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Protein

Colorectal mutant cancer protein

Gene

MCC

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 (PubMed:18591935, PubMed:19555689, PubMed:22480440). Represses the beta-catenin pathway (canonical Wnt signaling pathway) in a CCAR2-dependent manner by sequestering CCAR2 to the cytoplasm, thereby impairing its ability to inhibit SIRT1 which is involved in the deacetylation and negative regulation of beta-catenin (CTNB1) transcriptional activity (PubMed:24824780).4 Publications

GO - Molecular functioni

  • receptor activity Source: ProtInc

GO - Biological processi

  • establishment of protein localization Source: CACAO
  • negative regulation of canonical Wnt signaling pathway Source: UniProtKB
  • negative regulation of epithelial cell migration Source: UniProtKB
  • negative regulation of epithelial cell proliferation Source: UniProtKB
  • signal transduction Source: ProtInc
  • Wnt signaling pathway Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Wnt signaling pathway

Enzyme and pathway databases

BioCyciZFISH:ENSG00000171444-MONOMER.
SignaLinkiP23508.

Names & Taxonomyi

Protein namesi
Recommended name:
Colorectal mutant cancer protein
Short name:
Protein MCC
Gene namesi
Name:MCC
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:6935. MCC.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • lamellipodium Source: UniProtKB-SubCell
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi828S → A: Reduced binding to SCRIB. 1 Publication1
Mutagenesisi828S → D: Higher membrane localization, reduced formation of lamellipodia, accumulation of MYH10 at the cell cortex. 1 Publication1

Keywords - Diseasei

Tumor suppressor

Organism-specific databases

DisGeNETi4163.
MalaCardsiMCC.
OpenTargetsiENSG00000171444.
PharmGKBiPA30679.

Polymorphism and mutation databases

BioMutaiMCC.
DMDMi317373352.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000793331 – 829Colorectal mutant cancer proteinAdd BLAST829

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei828Phosphoserine1 Publication1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP23508.
MaxQBiP23508.
PaxDbiP23508.
PeptideAtlasiP23508.
PRIDEiP23508.

PTM databases

iPTMnetiP23508.
PhosphoSitePlusiP23508.

Expressioni

Tissue specificityi

Expressed in a variety of tissues.

Gene expression databases

BgeeiENSG00000171444.
CleanExiHS_MCC.
ExpressionAtlasiP23508. baseline and differential.
GenevisibleiP23508. HS.

Organism-specific databases

HPAiHPA037390.
HPA037391.

Interactioni

Subunit structurei

Interacts with SCRIB (via phosphorylated PDZ-binding motif), EZR, SNX27, SLC9A3R1 and SLC9A3R2. Interacts with CTNNB1; the interaction is enhanced upon Wnt stimulation. Interacts with MYH10. Interacts with CCAR2.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CSNK1EP496743EBI-307531,EBI-749343
GTF2E2P290842EBI-307531,EBI-2853321
SCRIBQ141608EBI-307531,EBI-357345

Protein-protein interaction databases

BioGridi110333. 48 interactors.
DIPiDIP-27599N.
IntActiP23508. 83 interactors.
MINTiMINT-1161194.
STRINGi9606.ENSP00000386227.

Structurei

3D structure databases

ProteinModelPortaliP23508.
SMRiP23508.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi766 – 782Nuclear localization signal1 PublicationAdd BLAST17
Motifi826 – 829PDZ-binding4

Sequence similaritiesi

Belongs to the MCC family.Curated

Phylogenomic databases

eggNOGiENOG410IESN. Eukaryota.
ENOG410XQHM. LUCA.
GeneTreeiENSGT00530000063974.
HOGENOMiHOG000111967.
HOVERGENiHBG004762.
InParanoidiP23508.
OMAiPGKECAD.
OrthoDBiEOG091G0GQZ.
PhylomeDBiP23508.
TreeFamiTF333056.

Family and domain databases

InterProiIPR019536. USH1C-bd_PDZ_domain.
[Graphical view]
PfamiPF10506. MCC-bdg_PDZ. 2 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P23508-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MNSGVAMKYG NDSSAELSEL HSAALASLKG DIVELNKRLQ QTERERDLLE
60 70 80 90 100
KKLAKAQCEQ SHLMREHEDV QERTTLRYEE RITELHSVIA ELNKKIDRLQ
110 120 130 140 150
GTTIREEDEY SELRSELSQS QHEVNEDSRS MDQDQTSVSI PENQSTMVTA
160 170 180 190 200
DMDNCSDLNS ELQRVLTGLE NVVCGRKKSS CSLSVAEVDK HIEQLTTASE
210 220 230 240 250
HCDLAIKTVE EIEGVLGRDL YPNLAEERSR WEKELAGLRE ENESLTAMLC
260 270 280 290 300
SKEEELNRTK ATMNAIREER DRLRRRVREL QTRLQSVQAT GPSSPGRLTS
310 320 330 340 350
TNRPINPSTG ELSTSSSSND IPIAKIAERV KLSKTRSESS SSDRPVLGSE
360 370 380 390 400
ISSIGVSSSV AEHLAHSLQD CSNIQEIFQT LYSHGSAISE SKIREFEVET
410 420 430 440 450
ERLNSRIEHL KSQNDLLTIT LEECKSNAER MSMLVGKYES NATALRLALQ
460 470 480 490 500
YSEQCIEAYE LLLALAESEQ SLILGQFRAA GVGSSPGDQS GDENITQMLK
510 520 530 540 550
RAHDCRKTAE NAAKALLMKL DGSCGGAFAV AGCSVQPWES LSSNSHTSTT
560 570 580 590 600
SSTASSCDTE FTKEDEQRLK DYIQQLKNDR AAVKLTMLEL ESIHIDPLSY
610 620 630 640 650
DVKPRGDSQR LDLENAVLMQ ELMAMKEEMA ELKAQLYLLE KEKKALELKL
660 670 680 690 700
STREAQEQAY LVHIEHLKSE VEEQKEQRMR SLSSTSSGSK DKPGKECADA
710 720 730 740 750
ASPALSLAEL RTTCSENELA AEFTNAIRRE KKLKARVQEL VSALERLTKS
760 770 780 790 800
SEIRHQQSAE FVNDLKRANS NLVAAYEKAK KKHQNKLKKL ESQMMAMVER
810 820
HETQVRMLKQ RIALLEEENS RPHTNETSL
Length:829
Mass (Da):93,027
Last modified:January 11, 2011 - v2
Checksum:iC90611B2E91A7F60
GO
Isoform 2 (identifier: P23508-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-19: MNSGVAMKYGNDSSAELSE → MMAAAAAAAA...GGSYLELANT

Show »
Length:1,019
Mass (Da):113,279
Checksum:i09C330B8B43832F1
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti353S → G in BAC87521 (PubMed:14702039).Curated1
Isoform 2 (identifier: P23508-2)
Sequence conflicti25S → GSSSG in BAC87521 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_050905190K → R.3 PublicationsCorresponds to variant rs6594681dbSNPEnsembl.1
Natural variantiVAR_005141267R → L in a colorectal cancer sample. 1 Publication1
Natural variantiVAR_005142486P → L in a colorectal cancer sample. 1 PublicationCorresponds to variant rs35269015dbSNPEnsembl.1
Natural variantiVAR_005143490S → L in a colorectal cancer sample. 1 PublicationCorresponds to variant rs760495893dbSNPEnsembl.1
Natural variantiVAR_005144506R → Q in colorectal cancer samples; somatic mutation; decreased binding to CCAR2; significant decrease in its ability to induce the relocalization of CCAR2 to the cytoplasm; loss of its ability to repress the beta-catenin pathway; loss of its ability to induce the SIRT1-mediated deacetylation of beta-catenin. 3 PublicationsCorresponds to variant rs121917732dbSNPEnsembl.1
Natural variantiVAR_005145698A → V in colorectal cancer samples; somatic mutation. 2 PublicationsCorresponds to variant rs121917731dbSNPEnsembl.1
Natural variantiVAR_033753751S → C.Corresponds to variant rs17313892dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0376601 – 19MNSGV…AELSE → MMAAAAAAAAGSSSSGGGGG GSGSSSSSSDTSSTGEEERM RRLFQTCDGDGDGYISRNDL LMVCRQLNMEESVAEIMNQL GADENGKISFQDFTRCRMQL VREIRKEEVDLSAKSDNSCT KKLRDRIASWPTSSDNSLGA LSAARESWEYDSGARDLQSP DVQSQSALQKLLEYGGSSLH QQAALHKLLTQSPHIGNSVG GSYLELANT in isoform 2. 1 PublicationAdd BLAST19

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS4111.1. [P23508-1]
CCDS43351.1. [P23508-2]
PIRiA38434. A33166.
RefSeqiNP_001078846.1. NM_001085377.1.
NP_002378.1. NM_002387.2.
UniGeneiHs.593171.

Genome annotation databases

EnsembliENST00000302475; ENSP00000305617; ENSG00000171444. [P23508-1]
ENST00000408903; ENSP00000386227; ENSG00000171444. [P23508-2]
GeneIDi4163.
KEGGihsa:4163.
UCSCiuc003kqj.5. human. [P23508-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS4111.1. [P23508-1]
CCDS43351.1. [P23508-2]
PIRiA38434. A33166.
RefSeqiNP_001078846.1. NM_001085377.1.
NP_002378.1. NM_002387.2.
UniGeneiHs.593171.

3D structure databases

ProteinModelPortaliP23508.
SMRiP23508.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110333. 48 interactors.
DIPiDIP-27599N.
IntActiP23508. 83 interactors.
MINTiMINT-1161194.
STRINGi9606.ENSP00000386227.

PTM databases

iPTMnetiP23508.
PhosphoSitePlusiP23508.

Polymorphism and mutation databases

BioMutaiMCC.
DMDMi317373352.

Proteomic databases

EPDiP23508.
MaxQBiP23508.
PaxDbiP23508.
PeptideAtlasiP23508.
PRIDEiP23508.

Protocols and materials databases

DNASUi4163.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000302475; ENSP00000305617; ENSG00000171444. [P23508-1]
ENST00000408903; ENSP00000386227; ENSG00000171444. [P23508-2]
GeneIDi4163.
KEGGihsa:4163.
UCSCiuc003kqj.5. human. [P23508-1]

Organism-specific databases

CTDi4163.
DisGeNETi4163.
GeneCardsiMCC.
HGNCiHGNC:6935. MCC.
HPAiHPA037390.
HPA037391.
MalaCardsiMCC.
MIMi159350. gene.
neXtProtiNX_P23508.
OpenTargetsiENSG00000171444.
PharmGKBiPA30679.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IESN. Eukaryota.
ENOG410XQHM. LUCA.
GeneTreeiENSGT00530000063974.
HOGENOMiHOG000111967.
HOVERGENiHBG004762.
InParanoidiP23508.
OMAiPGKECAD.
OrthoDBiEOG091G0GQZ.
PhylomeDBiP23508.
TreeFamiTF333056.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000171444-MONOMER.
SignaLinkiP23508.

Miscellaneous databases

ChiTaRSiMCC. human.
GeneWikiiMCC_(gene).
GenomeRNAii4163.
PROiP23508.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000171444.
CleanExiHS_MCC.
ExpressionAtlasiP23508. baseline and differential.
GenevisibleiP23508. HS.

Family and domain databases

InterProiIPR019536. USH1C-bd_PDZ_domain.
[Graphical view]
PfamiPF10506. MCC-bdg_PDZ. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCRCM_HUMAN
AccessioniPrimary (citable) accession number: P23508
Secondary accession number(s): D3DT05, Q6ZR04
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: January 11, 2011
Last modified: November 30, 2016
This is version 144 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.