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Protein

Guanylate cyclase soluble subunit alpha-2

Gene

GUCY1A2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.

Miscellaneous

There are two types of guanylate cyclases: soluble forms and membrane-associated receptor forms.

Catalytic activityi

GTP = 3',5'-cyclic GMP + diphosphate.

Enzyme regulationi

Activated by nitric oxide in the presence of magnesium or manganese ions.

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionLyase
Biological processcGMP biosynthesis
LigandGTP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi4.6.1.2 2681
ReactomeiR-HSA-392154 Nitric oxide stimulates guanylate cyclase
SIGNORiP33402

Names & Taxonomyi

Protein namesi
Recommended name:
Guanylate cyclase soluble subunit alpha-2 (EC:4.6.1.2)
Short name:
GCS-alpha-2
Gene namesi
Name:GUCY1A2
Synonyms:GUC1A2, GUCSA2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000152402.10
HGNCiHGNC:4684 GUCY1A2
MIMi601244 gene
neXtProtiNX_P33402

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

DisGeNETi2977
OpenTargetsiENSG00000152402
PharmGKBiPA186

Chemistry databases

ChEMBLiCHEMBL2111348
DrugBankiDB01020 Isosorbide Mononitrate
DB09241 Methylene blue
DB00435 Nitric Oxide
DB13170 Plecanatide
DB08931 Riociguat

Polymorphism and mutation databases

BioMutaiGUCY1A2
DMDMi461897

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000741131 – 732Guanylate cyclase soluble subunit alpha-2Add BLAST732

Proteomic databases

PaxDbiP33402
PeptideAtlasiP33402
PRIDEiP33402
ProteomicsDBi54910
54911 [P33402-2]

PTM databases

iPTMnetiP33402
PhosphoSitePlusiP33402

Expressioni

Tissue specificityi

Isoform 1 is expressed in fetal brain, liver, colon, endothelium and testis. Isoform 2 is expressed only in liver, colon and endothelium.

Gene expression databases

BgeeiENSG00000152402
CleanExiHS_GUCY1A2
GenevisibleiP33402 HS

Organism-specific databases

HPAiCAB009534

Interactioni

Subunit structurei

Heterodimer of an alpha and a beta chain.

Binary interactionsi

WithEntry#Exp.IntActNotes
SCRIBQ141603EBI-6911715,EBI-357345

Protein-protein interaction databases

BioGridi109232, 12 interactors
CORUMiP33402
IntActiP33402, 2 interactors
MINTiP33402
STRINGi9606.ENSP00000431245

Structurei

3D structure databases

ProteinModelPortaliP33402
SMRiP33402
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini521 – 648Guanylate cyclasePROSITE-ProRule annotationAdd BLAST128

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi51 – 76Ala-richAdd BLAST26
Compositional biasi51 – 58Poly-Ala8

Sequence similaritiesi

Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG4171 Eukaryota
COG2114 LUCA
GeneTreeiENSGT00760000118959
HOGENOMiHOG000220903
HOVERGENiHBG106603
InParanoidiP33402
KOiK12318
OMAiQNWPNIH
OrthoDBiEOG091G04KV
PhylomeDBiP33402
TreeFamiTF351403

Family and domain databases

Gene3Di3.30.70.1230, 1 hit
3.90.1520.10, 1 hit
InterProiView protein in InterPro
IPR001054 A/G_cyclase
IPR018297 A/G_cyclase_CS
IPR038158 H-NOX_domain_sf
IPR011644 Heme_NO-bd
IPR011645 HNOB_dom_associated
IPR024096 NO_sig/Golgi_transp_ligand-bd
IPR029787 Nucleotide_cyclase
PfamiView protein in Pfam
PF00211 Guanylate_cyc, 1 hit
PF07700 HNOB, 1 hit
PF07701 HNOBA, 1 hit
SMARTiView protein in SMART
SM00044 CYCc, 1 hit
SUPFAMiSSF111126 SSF111126, 1 hit
SSF55073 SSF55073, 1 hit
PROSITEiView protein in PROSITE
PS00452 GUANYLATE_CYCLASE_1, 1 hit
PS50125 GUANYLATE_CYCLASE_2, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P33402-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MSRRKISSES FSSLGSDYLE TSPEEEGECP LSRLCWNGSR SPPGPLEPSP
60 70 80 90 100
AAAAAAAAPA PTPAASAAAA AATAGARRVQ RRRRVNLDSL GESISRLTAP
110 120 130 140 150
SPQTIQQTLK RTLQYYEHQV IGYRDAEKNF HNISNRCSYA DHSNKEEIED
160 170 180 190 200
VSGILQCTAN ILGLKFEEIQ KRFGEEFFNI CFHENERVLR AVGGTLQDFF
210 220 230 240 250
NGFDALLEHI RTSFGKQATL ESPSFLCKEL PEGTLMLHYF HPHHIVGFAM
260 270 280 290 300
LGMIKAAGKK IYRLDVEVEQ VANEKLCSDV SNPGNCSCLT FLIKECENTN
310 320 330 340 350
IMKNLPQGTS QVPADLRISI NTFCRAFPFH LMFDPSMSVL QLGEGLRKQL
360 370 380 390 400
RCDTHKVLKF EDCFEIVSPK VNATFERVLL RLSTPFVIRT KPEASGSENK
410 420 430 440 450
DKVMEVKGQM IHVPESNSIL FLGSPCVDKL DELMGRGLHL SDIPIHDATR
460 470 480 490 500
DVILVGEQAK AQDGLKKRMD KLKATLERTH QALEEEKKKT VDLLYSIFPG
510 520 530 540 550
DVAQQLWQGQ QVQARKFDDV TMLFSDIVGF TAICAQCTPM QVISMLNELY
560 570 580 590 600
TRFDHQCGFL DIYKVETIGD AYCVAAGLHR KSLCHAKPIA LMALKMMELS
610 620 630 640 650
EEVLTPDGRP IQMRIGIHSG SVLAGVVGVR MPRYCLFGNN VTLASKFESG
660 670 680 690 700
SHPRRINVSP TTYQLLKREE SFTFIPRSRE ELPDNFPKEI PGICYFLEVR
710 720 730
TGPKPPKPSL SSSRIKKVSY NIGTMFLRET SL
Length:732
Mass (Da):81,750
Last modified:February 1, 1994 - v1
Checksum:i79465A7D3FE52DB7
GO
Isoform 2 (identifier: P33402-2) [UniParc]FASTAAdd to basket
Also known as: Alpha-2-I

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

Show »
Length:763
Mass (Da):85,259
Checksum:iE3493CCC508BE6EB
GO
Isoform 3 (identifier: P33402-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     402-402: K → KSKHVTEGHLTQLSVAGFNSLE

Note: No experimental confirmation available.
Show »
Length:753
Mass (Da):83,986
Checksum:i447CF8A2C77F249D
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_036420681E → V in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_036421685N → T in a colorectal cancer sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_054154402K → KSKHVTEGHLTQLSVAGFNS LE in isoform 3. 1 Publication1
Alternative sequenceiVSP_001814612Q → QPQRSELLFSFPVSIQLVPD QHQSETDLGTEK in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X63282 mRNA Translation: CAA44921.1
Z50053 mRNA Translation: CAA90393.1
AP001282 Genomic DNA No translation available.
AP001881 Genomic DNA No translation available.
AP003078 Genomic DNA No translation available.
AP005014 Genomic DNA No translation available.
CH471065 Genomic DNA Translation: EAW67081.1
BC130484 mRNA Translation: AAI30485.1
BC130488 mRNA Translation: AAI30489.1
BC144033 mRNA Translation: AAI44034.1
CCDSiCCDS58170.1 [P33402-2]
CCDS8335.1 [P33402-1]
PIRiS18325
RefSeqiNP_000846.1, NM_000855.2 [P33402-1]
NP_001243353.1, NM_001256424.1 [P33402-2]
UniGeneiHs.24321

Genome annotation databases

EnsembliENST00000282249; ENSP00000282249; ENSG00000152402 [P33402-2]
ENST00000347596; ENSP00000344874; ENSG00000152402 [P33402-3]
ENST00000526355; ENSP00000431245; ENSG00000152402 [P33402-1]
GeneIDi2977
KEGGihsa:2977
UCSCiuc001pjf.6 human [P33402-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiGCYA2_HUMAN
AccessioniPrimary (citable) accession number: P33402
Secondary accession number(s): A1L4C4, B7ZLT5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: June 20, 2018
This is version 163 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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