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Q96LT7 (CI072_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 84. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein C9orf72
Gene names
Name:C9orf72
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length481 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May play a role in endosomal trafficking and autophagy. Ref.8

Subunit structure

Interacts with HNRNPA1, HNRNPA2B1 and UBQLN2. Interacts with small Rab GTPases including RAB1A and RAB7A. Ref.8

Subcellular location

Nucleus. Cytoplasm. Endosome. Lysosome. Cytoplasmic vesicleautophagosome. Secreted. 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 Ref.8

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. In the first intron of the gene, the expansion of a GGGGCC hexanucleotide that can vary from 10 to thousands of repeats, represents the most common genetic cause of both familial and sporadic FTDALS. The hexanucleotide repeat expansion (HRE) is structurally polymorphic and during transcription, is responsible for the formation of RNA and DNA G-quadruplexes resulting in the production of aborted transcripts at the expense of functional transcripts. The accumulation of those aborted transcripts may cause nucleolar stress and indirectly cell death (Ref.9). Ref.1 Ref.6 Ref.7

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 481481Protein C9orf72
PRO_0000089711

Natural variations

Alternative sequence2221N → K in isoform 2.
VSP_014745
Alternative sequence223 – 481259Missing in isoform 2.
VSP_014746
Natural variant2071N → S.
Corresponds to variant rs17769294 [ dbSNP | Ensembl ].
VAR_050827

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 19, 2005. Version 2.
Checksum: B36C5576B3D268CE

FASTA48154,328
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 068FE35DB48FE903
Show »

FASTA22224,759

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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.
[8]"C9ORF72, implicated in amytrophic lateral sclerosis and frontotemporal dementia, regulates endosomal trafficking."
Farg M.A., Sundaramoorthy V., Sultana J.M., Yang S., Atkinson R.A., Levina V., Halloran M.A., Gleeson P.A., Blair I.P., Soo K.Y., King A.E., Atkin J.D.
Hum. Mol. Genet. 0:0-0(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ENDOSOMAL TRAFFICKING, INTERACTION WITH RAB GTPASES; HNRNPA1; HNRNPA2B1 AND UBQLN2, SUBCELLULAR LOCATION.
[9]"C9orf72 nucleotide repeat structures initiate molecular cascades of disease."
Haeusler A.R., Donnelly C.J., Periz G., Simko E.A., Shaw P.G., Kim M.S., Maragakis N.J., Troncoso J.C., Pandey A., Sattler R., Rothstein J.D., Wang J.
Nature 507:195-200(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: PATHOLOGICAL MECHANISM.
+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.
CCDSCCDS6522.1. [Q96LT7-1]
CCDS6523.1. [Q96LT7-2]
RefSeqNP_001242983.1. NM_001256054.1. [Q96LT7-1]
NP_060795.1. NM_018325.3. [Q96LT7-1]
NP_659442.2. NM_145005.5. [Q96LT7-2]
UniGeneHs.493639.

3D structure databases

ProteinModelPortalQ96LT7.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid128456. 5 interactions.
IntActQ96LT7. 3 interactions.
STRING9606.ENSP00000369339.

PTM databases

PhosphoSiteQ96LT7.

Polymorphism databases

DMDM71152412.

Proteomic databases

MaxQBQ96LT7.
PaxDbQ96LT7.
PRIDEQ96LT7.

Protocols and materials databases

DNASU203228.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000379995; ENSP00000369331; ENSG00000147894. [Q96LT7-2]
ENST00000379997; ENSP00000369333; ENSG00000147894. [Q96LT7-2]
ENST00000380003; ENSP00000369339; ENSG00000147894. [Q96LT7-1]
GeneID203228.
KEGGhsa:203228.
UCSCuc003zqq.3. human. [Q96LT7-1]
uc003zqr.2. human. [Q96LT7-2]

Organism-specific databases

CTD203228.
GeneCardsGC09M027539.
GeneReviewsC9orf72.
HGNCHGNC:28337. C9orf72.
HPAHPA023873.
MIM105550. phenotype.
614260. gene.
neXtProtNX_Q96LT7.
Orphanet803. Amyotrophic lateral sclerosis.
275864. Behavioral variant of frontotemporal dementia.
275872. Frontotemporal dementia with motor neuron disease.
100070. Progressive non-fluent aphasia.
100069. Semantic dementia.
PharmGKBPA134908144.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG40002.
HOGENOMHOG000231721.
HOVERGENHBG060354.
InParanoidQ96LT7.
OMAAQDTIIY.
OrthoDBEOG7H1JJZ.
PhylomeDBQ96LT7.
TreeFamTF313315.

Gene expression databases

ArrayExpressQ96LT7.
BgeeQ96LT7.
CleanExHS_C9orf72.
GenevestigatorQ96LT7.

Family and domain databases

InterProIPR027819. C9orf72-like.
[Graphical view]
PfamPF15019. C9orf72-like. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi203228.
NextBio90368.
SOURCESearch...

Entry information

Entry nameCI072_HUMAN
AccessionPrimary (citable) accession number: Q96LT7
Secondary accession number(s): A8K5W0 expand/collapse secondary AC list , D3DRK6, G8I0B6, Q6NUS9
Entry history
Integrated into UniProtKB/Swiss-Prot: July 19, 2005
Last sequence update: July 19, 2005
Last modified: July 9, 2014
This is version 84 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM