AP5Z1_HUMAN
ID AP5Z1_HUMAN Reviewed; 807 AA.
AC O43299; Q8N3X2; Q96H80;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2006, sequence version 2.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=AP-5 complex subunit zeta-1;
DE AltName: Full=Adaptor-related protein complex 5 zeta subunit;
DE Short=Zeta5;
GN Name=AP5Z1; Synonyms=KIAA0415, SPG48;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=9455477; DOI=10.1093/dnares/4.5.307;
RA Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. VIII. 78
RT new cDNA clones from brain which code for large proteins in vitro.";
RL DNA Res. 4:307-313(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 417-807 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH AP5S1; AP5B1; ZFYVE26 AND
RP SPG11, AND INVOLVEMENT IN SPG48.
RX PubMed=20613862; DOI=10.1371/journal.pbio.1000408;
RA Slabicki M., Theis M., Krastev D.B., Samsonov S., Mundwiller E.,
RA Junqueira M., Paszkowski-Rogacz M., Teyra J., Heninger A.K., Poser I.,
RA Prieur F., Truchetto J., Confavreux C., Marelli C., Durr A.,
RA Camdessanche J.P., Brice A., Shevchenko A., Pisabarro M.T., Stevanin G.,
RA Buchholz F.;
RT "A genome-scale DNA repair RNAi screen identifies SPG48 as a novel gene
RT associated with hereditary spastic paraplegia.";
RL PLoS Biol. 8:E1000408-E1000408(2010).
RN [5]
RP FUNCTION IN ENDOSOME TRANSPORT.
RX PubMed=22022230; DOI=10.1371/journal.pbio.1001170;
RA Hirst J., Barlow L.D., Francisco G.C., Sahlender D.A., Seaman M.N.,
RA Dacks J.B., Robinson M.S.;
RT "The fifth adaptor protein complex.";
RL PLoS Biol. 9:E1001170-E1001170(2011).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
CC -!- FUNCTION: As part of AP-5, a probable fifth adaptor protein complex it
CC may be involved in endosomal transport. According to PubMed:20613862 it
CC is a putative helicase required for efficient homologous recombination
CC DNA double-strand break repair. {ECO:0000269|PubMed:20613862,
CC ECO:0000269|PubMed:22022230}.
CC -!- SUBUNIT: Probably part of the adaptor protein complex 5 (AP-5) a
CC tetramer composed of AP5B1, AP5M1, AP5S1 and AP5Z1. Interacts with
CC ZFYVE26 and SPG11. {ECO:0000269|PubMed:20613862}.
CC -!- INTERACTION:
CC O43299; Q8N1F7: NUP93; NbExp=3; IntAct=EBI-740938, EBI-1042703;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:20613862}. Nucleus
CC {ECO:0000269|PubMed:20613862}. Note=By SDS-PAGE, 2 isoforms have been
CC observed, the shorter seems to be predominantly nuclear and the longer
CC is mostly cytoplasmic. {ECO:0000269|PubMed:20613862}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O43299-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O43299-2; Sequence=VSP_021673, VSP_021676;
CC Name=3;
CC IsoId=O43299-3; Sequence=VSP_021672, VSP_021674, VSP_021675;
CC -!- DISEASE: Spastic paraplegia 48, autosomal recessive (SPG48)
CC [MIM:613647]: A form of spastic paraplegia, a neurodegenerative
CC disorder characterized by a slow, gradual, progressive weakness and
CC spasticity of the lower limbs. Rate of progression and the severity of
CC symptoms are quite variable. Initial symptoms may include difficulty
CC with balance, weakness and stiffness in the legs, muscle spasms, and
CC dragging the toes when walking. In some forms of the disorder, bladder
CC symptoms (such as incontinence) may appear, or the weakness and
CC stiffness may spread to other parts of the body.
CC {ECO:0000269|PubMed:20613862}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA24845.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AC092610; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB007875; BAA24845.1; ALT_INIT; mRNA.
DR EMBL; BC008841; AAH08841.2; -; mRNA.
DR EMBL; BC037399; AAH37399.1; -; mRNA.
DR CCDS; CCDS47528.1; -. [O43299-1]
DR PIR; T00054; T00054.
DR RefSeq; NP_055670.1; NM_014855.2. [O43299-1]
DR AlphaFoldDB; O43299; -.
DR BioGRID; 115236; 29.
DR ComplexPortal; CPX-5181; AP-5 Adaptor complex.
DR CORUM; O43299; -.
DR IntAct; O43299; 6.
DR MINT; O43299; -.
DR STRING; 9606.ENSP00000297562; -.
DR iPTMnet; O43299; -.
DR PhosphoSitePlus; O43299; -.
DR BioMuta; AP5Z1; -.
DR EPD; O43299; -.
DR jPOST; O43299; -.
DR MassIVE; O43299; -.
DR MaxQB; O43299; -.
DR PaxDb; O43299; -.
DR PeptideAtlas; O43299; -.
DR PRIDE; O43299; -.
DR ProteomicsDB; 48872; -. [O43299-1]
DR ProteomicsDB; 48873; -. [O43299-2]
DR ProteomicsDB; 48874; -. [O43299-3]
DR Antibodypedia; 48203; 75 antibodies from 17 providers.
DR DNASU; 9907; -.
DR Ensembl; ENST00000648925.1; ENSP00000496830.1; ENSG00000242802.9. [O43299-2]
DR Ensembl; ENST00000649063.2; ENSP00000497815.1; ENSG00000242802.9. [O43299-1]
DR GeneID; 9907; -.
DR KEGG; hsa:9907; -.
DR MANE-Select; ENST00000649063.2; ENSP00000497815.1; NM_014855.3; NP_055670.1.
DR UCSC; uc003sne.4; human. [O43299-1]
DR CTD; 9907; -.
DR DisGeNET; 9907; -.
DR GeneCards; AP5Z1; -.
DR HGNC; HGNC:22197; AP5Z1.
DR HPA; ENSG00000242802; Low tissue specificity.
DR MalaCards; AP5Z1; -.
DR MIM; 613647; phenotype.
DR MIM; 613653; gene.
DR neXtProt; NX_O43299; -.
DR OpenTargets; ENSG00000242802; -.
DR Orphanet; 306511; Autosomal recessive spastic paraplegia type 48.
DR PharmGKB; PA162392841; -.
DR VEuPathDB; HostDB:ENSG00000242802; -.
DR eggNOG; ENOG502QVBK; Eukaryota.
DR GeneTree; ENSGT00390000017592; -.
DR HOGENOM; CLU_019553_0_0_1; -.
DR InParanoid; O43299; -.
DR OMA; GQHYTED; -.
DR OrthoDB; 414014at2759; -.
DR PhylomeDB; O43299; -.
DR TreeFam; TF331050; -.
DR PathwayCommons; O43299; -.
DR SignaLink; O43299; -.
DR BioGRID-ORCS; 9907; 5 hits in 1083 CRISPR screens.
DR ChiTaRS; AP5Z1; human.
DR GenomeRNAi; 9907; -.
DR Pharos; O43299; Tbio.
DR PRO; PR:O43299; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; O43299; protein.
DR Bgee; ENSG00000242802; Expressed in granulocyte and 148 other tissues.
DR ExpressionAtlas; O43299; baseline and differential.
DR Genevisible; O43299; HS.
DR GO; GO:0044599; C:AP-5 adaptor complex; IC:ComplexPortal.
DR GO; GO:0030119; C:AP-type membrane coat adaptor complex; NAS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005770; C:late endosome; IC:ComplexPortal.
DR GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IMP:UniProtKB.
DR GO; GO:0016197; P:endosomal transport; IMP:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0016192; P:vesicle-mediated transport; IC:ComplexPortal.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR028222; AP5Z1.
DR InterPro; IPR011989; ARM-like.
DR PANTHER; PTHR46488; PTHR46488; 1.
DR Pfam; PF14764; SPG48; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; DNA damage; DNA repair;
KW Hereditary spastic paraplegia; Neurodegeneration; Nucleus;
KW Protein transport; Reference proteome; Transport.
FT CHAIN 1..807
FT /note="AP-5 complex subunit zeta-1"
FT /id="PRO_0000261357"
FT VAR_SEQ 1..156
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_021672"
FT VAR_SEQ 602..625
FT /note="SVLSSQFLALCTLKPSLVVELARD -> RPDACRPILVPL (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:9455477"
FT /id="VSP_021673"
FT VAR_SEQ 602
FT /note="S -> R (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_021674"
FT VAR_SEQ 603..807
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_021675"
FT VAR_SEQ 626..807
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9455477"
FT /id="VSP_021676"
FT VARIANT 94
FT /note="S -> C (in dbSNP:rs11549839)"
FT /id="VAR_049511"
SQ SEQUENCE 807 AA; 88605 MW; AD02B2664838B739 CRC64;
MFSAGAESLL HQAREIQDEE LKKFCSRICK LLQAEDLGPD TLDSLQRLFL IISATKYSRR
LEKTCVDLLQ ATLGLPACPE QLQVLCAAIL REMSPSDSLS LAWDHTQNSR QLSLVASVLL
AQGDRNEEVR AVGQGVLRAL ESRQPEGPSL RHLLPVMAKV VVLSPGTLQE DQATLLSKRL
VDWLRYASLQ QGLPHSGGFF STPRARQPGP VTEVDGAVAT DFFTVLSSGH RFTDDQWLNV
QAFSMLRAWL LHSGPEGPGT LDTDDRSEQE GSTLSVISAT SSAGRLLPPR ERLREVAFEY
CQRLIEQSNR RALRKGDSDL QKACLVEAVL VLDVLCRQDP SFLYRSLSCL KALHGRVRGD
PASVRVLLPL AHFFLSHGEA AAVDSEAVYQ HLFTRIPVEQ FHSPMLAFEF IQFCRDNLHL
FSGHLSTLRL SFPNLFKFLA WNSPPLTSEF VALLPALVDA GTALEMLHAL LDLPCLTAVL
DLQLRSAPAA SERPLWDTSL RAPSCLEAFR DPQFQGLFQY LLRPKASGAT ERLAPLHQLL
QPMAGCARVA QCAQAVPTLL QAFFSAVTQV ADGSLINQLA LLLLGRSDSL YPAPGYAAGV
HSVLSSQFLA LCTLKPSLVV ELARDLLEFL GSVNGLCSRA SLVTSVVWAI GEYLSVTYDR
RCTVEQINKF FEALEALLFE VTQCRPSAAL PRCPPQVVTV LMTTLTKLAS RSQDLIPRAS
LLLSKMRTLA HSPATSSTHS EEGAEAIRTR ATELLTLLKM PSVAQFVLTP STEVCSPRYH
RDANTALPLA LRTVSRLVER EAGLMPG
