P33402 (GCYA2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Guanylate cyclase soluble subunit alpha-2
Short name=GCS-alpha-2
EC=4.6.1.2

Gene names

Name:	GUCY1A2
Synonyms:	GUC1A2, GUCSA2

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	732 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Has guanylyl cyclase on binding to the beta-1 subunit. Isoform 2 acts as a negative regulator of guanylyl cyclase activity as it forms non-functional heterodimers with the beta subunits.
Catalytic activity	GTP = 3',5'-cyclic GMP + diphosphate.
Enzyme regulation	Activated by nitric oxide in the presence of magnesium or manganese ions.
Subunit structure	Heterodimer of an alpha and a beta chain.
Subcellular location	Cytoplasm.
Tissue specificity	Isoform 1 is expressed in fetal brain, liver, colon, endothelium and testis. Isoform 2 is expressed only in liver, colon and endothelium.
Miscellaneous	There are two types of guanylate cyclases: soluble forms and membrane-associated receptor forms.
Sequence similarities	Belongs to the adenylyl cyclase class-4/guanylyl cyclase family. Contains 1 guanylate cyclase domain.

Ontologies

Keywords
Biological process	cGMP biosynthesis
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	GTP-binding Nucleotide-binding
Molecular function	Lyase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	blood coagulation Traceable author statement. Source: Reactome intracellular signal transduction Inferred from electronic annotation. Source: InterPro positive regulation of cGMP biosynthetic process Inferred from electronic annotation. Source: Compara signal transduction Traceable author statement Ref.1. Source: ProtInc
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	GTP binding Inferred from electronic annotation. Source: UniProtKB-KW guanylate cyclase activity Traceable author statement Ref.1. Source: ProtInc heme binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P33402-1)

Also known as: Alpha-2;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P33402-2)

Also known as: Alpha-2-I;

The sequence of this isoform differs from the canonical sequence as follows:
     612-612: Q → QPQRSELLFSFPVSIQLVPDQHQSETDLGTEK

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 732	732	Guanylate cyclase soluble subunit alpha-2		PRO_0000074113
Regions
	Domain	521 – 648	128	Guanylate cyclase
	Compositional bias	51 – 76	26	Ala-rich
	Compositional bias	51 – 58	8	Poly-Ala
Natural variations
	Alternative sequence	612	1	Q → QPQRSELLFSFPVSIQLVPD QHQSETDLGTEK in isoform 2.		VSP_001814
	Natural variant	681	1	E → V in a colorectal cancer sample; somatic mutation. Ref.5		VAR_036420
	Natural variant	685	1	N → T in a colorectal cancer sample; somatic mutation. Ref.5		VAR_036421

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Alpha-2) [UniParc]. Last modified February 1, 1994. Version 1. Checksum: 79465A7D3FE52DB7	FASTA	732	81,750
	10 20 30 40 50 60 MSRRKISSES FSSLGSDYLE TSPEEEGECP LSRLCWNGSR SPPGPLEPSP AAAAAAAAPA 70 80 90 100 110 120 PTPAASAAAA AATAGARRVQ RRRRVNLDSL GESISRLTAP SPQTIQQTLK RTLQYYEHQV 130 140 150 160 170 180 IGYRDAEKNF HNISNRCSYA DHSNKEEIED VSGILQCTAN ILGLKFEEIQ KRFGEEFFNI 190 200 210 220 230 240 CFHENERVLR AVGGTLQDFF NGFDALLEHI RTSFGKQATL ESPSFLCKEL PEGTLMLHYF 250 260 270 280 290 300 HPHHIVGFAM LGMIKAAGKK IYRLDVEVEQ VANEKLCSDV SNPGNCSCLT FLIKECENTN 310 320 330 340 350 360 IMKNLPQGTS QVPADLRISI NTFCRAFPFH LMFDPSMSVL QLGEGLRKQL RCDTHKVLKF 370 380 390 400 410 420 EDCFEIVSPK VNATFERVLL RLSTPFVIRT KPEASGSENK DKVMEVKGQM IHVPESNSIL 430 440 450 460 470 480 FLGSPCVDKL DELMGRGLHL SDIPIHDATR DVILVGEQAK AQDGLKKRMD KLKATLERTH 490 500 510 520 530 540 QALEEEKKKT VDLLYSIFPG DVAQQLWQGQ QVQARKFDDV TMLFSDIVGF TAICAQCTPM 550 560 570 580 590 600 QVISMLNELY TRFDHQCGFL DIYKVETIGD AYCVAAGLHR KSLCHAKPIA LMALKMMELS 610 620 630 640 650 660 EEVLTPDGRP IQMRIGIHSG SVLAGVVGVR MPRYCLFGNN VTLASKFESG SHPRRINVSP 670 680 690 700 710 720 TTYQLLKREE SFTFIPRSRE ELPDNFPKEI PGICYFLEVR TGPKPPKPSL SSSRIKKVSY 730 NIGTMFLRET SL
	Isoform 2 (Alpha-2-I) [UniParc]. Checksum: E3493CCC508BE6EB	FASTA	763	85,259
	10 20 30 40 50 60 MSRRKISSES FSSLGSDYLE TSPEEEGECP LSRLCWNGSR SPPGPLEPSP AAAAAAAAPA 70 80 90 100 110 120 PTPAASAAAA AATAGARRVQ RRRRVNLDSL GESISRLTAP SPQTIQQTLK RTLQYYEHQV 130 140 150 160 170 180 IGYRDAEKNF HNISNRCSYA DHSNKEEIED VSGILQCTAN ILGLKFEEIQ KRFGEEFFNI 190 200 210 220 230 240 CFHENERVLR AVGGTLQDFF NGFDALLEHI RTSFGKQATL ESPSFLCKEL PEGTLMLHYF 250 260 270 280 290 300 HPHHIVGFAM LGMIKAAGKK IYRLDVEVEQ VANEKLCSDV SNPGNCSCLT FLIKECENTN 310 320 330 340 350 360 IMKNLPQGTS QVPADLRISI NTFCRAFPFH LMFDPSMSVL QLGEGLRKQL RCDTHKVLKF 370 380 390 400 410 420 EDCFEIVSPK VNATFERVLL RLSTPFVIRT KPEASGSENK DKVMEVKGQM IHVPESNSIL 430 440 450 460 470 480 FLGSPCVDKL DELMGRGLHL SDIPIHDATR DVILVGEQAK AQDGLKKRMD KLKATLERTH 490 500 510 520 530 540 QALEEEKKKT VDLLYSIFPG DVAQQLWQGQ QVQARKFDDV TMLFSDIVGF TAICAQCTPM 550 560 570 580 590 600 QVISMLNELY TRFDHQCGFL DIYKVETIGD AYCVAAGLHR KSLCHAKPIA LMALKMMELS 610 620 630 640 650 660 EEVLTPDGRP IQPQRSELLF SFPVSIQLVP DQHQSETDLG TEKMRIGIHS GSVLAGVVGV 670 680 690 700 710 720 RMPRYCLFGN NVTLASKFES GSHPRRINVS PTTYQLLKRE ESFTFIPRSR EELPDNFPKE 730 740 750 760 IPGICYFLEV RTGPKPPKPS LSSSRIKKVS YNIGTMFLRE TSL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and expression of a new alpha-subunit of soluble guanylyl cyclase. Interchangeability of the alpha-subunits of the enzyme." Harteneck C., Wedel B., Koesling D., Malkewitz J., Boehme E., Schultz G. FEBS Lett. 292:217-222(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"A variant of the alpha 2 subunit of soluble guanylyl cyclase contains an insert homologous to a region within adenylyl cyclases and functions as a dominant negative protein." Behrends S., Harteneck C., Schultz G., Koesling D. J. Biol. Chem. 270:21109-21113(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	"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: VARIANTS [LARGE SCALE ANALYSIS] VAL-681 AND THR-685.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X63282 mRNA. Translation: CAA44921.1. Z50053 mRNA. Translation: CAA90393.1. CH471065 Genomic DNA. Translation: EAW67081.1. BC130484 mRNA. Translation: AAI30485.1. BC130488 mRNA. Translation: AAI30489.1.
IPI	IPI00217233. IPI00981500.
PIR	S18325.
RefSeq	NP_000846.1. NM_000855.2. NP_001243353.1. NM_001256424.1.
UniGene	Hs.24321.
3D structure databases
ProteinModelPortal	P33402.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000344874.
PTM databases
PhosphoSite	P33402.
Polymorphism databases
DMDM	461897.
Proteomic databases
PaxDb	P33402.
PRIDE	P33402.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000282249; ENSP00000282249; ENSG00000152402. ENST00000526355; ENSP00000431245; ENSG00000152402.
GeneID	2977.
KEGG	hsa:2977.
UCSC	uc001pjg.1. human. uc009yxn.1. human.
Organism-specific databases
CTD	2977.
GeneCards	GC11M106591.
HGNC	HGNC:4684. GUCY1A2.
HPA	CAB009534.
MIM	601244. gene.
neXtProt	NX_P33402.
PharmGKB	PA186.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG2114.
HOVERGEN	HBG106603.
KO	K12318.
OMA	ECENTNI.
Enzyme and pathway databases
Reactome	REACT_604. Hemostasis.
Gene expression databases
ArrayExpress	P33402.
Bgee	P33402.
CleanEx	HS_GUCY1A2.
Genevestigator	P33402.
GermOnline	ENSG00000152402. Homo sapiens.
Family and domain databases
Gene3D	3.30.70.1230. 1 hit.
InterPro	IPR001054. A/G_cyclase. IPR018297. A/G_cyclase_CS. IPR011645. Haem_no_assoc-bd. IPR011644. Heme_NO-bd. IPR024096. NO_sig/Golgi_transp_ligand-bd. [Graphical view]
Pfam	PF00211. Guanylate_cyc. 1 hit. PF07700. HNOB. 1 hit. PF07701. HNOBA. 1 hit. [Graphical view]
SMART	SM00044. CYCc. 1 hit. [Graphical view]
SUPFAM	SSF55073. A/G_cyclase. 1 hit. SSF111126. Haem_NO-bd. 1 hit.
PROSITE	PS00452. GUANYLATE_CYCLASE_1. 1 hit. PS50125. GUANYLATE_CYCLASE_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P33402.
ChEMBL	CHEMBL3303.
GenomeRNAi	2977.
NextBio	11808.
SOURCE	Search...

Entry information

Entry name

GCYA2_HUMAN

Accession

Primary (citable) accession number: P33402
Secondary accession number(s): A1L4C4

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	February 1, 1994
Last modified:	May 1, 2013
This is version 123 of the entry and version 1 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.