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Reviewed, UniProtKB/Swiss-Prot Q07666 (KHDR1_HUMAN)

Last modified November 4, 2008. Version 80. Feed History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    KH domain-containing, RNA-binding, signal transduction-associated protein 1
Alternative name(s):
    p21 Ras GTPase-activating protein-associated p62
    GAP-associated tyrosine phosphoprotein p62
    Src-associated in mitosis 68 kDa protein
      Short name=Sam68
    p68
Gene names
Name: KHDRBS1
Synonyms: SAM68
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length443 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

Recruited and tyrosine phosphorylated by several receptor systems, for example the T-cell, leptin and insulin receptors. Once phosphorylated, functions as an adapter protein in signal transduction cascades by binding to SH2 and SH3 domain-containing proteins. Role in G2-M progression in the cell cycle. Represses CBP-dependent transcriptional activation apparently by competing with other nuclear factors for binding to CBP. Also acts as a putative regulator of mRNA stability and/or translation rates and mediates mRNA nuclear export.

Isoform 3, which is expressed in growth-arrested cells only, inhibits S phase.

Subunit structure

Self-associates to form homo-oligomers when bound to RNA, oligomerization appears to be limited when binding to proteins. Interacts with CBL, KHDRBS3, LCK, GRB2, JAK3, PIK3R1, PLCG1, PTPN6, RASA1, RBMY1A1 and STAT3. Interacts with PRMT1. Binds the WW domains of WBP4/FBP21, FNBP4/FBP30 and the SH3 domain of FYN through the Arg/Gly-rich-flanked Pro-rich regions By similarity.

Subcellular location

Nucleus. Membrane.

Tissue specificity

Ubiquitously expressed in all tissue examined. Isoform 1 is expressed at lower levels in brain, skeletal muscle, and liver whereas isoform 3 is intensified in skeletal muscle and in liver.

Developmental stage

Isoform 3 is only expressed in growth-arrested cells.

Domain

The KH domain is required for binding to RNA By similarity.

The Pro-rich domains are flanked by Arg/Gly-rich motifs which can be asymmetric dimethylated on arginine residues to give the DMA/Gly-rich regions. Selective methlylation on these motifs can modulate protein-protein interactions By similarity.

Post-translational modification

Tyrosine phosphorylated by several non-receptor tyrosine kinases, for example LCK, FYN and JAK3. Negatively correlates with ability to bind RNA but required for many interactions with proteins.

Acetylated. Positively correlates with ability to bind RNA.

Arginine methylation is required for nuclear localization. Also can affect interaction with other proteins. Inhibits interaction with Src-like SH3 domains, but not interaction with WW domains of WBP4/FBP21 AND FNBP4/FBP30.

Arg-291, Arg-331 and Arg-346 are found to be also dimethylated, probably to asymmetric dimethylarginine.

Sequence similarities

Belongs to the KHDRBS family.

Contains 1 KH domain.

Sequence caution

The sequence AAH10132.1 differs from that shown. Reason: Miscellaneous discrepancy. Intron retention.

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Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q07666-1)

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: Q07666-2)

The sequence of this isoform differs from the canonical sequence as follows:
     37-61: Missing.
Notes: No experimental confirmation available.
Isoform 3 (identifier: Q07666-3)

Also known as: DeltaKH;

The sequence of this isoform differs from the canonical sequence as follows:
     169-207: Missing.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 443443KH domain-containing, RNA-binding, signal transduction-associated protein 1
PRO_0000050124

Regions

Domain171 – 19727KH
Compositional bias34 – 418Pro-rich
Compositional bias44 – 5512DMA/Gly-rich
Compositional bias59 – 8931Pro-rich
Compositional bias282 – 29211DMA/Gly-rich
Compositional bias295 – 3017Pro-rich
Compositional bias302 – 33231Arg/Gly-rich
Compositional bias334 – 36330Pro-rich

Amino acid modifications

Modified residue181Phosphoserine
Modified residue201Phosphoserine
Modified residue331Phosphothreonine
Modified residue451Asymmetric dimethylarginine; by PRMT1
Modified residue521Asymmetric dimethylarginine; partial; by PRMT1
Modified residue1131Phosphoserine By similarity
Modified residue2911Omega-N-methylated arginine; by PRMT1
Modified residue3041Asymmetric dimethylarginine; by PRMT1
Modified residue3101Omega-N-methylarginine; by PRMT1
Modified residue3151Omega-N-methylarginine; by PRMT1
Modified residue3201Omega-N-methylarginine; by PRMT1
Modified residue3251Omega-N-methylarginine; by PRMT1
Modified residue3311Omega-N-methylated arginine; by PRMT1
Modified residue3401Omega-N-methylarginine; by PRMT1
Modified residue3461Omega-N-methylated arginine; by PRMT1

Natural variations

Alternative sequence37 – 6125Missing in isoform 2.
VSP_051719
Alternative sequence169 – 20739Missing in isoform 3.
VSP_051720

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Sequences

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

Last modified November 1, 1996. Version 1.
Checksum: 59FB4DB6FB4DBE98

FASTA44348,227
        10         20         30         40         50         60 
MQRRDDPAAR MSRSSGRSGS MDPSGAHPSV RQTPSRQPPL PHRSRGGGGG SRGGARASPA 

        70         80         90        100        110        120 
TQPPPLLPPS ATGPDATVGG PAPTPLLPPS ATASVKMEPE NKYLPELMAE KDSLDPSFTH 

       130        140        150        160        170        180 
AMQLLTAEIE KIQKGDSKKD DEENYLDLFS HKNMKLKERV LIPVKQYPKF NFVGKILGPQ 

       190        200        210        220        230        240 
GNTIKRLQEE TGAKISVLGK GSMRDKAKEE ELRKGGDPKY AHLNMDLHVF IEVFGPPCEA 

       250        260        270        280        290        300 
YALMAHAMEE VKKFLVPDMM DDICQEQFLE LSYLNGVPEP SRGRGVPVRG RGAAPPPPPV 

       310        320        330        340        350        360 
PRGRGVGPPR GALVRGTPVR GAITRGATVT RGVPPPPTVR GAPAPRARTA GIQRIPLPPP 

       370        380        390        400        410        420 
PAPETYEEYG YDDTYAEQSY EGYEGYYSQS QGDSEYYDYG HGEVQDSYEA YGQDDWNGTR 

       430        440 
PSLKAPPARP VKGAYREHPY GRY

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Isoform 2 [UniParc].

Checksum: 36B5B877E35D9A2C
Show »

41845,861
Isoform 3 (DeltaKH) [UniParc].

Checksum: 0E6334E3447CCA5F
Show »

40444,027

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References

« Hide 'large scale' references
[1]"Molecular cloning and nucleic acid binding properties of the GAP-associated tyrosine phosphoprotein p62."
Wong G., Muller O., Clark R., Conroy L., Moran M.F., Polakis P., McCormick F.
Cell 69:551-558(1992) [PubMed: 1374686] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, RNA-BINDING, METHYLATION, INTERACTION WITH RASA1.
Tissue: Fetal brain.
[2]"A role for Sam68 in cell cycle progression antagonized by a spliced variant within the KH domain."
Barlat I., Maurier F., Duchesne M., Guitard E., Tocque B., Schweighoffer F.
J. Biol. Chem. 272:3129-3132(1997) [PubMed: 9013542] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
Tissue: Placenta.
[3]"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: 14702039] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Brain.
[4]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed: 16710414] [Abstract]
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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Lymph and Placenta.
[6]"Interaction between Sam68 and Src family tyrosine kinases, Fyn and Lck, in T cell receptor signaling."
Fusaki N., Iwamatsu A., Iwashima M., Fujisawa J.
J. Biol. Chem. 272:6214-6219(1997) [PubMed: 9045636] [Abstract]
Cited for: PROTEIN SEQUENCE OF 102-110 AND 169-175 (ISOFORMS 1/2), FUNCTION, PHOSPHORYLATION, INTERACTION WITH LCK; FYN; PTPN6; PLCG1; GRB2; CBL; JAK3 AND PIK3R1.
[7]"T-STAR/ETOILE: a novel relative of SAM68 that interacts with an RNA-binding protein implicated in spermatogenesis."
Venables J.P., Vernet C., Chew S.L., Elliott D.J., Cowmeadow R.B., Wu J., Cooke H.J., Artzt K., Eperon I.C.
Hum. Mol. Genet. 8:959-969(1999) [PubMed: 10332027] [Abstract]
Cited for: INTERACTION WITH KHDRBS3.
Tissue: Testis.
[8]"Human leptin signaling in human peripheral blood mononuclear cells: activation of the JAK-STAT pathway."
Sanchez-Margalet V., Martin-Romero C.
Cell. Immunol. 211:30-36(2001) [PubMed: 11585385] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION, INTERACTION WITH STAT3.
[9]"Sam68 RNA binding protein is an in vivo substrate for protein arginine N-methyltransferase 1."
Cote J., Boisvert F.-M., Boulanger M.-C., Bedford M.T., Richard S.
Mol. Biol. Cell 14:274-287(2003) [PubMed: 12529443] [Abstract]
Cited for: METHYLATION AT ARG-45; ARG-52; ARG-304; ARG-310; ARG-315; ARG-320 AND ARG-325, SUBCELLULAR LOCATION.
[10]"Identifying and quantifying in vivo methylation sites by heavy methyl SILAC."
Ong S.E., Mittler G., Mann M.
Nat. Methods 1:119-126(2004) [PubMed: 15782174] [Abstract]
Cited for: METHYLATION [LARGE SCALE ANALYSIS] AT ARG-291; ARG-325; ARG-331; ARG-340 AND ARG-346, MASS SPECTROMETRY.
[11]"The RNA binding protein Sam68 is acetylated in tumor cell lines, and its acetylation correlates with enhanced RNA binding activity."
Babic I., Jakymiw A., Fujita D.J.
Oncogene 23:3781-3789(2004) [PubMed: 15021911] [Abstract]
Cited for: ACETYLATION, INTERACTION WITH RNA.
[12]"Global phosphoproteome of HT-29 human colon adenocarcinoma cells."
Kim J.-E., Tannenbaum S.R., White F.M.
J. Proteome Res. 4:1339-1346(2005) [PubMed: 16083285] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20, MASS SPECTROMETRY.
[13]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed: 17081983] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18 AND SER-20, MASS SPECTROMETRY.
Tissue: Epithelium.
[14]"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra."
Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.
J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18 AND THR-33, MASS SPECTROMETRY.
Tissue: Epithelium.
[15]"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry."
Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A.
Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20, MASS SPECTROMETRY.
[16]"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20, MASS SPECTROMETRY.

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Cross-references

Sequence databases

M88108 mRNA. Translation: