SIM1

Protein identityUniProt · HPA

UniProt accession

P81133

Gene

SIM1

Ensembl

ENSG00000112246

Chromosome

6

Canonical length

766 aa

Protein class

Plasma proteins, Predicted intracellular proteins, Transcription factors

Subcellular location

Nuclear speckles

OverviewNCBI Gene

SIM1 and SIM2 genes are Drosophila single-minded (sim) gene homologs. SIM1 transcript was detected only in fetal kidney out of various adult and fetal tissues tested. Since the sim gene plays an important role in Drosophila development and has peak levels of expression during the period of neurogenesis,it was proposed that the human SIM gene is a candidate for involvement in certain dysmorphic features (particularly the facial and skull characteristics), abnormalities of brain development, and/or cognitive disability of Down syndrome. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

766 residues, UniProt reviewed canonical sequence.

>P81133|SIM1
     1  MKEKSKNAAR TRREKENSEF YELAKLLPLP SAITSQLDKA SIIRLTTSYL KMRVVFPEGL
    61  GEAWGHSSRT SPLDNVGREL GSHLLQTLDG FIFVVAPDGK IMYISETASV HLGLSQVELT
   121  GNSIYEYIHP ADHDEMTAVL TAHQPYHSHF VQEYEIERSF FLRMKCVLAK RNAGLTCGGY
   181  KVIHCSGYLK IRQYSLDMSP FDGCYQNVGL VAVGHSLPPS AVTEIKLHSN MFMFRASLDM
   241  KLIFLDSRVA ELTGYEPQDL IEKTLYHHVH GCDTFHLRCA HHLLLVKGQV TTKYYRFLAK
   301  HGGWVWVQSY ATIVHNSRSS RPHCIVSVNY VLTDTEYKGL QLSLDQISAS KPAFSYTSSS
   361  TPTMTDNRKG AKSRLSSSKS KSRTSPYPQY SGFHTERSES DHDSQWGGSP LTDTASPQLL
   421  DPADRPGSQH DASCAYRQFS DRSSLCYGFA LDHSRLVEER HFHTQACEGG RCEAGRYFLG
   481  TPQAGREPWW GSRAALPLTK ASPESREAYE NSMPHIASVH RIHGRGHWDE DSVVSSPDPG
   541  SASESGDRYR TEQYQSSPHE PSKIETLIRA TQQMIKEEEN RLQLRKAPSD QLASINGAGK
   601  KHSLCFANYQ QPPPTGEVCH GSALANTSPC DHIQQREGKM LSPHENDYDN SPTALSRISS
   661  PNSDRISKSS LILAKDYLHS DISPHQTAGD HPTVSPNCFG SHRQYFDKHA YTLTGYALEH
   721  LYDSETIRNY SLGCNGSHFD VTSHLRMQPD PAQGHKGTSV IITNGS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SIM1 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)

0.52

Highest tissue expression

9.2 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SIM1.

Disease | GeneticClinVar

12 pathogenic / likely-pathogenic of 457 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• SIM1-related disorder
• Obesity due to SIM1 deficiency
• Brachydactyly
• SIM1-associated metabolic syndrome
• Inborn genetic diseases

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)

0.25

gnomAD pLI

1

gnomAD missense Z

0.71

DepMap mean gene effect

0.03

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell differentiation
• nervous system development
• regulation of transcription by RNA polymerase II
• ureteric bud development

Molecular functions

• DNA binding
• DNA-binding transcription factor activity
• DNA-binding transcription factor activity, RNA polymerase II-specific
• protein heterodimerization activity
• RNA polymerase II transcription regulatory region sequence-specific DNA binding

Cellular components

• chromatin
• nucleus

Protein domainsUniProt · Pfam · InterPro

• PAS domain
• PAC motif
• Single-minded, C-terminal
• Myc-type, basic helix-loop-helix (bHLH) domain
• PAS fold 3
• PAS fold
• PAS domain superfamily
• Helix-loop-helix DNA-binding domain superfamily
• PAS fold
• Single-minded protein C-terminus
• PAS fold
• Hypoxia-inducible factor 1-alpha bHLH domain

KeywordsUniProt

• Developmental protein
• Differentiation
• DNA-binding
• Neurogenesis
• Nucleus
• Repeat
• Transcription
• Transcription regulation

InteractionsUniProt · HPA

Protein binding partners of SIM1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ARNT
• ARNT2