CKAP4

CKAP4
Identifikatori
Aliasi	CKAP4
Vanjski ID-jevi	MGI: 2444926 HomoloGene: 4970 GeneCards: CKAP4
Lokacija gena (čovjek)
Hrom.	Hromosom 12 (čovjek)
Kraj	106,304,279 bp
Lokacija gena (miš)
Hrom.	Hromosom 10 (miš)
Kraj	84,369,926 bp
Obrazac RNK ekspresije
	; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• vezivanje sa RNK;
Ćelijska komponenta	• citoplazma; • perinuklearno područje citoplazme; • integral component of membrane; • Lipidna kapljica; • ćelijska membrana; • lamellar granule; • Egzosom; • citoskelet; • endoplasmic reticulum membrane; • Endoplazmatski retikulum; • membrana; • GO:0005578 Vanćelijski matriks; • citosol; • nuclear speck; • azurophil granule membrane; • specific granule membrane; • endoplasmic reticulum lumen; • rough endoplasmic reticulum; • cytoplasmic ribonucleoprotein granule;
Biološki proces	• neutrophil degranulation; • Posttranslacione modifikacije;
	Izvori:Amigo / QuickGO
Ortolozi
	10970
	216197
	ENSG00000136026
	ENSMUSG00000046841
	Q07065
	Q8BMK4
	NM_006825
	NM_175451
	NP_006816
	NP_780660
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Citoskeletno pridruženi protein 4 je protein genkoji je kod ljudi kodirran genom CKAP4.^[5]^[6]

CKAP4 također historijski poznat kao CLIMP-63 (membranski protein 63 koji povezuje citoskelet) ili samo p63 (tokom 1990-ih) je obilan tip II transmembranskih proteina koji pretežno prebiva u endoplazmatskom retikulumu (ER) eukariotskih ćelija i kodiran kod viših kičmenjaka genom CKAP4.^[7]^[8]^[9]^[10]^[11]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 602 aminokiseline, a molekulska težina 66.022 Da.^[12].

10	20	30	40	50
MPSAKQRGSK	GGHGAASPSE	KGAHPSGGAD	DVAKKPPPAP	QQPPPPPAPH
PQQHPQQHPQ	NQAHGKGGHR	GGGGGGGKSS	SSSSASAAAA	AAAASSSASC
SRRLGRALNF	LFYLALVAAA	AFSGWCVHHV	LEEVQQVRRS	HQDFSRQREE
LGQGLQGVEQ	KVQSLQATFG	TFESILRSSQ	HKQDLTEKAV	KQGESEVSRI
SEVLQKLQNE	ILKDLSDGIH	VVKDARERDF	TSLENTVEER	LTELTKSIND
NIAIFTEVQK	RSQKEINDMK	AKVASLEESE	GNKQDLKALK	EAVKEIQTSA
KSREWDMEAL	RSTLQTMESD	IYTEVRELVS	LKQEQQAFKE	AADTERLALQ
ALTEKLLRSE	ESVSRLPEEI	RRLEEELRQL	KSDSHGPKED	GGFRHSEAFE
ALQQKSQGLD	SRLQHVEDGV	LSMQVASARQ	TESLESLLSK	SQEHEQRLAA
LQGRLEGLGS	SEADQDGLAS	TVRSLGETQL	VLYGDVEELK	RSVGELPSTV
ESLQKVQEQV	HTLLSQDQAQ	AARLPPQDFL	DRLSSLDNLK	ASVSQVEADL
KMLRTAVDSL	VAYSVKIETN	ENNLESAKGL	LDDLRNDLDR	LFVKVEKIHE
KV

Simboli

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

Lokalizacija, molekulske funkcije i regulacija

Ćelijska distribucija CLIMP-63 je procenjivana (i ponovo procenjivana) nekoliko puta u posljednje dva desetljeća. Protein uključuje citosolni segment, sastavljen od pozitivno nabijenih aminokiselina (2-23) koji bi mogao djelovati kao prevladavajući motiv za savijanje proteina i lokalizaciju ER.^[13]^[14] CLIMP-63 bio je jedan od prvootkrivenih proteina za oblikovanja ER-a^[15] i najpoznatiji učesnik u generiranju održsvnja listovs ER-a.^[16] Smatra se da se to događa nakon dimerizacije lumenskih upredenozavojničkih domena CLIMP-63 u cis (dva CLIMP-63 proteina istog ER membranskog sloja) i/ili trans položaju (između dva različita sloja ER membrane, preko lumena ER). Multimerizacija bi dodatno mogla ograničiti širenje CLIMP-63 iz ER-listova.^[17]

Pokazalo se i da CLIMP-63 veže mikrotubule, preko kroz citoplazmatskog poremećenog repa, što bi moglo pomoći u pričvršćivanju ER-listova za citoskelet. Ovo je regulirano fosforilacijom najmanje tri serinska ostatka citosolnog repa CLIMP-63 (S3, S17 i S19), jer fosforilacija ometa kapacitet vezanja mikrotubula CLIMP-63.^[18]

Osim toga, CLIMP-63 može proći još jednu posttranslacijsku modifikaciju, S-palmitoilaciju na cisteinu 100 svog citoplazmatskog domena. Do sada je samo palmitoil-aciltransferaza ZDHHC2 identificirana kao potencijalni regulator palmitoilacije CLIMP-63, ali kako se ZDHHC2 uglavnom nalazi na plazmamembrani, potrebna su dodatna istraživanja.^[19]^[20] Posljedice S-palmitoilacije tek treba istražiti, ali bi mogle imatiati ulogu u ćelijskom ciklusu, jer je prijavljeno da se tokom mitoze palmitoilacija CLIMP-63 snažno povećava.

Konačno, različite grupe pokazale su da CLIMP-63 služi kao receptor na ćelijskoj površini, za različite vanćelijske ligande, posebno za surfaktant-protein A (SP-A) u plućnim alveolama,Greška kod citiranja: Nedostaje oznaka za zatvaranje </ref> nakon <ref>

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000136026 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000046841 - 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.
^ Schweizer A, Rohrer J, Jenö P, DeMaio A, Buchman TG, Hauri HP (mart 1993). "A reversibly palmitoylated resident protein (p63) of an ER-Golgi intermediate compartment is related to a circulatory shock resuscitation protein". Journal of Cell Science. 104 (3): 685–94. PMID 8314870.
^ "Entrez Gene: CKAP4 cytoskeleton-associated protein 4".
^ "Gene: CKAP4 (ENSG00000136026) - Summary - Homo sapiens - Ensembl genome browser 89". may2017.archive.ensembl.org (jezik: engleski). Pristupljeno 26. 3. 2018.
^ "Gene: Ckap4 (ENSMUSG00000046841) - Summary - Mus musculus - Ensembl genome browser 89". may2017.archive.ensembl.org (jezik: engleski). Pristupljeno 26. 3. 2018.
^ pubmeddev. "PubMed Links for Gene (Select 10970) - PubMed - NCBI". www.ncbi.nlm.nih.gov. Pristupljeno 26. 3. 2018.
^ pubmeddev. "PubMed Links for Gene (Select 216197) - PubMed - NCBI". www.ncbi.nlm.nih.gov. Pristupljeno 26. 3. 2018.
^ "CKAP4 cytoskeleton associated protein 4 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Pristupljeno 26. 3. 2018.
^ "UniProt, Q07065". Pristupljeno 8. 8. 2021.
^ Schweizer A, Rohrer J, Hauri HP, Kornfeld S (juli 1994). "Retention of p63 in an ER-Golgi intermediate compartment depends on the presence of all three of its domains and on its ability to form oligomers". The Journal of Cell Biology. 126 (1): 25–39. doi:10.1083/jcb.126.1.25. PMC 2120087. PMID 8027183.
^ Schweizer A, Rohrer J, Slot JW, Geuze HJ, Kornfeld S (juni 1995). "Reassessment of the subcellular localization of p63". Journal of Cell Science. 108 (6): 2477–85. PMID 7673362.
^ Klopfenstein DR, Klumperman J, Lustig A, Kammerer RA, Oorschot V, Hauri HP (juni 2001). "Subdomain-specific localization of CLIMP-63 (p63) in the endoplasmic reticulum is mediated by its luminal alpha-helical segment". The Journal of Cell Biology. 153 (6): 1287–300. doi:10.1083/jcb.153.6.1287. PMC 2192027. PMID 11402071.
^ Shibata Y, Shemesh T, Prinz WA, Palazzo AF, Kozlov MM, Rapoport TA (novembar 2010). "Mechanisms determining the morphology of the peripheral ER". Cell. 143 (5): 774–88. doi:10.1016/j.cell.2010.11.007. PMC 3008339. PMID 21111237.
^ Nikonov AV, Hauri HP, Lauring B, Kreibich G (juli 2007). "Climp-63-mediated binding of microtubules to the ER affects the lateral mobility of translocon complexes". Journal of Cell Science. 120 (13): 2248–58. doi:10.1242/jcs.008979. PMID 17567679.
^ Vedrenne C, Klopfenstein DR, Hauri HP (april 2005). "Phosphorylation controls CLIMP-63-mediated anchoring of the endoplasmic reticulum to microtubules". Molecular Biology of the Cell. 16 (4): 1928–37. doi:10.1091/mbc.E04-07-0554. PMC 1073672. PMID 15703217.
^ Zhang J, Planey SL, Ceballos C, Stevens SM, Keay SK, Zacharias DA (juli 2008). "Identification of CKAP4/p63 as a major substrate of the palmitoyl acyltransferase DHHC2, a putative tumor suppressor, using a novel proteomics method". Molecular & Cellular Proteomics. 7 (7): 1378–88. doi:10.1074/mcp.M800069-MCP200. PMC 2493380. PMID 18296695.
^ Sandoz PA, van der Goot FG (april 2015). "How many lives does CLIMP-63 have?". Biochemical Society Transactions. 43 (2): 222–8. doi:10.1042/BST20140272. PMC 4627503. PMID 25849921.

Dopunska literatura

Sandoz PA, van der Goot FG (2015). "How many lives does CLIMP-63 have?". Biochemical Society Transactions. 43 (2): 222–228. doi:10.1042/BST20140272. PMC 4627503. PMID 25849921.
Tuffy KM, Planey SB (2012). "Cytoskeleton-Associated Protein 4: Functions Beyond the Endoplasmic Reticulum in Physiology and Disease". ISRN Cell Biology. 2012: 1–11. doi:10.5402/2012/142313.
Bates SR (2009). "P63 (CKAP4) as an SP-A receptor: implications for surfactant turnover". Cellular Physiology and Biochemistry. 25 (1): 41–54. doi:10.1159/000272062. PMC 3025887. PMID 20054143.

Vanjski linkovi

Lokacija ljudskog genoma CKAP4 i stranica sa detaljima o genu CKAP4 u UCSC Genome Browseru.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000136026 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000046841 - 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.

[pmid8314870-5] Schweizer A, Rohrer J, Jenö P, DeMaio A, Buchman TG, Hauri HP (mart 1993). "A reversibly palmitoylated resident protein (p63) of an ER-Golgi intermediate compartment is related to a circulatory shock resuscitation protein". Journal of Cell Science. 104 (3): 685–94. PMID 8314870.

[entrez-6] "Entrez Gene: CKAP4 cytoskeleton-associated protein 4".

[7] "Gene: CKAP4 (ENSG00000136026) - Summary - Homo sapiens - Ensembl genome browser 89". may2017.archive.ensembl.org (jezik: engleski). Pristupljeno 26. 3. 2018.

[8] "Gene: Ckap4 (ENSMUSG00000046841) - Summary - Mus musculus - Ensembl genome browser 89". may2017.archive.ensembl.org (jezik: engleski). Pristupljeno 26. 3. 2018.

[9] ubmeddev. "PubMed Links for Gene (Select 10970) - PubMed - NCBI". www.ncbi.nlm.nih.gov. Pristupljeno 26. 3. 2018.

[10] ubmeddev. "PubMed Links for Gene (Select 216197) - PubMed - NCBI". www.ncbi.nlm.nih.gov. Pristupljeno 26. 3. 2018.

[11] "CKAP4 cytoskeleton associated protein 4 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Pristupljeno 26. 3. 2018.

[UniProt-12] "UniProt, Q07065". Pristupljeno 8. 8. 2021.

[13] Schweizer A, Rohrer J, Hauri HP, Kornfeld S (juli 1994). "Retention of p63 in an ER-Golgi intermediate compartment depends on the presence of all three of its domains and on its ability to form oligomers". The Journal of Cell Biology. 126 (1): 25–39. doi:10.1083/jcb.126.1.25. PMC 2120087. PMID 8027183.

[14] Schweizer A, Rohrer J, Slot JW, Geuze HJ, Kornfeld S (juni 1995). "Reassessment of the subcellular localization of p63". Journal of Cell Science. 108 (6): 2477–85. PMID 7673362.

[Klopfenstein_2001-15] Klopfenstein DR, Klumperman J, Lustig A, Kammerer RA, Oorschot V, Hauri HP (juni 2001). "Subdomain-specific localization of CLIMP-63 (p63) in the endoplasmic reticulum is mediated by its luminal alpha-helical segment". The Journal of Cell Biology. 153 (6): 1287–300. doi:10.1083/jcb.153.6.1287. PMC 2192027. PMID 11402071.

[16] Shibata Y, Shemesh T, Prinz WA, Palazzo AF, Kozlov MM, Rapoport TA (novembar 2010). "Mechanisms determining the morphology of the peripheral ER". Cell. 143 (5): 774–88. doi:10.1016/j.cell.2010.11.007. PMC 3008339. PMID 21111237.

[17] Nikonov AV, Hauri HP, Lauring B, Kreibich G (juli 2007). "Climp-63-mediated binding of microtubules to the ER affects the lateral mobility of translocon complexes". Journal of Cell Science. 120 (13): 2248–58. doi:10.1242/jcs.008979. PMID 17567679.

[18] Vedrenne C, Klopfenstein DR, Hauri HP (april 2005). "Phosphorylation controls CLIMP-63-mediated anchoring of the endoplasmic reticulum to microtubules". Molecular Biology of the Cell. 16 (4): 1928–37. doi:10.1091/mbc.E04-07-0554. PMC 1073672. PMID 15703217.

[19] Zhang J, Planey SL, Ceballos C, Stevens SM, Keay SK, Zacharias DA (juli 2008). "Identification of CKAP4/p63 as a major substrate of the palmitoyl acyltransferase DHHC2, a putative tumor suppressor, using a novel proteomics method". Molecular & Cellular Proteomics. 7 (7): 1378–88. doi:10.1074/mcp.M800069-MCP200. PMC 2493380. PMID 18296695.

[20] Sandoz PA, van der Goot FG (april 2015). "How many lives does CLIMP-63 have?". Biochemical Society Transactions. 43 (2): 222–8. doi:10.1042/BST20140272. PMC 4627503. PMID 25849921.

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