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Protein

KH domain-containing, RNA-binding, signal transduction-associated protein 3

Gene

KHDRBS3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

RNA-binding protein that plays a role in the regulation of alternative splicing and influences mRNA splice site selection and exon inclusion. Binds preferentially to the 5'-[AU]UAAA-3' motif in vitro. Binds optimally to RNA containing 5'-[AU]UAA-3' as a bipartite motif spaced by more than 15 nucleotides. Binds poly(A). RNA-binding abilities are down-regulated by tyrosine kinase PTK6 (PubMed:10564820, PubMed:19561594, PubMed:26758068). Involved in splice site selection of vascular endothelial growth factor (PubMed:15901763). In vitro regulates CD44 alternative splicing by direct binding to purine-rich exonic enhancer (By similarity). Can regulate alternative splicing of neurexins NRXN1-3 in the laminin G-like domain 6 containing the evolutionary conserved neurexin alternative spliced segment 4 (AS4) involved in neurexin selective targeting to postsynaptic partners such as neuroligins and LRRTM family members (PubMed:26758068). Targeted, cell-type specific splicing regulation of NRXN1 at AS4 is involved in neuronal glutamatergic synapse function and plasticity (By similarity). May regulate expression of KHDRBS2/SLIM-1 in defined brain neuron populations by modifying its alternative splicing (By similarity). Can bind FABP9 mRNA (By similarity). May play a role as a negative regulator of cell growth. Inhibits cell proliferation.By similarity4 Publications
(Microbial infection) Involved in post-transcriptional regulation of HIV-1 gene expression.1 Publication

GO - Molecular functioni

  • identical protein binding Source: UniProtKB
  • protein domain specific binding Source: UniProtKB
  • RNA binding Source: UniProtKB
  • SH3 domain binding Source: UniProtKB-KW

GO - Biological processi

Keywordsi

Molecular functionRNA-binding
Biological processmRNA processing, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-8849468. PTK6 Regulates Proteins Involved in RNA Processing.

Names & Taxonomyi

Protein namesi
Recommended name:
KH domain-containing, RNA-binding, signal transduction-associated protein 3
Alternative name(s):
RNA-binding protein T-Star
Sam68-like mammalian protein 2
Short name:
SLM-2
Sam68-like phosphotyrosine protein
Gene namesi
Name:KHDRBS3
Synonyms:SALP, SLM2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000131773.13.
HGNCiHGNC:18117. KHDRBS3.

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

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi141Y → E: Fails to influence alternative splicing of CD44, NRXN2 and NRXN3. 1 Publication1
Mutagenesisi212 – 251Missing : Complete loss of SIAH1-mediated degradation. 1 PublicationAdd BLAST40
Mutagenesisi327 – 346Missing : Complete loss of nuclear sublocalization. 1 PublicationAdd BLAST20

Organism-specific databases

DisGeNETi10656.
OpenTargetsiENSG00000131773.
PharmGKBiPA30094.

Polymorphism and mutation databases

BioMutaiKHDRBS3.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002325221 – 346KH domain-containing, RNA-binding, signal transduction-associated protein 3Add BLAST346

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki4Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

Post-translational modificationi

Phosphorylated on tyrosine residues. Isoform 1 C-terminal region is tyrosine-rich, but isoform 2 lacking this C-terminal region is also tyrosine-phosphorylated.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO75525.
MaxQBiO75525.
PaxDbiO75525.
PeptideAtlasiO75525.
PRIDEiO75525.
TopDownProteomicsiO75525-2. [O75525-2]

PTM databases

iPTMnetiO75525.
PhosphoSitePlusiO75525.

Expressioni

Tissue specificityi

Ubiquitous with higher expression in testis, skeletal muscle and brain. Expressed in the kidney only in podocytes, the glomerular epithelial cells of the kidney. Strongly expressed after meiosis.3 Publications

Inductioni

Induced in proteinuric diseases. Down-regulated in immortalized fibroblasts isolated after a proliferative crisis accompanied with massive cell death.2 Publications

Gene expression databases

BgeeiENSG00000131773.
CleanExiHS_KHDRBS3.
ExpressionAtlasiO75525. baseline and differential.
GenevisibleiO75525. HS.

Organism-specific databases

HPAiHPA000275.
HPA000500.
HPA000981.

Interactioni

Subunit structurei

Self-associates to form homooligomers; dimerization increases RNA affinity (PubMed:26758068). Interacts with KHDRBS2/SLM-1 (By similarity). Interacts with KHDRBS1/SAM68; heterooligomer formation of KHDRBS family proteins may modulate RNA substrate specificity (PubMed:10332027). Interacts with the splicing regulatory proteins SFRS9, SAFB and YTHDC1. Interacts with HNRPL (By similarity). Interacts with RBMX, RBMY1A1, p85 subunit of PI3-kinase, SERPINB5 (PubMed:10564820, PubMed:10332027, PubMed:10749975, PubMed:21725612). Interacts with SIAH1 which promotes targeting for degradation (PubMed:15163637).By similarity5 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • identical protein binding Source: UniProtKB
  • protein domain specific binding Source: UniProtKB
  • SH3 domain binding Source: UniProtKB-KW

Protein-protein interaction databases

BioGridi115899. 39 interactors.
IntActiO75525. 54 interactors.
MINTiMINT-1411200.
STRINGi9606.ENSP00000348108.

Structurei

Secondary structure

1346
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi5 – 15Combined sources11
Helixi21 – 35Combined sources15
Turni48 – 50Combined sources3
Beta strandi54 – 61Combined sources8
Turni64 – 66Combined sources3
Helixi72 – 77Combined sources6
Helixi79 – 81Combined sources3
Helixi83 – 91Combined sources9
Beta strandi93 – 99Combined sources7
Beta strandi102 – 104Combined sources3
Helixi106 – 115Combined sources10
Helixi118 – 124Combined sources7
Beta strandi127 – 135Combined sources9
Helixi137 – 151Combined sources15
Helixi152 – 154Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5EL3X-ray1.59A/B/C/D50-160[»]
5ELRX-ray2.30C/D50-183[»]
5ELSX-ray2.87A/B/C/D/E/F50-160[»]
5ELTX-ray2.13A/B1-160[»]
5EMOX-ray3.03A/B1-183[»]
ProteinModelPortaliO75525.
SMRiO75525.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini61 – 127KHAdd BLAST67

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 160Involved in homodimerization1 PublicationAdd BLAST160
Regioni212 – 251Interaction with SIAH11 PublicationAdd BLAST40

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi250 – 261Pro-richAdd BLAST12
Compositional biasi266 – 316Tyr-richAdd BLAST51

Domaini

The proline-rich site binds the SH3 domain of the p85 subunit of PI3-kinase.1 Publication

Sequence similaritiesi

Belongs to the KHDRBS family.Curated

Keywords - Domaini

SH3-binding

Phylogenomic databases

eggNOGiKOG1588. Eukaryota.
COG5176. LUCA.
GeneTreeiENSGT00550000074434.
HOGENOMiHOG000230771.
HOVERGENiHBG079164.
InParanoidiO75525.
KOiK14942.
OMAiDDYYEYG.
OrthoDBiEOG091G0EED.
PhylomeDBiO75525.
TreeFamiTF314878.

Family and domain databases

Gene3Di3.30.1370.10. 1 hit.
InterProiView protein in InterPro
IPR004087. KH_dom.
IPR004088. KH_dom_type_1.
IPR036612. KH_dom_type_1_sf.
IPR032571. Qua1_dom.
IPR032335. Sam68-YY.
PfamiView protein in Pfam
PF00013. KH_1. 1 hit.
PF16274. Qua1. 1 hit.
PF16568. Sam68-YY. 1 hit.
SMARTiView protein in SMART
SM00322. KH. 1 hit.
SUPFAMiSSF54791. SSF54791. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O75525-1) [UniParc]FASTAAdd to basket
Also known as: SALP-alpha

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
MEEKYLPELM AEKDSLDPSF THALRLVNQE IEKFQKGEGK DEEKYIDVVI
60 70 80 90 100
NKNMKLGQKV LIPVKQFPKF NFVGKLLGPR GNSLKRLQEE TLTKMSILGK
110 120 130 140 150
GSMRDKAKEE ELRKSGEAKY FHLNDDLHVL IEVFAPPAEA YARMGHALEE
160 170 180 190 200
IKKFLIPDYN DEIRQAQLQE LTYLNGGSEN ADVPVVRGKP TLRTRGVPAP
210 220 230 240 250
AITRGRGGVT ARPVGVVVPR GTPTPRGVLS TRGPVSRGRG LLTPRARGVP
260 270 280 290 300
PTGYRPPPPP PTQETYGEYD YDDGYGTAYD EQSYDSYDNS YSTPAQSGAD
310 320 330 340
YYDYGHGLSE ETYDSYGQEE WTNSRHKAPS ARTAKGVYRD QPYGRY
Length:346
Mass (Da):38,800
Last modified:November 1, 1998 - v1
Checksum:iCA37968A4DF6D573
GO
Isoform 2 (identifier: O75525-2) [UniParc]FASTAAdd to basket
Also known as: SALP-beta

The sequence of this isoform differs from the canonical sequence as follows:
     270-271: DY → WC
     272-346: Missing.

Show »
Length:271
Mass (Da):30,250
Checksum:iC4E93A2824644224
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti41Missing in AAH68536 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_017905270 – 271DY → WC in isoform 2. 1 Publication2
Alternative sequenceiVSP_017906272 – 346Missing in isoform 2. 1 PublicationAdd BLAST75

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF051321 mRNA. Translation: AAC99294.1.
AF051322 mRNA. Translation: AAC99295.1.
AF069681 mRNA. Translation: AAC24857.1.
BC032606 mRNA. Translation: AAH32606.1.
BC068536 mRNA. Translation: AAH68536.1.
CCDSiCCDS6374.1. [O75525-1]
RefSeqiNP_006549.1. NM_006558.2. [O75525-1]
UniGeneiHs.444558.

Genome annotation databases

EnsembliENST00000355849; ENSP00000348108; ENSG00000131773. [O75525-1]
GeneIDi10656.
KEGGihsa:10656.
UCSCiuc003yuv.4. human. [O75525-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiKHDR3_HUMAN
AccessioniPrimary (citable) accession number: O75525
Secondary accession number(s): Q6NUL8, Q9UPA8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 18, 2006
Last sequence update: November 1, 1998
Last modified: October 25, 2017
This is version 154 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

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families