P61979 (HNRPK_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Heterogeneous nuclear ribonucleoprotein K
Short name=hnRNP K

Gene names

Name:	Hnrnpk
Synonyms:	Hnrpk

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	463 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	One of the major pre-mRNA-binding proteins. Binds tenaciously to poly(C) sequences. Likely to play a role in the nuclear metabolism of hnRNAs, particularly for pre-mRNAs that contain cytidine-rich sequences. Can also bind poly(C) single-stranded DNA. Plays an important role in p53/TP53 response to DNA damage, acting at the level of both transcription activation and repression. When sumoylated, acts as a transcriptional coactivator of p53/TP53, playing a role in p21/CDKN1A and 14-3-3 sigma/SFN induction By similarity. As far as transcription repression is concerned, acts by interacting with long intergenic RNA p21 (lincRNA-p21), a non-coding RNA induced by p53/TP53. This interaction is necessary for the induction of apoptosis, but not cell cycle arrest. Ref.11
Subunit structure	Identified in the spliceosome C complex By similarity. Interacts with ANKRD28 and RBM42. Interacts with DDX1 By similarity. Interacts with MDM2; this interaction leads to ubiquitination and proteasomal degradation By similarity. Interacts with p53/TP53 By similarity. Interacts with ZIK1. Interacts with BRDT. Ref.5 Ref.12
Subcellular location	Cytoplasm By similarity. Nucleus › nucleoplasm By similarity.
Induction	By DNA damage. This up-regulation is due to protein stabilization. The constitutive protein levels are controlled by MDM2-mediated ubiquitination and degradation via the proteasome pathway. Ref.7
Post-translational modification	Sumoylated by CBX4. Sumoylation is increased upon DNA damage, such as that produced by doxorubicin, etoposide, UV light and camptothecin, due to enhanced CBX4 phosphorylation by HIPK2 under these conditions By similarity. Ubiquitinated by MDM2. Doxorubicin treatment does not affect monoubiquitination, but slightly decreases HNRNPK poly-ubiquitination By similarity. O-glycosylated (O-GlcNAcylated), in a cell cycle-dependent manner By similarity.
Sequence similarities	Contains 3 KH domains.

Ontologies

Keywords
Biological process	Transcription Transcription regulation mRNA processing mRNA splicing
Cellular component	Cytoplasm Nucleus Spliceosome
Coding sequence diversity	Alternative splicing
Domain	Repeat
Ligand	DNA-binding RNA-binding
Molecular function	Activator Repressor Ribonucleoprotein
PTM	Acetylation Glycoprotein Isopeptide bond Methylation Phosphoprotein Ubl conjugation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	RNA splicing Inferred from electronic annotation. Source: UniProtKB-KW mRNA processing Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of low-density lipoprotein particle receptor biosynthetic process Inferred from electronic annotation. Source: Compara positive regulation of receptor-mediated endocytosis Inferred from electronic annotation. Source: Compara regulation of apoptotic process Inferred from mutant phenotype Ref.11. Source: MGI regulation of lipid transport by positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara regulation of low-density lipoprotein particle clearance Inferred from electronic annotation. Source: Compara
Cellular_component	catalytic step 2 spliceosome Inferred from electronic annotation. Source: Compara cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nuclear chromatin Inferred from electronic annotation. Source: Compara nucleoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	RNA binding Inferred from direct assay Ref.11. Source: MGI RNA polymerase II core promoter proximal region sequence-specific DNA binding Inferred from electronic annotation. Source: Compara RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P61979-1)

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: P61979-2)

The sequence of this isoform differs from the canonical sequence as follows:
     459-463: SGKFF → ADVEGF

Isoform 3 (identifier: P61979-3)

The sequence of this isoform differs from the canonical sequence as follows:
     111-134: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 463	463	Heterogeneous nuclear ribonucleoprotein K		PRO_0000050097
Regions
	Domain	42 – 104	63	KH 1
	Repeat	54 – 76	23	1-1
	Repeat	59 – 62	4	3-1
	Domain	144 – 209	66	KH 2
	Repeat	245 – 250	6	2-1
	Repeat	257 – 260	4	3-2
	Repeat	267 – 270	4	3-3
	Repeat	295 – 298	4	3-4
	Repeat	324 – 329	6	2-2
	Domain	387 – 451	65	KH 3
	Repeat	399 – 421	23	1-2
	Repeat	404 – 407	4	3-5
	Region	1 – 276	276	Necessary for interaction with DDX1 By similarity
	Region	54 – 421	368	2 X 22 AA approximate repeats
	Region	59 – 407	349	5 X 4 AA repeats of G-X-G-G
	Region	209 – 337	129	Interaction with ZIK1
	Region	236 – 273	38	RNA-binding RGG-box
	Region	245 – 329	85	2 X 6 AA approximate repeats
	Compositional bias	289 – 294	6	Poly-Pro
	Compositional bias	310 – 315	6	Poly-Pro
Amino acid modifications
	Modified residue	1	1	N-acetylmethionine By similarity
	Modified residue	116	1	Phosphoserine By similarity
	Modified residue	214	1	Phosphoserine By similarity
	Modified residue	216	1	Phosphoserine Ref.9
	Modified residue	284	1	Phosphoserine Ref.6 Ref.8 Ref.10
	Modified residue	296	1	Omega-N-methylated arginine By similarity
	Modified residue	299	1	Omega-N-methylated arginine By similarity
	Modified residue	379	1	Phosphoserine By similarity
	Modified residue	380	1	Phosphotyrosine By similarity
	Cross-link	422		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
Natural variations
	Alternative sequence	111 – 134	24	Missing in isoform 3.		VSP_012581
	Alternative sequence	459 – 463	5	SGKFF → ADVEGF in isoform 2.		VSP_010622
Experimental info
	Sequence conflict	132	1	C → V in AAA21731. Ref.1
	Sequence conflict	136	1	Q → P in AAA21731. Ref.1
	Sequence conflict	154	1	S → T in AAA21731. Ref.1
	Sequence conflict	334	1	D → S in AAA21731. Ref.1
	Sequence conflict	350	1	D → E in AAA21731. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 7, 2004. Version 1. Checksum: 0F70EE169B2A064A	FASTA	463	50,976
	10 20 30 40 50 60 METEQPEETF PNTETNGEFG KRPAEDMEEE QAFKRSRNTD EMVELRILLQ SKNAGAVIGK 70 80 90 100 110 120 GGKNIKALRT DYNASVSVPD SSGPERILSI SADIETIGEI LKKIIPTLEE GLQLPSPTAT 130 140 150 160 170 180 SQLPLESDAV ECLNYQHYKG SDFDCELRLL IHQSLAGGII GVKGAKIKEL RENTQTTIKL 190 200 210 220 230 240 FQECCPHSTD RVVLIGGKPD RVVECIKIIL DLISESPIKG RAQPYDPNFY DETYDYGGFT 250 260 270 280 290 300 MMFDDRRGRP VGFPMRGRGG FDRMPPGRGG RPMPPSRRDY DDMSPRRGPP PPPPGRGGRG 310 320 330 340 350 360 GSRARNLPLP PPPPPRGGDL MAYDRRGRPG DRYDGMVGFS ADETWDSAID TWSPSEWQMA 370 380 390 400 410 420 YEPQGGSGYD YSYAGGRGSY GDLGGPIITT QVTIPKDLAG SIIGKGGQRI KQIRHESGAS 430 440 450 460 IKIDEPLEGS EDRIITITGT QDQIQNAQYL LQNSVKQYSG KFF
	Isoform 2 [UniParc] [UniParc]. Checksum: 0B4EC22FE4534A06	FASTA	464	51,028
	10 20 30 40 50 60 METEQPEETF PNTETNGEFG KRPAEDMEEE QAFKRSRNTD EMVELRILLQ SKNAGAVIGK 70 80 90 100 110 120 GGKNIKALRT DYNASVSVPD SSGPERILSI SADIETIGEI LKKIIPTLEE GLQLPSPTAT 130 140 150 160 170 180 SQLPLESDAV ECLNYQHYKG SDFDCELRLL IHQSLAGGII GVKGAKIKEL RENTQTTIKL 190 200 210 220 230 240 FQECCPHSTD RVVLIGGKPD RVVECIKIIL DLISESPIKG RAQPYDPNFY DETYDYGGFT 250 260 270 280 290 300 MMFDDRRGRP VGFPMRGRGG FDRMPPGRGG RPMPPSRRDY DDMSPRRGPP PPPPGRGGRG 310 320 330 340 350 360 GSRARNLPLP PPPPPRGGDL MAYDRRGRPG DRYDGMVGFS ADETWDSAID TWSPSEWQMA 370 380 390 400 410 420 YEPQGGSGYD YSYAGGRGSY GDLGGPIITT QVTIPKDLAG SIIGKGGQRI KQIRHESGAS 430 440 450 460 IKIDEPLEGS EDRIITITGT QDQIQNAQYL LQNSVKQYAD VEGF
	Isoform 3 [UniParc]. Checksum: 7BCA66B4E39776DB	FASTA	439	48,510
	10 20 30 40 50 60 METEQPEETF PNTETNGEFG KRPAEDMEEE QAFKRSRNTD EMVELRILLQ SKNAGAVIGK 70 80 90 100 110 120 GGKNIKALRT DYNASVSVPD SSGPERILSI SADIETIGEI LKKIIPTLEE YQHYKGSDFD 130 140 150 160 170 180 CELRLLIHQS LAGGIIGVKG AKIKELRENT QTTIKLFQEC CPHSTDRVVL IGGKPDRVVE 190 200 210 220 230 240 CIKIILDLIS ESPIKGRAQP YDPNFYDETY DYGGFTMMFD DRRGRPVGFP MRGRGGFDRM 250 260 270 280 290 300 PPGRGGRPMP PSRRDYDDMS PRRGPPPPPP GRGGRGGSRA RNLPLPPPPP PRGGDLMAYD 310 320 330 340 350 360 RRGRPGDRYD GMVGFSADET WDSAIDTWSP SEWQMAYEPQ GGSGYDYSYA GGRGSYGDLG 370 380 390 400 410 420 GPIITTQVTI PKDLAGSIIG KGGQRIKQIR HESGASIKID EPLEGSEDRI ITITGTQDQI 430 QNAQYLLQNS VKQYSGKFF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Purification, cloning, and expression of a murine phosphoprotein that binds the kappa B motif in vitro identifies it as the homolog of the human heterogeneous nuclear ribonucleoprotein K protein. Description of a novel DNA-dependent phosphorylation process." Ostrowski J., van Seuningen I., Seger R., Rauch C.T., Sleath P.R., McMullen B.A., Bomsztyk K. J. Biol. Chem. 269:17626-17634(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PARTIAL PROTEIN SEQUENCE. Tissue: Lymphoma.
[2]	"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] (ISOFORMS 1; 2 AND 3). Strain: C57BL/6J and NOD. Tissue: Spinal ganglion, Testis and Thymus.
[3]	"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 2).
[4]	Lubec G., Klug S., Yang J.W., Zigmond M. Submitted (JUL-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 149-163 AND 207-219, MASS SPECTROMETRY. Tissue: Brain and Hippocampus.
[5]	"Zik1, a transcriptional repressor that interacts with the heterogeneous nuclear ribonucleoprotein particle K protein." Denisenko O.N., O'Neill B., Ostrowski J., Van Seuningen I., Bomsztyk K. J. Biol. Chem. 271:27701-27706(1996) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ZIK1.
[6]	"Identification of phosphoproteins and their phosphorylation sites in the WEHI-231 B lymphoma cell line." Shu H., Chen S., Bi Q., Mumby M., Brekken D.L. Mol. Cell. Proteomics 3:279-286(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-284, MASS SPECTROMETRY. Tissue: B-cell lymphoma.
[7]	"hnRNP K: an HDM2 target and transcriptional coactivator of p53 in response to DNA damage." Moumen A., Masterson P., O'Connor M.J., Jackson S.P. Cell 123:1065-1078(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
[8]	"Comprehensive identification of phosphorylation sites in postsynaptic density preparations." Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L. Mol. Cell. Proteomics 5:914-922(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-284, MASS SPECTROMETRY. Tissue: Brain.
[9]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-216, MASS SPECTROMETRY. Tissue: Liver.
[10]	"The phagosomal proteome in interferon-gamma-activated macrophages." Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P. Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-284, MASS SPECTROMETRY. Tissue: Macrophage.
[11]	"A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response." Huarte M., Guttman M., Feldser D., Garber M., Koziol M.J., Kenzelmann-Broz D., Khalil A.M., Zuk O., Amit I., Rabani M., Attardi L.D., Regev A., Lander E.S., Jacks T., Rinn J.L. Cell 142:409-419(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[12]	"The testis-specific double bromodomain-containing protein BRDT forms a complex with multiple spliceosome components and is required for mRNA splicing and 3'-UTR truncation in round spermatids." Berkovits B.D., Wang L., Guarnieri P., Wolgemuth D.J. Nucleic Acids Res. 40:7162-7175(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BRDT.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L31961 mRNA. Translation: AAA21731.1. AK011428 mRNA. Translation: BAB27614.1. AK051313 mRNA. Translation: BAC34601.1. AK078777 mRNA. Translation: BAC37389.1. AK088462 mRNA. Translation: BAC40368.1. BC006694 mRNA. Translation: AAH06694.1.
IPI	IPI00224575. IPI00890005. IPI00990152.
RefSeq	NP_079555.1. NM_025279.2.
UniGene	Mm.142872.
3D structure databases
ProteinModelPortal	P61979.
ModBase	Search...
Protein-protein interaction databases
IntAct	P61979. 6 interactions.
PTM databases
PhosphoSite	P61979.
2D gel databases
REPRODUCTION-2DPAGE	IPI00223253. P61979.
Proteomic databases
PaxDb	P61979.
PRIDE	P61979.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000043269; ENSMUSP00000039269; ENSMUSG00000021546. ENSMUST00000116403; ENSMUSP00000112104; ENSMUSG00000021546. ENSMUST00000176207; ENSMUSP00000135354; ENSMUSG00000021546.
GeneID	15387.
KEGG	mmu:15387.
UCSC	uc007qtw.1. mouse. uc007qty.1. mouse.
Organism-specific databases
CTD	3190.
MGI	MGI:99894. Hnrnpk.
Phylogenomic databases
eggNOG	NOG285495.
GeneTree	ENSGT00550000074311.
HOVERGEN	HBG051916.
KO	K12886.
OMA	KALRTDX.
Gene expression databases
ArrayExpress	P61979.
Bgee	P61979.
Genevestigator	P61979.
GermOnline	ENSMUSG00000063902. Mus musculus.
Family and domain databases
InterPro	IPR004087. KH_dom. IPR004088. KH_dom_type_1. IPR012987. ROK_N. [Graphical view]
Pfam	PF00013. KH_1. 3 hits. PF08067. ROKNT. 1 hit. [Graphical view]
SMART	SM00322. KH. 3 hits. [Graphical view]
PROSITE	PS50084. KH_TYPE_1. 3 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	12686.
SOURCE	Search...

Entry information

Entry name

HNRPK_MOUSE

Accession

Primary (citable) accession number: P61979
Secondary accession number(s): Q07244 , Q15671, Q60577, Q8BGQ8, Q922Y7, Q96J62

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 7, 2004
Last sequence update:	June 7, 2004
Last modified:	May 1, 2013
This is version 104 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program