PKHD1

Fibrocistin
Fibrocistin
	Pozicija gena za fibrocistin
Identifikatori
Simbol	PKHD1

PKHD1
Identifikatori
Aliasi	PKHD1
Vanjski ID-jevi	OMIM: 606702 MGI: 2155808 HomoloGene: 16336 GeneCards: PKHD1
Lokacija gena (čovjek)
Hrom.	Hromosom 6 (čovjek)
Kraj	52,087,613 bp
Lokacija gena (miš)
Hrom.	Hromosom 1 (miš)
Kraj	20,688,288 bp
Ontologija gena
Molekularna funkcija	• GO:0001948, GO:0016582 vezivanje za proteine; • signaling receptor activity;
Ćelijska komponenta	• citoplazma; • integral component of membrane; • ciliary basal body; • centrosom; • projekcija ćelije; • membrana; • ćelijska membrana; • Diobeno vreteno; • hromosom; • apical plasma membrane; • anchored component of external side of plasma membrane; • perinuklearno područje citoplazme; • mitotic spindle; • Primarno suženje; • Egzosom; • citoskelet; • Treplja;
Biološki proces	• negative regulation of protein kinase B signaling; • regulation of centrosome duplication; • regulation of TOR signaling; • Nefrogeneza; • cellular calcium ion homeostasis; • negative regulation of apoptotic process; • positive regulation of cell population proliferation; • regulation of ERK1 and ERK2 cascade; • negative regulation of NF-kappaB transcription factor activity; • homeostatic process; • cilium assembly; • cell-cell adhesion;
	Izvori:Amigo / QuickGO
Ortolozi
	5314
	241035
	ENSG00000170927
	ENSMUSG00000043760
	P08F94
	E9PZ36
	NM_138694; NM_170724
	NM_153179
	NP_619639; NP_733842
	NP_694819
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Fibrocistin je veliki, receptoroliki protein za koje se smatra da je uključen u tubulogenezu i/ili održavanje arhitekture lumena epitelnih kanala.^[5]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 4.o74 aminokiseline, a molekulska težina 446.702 Da.^[6].

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MTAWLISLMS	IEVLLLAVRH	LSLHIEPEEG	SLAGGTWITV	IFDGLELGVL
YPNNGSQLEI	HLVNVNMVVP	ALRSVPCDVF	PVFLDLPVVT	CRTRSVLSEA
HEGLYFLEAY	FGGQLVSSPN	PGPRDSCTFK	FSKAQTPIVH	QVYPPSGVPG
KLIHVYGWII	TGRLETFDFD	AEYIDSPVIL	EAQGDKWVTP	CSLINRQMGS
CYPIQEDHGL	GTLQCHVEGD	YIGSQNVSFS	VFNKGKSMVH	KKAWLISAKQ
DLFLYQTHSE	ILSVFPETGS	LGGRTNITIT	GDFFDNSAQV	TIAGIPCDIR
HVSPRKIECT	TRAPGKDVRL	TTPQPGNRGL	LFEVGDAVEG	LELTEATPGY
RWQIVPNASS	PFGFWSQEGQ	PFRARLSGFF	VAPETNNYTF	WIQADSQASL
HFSWSEEPRT	KVKVASISVG	TADWFDSWEQ	NRDEGTWQQK	TPKLELLGGA
MYYLEAEHHG	IAPSRGMRIG	VQIHNTWLNP	DVVTTYLREK	HQIRVRAQRL
PEVQVLNVSG	RGNFFLTWDN	VSSQPIPANA	TAHLIQTTIE	ELLAVKCKLE
PLWSNILLRL	GFERGPEVSN	SDGDLTSGTE	PFCGRFSLRQ	PRHLVLTPPA
AQKGYRLDQY	THLCLAYKGH	MNKILKMIVS	FTIGFQNMVK	NTTCDWSLTR
TSPESWQFDC	TDLWETCVRC	FGDLQPPPAN	SPVLVHQINL	LPLAQETGLF
YVDEIIIADT	NVTVSQADSG	TARPGGNLVE	SVSVVGSPPV	YSVTSWLAGC
GTELPLITAR	SVPTEGTEEG	SGLVLVTTQR	RQRTSPPLGG	HFRIQLPNTV
ISDVPVQISA	HHLHQLLQNN	ADDFTSRYLN	ASDFTVKEDL	YTCYEHVWTL
SWSTQIGDLP	NFIRVSDENL	TGVNPAAATR	VVYDGGVFLG	PIFGDMLATA
NQHTQVVVRV	NDVPAHCPGS	CSFQYLQGST	PCVHSVWYSI	DGDINLMIYI
TGTGFSGDSQ	FLQVTVNKTS	CKVIFSNQTN	VVCQTDLLPV	GMHRILMLVR
PSGLAISATG	EDLFLNVKPR	LDMVEPSRAA	DIGGLWATIR	GSSLEGVSLI
LFGSYSCAIN	VATSNSSRIQ	CKVPPRGKDG	RIVNVTVIRG	DYSAVLPRAF
TYVSSLNPVI	VTLSRNISNI	AGGETLVIGV	ARLMNYTDLD	VEVHVQDALA
PVHTQSAWGL	EVALPPLPAG	LHRISVSING	VSIHSQGVDL	HIQYLTEVFS
IEPCCGSLLG	GTILSISGIG	FSRDPALVWV	LVGNRSCDIV	NLTEASIWCE
TLPAPQIPDA	GAPTVPAAVE	VWAGNRFFAR	GPSPSLVGKG	FTFMYEAAAT
PVVTAMQGEI	TNSSLSLHVG	GSNLSNSVIL	LGNLNCDVET	QSFQGNVSLS
GCSIPLHSLE	AGIYPLQVRQ	KQMGFANMSV	VLQQFAVMPR	IMAIFPSQGS
ACGGTILTVR	GLLLNSRRRS	VRVDLSGPFT	CVILSLGDHT	ILCQVSLEGD
PLPGASFSLN	VTVLVNGLTS	ECQGNCTLFI	REEASPVMDA	LSTNTSGSLT
TVLIRGQRLA	TTADEPMVFV	DDQLPCNVTF	FNASHVVCQT	RDLAPGPHYL
SVFYTRNGYA	CSGNVSRHFY	IMPQVFHYFP	KNFSLHGGSL	LTIEGTGLRG
QNTTSVYIDQ	QTCLTVNIGA	ELIRCIVPTG	NGSVALEIEV	DGLWYHIGVI
GYNKAFTPEL	ISISQSDDIL	TFAVAQISGA	ANIDIFIGMS	PCVGVSGNHT
VLQCVVPSLP	AGEYHVRGYD	CIRGWASSAL	VFTSRVIITA	VTENFGCLGG
RLVHVFGAGF	SPGNVSAAVC	GAPCRVLANA	TVSAFSCLVL	PLDVSLAFLC
GLKREEDSCE	AARHTYVQCD	LTVAMATEQL	LESWPYLYIC	EESSQCLFVP
DHWAESMFPS	FSGLFISPKL	ERDEVLIYNS	SCNITMETEA	EMECETPNQP
ITVKITEIRK	RWGQNTQGNF	SLQFCRRWSR	THSWFPERLP	QDGDNVTVEN
GQLLLLDTNT	SILNLLHIKG	GKLIFMAPGP	IELRAHAILV	SDGGELRIGS
EDKPFQGRAQ	ITLYGSSYST	PFFPYGVKFL	AVRNGTLSLH	GSLPEVIVTC
LRATAHALDT	VLALEDAVDW	NPGDEVVIIS	GTGVKGAKPM	EEIVTVETVQ
DTDLYLKSPL	RYSHNFTENW	VAGEHHILKA	TVALLSRSIT	IQGNLTNERE
KLLVSCQEAN	APEGNLQHCL	YSMSEKMLGS	RDMGARVIVQ	SFPEEPSQVQ
LKGVQFQVLG	QAFHKHLSSL	TLVGAMRESF	IQGCTVRNSF	SRGLSMCGTL
GLKVDSNVFY	NILGHALLVG	TCTEMRYISW	EAIHGRKDDW	SGHGNIIRNN
VIIQVSGAEG	LSNPEMLTPS	GIYICSPTNV	IEGNRVCGAG	YGYFFHLMTN
QTSQAPLLSF	TQNIAHSCTR	YGLFVYPKFQ	PPWDNVTGTT	LFQSFTVWES
AGGAQIFRSS	NLRLKNFKVY	SCRDFGIDVL	ESDANTSVTD	SLLLGHFAHK
GSLCMSSGIK	TPKRWELMVS	NTTFVNFDLI	NCVAIRTCSD	CSQGQGGFTV
KTSQLKFTNS	SNLVAFPFPH	AAILEDLDGS	LSGKNRSHIL	ASMETLSASC
LVNSSFGRVV	HGSACGGGVL	FHRMSIGLAN	TPEVSYDLTM	TDSRNKTTTV
NYVRDTLSNP	RGWMALLLDQ	ETYSLQSENL	WINRSLQYSA	TFDNFAPGNY
LLLVHTDLPP	YPDILLRCGS	RVGLSFPFLP	SPGQNQGCDW	FFNSQLRQLT
YLVSGEGQVQ	VILRVKEGMP	PTISASTSAP	ESALKWSLPE	TWQGVEEGWG
GYNNTIPGPG	DDVLILPNRT	VLVDTDLPFF	KGLYVMGTLD	FPVDRSNVLS
VACMVIAGGE	LKVGTLENPL	EKEQKLLILL	RASEGVFCDR	MNGIHIDPGT
IGVYGKVHLY	SAYPKNSWTH	LGADIASGNE	RIIVEDAVDW	RPHDKIVLSS
SSYEPHEAEV	LTVKEVKGHH	VRIYERLKHR	HIGSVHVTED	GRHIRLAAEV
GLLTRNIQIQ	PDVSCRGRLF	VGSFRKSSRE	EFSGVLQLLN	VEIQNFGSPL
YSSVEFSNVS	AGSWIISSTL	HQSCGGGIHA	AASHGVLLND	NIVFGTAGHG
IDLEGQAYTV	TNNLVVLMTQ	PAWSTIWVAG	IKVNQVKDIN	LHGNVVAGSE
RLGFHIRGHK	CSSCELLWSD	NVAHSSLHGL	HLYKESGLDN	CTRISGFLAF
KNFDYGAMLH	VENSVEIENI	TLVDNTIGLL	AVVYVFSAPQ	NSVKKVQIVL
RNSVIVATSS	SFDCIQDKVK	PHSANLTSTD	RAPSNPRGGR	IGILWPVFTS
EPNQWPQEPW	HKVRNDHSIS	GIMKLQDVTF	SSFVKSCYSD	DLDVCILPNA
ENSGIMHPIT	AERTRMLKIK	DKNKFYFPSL	QPRKDLGKVV	CPELDCASPR
KYLFKDLDGR	ALGLPPPVSV	FPKTEAEWTA	SFFNAGTFRE	EQKCTYQFLM
QGFICKQTDQ	VVLILDSADA	IWAIQKLYPV	VSVTSGFVDV	FSSVNANIPC
STSGSVSTFY	SILPIRQITK	VCFMDQTPQV	LRFFLLGNKS	TSKLLLAVFY
HELQSPHVFL	GESFIPPTLV	QSASLLLNES	IGANYFNIMD	NLLYVVLQGE
EPIEIRSGVS	IHLALTVMVS	VLEKGWEIVI	LERLTNFLQI	GQNQIRFIHE
MPGHEETLKA	IADSRAKRKR	NCPTVTCTSH	YRRVGQRRPL	MMEMNSHRAS
PPMTVETISK	VIVIEIGDSP	TVRSTGMISS	LSSNKLQNLA	HRVITAQQTG
VLENVLNMTI	GALLVTQSKG	VIGYGNTSSF	KTGNLIYIRP	YALSILVQPS
DGEVGNELPV	QPQLVFLDEQ	NRRVESLGPP	SEPWTISASL	EGASDSVLKG
CTQAETQDGY	VSFYNLAVLI	SGSNWHFIFT	VTSPPGVNFT	ARSKPFAVLP
VTRKEKSTII	LAASLSSVAS	WLALSCLVCC	WLKRSKSRKT	KPEEIPESQT
NNQNIHIHIS	SKRRESQGPK	KEDTVVGEDM	RMKVMLGKVN	QCPHQLMNGV
SRRKVSRHIV	REEEAAVPAP	GTTGITSHGH	ICAPGAPAQQ	VYLQETGNWK
EGQEQLLRYQ	LAGQNQLLLL	CPDFRQERQQ	LPGQSRLSKQ	SGSLGLSQEK
KASCGATEAF	CLHSVHPETI	QEQL

Funkcija

FPC se povezuje s primarnim cilijama epitelnih ćelija i lokalizira se s proizvodom gena Pkd2 polikistinom-2 (PC2), sugerirajući da ova dva proteina mogu funkcionirati na zajedničkom molekulskom putu.^[7]

Klinički značaj

Mutacije njegovog kodirajućeg gena (hromosomski lokus 6p12.2) mogu uzrokovati autosomno recesivnu policistastu bolest bubrega. Kodirajući gen za fibrocistin je PKHD1. Fibrocistin se nalazi u epitelnim ćelijama bubrežnih tubula i žučnih kanala. Mutacija u PKHD1 (može biti autosomno recesivno nasljeđena ili spontana) koja dovodi do nedostatka fibrocistina uzrokujući karakterističnu policistastu dilataciju obje strukture.

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000170927 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000043760 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Zhang M, Mai W, Li C, Cho S, Hao C, Moeckel G, Zhao R, Kim I, Wang J, Xiong H, Wang H, Sato Y, Wu Y, Nakanuma Y, Lilova M, Pei Y, Harris R, Li S, Coffey R, Sun L, Wu D, Chen X, Breyer M, Zhao Z, McKanna J, Wu G (2004). "PKHD1 protein encoded by the gene for autosomal recessive polycystic kidney disease associates with basal bodies and primary cilia in renal epithelial cells". Proc Natl Acad Sci USA. 101 (8): 2311–2316. Bibcode:2004PNAS..101.2311Z. doi:10.1073/pnas.0400073101. PMC 356947. PMID 14983006.
^ "UniProt, P08F94" (jezik: engleski). Pristupljeno 4. 10. 2021.
^ Kim, Ingyu; Fu, Yulong; Hui, Kwokyin; Moeckel, Gilbert; Mai, Weiyi; Li, Cunxi; Liang, Dan; Zhao, Ping; Ma, Jie; Chen, Xing-Zhen; George, Alfred L.; Coffey, Robert J.; Feng, Zhong-Ping; Wu, Guanqing (mart 2008). "Fibrocystin/Polyductin Modulates Renal Tubular Formation by Regulating Polycystin-2 Expression and Function". Journal of the American Society of Nephrology. 19 (3): 455–468. doi:10.1681/ASN.2007070770. PMC 2391052. PMID 18235088.

Vanjski linkovi

GeneReviews/NIH/NCBI/UW entry on Polycystic Kidney Disease, Autosomal Recessive
fibrocystin protein, human na US National Library of Medicine Medical Subject Headings (MeSH)

Šablon:Cilijski proteini

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000170927 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000043760 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] Zhang M, Mai W, Li C, Cho S, Hao C, Moeckel G, Zhao R, Kim I, Wang J, Xiong H, Wang H, Sato Y, Wu Y, Nakanuma Y, Lilova M, Pei Y, Harris R, Li S, Coffey R, Sun L, Wu D, Chen X, Breyer M, Zhao Z, McKanna J, Wu G (2004). "PKHD1 protein encoded by the gene for autosomal recessive polycystic kidney disease associates with basal bodies and primary cilia in renal epithelial cells". Proc Natl Acad Sci USA. 101 (8): 2311–2316. Bibcode:2004PNAS..101.2311Z. doi:10.1073/pnas.0400073101. PMC 356947. PMID 14983006.

[UniProt-6] "UniProt, P08F94" (jezik: engleski). Pristupljeno 4. 10. 2021.

[7] Kim, Ingyu; Fu, Yulong; Hui, Kwokyin; Moeckel, Gilbert; Mai, Weiyi; Li, Cunxi; Liang, Dan; Zhao, Ping; Ma, Jie; Chen, Xing-Zhen; George, Alfred L.; Coffey, Robert J.; Feng, Zhong-Ping; Wu, Guanqing (mart 2008). "Fibrocystin/Polyductin Modulates Renal Tubular Formation by Regulating Polycystin-2 Expression and Function". Journal of the American Society of Nephrology. 19 (3): 455–468. doi:10.1681/ASN.2007070770. PMC 2391052. PMID 18235088.

[5]

[1]

[2]

[3]

[4]

[6]

[7]