NRCAM

Protein identityUniProt · HPA

UniProt accession

Q92823

Gene

NRCAM

Ensembl

ENSG00000091129

Chromosome

7

Canonical length

1304 aa

Protein class

Disease related genes, Plasma proteins, Predicted membrane proteins, Predicted secreted proteins

Subcellular location

Nucleoplasm,Vesicles,Plasma membrane,Primary cilium,Cytosol

Secretome location

Secreted in brain

OverviewNCBI Gene

Cell adhesion molecules (CAMs) are members of the immunoglobulin superfamily. This gene encodes a neuronal cell adhesion molecule with multiple immunoglobulin-like C2-type domains and fibronectin type-III domains. This ankyrin-binding protein is involved in neuron-neuron adhesion and promotes directional signaling during axonal cone growth. This gene is also expressed in non-neural tissues and may play a general role in cell-cell communication via signaling from its intracellular domain to the actin cytoskeleton during directional cell migration. Allelic variants of this gene have been associated with autism and addiction vulnerability. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

1304 residues, UniProt reviewed canonical sequence.

>Q92823|NRCAM
     1  MQLKIMPKKK RLSAGRVPLI LFLCQMISAL EVPLDPKLLE DLVQPPTITQ QSPKDYIIDP
    61  RENIVIQCEA KGKPPPSFSW TRNGTHFDID KDPLVTMKPG TGTLIINIMS EGKAETYEGV
   121  YQCTARNERG AAVSNNIVVR PSRSPLWTKE KLEPITLQSG QSLVLPCRPP IGLPPPIIFW
   181  MDNSFQRLPQ SERVSQGLNG DLYFSNVLPE DTREDYICYA RFNHTQTIQQ KQPISVKVIS
   241  VDELNDTIAA NLSDTEFYGA KSSRERPPTF LTPEGNASNK EELRGNVLSL ECIAEGLPTP
   301  IIYWAKEDGM LPKNRTVYKN FEKTLQIIHV SEADSGNYQC IAKNALGAIH HTISVRVKAA
   361  PYWITAPQNL VLSPGEDGTL ICRANGNPKP RISWLTNGVP IEIAPDDPSR KIDGDTIIFS
   421  NVQERSSAVY QCNASNEYGY LLANAFVNVL AEPPRILTPA NTLYQVIANR PALLDCAFFG
   481  SPLPTIEWFK GAKGSALHED IYVLHENGTL EIPVAQKDST GTYTCVARNK LGMAKNEVHL
   541  EIKDPTWIVK QPEYAVVQRG SMVSFECKVK HDHTLSLTVL WLKDNRELPS DERFTVDKDH
   601  LVVADVSDDD SGTYTCVANT TLDSVSASAV LSVVAPTPTP APVYDVPNPP FDLELTDQLD
   661  KSVQLSWTPG DDNNSPITKF IIEYEDAMHK PGLWHHQTEV SGTQTTAQLK LSPYVNYSFR
   721  VMAVNSIGKS LPSEASEQYL TKASEPDKNP TAVEGLGSEP DNLVITWKPL NGFESNGPGL
   781  QYKVSWRQKD GDDEWTSVVV ANVSKYIVSG TPTFVPYLIK VQALNDMGFA PEPAVVMGHS
   841  GEDLPMVAPG NVRVNVVNST LAEVHWDPVP LKSIRGHLQG YRIYYWKTQS SSKRNRRHIE
   901  KKILTFQGSK THGMLPGLEP FSHYTLNVRV VNGKGEGPAS PDRVFNTPEG VPSAPSSLKI
   961  VNPTLDSLTL EWDPPSHPNG ILTEYTLKYQ PINSTHELGP LVDLKIPANK TRWTLKNLNF
  1021  STRYKFYFYA QTSAGSGSQI TEEAVTTVDE AGILPPDVGA GKVQAVNPRI SNLTAAAAET
  1081  YANISWEYEG PEHVNFYVEY GVAGSKEEWR KEIVNGSRSF FGLKGLMPGT AYKVRVGAVG
  1141  DSGFVSSEDV FETGPAMASR QVDIATQGWF IGLMCAVALL ILILLIVCFI RRNKGGKYPV
  1201  KEKEDAHADP EIQPMKEDDG TFGEYSDAED HKPLKKGSRT PSDRTVKKED SDDSLVDYGE
  1261  GVNGQFNEDG SFIGQYSGKK EKEPAEGNES SEAPSPVNAM NSFV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NRCAM 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

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.35

Highest tissue expression

102 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NRCAM.

Disease | AllUniProt

Conditions NRCAM is implicated in, by any mechanism.

• Neurodevelopmental disorder with neuromuscular and skeletal abnormalities (NEDNMS) MIM:619833

Disease | GeneticClinVar

14 pathogenic / likely-pathogenic of 260 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• NRCAM-related disorder
• Neurodevelopmental disorder with neuromuscular and skeletal abnormalities

Disease | ImmuneIEDB

Conditions an epitope on NRCAM was assayed in.

• glioblastoma T cell
• malignant astrocytoma 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)

0.38

gnomAD pLI

0.02

gnomAD missense Z

1.91

DepMap mean gene effect

0.01

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• angiogenesis
• axon guidance
• axonal fasciculation
• axonogenesis
• brain development
• cell-cell adhesion
• central nervous system development
• clustering of voltage-gated sodium channels
• intracellular protein localization
• neuron migration
• neuronal action potential propagation
• positive regulation of neuron differentiation
• regulation of axon extension
• regulation of neuron projection development
• regulation of postsynapse organization
• retinal ganglion cell axon guidance
• synapse assembly

Molecular functions

• ankyrin binding
• cell-cell adhesion mediator activity
• protein binding involved in heterotypic cell-cell adhesion

Cellular components

• axon
• axon initial segment
• external side of plasma membrane
• extracellular region
• glutamatergic synapse
• neuron projection
• plasma membrane
• postsynaptic density membrane

Protein domainsUniProt · Pfam · InterPro

• Immunoglobulin/major histocompatibility complex, conserved site
• Immunoglobulin subtype 2
• Immunoglobulin domain subtype
• Fibronectin type III
• Immunoglobulin-like domain
• Immunoglobulin I-set
• Immunoglobulin-like fold
• Neurofascin/L1/NrCAM, C-terminal domain
• Fibronectin type III superfamily
• Immunoglobulin-like domain superfamily
• Neural and epithelial cell adhesion domain-containing protein
• Fibronectin type III domain
• Immunoglobulin I-set domain
• Bravo-like intracellular region
• Immunoglobulin domain

KeywordsUniProt

• Cell adhesion
• Cell membrane
• Cell projection
• Disulfide bond
• Glycoprotein
• Immunoglobulin domain
• Intellectual disability
• Membrane
• Phosphoprotein
• Repeat
• Secreted
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

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

• MYOC
• GLDN