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Q60749 (KHDR1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
KH domain-containing, RNA-binding, signal transduction-associated protein 1
Alternative name(s):
GAP-associated tyrosine phosphoprotein p62
Src-associated in mitosis 68 kDa protein
Short name=Sam68
p21 Ras GTPase-activating protein-associated p62
p68
Gene names
Name:Khdrbs1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length443 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

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. Positively regulates the association of constitutive transport element (CTE)-containing mRNA with large polyribosomes and translation initiation. May not be involved in the nucleocytoplasmic export of unspliced (CTE)-containing RNA species. Ref.6 Ref.7 Ref.9 UniProtKB Q07666

Subunit structure

Self-associates to form homooligomers 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. Forms a complex with ILF2, ILF3, YLPM1, RBMX, NCOA5 and PPP1CA By similarity. Interacts with PTK6 (via SH3 and SH2 domains). Does not interact with TPR By similarity. Ref.2 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10

Subcellular location

Nucleus. Membrane Ref.9.

Domain

The KH domain is required for binding to RNA. Ref.7

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 methylation on these motifs can modulate protein-protein interactions By similarity. UniProtKB Q91V33

Post-translational modification

Tyrosine phosphorylated by several non-receptor tyrosine kinases, LCK, FYN and JAK3. Phosphorylation by PTK6 negatively regulates its RNA binding ability. Phosphorylation by PTK6 at Tyr-440 dictates the nulear localization of KHDRBS1. Ref.6

Acetylated. Positively correlates with ability to bind RNA By similarity. UniProtKB Q07666

Arginine methylation is required for nuclear localization. Inhibits interaction with Src-like SH3 domains, but not interaction with WW domains of WBP4/FBP21 AND FNBP4/FBP30 By similarity. UniProtKB Q07666

Sequence similarities

Belongs to the KHDRBS family.

Contains 1 KH domain.

Ontologies

Keywords
   Biological processCell cycle
Transcription
Transcription regulation
   Cellular componentMembrane
Nucleus
   DomainSH3-binding
   LigandRNA-binding
   PTMAcetylation
Methylation
Phosphoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcell cycle

Inferred from electronic annotation. Source: UniProtKB-KW

cell surface receptor signaling pathway

Inferred from direct assay Ref.2. Source: UniProtKB

negative regulation of transcription, DNA-templated

Inferred from direct assay Ref.9. Source: MGI

positive regulation of RNA export from nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of signal transduction

Inferred from physical interaction Ref.2. Source: GOC

positive regulation of translational initiation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of RNA export from nucleus

Inferred from direct assay Ref.9. Source: MGI

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentGrb2-Sos complex

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from electronic annotation. Source: Ensembl

membrane

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionRNA binding

Inferred from direct assay Ref.7. Source: UniProtKB

SH3/SH2 adaptor activity

Inferred from physical interaction Ref.2. Source: UniProtKB

poly(A) binding

Inferred from sequence orthology PubMed 21984414. Source: MGI

poly(U) RNA binding

Inferred from sequence orthology PubMed 21984414. Source: MGI

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 443443KH domain-containing, RNA-binding, signal transduction-associated protein 1
PRO_0000050125

Regions

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

Amino acid modifications

Modified residue201Phosphoserine By similarity UniProtKB Q07666
Modified residue211N6-acetyllysine Ref.11
Modified residue291Phosphoserine By similarity
Modified residue451Asymmetric dimethylarginine; alternate By similarity UniProtKB Q07666
Modified residue451Omega-N-methylated arginine; by PRMT1; alternate By similarity
Modified residue521Asymmetric dimethylarginine; alternate By similarity UniProtKB Q07666
Modified residue521Omega-N-methylated arginine; by PRMT1; alternate By similarity
Modified residue581Phosphoserine By similarity
Modified residue1131Phosphoserine Ref.6
Modified residue1751N6-acetyllysine By similarity
Modified residue2911Omega-N-methylated arginine; by PRMT1 By similarity UniProtKB Q07666
Modified residue3041Asymmetric dimethylarginine; alternate By similarity UniProtKB Q07666
Modified residue3041Omega-N-methylated arginine; by PRMT1; alternate By similarity
Modified residue3101Omega-N-methylarginine; alternate By similarity UniProtKB Q07666
Modified residue3101Omega-N-methylated arginine; by PRMT1; alternate By similarity
Modified residue3151Omega-N-methylarginine; alternate By similarity UniProtKB Q07666
Modified residue3151Omega-N-methylated arginine; by PRMT1; alternate By similarity
Modified residue3201Dimethylated arginine; alternate By similarity UniProtKB Q07666
Modified residue3201Omega-N-methylarginine; alternate By similarity
Modified residue3201Omega-N-methylated arginine; by PRMT1; alternate By similarity
Modified residue3251Omega-N-methylarginine; alternate By similarity UniProtKB Q07666
Modified residue3251Omega-N-methylated arginine; by PRMT1; alternate By similarity
Modified residue3311Dimethylated arginine; alternate By similarity UniProtKB Q07666
Modified residue3311Omega-N-methylated arginine; by PRMT1; alternate By similarity
Modified residue3401Omega-N-methylarginine; alternate By similarity UniProtKB Q07666
Modified residue3401Omega-N-methylated arginine; by PRMT1; alternate By similarity
Modified residue3461Omega-N-methylated arginine; by PRMT1 By similarity UniProtKB Q07666
Modified residue4351Phosphotyrosine; by PTK6 By similarity
Modified residue4401Phosphotyrosine; by PTK6 By similarity
Modified residue4431Phosphotyrosine; by PTK6 By similarity

Experimental info

Sequence conflict1041L → P in AAA64997. Ref.2
Sequence conflict1471D → N AA sequence Ref.6
Sequence conflict1741G → R in AAA86693. Ref.1
Sequence conflict1971V → VS in AAA86693. Ref.1
Sequence conflict225 – 2306MDLHVF → LGENGL AA sequence Ref.6
Sequence conflict3271A → S in AAA86693. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q60749 [UniParc].

Last modified April 12, 2005. Version 2.
Checksum: D33DE960BEA9E5AA

FASTA44348,371
        10         20         30         40         50         60 
MQRRDDPASR LTRSSGRSCS KDPSGAHPSV RLTPSRPSPL PHRPRGGGGG PRGGARASPA 

        70         80         90        100        110        120 
TQPPPLLPPS TPGPDATVVG SAPTPLLPPS ATAAVKMEPE NKYLPELMAE KDSLDPSFTH 

       130        140        150        160        170        180 
AMQLLSVEIE KIQKGESKKD 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 SRGRGVSVRG RGAAPPPPPV 

       310        320        330        340        350        360 
PRGRGVGPPR GALVRGTPVR GSITRGATVT RGVPPPPTVR GAPTPRARTA GIQRIPLPPT 

       370        380        390        400        410        420 
PAPETYEDYG YDDTYAEQSY EGYEGYYSQS QGESEYYDYG HGELQDSYEA YGQDDWNGTR 

       430        440 
PSLKAPPARP VKGAYREHPY GRY 

« Hide

References

« Hide 'large scale' references
[1]"Purification and cDNA sequence of a murine protein homologous to the human p62 tyrosine phosphoprotein that associates with the Ras GTPase-activating protein p120 GAP."
Agger R., Freimuth P.
Gene 158:307-308(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 103-120 AND 139-150.
Strain: BALB/c X DBA/2.
Tissue: Dendritic cell.
[2]"Association of p62, a multifunctional SH2- and SH3-domain-binding protein, with src family tyrosine kinases, Grb2, and phospholipase C gamma-1."
Richard S., Yu D., Blumer K.J., Hausladen D., Olszowy M.W., Connelly P.A., Shaw A.S.
Mol. Cell. Biol. 15:186-197(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH FYN; GRB2 AND PLCG1.
Tissue: Thymus.
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Bone marrow and Pancreas.
[4]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[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].
Strain: FVB/N.
Tissue: Mammary gland.
[6]"A target for Src in mitosis."
Fumagalli S., Totty N.F., Hsuan J.J., Courtneidge S.A.
Nature 368:871-874(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 57-71; 103-131; 139-152; 158-165; 222-230; 273-282 AND 433-443, FUNCTION, PHOSPHORYLATION AT SER-113, INTERACTION WITH SRC.
[7]"Self-association of the single-KH-domain family members Sam68, GRP33, GLD-1, and Qk1: role of the KH domain."
Chen T., Damaj B.B., Herrera C., Lasko P., Richard S.
Mol. Cell. Biol. 17:5707-5718(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, RNA-BINDING, HOMOOLIGOMERIZATION.
[8]"A mammalian germ cell-specific RNA-binding protein interacts with ubiquitously expressed proteins involved in splice site selection."
Elliott D.J., Bourgeois C.F., Klink A., Stevenin J., Cooke H.J.
Proc. Natl. Acad. Sci. U.S.A. 97:5717-5722(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RBMY1A1.
[9]"Physical and functional interaction between the transcriptional cofactor CBP and the KH domain protein Sam68."
Hong W., Resnick R.J., Rakowski C., Shalloway D., Taylor S.J., Blobel G.A.
Mol. Cancer Res. 1:48-55(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CBP.
[10]"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PRMT1.
[11]"SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-21, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U17961 mRNA. Translation: AAA86693.1.
U17046 mRNA. Translation: AAA64997.1.
AK050520 mRNA. Translation: BAC34303.1.
AK152084 mRNA. Translation: BAE30934.1.
AL669834 Genomic DNA. Translation: CAM13766.1.
CU210913 Genomic DNA. Translation: CAQ51789.1.
BC002051 mRNA. Translation: AAH02051.1.
PIRI49140.
S43974.
RefSeqNP_035447.3. NM_011317.4.
UniGeneMm.489797.
Mm.8256.

3D structure databases

ProteinModelPortalQ60749.
SMRQ60749. Positions 98-276.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid203068. 14 interactions.
DIPDIP-2861N.
IntActQ60749. 12 interactions.
MINTMINT-1613905.

PTM databases

PhosphoSiteQ60749.

Proteomic databases

PaxDbQ60749.
PRIDEQ60749.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000066257; ENSMUSP00000066516; ENSMUSG00000028790.
ENSMUST00000129342; ENSMUSP00000115402; ENSMUSG00000028790.
GeneID20218.
KEGGmmu:20218.
UCSCuc008uyd.2. mouse.

Organism-specific databases

CTD10657.
MGIMGI:893579. Khdrbs1.

Phylogenomic databases

eggNOGCOG5176.
GeneTreeENSGT00550000074434.
HOVERGENHBG079164.
InParanoidB2KG38.
KOK13198.
OMAFMELSYL.
OrthoDBEOG75MVX3.
PhylomeDBQ60749.
TreeFamTF314878.

Gene expression databases

BgeeQ60749.
GenevestigatorQ60749.

Family and domain databases

Gene3D3.30.1370.10. 1 hit.
InterProIPR004087. KH_dom.
IPR004088. KH_dom_type_1.
[Graphical view]
PfamPF00013. KH_1. 1 hit.
[Graphical view]
SMARTSM00322. KH. 1 hit.
[Graphical view]
SUPFAMSSF54791. SSF54791. 1 hit.
PROSITEPS50084. KH_TYPE_1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSKHDRBS1. mouse.
NextBio297827.
PROQ60749.
SOURCESearch...

Entry information

Entry nameKHDR1_MOUSE
AccessionPrimary (citable) accession number: Q60749
Secondary accession number(s): A2ACH3 expand/collapse secondary AC list , B2KG38, Q3U8T3, Q60735, Q7M4N5, Q99M33
Entry history
Integrated into UniProtKB/Swiss-Prot: April 12, 2005
Last sequence update: April 12, 2005
Last modified: April 16, 2014
This is version 119 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot