Seroatlas · Human Serome Atlas

NTN4

Netrin-4

Also known as: NET4_HUMAN

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

Protein identityUniProt · HPA

UniProt accession: Q9HB63
Gene: NTN4
Ensembl: ENSG00000074527
Chromosome: 12
Canonical length: 628 aa
Protein class: Cancer-related genes, Predicted intracellular proteins, Predicted secreted proteins
Secretome location: Secreted to extracellular matrix
Quaternary structure: Homodimer

OverviewNCBI Gene

This gene encodes a member of the netrin family of proteins, which function in various biological processes including axon guidance, tumorogenesis, and angiogenesis. Netrins are laminin-related proteins that have an N-terminal laminin-type domain, epidermal growth factor-like repeat domain, and a positively charged heparin-binding domain at the C-terminus. The protein encoded by this gene is involved in processes including neurite growth and migration, angiogenesis and mural cell adhesion to endothelial cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

Canonical amino-acid sequenceUniProt

628 residues, UniProt reviewed canonical sequence.

>Q9HB63|NTN4
     1  MGSCARLLLL WGCTVVAAGL SGVAGVSSRC EKACNPRMGN LALGRKLWAD TTCGQNATEL
    61  YCFYSENTDL TCRQPKCDKC NAAYPHLAHL PSAMADSSFR FPRTWWQSAE DVHREKIQLD
   121  LEAEFYFTHL IVMFKSPRPA AMVLDRSQDF GKTWKPYKYF ATNCSATFGL EDDVVKKGAI
   181  CTSKYSSPFP CTGGEVIFKA LSPPYDTENP YSAKVQEQLK ITNLRVQLLK RQSCPCQRND
   241  LNEEPQHFTH YAIYDFIVKG SCFCNGHADQ CIPVHGFRPV KAPGTFHMVH GKCMCKHNTA
   301  GSHCQHCAPL YNDRPWEAAD GKTGAPNECR TCKCNGHADT CHFDVNVWEA SGNRSGGVCD
   361  DCQHNTEGQY CQRCKPGFYR DLRRPFSAPD ACKPCSCHPV GSAVLPANSV TFCDPSNGDC
   421  PCKPGVAGRR CDRCMVGYWG FGDYGCRPCD CAGSCDPITG DCISSHTDID WYHEVPDFRP
   481  VHNKSEPAWE WEDAQGFSAL LHSGKCECKE QTLGNAKAFC GMKYSYVLKI KILSAHDKGT
   541  HVEVNVKIKK VLKSTKLKIF RGKRTLYPES WTDRGCTCPI LNPGLEYLVA GHEDIRTGKL
   601  IVNMKSFVQH WKPSLGRKVM DILKRECK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NTN4 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: Secreted
Secreted: Yes
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.33
Highest tissue expression: 171 nTPM

Expression across tissuesHPA

Tissue

spleen: 171 nTPM
kidney: 101 nTPM
breast: 68 nTPM
lung: 66 nTPM
heart muscle: 63 nTPM
ovary: 60 nTPM

Single-cell type

renal collecting duct principal cells: 635 nCPM
papillary tip epithelial cells: 490 nCPM
loop of henle epithelial cells: 405 nCPM
urothelial cells: 389 nCPM
breast hormone-responsive cells: 386 nCPM
basal prostatic cells: 363 nCPM

Immune cell

MAIT T-cell: 1.6 nTPM
memory CD4 T-cell: 0.1 nTPM
memory CD8 T-cell: 0.1 nTPM
basophil: 0 nTPM
classical monocyte: 0 nTPM
eosinophil: 0 nTPM

Brain region

choroid plexus: 21 nTPM
cerebral cortex: 18 nTPM
midbrain: 14 nTPM
white matter: 14 nTPM
basal ganglia: 11 nTPM
hippocampal formation: 9.6 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): 0.34
gnomAD pLI: 0.92
gnomAD missense Z: 1.74
DepMap mean gene effect: -0.08
DepMap dependency class: none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

animal organ morphogenesis
axon guidance
basement membrane assembly
cell migration
neuron remodeling
substrate adhesion-dependent cell spreading
tissue development
regulation of branching involved in salivary gland morphogenesis by extracellular matrix-epithelial cell signaling

Molecular functions

laminin-1 binding

Cellular components

plasma membrane
laminin complex

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads NTN4 as an antibody target. Whether an autoantibody or antibody against NTN4 could matter depends on whether native NTN4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

NTN4 is annotated as secreted, so native NTN4 circulates and is directly accessible to antibodies. Secreted and cell-surface proteins are the autoantibody targets most likely to act like drugs, blocking or depleting the native protein.

Annotation status

The present source text does not explicitly label NTN4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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