SPEN

Protein identityUniProt · HPA

UniProt accession

Q96T58

Gene

SPEN

Ensembl

ENSG00000065526

Chromosome

1

Canonical length

3664 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins

Subcellular location

Nucleoplasm

OverviewNCBI Gene

This gene encodes a hormone inducible transcriptional repressor. Repression of transcription by this gene product can occur through interactions with other repressors, by the recruitment of proteins involved in histone deacetylation, or through sequestration of transcriptional activators. The product of this gene contains a carboxy-terminal domain that permits binding to other corepressor proteins. This domain also permits interaction with members of the NuRD complex, a nucleosome remodeling protein complex that contains deacetylase activity. In addition, this repressor contains several RNA recognition motifs that confer binding to a steroid receptor RNA coactivator; this binding can modulate the activity of both liganded and nonliganded steroid receptors. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

3664 residues, UniProt reviewed canonical sequence.

>Q96T58|SPEN
     1  MVRETRHLWV GNLPENVREE KIIEHFKRYG RVESVKILPK RGSEGGVAAF VDFVDIKSAQ
    61  KAHNSVNKMG DRDLRTDYNE PGTIPSAARG LDDTVSIASR SREVSGFRGG GGGPAYGPPP
   121  SLHAREGRYE RRLDGASDNR ERAYEHSAYG HHERGTGGFD RTRHYDQDYY RDPRERTLQH
   181  GLYYASRSRS PNRFDAHDPR YEPRAREQFT LPSVVHRDIY RDDITREVRG RRPERNYQHS
   241  RSRSPHSSQS RNQSPQRLAS QASRPTRSPS GSGSRSRSSS SDSISSSSST SSDSSDSSSS
   301  SSDDSPARSV QSAAVPAPTS QLLSSLEKDE PRKSFGIKVQ NLPVRSTDTS LKDGLFHEFK
   361  KFGKVTSVQI HGTSEERYGL VFFRQQEDQE KALTASKGKL FFGMQIEVTA WIGPETESEN
   421  EFRPLDERID EFHPKATRTL FIGNLEKTTT YHDLRNIFQR FGEIVDIDIK KVNGVPQYAF
   481  LQYCDIASVC KAIKKMDGEY LGNNRLKLGF GKSMPTNCVW LDGLSSNVSD QYLTRHFCRY
   541  GPVVKVVFDR LKGMALVLYN EIEYAQAAVK ETKGRKIGGN KIKVDFANRE SQLAFYHCME
   601  KSGQDIRDFY EMLAERREER RASYDYNQDR TYYESVRTPG TYPEDSRRDY PARGREFYSE
   661  WETYQGDYYE SRYYDDPREY RDYRNDPYEQ DIREYSYRQR ERERERERFE SDRDRDHERR
   721  PIERSQSPVH LRRPQSPGAS PSQAERLPSD SERRLYSRSS DRSGSCSSLS PPRYEKLDKS
   781  RLERYTKNEK TDKERTFDPE RVERERRLIR KEKVEKDKTD KQKRKGKVHS PSSQSSETDQ
   841  ENEREQSPEK PRSCNKLSRE KADKEGIAKN RLELMPCVVL TRVKEKEGKV IDHTPVEKLK
   901  AKLDNDTVKS SALDQKLQVS QTEPAKSDLS KLESVRMKVP KEKGLSSHVE VVEKEGRLKA
   961  RKHLKPEQPA DGVSAVDLEK LEARKRRFAD SNLKAEKQKP EVKKSSPEME DARVLSKKQP
  1021  DVSSREVILL REGEAERKPV RKEILKRESK KIKLDRLNTV ASPKDCQELA SISVGSGSRP
  1081  SSDLQARLGE LAGESVENQE VQSKKPIPSK PQLKQLQVLD DQGPEREDVR KNYCSLRDET
  1141  PERKSGQEKS HSVNTEEKIG IDIDHTQSYR KQMEQSRRKQ QMEMEIAKSE KFGSPKKDVD
  1201  EYERRSLVHE VGKPPQDVTD DSPPSKKKRM DHVDFDICTK RERNYRSSRQ ISEDSERTGG
  1261  SPSVRHGSFH EDEDPIGSPR LLSVKGSPKV DEKVLPYSNI TVREESLKFN PYDSSRREQM
  1321  ADMAKIKLSV LNSEDELNRW DSQMKQDAGR FDVSFPNSII KRDSLRKRSV RDLEPGEVPS
  1381  DSDEDGEHKS HSPRASALYE SSRLSFLLRD REDKLRERDE RLSSSLERNK FYSFALDKTI
  1441  TPDTKALLER AKSLSSSREE NWSFLDWDSR FANFRNNKDK EKVDSAPRPI PSWYMKKKKI
  1501  RTDSEGKMDD KKEDHKEEEQ ERQELFASRF LHSSIFEQDS KRLQHLERKE EDSDFISGRI
  1561  YGKQTSEGAN STTDSIQEPV VLFHSRFMEL TRMQQKEKEK DQKPKEVEKQ EDTENHPKTP
  1621  ESAPENKDSE LKTPPSVGPP SVTVVTLESA PSALEKTTGD KTVEAPLVTE EKTVEPATVS
  1681  EEAKPASEPA PAPVEQLEQV DLPPGADPDK EAAMMPAGVE EGSSGDQPPY LDAKPPTPGA
  1741  SFSQAESNVD PEPDSTQPLS KPAQKSEEAN EPKAEKPDAT ADAEPDANQK AEAAPESQPP
  1801  ASEDLEVDPP VAAKDKKPNK SKRSKTPVQA AAVSIVEKPV TRKSERIDRE KLKRSNSPRG
  1861  EAQKLLELKM EAEKITRTAS KNSAADLEHP EPSLPLSRTR RRNVRSVYAT MGDHENRSPV
  1921  KEPVEQPRVT RKRLERELQE AAAVPTTPRR GRPPKTRRRA DEEEENEAKE PAETLKPPEG
  1981  WRSPRSQKTA AGGGPQGKKG KNEPKVDATR PEATTEVGPQ IGVKESSMEP KAAEEEAGSE
  2041  QKRDRKDAGT DKNPPETAPV EVVEKKPAPE KNSKSKRGRS RNSRLAVDKS ASLKNVDAAV
  2101  SPRGAAAQAG ERESGVVAVS PEKSESPQKE DGLSSQLKSD PVDPDKEPEK EDVSASGPSP
  2161  EATQLAKQME LEQAVEHIAK LAEASASAAY KADAPEGLAP EDRDKPAHQA SETELAAAIG
  2221  SIINDISGEP ENFPAPPPYP GESQTDLQPP AGAQALQPSE EGMETDEAVS GILETEAATE
  2281  SSRPPVNAPD PSAGPTDTKE ARGNSSETSH SVPEAKGSKE VEVTLVRKDK GRQKTTRSRR
  2341  KRNTNKKVVA PVESHVPESN QAQGESPAAN EGTTVQHPEA PQEEKQSEKP HSTPPQSCTS
  2401  DLSKIPSTEN SSQEISVEER TPTKASVPPD LPPPPQPAPV DEEPQARFRV HSIIESDPVT
  2461  PPSDPSIPIP TLPSVTAAKL SPPVASGGIP HQSPPTKVTE WITRQEEPRA QSTPSPALPP
  2521  DTKASDVDTS SSTLRKILMD PKYVSATSVT STSVTTAIAE PVSAAPCLHE APPPPVDSKK
  2581  PLEEKTAPPV TNNSEIQASE VLVAADKEKV APVIAPKITS VISRMPVSID LENSQKITLA
  2641  KPAPQTLTGL VSALTGLVNV SLVPVNALKG PVKGSVTTLK SLVSTPAGPV NVLKGPVNVL
  2701  TGPVNVLTTP VNATVGTVNA APGTVNAAAS AVNATASAVT VTAGAVTAAS GGVTATTGTV
  2761  TMAGAVIAPS TKCKQRASAN ENSRFHPGSM PVIDDRPADA GSGAGLRVNT SEGVVLLSYS
  2821  GQKTEGPQRI SAKISQIPPA SAMDIEFQQS VSKSQVKPDS VTASQPPSKG PQAPAGYANV
  2881  ATHSTLVLTA QTYNASPVIS SVKADRPSLE KPEPIHLSVS TPVTQGGTVK VLTQGINTPP
  2941  VLVHNQLVLT PSIVTTNKKL ADPVTLKIET KVLQPANLGS TLTPHHPPAL PSKLPTEVNH
  3001  VPSGPSIPAD RTVSHLAAAK LDAHSPRPSG PGPSSFPRAS HPSSTASTAL STNATVMLAA
  3061  GIPVPQFISS IHPEQSVIMP PHSITQTVSL SHLSQGEVRM NTPTLPSITY SIRPEALHSP
  3121  RAPLQPQQIE VRAPQRASTP QPAPAGVPAL ASQHPPEEEV HYHLPVARAT APVQSEVLVM
  3181  QSEYRLHPYT VPRDVRIMVH PHVTAVSEQP RAADGVVKVP PASKAPQQPG KEAAKTPDAK
  3241  AAPTPTPAPV PVPVPLPAPA PAPHGEARIL TVTPSNQLQG LPLTPPVVVT HGVQIVHSSG
  3301  ELFQEYRYGD IRTYHPPAQL THTQFPAASS VGLPSRTKTA AQGPPPEGEP LQPPQPVQST
  3361  QPAQPAPPCP PSQLGQPGQP PSSKMPQVSQ EAKGTQTGVE QPRLPAGPAN RPPEPHTQVQ
  3421  RAQAETGPTS FPSPVSVSMK PDLPVSLPTQ TAPKQPLFVP TTSGPSTPPG LVLPHTEFQP
  3481  APKQDSSPHL TSQRPVDMVQ LLKKYPIVWQ GLLALKNDTA AVQLHFVSGN NVLAHRSLPL
  3541  SEGGPPLRIA QRMRLEATQL EGVARRMTVE TDYCLLLALP CGRDQEDVVS QTESLKAAFI
  3601  TYLQAKQAAG IINVPNPGSN QPAYVLQIFP PCEFSESHLS RLAPDLLASI SNISPHLMIV
  3661  IASV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SPEN can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0

Highest tissue expression

24 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SPEN.

Disease | AllUniProt

Conditions SPEN is implicated in, by any mechanism.

• Radio-Tartaglia syndrome (RATARS) MIM:619312

Disease | GeneticClinVar

104 pathogenic / likely-pathogenic of 977 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Radio-Tartaglia syndrome
• Inborn genetic diseases
• SPEN-related disorder
• Neurodevelopmental delay
• Encephalopathy

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.07

gnomAD pLI

1

gnomAD missense Z

2.89

DepMap mean gene effect

-0.05

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• negative regulation of DNA-templated transcription
• negative regulation of transcription by RNA polymerase II
• Notch signaling pathway
• positive regulation of neurogenesis
• random inactivation of X chromosome
• regulation of transcription by RNA polymerase II
• regulatory ncRNA-mediated heterochromatin formation

Molecular functions

• DNA binding
• mRNA binding
• RNA binding
• RNA polymerase II-specific DNA-binding transcription factor binding
• transcription corepressor activity

Cellular components

• extracellular exosome
• nucleoplasm
• nucleus
• transcription repressor complex

Protein domainsUniProt · Pfam · InterPro

• RNA recognition motif domain
• Spen paralogue/orthologue C-terminal, metazoa
• Nucleotide-binding alpha-beta plait domain superfamily
• Spen paralogue and orthologue SPOC, C-terminal
• SPOC-like, C-terminal domain superfamily
• RNA-binding domain superfamily
• RNA recognition motif
• SPOC domain
• SHARP, RNA recognition motif 1
• SHARP, RNA recognition motif 2
• SHARP, RNA recognition motif 3
• SHARP, RNA recognition motif 4
• Msx2-interacting protein, nuclear receptor-interacting domain
• Msx2-interacting protein, RAM7 domain
• Msx2-interacting protein, MID domain
• Msx2-interacting protein, RAM7 domain
• Msx2-interacting protein, MID domain
• Msx2-interacting protein, nuclear receptor-interacting domain

KeywordsUniProt

• Activator
• Coiled coil
• DNA-binding
• Host-virus interaction
• Intellectual disability
• Methylation
• Notch signaling pathway
• Nucleus
• Phosphoprotein
• Repeat
• Repressor
• RNA-binding
• Transcription
• Transcription regulation

InteractionsUniProt · HPA

Protein binding partners of SPEN in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• HDAC1
• HDAC2
• HIPK3
• MBD3
• MSX2
• MTA1L1
• NCOR2
• PPARD
• RAR
• RBBP4
• RBPSUH
• RBPJ