CRCM_HUMAN
ID CRCM_HUMAN Reviewed; 829 AA.
AC P23508; D3DT05; Q6ZR04;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 2.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Colorectal mutant cancer protein;
DE Short=Protein MCC;
GN Name=MCC;
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], AND VARIANTS ARG-190; GLN-506 AND VAL-698.
RC TISSUE=Brain;
RX PubMed=1848370; DOI=10.1126/science.1848370;
RA Kinzler K.W., Nilbert M.C., Vogelstein B., Bryan T.M., Levy D.B.,
RA Smith K.J., Preisinger A.C., Hamilton S.R., Hedge P., Markham A.,
RA Carlson M., Joslyn G., Groden J., White R., Miki Y., Miyoshi Y.,
RA Nishisho I., Nakamura Y.;
RT "Identification of a gene located at chromosome 5q21 that is mutated in
RT colorectal cancers.";
RL Science 251:1366-1370(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-190.
RC TISSUE=Muscle;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-779 (ISOFORM 2), AND VARIANT
RP ARG-190.
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 [6]
RP FUNCTION IN WNT SIGNALING, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP CTNNB1.
RX PubMed=18591935; DOI=10.1038/onc.2008.204;
RA Fukuyama R., Niculaita R., Ng K.P., Obusez E., Sanchez J., Kalady M.,
RA Aung P.P., Casey G., Sizemore N.;
RT "Mutated in colorectal cancer, a putative tumor suppressor for serrated
RT colorectal cancer, selectively represses beta-catenin-dependent
RT transcription.";
RL Oncogene 27:6044-6055(2008).
RN [7]
RP FUNCTION IN CELL MIGRATION, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP SCRIB; EZR; SNX27; SLC9A3R1 AND SLC9A3R2.
RX PubMed=19555689; DOI=10.1016/j.febslet.2009.06.034;
RA Arnaud C., Sebbagh M., Nola S., Audebert S., Bidaut G., Hermant A.,
RA Gayet O., Dusetti N.J., Ollendorff V., Santoni M.J., Borg J.P., Lecine P.;
RT "MCC, a new interacting protein for Scrib, is required for cell migration
RT in epithelial cells.";
RL FEBS Lett. 583:2326-2332(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [9]
RP FUNCTION, PDZ-BINDING MOTIF, PHOSPHORYLATION AT SER-828, INTERACTION WITH
RP SCRIB AND MYH10, SUBCELLULAR LOCATION, AND MUTAGENESIS OF SER-828.
RX PubMed=22480440; DOI=10.1016/j.bbamcr.2012.03.011;
RA Pangon L., Van Kralingen C., Abas M., Daly R.J., Musgrove E.A.,
RA Kohonen-Corish M.R.;
RT "The PDZ-binding motif of MCC is phosphorylated at position -1 and controls
RT lamellipodia formation in colon epithelial cells.";
RL Biochim. Biophys. Acta 1823:1058-1067(2012).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [11]
RP VARIANTS LEU-267; LEU-486; LEU-490; GLN-506 AND VAL-698.
RX PubMed=1651563; DOI=10.1126/science.1651563;
RA Nishisho I., Nakamura Y., Miyoshi Y., Miki Y., Ando H., Horii A.,
RA Koyama K., Utsunomiya J., Baba S., Hedge P., Markham A., Krush A.J.,
RA Petersen G.M., Hamilton S.R., Nilbert M.C., Levy D.B., Bryan T.M.,
RA Preisinger A.C., Smith K.J., Su L.-K., Kinzler K.W., Vogelstein B.;
RT "Mutations of chromosome 5q21 genes in FAP and colorectal cancer
RT patients.";
RL Science 253:665-669(1991).
RN [12]
RP CHARACTERIZATION OF VARIANT GLN-506, FUNCTION, SUBCELLULAR LOCATION,
RP INTERACTION WITH CCAR2, AND NUCLEAR LOCALIZATION SIGNAL.
RX PubMed=24824780; DOI=10.1002/ijc.28967;
RA Pangon L., Mladenova D., Watkins L., Van Kralingen C., Currey N.,
RA Al-Sohaily S., Lecine P., Borg J.P., Kohonen-Corish M.R.;
RT "MCC inhibits beta-catenin transcriptional activity by sequestering DBC1 in
RT the cytoplasm.";
RL Int. J. Cancer 136:55-64(2015).
RN [13]
RP VARIANT LYS-142.
RX PubMed=27932480; DOI=10.1681/asn.2016040387;
RG NephroS;
RG UK study of Nephrotic Syndrome;
RA Bierzynska A., Soderquest K., Dean P., Colby E., Rollason R., Jones C.,
RA Inward C.D., McCarthy H.J., Simpson M.A., Lord G.M., Williams M.,
RA Welsh G.I., Koziell A.B., Saleem M.A.;
RT "MAGI2 mutations cause congenital nephrotic syndrome.";
RL J. Am. Soc. Nephrol. 28:1614-1621(2017).
CC -!- FUNCTION: Candidate for the putative colorectal tumor suppressor gene
CC located at 5q21. Suppresses cell proliferation and the Wnt/b-catenin
CC pathway in colorectal cancer cells. Inhibits DNA binding of b-
CC catenin/TCF/LEF transcription factors. Involved in cell migration
CC independently of RAC1, CDC42 and p21-activated kinase (PAK) activation
CC (PubMed:18591935, PubMed:19555689, PubMed:22480440). Represses the
CC beta-catenin pathway (canonical Wnt signaling pathway) in a CCAR2-
CC dependent manner by sequestering CCAR2 to the cytoplasm, thereby
CC impairing its ability to inhibit SIRT1 which is involved in the
CC deacetylation and negative regulation of beta-catenin (CTNB1)
CC transcriptional activity (PubMed:24824780).
CC {ECO:0000269|PubMed:18591935, ECO:0000269|PubMed:19555689,
CC ECO:0000269|PubMed:22480440, ECO:0000269|PubMed:24824780}.
CC -!- SUBUNIT: Interacts with SCRIB (via phosphorylated PDZ-binding motif),
CC EZR, SNX27, SLC9A3R1 and SLC9A3R2. Interacts with CTNNB1; the
CC interaction is enhanced upon Wnt stimulation. Interacts with MYH10.
CC Interacts with CCAR2. {ECO:0000269|PubMed:18591935,
CC ECO:0000269|PubMed:19555689, ECO:0000269|PubMed:22480440,
CC ECO:0000269|PubMed:24824780}.
CC -!- INTERACTION:
CC P23508; O95696: BRD1; NbExp=3; IntAct=EBI-307531, EBI-714754;
CC P23508; Q9H7E9: C8orf33; NbExp=3; IntAct=EBI-307531, EBI-715389;
CC P23508; Q96LL4: C8orf48; NbExp=3; IntAct=EBI-307531, EBI-751596;
CC P23508; Q9HC52: CBX8; NbExp=3; IntAct=EBI-307531, EBI-712912;
CC P23508; Q8NEF3-2: CCDC112; NbExp=3; IntAct=EBI-307531, EBI-12095166;
CC P23508; Q8IYE0: CCDC146; NbExp=3; IntAct=EBI-307531, EBI-10749669;
CC P23508; Q8N715: CCDC185; NbExp=3; IntAct=EBI-307531, EBI-740814;
CC P23508; Q8IVW4: CDKL3; NbExp=3; IntAct=EBI-307531, EBI-3919850;
CC P23508; Q8IYX8: CEP57L1; NbExp=3; IntAct=EBI-307531, EBI-1104570;
CC P23508; Q96GE4: CEP95; NbExp=3; IntAct=EBI-307531, EBI-372775;
CC P23508; Q5T655: CFAP58; NbExp=3; IntAct=EBI-307531, EBI-10245749;
CC P23508; P49674: CSNK1E; NbExp=4; IntAct=EBI-307531, EBI-749343;
CC P23508; Q8WXU2-2: DNAAF4; NbExp=3; IntAct=EBI-307531, EBI-9381887;
CC P23508; Q14241: ELOA; NbExp=3; IntAct=EBI-307531, EBI-742350;
CC P23508; P62508-3: ESRRG; NbExp=3; IntAct=EBI-307531, EBI-12001340;
CC P23508; Q3B820: FAM161A; NbExp=3; IntAct=EBI-307531, EBI-719941;
CC P23508; O43320: FGF16; NbExp=3; IntAct=EBI-307531, EBI-11479104;
CC P23508; P29084: GTF2E2; NbExp=2; IntAct=EBI-307531, EBI-2853321;
CC P23508; Q9NV31: IMP3; NbExp=3; IntAct=EBI-307531, EBI-747481;
CC P23508; Q92993: KAT5; NbExp=3; IntAct=EBI-307531, EBI-399080;
CC P23508; O14782: KIF3C; NbExp=3; IntAct=EBI-307531, EBI-1104854;
CC P23508; Q9BVG8-5: KIFC3; NbExp=3; IntAct=EBI-307531, EBI-14069005;
CC P23508; Q96CN5: LRRC45; NbExp=3; IntAct=EBI-307531, EBI-2805176;
CC P23508; Q9HCI5: MAGEE1; NbExp=3; IntAct=EBI-307531, EBI-949966;
CC P23508; Q8IVT4: MGC50722; NbExp=3; IntAct=EBI-307531, EBI-14086479;
CC P23508; Q9UGY1: NOL12; NbExp=3; IntAct=EBI-307531, EBI-716098;
CC P23508; P05165: PCCA; NbExp=3; IntAct=EBI-307531, EBI-2211679;
CC P23508; Q96T60: PNKP; NbExp=3; IntAct=EBI-307531, EBI-1045072;
CC P23508; Q9UGP5-2: POLL; NbExp=3; IntAct=EBI-307531, EBI-10320765;
CC P23508; Q99633: PRPF18; NbExp=3; IntAct=EBI-307531, EBI-2798416;
CC P23508; P26045: PTPN3; NbExp=2; IntAct=EBI-307531, EBI-1047946;
CC P23508; Q9UJF2-2: RASAL2; NbExp=3; IntAct=EBI-307531, EBI-12171247;
CC P23508; Q9P2K3-2: RCOR3; NbExp=3; IntAct=EBI-307531, EBI-1504830;
CC P23508; Q14160: SCRIB; NbExp=14; IntAct=EBI-307531, EBI-357345;
CC P23508; Q9NWH9: SLTM; NbExp=3; IntAct=EBI-307531, EBI-2814558;
CC P23508; O95391: SLU7; NbExp=3; IntAct=EBI-307531, EBI-750559;
CC P23508; Q9BSW7: SYT17; NbExp=3; IntAct=EBI-307531, EBI-745392;
CC P23508; Q5T7P8-2: SYT6; NbExp=3; IntAct=EBI-307531, EBI-10246152;
CC P23508; Q15560: TCEA2; NbExp=3; IntAct=EBI-307531, EBI-710310;
CC P23508; Q8N8B7-2: TCEANC; NbExp=3; IntAct=EBI-307531, EBI-11955057;
CC P23508; Q9BT49: THAP7; NbExp=3; IntAct=EBI-307531, EBI-741350;
CC P23508; Q8IZ69: TRMT2A; NbExp=3; IntAct=EBI-307531, EBI-2515774;
CC P23508; Q9NRE2: TSHZ2; NbExp=3; IntAct=EBI-307531, EBI-10687282;
CC P23508; P40222: TXLNA; NbExp=3; IntAct=EBI-307531, EBI-359793;
CC P23508; Q5TAP6: UTP14C; NbExp=3; IntAct=EBI-307531, EBI-11737646;
CC P23508; P10074: ZBTB48; NbExp=3; IntAct=EBI-307531, EBI-744864;
CC P23508; P17014: ZNF12; NbExp=3; IntAct=EBI-307531, EBI-11278550;
CC P23508; O95125: ZNF202; NbExp=3; IntAct=EBI-307531, EBI-751960;
CC P23508; O43296: ZNF264; NbExp=3; IntAct=EBI-307531, EBI-4395808;
CC P23508; P17036: ZNF3; NbExp=3; IntAct=EBI-307531, EBI-1640965;
CC P23508; P13682: ZNF35; NbExp=3; IntAct=EBI-307531, EBI-11041653;
CC P23508; Q8TAU3: ZNF417; NbExp=3; IntAct=EBI-307531, EBI-740727;
CC P23508; Q7Z4V0: ZNF438; NbExp=3; IntAct=EBI-307531, EBI-11962468;
CC P23508; Q6ZNH5: ZNF497; NbExp=3; IntAct=EBI-307531, EBI-10486136;
CC P23508; Q08ER8: ZNF543; NbExp=3; IntAct=EBI-307531, EBI-10226133;
CC P23508; Q5T619: ZNF648; NbExp=3; IntAct=EBI-307531, EBI-11985915;
CC P23508; Q3KQV3: ZNF792; NbExp=3; IntAct=EBI-307531, EBI-10240849;
CC -!- SUBCELLULAR LOCATION: Cell membrane. Cell projection, lamellipodium.
CC Nucleus {ECO:0000269|PubMed:24824780}. Cytoplasm
CC {ECO:0000269|PubMed:24824780}. Note=Colocalizes with actin at the
CC leading edge of polarized cells.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P23508-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P23508-2; Sequence=VSP_037660;
CC -!- TISSUE SPECIFICITY: Expressed in a variety of tissues.
CC -!- SIMILARITY: Belongs to the MCC family. {ECO:0000305}.
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DR EMBL; M62397; AAA52069.1; -; mRNA.
DR EMBL; AC008536; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC010431; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC079465; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC093208; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC106750; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC126917; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471086; EAW48984.1; -; Genomic_DNA.
DR EMBL; CH471086; EAW48986.1; -; Genomic_DNA.
DR EMBL; BC009279; AAH09279.1; -; mRNA.
DR EMBL; BC018919; AAH18919.1; -; mRNA.
DR EMBL; AK128596; BAC87521.1; -; mRNA.
DR CCDS; CCDS4111.1; -. [P23508-1]
DR CCDS; CCDS43351.1; -. [P23508-2]
DR PIR; A38434; A33166.
DR RefSeq; NP_001078846.1; NM_001085377.1. [P23508-2]
DR RefSeq; NP_002378.1; NM_002387.2. [P23508-1]
DR PDB; 6MTU; X-ray; 2.14 A; C/D=822-829.
DR PDB; 6MTV; X-ray; 2.60 A; D/E=822-829.
DR PDBsum; 6MTU; -.
DR PDBsum; 6MTV; -.
DR AlphaFoldDB; P23508; -.
DR SMR; P23508; -.
DR BioGRID; 110333; 201.
DR CORUM; P23508; -.
DR DIP; DIP-27599N; -.
DR IntAct; P23508; 97.
DR MINT; P23508; -.
DR STRING; 9606.ENSP00000386227; -.
DR iPTMnet; P23508; -.
DR PhosphoSitePlus; P23508; -.
DR BioMuta; MCC; -.
DR DMDM; 317373352; -.
DR EPD; P23508; -.
DR jPOST; P23508; -.
DR MassIVE; P23508; -.
DR MaxQB; P23508; -.
DR PaxDb; P23508; -.
DR PeptideAtlas; P23508; -.
DR PRIDE; P23508; -.
DR ProteomicsDB; 54120; -. [P23508-1]
DR ProteomicsDB; 54121; -. [P23508-2]
DR Antibodypedia; 25386; 241 antibodies from 27 providers.
DR DNASU; 4163; -.
DR Ensembl; ENST00000302475.8; ENSP00000305617.4; ENSG00000171444.18. [P23508-1]
DR Ensembl; ENST00000408903.7; ENSP00000386227.3; ENSG00000171444.18. [P23508-2]
DR GeneID; 4163; -.
DR KEGG; hsa:4163; -.
DR MANE-Select; ENST00000408903.7; ENSP00000386227.3; NM_001085377.2; NP_001078846.2. [P23508-2]
DR UCSC; uc003kqj.5; human. [P23508-1]
DR CTD; 4163; -.
DR DisGeNET; 4163; -.
DR GeneCards; MCC; -.
DR HGNC; HGNC:6935; MCC.
DR HPA; ENSG00000171444; Tissue enhanced (ovary).
DR MalaCards; MCC; -.
DR MIM; 159350; gene.
DR neXtProt; NX_P23508; -.
DR OpenTargets; ENSG00000171444; -.
DR PharmGKB; PA30679; -.
DR VEuPathDB; HostDB:ENSG00000171444; -.
DR eggNOG; ENOG502QPWE; Eukaryota.
DR GeneTree; ENSGT00530000063974; -.
DR InParanoid; P23508; -.
DR OMA; KHAHDCR; -.
DR OrthoDB; 266426at2759; -.
DR PhylomeDB; P23508; -.
DR TreeFam; TF333056; -.
DR PathwayCommons; P23508; -.
DR SignaLink; P23508; -.
DR BioGRID-ORCS; 4163; 9 hits in 1073 CRISPR screens.
DR ChiTaRS; MCC; human.
DR GeneWiki; MCC_(gene); -.
DR GenomeRNAi; 4163; -.
DR Pharos; P23508; Tbio.
DR PRO; PR:P23508; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P23508; protein.
DR Bgee; ENSG00000171444; Expressed in gingival epithelium and 186 other tissues.
DR ExpressionAtlas; P23508; baseline and differential.
DR Genevisible; P23508; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:HPA.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0038023; F:signaling receptor activity; TAS:ProtInc.
DR GO; GO:0045184; P:establishment of protein localization; IDA:CACAO.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0010633; P:negative regulation of epithelial cell migration; IMP:UniProtKB.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IDA:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR040171; USBP1-like.
DR InterPro; IPR019536; USH1C-bd_PDZ_domain.
DR PANTHER; PTHR23347; PTHR23347; 1.
DR Pfam; PF10506; MCC-bdg_PDZ; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Cell projection;
KW Cytoplasm; Membrane; Nucleus; Phosphoprotein; Reference proteome;
KW Tumor suppressor; Wnt signaling pathway.
FT CHAIN 1..829
FT /note="Colorectal mutant cancer protein"
FT /id="PRO_0000079333"
FT REGION 114..139
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 282..320
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 672..700
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 766..782
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:24824780"
FT MOTIF 826..829
FT /note="PDZ-binding"
FT COMPBIAS 114..130
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 828
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:22480440"
FT VAR_SEQ 1..19
FT /note="MNSGVAMKYGNDSSAELSE -> MMAAAAAAAAGSSSSGGGGGGSGSSSSSS
FT DTSSTGEEERMRRLFQTCDGDGDGYISRNDLLMVCRQLNMEESVAEIMNQLGADENGKI
FT SFQDFTRCRMQLVREIRKEEVDLSAKSDNSCTKKLRDRIASWPTSSDNSLGALSAARES
FT WEYDSGARDLQSPDVQSQSALQKLLEYGGSSLHQQAALHKLLTQSPHIGNSVGGSYLEL
FT ANT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_037660"
FT VARIANT 142
FT /note="E -> K (in dbSNP:rs185322500)"
FT /evidence="ECO:0000269|PubMed:27932480"
FT /id="VAR_079267"
FT VARIANT 190
FT /note="K -> R (in dbSNP:rs6594681)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:1848370"
FT /id="VAR_050905"
FT VARIANT 267
FT /note="R -> L (in a colorectal cancer sample)"
FT /evidence="ECO:0000269|PubMed:1651563"
FT /id="VAR_005141"
FT VARIANT 486
FT /note="P -> L (in a colorectal cancer sample;
FT dbSNP:rs35269015)"
FT /evidence="ECO:0000269|PubMed:1651563"
FT /id="VAR_005142"
FT VARIANT 490
FT /note="S -> L (in a colorectal cancer sample;
FT dbSNP:rs760495893)"
FT /evidence="ECO:0000269|PubMed:1651563"
FT /id="VAR_005143"
FT VARIANT 506
FT /note="R -> Q (in colorectal cancer samples; somatic
FT mutation; decreased binding to CCAR2; significant decrease
FT in its ability to induce the relocalization of CCAR2 to the
FT cytoplasm; loss of its ability to repress the beta-catenin
FT pathway; loss of its ability to induce the SIRT1-mediated
FT deacetylation of beta-catenin; dbSNP:rs121917732)"
FT /evidence="ECO:0000269|PubMed:1651563,
FT ECO:0000269|PubMed:1848370, ECO:0000269|PubMed:24824780"
FT /id="VAR_005144"
FT VARIANT 698
FT /note="A -> V (in colorectal cancer samples; somatic
FT mutation; dbSNP:rs121917731)"
FT /evidence="ECO:0000269|PubMed:1651563,
FT ECO:0000269|PubMed:1848370"
FT /id="VAR_005145"
FT VARIANT 751
FT /note="S -> C (in dbSNP:rs17313892)"
FT /id="VAR_033753"
FT MUTAGEN 828
FT /note="S->A: Reduced binding to SCRIB."
FT /evidence="ECO:0000269|PubMed:22480440"
FT MUTAGEN 828
FT /note="S->D: Higher membrane localization, reduced
FT formation of lamellipodia, accumulation of MYH10 at the
FT cell cortex."
FT /evidence="ECO:0000269|PubMed:22480440"
FT CONFLICT 353
FT /note="S -> G (in Ref. 5; BAC87521)"
FT /evidence="ECO:0000305"
FT STRAND 825..829
FT /evidence="ECO:0007829|PDB:6MTU"
FT CONFLICT P23508-2:25
FT /note="S -> GSSSG (in Ref. 5; BAC87521)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 829 AA; 93027 MW; C90611B2E91A7F60 CRC64;
MNSGVAMKYG NDSSAELSEL HSAALASLKG DIVELNKRLQ QTERERDLLE KKLAKAQCEQ
SHLMREHEDV QERTTLRYEE RITELHSVIA ELNKKIDRLQ GTTIREEDEY SELRSELSQS
QHEVNEDSRS MDQDQTSVSI PENQSTMVTA DMDNCSDLNS ELQRVLTGLE NVVCGRKKSS
CSLSVAEVDK HIEQLTTASE HCDLAIKTVE EIEGVLGRDL YPNLAEERSR WEKELAGLRE
ENESLTAMLC SKEEELNRTK ATMNAIREER DRLRRRVREL QTRLQSVQAT GPSSPGRLTS
TNRPINPSTG ELSTSSSSND IPIAKIAERV KLSKTRSESS SSDRPVLGSE ISSIGVSSSV
AEHLAHSLQD CSNIQEIFQT LYSHGSAISE SKIREFEVET ERLNSRIEHL KSQNDLLTIT
LEECKSNAER MSMLVGKYES NATALRLALQ YSEQCIEAYE LLLALAESEQ SLILGQFRAA
GVGSSPGDQS GDENITQMLK RAHDCRKTAE NAAKALLMKL DGSCGGAFAV AGCSVQPWES
LSSNSHTSTT SSTASSCDTE FTKEDEQRLK DYIQQLKNDR AAVKLTMLEL ESIHIDPLSY
DVKPRGDSQR LDLENAVLMQ ELMAMKEEMA ELKAQLYLLE KEKKALELKL STREAQEQAY
LVHIEHLKSE VEEQKEQRMR SLSSTSSGSK DKPGKECADA ASPALSLAEL RTTCSENELA
AEFTNAIRRE KKLKARVQEL VSALERLTKS SEIRHQQSAE FVNDLKRANS NLVAAYEKAK
KKHQNKLKKL ESQMMAMVER HETQVRMLKQ RIALLEEENS RPHTNETSL
