Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
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. May play a role as a negative regulator of cell growth. Inhibits cell proliferation. Involved in splice site selection of vascular endothelial growth factor. Induces an increased concentration-dependent incorporation of exon in CD44 pre-mRNA by direct binding to purine-rich exonic enhancer. RNA-binding abilities are down-regulated by tyrosine kinase PTK6. Involved in post-transcriptional regulation of HIV-1 gene expression. Binds preferentially to the 5'-[AU]UAAA-3' motif in vitro.3 Publications

GO - Molecular functioni

  • poly(A) RNA binding Source: UniProtKB
  • RNA binding Source: UniProtKB

GO - Biological processi

  • regulation of transcription, DNA-templated Source: UniProtKB-KW
  • spermatogenesis Source: ProtInc
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

RNA-binding

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

HGNCiHGNC:18117. KHDRBS3.

Subcellular locationi

GO - Cellular componenti

  • nucleoplasm Source: HPA
  • nucleus Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi212 – 25140Missing : Complete loss of SIAH1-mediated degradation. 1 PublicationAdd
BLAST
Mutagenesisi327 – 34620Missing : Complete loss of nuclear sublocalization. 1 PublicationAdd
BLAST

Organism-specific databases

PharmGKBiPA30094.

Polymorphism and mutation databases

BioMutaiKHDRBS3.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 346346KH domain-containing, RNA-binding, signal transduction-associated protein 3PRO_0000232522Add
BLAST

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

Phosphoprotein

Proteomic databases

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

PTM databases

iPTMnetiO75525.
PhosphoSiteiO75525.

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

BgeeiO75525.
CleanExiHS_KHDRBS3.
ExpressionAtlasiO75525. baseline and differential.
GenevisibleiO75525. HS.

Organism-specific databases

HPAiHPA000275.
HPA000500.
HPA000981.

Interactioni

Subunit structurei

Self-associates to form homooligomers. Interacts with the splicing regulatory proteins SFRS9, SAFB and YTHDC1. Interacts also with HNRPL and SLM1/KHDRBS2 (By similarity). Interacts with KHDRBS1, RBMX, RBMY1A1 and with p85 subunit of PI3-kinase. Interacts also with SIAH1 which promotes targeting for degradation.By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BAHD1Q8TBE04EBI-722504,EBI-742750
DMRT3Q9NQL93EBI-722504,EBI-9679045
INPP5DQ928353EBI-722504,EBI-1380477
MARK4Q6IPE93EBI-722504,EBI-10250211
NELFBQ8WX922EBI-722504,EBI-347721
PRPF31F1T0A53EBI-722504,EBI-10177194
YTHDC1Q96MU73EBI-722504,EBI-2849854

Protein-protein interaction databases

BioGridi115899. 38 interactions.
IntActiO75525. 29 interactions.
MINTiMINT-1411200.
STRINGi9606.ENSP00000348108.

Structurei

Secondary structure

1
346
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi5 – 1511Combined sources
Helixi21 – 3515Combined sources
Turni48 – 503Combined sources
Beta strandi54 – 618Combined sources
Turni64 – 663Combined sources
Helixi72 – 776Combined sources
Helixi79 – 813Combined sources
Helixi83 – 919Combined sources
Beta strandi93 – 997Combined sources
Beta strandi102 – 1043Combined sources
Helixi106 – 11510Combined sources
Helixi118 – 1247Combined sources
Beta strandi127 – 1359Combined sources
Helixi137 – 15115Combined sources
Helixi152 – 1543Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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. Positions 2-183.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini61 – 12767KHAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni212 – 25140Interaction with SIAH1Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi250 – 26112Pro-richAdd
BLAST
Compositional biasi266 – 31651Tyr-richAdd
BLAST

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
Contains 1 KH domain.Curated

Keywords - Domaini

SH3-binding

Phylogenomic databases

eggNOGiKOG1588. Eukaryota.
COG5176. LUCA.
GeneTreeiENSGT00550000074434.
HOGENOMiHOG000230771.
HOVERGENiHBG079164.
InParanoidiO75525.
KOiK14942.
OMAiDDYYEYG.
OrthoDBiEOG75MVX3.
PhylomeDBiO75525.
TreeFamiTF314878.

Family and domain databases

Gene3Di3.30.1370.10. 1 hit.
InterProiIPR004087. KH_dom.
IPR004088. KH_dom_type_1.
IPR032571. Qua1_dom.
IPR032335. Sam68-YY.
[Graphical view]
PfamiPF00013. KH_1. 1 hit.
PF16274. Qua1. 1 hit.
PF16568. Sam68-YY. 1 hit.
[Graphical view]
SMARTiSM00322. KH. 1 hit.
[Graphical view]
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti41 – 411Missing in AAH68536 (PubMed:15489334).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei270 – 2712DY → WC in isoform 2. 1 PublicationVSP_017905
Alternative sequencei272 – 34675Missing in isoform 2. 1 PublicationVSP_017906Add
BLAST

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

Cross-referencesi

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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. Positions 2-183.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115899. 38 interactions.
IntActiO75525. 29 interactions.
MINTiMINT-1411200.
STRINGi9606.ENSP00000348108.

PTM databases

iPTMnetiO75525.
PhosphoSiteiO75525.

Polymorphism and mutation databases

BioMutaiKHDRBS3.

Proteomic databases

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

Protocols and materials databases

DNASUi10656.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi10656.
GeneCardsiKHDRBS3.
HGNCiHGNC:18117. KHDRBS3.
HPAiHPA000275.
HPA000500.
HPA000981.
MIMi610421. gene.
neXtProtiNX_O75525.
PharmGKBiPA30094.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1588. Eukaryota.
COG5176. LUCA.
GeneTreeiENSGT00550000074434.
HOGENOMiHOG000230771.
HOVERGENiHBG079164.
InParanoidiO75525.
KOiK14942.
OMAiDDYYEYG.
OrthoDBiEOG75MVX3.
PhylomeDBiO75525.
TreeFamiTF314878.

Miscellaneous databases

ChiTaRSiKHDRBS3. human.
GeneWikiiKHDRBS3.
GenomeRNAii10656.
NextBioi40513.
PROiO75525.
SOURCEiSearch...

Gene expression databases

BgeeiO75525.
CleanExiHS_KHDRBS3.
ExpressionAtlasiO75525. baseline and differential.
GenevisibleiO75525. HS.

Family and domain databases

Gene3Di3.30.1370.10. 1 hit.
InterProiIPR004087. KH_dom.
IPR004088. KH_dom_type_1.
IPR032571. Qua1_dom.
IPR032335. Sam68-YY.
[Graphical view]
PfamiPF00013. KH_1. 1 hit.
PF16274. Qua1. 1 hit.
PF16568. Sam68-YY. 1 hit.
[Graphical view]
SMARTiSM00322. KH. 1 hit.
[Graphical view]
SUPFAMiSSF54791. SSF54791. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Salpalpha and Salpbeta, growth-arresting homologs of Sam68."
    Lee J.-S., Burr J.G.
    Gene 240:133-147(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [MRNA] OF 8-346 (ISOFORM 2), FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH P85 SUBUNIT OF PI3-KINASE, PHOSPHORYLATION.
    Tissue: Retina.
  2. "T-STAR/ETOILE: a novel relative of SAM68 that interacts with an RNA-binding protein implicated in spermatogenesis."
    Venables J.P., Vernet C., Chew S.L., Elliott D.J., Cowmeadow R.B., Wu J., Cooke H.J., Artzt K., Eperon I.C.
    Hum. Mol. Genet. 8:959-969(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH KHDRBS1 AND RBMX, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
    Tissue: Testis.
  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 1).
    Tissue: Brain and Skin.
  4. Lubec G., Chen W.-Q.
    Submitted (JAN-2009) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 45-52 AND 154-164, IDENTIFICATION BY MASS SPECTROMETRY.
    Tissue: Fetal brain.
  5. "Characterization of Sam68-like mammalian proteins SLM-1 and SLM-2: SLM-1 is a Src substrate during mitosis."
    Di Fruscio M., Chen T., Richard S.
    Proc. Natl. Acad. Sci. U.S.A. 96:2710-2715(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
    Tissue: Brain.
  6. "RBMY, a probable human spermatogenesis factor, and other hnRNP G proteins interact with Tra2beta and affect splicing."
    Venables J.P., Elliott D.J., Makarova O.V., Makarov E.M., Cooke H.J., Eperon E.C.
    Hum. Mol. Genet. 9:685-694(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH RBMY1A1.
    Tissue: Testis.
  7. "Down-regulation of T-STAR, a growth inhibitory protein, after SV40-mediated immortalization."
    Kool J., van Zaane W., van der Eb A.J., Terleth C.
    Cell Growth Differ. 12:535-541(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION, MUTAGENESIS OF 327-LYS--TYR-346.
  8. "A role for KH domain proteins (Sam68-like mammalian proteins and quaking proteins) in the post-transcriptional regulation of HIV replication."
    Reddy T.R., Suhasini M., Xu W., Yeh L.-Y., Yang J.-P., Wu J., Artzt K., Wong-Staal F.
    J. Biol. Chem. 277:5778-5784(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. "SIAH1 targets the alternative splicing factor T-STAR for degradation by the proteasome."
    Venables J.P., Dalgliesh C., Paronetto M.P., Skitt L., Thornton J.K., Saunders P.T., Sette C., Jones K.T., Elliott D.J.
    Hum. Mol. Genet. 13:1525-1534(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SIAH1, DOMAIN, MUTAGENESIS OF 212-ARG--PRO-251.
  10. "Sam68-like mammalian protein 2, identified by digital differential display as expressed by podocytes, is induced in proteinuria and involved in splice site selection of vascular endothelial growth factor."
    Cohen C.D., Doran P.P., Blattner S.M., Merkle M., Wang G.Q., Schmid H., Mathieson P.W., Saleem M.A., Henger A., Rastaldi M.P., Kretzler M.
    J. Am. Soc. Nephrol. 16:1958-1965(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, INDUCTION, FUNCTION.
  11. "Rapid and systematic analysis of the RNA recognition specificities of RNA-binding proteins."
    Ray D., Kazan H., Chan E.T., Pena Castillo L., Chaudhry S., Talukder S., Blencowe B.J., Morris Q., Hughes T.R.
    Nat. Biotechnol. 27:667-670(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: RNA-BINDING.
  12. "Lysine acetylation targets protein complexes and co-regulates major cellular functions."
    Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
    Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiKHDR3_HUMAN
AccessioniPrimary (citable) accession number: O75525
Secondary accession number(s): Q6NUL8, Q9UPA8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 18, 2006
Last sequence update: November 1, 1998
Last modified: May 11, 2016
This is version 141 of the entry and version 1 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.