le Bivic A., Cremers F.P.M., Broccoli V., Roepman R.;
RT "FERM protein EPB41L5 is a novel member of the mammalian CRB-MPP5 polarity
RT complex.";
RL Exp. Cell Res. 313:3959-3970(2007).
CC -!- FUNCTION: Involved in the establishment of cell polarity in mammalian
CC epithelial cells (PubMed:12771187, PubMed:14718572). Regulates the
CC morphogenesis of tight junctions (PubMed:12771187, PubMed:14718572).
CC Involved in promoting phosphorylation and cytoplasmic retention of
CC transcriptional coactivators YAP1 and WWTR1/TAZ which leads to
CC suppression of TGFB1-dependent transcription of target genes such as
CC CCN2/CTGF, SERPINE1/PAI1, SNAI1/SNAIL1 and SMAD7 (By similarity).
CC {ECO:0000250|UniProtKB:Q8QZT4, ECO:0000269|PubMed:12771187,
CC ECO:0000269|PubMed:14718572}.
CC -!- SUBUNIT: Component of a complex composed of CRB3, PALS1 and PATJ (By
CC similarity). Interacts (via C-terminus) with PALS1 (via PDZ domain)
CC (PubMed:12527193, PubMed:12771187). Interacts with PARD6A
CC (PubMed:14718572). Interacts (via intracellular domain) with EPB41L5
CC (PubMed:17920587). {ECO:0000250|UniProtKB:A0A5F4BST2,
CC ECO:0000269|PubMed:12527193, ECO:0000269|PubMed:12771187,
CC ECO:0000269|PubMed:14718572, ECO:0000269|PubMed:17920587}.
CC -!- INTERACTION:
CC Q9BUF7; Q9HCM4: EPB41L5; NbExp=3; IntAct=EBI-9844372, EBI-1047162;
CC Q9BUF7; P25788: PSMA3; NbExp=3; IntAct=EBI-9844372, EBI-348380;
CC Q9BUF7-2; Q86W74-2: ANKRD46; NbExp=3; IntAct=EBI-17233035, EBI-12109402;
CC Q9BUF7-2; Q9BXK5: BCL2L13; NbExp=3; IntAct=EBI-17233035, EBI-747430;
CC Q9BUF7-2; O15155: BET1; NbExp=3; IntAct=EBI-17233035, EBI-749204;
CC Q9BUF7-2; Q9BWH2: FUNDC2; NbExp=3; IntAct=EBI-17233035, EBI-714482;
CC Q9BUF7-2; P09601: HMOX1; NbExp=3; IntAct=EBI-17233035, EBI-2806151;
CC Q9BUF7-2; P30519: HMOX2; NbExp=3; IntAct=EBI-17233035, EBI-712096;
CC Q9BUF7-2; O95167: NDUFA3; NbExp=3; IntAct=EBI-17233035, EBI-1246131;
CC Q9BUF7-2; Q9Y342: PLLP; NbExp=3; IntAct=EBI-17233035, EBI-3919291;
CC Q9BUF7-2; Q04941: PLP2; NbExp=3; IntAct=EBI-17233035, EBI-608347;
CC Q9BUF7-2; Q9NZ42: PSENEN; NbExp=3; IntAct=EBI-17233035, EBI-998468;
CC Q9BUF7-2; Q9UI14: RABAC1; NbExp=3; IntAct=EBI-17233035, EBI-712367;
CC Q9BUF7-2; O75920: SERF1B; NbExp=3; IntAct=EBI-17233035, EBI-2115181;
CC Q9BUF7-2; Q9Y6X1: SERP1; NbExp=3; IntAct=EBI-17233035, EBI-10329948;
CC Q9BUF7-2; Q9NUM3: SLC39A9; NbExp=3; IntAct=EBI-17233035, EBI-2823239;
CC Q9BUF7-2; Q13190: STX5; NbExp=3; IntAct=EBI-17233035, EBI-714206;
CC Q9BUF7-2; Q9NZ01: TECR; NbExp=3; IntAct=EBI-17233035, EBI-2877718;
CC Q9BUF7-2; Q9H0R3: TMEM222; NbExp=3; IntAct=EBI-17233035, EBI-347385;
CC Q9BUF7-2; Q9NSU2-1: TREX1; NbExp=3; IntAct=EBI-17233035, EBI-16746122;
CC Q9BUF7-2; Q9Y5Z9: UBIAD1; NbExp=3; IntAct=EBI-17233035, EBI-2819725;
CC Q9BUF7-2; P23763-3: VAMP1; NbExp=3; IntAct=EBI-17233035, EBI-12097582;
CC Q9BUF7-2; Q9UEU0: VTI1B; NbExp=3; IntAct=EBI-17233035, EBI-723716;
CC Q9BUF7-2; Q96EC8: YIPF6; NbExp=3; IntAct=EBI-17233035, EBI-751210;
CC PRO_0000021005; Q8N3R9-1: PALS1; NbExp=3; IntAct=EBI-25611611, EBI-8231026;
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:12527193, ECO:0000269|PubMed:12771187,
CC ECO:0000269|PubMed:14718572}; Single-pass type I membrane protein
CC {ECO:0000255}. Cell junction, tight junction
CC {ECO:0000269|PubMed:12527193}. Note=Localizes primarily to the apical
CC membrane with a small fraction in the upper part of tight junctions of
CC epithelial cells. {ECO:0000269|PubMed:14718572}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=A;
CC IsoId=Q9BUF7-1; Sequence=Displayed;
CC Name=2; Synonyms=B;
CC IsoId=Q9BUF7-2; Sequence=VSP_013989;
CC -!- TISSUE SPECIFICITY: Preferentially expressed in epithelial tissues
CC (PubMed:14718572). Expressed at high levels in lung, kidney, and colon
CC (PubMed:12527193, PubMed:14718572). Expressed at high levels in retina,
CC colon and mammary glands (PubMed:12527193). Moderately expressed in
CC liver, spleen, pancreas and prostate (PubMed:12527193). Moderately to
CC weakly expressed in the placenta (PubMed:14718572, PubMed:12527193).
CC Weakly expressed in skeletal muscle and small intestine
CC (PubMed:14718572). {ECO:0000269|PubMed:12527193,
CC ECO:0000269|PubMed:14718572}.
CC -!- DOMAIN: The PDZ-binding motif is involved in the interactions with
CC PARD6A and PALS1. {ECO:0000269|PubMed:12771187,
CC ECO:0000269|PubMed:14718572}.
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DR EMBL; AY103469; AAM44074.1; -; mRNA.
DR EMBL; AF503290; AAM23013.1; -; mRNA.
DR EMBL; AY358684; AAQ89047.1; -; mRNA.
DR EMBL; AK292956; BAF85645.1; -; mRNA.
DR EMBL; CH471139; EAW69084.1; -; Genomic_DNA.
DR EMBL; CH471139; EAW69085.1; -; Genomic_DNA.
DR EMBL; CH471139; EAW69086.1; -; Genomic_DNA.
DR EMBL; BC002652; AAH02652.2; -; mRNA.
DR EMBL; BC018409; AAH18409.1; -; mRNA.
DR CCDS; CCDS12166.1; -. [Q9BUF7-2]
DR CCDS; CCDS12167.1; -. [Q9BUF7-1]
DR RefSeq; NP_631900.1; NM_139161.4. [Q9BUF7-1]
DR RefSeq; NP_777377.1; NM_174881.3. [Q9BUF7-2]
DR RefSeq; NP_777378.1; NM_174882.2. [Q9BUF7-1]
DR PDB; 5I7Z; X-ray; 1.80 A; B=113-120.
DR PDBsum; 5I7Z; -.
DR AlphaFoldDB; Q9BUF7; -.
DR SMR; Q9BUF7; -.
DR BioGRID; 124940; 28.
DR ComplexPortal; CPX-6166; CRUMBS3-PALS1-PATJ cell polarity complex.
DR IntAct; Q9BUF7; 27.
DR MINT; Q9BUF7; -.
DR STRING; 9606.ENSP00000349204; -.
DR GlyGen; Q9BUF7; 1 site.
DR iPTMnet; Q9BUF7; -.
DR PhosphoSitePlus; Q9BUF7; -.
DR BioMuta; CRB3; -.
DR DMDM; 67460584; -.
DR EPD; Q9BUF7; -.
DR jPOST; Q9BUF7; -.
DR MassIVE; Q9BUF7; -.
DR MaxQB; Q9BUF7; -.
DR PeptideAtlas; Q9BUF7; -.
DR PRIDE; Q9BUF7; -.
DR ProteomicsDB; 79082; -. [Q9BUF7-1]
DR ProteomicsDB; 79083; -. [Q9BUF7-2]
DR Antibodypedia; 3003; 101 antibodies from 16 providers.
DR DNASU; 92359; -.
DR Ensembl; ENST00000308243.7; ENSP00000310123.6; ENSG00000130545.16. [Q9BUF7-1]
DR Ensembl; ENST00000356762.7; ENSP00000349204.2; ENSG00000130545.16. [Q9BUF7-2]
DR Ensembl; ENST00000598494.5; ENSP00000469707.1; ENSG00000130545.16. [Q9BUF7-1]
DR Ensembl; ENST00000600229.6; ENSP00000472010.1; ENSG00000130545.16. [Q9BUF7-1]
DR GeneID; 92359; -.
DR KEGG; hsa:92359; -.
DR MANE-Select; ENST00000600229.6; ENSP00000472010.1; NM_139161.5; NP_631900.1.
DR UCSC; uc002mey.4; human. [Q9BUF7-1]
DR CTD; 92359; -.
DR DisGeNET; 92359; -.
DR GeneCards; CRB3; -.
DR HGNC; HGNC:20237; CRB3.
DR HPA; ENSG00000130545; Tissue enhanced (esophagus).
DR MIM; 609737; gene.
DR neXtProt; NX_Q9BUF7; -.
DR OpenTargets; ENSG00000130545; -.
DR PharmGKB; PA134862130; -.
DR VEuPathDB; HostDB:ENSG00000130545; -.
DR eggNOG; ENOG502S74B; Eukaryota.
DR GeneTree; ENSGT00950000183101; -.
DR HOGENOM; CLU_2120342_0_0_1; -.
DR InParanoid; Q9BUF7; -.
DR OMA; WGQVWGQ; -.
DR OrthoDB; 1551105at2759; -.
DR PhylomeDB; Q9BUF7; -.
DR TreeFam; TF353183; -.
DR PathwayCommons; Q9BUF7; -.
DR Reactome; R-HSA-420029; Tight junction interactions.
DR Reactome; R-HSA-9705677; SARS-CoV-2 targets PDZ proteins in cell-cell junction.
DR SignaLink; Q9BUF7; -.
DR SIGNOR; Q9BUF7; -.
DR BioGRID-ORCS; 92359; 13 hits in 1065 CRISPR screens.
DR ChiTaRS; CRB3; human.
DR GeneWiki; CRB3; -.
DR GenomeRNAi; 92359; -.
DR Pharos; Q9BUF7; Tbio.
DR PRO; PR:Q9BUF7; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9BUF7; protein.
DR Bgee; ENSG00000130545; Expressed in lower esophagus mucosa and 152 other tissues.
DR Genevisible; Q9BUF7; HS.
DR GO; GO:0043296; C:apical junction complex; IC:ComplexPortal.
DR GO; GO:0016324; C:apical plasma membrane; IC:ComplexPortal.
DR GO; GO:0005923; C:bicellular tight junction; IEA:UniProtKB-SubCell.
DR GO; GO:0030054; C:cell junction; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0035003; C:subapical complex; IEA:Ensembl.
DR GO; GO:0019904; F:protein domain specific binding; IPI:BHF-UCL.
DR GO; GO:0017124; F:SH3 domain binding; IPI:BHF-UCL.
DR GO; GO:0045197; P:establishment or maintenance of epithelial cell apical/basal polarity; IC:ComplexPortal.
DR GO; GO:1901890; P:positive regulation of cell junction assembly; ISS:UniProtKB.
DR GO; GO:0072659; P:protein localization to plasma membrane; IDA:BHF-UCL.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell junction; Cell membrane;
KW Glycoprotein; Membrane; Reference proteome; Signal; Tight junction;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..120
FT /note="Protein crumbs homolog 3"
FT /id="PRO_0000021005"
FT TOPO_DOM 27..59
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 60..80
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 81..120
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 84..120
FT /note="Interaction with EPB41L5"
FT /evidence="ECO:0000269|PubMed:17920587"
FT REGION 87..120
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 117..120
FT /note="PDZ-binding"
FT CARBOHYD 36
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12527193"
FT VAR_SEQ 101..120
FT /note="VGARVPPTPNLKLPPEERLI -> FSHAAEARAPQDSKETVQGCLPI (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:12975309,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_013989"
FT MUTAGEN 36
FT /note="N->D: Abolishes N-glycosylation. No effect on
FT localization to the apical cell membrane."
FT /evidence="ECO:0000269|PubMed:12527193"
FT MUTAGEN 117..120
FT /note="Missing: Loss of interaction with PARD6A and PALS1.
FT No effect on interaction with EPB41L5."
FT /evidence="ECO:0000269|PubMed:12771187,
FT ECO:0000269|PubMed:14718572, ECO:0000269|PubMed:17920587"
FT STRAND 116..120
FT /evidence="ECO:0007829|PDB:5I7Z"
SQ SEQUENCE 120 AA; 12854 MW; F0CCDE3D91E7392D CRC64;
MANPGLGLLL ALGLPFLLAR WGRAWGQIQT TSANENSTVL PSSTSSSSDG NLRPEAITAI
IVVFSLLAAL LLAVGLALLV RKLREKRQTE GTYRPSSEEQ VGARVPPTPN LKLPPEERLI
