Reviewed, UniProtKB/Swiss-Prot P26378 (ELAV4_HUMAN)

Names and origin

Protein names

Recommended name:
    ELAV-like protein 4
Alternative name(s):
    Paraneoplastic encephalomyelitis antigen HuD
    Hu-antigen D

Gene names

Name:	ELAVL4
Synonyms:	HUD, PNEM

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	380 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	May play a role in neuron-specific RNA processing. Protects CDKN1A mRNA from decay by binding to its 3'-UTR By similarity.
Subunit structure	Component of a TAU mRNP complex, at least composed of IGF2BP1, ELAVL4 and G3BP By similarity.
Tissue specificity	Brain.
Post-translational modification	Methylation at Arg-243 by CARM1 weakens protective binding to the 3'-UTR of CDKN1A mRNA and down-regulates CDKN1A protein expression, thereby maintaining cells in a proliferative state. Methylation is inhibited by NGF, which facilitates neurite outgrowth By similarity.
Involvement in disease	Paraneoplastic encephalomyelitis sensory neuropathy is associated with small cell lung cancer and is characterized by dementia, sensory loss, and other neurological disabilities. It may result from an immune response primarily directed against a small cell lung tumor antigen which is misdirected against similar antigens expressed in brain.
Sequence similarities	Belongs to the RRM elav family. Contains 3 RRM (RNA recognition motif) domains.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat
Ligand	RNA-binding
PTM	Methylation
Technical term	3D-structure
Gene Ontology (GO)
Biological process	mRNA processing Traceable author statement. Source: ProtInc
Molecular function	mRNA 3'-UTR binding Traceable author statement. Source: ProtInc nucleotide binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: P26378-1)

Also known as: HUD1PRO;

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: P26378-2)

Also known as: HUD1;

The sequence of this isoform differs from the canonical sequence as follows:
     259-272: Missing.

Isoform 3 (identifier: P26378-3)

Also known as: HUD4;

The sequence of this isoform differs from the canonical sequence as follows:
     1-2: MV → MRLLLLREIVINESRNCSF
     259-272: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 380

380

ELAV-like protein 4

PRO_0000081583

Regions

Domain

46 – 124

79

RRM 1

Domain

132 – 212

81

RRM 2

Domain

297 – 375

79

RRM 3

Amino acid modifications

Modified residue

243

1

Omega-N-methylated arginine; by CARM1 Ref.4

Natural variations

Alternative sequence

1 – 2

2

MV → MRLLLLREIVINESRNCSF in isoform 3.

VSP_014150

Alternative sequence

259 – 272

14

Missing in isoform 2 and isoform 3.

VSP_005791

Natural variant

270

1

P → S: dbSNP rs2494876. Ref.1 Ref.2

VAR_052204

Secondary structure

1

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380

Helix Strand Turn

Details...

Beta strand

46 – 52

7

Helix

59 – 67

9

Beta strand

72 – 79

8

Turn

81 – 83

3

Beta strand

86 – 96

11

Helix

97 – 107

11

Beta strand

118 – 121

4

Helix

127 – 129

3

Beta strand

133 – 138

6

Helix

145 – 152

8

Helix

153 – 155

3

Beta strand

158 – 165

8

Turn

167 – 169

3

Beta strand

172 – 182

11

Helix

183 – 193

11

Beta strand

206 – 209

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (HUD1PRO) [UniParc]. Last modified February 10, 2009. Version 2. Checksum: 80E82D40FA5A05DE	FASTA	380	41,770
	10 20 30 40 50 60 MVMIISTMEP QVSNGPTSNT SNGPSSNNRN CPSPMQTGAT TDDSKTNLIV NYLPQNMTQE 70 80 90 100 110 120 EFRSLFGSIG EIESCKLVRD KITGQSLGYG FVNYIDPKDA EKAINTLNGL RLQTKTIKVS 130 140 150 160 170 180 YARPSSASIR DANLYVSGLP KTMTQKELEQ LFSQYGRIIT SRILVDQVTG VSRGVGFIRF 190 200 210 220 230 240 DKRIEAEEAI KGLNGQKPSG ATEPITVKFA NNPSQKSSQA LLSQLYQSPN RRYPGPLHHQ 250 260 270 280 290 300 AQRFRLDNLL NMAYGVKRLM SGPVPPSACP PRFSPITIDG MTSLVGMNIP GHTGTGWCIF 310 320 330 340 350 360 VYNLSPDSDE SVLWQLFGPF GAVNNVKVIR DFNTNKCKGF GFVTMTNYDE AAMAIASLNG 370 380 YRLGDRVLQV SFKTNKAHKS
	Isoform 2 (HUD1). Checksum: 9BB102A0AD7495F1	FASTA	366	40,379
	10 20 30 40 50 60 MVMIISTMEP QVSNGPTSNT SNGPSSNNRN CPSPMQTGAT TDDSKTNLIV NYLPQNMTQE 70 80 90 100 110 120 EFRSLFGSIG EIESCKLVRD KITGQSLGYG FVNYIDPKDA EKAINTLNGL RLQTKTIKVS 130 140 150 160 170 180 YARPSSASIR DANLYVSGLP KTMTQKELEQ LFSQYGRIIT SRILVDQVTG VSRGVGFIRF 190 200 210 220 230 240 DKRIEAEEAI KGLNGQKPSG ATEPITVKFA NNPSQKSSQA LLSQLYQSPN RRYPGPLHHQ 250 260 270 280 290 300 AQRFRLDNLL NMAYGVKRFS PITIDGMTSL VGMNIPGHTG TGWCIFVYNL SPDSDESVLW 310 320 330 340 350 360 QLFGPFGAVN NVKVIRDFNT NKCKGFGFVT MTNYDEAAMA IASLNGYRLG DRVLQVSFKT NKAHKS
	Isoform 3 (HUD4). Checksum: 4FA0B4DC38E805A2	FASTA	383	42,437
	10 20 30 40 50 60 MRLLLLREIV INESRNCSFM IISTMEPQVS NGPTSNTSNG PSSNNRNCPS PMQTGATTDD 70 80 90 100 110 120 SKTNLIVNYL PQNMTQEEFR SLFGSIGEIE SCKLVRDKIT GQSLGYGFVN YIDPKDAEKA 130 140 150 160 170 180 INTLNGLRLQ TKTIKVSYAR PSSASIRDAN LYVSGLPKTM TQKELEQLFS QYGRIITSRI 190 200 210 220 230 240 LVDQVTGVSR GVGFIRFDKR IEAEEAIKGL NGQKPSGATE PITVKFANNP SQKSSQALLS 250 260 270 280 290 300 QLYQSPNRRY PGPLHHQAQR FRLDNLLNMA YGVKRFSPIT IDGMTSLVGM NIPGHTGTGW 310 320 330 340 350 360 CIFVYNLSPD SDESVLWQLF GPFGAVNNVK VIRDFNTNKC KGFGFVTMTN YDEAAMAIAS 370 380 LNGYRLGDRV LQVSFKTNKA HKS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"HuD, a paraneoplastic encephalomyelitis antigen, contains RNA-binding domains and is homologous to Elav and Sex-lethal." Szabo A., Dalmau J., Manley G., Rosenfeld M., Wong E., Henson J., Posner J.B., Furneaux H.M. Cell 67:325-333(1991) [PubMed: 1655278] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANT SER-270. Tissue: Brain.
[2]	"Novel products of the HuD, HuC, NNP-1 and alpha-internexin genes identified by autologous antibody screening of a pediatric neuroblastoma library." Behrends U., Jandl T., Golbeck A., Lechner B., Mueller-Weihrich S., Schmid I., Till H., Berthold F., Voltz R., Mautner J.M. Int. J. Cancer 100:669-677(2002) [PubMed: 12209604] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), VARIANT SER-270. Tissue: Neuroblastoma.
[3]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"CARM1 regulates proliferation of PC12 cells by methylating HuD." Fujiwara T., Mori Y., Chu D.L., Koyama Y., Miyata S., Tanaka H., Yachi K., Kubo T., Yoshikawa H., Tohyama M. Mol. Cell. Biol. 26:2273-2285(2006) [PubMed: 16508003] [Abstract] Cited for: METHYLATION AT ARG-243.
[5]	"Structural basis for recognition of AU-rich element RNA by the HuD protein." Wang X., Tanaka Hall T.M. Nat. Struct. Biol. 8:141-145(2001) [PubMed: 11175903] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 44-210 IN COMPLEX WITH RNA.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M62843 mRNA. Translation: AAA58396.1.
AY033996 mRNA. Translation: AAK57539.1.
AY033997 mRNA. Translation: AAK57540.1.
AY033998 mRNA. Translation: AAK57541.1.
AL583843, AL592182 Genomic DNA. Translation: CAI14635.1.
AL592182, AL583843 Genomic DNA. Translation: CAI15789.1.

IPI

IPI00395507.
IPI00479625.
IPI00607677.

PIR

A40348.

RefSeq

NP_001138246.1.
NP_001138247.1.
NP_068771.2.

UniGene

Hs.213050

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1FXL	X-ray	1.80	A	44-210	[»]
1G2E	X-ray	2.30	A	44-210	[»]

ModBase

Search...

PTM databases

PhosphoSite

P26378.

Genome annotation databases

Ensembl

ENSG00000162374. Homo sapiens. [Contig view]

GeneID

1996.

KEGG

hsa:1996.

Organism-specific databases

GeneCards

GC01P050283.

H-InvDB

HIX0023614.

HGNC

HGNC:3315. ELAVL4.

HPA

CAB004442.

MIM

168360. gene.

PharmGKB

PA27743.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P26378.

Gene expression databases

ArrayExpress

P26378.

Bgee

P26378.

CleanEx

HS_ELAVL4.

GermOnline

ENSG00000162374. Homo sapiens.

Family and domain databases

InterPro

IPR012677. a_b_plait_nuc_bd.
IPR006548. ELAD_HUD_SF.
IPR002343. Hud_Sxl_RNA.
IPR000504. RRM_RNP1.
[Graphical view]

Gene3D

G3DSA:3.30.70.330. a_b_plait_nuc_bd. 3 hits.

Pfam

PF00076. RRM_1. 3 hits.
[Graphical view]

PRINTS

PR00961. HUDSXLRNA.

SMART

SM00360. RRM. 3 hits.
[Graphical view]

TIGRFAMs

TIGR01661. ELAV_HUD_SF. 1 hit.

PROSITE

PS50102. RRM. 3 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

8073.

SOURCE

Search...

Entry information

Entry name

ELAV4_HUMAN

Accession

Primary (citable) accession number: P26378
Secondary accession number(s): Q96J74

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	February 10, 2009
Last modified:	May 5, 2009
This is version 91 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)