Q60749 (KHDR1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	443 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Cell cycle Transcription Transcription regulation
Cellular component	Membrane Nucleus
Domain	SH3-binding
Ligand	RNA-binding
PTM	Acetylation Methylation Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cell 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-dependent 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 translational initiation Inferred from sequence or structural similarity. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	Grb2-Sos complex Inferred from electronic annotation. Source: Compara cytoplasm Inferred from electronic annotation. Source: Compara membrane Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	RNA binding Inferred from direct assay Ref.7. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Crebbp	P45481	7	EBI-519077,EBI-296306
Fyn	P39688	13	EBI-519077,EBI-524514
Prmt1	Q9JIF0	2	EBI-519077,EBI-519055

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 443	443	KH domain-containing, RNA-binding, signal transduction-associated protein 1		PRO_0000050125
Regions
	Domain	171 – 197	27	KH
	Compositional bias	34 – 41	8	Pro-rich
	Compositional bias	44 – 55	12	Arg/Gly-rich
	Compositional bias	59 – 89	31	Pro-rich
	Compositional bias	282 – 292	11	Arg/Gly-rich
	Compositional bias	295 – 301	7	Pro-rich
	Compositional bias	302 – 332	31	Arg/Gly-rich
	Compositional bias	334 – 363	30	Pro-rich
Amino acid modifications
	Modified residue	20	1	Phosphoserine By similarity UniProtKB Q07666
	Modified residue	29	1	Phosphoserine By similarity
	Modified residue	45	1	Asymmetric dimethylarginine; alternate By similarity
	Modified residue	45	1	Omega-N-methylated arginine; by PRMT1; alternate By similarity
	Modified residue	52	1	Asymmetric dimethylarginine; alternate By similarity
	Modified residue	52	1	Omega-N-methylated arginine; by PRMT1; alternate By similarity
	Modified residue	58	1	Phosphoserine By similarity
	Modified residue	113	1	Phosphoserine Ref.6
	Modified residue	175	1	N6-acetyllysine By similarity
	Modified residue	291	1	Omega-N-methylated arginine; by PRMT1 By similarity UniProtKB Q07666
	Modified residue	304	1	Asymmetric dimethylarginine; alternate By similarity
	Modified residue	304	1	Omega-N-methylated arginine; by PRMT1; alternate By similarity
	Modified residue	310	1	Omega-N-methylarginine; alternate By similarity
	Modified residue	310	1	Omega-N-methylated arginine; by PRMT1; alternate By similarity
	Modified residue	315	1	Omega-N-methylarginine; alternate By similarity
	Modified residue	315	1	Omega-N-methylated arginine; by PRMT1; alternate By similarity
	Modified residue	320	1	Dimethylated arginine; alternate By similarity
	Modified residue	320	1	Omega-N-methylarginine; alternate By similarity
	Modified residue	320	1	Omega-N-methylated arginine; by PRMT1; alternate By similarity
	Modified residue	325	1	Omega-N-methylarginine; alternate By similarity
	Modified residue	325	1	Omega-N-methylated arginine; by PRMT1; alternate By similarity
	Modified residue	331	1	Dimethylated arginine; alternate By similarity
	Modified residue	331	1	Omega-N-methylated arginine; by PRMT1; alternate By similarity
	Modified residue	340	1	Omega-N-methylarginine; alternate By similarity
	Modified residue	340	1	Omega-N-methylated arginine; by PRMT1; alternate By similarity
	Modified residue	346	1	Omega-N-methylated arginine; by PRMT1 By similarity UniProtKB Q07666
	Modified residue	435	1	Phosphotyrosine; by PTK6 By similarity
	Modified residue	440	1	Phosphotyrosine; by PTK6 By similarity
	Modified residue	443	1	Phosphotyrosine; by PTK6 By similarity
Experimental info
	Sequence conflict	104	1	L → P in AAA64997. Ref.2
	Sequence conflict	147	1	D → N AA sequence Ref.6
	Sequence conflict	174	1	G → R in AAA86693. Ref.1
	Sequence conflict	197	1	V → VS in AAA86693. Ref.1
	Sequence conflict	225 – 230	6	MDLHVF → LGENGL AA sequence Ref.6
	Sequence conflict	327	1	A → S in AAA86693. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q60749 [UniParc]. Last modified April 12, 2005. Version 2. Checksum: D33DE960BEA9E5AA	FASTA	443	48,371
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
+	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.
IPI	IPI00458765.
PIR	I49140. S43974.
RefSeq	NP_035447.3. NM_011317.4.
UniGene	Mm.489797. Mm.8256.
3D structure databases
ProteinModelPortal	Q60749.
SMR	Q60749. Positions 99-135, 155-276.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-2861N.
IntAct	Q60749. 8 interactions.
PTM databases
PhosphoSite	Q60749.
Proteomic databases
PaxDb	Q60749.
PRIDE	Q60749.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000066257; ENSMUSP00000066516; ENSMUSG00000028790. ENSMUST00000129342; ENSMUSP00000115402; ENSMUSG00000028790.
GeneID	20218.
KEGG	mmu:20218.
UCSC	uc008uyd.1. mouse.
Organism-specific databases
CTD	10657.
MGI	MGI:893579. Khdrbs1.
Phylogenomic databases
eggNOG	COG5176.
GeneTree	ENSGT00550000074434.
HOVERGEN	HBG079164.
InParanoid	B2KG38.
KO	K13198.
OMA	FMELSYL.
OrthoDB	EOG4JHCGB.
Gene expression databases
Bgee	Q60749.
Genevestigator	Q60749.
GermOnline	ENSMUSG00000028790. Mus musculus.
Family and domain databases
InterPro	IPR004087. KH_dom. IPR004088. KH_dom_type_1. [Graphical view]
Pfam	PF00013. KH_1. 1 hit. [Graphical view]
SMART	SM00322. KH. 1 hit. [Graphical view]
PROSITE	PS50084. KH_TYPE_1. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	KHDRBS1. mouse.
NextBio	297827.
SOURCE	Search...

Entry information

Entry name

KHDR1_MOUSE

Accession

Primary (citable) accession number: Q60749
Secondary accession number(s): A2ACH3 , B2KG38, Q3U8T3, Q60735, Q7M4N5, Q99M33

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 12, 2005
Last sequence update:	April 12, 2005
Last modified:	May 1, 2013
This is version 110 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program