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TKN1_RAT
ID   TKN1_RAT                Reviewed;         130 AA.
AC   P06767; P08856; P08857; P22356; Q6LD93;
DT   01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT   30-MAY-2000, sequence version 2.
DT   03-AUG-2022, entry version 172.
DE   RecName: Full=Protachykinin-1;
DE   AltName: Full=PPT;
DE   Contains:
DE     RecName: Full=Substance P;
DE   Contains:
DE     RecName: Full=Neurokinin A;
DE              Short=NKA;
DE     AltName: Full=Neuromedin L;
DE     AltName: Full=Substance K;
DE   Contains:
DE     RecName: Full=Neuropeptide K;
DE              Short=NPK;
DE   Contains:
DE     RecName: Full=Neuropeptide gamma;
DE   Contains:
DE     RecName: Full=C-terminal-flanking peptide;
DE   Flags: Precursor;
GN   Name=Tac1; Synonyms=Nka, Nkna, Tac2;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS ALPHA; BETA AND GAMMA).
RX   PubMed=1695945; DOI=10.1523/jneurosci.10-07-02203.1990;
RA   Carter M.S., Krause J.E.;
RT   "Structure, expression, and some regulatory mechanisms of the rat
RT   preprotachykinin gene encoding substance P, neurokinin A, neuropeptide K,
RT   and neuropeptide gamma.";
RL   J. Neurosci. 10:2203-2214(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA; BETA AND GAMMA).
RX   PubMed=2433692; DOI=10.1073/pnas.84.3.881;
RA   Krause J.E., Chirgwin J.M., Carter M.S., Xu Z.S., Hershey A.D.;
RT   "Three rat preprotachykinin mRNAs encode the neuropeptides substance P and
RT   neurokinin A.";
RL   Proc. Natl. Acad. Sci. U.S.A. 84:881-885(1987).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM GAMMA).
RX   PubMed=2429656; DOI=10.1016/s0006-291x(86)80282-0;
RA   Kawaguchi Y., Hoshimaru M., Nawa H., Nakanishi S.;
RT   "Sequence analysis of cloned cDNA for rat substance P precursor: existence
RT   of a third substance P precursor.";
RL   Biochem. Biophys. Res. Commun. 139:1040-1046(1986).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM DELTA).
RC   TISSUE=Spinal ganglion;
RX   PubMed=1702066; DOI=10.1016/0014-5793(90)81429-r;
RA   Harmar A.J., Hyde V., Chapman K.E.;
RT   "Identification and cDNA sequence of delta-preprotachykinin, a fourth
RT   splicing variant of the rat substance P precursor.";
RL   FEBS Lett. 275:22-24(1990).
RN   [5]
RP   NUCLEOTIDE SEQUENCE OF 1-41.
RX   PubMed=8448217; DOI=10.1016/0167-4781(93)90233-4;
RA   Chapman K.E., Lyons V., Harmar A.J.;
RT   "The sequence of 5' flanking DNA from the rat preprotachykinin gene;
RT   analysis of putative transcription factor binding sites.";
RL   Biochim. Biophys. Acta 1172:361-363(1993).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 48-125 (ISOFORM DELTA).
RX   PubMed=7519424; DOI=10.1006/bbrc.1994.2000;
RA   Khan I., Collins S.M.;
RT   "Fourth isoform of preprotachykinin messenger RNA encoding for substance P
RT   in the rat intestine.";
RL   Biochem. Biophys. Res. Commun. 202:796-802(1994).
RN   [7]
RP   IDENTIFICATION OF C-TERMINAL-FLANKING PEPTIDE.
RX   PubMed=2809597; DOI=10.1111/j.1471-4159.1989.tb09255.x;
RA   McGregor G.P., Kage R., Thim L., Conlon J.M.;
RT   "Quantitation and characterization of peptides from the C-terminal flanking
RT   region of rat and bovine preprotachykinins.";
RL   J. Neurochem. 53:1871-1877(1989).
CC   -!- FUNCTION: Tachykinins are active peptides which excite neurons, evoke
CC       behavioral responses, are potent vasodilators and secretagogues, and
CC       contract (directly or indirectly) many smooth muscles.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=4;
CC       Name=Beta;
CC         IsoId=P06767-1; Sequence=Displayed;
CC       Name=Alpha;
CC         IsoId=P06767-2; Sequence=VSP_006381, VSP_006382;
CC       Name=Gamma;
CC         IsoId=P06767-3; Sequence=VSP_006380;
CC       Name=Delta;
CC         IsoId=P06767-4; Sequence=VSP_006380, VSP_006381, VSP_006382;
CC   -!- PTM: [Substance P]: The substance P form is cleaved at Pro-59 by the
CC       prolyl endopeptidase FAP (seprase) activity (in vitro). Substance P is
CC       also cleaved and degraded by Angiotensin-converting enzyme (ACE) and
CC       neprilysin (MME). {ECO:0000250|UniProtKB:P20366}.
CC   -!- SIMILARITY: Belongs to the tachykinin family. {ECO:0000305}.
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DR   EMBL; M34162; AAA41926.1; -; Genomic_DNA.
DR   EMBL; M34159; AAA41926.1; JOINED; Genomic_DNA.
DR   EMBL; M34160; AAA41926.1; JOINED; Genomic_DNA.
DR   EMBL; M34161; AAA41926.1; JOINED; Genomic_DNA.
DR   EMBL; M34184; AAA41925.1; -; mRNA.
DR   EMBL; M34183; AAA41929.1; -; mRNA.
DR   EMBL; M15191; AAA41928.1; -; mRNA.
DR   EMBL; M14312; AAA41927.1; -; mRNA.
DR   EMBL; L07328; AAA41924.1; -; Genomic_DNA.
DR   EMBL; X56306; CAA39752.1; -; mRNA.
DR   EMBL; S72369; AAB31499.1; -; mRNA.
DR   PIR; A37163; SPRTB.
DR   PIR; B26590; SPRTA.
DR   PIR; S12958; S12958.
DR   RefSeq; NP_001118240.1; NM_001124768.1. [P06767-3]
DR   RefSeq; NP_001118241.1; NM_001124769.1. [P06767-4]
DR   RefSeq; NP_001118242.1; NM_001124770.1. [P06767-2]
DR   RefSeq; NP_036798.1; NM_012666.2. [P06767-1]
DR   AlphaFoldDB; P06767; -.
DR   STRING; 10116.ENSRNOP00000009888; -.
DR   BindingDB; P06767; -.
DR   PaxDb; P06767; -.
DR   GeneID; 24806; -.
DR   KEGG; rno:24806; -.
DR   UCSC; RGD:3807; rat. [P06767-1]
DR   CTD; 6863; -.
DR   RGD; 3807; Tac1.
DR   eggNOG; ENOG502S1KJ; Eukaryota.
DR   HOGENOM; CLU_149426_0_0_1; -.
DR   InParanoid; P06767; -.
DR   OMA; NQIQDDW; -.
DR   OrthoDB; 1504814at2759; -.
DR   PhylomeDB; P06767; -.
DR   TreeFam; TF333405; -.
DR   Reactome; R-RNO-380095; Tachykinin receptors bind tachykinins.
DR   Reactome; R-RNO-416476; G alpha (q) signalling events.
DR   PRO; PR:P06767; -.
DR   Proteomes; UP000002494; Chromosome 4.
DR   Bgee; ENSRNOG00000007374; Expressed in duodenum and 11 other tissues.
DR   Genevisible; P06767; RN.
DR   GO; GO:0030424; C:axon; ISO:RGD.
DR   GO; GO:0005576; C:extracellular region; ISO:RGD.
DR   GO; GO:0005615; C:extracellular space; IDA:RGD.
DR   GO; GO:0043025; C:neuronal cell body; ISO:RGD.
DR   GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR   GO; GO:0045202; C:synapse; IEA:GOC.
DR   GO; GO:0031837; F:substance K receptor binding; ISO:RGD.
DR   GO; GO:0031835; F:substance P receptor binding; IDA:RGD.
DR   GO; GO:0008306; P:associative learning; IDA:RGD.
DR   GO; GO:1990090; P:cellular response to nerve growth factor stimulus; ISO:RGD.
DR   GO; GO:0007268; P:chemical synaptic transmission; IEA:UniProtKB-KW.
DR   GO; GO:0006954; P:inflammatory response; ISO:RGD.
DR   GO; GO:0007616; P:long-term memory; IDA:RGD.
DR   GO; GO:0010459; P:negative regulation of heart rate; IDA:RGD.
DR   GO; GO:0007218; P:neuropeptide signaling pathway; IEA:UniProtKB-KW.
DR   GO; GO:0045760; P:positive regulation of action potential; IDA:RGD.
DR   GO; GO:0002675; P:positive regulation of acute inflammatory response; IDA:RGD.
DR   GO; GO:2000854; P:positive regulation of corticosterone secretion; IDA:RGD.
DR   GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IDA:RGD.
DR   GO; GO:0010634; P:positive regulation of epithelial cell migration; IDA:RGD.
DR   GO; GO:1902093; P:positive regulation of flagellated sperm motility; ISO:RGD.
DR   GO; GO:0050671; P:positive regulation of lymphocyte proliferation; IMP:RGD.
DR   GO; GO:0045778; P:positive regulation of ossification; IDA:RGD.
DR   GO; GO:0035815; P:positive regulation of renal sodium excretion; IDA:RGD.
DR   GO; GO:0046878; P:positive regulation of saliva secretion; IDA:RGD.
DR   GO; GO:0051496; P:positive regulation of stress fiber assembly; IDA:RGD.
DR   GO; GO:0032224; P:positive regulation of synaptic transmission, cholinergic; IDA:RGD.
DR   GO; GO:0032230; P:positive regulation of synaptic transmission, GABAergic; IDA:RGD.
DR   GO; GO:0008217; P:regulation of blood pressure; IDA:RGD.
DR   GO; GO:0009725; P:response to hormone; IMP:RGD.
DR   GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR   GO; GO:0043278; P:response to morphine; IEP:RGD.
DR   GO; GO:0048265; P:response to pain; ISO:RGD.
DR   GO; GO:0019233; P:sensory perception of pain; ISO:RGD.
DR   GO; GO:0007217; P:tachykinin receptor signaling pathway; IBA:GO_Central.
DR   InterPro; IPR013055; Tachy_Neuro_lke_CS.
DR   InterPro; IPR008215; Tachykinin_dom.
DR   InterPro; IPR008216; Tachykinin_fam.
DR   Pfam; PF02202; Tachykinin; 1.
DR   PRINTS; PR01829; PROTACHYKNIN.
DR   SMART; SM00203; TK; 2.
DR   PROSITE; PS00267; TACHYKININ; 2.
PE   2: Evidence at transcript level;
KW   Alternative splicing; Amidation; Cleavage on pair of basic residues;
KW   Neuropeptide; Neurotransmitter; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000255"
FT   PROPEP          20..56
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000033550"
FT   PEPTIDE         58..68
FT                   /note="Substance P"
FT                   /id="PRO_0000033551"
FT   PEPTIDE         72..107
FT                   /note="Neuropeptide K"
FT                   /id="PRO_0000033552"
FT   PEPTIDE         72..73
FT                   /note="Neuropeptide gamma, 1st part"
FT                   /id="PRO_0000033553"
FT   PEPTIDE         89..107
FT                   /note="Neuropeptide gamma, 2nd part"
FT                   /id="PRO_0000033554"
FT   PEPTIDE         98..107
FT                   /note="Neurokinin A"
FT                   /id="PRO_0000033555"
FT   PEPTIDE         111..126
FT                   /note="C-terminal-flanking peptide"
FT                   /id="PRO_0000033556"
FT   SITE            59..60
FT                   /note="Cleavage; by FAP"
FT                   /evidence="ECO:0000250|UniProtKB:P20366"
FT   SITE            63..64
FT                   /note="Cleavage; by MME"
FT                   /evidence="ECO:0000250|UniProtKB:P20366"
FT   SITE            64..65
FT                   /note="Cleavage; by MME"
FT                   /evidence="ECO:0000250|UniProtKB:P20366"
FT   SITE            65..66
FT                   /note="Cleavage; by ACE"
FT                   /evidence="ECO:0000250|UniProtKB:P20366"
FT   SITE            66..67
FT                   /note="Cleavage; by ACE and MME"
FT                   /evidence="ECO:0000250|UniProtKB:P20366"
FT   MOD_RES         68
FT                   /note="Methionine amide"
FT                   /evidence="ECO:0000250|UniProtKB:P20366"
FT   MOD_RES         107
FT                   /note="Methionine amide"
FT                   /evidence="ECO:0000250|UniProtKB:P20366"
FT   VAR_SEQ         74..88
FT                   /note="Missing (in isoform Gamma and isoform Delta)"
FT                   /evidence="ECO:0000303|PubMed:1702066,
FT                   ECO:0000303|PubMed:2429656, ECO:0000303|PubMed:2433692,
FT                   ECO:0000303|PubMed:7519424"
FT                   /id="VSP_006380"
FT   VAR_SEQ         97..114
FT                   /note="Missing (in isoform Alpha and isoform Delta)"
FT                   /evidence="ECO:0000303|PubMed:1702066,
FT                   ECO:0000303|PubMed:2433692, ECO:0000303|PubMed:7519424"
FT                   /id="VSP_006381"
FT   VAR_SEQ         115
FT                   /note="V -> M (in isoform Alpha and isoform Delta)"
FT                   /evidence="ECO:0000303|PubMed:1702066,
FT                   ECO:0000303|PubMed:2433692, ECO:0000303|PubMed:7519424"
FT                   /id="VSP_006382"
SQ   SEQUENCE   130 AA;  15001 MW;  B22EFE860DCCD75A CRC64;
     MKILVAVAVF FLVSTQLFAE EIGANDDLNY WSDWSDSDQI KEAMPEPFEH LLQRIARRPK
     PQQFFGLMGK RDADSSIEKQ VALLKALYGH GQISHKRHKT DSFVGLMGKR ALNSVAYERS
     AMQNYERRRK
 
 
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