Reviewed, UniProtKB/Swiss-Prot P61978 (HNRPK_HUMAN)

Names and origin

Protein names

Recommended name:
    Heterogeneous nuclear ribonucleoprotein K
      Short name=hnRNP K
Alternative name(s):
    Transformation up-regulated nuclear protein
      Short name=TUNP

Gene names

Name:	HNRNPK
Synonyms:	HNRPK

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	463 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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.
Subunit structure	Interacts with ZIK1 By similarity. Identified in the spliceosome C complex, at least composed of AQR, ASCC3L1, C19orf29, CDC40, CDC5L, CRNKL1, DDX23, DDX41, DDX48, DDX5, DGCR14, DHX35, DHX38, DHX8, EFTUD2, FRG1, GPATC1, HNRPA1, HNRPA2B1, HNRPA3, HNRPC, HNRPF, HNRPH1, HNRNPK, HNRPM, HNRPR, HNRPU, KIAA1160, KIAA1604, LSM2, LSM3, MAGOH, MORG1, PABPC1, PLRG1, PNN, PPIE, PPIL1, PPIL3, PPWD1, PRPF19, PRPF4B, PRPF6, PRPF8, RALY, RBM22, RBM8A, RBMX, SART1, SF3A1, SF3A2, SF3A3, SF3B1, SF3B2, SF3B3, SFRS1, SKIV2L2, SNRPA1, SNRPB, SNRPB2, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, SNW1, SRRM1, SRRM2, SYF2, SYNCRIP, TFIP11, THOC4, U2AF1, WDR57, XAB2 and ZCCHC8. Interacts with HCV core protein. Interacts with ANKRD28.
Subcellular location	Cytoplasm. Nucleus › nucleoplasm.
Post-translational modification	Arg-296 and Arg-299 are dimethylated, probably to asymmetric dimethylarginine.
Sequence similarities	Contains 3 KH domains.
Mass spectrometry	Molecular weight is 50976.25 Da from positions 1 - 463 (P61978-1). Determined by MALDI. Ref.10

Ontologies

Keywords
Biological process	Host-virus interaction mRNA processing mRNA splicing
Cellular component	Cytoplasm Nucleus Spliceosome
Coding sequence diversity	Alternative splicing
Domain	Repeat
Ligand	DNA-binding RNA-binding
Molecular function	Ribonucleoprotein
PTM	Acetylation Methylation Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	nuclear mRNA splicing, via spliceosome Inferred from Experiment. Source: Reactome signal transduction Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Traceable author statement. Source: ProtInc heterogeneous nuclear ribonucleoprotein complex Ref.2 Traceable author statement. Source: ProtInc nucleoplasm Ref.1 Traceable author statement. Source: ProtInc
Molecular function	RNA binding Ref.2 Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
HCK	P08631	1	EBI-304185,EBI-346340
QKI	Q96PU8	1	EBI-304185,EBI-945792

Alternative products

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

Isoform 1 (identifier: P61978-1)

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: P61978-2)

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

Isoform 3 (identifier: P61978-3)

The sequence of this isoform differs from the canonical sequence as follows:
     111-134: Missing.
     459-463: SGKFF → ADVEGF

Notes: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Chain

1 – 463

463

Heterogeneous nuclear ribonucleoprotein K

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

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 By similarity

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

Modified residue

3

1

Phosphothreonine

Modified residue

36

1

Phosphoserine

Modified residue

116

1

Phosphoserine

Modified residue

214

1

Phosphoserine

Modified residue

216

1

Phosphoserine

Modified residue

284

1

Phosphoserine

Modified residue

296

1

Omega-N-methylated arginine

Modified residue

299

1

Omega-N-methylated arginine

Modified residue

379

1

Phosphoserine

Natural variations

Alternative sequence

111 – 134

24

Missing in isoform 3.

Alternative sequence

459 – 463

5

SGKFF → ADVEGF in isoform 2 and isoform 3.

Experimental info

Sequence conflict

32

1

A → D in CAA51267. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

463

Helix Strand Turn

Details...

Beta strand

388 – 395

8

Turn

396 – 398

3

Helix

399 – 402

4

Helix

405 – 407

3

Helix

408 – 417

10

Beta strand

420 – 423

4

Beta strand

430 – 439

10

Helix

441 – 459

19

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]. Checksum: 0B4EC22FE4534A06		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: C98A78A7462BF776		440	48,562
	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 430 440 QNAQYLLQNS VKQYADVEGF

References

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[1]	"Characterization and primary structure of the poly(C)-binding heterogeneous nuclear ribonucleoprotein complex K protein." Matunis M.J., Michael W.M., Dreyfuss G. Mol. Cell. Biol. 12:164-171(1992) [PubMed: 1729596] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION.
[2]	"Identification, molecular cloning, expression and chromosome mapping of a family of transformation upregulated hnRNP-K proteins derived by alternative splicing." Dejgaard K., Leffers H., Rasmussen H.H., Madsen P., Kruse T.A., Gesser B., Nielsen H., Celis J.E. J. Mol. Biol. 236:33-48(1994) [PubMed: 8107114] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PHOSPHORYLATION.
[3]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Brain.
[4]	"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. , 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: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	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. , 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] (ISOFORMS 1 AND 2). Tissue: Muscle.
[7]	Bienvenut W.V., Vousden K.H., Lukashchuk N. Submitted (MAR-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 1-52; 70-103; 149-163; 192-201; 208-219; 317-325; 378-405 AND 423-456, ACETYLATION AT MET-1, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[8]	Lubec G., Afjehi-Sadat L. Submitted (MAR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 149-163, MASS SPECTROMETRY. Tissue: Brain and Cajal-Retzius cell.
[9]	"Hepatitis C virus core protein interacts with heterogeneous nuclear ribonucleoprotein K." Hsieh T.-Y., Matsumoto M., Chou H.-C., Schneider R., Hwang S.B., Lee A.S., Lai M.M.C. J. Biol. Chem. 273:17651-17659(1998) [PubMed: 9651361] [Abstract] Cited for: INTERACTION WITH HCV CORE PROTEIN.
[10]	"Cluster analysis of an extensive human breast cancer cell line protein expression map database." Harris R.A., Yang A., Stein R.C., Lucy K., Brusten L., Herath A., Parekh R., Waterfield M.D., O'Hare M.J., Neville M.A., Page M.J., Zvelebil M.J. Proteomics 2:212-223(2002) [PubMed: 11840567] [Abstract] Cited for: MASS SPECTROMETRY. Tissue: Mammary cancer.
[11]	"Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis." Jurica M.S., Licklider L.J., Gygi S.P., Grigorieff N., Moore M.J. RNA 8:426-439(2002) [PubMed: 11991638] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE SPICEOSOMAL C COMPLEX.
[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-284, MASS SPECTROMETRY.
[13]	"PITK, a PP1 targeting subunit that modulates the phosphorylation of the transcriptional regulator hnRNP K." Kwiek N.C., Thacker D.F., Datto M.B., Megosh H.B., Haystead T.A.J. Cell. Signal. 18:1769-1778(2006) [PubMed: 16564677] [Abstract] Cited for: INTERACTION WITH ANKRD28, PHOSPHORYLATION AT SER-284.
[14]	"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-296 AND ARG-299, MASS SPECTROMETRY.
[15]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-3; SER-116 AND SER-284, MASS SPECTROMETRY. Tissue: Epithelium.
[16]	"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-36; SER-216 AND SER-284, MASS SPECTROMETRY. Tissue: Epithelium.
[17]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-216; SER-284 AND SER-379, MASS SPECTROMETRY. Tissue: Epithelium.
[18]	"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-214; SER-216 AND SER-379, MASS SPECTROMETRY. Tissue: Epithelium.
[19]	"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-116 AND SER-284, MASS SPECTROMETRY.
[20]	"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calci