Seroatlas · Human Serome Atlas

SMCR8

Guanine nucleotide exchange protein SMCR8

Also known as: DENND8A, FLJ34716, SMCR8_HUMAN

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

Protein identityUniProt · HPA

UniProt accession: Q8TEV9
Gene: SMCR8
Ensembl: ENSG00000176994
Chromosome: 17
Canonical length: 937 aa
Protein class: Predicted intracellular proteins
Subcellular location: Nucleoplasm
Quaternary structure: Homodimer

OverviewNCBI Gene

Enables GTPase activator activity; protein kinase binding activity; and protein kinase inhibitor activity. Contributes to guanyl-nucleotide exchange factor activity. Involved in negative regulation of gene expression; regulation of TOR signaling; and regulation of macroautophagy. Located in Atg1/ULK1 kinase complex; chromatin; and nucleoplasm. Part of guanyl-nucleotide exchange factor complex. [provided by Alliance of Genome Resources, Jul 2025]

Canonical amino-acid sequenceUniProt

937 residues, UniProt reviewed canonical sequence.

>Q8TEV9|SMCR8
     1  MISAPDVVAF TKEEEYEEEP YNEPALPEEY SVPLFPFASQ GANPWSKLSG AKFSRDFILI
    61  SEFSEQVGPQ PLLTIPNDTK VFGTFDLNYF SLRIMSVDYQ ASFVGHPPGS AYPKLNFVED
   121  SKVVLGDSKE GAFAYVHHLT LYDLEARGFV RPFCMAYISA DQHKIMQQFQ ELSAEFSRAS
   181  ECLKTGNRKA FAGELEKKLK DLDYTRTVLH TETEIQKKAN DKGFYSSQAI EKANELASVE
   241  KSIIEHQDLL KQIRSYPHRK LKGHDLCPGE MEHIQDQASQ ASTTSNPDES ADTDLYTCRP
   301  AYTPKLIKAK STKCFDKKLK TLEELCDTEY FTQTLAQLSH IEHMFRGDLC YLLTSQIDRA
   361  LLKQQHITNF LFEDFVEVDD RMVEKQESIP SKPSQDRPPS SSLEECPIPK VLISVGSYKS
   421  SVESVLIKME QELGDEEYKE VEVTELSSFD PQENLDYLDM DMKGSISSGE SIEVLGTEKS
   481  TSVLSKSDSQ ASLTVPLSPQ VVRSKAVSHR TISEDSIEVL STCPSEALIP DDFKASYPSA
   541  INEEESYPDG NEGAIRFQAS ISPPELGETE EGSIENTPSQ IDSSCCIGKE SDGQLVLPST
   601  PAHTHSDEDG VVSSPPQRHR QKDQGFRVDF SVENANPSSR DNSCEGFPAY ELDPSHLLAS
   661  RDISKTSLDN YSDTTSYVSS VASTSSDRIP SAYPAGLSSD RHKKRAGQNA LKFIRQYPFA
   721  HPAIYSLLSG RTLVVLGEDE AIVRKLVTAL AIFVPSYGCY AKPVKHWASS PLHIMDFQKW
   781  KLIGLQRVAS PAGAGTLHAL SRYSRYTSIL DLDNKTLRCP LYRGTLVPRL ADHRTQIKRG
   841  STYYLHVQSM LTQLCSKAFL YTFCHHLHLP THDKETEELV ASRQMSFLKL TLGLVNEDVR
   901  VVQYLAELLK LHYMQESPGT SHPMLRFDYV PSFLYKI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SMCR8 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): 0.46
Highest tissue expression: 12 nTPM

Expression across tissuesHPA

Tissue

bone marrow: 12 nTPM
spleen: 7.9 nTPM
small intestine: 6.8 nTPM
cerebellum: 6.3 nTPM
salivary gland: 6.2 nTPM
skeletal muscle: 6 nTPM

Single-cell type

microglia: 12 nCPM
choroid plexus epithelial cells: 11 nCPM
proximal tubule cells: 9.1 nCPM
renal collecting duct intercalated cells: 8.7 nCPM
podocytes: 7.7 nCPM
loop of henle epithelial cells: 6.8 nCPM

Immune cell

basophil: 2.5 nTPM
non-classical monocyte: 0.7 nTPM
classical monocyte: 0.5 nTPM
neutrophil: 0.5 nTPM
eosinophil: 0.4 nTPM
intermediate monocyte: 0.3 nTPM

Brain region

choroid plexus: 8.7 nTPM
hypothalamus: 8.2 nTPM
thalamus: 8 nTPM
white matter: 7.8 nTPM
cerebellum: 7.7 nTPM
medulla oblongata: 7.4 nTPM

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): 0.65
gnomAD pLI: 0
gnomAD missense Z: -1.03
DepMap mean gene effect: -0.08
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

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of SMCR8 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads SMCR8 as an antibody target. Whether an autoantibody or antibody against SMCR8 could matter depends on whether native SMCR8 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

SMCR8 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 SMCR8 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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