Q96LT7 (CI072_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein C9orf72

Gene names

Name:

C9orf72

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 › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	481 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Subcellular location	Cytoplasm. Nucleus. Note: Detected in the cytoplasm of neurons from post mortem brain tissue (Ref.1). Detected in the nucleus in fibroblasts (Ref.6). Ref.1 Ref.6
Tissue specificity	Both isoforms are widely expressed, including kidney, lung, liver, heart, testis and several brain regions, such as cerebellum. Also expressed in the frontal cortex and in lymphoblasts (at protein level). Ref.1 Ref.6
Involvement in disease	Frontotemporal dementia and/or amyotrophic lateral sclerosis (FTDALS) [MIM:105550]: An autosomal dominant neurodegenerative disorder characterized by adult onset of frontotemporal dementia and/or amyotrophic lateral sclerosis in an affected individual. There is high intrafamilial variation. Frontotemporal dementia is characterized by frontal and temporal lobe atrophy associated with neuronal loss, gliosis, and dementia. Patients exhibit progressive changes in social, behavioral, and/or language function. Amyotrophic lateral sclerosis is characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis. Note: The disease is caused by mutations affecting the gene represented in this entry. Caused by a large expansion of a GGGGCC hexanucleotide within the first C9orf72 intron located between the first and the second non-coding exons. The expansion leads to the loss of transcription of one of the two transcripts encoding isoform 1 and to the formation of nuclear RNA foci. Ref.1 Ref.6 Ref.7

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Amyotrophic lateral sclerosis Neurodegeneration
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell death Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q96LT7-1)

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.

Note: Encoded by 2 transcripts differing in the 5' non-coding region.

Isoform 2 (identifier: Q96LT7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     222-222: N → K
     223-481: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 481	481	Protein C9orf72		PRO_0000089711
Natural variations
	Alternative sequence	222	1	N → K in isoform 2.		VSP_014745
	Alternative sequence	223 – 481	259	Missing in isoform 2.		VSP_014746
	Natural variant	207	1	N → S. Corresponds to variant rs17769294 [ dbSNP | Ensembl ].		VAR_050827

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 19, 2005. Version 2. Checksum: B36C5576B3D268CE	FASTA	481	54,328
	10 20 30 40 50 60 MSTLCPPPSP AVAKTEIALS GKSPLLAATF AYWDNILGPR VRHIWAPKTE QVLLSDGEIT 70 80 90 100 110 120 FLANHTLNGE ILRNAESGAI DVKFFVLSEK GVIIVSLIFD GNWNGDRSTY GLSIILPQTE 130 140 150 160 170 180 LSFYLPLHRV CVDRLTHIIR KGRIWMHKER QENVQKIILE GTERMEDQGQ SIIPMLTGEV 190 200 210 220 230 240 IPVMELLSSM KSHSVPEEID IADTVLNDDD IGDSCHEGFL LNAISSHLQT CGCSVVVGSS 250 260 270 280 290 300 AEKVNKIVRT LCLFLTPAER KCSRLCEAES SFKYESGLFV QGLLKDSTGS FVLPFRQVMY 310 320 330 340 350 360 APYPTTHIDV DVNTVKQMPP CHEHIYNQRR YMRSELTAFW RATSEEDMAQ DTIIYTDESF 370 380 390 400 410 420 TPDLNIFQDV LHRDTLVKAF LDQVFQLKPG LSLRSTFLAQ FLLVLHRKAL TLIKYIEDDT 430 440 450 460 470 480 QKGKKPFKSL RNLKIDLDLT AEGDLNIIMA LAEKIKPGLH SFIFGRPFYT SVQERDVLMT F
	Isoform 2 [UniParc]. Checksum: 068FE35DB48FE903	FASTA	222	24,759
	10 20 30 40 50 60 MSTLCPPPSP AVAKTEIALS GKSPLLAATF AYWDNILGPR VRHIWAPKTE QVLLSDGEIT 70 80 90 100 110 120 FLANHTLNGE ILRNAESGAI DVKFFVLSEK GVIIVSLIFD GNWNGDRSTY GLSIILPQTE 130 140 150 160 170 180 LSFYLPLHRV CVDRLTHIIR KGRIWMHKER QENVQKIILE GTERMEDQGQ SIIPMLTGEV 190 200 210 220 IPVMELLSSM KSHSVPEEID IADTVLNDDD IGDSCHEGFL LK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Expanded GGGGCC hexanucleotide repeat in noncoding region of C9orf72 causes chromosome 9p-linked FTD and ALS." Dejesus-Hernandez M., Mackenzie I.R., Boeve B.F., Boxer A.L., Baker M., Rutherford N.J., Nicholson A.M., Finch N.A., Flynn H., Adamson J., Kouri N., Wojtas A., Sengdy P., Hsiung G.Y., Karydas A., Seeley W.W., Josephs K.A., Coppola G. , Geschwind D.H., Wszolek Z.K., Feldman H., Knopman D.S., Petersen R.C., Miller B.L., Dickson D.W., Boylan K.B., Graff-Radford N.R., Rademakers R. Neuron 72:245-256(2011) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INVOLVEMENT IN FTDALS, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Frontal cortex.
[2]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 318-418 (ISOFORM 1). Tissue: Brain and Cerebellum.
[3]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Testis.
[6]	"A hexanucleotide repeat expansion in C9orf72 is the cause of chromosome 9p21-linked ALS-FTD." Renton A.E., Majounie E., Waite A., Simon-Sanchez J., Rollinson S., Gibbs J.R., Schymick J.C., Laaksovirta H., van Swieten J.C., Myllykangas L., Kalimo H., Paetau A., Abramzon Y., Remes A.M., Kaganovich A., Scholz S.W., Duckworth J., Ding J. , Harmer D.W., Hernandez D.G., Johnson J.O., Mok K., Ryten M., Trabzuni D., Guerreiro R.J., Orrell R.W., Neal J., Murray A., Pearson J., Jansen I.E., Sondervan D., Seelaar H., Blake D., Young K., Halliwell N., Callister J.B., Toulson G., Richardson A., Gerhard A., Snowden J., Mann D., Neary D., Nalls M.A., Peuralinna T., Jansson L., Isoviita V.M., Kaivorinne A.L., Holtta-Vuori M., Ikonen E., Sulkava R., Benatar M., Wuu J., Chio A., Restagno G., Borghero G., Sabatelli M., Heckerman D., Rogaeva E., Zinman L., Rothstein J.D., Sendtner M., Drepper C., Eichler E.E., Alkan C., Abdullaev Z., Pack S.D., Dutra A., Pak E., Hardy J., Singleton A., Williams N.M., Heutink P., Pickering-Brown S., Morris H.R., Tienari P.J., Traynor B.J. Neuron 72:257-268(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN FTDALS, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[7]	"Analysis of the C9orf72 gene in patients with amyotrophic lateral sclerosis in Spain and different populations worldwide." Garcia-Redondo A., Dols-Icardo O., Rojas-Garcia R., Esteban-Perez J., Cordero-Vazquez P., Munoz-Blanco J.L., Catalina I., Gonzalez-Munoz M., Varona L., Sarasola E., Povedano M., Sevilla T., Guerrero A., Pardo J., de Munain A.L., Marquez-Infante C., de Rivera F.J., Pastor P. , Jerico I., de Arcaya A.A., Mora J.S., Clarimon J., Gonzalo-Martinez J.F., Juarez-Rufian A., Atencia G., Jimenez-Bautista R., Moran Y., Mascias J., Hernandez-Barral M., Kapetanovic S., Garcia-Barcina M., Alcala C., Vela A., Ramirez-Ramos C., Galan L., Perez-Tur J., Quintans B., Sobrido M.J., Fernandez-Torron R., Poza J.J., Gorostidi A., Paradas C., Villoslada P., Larrode P., Capablo J.L., Pascual-Calvet J., Goni M., Morgado Y., Guitart M., Moreno-Laguna S., Rueda A., Martin-Estefania C., Cemillan C., Blesa R., Lleo A. Hum. Mutat. 34:79-82(2013) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN FTDALS.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	JN681271 mRNA. Translation: AET41697.1. AK057806 mRNA. Translation: BAB71583.1. AK291425 mRNA. Translation: BAF84114.1. AL451123 Genomic DNA. Translation: CAI13043.1. AL451123 Genomic DNA. Translation: CAI13044.1. CH471071 Genomic DNA. Translation: EAW58561.1. CH471071 Genomic DNA. Translation: EAW58558.1. CH471071 Genomic DNA. Translation: EAW58560.1. BC068445 mRNA. Translation: AAH68445.1.
IPI	IPI00065258. IPI00375463.
RefSeq	NP_001242983.1. NM_001256054.1. NP_060795.1. NM_018325.3. NP_659442.2. NM_145005.5.
UniGene	Hs.493639.
3D structure databases
ProteinModelPortal	Q96LT7.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q96LT7. 1 interaction.
STRING	9606.ENSP00000369339.
PTM databases
PhosphoSite	Q96LT7.
Polymorphism databases
DMDM	71152412.
Proteomic databases
PaxDb	Q96LT7.
PRIDE	Q96LT7.
Protocols and materials databases
DNASU	203228.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000379995; ENSP00000369331; ENSG00000147894. ENST00000379997; ENSP00000369333; ENSG00000147894. ENST00000380003; ENSP00000369339; ENSG00000147894.
GeneID	203228.
KEGG	hsa:203228.
UCSC	uc003zqq.2. human. uc003zqr.1. human.
Organism-specific databases
CTD	203228.
GeneCards	GC09M027539.
HGNC	HGNC:28337. C9orf72.
HPA	HPA023873.
MIM	105550. phenotype. 614260. gene.
neXtProt	NX_Q96LT7.
Orphanet	803. Amyotrophic lateral sclerosis. 275872. Frontotemporal dementia with motor neuron disease.
PharmGKB	PA134908144.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG40002.
HOGENOM	HOG000231721.
HOVERGEN	HBG060354.
InParanoid	Q96LT7.
OMA	TAFWRAT.
OrthoDB	EOG42V8G6.
Gene expression databases
ArrayExpress	Q96LT7.
Bgee	Q96LT7.
CleanEx	HS_C9orf72.
Genevestigator	Q96LT7.
GermOnline	ENSG00000147894. Homo sapiens.
Family and domain databases
ProtoNet	Search...
Other
GenomeRNAi	203228.
NextBio	90368.
SOURCE	Search...

Entry information

Entry name

CI072_HUMAN

Accession

Primary (citable) accession number: Q96LT7
Secondary accession number(s): A8K5W0 , D3DRK6, G8I0B6, Q6NUS9

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2005
Last sequence update:	July 19, 2005
Last modified:	May 1, 2013
This is version 72 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.