SASH1

Protein identityUniProt · HPA

UniProt accession

O94885

Gene

SASH1

Ensembl

ENSG00000111961

Chromosome

6

Canonical length

1247 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Cytosol

OverviewNCBI Gene

This gene encodes a scaffold protein involved in the TLR4 signaling pathway that may stimulate cytokine production and endothelial cell migration in response to invading pathogens. The encoded protein has also been described as a potential tumor suppressor that may negatively regulate proliferation, apoptosis, and invasion of cancer cells, and reduced expression of this gene has been observed in multiple human cancers. Mutations in this gene may be associated with abnormal skin pigmentation in human patients. [provided by RefSeq, Oct 2016]

Canonical amino-acid sequenceUniProt

1247 residues, UniProt reviewed canonical sequence.

>O94885|SASH1
     1  MEDAGAAGPG PEPEPEPEPE PEPAPEPEPE PKPGAGTSEA FSRLWTDVMG ILDGSLGNID
    61  DLAQQYADYY NTCFSDVCER MEELRKRRVS QDLEVEKPDA SPTSLQLRSQ IEESLGFCSA
   121  VSTPEVERKN PLHKSNSEDS SVGKGDWKKK NKYFWQNFRK NQKGIMRQTS KGEDVGYVAS
   181  EITMSDEERI QLMMMVKEKM ITIEEALARL KEYEAQHRQS AALDPADWPD GSYPTFDGSS
   241  NCNSREQSDD ETEESVKFKR LHKLVNSTRR VRKKLIRVEE MKKPSTEGGE EHVFENSPVL
   301  DERSALYSGV HKKPLFFDGS PEKPPEDDSD SLTTSPSSSS LDTWGAGRKL VKTFSKGESR
   361  GLIKPPKKMG TFFSYPEEEK AQKVSRSLTE GEMKKGLGSL SHGRTCSFGG FDLTNRSLHV
   421  GSNNSDPMGK EGDFVYKEVI KSPTASRISL GKKVKSVKET MRKRMSKKYS SSVSEQDSGL
   481  DGMPGSPPPS QPDPEHLDKP KLKAGGSVES LRSSLSGQSS MSGQTVSTTD SSTSNRESVK
   541  SEDGDDEEPP YRGPFCGRAR VHTDFTPSPY DTDSLKLKKG DIIDIISKPP MGTWMGLLNN
   601  KVGTFKFIYV DVLSEDEEKP KRPTRRRRKG RPPQPKSVED LLDRINLKEH MPTFLFNGYE
   661  DLDTFKLLEE EDLDELNIRD PEHRAVLLTA VELLQEYDSN SDQSGSQEKL LVDSQGLSGC
   721  SPRDSGCYES SENLENGKTR KASLLSAKSS TEPSLKSFSR NQLGNYPTLP LMKSGDALKQ
   781  GQEEGRLGGG LAPDTSKSCD PPGVTGLNKN RRSLPVSICR SCETLEGPQT VDTWPRSHSL
   841  DDLQVEPGAE QDVPTEVTEP PPQIVPEVPQ KTTASSTKAQ PLEQDSAVDN ALLLTQSKRF
   901  SEPQKLTTKK LEGSIAASGR GLSPPQCLPR NYDAQPPGAK HGLARTPLEG HRKGHEFEGT
   961  HHPLGTKEGV DAEQRMQPKI PSQPPPVPAK KSRERLANGL HPVPMGPSGA LPSPDAPCLP
  1021  VKRGSPASPT SPSDCPPALA PRPLSGQAPG SPPSTRPPPW LSELPENTSL QEHGVKLGPA
  1081  LTRKVSCARG VDLETLTENK LHAEGIDLTE EPYSDKHGRC GIPEALVQRY AEDLDQPERD
  1141  VAANMDQIRV KQLRKQHRMA IPSGGLTEIC RKPVSPGCIS SVSDWLISIG LPMYAGTLST
  1201  AGFSTLSQVP SLSHTCLQEA GITEERHIRK LLSAARLFKL PPGPEAM

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SASH1 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)

0.6

Highest tissue expression

71 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SASH1.

Disease | AllUniProt

Conditions SASH1 is implicated in, by any mechanism.

• Dyschromatosis universalis hereditaria 1 (DUH1) MIM:127500
• Cancer, alopecia, pigment dyscrasia, onychodystrophy, and keratoderma (CAPOK) MIM:618373

Disease | GeneticClinVar

14 pathogenic / likely-pathogenic of 356 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Dyschromatosis universalis hereditaria 1
• Ungual dystrophy
• dyschromatosis
• spino-cellular carcinoma
• Alopecia

Disease | ImmuneIEDB

Conditions an epitope on SASH1 was assayed in.

• skin melanoma T cell

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)

0.44

gnomAD pLI

0

gnomAD missense Z

0.6

DepMap mean gene effect

0.1

DepMap dependency class

none

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

• positive regulation of angiogenesis
• positive regulation of endothelial cell migration
• positive regulation of JUN kinase activity
• positive regulation of lipopolysaccharide-mediated signaling pathway
• positive regulation of non-canonical NF-kappaB signal transduction
• positive regulation of p38MAPK cascade
• protein polyubiquitination
• regulation of epithelial cell migration
• regulation of protein autoubiquitination
• regulation of protein K63-linked ubiquitination

Molecular functions

• G-protein alpha-subunit binding
• mitogen-activated protein kinase kinase kinase binding
• molecular adaptor activity
• protein kinase binding

Cellular components

• cytoplasm
• cytosol
• nucleoplasm
• protein-containing complex

Protein domainsUniProt · Pfam · InterPro

• SH3 domain
• Sterile alpha motif domain
• Sterile alpha motif/pointed domain superfamily
• SLy proteins associated disordered region
• SH3-like domain superfamily
• SAM and SH3 domain-containing protein
• SASH1/NUB1, homeodomain-like domain
• SAM domain (Sterile alpha motif)
• SAM domain (Sterile alpha motif)
• Variant SH3 domain
• SLy Proteins Associated Disordered Region
• SASH1 homeodomain-like domain
• SAM and SH3 domain-containing protein 1, SH3 domain
• SASH1, SAM domain repeat 1
• SASH1, SAM domain repeat 2

KeywordsUniProt

• Cytoplasm
• Hypotrichosis
• Palmoplantar keratoderma
• Phosphoprotein
• Repeat
• SH3 domain
• Tumor suppressor

InteractionsUniProt · HPA

Protein binding partners of SASH1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CHUK
• GNAS
• IKBKB
• IQGAP1
• MAP3K7
• TRAF6
• SFN
• YWHAZ