P23508 (CRCM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Colorectal mutant cancer protein
Short name=Protein MCC

Gene names

Name:

MCC

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	829 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Candidate for the putative colorectal tumor suppressor gene located at 5q21. Suppresses cell proliferation and the Wnt/b-catenin pathway in colorectal cancer cells. Inhibits DNA binding of b-catenin/TCF/LEF transcription factors. Involved in cell migration independently of RAC1, CDC42 and p21-activated kinase (PAK) activation. Ref.6 Ref.8
Subunit structure	Interacts with SCRIB, EZR, SNX27, SLC9A3R1 and SLC9A3R2. Interacts with CTNNB1; the interaction is enhanced upon Wnt stimulation. Ref.6 Ref.8
Subcellular location	Cell membrane. Nucleus. Cytoplasm Ref.6 Ref.8.
Tissue specificity	Expressed in a variety of tissues.
Sequence similarities	Belongs to the MCC family.

Ontologies

Keywords
Biological process	Wnt signaling pathway
Cellular component	Cell membrane Cytoplasm Membrane Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Tumor suppressor
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of canonical Wnt receptor signaling pathway Inferred from direct assay Ref.6. Source: UniProtKB negative regulation of epithelial cell migration Inferred from mutant phenotype Ref.8. Source: UniProtKB negative regulation of epithelial cell proliferation Inferred from direct assay Ref.6. Source: UniProtKB
Cellular component	cytoplasm Inferred from direct assay Ref.6. Source: UniProtKB nucleus Inferred from direct assay Ref.6. Source: UniProtKB plasma membrane Inferred from direct assay Ref.8. Source: UniProtKB
Molecular function	protein binding Inferred from physical interaction Ref.6Ref.8. Source: UniProtKB receptor activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GTF2E2	P29084	2	EBI-307531,EBI-2853321

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P23508-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P23508-2) The sequence of this isoform differs from the canonical sequence as follows:      1-19: MNSGVAMKYGNDSSAELSE → MMAAAAAAAA...GGSYLELANT
Sequence annotation (Features)
	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
	Sequence conflict	25	1	S → GSSSG in BAC87521. Ref.5

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 829	829	Colorectal mutant cancer protein		PRO_0000079333
Amino acid modifications
	Modified residue	294	1	Phosphoserine Ref.7
Natural variations
	Alternative sequence	1 – 19	19	MNSGV…AELSE → MMAAAAAAAAGSSSSGGGGG GSGSSSSSSDTSSTGEEERM RRLFQTCDGDGDGYISRNDL LMVCRQLNMEESVAEIMNQL GADENGKISFQDFTRCRMQL VREIRKEEVDLSAKSDNSCT KKLRDRIASWPTSSDNSLGA LSAARESWEYDSGARDLQSP DVQSQSALQKLLEYGGSSLH QQAALHKLLTQSPHIGNSVG GSYLELANT in isoform 2.		VSP_037660
	Natural variant	190	1	K → R. Ref.1 Ref.4 Ref.5 Corresponds to variant rs6594681 [ dbSNP | Ensembl ].		VAR_050905
	Natural variant	267	1	R → L in a colorectal cancer sample. Ref.9		VAR_005141
	Natural variant	486	1	P → L in a colorectal cancer sample. Ref.9 Corresponds to variant rs35269015 [ dbSNP | Ensembl ].		VAR_005142
	Natural variant	490	1	S → L in a colorectal cancer sample. Ref.9		VAR_005143
	Natural variant	506	1	R → Q in colorectal cancer samples; somatic mutation. Ref.1 Ref.9		VAR_005144
	Natural variant	698	1	A → V in colorectal cancer samples; somatic mutation. Ref.1 Ref.9		VAR_005145
	Natural variant	751	1	S → C. Corresponds to variant rs17313892 [ dbSNP | Ensembl ].		VAR_033753
Experimental info
	Sequence conflict	353	1	S → G in BAC87521. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 11, 2011. Version 2. Checksum: C90611B2E91A7F60	FASTA	829	93,027
	10 20 30 40 50 60 MNSGVAMKYG NDSSAELSEL HSAALASLKG DIVELNKRLQ QTERERDLLE KKLAKAQCEQ 70 80 90 100 110 120 SHLMREHEDV QERTTLRYEE RITELHSVIA ELNKKIDRLQ GTTIREEDEY SELRSELSQS 130 140 150 160 170 180 QHEVNEDSRS MDQDQTSVSI PENQSTMVTA DMDNCSDLNS ELQRVLTGLE NVVCGRKKSS 190 200 210 220 230 240 CSLSVAEVDK HIEQLTTASE HCDLAIKTVE EIEGVLGRDL YPNLAEERSR WEKELAGLRE 250 260 270 280 290 300 ENESLTAMLC SKEEELNRTK ATMNAIREER DRLRRRVREL QTRLQSVQAT GPSSPGRLTS 310 320 330 340 350 360 TNRPINPSTG ELSTSSSSND IPIAKIAERV KLSKTRSESS SSDRPVLGSE ISSIGVSSSV 370 380 390 400 410 420 AEHLAHSLQD CSNIQEIFQT LYSHGSAISE SKIREFEVET ERLNSRIEHL KSQNDLLTIT 430 440 450 460 470 480 LEECKSNAER MSMLVGKYES NATALRLALQ YSEQCIEAYE LLLALAESEQ SLILGQFRAA 490 500 510 520 530 540 GVGSSPGDQS GDENITQMLK RAHDCRKTAE NAAKALLMKL DGSCGGAFAV AGCSVQPWES 550 560 570 580 590 600 LSSNSHTSTT SSTASSCDTE FTKEDEQRLK DYIQQLKNDR AAVKLTMLEL ESIHIDPLSY 610 620 630 640 650 660 DVKPRGDSQR LDLENAVLMQ ELMAMKEEMA ELKAQLYLLE KEKKALELKL STREAQEQAY 670 680 690 700 710 720 LVHIEHLKSE VEEQKEQRMR SLSSTSSGSK DKPGKECADA ASPALSLAEL RTTCSENELA 730 740 750 760 770 780 AEFTNAIRRE KKLKARVQEL VSALERLTKS SEIRHQQSAE FVNDLKRANS NLVAAYEKAK 790 800 810 820 KKHQNKLKKL ESQMMAMVER HETQVRMLKQ RIALLEEENS RPHTNETSL
	Isoform 2 [UniParc]. Checksum: 09C330B8B43832F1	FASTA	1,019	113,279
	10 20 30 40 50 60 MMAAAAAAAA GSSSSGGGGG GSGSSSSSSD TSSTGEEERM RRLFQTCDGD GDGYISRNDL 70 80 90 100 110 120 LMVCRQLNME ESVAEIMNQL GADENGKISF QDFTRCRMQL VREIRKEEVD LSAKSDNSCT 130 140 150 160 170 180 KKLRDRIASW PTSSDNSLGA LSAARESWEY DSGARDLQSP DVQSQSALQK LLEYGGSSLH 190 200 210 220 230 240 QQAALHKLLT QSPHIGNSVG GSYLELANTL HSAALASLKG DIVELNKRLQ QTERERDLLE 250 260 270 280 290 300 KKLAKAQCEQ SHLMREHEDV QERTTLRYEE RITELHSVIA ELNKKIDRLQ GTTIREEDEY 310 320 330 340 350 360 SELRSELSQS QHEVNEDSRS MDQDQTSVSI PENQSTMVTA DMDNCSDLNS ELQRVLTGLE 370 380 390 400 410 420 NVVCGRKKSS CSLSVAEVDK HIEQLTTASE HCDLAIKTVE EIEGVLGRDL YPNLAEERSR 430 440 450 460 470 480 WEKELAGLRE ENESLTAMLC SKEEELNRTK ATMNAIREER DRLRRRVREL QTRLQSVQAT 490 500 510 520 530 540 GPSSPGRLTS TNRPINPSTG ELSTSSSSND IPIAKIAERV KLSKTRSESS SSDRPVLGSE 550 560 570 580 590 600 ISSIGVSSSV AEHLAHSLQD CSNIQEIFQT LYSHGSAISE SKIREFEVET ERLNSRIEHL 610 620 630 640 650 660 KSQNDLLTIT LEECKSNAER MSMLVGKYES NATALRLALQ YSEQCIEAYE LLLALAESEQ 670 680 690 700 710 720 SLILGQFRAA GVGSSPGDQS GDENITQMLK RAHDCRKTAE NAAKALLMKL DGSCGGAFAV 730 740 750 760 770 780 AGCSVQPWES LSSNSHTSTT SSTASSCDTE FTKEDEQRLK DYIQQLKNDR AAVKLTMLEL 790 800 810 820 830 840 ESIHIDPLSY DVKPRGDSQR LDLENAVLMQ ELMAMKEEMA ELKAQLYLLE KEKKALELKL 850 860 870 880 890 900 STREAQEQAY LVHIEHLKSE VEEQKEQRMR SLSSTSSGSK DKPGKECADA ASPALSLAEL 910 920 930 940 950 960 RTTCSENELA AEFTNAIRRE KKLKARVQEL VSALERLTKS SEIRHQQSAE FVNDLKRANS 970 980 990 1000 1010 NLVAAYEKAK KKHQNKLKKL ESQMMAMVER HETQVRMLKQ RIALLEEENS RPHTNETSL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of a gene located at chromosome 5q21 that is mutated in colorectal cancers." Kinzler K.W., Nilbert M.C., Vogelstein B., Bryan T.M., Levy D.B., Smith K.J., Preisinger A.C., Hamilton S.R., Hedge P., Markham A., Carlson M., Joslyn G., Groden J., White R., Miki Y., Miyoshi Y., Nishisho I., Nakamura Y. Science 251:1366-1370(1991) [PubMed: 1848370] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ARG-190; GLN-506 AND VAL-698. Tissue: Brain.
[2]	"The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M. Nature 431:268-274(2004) [PubMed: 15372022] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ARG-190. Tissue: Muscle.
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-779 (ISOFORM 2), VARIANT ARG-190. Tissue: Trachea.
[6]	"Mutated in colorectal cancer, a putative tumor suppressor for serrated colorectal cancer, selectively represses beta-catenin-dependent transcription." Fukuyama R., Niculaita R., Ng K.P., Obusez E., Sanchez J., Kalady M., Aung P.P., Casey G., Sizemore N. Oncogene 27:6044-6055(2008) [PubMed: 18591935] [Abstract] Cited for: FUNCTION IN WNT SIGNALING, SUBCELLULAR LOCATION, INTERACTION WITH CTNNB1.
[7]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-294, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[8]	"MCC, a new interacting protein for Scrib, is required for cell migration in epithelial cells." Arnaud C., Sebbagh M., Nola S., Audebert S., Bidaut G., Hermant A., Gayet O., Dusetti N.J., Ollendorff V., Santoni M.J., Borg J.P., Lecine P. FEBS Lett. 583:2326-2332(2009) [PubMed: 19555689] [Abstract] Cited for: FUNCTION IN CELL MIGRATION, SUBCELLULAR LOCATION, INTERACTION WITH SCRIB; EZR; SNX27; SLC9A3R1 AND SLC9A3R2.
[9]	"Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients." Nishisho I., Nakamura Y., Miyoshi Y., Miki Y., Ando H., Horii A., Koyama K., Utsunomiya J., Baba S., Hedge P., Markham A., Krush A.J., Petersen G.M., Hamilton S.R., Nilbert M.C., Levy D.B., Bryan T.M., Preisinger A.C. , Smith K.J., Su L.-K., Kinzler K.W., Vogelstein B. Science 253:665-669(1991) [PubMed: 1651563] [Abstract] Cited for: VARIANTS LEU-267; LEU-486; LEU-490; GLN-506 AND VAL-698.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M62397 mRNA. Translation: AAA52069.1. AC008536 Genomic DNA. No translation available. AC010431 Genomic DNA. No translation available. AC079465 Genomic DNA. No translation available. AC093208 Genomic DNA. No translation available. AC106750 Genomic DNA. No translation available. AC126917 Genomic DNA. No translation available. CH471086 Genomic DNA. Translation: EAW48984.1. CH471086 Genomic DNA. Translation: EAW48986.1. BC009279 mRNA. Translation: AAH09279.1. BC018919 mRNA. Translation: AAH18919.1. AK128596 mRNA. Translation: BAC87521.1.
IPI	IPI00011957. IPI00443415.
PIR	A33166. A38434.
RefSeq	NP_001078846.1. NM_001085377.1. NP_002378.1. NM_002387.2.
UniGene	Hs.593171.
3D structure databases
ProteinModelPortal	P23508.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-27599N.
IntAct	P23508. 4 interactions.
MINT	MINT-1161194.
STRING	P23508.
PTM databases
PhosphoSite	P23508.
Polymorphism databases
DMDM	117424.
Proteomic databases
PRIDE	P23508.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000302475; ENSP00000305617; ENSG00000171444.
GeneID	4163.
KEGG	hsa:4163.
UCSC	uc003kqj.2. human.
Organism-specific databases
CTD	4163.
GeneCards	GC05M112388.
H-InvDB	HIX0020315.
HGNC	HGNC:6935. MCC.
HPA	HPA037391.
MIM	159350. gene.
neXtProt	NX_P23508.
PharmGKB	PA30679.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG15810.
HOGENOM	HBG357807.
HOVERGEN	HBG004762.
OMA	CADAASP.
OrthoDB	EOG4ZS92H.
Gene expression databases
ArrayExpress	P23508.
Bgee	P23508.
CleanEx	HS_MCC.
Genevestigator	P23508.
GermOnline	ENSG00000171444. Homo sapiens.
Family and domain databases
InterPro	IPR019536. USH1C-bd_PDZ_domain. [Graphical view]
Pfam	PF10506. MCC-bdg_PDZ. 3 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	16402.
SOURCE	Search...

Entry information

Entry name

CRCM_HUMAN

Accession

Primary (citable) accession number: P23508
Secondary accession number(s): D3DT05, Q6ZR04

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1991
Last sequence update:	January 11, 2011
Last modified:	January 25, 2012
This is version 98 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.