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Reviewed, UniProtKB/Swiss-Prot P35348 (ADA1A_HUMAN)

Last modified July 22, 2008. Version 87. Feed History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Alpha-1A adrenergic receptor
Alternative name(s):
    Alpha 1A-adrenoreceptor
    Alpha 1A-adrenoceptor
    Alpha-1C adrenergic receptor
    Alpha-adrenergic receptor 1c
Gene names
Name: ADRA1A
Synonyms: ADRA1C
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length466 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at transcript level.

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General annotation (Comments)

Function

This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins.

Subcellular location

Cell membrane; Multi-pass membrane protein.

Tissue specificity

Heart, brain, liver and prostate, but not in kidney, lung, adrenal, aorta and pituitary. Isoform 4 is the most abundant isoform expressed in the prostate with high levels also detected in liver and heart.

Post-translational modification

Carboxyl-terminal Ser or Thr residues may be phosphorylated By similarity.

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

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Alternative products

This entry describes 9 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P35348-1)

Also known as: Alpha 1c-1; Alpha(1A-1);

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: P35348-2)

Also known as: Alpha 1c-2; Alpha(1A-2);

The sequence of this isoform differs from the canonical sequence as follows:
     424-466: VRSKSFLQVC...ISLSENGEEV → TKSRSVTRLE...GQDDLDLLTS
Isoform 3 (identifier: P35348-3)

Also known as: Alpha 1c-3; Alpha(1A-3);

The sequence of this isoform differs from the canonical sequence as follows:
     424-429: VRSKSF → GHTPMT
     430-466: Missing.
Isoform 4 (identifier: P35348-4)

Also known as: Alpha(1A-4);

The sequence of this isoform differs from the canonical sequence as follows:
     424-466: VRSKSFLQVCCCVGPSTPSLDKNHQVPTIKVHTISLSENGEEV → RGMDCRYFTKNCREHIKHVNFMMPPWRKGLEC
Isoform 5 (identifier: P35348-5)

The sequence of this isoform differs from the canonical sequence as follows:
     296-297: SF → KS
     298-466: Missing.
Isoform 6 (identifier: P35348-6)

The sequence of this isoform differs from the canonical sequence as follows:
     295-342: GSFFPDFKPS...FKKAFQNVLR → DEETEAQQGK...VSRKDTCGVW
     343-466: Missing.
Isoform 2b/3b (identifier: P35348-7)

The sequence of this isoform differs from the canonical sequence as follows:
     296-324: SFFPDFKPSETVFKIVFWLGYLNSCINPI → TYILKYDVLFWRKGLSVCTRLRERKEIKN
     325-466: Missing.
Isoform 2c (identifier: P35348-8)

The sequence of this isoform differs from the canonical sequence as follows:
     295-466: GSFFPDFKPS...ISLSENGEEV → DEVSLCHQAG...GQDDLDLLTS
Isoform 3c (identifier: P35348-9)

The sequence of this isoform differs from the canonical sequence as follows:
     296-466: SFFPDFKPSE...ISLSENGEEV → THTHDMKPAS...TVTDTGKTVT

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical view

Molecule processing

Chain1 – 466466Alpha-1A adrenergic receptor

Regions

Topological domain1 – 2727Extracellular Potential
Transmembrane28 – 51241 Potential
Topological domain52 – 6413Cytoplasmic Potential
Transmembrane65 – 88242 Potential
Topological domain89 – 9911Extracellular Potential
Transmembrane100 – 122233 Potential
Topological domain123 – 14321Cytoplasmic Potential
Transmembrane144 – 167244 Potential
Topological domain168 – 18114Extracellular Potential
Transmembrane182 – 205245 Potential
Topological domain206 – 27368Cytoplasmic Potential
Transmembrane274 – 297246 Potential
Topological domain298 – 3058Extracellular Potential
Transmembrane306 – 329247 Potential
Topological domain330 – 466137Cytoplasmic Potential

Amino acid modifications

Modified residue2151Phosphoserine; by PKA Potential
Lipidation3451S-palmitoyl cysteine Potential
Glycosylation71N-linked (GlcNAc...) Potential
Glycosylation131N-linked (GlcNAc...) Potential
Glycosylation221N-linked (GlcNAc...) Potential
Disulfide bond99 ↔ 176 By similarity

Natural variations

Alternative sequence295 – 466172GSFFP…NGEEV → DEVSLCHQAGVQWHDLGSLQ PPPPGFKRFSCLSLPSSWDY RDVPPGRRHQAQLIFVFLVE TGFHHVGQDDLDLLTS in isoform 2c.
Alternative sequence295 – 34248GSFFP…QNVLR → DEETEAQQGKNDSPSFKQPV HHAAVLGLEVMEKENLEGVS RKDTCGVW in isoform 6.
Alternative sequence296 – 466171SFFPD…NGEEV → THTHDMKPASRPRLLSLLPK EGEHETHHWSCDPLSLESTP GAQEPCLTLGFTSLSSIHLT KAQIQHVTVTDTGKTVT in isoform 3c.
Alternative sequence296 – 32429SFFPD…CINPI → TYILKYDVLFWRKGLSVCTR LRERKEIKN in isoform 2b/3b.
Alternative sequence296 – 2972SF → KS in isoform 5.
Alternative sequence298 – 466169Missing in isoform 5.
Alternative sequence325 – 466142Missing in isoform 2b/3b.
Alternative sequence343 – 466124Missing in isoform 6.
Alternative sequence424 – 46643VRSKS…NGEEV → TKSRSVTRLECSGMILAHCN LRLPGSRDSPASASQAAGTT GDVPPGRRHQAQLIFVFLVE TGFHHVGQDDLDLLTS in isoform 2.
Alternative sequence424 – 46643VRSKS…NGEEV → RGMDCRYFTKNCREHIKHVN FMMPPWRKGLEC in isoform 4.
Alternative sequence424 – 4296VRSKSF → GHTPMT in isoform 3.
Alternative sequence430 – 46637Missing in isoform 3.
Natural variant401G → W in a breast cancer sample; somatic mutation.
Natural variant3471C → R Frequent polymorphism.

Experimental info

Sequence conflict431G → C in AAA93114. Ref.4
Sequence conflict1291S → T in AAA93114. Ref.4
Sequence conflict3381Q → C Ref.2
Sequence conflict3591T → P in AAA93114. Ref.4
Sequence conflict4311Q → E in BAA04960. Ref.1
Sequence conflict4421S → C in AAA93114. Ref.4

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Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Alpha 1c-1) (Alpha(1A-1)) [UniParc].

Last modified November 1, 1995. Version 2.
Checksum: 1A50487531DECDF0

FASTA46651,487
        10         20         30         40         50         60 
MVFLSGNASD SSNCTQPPAP VNISKAILLG VILGGLILFG VLGNILVILS VACHRHLHSV 

        70         80         90        100        110        120 
THYYIVNLAV ADLLLTSTVL PFSAIFEVLG YWAFGRVFCN IWAAVDVLCC TASIMGLCII 

       130        140        150        160        170        180 
SIDRYIGVSY PLRYPTIVTQ RRGLMALLCV WALSLVISIG PLFGWRQPAP EDETICQINE 

       190        200        210        220        230        240 
EPGYVLFSAL GSFYLPLAII LVMYCRVYVV AKRESRGLKS GLKTDKSDSE QVTLRIHRKN 

       250        260        270        280        290        300 
APAGGSGMAS AKTKTHFSVR LLKFSREKKA AKTLGIVVGC FVLCWLPFFL VMPIGSFFPD 

       310        320        330        340        350        360 
FKPSETVFKI VFWLGYLNSC INPIIYPCSS QEFKKAFQNV LRIQCLCRKQ SSKHALGYTL 

       370        380        390        400        410        420 
HPPSQAVEGQ HKDMVRIPVG SRETFYRISK TDGVCEWKFF SSMPRGSARI TVSKDQSSCT 

       430        440        450        460 
TARVRSKSFL QVCCCVGPST PSLDKNHQVP TIKVHTISLS ENGEEV

« Hide

Isoform 2 (Alpha 1c-2) (Alpha(1A-2)) [UniParc].

Checksum: B0D5208A6092738C
Show »

49954,947
Isoform 3 (Alpha 1c-3) (Alpha(1A-3)) [UniParc].

Checksum: E67B19B5CA668687
Show »

42947,461
Isoform 4 (Alpha(1A-4)) [UniParc].

Checksum: 80C60918FA608B6C
Show »

45550,803
Isoform 5 [UniParc].

Checksum: 4871F9BE42A87D6E
Show »

29732,433
Isoform 6 [UniParc].

Checksum: 3B3F39CC1B9CBE50
Show »

34237,467
Isoform 2b/3b [UniParc].

Checksum: 608DACD5497EE83E
Show »

32435,829
Isoform 2c [UniParc].

Checksum: F00E717A4C4A59AC
Show »

37040,725
Isoform 3c [UniParc].

Checksum: 839C5750F9B428F5
Show »

37240,638

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References

« Hide 'large scale' references
[1]"Cloning, functional expression and tissue distribution of human cDNA for the alpha 1C-adrenergic receptor."
Hirasawa A., Horie K., Tanaka T., Takagaki K., Murai M., Yano J., Tsujimoto G.
Biochem. Biophys. Res. Commun. 195:902-909(1993) [PubMed: 8396931] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), VARIANT ARG-347.
Tissue: Prostate.
[2]"Cloning, expression and characterization of human alpha adrenergic receptors alpha 1a, alpha 1b and alpha 1c."
Weinberg D.H., Trivedi P., Tan C.P., Mitra S., Perkins-Barrow A., Borkowski D., Strader C.D., Bayne M.
Biochem. Biophys. Res. Commun. 201:1296-1304(1994) [PubMed: 8024574] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1), VARIANT ARG-347.
Tissue: Heart.
[3]"The alpha 1-adrenergic receptor that mediates smooth muscle contraction in human prostate has the pharmacological properties of the cloned human alpha 1c subtype."
Forray C., Bard J.A., Wetzel J.M., Chiu G., Shapiro E., Tang R., Lepor H., Hartig P.R., Weinshank R.L., Branchek T.A., Gluchowski C.
Mol. Pharmacol. 45:703-708(1994) [PubMed: 8183249] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
Tissue: Hippocampus and Lymphocyte.
[4]"The alpha 1C-adrenoceptor in human prostate: cloning, functional expression, and localization to specific prostatic cell types."
Tseng-Crank J., Kost T., Goetz A., Hazum S., Roberson K.M., Haizlip J., Godinot N., Robertson C.N., Saussy D.
Br. J. Pharmacol. 115:1475-1485(1995) [PubMed: 8564208] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ARG-347.
[5]"Cloning and pharmacological characterization of human alpha-1 adrenergic receptors: sequence corrections and direct comparison with other species homologues."
Schwinn D.A., Johnston G.I., Page S.O., Mosley M.J., Wilson K.H., Worman N.P., Campbell S., Fidock M.D., Furness L.M., Parry-Smith D.J., Peter B., Bailey D.S.
J. Pharmacol. Exp. Ther. 272:134-142(1995) [PubMed: 7815325] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ARG-347.
[6]"Cloning, functional expression and tissue distribution of human alpha 1c-adrenoceptor splice variants."
Hirasawa A., Shibata K., Horie K., Takei Y., Obika K., Tanaka T., Muramoto N., Takagaki K., Yano J., Tsujimoto G.
FEBS Lett. 363:256-260(1995) [PubMed: 7737411] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), VARIANT ARG-347, TISSUE SPECIFICITY.
Tissue: Prostate.
[7]"Molecular cloning, genomic characterization and expression of novel human alpha1A-adrenoceptor isoforms."
Chang D.J., Chang T.K., Yamanishi S.S., Salazar F.H.R., Kosaka A.H., Khare R., Bhakta S., Jasper J.R., Shieh I.-S., Lesnick J.D., Ford A.P.D.W., Daniels D.V., Clarke D.E., Bach C.T., Chan H.W.
FEBS Lett. 422:279-283(1998) [PubMed: 9490024] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), TISSUE SPECIFICITY.
Tissue: Prostate.
[8]"Truncated isoforms inhibit [3H]prazosin binding and cellular trafficking of native human alpha1A-adrenoceptors."
Coge F., Guenin S.P., Renouard-Try A., Rique H., Ouvry C., Fabry N., Beauverger P., Nicolas J.P., Galizzi J.-P., Boutin J.A., Canet E.
Biochem. J. 343:231-239(1999) [PubMed: 10493934] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2B/3B; 2C; 3C; 5 AND 6).
Tissue: Liver.
[9]"Genome-wide discovery and analysis of human seven transmembrane helix receptor genes."
Suwa M., Sato T., Okouchi I., Arita M., Futami K., Matsumoto S., Tsutsumi S., Aburatani H., Asai K., Akiyama Y.
Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[10]"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
Kopatz S.A., Aronstam R.S., Sharma S.V.
Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[11]"Alpha 1a-adrenoceptor polymorphism: pharmacological characterization and association with benign prostatic hypertrophy."
Shibata K., Hirasawa A., Moriyama N., Kawabe K., Ogawa S., Tsujimoto G.
Br. J. Pharmacol. 118:1403-1408(1996) [