P17677 (NEUM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Neuromodulin

Alternative name(s):
Axonal membrane protein GAP-43
Growth-associated protein 43
Neural phosphoprotein B-50
pp46

Gene names

Name:

GAP43

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	238 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	This protein is associated with nerve growth. It is a major component of the motile "growth cones" that form the tips of elongating axons. Plays a role in axonal and dendritic filopodia induction. Ref.8 Ref.9
Subunit structure	Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN By similarity. Binds calmodulin with a greater affinity in the absence of Ca2+ than in its presence By similarity.
Subcellular location	Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cell projection › growth cone membrane; Peripheral membrane protein; Cytoplasmic side. Cell junction › synapse. Cell projection › filopodium membrane; Peripheral membrane protein. Note: Cytoplasmic surface of growth cone and synaptic plasma membranes. Ref.8
Post-translational modification	Phosphorylated at Ser-41 by PHK. Phosphorylation of this protein by a protein kinase C is specifically correlated with certain forms of synaptic plasticity. Palmitoylation by ARF6 is essential for plasma membrane association and axonal and dendritic filopodia induction. Deacylated by LYPLA2.
Sequence similarities	Belongs to the neuromodulin family. Contains 1 IQ domain.

Ontologies

Keywords
Biological process	Differentiation Growth regulation Neurogenesis
Cellular component	Cell junction Cell membrane Cell projection Membrane Synapse
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Calmodulin-binding
Molecular function	Developmental protein
PTM	Lipoprotein Palmitate Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	axon choice point recognition Inferred from electronic annotation. Source: Compara cell fate commitment Inferred from electronic annotation. Source: Compara glial cell differentiation Inferred from electronic annotation. Source: Compara protein kinase C-activating G-protein coupled receptor signaling pathway Traceable author statement Ref.1. Source: ProtInc regulation of filopodium assembly Inferred from direct assay Ref.8. Source: UniProtKB regulation of growth Inferred from electronic annotation. Source: UniProtKB-KW response to wounding Traceable author statement Ref.1. Source: ProtInc tissue regeneration Inferred from electronic annotation. Source: Compara
Cellular_component	axon Inferred from electronic annotation. Source: Compara cell junction Inferred from electronic annotation. Source: UniProtKB-KW filopodium membrane Inferred from direct assay Ref.8. Source: UniProtKB growth cone membrane Inferred from electronic annotation. Source: UniProtKB-SubCell synapse Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PRKCD	Q05655	4	EBI-1267511,EBI-704279

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P17677-1)

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: P17677-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-10: MLCCMRRTKQ → MTKSCSELCHPALHFLPCLGGLRKNLQRAVRPSPYSLGFLTFWISR

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 238	238	Neuromodulin		PRO_0000159596
Regions
	Domain	31 – 60	30	IQ
	Region	1 – 4	4	Important for membrane binding
Amino acid modifications
	Modified residue	41	1	Phosphoserine; by PHK and PKC By similarity
	Modified residue	94	1	Phosphothreonine By similarity
	Modified residue	181	1	Phosphothreonine By similarity
	Modified residue	202	1	Phosphoserine; by CK2 By similarity
	Modified residue	203	1	Phosphoserine; by CK2 By similarity
	Lipidation	3	1	S-palmitoyl cysteine By similarity
	Lipidation	4	1	S-palmitoyl cysteine By similarity
Natural variations
	Alternative sequence	1 – 10	10	MLCCMRRTKQ → MTKSCSELCHPALHFLPCLG GLRKNLQRAVRPSPYSLGFL TFWISR in isoform 2.		VSP_042783
	Natural variant	59	1	V → I. Ref.11 Corresponds to variant rs6291 [ dbSNP | Ensembl ].		VAR_014172
	Natural variant	162	1	K → E. Corresponds to variant rs11557762 [ dbSNP | Ensembl ].		VAR_050271
Experimental info
	Mutagenesis	3 – 4	2	CC → SS: Inhibits axonal and dendritic filopodia formation and reduces dendritic and axonal branching. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified August 1, 1990. Version 1. Checksum: B3536D012A127CC8	FASTA	238	24,803
	10 20 30 40 50 60 MLCCMRRTKQ VEKNDDDQKI EQDGIKPEDK AHKAATKIQA SFRGHITRKK LKGEKKDDVQ 70 80 90 100 110 120 AAEAEANKKD EAPVADGVEK KGEGTTTAEA APATGSKPDE PGKAGETPSE EKKGEGDAAT 130 140 150 160 170 180 EQAAPQAPAS SEEKAGSAET ESATKASTDN SPSSKAEDAP AKEEPKQADV PAAVTAAAAT 190 200 210 220 230 TPAAEDAAAK ATAQPPTETG ESSQAEENIE AVDETKPKES ARQDEGKEEE PEADQEHA
	Isoform 2 [UniParc]. Checksum: 5FC56C8954970362	FASTA	274	28,766
	10 20 30 40 50 60 MTKSCSELCH PALHFLPCLG GLRKNLQRAV RPSPYSLGFL TFWISRVEKN DDDQKIEQDG 70 80 90 100 110 120 IKPEDKAHKA ATKIQASFRG HITRKKLKGE KKDDVQAAEA EANKKDEAPV ADGVEKKGEG 130 140 150 160 170 180 TTTAEAAPAT GSKPDEPGKA GETPSEEKKG EGDAATEQAA PQAPASSEEK AGSAETESAT 190 200 210 220 230 240 KASTDNSPSS KAEDAPAKEE PKQADVPAAV TAAAATTPAA EDAAAKATAQ PPTETGESSQ 250 260 270 AEENIEAVDE TKPKESARQD EGKEEEPEAD QEHA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human GAP-43: its deduced amino acid sequence and chromosomal localization in mouse and human." Kosik K.S., Orecchio L.D., Bruns G.A.P., Benowitz L.I., McDonald G.P., Cox D.R., Neve R. Neuron 1:127-132(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Cloning of human GAP-43: growth association and ischemic resurgence." Ng S.-C., de la Monte S.M., Conboy G.L., Karns L.R., Fishman M.C. Neuron 1:133-139(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"Structure of the human gene for the neural phosphoprotein B-50 (GAP-43)." Nielander H.B., de Groen P.C., Eggen B.J., Schrama L.H., Gispen W.H., Schotman P. Brain Res. Mol. Brain Res. 19:293-302(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	NIEHS SNPs program Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain cortex and Subthalamic nucleus.
[6]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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 1). Tissue: Brain.
[8]	"Regulation of dendritic branching and filopodia formation in hippocampal neurons by specific acylated protein motifs." Gauthier-Campbell C., Bredt D.S., Murphy T.H., El-Husseini A. Mol. Biol. Cell 15:2205-2217(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF 3-CYS-CYS-4.
[9]	"Acyl-protein thioesterase 2 catalyzes the deacylation of peripheral membrane-associated GAP-43." Tomatis V.M., Trenchi A., Gomez G.A., Daniotti J.L. PLoS ONE 5:E15045-E15045(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEACYLATION BY LYPLA2.
[10]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]	"Characterization of single-nucleotide polymorphisms in coding regions of human genes." Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S. Nat. Genet. 22:231-238(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ILE-59.
[12]	Erratum Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S. Nat. Genet. 23:373-373(1999)
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Wikipedia

Gap-43 entry

Cross-references

Sequence databases
EMBL GenBank DDBJ	M25667 mRNA. Translation: AAA52516.1. S66541, S66533, S66534 Genomic DNA. Translation: AAB28649.1. AY842481 Genomic DNA. Translation: AAV88094.1. AK289699 mRNA. Translation: BAF82388.1. AK290100 mRNA. Translation: BAF82789.1. AC012598 Genomic DNA. No translation available. AC092468 Genomic DNA. No translation available. AC119795 Genomic DNA. No translation available. BC007936 mRNA. Translation: AAH07936.1.
IPI	IPI00015964. IPI00791316.
PIR	I52638.
RefSeq	NP_001123536.1. NM_001130064.1. NP_002036.1. NM_002045.3.
UniGene	Hs.134974.
3D structure databases
ProteinModelPortal	P17677.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-452N.
IntAct	P17677. 1 interaction.
STRING	9606.ENSP00000377372.
Protein family/group databases
TCDB	1.A.71.2.1. brain acid-soluble protein channel (BASP1 Channel) family.
PTM databases
PhosphoSite	P17677.
Polymorphism databases
DMDM	128100.
Proteomic databases
PaxDb	P17677.
PRIDE	P17677.
Protocols and materials databases
DNASU	2596.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000305124; ENSP00000305010; ENSG00000172020. ENST00000393780; ENSP00000377372; ENSG00000172020.
GeneID	2596.
KEGG	hsa:2596.
UCSC	uc003ebq.2. human.
Organism-specific databases
CTD	2596.
GeneCards	GC03P115342.
HGNC	HGNC:4140. GAP43.
HPA	CAB004417. HPA013392. HPA015600.
MIM	162060. gene.
neXtProt	NX_P17677.
PharmGKB	PA28553.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG120480.
HOGENOM	HOG000013014.
HOVERGEN	HBG006468.
OMA	VEKKGEG.
Gene expression databases
ArrayExpress	P17677.
Bgee	P17677.
CleanEx	HS_GAP43.
Genevestigator	P17677.
GermOnline	ENSG00000172020. Homo sapiens.
Family and domain databases
InterPro	IPR000048. IQ_motif_EF-hand-BS. IPR001422. Neuromodulin. IPR017454. Neuromodulin_C. IPR018947. Neuromodulin_gap-junction_N. IPR018243. Neuromodulin_palmitoyl/P_site. [Graphical view]
Pfam	PF00612. IQ. 1 hit. PF06614. Neuromodulin. 1 hit. PF10580. Neuromodulin_N. 1 hit. [Graphical view]
PRINTS	PR00215. NEUROMODULIN.
SMART	SM00015. IQ. 1 hit. [Graphical view]
PROSITE	PS50096. IQ. 1 hit. PS00412. NEUROMODULIN_1. 1 hit. PS00413. NEUROMODULIN_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	GAP43. human.
GenomeRNAi	2596.
NextBio	10267.
SOURCE	Search...

Entry information

Entry name

NEUM_HUMAN

Accession

Primary (citable) accession number: P17677
Secondary accession number(s): A8K0Y4

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	August 1, 1990
Last modified:	April 3, 2013
This is version 139 of the entry and version 1 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.