P51841 (GUC2F_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Retinal guanylyl cyclase 2
Short name=RETGC-2
EC=4.6.1.2

Alternative name(s):
Guanylate cyclase 2F, retinal
Guanylate cyclase F
Short name=GC-F
Rod outer segment membrane guanylate cyclase 2
Short name=ROS-GC2

Gene names

Name:	GUCY2F
Synonyms:	GUC2F, RETGC2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1108 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Probably plays a specific functional role in the rods and/or cones of photoreceptors. It may be the enzyme involved in the resynthesis of cGMP required for recovery of the dark state after phototransduction.
Catalytic activity	GTP = 3',5'-cyclic GMP + diphosphate.
Enzyme regulation	Activated by GCAP-1; inhibited by calcium.
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Retina. Localized exclusively in the outer nuclear layer and inner segments of the rod and cone photoreceptor cells.
Domain	The protein kinase domain is predicted to be catalytically inactive.
Post-translational modification	There are 9 conserved cysteine residues in sensory guanylate cyclases, 6 in the extracellular domain, which may be involved in intra- or interchain disulfide bonds.
Sequence similarities	Belongs to the adenylyl cyclase class-4/guanylyl cyclase family. Contains 1 guanylate cyclase domain. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Sensory transduction Vision cGMP biosynthesis
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Ligand	GTP-binding Nucleotide-binding
Molecular function	Lyase
PTM	Disulfide bond
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	intracellular signal transduction Inferred from electronic annotation. Source: InterPro receptor guanylyl cyclase signaling pathway Traceable author statement Ref.1. Source: ProtInc visual perception Traceable author statement Ref.1. Source: ProtInc
Cellular_component	integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc nuclear outer membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	ATP binding Inferred from electronic annotation. Source: InterPro GTP binding Inferred from electronic annotation. Source: UniProtKB-KW guanylate cyclase activity Traceable author statement Ref.1. Source: ProtInc protein kinase activity Inferred from electronic annotation. Source: InterPro receptor activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 50	50	Potential
	Chain	51 – 1108	1058	Retinal guanylyl cyclase 2		PRO_0000012386
Regions
	Topological domain	51 – 467	417	Extracellular Potential
	Transmembrane	468 – 490	23	Helical; Potential
	Topological domain	491 – 1108	618	Cytoplasmic Potential
	Domain	532 – 812	281	Protein kinase
	Domain	884 – 1014	131	Guanylate cyclase
Amino acid modifications
	Disulfide bond	104 ↔ 132		By similarity
	Disulfide bond	452		Interchain By similarity
	Disulfide bond	460		Interchain By similarity
Natural variations
	Natural variant	10	1	R → P in a breast cancer sample; somatic mutation. Ref.3		VAR_036419
	Natural variant	40	1	S → C. Ref.4 Corresponds to variant rs34228145 [ dbSNP | Ensembl ].		VAR_042233
	Natural variant	160	1	I → N. Ref.4 Corresponds to variant rs33971675 [ dbSNP | Ensembl ].		VAR_042234
	Natural variant	230	1	R → W. Ref.4 Corresponds to variant rs33973457 [ dbSNP | Ensembl ].		VAR_042235
	Natural variant	284	1	L → P. Ref.4 Corresponds to variant rs12008095 [ dbSNP | Ensembl ].		VAR_009136
	Natural variant	296	1	R → Q. Ref.1 Corresponds to variant rs502209 [ dbSNP | Ensembl ].		VAR_009137
	Natural variant	305	1	R → Q. Ref.4 Corresponds to variant rs55966326 [ dbSNP | Ensembl ].		VAR_042236
	Natural variant	308	1	Y → C. Ref.4 Corresponds to variant rs16985750 [ dbSNP | Ensembl ].		VAR_030633
	Natural variant	380	1	Q → H. Ref.4 Corresponds to variant rs2272925 [ dbSNP | Ensembl ].		VAR_030634
	Natural variant	434	1	G → R. Ref.4 Corresponds to variant rs56293008 [ dbSNP | Ensembl ].		VAR_042237
	Natural variant	568	1	G → D in a glioblastoma multiforme sample; somatic mutation. Ref.4		VAR_042238
	Natural variant	628	1	R → Q. Ref.4 Corresponds to variant rs7883913 [ dbSNP | Ensembl ].		VAR_030635
	Natural variant	677	1	V → L. Ref.4 Corresponds to variant rs35474112 [ dbSNP | Ensembl ].		VAR_042239
	Natural variant	794	1	E → K. Ref.4 Corresponds to variant rs35726803 [ dbSNP | Ensembl ].		VAR_042240
	Natural variant	1010	1	A → V. Ref.4 Corresponds to variant rs55735218 [ dbSNP | Ensembl ].		VAR_042241
	Natural variant	1052	1	K → R in a lung adenocarcinoma sample; somatic mutation. Ref.4		VAR_042242
	Natural variant	1055	1	E → D in a lung squamous cell carcinoma sample; somatic mutation. Ref.4		VAR_042243

Sequences

	Sequence		Length	Mass (Da)
	P51841 [UniParc]. Last modified November 2, 2010. Version 2. Checksum: B047BBF1A3C009F9	FASTA	1,108	124,850
	10 20 30 40 50 60 MFLGLGRFSR LVLWFAAFRK LLGHHGLASA KFLWCLCLLS VMSLPQQVWT LPYKIGVVGP 70 80 90 100 110 120 WACDSLFSKA LPEVAARLAI ERINRDPSFD LSYSFEYVIL NEDCQTSRAL SSFISHHQMA 130 140 150 160 170 180 SGFIGPTNPG YCEAASLLGN SWDKGIFSWA CVNYELDNKI SYPTFSRTLP SPIRVLVTVM 190 200 210 220 230 240 KYFQWAHAGV ISSDEDIWVH TANRVASALR SHGLPVGVVL TTGQDSQSMR KALQRIHQAD 250 260 270 280 290 300 RIRIIIMCMH SALIGGETQM HLLECAHDLK MTDGTYVFVP YDALLYSLPY KHTPYRVLRN 310 320 330 340 350 360 NPKLREAYDA VLTITVESQE KTFYQAFTEA AARGEIPEKL EFDQVSPLFG TIYNSIYFIA 370 380 390 400 410 420 QAMNNAMKEN GQAGAASLVQ HSRNMQFHGF NQLMRTDSNG NGISEYVILD TNLKEWELHS 430 440 450 460 470 480 TYTVDMEMEL LRFGGTPIHF PGGRPPRADA KCWFAEGKIC HGGIDPAFAM MVCLTLLIAL 490 500 510 520 530 540 LSINGFAYFI RRRINKIQLI KGPNRILLTL EDVTFINPHF GSKRGSRASV SFQITSEVQS 550 560 570 580 590 600 GRSPRLSFSS GSLTPATYEN SNIAIYEGDW VWLKKFSLGD FGDLKSIKSR ASDVFEMMKD 610 620 630 640 650 660 LRHENINPLL GFFYDSGMFA IVTEFCSRGS LEDILTNQDV KLDWMFKSSL LLDLIKGMKY 670 680 690 700 710 720 LHHREFVHGR LKSRNCVVDG RFVLKVTDYG FNDILEMLRL SEEESSMEEL LWTAPELLRA 730 740 750 760 770 780 PRGSRLGSFA GDVYSFAIIM QEVMVRGTPF CMMDLPAQEI INRLKKPPPV YRPVVPPEHA 790 800 810 820 830 840 PPECLQLMKQ CWAEAAEQRP TFDEIFNQFK TFNKGKKTNI IDSMLRMLEQ YSSNLEDLIR 850 860 870 880 890 900 ERTEELEIEK QKTEKLLTQM LPPSVAESLK KGCTVEPEGF DLVTLYFSDI VGFTTISAMS 910 920 930 940 950 960 EPIEVVDLLN DLYTLFDAII GSHDVYKVET IGDAYMVASG LPKRNGSRHA AEIANMSLDI 970 980 990 1000 1010 1020 LSSVGTFKMR HMPEVPVRIR IGLHSGPVVA GVVGLTMPRY CLFGDTVNTA SRMESTGLPY 1030 1040 1050 1060 1070 1080 RIHVSLSTVT ILQNLSEGYE VELRGRTELK GKGTEETFWL IGKKGFMKPL PVPPPVDKDG 1090 1100 QVGHGLQPVE IAAFQRRKAE RQLVRNKP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression of a second photoreceptor-specific membrane retina guanylyl cyclase (RetGC), RetGC-2." Lowe D.G., Dizhoor A.M., Liu K., Gu Q., Spencer M., Laura R., Lu L., Hurley J.B. Proc. Natl. Acad. Sci. U.S.A. 92:5535-5539(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLN-296. Tissue: Retina.
[2]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] PRO-10.
[4]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] CYS-40; ASN-160; TRP-230; PRO-284; GLN-305; CYS-308; HIS-380; ARG-434; ASP-568; GLN-628; LEU-677; LYS-794; VAL-1010; ARG-1052 AND ASP-1055.
+	Additional computationally mapped references.

Web resources

Mutations of the GUCY2F gene

Retina International's Scientific Newsletter

Cross-references

Sequence databases
EMBL GenBank DDBJ	L37378 mRNA. Translation: AAA74451.1. AL031387 Genomic DNA. Translation: CAB41303.1.
IPI	IPI00020942.
PIR	I59385.
RefSeq	NP_001513.2. NM_001522.2.
UniGene	Hs.123074.
3D structure databases
ProteinModelPortal	P51841.
SMR	P51841. Positions 573-839, 883-1083.
ModBase	Search...
Protein-protein interaction databases
IntAct	P51841. 1 interaction.
STRING	9606.ENSP00000218006.
PTM databases
PhosphoSite	P51841.
Polymorphism databases
DMDM	311033391.
Proteomic databases
PaxDb	P51841.
PRIDE	P51841.
Protocols and materials databases
DNASU	2986.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000218006; ENSP00000218006; ENSG00000101890.
GeneID	2986.
KEGG	hsa:2986.
UCSC	uc004eod.4. human.
Organism-specific databases
CTD	2986.
GeneCards	GC0XM108616.
H-InvDB	HIX0056276.
HGNC	HGNC:4691. GUCY2F.
HPA	HPA000734. HPA027473.
MIM	300041. gene.
neXtProt	NX_P51841.
PharmGKB	PA29071.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000293307.
HOVERGEN	HBG098487.
InParanoid	P51841.
KO	K12321.
OMA	NSIYFIA.
OrthoDB	EOG4XD3QC.
PhylomeDB	P51841.
Enzyme and pathway databases
Pathway_Interaction_DB	cone_pathway. Visual signal transduction: Cones. rhodopsin_pathway. Visual signal transduction: Rods.
Gene expression databases
Bgee	P51841.
CleanEx	HS_GUCY2F.
Genevestigator	P51841.
GermOnline	ENSG00000101890. Homo sapiens.
Family and domain databases
Gene3D	3.30.70.1230. 1 hit.
InterPro	IPR001054. A/G_cyclase. IPR018297. A/G_cyclase_CS. IPR001828. ANF_lig-bd_rcpt. IPR011645. Haem_no_assoc-bd. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR001245. Ser-Thr/Tyr_kinase_cat_dom. [Graphical view]
Pfam	PF01094. ANF_receptor. 1 hit. PF00211. Guanylate_cyc. 1 hit. PF07701. HNOBA. 1 hit. PF07714. Pkinase_Tyr. 1 hit. [Graphical view]
PRINTS	PR00109. TYRKINASE.
SMART	SM00044. CYCc. 1 hit. [Graphical view]
SUPFAM	SSF55073. A/G_cyclase. 1 hit. SSF56112. Kinase_like. 1 hit.
PROSITE	PS00452. GUANYLATE_CYCLASE_1. 1 hit. PS50125. GUANYLATE_CYCLASE_2. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	2986.
NextBio	11840.
SOURCE	Search...

Entry information

Entry name

GUC2F_HUMAN

Accession

Primary (citable) accession number: P51841
Secondary accession number(s): Q9UJF1

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	November 2, 2010
Last modified:	May 1, 2013
This is version 131 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.