O43299 (AP5Z1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
AP-5 complex subunit zeta-1

Alternative name(s):
Adapter-related protein complex 5 zeta subunit
Short name=Zeta5

Gene names

Name:	AP5Z1
Synonyms:	KIAA0415, SPG48

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	807 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	As part of AP-5, a probable fifth adapter protein complex it may be involved in endosomal transport. According to Ref.4 it is a putative helicase required for efficient homologous recombination DNA double-strand break repair. Ref.4 Ref.5
Subunit structure	Probably part of the adapter protein complex 5 (AP-5) a tetramer composed of AP5B1, AP5M1, AP5S1 and AP5Z1. Interacts with ZFYVE26 and SPG11. Ref.4
Subcellular location	Cytoplasm. Nucleus. Note: By SDS-PAGE, 2 isoforms have been observed, the shorter seems to be predominantly nuclear and the longer is mostly cytoplasmic (Ref.4). Ref.4
Involvement in disease	Spastic paraplegia autosomal recessive 48 (SPG48) [MIM:613647]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4
Sequence caution	The sequence BAA24845.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	DNA damage DNA repair Protein transport Transport
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Hereditary spastic paraplegia Neurodegeneration
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell death Inferred from electronic annotation. Source: UniProtKB-KW double-strand break repair via homologous recombination Inferred from mutant phenotype Ref.4. Source: UniProtKB endosomal transport Inferred from mutant phenotype Ref.5. Source: UniProtKB protein transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	AP-type membrane coat adaptor complex Non-traceable author statement Ref.5. Source: UniProtKB nucleolus Inferred from direct assay. Source: HPA
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O43299-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O43299-2)

The sequence of this isoform differs from the canonical sequence as follows:
     602-625: SVLSSQFLALCTLKPSLVVELARD → RPDACRPILVPL
     626-807: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: O43299-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-156: Missing.
     602-602: S → R
     603-807: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 807	807	AP-5 complex subunit zeta-1		PRO_0000261357
Regions
	Compositional bias	579 – 584	6	Poly-Leu
Natural variations
	Alternative sequence	1 – 156	156	Missing in isoform 3.		VSP_021672
	Alternative sequence	602 – 625	24	SVLSS…ELARD → RPDACRPILVPL in isoform 2.		VSP_021673
	Alternative sequence	602	1	S → R in isoform 3.		VSP_021674
	Alternative sequence	603 – 807	205	Missing in isoform 3.		VSP_021675
	Alternative sequence	626 – 807	182	Missing in isoform 2.		VSP_021676
	Natural variant	94	1	S → C. Corresponds to variant rs11549839 [ dbSNP | Ensembl ].		VAR_049511

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 28, 2006. Version 2. Checksum: AD02B2664838B739	FASTA	807	88,605
	10 20 30 40 50 60 MFSAGAESLL HQAREIQDEE LKKFCSRICK LLQAEDLGPD TLDSLQRLFL IISATKYSRR 70 80 90 100 110 120 LEKTCVDLLQ ATLGLPACPE QLQVLCAAIL REMSPSDSLS LAWDHTQNSR QLSLVASVLL 130 140 150 160 170 180 AQGDRNEEVR AVGQGVLRAL ESRQPEGPSL RHLLPVMAKV VVLSPGTLQE DQATLLSKRL 190 200 210 220 230 240 VDWLRYASLQ QGLPHSGGFF STPRARQPGP VTEVDGAVAT DFFTVLSSGH RFTDDQWLNV 250 260 270 280 290 300 QAFSMLRAWL LHSGPEGPGT LDTDDRSEQE GSTLSVISAT SSAGRLLPPR ERLREVAFEY 310 320 330 340 350 360 CQRLIEQSNR RALRKGDSDL QKACLVEAVL VLDVLCRQDP SFLYRSLSCL KALHGRVRGD 370 380 390 400 410 420 PASVRVLLPL AHFFLSHGEA AAVDSEAVYQ HLFTRIPVEQ FHSPMLAFEF IQFCRDNLHL 430 440 450 460 470 480 FSGHLSTLRL SFPNLFKFLA WNSPPLTSEF VALLPALVDA GTALEMLHAL LDLPCLTAVL 490 500 510 520 530 540 DLQLRSAPAA SERPLWDTSL RAPSCLEAFR DPQFQGLFQY LLRPKASGAT ERLAPLHQLL 550 560 570 580 590 600 QPMAGCARVA QCAQAVPTLL QAFFSAVTQV ADGSLINQLA LLLLGRSDSL YPAPGYAAGV 610 620 630 640 650 660 HSVLSSQFLA LCTLKPSLVV ELARDLLEFL GSVNGLCSRA SLVTSVVWAI GEYLSVTYDR 670 680 690 700 710 720 RCTVEQINKF FEALEALLFE VTQCRPSAAL PRCPPQVVTV LMTTLTKLAS RSQDLIPRAS 730 740 750 760 770 780 LLLSKMRTLA HSPATSSTHS EEGAEAIRTR ATELLTLLKM PSVAQFVLTP STEVCSPRYH 790 800 RDANTALPLA LRTVSRLVER EAGLMPG
	Isoform 2 [UniParc]. Checksum: 05CA8723DAE26D36	FASTA	613	67,454
	10 20 30 40 50 60 MFSAGAESLL HQAREIQDEE LKKFCSRICK LLQAEDLGPD TLDSLQRLFL IISATKYSRR 70 80 90 100 110 120 LEKTCVDLLQ ATLGLPACPE QLQVLCAAIL REMSPSDSLS LAWDHTQNSR QLSLVASVLL 130 140 150 160 170 180 AQGDRNEEVR AVGQGVLRAL ESRQPEGPSL RHLLPVMAKV VVLSPGTLQE DQATLLSKRL 190 200 210 220 230 240 VDWLRYASLQ QGLPHSGGFF STPRARQPGP VTEVDGAVAT DFFTVLSSGH RFTDDQWLNV 250 260 270 280 290 300 QAFSMLRAWL LHSGPEGPGT LDTDDRSEQE GSTLSVISAT SSAGRLLPPR ERLREVAFEY 310 320 330 340 350 360 CQRLIEQSNR RALRKGDSDL QKACLVEAVL VLDVLCRQDP SFLYRSLSCL KALHGRVRGD 370 380 390 400 410 420 PASVRVLLPL AHFFLSHGEA AAVDSEAVYQ HLFTRIPVEQ FHSPMLAFEF IQFCRDNLHL 430 440 450 460 470 480 FSGHLSTLRL SFPNLFKFLA WNSPPLTSEF VALLPALVDA GTALEMLHAL LDLPCLTAVL 490 500 510 520 530 540 DLQLRSAPAA SERPLWDTSL RAPSCLEAFR DPQFQGLFQY LLRPKASGAT ERLAPLHQLL 550 560 570 580 590 600 QPMAGCARVA QCAQAVPTLL QAFFSAVTQV ADGSLINQLA LLLLGRSDSL YPAPGYAAGV 610 HRPDACRPIL VPL
	Isoform 3 [UniParc]. Checksum: 4B48C08285BAE35D	FASTA	446	49,020
	10 20 30 40 50 60 MAKVVVLSPG TLQEDQATLL SKRLVDWLRY ASLQQGLPHS GGFFSTPRAR QPGPVTEVDG 70 80 90 100 110 120 AVATDFFTVL SSGHRFTDDQ WLNVQAFSML RAWLLHSGPE GPGTLDTDDR SEQEGSTLSV 130 140 150 160 170 180 ISATSSAGRL LPPRERLREV AFEYCQRLIE QSNRRALRKG DSDLQKACLV EAVLVLDVLC 190 200 210 220 230 240 RQDPSFLYRS LSCLKALHGR VRGDPASVRV LLPLAHFFLS HGEAAAVDSE AVYQHLFTRI 250 260 270 280 290 300 PVEQFHSPML AFEFIQFCRD NLHLFSGHLS TLRLSFPNLF KFLAWNSPPL TSEFVALLPA 310 320 330 340 350 360 LVDAGTALEM LHALLDLPCL TAVLDLQLRS APAASERPLW DTSLRAPSCL EAFRDPQFQG 370 380 390 400 410 420 LFQYLLRPKA SGATERLAPL HQLLQPMAGC ARVAQCAQAV PTLLQAFFSA VTQVADGSLI 430 440 NQLALLLLGR SDSLYPAPGY AAGVHR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	"Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro." Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 4:307-313(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 417-807 (ISOFORM 1). Tissue: Brain.
[4]	"A genome-scale DNA repair RNAi screen identifies SPG48 as a novel gene associated with hereditary spastic paraplegia." Slabicki M., Theis M., Krastev D.B., Samsonov S., Mundwiller E., Junqueira M., Paszkowski-Rogacz M., Teyra J., Heninger A.K., Poser I., Prieur F., Truchetto J., Confavreux C., Marelli C., Durr A., Camdessanche J.P., Brice A., Shevchenko A. , Pisabarro M.T., Stevanin G., Buchholz F. PLoS Biol. 8:E1000408-E1000408(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH AP5S1; AP5B1; ZFYVE26 AND SPG11, INVOLVEMENT IN SPG48.
[5]	"The fifth adaptor protein complex." Hirst J., Barlow L.D., Francisco G.C., Sahlender D.A., Seaman M.N., Dacks J.B., Robinson M.S. PLoS Biol. 9:E1001170-E1001170(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN ENDOSOME TRANSPORT.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AC092610 Genomic DNA. No translation available. AB007875 mRNA. Translation: BAA24845.1. Different initiation. BC008841 mRNA. Translation: AAH08841.2. BC037399 mRNA. Translation: AAH37399.1.
IPI	IPI00465123. IPI00807569. IPI00872712.
PIR	T00054.
RefSeq	NP_055670.1. NM_014855.2.
UniGene	Hs.558440.
3D structure databases
ProteinModelPortal	O43299.
ModBase	Search...
Protein-protein interaction databases
IntAct	O43299. 2 interactions.
MINT	MINT-1452394.
STRING	9606.ENSP00000297562.
PTM databases
PhosphoSite	O43299.
Proteomic databases
PaxDb	O43299.
PRIDE	O43299.
Protocols and materials databases
DNASU	9907.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000348624; ENSP00000297562; ENSG00000242802. ENST00000401897; ENSP00000384980; ENSG00000242802.
GeneID	9907.
KEGG	hsa:9907.
UCSC	uc003sne.3. human.
Organism-specific databases
CTD	9907.
GeneCards	GC07P004816.
HGNC	HGNC:22197. AP5Z1.
HPA	HPA035693.
MIM	613647. phenotype. 613653. gene.
neXtProt	NX_O43299.
PharmGKB	PA162392841.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG26605.
HOGENOM	HOG000113147.
HOVERGEN	HBG061547.
InParanoid	O43299.
OMA	AQFFLNH.
OrthoDB	EOG48D0TW.
Gene expression databases
ArrayExpress	O43299.
Bgee	O43299.
CleanEx	HS_KIAA0415.
Genevestigator	O43299.
GermOnline	ENSG00000164917. Homo sapiens.
Family and domain databases
ProtoNet	Search...
Other
ChiTaRS	AP5Z1. human.
GenomeRNAi	9907.
NextBio	37361.
SOURCE	Search...

Entry information

Entry name

AP5Z1_HUMAN

Accession

Primary (citable) accession number: O43299
Secondary accession number(s): Q8N3X2, Q96H80

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	November 28, 2006
Last modified:	May 1, 2013
This is version 87 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.