Reviewed, UniProtKB/Swiss-Prot Q60I27 (AL2CL_HUMAN)

Names and origin

Protein names

Recommended name:
    ALS2 C-terminal-like protein

Gene names

Name:

ALS2CL

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	953 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Acts as a guanine nucleotide exchange factor (GEF) for Rab5 GTPase. Regulates the ALS2-mediated endosome dynamics. Ref.1 Ref.6 Ref.7
Subunit structure	Homodimer. Forms a heteromeric complex with ALS2 By similarity. Interacts with ALS2 and RAB5A.
Subcellular location	Cytoplasm. Note: Distributed onto the vesicular compartments in the cytoplasm with strong punctated staining. Colocalizes with RAB5A onto the vesicular/membranous compartments in the cytoplasm, particularly to the leading edges of the cells. Ref.1 Ref.7
Tissue specificity	Expressed in heart and kidney. Ref.1
Sequence similarities	Contains 8 MORN repeats. Contains 1 VPS9 domain.
Sequence caution	The sequence BAD18450.1 differs from that shown. Reason: Frameshift at position 878.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat
Molecular function	GTPase activation
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	endosome organization Ref.7 Inferred from genetic interaction. Source: MGI
Molecular function	GTPase activator activity Inferred from electronic annotation. Source: UniProtKB-KW identical protein binding Ref.7 Inferred from physical interaction. Source: MGI
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q60I27-1)

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: Q60I27-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-199: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: Q60I27-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-485: Missing.

Note: No experimental confirmation available.

Isoform 4 (identifier: Q60I27-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-763: Missing.
     896-953: IQHLGAEIHL...PGHWHSRELW → WGSQGPEKGG...APGSRDPPDP

Note: No experimental confirmation available.

Isoform 5 (identifier: Q60I27-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-763: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 953	953	ALS2 C-terminal-like protein		PRO_0000313849
Regions
	Repeat	358 – 380	23	MORN 1
	Repeat	381 – 403	23	MORN 2
	Repeat	409 – 431	23	MORN 3
	Repeat	432 – 452	21	MORN 4
	Repeat	459 – 479	21	MORN 5
	Repeat	483 – 505	23	MORN 6
	Repeat	506 – 528	23	MORN 7
	Repeat	529 – 552	24	MORN 8
	Domain	796 – 942	147	VPS9
Natural variations
	Alternative sequence	1 – 763	763	Missing in isoform 4 and isoform 5.		VSP_030168
	Alternative sequence	1 – 485	485	Missing in isoform 3.		VSP_030169
	Alternative sequence	1 – 199	199	Missing in isoform 2.		VSP_030170
	Alternative sequence	896 – 953	58	IQHLG…SRELW → WGSQGPEKGGSQPGCWGARG RVRTTPQVSSHPGQRSFPSC LSATGLFSLSPSLSWWGGVL QNSAPGSRDPPDP in isoform 4.		VSP_030171
	Natural variant	45	1	E → Q: dbSNP rs7642448. Ref.5		VAR_037791
	Natural variant	280	1	Q → E in a breast cancer sample; somatic mutation. Ref.8		VAR_037792
	Natural variant	576	1	L → F in a breast cancer sample; somatic mutation. Ref.8		VAR_037793
Experimental info
	Sequence conflict	172	1	L → P in BAD18448. Ref.2
	Sequence conflict	430	1	E → G in BAD18448. Ref.2
	Sequence conflict	711	1	E → G in BAD18450. Ref.2
	Sequence conflict	893	1	R → H in BAD18448. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 23, 2004. Version 1. Checksum: 1BBC38A16E6A1168	FASTA	953	107,748
	10 20 30 40 50 60 MCNPEEAALL RLEEVFSATL AHVNSLVLQP LLPAAPDPSD PWGRECLRLL QQLHKSSQQL 70 80 90 100 110 120 WEVTEESLHS LQERLRYPDS TGLESLLLLR GADRVLQAHI EYIESYTSCM VVQAFQKAAK 130 140 150 160 170 180 RRSEYWRGQR KALRQLLSGV SSEGSVGASL GQALHQPLAH HVQQYVLLLL SLGDTIGEHH 190 200 210 220 230 240 PTRELVVNAV TLFGNLQSFM KQELDQAVAT QALWHTLRGR LRDVLCTPAH RLLQDSQDVP 250 260 270 280 290 300 VTVAPLRAER VLLFDDALVL LQGHNVHTFD LKLVWVDPGQ DGCTFHLLTP EEEFSFCAKD 310 320 330 340 350 360 SQGQAVWQWK VTWAVHQALH GKKDFPVLGA GLEPSQPPDC RCAEYTFQAE GRLCQATYEG 370 380 390 400 410 420 EWCRGRPHGK GTLKWPDGRN HVGNFCQGLE HGFGIRLLPQ ASEDKFDCYK CHWREGSMCG 430 440 450 460 470 480 YGICEYSTDE VYKGYFQEGL RHGFGVLESG PQAPQPFRYT GHWERGQRSG YGIEEDGDRG 490 500 510 520 530 540 ERYIGMWQAG QRHGPGVMVT QAGVCYQGTF QADKTVGPGI LLSEDDSLYE GTFTRDLTLM 550 560 570 580 590 600 GKGKVTFPNG FTLEGSFGSG AGRGLHTQGV LDTAALPPDP SSTCKRQLGV GAFPVESRWQ 610 620 630 640 650 660 GVYSPFRDFV CAGCPRDLQE ALLGFDVQSS RELRRSQDYL SCERTHPEDS VGSMEDILEE 670 680 690 700 710 720 LLQHREPKAL QLYLRKALSN SLHPLGKLLR TLMLTFQATY AGVGANKHLQ ELAQEEVKQH 730 740 750 760 770 780 AQELWAAYRG LLRVALERKG QALEEDEDTE TRDLQVHGLV LPLMLPSFYS ELFTLYLLLH 790 800 810 820 830 840 EREDSFYSQG IANLSLFPDT QLLEFLDVQK HLWPLKDLTL TSNQRYSLVR DKCFLSATEC 850 860 870 880 890 900 LQKIMTTVDP REKLEVLERT YGEIEGTVSR VLGREYKLPM DDLLPLLIYV VSRARIQHLG 910 920 930 940 950 AEIHLIRDMM DPNHTGGLYD FLLTALESCY EHIQKEDMRL HRLPGHWHSR ELW
	Isoform 2. Checksum: 16CC02DED68F8FBD	FASTA	754	85,486
	10 20 30 40 50 60 MKQELDQAVA TQALWHTLRG RLRDVLCTPA HRLLQDSQDV PVTVAPLRAE RVLLFDDALV 70 80 90 100 110 120 LLQGHNVHTF DLKLVWVDPG QDGCTFHLLT PEEEFSFCAK DSQGQAVWQW KVTWAVHQAL 130 140 150 160 170 180 HGKKDFPVLG AGLEPSQPPD CRCAEYTFQA EGRLCQATYE GEWCRGRPHG KGTLKWPDGR 190 200 210 220 230 240 NHVGNFCQGL EHGFGIRLLP QASEDKFDCY KCHWREGSMC GYGICEYSTD EVYKGYFQEG 250 260 270 280 290 300 LRHGFGVLES GPQAPQPFRY TGHWERGQRS GYGIEEDGDR GERYIGMWQA GQRHGPGVMV 310 320 330 340 350 360 TQAGVCYQGT FQADKTVGPG ILLSEDDSLY EGTFTRDLTL MGKGKVTFPN GFTLEGSFGS 370 380 390 400 410 420 GAGRGLHTQG VLDTAALPPD PSSTCKRQLG VGAFPVESRW QGVYSPFRDF VCAGCPRDLQ 430 440 450 460 470 480 EALLGFDVQS SRELRRSQDY LSCERTHPED SVGSMEDILE ELLQHREPKA LQLYLRKALS 490 500 510 520 530 540 NSLHPLGKLL RTLMLTFQAT YAGVGANKHL QELAQEEVKQ HAQELWAAYR GLLRVALERK 550 560 570 580 590 600 GQALEEDEDT ETRDLQVHGL VLPLMLPSFY SELFTLYLLL HEREDSFYSQ GIANLSLFPD 610 620 630 640 650 660 TQLLEFLDVQ KHLWPLKDLT LTSNQRYSLV RDKCFLSATE CLQKIMTTVD PREKLEVLER 670 680 690 700 710 720 TYGEIEGTVS RVLGREYKLP MDDLLPLLIY VVSRARIQHL GAEIHLIRDM MDPNHTGGLY 730 740 750 DFLLTALESC YEHIQKEDMR LHRLPGHWHS RELW
	Isoform 3. Checksum: 4CB253A0BCBE0773	FASTA	468	53,078
	10 20 30 40 50 60 MWQAGQRHGP GVMVTQAGVC YQGTFQADKT VGPGILLSED DSLYEGTFTR DLTLMGKGKV 70 80 90 100 110 120 TFPNGFTLEG SFGSGAGRGL HTQGVLDTAA LPPDPSSTCK RQLGVGAFPV ESRWQGVYSP 130 140 150 160 170 180 FRDFVCAGCP RDLQEALLGF DVQSSRELRR SQDYLSCERT HPEDSVGSME DILEELLQHR 190 200 210 220 230 240 EPKALQLYLR KALSNSLHPL GKLLRTLMLT FQATYAGVGA NKHLQELAQE EVKQHAQELW 250 260 270 280 290 300 AAYRGLLRVA LERKGQALEE DEDTETRDLQ VHGLVLPLML PSFYSELFTL YLLLHEREDS 310 320 330 340 350 360 FYSQGIANLS LFPDTQLLEF LDVQKHLWPL KDLTLTSNQR YSLVRDKCFL SATECLQKIM 370 380 390 400 410 420 TTVDPREKLE VLERTYGEIE GTVSRVLGRE YKLPMDDLLP LLIYVVSRAR IQHLGAEIHL 430 440 450 460 IRDMMDPNHT GGLYDFLLTA LESCYEHIQK EDMRLHRLPG HWHSRELW
	Isoform 4. Checksum: 2801624E1A7964C2	FASTA	205	23,054
	10 20 30 40 50 60 MLPSFYSELF TLYLLLHERE DSFYSQGIAN LSLFPDTQLL EFLDVQKHLW PLKDLTLTSN 70 80 90 100 110 120 QRYSLVRDKC FLSATECLQK IMTTVDPREK LEVLERTYGE IEGTVSRVLG REYKLPMDDL 130 140 150 160 170 180 LPLLIYVVSR ARWGSQGPEK GGSQPGCWGA RGRVRTTPQV SSHPGQRSFP SCLSATGLFS 190 200 LSPSLSWWGG VLQNSAPGSR DPPDP
	Isoform 5. Checksum: D905F5101A2A5596	FASTA	190	22,425
	10 20 30 40 50 60 MLPSFYSELF TLYLLLHERE DSFYSQGIAN LSLFPDTQLL EFLDVQKHLW PLKDLTLTSN 70 80 90 100 110 120 QRYSLVRDKC FLSATECLQK IMTTVDPREK LEVLERTYGE IEGTVSRVLG REYKLPMDDL 130 140 150 160 170 180 LPLLIYVVSR ARIQHLGAEI HLIRDMMDPN HTGGLYDFLL TALESCYEHI QKEDMRLHRL 190 PGHWHSRELW

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"ALS2CL, the novel protein highly homologous to the carboxy-terminal half of ALS2, binds to Rab5 and modulates endosome dynamics." Hadano S., Otomo A., Suzuki-Utsunomiya K., Kunita R., Yanagisawa Y., Showguchi-Miyata J., Mizumura H., Ikeda J.-E. FEBS Lett. 575:64-70(2004) [PubMed: 15388334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH RAB5A, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Liver.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2; 3 AND 4). Tissue: Tongue, Trachea and Uterus.
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 293-953 (ISOFORM 1). Tissue: Prostate.
[5]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-392 (ISOFORM 1), VARIANT GLN-45. Tissue: Cervix.
[6]	"Purification and functional analyses of ALS2 and its homologue." Hadano S., Ikeda J.-E. Methods Enzymol. 403:310-321(2005) [PubMed: 16473597] [Abstract] Cited for: FUNCTION.
[7]	"ALS2CL, a novel ALS2-interactor, modulates ALS2-mediated endosome dynamics." Suzuki-Utsunomiya K., Hadano S., Otomo A., Kunita R., Mizumura H., Osuga H., Ikeda J.-E. Biochem. Biophys. Res. Commun. 354:491-497(2007) [PubMed: 17239822] [Abstract] Cited for: FUNCTION, HOMODIMERIZATION, INTERACTION WITH ALS2, SUBCELLULAR LOCATION.
[8]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLU-280 AND PHE-576.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB107015 mRNA. Translation: BAD51817.1. AK093844 mRNA. Translation: BAC04237.1. AK131273 mRNA. Translation: BAD18450.1. Frameshift. AK131270 mRNA. Translation: BAD18448.1. AK126505 mRNA. Translation: BAC86572.1. CH471055 Genomic DNA. Translation: EAW64777.1. BC042906 mRNA. Translation: AAH42906.1. BC061883 mRNA. Translation: AAH61883.1. BC075825 mRNA. Translation: AAH75825.1. BC109233 mRNA. Translation: AAI09234.1. CR627258 mRNA. Translation: CAH10367.1.
IPI	IPI00329369. IPI00418601. IPI00445149. IPI00879806. IPI00879941.
RefSeq	NP_667340.2. NP_877576.1.
UniGene	Hs.517937
3D structure databases
ModBase	Search...
Proteomic databases
PRIDE	Q60I27.
Genome annotation databases
Ensembl	ENST00000318962; ENSP00000313670; ENSG00000178038; Homo sapiens. [Genome view] ENST00000415953; ENSP00000413223; ENSG00000178038; Homo sapiens. [Genome view]
GeneID	259173.
KEGG	hsa:259173.
UCSC	uc003cpx.1. human. uc003cqa.1. human.
Organism-specific databases
CTD	259173.
GeneCards	GC03M046685.
HGNC	HGNC:20605. ALS2CL.
MIM	612402. gene.
PharmGKB	PA134949717.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q60I27.
OMA	GTFQADK
OrthoDB	EOG9RV59P
Gene expression databases
ArrayExpress	Q60I27.
Bgee	Q60I27.
CleanEx	HS_ALS2CL.
Genevestigator	Q60I27.
Family and domain databases
InterPro	IPR003409. MORN. IPR003123. VPS9. [Graphical view]
Pfam	PF02493. MORN. 8 hits. PF02204. VPS9. 1 hit. [Graphical view]
SMART	SM00698. MORN. 7 hits. [Graphical view]
PROSITE	PS51205. VPS9. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	93040.
SOURCE	Search...

Entry information

Entry name

AL2CL_HUMAN

Accession

Primary (citable) accession number: Q60I27
Secondary accession number(s): Q32MA1 , Q6AI56, Q6ZNC5, Q6ZNC7, Q6ZTL4, Q86YD2, Q8N9U1

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 15, 2008
Last sequence update:	November 23, 2004
Last modified:	November 24, 2009
This is version 42 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.