Molecule Information

General Information of the Molecule (ID: Mol04291)

• Name: Xin actin-binding repeat-containing protein 2 (XIRP2) ,Homo sapiens
• Synonyms: Beta-xin; Cardiomyopathy-associated protein 3; Xeplin
• Molecule Type: Protein
• Gene Name: XIRP2
• Gene ID: 129446
• Sequence:
  MSPESGHSRIFEATAGPNKPESGFAEDSAARGEGVSDLHEVVSLKERMARYQAAVSRGDC
  RSFSANMMEESEMCAVPGGLAKVKKQFEDEITSSRNTFAQYQYQHQNRSEQEAIHSSQV
  G TSRSSQEMARNEQEGSKVQKIDVHGTEMVSHLEKHTEEVNQASQFHQYVQETVIDTPE
  DE EIPKVSTKLLKEQFEKSAQEKILYSDKEMTTPAKQIKTESEYEETFKPSSVVSTSST
  SCV STSQRKETSTTRYSDHSVTSSTLAQINATSSGMTEEFPPPPPDVLQTSVDVTAFSQ
  SPEL PSPPRRLPVPKDVYSKQRNLYELNRLYKHIHPELRKNLEKDYISEVSEIVSSQMN
  SGSSV SADVQQARYVFENTNDSSQKDLNSEREYLEWDEILKGEVQSIRWIFENQPLDSI
  NNGSPD EGDISRGIADQEIIAGGDVKYTTWMFETQPIDTLGAYSSDTVENAEKIPELAR
  GDVCTAR WMFETRPLDSMNKMHQSQEESAVTISKDITGGDVKTVRYMFETQHLDQLGQL
  HSVDEVHL LQLRSELKEIKGNVKRSIKCFETQPLYVIRDGSGQMLEIKTVHREDVEKGD
  VRTARWMFE TQPLDTINKDITEIKVVRGISMEENVKGGVSKAKWLFETQPLEKIKESEE
  VIIEKEKIIG TDVSRKCWMFETQPLDILKEVPDADSLQREEIIGGDVQTTKHLFETLPI
  EALKDSPDIGK LQKITASEEEKGDVRHQKWIFETQPLEDIRKDKKEYTRTVKLEEVDRG
  DVKNYTHIFESN NLIKFDASHKIEVEGVTRGAVELNKSLFETTPLYAIQDPLGKYHQVK
  TVQQEEIVRGDVR SCRWLFETRPIDQFDESIHKFQIIRGISAQEIQTGNVKSAKWLFET
  QPLDSIKYFSDVEE TESKTEQTRDIVKGDVKTCKWLFETQPMESLYEKVSLMTSSEEIH
  KGDVKTCTWLFETQP LDTIKDDSETAVKLQTVKQEEIQGGDVRTACFLFETENLDSIQG
  EEVKEIKPVEMDIQAG DVSSMRYKFENQSLDSISSSSEEVLKKIKTLKTEDIQKGNVLN
  CRWLFENQPIDKIKESQ EGDECVKTVTDIQGGDVRKGCFIFETFSLDEIKEESDYISTK
  KTITEEVIQGDVKSYRML FETQPLYAIQDREGSYHEVTTVKKEEVIHGDVRGTRWLFET
  KPLDSINKSETVYVIKSVT QEDIQKGDVSSVRYRFETQPLDQISEESHNIMPSIDHIQG
  GNVKTSRQFFESENFDKNNY IRTVSVNEIQKGNVKTSTWLFETHTMDELRGEGLEYENI
  KTVTQEDVQKGDVKQAVWLFE NRTFDSIMEAHKGITKMTKEEIPPSDVKTTTWLFETTP
  LHEFNETRVEKIEIIGKSIKET LEDLYSQKVIQAPGIIIEADEIGDVRMAKYKLMNQAS
  PEIQKEEIIRADLRNIMVNLLSK RDCTEREILISEEEKGNVNLTKTQLLNRSTEFHAEK
  EEIVKGDVQQAIKNLFSEERSVKK GILIQEDEKGDINMTIYCLLHENDGDTIEREEVIG
  GDVKRTIHNLLSSTSNNKISERAKI DASERGNVQFFTTCIEAGALDYLKQLHTESNETL
  TAKKQEGEKEIIGGDVEGTKLLLKKR QSLVERTVSETDIIPGDVHNTVKVFMTEPQSTF
  GKIPKEEIIKGDLTSTLNSLSQAVNQK TVTKTEEIIKGNMLATLKSLKESSHRWKESKQ
  PDAIPGDIEKAIECLEKATNTKTEILKK ELLKDDLETSLRSLKEAQRSFKEVHKEGVIK
  KDAKAVMAGSSGEQKTDIHQVAVQRNKNS LLQPKPGPFEPAAKWQGGADTLSQTMGKSC
  HGNLVEERTEVNLPKAPKGTVKIVIDREQN NDALEKSLRRLSNSHHKSNVLESGDKTGV
  WTDTTGEQHLRDEYMSRQLTSTVSVKNNLTT KESDRAVRELKKDDVFNSIQSAGKTVGK
  QQTYELRNDHQKMEGFHIKSPKKTKNIKILTD TQSSKPSPTQHPVSMPVGGTYDLSGDF
  QKQTLLKQETKYSNKDIKKKNINLQPMWQLLPV EQDTSNVTEMKVSEKSHNTFKATNKK
  RETDVHLKSQDFLMKTNTSTGLKMAMERSLNPIN FNPENNVKESECPLPPPSPPPPPPS
  NASSEIEFPLPPPPPLMMFPEKNGFLPSLSTEKIK AEFESFPGLPLPPPPVDEKSERES
  SSMFLPPPPPPTPSQKPAHLLSSSAPEKHSGDFMQQ YSQKEASNSQNSQAKIITGKTGV
  LPPPTLPKPKLPKHIKDNKNDFSPKVELATSLSDMEC KITTSKDQKKVMVMTSSEHTET
  KQNVISKSLDERKQLSIDSANCLSHTVPGTSAPRKKQI APLIKSHSFPESSGQQNPKPY
  MRKFKTPLMIAEEKYRQQKEEIEKQKQESSYYNIVKTQS QNQHITEVEKEMPLQKTNEE
  VSLSGIDSECTVVQPSPGSQSNARILGVCSDNQLSTTSPE TVAAKRLHHVLAASEDKDK
  MKKEVLQSSRDIMQSKSACEIKQSHQECSTQQTQQKKYLEQ LHLPQSKPISPNFKVKTI
  KLPTLDHTLNETDHSYESHKQQSEIDVQTFTKKQYLKTKKTE ASTECSHKQSLAERHYQ
  LPKKEKRVTVQLPTESIQKNQEDKLKMVPRKQREFSGSDRGKL PGSEEKNQGPSMIGRK
  EERLITERKHEHLKNKSAPKVVKQKVIDAHLDSQTQNFQQTQIQ TAESKAEHKKLPQPY
  NSLQEEKCLEVKGIQEKQVFSNTKDSKQEITQNKSFFSSVKESQR DDGKGALNIVEFLR
  KREELQQILSRVKQFEAEPNKSGLKTFQTLLNTIPGWLISEDKREY AVHIAMENNLEKV
  KEEITHIKTQAEDMLVSYENIIQTAMMSSKTGKPGNKPTSLDETSSK VSNVHVSNNKNS
  EQKENKIAKEKTVQHQVAAHHEATVRSHVKTHQEIKLDDSNIPPPSLK TRPPSPTFITI
  ESTARRTENPTKNELSQSPKKDSYVEPPPRRPMSQKSEIHRANTSPSPP RSRSEQLVRL
  KDTTAKLSKGAIPCPAATPVPIVEKRSEIIMSPATLRRQIKIETRGRDSP PTITIPVNI
  NHAASGSFRESVDAQEEIRKVEKRATYVHKDGLNSTDHMVPDTESYDAVEI IRKVAVPP
  RLSEHTQRYEAANRTVQMAENFVNDPENEINRWFREFEHGPVSEAKSNRRVY AKGETNH
  NIQQESRTFCKEEFGLTSLGNTSFTDFSCKHPRELREKIPVKQPRICSETRSL SEHFSG
  MDAFESQIVESKMKTSSSHSSEAGKSGCDFKHAPPTYEDVIAGHILDISDSPKE VRKNF
  QKTWQESGRVFKGLGYATADASATEMRTTFQEESAFISEAAAPRQGNMYTLSKDS LSNG
  VPSGRQAEFS
• Function: Protects actin filaments from depolymerization. Required for correct morphology of cell membranesand maturation of intercalated disks of cardiomyocytes via facilitatinglocalization of XIRP1 and CDH2 to the termini of aligned maturecardiomyocytes . Thereby required for correct postnatalheart development and growth regulation that is crucial for overallheart morphology and diastolic function . Required fornormal electrical conduction in the heart including formation of theinfranodal ventricular conduction system and normal action potentialconfiguration, as a result of its interaction with the cardiac ionchannel components Scn5a/Nav1.5 and Kcna5/Kv1.5 .Required for regular actin filament spacing of the paracrystallinearray in both inner and outer hair cells of the cochlea, therebyrequired for maintenance of stereocilia morphology .{ECO:0000250|UniProtKB:Q4U4S6, ECO:0000269|PubMed:15454575}.
• Uniprot ID: XIRP2_HUMAN
• Ensembl ID: ENSG0000016309222
• HGNC ID: HGNC:14303

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Fludarabine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Cholangiocarcinoma [ICD-11: 2C12.0] [1]

• Resistant Disease: Cholangiocarcinoma [ICD-11: 2C12.0]
• Resistant Drug: Fludarabine
• Molecule Alteration: Mutation; I828V
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SNU475 cells; Liver; Homo sapiens (Human); CVCL_0497
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: CCK-8 assays demonstrated that HCC cells carrying the?XIRP2?mutation exhibited increased resistance to fludarabine and oxaliplatin, but enhanced sensitivity to WEHI-539 and LCL-161 as compared with those HCC cells with the?XIRP2?wildtype. The?XIRP2?mutation was found to have no impact on the mRNA levels of XIRP2 in tissues and cells, but it did enhance the stability of the XIRP2 protein. Mechanically, the inhibition of?XIRP2?resulted in a significant increase in sensitivity to oxaliplatin through an elevation in zinc ions and a calcium ion overload. In conclusion, the?XIRP2?mutation holds potential as a biomarker for predicting the prognosis and drug sensitivity of HCC and serves as a therapeutic target to enhance the efficacy of oxaliplatin.

Oxaliplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Cholangiocarcinoma [ICD-11: 2C12.0] [1]

• Resistant Disease: Cholangiocarcinoma [ICD-11: 2C12.0]
• Resistant Drug: Oxaliplatin
• Molecule Alteration: Mutation; I829V
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SNU475 cells; Liver; Homo sapiens (Human); CVCL_0497
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: CCK-8 assays demonstrated that HCC cells carrying the?XIRP2?mutation exhibited increased resistance to fludarabine and oxaliplatin, but enhanced sensitivity to WEHI-539 and LCL-161 as compared with those HCC cells with the?XIRP2?wildtype. The?XIRP2?mutation was found to have no impact on the mRNA levels of XIRP2 in tissues and cells, but it did enhance the stability of the XIRP2 protein. Mechanically, the inhibition of?XIRP2?resulted in a significant increase in sensitivity to oxaliplatin through an elevation in zinc ions and a calcium ion overload. In conclusion, the?XIRP2?mutation holds potential as a biomarker for predicting the prognosis and drug sensitivity of HCC and serves as a therapeutic target to enhance the efficacy of oxaliplatin.

References

• Ref 1: Identification of Clinical Value and Biological Effects of XIRP2 Mutation in Hepatocellular Carcinoma. Biology (Basel). 2024 Aug 19;13(8):633.