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Protein

Heterogeneous nuclear ribonucleoprotein K

Gene

HNRNPK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.By similarity3 Publications

Caution

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • identical protein binding Source: IntAct
  • protein domain specific binding Source: UniProtKB
  • RNA binding Source: UniProtKB
  • RNA polymerase II proximal promoter sequence-specific DNA binding Source: BHF-UCL
  • single-stranded DNA binding Source: BHF-UCL
  • transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding Source: BHF-UCL

GO - Biological processi

  • mRNA splicing, via spliceosome Source: Reactome
  • negative regulation of apoptotic process Source: MGI
  • negative regulation of mRNA splicing, via spliceosome Source: Ensembl
  • positive regulation of low-density lipoprotein particle receptor biosynthetic process Source: BHF-UCL
  • positive regulation of receptor-mediated endocytosis Source: BHF-UCL
  • positive regulation of transcription by RNA polymerase II Source: BHF-UCL
  • regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: Ensembl
  • regulation of lipid transport by positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • regulation of low-density lipoprotein particle clearance Source: BHF-UCL
  • RNA metabolic process Source: Reactome
  • RNA processing Source: ProtInc
  • signal transduction Source: ProtInc
  • viral process Source: UniProtKB-KW

Keywordsi

Molecular functionActivator, DNA-binding, Repressor, Ribonucleoprotein, RNA-binding
Biological processHost-virus interaction, mRNA processing, mRNA splicing, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-4570464 SUMOylation of RNA binding proteins
R-HSA-72163 mRNA Splicing - Major Pathway
R-HSA-72203 Processing of Capped Intron-Containing Pre-mRNA
SIGNORiP61978

Names & Taxonomyi

Protein namesi
Recommended name:
Heterogeneous nuclear ribonucleoprotein K
Short name:
hnRNP K
Alternative name(s):
Transformation up-regulated nuclear protein
Short name:
TUNP
Gene namesi
Name:HNRNPK
Synonyms:HNRPK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000165119.18
HGNCiHGNC:5044 HNRNPK
MIMi600712 gene
neXtProtiNX_P61978

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cell projection, Cytoplasm, Nucleus, Spliceosome

Pathology & Biotechi

Involvement in diseasei

Au-Kline syndrome (AUKS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by intellectual disability, facial dysmorphism, cardiac defects, and connective tissue and skeletal abnormalities. Dysmorphic features include long palpebral fissures, ptosis, a broad prominent nasal bridge, hypoplastic alae nasi, an open downturned mouth, ears with underdeveloped and thick helices, high palate, and a unique tongue with a prominent median crease. Hypotonia, hyporeflexia, and high pain tolerance are additional features.
See also OMIM:616580

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi422K → R: Loss of sumoylation. Loss of TP53 transcriptional stimulation. 1 Publication1
Mutagenesisi424D → A: Loss of sumoylation. 1 Publication1

Keywords - Diseasei

Mental retardation

Organism-specific databases

DisGeNETi3190
MalaCardsiHNRNPK
MIMi616580 phenotype
OpenTargetsiENSG00000165119
PharmGKBiPA162391350

Polymorphism and mutation databases

BioMutaiHNRNPK
DMDMi48429103

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000500961 – 463Heterogeneous nuclear ribonucleoprotein KAdd BLAST463

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1 Publication1
Modified residuei34N6-acetyllysine; alternateBy similarity1
Cross-linki34Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateCombined sources
Cross-linki34Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei36PhosphoserineCombined sources1
Modified residuei39PhosphothreonineBy similarity1
Cross-linki52Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki60Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei75PhosphoserineCombined sources1
Modified residuei116PhosphoserineCombined sources1
Cross-linki163Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateCombined sources
Cross-linki163Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei198N6-acetyllysineBy similarity1
Modified residuei214PhosphoserineCombined sources1
Modified residuei216PhosphoserineCombined sources1
Modified residuei219N6-succinyllysine; alternateBy similarity1
Cross-linki219Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei284PhosphoserineCombined sources1 Publication1
Modified residuei316Omega-N-methylarginineCombined sources1
Modified residuei377Omega-N-methylarginineBy similarity1
Modified residuei379PhosphoserineCombined sources1
Modified residuei380PhosphotyrosineCombined sources1
Modified residuei405N6-acetyllysine; alternateBy similarity1
Cross-linki405Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei420PhosphoserineCombined sources1
Cross-linki422Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate
Cross-linki422Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateCombined sources
Cross-linki422Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources

Post-translational modificationi

Arg-296 and Arg-299 are dimethylated, probably to asymmetric dimethylarginine.
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.3 Publications
Ubiquitinated by MDM2. Doxorubicin treatment does not affect monoubiquitination, but slightly decreases HNRNPK poly-ubiquitination.2 Publications
O-glycosylated (O-GlcNAcylated), in a cell cycle-dependent manner.1 Publication

Keywords - PTMi

Acetylation, Glycoprotein, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP61978
PaxDbiP61978
PeptideAtlasiP61978
PRIDEiP61978
TopDownProteomicsiP61978-1 [P61978-1]

2D gel databases

SWISS-2DPAGEiP61978

PTM databases

iPTMnetiP61978
PhosphoSitePlusiP61978
SwissPalmiP61978

Miscellaneous databases

PMAP-CutDBiP61978

Expressioni

Inductioni

By DNA damage, including ionizing radiations and phleomycin treatment or UV irradiation. This induction requires ATM kinase activity (ionizing radiations and phleomycin) or ATR activity (UV irradiation). Up-regulation is due to protein stabilization. Constitutive protein levels are controlled by MDM2-mediated ubiquitination and degradation via the proteasome pathway.1 Publication

Gene expression databases

BgeeiENSG00000165119
CleanExiHS_HNRNPK
ExpressionAtlasiP61978 baseline and differential
GenevisibleiP61978 HS

Organism-specific databases

HPAiCAB004435
CAB016225
HPA007644
HPA044105

Interactioni

Subunit structurei

Interacts with RBM42 and ZIK1. Interacts with BRDT (By similarity). Identified in the spliceosome C complex. Interacts with ANKRD28. Interacts with HCV core protein. Interacts with ASFV p30 protein. Interacts with DDX1. Interacts with MDM2; this interaction leads to ubiquitination and proteasomal degradation. Interacts with p53/TP53.By similarity7 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • identical protein binding Source: IntAct
  • protein domain specific binding Source: UniProtKB

Protein-protein interaction databases

BioGridi109431278 interactors.
CORUMiP61978
DIPiDIP-31805N
IntActiP61978 176 interactors.
MINTiP61978
STRINGi9606.ENSP00000365439

Structurei

Secondary structure

1463
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi377 – 380Combined sources4
Helixi381 – 384Combined sources4
Beta strandi388 – 395Combined sources8
Turni396 – 398Combined sources3
Helixi399 – 402Combined sources4
Helixi405 – 407Combined sources3
Helixi408 – 417Combined sources10
Beta strandi420 – 423Combined sources4
Beta strandi430 – 439Combined sources10
Helixi441 – 459Combined sources19

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1J5KNMR-A379-463[»]
1KHMNMR-A379-463[»]
1ZZIX-ray1.80A/B385-463[»]
1ZZJX-ray2.30A/B/C385-463[»]
1ZZKX-ray0.95A385-463[»]
ProteinModelPortaliP61978
SMRiP61978
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP61978

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini42 – 104KH 1PROSITE-ProRule annotationAdd BLAST63
Repeati54 – 761-1Add BLAST23
Repeati59 – 623-14
Domaini144 – 209KH 2PROSITE-ProRule annotationAdd BLAST66
Repeati245 – 2502-16
Repeati257 – 2603-24
Repeati267 – 2703-34
Repeati295 – 2983-44
Repeati324 – 3292-26
Domaini387 – 451KH 3PROSITE-ProRule annotationAdd BLAST65
Repeati399 – 4211-2Add BLAST23
Repeati404 – 4073-54

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 276Necessary for interaction with DDX11 PublicationAdd BLAST276
Regioni35 – 197Interaction with ASFV p30Add BLAST163
Regioni54 – 4212 X 22 AA approximate repeatsAdd BLAST368
Regioni59 – 4075 X 4 AA repeats of G-X-G-GAdd BLAST349
Regioni209 – 337Interaction with ZIK1By similarityAdd BLAST129
Regioni236 – 273RNA-binding RGG-boxAdd BLAST38
Regioni245 – 3292 X 6 AA approximate repeatsAdd BLAST85

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi289 – 294Poly-Pro6
Compositional biasi310 – 315Poly-Pro6

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG2192 Eukaryota
ENOG4111GSB LUCA
GeneTreeiENSGT00760000119144
HOVERGENiHBG051916
InParanoidiP61978
KOiK12886
OMAiNIPQGHD
OrthoDBiEOG091G0DHI
PhylomeDBiP61978
TreeFamiTF316335

Family and domain databases

Gene3Di3.30.1370.103 hits
InterProiView protein in InterPro
IPR033090 hnRNP_K
IPR004087 KH_dom
IPR004088 KH_dom_type_1
IPR036612 KH_dom_type_1_sf
IPR012987 ROK_N
PANTHERiPTHR10288:SF221 PTHR10288:SF221, 1 hit
PfamiView protein in Pfam
PF00013 KH_1, 3 hits
PF08067 ROKNT, 1 hit
SMARTiView protein in SMART
SM00322 KH, 3 hits
SUPFAMiSSF54791 SSF54791, 3 hits
PROSITEiView protein in PROSITE
PS50084 KH_TYPE_1, 3 hits

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P61978-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
METEQPEETF PNTETNGEFG KRPAEDMEEE QAFKRSRNTD EMVELRILLQ
60 70 80 90 100
SKNAGAVIGK GGKNIKALRT DYNASVSVPD SSGPERILSI SADIETIGEI
110 120 130 140 150
LKKIIPTLEE GLQLPSPTAT SQLPLESDAV ECLNYQHYKG SDFDCELRLL
160 170 180 190 200
IHQSLAGGII GVKGAKIKEL RENTQTTIKL FQECCPHSTD RVVLIGGKPD
210 220 230 240 250
RVVECIKIIL DLISESPIKG RAQPYDPNFY DETYDYGGFT MMFDDRRGRP
260 270 280 290 300
VGFPMRGRGG FDRMPPGRGG RPMPPSRRDY DDMSPRRGPP PPPPGRGGRG
310 320 330 340 350
GSRARNLPLP PPPPPRGGDL MAYDRRGRPG DRYDGMVGFS ADETWDSAID
360 370 380 390 400
TWSPSEWQMA YEPQGGSGYD YSYAGGRGSY GDLGGPIITT QVTIPKDLAG
410 420 430 440 450
SIIGKGGQRI KQIRHESGAS IKIDEPLEGS EDRIITITGT QDQIQNAQYL
460
LQNSVKQYSG KFF
Length:463
Mass (Da):50,976
Last modified:June 7, 2004 - v1
Checksum:i0F70EE169B2A064A
GO
Isoform 2 (identifier: P61978-2) [UniParc] [UniParc]FASTAAdd to basket

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

Show »
Length:464
Mass (Da):51,028
Checksum:i0B4EC22FE4534A06
GO
Isoform 3 (identifier: P61978-3) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:440
Mass (Da):48,562
Checksum:iC98A78A7462BF776
GO

Sequence cautioni

The sequence BAD92799 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti32A → D in CAA51267 (PubMed:8107114).Curated1

Mass spectrometryi

Isoform 1 : Molecular mass is 50976.25 Da from positions 1 - 463. Determined by MALDI. 1 Publication

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_021669111 – 134Missing in isoform 3. 1 PublicationAdd BLAST24
Alternative sequenceiVSP_002822459 – 463SGKFF → ADVEGF in isoform 2 and isoform 3. 2 Publications5

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S74678 mRNA Translation: AAB20770.1
X72727 mRNA Translation: CAA51267.1
CR456771 mRNA Translation: CAG33052.1
AB209562 mRNA Translation: BAD92799.1 Different initiation.
AK291336 mRNA Translation: BAF84025.1
AB451263 mRNA Translation: BAG70077.1
AB451390 mRNA Translation: BAG70204.1
AL354733 Genomic DNA No translation available.
CH471089 Genomic DNA Translation: EAW62675.1
CH471089 Genomic DNA Translation: EAW62677.1
BC000355 mRNA Translation: AAH00355.1
BC014980 mRNA Translation: AAH14980.1
CCDSiCCDS6667.1
CCDS6668.1 [P61978-2]
PIRiS43363
RefSeqiNP_001305115.1, NM_001318186.1
NP_001305116.1, NM_001318187.1 [P61978-3]
NP_001305117.1, NM_001318188.1 [P61978-1]
NP_002131.2, NM_002140.4 [P61978-2]
NP_112552.1, NM_031262.3 [P61978-1]
NP_112553.1, NM_031263.3 [P61978-2]
XP_005252017.1, XM_005251960.2 [P61978-2]
XP_005252020.1, XM_005251963.3 [P61978-3]
XP_005252022.1, XM_005251965.2 [P61978-3]
XP_016870157.1, XM_017014668.1 [P61978-1]
UniGeneiHs.522257

Genome annotation databases

EnsembliENST00000351839; ENSP00000317788; ENSG00000165119 [P61978-1]
ENST00000360384; ENSP00000353552; ENSG00000165119 [P61978-1]
ENST00000376263; ENSP00000365439; ENSG00000165119 [P61978-2]
ENST00000376281; ENSP00000365458; ENSG00000165119 [P61978-2]
GeneIDi3190
KEGGihsa:3190
UCSCiuc004anf.5 human
uc004ang.5 human

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiHNRPK_HUMAN
AccessioniPrimary (citable) accession number: P61978
Secondary accession number(s): Q07244
, Q15671, Q59F98, Q5T6W4, Q60577, Q6IBN1, Q922Y7, Q96J62
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 7, 2004
Last sequence update: June 7, 2004
Last modified: April 25, 2018
This is version 179 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome