Seroatlas · Human Serome Atlas

SACS

Sacsin

Also known as: ARSACS, DKFZp686B15167, DNAJC29, KIAA0730, PPP1R138, SACS_HUMAN, SPAX6

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q9NZJ4
Gene: SACS
Ensembl: ENSG00000151835
Chromosome: 13
Canonical length: 4579 aa
Protein class: Cancer-related genes, Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins

OverviewNCBI Gene

This gene encodes the sacsin protein, which includes a UbL domain at the N-terminus, a DnaJ domain, and a HEPN domain at the C-terminus. The gene is highly expressed in the central nervous system, also found in skin, skeletal muscles and at low levels in the pancreas. This gene includes a very large exon spanning more than 12.8 kb. Mutations in this gene result in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), a neurodegenerative disorder characterized by early-onset cerebellar ataxia with spasticity and peripheral neuropathy. The authors of a publication on the effects of siRNA-mediated sacsin knockdown concluded that sacsin protects against mutant ataxin-1 and suggest that """"""""""""""""""""""""""""""""the large multi-domain sacsin protein is able to recruit Hsp70 chaperone action and has the potential to regulate the effects of other ataxia proteins"""""""""""""""""""""""""""""""" (Parfitt et al., PubMed: 19208651). A pseudogene associated with this gene is located on chromosome 11. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]

Canonical amino-acid sequenceUniProt

4579 residues, UniProt reviewed canonical sequence.

>Q9NZJ4|SACS
     1  METKENRWVP VTVLPGCVGC RTVAALASWT VRDVKERIFA ETGFPVSEQR LWRGGRELSD
    61  WIKIGDLTSK NCHLFVNLQS KGLKGGGRFG QTTPPLVDFL KDILRRYPEG GQILKELIQN
   121  AEDAGATEVK FLYDETQYGT ETLWSKDMAP YQGPALYVYN NAVFTPEDWH GIQEIARSRK
   181  KDDPLKVGRF GIGFNSVYHI TDVPCIFSGD QIGMLDPHQT LFGPHESGQC WNLKDDSKEI
   241  SELSDQFAPF VGIFGSTKET FINGNFPGTF FRFPLRLQPS QLSSNLYNKQ KVLELFESFR
   301  ADADTVLLFL KSVQDVSLYV READGTEKLV FRVTSSESKA LKHERPNSIK ILGTAISNYC
   361  KKTPSNNITC VTYHVNIVLE EESTKDAQKT SWLVCNSVGG RGISSKLDSL ADELKFVPII
   421  GIAMPLSSRD DEAKGATSDF SGKAFCFLPL PPGEESSTGL PVHISGFFGL TDNRRSIKWR
   481  ELDQWRDPAA LWNEFLVMNV VPKAYATLIL DSIKRLEMEK SSDFPLSVDV IYKLWPEASK
   541  VKVHWQPVLE PLFSELLQNA VIYSISCDWV RLEQVYFSEL DENLEYTKTV LNYLQSSGKQ
   601  IAKVPGNVDA AVQLTAASGT TPVRKVTPAW VRQVLRKCAH LGCAEEKLHL LEFVLSDQAY
   661  SELLGLELLP LQNGNFVPFS SSVSDQDVIY ITSAEYPRSL FPSLEGRFIL DNLKPHLVAA
   721  LKEAAQTRGR PCTQLQLLNP ERFARLIKEV MNTFWPGREL IVQWYPFDEN RNHPSVSWLK
   781  MVWKNLYIHF SEDLTLFDEM PLIPRTILEE GQTCVELIRL RIPSLVILDD ESEAQLPEFL
   841  ADIVQKLGGF VLKKLDASIQ HPLIKKYIHS PLPSAVLQIM EKMPLQKLCN QITSLLPTHK
   901  DALRKFLASL TDSSEKEKRI IQELAIFKRI NHSSDQGISS YTKLKGCKVL HHTAKLPADL
   961  RLSISVIDSS DEATIRLANM LKIEQLKTTS CLKLVLKDIE NAFYSHEEVT QLMLWVLENL
  1021  SSLKNENPNV LEWLTPLKFI QISQEQMVSA GELFDPDIEV LKDLFCNEEG TYFPPSVFTS
  1081  PDILHSLRQI GLKNEASLKE KDVVQVAKKI EALQVGACPD QDVLLKKAKT LLLVLNKNHT
  1141  LLQSSEGKMT LKKIKWVPAC KERPPNYPGS LVWKGDLCNL CAPPDMCDVG HAILIGSSLP
  1201  LVESIHVNLE KALGIFTKPS LSAVLKHFKI VVDWYSSKTF SDEDYYQFQH ILLEIYGFMH
  1261  DHLNEGKDSF RALKFPWVWT GKKFCPLAQA VIKPIHDLDL QPYLHNVPKT MAKFHQLFKV
  1321  CGSIEELTSD HISMVIQKIY LKSDQDLSEQ ESKQNLHLML NIIRWLYSNQ IPASPNTPVP
  1381  IHHSKNPSKL IMKPIHECCY CDIKVDDLND LLEDSVEPII LVHEDIPMKT AEWLKVPCLS
  1441  TRLINPENMG FEQSGQREPL TVRIKNILEE YPSVSDIFKE LLQNADDANA TECSFLIDMR
  1501  RNMDIRENLL DPGMAACHGP ALWSFNNSQF SDSDFVNITR LGESLKRGEV DKVGKFGLGF
  1561  NSVYHITDIP IIMSREFMIM FDPNINHISK HIKDKSNPGI KINWSKQQKR LRKFPNQFKP
  1621  FIDVFGCQLP LTVEAPYSYN GTLFRLSFRT QQEAKVSEVS STCYNTADIY SLVDEFSLCG
  1681  HRLIIFTQSV KSMYLKYLKI EETNPSLAQD TVIIKKKSCS SKALNTPVLS VLKEAAKLMK
  1741  TCSSSNKKLP SDEPKSSCIL QITVEEFHHV FRRIADLQSP LFRGPDDDPA ALFEMAKSGQ
  1801  SKKPSDELSQ KTVECTTWLL CTCMDTGEAL KFSLSESGRR LGLVPCGAVG VQLSEIQDQK
  1861  WTVKPHIGEV FCYLPLRIKT GLPVHINGCF AVTSNRKEIW KTDTKGRWNT TFMRHVIVKA
  1921  YLQVLSVLRD LATSGELMDY TYYAVWPDPD LVHDDFSVIC QGFYEDIAHG KGKELTKVFS
  1981  DGSTWVSMKN VRFLDDSILK RRDVGSAAFK IFLKYLKKTG SKNLCAVELP SSVKLGFEEA
  2041  GCKQILLENT FSEKQFFSEV FFPNIQEIEA ELRDPLMIFV LNEKVDEFSG VLRVTPCIPC
  2101  SLEGHPLVLP SRLIHPEGRV AKLFDIKDGR FPYGSTQDYL NPIILIKLVQ LGMAKDDILW
  2161  DDMLERAVSV AEINKSDHVA ACLRSSILLS LIDEKLKIRD PRAKDFAAKY QTIRFLPFLT
  2221  KPAGFSLDWK GNSFKPETMF AATDLYTAEH QDIVCLLQPI LNENSHSFRG CGSVSLAVKE
  2281  FLGLLKKPTV DLVINQLKEV AKSVDDGITL YQENITNACY KYLHEALMQN EITKMSIIDK
  2341  LKPFSFILVE NAYVDSEKVS FHLNFEAAPY LYQLPNKYKN NFRELFETVG VRQSCTVEDF
  2401  ALVLESIDQE RGTKQITEEN FQLCRRIISE GIWSLIREKK QEFCEKNYGK ILLPDTNLML
  2461  LPAKSLCYND CPWIKVKDTT VKYCHADIPR EVAVKLGAVP KRHKALERYA SNVCFTTLGT
  2521  EFGQKEKLTS RIKSILNAYP SEKEMLKELL QNADDAKATE ICFVFDPRQH PVDRIFDDKW
  2581  APLQGPALCV YNNQPFTEDD VRGIQNLGKG TKEGNPYKTG QYGIGFNSVY HITDCPSFIS
  2641  GNDILCIFDP HARYAPGATS ISPGRMFRDL DADFRTQFSD VLDLYLGTHF KLDNCTMFRF
  2701  PLRNAEMAKV SEISSVPASD RMVQNLLDKL RSDGAELLMF LNHMEKISIC EIDKSTGALN
  2761  VLYSVKGKIT DGDRLKRKQF HASVIDSVTK KRQLKDIPVQ QITYTMDTED SEGNLTTWLI
  2821  CNRSGFSSME KVSKSVISAH KNQDITLFPR GGVAACITHN YKKPHRAFCF LPLSLETGLP
  2881  FHVNGHFALD SARRNLWRDD NGVGVRSDWN NSLMTALIAP AYVELLIQLK KRYFPGSDPT
  2941  LSVLQNTPIH VVKDTLKKFL SFFPVNRLDL QPDLYCLVKA LYNCIHEDMK RLLPVVRAPN
  3001  IDGSDLHSAV IITWINMSTS NKTRPFFDNL LQDELQHLKN ADYNITTRKT VAENVYRLKH
  3061  LLLEIGFNLV YNCDETANLY HCLIDADIPV SYVTPADIRS FLMTFSSPDT NCHIGKLPCR
  3121  LQQTNLKLFH SLKLLVDYCF KDAEENEIEV EGLPLLITLD SVLQTFDAKR PKFLTTYHEL
  3181  IPSRKDLFMN TLYLKYSNIL LNCKVAKVFD ISSFADLLSS VLPREYKTKS CTKWKDNFAS
  3241  ESWLKNAWHF ISESVSVKED QEETKPTFDI VVDTLKDWAL LPGTKFTVSA NQLVVPEGDV
  3301  LLPLSLMHIA VFPNAQSDKV FHALMKAGCI QLALNKICSK DSAFVPLLSC HTANIESPTS
  3361  ILKALHYMVQ TSTFRAEKLV ENDFEALLMY FNCNLNHLMS QDDIKILKSL PCYKSISGRY
  3421  VSIGKFGTCY VLTKSIPSAE VEKWTQSSSS AFLEEKIHLK ELYEVIGCVP VDDLEVYLKH
  3481  LLPKIENLSY DAKLEHLIYL KNRLSSAEEL SEIKEQLFEK LESLLIIHDA NSRLKQAKHF
  3541  YDRTVRVFEV MLPEKLFIPN DFFKKLEQLI KPKNHVTFMT SWVEFLRNIG LKYILSQQQL
  3601  LQFAKEISVR ANTENWSKET LQNTVDILLH HIFQERMDLL SGNFLKELSL IPFLCPERAP
  3661  AEFIRFHPQY QEVNGTLPLI KFNGAQVNPK FKQCDVLQLL WTSCPILPEK ATPLSIKEQE
  3721  GSDLGPQEQL EQVLNMLNVN LDPPLDKVIN NCRNICNITT LDEEMVKTRA KVLRSIYEFL
  3781  SAEKREFRFQ LRGVAFVMVE DGWKLLKPEE VVINLEYESD FKPYLYKLPL ELGTFHQLFK
  3841  HLGTEDIIST KQYVEVLSRI FKNSEGKQLD PNEMRTVKRV VSGLFRSLQN DSVKVRSDLE
  3901  NVRDLALYLP SQDGRLVKSS ILVFDDAPHY KSRIQGNIGV QMLVDLSQCY LGKDHGFHTK
  3961  LIMLFPQKLR PRLLSSILEE QLDEETPKVC QFGALCSLQG RLQLLLSSEQ FITGLIRIMK
  4021  HENDNAFLAN EEKAIRLCKA LREGLKVSCF EKLQTTLRVK GFNPIPHSRS ETFAFLKRFG
  4081  NAVILLYIQH SDSKDINFLL ALAMTLKSAT DNLISDTSYL IAMLGCNDIY RIGEKLDSLG
  4141  VKYDSSEPSK LELPMPGTPI PAEIHYTLLM DPMNVFYPGE YVGYLVDAEG GDIYGSYQPT
  4201  YTYAIIVQEV EREDADNSSF LGKIYQIDIG YSEYKIVSSL DLYKFSRPEE SSQSRDSAPS
  4261  TPTSPTEFLT PGLRSIPPLF SGRESHKTSS KHQSPKKLKV NSLPEILKEV TSVVEQAWKL
  4321  PESERKKIIR RLYLKWHPDK NPENHDIANE VFKHLQNEIN RLEKQAFLDQ NADRASRRTF
  4381  STSASRFQSD KYSFQRFYTS WNQEATSHKS ERQQQNKEKC PPSAGQTYSQ RFFVPPTFKS
  4441  VGNPVEARRW LRQARANFSA ARNDLHKNAN EWVCFKCYLS TKLALIAADY AVRGKSDKDV
  4501  KPTALAQKIE EYSQQLEGLT NDVHTLEAYG VDSLKTRYPD LLPFPQIPND RFTSEVAMRV
  4561  MECTACIIIK LENFMQQKV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SACS 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: 14 nTPM

Expression across tissuesHPA

Tissue

parathyroid gland: 14 nTPM
tongue: 13 nTPM
skeletal muscle: 9.2 nTPM
cerebral cortex: 8.9 nTPM
basal ganglia: 6.5 nTPM
blood vessel: 6.2 nTPM

Single-cell type

myonuclei: 516 nCPM
cardiomyocytes: 472 nCPM
thymic myoid cells: 271 nCPM
myosatellite cells: 148 nCPM
brain inhibitory neurons: 139 nCPM
thyrotrophs: 135 nCPM

Immune cell

T-reg: 0.9 nTPM
myeloid DC: 0.4 nTPM
naive B-cell: 0.4 nTPM
memory CD4 T-cell: 0.3 nTPM
plasmacytoid DC: 0.3 nTPM
gdT-cell: 0.2 nTPM

Brain region

cerebral cortex: 68 nTPM
white matter: 57 nTPM
thalamus: 53 nTPM
pons: 51 nTPM
basal ganglia: 49 nTPM
cerebellum: 46 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SACS.

Disease | AllUniProt

Conditions SACS is implicated in, by any mechanism.

Spastic ataxia Charlevoix-Saguenay type (SACS) MIM:270550

Disease | GeneticClinVar

993 pathogenic / likely-pathogenic of 4,938 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Charlevoix-Saguenay spastic ataxia
Spastic paraplegia
Hereditary spastic paraplegia
Inborn genetic diseases
SACS-related disorder

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): 0.54
gnomAD pLI: 0
gnomAD missense Z: 0.94
DepMap mean gene effect: -0.16
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

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

Ubiquitin-like domain
DnaJ domain
Ubiquitin-like domain superfamily
Chaperone J-domain superfamily
Histidine kinase/HSP90-like ATPase superfamily
Ubiquitin family
HEPN domain
Sacsin chaperone regulator
Sacsin/Nov domain
HEPN domain
Sacsin domain

KeywordsUniProt

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads SACS as an antibody target. Whether an autoantibody or antibody against SACS could matter depends on whether native SACS is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

SACS is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label SACS as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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