LOCUS       NP_002214               2701 aa            linear   PRI 27-APR-2025
DEFINITION  inositol 1,4,5-trisphosphate-gated calcium channel ITPR2 isoform 1
            [Homo sapiens].
ACCESSION   NP_002214
VERSION     NP_002214.2
DBSOURCE    REFSEQ: accession NM_002223.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 2701)
  AUTHORS   Zhou,S., Wang,Z., Liu,Z., Mu,G., Xie,Q., Wang,Z., Xiang,Q., Gong,Y.
            and Cui,Y.
  TITLE     Candidate Gene of NOS3, MMP3, AGT, and AGT1R and Pathway Analyses
            for Platelet Reactivity and Clinical Outcomes of Repeat
            Revascularization After First PCI in Chinese Patients
  JOURNAL   Cardiovasc Drugs Ther 37 (3), 507-518 (2023)
   PUBMED   34860335
  REMARK    GeneRIF: Candidate Gene of NOS3, MMP3, AGT, and AGT1R and Pathway
            Analyses for Platelet Reactivity and Clinical Outcomes of Repeat
            Revascularization After First PCI in Chinese Patients.
REFERENCE   2  (residues 1 to 2701)
  AUTHORS   Chen,J., Zhou,J., Jiang,Y., Wang,Y., Chen,C., Jiang,T. and Du,J.
  TITLE     Inositol 1,4,5-trisphosphate receptor gene variants are related to
            the risk of breast cancer in a Chinese population
  JOURNAL   J Gene Med 25 (2), e3463 (2023)
   PUBMED   36350267
  REMARK    GeneRIF: Inositol 1,4,5-trisphosphate receptor gene variants are
            related to the risk of breast cancer in a Chinese population.
REFERENCE   3  (residues 1 to 2701)
  AUTHORS   Ziegler,D.V., Vindrieux,D., Goehrig,D., Jaber,S., Collin,G.,
            Griveau,A., Wiel,C., Bendridi,N., Djebali,S., Farfariello,V.,
            Prevarskaya,N., Payen,L., Marvel,J., Aubert,S., Flaman,J.M.,
            Rieusset,J., Martin,N. and Bernard,D.
  TITLE     Calcium channel ITPR2 and mitochondria-ER contacts promote cellular
            senescence and aging
  JOURNAL   Nat Commun 12 (1), 720 (2021)
   PUBMED   33526781
  REMARK    GeneRIF: Calcium channel ITPR2 and mitochondria-ER contacts promote
            cellular senescence and aging.
            Publication Status: Online-Only
REFERENCE   4  (residues 1 to 2701)
  AUTHORS   Klar,J., Hisatsune,C., Baig,S.M., Tariq,M., Johansson,A.C.,
            Rasool,M., Malik,N.A., Ameur,A., Sugiura,K., Feuk,L., Mikoshiba,K.
            and Dahl,N.
  TITLE     Abolished InsP3R2 function inhibits sweat secretion in both humans
            and mice
  JOURNAL   J Clin Invest 124 (11), 4773-4780 (2014)
   PUBMED   25329695
  REMARK    GeneRIF: Loss of InsP3R2-mediated calcium release causes isolated
            anhidrosis in humans.
REFERENCE   5  (residues 1 to 2701)
  AUTHORS   Sankar,N., deTombe,P.P. and Mignery,G.A.
  TITLE     Calcineurin-NFATc regulates type 2 inositol 1,4,5-trisphosphate
            receptor (InsP3R2) expression during cardiac remodeling
  JOURNAL   J Biol Chem 289 (9), 6188-6198 (2014)
   PUBMED   24415751
  REMARK    GeneRIF: ITPR2 and hypertrophy specific gene expression is
            regulated, in part, by a positive feedback regulation between
            InsP3R2 and calcineurin-NFATc signaling pathways.
REFERENCE   6  (residues 1 to 2701)
  AUTHORS   Tanimura,A., Tojyo,Y. and Turner,R.J.
  TITLE     Evidence that type I, II, and III inositol 1,4,5-trisphosphate
            receptors can occur as integral plasma membrane proteins
  JOURNAL   J Biol Chem 275 (35), 27488-27493 (2000)
   PUBMED   10874040
REFERENCE   7  (residues 1 to 2701)
  AUTHORS   Mayne,M., Holden,C.P., Nath,A. and Geiger,J.D.
  TITLE     Release of calcium from inositol 1,4,5-trisphosphate
            receptor-regulated stores by HIV-1 Tat regulates TNF-alpha
            production in human macrophages
  JOURNAL   J Immunol 164 (12), 6538-6542 (2000)
   PUBMED   10843712
REFERENCE   8  (residues 1 to 2701)
  AUTHORS   El-Daher,S.S., Patel,Y., Siddiqua,A., Hassock,S., Edmunds,S.,
            Maddison,B., Patel,G., Goulding,D., Lupu,F., Wojcikiewicz,R.J. and
            Authi,K.S.
  TITLE     Distinct localization and function of (1,4,5)IP(3) receptor
            subtypes and the (1,3,4,5)IP(4) receptor GAP1(IP4BP) in highly
            purified human platelet membranes
  JOURNAL   Blood 95 (11), 3412-3422 (2000)
   PUBMED   10828023
  REMARK    Erratum:[Blood 2000 Sep 1;96(5):1684]
REFERENCE   9  (residues 1 to 2701)
  AUTHORS   Futatsugi,A., Kuwajima,G. and Mikoshiba,K.
  TITLE     Muscle-specific mRNA isoform encodes a protein composed mainly of
            the N-terminal 175 residues of type 2 Ins(1,4,5)P3 receptor
  JOURNAL   Biochem J 334 (Pt 3) (Pt 3), 559-563 (1998)
   PUBMED   9729462
REFERENCE   10 (residues 1 to 2701)
  AUTHORS   Yamamoto-Hino,M., Sugiyama,T., Hikichi,K., Mattei,M.G.,
            Hasegawa,K., Sekine,S., Sakurada,K., Miyawaki,A., Furuichi,T.,
            Hasegawa,M. et al.
  TITLE     Cloning and characterization of human type 2 and type 3 inositol
            1,4,5-trisphosphate receptors
  JOURNAL   Recept Channels 2 (1), 9-22 (1994)
   PUBMED   8081734
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC024093.46, D26350.1,
            BX495410.1, AL711179.1, BP314401.1, BP364657.1, BU173910.1,
            DB144849.1, AC055720.17, BE439696.1, AI339141.1 and CA419735.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On May 13, 2006 this sequence version replaced NP_002214.1.
            
            Summary: The protein encoded by this gene belongs to the inositol
            1,4,5-triphosphate receptor family, whose members are second
            messenger intracellular calcium release channels. These proteins
            mediate a rise in cytoplasmic calcium in response to receptor
            activated production of inositol triphosphate. Inositol
            triphosphate receptor-mediated signaling is involved in many
            processes including cell migration, cell division, smooth muscle
            contraction, and neuronal signaling. This protein is a type 2
            receptor that consists of a cytoplasmic amino-terminus that binds
            inositol triphosphate, six membrane-spanning helices that
            contribute to the ion pore, and a short cytoplasmic
            carboxy-terminus. A mutation in this gene has been associated with
            anhidrosis, suggesting that intracellular calcium release mediated
            by this protein is required for eccrine sweat production. [provided
            by RefSeq, Apr 2015].
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: D26350.1, SRR1803613.259045.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000381340.8/ ENSP00000370744.3
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..2701
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="12"
                     /map="12p11.23"
     Protein         1..2701
                     /product="inositol 1,4,5-trisphosphate-gated calcium
                     channel ITPR2 isoform 1"
                     /note="IP3R 2; type 2 InsP3 receptor; IP3 receptor; cilia
                     and flagella associated protein 48; inositol
                     1,4,5-trisphosphate-gated calcium channel ITPR2"
                     /calculated_mol_wt=307934
     Region          5..228
                     /region_name="Ins145_P3_rec"
                     /note="Inositol 1,4,5-trisphosphate/ryanodine receptor;
                     pfam08709"
                     /db_xref="CDD:462572"
     Region          218..439
                     /region_name="beta-trefoil_MIR_ITPR2"
                     /note="MIR domain, beta-trefoil fold, found in inositol
                     1,4,5-trisphosphate receptor type 2 (ITPR2) and similar
                     proteins; cd23288"
                     /db_xref="CDD:467759"
     Site            order(245..246,386)
                     /site_type="other"
                     /note="putative homotetramer interface [polypeptide
                     binding]"
                     /db_xref="CDD:467759"
     Site            order(265,267..269,275)
                     /site_type="other"
                     /note="putative ligand binding site [chemical binding]"
                     /db_xref="CDD:467759"
     Region          475..670
                     /region_name="RYDR_ITPR"
                     /note="RIH domain; pfam01365"
                     /db_xref="CDD:460175"
     Site            937
                     /site_type="phosphorylation"
                     /note="Phosphoserine, by PKA.
                     /evidence=ECO:0000250|UniProtKB:Q9Z329; propagated from
                     UniProtKB/Swiss-Prot (Q14571.2)"
     Region          1140..1174
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (Q14571.2)"
     Site            1160
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:18669648,
                     ECO:0007744|PubMed:23186163; propagated from
                     UniProtKB/Swiss-Prot (Q14571.2)"
     Region          1202..1344
                     /region_name="RYDR_ITPR"
                     /note="RIH domain; pfam01365"
                     /db_xref="CDD:460175"
     Site            1709
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000250|UniProtKB:Q9Z329; propagated from
                     UniProtKB/Swiss-Prot (Q14571.2)"
     Region          1915..2022
                     /region_name="RIH_assoc"
                     /note="RyR and IP3R Homology associated; pfam08454"
                     /db_xref="CDD:462482"
     Site            2228..2248
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q14571.2)"
     Site            2261..2281
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q14571.2)"
     Region          2290..2552
                     /region_name="Ion_trans"
                     /note="Ion transport protein; pfam00520"
                     /db_xref="CDD:459842"
     Site            2308..2328
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q14571.2)"
     Site            2352..2372
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q14571.2)"
     Site            2395..2415
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q14571.2)"
     Site            2522..2542
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q14571.2)"
     Site            2607
                     /site_type="phosphorylation"
                     /note="Phosphotyrosine. /evidence=ECO:0000255; propagated
                     from UniProtKB/Swiss-Prot (Q14571.2)"
     Site            2633
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000250|UniProtKB:Q9Z329; propagated from
                     UniProtKB/Swiss-Prot (Q14571.2)"
     Site            2636
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000250|UniProtKB:Q9Z329; propagated from
                     UniProtKB/Swiss-Prot (Q14571.2)"
     CDS             1..2701
                     /gene="ITPR2"
                     /gene_synonym="ANHD; CFAP48; INSP3R2; IP3R2"
                     /coded_by="NM_002223.4:414..8519"
                     /note="isoform 1 is encoded by transcript variant 1"
                     /db_xref="CCDS:CCDS41764.1"
                     /db_xref="GeneID:3709"
                     /db_xref="HGNC:HGNC:6181"
                     /db_xref="MIM:600144"
ORIGIN      
        1 mtekmssfly igdivslyae gsvngfistl glvddrcvvh peagdlanpp kkfrdclfkv
       61 cpmnrysaqk qywkakqakq gnhteaallk klqhaaeleq kqnesenkkl lgeivkysnv
      121 iqllhiksnk yltvnkrlpa lleknamrvs ldaagnegsw fyihpfwklr segdnivvgd
      181 kvvlmpvnag qplhasniel ldnpgckevn avncntswki tlfmkyssyr edvlkggdvv
      241 rlfhaeqekf ltcdeyekkq hiflrttlrq satsatsska lweievvhhd pcrggagqwn
      301 slfrfkhlat gnylaaelnp dyrdaqnegk nvrdgvppts kkkrqageki mytlvsvphg
      361 ndiaslfeld attlqradcl vprnsyvrlr hlctntwvts tsipidtdee rpvmlkigtc
      421 qtkedkeafa ivsvplsevr dldfandank vlattvkkle ngtitqnerr fvtklledli
      481 ffvadvpnng qevldvvitk pnrerqklmr eqnilaqvfg ilkapfkeka gegsmlrled
      541 lgdqryapyk ymlrlcyrvl rhsqqdyrkn qeyiaknfcv mqsqigydil aedtitallh
      601 nnrkllekhi takeietfvs llrrnreprf ldylsdlcvs nttaipvtqe lickfmlspg
      661 nadiliqtkv vsmqadnpme ssilsddidd eevwlywids nkephgkair hlaqeakegt
      721 kadlevltyy ryqlnlfarm cldrqylain qistqlsvdl ilrcvsdesl pfdlrasfcr
      781 lmlhmhvdrd pqesvvpvry arlwteiptk itiheydsit dssrndmkrk faltmefvee
      841 ylkevvnqpf pfgdkeknkl tfevvhlarn liyfgfysfs ellrltrtll aildivqapm
      901 ssyferlskf qdggnnvmrt ihgvgemmtq mvlsrgsifp msvpdvppsi hpskqgspte
      961 hedvtvmdtk lkiieilqfi lsvrldyris ymlsiykkef gedndnaets asgspdtllp
     1021 saivpdidei aaqaetmfag rkeknpvqld deggrtflrv lihlimhdyp pllsgalqll
     1081 fkhfsqraev lqafkqvqll vsnqdvdnyk qikadldqlr ltvekselwv ekssnyenge
     1141 igesqvkgge epieesnils pvqdgtkkpq idsnksnnyr ivkeilirls klcvqnkkcr
     1201 nqhqrllknm gahsvvldll qipyekndek mnevmnlaht flqnfcrgnp qnqvllhkhl
     1261 nlfltpglle aetmrhifmn nyhlcneise rvvqhfvhci ethgrhveyl rflqtivkad
     1321 gkyvkkcqdm vmtelingge dvlifyndra sfpillhmmc serdrgdesg playhitlve
     1381 llaactegkn vyteikcnsl lplddivrvv thddcipevk iayvnfvnhc yvdtevemke
     1441 iytsnhiwkl fenflvdmar vcntttdrkh adiflekcvt esimnivsgf fnspfsdnst
     1501 slqthqpvfi qllqsafriy nctwpnpaqk asvescirtl aevaknrgia ipvdldsqvn
     1561 tlfmkshsnm vqraamgwrl sarsgprfke alggpawdyr niieklqdvv aslehqfspm
     1621 mqaefsvlvd vlyspellfp egsdarircg afmsklinht kklmekeekl cikilqtlre
     1681 mlekkdsfve egntlrkill nryfkgdysi gvnghlsgay sktaqvggsf sgqdsdkmgi
     1741 smsdiqclld kegaselvid vivntkndri fsegiflgia lleggntqtq ysfyqqlheq
     1801 kksekffkvl ydrmkaaqke irstvtvnti dlgnkkrddd nelmtsgprm rvrdstlhlk
     1861 egmkgqltea ssatskaycv yrremdpeid imctgpeagn teeksaeevt mspaiaimqp
     1921 ilrflqllce nhnrelqnfl rnqnnktnyn lvcetlqfld cicgsttggl gllglyinek
     1981 nvalvnqnle slteycqgpc henqtciath esngidiiia lilndinplg kyrmdlvlql
     2041 knnaskllla imesrhdsen aerilfnmrp relvdvmkna ynqglecdhg ddeggddgvs
     2101 pkdvghniyi lahqlarhnk llqqmlkpgs dpdegdealk yyanhtaqie ivrhdrtmeq
     2161 ivfpvpnice yltreskcrv fntterdeqg skvndffqqt edlynemkwq kkirnnpalf
     2221 wfsrhislwg sisfnlavfi nlavalfypf gddgdegtls plfsvllwia vaictsmlff
     2281 fskpvgirpf lvsimlrsiy tiglgptlil lgaanlcnki vflvsfvgnr gtftrgyrav
     2341 ildmaflyhv ayvlvcmlgl fvheffysfl lfdlvyreet llnviksvtr ngrsiiltav
     2401 lalilvylfs iigflflkdd ftmevdrlkn rtpvtgshqv ptmtlttmme acakencspt
     2461 ipasntadee yedgiertcd tllmcivtvl nqglrngggv gdvlrrpskd eplfaarvvy
     2521 dllfyfivii ivlnlifgvi idtfadlrse kqkkeeilkt tcficglerd kfdnktvsfe
     2581 ehiksehnmw hylyfivlvk vkdpteytgp esyvaqmive knldwfprmr amslvsnegd
     2641 seqneirslq eklestmslv kqlsgqlael keqmteqrkn kqrlgflgsn tphvnhhmpp
     2701 h
//
