GUCY2D

Protein identityUniProt · HPA

UniProt accession

Q02846

Gene

GUCY2D

Ensembl

ENSG00000132518

Chromosome

17

Canonical length

1103 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted membrane proteins, Transporters

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes a retina-specific guanylate cyclase, which is a member of the membrane guanylyl cyclase family. Like other membrane guanylyl cyclases, this enzyme has a hydrophobic amino-terminal signal sequence followed by a large extracellular domain, a single membrane spanning domain, a kinase homology domain, and a guanylyl cyclase catalytic domain. In contrast to other membrane guanylyl cyclases, this enzyme is not activated by natriuretic peptides. Mutations in this gene result in Leber congenital amaurosis and cone-rod dystrophy-6 diseases. [provided by RefSeq, Dec 2008]

Canonical amino-acid sequenceUniProt

1103 residues, UniProt reviewed canonical sequence.

>Q02846|GUCY2D
     1  MTACARRAGG LPDPGLCGPA WWAPSLPRLP RALPRLPLLL LLLLLQPPAL SAVFTVGVLG
    61  PWACDPIFSR ARPDLAARLA AARLNRDPGL AGGPRFEVAL LPEPCRTPGS LGAVSSALAR
   121  VSGLVGPVNP AACRPAELLA EEAGIALVPW GCPWTQAEGT TAPAVTPAAD ALYALLRAFG
   181  WARVALVTAP QDLWVEAGRS LSTALRARGL PVASVTSMEP LDLSGAREAL RKVRDGPRVT
   241  AVIMVMHSVL LGGEEQRYLL EAAEELGLTD GSLVFLPFDT IHYALSPGPE ALAALANSSQ
   301  LRRAHDAVLT LTRHCPSEGS VLDSLRRAQE RRELPSDLNL QQVSPLFGTI YDAVFLLARG
   361  VAEARAAAGG RWVSGAAVAR HIRDAQVPGF CGDLGGDEEP PFVLLDTDAA GDRLFATYML
   421  DPARGSFLSA GTRMHFPRGG SAPGPDPSCW FDPNNICGGG LEPGLVFLGF LLVVGMGLAG
   481  AFLAHYVRHR LLHMQMVSGP NKIILTVDDI TFLHPHGGTS RKVAQGSRSS LGARSMSDIR
   541  SGPSQHLDSP NIGVYEGDRV WLKKFPGDQH IAIRPATKTA FSKLQELRHE NVALYLGLFL
   601  ARGAEGPAAL WEGNLAVVSE HCTRGSLQDL LAQREIKLDW MFKSSLLLDL IKGIRYLHHR
   661  GVAHGRLKSR NCIVDGRFVL KITDHGHGRL LEAQKVLPEP PRAEDQLWTA PELLRDPALE
   721  RRGTLAGDVF SLAIIMQEVV CRSAPYAMLE LTPEEVVQRV RSPPPLCRPL VSMDQAPVEC
   781  ILLMKQCWAE QPELRPSMDH TFDLFKNINK GRKTNIIDSM LRMLEQYSSN LEDLIRERTE
   841  ELELEKQKTD RLLTQMLPPS VAEALKTGTP VEPEYFEQVT LYFSDIVGFT TISAMSEPIE
   901  VVDLLNDLYT LFDAIIGSHD VYKVETIGDA YMVASGLPQR NGQRHAAEIA NMSLDILSAV
   961  GTFRMRHMPE VPVRIRIGLH SGPCVAGVVG LTMPRYCLFG DTVNTASRME STGLPYRIHV
  1021  NLSTVGILRA LDSGYQVELR GRTELKGKGA EDTFWLVGRR GFNKPIPKPP DLQPGSSNHG
  1081  ISLQEIPPER RRKLEKARPG QFS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GUCY2D 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

Other membrane

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.3

Highest tissue expression

32 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GUCY2D.

Disease | AllUniProt

Conditions GUCY2D is implicated in, by any mechanism.

• Leber congenital amaurosis 1 (LCA1) MIM:204000
• Cone-rod dystrophy 6 (CORD6) MIM:601777
• Choroidal dystrophy, central areolar, 1 (CACD1) MIM:215500
• Night blindness, congenital stationary, 1I (CSNB1I) MIM:618555

Disease | GeneticClinVar

256 pathogenic / likely-pathogenic of 1,697 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Leber congenital amaurosis 1
• Cone-rod dystrophy 6
• GUCY2D-related recessive retinopathy
• Retinal dystrophy
• Night blindness, congenital stationary, type1i

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)

0.75

gnomAD pLI

0

gnomAD missense Z

0.78

DepMap mean gene effect

-0.08

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cGMP biosynthetic process
• cGMP-mediated signaling
• receptor guanylyl cyclase signaling pathway
• regulation of opsin-mediated signaling pathway
• visual perception

Molecular functions

• ATP binding
• GTP binding
• guanylate cyclase activity
• peptide receptor activity
• protein homodimerization activity
• protein kinase activity
• protein-containing complex binding
• signaling receptor activity

Cellular components

• endoplasmic reticulum membrane
• nuclear outer membrane
• photoreceptor disc membrane
• photoreceptor outer segment
• photoreceptor outer segment membrane
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Protein kinase domain
• Adenylyl cyclase class-3/4/guanylyl cyclase
• Serine-threonine/tyrosine-protein kinase, catalytic domain
• Receptor, ligand binding region
• Protein kinase-like domain superfamily
• Haem NO binding associated
• Adenylyl cyclase class-4/guanylyl cyclase, conserved site
• Periplasmic binding protein-like I
• Nucleotide cyclase
• Cyclic nucleotide synthase
• Adenylate and Guanylate cyclase catalytic domain
• Receptor family ligand binding region
• Heme NO binding associated
• Protein tyrosine and serine/threonine kinase

KeywordsUniProt

• Cell projection
• cGMP biosynthesis
• Cone-rod dystrophy
• Congenital stationary night blindness
• Disulfide bond
• Endoplasmic reticulum
• Glycoprotein
• GTP-binding
• Leber congenital amaurosis
• Lyase
• Membrane
• Nucleotide-binding
• Sensory transduction
• Signal
• Transmembrane
• Transmembrane helix
• Vision

InteractionsUniProt · HPA

Protein binding partners of GUCY2D in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• RD3
• NCALD