Q9Y2G1 (MRF_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Myelin regulatory factor
EC=3.4.-.-

Alternative name(s):
Myelin gene regulatory factor

Cleaved into the following 2 chains:

1. Myelin regulatory factor, N-terminal
2. Myelin regulatory factor, C-terminal

Gene names

Name:	MYRF
Synonyms:	C11orf9, KIAA0954, MRF

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1151 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Myelin regulatory factor: Consitutes a precursor of the transcription factor. Mediates the autocatalytic cleavage that releases the Myelin regulatory factor, N-terminal component that specifically activates transcription of central nervous system (CNS) myelin genes (Ref.7). Myelin regulatory factor, C-terminal: Membrane-bound part that has no transcription factor activity and remains attached to the endoplasmic reticulum membrane following cleavage (Ref.7). Myelin regulatory factor, N-terminal: Transcription factor that specifically activates expression of myelin genes such as MBP, MOG, MAG and PLP1 during oligodendrocyte (OL) maturation, thereby playing a central role in oligodendrocyte maturation and CNS myelination. Specifically recognizes and binds DNA sequence 5'-CTGGYAC-3' in the regulatory regions of myelin-specific genes and directly activates their expression. Not only required during oligodendrocyte differentiation but is also required on an ongoing basis for the maintenance of expression of myelin genes and for the maintenance of a mature, viable oligodendrocyte phenotype (Ref.7).
Subunit structure	Homotrimer. Ref.7
Subcellular location	Myelin regulatory factor: Endoplasmic reticulum membrane; Single-pass membrane protein Ref.7. Myelin regulatory factor, N-terminal: Nucleus. Cytoplasm. Note: Translocates from the cytoplasm to the nucleus upon autocatalytic cleavage. Ref.7 Myelin regulatory factor, C-terminal: Endoplasmic reticulum membrane; Single-pass membrane protein Ref.7.
Tissue specificity	Expressed in lung, ARPE-19 cell line, brainstem, uterus and, to a lesser extent, in basal ganglion and liver. Weakly expressed in cerebellum and retina. Ref.1
Domain	Myelin regulatory factor, N-terminal: The nuclear localization signals mediate translocation to the nucleus (Ref.7). Myelin regulatory factor: The peptidase S74 domain, also named Intramolecular Chaperone Auto-processed (ICA) domain or Intramolecuar Chaperone Domain (ICD), has protease activity and mediates autocatalytic processing of the protein to generate the Myelin regulatory factor, N-terminal active transcription factor and the Myelin regulatory factor, C-terminal components (Ref.7).
Post-translational modification	Myelin regulatory factor, C-terminal: Glycosylated. Ref.7 Myelin regulatory factor: Follows autocatalytic cleavage via the peptidase S74 domain. Autoprocessing is apparently constitutive and is essential for transcriptional activity (Ref.7).
Sequence similarities	Belongs to the MRF family. Contains 1 NDT80 DNA-binding domain. Contains 1 peptidase S74 domain.
Sequence caution	The sequence BAA76798.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Differentiation Transcription Transcription regulation
Cellular component	Cytoplasm Endoplasmic reticulum Membrane Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil Transmembrane Transmembrane helix
Ligand	DNA-binding
Molecular function	Activator Hydrolase Protease
PTM	Acetylation Autocatalytic cleavage Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	central nervous system myelin maintenance Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of myelination Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription, DNA-dependent Inferred from sequence or structural similarity. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW nucleus Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9Y2G1-1)

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: Q9Y2G1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-15: MEVVDETEALQRFFE → MHWLPA
     803-829: SFAVSTSCLLALLRPQPPGGSEALCPW → R
     1006-1010: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1151	1151	Myelin regulatory factor		PRO_0000318919
	Chain	1 – 586	586	Myelin regulatory factor, N-terminal		PRO_0000424310
	Chain	587 – 1151	565	Myelin regulatory factor, C-terminal		PRO_0000424311
Regions
	Topological domain	1 – 768	768	Cytoplasmic Potential
	Transmembrane	769 – 789	21	Helical; Potential
	Topological domain	790 – 1151	362	Lumenal Potential
	Domain	587 – 696	110	Peptidase S74
	DNA binding	250 – 541	292	NDT80
	Coiled coil	680 – 711	32	Potential
	Motif	254 – 257	4	Nuclear localization signal
	Motif	491 – 494	4	Nuclear localization signal
	Compositional bias	77 – 330	254	Pro-rich
Sites
	Site	586 – 587	2	Cleavage; by autocatalysis
Amino acid modifications
	Modified residue	123	1	N6-acetyllysine Ref.6
	Glycosylation	919	1	N-linked (GlcNAc...) Potential
	Glycosylation	1043	1	N-linked (GlcNAc...) Potential
	Glycosylation	1065	1	N-linked (GlcNAc...) Potential
	Glycosylation	1129	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 15	15	MEVVD…QRFFE → MHWLPA in isoform 2.		VSP_031300
	Alternative sequence	803 – 829	27	SFAVS…ALCPW → R in isoform 2.		VSP_031301
	Alternative sequence	1006 – 1010	5	Missing in isoform 2.		VSP_031302
	Natural variant	723	1	A → T. Corresponds to variant rs34038946 [ dbSNP | Ensembl ].		VAR_038907
Experimental info
	Mutagenesis	587	1	S → A: Prevents autocatalytic cleavage and generation of Myelin regulatory factor, N-terminal part. Ref.7
	Mutagenesis	588	1	D → A: Reduces autocatalytic cleavage and generation of Myelin regulatory factor, N-terminal part. Ref.7
	Mutagenesis	592	1	K → A: Prevents autocatalytic cleavage and generation of Myelin regulatory factor, N-terminal part. Ref.7
	Mutagenesis	608	1	S → A: Does not affect autocatalytic cleavage. Ref.7
	Mutagenesis	635	1	G → A: Reduces autocatalytic cleavage and generation of Myelin regulatory factor, N-terminal part. Ref.7
	Mutagenesis	688	1	L → A: Does not affect autocatalytic cleavage. Ref.7
	Mutagenesis	699	1	L → A: Prevents autocatalytic cleavage and generation of Myelin regulatory factor, N-terminal part. Ref.7
	Sequence conflict	478 – 484	7	RLHFSET → GGCIQRD in AAB92668. Ref.5
	Sequence conflict	606	1	R → K in AAB92668. Ref.5
	Sequence conflict	657 – 658	2	FA → LP in AAB92668. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 26, 2008. Version 3. Checksum: 9875DE9D72B6C50C	FASTA	1,151	124,397
	10 20 30 40 50 60 MEVVDETEAL QRFFEGHDIN GALEPSNIDT SILEEYISKE DASDLCFPDI SAPASSASYS 70 80 90 100 110 120 HGQPAMPGSS GVHHLSPPGG GPSPGRHGPL PPPGYGTPLN CNNNNGMGAA PKPFPGGTGP 130 140 150 160 170 180 PIKAEPKAPY APGTLPDSPP DSGSEAYSPQ QVNEPHLLRT ITPETLCHVG VPSRLEHPPP 190 200 210 220 230 240 PPAHLPGPPP PPPPPPHYPV LQRDLYMKAE PPIPHYAAMG QGLVPTDLHH TQQSQMLHQL 250 260 270 280 290 300 LQQHGAELPT HPSKKRKHSE SPPSTLNAQM LNGMIKQEPG TVTALPLHPT RAPSPPWPPQ 310 320 330 340 350 360 GPLSPGPGSL PLSIARVQTP PWHPPGAPSP GLLQDSDSLS GSYLDPNYQS IKWQPHQQNK 370 380 390 400 410 420 WATLYDANYK ELPMLTYRVD ADKGFNFSVG DDAFVCQKKN HFQVTVYIGM LGEPKYVKTP 430 440 450 460 470 480 EGLKPLDCFY LKLHGVKLEA LNQSINIEQS QSDRSKRPFN PVTVNLPPEQ VTKVTVGRLH 490 500 510 520 530 540 FSETTANNMR KKGKPNPDQR YFMLVVALQA HAQNQNYTLA AQISERIIVR ASNPGQFESD 550 560 570 580 590 600 SDVLWQRAQV PDTVFHHGRV GINTDRPDEA LVVHGNVKVM GSLMHPSDLR AKEHVQEVDT 610 620 630 640 650 660 TEQLKRISRM RLVHYRYKPE FAASAGIEAT APETGVIAQE VKEILPEAVK DTGDMVFANG 670 680 690 700 710 720 KTIENFLVVN KERIFMENVG AVKELCKLTD NLETRIDELE RWSHKLAKLR RLDSLKSTGS 730 740 750 760 770 780 SGAFSHAGSQ FSRAGSVPHK KRPPKVASKS SSVVPDQACI SQRFLQGTII ALVVVMAFSV 790 800 810 820 830 840 VSMSTLYVLS LRTEEDLVDT DGSFAVSTSC LLALLRPQPP GGSEALCPWS SQSFGTTQLR 850 860 870 880 890 900 QSPLTTGLPG IQPSLLLVTT SLTSSAPGSA VRTLDMCSSH PCPVICCSSP TTNPTTGPSL 910 920 930 940 950 960 GPSFNPGHVL SPSPSPSTNR SGPSQMALLP VTNIRAKSWG LSVNGIGHSK HHKSLEPLAS 970 980 990 1000 1010 1020 PAVPFPGGQG KAKNSPSLGF HGRARRGALQ SSVGPAEPTW AQGQSASLLA EPVPSLTSIQ 1030 1040 1050 1060 1070 1080 VLENSMSITS QYCAPGDACR PGNFTYHIPV SSGTPLHLSL TLQMNSSSPV SVVLCSLRSK 1090 1100 1110 1120 1130 1140 EEPCEEGSLP QSLHTHQDTQ GTSHRWPITI LSFREFTYHF RVALLGQANC SSEALAQPAT 1150 DYHFHFYRLC D
	Isoform 2 [UniParc]. Checksum: 5B9CAAD3EC8C8B03	FASTA	1,111	120,225
	10 20 30 40 50 60 MHWLPAGHDI NGALEPSNID TSILEEYISK EDASDLCFPD ISAPASSASY SHGQPAMPGS 70 80 90 100 110 120 SGVHHLSPPG GGPSPGRHGP LPPPGYGTPL NCNNNNGMGA APKPFPGGTG PPIKAEPKAP 130 140 150 160 170 180 YAPGTLPDSP PDSGSEAYSP QQVNEPHLLR TITPETLCHV GVPSRLEHPP PPPAHLPGPP 190 200 210 220 230 240 PPPPPPPHYP VLQRDLYMKA EPPIPHYAAM GQGLVPTDLH HTQQSQMLHQ LLQQHGAELP 250 260 270 280 290 300 THPSKKRKHS ESPPSTLNAQ MLNGMIKQEP GTVTALPLHP TRAPSPPWPP QGPLSPGPGS 310 320 330 340 350 360 LPLSIARVQT PPWHPPGAPS PGLLQDSDSL SGSYLDPNYQ SIKWQPHQQN KWATLYDANY 370 380 390 400 410 420 KELPMLTYRV DADKGFNFSV GDDAFVCQKK NHFQVTVYIG MLGEPKYVKT PEGLKPLDCF 430 440 450 460 470 480 YLKLHGVKLE ALNQSINIEQ SQSDRSKRPF NPVTVNLPPE QVTKVTVGRL HFSETTANNM 490 500 510 520 530 540 RKKGKPNPDQ RYFMLVVALQ AHAQNQNYTL AAQISERIIV RASNPGQFES DSDVLWQRAQ 550 560 570 580 590 600 VPDTVFHHGR VGINTDRPDE ALVVHGNVKV MGSLMHPSDL RAKEHVQEVD TTEQLKRISR 610 620 630 640 650 660 MRLVHYRYKP EFAASAGIEA TAPETGVIAQ EVKEILPEAV KDTGDMVFAN GKTIENFLVV 670 680 690 700 710 720 NKERIFMENV GAVKELCKLT DNLETRIDEL ERWSHKLAKL RRLDSLKSTG SSGAFSHAGS 730 740 750 760 770 780 QFSRAGSVPH KKRPPKVASK SSSVVPDQAC ISQRFLQGTI IALVVVMAFS VVSMSTLYVL 790 800 810 820 830 840 SLRTEEDLVD TDGRSSQSFG TTQLRQSPLT TGLPGIQPSL LLVTTSLTSS APGSAVRTLD 850 860 870 880 890 900 MCSSHPCPVI CCSSPTTNPT TGPSLGPSFN PGHVLSPSPS PSTNRSGPSQ MALLPVTNIR 910 920 930 940 950 960 AKSWGLSVNG IGHSKHHKSL EPLASPAVPF PGGQGKAKNS PSLGFHGRAR RGALQSSVGP 970 980 990 1000 1010 1020 AEPTWAQGQS EPVPSLTSIQ VLENSMSITS QYCAPGDACR PGNFTYHIPV SSGTPLHLSL 1030 1040 1050 1060 1070 1080 TLQMNSSSPV SVVLCSLRSK EEPCEEGSLP QSLHTHQDTQ GTSHRWPITI LSFREFTYHF 1090 1100 1110 RVALLGQANC SSEALAQPAT DYHFHFYRLC D

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning and genomic structure of a novel gene (C11orf9) localized to chromosome 11q12-->q13.1 which encodes a highly conserved, potential membrane-associated protein." Stoehr H., Marquardt A., White K., Weber B.H.F. Cytogenet. Cell Genet. 88:211-216(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY.
[2]	"Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 6:63-70(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[3]	"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones." Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T. DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SEQUENCE REVISION.
[4]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"Transcript mapping of the human chromosome 11q12-q13.1 gene-rich region identifies several newly described conserved genes." Cooper P.R., Nowak N.J., Higgins M.J., Church D.M., Shows T.B. Genomics 49:419-429(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 476-660.
[6]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-123, MASS SPECTROMETRY.
[7]	"A bacteriophage tailspike domain promotes self-cleavage of a human membrane-bound transcription factor, the myelin regulatory factor MYRF." Li Z., Park Y., Marcotte E.M. PLoS Biol. 11:E1001624-E1001624(2013) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, SUBUNIT, PROTEOLYTIC PROCESSING, GLYCOSYLATION, AUTOCATALYTIC CLEAVAGE, TOPOLOGY, MUTAGENESIS OF SER-587; ASP-588; LYS-592; SER-608; GLY-635; LEU-688 AND LEU-699.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF086762 mRNA. Translation: AAF28400.1. AB023171 mRNA. Translation: BAA76798.2. Different initiation. CH471076 Genomic DNA. Translation: EAW73968.1. AF038536 mRNA. Translation: AAB92668.1.
IPI	IPI00179851. IPI00180971.
RefSeq	NP_001120864.1. NM_001127392.1. NP_037411.1. NM_013279.2.
UniGene	Hs.473109.
3D structure databases
ProteinModelPortal	Q9Y2G1.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000278836.
PTM databases
PhosphoSite	Q9Y2G1.
Polymorphism databases
DMDM	182637560.
Proteomic databases
PaxDb	Q9Y2G1.
PRIDE	Q9Y2G1.
Protocols and materials databases
DNASU	745.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000265460; ENSP00000265460; ENSG00000124920. ENST00000278836; ENSP00000278836; ENSG00000124920.
GeneID	745.
KEGG	hsa:745.
UCSC	uc001nsc.1. human.
Organism-specific databases
CTD	745.
GeneCards	GC11P061521.
HGNC	HGNC:1181. MYRF.
HPA	HPA018310.
MIM	608329. gene.
neXtProt	NX_Q9Y2G1.
PharmGKB	PA25500.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG253930.
HOGENOM	HOG000111718.
InParanoid	Q9Y2G1.
OMA	RAKSWGL.
OrthoDB	EOG77M8N4.
Gene expression databases
ArrayExpress	Q9Y2G1.
Bgee	Q9Y2G1.
CleanEx	HS_C11orf9.
Genevestigator	Q9Y2G1.
Family and domain databases
Gene3D	2.60.40.1390. 1 hit.
InterPro	IPR026933. MRF. IPR026932. MRF_C1. IPR025719. MRF_C2. IPR024061. NDT80_DNA-bd_dom. IPR008967. p53-like_TF_DNA-bd. [Graphical view]
PANTHER	PTHR13029:SF9. PTHR13029:SF9. 1 hit.
Pfam	PF13887. MRF_C1. 1 hit. PF13888. MRF_C2. 1 hit. PF05224. NDT80_PhoG. 1 hit. [Graphical view]
SUPFAM	SSF49417. SSF49417. 1 hit.
PROSITE	PS51688. ICA. 1 hit. PS51517. NDT80. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	C11orf9. human.
GeneWiki	Myelin_gene_Regulatory_Factor.
GenomeRNAi	745.
NextBio	3016.
SOURCE	Search...

Entry information

Entry name

MRF_HUMAN

Accession

Primary (citable) accession number: Q9Y2G1
Secondary accession number(s): O43582, Q9P1Q6

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 26, 2008
Last sequence update:	February 26, 2008
Last modified:	November 13, 2013
This is version 83 of the entry and version 3 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.