P50539 (MXI1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Max-interacting protein 1
Short name=Max interactor 1

Alternative name(s):
Class C basic helix-loop-helix protein 11
Short name=bHLHc11

Gene names

Name:	MXI1
Synonyms:	BHLHC11

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	228 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcriptional repressor. MXI1 binds with MAX to form a sequence-specific DNA-binding protein complex which recognizes the core sequence 5'-CAC[GA]TG-3'. MXI1 thus antagonizes MYC transcriptional activity by competing for MAX.
Subunit structure	Interacts with SMC3 By similarity. Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a heterodimer with MAX. Interacts with RNF17 By similarity.
Subcellular location	Nucleus.
Tissue specificity	High levels found in the brain, heart and lung while lower levels are seen in the liver, kidney and skeletal muscle.
Involvement in disease	Defects in MXI1 may be a cause of susceptibility to prostate cancer (PC) [MIM:176807]. It is a malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma.
Sequence similarities	Contains 1 basic helix-loop-helix (bHLH) domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Proto-oncogene
Ligand	DNA-binding
Molecular function	Repressor
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cytoplasmic sequestering of transcription factor Traceable author statement. Source: ProtInc negative regulation of cell proliferation Traceable author statement. Source: ProtInc regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Traceable author statement. Source: ProtInc
Molecular function	DNA binding Traceable author statement. Source: ProtInc transcription corepressor activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P50539-1)

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: P50539-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: Missing.

Isoform 3 (identifier: P50539-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-25: MERVKMINVQRLLEAAEFLERRERE → MGKRGRPRKE...LEQIEKENKK

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 228	228	Max-interacting protein 1		PRO_0000127285
Regions
	Domain	81 – 120	40	Helix-loop-helix motif
	DNA binding	69 – 80	12	Basic motif
Natural variations
	Alternative sequence	1 – 36	36	Missing in isoform 2.		VSP_012825
	Alternative sequence	1 – 25	25	MERVK…RRERE → MGKRGRPRKEARCEGAGLAP AAPPAVPPAVAAPQPPALPE DPAGAKPRCPFSDIFNTSEN SMEKHINTFLQNVQILLEAA SYLEQIEKENKK in isoform 3.		VSP_037943
	Natural variant	152	1	E → A in prostate cancer. Ref.10		VAR_004499
Experimental info
	Sequence conflict	61	1	S → T in AAA75508. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 17, 2006. Version 2. Checksum: 82F83F499B907DD3	FASTA	228	26,062
	10 20 30 40 50 60 MERVKMINVQ RLLEAAEFLE RRERECEHGY ASSFPSMPSP RLQHSKPPRR LSRAQKHSSG 70 80 90 100 110 120 SSNTSTANRS THNELEKNRR AHLRLCLERL KVLIPLGPDC TRHTTLGLLN KAKAHIKKLE 130 140 150 160 170 180 EAERKSQHQL ENLEREQRFL KWRLEQLQGP QEMERIRMDS IGSTISSDRS DSEREEIEVD 190 200 210 220 VESTEFSHGE VDNISTTSIS DIDDHSSLPS IGSDEGYSSA SVKLSFTS
	Isoform 2 [UniParc]. Checksum: 3D8B586EEA033591	FASTA	192	21,767
	10 20 30 40 50 60 MPSPRLQHSK PPRRLSRAQK HSSGSSNTST ANRSTHNELE KNRRAHLRLC LERLKVLIPL 70 80 90 100 110 120 GPDCTRHTTL GLLNKAKAHI KKLEEAERKS QHQLENLERE QRFLKWRLEQ LQGPQEMERI 130 140 150 160 170 180 RMDSIGSTIS SDRSDSEREE IEVDVESTEF SHGEVDNIST TSISDIDDHS SLPSIGSDEG 190 YSSASVKLSF TS
	Isoform 3 [UniParc]. Checksum: CD3E9228C9DB7660	FASTA	295	32,820
	10 20 30 40 50 60 MGKRGRPRKE ARCEGAGLAP AAPPAVPPAV AAPQPPALPE DPAGAKPRCP FSDIFNTSEN 70 80 90 100 110 120 SMEKHINTFL QNVQILLEAA SYLEQIEKEN KKCEHGYASS FPSMPSPRLQ HSKPPRRLSR 130 140 150 160 170 180 AQKHSSGSSN TSTANRSTHN ELEKNRRAHL RLCLERLKVL IPLGPDCTRH TTLGLLNKAK 190 200 210 220 230 240 AHIKKLEEAE RKSQHQLENL EREQRFLKWR LEQLQGPQEM ERIRMDSIGS TISSDRSDSE 250 260 270 280 290 REEIEVDVES TEFSHGEVDN ISTTSISDID DHSSLPSIGS DEGYSSASVK LSFTS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mxi1, a protein that specifically interacts with Max to bind Myc-Max recognition sites." Zervos A.S., Gyuris J., Brent R. Cell 72:223-232(1993) [PubMed: 8425219] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	Erratum Zervos A.S., Gyuris J., Brent R. Cell 79:388-388(1994)
[3]	"Genomic organization of human MXI1, a putative tumor suppressor gene." Wechsler D.S., Shelly C.A., Dang C.V. Genomics 32:466-470(1996) [PubMed: 8838813] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Expression, regulation and polymorphism of the mxi1 genes." Shimizu E., Shirasawa H., Kodama K., Sato T., Shimizu B. Gene 176:45-48(1996) [PubMed: 8918230] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[5]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	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].
[8]	"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] (ISOFORM 3). Tissue: Hippocampus.
[9]	"Redefinition of the coding sequence of the MXI1 gene and identification of a polymorphic repeat in the 3' non-coding region that allows the detection of loss of heterozygosity of chromosome 10q25 in glioblastomas." Albarosa R., Didonato S., Finocchiaro G. Hum. Genet. 95:709-711(1995) [PubMed: 7789959] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 216-228.
[10]	"Mutation of the MXI1 gene in prostate cancer." Eagle L.R., Yin X., Brothman A.R., Williams B.J., Atkin N.B., Prochownik E.V. Nat. Genet. 9:249-255(1995) [PubMed: 7773287] [Abstract] Cited for: VARIANT PROSTATE CANCER ALA-152.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	L07648 mRNA. Translation: AAA75508.1. U32515 , U32512, U32513, U32514 Genomic DNA. Translation: AAC50446.1. D63940 mRNA. Translation: BAA09972.1. CR536576 mRNA. Translation: CAG38813.1. AL360182 Genomic DNA. Translation: CAI15475.1. AL360182 Genomic DNA. Translation: CAI15476.1. AL360182 Genomic DNA. Translation: CAI15479.1. CH471066 Genomic DNA. Translation: EAW49567.1. CH471066 Genomic DNA. Translation: EAW49568.1. CH471066 Genomic DNA. Translation: EAW49569.1. CH471066 Genomic DNA. Translation: EAW49570.1. BC035128 mRNA. Translation: AAH35128.2. S78470 Genomic DNA. Translation: AAD14282.1.
IPI	IPI00107617. IPI00301031. IPI00552166.
PIR	A45182.
RefSeq	NP_001008541.1. NM_001008541.1. NP_005953.4. NM_005962.4. NP_569157.2. NM_130439.3.
UniGene	Hs.602078. Hs.676603.
3D structure databases
ProteinModelPortal	P50539.
SMR	P50539. Positions 68-144.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-205N.
STRING	P50539.
Polymorphism databases
DMDM	116242666.
Proteomic databases
PRIDE	P50539.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000239007; ENSP00000239007; ENSG00000119950.
GeneID	4601.
KEGG	hsa:4601.
NMPDR	fig|9606.3.peg.4635.
UCSC	uc001kyy.1. human. uc001kza.1. human.
Organism-specific databases
CTD	4601.
GeneCards	GC10P111957.
HGNC	HGNC:7534. MXI1.
HPA	HPA035319.
MIM	176807. phenotype. 600020. gene.
neXtProt	NX_P50539.
Orphanet	1331. Familial prostate cancer.
PharmGKB	PA31335.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG15426.
GeneTree	ENSGT00510000046360.
HOVERGEN	HBG006314.
OMA	FNTTENT.
Gene expression databases
ArrayExpress	P50539.
Bgee	P50539.
CleanEx	HS_MXI1.
Genevestigator	P50539.
GermOnline	ENSG00000119950. Homo sapiens.
Family and domain databases
InterPro	IPR011598. HLH_DNA-bd. [Graphical view]
Gene3D	G3DSA:4.10.280.10. HLH_DNA_bd. 1 hit.
KO	K09114.
Pfam	PF00010. HLH. 1 hit. [Graphical view]
SMART	SM00353. HLH. 1 hit. [Graphical view]
SUPFAM	SSF47459. HLH_basic. 1 hit.
PROSITE	PS50888. HLH. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	17692.
SOURCE	Search...

Entry information

Entry name

MXI1_HUMAN

Accession

Primary (citable) accession number: P50539
Secondary accession number(s): B1ANN7 , D3DR25, D3DRA9, Q15887, Q6FHW2

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 17, 2006
Last modified:	January 25, 2012
This is version 111 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.